Registration Dossier

Administrative data

Description of key information

NOAEL (rat, oral) ≥ 800 mg/kg bw/day

Key value for chemical safety assessment

Toxic effect type:
dose-dependent

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
800 mg/kg bw/day
Study duration:
subacute
Species:
rat

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

OECD Guideline 422 (2016): Differences in body weight in high-dose females was thought to be a result of foetal toxicity and not dam toxicity; and other differences observed between control and treated groups were not found to be of toxicological importance. No other statistically significant, adverse effects relating to the toxicity of the test item were identified. The NOAEL for short-term repeated dose oral toxicity was subsequently considered to be at least 800 mg/kg/day in both male and female rats.

Justification for classification or non-classification

According to the CLP Regulation (EC) No. 1272/2008, substances are classified as specific target organ toxicants following repeated exposure, and are placed in one of two categories, depending on the nature and severity of the effect(s) observed. Substances that have produced significant toxicity in humans or that, on the basis of evidence from studies in experimental animals, can be presumed to have the potential to produce significant toxicity in humans following repeated exposure, are classified in Category 1 for target organ toxicity (repeat exposure). Classification in Category 1 is applicable when significant toxic effects are observed in a 90-day repeated-dose animal study at low concentrations (< 10 mg/kg bw/day in oral studies, and < 20 mg/kg bw/day in dermal studies) (CLP Regulation (EC) No. 1272/2008: Annex 1, Part 3, Table 3.9.2).

Substances which can be presumed to have the potential to be harmful to human health following repeated exposure, based on evidence from animal studies, are classified in Category 2. Classification in Category 2 is applicable when significant toxic effects are observed in a 90-day repeated-dose animal study at generally moderate exposure concentrations (10 to 100 mg/kg bw/day in oral studies, and 20 to 200 mg/kg bw/day in dermal studies) (CLP Regulation (EC) No. 1272/2008: Annex 1, Part 3, Table 3.9.3).

Equivalent guidance values for an equivalent 28-day study period raises the concentration values for classification by three-fold: classification in category 1 is applicable at low concentrations (< 30 mg/kg bw/day in oral studies; < 60 mg/kg bw/day in dermal studies) and in Category 2 at generally moderate concentrations (30 to 300 mg/kg bw/day in oral studies, 60 to 600 mg/kg bw/day in dermal studies).

Based on the short-term, repeated dose toxicity study (combined with reproductive and developmental toxicity) according to the OECD Guildeline 422 (2016), the test item did not produce adverse toxicity in male or female rats when administered at 800 mg/kg bw/day for 34 and 50 to 60 days, respectively. Therefore, no classification of the test item is warranted for specific target organ toxicity – repeated exposure according to the CLP Regulation (EC) No. 1272/2008.