Allyl isothiocyanate: comparative disposition in rats and mice

Area of Science:

• Toxicology
• Metabolism
• Comparative Biology

Background:

• Allyl isothiocyanate (AITC), found in mustard oil, induces urinary bladder tumors in male rats but not females or mice.
• Investigating sex and species differences in AITC disposition is crucial for understanding toxicity susceptibility.

Purpose of the Study:

• To compare the disposition of AITC in male and female rats and mice.
• To identify potential sex or species differences that explain AITC's toxicity.

Main Methods:

• Administered radiolabeled AITC to rats and mice.
• Measured AITC-derived radioactivity in tissues and excreta (urine, feces, exhaled air).
• Identified urinary metabolites using NMR spectroscopy.

Main Results:

• AITC was rapidly cleared from tissues; <5% remained within 24 hours.
• Highest AITC-derived radioactivity concentrated in male rat bladders.
• Primary excretion routes were urine (70-80%) and exhaled air (13-15%).
• Rats and mice excreted N-acetyl-S-(N-allylthiocarbamoyl)-L-cysteine as a major urinary metabolite.
• Female rats excreted over twice the urine volume of males, with sex-related variations in metabolite profiles.

Conclusions:

• Male rat bladders showed the highest AITC-derived radioactivity concentration.
• Excretion of more concentrated AITC metabolites in male rat urine may cause bladder toxicity.