title: Species differences in the metabolism of di(2-ethylhexyl) phthalate (DEHP) in several organs of mice, rats, and marmosets.
abstract: To clarify species differences in the metabolism of di(2-ethylhexyl) phthalate (DEHP) we measured the activity of four DEHP-metabolizing enzymes (lipase, UDP-glucuronyltransferase (UGT), alcohol dehydrogenase (ADH), and aldehyde dehydrogenase (ALDH)) in several organs (the liver, lungs, kidneys, and small intestine) of mice (CD-1), rats (Sprague-Dawley), and marmosets (Callithrix jacchus). Lipase activity, measured by the rate of formation of mono(2-ethylhexyl) phthalate (MEHP) from DEHP, differed by 27- to 357-fold among species; the activity was highest in the small intestines of mice and lowest in the lungs of marmosets. This might be because of the significant differences between Vmax/Km values of lipase for DEHP among the species. UGT activity for MEHP in the liver microsomes was highest in mice, followed by rats and marmosets. These differences, however, were only marginal compared with those for lipase activity. ADH and ALDH activity also differed among species; the activity of the former in the livers of marmosets was 1.6-3.9 times greater than in those of rats or mice; the activity of the latter was higher in rats and marmosets (2-14 times) than in mice. These results were quite different from those for lipase or UGT activity. Because MEHP is considered to be the more potent ligand to peroxisome proliferator-activated receptor alpha involved in different toxic processes, a possibly major difference in MEHP-formation capacity could be also considered on extrapolation from rodents to humans.
authors.affiliation: Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, 466-8550, Nagoya, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Ito
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yokota
authors.forename: Ruisheng
authors.initials: R
authors.lastname: Wang
authors.forename: Osamu
authors.initials: O
authors.lastname: Yamanoshita
authors.forename: Gaku
authors.initials: G
authors.lastname: Ichihara
authors.forename: Hailan
authors.initials: H
authors.lastname: Wang
authors.forename: Yoshimasa
authors.initials: Y
authors.lastname: Kurata
authors.forename: Kenji
authors.initials: K
authors.lastname: Takagi
authors.forename: Tamie
authors.initials: T
authors.lastname: Nakajima
mesh_terms: D000426:Alcohol Dehydrogenase / Q000378:metabolism; D000444:Aldehyde Dehydrogenase / Q000378:metabolism; D000818:Animals; D002144:Callithrix / Q000378:metabolism*; D004051:Diethylhexyl Phthalate / Q000493:pharmacokinetics*; D014453:Glucuronosyltransferase / Q000378:metabolism; D007421:Intestine, Small / Q000187:drug effects / Q000201:enzymology; D007668:Kidney / Q000187:drug effects / Q000201:enzymology; D008049:Lipase / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008168:Lung / Q000187:drug effects / Q000201:enzymology; D051379:Mice; D008815:Mice, Inbred Strains / Q000378:metabolism*; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D051381:Rats; D017207:Rats, Sprague-Dawley / Q000378:metabolism*; D013045:Species Specificity
chemical_list: D004051:Diethylhexyl Phthalate; D000426:Alcohol Dehydrogenase; D000444:Aldehyde Dehydrogenase; D014453:Glucuronosyltransferase; D008049:Lipase