Registration Dossier

Administrative data

Key value for chemical safety assessment

Additional information

In vitro:

In the chosen key study for mutagenicity in bacteria, i.e. an Ames test, 5 Salmonella typhimurium strains (TA 1535, TA 1537, TA 1538, TA98, and TA 100) were used to test the mutagenic potential of 3,7-dimethyloct-6-enenitrile (0, 0.0007, 0.002, 0.007, 0.02, and 0.06 mg test liquid per 0.1 mL methanol per plate), both with and without metabolic activation (TNO 1980). 3,7-dimethyloct-6-enenitrile did not show any mutagenic activity in any strain up to the bacterial toxic concentrations under the chosen testing conditions.

 

In the chosen key study for mutagenicity in mammalian cells, i.e. a GLP-compliant gene (HPRT) mutation assay according to OECD guideline 476, chinese hamster lung fibroblast (V79) were exposed to 3,7-dimethyloct-6-enenitrile with and without metabolic activation (Harlan, 2012). No relevant and reproducible increase in mutant colony cells was observed up to the cytotoxic concentration. Therefore, 3,7-dimethyloct-6-enenitrile, is considered to be non-mutagenic in this HPRT assay.

 

In the chosen key study for cytogenicity in mammalian cells, i.e. a GLP-compliant chromosome aberration test according to OECD guideline 473, chinese hamster lung fibroblast (V79) were exposed to 3,7-dimethyloct-6-enenitrile with and without metabolic activation (RCC, 2008). In the presence of S9 mix, a statistically significant and biologically relevant increase in the number of aberrant cells, excluding gaps was observed after 4 hrs treatment with 500 µg/mL (14.0% aberrant cells, excluding gaps). In addition, in the presence of S9 mix after 4 hrs treatment with 500 µg/mL the rate of polyploid cells (5.7 %) as well as endomitotic cells (1.5 %) and after the 4 hrs treatment with 125 µg/mL the rate of endomitotic cells (0.4 %) were statistically significant increased. Therefore, 3,7-dimethyloct-6-enenitrile is considered to be clastogenic in this chromosome aberration test in the presence of S9 mix. In addition, 3,7-dimethyloct-6-enenitrile, is considered to inhibit mitotic processes and to induce numerical chromosome aberrations in this chromosome aberration test.

 

 

In vivo:

In the chosen key study for cytogenicity in vivo, i.e. a GLP-compliant erythrocyte micronucleus test according to OECD guideline 474, 5 NMRI mice per sex per dose were treated once by oral gavage with 3,7-dimethyloct-6-enenitrile (500, 1000, 2000 mg/kg bw) dissolved in olive oil followed by a 24 hour (500, 1000, 2000 mg/kg bw) and 48 hour (2000 mg/kg bw) post-exposure period before sacrificing the animals (BASF, 2004). 3,7-dimethyloct-6-enenitrile did not result in any increase in the rate of micronuclei. The number of normochromatic or polychromatic erythrocytes containing small micronuclei (d < D/4) or large micronuclei (d ≥ D/4) did not deviate from the vehicle control value at any of the sacrifice intervals and was within the historical control range. A slight inhibition of erythropoiesis induced by the treatment of mice with 3,7-dimethyloct-6-enenitrile was detected from about 500 mg/kg body weight onward. Overall, 3,7-dimethyloct-6-enenitrile 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:
Ames test: negative (TNO 1980)
HPRT test (OECD 476, GLP): negative (Harlan 2012)
Chromosome aberration (OECD 473, GLP): positive (RCC 2008)
Micronucleus test in vivo (OECD 474, GLP): negative (BASF 2004)

Endpoint Conclusion:

Justification for classification or non-classification

Based on the available genotoxicity tests, 3,7-dimethyloct-6-enenitrile does not need to be classified for genotoxicity according to the Directive 67/548/EEC and according to the EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.