skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Distribution of bisphenol A into tissues of adult, neonatal, and fetal Sprague-Dawley rats

Abstract

Bisphenol A (BPA) is an important industrial chemical used in the manufacture of polycarbonate plastic products and epoxy resin-based food can liners. The presence of BPA metabolites in urine of > 90% of Americans aged 6-60 suggests ubiquitous and frequent exposure in the range of 0.02-0.2 {mu}g/kg bw/d (25th-95th percentiles). The current study used LC/MS/MS to measure placental transfer and concentrations of aglycone (receptor-active) and conjugated (inactive) BPA in tissues from Sprague-Dawley rats administered deuterated BPA (100 {mu}g/kg bw) by oral and IV routes. In adult female rat tissues, the tissue/serum concentration ratios for aglycone BPA ranged from 0.7 in liver to 5 in adipose tissue, reflecting differences in tissue perfusion, composition, and metabolic capacity. Following IV administration to dams, placental transfer was observed for aglycone BPA into fetuses at several gestational days (GD), with fetal/maternal serum ratios of 2.7 at GD 12, 1.2 at GD 16, and 0.4 at GD 20; the corresponding ratios for conjugated BPA were 0.43, 0.65, and 3.7. These ratios were within the ranges observed in adult tissues and were not indicative of preferential accumulation of aglycone BPA or hydrolysis of conjugates in fetal tissue in vivo. Concentrations of aglycone BPA in GD 20 fetalmore » brain were higher than in liver or serum. Oral administration of the same dose did not produce measurable levels of aglycone BPA in fetal tissues. Amniotic fluid consistently contained levels of BPA at or below those in maternal serum. Concentrations of aglycone BPA in tissues of neonatal rats decreased with age in a manner consistent with the corresponding circulating levels. Phase II metabolism of BPA increased with fetal age such that near-term fetus was similar to early post-natal rats. These results show that concentrations of aglycone BPA in fetal tissues are similar to those in other maternal and neonatal tissues and that maternal Phase II metabolism, especially following oral administration, and fetal age are critical in reducing exposures to the fetus. - Highlights: > Studies of BPA in rat tissues showed placental transfer and fetal metabolism. > Levels in fetus are similar to maternal tissues. > Fetal metabolism can reduce levels.« less

Authors:
 [1]; ;  [1];  [2];  [1]
  1. Division of Biochemical Toxicology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR 72079 (United States)
  2. Center for Devices and Radiological Health, U.S. Food and Drug Administration, Silver Spring, MD (United States)
Publication Date:
OSTI Identifier:
21587836
Resource Type:
Journal Article
Journal Name:
Toxicology and Applied Pharmacology
Additional Journal Information:
Journal Volume: 255; Journal Issue: 3; Other Information: DOI: 10.1016/j.taap.2011.07.009; PII: S0041-008X(11)00269-9; Copyright (c) 2011 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0041-008X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ADIPOSE TISSUE; AMNIOTIC FLUID; CONCENTRATION RATIO; FETUSES; HYDROLYSIS; IN VIVO; LIVER; METABOLISM; METABOLITES; ORAL ADMINISTRATION; POLYCARBONATES; RATS; ANIMAL TISSUES; ANIMALS; BIOLOGICAL MATERIALS; BODY; BODY FLUIDS; CARBON COMPOUNDS; CARBONATES; CHEMICAL REACTIONS; CONNECTIVE TISSUE; DECOMPOSITION; DIGESTIVE SYSTEM; DIMENSIONLESS NUMBERS; GLANDS; INTAKE; LYSIS; MAMMALS; MATERIALS; ORGANIC COMPOUNDS; ORGANIC POLYMERS; ORGANS; OXYGEN COMPOUNDS; POLYMERS; RODENTS; SOLVOLYSIS; VERTEBRATES

Citation Formats

Doerge, Daniel R., E-mail: daniel.doerge@fda.hhs.gov, Twaddle, Nathan C., Vanlandingham, Michelle, Brown, Ronald P., and Fisher, Jeffrey W. Distribution of bisphenol A into tissues of adult, neonatal, and fetal Sprague-Dawley rats. United States: N. p., 2011. Web. doi:10.1016/j.taap.2011.07.009.
Doerge, Daniel R., E-mail: daniel.doerge@fda.hhs.gov, Twaddle, Nathan C., Vanlandingham, Michelle, Brown, Ronald P., & Fisher, Jeffrey W. Distribution of bisphenol A into tissues of adult, neonatal, and fetal Sprague-Dawley rats. United States. doi:10.1016/j.taap.2011.07.009.
Doerge, Daniel R., E-mail: daniel.doerge@fda.hhs.gov, Twaddle, Nathan C., Vanlandingham, Michelle, Brown, Ronald P., and Fisher, Jeffrey W. Thu . "Distribution of bisphenol A into tissues of adult, neonatal, and fetal Sprague-Dawley rats". United States. doi:10.1016/j.taap.2011.07.009.
@article{osti_21587836,
title = {Distribution of bisphenol A into tissues of adult, neonatal, and fetal Sprague-Dawley rats},
author = {Doerge, Daniel R., E-mail: daniel.doerge@fda.hhs.gov and Twaddle, Nathan C. and Vanlandingham, Michelle and Brown, Ronald P. and Fisher, Jeffrey W.},
abstractNote = {Bisphenol A (BPA) is an important industrial chemical used in the manufacture of polycarbonate plastic products and epoxy resin-based food can liners. The presence of BPA metabolites in urine of > 90% of Americans aged 6-60 suggests ubiquitous and frequent exposure in the range of 0.02-0.2 {mu}g/kg bw/d (25th-95th percentiles). The current study used LC/MS/MS to measure placental transfer and concentrations of aglycone (receptor-active) and conjugated (inactive) BPA in tissues from Sprague-Dawley rats administered deuterated BPA (100 {mu}g/kg bw) by oral and IV routes. In adult female rat tissues, the tissue/serum concentration ratios for aglycone BPA ranged from 0.7 in liver to 5 in adipose tissue, reflecting differences in tissue perfusion, composition, and metabolic capacity. Following IV administration to dams, placental transfer was observed for aglycone BPA into fetuses at several gestational days (GD), with fetal/maternal serum ratios of 2.7 at GD 12, 1.2 at GD 16, and 0.4 at GD 20; the corresponding ratios for conjugated BPA were 0.43, 0.65, and 3.7. These ratios were within the ranges observed in adult tissues and were not indicative of preferential accumulation of aglycone BPA or hydrolysis of conjugates in fetal tissue in vivo. Concentrations of aglycone BPA in GD 20 fetal brain were higher than in liver or serum. Oral administration of the same dose did not produce measurable levels of aglycone BPA in fetal tissues. Amniotic fluid consistently contained levels of BPA at or below those in maternal serum. Concentrations of aglycone BPA in tissues of neonatal rats decreased with age in a manner consistent with the corresponding circulating levels. Phase II metabolism of BPA increased with fetal age such that near-term fetus was similar to early post-natal rats. These results show that concentrations of aglycone BPA in fetal tissues are similar to those in other maternal and neonatal tissues and that maternal Phase II metabolism, especially following oral administration, and fetal age are critical in reducing exposures to the fetus. - Highlights: > Studies of BPA in rat tissues showed placental transfer and fetal metabolism. > Levels in fetus are similar to maternal tissues. > Fetal metabolism can reduce levels.},
doi = {10.1016/j.taap.2011.07.009},
journal = {Toxicology and Applied Pharmacology},
issn = {0041-008X},
number = 3,
volume = 255,
place = {United States},
year = {2011},
month = {9}
}