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The NAS Perchlorate Review: Is the RfD Acceptable?

2005; National Institute of Environmental Health Sciences; Volume: 113; Issue: 11 Linguagem: Inglês

10.1289/ehp.113-a729

1552-9924

Joan Strawson, Michael L. Dourson, Qiyu Zhao,

Radioactive contamination and transfer

Vol. 113, No. 11 PerspectivesOpen AccessThe NAS Perchlorate Review: Is the RfD Acceptable?is companion ofThe NAS Perchlorate Review: Ginsberg et al. Respond Joan Strawson, Michael L. Dourson, and Qiyu (Jay) Zhao Joan Strawson Search for more papers by this author , Michael L. Dourson Search for more papers by this author , and Qiyu (Jay) Zhao Search for more papers by this author Published:1 November 2005https://doi.org/10.1289/ehp.113-a729Cited by:3AboutSectionsPDF ToolsDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InReddit Risk assessors should always carefully evaluate whether a given reference dose (RfD) is the most appropriate choice for assessing risk. In the case of perchlorate, Ginsberg and Rice (2005) suggested that the RfD proposed by the National Research Council (NRC) is inappropriate because the NRC did not thoroughly evaluate the underlying science. However, we suggest that the NRC RfD is inappropriate because of the NRC’s “unconventional” approach.In contrast to Ginsberg and Rice (2005), we applaud the insightful and conclusive discussion of the science of perchlorate and the thyroid by the NRC (2005). The NRC concluded that human studies are the most relevant for risk assessment, and that the thyroid has a remarkable ability to compensate for iodine deficiency, so that hypothyroidism would be the first observed adverse effect. By definition, this is perchlorate’s critical effect (Faustman and Omenn 2001), although U.S. Environmental Protection Agency (EPA) methods allow for the use of a known and immediate precursor (the choice of immediate precursor is based on practice of using the highest no observed adverse effect level (NOAEL) of the critical effect and is codified in several places (e.g., Barnes and Dourson 1988, p. 473). The NRC also concluded that in healthy adults the perchlorate dose required to cause hypothyroidism would be > 0.4 mg/kg-day.In risk assessment parlance, this dose would be a NOAEL of the critical effect. The practice of risk assessment allows us to draw conclusions about public health in the absence of observable data and in the presence of scientific uncertainty. The traditional practice of developing RfD, a dose–response part of risk assessment (Barnes and Dourson 1988), would suggest two possible approaches to developing an RfD from the perchlorate data. The first would be to use the NOAEL of the critical effect from an adult population and apply uncertainty factors to account for sensitive populations and for lack of precision in defining a NOAEL. The second approach would be to use the NOAEL of an immediate precursor effect in a sensitive population and apply appropriate uncertainty factors.Using the first approach with the NRC NOAEL, the RfD would lie in the range of 0.04–0.004 mg/kg-day depending on the choice of uncertainty factor. Using the second approach, a NOAEL of 0.005 mg/kg-day (Gibbs et al. 2004) can be identified from thyroid hormone and goiter data in a sensitive population. The RfD based on this approach would lie near the value of 0.002 mg/kg-day proposed by Strawson et al. (2004).In contrast, the approach the NRC actually used was a nonstandard approach for developing an RfD based on the inhibition of iodine uptake, a distant precursor to the critical effect. This nonstandard approach yields a safe dose, but it is not an RfD, by definition, because, according to the NRC’s own scheme, it is not based on the critical effect or its known and immediate precursor.We continue to advocate that the best risk assessment approach for perchlorate is to use data collected from sensitive populations such as children and, in particular, the published and ongoing work in Chile. This is consistent with the NRC’s conclusion that the data from Chile could be considered in the evaluation of the U.S. experience with perchlorate in drinking water (NRC 2005). Specifically, the Chilean experience (Crump et al. 2000; Tellez et al. 2005) can be used to help frame the public debate in the United States, which suggests perchlorate water standards as low as 1 ppb. In Chile, perchlorate water concentrations of 100–120 ppb do not result in an exposure that would inhibit iodine uptake inhibition in adults. In fact, these concentrations have not caused any adverse effects in pregnant women, neonates, or older children exposed chronically. Following traditional RfD methods and using data from a sensitive human population results in an RfD that can be used with high confidence in the United States.ReferencesBarnes DG, Dourson ML. 1988. Reference dose (RfD): description and use in health risk assessments. Regul Toxicol Pharmacol 8:471-4863222488. Crossref, Medline, Google ScholarCrump C, Michaud P, Tellez R, Reyes C, Gonzalez G, Montgomery ELet al.nction in newborns or school-age children?J Occup Environ Med 42:603-61210874653. Crossref, Medline, Google ScholarFaustman EM, Omenn GS 2001. Risk Assessment. In: Casarett and Doull’s Toxicology: The Basic Science of Poisons (Klaassen CD, ed.). 6th ed. New York:McGraw-Hill, 92. Google ScholarGibbs JP, Narayanan L, Mattie DR. 2004. Crump et al. study among school children in Chile: subsequent urine and serum perchlorate levels are consistent with perchlorate in water in Taltal. J Occup Environ Med 46(6):516-51715213511. Crossref, Medline, Google ScholarGinsberg G, Rice D. 2005. The NAS perchlorate review: questions remain about the perchlorate RfD. Environ Health Perspect Environ Health Perspect 113:1117-1119doi:10.1289/ehp.8254. Link, Google ScholarNRC (National Research Council) 2005. Health Implications of Perchlorate Ingestion. Washington, DC:National Academies Press. Google ScholarStrawson J, Zhao Q, Dourson M. 2004. Reference dose for perchlorate based on thyroid hormone change in pregnant women as the critical effect. Regul Toxicol Pharmacol 39:44-6514746779. Crossref, Medline, Google ScholarTellez RT, Michaud P, Reyes C, Blount BC, Van Landingham CB, Crump KSet al.. 2005. Long-term environmental exposure to perchlorate through drinking water and thyroid function during pregnancy and the neonatal period. Thyroid 15(9):963-97516187904. Crossref, Medline, Google ScholarFiguresReferencesRelatedDetailsCited By Dohán O, Portulano C, Basquin C, Reyna-Neyra A, Amzel L and Carrasco N (2007) The Na + /I − symporter (NIS) mediates electroneutral active transport of the environmental pollutant perchlorate , Proceedings of the National Academy of Sciences, 10.1073/pnas.0707207104, 104:51, (20250-20255), Online publication date: 18-Dec-2007. DEARWENT S, MUMTAZ M, GODFREY G, SINKS T and FALK H (2006) Health Effects of Hazardous Waste, Annals of the New York Academy of Sciences, 10.1196/annals.1371.043, 1076:1, (439-448), Online publication date: 1-Sep-2006. Dasgupta P, Dyke J, Kirk A and Jackson W (2006) Perchlorate in the United States. Analysis of Relative Source Contributions to the Food Chain, Environmental Science & Technology, 10.1021/es061321z, 40:21, (6608-6614), Online publication date: 1-Nov-2006. Related articlesThe NAS Perchlorate Review: Ginsberg et al. Respond1 November 2005Environmental Health Perspectives Vol. 113, No. 11 November 2005Metrics About Article Metrics Publication History Originally published1 November 2005Published in print1 November 2005 Financial disclosuresPDF download License information EHP is an open-access journal published with support from the National Institute of Environmental Health Sciences, National Institutes of Health. All content is public domain unless otherwise noted. Note to readers with disabilities EHP strives to ensure that all journal content is accessible to all readers. However, some figures and Supplemental Material published in EHP articles may not conform to 508 standards due to the complexity of the information being presented. If you need assistance accessing journal content, please contact [email protected]. Our staff will work with you to assess and meet your accessibility needs within 3 working days.