Bicyclo[3.1.1]hept-2-ene-2-ethanol, 6,6-dimethyl-, 2-acetate, (1R,5S)-

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

Negative results were obtained with nopyl acetate in two in vitro mutagenicity tests (Ames test and HPRT test). The results of a chromosome aberration test were also negative except for the test condition 20h exposure without S9. However, the toxicological significance of this observation was considered questionable and the substance was reinvestigated immediately in an in vitro micronucleus test performed under the same experimental conditions (20h exposure without S9) and with the same test system (cultured human lymphocytes). The result was then clearly negative.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Genetic toxicity in vivo

Description of key information

Nopyl acetate was tested in comet assay performed according to OECD guideline 489 and in compliance with GLP, in rats. It was concluded that under the conditions of this study, the test item did not induce biologically relevant increases in DNA strand breaks in the liver, stomach, duodenum or gonad when tested up to 1000 mg/kg/day (the maximum tolerated dose level for this study). Any increases in DNA strand breaks were considered small, were variable in individual animals within the group and in the liver were generally concomitant with clinical chemistry and/or histopathological findings suggestive of hepatotoxicity and not genotoxicity.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Additional information

In vitro tests

*Nopyl acetate was tested in a reverse gene mutation assay in bacteria, performed according to OECD guideline 471 and in compliance with GLP, in S. typhimurium strains (TA 1535, TA 1537, TA 98, TA 100 and TA 102), either with or without metabolic activation, up to a limiting plate incorporation of 5000 micrograms/plate or up to cytotoxic concentrations. The results were negative.

 

*Nopyl acetate was also tested, in presence and in absence of metabolic activation, in a chromosome aberration test performed in cultured human lymphocytes according to OECD guideline 473 and in compliance with GLP. The substance did not increase the rate of chromosomal aberrations except under the test condition 20h exposure without S9. This result was judged equivocal and nopyl acetate was reinvestigated in an in vitro micronucleus test under the same experimental conditions (20h exposure without S9) in the same test system (cultured human lymphocytes). The result was clearly negative.

 

*The results of a gene mutation test (HPRT) in CHO cells were also negative. Nopyl acetate was tested with and without metabolic activation. The study was performed according to OECD guideline 476 and in compliance with GLP.

 

In vivo test

Nopyl acetate was tested in comet assay performed according to OECD guideline 489 and in compliance with GLP, in rats. It was concluded that under the conditions of this study, the test item did not induce biologically relevant increases in DNA strand breaks in the liver, stomach, duodenum or gonad when tested up to 1000 mg/kg/day (the maximum tolerated dose level for this study). Any increases in DNA strand breaks were considered small, were variable in individual animals within the group and in the liver were generally concomitant with clinical chemistry and/or histopathological findings suggestive of hepatotoxicity and not genotoxicity.

 

Justification for classification or non-classification

The results of the in vitro tests (mutagenicity in bacteria, mutagenicity in mammlian cells and clastogenicity tests) and the in vivo test (comet assay) performed with nopyl acetate were negative. Based on these studies, nopyl acetate is therefore not classified for mutagenicity/genotoxicity according to Directive 67/548/EEC and CLP Regulation (EC) No 1272/2008.