Journal Article

Comparison of Pharmacokinetic Interactions and Physiologically Based Pharmacokinetic Modeling of PCB 153 and PCB 126 in Nonpregnant Mice, Lactating Mice, and Suckling Pups

Sun Ku Lee, Ying C. Ou and Raymond S. H. Yang

in Toxicological Sciences

Volume 65, issue 1, pages 26-34
Published in print January 2002 | ISSN: 1096-6080
Published online January 2002 | e-ISSN: 1096-0929 | DOI: http://dx.doi.org/10.1093/toxsci/65.1.26
Comparison of Pharmacokinetic Interactions and Physiologically Based Pharmacokinetic Modeling of PCB 153 and PCB 126 in Nonpregnant Mice, Lactating Mice, and Suckling Pups

More Like This

Show all results sharing these subjects:

  • Medical Toxicology
  • Toxicology (Non-medical)

GO

Show Summary Details

Preview

Polychlorinated biphenyls (PCBs) are ubiquitous environmental contaminants that can induce neurological defects in infants and children via placental and lactational transfer. To investigate the lactational transfer of PCBs and compare pharmacokinetic interactions among nonpregnant, lactating mice and suckling pups, quantitative time-course measurements of PCB accumulation in tissues were performed. On postnatal day 1, nonpregnant and lactating C57BL/6 mice were exposed to PCB 153 (2,2′,4,4′,5,5′-hexachlorobiphenyl, 20 mg/kg) alone or a mixture of PCB 153 (20 mg/kg) and PCB 126 (3,3′,4,4′,5-pentachlorobiphenyl, 0.2 mg/kg) by oral gavage. At 1, 3, 6, and 13 days after treatment, PCB 153 and PCB 126 were determined in nonpregnant and maternal tissues as well as in neonatal tissues by gas chromatography (GC). Coadministration of PCB 153 and PCB 126 increased PCB 153 retention in the liver and decreased PCB 153 accumulation in the fat of nonpregnant mice. Lactational transfer was confirmed to be an efficient elimination mechanism for the lactating mice but a major source of exposure in the pups. However, little or no significant pharmacokinetic interactions were observed in lactating mice and suckling pups. To describe pharmacokinetic interactions between PCB 153 and PCB 126, a physiologically based pharmacokinetic model for PCB 153 disposition was developed. The effects of PCB 126 on the fat content in liver and a diffusion permeation constant in fat were incorporated into the physiologically based pharmacokinetic (PBPK) model. This model successfully describes PCB 153 disposition altered by PCB 126 in nonpregnant mice.

Keywords: PCB; lactational transfer; pharmacokinetic interactions; mixture; PBPK modeling; fat content; diffusion permeation constant

Journal Article.  6586 words.  Illustrated.

Subjects: Medical Toxicology ; Toxicology (Non-medical)

Full text: subscription required

How to subscribe Recommend to my Librarian

Users without a subscription are not able to see the full content. Please, subscribe or login to access all content.