Impact/Purpose:

An issue of high priority for OPPTS is the class of perfluorinated surfactants that have anomalous behavior in risk assessment models. In order to provide OPPTS with a sound scientific basis for potential regulatory action on this class of chemicals, research efforts have been initiated by NHEERL to examine perfluorooctane sulfonate (PFOS) as a prototype for the class of organic fluorochemicals. As we gain a better understanding of this particular chemical, investigation will be extended to other related compounds such as PFOA and shorter carbon chains of the perfluoro-sulfonates and carboxylates to determine if certain characteristics are common to this class of chemicals.

Description:

A host of organic fluorochemicals increasingly are being used as surfactant coatings for fabrics and paper products, fire-fighting foams, electronic etching baths and insecticides. Concern for the potential toxicological risk of these types of chemicals had been minimal until recent documentation of the extensive distribution and persistence in both humans and wildlife of PFOS and PFOA, the primary degradation product of a widely-used class of sulfonyl-based fluorochemicals primarily manufactured by 3M amd telomer-based products from DuPont. There is some recent information, mostly derived from rodent and monkey studies, concerning the potential developmental, reproductive and systemic toxicity of PFOS. Alternative chemicals such as perfluorooctanoic acid (PFOA), or re-formulation of PFOS with shorter carbon chain products have emerged in the commercial market, but at present, little to no information is available concerning the environmental distribution and adverse health effect potentials of these substituting organic fluorochemicals. In order to assess the adverse health effect potential of these chemicals, this research will characterize the reproductive and developmental toxicity of PFOS in laboratory rodent models; ascertain whether the toxic effects are dependent on the windows of exposure during development; construct a pharmacokinetic (PK) model for PFOS; elucidate the modes and/or mechanisms of actions for PFOS that are related to its toxic effects; compare the reproductive and developmental toxicity among the various perfluorinated organic chemicals using relevant endpoints derived from the PFOS studies; and evaluate the usefulness of genomic and proteomic techniques to identify the mechanisms of PFOS toxicity and the applicability of these experimental tools to screen for common features/indicators of toxicity among the various perfluorinated organic chemicals. Compared to information derived from laboratory animals models, even less is known about the toxicity of the organic fluorochemicals in wildlife. This is of particular concern given the relatively high concentrations of PFOS that have been reported in mammals, birds and fish from locations throughout the world. To complement the above-described research, parallel studies will be undertaken to develop techniques for assessing the ecological risk of these perfluorinated organic chemicals. A critical aspect of this research will be identification of biological models (species, life stages, endpoints) that effectively reflect both conditions of the greatest sensitivity to PFOS, and result in data of utility for predicting population-level effects. This work will examine reproduction and development in a small fish model(s) and development in amphibians. Toxicology studies will be conducted with careful attention to dosimetry issues (uptake, metabolism, distribution) to enhance development of credible exposure approaches, as well as support derivation of models suitable for extrapolation across species. Characterization of dosimetry under controlled conditions will be complemented with hypothesis-driven analyses of key environmental samples to facilitate extrapolation from the laboratory to the field. Attempts will also be made to gain insights as to toxic MOA of PFOS through the use of DNA microarrays currently under development for amphibians.

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