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Administrative data

Key value for chemical safety assessment

Additional information

1. Genetic toxicity in-vitro

Two reverse gene mutation assays in bacteria according to OECD TG 471 and GLP were conducted with Uvinul A Plus (key study: BASFAG40M0636/02414; additional study: BASFAG40M0408/994145). In the key study, the Uvinul A Plus was used in its pasty melt form representing the form manufactured by the applicant.

In both studies, S. typhimurium (TA1535, TA100, TA1537, TA98) and the WP2 uvrA strain of E.coli were exposed to Uvinul A plus in DMSO at dose range of 20 µg - 5000 µg/plate in the standard plate test (SPT) and 4 µg – 2500 µg/plate in the preincubation test (PIT) in the presence and absence of mammalian metabolic activation. In both tests (SPT and PIT) 3 test plates per dose and per control (vehicle and positive) were used. No increase in the number of his+ or trp+ revertants was observed in the standard plate test or in the preincubation test either with or without S-9 mix. Thus, it can be stated that under the experimental conditions Uvinul A Plus was not found to be mutagenic in the Salmonella typhimurium/Escherichia coli reverse mutation assay.

 

In the key study for mammalian cell cytogenicity, a chromosomal aberration test according to OECD TG 473 and GLP, V79 cells were exposed to Uvinul A Plus dissolved in DMSO (BASFAG32M0408/994163). The negative controls (vehicle controls) gave frequencies of aberrations within the range expected for the V79 cell line. The test substance did not cause any increase in the number of structurally aberrant metaphases incl. and excl. gaps, with and without a metabolizing system up to cytotoxic concentrations. In addition no increase in the frequency of cells containing numerical aberrations was noted. 

Thus, there was no evidence found in this assay that Uvinul A Plus might cause chromosome aberrations in vitro.

 

In the key study for mammalian cell mutageniciy, a gene mutation assay at the thymidine kinase locus in mouse lymphoma L5178Y cells according to OECD TG 476 and GLP, cells were exposed to Uvinul A Plus in DMSO (BASF52M0636/029033). No substantial and reproducible dose dependent increase of the mutation frequency was observed up to cytotoxic concentrations with and without metabolic activation.

Consequently, the test item is evaluated as non-mutagenic in this test system. 

 

 

2. Genetic toxicity in-vivo

In the key study, a NMRI mouse bone marrow micronucleus assay according to OECD TG 474 and GLP, 5 male mice per dose were treated intraperitoneally with Uvinul A Plus dissolved in DMSO at doses of 0, 500, 1000 and 2000 mg/kg bw (BASFAG26M0636/024140). Bone marrow cells were harvested 24 hours after the last treatment. Some clinical signs of toxicity were observed during the study. In addition a sight and dose-dependent inhibition of erythropiesis was detected at doses of 500 mg/kg bw onwards, indicating that the target tissue was reached by the test item. There was no increase in the number of the micronucleated polychromatic erythrocytes containing either small or large micronuclei.

Thus, Uvinul A Plus does not have any chromosome-damaging (clastogenic) effect, and there were no indications of any impairment of chromosome distribution in the course of mitosis (aneugenic activity) in bone marrow cells in vivo.

 


Short description of key information:
In reverse gene mutation assays in bacteria (Ames test) according to OECD TG 471 and in a mammalian cell gene mutation assay in mouse lymphoma cells according to OECD TG 476, no evidence was found that Uvinul A Plus might cause mutagenic effects in vitro. In a mammalian cell cytogenetic assay according to OECD TG 473, no evidence for a chromosome aberration potential by Uvinul A Plus in vitro was found. A clastogenic and aneugenic effect was also not observed in an in vivo study in a mouse bone marrow micronucleus assay according to OECD TG 474 after intraperitoneal application of Uvinul A Plus. Consequently, no indication was found that Uvinul A might be genotoxic in vitro or in vivo.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

The present data on genetic toxicity do not fulfill the criteria laid down in 67/548/EEC and 1272/2008/EEC and therefore, a non-classification is warranted.