A mixture of branched and linear C7-C9 alkyl 3-[3-(2H-benzotriazol-2-yl)-5-(1,1-dimethylethyl)-4-hydroxyphenyl]propionates

Endpoint summary

Additional information

In vitro

Gene mutation (Bacterial Reverse Mutation Assay/Ames test):

The substance Chiguard 5599 was tested in two in vitro gene mutation studies in bacteria (Bacterial Reverse Mutation Assay/Ames Test). In the supporting study (84/449/EEC, B.14/GLP), bacterial strains (Salmonella typhimurium TA98, TA100, TA1535, TA1537, E. Coli WP urvA) were exposed to the substance in acetone at concentrations of 312.5 – 5000 µg/plate in the presence and absence of mammalian metabolic activation (Aroclor induced rat-liver S9). Precipitation was observed at 313 µg/plate. No mutagenic effects were observed in the original or in the confirmatory experiment. The substance was negative in the presence and absence of metabolic activation in the Bacterial Reverse Mutation Assay/Ames test.

In the bacterial in vitro gene mutation key study (Annex V/GLP), bacterial strains (Salmonella typhimurium TA98, TA100, TA1535, TA1537, TA 1538 and E. Coli WPurvA) were exposed to the substance in acetone at concentrations of 312.5 – 5000 µg/plate in the presence and absence of mammalian metabolic activation (Aroclor induced rat-liver S9). The substance was tested up to cytotoxic concentrations and no precipitation was noted. The substance was negative in the presence and absence of metabolic activation in the Bacterial Reverse Mutation Assay/Ames Test.

Gene mutation (in vitro mammalian cell gene mutation):

A read-across unscheduled DNA synthesis in mammalian cells in vitro study from Tinuvin 1130 (EC No. 400-830-7), as the analogue of Chiguard (EC No. 407-000-3), was submitted to fill this data gap. In the unscheduled DNA synthesis in mammalian cells in vitro study (Similar to OECD 482/GLP), rat hepatocytes were exposed to Tinuvin 1130 in DMSO at concentrations of 0.2 to 400 µg /mL for 16-18 hours. Positive controls gave the expected responses and the results were confirmed in an independent confirmatory study. No evidence of induction of DNA damage by the test substance or its metabolites was detected. Tinuvin 1130 was negative in the unscheduled DNA synthesis in mammalian cells in vitro.

The full read-across report justification is attached.

In vivo

Chromosome aberration (In vivo micronucleus assay):

The substance Chiguard 5599 was tested in two in vivo micronucleus assays. In a supporting study, a mouse bone marrow micronucleus assay (Annex V/GLP), groups of mice (5/sex/dose) were treated intraperitoneally with Chiguard 5599 in arachis oil at doses of 0 and 5000 mg/kg bw. Bone marrow cells were harvested at 16, 24 and 48 hrs post-treatment. At the dose producing toxicity, there was no apparent effect on the P/N ratio. The substance was negative in the in vivo micronucleus assay (Chromosome aberration) in mice.

In the key study, a mouse bone marrow micronucleus assay (84/449/EEC, B.12, GLP /GLP), groups of mice (5/sex/dose) were treated orally with Chiguard 5599 in peanut oil at doses of 0 and 5000 mg/kg bw. Bone marrow cells were harvested at 16, 24 and 48 hrs post-treatment. The substance was negative in the in vivo micronucleus assay (Chromosome aberration) in mice.

Justification for selection of genetic toxicity endpoint
No study was selected as all three studies (two in vitro and one in vivo) were negative.

Short description of key information:
In vitro
Gene mutation (Bacterial Reverse Mutation Assay/Ames test): the substance Chiguard 5599 did not induce mutagenicity in S. typhimurium TA 98, TA 100, TA 1535, TA 1537 and TA 102 and E. Coli WP2 uvrA in the presence or absence of Aroclor-induced rat liver S9 metabolic activation (Annex V, GLP);

Gene mutation (in vitro mammalian cell gene mutation): A read-across unscheduled DNA synthesis in mammalian cells in vitro study (Similar to OECD 482, GLP) from Tinuvin 1130 (EC No. 400-830-7), as the analogue of Chiguard (EC No. 407-000-3), was submitted to fill this data gap. The results of this study were concluded to be negative.

In vivo
Chromosome aberration (In vivo micronucleus assay): the substance Chiguard 5599 shows no evidence of mutagenic potential or bone marrow cell toxicity in an in vivo mouse assay (84/449/EEC, B.12, GLP).

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Based on the available information in the dossier, the substance Chiguard (CAS No. 127519-17-9) does not need to be classified for germ cell mutagenicity when the criteria outlined in Annex I of 1272/2008/EC are applied.