title: Benchmark calculations for perchlorate from three human cohorts.
abstract: The presence of low concentrations of perchlorate in some drinking water sources has led to concern regarding potential effects on the thyroid. In a recently published report, the National Academy of Sciences indicated that the perchlorate dose required to cause hypothyroidism in adults would probably be > 0.40 mg/kg-day for months or longer. In this study, we calculated benchmark doses for perchlorate from thyroid-stimulating hormone (TSH) and free thyroxine (T4) serum indicators from two occupational cohorts with long-term exposure to perchlorate, and from a clinical study of volunteers exposed to perchlorate for 2 weeks. The benchmark dose for a particular serum indicator was defined as the dose predicted to cause an additional 5 or 10% of persons to have a serum measurement outside of the normal range. Using the data from the clinical study, we estimated the half-life of perchlorate in serum at 7.5 hr and the volume of distribution at 0.34 L/kg. Using these estimates and measurements of perchlorate in serum or urine, doses in the occupational cohorts were estimated and used in benchmark calculations. Because none of the three studies found a significant effect of perchlorate on TSH or free T4, all of the benchmark dose estimates were indistinguishable from infinity. The lower 95% statistical confidence limits on benchmark doses estimated from a combined analysis of the two occupational studies ranged from 0.21 to 0.56 mg/kg-day for free T4 index and from 0.36 to 0.92 mg/kg-day for TSH. Corresponding estimates from the short-term clinical study were within these ranges.
authors.affiliation: Environ Health Sciences Institute, Ruston, Louisiana 71270, USA. kcrump@environcorp.com
authors.forename: Kenny S
authors.initials: KS
authors.lastname: Crump
authors.forename: John P
authors.initials: JP
authors.lastname: Gibbs
mesh_terms: D000395:Air Pollutants, Occupational / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology / Q000652:urine; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D008297:Male; D019055:No-Observed-Adverse-Effect Level; D016273:Occupational Exposure; D010472:Perchlorates / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology* / Q000652:urine; D018570:Risk Assessment / Q000379:methods*; D013961:Thyroid Gland / Q000187:drug effects / Q000378:metabolism; D013972:Thyrotropin / Q000097:blood*; D013974:Thyroxine / Q000097:blood*; D014874:Water Pollutants, Chemical / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology / Q000652:urine
chemical_list: D000395:Air Pollutants, Occupational; D010472:Perchlorates; D014874:Water Pollutants, Chemical; D013972:Thyrotropin; D013974:Thyroxine