Incorporation of fetal and child PFOA dosimetry in the derivation of health-based toxicity values

• Published in: Environment international Vol. 111; pp. 260 - 267
• Main Authors: Kieskamp, Kyra Kimberly, Worley, Rachel Rogers, McLanahan, Eva D., Verner, Marc-André
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01-02-2018
• Subjects: Adult; Animals; Breast Feeding; Caprylates - pharmacokinetics; Caprylates - toxicity; Child; Female; Fetus; Fluorocarbons - pharmacokinetics; Fluorocarbons - toxicity; Half-Life; Humans; Lactation; Maternal Exposure; Mice; Models, Biological; Pregnancy
• ISSN: 0160-4120; 1873-6750
• DOI: 10.1016/j.envint.2017.12.019

Multiple agencies have developed health-based toxicity values for exposure to perfluorooctanoic acid (PFOA). Although PFOA exposure occurs in utero and through breastfeeding, current health-based toxicity values have not been derived using fetal or child dosimetry. Therefore, current values may underestimate the potential risks to fetuses and nursing infants.
Using fetal and child dosimetry, we aimed to calculate PFOA maternal human equivalent doses (HEDs), corresponding to a developmental mouse study lowest observed adverse effect level (LOAEL, 1mg/kg/day). Further, we investigated the impact of breastfeeding duration and PFOA half-life on the estimated HEDs.
First, a pharmacokinetic model of pregnancy and lactation in mice was used to estimate plasma PFOA levels in pups following a maternal exposure to 1mg PFOA/kg/day for gestational days 1–17. Four plasma PFOA concentration metrics were estimated in pups: i) average prenatal; ii) average postnatal; iii) average overall (prenatal and postnatal); and iv) maximum. Then, Monte Carlo simulations were performed using a pharmacokinetic model of pregnancy and lactation in humans to generate distributions of maternal HEDs that would result in fetal/child plasma levels equivalent to those estimated in pups using the mouse model. Median (HED50) and 1st percentile (HED01) of calculated HEDs were calculated.
Estimated PFOA maternal HED50s ranged from 3.0×10−4 to 1.1×10−3mg/kg/day and HED01s ranged from 4.7×10−5 to 2.1×10−4mg/kg/day. All calculated HEDs were lower than the HED based on adult dosimetry derived by the Environmental Protection Agency (EPA) (5.3×10−3mg/kg/day).
Our results suggest that fetal/child dosimetry should be considered when deriving health-based toxicity values for potential developmental toxicants.
•We calculated human equivalent doses (HEDs) for PFOA based on fetal/child dosimetry.•Mouse and human pharmacokinetic models were used to calculate HEDs.•Calculated HED values ranged from 8.4×10−5 to 1.1×10−3mg/kg/day.•All calculated HEDs were lower than EPA's HED based on adult dosimetry.•HEDs should be based on fetal/child dosimetry for developmental toxicants.