The fate of [ 14C]thiodipropionates in rats

Abstract

Thiodipropionic acid and its esters are preservatives and stabilizers used in food and food packaging. The oral fate in rats, hitherto unknown, of thiodipropionic acid (TDPA), didodecyl thiodipropionate (DDTDP), and of a polyester of thiodipropionic acid with cyclohexane-1,4-dimethanol partially terminated with stearyl alcohol, POLY-TDPS-2000 (TDPS), was elucidated in evaluating TDPS as a polymer stabilizer. Single doses of [1- 14C]TDPA were rapidly eliminated, 87–95% of 241–650 mg/kg doses being recovered in 4 days in urine (78–88%), and feces (0.1–0.9%) and as 14CO 2 (3–8%). Radioactivity in tissues and organs was less than 1.5 × background. A 3-mg/kg dose of [1- 14C]TDPA was handled similarly. Urinary radioactivity at the higher dose was due almost entirely to unchanged TDPA, while the lower dose apparently gave an acid-labile conjugate of TDPA. Single oral doses of [1- 14C]DDTDP (107 and 208 mg/kg) were rapidly eliminated, mostly in the urine (85–88%), with less in feces (1.8–3.5%) and as 14CO 2 (3–4%, by day 4); 1-day dietary feeding of 166 mg/kg gave similar results. Tissue and organ levels of radioactivity at sacrifice were close to background, with the exception of fat levels, which were elevated 34 days after dosing. Urinary radioactivity was mostly unchanged TDPA or an acid-labile conjugate. Five-hour feeding in the diet of each of 3 rats of 4.7–5.6 mg/kg of 14C-labeled TDPS prepared from [1- 14C]TDPA, was almost entirely eliminated by 4 days in urine (95%) and feces (0.7%) and as 14CO 2 (approx. 6%). At sacrifice 4 days after dosing, tissue and organ radioactivity was slightly above background, and at 34 days essentially normal. Almost two-thirds of the urine radioactivity was due to [1- 14C]TDPA or a conjugate. TDPA is in many respects similar to a typical dicarboxylic acid after oral intake in being rapidly absorbed and eliminated in the urine largely unchanged. Simple esters and polyesters of TDPA appear to be readily hydrolyzed in the organism to the parent acid, which is then eliminated similarly to TDPA given orally.