Environ. Sci. Technol. 2009, 43, 8699–8700
Response to Comment on “Occurrence and Potential Significance of Perfluorooctanoic Acid (PFOA) Detected in New Jersey Public Drinking Water Systems” Our health-based drinking water concentration for PFOA (1), 0.04 µg/L, is based on risk assessment approaches established by USEPA and NJ for development of drinking water concentrations protective for lifetime exposure. In contrast, the concentrations given by Tardiff (2) as safe for lifetime exposure, 0.9-7.7 µg/L (3), are not based on established risk assessment methodology, particularly regarding use of uncertainty factors (UFs). Tardiff criticizes the 100:1 ratio of internal dose (serum level) to external dose (drinking water concentration) based on observed data. However, Tardiff’s analysis (3) relies on a similar ratio predicted by an unpublished model (4) validated with the same data that are the source of the 100:1 ratio (5). The model predicts factors of 0.1 (4) and 0.127 (3) relating intake (µg/kg/day) to serum concentration (µg/mL) which, based on mean water ingestion of 17 mL/ kg/day (6), are equivalent to serum:water ratios of 167:1 and 133:1. Drinking water concentrations based on these ratios are lower than the concentration based on our 100:1 ratio. Although upper percentile exposure factors are typically used in risk assessment to protect public health, 100:1 represents the median observed ratio and is significantly below the ratio observed in young children and older adults (5). We determined that the 100:1 ratio applies to communities with lower water concentrations such as those detected in NJ, as well as in the highly exposed community where it was first reported (5) and that it is consistent with a published kinetic model (7). A value for PFOA’s human half-life is not required for our approach. Our health-based concentration, 0.04 µg/L, is based on noncancer effects, which were more sensitive than carcinogenicity at the 10-6 risk level (Table 4 of our paper). Thus, whether cancer risk assessment is based on a nonthreshold or threshold approach is irrelevant to our conclusion. We considered only studies included in USEPA’s 2005 draft risk assessment (8). More recent studies showing serious developmental effects in mice at lower doses, including some which are irreversible and/or not evident until adulthood (9), further support the conclusion that our health-based concentration is not overly stringent. Tardiff’s use of UFs does not follow established risk assessment methodology. We disagree that an interspecies UF of 10 is overly conservative. Many uncertainties exist about PFOA’s effects in animals and humans, and we concur with USEPA’s Science Advisory Board (10) that use of serum concentrations for interspecies comparison does not “sufficiently reduce overall uncertainty to eliminate or modify the current default value.” We strongly disagree that a subchronic-to-chronic UF is unnecessary because PFOA reaches steady-state during the study’s time period. This UF does not account for increased body-burden over time, but rather for toxicity resulting from longer exposure duration. Furthermore, Tardiff did not use the established UF for Lowest-Observed-Adverse-Effect-Level to NoObserved-Adverse-Effect-Level (3). 10.1021/es9027524 CCC: $40.75
Published on Web 10/05/2009
2009 American Chemical Society
As is the case for most risk assessments for environmental contaminants, we relied primarily on animal studies, with human data providing supporting information; we did not intend to comprehensively review the epidemiology literature. Tardiff’s statements that epidemiology studies have not found associations with reproductive endpoints or cancer and noncancer morbidity or mortality are incorrect and contradict his own discussions (3). Some occupational studies found associations, including with end points which could stem from increased cholesterol, while others did not (3). For example, increased risk of prostate cancer, cerebrovascular disease, and diabetes were found in exposed versus unexposed workers in one study (3). At another facility, significantly increased mortality compared to regional workers was found for diabetes in a 2008 study and for bladder and kidney cancer, acute myocardial infarction, aneurysm, and atherosclerosis in an earlier study (3). Significant associations with reproductive endpoints in the general population, including fetal growth and time to pregnancy, were found in some studies but not others (3); differing results may arise from degree of adjustment for confounders or differing PFOA serum concentrations in study populations. We did not accept the findings of the C8 Study “without qualification,” and we used the term “association” which does not imply causality. Our discussions of associations reported after adjustment for confounding factors were qualified by saying “these studies are ongoing and the results are currently undergoing peer review.” Our phrase, “...suggests that biological effects may occur in humans in the range of the target serum levels,” was properly qualified by “suggests” and “may occur” and is quoted out of context by Tardiff. Over time, the drinking water concentrations recommended by Tardiff, 0.9-7.7 µg/L, would result in serum concentrations of approximately 90-770 µg/L, about 20200 times above the general population’s mean, 4 µg/L. These serum concentrations exceed both target human serum levels based on application of standard UFs to animal data and serum levels associated with changes in multiple biological parameters in humans. Thus, lifetime exposure to these drinking water concentrations could potentially impact public health.
Literature Cited (1) Post, G. B.; Louis, J. B.; Cooper, K. R.; Boros-Russo, B. J.; Lippincott, R. L. Occurrence and potential significance of perfluorooctanoic acid (PFOA) detected in New Jersey public drinking water systems. Environ. Sci. Technol. 2009, 43 (12), 4547–4554. (2) Tardiff, R. G. Comment on “Occurrence and potential significance of perfluorooctanoic acid (PFOA) detected in New Jersey public drinking water systems”. Environ. Sci. Technol. 2009, 43, DOI:10.1021/es902326f. (3) Tardiff, R. G.; Carson, M. L.; Sweeney, L. M.; Kirman, C. R.; Tan, Y.-M.; Andersen, M.; Bevan, C.; Gargas, M. L. Derivation of a Drinking Water Equivalent Level (DWEL) related to the Maximum Contaminant Level Goal for PFOA, a persistent water soluble compound. Food Chem. Toxicol. 2009; DOI:10.1016/j.fct.2009.07.016. (4) Clewell, H. J. Application of pharmacokinetic modeling to estimate PFOA exposure associated with measured blood concentrations in human populations. Powerpoint presentation at Society for Risk Analysis Annual Meeting; 2006. (5) Emmett, E. A.; Shofer, F. S.; Zhang, H.; Freeman, D.; Desai, C.; Shaw, L. M. Community exposure to perfluorooctanoate: Relationships between serum concentrations and expoVOL. 43, NO. 22, 2009 / ENVIRONMENTAL SCIENCE & TECHNOLOGY
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sure sources. J. Occup. Environ. Med. 2006, 48, 759– 770. USEPA. Estimated Per Capita Water Ingestion and Body Weight in the US; EPA-822-R-00-001; Washington, DC, 2004. Harada, K.; Inoue, K.; Morikawa, A.; Yoshinaga, T.; Saito, N.; Koizumi, A. Renal clearance of perfluorooctane sulfonate and perfluorooctanoate in humans and their speciesspecific excretion. Environ. Res. 2005, 99, 253–261. Rosen, M. B.; Lau, C.; Corton, J. C. Does Exposure to Perfluoroalkyl Acids Present a Risk to Human Health? Toxicol. Sci. 2009, 111, 1–3. USEPA. Draft Risk Assessment of the Potential Human Health Effects Associated with Exposure to PFOA and Its Salts; Washington, DC, January 4, 2005. USEPA. SAB Review of EPA’s Draft Risk Assessment of Potential Human Health Effects Associated with PFOA and Its Salts; Washington, DC, May 30, 2006.
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Gloria B. Post Office of Science, New Jersey Department of Environmental Protection, Trenton, New Jersey
Keith R. Cooper Department of Biochemistry and Microbiology, Rutgers University, New Brunswick, New Jersey
Judith B. Louis and R. Lee Lippincott Office of Science, New Jersey Department of Environmental Protection, Trenton, New Jersey ES9027524
