Registration Dossier

Administrative data

Key value for chemical safety assessment

Effects on fertility

Description of key information
No effects on fertility as reported in an OECD 421 study. An OECD 443 study is ongoing for a read-across substance, the information from which will be applied to the registration substance on completion. 
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
Quality of whole database:
OECD 421 study conducted to GLP on registration substance, high quality. Dose adjusted for 43% purity (original doses 500mg/kg)
Additional information

In a modern GLP study (OECD 421) it was shown that male and female reproductive parameters were unaffected by test material administration up to the maximum dose tested, and no evidence of parental systemic toxicity was noted in any of the three dose groups.

The doses were adjusted for purity (43% A.I.) and so the NOAEL was 215mg/kg bw/day (highest dose tested).

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.


Short description of key information:
GLP study reporting NOAEL for F0 and F1 as 215 mg/kg/day (following dose adjustment for oil) after oral exposure (OECD 421). There is also a Non-GLP study of lower quality supporting this, reporting no effect on reproductive capacity of male rabbits after dermal exposure over a period of ten weeks before mating

Justification for selection of Effect on fertility via oral route:
No effects observed at maximum dose tested

Effects on developmental toxicity

Description of key information
GLP study reporting NOAEL for F1 as 300 mg/kg/day after oral exposure (OECD 414). This study is from a read-across substance which is considered to be applicable to the registration substance (also by ECHA). THese data are supported by the OECD 421 screening study on the registration substance. 
Effect on developmental toxicity: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
300 mg/kg bw/day
Study duration:
subacute
Species:
rat
Quality of whole database:
Read-across study OECD 414, conducted to GLP and reliable. SUpported by results of OECD 421 on registration substance.
Additional information

In a GLP OECD 414 study, the NOAEL for F1 (neonatal and developmental toxicity) is reported as 300 mg/kg/day after oral exposure. This study is from a read-across substance which is considered to be applicable to the registration substance (also by ECHA). THese data are further supported by the OECD 421 screening study on the registration substance.

Toxicity to reproduction: other studies

Additional information

The data set comprise an OECD 414 developmental toxicity study on a read-across surrogate which has been accepted as applicable by ECHA, and a reproductive toxicity screening study OECD 421 on the registration substance. There are also some lower quality supporting data for the registration substance. There is a consistent picture; there are no effects on parental animals or offspring at all doses tested in the screening study, and no effects on the development of pups at the highest dose tested in the developmental study. The NOAEL for reproductive toxicity (fertility and other indices) is 215 mg/kg bw/day, while that for developmental toxicity is 300mg/kg bw/day.

Justification for classification or non-classification

There were no effects recorded on any reproductive organs or on reproductive indices in parental animals at the maximum dose tested in the 421 study so the NOAEL for reprotox/fertility is 215mg/kg bw/day. For developmental toxicity, the NOAEL was 300mg/kg bw/day, hence under the terms of Directive 67/548/EEC or GHS as reflected by Regulation (EC) 1272/2008 this material does not meet the criteria for classification.

Additional information