Registration Dossier

Administrative data

Description of key information

Oral: NOAEL (rat, 28d, OECD 407) ≥ 1000 mg/kg bw/d 

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Dose descriptor:
NOAEL
1 000 mg/kg bw/day
Study duration:
subacute
Species:
rat

Additional information

An oral repeated dose toxicity study was performed with TS-2863 (2 –(2-hexyl-decyloxy)-benzamide) according to OECD 407 (Pels Rijcken, 1998). Rats (5/sex/dose) were administered 0, 50, 200 and 1000 mg/kg of the test substance daily by gavage for 28 days.

One female receiving 50 mg/kg bw/d was found dead on day 28. Based on the hunched posture and laboured breathing observed prior to mortality, and findings during the necropsy, the death may have been related to mis-dosing. One male and 1 female in the 50 mg/kg bw/d group, and all (5/5) the females in the 1000 mg/kg bw/d group had red staining of the fur from week 2 or 3 onwards during the study period. A red liquid is excreted from the nose and eyes of the rat and commonly spread over the fur by grooming. The excretion rate may be increased when the rats are subjected to stress, like daily dosing by gavage. Based on the lack of other clinical signs of discomfort and pathological results, the effect is not considered to be a sign of systemic toxicity.

Females administered 1000 mg/kg bw/d had a statistically significant increase in potassium levels (4.98 mmol/L) compared to the control group (4.05 mmol/L). The significance may be due to a low control group level, as the low- and mid-dose group levels were 4.77 and 4.38 mmol/L, respectively. As there were no similar effects in males and no related histopathological effects, this result is not considered to be of toxicological relevance. There were no treatment-related effects on body weight and body weight gain, food intake, and absolute and relative organ weight during the study period. No effects on the neurobehaviour was observed in male or female rats treated with the test substance in the functional observation tests (including grip strength and reflex testing) and motor activity tests.

No treatment-related effects were observed during the gross pathology and histopathology examinations in any of the treated or control animals. Haemorrhage in the lungs, a thickened limiting ridge in the stomach and discolouration of the mandibular lymph node was noted in the animal that died on day 28 following a suspected mis-dosing.

In conclusion, no treatment-related effects were observed up to and including the highest dose level. Therefore, the NOAEL for TS-2863 is considered to be 1000 mg/kg bw/d for male and female rats.

Justification for classification or non-classification

The available data on the repeated dose toxicity of the test substance do not meet the criteria for classification according to Regulation (EC) 1272/2008 or Directive 67/548/EEC, and are therefore conclusive but not sufficient for classification.