Metabolomics approach to risk assessment: methoxyclor exposure in rats.
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 (1)H 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 ((1)H 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 manner which, was confirmed by the uterotrophic assay. MTC [50, 100, or 200 m g/kg/d, orally (p.o.) or subcutaneously (s.c.)] was administered to ovariectomized 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 s.c. route, only a high dose of 200 mg MTC/kg induced a significant increase in uterine and vaginal weight. (1)H 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.
Kim
Kyu-Bong
KB
Korea Food and Drug Administration, Korea Food and Drug Administration, Seoul, South Korea.
Kim
Seon Hwa
SH
Um
So Young
SY
Chung
Myeon Woo
MW
Oh
Ji Seon
JS
Jung
Seung-Chul
SC
Kim
Tae Sung
TS
Moon
Hyun Joo
HJ
Han
Soon Young
SY
Oh
Hye Young
HY
Lee
Byung Mu
BM
Choi
Ki Hwan
KH
D000284:Administration, Oral; D000818:Animals; D004305:Dose-Response Relationship, Drug; D052244:Endocrine Disruptors / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity; D005260:Female; D020869:Gene Expression Profiling; D007279:Injections, Subcutaneous; D007306:Insecticides / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity*; D055432:Metabolomics / Q000379:methods*; D008731:Methoxychlor / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity*; D015394:Molecular Structure; D051381:Rats; D017207:Rats, Sprague-Dawley; D012307:Risk Factors
D052244:Endocrine Disruptors; D007306:Insecticides; D008731:Methoxychlor