Perchlorate: Overview of risks and regulation

Abstract

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.

Introduction

Perchlorate is a substance that has recently been receiving prominent legislative and regulatory attention in the US by both federal and state governments. Initially identified as a groundwater contaminant associated primarily with rocket fuel spillage, perchlorate is now found to be ubiquitous. Widespread human exposure to both anthropogenic and naturally occurring perchlorate occurs primarily via ingestion. Like several other dietary goitrogens, perchlorate can interfere with iodine uptake by the thyroid gland, potentially disrupting thyroid hormone levels responsible for regulating many of the body’s metabolic and developmental functions. Because thyroid hormones are critical for normal fetal and neonatal development, perchlorate has the potential to pose a risk to children although no specific cases have been identified, even in areas where exposure occurs to high levels of naturally occurring perchlorate. Because there are incomplete data on perchlorate’s potential risks, however, the US Environmental Protection Agency (US EPA) has developed a precautionary limit on lifetime exposure intended to prevent adverse effects that might have an impact on the developing child. The adequacy of that exposure limit is debated, with some stakeholders believing it is too stringent and others believing it is not stringent enough.

This article provides an overview of the scientific basis for the controversy, exploring what is known about perchlorate exposure and effects and describing its risks in the context of potential risks from other iodine-uptake-inhibiting goitrogens as well as goitrogens that do not inhibit iodine uptake. In particular, the apparent discrepancy between the reported associations between exposure and effects at current low, background levels of exposure in the US and the reported absence of effects at much higher levels of exposure is discussed.