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

Details

• Alternative Title:
  Environ Int
• Personal Author:
  Kieskamp, Kyra Kimberly ; Worley, Rachel Rogers ; McLanahan, Eva D. ; Verner, Marc-André
• Description:
  Background:
  
  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.
  
  Objective:
  
  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, 1 mg/kg/day). Further, we investigated the impact of breastfeeding duration and PFOA half-life on the estimated HEDs.
  
  Methods:
  
  First, a pharmacokinetic model of pregnancy and lactation in mice was used to estimate plasma PFOA levels in pups following a maternal exposure to 1 mg 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.
  
  Results:
  
  Estimated PFOA maternal HED50s ranged from 3.0 × 10−4 to 1.1 × 10−3 mg/kg/day and HED01s ranged from 4.7 × 10−5 to 2.1 × 10−4 mg/kg/day. All calculated HEDs were lower than the HED based on adult dosimetry derived by the Environmental Protection Agency (EPA) (5.3 × 10−3 mg/kg/day).
  
  Conclusion:
  
  Our results suggest that fetal/child dosimetry should be considered when deriving health-based toxicity values for potential developmental toxicants.
  
  
• Subjects:
  Adult Animals Article Breast Feeding Caprylates Child Female Fetus Fluorocarbons Half-Life Humans Lactation Maternal Exposure Mice Models, Biological Pregnancy

  More +
• Source:
  Environ Int. 111:260-267
• Pubmed ID:
  29325971
• Pubmed Central ID:
  PMC6234970
• Document Type:
  Journal Article
• Funding:
  CC999999/Intramural CDC HHS/United States
• Volume:
  111
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:0d8f5a4dbee22a3f7d5f7c99d28793c66360ce9cd588bee093e20e8bde87053c
• Download URL:
  https://stacks.cdc.gov/view/cdc/60716/cdc_60716_DS1.pdf
• File Type:
  [PDF - 436.87 KB ]