Registration Dossier

Administrative data

Description of key information

repeated dose oral dietary administration (90 days) -NOAEL 406.4 mg/kg bw/day
repeated dose oral gavage (28 days) -NOAEL 1000mg/kg bw/day

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
406.4 mg/kg bw/day
Study duration:
subchronic
Species:
rat

Additional information

A 28 day sub acute repeat dose toxicity study (Hita reserach laboratories, 2001) was conducted to determine the effect of repeated oral administration of T-1540N to rats. The study was conducted according to Annex V Guideline . Test groups of 30 male and 30 female rats were administered test material by oral gavage at the following concentrations; 0 (untreated control group), 8, 40, 200 and 1000 mg/kg/bw/day.

No rats died during the study and no abnormalities were found during necropsy at the end of the study period. Increased absolute and relative liver weights were noted in males of the 1000 mg/kg/day dose group. No other related changes were noted.

On this basis, it was concluded that the NOAEL for T-1540N following 28 -day administration to rats was 1000mg/kg/bw/day.

A 90 day sub chronic repeat dose toxicity study (Pharmakon Europe, 2001) was conducted to determine the effect of repeated oral administration of T-1540N to rats. The study was conducted according to OECD Guideline 408 . Test groups of 90 male and 90 female rats were administered test material by oral gavage at the following concentrations; 0 (untreated control group), 123.1, 406.4, 1261.3 mg/kg/bw/day.

No mortality and no treatment-related clinical signs were noted. A decreased body weight gain was noted for group 3 males (not significant) and group 4 males and females (statistically significant). Considering weakness of the reactions noted during the study, the histopathological results should not modify the Classification of the substance. Only some kidney lesions may be noted, at the highest dose level group.

On this basis, it was concluded that the NOEL for T-1540N following 90 -day administration to rats was 123.1 mg/kg/bw/day.

Justification for classification or non-classification

In the repeat oral toxicity study noted above, no deaths were seen following 28 -day and 90 -day administration of T-1540N, and no toxic signs in any examined organs were noted. This result is considered to have conclusively demonstrated that classification for STOT (repeat dose) is not required for T-1540N by the oral route. During the 90 day study an adverse effect was observed at the higher dose group however this effect was still above the concentration for toxicity and therefore was not considered for classification.

No information is available for repeated dose administration by either dermal or inhaled routes, and so it is not possible to reach a definitive conclusion regarding STOT (repeat dose) overall (all routes of exposure).