gland, which could potentially lead to iodide deficiency and decreased synthesis of T3 and T4. The thyroid hormones are critical determinants of growth and development in fetuses, infants, and young children. Thus, fetuses and preterm newborns constitute the most sensitive populations although infants and developing children are also considered sensitive populations. People who have compromised thyroid function resulting from conditions that reduce thyroid hormone production and people who are iodide-deficient also constitute potentially sensitive populations.


Several issues have been repeatedly raised at conferences and in peer reviews concerning EPA’s assessment of potential adverse health effects of perchlorate exposure (EPA 2002b; Schwartz et al. 2004). The adequacy and relevance of available human data for assessing health risks posed by perchlorate exposure have been debated. Clinical, occupational, and epidemiologic data are available, and some argue that they should be used to determine the RfD, the key value used to derive the drinking-water standard. However, others state that the human studies should not be used as the basis of the RfD, because they contain one or more of the following limitations: lack of control of confounding factors, evaluation only of healthy adults, inadequate exposure information, evaluation of effects over short exposure durations, and assessment of a narrow set of toxicity end points.

The quality and validity of some animal data have also been debated (EPA 2002b; Schwartz et al. 2004). Specifically, questions have been raised about neurodevelopmental studies in which rats were exposed to perchlorate in utero and postnatally and then examined for changes in specific areas of the brain. Many have challenged the experimental methods, the statistical analysis of the data, the interpretation of the reported findings, and the inconsistencies between the reported findings and the general literature on thyroid hormones and brain development. Others have argued that those data cannot be disregarded in the assessment of potential adverse health effects of perchlorate ingestion.

Another point of contention is the definition of the adverse health effect associated with perchlorate ingestion (EPA 2002b; Schwartz et al. 2004). EPA has proposed a mode-of-action model for perchlorate toxicity, which shows a continuum of possible health effects of perchlorate exposure (see Figure 1-2). The effect that is defined as the adverse effect is a matter of

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