Hydrolysis, absorption and metabolism of di(2-ethylhexyl) terephthalate in the rat

Abstract

1. The hydrolysis of di(2-ethylhexyl) terephthalate (DEHT) and di(2-ethylhexyl) phthalate (DEHP) were studied using rat gut homogenate fractions in vitro. Both isomers were hydrolysed by the intestinal fraction; however, DEHP was hydrolysed to 2-ethylhexanol (2-EH) and mono(2-ethylhexyl) phthalate (MEHP) in about equal proportions, whereas DEHT was hydrolysed to 2-EH and terephthalic acid (TPA). The half-lives for disappearance of the diesters were determined to be 12.6 min for DEHP and 53.3 min for DEHT. 2. The absorption and metabolism of DEHT were studied by administering [hexyl-2-14C]DEHT (in corn oil) by oral gavage at a dose level of 100 mg/kg to 10 adult male Sprague-Dawley rats. Urine, faeces and expired air were collected for 144 h and analysed for the presence of radioactivity, and faeces and urine were analysed for unlabelled metabolites. 3. Radioactivity was eliminated in faeces (56.5 +/- 12.1% of dose) primarily as unchanged DEHT, small amounts of MEHT and polar metabolites; excreted in urine (31.9 +/- 10.9% of dose) principally as MEHT and metabolic products of 2-EH; and expired as 14CO2 (3.6 +/- 0.9% of dose). Less than 2% of the administered radioactivity was found in the carcass. Small amounts of 14C were found in the tissues with the highest amounts found in liver and fat. 4. Metabolites identified in urine included terephthalic acid (equivalent to 51% of dose), oxidized metabolites of 2-EH and MEHT, and glucuronic and sulphuric acid conjugates (equivalent to about 10% of dose).(ABSTRACT TRUNCATED AT 250 WORDS)

Rodent Thyroid, Liver, and Fetal Testis Toxicity of the Monoester Metabolite of Bis-(2-ethylhexyl) Tetrabromophthalate (TBPH), a Novel Brominated Flame Retardant Present in Indoor Dust

“…In rats, DEHP is hydrolyzed to MEHP in the intestines via the action of gut esterases (Albro 1986; Albro et al 1982; Barber et al 1994). However, at DEHP doses of 100 mg/kg in rats, DEHP can be measured in the feces, representing unabsorbed compound that is unavailable for hydrolysis to MEHP (Keys et al 1999).…”

Identification of di-2-ethylhexyl terephthalate (DEHTP) metabolites using human liver microsomes for biomonitoring applications

“…Rats dosed with 14 C-DEHTP eliminated most of its radioactivity in feces as unchanged DEHTP and excreted smaller amounts of mono-2-ethylhexyl terephthalate (MEHTP), terephthalic acid (TPA) and other polar metabolites in urine (Barber et al, 1994). However, human metabolites of DEHTP are unknown.…”

Polyester monomers lack ability to bind and activate both androgenic and estrogenic receptors as determined by In Vitro and In Silico methods

“…Although no data exist specifically for DMCD, it has been demonstrated that the enzymatic cleavage of short to medium length alkyl chain esters is located in the one and four positions on similar compounds. Specifically, the methyl units of 1,4-benzenedicarboxylic acid, dimethyl ester (dimethylterephthalate; DMT) and the ethylhexyl moieties of 1,4-benzenedicarboxylic acid, bis(2-ethylhexyl) ester are readily removed to form 1,4-benzenedicarboxylic acid (terephthalic acid; TPA) (Barber et al, 1994; Heck and Kluwe, 1980). …”