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443 Yui H IBINO , et al.: Metabolism of TRI and TCEbut did in wild-type mice, suggesting the involvement of CYP2E1 in the metabolism from TCE to TCA. The constitutive expression of CYP2E1 in the liver of guinea pigs was greater in females than males. Conclusions: The sex difference in urinary TCA excretion after TRI and TCE treatments may be due to variation of the constitutive expression of CYP2E1.(J Occup Health 2013; 55: 443–449)Key words: Cytochrome P450 2E1, Guinea pig, Trichloroacetic acid, Trichloroethanol, TrichloroethyleneTrichloroethylene (TRI) has been used industrially as a degreasing agent for metal materials and lenses. Its use has been decreasing in the developed countries, however, it is still used in industrializing countries because of its superior degreasing power, noncombus-tibility and cheaper cost 1) .TRI is carcinogenic to humans 2) and poses potential adverse effects on the human central nervous system, liver, kidney, and immune system, and also on animal reproductive organs 3, 4) . Regarding its influence on the immune system, there are at least two kinds of patho-logical abnormality: one is generalized hypersensitive dermatitis complicated with severe hepatitis 5, 6) , and another is autoimmune hepatitis, which is observed in patients with scleroderma or systemic lupus erythe-matosus 7, 8) . In the former case, typical pathogenesis is to be lain in the onset time: this disease cannot occur immediately after TRI exposure, but only after repeated exposure to TRI for 3−4 weeks 9) . Therefore, patients with this disease may have delayed-type hypersensitivity.In mammals, TRI is metabolized mainly by cyto-chrome P450 (CYP) 2E1 to chloral hydrate 10, 11) , and Abstract: Sex Differences in Metabolism of Trichlo-roethylene and Trichloroethanol in Guinea Pigs: Yui H IBINO , et al. Department of Occupational and Envi-ronmental Health, Nagoya University Graduate School of Medicine—Objectives: Trichloroethylene (TRI) has the potential to cause generalized dermatitis complicated with hepatitis. The guinea pig maximization test (GPMT) also suggests that both TRI and its metab-olite trichloroethanol (TCE) exhibit immunogenicity and possible sex differences in guinea pigs. However, TRI and TCE metabolisms in guinea pigs have not been elucidated in detail. The first issue to clarify may be the sex differences in relation to the immunogenicity. Meth-ods: We collected urine from Hartley male and female guinea pigs 24 hours after intracutaneous injection of TRI, TCE or trichloroacetic acid (TCA) during a GPMT and measured the urinary metabolites by gas chroma-tography-mass spectrometry. Results: After TRI treat-ment, the amount of TCA was significantly greater in females than males, while there was no sex difference in the total amount (TCA + TCE). TCA was only detected in urine after TCA treatment. Interestingly, not only TCE but also TCA was detected in urine of both sexes after TCE treatment, and the amount of TCA was also greater in females than males. An additional experiment showed that TCE treatment did not result in the detection of urinary TCA in cytochrome P450 (CYP)2E1-null mice Sex Differences in Metabolism of Trichloroethylene and Trichloroethanol in Guinea PigsYui Hibino 1 , Hailan Wang 2 , Hisao Naito 1 , Na Zhao 2 , Dong Wang 1 , Xiaofang Jia 1 , Hongling Li 2 , Xiangrong Song 2 , Lili Liu 2 , Yongshun Huang 2 , Yuki Ito 3 , Hanlin Huang 2 , Michihiro Kamijima 3 and Tamie Nakajima 1,41 Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Japan, 2 Hospital for Occupational Diseases Control of Guangdong Province, Guangzhou, China, 3 Department of Occupational and Environmental Health, Nagoya City University Graduate School of Medical Sciences, Japan and 4 College of Life and Health Sciences, Chubu University, JapanJ Occup Health 2013; 55: 443–449Journal ofOccupational HealthReceived Apr 23, 2013; Accepted Jul 3, 2013Published online in J-STAGE Sept 10, 2013Correspondence to: H. Naito, Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8550, Japan (e-mail: naitoh@med.nagoya-u.ac.jp)Abbreviations: CYP2E1, cytochrome P450 2E1; GC-MS, gas chromatography-mass spectrometry; GPMT, guinea pig maximization test; TCA, trichloroacetic acid; TCE, trichloroethanol; TRI, trichloroethylene