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Description of key information

No specific toxicokinetic studies are available on THPC-urea-amine. A toxicokinetic assessment has been made of data from general toxicity studies performed on THPC-urea-amine and on ITC 826.

Key value for chemical safety assessment

Additional information

The toxicokinetic assessment was based on the physico-chemical properties of the test substance, scientific literature and the results of toxicity studies (acute oral and dermal toxicity, 28 and 90 days oral toxicity studies, skin irritation and sensitisation, mutagenicity in vitro)

Basic Toxicokinetics

Liver and clinical chemistry changes in the 90-day oral study on THPC-urea-amine (CIT, 2014) and in the 28 -day oral study on the closely-related substance ITC 826 Concentrate (7.5.1: Rattray, 1996) indicate absorption of the test substance from the gastrointestinal tract, which appears to be dose-related. The various absorbed components would be either excreted directly in the urine or be subject to metabolism to a range of polar metabolites, which would also be expected to be excreted mainly in the urine. At least one of the species in the test substance appears to be mutagenic in vitro, however the elimination of the mutagenic response in theAmestest (7.6.1: Callendar, 1995) by rat microsomal enzymes suggests that metabolisation of some components of the test substance would occur in vivo.

THPC-urea-amine is an acidic mixture, miscible with water, containing approximately equal proportions of low molecular weight components, principally THPC, and charged polymer chains. The low molecular weight components would be expected to diffuse well through the gastrointestinal mucosa, with a lesser degree of absorption of the higher molecular weight polymer chains. Oral absorption of 100% has been taken for DNEL calculation (worst case).

Dermal Absorption

No specific study on dermal absorption is available. The finding that the test substance has potential to cause skin sensitisation (7.4.1: Lees, 1996) implies some degree of dermal absorption of the test substance.

Based on physicochemical properties and a dermal absorption study on THPS which indicated a maximum dermal absorption of 4.80% over a 24 hour period, dermal absorption of 10% has been taken for DNEL calculation.