Perchlorate: overview of risks and regulation.

The extent to which perchlorate, which occurs naturally and as an industrial contaminant, should or should not be regulated has become controversial. This review examines a number of inconsistent conclusions that have been drawn based on thyroid hormone serum concentrations, urinary iodine concentrations, and perchlorate exposure among women participating in the 2000-2001 National Health and Nutrition Examination Survey (NHANES) and based on the body of epidemiologic and clinical evidence reporting no associations between effects on thyroid hormones and similar or much higher levels of perchlorate exposure. For example, studies associating perchlorate with thyroid effects at low exposures did not control for anti-thyroid agents with modes of action that differ from that of perchlorate, such as some organochlorines. Available evidence does not support a causal relationship between changes in thyroid hormone levels and current environmental levels of perchlorate exposure but does support the conclusion that the US Environmental Protection Agency's reference dose (RfD) for perchlorate is conservatively health-protective. However, potential perchlorate risks are unlikely to be distinguishable from the ubiquitous background of naturally occurring substances present at much higher exposures that can affect the thyroid via the same biological mode of action as perchlorate, such as nitrate and thiocyanate. Risk management approaches that account for both aggregate and cumulative exposures and that consider the larger public health context in which exposures are occurring are desirable.