Application of Systemic Review Methods in an Overall Strategy for Evaluating Low – Dose Toxicity from Endocrine Active Chemicals

November 3, 2017 -

A recent report was released on how the US Environmental Protection Agency (EPA) can better safeguard public health, by employing such methods as keeping on top of new scientific information and emerging technologies applicable to its regulatory decision making; determining how to incorporate animal-testing data to use to make predictions about negative human health effects; performing dose-response extrapolations; identifying and protecting susceptible population groups; and better addressing uncertainties.


EPA has used traditional used toxicity testing in the past, but new evidence demonstrates that some chemicals have effects at doses lower than those used in traditional toxicity testing, thus they are inadequate to identify all potential hazards to humans. Such chemicals are endocrine active chemicals (EACs), or endocrine disruptors, which modulate normal hormone function and can cause alterations in hormone concentrations with life-long effects.


To address concerns about potential human health effects from EACs at low doses, EPA requested that the National Academies of Sciences, Engineering, and Medicine develop a strategy to evaluate the evidence for such low-dose effects. A systematic review of animal

and human studies on at least two chemicals, in this case, phthalates and polybrominated diphenyl ethers (PBDEs), was performed.


This report describes the strategy developed and the three broad steps that can help evaluate evidence of impacts from low-dose chemical exposure:


•             Surveillance –Detecting signals of possible health effects by actively monitoring new data, scientific literature, nontraditional information sources, and stakeholder input to ensure health effects are being identified and analyzed on a regular basis.


•             Investigation and Analysis –Reviewing existing data, generating new data to fill gaps, conducting a systematic review of evidence, or integrating evidence from human and animal studies. 


•             Action –Updating chemical assessments, regularly monitoring for new data, requiring new data or models to reduce uncertainties, or updating toxicity-testing designs and practices.


Some of the findings and recommendations for the EPA in the report were as follows:


Recommendation: EPA should develop an active surveillance program focused specifically on low- dose exposures to EACs. This would involve monitoring published research and other information sources, gathering input from stakeholders, and considering human exposure information.


Recommendation: After a topic is selected for further evaluation, the agency should plan its investigation by identifying key questions to be addressed and determining the types of data and analyses needed to answer the questions and to support future agency actions. The specific approaches and tools used to implement the strategy to address issues related to low-dose endocrine effects will need to be considered on a case-by-case basis and should be guided by the questions under study.


Recommendation: Human environmental exposure or biomonitoring data should be used, if available, to define what subset of the data should be considered as reflective of low-dose exposure.


The full report is now available:




Disclaimer: The opinions expressed within this article are the views of the writer and do not necessarily reflect the views and opinions of ASME.

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