Registration Dossier

Administrative data

Key value for chemical safety assessment

Effects on fertility

Description of key information

The substance is considered to cause no adverse effects on fertility based on the absence of histopathology findings in organs related to male and female reproduction, absence of distribution into organs other than liver and kidney upon subchronic exposure (Knight 2007) as well as on the absence of findings in a screening study (OECD 422) (MHLW 2007).

Effect on fertility: via oral route
Endpoint conclusion:
no adverse effect observed
Study duration:
subacute
Species:
rat
Effect on fertility: via inhalation route
Endpoint conclusion:
no study available
Effect on fertility: via dermal route
Endpoint conclusion:
no study available
Additional information

A screening study for reproductive toxicity (OECD 422) was performed in 2006, and a summary report was published in 2007 in Japanese the sponsor MHLW Japan (MHLW 2007). This summary report was translated into English. Although it is not a full study report, it contains sufficient information for evaluation and interpretation of the study. The study is indicated to be GLP and OECD guideline compliant. It was performed with gavage dosing of 30, 100 and 300 mg/kg bw using olive oil as vehicle and doses were based on systemic toxicity on parental animals. A NOAEL of 30 mg/kg bw was shown for systemic toxicity of parental animals. No effect of the compound was observed on the reproductive performances, such as the estrous cycle, copulation, fertility, delivery and lactation. No effect of the compound was observed on the implantation, the number of pups, sex ratio of pups, viability of the pups during 4 days of lactation and weights of the pups. No external abnormalities or macroscopic findings were detected in any pup.

The substance did not cause adverse effects on reproductive organs upon subchronic and chronic exposure feeding studies. For details it is referred to the chapter on repeated dose toxicity.

Taken together, the substance is not considered to cause adverse effects on fertility.


Short description of key information:
The substance is considered to cause no adverse effects on fertility based on the absence of histopathology findings in organs related to male and female reproduction, absence of distribution into organs other than liver and kidney upon subchronic exposure (Knight 2007) as well as on the absence of findings in a screening study (OECD 422) (MHLW 2007).

Effects on developmental toxicity

Description of key information
No developmental toxicity and teratogenicity was observed in two studies with rats and mice (Fritz 1975b and c). The design of both studies is sufficiently similar to OECD testing guideline 414 and the reporting details are adequate for study assessment. Both studies were performed prior to the introduction of GLP. 
Effect on developmental toxicity: via oral route
Endpoint conclusion:
no adverse effect observed
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

For developmental toxicity and teratogenicity, two valid rodent studies are available, and both of them can serve as key studies. The design of both studies is sufficiently similar to OECD testing guideline 414 and the reporting details are adequate for study assessment. Both studies were performed prior to the introduction of GLP.

In the teratology study in rats (Fritz 1975b) a total of 105 Sprague-Dawley pregnant females (25 per dose group, except control with 30) were dosed by gavage with 0, 150, 500 and 1000 mg/kg bw from day 6 through 15 of pregnancy.

In the mouse teratology study (Fritz 1975c) a total of 150 NMRI derived (SPF) females (30 per dose group, except control with 60) were dosed by gavage with 0, 150, 500 and 1000 mg/kg bw from day 6 through 15 of pregnancy.

There were no treatment related reactions noted, with the exception of the mouse study where increased feed intake at the high dose level as well as a slightly decreased feed intake at the intermediate dose level was noted. Embryonic development was not impaired and no teratogenic effects were noted.

In addition, no indication of developmental toxicity was observed in the screening study (OECD 422) performed with gavage application using olive oil as vehicle (MHLW 2007). For this study, 300 mg/kg bw was used as the highest dosed.

Justification for classification or non-classification

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.