Registration Dossier

Administrative data

Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route
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).
Effect on fertility: via inhalation route
Endpoint conclusion:
no study available
Effect on fertility: via dermal route
Endpoint conclusion:
no study available
Additional information

Effect on fertility: via oral route

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 reproductive parameters.

 

In accordance with Section 1 of Annex XI of the Regulation (EC) No. 1907/2006 (REACH), it is considered justified to omit the two-generation reproductive toxicity study (required in section 8.7.3 of Annex IX) as testing does not appear scientifically necessary.

The substance is unreactive, insoluble and not inhalable and there is no evidence of absorption and no evidence of reproductive toxicity in an oral study conducted to OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test).

It is therefore considered that the available data already sufficiently addresses the reproductive toxicity data requirements and that further animal testing would not add substantial value to the dataset. 


Short description of key information:
TOXICITY TO REPRODUCTION
NOAEL: 1000 mg/kg/day male and female Wistar Han strain rats

Justification for selection of Effect on fertility via oral route:
Only one study available.

Effects on developmental toxicity

Description of key information
DEVELOPMENTAL TOXICITY / TERATOGENICITY 
NOAEL: 1000 mg/kg/day Wistar Han strain rats
Effect on developmental toxicity: via oral route
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).
Effect on developmental toxicity: via inhalation route
Endpoint conclusion:
no study available
Effect on developmental toxicity: via dermal route
Endpoint conclusion:
no study available
Additional information

Effect on developmental toxicity: via oral route

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 developmental toxicity.

 

In accordance with Section 1 of Annex XI of the Regulation (EC) No. 1907/2006 (REACH), it is considered justified to omit the pre-natal development toxicity study (required in section 8.7.2 of Annex IX) as testing does not appear scientifically necessary.

The substance is unreactive, insoluble and not inhalable and there is no evidence of absorption and no evidence of developmental toxicity in an oral study conducted to OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test).

It is therefore considered that the available data already sufficiently addresses the developmental toxicity data requirements and that further animal testing would not add substantial value to the dataset. 


Justification for selection of Effect on developmental toxicity: via oral route:
Only one study available.

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 toxicity to reproduction.