Registration Dossier

Administrative data

Key value for chemical safety assessment

Effects on fertility

Description of key information
No evidence of any adverse effects on fertility. 
Effect on fertility: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
215 mg/kg bw/day
Study duration:
subacute
Species:
rat
Additional information

In a modern GLP study (OECD 421) on a very similar material, it was shown that male and female reproductive parameters were unaffected by test material administration and no evidence of parental systemic toxicity was noted in any of the three dose groups. The NOAEL in the study after correction for the presence of oil were 215mg/kg bw/day for parental toxicity, reproductive indices and effects on the litters.

This finding was supported by a second non-GLP study conducted previously which showed that repeated topical application of a 20 % dilution of test material to male rabbits, over the duration of the spermatogenic cycle, did not adversely affect their reproductive capacity. These results are considered suitable to be used for the target material to be Registered based on read-across accepted by ECHA.



Short description of key information:
GLP study reporting NOAEL for F0 and F1 as 215 mg/kg/day after oral exposure to a close structural analogue of the test material (OECD 421). These data are supported by a non-GLP study reporting no effect on reproductive capacity of male rabbits after dermal exposure to the same structural analogue of the test material over a period of ten weeks before mating.

Justification for selection of Effect on fertility via oral route:
Highest dose tested in an OECD 421 screening study performed on a read-across substance (read-across agreed by ECHA as applicable for this substance), no effects reported on either parental animals or reproductive organs or indices (or pups).

Effects on developmental toxicity

Description of key information
In a modern GLP study (OECD 414) EXP1503090 was administered by gavage to groups of female Sprague Dawley rats from gestation days 6 through 19 at 30, 100 and 300 mg/kg bw/d.   No treatment-related effect on intrauterine growth and survival, fetal malformations or developmental variations were noted in this study. Based on these observations, the oral NOAEL in rat for maternal toxicity was established at 100 mg/kg bw/d and the NOAEL for developmental toxicity was set at 300 mg/kg bw/d.
Effect on developmental toxicity: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
300 mg/kg bw/day
Species:
rat
Quality of whole database:
Testing conducted using GLP study (OECD 414). Supported by results of OECD 421 on read-across substance.
Additional information

In a modern GLP study (OECD 414) EXP1503090 was administered by gavage to groups of female Sprague Dawley rats from gestation days 6 through 19 at 30, 100 and 300 mg/kg bw/d. A concurrent control group receiving vehicle control (mineral oil and corn oil) was included. Dams showed no test substance-related effects for clinical signs, body weight, food consumption or macroscopic examination. Statistically significant, higher alkaline phosphatase, alanine aminotransferase and triglyceride levels were noted at 300 mg/kg bw/d. No treatment-related effect on intrauterine growth and survival, fetal malformations or developmental variations were noted in this study.

Based on these observations, the oral NOAEL in rat for maternal toxicity was established at 100 mg/kg bw/d and the NOAEL for developmental toxicity was set at 300 mg/kg bw/d.


Justification for selection of Effect on developmental toxicity: via oral route:
In a modern GLP study (OECD 414) EXP1503090 was administered by gavage to groups of female Sprague Dawley rats from gestation days 6 through 19 at 30, 100 and 300 mg/kg bw/d. A concurrent control group receiving vehicle control (mineral oil and corn oil) was included. Dams showed no test substance-related effects for clinical signs, body weight, food consumption or macroscopic examination. Statistically significant, higher alkaline phosphatase, alanine aminotransferase and triglyceride levels were noted at 300 mg/kg bw/d. No treatment-related effect on intrauterine growth and survival, fetal malformations or developmental variations were noted in this study.
Based on these observations, the oral NOAEL in rat for maternal toxicity was established at 100 mg/kg bw/d and the NOAEL for developmental toxicity was set at 300 mg/kg bw/d.

Justification for classification or non-classification

A close chemical analogue did not influence fertility or the next generation at the highest dose tested (215mg/kg bw/day). The registration substance was tested in an OECD 414 developmental toxicity study and the NOAEL for developmental effects was 300mg/kg bw/day. Based on these data, the substance is not considered to meet criteria for classification under the terms of Directive 67/548/EEC or GHS as reflected by Regulation (EC) 1272/2008.