Consensus Report

Application of Systematic Review Methods in an Overall Strategy for Evaluating Low-Dose Toxicity from Endocrine Active Chemicals (2017)

Each report is produced by a committee of experts selected by the Academy to address a particular statement of task and is subject to a rigorous, independent peer review; while the reports represent views of the committee, they also are endorsed by the Academy. Learn more on our expert consensus reports.

The U.S. Environmental Protection Agency (EPA) regulates toxic chemicals as part of its mission to protect human health and the environment. Traditional toxicity testing relies heavily on studies that expose test animals to chemicals at amounts much higher than typical human exposures (i.e., low doses). However, some chemicals can cause health effects at low doses. This report outlines a strategy to improve EPA's ability to evaluate evidence of low-dose effects of endocrine active chemicals (EACs), also known as endocrine disruptors. EACs are of particular concern because they can alter normal hormone function, and even small changes in hormone concentrations, particularly during sensitive life stages, can have lasting effects.

The committee developed a strategy for evaluating evidence of low-dose effects of EACs that involves three broad phases: (1) surveillance to detect signals of possible health effects by actively monitoring new data, the scientific literature, and nontraditional information sources; (2) investigation and analysis to further investigate any signals identified; and (3) actions that might include updating chemical assessments, regularly monitoring for new data, requiring new data or models to reduce uncertainties, or updating toxicity-testing designs and practices. EPA is already conducting many activities consistent with the proposed strategy, although not necessarily in the context of assessing low-dose exposure to EACs.

In addition to developing a strategy, the committee was charged with conducting systematic reviews of animal and human toxicology data for two or more EACs. The committee chose phthalates and polybrominated diphenyl ethers (PBDEs) for the reviews. One example from the reviews showed that exposure of the fetus to DEHP -- a type of phthalate used as a plasticizer -- is presumed to be a reproductive hazard to humans. A second set of reviews showed sufficient evidence that PBDEs are a presumed hazard to humans with respect to effects on intelligence. For these specific cases, the committee concluded that current toxicity-testing methods can identify a hazard that is presumed to be of concern to humans, but current methods might not be able to accurately predict the specific level of exposure at which humans are affected.