The metabolism of mono-(2-ethylhexyl) phthalate (MEHP) and liver peroxisome proliferation in the hamster.
This study has investigated the in vivo metabolism of mono-(2-ethylhexyl) phthalate (MEHP), the initial metabolite of di-(2-ethylhexyl) phthalate in mammals, and the hepatic peroxisome proliferation induced by this compound following multiple oral administration to hamsters. Hamsters received [14C]-MEHP, by gavage, at doses of 50 and 500 mg/kg body wt on each of three consecutive days. Urine was collected every 24 hours and metabolite profiles were determined using capillary gas-chromatography. Multiple high doses of MEHP (500 mg/kg) induced a change in the relative proportions of metabolites produced. As previously reported for the rat, metabolites derived from sequential omega- following by beta-oxidation were increased. This increase was correlated with a parallel 3-fold increase in peroxisomal beta-oxidation--a marker for peroxisome proliferation. Hamsters were less responsive than rats to peroxisome proliferation elicited by MEHP. In contrast to the rat, a large proportion of hamster omega-1 oxidation products of MEHP (metabolites 6 and 9, mono (2-ethylhexyl-5-oxohexyl) phthalate and mono (2-ethyl-5-hydroxyhexyl) phthalate, respectively) were found as their glucuronide conjugates. This metabolic species difference may relate to differences in sensitivity to MEHP as a peroxisome proliferator. The relationship between metabolite conjugation, peroxisome proliferation and production of omega-oxidation metabolites is discussed.
Lhuguenot
J C
JC
Department de Biochimie et Toxicologie Alimentaires, ENS.BANA Université de Bourgogne, Campus universitaire, Dijon, France.
Mitchell
A M
AM
Elcombe
C R
CR
D000818:Animals; D006224:Cricetinae; D004051:Diethylhexyl Phthalate / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000378:metabolism* / Q000633:toxicity; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D008830:Microbodies / Q000187:drug effects* / Q000378:metabolism; D010084:Oxidation-Reduction; D010795:Phthalic Acids / Q000378:metabolism*; D051381:Rats
D010795:Phthalic Acids; D004051:Diethylhexyl Phthalate; C016599:mono-(2-ethylhexyl)phthalate