Mono-n-butyl phthalate distributes to the mouse ovary and liver and alters the expression of phthalate-metabolizing enzymes in both tissues

Estela J. Jauregui, Jasmine Lock, Lindsay Rasmussen, Zelieann R. Craig

Research output: Contribution to journalArticlepeer-review

Abstract

Humans are exposed to phthalates daily via items such as personal care products and medications. Reproductive toxicity has been documented in mice exposed to di-n-butyl phthalate (DBP); however, quantitative evidence of its metabolite, mono-n-butyl phthalate (MBP), reaching the mouse ovary and its effects on hepatic and ovarian biotransformation enzymes in treated mice is still lacking. Liquid chromatography/tandem mass spectrometry (LC-MS/MS) was employed to quantify MBP levels in liver, serum, and ovary from mice treated with a single or repeated exposure to the parent compound, DBP. Adult CD-1 females were pipet fed once or for 10 days with vehicle (tocopherol-stripped corn oil) or DBP at 1, 10, and 1000 mg/kg/day. Tissues and serum were collected at 2, 6, 12, and 24 h after the single or final dose and subjected to LC-MS/MS. Ovaries and livers were processed for qPCR analysis of selected phthalate-associated biotransformation enzymes. Regardless of duration of exposure (single vs repeated), MBP was detected in the tissues of DBP-treated mice. In single dose mice, MBP levels peaked at ≤6 h and fell close to background levels by 24 h post-exposure. Following the last repeated dose, MBP levels peaked at ≤2 h and fell to background levels by 12 h. Hepatic and ovarian expression of Lpl, Aldh1a1, Adh1, Ugt1a6a, and Cyp1b1 were altered in DBP-treated mice in a time- and dose-specific manner. These findings confirm that MBP reaches the mouse liver and ovary after oral exposure to DBP and influences the expression of hepatic and ovarian phthalate-associated biotransformation enzymes.

Original languageEnglish (US)
Pages (from-to)117-127
Number of pages11
JournalToxicological Sciences
Volume183
Issue number1
DOIs
StatePublished - Sep 1 2021

Keywords

  • dibutyl phthalate
  • liver
  • ovary
  • phthalate-metabolizing enzymes
  • toxicology

ASJC Scopus subject areas

  • Toxicology

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