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Similarity of Bisphenol A Pharmacokinetics in Rhesus Monkeys and Mice: Relevance for Human Exposure

OBJECTIVE: Daily adult human exposure to bisphenol A (BPA) has been estimated at < 1 μg/kg, with virtually complete first-pass conjugation in the liver in primates but not in mice. We measured unconjugated and conjugated BPA levels in serum from adult female rhesus monkeys and adult female mice a...

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Autores principales: Taylor, Julia A., vom Saal, Frederick S., Welshons, Wade V., Drury, Bertram, Rottinghaus, George, Hunt, Patricia A., Toutain, Pierre-Louis, Laffont, Céline M., VandeVoort, Catherine A.
Formato: Texto
Lenguaje:English
Publicado: National Institute of Environmental Health Sciences 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3080921/
https://www.ncbi.nlm.nih.gov/pubmed/20855240
http://dx.doi.org/10.1289/ehp.1002514
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author Taylor, Julia A.
vom Saal, Frederick S.
Welshons, Wade V.
Drury, Bertram
Rottinghaus, George
Hunt, Patricia A.
Toutain, Pierre-Louis
Laffont, Céline M.
VandeVoort, Catherine A.
author_facet Taylor, Julia A.
vom Saal, Frederick S.
Welshons, Wade V.
Drury, Bertram
Rottinghaus, George
Hunt, Patricia A.
Toutain, Pierre-Louis
Laffont, Céline M.
VandeVoort, Catherine A.
author_sort Taylor, Julia A.
collection PubMed
description OBJECTIVE: Daily adult human exposure to bisphenol A (BPA) has been estimated at < 1 μg/kg, with virtually complete first-pass conjugation in the liver in primates but not in mice. We measured unconjugated and conjugated BPA levels in serum from adult female rhesus monkeys and adult female mice after oral administration of BPA and compared findings in mice and monkeys with prior published data in women. METHODS: Eleven adult female rhesus macaques were fed 400 μg/kg deuterated BPA (dBPA) daily for 7 days. Levels of serum dBPA were analyzed by isotope-dilution liquid chromatography–mass spectrometry (0.2 ng/mL limit of quantitation) over 24 hr on day 1 and on day 7. The same dose of BPA was fed to adult female CD-1 mice; other female mice were administered (3)H-BPA at doses ranging from 2 to 100,000 μg/kg. RESULTS: In monkeys, the maximum unconjugated serum dBPA concentration of 4 ng/mL was reached 1 hr after feeding and declined to low levels by 24 hr, with no significant bioaccumulation after seven daily doses. Mice and monkeys cleared unconjugated serum BPA at virtually identical rates. We observed a linear (proportional) relationship between administered dose and serum BPA in mice. CONCLUSIONS: BPA pharmacokinetics in women, female monkeys, and mice is very similar. By comparison with approximately 2 ng/mL unconjugated serum BPA reported in multiple human studies, the average 24-hr unconjugated serum BPA concentration of 0.5 ng/mL in both monkeys and mice after a 400 μg/kg oral dose suggests that total daily human exposure is via multiple routes and is much higher than previously assumed.
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spelling pubmed-30809212011-05-03 Similarity of Bisphenol A Pharmacokinetics in Rhesus Monkeys and Mice: Relevance for Human Exposure Taylor, Julia A. vom Saal, Frederick S. Welshons, Wade V. Drury, Bertram Rottinghaus, George Hunt, Patricia A. Toutain, Pierre-Louis Laffont, Céline M. VandeVoort, Catherine A. Environ Health Perspect Review OBJECTIVE: Daily adult human exposure to bisphenol A (BPA) has been estimated at < 1 μg/kg, with virtually complete first-pass conjugation in the liver in primates but not in mice. We measured unconjugated and conjugated BPA levels in serum from adult female rhesus monkeys and adult female mice after oral administration of BPA and compared findings in mice and monkeys with prior published data in women. METHODS: Eleven adult female rhesus macaques were fed 400 μg/kg deuterated BPA (dBPA) daily for 7 days. Levels of serum dBPA were analyzed by isotope-dilution liquid chromatography–mass spectrometry (0.2 ng/mL limit of quantitation) over 24 hr on day 1 and on day 7. The same dose of BPA was fed to adult female CD-1 mice; other female mice were administered (3)H-BPA at doses ranging from 2 to 100,000 μg/kg. RESULTS: In monkeys, the maximum unconjugated serum dBPA concentration of 4 ng/mL was reached 1 hr after feeding and declined to low levels by 24 hr, with no significant bioaccumulation after seven daily doses. Mice and monkeys cleared unconjugated serum BPA at virtually identical rates. We observed a linear (proportional) relationship between administered dose and serum BPA in mice. CONCLUSIONS: BPA pharmacokinetics in women, female monkeys, and mice is very similar. By comparison with approximately 2 ng/mL unconjugated serum BPA reported in multiple human studies, the average 24-hr unconjugated serum BPA concentration of 0.5 ng/mL in both monkeys and mice after a 400 μg/kg oral dose suggests that total daily human exposure is via multiple routes and is much higher than previously assumed. National Institute of Environmental Health Sciences 2011-04 2010-09-20 /pmc/articles/PMC3080921/ /pubmed/20855240 http://dx.doi.org/10.1289/ehp.1002514 Text en http://creativecommons.org/publicdomain/mark/1.0/ Publication of EHP lies in the public domain and is therefore without copyright. All text from EHP may be reprinted freely. Use of materials published in EHP should be acknowledged (for example, ?Reproduced with permission from Environmental Health Perspectives?); pertinent reference information should be provided for the article from which the material was reproduced. Articles from EHP, especially the News section, may contain photographs or illustrations copyrighted by other commercial organizations or individuals that may not be used without obtaining prior approval from the holder of the copyright.
spellingShingle Review
Taylor, Julia A.
vom Saal, Frederick S.
Welshons, Wade V.
Drury, Bertram
Rottinghaus, George
Hunt, Patricia A.
Toutain, Pierre-Louis
Laffont, Céline M.
VandeVoort, Catherine A.
Similarity of Bisphenol A Pharmacokinetics in Rhesus Monkeys and Mice: Relevance for Human Exposure
title Similarity of Bisphenol A Pharmacokinetics in Rhesus Monkeys and Mice: Relevance for Human Exposure
title_full Similarity of Bisphenol A Pharmacokinetics in Rhesus Monkeys and Mice: Relevance for Human Exposure
title_fullStr Similarity of Bisphenol A Pharmacokinetics in Rhesus Monkeys and Mice: Relevance for Human Exposure
title_full_unstemmed Similarity of Bisphenol A Pharmacokinetics in Rhesus Monkeys and Mice: Relevance for Human Exposure
title_short Similarity of Bisphenol A Pharmacokinetics in Rhesus Monkeys and Mice: Relevance for Human Exposure
title_sort similarity of bisphenol a pharmacokinetics in rhesus monkeys and mice: relevance for human exposure
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3080921/
https://www.ncbi.nlm.nih.gov/pubmed/20855240
http://dx.doi.org/10.1289/ehp.1002514
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