#18-panel nail drug test

[amhnationwide]

Drug test for Kratom 18 panel drug test

New Post has been published on https://amhnationwide.com/drug-testing/drug-test-for-kratom-18-panel-drug-test/

Drug test for Kratom 18 panel drug test

categories: #DrugTesting tags: #18PanelDrugTest, #18PanelHairDrugTest, #18PanelNailDrugTest, #DrugTestForChild, #DrugTestForKratom, #HairTestForKratom, #KratomDrugTest, #NailTestForKratom

[chidoroki]

The Promised Neverland S2EP6

aka: manga content is bliss!!!!

I will never get over how perfect those match cuts between the demon/human handshake, the chains & Emma are during the OP.. and how it builds up to the chorus is just.. aaahh, fantastic.

Oh! Lambda crew was added to the OP alongside the GF escapees. Norman too!

AAhh they really did fill in that empty spot with him during the last shot of Emma and Ray.. that’s wonderful!

“Emma’s Determination” starts up as I realize how foolish these kids are right now. Y’all are really about to have a touching reunion with each other in the middle of a demon town? With your disguises off?

Aaaaww that hug though!!

Look at her touching his face to make sure he’s real! I’m so glad they kept that panel! And how he noticed her missing ear too!

“I brought Ray out, too.” Well no shit honey.

YAAAYYY BEST BOY SLAPPED NORMAN!! Too bad it wasn’t hard enough to knock him to the ground like in manga but I’ll take it!

“But you say something cool, right?” “Yeah. Thanks to you. I’m glad I’m alive.” Dude, my heart.. aahhh!

The trio hug!! They’re all so cute!! I can’t handle all these happy feelings!

The Lambda crew is just standing there in the back like.. yeah, okay.

The younger kids are so happy to see Norman too.. but again manga did it better when they all tackled him to the ground. Granted that was a different scene but I would’ve loved to see it happen still.

Ah there’s his Lambda marking.

“I only took tests, so I’m fine.” Are you sure? Or are you just saying that so they won’t worry? Kind of like how he told the Lambda crew he didn’t get seizures when he actually did.

Also, I know some might think what was just said is true since Norman looks young and not like the “boss” Norman we were hoping for, but the anime is actually accurate in regards to that. Ch129 shows a flashback that takes place in February 2047 where Norman still looks younger. When the initial reunion in ch118/119 happens in November 2047, so perhaps the experiments/drugs manga Norman was given take time to affect his physical state or whatever. What I’m getting at is the anime isn’t denying us of “boss” Norman, it just hasn’t happened yet in this timeline.

Oh, Smee was actually mentioned!

Here comes the demon chatter and the poison.

“No, we’d fare better than going against a smarter demon.” True, not that anyone would truly know that because, you know, no GP..

“We’ll make the demons extinct. There will be no more Neverland.” Okay yeah, Norman takes Emma’s wish to heart by trying to create a world in which their family can live happily, but do you have to go through such extremes dude?

“Let’s establish a paradise for all of us in this demon world.” Manga Norman accomplished that, anime Norman.

Ohhh Ray notices Emma’s bluff, doesn’t he?

“If I give the word, even as early as tomorrow.” That’s quick, but fits with the pace of this season well enough..

“Now we can move forward, thanks to Norman.” Ah yes, we’re all saved thanks to our main character. Oh, wait.. that’s right. She’s over here being disrespected!

The base Smee left them? Is that the Paradise hideout? I forget.. or are we talking about the D100 location now?

Norman’s going back somewhere?

“It’s great.” “Is it really, though?” AH! Shut the fuck up! Are we getting the balcony scene here?? Right now?? Sure the duo is on top of a tower right now but y’all know what conversation I’m referring to!!

“About Norman’s plan.. you actually don’t want that, right?” IT’S HAPPENING!!! Oooh my god!!!

“But that’s not the future you want, is it?” “Something’s wrong with me.” Quick! Someone hold me! I’m not ready!!

Aww, Gilda helping Alicia with her nightmare.. that’s so precious!

Emma’s voice actor is totally nailing this scene so far.

“Yeah, nothing can be done.” Y’all, the way his voice became significantly confident and so positive and Emma’s reaction to him were perfect!!

“Don’t dig up my buried feelings, you jerk!” Emma sweetheart, I love you so much!

“If you’re going to bury your feelings, then take them to your gave, no matter what.” I know I said this once in the past, but after what happens in ch180, yeeaahh she takes his advice reaaallly well.

Oh they brought back “Emma’s Sorrow” to really make me even more emotional during this scene!!

You can always count on Ray to be completely blunt.

“Depending on the circumstances, we might get a clue on how humans and demons can coexist.” “Ray!” Bro she looked so hopeful and thankful that he’s even considering it! You could literally hear the relief in Emma’s voice!

“Choose what you want to do, and I’ll support you. No matter what you choose, you’ll be okay.” AAAAAAAAAAAAHHHHHHHHH!!!! HE SAID IT!!

“You can do the impossible. That’s your specialty, right? Let’s create a future we won’t regret.” “Okay! Thanks, Ray!” AAH I AM SO FUCKING HAPPY!!! And the sunrise makes this scene so beautiful!!!

“My head feels clearer now.” “You’re too easy!” They even remembered those tiny lines too!!!

Y’ALL!! I am feeling.. SO DAMN SOFT RIGHT NOW!! Holy shit.. yes, this scene would’ve been 5x better in terms of weight and importance if we saw every manga event that built up their bond and led up to this scene, but still!! The dialogue was on point! The emotion in their voices was everything I hoped for! The animation itself was good too!

Also, the sunrise?? Genius! Here we have our girl lost within her own mind and feeling completely alone due to her ideals, then BAM! Ray listens to her concerns, lends his assistance by thinking through a different course of action that would ease her wavering heart and restores some of her usual optimistic attitude. My boy literally helps our girl out of the dark and shined light on her mood/plan and that’s absolute perfection. (my ship bias is real obvious right now huh?)

Did we get the head pat? No, of course we didn’t. But I’m so happy to actually see & hear this conversation that I don’t care! I love these two so much. I honestly didn’t think we would get this scene. Even after the episode preview yesterday I still had my doubts but aahh my heart is so insanely happy right now!!

Oh? The duo is off to the location Norman gave them? This random, small house in the middle of no where?

Aaah Lambda crew! And THEY SPOKE WORDS!

Pfft they still had Barbara mix up “shield” and “field” and I love it.

Look how much shorter the duo is compared to Vincent!!

“He’s with Boss now, they’re..” Okay, one: I love that they still refer to Norman as “boss” despite him still looking like a child. Two: is he making the fake alliance with that demon clan already or nah?

Haahaha YEESS! They still had Ray choke on his drink!!

Vincent has such a deep voice.. he’s what, 17? 18? But damn.. who is his voice actor?

Also, just noticed the star on Barbara’s shirt doesn’t have the little face on it.

Mmhhmm, Barbara’s frustration was nice.

Oh, Norman returned.. and left as quick as he came.

Ahh! This is the conversation the duo had at the start of ch126!

Well, a real tiny part of it.. thanks for cutting it short, Norman.

“The Evil-Blooded girl is still alive?” Aayy the anime did their best with that panel. I’ll give them that much.

Okay.. that episode was great. Ya see what happens when you actually follow the manga? Sure some scenes/locations/panels were off but overall it was just so wonderful.

I’m happy. Granted the RE scene put me on a real high but yeah.. anime, I’m praising you! Keep it up!

(though I’ll be salty over no GP for the rest of my life, don’t worry.)

[kathleenseiber]

Inside Biology’s Black Box

This article from the March issue of Cosmos has been shortlisted for the 2020 Eureka Prize for Long-Form Science Journalism. The prize will be announced November 20.

A new device for bioengineering embryo-like structures is shedding fresh light on those earliest, most mysterious – and largely unobservable – moments of human development. Great leaps forward in safe, successful pregnancies and congenital defect prevention await, but so do a host of ethical questions.

The development of two stem cell groupings at 6 hour increments. Credit: Jianping Fu

I count six little ziggurats side by side, stolid and squat and obviously man-made. They are not going anywhere, but in between them things are on the move.

Circles of dots have begun to roil and rotate, angry blimps rising up  among the static trapezoids, their contents swirling in a frenzy of disorder. Then, in each one, a ring solidifies and grows in the chaos.

It’s fleeting, and the jiggling hoop is soon churned back into the mass as the riot spreads unchecked.

These dots are human cells and their acrobatics are the beginnings of human life, though not as we know it. There is no womb, no pulsing maternal heart. Instead, the cells are born in an elaborate plastic chamber under constant video surveillance, and I am witness to their first two days of existence, compressed into a sparse 18 seconds by the wonders of time-lapse video.

The architect of this dazzling piece of cellular music hall is bioengineer Jianping Fu, whose field of expertise – mechanobiology – tries to understand how living cells change in response to physical forces.

Working from his University of Michigan lab on the outskirts of industrial Detroit, Fu is bringing the measured mindset of the machine-builder to the job of constructing life. He is one of an elite cohort of scientists trying to build a replica of the human embryo from the ground up to try to understand just how we are made – and where it can all go horribly wrong.

This area of science aims to alleviate the gamut of reproductive misery, from the anguish of infertility and miscarriage to gathering information about drugs like Thalidomide, which seem innocuous but have grave consequences if taken during pregnancy.

Fu’s bundles of cells, dubbed embryoids, could be used to screen drugs for toxicity in the womb. They might also unravel the mystery of why two out of every five pregnancies fail before 20 weeks. But these scientists, tinkering at the dawn of life, don’t know how far the cells can develop. There is talk their creations could one day provide a source of organs for transplant. The spectre of a baby in a dish looms ominously in the public imagination.

Which is why Fu’s bit of kit, written up in Nature in September and described by leading embryologist Ali Brivanlou as “a major advance in the knowledge of early human development”, is also an invitation for humanity to do some circle time on what it means to build a human.

The invention that’s created this excitement is a simple-looking chamber with three channels. In one, Fu places pluripotent stem cells, blue-sky building blocks that can become almost any human cell. They are immortal and can be frozen and thawed, forming a renewable resource that can be used for years.

Some of these are embryonic stem cells, originally derived from human IVF embryos. Fu also uses “induced pluripotent stem cells” – iPS cells for short – that come from adult skin cells re-programmed back to a primal state.

In the second channel Fu pours a liquid containing morphogens, the fertilisers that hurry stem cells on with the job of remaking themselves over and over. In the third, he lays a gel to support the growing masses, each one hived into its own mini-domain by evenly spaced support posts – the ziggurats.

In many respects there’s nothing novel about this. Researchers the world over are growing stem cells into structures that mimic the early embryo, before getting them to switch course in the first few weeks and become heart, brain or kidney cells.

These grow to make mini organs or “organoids”, about the size of a stunted chickpea, that are used to model diseases on the lab bench and test if drugs or gene tweaks might be a cure.

But Fu is aiming to make the whole shebang.

There’s no diverting cells off into hearts and brains – rather, he wants them to run their course and become something that resembles the early human embryo.

Fu has pushed these embryoids as far as anyone’s been yet and, true to his engineering pedigree, he’s done much of it by inventing a new 3D world for the stem cell colonies to grow in.

“Most excitingly… in this first set of experiments, is the fact that in a subset of those colonies we start to see some asymmetric tissues, asymmetric embryonic structures,” he tells me by phone.

Credit: Jianping Fu

Embryologists tend to get breathless about symmetry, or lack of it. After natural conception, when the sperm fuses with the egg to form the singlecelled zygote, there follows a cascade of dividing, with new cells budding outwards in a uniform ball which, at day three, becomes the 16-cell morula – Latin for mulberry, which it resembles.

But around day six there is a major break from the order of symmetry, as the front-to-back, belly-to-spine axis appears. Anyone aiming to make a human embryo needs to nail this. Fu didn’t just meet the milestone; he also produced the cells that become the amniotic sac – the fluid-filled bag in which the foetus floats.

“These asymmetric structures, basically they resemble the core of the peri-implantation human embryo,” he says.

Implantation. It strikes at the heart of this project. Somewhere between six and 12 days after conception, the human embryo nestles into the fleshy wall of the uterus. This is essential if the pregnancy is to continue. But when it goes wrong, it’s disastrous. Nearly three quarters of all pregnancies that miscarry by 20 weeks are a failure to implant. And the two months after implantation are when the embryo is most vulnerable to the effects of drugs or maternal infections that cause birth defects.

Given the gravity of these issues, you’d think an avalanche of research would have shed light on them. In fact, we know so little about the period it’s called the ‘black box’ of embryology.

The implanted embryo, key to the enigma of early life, is mostly invisible to science. The first reason is structural: the embryo is sequestered in a uterus beyond our gaze. The second is ethical: scientists have grown human IVF embryos for 13 days in the lab, but no one has gone beyond two weeks.

Endorsed by the UK’s Warnock Committee in 1984 and then by the US National Institutes of Health’s Human Embryo Research Panel in 1994, the 14-day rule bans lab research on embryos beyond that point.

It is around this time that a groove called the primitive streak appears in the embryo: among other things this marks a cut-off beyond which twinning is impossible. This is the defining line of the individual human which, some believe, is morally significant. The 14-day rule is enforced by legislation in at least 12 countries.

The reasoning is clear, but the effect is to keep the black box in shadow; science hasn’t had a way to illuminate it.

Now the spotlight falls on Fu’s plastic channels, properly called microfluidic devices. In Fu’s earlier experiments, only around 5-10% of his embryoids reached that asymmetry waypost. But in his lab just a short drive from the factory where Henry Ford christened the first of his Model Ts, Fu has rewritten the rules of embryoid production.

“With this microfluidic system, now we can generate such human embryo-like structures with very high efficiency, up to about 95%,” he says.

Fu’s system isn’t just meeting quality benchmarks, and this is where the parallels with Motor City’s early denizens become a little more pronounced. “It is a scalable system,” he says. “I would even say that now… it becomes a manufacturing system, depending on the needs, right? Depending on how many you need.”

Fu’s tone is measured, matter of fact. But on this moonshot to the dark side of our collective beginning he carries the interests of Everyman, so be reassured that he tells his tale with deep concern for our wellbeing.

What if we could develop a screening mechanism, that’s an adjunct to pharmaceutical development, that enabled us to provide a safeguard for a new drug?

When he says the system “will be very useful for high throughput screening”, that clinical parlance describes the potentially vast benefits to real embryos of testing hundreds of drugs on embryoids first. His work could also show why so many pregnancies miscarry – and improve our measly IVF success rate of 20%.

Indeed, his precision-tooled temperament may be a prerequisite for the kind of slog needed here, to get an embryoid to trace the footsteps of a real human embryo, in something the scientists call recapitulation. It is only by mimicking the true-life course that a dish-bound doppelganger can give test results that are valid.

And that is a big ask, not least because there is no gold standard; the ‘black box’ means there is no definitive embryo library to provide reference points for the journey. Then there are the endless variables in embryoid research: the physical layout of the device, when to add morphogens and chemical signals, and countless other tiny details.

Which is where Fu took his Enterprise into deep space. His embryoids reached the early phase of another critical developmental stage called gastrulation. When the furrow-like primitive streak appears at 14 days, it signals that the cells below, a little like the settling of ploughed earth, are falling into three layers: the ectoderm, mesoderm and endoderm, respective precursors of skin and brain, muscle, and internal organs. Their emergence heralds the laying down of the body plan.

But Fu’s embryoids also showed something else undeniably human. Budding off from those furiously dividing balls were the barely discernible outlines of germ cells. These define the male and female sex – they are the cells that go on to produce sperm or eggs.

Megan Munsie is Deputy Director of the Centre for Stem Cell Systems at the University of Melbourne and has been entangled with the stem cell story for two decades, first as a researcher and now as an expert on policy and ethics. The appearance of these sex cells left a deep impression.

“This is a part of human development that we just really can’t follow,” she says. “The start of the germ lineage I think is absolutely fascinating.”

Nor was it the only aspect of Fu’s achievement that gave her pause.

“When we looked across his images I found them quite extraordinary,” she says. “In almost all the clusters in the wells the patterning was consistent, and as you can imagine in this area of biology there is often quite a lot of inconsistency.”

That cookie cutter reliability is essential if you want to screen a bunch of drugs for harmful effects; the substrate has to repeat faithfully across each test. One example, of course, stands out.

“Thalidomide, who was expecting that? What if we could develop a screening mechanism, that is an adjunct to pharmaceutical development, that enabled us to provide a safeguard for a new drug?” asks Munsie.

Barely a kilometre from Munsie’s office, across Melbourne’s verdant and expansive Royal Park, Andrew Elefanty is using stem cells to try to make bespoke blood for people whose bone marrow has failed, or is in overdrive making blood cells that don’t work properly – the leukaemias.

It is the kind of medicine that shows just how personalised the embryoid project could become.

Credit: University of Michigan Engineering

In order to create the customised blood, Elefanty’s team at the Murdoch Children’s Research Institute takes blood samples from volunteers. The immature red cells are removed and, with the help of genes delivered in a virus, programmed back to a pluripotent state – they become iPS cells.

In crimson culture fluid in blue-capped flasks, these iPS cells are then urged by the team towards the embryoid stage. But, unlike Fu, the team halts development at the point of gastrulation, directing the cells to become mesoderm alone.

Why? Because it is that layer, as Elefanty shows me in a stunning photo, that fashions the seminal version of our biggest blood vessel, the aorta, in whose walls, at this rudimentary time, the red blood cells are made.

Duplicate Elefanty’s process with the blood of someone with leukaemia and the hope is that, one day, you could make healthy blood for them that’s a perfect match.

But I’m confused about something.

Since stem cells were first coaxed into tiny 3D brain-like structures in 2008, scientists have produced a cornucopia of organoids. All of these – mini brains, hearts, kidneys and even blood cells – can be made directly from pluripotent stem cells. Why, then, would you want to push them through the embryoid pathway first, which seems to be taking the long way round?

“The way that works the best, if you like, is if you try to direct them via a trajectory where you do actually try to replicate some of the steps during embryonic differentiation,” says Elefanty. “That’s the road map that you’re following.”

The whole process is artificial, but there’s something of a “nature knows best” adage at its heart. Elefanty is leveraging nature’s navigational toolbox, whose items have been checked off by the rigorous oversight of evolution, to make a better blood cell.

The embryoid pathway could also be a way forward for organ replacement.

Writing in Nature in 2018, stem cell pioneer Martin Pera and colleagues noted that mini brains, livers and kidneys made from stem cells are pretty basic, and that maybe we can do better.

“Initiating organ development in an environment as similar as possible to the developing embryo might… generate structures that more closely resemble mature, functional organs, for drug screens or even for transplantation,” they write.

Usable organs, however, both in terms of sophistication and size, would need the embryoid to be pushed much further along the developmental path than it has been. Elefanty points out two largish hurdles to that ever happening.

“If you don’t have the right cell type you can’t make a whole embryo. And secondly, what people can’t underestimate is the difficulty in reproducing the environment that is the same as the implanted embryo,” he says.

Here’s the rub. Fu’s whirling cell clusters are the right ones to make the headline act of the embryo, but are missing the supporting entourage: the trophoblasts that become the placenta, and the hypoblasts that go on to make the yolk sac, needed to nourish the early embryo.

These are critical kit in their own right, but they also play a key role in what is called patterning, which plots the layout of the body – for example, getting your liver and spleen in the right spot or crystallising the geography of the brain’s bumps and folds.

Here, however, the incoming breakers of science seem relentless.

In 2018, Japanese researchers cultured human trophoblast stem cells for the first time, raising the prospect of an artificially grown placenta. Another announcement last June, however, may have leapfrogged that altogether.

A group led by Xuefei Gao from the University of Hong Kong created something called “expanded potential stem cells”. With some clever chemical coaxing they heightened the potency of human embryonic stem cells and iPS cells – stem cells on steroids if you like. Crucially, expanded potential stem cells can make those missing bits – the placenta and yolk sac.

The final step would be replicating implantation, and in October 2019 the Salk Institute’s Juan Carlos Izpisua Belmonte led a team that created expanded potential stem cells from mice, some by reprogramming cells from the critters’ ears, to make what they say “could potentially be… fully functional synthetic embryos in vitro”.

Jianping Fu looks on as postdoctoral fellow Yi Zheng examines stained stem cells. Credit: Jianping Fu.

Equipped with placenta and yolk sac, these are primed to become fully fledged foetuses – and Belmonte successfully implanted the structures in a mouse uterus. Only 7% took and, after a week, they were badly malformed. But it is early days.

As the science rushes onwards it is hard enough to understand it, let alone pass judgment on how far it should all be allowed to go. There are ground rules in place. The 14-day rule is as bedrock as ethics gets, exerting global influence. But, for the purposes of regulation, is an embryoid an embryo?

In Australia it probably is, even though no one is pushing the experimental agenda at anywhere near Fu’s level.

Dianne Nicol is Chair of Australia’s Embryo Research Licensing Committee, which would make any such adjudication should the question arise. It hasn’t – yet. She originally trained as a developmental biologist and is now a Professor of Law at the University of Tasmania.

Nicol directs me to The Research Involving Human Embryos Act 2002, which defines a human embryo as something made by fertilisation of a human egg by a sperm. But it goes beyond that, to things with a human nuclear genome that have “the potential to develop up to, or beyond, the stage at which the primitive streak appears”.

“That does seem to me to include these embryoids that have a capacity to develop to the primitive streak. And if that’s the case then we have a regulatory environment to deal with them,” she says, careful to stress she’s speaking in her capacity as legal academic, not Committee chair. Should the Committee decide similarly, research like Fu’s in Australia would require a licence.

The Act specifies that any research on human embryos must be done under a licence issued by the Committee, a second layer of scrutiny after review by an institutional ethics committee. The decision whether or not to grant such a licence would, almost certainly, take cues from philosophers who specialise in stem cell ethics.

One job for those professional thinkers is to look at why the primitive streak is a moral line in the sand, beyond the question of individuation.

The standard answer is that it heralds the arrival of ectoderm, which prefigures the nervous system, which transmits pain that will, way on down the track, be perceived by a conscious brain. So the primitive streak seems to mark a point beyond which harm could be inflicted.

I asked Insoo Hyun, a Professor of Bioethics and Philosophy at Case Western Reserve University in the US, if the moral weight attached to the primitive streak is justified.

“I think, from a secular point of view, it is very hard to defend that, because we’re not even at the point where we’ve got functioning neurons or any kind of capacity for experience or pain,” he says.

Hyun also notes that many versions of the 14-day rule are nuanced, specifying that culture of embryos cannot go beyond 14 days or the appearance of the primitive streak, whichever comes first.

That points to 14 days being relevant only because it coincides with primitive streak formation. But the whole embryoid project could rejig the developmental order – scientists could, theoretically, make the primitive streak happen earlier or later.

Adding to the regulatory imbroglio are the tectonic shifts we’ve seen in the ways of concocting human life, from test tube babies to reproductive cloning.

In 1996, biology superstar Dolly the sheep was the first mammal to be cloned from an adult cell. Fashioned by putting DNA from a sheep’s udder cell into a sheep embryo – a process called somatic cell nuclear transfer – Dolly was proof of concept for reproductive cloning, which remains universally banned in humans.

Along with those reproductive advances, Hyun tells me, the laws that define embryos have shifted focus. “You’re seeing embryo definitions in legislation that have less and less to do with how it was created and more and more to do with what they can become,” he says.

You’re seeing embryo definitions in legislation that have less and less to do with how it was created and more and more to do with what they can become.

Which suggests, he adds, that the lawmakers are preoccupied with one big issue when it comes to reproductive technology: “Does the thing in question have the power to make a baby if transferred into the womb?”

When the moral rightness of something hinges on what it could become, you have what philosophers call an “argument from potential”. But such arguments, says Hyun, can get hoisted on their own petard as science advances.

What would happen if, following Belmonte’s work, you could program a human skin cell into an expanded potential stem cell that could ultimately make a baby under the right conditions? In that brave new world, would a flake of dandruff meet a requirement for moral protection?

And what of social potential? If regulation itself prohibits transfer of research embryos into a womb, should that allay concerns about what they might become?

Good ethics, of course, starts with good facts, and Elefanty reminds me that our capabilities are limited.

“There is still a considerable degree of concern over making embryos in a dish which will make viable organisms and so forth because that’s still got a degree of playing God associated with it,” he says.

“I think it is partly moot because I think the technology is nowhere near there.”

Elefanty could well be right. And no one is even remotely suggesting we could, or should, grow a baby in a lab. But the science is moving at speed, and so it may be prudent to get our ethical ducks in a row sooner rather than later.

Just in case.

This article appeared in the March 2020 issue of Cosmos magazine. You can subscribe to the magazine here.

Inside Biology’s Black Box published first on https://triviaqaweb.weebly.com/

[batterymonster2021]

Chronic Hazard Advisory Panel: Phthalates Afternoon Session

New Post has been published on https://hititem.kr/chronic-hazard-advisory-panel-phthalates-afternoon-session/

Chronic Hazard Advisory Panel: Phthalates Afternoon Session

>> ok i’d wish to reconvene the chap. And as a first order of trade I suppose we have to talk about our calendars and when we will have the next chap assembly. So Mike, could you’re taking over on that? >> I do not know about you Bern, however my agenda for the autumn, i’m going to be teaching but i’m beautiful flexible. But is that the equal for you? >> Bernard A. Schwetz: i am lovely bendy too, yeah, so I just isn’t a limiting element in when we have this. >> right, good what we need to do is talk to the other individuals of the committee and spot there are distinct dates that they are not able to meet. I think we’re speaking about regularly October, November. >> Late November could be all correct with me. >> Does that imply the fourth of November, or the 1/3 week k? >> The fourth week would be higher.>> Huh? >> that’s what, Thanksgiving. >> Oh. >> Yeah. Yup. Well, November. >> possibly the 15th would work. The week of the 15th. No? >> I could do the week beginning with twenty second of November. >> All right. >> It was once vacation. >> Is. >> typically it can be a nasty time to journey. >> travel, yeah. >> It is one of the busiest days. >> How about the subsequent week? >> Yeah, possible. >> Holger? I am sorry. >> Holger M. Koch: My Outlook just broke down.>> Oh okay. >> Holger M. Koch: just a 2d ago. >> Oh that you could make it your self. >> very good. >> Or seem at Russ. >> the primary week in, well. >> The 29th. >> The 29th, thirtieth, and December 1st time period? >> Chris? >> Chris Gennings: Works for me. I’ve obtained somebody scheduled for a seminar that Friday that I’ve invited, however that could be rescheduled. >> The front end of the week is ok. >> Chris Gennings: Yeah. >> Russ how’s that for you? >> Russell Hauser: excellent. The 6th is out for me, but I might do 1, 2, 3, 1st, 2nd, third, no hindrance.>> Yeah. Holger? Okay. The next choice is do we wish to schedule a two day or three day meeting. Two. Thoughts? Holger. >> Holger Koch: do we plan to ask other company? Have we mentioned that? >> now we have no longer mentioned that but. So. >> Holger Koch: I feel it might be good to renew the invitation to Tom Burg. But other than that I consider, i don’t consider we, i don’t think there may be a have got to invite anybody else at this stage. >> I want to invite an individual who could aid us to interpret the In-Hanes data. Considering that the deeper I get into the In-Hanes data and extrapolating from the bio-monitoring knowledge of the dose, the trouble is that the In-Hanes information is generated after fasting. So i’d have liked to have a person who can mannequin out the fasting interval. And what’s it in phrases of publicity. Since we all know the various delays, on the foot board, and when you’ve got fasting interval of 12, 14 hours. That is a predominant have an effect on on, on the secretion and then of direction in back calculating to the dose.Chris do you believe that you would be able to manage that? Was that test need to do with kinetics and, and. Given that I believe that is going to be a primary point, those calculations. >> Do you may have anybody in mind? >> no longer yet. But it surely’s open for discussion. >> I imply i’m sure Antonia can be inclined to come back up, but you recognize her, she does the analytical phase. The other matters, i am not certain she’s the correct person. But she might be aware of who’s. >> I learn some publications with Rick Stallard; he did some calculations headquartered on together with the fasting period. Rick Stallard. >> that is for the modeling, yeah, he’s more of a statistician. >> competent. >> Yeah. >> When is the date? The question of whether it can be a two day meeting or instead of that, then that question of when it’s. Higher nail a type of down before we get more matters on the desk. >> k. >> i might recommend we’ve got a two day assembly and explore the agenda and then if it desires, if it may be quality, if it needs to be three high-quality.However let’s as a default for a two day assembly. Okay. Mike where’d you arrive in terms of dates? >> Mike: ok. I had the options of member somewhere between November 29th and December third, with the, I believe the caveat that the twenty ninth shouldn’t be a whats up, or the twenty eighth is not a good travel day. >> correct. >> The ninth, was it the Tuesday used to be the thirtieth? >> Chris Gennings: So we need to think concerning the 1st as being the primary day of. >> the first is the first day of Hanukah. Which, it’s not a religious holiday, but just with babies. Just for me. However that, I, I would come if I needed to. >> Why, why do not we are saying the 2nd and 3rd then? >> yes. >> Rick.>> that is k. >> but that suggests flying on the first. Ok. >> ok. I guess the Hanukah’s the night of the 1st? >> sure the 1st. >> Does this imply chaos for us worldwide travelers? >> Or are we the 2nd to 3rd? >> Yeah. >> even as we’re at the side of calendars should we explore and alternate to that in case we need on? >> We would try this. >> We’re getting closer by means of the tip 12 months which is not a excellent time. Proper. Okay. >> The 13th would be viable as a fall again, however i might pick the date we agreed on first.>> That stands out as the first option, however i am simply watching for a again up in case we’d like it. >> definite. Week of the thirteenth? >> Yeah. >> The 13th, 14th would be, as a fall again. >> Yeah. >> thirteen, 14? >> you know while you. >> The 13th and 14th is just not going to work for every body. >> No. >> good I suppose that going the following week we’re getting too virtually the holiday. So let’s go into January. >> Andreas is not to be had. >> ok. >> January. >> January. January is beautiful open for me. Besides for the 24th and twenty fifth, a further veteran agent orange in California. In order that week would not be just right for me, the twenty fourth. >> How concerning the week of the 10th? >> excellent.>> Chris Gennings: now not excellent for me sorry. >> . It’s nice with me. >> When, when is? Ok be we don’t have the constructing. 18th, Holger, Chris, Russ? Ok, January 18th, 19th as an alternative. >> That work okay? >> 18 yeah. I think that, it can be the 17th so. >> January, are you going to go to that? Yeah. >> Yeah usually. >> i don’t, I didn’t be aware of that they had set a date. K that, that’s just right. It can be SVOC’s.So it involves and likewise flame retardants and other that you in finding in house dust and window film. So it can be informative. >> ok, so now we have got dates December 2 through three as a important, and January 18th and nineteenth as an alternative is December dates don’t work. >> k. >> Then Mike, you are going to work with the EPA in phrases of fall work shop on. >> Mike: Yeah now it was once January 18th to 19th because the backup? >> sure. >> Mike: k. I will coordinate with the EPA. The so are viable dates, we do need to invite again Tom Burke. Probably. >> For an additional agenda object, knowledge that we did not get the day prior to this, seeing that we proceed to struggle with this question of the place does it come from in food, and we did not have the food center with us the previous day appears as if we should both. Perhaps first alternative is to ask them to provide a written abstract, a desk for us that will be effectively understood about what the levels are. And what the FDA assumes is the supply of in those foods the place it’s measurable. 2d alternative to have a person come and talk to us next time.If they could get these data to us now it could be worthy to us to feel through what we wish as a substitute than reply to it for the first time in December. >> I believe, you know, the answer is that what they, if they have knowledge it can be often not. >> it would be necessary to grasp additionally what are their plans for gathering extra data. Proper. >> and in addition there was once a question raised, the offer was raised the day gone by whether or not we need to be aware of whatever more distinctive about medicinal drugs. >> correct, and. >> by, by using type, by agent, composition, through , by using age of patient. >> And that was once normally for diethyl valley too. Good most of their information are diethyl; I mean I think they stated they’ve one. >> last dibutal, after which the supplements and the . I mean that is the one of a kind a part of the FDA i suppose, or a different part of the federal government.But. >> Is there any purpose why it will be on account that of the compounding of the tablet? >> I think Helga you, you will have German data proper, on. >> Holgar Koch: I could provide for the subsequent meeting the info from Germany in which drugs, tribunal and are. I wouldn’t have any information on the meals supplements. But in all probability, it’s possible that that is there too. So I believe we should really pinpoint it to prescription medicinal drugs, over-the-counter medications and meals supplements. And within the mild of the truth that the info from In Hanes is from the years 2003 and 2004, i would be interested in the late containing drugs at that time too. Since we might need this expertise for interpreting the information. Considering the fact that there are a couple of publications hyperlink hello dibutal exposures to the usage of medicine. >> Yeah and we, we had released on using the In Hanes knowledge. Utilising the urinary levels and self reportive medication use. And it was, most, I feel it was once 2003, 2004, yeah. >> In Hanes it was two to three, or, i’ll, i’ll verify. But. >> From the fourth document is 2003 to 2004. That’s the. >> Three to four. That is the, however i’m going to investigate. >> dates. >> And are we in a position to tell Abby and Steven precisely how, what kind we would like the data, like age corporations or something, or do we wish, we could continue to feel about that? >> It was the experience from the rest of you that what they needed to do used to be generate these knowledge? Or is it a matter of what they ship us? >> No I consider it is an information base they usually could summarize it in many distinctive ways. So. >> To be honest I needed to appear into this database, one of the information, it didn’t help me much but. >> Yeah I, but, I suppose they’ve extra information, they’ll have more understanding then is in the public database. And so they might, you already know classification matters by form of drug or some thing like that. I believe that’s the. I think that is the difference.>> I think without seeing anything of what they, it can be difficult what to ask for. At the least from my point of view. So I mean I would take a, take a stab at, you realize if we ask them to stratify it via age and with the aid of gender or anything like that. >> Yeah, just so we get to peer what they have. >> Yeah. >> Are we assuming that they might give us a urine knowledge as good as blood data? >> Now you, we’re talking about In Hanes. >> Oh yeah, i’m sorry. >> The FDA, or the medicines. Drugs we’re speaking about what’s within the components. >> Oh so it’s just publicity. As a. >> proper, correct. >> A particular point for exposure. >> it could be the variety of situation situated exposure.In Hanes we’re speakme about it’s practically, I think it can be all. And i am not, well anyway i’m now not certain, I have no idea for exact that FDA can go back to 2003 but they customarily can. >> Age, gender and 12 months, some thing like that. >> Yeah. >> k so we’ve, is that the whole lot that we suppose we want for the following meeting? Might be. >> good i’ll ask about pesticides. Despite the fact that it, there will not be. I suppose like plenty of things, the whole lot’s being reformulated. But i will ask that a part of EPA. >> Holgar did you have got another? >> Holgar Koch: I used to be, it used to be a separate subject, however concerning the choices to get more knowledge. >> sure. >> Holgar Koch: Jay has, I imply if there is more know-how.>> good I believe, I mean I consider we now have what there is. The Versa report and the Nick, there is a Nick Nash report, which i’ll ensure, if I did not send it to you i will ensure you get it. >> and then back to Holgar’s advice about Rick Stallard. I believe Rick might at least reward the information from his paper. I mean he would do it reasonably rapidly I suppose in 20 minutes. But in phrases of anybody within the subject of formal kinetics, I can not consider of any individual with close . I imply there is quite a few people that have completed this with dioxins or pesticides, other chemical substances.I might feel that it’s the same concepts that they could observe. >> Holger Koch: i have a just right working relationship with Med Lober from USEB. He’s residing around the nook. He has experience and i believe he could provide us a bit of introduction to the, to the drawback. I believe it’s, it’s the quandary of In Hanes with the fasting. We have now the information generated after fasting is a important quandary we ought to talk about. What’s the have an impact on of fasting, on publicity to none persistent chemicals? That are usually food born. >> And primarily for DDHP and the. >> And the high . >> Do, are they normally take the samples after fasting? >> Requirement. They’re asked to rapid. I believe its in a single day.And people seen within the afternoon I feel its six hours as a minimum. >> Chris Gennings: Is there a variable that describes how lengthy they quick then? I do not suppose I’ve ever appeared. There may be? >> nevertheless it’s, it’s in the questionnaire. >> In that’s, I mean is that because they’re gathering lots of other matters, like cholesterol and, yeah, geez. So that, you know, could good, well underestimate the contribution from food which is gigantic. >> Chris Gennings: the place on your paper you’ve got bought some best graphs displaying phases shedding with 48 hour fasting, correct? So I mean cannot. >> They considerably drop after 12 hours of fasting. >> Yeah. >> however i’m no longer the knowledgeable in interpret this knowledge for the whole populace. >> Chris Gennings: but the graphs that you’ve got bought to your paper might be priceless in, to model it because the point.>> you should utilize the entire graphs removal kinetics from the experiments, and the fasting graphs are the same. So there is the info, it is out of it it simply desires anyone with, with farmaco kinetics toxicol kinetic historical past to model this into the In Hanes population. So the names that come to my mind. >> It seems to me that’s a, that is a research venture. >> i would not make it that tricky, do you think it is that elaborate, Russ? >> Russ: it can be but i do not consider it needs to be. >> okay. >> i admire things easy. >> Russ: probably, you recognize whether or not the levels are 20 percentage shrink than you can anticipate since of fasting are 50 percentage. I imply more of a range i’d believe. >> So yeah, I mean you’re speakme about correcting for them, or just assessing the have an effect on? >> You must proper for it.Good if you’re in a fasting window of 12 to 24 hours, it’s a dramatic correction. >> And surely six is, you already know in a technique it can be worse due to the fact it can be somewhere in between, and however the slope is on the whole . >> I suppose this can be a foremost quandary that has most of the time to be mentioned related to more advantageous data. >> And frequently most knowledge, since i know most studies probably don’t collect that knowledge. You understand when was once the last time you ate some thing with the spot urine samples? >> you understand from the German environmental survey there’s no fasting period. That’s the main change between the German data from the environmental survey and from In Hanes. >> Chris Gennings: would we strategy it style of in a two, in a tiered degree.One being a type of a simplified process where we simply do some corrections established on the info that you’ve got bought in your paper, after which, and then get perhaps a person perhaps extra of an talents of farmaco kinetics that may evaluate how close or a long way off that straightforward. >> My factor with that possibly a undertaking was once simply i will rephrase this and ask do you consider that if we confront Matt Lobo with that that he can do it as a part of a presentation for us? >> i might think that will be possible. Possibly in conjunction with Rick’s expertise. Or with, with the expertise he made. >> right, yeah, i might believe you would examine it with Rick Stallard. Yeah. >> I feel it will be a high-quality suggestion.>> that is something that might be finished earlier than our subsequent assembly. >> comprehensive after which presented at the next meeting, or? >> yes. >> Yeah. So. >> So we would have to technique these two entry researchers. >> So we would want both. >> Matt Lobo and wealthy Stallard. >> it is Stalhart. >> I have no idea. >> Yeah. The place’s Rick? >> institution of Rochester with Shawna. >> Oh. >> i will want Holgar to support me give an explanation for to them what it is we wish, or maybe have you ever do it. >> Holgar Koch: They, they both of them perfectly comprehend the challenge. They will understand what you are speakme about. >> What we’re asking is how you can adjust or at least to provide an explanation for challenge. >> I feel Rick can be in a position to provide an explanation for the limitation, and than Matt in phrases of regulate or what variety of magnitude of the differences may just make. Yeah. >> Chris Gennings: i admire Andreas’ factor. If we might get them to absolutely do it and not just speak about it.>> Yeah. >> Chris Gennings: And gift this. >> good. >> really I would love to have a compilation as Russ mentioned it, of which of the reports in our focal point are centered on, or are collected after fasting, and which now not. And it can be very intricate to, to find this in the materials, math substances description. So irregarding it just got here to my intellect a couple of, to my awareness a couple of months in the past. As I believe it slipped the attention of many of the researchers in this field. And as you recounted it, Mike, like the various stories are initiated to get scientific parameters. And they’re no, you get them after fasting. >> I imply we do, kit Carlson my colleague here is attempting to keep monitor of the exclusive reviews and i have no idea if he is aware of that however probably he might discover what the procedures are within the specific reviews around the world. Yeah I mean you realize what the German gain knowledge of is doing, but i will ask him if he is aware of about, something concerning the.Since I believe once these matters begin, they have a tendency to sort of comply with methodology clever, they have an inclination to comply with one an additional. >> On a broader obstacle, I think we need to discuss are we going to do a chance assessment, what form of chance comparison are we going to do? Are we going to do it as a committee, or are we going to ask anybody external to do that and furnish it to us? Because i am somewhat bit unclear as to what our direction is to finishing our cost. >> Yeah. I mean if you’re talking about how the chap operates, the proposal is for the panel to do it, even though it is usually possible to get help with some specified things, targeted steps or anything so long as it’s executed to your requirements. That is allowed. But frequently it’ll be the panels, it should be the panels risk comparison. Now as far as operationally what to do and what to include, I mean that is up for dialogue I believe.You realize the nuts and bolts of, of doing it. However I feel the expectation, I imply it is the risk comparison. And. >> again, not being my subject, i am. >> Yeah. >> I is also asking some. >> well no this. >> Unintelligent questions right here. >> this is you already know other committees may, I imply I have no idea exactly how they work, however i know they contract out quite a few fabric. Quite a lot of the work. And that is just a little bit distinctive. That is no longer how the chaps had been carried out prior to now, but of direction given the dimensions of the challenge we will get as so much support as we are able to. >> good let me attempt to make my questions just a little bit more unique. EPA is going to have a workshop had been they’ll be looking at . >> Yeah. >> And they are going to do accumulative chance assessment. >> ultimately. >> eventually. I think this risk evaluation, or this workshop goes to be simply to listen to to discuss and to listen to from like we did the day prior to this, learn how to go about it. What are the end points and all the identical stuff, all it talks about the day before today. >> Yeah. >> The matters that we discovered quite a bit yesterday but I suppose the, we have to sit down and say you recognize that is in, this is out.We will do it this way, no longer that manner. But my point is that eventually they are going to do what we, I suppose, are being requested to do. >> What they’re, what the EPA Iris software is going to do is well they are sort of in, in new territory. Given that quite often Iris does, they do the hazard identification in the dose response comparison. And of direction we’re doing the entire thing, that’s the change between us and Iris. At EPA any individual else, you already know, they do this and then other men and women take the Iris and, they usually’re Iris record might be utilized to many distinctive threat assessments. >> however can i expect effectively that given the EPA has gotten smaller an NAS panel to inform them you already know chance evaluation in 2010, that is been published.>> Yeah. >> That that is what finally they are going to do. >> I consider without doubt. I mean why, I mean I feel it’s an excellent file. >> sure. >> And it is pretty clear, I mean not that I understand the entire subtleties nevertheless it’s beautiful clear what the course is. >> sure. So my question is, if that’s what they will do, is that what we should do? In different phrases is that the state-of-the-art? >> good I consider that document is, it’s the state of the art for Valley Syndrome effects. >> can i simply, I think it would aid at this stage to if we turn once more to the chart and the regulation of abridge 26 and 27 of the unofficial compilation.>> Yeah. >> What, what it says there in my, well it is more commonly open to dialogue, but i might say that what we’re charged with, and B examination does now not always imply that we ought to do a risk evaluation within the feel of a threat characterization according to the silver publication. >> correct. >> What it says is, is we’re purported to compare the entire capabilities wellness effects.Now I think it can be slightly open to interpretation what exactly does that imply. However I read into this that this isn’t always a full blow hazard assessment in the sense of threat characterization where you first recollect exposures, then map it in opposition to assumed secure phases after which come to a choice are we now in deserving now that the purple light starts offevolved to flicker or now not. You see what I imply? >> well I agree, it can be a determination, I consider it is a resolution factor that chap has to make as to whether to focus on those syndrome, or to really go the, the space on all of those different, or other finish points past that. >> No, no. I think we misunderstand every different. >> Yeah. >> What i’m pronouncing is, I think without doubt what we are purported to do, how I interpret these below B what is listed within the legislation, we undoubtedly need to do what i might call, and what’s on the whole referred to as a hazard comparison.>> proper, proper. >> however now not necessarily a hazard evaluation. >> correct, and, and that is what i’m looking to say. I consider that, well the important thing word it’s no longer necessarily. And that i suppose that chap has to come to a decision. >> Yeah, yeah. >> whether or not you do the quantitative on multiple finish features or just the one. I mean that is your decision. >> Now even, even though say we made up our minds on a important end factor shall we say, hypothetically of syndrome. >> Yeah.>> I, what I read here, i do not always appreciate to mean that even for the syndrome we have got to do a full hazard characterization within the sense of a risk evaluation. In other words, seeing that exposure first, then on the grounds that hazards, after which come to a conclusion about risks, even as we ought to be clear about the language right here, some folks comprehend when matters by way of chance assessment and chance characterization. However I consider that’s my individual interpretation, please proper me, possibly we ought to come to contract right here now. I learn this to mean some thing with an emphasis on hazard comparison, definitely. >> Yeah. >> We also have to look at publicity so there is a quantity, what was once it, sure quantity three. >> Yeah. >> take into account the stages likely in youngsters, and so forth., and so forth. >> Yeah. >> but I consider i might ask the panel to don’t forget whether they, whether or not you see, whether or not you interpret whatever written down here to intend a threat evaluation or a threat characterization by means of you compare quantitative stages, dosages, exposures, related to special hazards, after which make the comparisons with exposures. >> Yeah and that is why I brought up this dialogue, given that i do not think we’ve got resolved, as a minimum i have not in my mind with how we’ll go on this.And it seems to me that we, that’s a significant decision we have to make up since if we go, we are saying we must do a quantitative cumulative risk assessment. Then do we’ve got the capabilities to try this is the subsequent question. So I think we ought to resolve what it is we are going to do and also have a justification for that. >> Chris Gennings: So. >> for the reason that it appears to me the state of the art, I could also be unsuitable since this is not my discipline, is that silver guide, in terms of do the varieties of matters that we.>> Or the quite more like, I suppose, the blue inexperienced guide. In our, the. >> Yeah or that one. >> The one yeah. >> Chris Gennings: am i able to simply ask a point of clarification? So Andreas are you announcing, i am considering again to the court and camp speedy paper offered to us at our last assembly. Where are you relative to what that approach that you have in that paper? Are you pronouncing that is the method you don’t believe we ought to do? I am not sure i do know what you are pronouncing? >> Andreas Kortenkamp: sure that is what i’m pronouncing, yeah.>> Chris Gennings: You think we don’t need it. >> Andreas Kortenkamp: No. What, what we did there in the court and camp fast paper is an awfully crude, first technique at some style of danger assessment, cumulative hazard comparison. What this paper does greater than something is highlight the talents gaps. And normally maps out a viable modus apperandi very crude there are possible choices that wants to be subtle. But I see nothing in these, underneath B examination here, that may advise that you simply will have to carry out .I feel the emphasis, that’s my interpretation, is more on hazard comparison. >> Chris Gennings: What do you imply by hazard evaluation? >> Andreas Kortenkamp: well it can be the average, the ordinary triple jump. In danger evaluation you appear at publicity you seem at hazards of chemical substances, and then you definately put it collectively and carry out what’s known as a hazard evaluation or risk characterization by way of comparing, by means of asking the query having established a level quantitatively of a chemical what we consider it isn’t risk-free anymore. And then you definitely ask it to do current exposures exceed that or come close it. Sure or no. And that is called danger comparison. I do not believe we must do that last step. I suppose we should talk about that. >> Yeah. Good I feel, I consider it’s implied. It does not say it explicitly, however I suppose it’s implied. >> Andreas how about number four below there, recall the cumulative effect of the complete publicity. I imply how, how would you try this or else? >> Andreas Kortenkamp: yes I suppose that’s, that is a factor. Good it says take into account, well, here. Of path we are able to do not forget, however yeah I think that’s, good sure.We need to come to an agreement there. I think it is open to interpretation. >> Our consideration there could be a suggestion and encouragement the EPA would proceed with an accumulative danger comparison of . That probably conscious of that, simply without difficulty to say that with out the necessity for us to do it ourselves. I would like to proceed what Andreas has prompted us to think about. I feel that’s something that we have got to have this dialogue or we will be able to proceed to acquire information and now not be aware of what we’ll do with it, with the probability that we will become collecting knowledge that we do not definitely ought to reply the particular questions. And we will not have the understanding that it does take to reply the query. So my inspiration was once to step forward and seem in particular at what CPSC has requested us to handle. And in addition to this, there was once a request for us to have some recommendation on what to do with these which have already been banned, briefly. And will have to that be accelerated or should it be dropped. What about different , and what about possible choices? Should there be some thing else banned? Should there be some restrictions that we would propose versus banning? So i’d use that as an extraordinarily designated request the CPSC has made to us.And if we do not reply that and we reply various different stuff, they may consider that they failed to get from us what they relatively requested us for. So watching, if we will comply with the interpretation of mainly what Mike has told us about these banned and unbanned , I believe that leads to a discussion of what can we have to have in hand to be ready to reply that detailed question. And if cumulative danger comparison is required to do that, which i do not believe it is, then we’d must try this. Or we would defer to EPA, given that they are mostly going to do it anyhow. At the risk of two of us doing it is that they’re going to no longer agree. That might be unhealthy for regulators. >> good I consider we do not have to agree.And it also is determined by what the disagreements are and why. >> yes, surely. >> however I consider, you realize, you made the factor the other day, the bottom line is that we’re asking the chap (a) shall learn blah, blah, blah, make suggestions to the commission involving any or combos in addition to these identified in subsection A. Or choices that will have to be declared banned has materials. In different words, is just not in a few of these equal children’s merchandise.After which a little farther down I believe based on that, the staff additionally has to come to a decision whether to make the meantime band everlasting. >> So if we can work from those certain question and back away somewhat bit and Richard do we ought to reply these precise questions. Then we at the least are being attentive to the rather slender question that they’ve asked of us. After which if we want to deal with matters which are out on the threshold of that that need to do with more commonly, or different associated disorders which can be might be adjacent to the unique ones the CPSC has requested us to handle. We are able to do this if we wish and if we have time.If we now have the understanding. But my recommendation is that we are able to, I just like the hazard assessment technique, might be considering that that’s what i have performed in my profession as opposed to the extra distinct modeling. And i’m not towards modeling if that’s how you can go. But I consider we are able to maybe reply these questions by way of a hazard assessment strategy and probably the data, I mean we now have finished this, we have done hazard assessments with less data than are on hand on . So I think it is practicable. And i consider if we can reach agreement beginning from the top factor and dealing back just a little bit, we will be more effective in being able to get this achieved. >> well if we simply focus on the thalaids which can be presently banned, I imply is is reliable to expect, and i have no idea this field that these weren’t banned on the foundation of accumulative threat comparison? Right.>> Yeah. >> It was once, they were banned on the hazard assessment process that you are speaking about. Is that right? >> I consider most of the time it. I imply I, there was once no cumulative threat evaluation per se. I suppose they had been involved about cumulative effects. >> Chris Gennings: i might ask if we might be somewhat more unique. I think you guys are making use of phrases and i’m not sure of the glory. If i am being I apologize.However the hazard evaluation as opposed to hazard evaluation, i don’t, I do not know precisely what you’re announcing. If any one, if both Bern or could be extra targeted it could aid me so much. >> Yeah what are, what are the steps that we’d take to head and. >> Chris Gennings: And in distinct. >> And in exact with the three which might be band stay banned. What would we do? >> Chris Gennings: And in particular, i would like to listen to relative to what I understand Andres, and Andreas, sorry and paper relative to that, what’s on the desk or off the table from that. >> exactly. >> Andreas Kortenkamp: I wholly believe what Brian just stated. We, I think that’s the backside line we, let’s work backwards and ask the question what variety of know-how do we want in answer to meet the charges. And what would be very helpful and you stated it already could be to get expertise about what standards were used with a view to come to the resolution to 3 ones in the legislation. Is that documented somewhere? What criteria were used. >> i do not feel it’s that well documented. I think that’s the concern.I believe that the european band is, there is a little rationalization in the documents. But in ours there is not, the legislation itself doesn’t quite have the justification. And there is, so far as i do know, there is now not so much of a written history of how and why matters have been achieved. >> Andreas Kortenkamp: k if that’s now not the case then, I believe we will have to, a primary step would be for us to think of standards that will support a resolution to band anything. However I do not know what they’re but I suppose we should be clear about them. And secondly in answer to your points, Chris, i am also competent the terminology and use of phrases on this subject is in many instances a little bit confusing, and i would strongly endorse, for the reason that we’re working in america to comply with the terminology utilized by NRC and commencing with the crimson guide, ending with the silver guide.That, shall we agree on that? These terms are very evidently outlined within the silver guide. I mean we can take the silver booklet. It goes again and explains the whole historical past of how they strengthen this entire danger assessment framework and the terms they use. Shall we agree on that for simplicity? >> undoubtedly believe that. >> I believe for my enlightenment and probably Chris as well, if one in all you might define mainly phrases what the system is. That would be useful to me. Ok. >> Andreas Kortenkamp: i will need to cross over to a few of my colleagues here. However regularly the, and that’s terribly foremost and more often than not uncared for and i believe that is what we must apply ourselves here to. The system starts with a state of predicament method, and defining the context. And i think we’re about to try this and we’re very close to that. So that step is so most important.It then asks outlined already. That helps us to make a decision what sort of information can we truly want. So we have to define the context and the drawback. I do not think that should be very complex. After which the core of hazard comparison or threat characterization starts offevolved with publicity evaluation, and Olga, for example is an trained there. It asks the question what are, what are possible exposures to the chemical viewed. This will likely differ in step with population, subgroups A, and so on., and so on. But it clearly asks that. In parallel, a system goes on which is handiest known as hazard assessment. It asks the query what knowledge do we’ve to begin with on the result profile produced with the aid of the chemical in query.Yeah. We have already additionally considered section, you realize . All of the finish points. What’s going down. And secondly it asks the question, is there quantitative dose response expertise available for any of those finish facets. And if ye, it then, if feasible concludes with the approach whereby risks associated with unique exposures or dosages are quantified. So that is that box. So publicity assessment, hazard comparison, goes on in parallel. Then the step of risk comparison, or chance characterization is to unit these two steps through asking the question are the phases that we’ve got founded as more likely to occur by way of exposure evaluation.Are they attaining a zone which the hazard comparison tells us is associated with danger. >> Chris Gennings: All this must be carried out in phrases of a blend not a single chemical. >> Andreas Kortenkamp: sure that is all a different problem, but there are, there are methods of doing this. Systems had been mapped out how to do this. >> Yeah. I mean in, in a sense, if you’re going to do combinations, you sort of might in every single place. I imply do a hazard identification for the members, however then for the combos. And does response the place the contributors and then for the combinations. So it can be, it complicates it that rather more. >> Chris Gennings: So Andreas you wouldn’t support us utilising a hazard index strategy? >> Andreas Kortenkamp: A hazard index or some thing is far too specified an technique. I mean that is only one manner of, of doing accumulative threat comparison. There are others. But let’s no longer get too hung up a few hazard index approach or not at this stage. >> Chris Gennings: i am sorry to keep pushing you, but why now not? It helps me if i will think through these varieties of steps. What are we going to, when we talk about data, what are we going to do with the info? We hold speaking about bio monitoring studies.Trying to, and that i was considering of mixing non-atmosphere knowledge into… >> Andreas Kortenkamp: No I suppose I consider Bern. What Bern says if we have to be clear what, what we’re, what we’re aiming for. And my feeling is that so as to reach decisions about continuation of prohibitions and bands. I’m no longer certain we have to get quantitative and let on my own recover from complex with mixtures, threat assessments or cumulative risk assessments. That’s my opinion, however we should don’t forget that first and in order to simplify for the reason that in any other case, as Bern mentioned we end up in a difficulty of having assembled info which then we appreciate that a letter stated we don’t need in any respect. >> Am I proper then in this strategy you’ve outlined, if, if Holger have been to convince us that cumulatively we had been being uncovered to at least one milligram per kilogram pre day of and we know from animal knowledge that three milligrams per day, kilogram per day factors an opposed impact. Then we’d follow some element to claim that that is close adequate to the animal knowledge that tells us that it can be antagonistic that we will say this is a situation in people.>> And yeah that is a method but i would say that’s already very quantitative and possibly difficult. I imply in my intellect, mix cumulative hazard comparison. Would to begin with begin questions reminiscent of what’s the proof that coexposure to a couple of actually qualitative exacerbates hazard. You don’t have to be too quantitative. You ask questions in what direction would this possible move a dose response for an person . Questions like this. With no need to be too quantitative at this stage. Or similarly, what is the probably expected outcome of , and many others. >> Chris Gennings: but is it that type of strategy primary, possibly probably the predominant when it can be the, when you’re in the procedure of attempting together information. So in case you do not have to exit and get the quantitative information then you could asking qualitative questions. After which along the way in which decide sure we must go additional, or no we don’t have got to go additional.But I consider we’re competent the place we now have visible various data. And we’ve it at our fingertips already. >> Yeah. >> Chris Gennings: So i’d recommend that we go ahead and consider about more of a quantitative technique. >> Whoa, whoa, I consider steady, steady. In view that why would you, why would you want quantitative knowledge on something very complicated cumulative danger evaluation. If the query is to decide whether we’re to, whether we are of the opinion that the prevailing band on particular must be persevered or not. In my intellect you don’t need this know-how. In my mind what you need with a purpose to reply these question is a hazard evaluation. >> i suppose the trouble will get again to what do you mean by way of that, by using hazard assessment.Due to the fact that i don’t rather follow how you might do that in a qualitative feel simplest. Come to the conclusion that whatever is, on account that to me that virtually implied that there needs to be some quantitative facet of that. Am I mistaken? >> well I see it that method. Or path that is what I do. However. >> however the hazard comparison has quantitative facets. Does response analysis. >> when you do dose response then you’re relocating past just the hazard assessment, I feel. >> okay that is a terminology drawback. In step with the silver ebook you, I think we should look at that and. >> Yeah. But well, if believe we did a, the most simple minded variety of a quantitative evaluation? Not fear too much about you realize advancing the state of the art.Making use of the principles, applying the concepts in the, the NRC report on . ABE limiting it handiest the syndrome effects, for starters as a minimum. Is, is that conceivable? >> Of path, of course. But here is a concept which, which i might like to place to your for dialogue. Possibly that makes it clear. Individually it is extremely troublesome to aid the determination for or against the band by means of doing a full blown danger characterization, hazard assessment.The concern is this. Holger has very eloquently told us about these substitution procedures. So good exposures to are, they are like moving gold posts. There is already, we’re wholly aware of this. A substitution method happening. Given that choices are made via industry to restrict the use of special which regard us complex are for some thing cause, and there is a transfer towards others. So for example, hypothetically, as a result of this process a hazard assessment for DEHP could conclude that since the present publicity phases have gone down that the hazard because of DEHP is now, i am making up an instance, negligible.Right. >>correct. >> Then if you wish to use that effect of a risk characterization, risk evaluation procedure, that might be average. So if you want to use that to now as a criterion to select a ban or not, you can also end up in a very absurd predicament. Then you definately make a decision k, currently nothing to worry from DEHP. The reaction to that and so then hypothetically you would argue no have to band DEHP. If this happens, then there will likely be a substitution process occurring in the different direction.>> proper. >> we can then see it extra to DEHP. And then in he future you would to find yourself confronted with a obstacle, ah ha, now exposure to DEHP are so high they may be getting us into the zone of attributable dangers, hypothetically. >> correct. And i think that. >> So I conclude from that that a full blown hazard comparison is unsuitable as a basis to come to a decision for or in opposition to the band. It has to be situated on the hazard comparison. Does that make experience? >> Chris Gennings: however could not a risk evaluation inform a hazard assessment inform a hazard evaluation. In different words, I have an understanding of what you are pronouncing, there may be a moving target in terms of the exposure levels of those chemicals. And we ordinarily might even gain knowledge of that in In Hanes if we had the opportunity to look from 12 months to yr to year, right. But we might additionally , make up, I should not say make up, however take into account eventualities the place we say ok now if DEHP clearly did expand via 20 percent, then this is where you’re.We would remember it in numerous one-of-a-kind cases. >> correct, or one thing I’ve completed is for those who, you understand, flip back the clock to a unique data and say well you know when this whole trade started, you are darn correct, you wouldn’t, you could definitely ban this chemical and also you wouldn’t need to change it. I imply there is methods to deal with all of the relocating target predicament. I consider that is a, in comparison with the opposite disorders, no longer insurmountable.However. >> i know, i know. However it helps us. >> Yeah. >> reply the question in step with Bern, which Bern, Bern contact has introduced up. What sort of expertise do you want? If for illustration, contemplate this a little more, then it instantly turns into clear that for these discussions we are not looking for publicity data. >> well the. >> There are other, there are other facets here in the chart the place. >> Yeah. >> We do want exported knowledge. However as a way to argue for or in opposition to a ban of designated , we do not want publicity information. >> well it. >> We ought to have the . >> however when you say publicity knowledge, do you mean like bio monitoring knowledge, or do you mean hypothetically like for instance, we’ve got data migration from the merchandise. And so you might say you understand given the identified toxicity traits, and this amount of publicity it could be below any stage of trouble or above.And asses the choices that approach. So you understand it, if a detailed alternative say failed to migrate, it would have a better toxicity, if it migrated so much it might have got to have a a lot minimize toxicity. But I mean you are, you elevate good features, and it’s, however you are right, I think we have got to form of believe through what are the steps that we wish to do to answer these special questions.And what can we have to do, what will we want to do, or and what do we do. >> Yeah and i am just questioning Andreas starting this off of the beginning gate right here. I am an awfully visible learner, so I must see matters. >> Yeah. >> To particularly analyze and digest. Wouldn’t it support us if you were to make use of the procedure you will have been speakme about with relationship to the three that have been banned. And go by way of your approach. And so us, , what that would lead us to.That way we might say that is, oh yeah. >> Oh yeah, i am being put on the spot. I can, I have no idea. I can do this. However that is why I asked is there documentation of the determination making method, what standards we’re used to reach at the determination to band the three and the regulation. Yeah and i don’t consider there may be lots. Well Phil. >> Go ahead. >> receive that’s priceless. >> Ann Clauson: Ann Clauson with Latham and Watkins.In 2005 there was once legislation in the european which seemed very much the equal. It put a traditionally permanent, good not on any of them, was it permanent. However it was a fuller ban on the three curb molecular way. After which period in-between sort band on the higher moleculades. It did provide for a reassessment of that, which is going down right now. With reference to the better molecular weight, in particular DINP and DIDP. They had additionally completed risk assessments that confirmed no chance.But they determined t go forward with the laws and explicitly recounted that was on the groundwork of the precautionary principle. After that used to be passed, California handed legislation that was once explicitly modeled on the european. And the legislature did no variety of hazard assessment. They only picked up on what the european had achieved. When the CPSIA was being promulgated, Senator Feinstein from California desired the brought to the CPSIA on the identical foundation that it used to be in California.So once more it was delivered to the laws, fairly as a political process with no sort of hazard comparison explicitly accomplished via the legislators. >> And it can be, thank you. I am of the approach. I don’t know that there’s a written document that we might refer to. It can be for me at the least, it’s 2nd hand know-how, 0.33 hand, fourth, whatever. However that is my working out of the approach. But there wasn’t a, you understand it’s not like a proper rule making the place you do a hazard assessment and many others. There were hazard assessments carried out within the european.And it can be controversial, the don’t necessarily, they did not always support the band, the ecu ban. I think the european ban was once extra of a precautionary, as they name it within the eu, if you’re no longer sure ban it variety of procedure. And that i feel something after that effectively mirrored what was once in the European, or roughly mirrored what was once in the European ban. And the, as a part of this, they mentioned oh well we’ll have a chap. And the chap is to, used to be kind of a multiply motive to appear at the fee possible choices and also to do the exact hazard on the three intervening time ban ones.Or weigh in on the three intervening time ban ones, and to do the danger assessment. I mean I, i do not believe any individual would argue with the three permanently banned ones. Good, there isn’t a danger assessment partly, due to the fact they weren’t rather being used. I consider that in he ecu ban they stated we did the, put the three permanently ban, now not a lot considering that they were being used, however since we didn’t want them to become substitutes. It was once a pre emptive act. You realize the other three, the meantime unhealthy one it’s, you already know we’re now not, it’s now not so clear you already know.The INP is, may match in the syndrome category. But it’s weaker. The opposite two, I ‘m no longer so certain i don’t consider there is any robust proof that they cause the syndrome so you know those, they’re in variety of an in between class. So for us they ended up as a, as an meantime ban. And they speak about this a bit of bit in the European record which is on your CD, but i’ll make certain you’ll find it if you want to read what’s there.But that is that. I imply the, i suppose the reply to all of the, one of the crucial questions you recognize why are you doing this this way. Why is Congress doing it this way. I mean the chap is to answer some of these questions. >>sure thank you very much for these explanations. But I consider it could be slightly unfair to summarize the precautionary essential as utilized in the european by using if you’re not sure ban it’s more like that. >> If we did it, if we did this fashion, we might have chemical compounds. >> we are going to train the jury to ignore that remark.But having said that, if we are able to find that being, if we find that the standards used are let’s assume a bit imprecise then i would believe it would be one in all our key tasks to reflect just a little on these standards that we undoubtedly obvious. And a good way to could be the three that are banned already and to reflect, consider standards and arguments which we suppose would aid and justify that with the aim of applying it to the others. And then see the place we turn out to be. Is that a practicable way forward? I think we will have got to be transparent and clear. >> sure. >> With standards. >> Is, Bern you had a comment. >> Bernard Schwetz: sure my, my assumption that once a selection is made beneath the precautionary fundamental there is an expectation that once data are on hand it is going to be analyzed. And it isn’t a topic of 2d guessing how somebody else made a determination. That decision wasn’t on knowledge. It’s based on a composite of matters that had been proper at the time, considered one of which used to be there wasn’t adequate data to rather make a firm decision, or when to make one anyhow.So we’re now not, we’re now not at risk of second guessing anyone, for the reason that now we’ve data. And that’s how the method must work. But would the question of you with the options are, we have handiest pointed out banning or now not banning, isn’t it viable that anything could be limited in an, without banning it. And it would still accordingly be useful in merchandise but we have now confined the extent in it in order that what migrates out into kid’s mouths or skins someplace or within the food plan, is restrained all the way down to a stage the place it represents an acceptable hazard. Possibly that level would must be at a concentration where the product no longer is flexible and for this reason the further plasticizer is a moot factor considering that it would not work at that level.However it style of maintains us out of the mentality of claiming that it either has to be banned or no longer. >> In, that is a just right point. And i used the term, ban hazard is substance. I believe that it literally means whatever that doesn’t comply with our regulations. So it’s an unfortunate to have the word ban in there, nevertheless it particularly manner good the other, the six are confined to .1 percent. So in effect it can be particularly a efficiency normal you would say. Or some thing like that. It can be a regulation, not a lot as a ban. We do not, we are able to avoid utilising that phrase and say regulator restrict. >> It already does what you, what you simply stated. It regulates it to a specific stage. >> proper. And we, we don’t, you realize I suppose it is ok to think outside the field just a little bit. It does not always have to be a thumbs up, thumbs down.It is a, it could be some, none of the above it that’s what you wish to have to say. >> Managing it, I imply the step that wasn’t delivered here is danger management. And if the dangers may also be managed with the aid of reducing the extent to an extent the place the publicity is just not high sufficient toxicity, then it is successfully managed. We’ve not talked about for what a part of the population is it for everybody, or just a subset. Or if we’re just, these were incentive. These are other issues that we need to maintain as we talk about, are we relaxed or now not with the unique degree of exposure. Nevertheless it make, via managing it to a unique level makes it extra of a quantitative process.And no longer just an all or none system. I guess absolutely that suggestion method is, could be a criteria and to aid this decision making. That is a technique. But there are others. But that is obviously a technique. >> I suppose, all i am pronouncing is we need to be clear about, about this. And also let me add i do not think that is solvable in a Wednesday afternoon. It requires careful situation and probably that is one of the crucial portions of homework we will have to agree on for next time. >> That was once my query is how do we proceed so that we meet again in December of January. We’ve something that we will talk about and then make the next move forward.It, in quantitative risk assessment is a option to remedy, to make these decisions and it is not the only approach. However you are aware of it’s no longer a bad manner both. >> it can be variety of in a apart. Wouldn’t there be president for other chemical compounds or metals. In terms of you already know led and merchandise or or you recognize. You know are just one out of a universe. And there’s been other uses, and there’s been other percent of, you realize, a steel or chemical allowed in terms of. >> well in, led for instance the best way our regulations as a minimum earlier than this PSAA, the reason used to be leds naturally occurring for one factor. It tends to be, however it’s a containment. And so we would count on a distinct background low exposure. And take that into account in the danger calculations. And that’s how they might arrive at, you recognize, going that calculating a stage of publicity that is allowed.For other things like we would recollect well are these matters that can be regulated by means of other groups, you recognize. If it is deliberately delivered to medicines or whatever, you understand we might say, or well you recognize this isn’t a traditional danger comparison approach we’re talking about. However customarily we would say well if it may be, if lots of the publicity is from something underneath FDA or eu jurisdiction, we will say good let them maintain it.However on this case the place you understand, you have got various stuff that is in food and within the environment and it can be now not clear whether it is something that is, can be addressed. We, it can be coming from so many sources in, and you already know some of them are certainly in an individual’s jurisdiction, however others like the way it gets into meals probably no longer. You already know, possibly that is just on the grounds that it finally ends up with the environment.I am form of considering out loud right here. But. >> but lead is similar to that. You recognize if you go back and even now it can be purposely added to products. And it’s in the environmental from gasoline. It is probably in our food supplies, our dos, and decisions. I was once just questioning if there’s, as a substitute than looking to, yeah reinvent the.>> well lead we might anticipate that there’s a precise background stage that’s consistently going to be there in that it can not be regulated via EPA taking it out of gas. You now there may be some background stage left that we need to take delivery of. So we sort of subtract that our of what we are saying that you may be uncovered to. For i guess we would simply appear at whole, I mean if there have been a way. For the reason that this got here up with the DINP. If there have been a strategy to do it, i would have said gee yeah this much whole publicity, you understand, how much type of room does that leave? In other words, good if DINP is adding to that threat, we might have explicitly taken that into account in as a minimum my chance comparison i might have completed it that approach.I would have stated you know there is this a lot danger from the DINP which is not unhealthy, however should you add within the historical past and it puts you over the extent of crisis, you then understand it is a situation. In order that, you already know perhaps that is one approach we are able to take is you understand you’ve gotten complete exposure depending on what the hazard from that is, seeing that i’m now not certain what it is, if it’s you recognize over or beneath that sort of stage of main issue, whatever you need to call it.But if that’s really that top, you know adding to that I believe does make a change, even small quantities. However I, you understand that’s one, it’s one is whatever complete exposure is, after which say do these toys, you know put you over a distinct stage. >> good am I flawed Andreas, that what you have been pronouncing that you do not want to move that manner. You do not need to say there may be some degree that if we go above that we’ve got a challenge. You need to say there are qualitative if it shifts. >> Andreas Kortenkamp: No, no, no, i don’t, I are not able to, i do not agree prescriptive at this stage. But I feel we have to enter a system whereby we map out choices. >> Yeah. >> What, what you may have just said is certainly one. However there are others. We ought to map them out, be clear about it after which appear at it and make a decision. And work from there and then answer the question what if we own a specific choice, or a modus operandi then the subsequent query is what data will we rather need.>> Yeah, yeah. I didn’t you should be descriptive. It’s just, how can we outline the choices and, and move forward? >> Andreas Kortenkamp: One alternative certainly is the one left by means of Bernard, where you bear in mind exposures. This is the, the, that might lead us into full blown hazard characterization, risk assessment product. After which ask the question, can the exposures on account of toys can this be managed in toys, if that’s now not viable for technical motives. For illustration, that is one feasible line of argumentation. Then there is a just right case for a ban. That is one, a method of doing it. However I believe there are other choices as good. And these ought to be mapped out. One other option is one I mentioned. I have never made up my intellect in any respect. It would be, go the way of hazard characterization. >> In, in, by means of hazard you mean not going, you mean going as far as a dose response? >> yes, dose response, yes. >> And, in a single, and, however to what finish? If we’re not doing publicity? >> Andreas Kortenkamp: For example, that’s a excellent query.Can we rather need a quantitative hazard assessment? Or and questions along the strains of how seemingly is it that this and that chemical induces a , etc., etc. You understand, and i am no longer most likely clear about this at this stage. However we have got to think of questions of that nature. >> Would, would clarification come by using, again, making use of something process you want to the three that are banned, and/or the three that are period in-between banned, and allow us to as a committee see what the extraordinary choices inform us. And or do not. >> Yeah, that absolutely. Yes I believe the way of doing it will be to peer what the Europeans have finished. The notion process there. No longer that we would want to mannequin ourselves on Europeans wholly. We’re in the usa right here.However simply keep an eye fixed. >> well I feel what, what they did, the scientists, the programs did danger assessments of man or woman . Although they were conscious of the possibility of accumulative dangers. And you know after which by some means the, the legislature, the voted you know, as we did within the U.S., it was a legislation that did the ban. So there wasn’t necessarily an immediate link between the science and the, and the, and the regulation. Correctly we had some file, after the dirt settled, we had some follow up conversations with the scientists there.And our, we you realize, any person mentioned well how come they banned it and you failed to. And at that degree, threat assert, or danger assessor we had been generally in contract on, on things. But the selection to ban it used to be headquartered on precaution. >> And might be it will be productive for us to recollect that this method may also be carried out utterly with out fully, or say unbiased of this classic chance evaluation, where we’re all used to. I imply any person stated it. It might be situated on their resolution to say we don’t want substitution to head in to, to go in desire of a certain . If we do not ban it this may increasingly occur. We don’t want that accordingly we ban it. Simplified argumentation. But in no, if, should you consider this idea system you’re going to realize that, well you’ll ought to ask the question, another question why do you not wish to go substitution to go that means. So what health hazards are you involved about. After which you have a wellness hazard comparison step recreation. This does not always have to be quantitative. >> That makes, makes various feel.>> Yeah. Hypothetically to be able to be one alternative to go. >> Or. Sure. >> I, I imply you need to, it’s quantitative within the feel you do not want to head to something that’s extra poisonous, but you also must consider of the publicity advantage. I consider for a majority of these, the, the specific exposure migration sees to be about the equal. However in case it can be not, you could possibly have got to bear in mind that as well but it would be kind of a semi-quantitative technique. >>Yeah. >> Holger. >> Holger Koch: too much hypothetic discussion right now. Considering I suppose we’re nonetheless in the stage of information collection. And i think no matter, irrespective of which method the discussion may lead us in, we have to face the truth that we have to type out the elemental information. As you said, we need discussion concerning the finish aspects. We need to cut back all of the rates in terms of the top facets, plus the substitution merchandise.We have to collect the information. We have to have a look what toxicity data for the Is there in regard to the end point more sensitive. We need to assess if this knowledge is gift for the substitution merchandise. And we’d like this information for the substitution products too. So I feel it can be a perfect discussion right now. But that is going to be a discussion for the next assembly in time. >> yes that is true, however it is rather principal one for the reason that good in the silver guide that will fall underneath drawback definition, contacts definition. It is extremely foremost to do that given that we may find, on account that something resolution we now take at that stage will then drive what information we need.However let me come to the text, the cost. I think the legislator had whatever in intellect once they, and right here I believe Holger when I listed unique matters we also must compare. For illustration, the like stages in children and so forth., and so forth., possibly the legislature had in intellect that deliberation follow a specific structure. So there are certainly knowledge we have got to appear at and analyze due to the fact that it is listed right here. And definitely this may support in this suggestion system to decide in desire or in opposition to the ban of targeted chemical compounds. >> Holger I accept as true with you at one stage, however at one other stage i am a bit of bit unclear. In the event you just take the drawback of which might be we talking about, or which choices we haven’t even come practically speakme about that. How are we going to decide. The universe of and alternatives, the ones that we’re going to be involved with, is it going to be all of those.And whether it is, I mean then you are announcing to me that we must have a matrix. Now on this facet the entire and all the alternatives after which over here in one of a kind columns publicity data, in special children, within the fetus and pregnant ladies, is that what you are suggesting that we’d like, and if that is the case and we agree on that, how are we going to get that put collectively, that matrix. >> Holger Koch: I think data is underneath six right here. And as I stated we want knowledge about exposure and exposure. And that i imply as Mike said, each founded on bio monitoring information, but also on usage knowledge migration experiments, and many others. And as Andreas brought up, we have got to be as soon as we deal with one it is probably that different or substitution products come into the market with the identical amount of creation volume. So we’d like know-how on these viable doubtless substitution products.I consider it is considering of these products, considering that did it too. We discussed DEHP and there are almost certainly different substitution products, however we have got to maintain these merchandise in mind right now. >> you utilize the word doubtless. And when you seem on the, one of the crucial EPA records that we receive there is a entire record there of choices that both are getting used or possible to be used. Are we going to head by means of that list one at a time and say this is the one we’ll be speakme about, and this one we’re now not fascinated with. And if that is so then what standards are we going to use. So this leads to, , this is not a simple topic. >> No nevertheless it, the selection on acceptability of an substitute is a choice of the longer term. We are not able to decide whether or to not make some recommendation on a based on what we feel the replacement that we feel the enterprise would go to, or we are going to not ever make a decision on the . A determination of whether or not or now not an alternative is acceptable is within the arms of the regulators.We can not particularly make a judgment in order to avoid the probability that some enterprise will make, will process EPA or CPSC or FDA. Their alternative. And the agency says definitely not. We don’t need to have the chemical like that instead to the one who we’re watching at from the standpoint of managing. So I suppose it is major for us to grasp that there are choices, but i do not feel we are able to make a decision on a headquartered on what we worry maybe an alternative unless it occurs. However number 2B7 stated explicitly we will have to keep in mind the alternatives. >> well it says, we have now some substitute, good remember feasible equivalent wellness defect right here. I mean a few of there are already getting used. So you know the hypothetically you recognize there are some things that would be used, I believe we must take our high-quality shot and with those that we all know are being used in, if it can be, if there may be anything that looks like it will be used.We will add it however it’s we can not hope to have the whole lot quilt each alternative. >> it is again to, if we need this matrix that Holger is arguing for then we’ve got received to make some selections. And special and possible choices. And i might expect we ought to have a cause for why we select one and now not an additional. >> I believe Paul and Earl the day gone by point approach. Given that we’re specializing in the syndrome. So watching structure smart at the chemical substances, which probably the products, we could have to you realize if these are similar merchandise. Or basement products would have identical results. >> i do not feel now we have made that choice but. >> No we did not make any of it. >> Of course syndrome of end point, i don’t think we’ve got made that choice. >> I mean wouldn’t it support to write down a few of these matters down. Like write a list of matters, decisions you must make. Probably write down some possible procedures, qualitative and quantitative approach. >> that is what just taking note of this I was going to suggest. Since it seems like we’re talking about two or three one-of-a-kind things, type of while.And that i feel at least in terms of processes, fascinated with the one-of-a-kind techniques which can be available. After which what’s needed for the special tactics. What we’ve to be had. And then we are able to make a way more advised decision. You know we have these, you realize anything, three or four viable techniques. What’s wanted, what’s on hand and the how do we go forward. After which of course opting for one of the systems.Seeing that there’s a, just paying attention to different, you understand the discussions no longer fully meshing in terms of. >> What I consider we’re additionally speakme on one of a kind phases. I, you already know, I feel this is the perfect stage. What’s the bottom line once we’re all done. The way to do it’s, is a further degree. And then one of the most nitty gritty details is but one more. >> And the point i attempt to make is how are we going to get there. How can we transfer forward? Are we going to do it here? Are we going to try to hash out what you just said that we must do. Or are we going to add ask the to try this supply it again to us and we advised and comment and made alterations. >> No I believe we have, that is a challenge we should not delegate. >> I consider we ought to try this ourselves. However we can not do it within the, in the remainder of these days. So nor should we rush. My recommendation would be we might all independently feel about this and each and every of us might be put together what can we name it form of a submission or discussion paper for subsequent time.This would be circulated well prematurely and refined and that’s then for subsequent time to discussion subject. >> and that i was going to suggest that we every jot down what we’re on paper a go with the flow chart or bullets or some thing. After which get it, do it well before the subsequent assembly so that the subsequent meeting we are able to see what we agree on. >> I was going to without a doubt propose that as good. However you recognize potentially since our next meeting’s not except December, on the earliest. You understand possibly a convention call the place we are able to spend just a few hours in October, November speakme about one of the crucial tactics. Since I consider if we do come collectively and December or January we it will be fine to have a resolution in terms of procedures and desires earlier than then. And agree upon at the moment. >> Like in terms that these are from sampling, that these are a public meetings. Can we have now a convention name. >> Yeah we have had conference calls up to now and this can be a form of a nuts and bolts style of factor and it can be only a fairly, simply to organize us for the, for the real assembly.>> okay so I believe that may be ok. >> So then the plan would be it can be relatively as committee members to provide you with a report that would flow into among the different committee individuals. After which we can have a convention call the place we can speak about what each of us has proposed. After which with a bit of luck come to a consensus with the intention to pressure the assembly in December. >> are you able to be extra special of what we will have to have in that file so that we do not emerge as with apples and oranges, and nuts and bolts. >> Yeah I was once sincerely considering sort of the identical factor. On the grounds that there are, you already know, one of a kind portions and each of us have distinctive advantage.So might be you understand I don’t know Mike or a method of framing the predominant elements after which each and every proceed to stipulate it or fill it in since for distinct aspects i know I will not have the advantage. And for other aspects i will. But it will aid, you already know, frame precisely what is needed in this report and go on to one of the vital question. >> it would be worthwhile if we had a way of what exceptional individuals are going to handle.I imply established to your potential. Despite the fact that you would not be limited to that. It could make sure we cover all of these matters. I am not definite if we, would we start with the framework, or i guess, or get the submission. Some submissions first. I feel we, i suppose it might make feel to have some style of a framework. >> you know very normal in terms of the questions. >> Yeah. >> To answer the strategies which can be on hand. The information needs. Choices.I imply you recognize more of a, you already know, very basic outline that we are able to. >> Yeah ok. >> Take portions to fill in. >> k. Could it, Mike might or not it’s established on the various elements of our cost? >> Mike: I think that’s a part of it. And then substances that maintain each and every of these. Now what do we ought to do with this. >> Yeah. >> also comes again to the place we were the day before today with . What age staff. What . And yet these are all motives that we’d have got to bear in mind in order that we begin to segregate that small number of which are of perfect priority versus these which might be out on the margins. Those which are the perfect toxicity versus those that are out on the margins. And people are the matters that will allow me to be in a position to claim good the 4 that I relatively feel we have got to focal point on and these two finish elements, that that’s the place the meat of this is.And the opposite matters we can have much less sure bet. It can be toxic, they’re less exposure, anything the reasons might be. So i might hope that as a group we will start to slender down those kinds of, as good to get us involved in where to spend our power. >> And it will additionally help if we would get faster than later Paul’s and Earl’s slides from the previous day. Copies of those. I do not think we acquired these but. >> yes. >> I suppose in answer to Bernard’s factor, I suppose there can be no dialogue that the six in the laws are those that that is the minimum. And i might say in terms of substitution or proposed substitution products it’s DHPH, on the very least worry.Very likely extra. But so we’re eight already. Minimum. >> good there’s a handful which might be clearly in use. DPHP we now have, i don’t feel now we have noticeable but. However it’s a capabilities. >> Mike is that whatever that, that your office could put together for us? In an awfully. >> Mike: A framework? >> well that and, and also in phrases of Bern’s factor of opting for the if these would be simply the, enumerated and you recognize why we wouldn’t do not forget some of the choices that they are no longer in creation or they may be, no knowledge. >> Yeah. And we’re variety of engaged on that in specific, and i am definitely going to check out to get in contact with some of the industry individuals to, to get extra expertise on that record. About the chemical substances on that record. You recognize which ones are really used and so forth. I don’t consider we have got to go too some distance down that list. I consider, you understand, with this six. You understand there may be a couple of areas just like the not on there. There is every person has just a few, or that they might add to that list and we might definitely do that.>> i spotted the EPA record had eight . >> correct, proper. >> And a part of that, I mean the pental is there not considering it’s used, but in view that of it is activity in that assay so it can be practically like a mannequin compound. You understand some of those like the as much as, and hexel I, anyone advised me that in hexel no one fairly makes use of anymore. But it surely’s given that it’s lively in that assay it’s something we might consider as a minimum one phase, the hazard identity part or whatever like that. And i could also you realize conceive of you realize considering we now have so many chemical compounds. Whatever the final method is, all the chemical compounds don’t necessarily must make all of it via. >> Envision the file that we put collectively would have whatever as simple as a table of the entire and alternatives after which a short dialogue of why we selected some and no longer others to rather, and if anybody used or concept about utilizing a substitute that you recognize wasn’t excessive on our record, it wouldn’t be that hard for either them or us.We’d have the framework to move by means of. Yes. >> One more thing that we have not mentioned and that is the function of judgment on this procedure of us being capable to make suggestions. I don’t suppose any of the systems that we now have talked about leads you down a line within the evaluation that claims yes or no. It’s a topic of our judgment on whilst you get down where you’ve acquired all of the matters on a page that are essential to make a decision.The choice is not there. The decision comes from us. And it’s a matter of judgment of whether or not the differential between exposure and toxicity is enough that i would be given this as a suitable threat. And what you would take delivery of maybe different from what i would take delivery of. But nevertheless this, there is no recipe for taking this definitively to a yes or no reply. And i consider we have got to be ready to have a discussion when we arrive at our interpretation of what is to be had to make a choice, then there may be yet another step forward of us to make a judgment to what it way. And does it translate into a recommendation to restrict or not.We’ve not mentioned that. But that is another venture that’s now not convenient. >> I mean alongside the identical occasions, I mean uncertainty is some thing we have to believe of, I imply whatever, every step of the way in which we would as well do it as we go alongside is these are what the uncertainties are, since. >> Yeah. We ought to be ready to document well what that judgment is. >> Yeah. >> considering what the approach in which the judgment is mainly extra important than the determination.Is that indicates the force of what your conviction. And if we end up looking at person , but admire that it can be part of a loved ones of in the market and exposure. That turns into a part of the judgment if we shouldn’t have a quantitative means of adjusting a stage of anything to consider that it is accumulative outcomes. We at the least need to have that as some of the judgments that we have now offered an extra component that we have now introduced an extra factor based on the exposure to multiple . And that’s maybe why we are as conservative as we’re on this judgment seeing that of that nature of the exposure. >> I need to have a damage. I think others may just as good. So let’s reconvene 15/20 minutes. >> okay. >> okay let’s reconvene. Is there anymore discussion in regards to the challenge that we were talking about earlier than we broke for lunch.Or will we bear in mind that completed? Mike is going to position collectively a framework, and then personally we’re going to build on that. And share our contributions by using, before our convention call. K. Listening to no extra discussion on that, i might like to move on in the temporary time that we have now, two members must go away quickly after lunch. So I thought we’d take what time we’ve got to be had to talk about a couple of different disorders. And one of the vital issues that I, we must speak about is what are the top features that we are going to use in our assessments, some thing they could also be. Is it going to be the syndrome. Are we going to be more inclusive on that? I might prefer to open up that discussion at this factor.Any feedback? >> Chris Gennings: do we agree that almost all of the data, at the least from the animal reports goes to be syndrome? Might be human knowledge we have extra type of end elements. >> It seems like the syndrome would be the default for the reason that it is the person who seems to appear at the lowest stage. The person who has the . It does not have consistency across species. However there are so many studies now which have explored this in rats that it has that inner consistency that has been repeated.So I suppose with those, and there are ingredients of the syndrome that resemble the challenge in people. And in phrases of finish features. So I think it could be rough to provide you with different end features which have traits, a sample like that that may force us to an extra one. >> Chris Gennings: but maybe we might, if we feel about the syndrome as might be the position the place you set initial focus, after which come back and ask, if we had chosen, is there any proof that different finish points might were affected at scale down levels than what we could find syndrome? >> Yeah i’d agree information and the syndrome is where most of the knowledge is and most touchy. In people of direction you already know there may be other end facets, neuro development, progress, physique composition. However there’s, there’s not a lot comparison data within the animals. So and then on the opposite facet there may be no longer numerous human knowledge on the of the .However from paper. There is not a variety of, or nothing. >> So then do I have an understanding of from that that going down to our 2nd question that we’re going to focus, not hinder, but focus our awareness on prenatal exposures. >> It raises a question and Paul talked about somewhat bit. And it’s prenatal in the rat, but what’s the time of exposure within the human that it corresponds to that prenatal interval within the rat. >> I feel Paul had acknowledged notably give a definitive reply but I consider he stated from about eight weeks to fifteen weeks or so. So we feel probably as early as six weeks. >> however I suppose we must have that footmark in there at that time isn’t the identical in rats as it’s in people. But what we’re specializing in is when the time of exposure in the course of that period is what we are fairly worried about.>> correct. So that, Holger. >> Holger Koch: Plus there probably more than one testosterone modulated home windows of sustainability in the human. Even after beginning. >> that’s, that’s the question i want us to speak about. So do, we’re particularly constructive to examine the, the gestational date 16 to 17 within the pink with the top of the first trimester of humans, but we’ve different windows of sustainability. Probably in the human. Delivery. >> there are various puberty at three to six months, after which of path development. But at the least from the rat knowledge they advocate that the fetal window is more touchy, although they see effects for the duration of pubertal exposure.So maybe related in people. >> there’s latest new experimental evidence from Richard lab to exhibit that continuation of effects within the neonatal period will make certain that the results persist. That is fairly predominant as good I think. >> Bern. >> Bernard Schwetz: These are dated in rodents, in rats. >> k so we’re, we’re, we’ll expand the period of time of our consideration to the neonatal interval as good? >> invariably if the human puberty is it regulated by testosterone? >> sure in boys, yeah. >> So. >> And the opposite, whilst you think about life phases, the other part of it’s, the exposures obviously the neonatal exposure pathways are going to be unique than the, the, you recognize, babies and tots and so forth. >> good am I hearing then that we’re going to go all of the method by means of the period of, of exposure for our consideration, okay.The place does that take us in phrases of time frame? Human progress? From eight weeks prenatal to. >> For puberty? When is it entire within the male? >> Yeah. >> The, in general would say good obviously by 17, 18, but frequently sixteen, 17. I imply it varies of direction. >> Yeah, by concerning the time that you call, be known as into the military within the U.S., but still allowed to have a drink of beer. >> Earl. Earl suggested that the mind would not mature except so much later. But that is an extra drawback, I consider I will have to communicate for himself. >> ok. I was once simply watching at our list of important disorders, I think we have now, we have now mentioned. The 0.33 one which is important. Now we have, now we have mentioned that, have not come to a conclusion yet, we’re going to investigate that. After which the problem about constructing on the.>> Philip? >> Philip: yes. I think we should follow factor, with point three. Since. >> ok. >> If we take the long winding avenue by means of cumulative hazard comparison. We want fashioned end features. So I suppose we will have to talk about on which of the or substitution merchandise we center of attention. And if we have now the needed understanding on the respective finish points. >> I suggestion Mike was once going to get that collectively for us. Did I miss that? >> Mike: good i am, i’m obviously going to check out to get extra understanding in regards to the, the makes use of and potential exposures of that lengthy record of . >> I suppose we should preserve it pragmatic right here. We are able to intricate the list. >> Yeah. >> however I consider for a just right beginning point we will have to just throw these related substitution tactics within the realm and in a few minutes talk about if now we have the central finish features and information on these end elements present. >> k. That is, why don’t you . >> Yeah. So I suppose for lots of the in query we have now the central data.But when my recollection is correct for some of the substitution merchandise we should not have the valuable data. So i’d say that the relevant end factor is the syndrome with probably the most touchy parameter being the specified testosterone level. And the HED for instance. So my question now could be, do we have this data for instance for the EPHP? Do we’ve it for ? >> good now we have, for, in Earl’s talk yesterday for the, his essay on testosterone creation he had one test on dinch which was once negative. Sort of a screening. DPHP was on his lit however has no longer been executed but. As well as DIDP which is of course one of the period in-between band ones. He hasn’t gotten to that both. And i feel that might be very priceless expertise. So far as he range of substitutes, you recognize we have amongst other matters, we have the Versa file which lists capabilities substitutes and we also have our possess record where we measured what used to be simply within the toys about a yr ago.And you recognize there have been 5 or anything, there have been five or so very common ones. Ordinarily ditch in, you already know, the normal, those you possibly can expect and so one. DEHT was original. Of these i do know DEHT i’m beautiful certain was bad in, all fosters experiments from the last century. So probably the most others you realize perhaps they will have to be, maybe you realize, might be we could, we are able to propose to Earl and Paul that they look at one of the most other citrates given that i’m not so certain if we now have the, those data. >> yesterday after we discussed this, Earl cited, gray brought up that skinny sheet proven. But it surely was once a screening test with I feel three were dosed.And he, he admitted that had he, he stated he are not able to exclude to have as a rule visible in influence had he achieved an escalation learn. So it is entertaining to hear from him that there was no outcomes. But he himself was once not undoubtedly sure targeted that with the dose escalation, such an outcome would no longer show up. From the amazing summary which we’ve in front of us, from BASF regarding Hex dinge, I think what we can glen right here is that within the learn according to scan directions, which they carried out. They used a a long way high powered experiment. 25 dims or something. But I can’t become aware of from that potent abstract whether or not or no longer there are the critical information to us, valuable information gathered, whether or not reduction in testosterone, whether or not it was once measured, I count on it wasn’t.So I conclude that involving dinch the significant data are usually not on hand relatively to us. Both to us or now not available at all. >> Yeah I imply the specific studies should not to be had right now and that’s, that’s an obstacle, that’s an foremost predicament. >> What other either or possible choices do you wish to talk about? >> The EHP Robert. >> What can we know about that? >> good I, I instructed to Earl and Paul that they scan DPHP due to the fact it’s three you already know the branching, now not just like DEHP.So I obviously wanted that confirmed. And although it can be, it is no longer, i do not feel it is being used in toys yet, and BASF says they would not always recommend it for that use, but nonetheless, it’s such an obvious, to me it’s an obvious talents substitute. Anyone’s ordinarily going to use it. So that was once excessive on my list to nominate for them. However once more, that is within the equal class. There are information that we should not have access to the original experiences.>> So enterprise gain knowledge of we wouldn’t have. >> correct. >> Chris Gennings: I suppose Andreas’ point is that after we have such information, instead of simply having a screening model, if we might have more amazing studies. >> proper, correct. >> With 25 dams in a group, or anything, I mean some thing the standard is. >> right and that is of direction, we are not able to do it. Or tell them to do it. We could ask them to do it. We could dominate it to NTP or you know, we are able to try to get it completed.That, I feel that comes below the quantity five. Are there any primary studies, we will obviously ask for them. >> is it cheap, with the dearth of data, to make conservative assumptions concerning the knowledge risk for such chemical compounds the place we wouldn’t have data, and anticipate that. >> i’m no longer certain we can, i am no longer definite we are able to. >> Or. >> Yeah. >> i suppose that is a question of judgment.Precautionary principle. I imply it is probably the most competencies steps is to, we do have experiences of these than to only swiftly go by means of and say what do they have got and is that going to be enough or, or now not. >> however lack of information does not imply safety. >> No. No. I suppose you have, we need to be careful. >> Oh most likely. I mean it, we will say you already know maybe we can assessment it, that doesn’t make it secure. Or you know prove that there isn’t any hazard or no danger. And we have got to be clear about that. >> however Mike you don’t, the CPSC does now not have the regulatory authority to ask for distinctive varieties of information on any new product coming in. >> Mike: well we cannot that’s most likely, we don’t the authority to, good we cannot are to nominate it to NT, good ask the enterprise, nominate to NTP, or work via the EPA’s interagency trying out committee and spot if they are able to get the organizations to do it. I mean those are our options. We cannot demand that anybody do it.And we can’t, we shouldn’t have the, the labs anymore to, to do it ourselves. >> any other alternatives you want to talk about? >> aside from the alternatives we, additionally the animal knowledge just isn’t indicative we would have to evaluation additionally considering that of the, of the, well suggestive. >> We’re most likely for the the . Oh you mean what are the top features? >> No what’s it used for. What is it used for. Why are you saying for humans? >> Oh in view that there’s human knowledge showing associations between mono Ethel and, it can be utilized in individual care products. But yeah. >> So that would be a we need to add to our record. Our record. Now not an substitute. >> Yeah so DEP. >> So we’re DEHP, BBP and DBP are the ones which are quote banned. We’ll seem at these. DINP, DI, DP, DNOP, the meantime we are going to seem at. DEP. INBP ISO. >> . >>Any others? >> For the and the octal there is now not quite a lot of animal information i do not consider . >> but for the topic of completeness, the, the, we should incorporate this one too. And likewise the . >> The linears. >> Yeah. >> I want we had Earl’s slide. I recall the slide that he had the record of all of the chemical compounds that he checked out.I do not bear in mind what was on that and what was which can we think that the entire chemical substances we have listed at on that web page, whether or not or not they have been evaluated? Most of the time, good yeah for the . >> a number of the excessive, a variety of them. >> And, and have we requested him if we will have the data? >> now not yet. But will. And i consider the underlying knowledge on these slides, I believe are published.It’s simply that I was having trouble tracking all of it down and recreating so we’ll, we will get what we will from him. >> good the new stuff, they are doing this, are doing the testosterone and that is no longer, that’s not published i do not consider. >> however will we as a minimum have the slides. We will ensure something they do submit, we will ensure we get it. We’re on their record of to get copies of it when it is published, or get an alert. >> any other nominations to our universe of. Good I just desired to make clear the DEP, it is virtually a solvent. It’s not going to be in, within the toys. Probably not going to be in the, what we name childcare products. Although until, even though the cosmetic childcare products. It could be in. However it’s a different publicity supply. >> Yeah. >> however possibly a excessive publicity. >> well in. >> it is a excessive publicity. >> It falls beneath Roman III which we examine probably publicity of youngsters, pregnant females, pregnant women are almost certainly to specific it to be uncovered.>> Oh sure, most likely, yeah. >> No extra feedback? Nominations? Well number C, yeah. >> factor quantity 4, I do not know whether we ought to talk about that any extra. I think we agree that we’re no longer going to, wow new floor within the, ignore what’s been summarized very well in the NRC files. >> however is there any, any remark? Then number five, we, we have now touched on. I’m not sure we have, now we have, expressed definitively that we would like some thing achieved. But are there, are there crucial gaps almost that, that some learn, given the lifetime of this committee would be finished that might aid us in our achieving our charge. Bern. >> Bernard Schwetz: however i’m definite there are significant gaps. I feel what used to be on my intellect when we talked about this earlier was once the probability that there are some gaps that if we proceeded without understanding, we might regret it. As opposed to just quality to have additional knowledge. And it doesn’t seem like we now have identified gaps that if we do not fill them earlier than we proceed, we will be remiss. So it’s not clear that there are experiences that may maintain us from proceeding.The, that might need to be executed. If he nominates for stories to the NTP it will be a few years before you see the results. If we ask enterprise, it will take time. Should you nominate to the NDP, it prompts three to do their possess stories. And you, I have no idea for those who remember what different choices you have for filling data gaps. Well we can go to Earl or to others. >> Yeah that probably the quickest. >> Quickest. Yeah. >> but there is not any one of these that might generate knowledge before even the following assembly to be of that a lot support to us. Again imaginative and prescient stories being carried out before we’re completed. >> It definitely is correct for human experiences as good.>> definite. >> not going for some thing would grow to be available for the time hole. >> good I consider Shawna said she’d have some, some knowledge. No longer a lot on the . But I believe the AGD in relation to other end aspects. So. Yeah. >> good one thing, you realize we tried to just do discover what’s close to done. >> And that, I think we now have discussed six quite considerably this morning. >> i don’t. We are able to, we are able to appear at seven and talk about that. We may not do a cumulative hazard evaluation which makes, if that’s the case that makes this one moot. But I think the thought of, of are we going to include different anti-androgens in our evaluation should be mentioned. >> good again, I feel the distinction is quantitative, cumulative hazard assessment or in phrases of you recognize that you would be able to do not forget whether or not or no longer coexposure to distinctive materials will, for example shift these responses for . And that i believe we can, on the foundation of evidence awarded to us the day before today via Earl gray there are some chemicals where we are able to make such statements, or be it not in a, in a quantifying approach.I feel that is premature. However in my intellect, what’s asked of us, explicitly in the cost, would imply that we’d have to don’t forget such explanations. >> I imply what I did not get from the day before today was a sense of you already know that is person who we’re all uncovered to and also you have to incorporate this. I suppose i have not, or I hold asking people what are the ones which can be you know where there may be plenty of exposure, universal exposure that must be included in this.And i have never gotten it an answer yet. >> well I notion Earl grey stated TCTD. >> ok yeah, yeah, good, that is without doubt universal in. >> EED, para EED. >> Oh too. Which used to be shown to be anti . >> there is additionally a question extra concerning distinct anti pesticides. However I do not know what the drawback is the U.S. However in Europe you could surely say yeah there may be exposure to those as well. But we’d know which chemical compounds to appear at there. >> there is one in but we at least within the do not need through the monitoring information this pesticide. There is no data in the ninth. We know there is exposure to . Or it can be metabolites. In Europe, after consuming targeted types of pink wine. >> The all pesticides truly are, must be checked out. >> whether or not that’s viable in a quantitative way, whether the info are right here for the U.S., is a 2d subject. However often in order to be one factor to be able to roughly be self limiting. However the. >> They probably more like a qualitative undertaking. >> I mean going, going back to number six, I notion from Earl’s slides, that there is hope for having, you recognize, customary finish elements and long-established dose response shapes and so forth.So that would not be so unhealthy. It, I consider it is usually a challenge if you happen to include different pesticides and different non-folly compounds. It perhaps an problem of diethyl but as far as the syndrome goes, good the animal information it looks beautiful excellent. >> it’s going to. >> I think we, we have mentioned eight. >> Yeah. >> That sort of corresponds to the populations. >> precisely. I assume however we might bear in mind what are the sources of exposure. We have talked a lot about that. >> i don’t believe we’re overlooking plenty of any main sources. I mean i will try to see what i will be able to discover concerning the pesticides.But, i do not consider we’re missing an excessive amount of. >> instead of the, from foods, yeah. I imply we’re mindful of the foremost sources. >> Yeah. >> whether or not now we have the information, I imply even though we had information in phases of meals in the U.S., it could nonetheless be a very problematic undertaking to estimate exposures. >> Holger. >> Holger Koch: I feel a point that needs to be made clear can also be what’s the distribution of the exposures we are taken with median exposures.I will have an interest within the 90th percentile of exposures. I will be interested in the 99th percentile or in highest values. It is a question of significance for decoding monitoring the bio monitoring information. But in addition for interpreting the mannequin data from modeling experiments and many others. >> i’m pointing this out because on Monday most of the knowledge awarded through designated precedents had been enthusiastic about medium exposures. And that i think this doesn’t help us at all. >> I imply it’s, and it is, , it is one thing to have percentile exposures to the individual . How do you mix that to the person who is within the ninety fifth percentile for DINP perhaps within the 50th percentile for some thing else. >> I consider that is lovely simple. We now have the data on the . You know what individual has and wishes exposure or is publicity to the C. And the query is do we need to stick to the conservative process and on the exposure of every individual.Or do we type of want to make a precise worst case projection. And adding up the ninety fifth percentiles for each and every price and the would assume that the worst case technique there might be members taking on the entire within the higher percentiles. So in the, I feel within the migration strategy, you do, you utilize this primary case, a case assumption. So in my, in my feeling there is not any argument in opposition to doing this also in the bio information. I think this can be a point we could discuss. >> I feel that that, I imply that will be an awfully conservative approach.There probably are statistical approaches to estimate 99th percentile of the multi-dimensional set of . I do not believe that’s a simple mission. >> i will be able to without doubt seem into that. But I, I, you realize when you consider that it relies on, it is going to depend upon what else is there. You could say you’re o the boundary of some cloud. However in which path? I imply we would try to investigate that somewhat further and notice. If you’re nonetheless on that percentile, you realize what’s the worst case of that percentile in terms of rest or anything. >> it will be helpful should you would suppose about that and comprise that for your contribution. >> Yeah. >> and i mean it is, it is best to be conservative in, and you realize, add the 95th percentiles, primarily as a primary cut.However in case you do this and then you definately say the risk is simply too high, then the question is do you want to refine that. Additionally in, in the event you do, with man or woman information, I imply do you, would you weight the exclusive another way? You would, as a result of potency differences, or, or how would you do that. >> My reconnection is there. I know the differences. >> besides possibly DINP. I mean the others are beautiful shut ample however k. I’m just wondering about that, but i might agree with Holger, you understand in utilising the ninety fifth percentile of a couple of . On the grounds that you realize it’s not unreasonable you know might be in the In Hanes it can be some thing 1500 folks, but which seems like rather a lot nevertheless it’s no longer unreasonable to believe that humans could have more than one exposures to those considering they are from extraordinary sources and one would not preclude the other, so you could probably have an exposure to DEHP, and so on. That are in the higher variety. And then there’s of direction the distinct situations where you will have, whether or not it is for medications, medical gadgets, etc., you could have exposures which are a hundred or 1,000 instances larger. >> some other comments? >> It sounded to me the day gone by like distinction between EPA and FDA is particularly clear and possibly a subject matter of on-going dialogue this time as wanted. But the difference between the regulatory realm for EPA and CPSC isn’t as good outlined. Is that proper? >> well within the sense, I imply EPA has what 5 special pursuits occurring correct now involving . So they are most likely energetic for exact. And there’s significant overlap between our preview and and we’re used to working with them. I mean now not that we do not work with FDA. However most likely mostly work with OPPT greater than than various different corporations. >> guess what I was watching for rather than exercise, was once the question if in case you have buyers who’ve end up alarmed due to the fact of an exposure, and possibly a response and they say what, who regulates this. Who do i go to. Do they turn out to be listening to from EPA? No we do not try this. CPSC does. And CPSC says no we do not, that is the EPA’s. However are there gaps of that sort? >> I feel frequently it can be more lap than a gap. >> however in phrases of publicity, I mean I have no idea that i have a powerful experience that this definitely happens, but if the EPA ended up doing regulatory, making regulatory choices centered on exposure best to pesticides, however then we knew there was once publicity.I mean you realize, the science wishes to be. >> good yeah EPA and F, I mean FDA are almost like five specific marketers. , and of path we quite are a different company. And that makes it difficult to do matters like this. However we are, we’re looking for ways to work collectively. Any person instructed that the publicity in view that it’s the factor to do on the grounds that we’ve, no one began that but. There is a skills with the IRS exercise. And their workshop developing. There may be a skills that we will, if not work together, as a minimum share information and make our jobs respective jobs easier. However I imply it is no longer unprecedented for, to have an interagency recreation. Good we did it a very long time in the past for dioxin where FDA, the one of a kind ingredients of FDA and EPA and CPSC contributed to a multi, then it was a multi-media. Hazard comparison was once determined that they used, and we have collaborated on different movements as well. So it, , it’s a possibility, the trick is to line up our, now not just out, you already know program wishes, but also the timing. >> okay it is nearly the midday smash for lunch. On the grounds that we will lose two of the members of the committee before we reconvene, do, is there another industry that the rest of us want to discuss between the top of lunch and 2:00 p.M. When the rest of us have got to leave. Or will have to we adjourn the assembly at this factor? >> k. Can i, if we make a decision to adjourn, i’m looking to feel, are there any little business matters.The, the books have two CDs, all people will have to have two CDs. One who I prepared that’s very nearly what’s within the e-book. But plus just a few extras that were too huge to put in the publication. The opposite CD is from Exxon cellular. And that has now not only their displays, but there’s a variety of knowledge in there. Correctly there is a database in there that Dr. Clark pointed out the day gone by when she was speaking about publicity. There may be a whole database in there. So I, there’s like various know-how, released papers, unpublished stories. Etc. Anyway there is quite a few, you will have to have two of those, at the least, when you leave. We would, if you are on an airplane we will mail you the, the e-book itself in case you like. But, you would want to take these CDs. I even have some difficult copies of one of the crucial, of Dr.Godwin’s slides from the previous day that you are, can take with you when you like. In case you have them, have them prematurely. Yeah. >> And Mike you can from the presenters that. >> Mike: i’m going to ensure, i will monitor them down and get everything. I can even, i will appear via my notes in, in, as I did final time. Summarize any to do, a list of to do matters. >> will we wish to make a when we can each of us on the committee on the way to have our, whatever it’s we put collectively do. >> Oh yeah. >> To the committee. We’ll meet, presumably in December. >> can we no longer, do we no longer make the date corporation? The dates we agreed on, and assume that it will go forward unless we hear in any other case when.>> good the assembly date, I consider. >> company. >> Is corporation. Yeah. A date for submitting your entire, distributing your entire thoughts on learn how to proceed. >> yes. >> will we wish to try this a month earlier than the meeting. Or. >> Yeah we would like Andreas as cumulative danger evaluation. >> Yeah. >> To us. >> A draft will be k. >> A draft is great. Not more than a hundred pages. >> Yeah and you understand two or three enormous pages digits will suffice. However will we want to get those matters a month before, or a month, two months earlier than and speak about them a month before. >> A 2d month. >> So do the primary week in November? When should we choose a date for a conference call? Which you’re no longer definite we, i might guess we’d need to do it late in the day right here.Or early. >> Early within the morning U.S. Time. >> Oh yeah, yeah, I got it backwards. Which means that it’s quite early. >> really early on the West Coast. >> the hardest, we had one the place we had Europe, Canada, Australia, and that i do not know if we had Japan, however I imply it was, it was once form of tricky. So 5:00 a.M. Portland time is, nine hours change from Germany? I believe? >> Yeah. We’re in the graveyard after lunch then. Yeah. >> 5 my time can be 4:00 you are time in the afternoon.>> but if we say we’re backwards, 4:00 Germany, no 5:00 in Germany is four:00 in Britain, and that is 9:00 here. And 6:00 there? >> is that this okay for you? It is k for you? I do not need to. >> as long as i have my coffee i’m first-class. >> well and the query is would you two rather do it at the end of the day from work, or at night from dwelling? I imply it’s an alternative.>> finish of, finish of day from work can be first-rate. We do not always discontinue at 5:00 on the British universities. >> k. >> So 6:00. >> we are in the pub at that factor. >> Yeah. >> well there’s that too. >> At 2:00. >> So on the way to be, or is it 7:00, that may be 7:00 a.M. On the East Coast? >> 9, 9:00 a.M. East Coast. >> Oh 9:00 a.M. East Coast. >> Six West Coast. >> 4:00 p.M., right.What number of hours between ny and London? >> five. We can do it, we are able to do it at 5:00 or 6:00 p.M. German time. So rather that is k. >> I mean is, is Germany an hour at the back of? >> Yeah an hour forward. >> forward. You’re ahead. You’re ahead of Andreas. >> No Germany’s constantly ahead in terms of time. So Britain is an hour in the back of Germany. So when it’s 5:00 p.M. In Germany, it is 4:00 p.M. In Britain. >> So let’s make it 6:00 p.M. German time. 5:00 p.M. London time. So that might be 10:00. >> noon. >> midday in the big apple. And after breakfast in. >> That works for me. I will be able to quite often get, be to work by using noon. >> So do we pick a day? >> Now the day but, but we were. >> Mike. >> Yeah well if we the, if we get the stuff up by using November 1st, when would you like to, how long do you want, do you want to read it, per week? >> per week to digest. >> Yeah. >> i am doing an NIH evaluate the eighth and ninth of November. So if we could do it after that. >> that is first-rate. >> How about Friday the 12th? >> not excellent for you.Good k, Friday’s not just right interval? >> No . >> I may be in Portland. >> seem me up if you’re. >> ok. >> watching at that week of November 8th. >> ok. >> How is the 18th, the 18th of November, i am teaching that day so i will do this. Holger that just right for you? The 18th of November? Not good. >> 15th or 16th. >> 16th. So it’s okay with you? >> that’s the day I instruct, but that’s k. I can do this. But i do not instruct unless the afternoon, so. >> So we’re speakme about the fifteenth then? >> fifteenth of November, work for everyone? Holger? >> Yeah that’s best. Ok, that’s it. >> On the East Coast? >> I consider it can be 9:00 East Coast, correct. >> November 15th. >> another industry? Mike? >> Mike: I believe that is it.Some of them, a couple, a couple of you ought to see Lisa before you go. >> okay if there’s, so Monday, November 15th. At 6:00 p.M. Germany, or 5:00 p.M. England, or 5:00 p.M. Is, is that ? >> yes. >> GMT. >> okay. The second meeting of the chap is adjourned. .

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Chronic Hazard Advisory Panel: Phthalates Afternoon Session

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Chronic Hazard Advisory Panel: Phthalates Afternoon Session

>> ok i’d wish to reconvene the chap. And as a first order of trade I suppose we have to talk about our calendars and when we will have the next chap assembly. So Mike, could you’re taking over on that? >> I do not know about you Bern, however my agenda for the autumn, i’m going to be teaching but i’m beautiful flexible. But is that the equal for you? >> Bernard A. Schwetz: i am lovely bendy too, yeah, so I just isn’t a limiting element in when we have this. >> right, good what we need to do is talk to the other individuals of the committee and spot there are distinct dates that they are not able to meet. I think we’re speaking about regularly October, November. >> Late November could be all correct with me. >> Does that imply the fourth of November, or the 1/3 week k? >> The fourth week would be higher.>> Huh? >> that’s what, Thanksgiving. >> Oh. >> Yeah. Yup. Well, November. >> possibly the 15th would work. The week of the 15th. No? >> I could do the week beginning with twenty second of November. >> All right. >> It was once vacation. >> Is. >> typically it can be a nasty time to journey. >> travel, yeah. >> It is one of the busiest days. >> How about the subsequent week? >> Yeah, possible. >> Holger? I am sorry. >> Holger M. Koch: My Outlook just broke down.>> Oh okay. >> Holger M. Koch: just a 2d ago. >> Oh that you could make it your self. >> very good. >> Or seem at Russ. >> the primary week in, well. >> The 29th. >> The 29th, thirtieth, and December 1st time period? >> Chris? >> Chris Gennings: Works for me. I’ve obtained somebody scheduled for a seminar that Friday that I’ve invited, however that could be rescheduled. >> The front end of the week is ok. >> Chris Gennings: Yeah. >> Russ how’s that for you? >> Russell Hauser: excellent. The 6th is out for me, but I might do 1, 2, 3, 1st, 2nd, third, no hindrance.>> Yeah. Holger? Okay. The next choice is do we wish to schedule a two day or three day meeting. Two. Thoughts? Holger. >> Holger Koch: do we plan to ask other company? Have we mentioned that? >> now we have no longer mentioned that but. So. >> Holger Koch: I feel it might be good to renew the invitation to Tom Burg. But other than that I consider, i don’t consider we, i don’t think there may be a have got to invite anybody else at this stage. >> I want to invite an individual who could aid us to interpret the In-Hanes data. Considering that the deeper I get into the In-Hanes data and extrapolating from the bio-monitoring knowledge of the dose, the trouble is that the In-Hanes information is generated after fasting. So i’d have liked to have a person who can mannequin out the fasting interval. And what’s it in phrases of publicity. Since we all know the various delays, on the foot board, and when you’ve got fasting interval of 12, 14 hours. That is a predominant have an effect on on, on the secretion and then of direction in back calculating to the dose.Chris do you believe that you would be able to manage that? Was that test need to do with kinetics and, and. Given that I believe that is going to be a primary point, those calculations. >> Do you may have anybody in mind? >> no longer yet. But it surely’s open for discussion. >> I imply i’m sure Antonia can be inclined to come back up, but you recognize her, she does the analytical phase. The other matters, i am not certain she’s the correct person. But she might be aware of who’s. >> I learn some publications with Rick Stallard; he did some calculations headquartered on together with the fasting period. Rick Stallard. >> that is for the modeling, yeah, he’s more of a statistician. >> competent. >> Yeah. >> When is the date? The question of whether it can be a two day meeting or instead of that, then that question of when it’s. Higher nail a type of down before we get more matters on the desk. >> k. >> i might recommend we’ve got a two day assembly and explore the agenda and then if it desires, if it may be quality, if it needs to be three high-quality.However let’s as a default for a two day assembly. Okay. Mike where’d you arrive in terms of dates? >> Mike: ok. I had the options of member somewhere between November 29th and December third, with the, I believe the caveat that the twenty ninth shouldn’t be a whats up, or the twenty eighth is not a good travel day. >> correct. >> The ninth, was it the Tuesday used to be the thirtieth? >> Chris Gennings: So we need to think concerning the 1st as being the primary day of. >> the first is the first day of Hanukah. Which, it’s not a religious holiday, but just with babies. Just for me. However that, I, I would come if I needed to. >> Why, why do not we are saying the 2nd and 3rd then? >> yes. >> Rick.>> that is k. >> but that suggests flying on the first. Ok. >> ok. I guess the Hanukah’s the night of the 1st? >> sure the 1st. >> Does this imply chaos for us worldwide travelers? >> Or are we the 2nd to 3rd? >> Yeah. >> even as we’re at the side of calendars should we explore and alternate to that in case we need on? >> We would try this. >> We’re getting closer by means of the tip 12 months which is not a excellent time. Proper. Okay. >> The 13th would be viable as a fall again, however i might pick the date we agreed on first.>> That stands out as the first option, however i am simply watching for a again up in case we’d like it. >> definite. Week of the thirteenth? >> Yeah. >> The 13th, 14th would be, as a fall again. >> Yeah. >> thirteen, 14? >> you know while you. >> The 13th and 14th is just not going to work for every body. >> No. >> good I suppose that going the following week we’re getting too virtually the holiday. So let’s go into January. >> Andreas is not to be had. >> ok. >> January. >> January. January is beautiful open for me. Besides for the 24th and twenty fifth, a further veteran agent orange in California. In order that week would not be just right for me, the twenty fourth. >> How concerning the week of the 10th? >> excellent.>> Chris Gennings: now not excellent for me sorry. >> . It’s nice with me. >> When, when is? Ok be we don’t have the constructing. 18th, Holger, Chris, Russ? Ok, January 18th, 19th as an alternative. >> That work okay? >> 18 yeah. I think that, it can be the 17th so. >> January, are you going to go to that? Yeah. >> Yeah usually. >> i don’t, I didn’t be aware of that they had set a date. K that, that’s just right. It can be SVOC’s.So it involves and likewise flame retardants and other that you in finding in house dust and window film. So it can be informative. >> ok, so now we have got dates December 2 through three as a important, and January 18th and nineteenth as an alternative is December dates don’t work. >> k. >> Then Mike, you are going to work with the EPA in phrases of fall work shop on. >> Mike: Yeah now it was once January 18th to 19th because the backup? >> sure. >> Mike: k. I will coordinate with the EPA. The so are viable dates, we do need to invite again Tom Burke. Probably. >> For an additional agenda object, knowledge that we did not get the day prior to this, seeing that we proceed to struggle with this question of the place does it come from in food, and we did not have the food center with us the previous day appears as if we should both. Perhaps first alternative is to ask them to provide a written abstract, a desk for us that will be effectively understood about what the levels are. And what the FDA assumes is the supply of in those foods the place it’s measurable. 2d alternative to have a person come and talk to us next time.If they could get these data to us now it could be worthy to us to feel through what we wish as a substitute than reply to it for the first time in December. >> I believe, you know, the answer is that what they, if they have knowledge it can be often not. >> it would be necessary to grasp additionally what are their plans for gathering extra data. Proper. >> and in addition there was once a question raised, the offer was raised the day gone by whether or not we need to be aware of whatever more distinctive about medicinal drugs. >> correct, and. >> by, by using type, by agent, composition, through , by using age of patient. >> And that was once normally for diethyl valley too. Good most of their information are diethyl; I mean I think they stated they’ve one. >> last dibutal, after which the supplements and the . I mean that is the one of a kind a part of the FDA i suppose, or a different part of the federal government.But. >> Is there any purpose why it will be on account that of the compounding of the tablet? >> I think Helga you, you will have German data proper, on. >> Holgar Koch: I could provide for the subsequent meeting the info from Germany in which drugs, tribunal and are. I wouldn’t have any information on the meals supplements. But in all probability, it’s possible that that is there too. So I believe we should really pinpoint it to prescription medicinal drugs, over-the-counter medications and meals supplements. And within the mild of the truth that the info from In Hanes is from the years 2003 and 2004, i would be interested in the late containing drugs at that time too. Since we might need this expertise for interpreting the information. Considering the fact that there are a couple of publications hyperlink hello dibutal exposures to the usage of medicine. >> Yeah and we, we had released on using the In Hanes knowledge. Utilising the urinary levels and self reportive medication use. And it was, most, I feel it was once 2003, 2004, yeah. >> In Hanes it was two to three, or, i’ll, i’ll verify. But. >> From the fourth document is 2003 to 2004. That’s the. >> Three to four. That is the, however i’m going to investigate. >> dates. >> And are we in a position to tell Abby and Steven precisely how, what kind we would like the data, like age corporations or something, or do we wish, we could continue to feel about that? >> It was the experience from the rest of you that what they needed to do used to be generate these knowledge? Or is it a matter of what they ship us? >> No I consider it is an information base they usually could summarize it in many distinctive ways. So. >> To be honest I needed to appear into this database, one of the information, it didn’t help me much but. >> Yeah I, but, I suppose they’ve extra information, they’ll have more understanding then is in the public database. And so they might, you already know classification matters by form of drug or some thing like that. I believe that’s the. I think that is the difference.>> I think without seeing anything of what they, it can be difficult what to ask for. At the least from my point of view. So I mean I would take a, take a stab at, you realize if we ask them to stratify it via age and with the aid of gender or anything like that. >> Yeah, just so we get to peer what they have. >> Yeah. >> Are we assuming that they might give us a urine knowledge as good as blood data? >> Now you, we’re talking about In Hanes. >> Oh yeah, i’m sorry. >> The FDA, or the medicines. Drugs we’re speaking about what’s within the components. >> Oh so it’s just publicity. As a. >> proper, correct. >> A particular point for exposure. >> it could be the variety of situation situated exposure.In Hanes we’re speakme about it’s practically, I think it can be all. And i am not, well anyway i’m now not certain, I have no idea for exact that FDA can go back to 2003 but they customarily can. >> Age, gender and 12 months, some thing like that. >> Yeah. >> k so we’ve, is that the whole lot that we suppose we want for the following meeting? Might be. >> good i’ll ask about pesticides. Despite the fact that it, there will not be. I suppose like plenty of things, the whole lot’s being reformulated. But i will ask that a part of EPA. >> Holgar did you have got another? >> Holgar Koch: I used to be, it used to be a separate subject, however concerning the choices to get more knowledge. >> sure. >> Holgar Koch: Jay has, I imply if there is more know-how.>> good I believe, I mean I consider we now have what there is. The Versa report and the Nick, there is a Nick Nash report, which i’ll ensure, if I did not send it to you i will ensure you get it. >> and then back to Holgar’s advice about Rick Stallard. I believe Rick might at least reward the information from his paper. I mean he would do it reasonably rapidly I suppose in 20 minutes. But in phrases of anybody within the subject of formal kinetics, I can not consider of any individual with close . I imply there is quite a few people that have completed this with dioxins or pesticides, other chemical substances.I might feel that it’s the same concepts that they could observe. >> Holger Koch: i have a just right working relationship with Med Lober from USEB. He’s residing around the nook. He has experience and i believe he could provide us a bit of introduction to the, to the drawback. I believe it’s, it’s the quandary of In Hanes with the fasting. We have now the information generated after fasting is a important quandary we ought to talk about. What’s the have an impact on of fasting, on publicity to none persistent chemicals? That are usually food born. >> And primarily for DDHP and the. >> And the high . >> Do, are they normally take the samples after fasting? >> Requirement. They’re asked to rapid. I believe its in a single day.And people seen within the afternoon I feel its six hours as a minimum. >> Chris Gennings: Is there a variable that describes how lengthy they quick then? I do not suppose I’ve ever appeared. There may be? >> nevertheless it’s, it’s in the questionnaire. >> In that’s, I mean is that because they’re gathering lots of other matters, like cholesterol and, yeah, geez. So that, you know, could good, well underestimate the contribution from food which is gigantic. >> Chris Gennings: the place on your paper you’ve got bought some best graphs displaying phases shedding with 48 hour fasting, correct? So I mean cannot. >> They considerably drop after 12 hours of fasting. >> Yeah. >> however i’m no longer the knowledgeable in interpret this knowledge for the whole populace. >> Chris Gennings: but the graphs that you’ve got bought to your paper might be priceless in, to model it because the point.>> you should utilize the entire graphs removal kinetics from the experiments, and the fasting graphs are the same. So there is the info, it is out of it it simply desires anyone with, with farmaco kinetics toxicol kinetic historical past to model this into the In Hanes population. So the names that come to my mind. >> It seems to me that’s a, that is a research venture. >> i would not make it that tricky, do you think it is that elaborate, Russ? >> Russ: it can be but i do not consider it needs to be. >> okay. >> i admire things easy. >> Russ: probably, you recognize whether or not the levels are 20 percentage shrink than you can anticipate since of fasting are 50 percentage. I imply more of a range i’d believe. >> So yeah, I mean you’re speakme about correcting for them, or just assessing the have an effect on? >> You must proper for it.Good if you’re in a fasting window of 12 to 24 hours, it’s a dramatic correction. >> And surely six is, you already know in a technique it can be worse due to the fact it can be somewhere in between, and however the slope is on the whole . >> I suppose this can be a foremost quandary that has most of the time to be mentioned related to more advantageous data. >> And frequently most knowledge, since i know most studies probably don’t collect that knowledge. You understand when was once the last time you ate some thing with the spot urine samples? >> you understand from the German environmental survey there’s no fasting period. That’s the main change between the German data from the environmental survey and from In Hanes. >> Chris Gennings: would we strategy it style of in a two, in a tiered degree.One being a type of a simplified process where we simply do some corrections established on the info that you’ve got bought in your paper, after which, and then get perhaps a person perhaps extra of an talents of farmaco kinetics that may evaluate how close or a long way off that straightforward. >> My factor with that possibly a undertaking was once simply i will rephrase this and ask do you consider that if we confront Matt Lobo with that that he can do it as a part of a presentation for us? >> i might think that will be possible. Possibly in conjunction with Rick’s expertise. Or with, with the expertise he made. >> right, yeah, i might believe you would examine it with Rick Stallard. Yeah. >> I feel it will be a high-quality suggestion.>> that is something that might be finished earlier than our subsequent assembly. >> comprehensive after which presented at the next meeting, or? >> yes. >> Yeah. So. >> So we would have to technique these two entry researchers. >> So we would want both. >> Matt Lobo and wealthy Stallard. >> it is Stalhart. >> I have no idea. >> Yeah. The place’s Rick? >> institution of Rochester with Shawna. >> Oh. >> i will want Holgar to support me give an explanation for to them what it is we wish, or maybe have you ever do it. >> Holgar Koch: They, they both of them perfectly comprehend the challenge. They will understand what you are speakme about. >> What we’re asking is how you can adjust or at least to provide an explanation for challenge. >> I feel Rick can be in a position to provide an explanation for the limitation, and than Matt in phrases of regulate or what variety of magnitude of the differences may just make. Yeah. >> Chris Gennings: i admire Andreas’ factor. If we might get them to absolutely do it and not just speak about it.>> Yeah. >> Chris Gennings: And gift this. >> good. >> really I would love to have a compilation as Russ mentioned it, of which of the reports in our focal point are centered on, or are collected after fasting, and which now not. And it can be very intricate to, to find this in the materials, math substances description. So irregarding it just got here to my intellect a couple of, to my awareness a couple of months in the past. As I believe it slipped the attention of many of the researchers in this field. And as you recounted it, Mike, like the various stories are initiated to get scientific parameters. And they’re no, you get them after fasting. >> I imply we do, kit Carlson my colleague here is attempting to keep monitor of the exclusive reviews and i have no idea if he is aware of that however probably he might discover what the procedures are within the specific reviews around the world. Yeah I mean you realize what the German gain knowledge of is doing, but i will ask him if he is aware of about, something concerning the.Since I believe once these matters begin, they have a tendency to sort of comply with methodology clever, they have an inclination to comply with one an additional. >> On a broader obstacle, I think we need to discuss are we going to do a chance assessment, what form of chance comparison are we going to do? Are we going to do it as a committee, or are we going to ask anybody external to do that and furnish it to us? Because i am somewhat bit unclear as to what our direction is to finishing our cost. >> Yeah. I mean if you’re talking about how the chap operates, the proposal is for the panel to do it, even though it is usually possible to get help with some specified things, targeted steps or anything so long as it’s executed to your requirements. That is allowed. But frequently it’ll be the panels, it should be the panels risk comparison. Now as far as operationally what to do and what to include, I mean that is up for dialogue I believe.You realize the nuts and bolts of, of doing it. However I feel the expectation, I imply it is the risk comparison. And. >> again, not being my subject, i am. >> Yeah. >> I is also asking some. >> well no this. >> Unintelligent questions right here. >> this is you already know other committees may, I imply I have no idea exactly how they work, however i know they contract out quite a few fabric. Quite a lot of the work. And that is just a little bit distinctive. That is no longer how the chaps had been carried out prior to now, but of direction given the dimensions of the challenge we will get as so much support as we are able to. >> good let me attempt to make my questions just a little bit more unique. EPA is going to have a workshop had been they’ll be looking at . >> Yeah. >> And they are going to do accumulative chance assessment. >> ultimately. >> eventually. I think this risk evaluation, or this workshop goes to be simply to listen to to discuss and to listen to from like we did the day prior to this, learn how to go about it. What are the end points and all the identical stuff, all it talks about the day before today. >> Yeah. >> The matters that we discovered quite a bit yesterday but I suppose the, we have to sit down and say you recognize that is in, this is out.We will do it this way, no longer that manner. But my point is that eventually they are going to do what we, I suppose, are being requested to do. >> What they’re, what the EPA Iris software is going to do is well they are sort of in, in new territory. Given that quite often Iris does, they do the hazard identification in the dose response comparison. And of direction we’re doing the entire thing, that’s the change between us and Iris. At EPA any individual else, you already know, they do this and then other men and women take the Iris and, they usually’re Iris record might be utilized to many distinctive threat assessments. >> however can i expect effectively that given the EPA has gotten smaller an NAS panel to inform them you already know chance evaluation in 2010, that is been published.>> Yeah. >> That that is what finally they are going to do. >> I consider without doubt. I mean why, I mean I feel it’s an excellent file. >> sure. >> And it is pretty clear, I mean not that I understand the entire subtleties nevertheless it’s beautiful clear what the course is. >> sure. So my question is, if that’s what they will do, is that what we should do? In different phrases is that the state-of-the-art? >> good I consider that document is, it’s the state of the art for Valley Syndrome effects. >> can i simply, I think it would aid at this stage to if we turn once more to the chart and the regulation of abridge 26 and 27 of the unofficial compilation.>> Yeah. >> What, what it says there in my, well it is more commonly open to dialogue, but i might say that what we’re charged with, and B examination does now not always imply that we ought to do a risk evaluation within the feel of a threat characterization according to the silver publication. >> correct. >> What it says is, is we’re purported to compare the entire capabilities wellness effects.Now I think it can be slightly open to interpretation what exactly does that imply. However I read into this that this isn’t always a full blow hazard assessment in the sense of threat characterization where you first recollect exposures, then map it in opposition to assumed secure phases after which come to a choice are we now in deserving now that the purple light starts offevolved to flicker or now not. You see what I imply? >> well I agree, it can be a determination, I consider it is a resolution factor that chap has to make as to whether to focus on those syndrome, or to really go the, the space on all of those different, or other finish points past that. >> No, no. I think we misunderstand every different. >> Yeah. >> What i’m pronouncing is, I think without doubt what we are purported to do, how I interpret these below B what is listed within the legislation, we undoubtedly need to do what i might call, and what’s on the whole referred to as a hazard comparison.>> proper, proper. >> however now not necessarily a hazard evaluation. >> correct, and, and that is what i’m looking to say. I consider that, well the important thing word it’s no longer necessarily. And that i suppose that chap has to come to a decision. >> Yeah, yeah. >> whether or not you do the quantitative on multiple finish features or just the one. I mean that is your decision. >> Now even, even though say we made up our minds on a important end factor shall we say, hypothetically of syndrome. >> Yeah.>> I, what I read here, i do not always appreciate to mean that even for the syndrome we have got to do a full hazard characterization within the sense of a risk evaluation. In other words, seeing that exposure first, then on the grounds that hazards, after which come to a conclusion about risks, even as we ought to be clear about the language right here, some folks comprehend when matters by way of chance assessment and chance characterization. However I consider that’s my individual interpretation, please proper me, possibly we ought to come to contract right here now. I learn this to mean some thing with an emphasis on hazard comparison, definitely. >> Yeah. >> We also have to look at publicity so there is a quantity, what was once it, sure quantity three. >> Yeah. >> take into account the stages likely in youngsters, and so forth., and so forth. >> Yeah. >> but I consider i might ask the panel to don’t forget whether they, whether or not you see, whether or not you interpret whatever written down here to intend a threat evaluation or a threat characterization by means of you compare quantitative stages, dosages, exposures, related to special hazards, after which make the comparisons with exposures. >> Yeah and that is why I brought up this dialogue, given that i do not think we’ve got resolved, as a minimum i have not in my mind with how we’ll go on this.And it seems to me that we, that’s a significant decision we have to make up since if we go, we are saying we must do a quantitative cumulative risk assessment. Then do we’ve got the capabilities to try this is the subsequent question. So I think we ought to resolve what it is we are going to do and also have a justification for that. >> Chris Gennings: So. >> for the reason that it appears to me the state of the art, I could also be unsuitable since this is not my discipline, is that silver guide, in terms of do the varieties of matters that we.>> Or the quite more like, I suppose, the blue inexperienced guide. In our, the. >> Yeah or that one. >> The one yeah. >> Chris Gennings: am i able to simply ask a point of clarification? So Andreas are you announcing, i am considering again to the court and camp speedy paper offered to us at our last assembly. Where are you relative to what that approach that you have in that paper? Are you pronouncing that is the method you don’t believe we ought to do? I am not sure i do know what you are pronouncing? >> Andreas Kortenkamp: sure that is what i’m pronouncing, yeah.>> Chris Gennings: You think we don’t need it. >> Andreas Kortenkamp: No. What, what we did there in the court and camp fast paper is an awfully crude, first technique at some style of danger assessment, cumulative hazard comparison. What this paper does greater than something is highlight the talents gaps. And normally maps out a viable modus apperandi very crude there are possible choices that wants to be subtle. But I see nothing in these, underneath B examination here, that may advise that you simply will have to carry out .I feel the emphasis, that’s my interpretation, is more on hazard comparison. >> Chris Gennings: What do you imply by hazard evaluation? >> Andreas Kortenkamp: well it can be the average, the ordinary triple jump. In danger evaluation you appear at publicity you seem at hazards of chemical substances, and then you definately put it collectively and carry out what’s known as a hazard evaluation or risk characterization by way of comparing, by means of asking the query having established a level quantitatively of a chemical what we consider it isn’t risk-free anymore. And then you definitely ask it to do current exposures exceed that or come close it. Sure or no. And that is called danger comparison. I do not believe we must do that last step. I suppose we should talk about that. >> Yeah. Good I feel, I consider it’s implied. It does not say it explicitly, however I suppose it’s implied. >> Andreas how about number four below there, recall the cumulative effect of the complete publicity. I imply how, how would you try this or else? >> Andreas Kortenkamp: yes I suppose that’s, that is a factor. Good it says take into account, well, here. Of path we are able to do not forget, however yeah I think that’s, good sure.We need to come to an agreement there. I think it is open to interpretation. >> Our consideration there could be a suggestion and encouragement the EPA would proceed with an accumulative danger comparison of . That probably conscious of that, simply without difficulty to say that with out the necessity for us to do it ourselves. I would like to proceed what Andreas has prompted us to think about. I feel that’s something that we have got to have this dialogue or we will be able to proceed to acquire information and now not be aware of what we’ll do with it, with the probability that we will become collecting knowledge that we do not definitely ought to reply the particular questions. And we will not have the understanding that it does take to reply the query. So my inspiration was once to step forward and seem in particular at what CPSC has requested us to handle. And in addition to this, there was once a request for us to have some recommendation on what to do with these which have already been banned, briefly. And will have to that be accelerated or should it be dropped. What about different , and what about possible choices? Should there be some thing else banned? Should there be some restrictions that we would propose versus banning? So i’d use that as an extraordinarily designated request the CPSC has made to us.And if we do not reply that and we reply various different stuff, they may consider that they failed to get from us what they relatively requested us for. So watching, if we will comply with the interpretation of mainly what Mike has told us about these banned and unbanned , I believe that leads to a discussion of what can we have to have in hand to be ready to reply that detailed question. And if cumulative danger comparison is required to do that, which i do not believe it is, then we’d must try this. Or we would defer to EPA, given that they are mostly going to do it anyhow. At the risk of two of us doing it is that they’re going to no longer agree. That might be unhealthy for regulators. >> good I consider we do not have to agree.And it also is determined by what the disagreements are and why. >> yes, surely. >> however I consider, you realize, you made the factor the other day, the bottom line is that we’re asking the chap (a) shall learn blah, blah, blah, make suggestions to the commission involving any or combos in addition to these identified in subsection A. Or choices that will have to be declared banned has materials. In different words, is just not in a few of these equal children’s merchandise.After which a little farther down I believe based on that, the staff additionally has to come to a decision whether to make the meantime band everlasting. >> So if we can work from those certain question and back away somewhat bit and Richard do we ought to reply these precise questions. Then we at the least are being attentive to the rather slender question that they’ve asked of us. After which if we want to deal with matters which are out on the threshold of that that need to do with more commonly, or different associated disorders which can be might be adjacent to the unique ones the CPSC has requested us to handle. We are able to do this if we wish and if we have time.If we now have the understanding. But my recommendation is that we are able to, I just like the hazard assessment technique, might be considering that that’s what i have performed in my profession as opposed to the extra distinct modeling. And i’m not towards modeling if that’s how you can go. But I consider we are able to maybe reply these questions by way of a hazard assessment strategy and probably the data, I mean we now have finished this, we have done hazard assessments with less data than are on hand on . So I think it is practicable. And i consider if we can reach agreement beginning from the top factor and dealing back just a little bit, we will be more effective in being able to get this achieved. >> well if we simply focus on the thalaids which can be presently banned, I imply is is reliable to expect, and i have no idea this field that these weren’t banned on the foundation of accumulative threat comparison? Right.>> Yeah. >> It was once, they were banned on the hazard assessment process that you are speaking about. Is that right? >> I consider most of the time it. I imply I, there was once no cumulative threat evaluation per se. I suppose they had been involved about cumulative effects. >> Chris Gennings: i might ask if we might be somewhat more unique. I think you guys are making use of phrases and i’m not sure of the glory. If i am being I apologize.However the hazard evaluation as opposed to hazard evaluation, i don’t, I do not know precisely what you’re announcing. If any one, if both Bern or could be extra targeted it could aid me so much. >> Yeah what are, what are the steps that we’d take to head and. >> Chris Gennings: And in distinct. >> And in exact with the three which might be band stay banned. What would we do? >> Chris Gennings: And in particular, i would like to listen to relative to what I understand Andres, and Andreas, sorry and paper relative to that, what’s on the desk or off the table from that. >> exactly. >> Andreas Kortenkamp: I wholly believe what Brian just stated. We, I think that’s the backside line we, let’s work backwards and ask the question what variety of know-how do we want in answer to meet the charges. And what would be very helpful and you stated it already could be to get expertise about what standards were used with a view to come to the resolution to 3 ones in the legislation. Is that documented somewhere? What criteria were used. >> i do not feel it’s that well documented. I think that’s the concern.I believe that the european band is, there is a little rationalization in the documents. But in ours there is not, the legislation itself doesn’t quite have the justification. And there is, so far as i do know, there is now not so much of a written history of how and why matters have been achieved. >> Andreas Kortenkamp: k if that’s now not the case then, I believe we will have to, a primary step would be for us to think of standards that will support a resolution to band anything. However I do not know what they’re but I suppose we should be clear about them. And secondly in answer to your points, Chris, i am also competent the terminology and use of phrases on this subject is in many instances a little bit confusing, and i would strongly endorse, for the reason that we’re working in america to comply with the terminology utilized by NRC and commencing with the crimson guide, ending with the silver guide.That, shall we agree on that? These terms are very evidently outlined within the silver guide. I mean we can take the silver booklet. It goes again and explains the whole historical past of how they strengthen this entire danger assessment framework and the terms they use. Shall we agree on that for simplicity? >> undoubtedly believe that. >> I believe for my enlightenment and probably Chris as well, if one in all you might define mainly phrases what the system is. That would be useful to me. Ok. >> Andreas Kortenkamp: i will need to cross over to a few of my colleagues here. However regularly the, and that’s terribly foremost and more often than not uncared for and i believe that is what we must apply ourselves here to. The system starts with a state of predicament method, and defining the context. And i think we’re about to try this and we’re very close to that. So that step is so most important.It then asks outlined already. That helps us to make a decision what sort of information can we truly want. So we have to define the context and the drawback. I do not think that should be very complex. After which the core of hazard comparison or threat characterization starts offevolved with publicity evaluation, and Olga, for example is an trained there. It asks the question what are, what are possible exposures to the chemical viewed. This will likely differ in step with population, subgroups A, and so on., and so on. But it clearly asks that. In parallel, a system goes on which is handiest known as hazard assessment. It asks the query what knowledge do we’ve to begin with on the result profile produced with the aid of the chemical in query.Yeah. We have already additionally considered section, you realize . All of the finish points. What’s going down. And secondly it asks the question, is there quantitative dose response expertise available for any of those finish facets. And if ye, it then, if feasible concludes with the approach whereby risks associated with unique exposures or dosages are quantified. So that is that box. So publicity assessment, hazard comparison, goes on in parallel. Then the step of risk comparison, or chance characterization is to unit these two steps through asking the question are the phases that we’ve got founded as more likely to occur by way of exposure evaluation.Are they attaining a zone which the hazard comparison tells us is associated with danger. >> Chris Gennings: All this must be carried out in phrases of a blend not a single chemical. >> Andreas Kortenkamp: sure that is all a different problem, but there are, there are methods of doing this. Systems had been mapped out how to do this. >> Yeah. I mean in, in a sense, if you’re going to do combinations, you sort of might in every single place. I imply do a hazard identification for the members, however then for the combos. And does response the place the contributors and then for the combinations. So it can be, it complicates it that rather more. >> Chris Gennings: So Andreas you wouldn’t support us utilising a hazard index strategy? >> Andreas Kortenkamp: A hazard index or some thing is far too specified an technique. I mean that is only one manner of, of doing accumulative threat comparison. There are others. But let’s no longer get too hung up a few hazard index approach or not at this stage. >> Chris Gennings: i am sorry to keep pushing you, but why now not? It helps me if i will think through these varieties of steps. What are we going to, when we talk about data, what are we going to do with the info? We hold speaking about bio monitoring studies.Trying to, and that i was considering of mixing non-atmosphere knowledge into… >> Andreas Kortenkamp: No I suppose I consider Bern. What Bern says if we have to be clear what, what we’re, what we’re aiming for. And my feeling is that so as to reach decisions about continuation of prohibitions and bands. I’m no longer certain we have to get quantitative and let on my own recover from complex with mixtures, threat assessments or cumulative risk assessments. That’s my opinion, however we should don’t forget that first and in order to simplify for the reason that in any other case, as Bern mentioned we end up in a difficulty of having assembled info which then we appreciate that a letter stated we don’t need in any respect. >> Am I proper then in this strategy you’ve outlined, if, if Holger have been to convince us that cumulatively we had been being uncovered to at least one milligram per kilogram pre day of and we know from animal knowledge that three milligrams per day, kilogram per day factors an opposed impact. Then we’d follow some element to claim that that is close adequate to the animal knowledge that tells us that it can be antagonistic that we will say this is a situation in people.>> And yeah that is a method but i would say that’s already very quantitative and possibly difficult. I imply in my intellect, mix cumulative hazard comparison. Would to begin with begin questions reminiscent of what’s the proof that coexposure to a couple of actually qualitative exacerbates hazard. You don’t have to be too quantitative. You ask questions in what direction would this possible move a dose response for an person . Questions like this. With no need to be too quantitative at this stage. Or similarly, what is the probably expected outcome of , and many others. >> Chris Gennings: but is it that type of strategy primary, possibly probably the predominant when it can be the, when you’re in the procedure of attempting together information. So in case you do not have to exit and get the quantitative information then you could asking qualitative questions. After which along the way in which decide sure we must go additional, or no we don’t have got to go additional.But I consider we’re competent the place we now have visible various data. And we’ve it at our fingertips already. >> Yeah. >> Chris Gennings: So i’d recommend that we go ahead and consider about more of a quantitative technique. >> Whoa, whoa, I consider steady, steady. In view that why would you, why would you want quantitative knowledge on something very complicated cumulative danger evaluation. If the query is to decide whether we’re to, whether we are of the opinion that the prevailing band on particular must be persevered or not. In my intellect you don’t need this know-how. In my mind what you need with a purpose to reply these question is a hazard evaluation. >> i suppose the trouble will get again to what do you mean by way of that, by using hazard assessment.Due to the fact that i don’t rather follow how you might do that in a qualitative feel simplest. Come to the conclusion that whatever is, on account that to me that virtually implied that there needs to be some quantitative facet of that. Am I mistaken? >> well I see it that method. Or path that is what I do. However. >> however the hazard comparison has quantitative facets. Does response analysis. >> when you do dose response then you’re relocating past just the hazard assessment, I feel. >> okay that is a terminology drawback. In step with the silver ebook you, I think we should look at that and. >> Yeah. But well, if believe we did a, the most simple minded variety of a quantitative evaluation? Not fear too much about you realize advancing the state of the art.Making use of the principles, applying the concepts in the, the NRC report on . ABE limiting it handiest the syndrome effects, for starters as a minimum. Is, is that conceivable? >> Of path, of course. But here is a concept which, which i might like to place to your for dialogue. Possibly that makes it clear. Individually it is extremely troublesome to aid the determination for or against the band by means of doing a full blown danger characterization, hazard assessment.The concern is this. Holger has very eloquently told us about these substitution procedures. So good exposures to are, they are like moving gold posts. There is already, we’re wholly aware of this. A substitution method happening. Given that choices are made via industry to restrict the use of special which regard us complex are for some thing cause, and there is a transfer towards others. So for example, hypothetically, as a result of this process a hazard assessment for DEHP could conclude that since the present publicity phases have gone down that the hazard because of DEHP is now, i am making up an instance, negligible.Right. >>correct. >> Then if you wish to use that effect of a risk characterization, risk evaluation procedure, that might be average. So if you want to use that to now as a criterion to select a ban or not, you can also end up in a very absurd predicament. Then you definately make a decision k, currently nothing to worry from DEHP. The reaction to that and so then hypothetically you would argue no have to band DEHP. If this happens, then there will likely be a substitution process occurring in the different direction.>> proper. >> we can then see it extra to DEHP. And then in he future you would to find yourself confronted with a obstacle, ah ha, now exposure to DEHP are so high they may be getting us into the zone of attributable dangers, hypothetically. >> correct. And i think that. >> So I conclude from that that a full blown hazard comparison is unsuitable as a basis to come to a decision for or in opposition to the band. It has to be situated on the hazard comparison. Does that make experience? >> Chris Gennings: however could not a risk evaluation inform a hazard assessment inform a hazard evaluation. In different words, I have an understanding of what you are pronouncing, there may be a moving target in terms of the exposure levels of those chemicals. And we ordinarily might even gain knowledge of that in In Hanes if we had the opportunity to look from 12 months to yr to year, right. But we might additionally , make up, I should not say make up, however take into account eventualities the place we say ok now if DEHP clearly did expand via 20 percent, then this is where you’re.We would remember it in numerous one-of-a-kind cases. >> correct, or one thing I’ve completed is for those who, you understand, flip back the clock to a unique data and say well you know when this whole trade started, you are darn correct, you wouldn’t, you could definitely ban this chemical and also you wouldn’t need to change it. I imply there is methods to deal with all of the relocating target predicament. I consider that is a, in comparison with the opposite disorders, no longer insurmountable.However. >> i know, i know. However it helps us. >> Yeah. >> reply the question in step with Bern, which Bern, Bern contact has introduced up. What sort of expertise do you want? If for illustration, contemplate this a little more, then it instantly turns into clear that for these discussions we are not looking for publicity data. >> well the. >> There are other, there are other facets here in the chart the place. >> Yeah. >> We do want exported knowledge. However as a way to argue for or in opposition to a ban of designated , we do not want publicity information. >> well it. >> We ought to have the . >> however when you say publicity knowledge, do you mean like bio monitoring knowledge, or do you mean hypothetically like for instance, we’ve got data migration from the merchandise. And so you might say you understand given the identified toxicity traits, and this amount of publicity it could be below any stage of trouble or above.And asses the choices that approach. So you understand it, if a detailed alternative say failed to migrate, it would have a better toxicity, if it migrated so much it might have got to have a a lot minimize toxicity. But I mean you are, you elevate good features, and it’s, however you are right, I think we have got to form of believe through what are the steps that we wish to do to answer these special questions.And what can we have to do, what will we want to do, or and what do we do. >> Yeah and i am just questioning Andreas starting this off of the beginning gate right here. I am an awfully visible learner, so I must see matters. >> Yeah. >> To particularly analyze and digest. Wouldn’t it support us if you were to make use of the procedure you will have been speakme about with relationship to the three that have been banned. And go by way of your approach. And so us, , what that would lead us to.That way we might say that is, oh yeah. >> Oh yeah, i am being put on the spot. I can, I have no idea. I can do this. However that is why I asked is there documentation of the determination making method, what standards we’re used to reach at the determination to band the three and the regulation. Yeah and i don’t consider there may be lots. Well Phil. >> Go ahead. >> receive that’s priceless. >> Ann Clauson: Ann Clauson with Latham and Watkins.In 2005 there was once legislation in the european which seemed very much the equal. It put a traditionally permanent, good not on any of them, was it permanent. However it was a fuller ban on the three curb molecular way. After which period in-between sort band on the higher moleculades. It did provide for a reassessment of that, which is going down right now. With reference to the better molecular weight, in particular DINP and DIDP. They had additionally completed risk assessments that confirmed no chance.But they determined t go forward with the laws and explicitly recounted that was on the groundwork of the precautionary principle. After that used to be passed, California handed legislation that was once explicitly modeled on the european. And the legislature did no variety of hazard assessment. They only picked up on what the european had achieved. When the CPSIA was being promulgated, Senator Feinstein from California desired the brought to the CPSIA on the identical foundation that it used to be in California.So once more it was delivered to the laws, fairly as a political process with no sort of hazard comparison explicitly accomplished via the legislators. >> And it can be, thank you. I am of the approach. I don’t know that there’s a written document that we might refer to. It can be for me at the least, it’s 2nd hand know-how, 0.33 hand, fourth, whatever. However that is my working out of the approach. But there wasn’t a, you understand it’s not like a proper rule making the place you do a hazard assessment and many others. There were hazard assessments carried out within the european.And it can be controversial, the don’t necessarily, they did not always support the band, the ecu ban. I think the european ban was once extra of a precautionary, as they name it within the eu, if you’re no longer sure ban it variety of procedure. And that i feel something after that effectively mirrored what was once in the European, or roughly mirrored what was once in the European ban. And the, as a part of this, they mentioned oh well we’ll have a chap. And the chap is to, used to be kind of a multiply motive to appear at the fee possible choices and also to do the exact hazard on the three intervening time ban ones.Or weigh in on the three intervening time ban ones, and to do the danger assessment. I mean I, i do not believe any individual would argue with the three permanently banned ones. Good, there isn’t a danger assessment partly, due to the fact they weren’t rather being used. I consider that in he ecu ban they stated we did the, put the three permanently ban, now not a lot considering that they were being used, however since we didn’t want them to become substitutes. It was once a pre emptive act. You realize the other three, the meantime unhealthy one it’s, you already know we’re now not, it’s now not so clear you already know.The INP is, may match in the syndrome category. But it’s weaker. The opposite two, I ‘m no longer so certain i don’t consider there is any robust proof that they cause the syndrome so you know those, they’re in variety of an in between class. So for us they ended up as a, as an meantime ban. And they speak about this a bit of bit in the European record which is on your CD, but i’ll make certain you’ll find it if you want to read what’s there.But that is that. I imply the, i suppose the reply to all of the, one of the crucial questions you recognize why are you doing this this way. Why is Congress doing it this way. I mean the chap is to answer some of these questions. >>sure thank you very much for these explanations. But I consider it could be slightly unfair to summarize the precautionary essential as utilized in the european by using if you’re not sure ban it’s more like that. >> If we did it, if we did this fashion, we might have chemical compounds. >> we are going to train the jury to ignore that remark.But having said that, if we are able to find that being, if we find that the standards used are let’s assume a bit imprecise then i would believe it would be one in all our key tasks to reflect just a little on these standards that we undoubtedly obvious. And a good way to could be the three that are banned already and to reflect, consider standards and arguments which we suppose would aid and justify that with the aim of applying it to the others. And then see the place we turn out to be. Is that a practicable way forward? I think we will have got to be transparent and clear. >> sure. >> With standards. >> Is, Bern you had a comment. >> Bernard Schwetz: sure my, my assumption that once a selection is made beneath the precautionary fundamental there is an expectation that once data are on hand it is going to be analyzed. And it isn’t a topic of 2d guessing how somebody else made a determination. That decision wasn’t on knowledge. It’s based on a composite of matters that had been proper at the time, considered one of which used to be there wasn’t adequate data to rather make a firm decision, or when to make one anyhow.So we’re now not, we’re now not at risk of second guessing anyone, for the reason that now we’ve data. And that’s how the method must work. But would the question of you with the options are, we have handiest pointed out banning or now not banning, isn’t it viable that anything could be limited in an, without banning it. And it would still accordingly be useful in merchandise but we have now confined the extent in it in order that what migrates out into kid’s mouths or skins someplace or within the food plan, is restrained all the way down to a stage the place it represents an acceptable hazard. Possibly that level would must be at a concentration where the product no longer is flexible and for this reason the further plasticizer is a moot factor considering that it would not work at that level.However it style of maintains us out of the mentality of claiming that it either has to be banned or no longer. >> In, that is a just right point. And i used the term, ban hazard is substance. I believe that it literally means whatever that doesn’t comply with our regulations. So it’s an unfortunate to have the word ban in there, nevertheless it particularly manner good the other, the six are confined to .1 percent. So in effect it can be particularly a efficiency normal you would say. Or some thing like that. It can be a regulation, not a lot as a ban. We do not, we are able to avoid utilising that phrase and say regulator restrict. >> It already does what you, what you simply stated. It regulates it to a specific stage. >> proper. And we, we don’t, you realize I suppose it is ok to think outside the field just a little bit. It does not always have to be a thumbs up, thumbs down.It is a, it could be some, none of the above it that’s what you wish to have to say. >> Managing it, I imply the step that wasn’t delivered here is danger management. And if the dangers may also be managed with the aid of reducing the extent to an extent the place the publicity is just not high sufficient toxicity, then it is successfully managed. We’ve not talked about for what a part of the population is it for everybody, or just a subset. Or if we’re just, these were incentive. These are other issues that we need to maintain as we talk about, are we relaxed or now not with the unique degree of exposure. Nevertheless it make, via managing it to a unique level makes it extra of a quantitative process.And no longer just an all or none system. I guess absolutely that suggestion method is, could be a criteria and to aid this decision making. That is a technique. But there are others. But that is obviously a technique. >> I suppose, all i am pronouncing is we need to be clear about, about this. And also let me add i do not think that is solvable in a Wednesday afternoon. It requires careful situation and probably that is one of the crucial portions of homework we will have to agree on for next time. >> That was once my query is how do we proceed so that we meet again in December of January. We’ve something that we will talk about and then make the next move forward.It, in quantitative risk assessment is a option to remedy, to make these decisions and it is not the only approach. However you are aware of it’s no longer a bad manner both. >> it can be variety of in a apart. Wouldn’t there be president for other chemical compounds or metals. In terms of you already know led and merchandise or or you recognize. You know are just one out of a universe. And there’s been other uses, and there’s been other percent of, you realize, a steel or chemical allowed in terms of. >> well in, led for instance the best way our regulations as a minimum earlier than this PSAA, the reason used to be leds naturally occurring for one factor. It tends to be, however it’s a containment. And so we would count on a distinct background low exposure. And take that into account in the danger calculations. And that’s how they might arrive at, you recognize, going that calculating a stage of publicity that is allowed.For other things like we would recollect well are these matters that can be regulated by means of other groups, you recognize. If it is deliberately delivered to medicines or whatever, you understand we might say, or well you recognize this isn’t a traditional danger comparison approach we’re talking about. However customarily we would say well if it may be, if lots of the publicity is from something underneath FDA or eu jurisdiction, we will say good let them maintain it.However on this case the place you understand, you have got various stuff that is in food and within the environment and it can be now not clear whether it is something that is, can be addressed. We, it can be coming from so many sources in, and you already know some of them are certainly in an individual’s jurisdiction, however others like the way it gets into meals probably no longer. You already know, possibly that is just on the grounds that it finally ends up with the environment.I am form of considering out loud right here. But. >> but lead is similar to that. You recognize if you go back and even now it can be purposely added to products. And it’s in the environmental from gasoline. It is probably in our food supplies, our dos, and decisions. I was once just questioning if there’s, as a substitute than looking to, yeah reinvent the.>> well lead we might anticipate that there’s a precise background stage that’s consistently going to be there in that it can not be regulated via EPA taking it out of gas. You now there may be some background stage left that we need to take delivery of. So we sort of subtract that our of what we are saying that you may be uncovered to. For i guess we would simply appear at whole, I mean if there have been a way. For the reason that this got here up with the DINP. If there have been a strategy to do it, i would have said gee yeah this much whole publicity, you understand, how much type of room does that leave? In other words, good if DINP is adding to that threat, we might have explicitly taken that into account in as a minimum my chance comparison i might have completed it that approach.I would have stated you know there is this a lot danger from the DINP which is not unhealthy, however should you add within the historical past and it puts you over the extent of crisis, you then understand it is a situation. In order that, you already know perhaps that is one approach we are able to take is you understand you’ve gotten complete exposure depending on what the hazard from that is, seeing that i’m now not certain what it is, if it’s you recognize over or beneath that sort of stage of main issue, whatever you need to call it.But if that’s really that top, you know adding to that I believe does make a change, even small quantities. However I, you understand that’s one, it’s one is whatever complete exposure is, after which say do these toys, you know put you over a distinct stage. >> good am I flawed Andreas, that what you have been pronouncing that you do not want to move that manner. You do not need to say there may be some degree that if we go above that we’ve got a challenge. You need to say there are qualitative if it shifts. >> Andreas Kortenkamp: No, no, no, i don’t, I are not able to, i do not agree prescriptive at this stage. But I feel we have to enter a system whereby we map out choices. >> Yeah. >> What, what you may have just said is certainly one. However there are others. We ought to map them out, be clear about it after which appear at it and make a decision. And work from there and then answer the question what if we own a specific choice, or a modus operandi then the subsequent query is what data will we rather need.>> Yeah, yeah. I didn’t you should be descriptive. It’s just, how can we outline the choices and, and move forward? >> Andreas Kortenkamp: One alternative certainly is the one left by means of Bernard, where you bear in mind exposures. This is the, the, that might lead us into full blown hazard characterization, risk assessment product. After which ask the question, can the exposures on account of toys can this be managed in toys, if that’s now not viable for technical motives. For illustration, that is one feasible line of argumentation. Then there is a just right case for a ban. That is one, a method of doing it. However I believe there are other choices as good. And these ought to be mapped out. One other option is one I mentioned. I have never made up my intellect in any respect. It would be, go the way of hazard characterization. >> In, in, by means of hazard you mean not going, you mean going as far as a dose response? >> yes, dose response, yes. >> And, in a single, and, however to what finish? If we’re not doing publicity? >> Andreas Kortenkamp: For example, that’s a excellent query.Can we rather need a quantitative hazard assessment? Or and questions along the strains of how seemingly is it that this and that chemical induces a , etc., etc. You understand, and i am no longer most likely clear about this at this stage. However we have got to think of questions of that nature. >> Would, would clarification come by using, again, making use of something process you want to the three that are banned, and/or the three that are period in-between banned, and allow us to as a committee see what the extraordinary choices inform us. And or do not. >> Yeah, that absolutely. Yes I believe the way of doing it will be to peer what the Europeans have finished. The notion process there. No longer that we would want to mannequin ourselves on Europeans wholly. We’re in the usa right here.However simply keep an eye fixed. >> well I feel what, what they did, the scientists, the programs did danger assessments of man or woman . Although they were conscious of the possibility of accumulative dangers. And you know after which by some means the, the legislature, the voted you know, as we did within the U.S., it was a legislation that did the ban. So there wasn’t necessarily an immediate link between the science and the, and the, and the regulation. Correctly we had some file, after the dirt settled, we had some follow up conversations with the scientists there.And our, we you realize, any person mentioned well how come they banned it and you failed to. And at that degree, threat assert, or danger assessor we had been generally in contract on, on things. But the selection to ban it used to be headquartered on precaution. >> And might be it will be productive for us to recollect that this method may also be carried out utterly with out fully, or say unbiased of this classic chance evaluation, where we’re all used to. I imply any person stated it. It might be situated on their resolution to say we don’t want substitution to head in to, to go in desire of a certain . If we do not ban it this may increasingly occur. We don’t want that accordingly we ban it. Simplified argumentation. But in no, if, should you consider this idea system you’re going to realize that, well you’ll ought to ask the question, another question why do you not wish to go substitution to go that means. So what health hazards are you involved about. After which you have a wellness hazard comparison step recreation. This does not always have to be quantitative. >> That makes, makes various feel.>> Yeah. Hypothetically to be able to be one alternative to go. >> Or. Sure. >> I, I imply you need to, it’s quantitative within the feel you do not want to head to something that’s extra poisonous, but you also must consider of the publicity advantage. I consider for a majority of these, the, the specific exposure migration sees to be about the equal. However in case it can be not, you could possibly have got to bear in mind that as well but it would be kind of a semi-quantitative technique. >>Yeah. >> Holger. >> Holger Koch: too much hypothetic discussion right now. Considering I suppose we’re nonetheless in the stage of information collection. And i think no matter, irrespective of which method the discussion may lead us in, we have to face the truth that we have to type out the elemental information. As you said, we need discussion concerning the finish aspects. We need to cut back all of the rates in terms of the top facets, plus the substitution merchandise.We have to collect the information. We have to have a look what toxicity data for the Is there in regard to the end point more sensitive. We need to assess if this knowledge is gift for the substitution merchandise. And we’d like this information for the substitution products too. So I feel it can be a perfect discussion right now. But that is going to be a discussion for the next assembly in time. >> yes that is true, however it is rather principal one for the reason that good in the silver guide that will fall underneath drawback definition, contacts definition. It is extremely foremost to do that given that we may find, on account that something resolution we now take at that stage will then drive what information we need.However let me come to the text, the cost. I think the legislator had whatever in intellect once they, and right here I believe Holger when I listed unique matters we also must compare. For illustration, the like stages in children and so forth., and so forth., possibly the legislature had in intellect that deliberation follow a specific structure. So there are certainly knowledge we have got to appear at and analyze due to the fact that it is listed right here. And definitely this may support in this suggestion system to decide in desire or in opposition to the ban of targeted chemical compounds. >> Holger I accept as true with you at one stage, however at one other stage i am a bit of bit unclear. In the event you just take the drawback of which might be we talking about, or which choices we haven’t even come practically speakme about that. How are we going to decide. The universe of and alternatives, the ones that we’re going to be involved with, is it going to be all of those.And whether it is, I mean then you are announcing to me that we must have a matrix. Now on this facet the entire and all the alternatives after which over here in one of a kind columns publicity data, in special children, within the fetus and pregnant ladies, is that what you are suggesting that we’d like, and if that is the case and we agree on that, how are we going to get that put collectively, that matrix. >> Holger Koch: I think data is underneath six right here. And as I stated we want knowledge about exposure and exposure. And that i imply as Mike said, each founded on bio monitoring information, but also on usage knowledge migration experiments, and many others. And as Andreas brought up, we have got to be as soon as we deal with one it is probably that different or substitution products come into the market with the identical amount of creation volume. So we’d like know-how on these viable doubtless substitution products.I consider it is considering of these products, considering that did it too. We discussed DEHP and there are almost certainly different substitution products, however we have got to maintain these merchandise in mind right now. >> you utilize the word doubtless. And when you seem on the, one of the crucial EPA records that we receive there is a entire record there of choices that both are getting used or possible to be used. Are we going to head by means of that list one at a time and say this is the one we’ll be speakme about, and this one we’re now not fascinated with. And if that is so then what standards are we going to use. So this leads to, , this is not a simple topic. >> No nevertheless it, the selection on acceptability of an substitute is a choice of the longer term. We are not able to decide whether or to not make some recommendation on a based on what we feel the replacement that we feel the enterprise would go to, or we are going to not ever make a decision on the . A determination of whether or not or now not an alternative is acceptable is within the arms of the regulators.We can not particularly make a judgment in order to avoid the probability that some enterprise will make, will process EPA or CPSC or FDA. Their alternative. And the agency says definitely not. We don’t need to have the chemical like that instead to the one who we’re watching at from the standpoint of managing. So I suppose it is major for us to grasp that there are choices, but i do not feel we are able to make a decision on a headquartered on what we worry maybe an alternative unless it occurs. However number 2B7 stated explicitly we will have to keep in mind the alternatives. >> well it says, we have now some substitute, good remember feasible equivalent wellness defect right here. I mean a few of there are already getting used. So you know the hypothetically you recognize there are some things that would be used, I believe we must take our high-quality shot and with those that we all know are being used in, if it can be, if there may be anything that looks like it will be used.We will add it however it’s we can not hope to have the whole lot quilt each alternative. >> it is again to, if we need this matrix that Holger is arguing for then we’ve got received to make some selections. And special and possible choices. And i might expect we ought to have a cause for why we select one and now not an additional. >> I believe Paul and Earl the day gone by point approach. Given that we’re specializing in the syndrome. So watching structure smart at the chemical substances, which probably the products, we could have to you realize if these are similar merchandise. Or basement products would have identical results. >> i do not feel now we have made that choice but. >> No we did not make any of it. >> Of course syndrome of end point, i don’t think we’ve got made that choice. >> I mean wouldn’t it support to write down a few of these matters down. Like write a list of matters, decisions you must make. Probably write down some possible procedures, qualitative and quantitative approach. >> that is what just taking note of this I was going to suggest. Since it seems like we’re talking about two or three one-of-a-kind things, type of while.And that i feel at least in terms of processes, fascinated with the one-of-a-kind techniques which can be available. After which what’s needed for the special tactics. What we’ve to be had. And then we are able to make a way more advised decision. You know we have these, you realize anything, three or four viable techniques. What’s wanted, what’s on hand and the how do we go forward. After which of course opting for one of the systems.Seeing that there’s a, just paying attention to different, you understand the discussions no longer fully meshing in terms of. >> What I consider we’re additionally speakme on one of a kind phases. I, you already know, I feel this is the perfect stage. What’s the bottom line once we’re all done. The way to do it’s, is a further degree. And then one of the most nitty gritty details is but one more. >> And the point i attempt to make is how are we going to get there. How can we transfer forward? Are we going to do it here? Are we going to try to hash out what you just said that we must do. Or are we going to add ask the to try this supply it again to us and we advised and comment and made alterations. >> No I believe we have, that is a challenge we should not delegate. >> I consider we ought to try this ourselves. However we can not do it within the, in the remainder of these days. So nor should we rush. My recommendation would be we might all independently feel about this and each and every of us might be put together what can we name it form of a submission or discussion paper for subsequent time.This would be circulated well prematurely and refined and that’s then for subsequent time to discussion subject. >> and that i was going to suggest that we every jot down what we’re on paper a go with the flow chart or bullets or some thing. After which get it, do it well before the subsequent assembly so that the subsequent meeting we are able to see what we agree on. >> I was going to without a doubt propose that as good. However you recognize potentially since our next meeting’s not except December, on the earliest. You understand possibly a convention call the place we are able to spend just a few hours in October, November speakme about one of the crucial tactics. Since I consider if we do come collectively and December or January we it will be fine to have a resolution in terms of procedures and desires earlier than then. And agree upon at the moment. >> Like in terms that these are from sampling, that these are a public meetings. Can we have now a convention name. >> Yeah we have had conference calls up to now and this can be a form of a nuts and bolts style of factor and it can be only a fairly, simply to organize us for the, for the real assembly.>> okay so I believe that may be ok. >> So then the plan would be it can be relatively as committee members to provide you with a report that would flow into among the different committee individuals. After which we can have a convention call the place we can speak about what each of us has proposed. After which with a bit of luck come to a consensus with the intention to pressure the assembly in December. >> are you able to be extra special of what we will have to have in that file so that we do not emerge as with apples and oranges, and nuts and bolts. >> Yeah I was once sincerely considering sort of the identical factor. On the grounds that there are, you already know, one of a kind portions and each of us have distinctive advantage.So might be you understand I don’t know Mike or a method of framing the predominant elements after which each and every proceed to stipulate it or fill it in since for distinct aspects i know I will not have the advantage. And for other aspects i will. But it will aid, you already know, frame precisely what is needed in this report and go on to one of the vital question. >> it would be worthwhile if we had a way of what exceptional individuals are going to handle.I imply established to your potential. Despite the fact that you would not be limited to that. It could make sure we cover all of these matters. I am not definite if we, would we start with the framework, or i guess, or get the submission. Some submissions first. I feel we, i suppose it might make feel to have some style of a framework. >> you know very normal in terms of the questions. >> Yeah. >> To answer the strategies which can be on hand. The information needs. Choices.I imply you recognize more of a, you already know, very basic outline that we are able to. >> Yeah ok. >> Take portions to fill in. >> k. Could it, Mike might or not it’s established on the various elements of our cost? >> Mike: I think that’s a part of it. And then substances that maintain each and every of these. Now what do we ought to do with this. >> Yeah. >> also comes again to the place we were the day before today with . What age staff. What . And yet these are all motives that we’d have got to bear in mind in order that we begin to segregate that small number of which are of perfect priority versus these which might be out on the margins. Those which are the perfect toxicity versus those that are out on the margins. And people are the matters that will allow me to be in a position to claim good the 4 that I relatively feel we have got to focal point on and these two finish elements, that that’s the place the meat of this is.And the opposite matters we can have much less sure bet. It can be toxic, they’re less exposure, anything the reasons might be. So i might hope that as a group we will start to slender down those kinds of, as good to get us involved in where to spend our power. >> And it will additionally help if we would get faster than later Paul’s and Earl’s slides from the previous day. Copies of those. I do not think we acquired these but. >> yes. >> I suppose in answer to Bernard’s factor, I suppose there can be no dialogue that the six in the laws are those that that is the minimum. And i might say in terms of substitution or proposed substitution products it’s DHPH, on the very least worry.Very likely extra. But so we’re eight already. Minimum. >> good there’s a handful which might be clearly in use. DPHP we now have, i don’t feel now we have noticeable but. However it’s a capabilities. >> Mike is that whatever that, that your office could put together for us? In an awfully. >> Mike: A framework? >> well that and, and also in phrases of Bern’s factor of opting for the if these would be simply the, enumerated and you recognize why we wouldn’t do not forget some of the choices that they are no longer in creation or they may be, no knowledge. >> Yeah. And we’re variety of engaged on that in specific, and i am definitely going to check out to get in contact with some of the industry individuals to, to get extra expertise on that record. About the chemical substances on that record. You recognize which ones are really used and so forth. I don’t consider we have got to go too some distance down that list. I consider, you understand, with this six. You understand there may be a couple of areas just like the not on there. There is every person has just a few, or that they might add to that list and we might definitely do that.>> i spotted the EPA record had eight . >> correct, proper. >> And a part of that, I mean the pental is there not considering it’s used, but in view that of it is activity in that assay so it can be practically like a mannequin compound. You understand some of those like the as much as, and hexel I, anyone advised me that in hexel no one fairly makes use of anymore. But it surely’s given that it’s lively in that assay it’s something we might consider as a minimum one phase, the hazard identity part or whatever like that. And i could also you realize conceive of you realize considering we now have so many chemical compounds. Whatever the final method is, all the chemical compounds don’t necessarily must make all of it via. >> Envision the file that we put collectively would have whatever as simple as a table of the entire and alternatives after which a short dialogue of why we selected some and no longer others to rather, and if anybody used or concept about utilizing a substitute that you recognize wasn’t excessive on our record, it wouldn’t be that hard for either them or us.We’d have the framework to move by means of. Yes. >> One more thing that we have not mentioned and that is the function of judgment on this procedure of us being capable to make suggestions. I don’t suppose any of the systems that we now have talked about leads you down a line within the evaluation that claims yes or no. It’s a topic of our judgment on whilst you get down where you’ve acquired all of the matters on a page that are essential to make a decision.The choice is not there. The decision comes from us. And it’s a matter of judgment of whether or not the differential between exposure and toxicity is enough that i would be given this as a suitable threat. And what you would take delivery of maybe different from what i would take delivery of. But nevertheless this, there is no recipe for taking this definitively to a yes or no reply. And i consider we have got to be ready to have a discussion when we arrive at our interpretation of what is to be had to make a choice, then there may be yet another step forward of us to make a judgment to what it way. And does it translate into a recommendation to restrict or not.We’ve not mentioned that. But that is another venture that’s now not convenient. >> I mean alongside the identical occasions, I mean uncertainty is some thing we have to believe of, I imply whatever, every step of the way in which we would as well do it as we go alongside is these are what the uncertainties are, since. >> Yeah. We ought to be ready to document well what that judgment is. >> Yeah. >> considering what the approach in which the judgment is mainly extra important than the determination.Is that indicates the force of what your conviction. And if we end up looking at person , but admire that it can be part of a loved ones of in the market and exposure. That turns into a part of the judgment if we shouldn’t have a quantitative means of adjusting a stage of anything to consider that it is accumulative outcomes. We at the least need to have that as some of the judgments that we have now offered an extra component that we have now introduced an extra factor based on the exposure to multiple . And that’s maybe why we are as conservative as we’re on this judgment seeing that of that nature of the exposure. >> I need to have a damage. I think others may just as good. So let’s reconvene 15/20 minutes. >> okay. >> okay let’s reconvene. Is there anymore discussion in regards to the challenge that we were talking about earlier than we broke for lunch.Or will we bear in mind that completed? Mike is going to position collectively a framework, and then personally we’re going to build on that. And share our contributions by using, before our convention call. K. Listening to no extra discussion on that, i might like to move on in the temporary time that we have now, two members must go away quickly after lunch. So I thought we’d take what time we’ve got to be had to talk about a couple of different disorders. And one of the vital issues that I, we must speak about is what are the top features that we are going to use in our assessments, some thing they could also be. Is it going to be the syndrome. Are we going to be more inclusive on that? I might prefer to open up that discussion at this factor.Any feedback? >> Chris Gennings: do we agree that almost all of the data, at the least from the animal reports goes to be syndrome? Might be human knowledge we have extra type of end elements. >> It seems like the syndrome would be the default for the reason that it is the person who seems to appear at the lowest stage. The person who has the . It does not have consistency across species. However there are so many studies now which have explored this in rats that it has that inner consistency that has been repeated.So I suppose with those, and there are ingredients of the syndrome that resemble the challenge in people. And in phrases of finish features. So I think it could be rough to provide you with different end features which have traits, a sample like that that may force us to an extra one. >> Chris Gennings: but maybe we might, if we feel about the syndrome as might be the position the place you set initial focus, after which come back and ask, if we had chosen, is there any proof that different finish points might were affected at scale down levels than what we could find syndrome? >> Yeah i’d agree information and the syndrome is where most of the knowledge is and most touchy. In people of direction you already know there may be other end facets, neuro development, progress, physique composition. However there’s, there’s not a lot comparison data within the animals. So and then on the opposite facet there may be no longer numerous human knowledge on the of the .However from paper. There is not a variety of, or nothing. >> So then do I have an understanding of from that that going down to our 2nd question that we’re going to focus, not hinder, but focus our awareness on prenatal exposures. >> It raises a question and Paul talked about somewhat bit. And it’s prenatal in the rat, but what’s the time of exposure within the human that it corresponds to that prenatal interval within the rat. >> I feel Paul had acknowledged notably give a definitive reply but I consider he stated from about eight weeks to fifteen weeks or so. So we feel probably as early as six weeks. >> however I suppose we must have that footmark in there at that time isn’t the identical in rats as it’s in people. But what we’re specializing in is when the time of exposure in the course of that period is what we are fairly worried about.>> correct. So that, Holger. >> Holger Koch: Plus there probably more than one testosterone modulated home windows of sustainability in the human. Even after beginning. >> that’s, that’s the question i want us to speak about. So do, we’re particularly constructive to examine the, the gestational date 16 to 17 within the pink with the top of the first trimester of humans, but we’ve different windows of sustainability. Probably in the human. Delivery. >> there are various puberty at three to six months, after which of path development. But at the least from the rat knowledge they advocate that the fetal window is more touchy, although they see effects for the duration of pubertal exposure.So maybe related in people. >> there’s latest new experimental evidence from Richard lab to exhibit that continuation of effects within the neonatal period will make certain that the results persist. That is fairly predominant as good I think. >> Bern. >> Bernard Schwetz: These are dated in rodents, in rats. >> k so we’re, we’re, we’ll expand the period of time of our consideration to the neonatal interval as good? >> invariably if the human puberty is it regulated by testosterone? >> sure in boys, yeah. >> So. >> And the opposite, whilst you think about life phases, the other part of it’s, the exposures obviously the neonatal exposure pathways are going to be unique than the, the, you recognize, babies and tots and so forth. >> good am I hearing then that we’re going to go all of the method by means of the period of, of exposure for our consideration, okay.The place does that take us in phrases of time frame? Human progress? From eight weeks prenatal to. >> For puberty? When is it entire within the male? >> Yeah. >> The, in general would say good obviously by 17, 18, but frequently sixteen, 17. I imply it varies of direction. >> Yeah, by concerning the time that you call, be known as into the military within the U.S., but still allowed to have a drink of beer. >> Earl. Earl suggested that the mind would not mature except so much later. But that is an extra drawback, I consider I will have to communicate for himself. >> ok. I was once simply watching at our list of important disorders, I think we have now, we have now mentioned. The 0.33 one which is important. Now we have, now we have mentioned that, have not come to a conclusion yet, we’re going to investigate that. After which the problem about constructing on the.>> Philip? >> Philip: yes. I think we should follow factor, with point three. Since. >> ok. >> If we take the long winding avenue by means of cumulative hazard comparison. We want fashioned end features. So I suppose we will have to talk about on which of the or substitution merchandise we center of attention. And if we have now the needed understanding on the respective finish points. >> I suggestion Mike was once going to get that collectively for us. Did I miss that? >> Mike: good i am, i’m obviously going to check out to get extra understanding in regards to the, the makes use of and potential exposures of that lengthy record of . >> I suppose we should preserve it pragmatic right here. We are able to intricate the list. >> Yeah. >> however I consider for a just right beginning point we will have to just throw these related substitution tactics within the realm and in a few minutes talk about if now we have the central finish features and information on these end elements present. >> k. That is, why don’t you . >> Yeah. So I suppose for lots of the in query we have now the central data.But when my recollection is correct for some of the substitution merchandise we should not have the valuable data. So i’d say that the relevant end factor is the syndrome with probably the most touchy parameter being the specified testosterone level. And the HED for instance. So my question now could be, do we have this data for instance for the EPHP? Do we’ve it for ? >> good now we have, for, in Earl’s talk yesterday for the, his essay on testosterone creation he had one test on dinch which was once negative. Sort of a screening. DPHP was on his lit however has no longer been executed but. As well as DIDP which is of course one of the period in-between band ones. He hasn’t gotten to that both. And i feel that might be very priceless expertise. So far as he range of substitutes, you recognize we have amongst other matters, we have the Versa file which lists capabilities substitutes and we also have our possess record where we measured what used to be simply within the toys about a yr ago.And you recognize there have been 5 or anything, there have been five or so very common ones. Ordinarily ditch in, you already know, the normal, those you possibly can expect and so one. DEHT was original. Of these i do know DEHT i’m beautiful certain was bad in, all fosters experiments from the last century. So probably the most others you realize perhaps they will have to be, maybe you realize, might be we could, we are able to propose to Earl and Paul that they look at one of the most other citrates given that i’m not so certain if we now have the, those data. >> yesterday after we discussed this, Earl cited, gray brought up that skinny sheet proven. But it surely was once a screening test with I feel three were dosed.And he, he admitted that had he, he stated he are not able to exclude to have as a rule visible in influence had he achieved an escalation learn. So it is entertaining to hear from him that there was no outcomes. But he himself was once not undoubtedly sure targeted that with the dose escalation, such an outcome would no longer show up. From the amazing summary which we’ve in front of us, from BASF regarding Hex dinge, I think what we can glen right here is that within the learn according to scan directions, which they carried out. They used a a long way high powered experiment. 25 dims or something. But I can’t become aware of from that potent abstract whether or not or no longer there are the critical information to us, valuable information gathered, whether or not reduction in testosterone, whether or not it was once measured, I count on it wasn’t.So I conclude that involving dinch the significant data are usually not on hand relatively to us. Both to us or now not available at all. >> Yeah I imply the specific studies should not to be had right now and that’s, that’s an obstacle, that’s an foremost predicament. >> What other either or possible choices do you wish to talk about? >> The EHP Robert. >> What can we know about that? >> good I, I instructed to Earl and Paul that they scan DPHP due to the fact it’s three you already know the branching, now not just like DEHP.So I obviously wanted that confirmed. And although it can be, it is no longer, i do not feel it is being used in toys yet, and BASF says they would not always recommend it for that use, but nonetheless, it’s such an obvious, to me it’s an obvious talents substitute. Anyone’s ordinarily going to use it. So that was once excessive on my list to nominate for them. However once more, that is within the equal class. There are information that we should not have access to the original experiences.>> So enterprise gain knowledge of we wouldn’t have. >> correct. >> Chris Gennings: I suppose Andreas’ point is that after we have such information, instead of simply having a screening model, if we might have more amazing studies. >> proper, correct. >> With 25 dams in a group, or anything, I mean some thing the standard is. >> right and that is of direction, we are not able to do it. Or tell them to do it. We could ask them to do it. We could dominate it to NTP or you know, we are able to try to get it completed.That, I feel that comes below the quantity five. Are there any primary studies, we will obviously ask for them. >> is it cheap, with the dearth of data, to make conservative assumptions concerning the knowledge risk for such chemical compounds the place we wouldn’t have data, and anticipate that. >> i’m no longer certain we can, i am no longer definite we are able to. >> Or. >> Yeah. >> i suppose that is a question of judgment.Precautionary principle. I imply it is probably the most competencies steps is to, we do have experiences of these than to only swiftly go by means of and say what do they have got and is that going to be enough or, or now not. >> however lack of information does not imply safety. >> No. No. I suppose you have, we need to be careful. >> Oh most likely. I mean it, we will say you already know maybe we can assessment it, that doesn’t make it secure. Or you know prove that there isn’t any hazard or no danger. And we have got to be clear about that. >> however Mike you don’t, the CPSC does now not have the regulatory authority to ask for distinctive varieties of information on any new product coming in. >> Mike: well we cannot that’s most likely, we don’t the authority to, good we cannot are to nominate it to NT, good ask the enterprise, nominate to NTP, or work via the EPA’s interagency trying out committee and spot if they are able to get the organizations to do it. I mean those are our options. We cannot demand that anybody do it.And we can’t, we shouldn’t have the, the labs anymore to, to do it ourselves. >> any other alternatives you want to talk about? >> aside from the alternatives we, additionally the animal knowledge just isn’t indicative we would have to evaluation additionally considering that of the, of the, well suggestive. >> We’re most likely for the the . Oh you mean what are the top features? >> No what’s it used for. What is it used for. Why are you saying for humans? >> Oh in view that there’s human knowledge showing associations between mono Ethel and, it can be utilized in individual care products. But yeah. >> So that would be a we need to add to our record. Our record. Now not an substitute. >> Yeah so DEP. >> So we’re DEHP, BBP and DBP are the ones which are quote banned. We’ll seem at these. DINP, DI, DP, DNOP, the meantime we are going to seem at. DEP. INBP ISO. >> . >>Any others? >> For the and the octal there is now not quite a lot of animal information i do not consider . >> but for the topic of completeness, the, the, we should incorporate this one too. And likewise the . >> The linears. >> Yeah. >> I want we had Earl’s slide. I recall the slide that he had the record of all of the chemical compounds that he checked out.I do not bear in mind what was on that and what was which can we think that the entire chemical substances we have listed at on that web page, whether or not or not they have been evaluated? Most of the time, good yeah for the . >> a number of the excessive, a variety of them. >> And, and have we requested him if we will have the data? >> now not yet. But will. And i consider the underlying knowledge on these slides, I believe are published.It’s simply that I was having trouble tracking all of it down and recreating so we’ll, we will get what we will from him. >> good the new stuff, they are doing this, are doing the testosterone and that is no longer, that’s not published i do not consider. >> however will we as a minimum have the slides. We will ensure something they do submit, we will ensure we get it. We’re on their record of to get copies of it when it is published, or get an alert. >> any other nominations to our universe of. Good I just desired to make clear the DEP, it is virtually a solvent. It’s not going to be in, within the toys. Probably not going to be in the, what we name childcare products. Although until, even though the cosmetic childcare products. It could be in. However it’s a different publicity supply. >> Yeah. >> however possibly a excessive publicity. >> well in. >> it is a excessive publicity. >> It falls beneath Roman III which we examine probably publicity of youngsters, pregnant females, pregnant women are almost certainly to specific it to be uncovered.>> Oh sure, most likely, yeah. >> No extra feedback? Nominations? Well number C, yeah. >> factor quantity 4, I do not know whether we ought to talk about that any extra. I think we agree that we’re no longer going to, wow new floor within the, ignore what’s been summarized very well in the NRC files. >> however is there any, any remark? Then number five, we, we have now touched on. I’m not sure we have, now we have, expressed definitively that we would like some thing achieved. But are there, are there crucial gaps almost that, that some learn, given the lifetime of this committee would be finished that might aid us in our achieving our charge. Bern. >> Bernard Schwetz: however i’m definite there are significant gaps. I feel what used to be on my intellect when we talked about this earlier was once the probability that there are some gaps that if we proceeded without understanding, we might regret it. As opposed to just quality to have additional knowledge. And it doesn’t seem like we now have identified gaps that if we do not fill them earlier than we proceed, we will be remiss. So it’s not clear that there are experiences that may maintain us from proceeding.The, that might need to be executed. If he nominates for stories to the NTP it will be a few years before you see the results. If we ask enterprise, it will take time. Should you nominate to the NDP, it prompts three to do their possess stories. And you, I have no idea for those who remember what different choices you have for filling data gaps. Well we can go to Earl or to others. >> Yeah that probably the quickest. >> Quickest. Yeah. >> but there is not any one of these that might generate knowledge before even the following assembly to be of that a lot support to us. Again imaginative and prescient stories being carried out before we’re completed. >> It definitely is correct for human experiences as good.>> definite. >> not going for some thing would grow to be available for the time hole. >> good I consider Shawna said she’d have some, some knowledge. No longer a lot on the . But I believe the AGD in relation to other end aspects. So. Yeah. >> good one thing, you realize we tried to just do discover what’s close to done. >> And that, I think we now have discussed six quite considerably this morning. >> i don’t. We are able to, we are able to appear at seven and talk about that. We may not do a cumulative hazard evaluation which makes, if that’s the case that makes this one moot. But I think the thought of, of are we going to include different anti-androgens in our evaluation should be mentioned. >> good again, I feel the distinction is quantitative, cumulative hazard assessment or in phrases of you recognize that you would be able to do not forget whether or not or no longer coexposure to distinctive materials will, for example shift these responses for . And that i believe we can, on the foundation of evidence awarded to us the day before today via Earl gray there are some chemicals where we are able to make such statements, or be it not in a, in a quantifying approach.I feel that is premature. However in my intellect, what’s asked of us, explicitly in the cost, would imply that we’d have to don’t forget such explanations. >> I imply what I did not get from the day before today was a sense of you already know that is person who we’re all uncovered to and also you have to incorporate this. I suppose i have not, or I hold asking people what are the ones which can be you know where there may be plenty of exposure, universal exposure that must be included in this.And i have never gotten it an answer yet. >> well I notion Earl grey stated TCTD. >> ok yeah, yeah, good, that is without doubt universal in. >> EED, para EED. >> Oh too. Which used to be shown to be anti . >> there is additionally a question extra concerning distinct anti pesticides. However I do not know what the drawback is the U.S. However in Europe you could surely say yeah there may be exposure to those as well. But we’d know which chemical compounds to appear at there. >> there is one in but we at least within the do not need through the monitoring information this pesticide. There is no data in the ninth. We know there is exposure to . Or it can be metabolites. In Europe, after consuming targeted types of pink wine. >> The all pesticides truly are, must be checked out. >> whether or not that’s viable in a quantitative way, whether the info are right here for the U.S., is a 2d subject. However often in order to be one factor to be able to roughly be self limiting. However the. >> They probably more like a qualitative undertaking. >> I mean going, going back to number six, I notion from Earl’s slides, that there is hope for having, you recognize, customary finish elements and long-established dose response shapes and so forth.So that would not be so unhealthy. It, I consider it is usually a challenge if you happen to include different pesticides and different non-folly compounds. It perhaps an problem of diethyl but as far as the syndrome goes, good the animal information it looks beautiful excellent. >> it’s going to. >> I think we, we have mentioned eight. >> Yeah. >> That sort of corresponds to the populations. >> precisely. I assume however we might bear in mind what are the sources of exposure. We have talked a lot about that. >> i don’t believe we’re overlooking plenty of any main sources. I mean i will try to see what i will be able to discover concerning the pesticides.But, i do not consider we’re missing an excessive amount of. >> instead of the, from foods, yeah. I imply we’re mindful of the foremost sources. >> Yeah. >> whether or not now we have the information, I imply even though we had information in phases of meals in the U.S., it could nonetheless be a very problematic undertaking to estimate exposures. >> Holger. >> Holger Koch: I feel a point that needs to be made clear can also be what’s the distribution of the exposures we are taken with median exposures.I will have an interest within the 90th percentile of exposures. I will be interested in the 99th percentile or in highest values. It is a question of significance for decoding monitoring the bio monitoring information. But in addition for interpreting the mannequin data from modeling experiments and many others. >> i’m pointing this out because on Monday most of the knowledge awarded through designated precedents had been enthusiastic about medium exposures. And that i think this doesn’t help us at all. >> I imply it’s, and it is, , it is one thing to have percentile exposures to the individual . How do you mix that to the person who is within the ninety fifth percentile for DINP perhaps within the 50th percentile for some thing else. >> I consider that is lovely simple. We now have the data on the . You know what individual has and wishes exposure or is publicity to the C. And the query is do we need to stick to the conservative process and on the exposure of every individual.Or do we type of want to make a precise worst case projection. And adding up the ninety fifth percentiles for each and every price and the would assume that the worst case technique there might be members taking on the entire within the higher percentiles. So in the, I feel within the migration strategy, you do, you utilize this primary case, a case assumption. So in my, in my feeling there is not any argument in opposition to doing this also in the bio information. I think this can be a point we could discuss. >> I feel that that, I imply that will be an awfully conservative approach.There probably are statistical approaches to estimate 99th percentile of the multi-dimensional set of . I do not believe that’s a simple mission. >> i will be able to without doubt seem into that. But I, I, you realize when you consider that it relies on, it is going to depend upon what else is there. You could say you’re o the boundary of some cloud. However in which path? I imply we would try to investigate that somewhat further and notice. If you’re nonetheless on that percentile, you realize what’s the worst case of that percentile in terms of rest or anything. >> it will be helpful should you would suppose about that and comprise that for your contribution. >> Yeah. >> and i mean it is, it is best to be conservative in, and you realize, add the 95th percentiles, primarily as a primary cut.However in case you do this and then you definately say the risk is simply too high, then the question is do you want to refine that. Additionally in, in the event you do, with man or woman information, I imply do you, would you weight the exclusive another way? You would, as a result of potency differences, or, or how would you do that. >> My reconnection is there. I know the differences. >> besides possibly DINP. I mean the others are beautiful shut ample however k. I’m just wondering about that, but i might agree with Holger, you understand in utilising the ninety fifth percentile of a couple of . On the grounds that you realize it’s not unreasonable you know might be in the In Hanes it can be some thing 1500 folks, but which seems like rather a lot nevertheless it’s no longer unreasonable to believe that humans could have more than one exposures to those considering they are from extraordinary sources and one would not preclude the other, so you could probably have an exposure to DEHP, and so on. That are in the higher variety. And then there’s of direction the distinct situations where you will have, whether or not it is for medications, medical gadgets, etc., you could have exposures which are a hundred or 1,000 instances larger. >> some other comments? >> It sounded to me the day gone by like distinction between EPA and FDA is particularly clear and possibly a subject matter of on-going dialogue this time as wanted. But the difference between the regulatory realm for EPA and CPSC isn’t as good outlined. Is that proper? >> well within the sense, I imply EPA has what 5 special pursuits occurring correct now involving . So they are most likely energetic for exact. And there’s significant overlap between our preview and and we’re used to working with them. I mean now not that we do not work with FDA. However most likely mostly work with OPPT greater than than various different corporations. >> guess what I was watching for rather than exercise, was once the question if in case you have buyers who’ve end up alarmed due to the fact of an exposure, and possibly a response and they say what, who regulates this. Who do i go to. Do they turn out to be listening to from EPA? No we do not try this. CPSC does. And CPSC says no we do not, that is the EPA’s. However are there gaps of that sort? >> I feel frequently it can be more lap than a gap. >> however in phrases of publicity, I mean I have no idea that i have a powerful experience that this definitely happens, but if the EPA ended up doing regulatory, making regulatory choices centered on exposure best to pesticides, however then we knew there was once publicity.I mean you realize, the science wishes to be. >> good yeah EPA and F, I mean FDA are almost like five specific marketers. , and of path we quite are a different company. And that makes it difficult to do matters like this. However we are, we’re looking for ways to work collectively. Any person instructed that the publicity in view that it’s the factor to do on the grounds that we’ve, no one began that but. There is a skills with the IRS exercise. And their workshop developing. There may be a skills that we will, if not work together, as a minimum share information and make our jobs respective jobs easier. However I imply it is no longer unprecedented for, to have an interagency recreation. Good we did it a very long time in the past for dioxin where FDA, the one of a kind ingredients of FDA and EPA and CPSC contributed to a multi, then it was a multi-media. Hazard comparison was once determined that they used, and we have collaborated on different movements as well. So it, , it’s a possibility, the trick is to line up our, now not just out, you already know program wishes, but also the timing. >> okay it is nearly the midday smash for lunch. On the grounds that we will lose two of the members of the committee before we reconvene, do, is there another industry that the rest of us want to discuss between the top of lunch and 2:00 p.M. When the rest of us have got to leave. Or will have to we adjourn the assembly at this factor? >> k. Can i, if we make a decision to adjourn, i’m looking to feel, are there any little business matters.The, the books have two CDs, all people will have to have two CDs. One who I prepared that’s very nearly what’s within the e-book. But plus just a few extras that were too huge to put in the publication. The opposite CD is from Exxon cellular. And that has now not only their displays, but there’s a variety of knowledge in there. Correctly there is a database in there that Dr. Clark pointed out the day gone by when she was speaking about publicity. There may be a whole database in there. So I, there’s like various know-how, released papers, unpublished stories. Etc. Anyway there is quite a few, you will have to have two of those, at the least, when you leave. We would, if you are on an airplane we will mail you the, the e-book itself in case you like. But, you would want to take these CDs. I even have some difficult copies of one of the crucial, of Dr.Godwin’s slides from the previous day that you are, can take with you when you like. In case you have them, have them prematurely. Yeah. >> And Mike you can from the presenters that. >> Mike: i’m going to ensure, i will monitor them down and get everything. I can even, i will appear via my notes in, in, as I did final time. Summarize any to do, a list of to do matters. >> will we wish to make a when we can each of us on the committee on the way to have our, whatever it’s we put collectively do. >> Oh yeah. >> To the committee. We’ll meet, presumably in December. >> can we no longer, do we no longer make the date corporation? The dates we agreed on, and assume that it will go forward unless we hear in any other case when.>> good the assembly date, I consider. >> company. >> Is corporation. Yeah. A date for submitting your entire, distributing your entire thoughts on learn how to proceed. >> yes. >> will we wish to try this a month earlier than the meeting. Or. >> Yeah we would like Andreas as cumulative danger evaluation. >> Yeah. >> To us. >> A draft will be k. >> A draft is great. Not more than a hundred pages. >> Yeah and you understand two or three enormous pages digits will suffice. However will we want to get those matters a month before, or a month, two months earlier than and speak about them a month before. >> A 2d month. >> So do the primary week in November? When should we choose a date for a conference call? Which you’re no longer definite we, i might guess we’d need to do it late in the day right here.Or early. >> Early within the morning U.S. Time. >> Oh yeah, yeah, I got it backwards. Which means that it’s quite early. >> really early on the West Coast. >> the hardest, we had one the place we had Europe, Canada, Australia, and that i do not know if we had Japan, however I imply it was, it was once form of tricky. So 5:00 a.M. Portland time is, nine hours change from Germany? I believe? >> Yeah. We’re in the graveyard after lunch then. Yeah. >> 5 my time can be 4:00 you are time in the afternoon.>> but if we say we’re backwards, 4:00 Germany, no 5:00 in Germany is four:00 in Britain, and that is 9:00 here. And 6:00 there? >> is that this okay for you? It is k for you? I do not need to. >> as long as i have my coffee i’m first-class. >> well and the query is would you two rather do it at the end of the day from work, or at night from dwelling? I imply it’s an alternative.>> finish of, finish of day from work can be first-rate. We do not always discontinue at 5:00 on the British universities. >> k. >> So 6:00. >> we are in the pub at that factor. >> Yeah. >> well there’s that too. >> At 2:00. >> So on the way to be, or is it 7:00, that may be 7:00 a.M. On the East Coast? >> 9, 9:00 a.M. East Coast. >> Oh 9:00 a.M. East Coast. >> Six West Coast. >> 4:00 p.M., right.What number of hours between ny and London? >> five. We can do it, we are able to do it at 5:00 or 6:00 p.M. German time. So rather that is k. >> I mean is, is Germany an hour at the back of? >> Yeah an hour forward. >> forward. You’re ahead. You’re ahead of Andreas. >> No Germany’s constantly ahead in terms of time. So Britain is an hour in the back of Germany. So when it’s 5:00 p.M. In Germany, it is 4:00 p.M. In Britain. >> So let’s make it 6:00 p.M. German time. 5:00 p.M. London time. So that might be 10:00. >> noon. >> midday in the big apple. And after breakfast in. >> That works for me. I will be able to quite often get, be to work by using noon. >> So do we pick a day? >> Now the day but, but we were. >> Mike. >> Yeah well if we the, if we get the stuff up by using November 1st, when would you like to, how long do you want, do you want to read it, per week? >> per week to digest. >> Yeah. >> i am doing an NIH evaluate the eighth and ninth of November. So if we could do it after that. >> that is first-rate. >> How about Friday the 12th? >> not excellent for you.Good k, Friday’s not just right interval? >> No . >> I may be in Portland. >> seem me up if you’re. >> ok. >> watching at that week of November 8th. >> ok. >> How is the 18th, the 18th of November, i am teaching that day so i will do this. Holger that just right for you? The 18th of November? Not good. >> 15th or 16th. >> 16th. So it’s okay with you? >> that’s the day I instruct, but that’s k. I can do this. But i do not instruct unless the afternoon, so. >> So we’re speakme about the fifteenth then? >> fifteenth of November, work for everyone? Holger? >> Yeah that’s best. Ok, that’s it. >> On the East Coast? >> I consider it can be 9:00 East Coast, correct. >> November 15th. >> another industry? Mike? >> Mike: I believe that is it.Some of them, a couple, a couple of you ought to see Lisa before you go. >> okay if there’s, so Monday, November 15th. At 6:00 p.M. Germany, or 5:00 p.M. England, or 5:00 p.M. Is, is that ? >> yes. >> GMT. >> okay. The second meeting of the chap is adjourned. .

[windycityparrot]

Does UV Light Really Help Produce Vitamin D3 in Birds?

Have you ever wished you could see the additional ultraviolet light spectrum that birds can? I've been a strong proponent of using light cycles to interrupt the circadian rhythms of our pet birds  I'm also fully convinced that no amount of artificial lighting over birdcage will help a bird produce vitamin D3 regardless of the lumens, quality of the ultraviolet spectrum emitted or the distance from the light source to the cage  editors note: Vitamin D3 is used by your bird's body to help assimilate calcium. Calcium is more important to hens who may go through egg laying cycles. The only way to know if your bird is deficient in calcium is by a blood panel work up through your avian vet. The lack of eggs is no guarantee you have a male as eggs can get stuck any number of ways in a birds reproductive system, especially in over weigh birds. You can have your bird surgically sexed by your vet or spend $18 for a DNA test kit The only way to know if your bird is over weight - is to weigh it - regularly. Regular weight checking is a front line defense against illness detection as rapid weight gains or losses may indicate a health problem not apparent by visual inspection of the bird https://www.youtube.com/watch?v=1eMEtQWDy7A I'm assuming every one of you reading these words has, will be getting or has had a pet bird at some point in their life. You may have interacted with a veterinarian or better yet a board certified avian veterinarian for well bird examinations or God forbid, an emergency  Scientists, ornithologists and researchers know unequivocally that sunlight cycles, moonlight cycles, ambient temperatures all impact every living organism's circadian rhythms - especially birds.  Notably because they can see areas of the light spectrum that few animals and organisms can see.  Controlled by circadian oscillations, circadian rhythm indicate to birds when to molt, when to breed and when to migrate. In humans circadian rhythms make us depressed during the shortened light cycle days of winter. These aren't hunches, these are facts.  How many veterinarians have asked any of you about  lighting and light cycles the suggesting the introduction of timed light cycles to help your bird keep an even keel hormonally?  Whenever I post and/or ask the question about why isn't a particular captive bird keeper whose bird is exhibiting hormonal behavior like prolific egg laying, using light to control this - it’s treated as heresy.  I've had Facebook fans reply that "I shouldn't believe everything you read on the Internet" a couple of injections of Lupron isn't going to hurt a bird. You know Lupron, the drug that’s caused things like teeth enamel delamination, fibromyalgia and broken bones more than 10,000 post pubescent women - 10 years after the treatment?  Yet avian veterinarians have been using Lupron off script for years  I've seen no research studies on either side of that question. I work closely with the folks at HARI who care for close to 500 birds with on-site avian veterinarians testing for efficacy of Hagen bird foods.  They work  closely with the veterinary school in Guelph Ontario Canada.  https://www.youtube.com/watch?v=YGGEkUBpZOA&t=7s Dr. Gregory Harrison the founder and producer of the only organic and non-GMO bird food manufactured today Harrisons bird food, recommends light cycle therapy on the Harrisons bird food website.  I've seen light cycle disruption work myself and for our customers. Why can't I get any avian veterinarians who endorse this? Why can't I get bird keepers in general to understand the birds are unlike all of the creatures. I can see how UV  can produce D3 fir reptiles who have exposed skin and sit motionless on a rock under the UV light for hours. Birds on the other hand tend to be more mobile. Birds need to obtain from the uropygial (preening) gland and as they preen residue from the feathers may come in contact with their skin. An what about Amazons? Amazons have no preening gland - fyi. From Wikipedia: The integumentary system is the organ system that protects the body from various kinds of damage, such as loss of water or abrasion from outside. The system comprises the skin and its appendages (including hair, scales, feathers, hooves, and nails). Vitamin D# deficiencies can result from low calcium levels If you have an egg producing hen but clutches are small and  egg quality is low your bird may be vitamin D3 deficient Bone fractures - Seizures - Overgrown beak - Splayed legs can be a  all be indicators of vitamin D3 deficiency. https://www.youtube.com/watch?v=msIjZZryufs African greys are susceptible to hypocalcaemia which may be the result ofa vitamin D deficiency not low calcium levels. It's best to address any vitamin deficiencies in pet birds with proper nutrition like Prime supplement from Hagen. Donna Replied  Hi Mitch, I am fairly new to reading your blog, so I hope I am not asking questions that are too redundant. I have three birds - a almost 4 year old male Bodini Amazon, a 2 year old male Blue-headed Pionus, and a fiesty little female Parrotlet. I have two questions really. First , I would like to know if what I am currently doing is adequate or not. My birds have their own room where their cages are. The room is furnished with a fountain, a tree, hanging toys, etc. - basically a parrot playground. There is only one overhead light in the room that is just an LED daylight bulb. They spend most of the day out of their cages in their room or in other rooms of the house with me on stands. So, that being said should I be making other lighting arrangements. I ask because you say to put the light above their cages, but I assume that is for birds that spend more time in their cages than mine? There is a bit of screaming on and off. There seems to be more lately for reasons I can't figure out? Idk is it's light related or not? My second question is about food. I wonder if you suggest something different than what I am doing? They eat Zupreem fruit pellets as their primary diet, but they also get fresh vegetables, and Higgins fruit and nut mixes fairly freely. I would love your opinion and suggestions for my flock. Thank you so much for your time! https://www.youtube.com/watch?v=Pg5smWl_SzA Hi Donna  - Thank you for writing Other than keeping the bird room from darkness the overhead bulb in the bird room doesn't bring much to the party. Having lights above the cages is only half the equation. A timer is essential to indicate to your birds when the day begins and ends. You may have a morning routine during the week when you come into the room every morning, turn on the bird room light and uncover the cages. But if you sleep in on the week end, even if the ceiling light was on a timer, the cages are probably covered. Birds don’t know what day it is but they can tell time more accurately than a Rolex. Having a consistent light source is one of the many signals the pineal gland signaling “well being” messages to our birds. We currently have a Senegal and 4 budgies - the budgies have their cage and Peaches has hers. The are in the same “space” but they can’t see each other when caged. The times go on and off at 7:20 am/pm respectively. When daylight savings time arrives - we will not respect it and the time will be 8:20 on/off for consistently. Peaches has bonded with me, she tolerates Catherine. Normally Catherine is up early and will uncover Peaches (and the Breakfast Club) when her light comes on. This morning she left for work early. I got up about 8, uncovered Peaches cage (now 40 minutes late opened the door, sought a step up as I always do - but got bit. I never get bit. I instantly knew it was Peaches communicating to me, her unhappiness at the delayed cage unveiling. I closed the cage door, came back in 10 minutes and she was happy to hop on my shoulder so we could embark on our morning chores. Which takes us to your screaming issue. Days are now once again getting longer which is very confusing to birds. I haven’t found a lot of information on cross (bird) species communication but this is an interesting article assuming the parrotlet is part of the conversation. When birds scream, they are communicating. Your zons might be saying “hey where’s the girls - we have urges” Is the screaming more pronounced in the bird room or when they out and about the house with you? Which now takes us to the food issue (all bird issues are intertwined) Before I get into food recommendations, how is food dispensed to your birds. Dishes filled with an unlimited supply of kibble in their cages and stands? Lack of enrichment can be a contributing factor The screaming could me “WE’RE BORED - WE ATE AND NOW GOT NUTTIN’ TO DO CEPT WATCH YOU” This is one of my favorite videos. Birds with a cages filled with endless food sources next to interactive toys where getting food is a difficult task. https://www.youtube.com/watch?v=DgLd5nUR55Q To the food question. Zupreem adds sugar to its pellets for patibility making it very  popular with birds. I question how that sugar affects birds for the 6  hours it spends in their crop. Sugar has a low ph making it acidic - for 6 hours. I’d recommend either Hagen Tropimix Or Higgins Safflower gold Both blends have seeds fruits nuts and pellets providing more of an enrichment diet. Fresh vegetables, and Higgins fruit and nut could still be part of the diet. Just try to make it fun :-) written by mitch rezman approved by catherine tobsing your zygodactyl footnote https://www.youtube.com/watch?v=DteD7BpZIig   Click to Post