Hydrolysis of di(2-ethylhexyl) phthalate in humans, monkeys, dogs, rats, and mice: An in vitro analysis using liver and intestinal microsomes
Autor: | Nobumitsu Hanioka, Takashi Isobe, Hideto Jinno, Toshiko Tanaka-Kagawa, Sadayuki Ochi, Susumu Ohkawara |
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Rok vydání: | 2019 |
Předmět: |
Adult
0301 basic medicine endocrine system medicine.medical_specialty Adolescent Rodent Toxicology Rats Sprague-Dawley In vitro analysis Mice Young Adult 03 medical and health sciences chemistry.chemical_compound Hydrolysis Dogs 0302 clinical medicine Species Specificity Plasticizers Diethylhexyl Phthalate Microsomes Internal medicine biology.animal medicine Animals Humans Liver microsomes Active metabolite Aged biology Phthalate General Medicine Middle Aged Intestines Macaca fascicularis 030104 developmental biology Endocrinology Liver chemistry 030220 oncology & carcinogenesis Toxicity Microsome |
Zdroj: | Toxicology in Vitro. 54:237-242 |
ISSN: | 0887-2333 |
Popis: | Di(2-ethylhexyl) phthalate (DEHP) is a widely used plasticizer that is rapidly metabolized to mono(2-ethylhexyl) phthalate (MEHP), an active metabolite, in mammals. In the present study, the hydrolysis of DEHP by the liver and intestinal microsomes of humans, monkeys, dogs, rats, and mice was examined. The kinetics of liver microsomes fit the Michaelis-Menten model for humans, monkeys, and rats, and the Hill model for dogs and mice. Km or S50 values were similar among species, whereas Vmax exhibited species differences of approximately 9-fold. CLint or CLmax values were in the order of mice > dogs > monkeys ≥ rats > humans. Hydrolytic activity towards DEHP was not detected in the intestinal microsomes of humans or dogs. The kinetics of monkeys, rats, and mice followed the Hill model. In comparisons of the liver microsomes of each species, S50 values were similar, while Vmax and CLmax values (mice > rats > monkeys) were considerably lower (approximately 5–25%). These results suggest that hydrolytic activity towards DEHP in the liver and intestines markedly differ among humans and non-rodent and rodent experimental animals, and imply that species differences are closely associated with the toxicity of DEHP. |
Databáze: | OpenAIRE |
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