Registration Dossier

Administrative data

Description of key information

GLP study reporting an oral NOAEL of 100 mg/kg/day in the rat (OECD 408, read-across substance, data considered applicable by ECHA). 

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Dose descriptor:
NOAEL
100 mg/kg bw/day
Study duration:
subchronic
Species:
rat

Additional information

While the key data is for a read-across substance, it is considered to be applicable to the registration substance (by ECHA) and accepted as valid. The 90d study is the longest exposure duration and provides the best indicator of the effects (subtle or more significant).

Based on the results of the key study (oral administration of EXP1503090 to Crl:CD(SD) rats at dosage levels of 30, 100, and 300 mg/kg/day for a minimum of 90 consecutive days) an oral NOAEL of 100 mg/kg/day in the rat was established. There were reduced body weights in males (up to 13.9% lower) with corresponding lower food consumption, in the 300 mg/kg/day group. This large drop in bodyweight did not recover after testing (recovery group) and there were secondary toxicity effects noted elsewhere in the animals which resulted from this. Hence the bodyweight effects were considered to be adverse and were the basis for the NOAEL. All other test article-related effects were either adaptive in nature or tended to reverse following the cessation of exposure. THe NOAEL in females was 300mg/kg bw/day.

This NOAEL is further supported by the 28d toxicity study in the registration substance, as well as the OECD 421 reproductive toxicity screening study in the registration substance, and finally the developmental toxicity study (414) in the read-across substance; all of these provide a similar effects and dose profile and support the NOAEL for systemic toxicity on repeated exposure as 100mg/kg bw/day.

Justification for classification or non-classification

The NOAEL established for repeat dose toxicity is 100mg/kg bw/day in males, and this is likely to be conservative (the true NOAEL may be somewhat higher). No adverse effects are recorded for this substance or the read-across surrogate below 300mg/kg.

Therefore the registration substance does not require classification under the terms of Directive 67/548/EEC, or CLP or GHS as reflected by Regulation (EC) 1272/2008.