Identification of a Toxic Mechanism of the Plasticizers, Phtahlic Acid Esters, which are Putative Endocrine Disrupters: Time-dependent Increase in Quinolinic Acid and Its Metabolites in

• Published in: Bioscience, biotechnology, and biochemistry biotechnology, and biochemistry, 2002-01, Vol.66 (12), p.2687-2691
• Main Authors: FUKUWATARI, Tsutomu, SUZUKI, Yuko, SUGIMOTO, Etsuro, SHIBATA, Katsumi
• Format: Article
• Language: English
• Subjects: di(2-ethylhexyl)phthalate; endocrine disrupters; phthalate ester; quinolinic acid; tryptophan metabolism
• ISSN: 0916-8451; 1347-6947
• DOI: 10.1271/bbb.66.2687

We have reported that the administration of di(2-ethylhexyl)phthalate (DEHP) increased the formations of quinolinic acid (QA) and its lower metabolites on the tryptophan-niacin pathway. To discover the mechanism involved in disruption of the tryptophan-niacin pathway by DEHP, we assessed the daily urinary excretion of QA and its lower metabolites, and enzyme activities on the tryptophan-niacin pathway. Rats were fed with a niacin-free, 20% casein diet or the same diet supplemented with 0.1% DEHP or 0.043% phthalic acid and 0.067% 2-ethylhexanol added for 21 days. Feeding of DEHP increased the urinary excretions of QA and its lower metabolites in a time-dependent manner, and the increase of these excretions reached a peak at 11 days, but feeding of phthalic acid and 2-ethylhexanol had no effect. Feeding of DEHP, however, did not affect any enzyme activity including α-amino-β-carboxymuconate-ε-semialdehyde decarboxylase (ACMSD), affecting the formation of QA, on the tryptophan-niacin pathway.