Designing the next generation of sustainable chemicals.

Environmental Factor, November 2012 see original article here.

By Thaddeus Schug

Tom Zoeller, Ph.D., Jerry Heindel, Ph.D., and Wim Thielemans, Ph.D.  Heindel, center, goes to work creating a toxic pumpkin, while Tom Zoeller, Ph.D., left, and Wim Thielemans, Ph.D., take part in the fun. (Photo courtesy of Pete Myers)

Scientists committed to developing green solutions for replacing problem chemicals in the marketplace gathered Oct. 15-17 for a meeting on “Building the Path Forward for the Next Generation of Sustainable Chemicals,” held at the Rockefeller Brothers Fund Pocantico Center in Tarrytown, N.Y.

The meeting, sponsored by the non-government organizations Advancing Green Chemistry  and Environmental Health Sciences,  brought together a mixture of chemists, toxicologists, and biologists. Representatives from NIEHS and NTP included Division of Extramural Research and Training program administrators Jerry Heindel, Ph.D., and Thaddeus Schug, Ph.D.; Kristina Thayer, Ph.D., director of the newly named NTP Office of Health Assessment and Translation; and NTP Biomolecular Screening Branch Chief Ray Tice, Ph.D.

Designing safer chemicals

There are more than 83,000 chemicals in commerce today, many of which pose potential toxic hazards to human health and the environment. The challenge facing chemists designing replacement materials involves figuring out what kind of testing will need to be done to determine if the new chemical is safer than current ones to human health and the environment. One area of growing concern is how to ensure that the next generation of chemicals does not have the potential to act as endocrine disrupting compounds.

The meeting at Pocantico aimed to build upon a new set of testing tools — the Tiered Protocol for Endocrine Disruptors (TiPED) — developed by the group over the past two years. The protocol, which will be published online Dec. 6 in the Royal Society of Chemistry journal Green Chemistry,  is not regulatory, but rather a tool to guide chemists as they develop a new chemical, to give them confidence as to whether the substance is or is not likely to be an endocrine disruptor.

The TiPED protocol offers a five-tiered approach, starting with what should be the fastest and cheapest assays, and working through increasingly specialized tests. 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 goal of refining, reducing, and replacing animal testing as much as possible. The last two tiers are whole animal assays, to be used for looking for integrated endpoints and less understood systemic responses.

“The idea is that if chemists hit a positive early on, they would either go back to the drawing board or, if that positive was in a specific area, such as an estrogen receptor in a high throughput assay, they would follow that up with more comprehensive assays,” said Heindel. “A hit anywhere along the tiered system means chemists need to pull back, reanalyze, or throw the chemical out.”

The project emphasizes fundamental changes in the way that scientists design new chemicals, and in the process of bringing them into the marketplace. Chemists generally have little training in toxicology, so this plan offers guidelines they can follow early on in the product development process.

Moving forward with the plan

Following a team-building exercise on the evening of Oct. 15, involving pumpkins and toxicological design criteria, the first full day of the meeting was divided into discussion sessions aimed toward refining the specific testing strategies within each phase of the screening model. A good deal of time was dedicated to establishing criteria needed to assess the quality of assays within each tier of the protocol.

The meeting wrapped up with a discussion on strategies to conduct test runs of the protocol, using test chemicals synthesized by John Warner, Ph.D., president and founder of the Warner Babcock Institute for Green Chemistry.

(Thaddeus Schug, Ph.D., is a health scientist in the NIEHS Division of Extramural Research and Training and a regular contributor to the Environmental Factor.)

Disclaimer: This report was written by members of the NIEHS staff based on materials prepared for this meeting and the discussions that took place there. It reflects the views of the authors and not necessarily those of the Rockefeller Brothers Fund, its trustees, or its staff.

 

Coach Barn of the Pocantico Center, which is also known as the John D. Rockefeller Estate  The meeting was held on the ground floor of the Coach Barn of the Pocantico Center, which is also known as the John D. Rockefeller Estate. Take a video tour.  (Photo courtesy of Ray Tice)
Ray Tice, Ph.D., and Kristina Thayer, Ph.D.  Tice, left, and Thayer take part in a discussion of the endocrine disruptor screening protocol. (Photo courtesy of Pete Myers)
Tiered Protocol for Endocrine Disruptors (TiPED) working group  The TiPED working group enjoyed the fall weather and the beautiful scenery at the Pocantico Center in Tarrytown, N.Y. (Photo courtesy of Ray Tice)