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 (Sprague Dawley [Crl:CD(SD)BR]), 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) MAPTAC was administered to 10 Sprague Dawley [Crl:CD(SD)BR] rats/sex/dose orally by gavage at dose levels of 0 (control), 100, 300 and 1000 mg/kg bw/d. Males were treated for a total of 38 days including 2 weeks prior to pairing and continuously thereafter, up to the day before necropsy.

Females were dosed throughout the study including 2 weeks before pairing, thereafter during pairing, gestation and lactation periods until Day 3 post partum.

Observation of animals at removal from the cage and in an open arena (neurotoxicity assessment) did not reveal changes attributable to the test item. Reduction in motor activity and reduced grip strength (first trial only) observed in males of the high dose group were noted at the end of treatment period when compared to controls. Considering that no differences were noted in other correlated neuromotory tests (second trial of grip strength, landing footsplay and rearing measurements in the open arena) this finding was considered incidental.

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 MAPTAC 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.