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Key value for chemical safety assessment

Additional information

In the chosen key study, addressing in vitro gene mutation in bacteria, octocrilene was tested in an AMES test according to OECD TG 471 and GLP using Salmonella typhimurium strain TA1535, TA1537, TA98, TA100 and Escherichia coli strain WP2 uvr A (BASF 40M0495/004104). An increase in the number of his+ or trp+ revertants was not observed in the standard plate test or in the preincubation test either without S-9 mix or after the addition of a metabolizing system.

Further data from other AMES tests, available either as study report or literature, confirm the absent genotoxic potential of octocrilene in different Salmonella typhimurium strains.

In the chosen key study for in vitro gene mutation in mammalian cells, octocrilene was tested for mutation at the hprt locus (6-thioguanine resistance) in mouse lymphoma L5178Y cells according to OECD TG 476 (Hazelton/BASF 729/180). No statistically significant increases in mutant frequencies were observed following treatment at any dose level up to cytotoxic and precipitating concentrations in the absence or presence of an S-9 mix. In line, findings in literature were reported, confirming octocrilene not to induce any significant increase in mutant frequencies in a mouse lymphoma assay (Odio 1994).

In the chosen key study for in vitro cytogenicity in mammalian cells, the chromosomal aberration test according OECD TG 473 and GLP using Chinese hamster lung fibroblasts V79 was performed (BASF 32M0495/004099). On the basis of the results of this study, octocrilene up to cytotoxic concentrations did not cause any relevant increase in the number of structurally aberrant metaphases incl. and excl. gaps at different incubation (i.e. 4/18 hours) and sampling times (i.e. 18/28 hours) either without S-9 mix or after adding a metabolizing system. No increase in the frequency of cells containing numerical aberrations was found.

Furthermore, octocrilene was reported not to induce chromosome aberrations in Chinese hamster ovary (CHO) cells when tested to its limit of solubility and cytototoxicity in either the absence or presence of S-9 mix in another chromosomal aberration test according to OECD TG 473 and GLP (Hazelton/BASF 729/176). Further evidence for the absence of any clastogenic potential of octocrilene are given in a further chromosomal aberration test in CHO cells (Odio 1994).  

 

In the chosen key study for in vivo cytogenicity, octocrilene was tested in NMRI mice (5 male and 5 female per group) using the micronucleus test method according to OECD TG 474 and GLP (BASF 26M0227/924248). The test substance in olive oil was administered once via gavage at dose levels of 500, 1000 and 2000 mg/kg body weight and animals were sacrificed at 16, 24 and 48 hours after dosing. After test substance application only transient piloerection was observed at all dose levels. No inhibition of erythropoiesis determined from the ratio of polychromatic to normochromatic erythrocytes was detected at any dose level. No increase in the number of polychromatic erythrocytes containing either small or large micronuclei was observed since the rate of micronuclei was in the same range as that of the negative control in all dose groups and at all sacrifice intervals.

 


Short description of key information:
In an AMES test according to OECD TG 471 and GLP using Salmonella typhimurium strain TA1535, TA1537, TA98, TA100 and Escherichia coli strain WP2 uvr A, no increase in the number of revertants was observed in the standard plate test or in the preincubation test either without S-9 mix or after the addition of a metabolizing system.
In a HPRT assay according to OECD TG 476, no statistically significant increases in mutant frequencies were observed at any dose level up to cytotoxic and precipitating concentrations in the absence or presence of an S-9 mix.
In a chromosomal aberration test according OECD TG 473 and GLP, octocrilene up to cytotoxic concentrations did not cause any relevant increase in the number of structurally aberrant metaphases either without S-9 mix or after adding a metabolizing system. No increase in the frequency of cells containing numerical aberrations was found either.
In an in vivo micronucleus test method according to OECD TG 474 and GLP, no increase in the number of polychromatic erythrocytes containing either small or large micronuclei was observed.

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 CLP, and therefore, a non-classification is warranted.