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).

5. These findings indicate that DEHT was hydrolysed more extensively than DEHP, and consequently the urinary metabolite profiles for these two isomeric plasticizers were very different. The hydrolysis and metabolism of DEHT were found to be similar to those of di(2-ethylhexyl) adipate (DEHA) in that hydrolysis of both ester bonds occurs.