Registration Dossier

Administrative data

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

Five in vitro relevant studies were availables to evaluate the potential mutagenic effect of the substance. Two Ames tests showed no mutagenic effect on gene mutation in bacteria in presence/absence of metabolic activation system. Two Mouse Lymphoma Assay in cell line L5178Y were performed to assess mutagenic potential on Mammalian cells. In one study, the substance induced mutagenic effect for Thymidine kinase locus in presence of metabolic activation system. In the second study, the substance did not showed mutagenic effect for HPRT locus with/without metabolic activation. The Micronucleus Assay on Human lyphocytes did not show any genotoxic effect with/without effect.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Genetic toxicity in vivo

Description of key information

Two in vivo relevant studies were available to assess clastogenic/mutagenic effect of substance. In micronucleus test, the substance did not produce cytogenic damage leading to micronucleus formation in the bone marrow of rats treated orally up to 2000 mg/kg, the assay limit dose. Bone marrow toxicity was not demonstrated, but clinical signs of toxicity indicate systemic exposure. In the second experiment, rats were treated orally for an UDS test on hepatocytes. There was no DNA damage leading to unscheduled DNA synthesis in hepatocytes derived from rats treated orally with 1-phenyl-3-methyl-5-pyrazolone up to the maximum tolerated dose of 1000 mg/kg. There was an indication of cytotoxic effect in the liver after exposure to the test substance.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Additional information

Justification for classification or non-classification

Phenyl methyl pyrazolone did not induce gene mutations in bacteria. It was also not mutagenic in an in vitro gene mutation test with mammalian cells (hprt locus). A mutagenic response was observed in the Mouse Lymphoma assay (tk locus) but only in the presence of S9. In an in vitro micronucleus assay no genotoxic effect (structural and/or numerical chromosomal aberrations) was observed. In an in vivo bone marrow micronucleus assay in mice and in an in vivo UDS assay in rats, negative results were observed. The results of the tests performed indicate that phenyl methyl pyrazolone itself is not mutagenic in vivo.