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EC number: 218-645-3 | CAS number: 2210-79-9
Endpoint summary
Administrative data
Link to relevant study record(s)
Description of key information
In vitro metabolisnof 2,3-epoxypropyl o-tolyl ether (o-Cresyl glycidyl ether/o-CGE) was conducted with human, rat and mouse cytosol and microsomes. Urinary metabolites were measured in the rat and in vitro dermal penetration was evaluated in human, rat and mouse skin by diffusion cell.
Key value for chemical safety assessment
Additional information
The detoxification of o -CGE (2,3 -epoxypropylo-tolyl ether) was assessed in vitro in human, rat and mouse subcellular cytosolic and microsome fractions. The rate of o-CGE conjugation to glutathione by glutathione-S-trasnferase and of hydrolysis by Epoxide hydrolase was determined. Generally, conjucation of o-CGE (2,3-epoxypropyl o-tolyl ether ) to glutathione by Gultathione-S-transferase by rodent and human subcellular cytosol fractions from the liver and lung was similar. Hydrolysis of o-CGE by Epoxide hydrolase was the most efficient means of detoxification. Human liver Epoxide hydrolase was approximately 4-10-fold more efficient than rodent Epoxide hydrolase in the hydrolysis of o-CGE. Mouse lung Epoxide hydrolase was approximately 2-fold more efficient compared to human lung Epoxide hydrolase. Generally, rat Epoxide hydrolase was the least efficient in the detoxification of o-CGE.
Urinary metabolites of the test substance,2,3-epoxypropylo-tolyl ether (o-Cresyl glycidyl ether/o-CGE) were identified and excreation kinetics determined following IP administration of male rats. Generally, the three identified unrinary metabolites of o-CGE (2,3-epoxypropyl o-tolyl ether ) 3-(o-cresyloxy)lactic acid, o-cresyl glycidyl ether mercapturic acid and N-acetyl-o-(o-cresyflserine) were excreated within six hr following the IP injection. However, the three urinary metabolites described in the publication account for only approximately 50% of the o-CGE dose.
The test substance,2,3-epoxypropylo-tolyl ether (o-Cresyl glycidyl ether/o-CGE) was assessed for dermal penetration in vitro in diffusion cells with human, rat and mouse skin samples. Only approximately 10-22% of the applied dose of o-CGE (2,3-epoxypropyl o-tolyl ether ) penetrated the skin samples. Furthermore, total recovery was only13-26%. The low perneability and recovery of o-CGE is believed to be due to its volatility. Occlusion of the diffusion cells resulted in an approximately doubling of the precent absorption. Approximately 86-88% of the penetrated dose of o-CGE was hydrolysed to mephenesin (the glycerol ether of o-cresol) during the first hours of penetration in human, rat as well as mouse skin.
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