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Description of key information

Repeated Dose Toxicity – Oral NOAEL 1000 mg/kg (OECD TG 417) highest dose tested, no adverse effects.
Repeated Dose Toxicity (read across) – Oral NOAEC 100 mg/m3 (OECD TG 420).

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Dose descriptor:
NOAEL
1 000 mg/kg bw/day

Additional information

A 90-day repeated dose (oral, dermal, or inhlation) study is not scientifically justified for the registered substance. First, a substance with a similar compositional profile (CAS # 68526-82-9) has had a U.S. Environmental Protection Agency (EPA) High Production Volume (HPV) Challenge Program Submission (#201-15013). In this submission, it was reported that CAS # 68526-82-9 was tested in a 90-day repeated dose inhalation exposure in rats at doses of 100, 300, and 1000 mg/m3. The NOAEC for the study is 100 mg/m3; reduced body weight gains, increased lung weights, and microscopic pulmonary morphology were noted. Second, in a 28-day repeated dose oral toxicity study with the registered substance, subject of this registration and described in detail below, a NOAEL of 1000 mg/kg/day (the highest dose tested) was identified. Third, the registered substance is not genotoxic in OECD Guideline 473 (In vitro Mammalian Chromosome Aberration Test) or OECD Guideline 476 (In vitro Mammalian Cell Gene Mutation Test). The overall weight of the evidence does not justifiy the additional use of animal testing.

 

The registered substance, when administered by the oral route after a period of 29 days, was not toxic even at the highest dose of 1.0 g/kg as indicated by the absence of treatment related mortality and clinical effects. Additionally, there were no statistically significant differences between the treated and control body weight or food consumption values. Analysis of the organ and relative organ weights did reveal a dose related increase in the mean liver and relative liver weights in the female rats, however these increases were not statistically significant. Hematology and serum chemistry analyses revealed minimal changes, none of which were considered biologically significant. Postmortem examination revealed no observable abnormalities in the majority of animals with no apparent trends within the treatment or control groups. Histopathological evaluation also revealed minimal findings, all of which were considered to be incidental and unrelated to treatment. Overall, all of the findings were slight and not considered indicative of a treatment related response. A NOAEL of 1000 mg/kg/day (the highest dose tested) was identified. 

Justification for classification or non-classification

No classification for repeated dose toxicity is indicated according to the general classification and labeling requirements for dangerous substances and preparations (Directive 67-548-EEC) or the classification, labeling and packaging (CLP) regulation (EC) No 1272/2008.

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