By Thaddeus Schug
April 2011
NIEHS/NTP scientists joined forces with leaders in the field of green chemistry in what may turn out to be a groundbreaking meeting, “Green Chemistry and Environmental Health Sciences — Designing Endocrine Disruption Out of the Next Generation of Materials,” held March 21-23 in Sausalito, Calif.
The challenges facing scientists trying to design such new materials are daunting. Say a chemist has developed a compound that he or she believes could be a replacement for bisphenol A (BPA). How will the scientist determine if the molecule is safer to human health and the environment? What testing will need to be done and what will guide scientists through this process?
The goals of the meeting in Sausalito were ambitious — to develop a consensus statement on the principles that guide the science needed to assess risks of potential endocrine disruptors, and to develop a reliable and rational testing protocol to aid chemists as they develop and bring the next generation of chemicals into the marketplace.
The intersection of green chemistry and environmental health science
Karen O’Brien, Ph.D., from Advancing Green Chemistry (AGC) and Pete Myers, Ph.D., of Environmental Health Sciences (EHS), welcomed participants to the event, which brought together an equal mix of biologists and chemists. Representatives from NIEHS and NTP included Division of Extramural Research and Training (DERT) program administrator Jerry Heindel, Ph.D., and Kristina Thayer, Ph.D., director of the NTP Center for the Evaluation of Risks to Human Reproduction (CERHR).
Following a social ice-breaking exercise on the evening of March 21, the first full day of the meeting opened with presentations from Terry Collins, Ph.D., the Teresa Heinz Professor of Green Chemistry at Carnegie Mellon University, and John Warner, Ph.D., president and founder of the Warner Babcock Institute for Green Chemistry.
Both Collins and Warner stressed the need for fundamental changes in the way that scientists design new chemicals and the process of bringing them into the marketplace. “We must also pay close attention to the environmental impact and the effects on human health posed by these chemicals, and for those reasons chemists need to work hand-in-hand with biologists,” said Warner. He also stressed that chemists generally have no background in toxicology, but that they need to be able to test the chemicals being developed for endocrine activity and to do it early on in the product development process.
Designing a chemical screening protocol
The remainder of the day was divided into discussion sessions covering each phase of a newly developed screening model, designed by a science advisory board formed by meeting organizers that met monthly, via teleconference, for six months prior to the workshop. The protocol is geared towards identifying a wide-range of endocrine-active chemicals, such as atrazine, BPA, brominated flame retardants, organotins, perchlorates, and phthalates. The Board conducted interviews with scientists with expertise in specific areas of toxicology, endocrine disruption, and assay development.
The testing paradigm proposed involves a five-tiered approach, starting with the fastest and cheapest assays and working through more specialized tests to determine whether a new chemical has endocrine disrupting characteristics. The initial two phases rely on predictive computer modeling and high-throughput screening to quickly weed out problem chemicals. These tests are followed by more specific in vitro cell-based screening assays with a mind to refining, reducing, and replacing animal testing as much as possible.
The final two phases involve use of fish, amphibian, and mammalian in vivo modeling systems. Overall, the protocol is intended to help green chemists establish a high degree of confidence that the replacements they are developing are unlikely to be harmful to humans or the environment.
The next steps
The meeting wrapped up with discussion on how to proceed with development of the testing protocol as well as plans for implementation. The advisory board plans to use input from the meeting to develop and publish a white paper outlining guidelines that chemists can use to assess the quality of protocols and tests used to assess endocrine disruption.
(Thaddeus Schug, Ph.D., is a postdoctoral research fellow currently on detail as a program analyst in the NIEHS Division of Extramural Research and Training. He was part of the NIEHS/NTP delegation and a presenter at the meeting.)

A representative diagram of the draft screening protocol unveiled at the meeting. The protocol is designed in a tiered approach, with rapid and cost effective screens conducted in the early phases and more extensive testing toward the end. (Slide courtesy of Pete Myers)

Left to right, Collins, Heindel, and Warner mix ingredients for a batch of salmon tartare. The cooking exercise was used as an ice-breaking event to demonstrate how environmental health scientists and chemists can work together to solve complex issues. (Photo courtesy of Pete Myers)

Laura Vandenberg, Ph.D., left, contributes to the discussion on assay development, as Tom Zoeller, Ph.D., center, and Wim Thielemans, Ph.D., look on. Vandenberg, a postdoctoral fellow at Tufts University, studies the developmental effects of endocrine disrupting chemicals. (Photo courtesy of Pete Myers)

Left to right, Bruce Blumberg, Ph.D., Thayer, and Andreas Kortenkamp, Ph.D., served as panel members for a discussion on in vitro screening assays. (Photo courtesy of Pete Myers)

A group photo of the meeting attendees. The meeting was held at the Cavallo Point Lodge, which sits adjacent to the Golden Gate Bridge. (Photo courtesy of Pete Myers)

NIEHS grantees Andrea Gore, Ph.D., left, and Frederick vom Saal, Ph.D., were among panel members for the discussion on in vivo assays. Both Gore and vom Saal are members of the project’s scientific advisory board. (Photo courtesy of Pete Myers)



Scientists constructing tool for chemists to flag endocrine disruptors early in chemical development.
Tuesday, September 27th, 2011The reporter got the attribution for our project wrong (NIEHS is not financially supporting this work, but is supporting it in kind. AGC and sister organization, Environmental Health Sciences, are funded to do the project). Still though: we are glad people are interested.
Pesticide and Toxic Chemical News
Friday September 23 2011
A group of biologists and green chemists, supported by the extramural research division of the National Institute of Environmental Health Sciences, is developing a protocol for chemists to use to determine if the chemical they are developing is an endocrine disruptor.
Thaddeus Schug, who manages a portfolio of grants in the NIEHS Cellular, Organs and Systems Pathobiology Branch, highlighted the project during a panel discussion on practical approaches to integrating rapid testing into the chemical design process. The discussion took place Sept. 21, the second day of a workshop, “Applying 21st Century Toxicology to Green Chemical and Material Design,” which was sponsored by the National Academies’ Standing Committee on Use of Emerging Science for Environmental Health Decisions. Schug says the group has been working for the last year on developing a protocol, and the guiding principles behind it, to determine whether a chemical under development is toxic, and how and where testing should be performed.
“We focus on endocrine disruption, but our guiding principles and protocol could be developed to capture all forms of toxicity,” he said. The protocol is not regulatory, Schug said, but a guide chemists can follow – as they develop a chemical – to give them confidence as to whether the substance is or is not an endocrine disruptor.
The group, which includes non-governmental organizations, academics and green chemistry leaders, has come up with a tiered system. “What we propose to do is put the fastest, cheapest testing up front – the computational modeling, followed by high throughput screening and the zebrafish models,” Schug said. That would be followed up with more specific testing as a chemical moves further along the development process.
“The idea is if a chemist hits a positive early on, he’d either go back to the drawing board, or if that positive was in a specific area [i.e. an estrogen receptor in a high throughput assay], he’d follow that up with more comprehensive assays,” Schug said. “A hit anywhere along the tiered system” means the chemist has to pull back, reanalyze or throw the chemical out, he said.
“The idea is to do the fastest, cheapest test early on, so the chemist can weed out those problem chemicals early on in development so it’s not a costly procedure,” Schug said.
The idea of the protocol “arose from a great sense of frustration” in the endocrine disruptor community, Bruce Blumberg, a professor of developmental and cell biology at the University of California, Irvine who also is working on the project, said during the panel discussion. This frustration stemmed from “hearing things like, ‘Well, you can’t test for endocrine disruptors,’ which the American Chemistry Council says,” Blumberg noted. “We know very well how to test for endocrine disruptors, how to test for endocrine disruptor activities from in vitro all the way to animal studies,” he said. “So we said this is a gap that has to be filled, and we got together to fill that gap.”
The protocol is voluntary, Blumberg noted. “We suggest this if you want to screen for endocrine activity in your chemicals and make them more green – this is the way we think you should do it. We’re providing an alternative approach interested parties can use to make the best chemicals they can,” he said.
Richard Denison, senior scientist at Environmental Defense Fund, welcomed the protocol’s development, saying “it really flips the concept of tiered testing around.”
Usually in tiered testing, a chemical only advances to the next level of testing if it is flagged for an effect at an earlier level, “which puts a huge question mark around the extent to which false negatives are being missed.”
But in the case of the protocol, “you’re advancing things that don’t raise red flags to the next level [of testing], increasing the confidence that you didn’t miss anything,” Denison said. “I think that’s a really intriguing approach.”
(Read full article here.)
- Liz Buckley
Tags: endocrine disruptors, GREEN CHEMISTRY, metrics, safety testing
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