Registration Dossier

Administrative data

Key value for chemical safety assessment

Effects on fertility

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

Based on the absence of adverse effects on reproductive organs in rats at the limit dose of 1000 mg/kg bw the substance is unlikely to have adverse on reproductive function.


Short description of key information:
No adverse effects on reproductive organs were observed after subchronic treatment of rats at doses of up to 1000 mg/kg bw. (OECD 408, GLP) BASF 2013). A testing proposal for a functional study for fertility has been propsed to ECHA and will be performed once a final decision has been issued.

Effects on developmental toxicity

Description of key information
Females at 900 mg/kg bw/day showed transient clinical signs like piloerection and lethargy. Additionally, high dose females had lower body weights and weight gains from Days 15-20 post coitum and absolute and relative food consumption was also lower Days 6-17 post coitum. No maternal toxicity was observed in the 100 or 300 mg/kg bw/day groups. No developmental toxicity was observed in the 100, 300 and 900 mg/kg bw/day groups. Based on the results in this prenatal developmental toxicity study the maternal NOAEL was established as being 300 mg/kg bw/day and developmental NOAEL was established as 900 mg/kg bw/day.
Effect on developmental toxicity: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
900 mg/kg bw/day
Study duration:
subacute
Species:
rat
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

Eighty-eight mated female Wistar Han rats were assigned to four dose groups. The test item was administered once daily by oral gavage from Days 6 to 19 post-coitum at doses of 100, 300 and 900 mg/kg bw/day (Groups 2, 3 and 4 respectively). The rats of the control group received the vehicle, polyethylene glycol 400, alone. Females were checked daily for the presence of clinical signs. Food consumption of females was determined at periodic intervals; body weight was determined daily during treatment and at periodic intervals in the other periods. On Day 20 post-coitum, all animals were subjected to an examination post-mortem and external, thoracic and abdominal macroscopic findings were recorded. A laparohysterectomy was performed on each surviving female of the groups. The uteri, placentae and ovaries were examined, and the numbers of fetuses, early and late resorptions, total implantations and corpora lutea were recorded. Gravid uterine weights were recorded, and corrected body weights (changes) were calculated. The fetuses were weighed, sexed and examined for external, visceral and skeletal malformations and developmental variations. All live fetuses were euthanized. One half of the fetuses were decapitated and the heads were fixed in Bouin’s fixative, all fetuses were dissected and examined for visceral anomalies and subsequently fixed in 96% aqueous ethanol and stained with Alizarin Red S for skeletal examinations. Skeletal examinations were performed on approximately one-half of the fetuses.

Females at 900 mg/kg bw/day had treatment related clinical signs like piloerection and lethargy, among others, that occurred over several days but mostly resolved by the end of treatment. Females had lower body weights and weight gains from Days 15-20 post coitum and absolute and relative food consumption was also lower Days 6-17 post coitum. No maternal toxicity was observed in the 100 or 300 mg/kg bw/day groups. No developmental toxicity was observed in the 100, 300 and 900 mg/kg bw/day groups.

Based on the results in this prenatal developmental toxicity study the maternal No Observed Adverse Effect Level (NOAEL) was established as being 300 mg/kg bw/day and developmental NOAEL was established as 900 mg/kg bw/day.


Justification for selection of Effect on developmental toxicity: via oral route:
GLP and guideline compliant study

Justification for classification or non-classification

Dangerous Substance Directive (67/548/EEC)

The available studies are considered reliable and suitable for classification purposes under 67/548/EEC. As a result the substance is not considered to be classified for reproductive toxicity under Directive 67 / 548 / EEC.

  

Classification, Labeling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. As a result the substance is not considered to be classified for reproductive toxicity under Regulation (EC) No. 1272/2008.