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Endocrine Disruptors: Atypical Toxicity Curves Present Challenges For Risk Assessment

by Britt Erickson
May 19, 2014 | A version of this story appeared in Volume 92, Issue 20

EPA’s risk assessment process is built around the assumption that chemicals exhibit greater effects at higher concentrations. A growing number of studies, however, have shown that lower doses of some chemicals, particularly endocrine disruptors, are associated with greater health effects than higher doses.

Much of the current debate in the regulatory toxicology community is focused on whether standard toxicity tests miss low-dose effects for chemicals that don’t exhibit typical dose-response curves. These atypical curves, often called nonmonotonic dose-response curves, have been hugely controversial because of their implications for how chemicals should be evaluated for safety.

In a draft report released last year, EPA concluded that its risk assessment process is adequate for evaluating endocrine-disrupting chemicals, even those with atypical dose-response curves. A committee convened by the National Research Council to study the draft report, however, says there is insufficient evidence to support that conclusion.

Credit: EPA
EPA’s risk assessment process may not detect health effects of chemicals that have larger responses at lower doses than at higher doses.
Examples of monotonic and nonmonotonic dose-response curves.
Credit: EPA
EPA’s risk assessment process may not detect health effects of chemicals that have larger responses at lower doses than at higher doses.

In a May 2 report, the NRC committee recommends that EPA develop a standard set of methods to evaluate its risk assessment process for chemicals that disrupt estrogen-, androgen-, and thyroid-hormone pathways. EPA’s process for evaluating its risk assessment approach is “poorly described and inconsistent,” across the three hormone pathways, the report says.

EPA should also evaluate whether current toxicity tests can detect adverse health effects associated with chemicals that have nonmonotonic dose-response curves, the report says. “EPA provided no analysis to support its conclusion that such curves can have both qualitative and quantitative effects and that current risk-assessment practices will consider the evidence appropriately.”

The recommendations provided by the NRC committee will help make EPA’s science stronger and improve last year’s draft report, the agency says. Once finalized, EPA intends to use that report to determine whether current toxicity tests are protective of public health with respect to endocrine-disrupting chemicals.



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