A transgenerational toxicokinetic model and its use in derivation of Minnesota PFOA water guidance

Abstract

Minnesota has been grappling with extensive per- and polyfluoroalkyl substances (PFASs) groundwater contamination since 2002, in a major metropolitan setting. As toxicological information has accumulated for these substances, the public health community has become increasingly aware of critically sensitive populations. The accumulation of some PFAS in women of childbearing age, and the placental and breastmilk transfer to their offspring, require new risk assessment methods to protect public health. The traditional water guidance paradigm is inadequate to address maternal-to-infant transfer of accumulated levels of perfluorooctanoate (PFOA), in particular. Even short exposures during infancy have dramatic impacts on serum levels for many years. In addition, developmental effects are the critical effects anchoring recent risk assessments. In response, the Minnesota Department of Health created an Excel-based model that incorporates chemical-specific properties and exposure parameters for early life stages. Serum levels were assessed in both formula-fed and breastfed infants, with placental transfer in both scenarios. Peak breastfed infant serum levels were 4.4-fold higher than in formula-fed infants, with both of these scenarios producing serum levels in excess of the adult steady-state level. The development and application of this model to PFOA are described.

Risk to human health related to the presence of perfluoroalkyl substances in food

“…Moreover, both models can reproduce with accuracy the observed value reported by Fromme et al. (Goeden et al., ).…”

Tap Water Contributions to Plasma Concentrations of Poly- and Perfluoroalkyl Substances (PFAS) in a Nationwide Prospective Cohort of U.S. Women

“…TK models can be used to assess the relative importance of different exposure sources (Lorber and Egeghy 2011; Trudel et al. 2008; Vestergren and Cousins 2009) and to establish benchmark doses for PFAS from toxicological and epidemiological studies (Goeden et al 2019). For example, Grandjean and Budtz-Jørgensen (2013) used such modeling to suggest a health advisory level for perfluorooctanoic acid (PFOA) in drinking water of 1 ng/L based on vaccine antibody responses in children and an uncertainty factor of 10 (Grandjean and Budtz-Jørgensen 2013).…”

Regulation of Perfluorooctanoic Acid (PFOA) and Perfluorooctane Sulfonic Acid (PFOS) in Drinking Water: A Comprehensive Review

“…At a relative source contribution of 50%, the calculated serum concentration allocated or 'allowed' to result from ingestion of water was 0.065 mg/L. The water concentration calculated to maintain a PFOA serum concentration at or below 0.065 mg/L throughout life for the formula-fed reasonable maximally exposed (RME) scenario and the breast-fed RME scenario was 0.15 µg/L and 0.035 µg/L, respectively [7]. Based on this assessment MDH set its final health-based PFOA guidance value at 0.035 µg/L.…”

“…An Excel-based toxicokinetic model was constructed and applied to derive a guidance value for PFOA. The model incorporates body burden at birth (placental transfer), ingestion of breastmilk, and age-specific water intake rates [7]. At a relative source contribution of 50%, the calculated serum concentration allocated or 'allowed' to result from ingestion of water was 0.065 mg/L.…”

“…In 2009 the US Environmental Protection Agency (USEPA) identified PFOA and PFOS as contaminants of potential concern in drinking water. Major PFOA and PFOS contamination of the environment and drinking water supplies had been discovered in several states, in particular West Virginia [5], Ohio [6], and Minnesota [7]. PFOA and PFOS were included on the third drinking water contaminant candidate list (CCL) [8].…”