DOSE-DEPENDENT EXCRETION OF UNCONJUGATED 3-BUTENE-1,2-DIOL MEASURED IN URINE WITH A GC/MS AFTER 1,3-BUTADIENE EXPOSURE

Abstract

1,3-Butadiene is clearly carcinogenic, and it has a complex pathway of metabolic transformation, as it forms several reactive intermediates. We have previously shown that butadiene diolepoxide is a key metabolite in DNA and hemoglobin adduct formation. Here we report the analysis of 3-buten-1,2-diol—the precursor of butadiene diolepoxide—in urine samples from rats exposed to butadiene by means of inhalation. Urine samples were extracted with isopropanol, and extracts were analyzed using a gas chromatograph and mass spectrometer. Selected ion monitoring was performed by using ion 57 m/z; a retention time allowed reliable analysis. The analysis showed a linear excretion of 3-buten-1,2-diol during the 5 days of 6-h exposures and 18-h recovery times between exposures. The daily correlation coefficient (r) values varied from 0.9945 to 0.9999. A 6-h exposure of rats to 1000 ppm 1,3-butadiene resulted in a mean urinary concentration of 3-buten-1,2-diol of approximately 38 mg/L. Urine samples were also collected during the recovery times, and the extracts were analyzed. The linearity of the excretion during the recovery times showed r values ranging from 0.6932 to 0.9813; 0.5 mg/L of 3-butene-1,2-diol was detected in urine samples excreted after exposure to 1000 ppm 1,3-butadiene. The data demonstrated that butadiene monoepoxide was converted into 3-buten-1,2-diol which, to some extent, was excreted in urine in a nonconjugated form. The excretion of 3-buten-1,2-diol was prompt, with about 98% of the compound being excreted during exposure.

We acknowledge Mr. Yrjö Peltonen for his very skillful assistance in maintaining a stable BD atmosphere during animal exposure, and we thank Ms. Marja Pihlaja for the animal care.

Keywords: :

• conjugation
• metabolites
• 1,3-butadiene
• 3-butene-1,2-diol

Notes

We acknowledge Mr. Yrjö Peltonen for his very skillful assistance in maintaining a stable BD atmosphere during animal exposure, and we thank Ms. Marja Pihlaja for the animal care.