title: Sex differences in metabolism of trichloroethylene and trichloroethanol in guinea pigs.
abstract: OBJECTIVE
  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 metabolite 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.
  
  
  METHODS
  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 chromatography-mass spectrometry.
  
  
  RESULTS
  After TRI treatment, 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 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.
authors.affiliation: Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine.
authors.forename: Yui
authors.initials: Y
authors.lastname: Hibino
authors.forename: Hailan
authors.initials: H
authors.lastname: Wang
authors.forename: Hisao
authors.initials: H
authors.lastname: Naito
authors.forename: Na
authors.initials: N
authors.lastname: Zhao
authors.forename: Dong
authors.initials: D
authors.lastname: Wang
authors.forename: Xiaofang
authors.initials: X
authors.lastname: Jia
authors.forename: Hongling
authors.initials: H
authors.lastname: Li
authors.forename: Xiangrong
authors.initials: X
authors.lastname: Song
authors.forename: Lili
authors.initials: L
authors.lastname: Liu
authors.forename: Yongshun
authors.initials: Y
authors.lastname: Huang
authors.forename: Yuki
authors.initials: Y
authors.lastname: Ito
authors.forename: Hanlin
authors.initials: H
authors.lastname: Huang
authors.forename: Michihiro
authors.initials: M
authors.lastname: Kamijima
authors.forename: Tamie
authors.initials: T
authors.lastname: Nakajima
mesh_terms: D000485:Allergens / Q000378:metabolism* / Q000633:toxicity / Q000652:urine; D000818:Animals; D017449:Dermatitis, Allergic Contact / Q000276:immunology; D005023:Ethylene Chlorohydrin / Q000031:analogs & derivatives* / Q000378:metabolism / Q000633:toxicity / Q000652:urine; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006168:Guinea Pigs; D007273:Injections, Intramuscular; D008297:Male; D014238:Trichloroacetic Acid / Q000378:metabolism* / Q000633:toxicity / Q000652:urine; D014241:Trichloroethylene / Q000378:metabolism* / Q000633:toxicity / Q000652:urine
chemical_list: D000485:Allergens; D014241:Trichloroethylene; D014238:Trichloroacetic Acid; D005023:Ethylene Chlorohydrin; C005849:2,2,2-trichloroethanol