Registration Dossier

Administrative data

Description of key information

Oral: Testing has been waived.  Inhalation is the most plausible route for repeated exposures.
Dermal: Testing has been waived. Inhalation is the most plausible route for repeated exposures.
Inhalation: OECD 413. 90-day inhalation, 6 hr/day, rats. No local effects observed. No effects observed at 5154 mg/m3. Systemic effects (central nervous system) were observed at 20618 mg/m3 and higher. Effects were the same as those observed in acute toxicity studies, and neither severity nor rate of incurrence increased with increasing exposure duration, e.g., toxicity was not progressive with exposure. Therefore, there is no repeated exposure contribution to toxicity. When all of the relevant data were considered, the NOAEL for central nervous system effects (in both extended repeated exposures or acute exposures) was 15463 mg/m3. Not classified as a repeated exposure toxin. Reliability = 1.

Key value for chemical safety assessment

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion
Dose descriptor:
NOAEC
15 463 mg/m³
Study duration:
subchronic
Species:
rat

Mode of Action Analysis / Human Relevance Framework

Additional information

The only toxicity observed in the subchronic study was associated with central nervous system effects, e. g. tremors and convulsions, which occur at a threshold exposure concentration of 20618 mg/m3. No adverse effects were observed at 5154 mg/m3 and lower. The central nervous system effects in the subchronic study were the same as those observed in acute toxicity studies, and neither severity nor rate of occurrence changed with increasing exposure duration, e.g. toxicity was not progressive with exposure. There is no apparent concentration/time (C x T) relationship that would support treating the toxicity as increasing with exposure duration or time span. Therefore, acute and repeated exposure toxicity effects are identical for this substance. If the 90-day inhalation study is taken in isolation, the NOAEL would be 500 ppm (5154 mg/m3) for males and females based on the clinical signs of central nervous system toxicity observed during exposure concentrations of 2000 ppm (20618 mg/m3) and above. However, in the 90-day study, all adverse central nervous system effects occurred very early in the exposure and presented in the same manner as the effects in the acute inhalation, neurotoxicity, developmental and reproductive studies. The adverse effects did not increase in severity or occurrence with increasing exposure duration. Therefore, the nature of the adverse effects associated with test substance provided a unique opportunity to use a 2-hr neurotoxicity study (DI.K2.2-hr.NEURO.HLR-395-95) to evaluate the toxicity between the 500 and 2000 ppm exposure levels used in the 90-day subchronic study. When all of the relevant data were considered, the NOAEL for central nervous system effects (in both extended repeated exposures or acute exposures) was 15463 mg/m3.


Repeated dose toxicity: inhalation - systemic effects (target organ) neurologic: central nervous system

Justification for classification or non-classification

Based on the high exposure concentrations necessary to produce adverse effects, and the observations during the acute and repeated exposure inhalation exposures, the substance does not need to be classified for repeated dose toxicity according the EU Directive 67/548/EEC and EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.