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Di-(2-ethylhexyl)adipate: absorption, autoradiographic distribution and elimination in mice and rats
Authors:K Bergman  L Albanus
Affiliation:1. School of Public Health, Xinxiang Medical University, 601 Jinsui Road, Xinxiang, Henan, 453003, China;2. Department of Toxicology, College of Public Health, Zhengzhou University, 100 Science Road, Zhengzhou, Henan, 450001, China;3. School of Life Sciences and Technology, Xinxiang Medical University, 601 Jinsui Avenue, Xinxiang 453003, China;1. Department of Chemistry, Chaudhary Charan Singh Haryana Agricultural University, Hisar 125 004, India;2. Department of Agronomy, Chaudhary Charan Singh Haryana Agricultural University, Hisar 125 004, India;3. Department of Biochemistry, Chaudhary Charan Singh Haryana Agricultural University, Hisar 125 004, India;4. Department of Microbiology, Chaudhary Charan Singh Haryana Agricultural University, Hisar 125 004, India;5. Department of Biochemistry, All India Institute of Medical Science, AIIMS New Delhi, 110 029, India;1. Division of Pharmacokinetics, Toxicology and Targeting, Department of Pharmacy, University of Groningen, The Netherlands;2. Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Chiba University, Japan;1. Université Clermont Auvergne, INSERM, U1240 Imagerie Moléculaire et Stratégies Théranostiques, F-63000 Clermont Ferrand, France;2. CHU Clermont-Ferrand, Pôle Pharmacie, rue Montalembert, 63003 Clermont-Ferrand, France;3. France Université de Nantes, INSERM, U791, LIOAD, Nantes, F-44042, France;4. Service de Pharmacologie, Hôpital Gabriel-Montpied, CHU de Clermont-Ferrand, Clermont-Ferrand, France;5. Nutrition Physiology and Toxicology Team (NUTox), UMR U866 INSERM, Université de Bourgogne Franche-Comté, AgroSup Dijon, 1 Esplanade Erasme, 21000 Dijon, France;6. Clermont Université, Université d''Auvergne, EA 4676C-BIOSENSS, 63000 Clermont-Ferrand, France
Abstract:Whole-body autoradiography was used to study the tissue distribution of the plasticizer di-(2-ethylhexyl) adipate (DEHA), labelled in the acid [carbonyl-14C] or alcohol [2-ethylhexyl-1-14C]moiety, after iv or ig administration to male mice and rats and pregnant mice. With both DEHA preparations, during the first 24 hr after administration high levels of radioactivity were observed particularly in the body fat, liver and kidneys (after iv and ig administration) and in the intestinal contents (after ig administration) of both species. After administration of [carbonyl-14C]DEHA, radioactivity was also registered in the adrenal cortex, corpora lutea of the ovary, bone marrow, forestomach mucosa, salivary glands and Harder's gland in both species. [2-ethylhexyl-1-14C]DEHA derived radioactivity was found in the bronchi in male mice. Radioactivity was observed in the foetal liver, intestine and bone marrow during the first 24 hr after iv or ig administration of [carbonyl-14C]DEHA to pregnant mice. There was very little accumulation of [2-ethylhexyl-1-14C]DEHA in the mouse foetus but some was found in the urinary bladder, liver and intestinal contents as well as in the amniotic fluid. In an absorption/elimination study in rats of doses of 25 microCi/kg body weight of [14C]DEHA administered ig, dissolved in corn oil or dimethylsulphoxide, blood levels of radioactivity increased somewhat faster and were two or three times higher when DMSO was the vehicle indicating poor absorption of DEHA from the corn oil solution which more accurately reflects human contact with DEHA. Little radioactivity from [carbonyl-14C]DEHA was recovered in the bile, whereas [2-ethylhexyl-1-14C]DEHA was excreted in the bile in significant amounts particularly when DMSO was the vehicle. There was evidence of enterohepatic circulation of DEHA. Radioactivity was also excreted in the urine. As shown by autoradiograms obtained 4 days after the administration of [14C]DEHA there was no retention of DEHA and/or its metabolites in the tissues of mice.
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