Metabolomics Approach to Risk Assessment: Methoxyclor Exposure in Rats

Abstract

The primary objective of this study was to develop exposure biomarkers that “correlate with the endocrine-disrupting effects induced by methoxyclor (MTC), an organochlorine pesticide, using” urinary ¹H nuclear magnetic resonance (NMR) spectral data. Exposure biomarkers play an important role in risk assessment. MTC is an environmental endocrine disruptor with estrogenic, anti-estrogenic, and anti-androgenic properties. A new approach of proton nuclear magnetic resonance (¹H NMR) urinalysis using pattern recognition was proposed for exposure biomarkers of MTC in female rats. The endocrine disruptor was expected to induce estrogenic effects in a dose dependent mamer which, was confirmed by the uterotrophic assay. MTC [50, 100, or 200 m g/kg/d, orally (po) or subcutaneously (sc)] was administered to ovarectomized female Sprague-Dawley (SD) rats for 3 d consecutively and urine was collected every 24 h. The animals were sacrificed 24 h after the last dose. All animals treated orally with MTC showed a significant increase in uterine and vaginal weight at all doses. However, in the sc route, only a high dose of 200 mg MTC/kg induced a significant increase in uterine and vaginal weight. ¹H NMR spectroscopy revealed evident separate clustering between pre- and post-treatment groups using global metabolic profiling through principal component analysis (PCA) and partial least square (PLS) discrimination analysis (DA) after different exposure routes. With targeted profiling, the endogenous metabolites of acetate, alanine, benzoate, lactate, and glycine were selected as putative exposure biomarkers for MTC. Data suggest that the proposed putative exposure biomarkers may be useful in a risk assessment of the endocrine-disrupting effects produced by MTC.

This research was supported by a grant (07151KFDA637) from the Korea Food and Drug Administration in 2007. The authors thank Dr. Geum-Sook Hwang for technical assistance in NMR urinalysis at Korea Basic Science Institute (Seoul, Korea).