Mono-n-Butyl Phthalate Distributes to the Mouse Ovary and Liver and Alters the Expression of Phthalate-Metabolizing Enzymes in Both Tissues

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 10days with vehicle (tocopherol-stripped corn oil) or DBP at 1, 10, and 1000mg/kg/day. Tissues and serum were collected at 2, 6, 12, and 24h 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 <= 6h and fell close to background levels by 24h post-exposure. Following the last repeated dose, MBP levels peaked at <= 2h and fell to background levels by 12h. 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.

Automated summary

Exposure to di-n-butyl phthalate (DBP) in mice has reproductive toxicity, with its metabolite mono-n-butyl phthalate (MBP) detected in the ovaries and livers, altering the expression of biotransformation enzymes.