3,7-dimethyloct-6-enenitrile

Endpoint summary

Description of key information

90 day repeated dose toxicity study, rat, oral (OECD 408, GLP): NOAEL = 300 mg/kg bw/d (highest dose tested; Safepharm Laboratories, 2008)

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Dose descriptor:

NOAEL

300 mg/kg bw/day

Study duration:

subchronic

Species:

rat

Additional information

In the chosen key study, a GLP compliant 90 -day repeated dose toxicity study (Safepharm Laboratories, 2008) according to OECD guideline 408, 10 Spraque-Dawley rats/dose/sex were exposed by oral gavage to 3,7-dimethyloct-6-enenitrile dissolved in corn oil (10, 30, 100, and 300 mg/kg/day). Incidental findings of increased salivation were evident in 300 mg/kg/day animals and in 100, 30 and 10 (males only) mg/kg/day animals, being presumably due to an unpalatable or slightly initant test material formulation and therefore considered not to be an indication of systemic toxicity. No treatment related effects were observed on mortality, clinical signs, (neuro)behaviour, body weight, food and water consumption, ocular examination, haematological and urinalytical parameters, oestrous cycle and sperm parameters. At the highest dose level, a statistically significant increase in total protein levels were observed in females and a statistically significant increase in albumin levels were observed in the male treatment group (300 mg/kg/bw). A statistically significant increase in abs./rel. liver weights was observed in both sexes treated with 300 mg/kg/day (>10% higher vs respective controls). Abs./rel. liver weights were also significantly increased in males treated with 100 mg/kg/day (<10% higher vs. respective controls). Histopathological examinations showed marginal centrilobular hepatocyte enlargement in both sexes treated with 300 mg/kg/day (p <0.05). Two cases of centrilobular hepatocyte enlargement were seen among males and one female treated with 100 mg/kg/day. In the bone marrow, a higher incidence of lower grades of severity of adipose infiltration, indicative of increased marrow cellularity, was seen for females treated with 300 mg/kg/day, but this was not statitically significant and no hematological correlation was observed. Based on these observations, the NOEL was determined to be 30 mg/kg/day and the NOAEL 300 mg/kg/day.

Justification for classification or non-classification

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