oligomeric reaction product of 2-hydroxybenzaldehyde with 1-chloro-2,3-epoxypropane and phenol

Endpoint summary

Description of key information

The physicochemical and biological data on EPICLON EXA-7250 suggest it is has a low bioavailability from the oral route, and very low by the dermal route. Most material taken in orally would probably pass through in the faeces. There is no evidence for any bioaccumulation, there is some evidence for detoxification/metabolism. It is considered likely that any absorbed substance would be detoxified and eliminated relatively quickly, with no bioaccumulation.

Please refur to the full report attached titled _15_289-412ET_EPICLON EXA-7250_Evaluation and Assessment of the Toxicokinetics.

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Additional information

SUMMARY: Potential for Bioavailability and Bioaccumulation

The studies performed and the available physicochemical data are consistent with an organic molecule with a very low bioavailability and no significant indication or evidence for potential for toxicity or bioaccumulation in vivo.

The physical properties and mammalian data indicate a low bioavailability. Evidence from in vitro cytotoxicity shows reduced toxicity in the presence of S9 liver enzymes, suggesting detoxification/metabolism can occur. Also rats given >28 days of a daily dose of the maximum dose of close to 1 OOO mglkg/d, had no major toxic or reprotoxic effects; this indicates no evidence for bioaccumulation. For exposure by the oral route, there is evidence that no significant effects occur with repeated exposure; it is considered that based on limited animal studies and/or the physicochemistry of the substance, that dermal absorption would be minimal and inhalation exposure is very unlikely.

SUMMARY: Potential for Distribution and Metabolism

The large molecular weight (>500) and the very low water solubility, with a LogP of approx. 4, plus the lack of effects from maximal oral doses, would suggest that the majority of the substance would not be absorbed form an oral exposure, with most material being eliminated with the faeces. There is limited evidence that detoxification/metabolism would occur to any absorbed substance; a large molecule like this would likely be eliminated via the bile rather than the urine. The epoxide groups on the molecule would be metabolised to hydrophilic -OH groups by the Epoxide hydrolases which are present in mammalian tissues, meaning the detoxified substance would be hydrophilic and very unlikely to accumulate in fatty tissues, but would be eliminated.