Applying 21st century toxicology to green chemistry.

By Eddy Ball
October 2011

Scientists aiming to develop real-world solutions for problem chemicals gathered at a workshop on “Applying 21st Century Toxicology to Green Chemical and Material Design” Sept. 20-21, at the House of Sweden Event Center in Washington, D.C. The workshop was part of the National Academy of Sciences (NAS) ongoing series organized by the Committee on Emerging Science for Environmental Health Decisions sponsored by NIEHS. This workshop was unique in that it was co-hosted by the National Science and Technology Councils (NSTC) Committee on Environment, Natural Resources, and Sustainability (CENRS) Subcommittee on Toxics and Risks.

With more than 83,000 chemicals available for use in the U.S. today, there is rising concern about potential toxic properties these chemicals pose in relation to human health and the environment. This issue has given rise to the field of green chemistry — the science-based design of chemicals to minimize the use and generation of hazardous substances.

Visioning a green future

The workshop brought together chemists, toxicologists, and biologists to define common goals, identify knowledge gaps, and promote applied research aimed at expediting the application of new approaches to toxicology to the emerging field of green chemistry. As he opened the meeting, NIEHS Toxicology Liaison and co-chair of the NSTC Subcommittee on Toxics and Risks Christopher Weis, Ph.D., challenged participants to think of a future with safer chemicals and less need for regulation.

Paul Anastas, Ph.D., assistant administrator of the U.S. Environmental Protection Agency Office of Research and Development, who is often referred to as the father of green chemistry, then set the stage for the meeting’s three sessions with a presentation, titled “Vision of a Green Chemical Future.” Anastas told participants, “There are tremendous advantages — environmental, economic, and health-related — in implementing green chemistry into the design and production of the next generation of chemicals.”

The main focus of the sessions centered on identifying replacements for problematic chemicals and the emerging tools available for toxicology testing. Representatives from industry, academia, and government agencies discussed the utility of rapid assessment approaches in toxicology, including high-throughput biochemical screening, in vitro cellular approaches, and rapid assessments using aquatic organisms.

Putting the plan to action

During session three, Thaddeus Schug, Ph.D., a postdoctoral fellow on detail to the NIEHS Division of Extramural Research and Training, highlighted a collaborative project that is constructing a protocol for chemists to flag endocrine disruptors early in chemical development. “The protocol is not regulatory,” Schug emphasized, “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.”

Thaddeus Schug, Ph.D.
“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 explained. The first-tier testing would be followed up with more specific testing as a chemical moves farther along the developmental process. (Photo courtesy of Steve McCaw)

The project, which is sponsored by the groups Advancing Green Chemistry and Environmental Health Sciences, publisher of Environmental Health News, has come up with a tiered system.

“The idea is 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’d follow that up with more comprehensive assays,” Schug continued. “A hit anywhere along the tiered system means chemists need to pull back, reanalyze, or throw the chemical out.”

The protocol is voluntary, explained Bruce Blumberg, Ph.D., a professor of developmental and cell biology at the University of California, Irvine. “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, Ph.D., 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. “[That] puts a huge question mark around the extent to which false negatives are being missed,” Denison added.

Christopher Weis, Ph.D.
“Dream big of a future in which green chemistry will move into the marketplace to the extent that this science will ultimately short-circuit the need for regulation,” Weis told workshop participants. “This will allow us to think ahead about potential chemical effects, rather than respond to problems that arise after chemicals are introduced.” (Photo courtesy of Steve McCaw)