Draft report urges inclusion of mixtures in endocrine disrupter testing program A federal advisory committee has developed a screening program for chemicals and pesticides suspected of endocrine disruption. The report, which goes beyond what Congress mandated by asserting that chemical mixtures should be tested, provides a first look at how the government may meet the enormous challenge of evaluating tens of thousands of chemical substances for their endocrine-disrupting potential. Congress directed EPA in 1996 to develop a program to screen and test chemicals and pesticides for their potential to disrupt human endocrine systems. EPA formed the Endocrine Disrupter Screening and Testing Advisory Committee (EDSTAC), an advisory panel composed of several federal agencies—including the Food and Drug Administration and the National Institutes of Health as well as industry, academic, and environmental representatives—to provide advice on developing such a program. Many committee members believe EPA is ready to meet the August deadline set by Congress for the screening program. The report suggests that work should begin immediately on six chemical mixtures. Investigating mixtures is necessary to catch possible additive, synergistic, or antagonistic effects caused by the interactions of the compounds in the mixtures, according to the report. The mixtures are contaminants in
human breast milk, phytoestrogens in soy-based infant formulas, mixtures of chemicals commonly found at Superfund sites, pesticidefertilizer mixtures, water disinfection byproducts, and gasoline. By including mixtures, the recommendations break new ground. Regulators around the world have made many attempts to deal with the toxicity of mixtures, which are commonly found combinations of chemicals, but most efforts have stalled because of the enormity of the task. "Addressing mixtures is a
"Addressing [chemical] mixtures is a major advance." —Peter de Fur, Virginia Commonwealth University major advance," said Peter de Fur, a comparative biologist at Virginia Commonwealth University in Richmond, Va., and one of EDSTAC's 40 members. By subjecting mixtures to the same testing regime as single compounds, the draft recommendations mark the first rigorous attempt to regulate mixtures, de Fur noted. The recommendation to tackle mixtures accords with the overall perspective of the report, which urges EPA to go beyond the specific requirements of the 1996 legislation. For example, the draft
EDSTAC's key recommendations EDSTAC, an advisory panel composed of industry, environmental, and government representatives, agreed to a chemical-screening program. Below are highlights of the February draft report. • Apply automated prescreening to 15,000 high-production-volume chemicals. • Complete development of the endocrine disrupter priority-setting database initiated by EDSTAC. • Establish a program to validate recommended Tier 1 and Tier 2 tests. • Prioritize chemicals on the basis of effects, exposure, and statutory requirements, each considered independently. • Evaluate the potential for endocrine disruption through the use of a battery of in vitro and in vivo tests (Tier 1). • Use Tier 2 tests to assess the consequences of endocrine-disrupting potential.
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report strongly recommends that the program screen for endocrine effects in wildlife as well as humans, although Congress did not mention wildlife in its mandate. Accomplishing what once appeared to be an impossible task, EDSTAC agreed to a three-tiered screening and testing program. The prescreening stage consists of automated assays to detect the ability of chemicals to interact with hormone receptors in humans and wildlife. Such techniques, currently used to evaluate new drugs, have never before been used on such a wide range of chemicals. This high-throughput prescreening would be applied to the 15,000 chemicals produced in the United States with annual production volumes greater than 10,000 lb. EPA has already started work on a project to demonstrate that this technique is viable for the wide range of chemicals to be evaluated. A battery of in vitro and in vivo assays designed to detect the potential of a chemical to disrupt the endocrine system is proposed for the next stage, known as Tier .1. Committee members agree that the proposed battery will detect all known disrupters of estrogen, androgen, and thyroid function. After Tier 1 screening, chemicals judged to have endocrine-disrupting potential will be subjected to Tier 2 tests designed to characterize the nature, likelihood, and dose-response relationship of endocrine disruption in humans and wildlife. EPA is expected to accept the recommendations "because the committee has made it clear they are necessary for a scientifically defensible program," said Anthony Maciorowski, chief of the ecological effects branch of EPA's Office of Pesticide Programs. Several significant issues remain, and officials are hoping these issues can be resolved before the report is reviewed by the Science Advisory Board in May. The final report, which will incorporate the findings of a National Academy of Sciences report on the state of scientific knowledge about endocrine disrupters, is set to be presented to EPA in June. —REBECCA RENNER
