Hexanedioic acid, polymer with 2,2'-oxybis[ethanol]

Endpoint summary

Additional information

The pH-dependent hydrolysis of Polyesterol 90212 in water was determined in a GLP-compliant study performed according to OECD Guideline 111 (see chapter 4 of the IUCLID). In a first tier, solutions of the test substance in H₂O with a concentration of 1553 mg/L were adjusted to pH values of 4.0, 7.0 and 9.0. The resulting solutions were stored in sealed and purged vials at 50°C for 5 days. Samples were taken at the beginning and after 5 days and the content of the test item was determined using HPLC/UVD. After 5 days 33.01%, 70.50%, and 100% of the test substance were hydrolyzed at pH 4, 7, and 9, respectively.

A substance which is structurally related to Polyesterol 90212, namely the cyclic ester of adipic acid with diethyleneglycol (CAS 6607-34-7), was tested regarding its stability in rat plasma in vitro. Before investigating enzymatic hydrolysis in rat plasma, it was checked whether the test substance is non-enzymatically hydrolyzed in phosphate buffer (pH 7.1) and hydrochloric acid (pH 3.0). No hydrolysis was detected after 4 hours incubation in the two respective buffers.
To determine enzymatic hydrolysis of the test substance, nominal concentrations of 1068 and 5335µg/ml were freshly prepared in rat plasma. Beginning hydrolysis could already be observed 1 hour after starting the test at both concentrations. After 4 hours, 18.18% of the test substance were hydrolyzed at 1068µg/ml, whereas 90.53% were hydrolyzed at 5335µg/ml. It was anticipated that enzymatic hydrolysis is more pronounced at higher concentrations due to saturation of plasma protein binding the test substance and a consequently higher concentration of free substance in plasma which is available for enzymatic hydrolysis.

The data above indicate that Polyesterol 90212 is hydrolytically instable. Enzymatic hydrolysis is more pronounced at higher concentrations of the test substance, whereas non-enzymatic hydrolysis is more pronounced at higher pH values. The observation that the test substance is almost completely hydrolyzed in plasma after 4 hours indicates that the systemically available species and will be the hydrolysis products, namely adipic acid and ethylene glycol. It can thus be anticipated that the effects of the test substance on human health can be derived from data for the hydrolysis products. In accordance with REACH Annex XI, section 1.5, read-across to the hydrolysis products is considered appropriate to cover the endpoints which require repeated dose toxicity studies under REACH Tier 3.