The NAS perchlorate review: second-guessing the experts.

The Committee to Assess the Health Implications of Perchlorate Ingestion [National Academy of Sciences (NAS)] released its final report [National Research Council (NRC) 2005] in January 2005, recommending a reference dose (RfD) for perchlorate of 0.0007 mg/kg-day. In a commentary published online on 25 May 2005, Ginsberg and Rice (2005) criticized the adequacy of the NAS committee's scientific deliberations, mischaracterizing the studies reviewed by the committee and second-guessing its conclusions. Ginsberg and Rice (2005) implied that the U.S. Environmental Protections Agency's (EPA's) previous draft RfD of 0.00003 mg/kg-day (U.S. EPA 2002)--and by inference the Massachusetts perchlorate risk assessment [Massachusetts Department of Environmental Protection (Mass DEP) 2004] that mirrored the U.S. EPA's approach and which Ginsberg and Rice peer reviewed--is more scientifically defensible.

The NAS committee was composed of 15 leading physicians and scientists with combined range of expertise to evaluate every scientific aspect of the perchlorate database and of the U.S. EPA's assessment of that database. The makeup of this committee and its credentials are available on the NAS website (NAS 2004). The NAS committee studied and deliberated for more than 15 months before issuing its report. Those deliberations included three public meetings during which it accepted verbal and/or written comments from the U.S. EPA, other government agencies, industry, states, environmental groups, and attorneys. After careful study and consideration of the scientific studies that formed the basis for the U.S. EPA's 2002 draft RfD as well as the 2004 Massachusetts risk assessment (Mass DEP 2004), the NAS committee considered

   several of the animal studies ... to be flawed in
   their design and execution. Conclusions based on
   those studies, particularly the neurodevelopmental
   studies, were not supported by the results of the
   studies.

Although Ginsberg and Rice (2005) implied that the NAS committee should have considered the threshold for measurable iodine uptake inhibition "adverse" and that the NAS inadvertently left out the "A" in NOAEL (no observed adverse effect level), the committee decisively stated that "inhibition of iodide uptake by the thyroid clearly is not an adverse effect." The committee carefully considered the issue of a NOEL (no observed effect level) and a NOAEL. Based on a clinical study of patients receiving perchlorate long term, the NAS established the NOAEL as 0.4 mg/kg-day (57 times higher than its identified NOEL).

Ginsberg and Rice (2005) further expressed concerns regarding perchlorate in breast milk and the subsequent possibility of decreased breast milk iodine, citing Kirk et al. (2005) and Gibbs (2004). Kirk et al. (2005) reported perchlorate and iodide levels in breast milk samples and noted that "if we take all the available data, there is no meaningful correlation between the perchlorate and iodide levels in breast milk." The study from Chile that Ginsberg and Rice refer to as Gibbs (2004) is now published as Tellez et al. (2005). The study found that iodine nutrition of pregnant women in Chile is very similar to that in the United States. Tellez et al. (2005) found no maternal or neonatal perchlorate-related thyroid effects or decreases in breast milk iodine with perchlorate doses spanning the 0.0007-0.007 mg/kg-day range.

Ginsberg and Rice (2005) argued that perchlorate database deficiencies require an additional uncertainty factor of 3-10 because of key data gaps, citing breast milk concerns and the extrapolation from a 14-day exposure study to chronic exposure. The NAS committee (NRC 2005) considered this and concluded that

   if inhibition of iodide uptake by the thyroid is
   duration-dependent, the effect should decrease
   rather than increase with time, because compensation
   would increase the activity of the sodiumiodide
   symporter and therefore increase iodide
   transport into the thyroid.

Evidence has subsequently shown this to be the case (Braverman et al. 2005).

The California EPA perchlorate risk assessment (California EPA 2004) relied on the same studies as the NRC report (NRC 2005). The "point of departure" was based on iodine uptake inhibition by Greet et al. (2002), and a total uncertainty factor of 10 was applied to account for interindividual variability. After reviewing the NRC report (NRC 2005), the California EPA elected not to change its risk assessment or public health goal (California EPA 2005).

In summary, the concerns presented by Ginsberg and Rice (2005) have already been addressed thoroughly by experts on perchlorate and thyroid toxicology and were found to be unsubstantiated. The NAS committee and other experts came to this conclusion based on a comprehensive review of the science in the field, not based entirely on an individual study, which has been mischaracterized by Ginsberg and Rice.

Kerr-McGee Chemical LLC previously manufactured ammonium perchlorate at Henderson, Nevada, and currently is remediating perchlorate at that site. J.G. has co-authored several perchlorate studies, as has S.H.L. S.H.L. is a consultant to companies that manufacture and/or use perchlorates. A.E. works with S.H.L. at Consultants in Epidemiology & Occupational Health, LLC.

REFERENCES

Braverman LE, He X, Pino S, Cross M, Magnani B, Lamm SH, et al. 2005. The effect of perchlorate, thiocyanate, and nitrate on thyroid function in workers exposed to perchlorate long-term. J Clin Endocrinol Metab 90(2):700-706.

California EPA (Environmental Protection Agency). 2004. Public Health Goals for Perchlorate in Drinking Water. Available: http://www.oehha.org/water/phg/pdf/ finalperchlorate31204.pdf [accessed 21 June 2005].

California EPA (Environmental Protection Agency). 2005. State's Drinking Water Goal For Perchlorate Consistent With Findings of Major Federal Study. Available: http:// www.oehha.ca.gov/public_info/press/perchloratepressrel040105.pdf [accessed 21 June 2005].

Gibbs JP. 2004. Chronic Environmental Exposure to Perchlorate in Drinking Water and Thyroid Function during Pregnancy and the Neonatal Period. 8 August 2004 Update. Letter to Richard Johnston, Chair NAS Perchlorate Committee, from John P. Gibbs, Kerr-McGee Corp.

Ginsberg G, Rice D. 2005. The NAS perchlorate review: questions remain about the perchlorate RfD. Environ Health Perspect 113:1117-1119; doi:10.1289/ehp.8254 [Online 25 May 2005].

Greer MA, Goodman G, Pleus RC, Greer SE. 2002. Health effects assessment for environmental perchlorate contamination: the dose response for inhibition of thyroidal radioiodine uptake in humans. Environ Health Perspect 110:927-937.

Kirk AB, Mattinelango PK, Tian K, Dutt, A, Smith EE, Dasgupta PK. 2005. Perchlorate and iodide in dairy and breast milk. Environ Sci Technol 39:2011-2017.

Mass DEP (Massachusetts Department of Environmental Protection). 2004 Final Draft. Perchlorate Toxicological Profile and Health Assessment. Available: http://www. mass.gov/dep/ors/files/perchlor.pdf [accessed 22 June 2005].

NAS (National Academy of Sciences). 2004. Committee to Assess the Health Implications of Perchlorate Ingestion. Available: http://www4.nas.edu/cp.nsf/Projects%20_ by%20_PIN/BEST-K-03-05-A?OpenDocument [accessed 21 June 2005].

NRC (National Research Council). 2005. Health Implications of Perchlorate Ingestion. Washington, DC:National Academies Press.

Tellez RT, Michaud P, Reyes C, Blount BC, Van Landingham CB, Crump KS, et al. 2005. Long-term environmental exposure to perchlorate through drinking water and thyroid function during pregnancy and the neonatal period. Thyroid 15(9):963-975.

U.S. EPA. 2002. Perchlorate Environmental Contamination: Toxicological Review and Risk Characterization. External Review Draft. NCEA-1-0503. Washington, DC: National Center for Environmental Assessment, Office of Research and Development.

John P. Gibbs

Kerr-McGee Shared Services LLC

Oklahoma City, Oklahoma

E-mail: [e-mail]

Arnold Engel

Steven H. Lamm

Consultants in Epidemiology &

Occupational Health, LLC

Washington, DC