title: Effect of a Large Dose of Di (2-ethylhexyl) phthalate (DEHP) on Hepatic Peroxisome in Cynomolgus Monkeys (Macaca Fascicularis).
abstract: To elucidate the effect of a large dose of di (2-ethylhexyl) phthalate (DEHP), a plasticizer and peroxisome proliferator-activated receptor-α (PPARα) agonist, on hepatic peroxisomes, we orally administered 1,000 mg/kg/day, once daily, to 3 male and 4 female cynomolgus monkeys for 28 days consecutively. Light-microscopic and electron microscopic examinations of the liver were carried out in conjunction with measurement of the hepatic fatty acid β-oxidation system (FAOS), carnitine acetyltransferase (CAT) and carnitine palmitoyltransferase (CPT) activities, which are peroxisomal and/or mitochondrial enzyme activities. Electron microscopically, enlargement of the mitochondria was observed with lamellar orientation of the cristae along the major axis. Although the number of peroxisomes showed a tendency to increase when compared with those in a biopsied specimen before treatment, no abnormality in morphology was observed. A slight increase in CPT activity was noted at termination. No changes were noted in hepatic FAOS or CAT activity. In conclusion, although repeated oral treatment of cynomolgus monkeys with a large dose of DEHP induced a subtle increase in the numbers of peroxisomes with slight enlargements of the mitochondria, this low-sensitivity response to peroxisome proliferators in cynomolgus monkeys was considered to be closer to the response in humans than that in rodents.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Satake
authors.forename: Chika
authors.initials: C
authors.lastname: Nakamura
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Minamide
authors.forename: Shinobu
authors.initials: S
authors.lastname: Kudo
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Maeda
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Chihaya
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Kamimura
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Miyajima
authors.forename: Jun
authors.initials: J
authors.lastname: Sasaki
authors.forename: Masanobu
authors.initials: M
authors.lastname: Goryo
authors.forename: Kosuke
authors.initials: K
authors.lastname: Okada