Registration Dossier

Administrative data

Description of key information

REPEATED DOSE TOXICITY: ORAL
NOAEL 1000 mg/kg/day for male and female Wistar Han rats

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
1 000 mg/kg bw/day
Study duration:
subacute
Species:
rat
Quality of whole database:
The key study was conducted in accordance with the standardised guidelines OECD 422 and EPA OPPTS 870.3650 under GLP conditions. It was assigned a reliability score of 1 in accordance with the criteria set forth by Klimisch (1997).

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

Repeated Dose Toxicity: Oral

A combined repeated dose toxicity study with reproduction/developmental toxicity screening test was carried out in order to assess the test material in accordance with the standardised guidelines OECD 422 and EPA OPPTS 870.3650 under GLP conditions.

Four groups of ten male and ten female Wistar Han rats were exposed by oral gavage to the test material at 0, 100, 300 and 1000 mg/kg/day.

Males were exposed for 29 days: 2 weeks prior to mating, during mating, and up to termination. Females were exposed for 42 to 45 days: 2 weeks prior to mating, during mating, during post-coitum and during at least 4 days of lactation.

Animals were evaluated for mortality / viability, clinical signs, functional observations and locomotor activity, bodyweight and food consumption, clinical pathology, macroscopy at termination, organ weights and histopathology on a selection of tissues and reproduction / developmental parameters.

No parental toxicity was observed up to 1000 mg/kg.

Under the conditions of this study, the NOAEL was determined to be 1000 mg/kg bw/day for repeated dose toxicity.

 

In accordance with the Column 2 adaptation of Annex IX of Regulation (EC) No. 1907/2006 (REACH), it is considered justified to omit the 90 day sub-chronic toxicity study (required under point 8.6.2) if the substance is unreactive, insoluble and not inhalable and if there is no evidence of absorption and no evidence of toxicity in a 28-day 'limit test'.

From experience in use, the test substance in known to be largely unreactive and stable under normal conditions.

In a reliable, well reported water solubility study, the solubility in water, determined as mean TOC concentration, was found to be ≤ 5.6 mg/L at 20.0 ± 0.5 °C.

In a reliable, well reported vapour pressure study, the vapour pressure of the test substance at 25.0 °C was found to be 0.052 Pa. The low vapour pressure combined with large particle size make inhalation of the test substance unlikely.

In a reliable, well reported combined repeated dose oral toxicity and reproduction/developmental screening study in rats, there was no evidence of toxicity over the 28 day dosing period and the NOAEL was determined to be 1000 mg/kg bw/day (actual dose received).

In light of the information available on the test substance, the 90 day sub-chronic toxicity study has been omitted.

 

Repeated Dose Toxicity: Inhalation

In accordance with the Column 2 adaptation of Annex VIII of Regulation (EC) No. 1907/2006 (REACH), it is considered justified to omit the repeated dose toxicity by the inhalation route study as specified in section 8.6.1, as testing by this route is inappropriate. Exposure via the inhalation route is not relevant due to the substance being a liquid with a low vapour pressure. Testing via the oral route is considered more appropriate.

 

Repeated Dose Toxicity: Dermal

In accordance with the Column 2 adaptation of Annex VIII of Regulation (EC) No. 1907/2006 (REACH), it is considered justified to omit the repeated dose toxicity study by the dermal route as specified in section 8.6.1. as testing by this route is deemed inappropriate. Exposure via the dermal route is not anticipated in production or use and the physicochemical properties of the substance suggest that it does not have the potential for significant absorption through the skin. In addition, a reliable, well reported acute dermal toxicity study showed no evidence of systemic toxicity.

Testing via the oral route is considered more appropriate.


Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:
Only one study available.

Justification for selection of repeated dose toxicity inhalation - systemic effects endpoint:
A data waiver has been submitted to address this endpoint.

Justification for selection of repeated dose toxicity inhalation - local effects endpoint:
A data waiver has been submitted to address this endpoint.

Justification for selection of repeated dose toxicity dermal - systemic effects endpoint:
A data waiver has been submitted to address this endpoint.

Justification for selection of repeated dose toxicity dermal - local effects endpoint:
A data waiver has been submitted to address this endpoint.

Justification for classification or non-classification

In accordance with the criteria for classification as defined in Annex I, Regulation (EC) No. 1272/2008, the test material does not require classification for repeated dose toxicity.