Registration Dossier

Administrative data

Description of key information

REPEATED DOSE TOXICITY: ORAL
NOAEL 75 mg/kg/day for male and female Wistar rats

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
NOAEL
75 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, 75, 250 and 750 mg/kg/day in propylene glycol. Males were exposed for 28 days (2 weeks prior to mating, during mating, and up to termination) and females were exposed for 41 to 55 days (2 weeks prior to mating, during mating, during postcoitum and during at least 4 days of lactation).

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

Changes in clinical biochemistry parameters, increased organ weights, macroscopically enlarged livers and microscopic findings in the liver (centrilobular hepatocytic hypertrophy) and thyroids (follicular hyperplasia and hypertrophy) characterised parental toxicity at 750 mg/kg. Higher liver weights and liver to body weight ratios were seen for both sexes and a slight degree of centrilobular hypertrophy of the liver was also seen for females at 250 mg/kg.

No toxicologically relevant changes were noted in any of the remaining parental parameters.

Under the conditions of this study, the NOAEL was determined to be 75 mg/kg bw/day for repeated dose toxicity. As no significant or severe effects were seen at the 250 mg/kg bw/day dose group, no classification for specific target organ toxicity due to repeat exposure (STOT RE) is necessary in accordance with EU criteria.

 

Repeated Dose Toxicity: Inhalation

In accordance with the Column 2 adaptation of Annex VIII of Regulation (EC) 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 viscous liquid with a low vapour pressure.

 

Repeated Dose Toxicity: Dermal

In accordance with the Column 2 adaptation of Annex VIII of Regulation (EC) 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 and toxicological properties of the substance suggest that it does not have the potential for significant absorption through the skin.


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.

Repeated dose toxicity: via oral route - systemic effects (target organ) digestive: liver; glandular: thyroids

Justification for classification or non-classification

In accordance with the criteria for classification as defined in Annex I, Regulation (EC) 1272/2008, the test material requires no classification for STOT RE in accordance with EU criteria.