Registration Dossier

Administrative data

Description of key information

Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test including neurotoxicity

assessment oral (gavage); rat (Hsd: Sprague Dawley SD, m/f (OECD guideline 422, GLP): NOAEL(neurotoxicity) = 1000 mg/kg bw/d

Key value for chemical safety assessment

Effect on neurotoxicity: via oral route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
1 000 mg/kg bw/day
Study duration:
subacute
Species:
rat

Effect on neurotoxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Effect on neurotoxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

No indication of neurotoxicity was found in a Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test according to OECD Guideline 422 (22 March 1996) which included a Functional Observation Battery, examination of grip strength and sensory reactivity to stimuli as well as motor activity assessment:

TREGDMA (95.8% a.i.) was administered to 10 Hsd: Sprague Dawley SD rats/sex/dose orally by gavage at dose levels of 0 (control), 100, 300 and 1000 mg/kg bw/d. The treatment schedule included 2 weeks before pairing, during pairing, post coitum and post partum periods up to day 3 post partum. Animals were administered for approximately 5 and 8 weeks for males and females, respectively.  

Observation of animals at removal from the cage and in an open arena (neurotoxicity assessment) did not reveal changes attributable to the test item. No relevant differences were noted in motor activity and sensory reaction to stimuli between control and treated groups.

On the basis of the results obtained in the study, the NOAEL for neurotoxicity was 1000 mg/kg bw/d (males/females). 

 

No human data are available for neurotoxicity. However, there is no reason to believe that these results from rat would not be applicable to humans.


Justification for selection of effect on neurotoxicity via oral route endpoint:
OECD guideline 422 study including neurotoxicity assessment, no deviations, GLP

Justification for classification or non-classification

Based on the available data TREGDMA does not need to be classified for neurotoxicity according to Directive 67/548/EEC as well as CLP, EU GHS (Regulation 1272/2008/EC) and therefore labelling is not necessary.