Registration Dossier

Toxicological information

Specific investigations: other studies

Currently viewing:

Administrative data

Link to relevant study record(s)

Description of key information

Additional information

Metabolome analysis

1-Methylimidazol was administered daily for 30 days to 10 males and for 51 days to 10 female Wistar rats (Crl:Wi(Han)) per dose group via gavage at dose levels of 30 and 90 mg/kg weight/day (OECD 422, Combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening Test, 2013). Blood samples for metabolome analysis were taken retroorbitally on study day 30 for male and on day 51 for female animals.

The metabolome analysis and evaluation for 1-Methylimidazol in plasma after administration of 90 and 30 mg/kg bw/day of the test substance via gavage for 30 days, gives slight evidence for kidney and liver toxicity in males. This finding is based on the metabolite changes induced by 1-Methylimidazol, similarities of the 1-Methylimidazol-induced changes to specific toxicity patterns and the correlation of the whole profile changes induced by 1-Methylimidazol with those of reference compounds within MetaMap®Tox.

On the other hand, in females the whole metabolite profile of 1-Methylimidazol in plasma after administration of 90 and 30 mg/kg bw/day of the test substance via gavage for 51 days did not match well with any metabolite profiles of the reference compounds in the MetaMap®Tox data base. No clear evidence for organ specific toxicological modes of action could be deduced from this metabolome analysis.

 

Enzyme induction

The goal of the study was to determine the total Cyp 450 content as well as activities of defined xenobiotic metabolizing enzymes in livers of male and female rats.

Wistar rats originating from a Combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening Test (OECD 422, study no. 85R0492/11R130), treated via oral administration with 1-Methylimidazol at nominal dose levels up to 90 mg/kg bw/d showed a weak test substance induced increase of the hepatic total Cyp 450 content for high dosed male rats. In microsomes prepared from liver aliquots of the animals, EROD-activities were slightly increased for male and PROD-activities were slightly increased for male and female rats. Repeated treatment of the rats with 1-Methylimidazol did neither induce total hepatic Cyp 450 nor EROD-activities in liver microsomes of female rats. In both sexes, BROD-activities as well as activities of glucuronosyltransferases MUF-GT and HOBI-GT were not induced in liver microsomes of treated dose groups versus appropriate controls.

 In conclusion, weak effects on liver enzyme induction may be discussed for treatment of rats with 1-Methylimidazol, but compared to known potent enzyme inducers such as typical ligands of the AhR or CAR, observed effects are negligible.