title: Evaluation of the risk of perchlorate exposure in a population of late-gestation pregnant women in the United States: Application of probabilistic biologically-based dose response modeling.
abstract: The risk of ubiquitous perchlorate exposure and the dose-response on thyroid hormone levels in pregnant women in the United States (U.S.) have yet to be characterized. In the current work, we integrated a previously developed perchlorate submodel into a recently developed population-based pregnancy model to predict reductions in maternal serum free thyroxine (fT4) levels for late-gestation pregnant women in the U.S. Our findings indicated no significant difference in geometric mean estimates of fT4 when perchlorate exposure from food only was compared to no perchlorate exposure. The reduction in maternal fT4 levels reached statistical significance when an added contribution from drinking water (i.e., 15μg/L, 20μg/L, or 24.5μg/L) was assumed in addition to the 90th percentile of food intake for pregnant women (0.198μg/kg/day). We determined that a daily intake of 0.45 to 0.50μg/kg/day of perchlorate was necessary to produce results that were significantly different than those obtained from no perchlorate exposure. Adjusting for this food intake dose, the relative source contribution of perchlorate from drinking water (or other non-dietary sources) was estimated to range from 0.25-0.3μg/kg/day. Assuming a drinking water intake rate of 0.033L/kg/day, the drinking water concentration allowance for perchlorate equates to 7.6-9.2μg/L. In summary, we have demonstrated the utility of a probabilistic biologically-based dose-response model for perchlorate risk assessment in a sensitive life-stage at a population level; however, there is a need for continued monitoring in regions of the U.S. where perchlorate exposure may be higher.
authors.affiliation: Division of Biochemical Toxicology, National Center for Toxicological Research, U.S. Food and Drug Administration, 3900 NCTR Rd, HFT-110, Jefferson, AR 72079, USA. Electronic address: Annie.Lumen@fda.hhs.gov.
authors.forename: A
authors.initials: A
authors.lastname: Lumen
authors.affiliation: Division of Bioinformatics and Biostatistics, National Center for Toxicological Research, U.S. Food and Drug Administration, 3900 NCTR Rd, HFT-20, Jefferson, AR 72079, USA. Electronic address: Nysia.George@fda.hhs.gov.
authors.forename: N I
authors.initials: NI
authors.lastname: George
mesh_terms: D000328:Adult; D060766:Drinking Water / Q000009:adverse effects / Q000592:standards; D004781:Environmental Exposure / Q000009:adverse effects / Q000592:standards; D005260:Female; D006801:Humans; D015233:Models, Statistical; D010472:Perchlorates / Q000097:blood* / Q000633:toxicity* / Q000652:urine; D011247:Pregnancy; D011263:Pregnancy Trimester, Third / Q000097:blood* / Q000187:drug effects / Q000652:urine; D018570:Risk Assessment; D013974:Thyroxine / Q000097:blood*; D014481:United States / Q000453:epidemiology; D014874:Water Pollutants, Chemical / Q000097:blood* / Q000633:toxicity / Q000652:urine; D014881:Water Supply / Q000592:standards
chemical_list: D060766:Drinking Water; D010472:Perchlorates; D014874:Water Pollutants, Chemical; D013974:Thyroxine; C494474:perchlorate
keywords: Biologically based dose-response modeling; Perchlorate; Probabilistic risk assessment