1754 EXPOSURE ASSESSMENT FOR PERCHLORATE IN DRINKING WATER

of perchlorate are well known and have been extensively reviewed (Wolff 1998; Goodman 2003). Traditionally toxicologists test chemicals by looking for clear indications of adverse effects in laboratory animals. Such indications might include tumors, hyperplasia, microscopic lesions, and structural abnormalities. Once adverse effects have been characterized, toxicological testing evolves by lowering the exposure dose in order to define a no-observable-adverse-effect level (NOAEL) or failing that, a lowest-observable-adverse-effect level (LOAEL). When these doses are established, uncertainty factors are applied to establish safe values for human exposure. However, when the pharmacology of an agent is known, this knowledge can be used to establish with virtual certainty a lower bound other than zero for a safe exposure level. Identifying the threshold of a precursor to a precursor to a possible adverse effect in humans logically increases both precision and certainty, and thus overcomes the limitations of the traditional uncertainty factor approach. For perchlorate, iodide uptake is the initial step (precursor) of the biochemical pathway that could lead to a clinically significant reduction in circulating thyroid hormones (TH). Such a change in TH could lead to developmental deficits in the fetus, the accepted population of concern. Greer et al. (2002) measured a no-observed-effect level (NOEL) of 0.007 mg/kg-day and estimated a true no-effect level (NEL) of 0.005 to 0.006 mg/kg-day for inhibition of radioiodine uptake (RAIU) by perchlorate in men and women. Apart from being an inherently safe dose, the estimated NEL provides a plausible lower bound for a reference dose derived from traditional animal toxicology studies. Further, the NEL has inherently greater precision than a NOAEL or LOAEL and this precision should be reflected when choosing values for uncertainty factors.