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Description of key information

In a 28-day repeated dose toxicity study in rats, the test article caused mortality and gastric irritation at the high dose level (200 mg/kg bw) due to its corrosivity and the NOEL was determined at 60 mg/kg body weight per day.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
NOAEL
60 mg/kg bw/day
Study duration:
subacute
Species:
rat

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

In a GLP-compliant 28-day repeated dose toxicity study equivalent to OECD test guideline No. 407, four groups of 5 male and 5 female Sprague Dawley rats each were given the test substance by oral gavage at dose levels of 0, 20, 60 and 200 mg/kg body weight per day (C.I.T., Project No. 850311, 1990). No treatment-related clinical signs were noted in all treated animals. The very slight changes recorded in bodyweight or food consumption were without toxicological significance. Mortality was limited to one male of the 20 mg/kg group without demonstration of any clinical sign during the period preceding death. In addition, three females were found dead in the 200 mg/kg/day group, without clinical signs preceding death. During hematology analysis, a very slight decrease in platelet count was noted in males from the 60 and 200 mg/kg/day groups. However, the individual values were within normal limits, and therefore this change has no clear toxicological significance. In blood chemistry investigation, slight increase of urea and creatinine level was noted as statistically significant in males from the 60 and 200 mg/kg/day groups, in comparison with control values. This significance was due to low values noted in three control males out of five. All the individual values were within normal limits. Furthermore, in females from the 60 mg/kg/day group and in the males from the 60 and 200 mg/kg/day groups, slight changes in protein electrophoresis parameters (albumin, α1-globulin, α2-globulin, β-globulin) were recorded. Due to their marginal character, these changes are considered to be of no toxicological significance. There were no changes in urinalysis in males and females from all treated groups. At macroscopic examinations, signs of gastric irritation consisting in wall thickening and/or focal hemorrhages of the forestomach were observed in 5 out of 7 surviving rats from the 200 mg/kg/day group. The abnormalities seen at necropsy in the respiratory tract of two rats (200 mg group) found dead during the study were attributed to a gavage error. Due to cannibalism, the cause of the death of the third rat was not established. The animal of the 20 mg/kg group found dead showed a dilatation of the forestomach. In the treated groups, no difference in the organ weights when compared to the control groups, presented any dose response relationship. Microscopic examinations revealed changes in the stomach of the 7 surviving rats from the 200 mg/kg/day group: moderate or marked signs of irritation in 5 animals (4 males and 1 female); a slight submucosal edema in the 2 other rats. One female from the 60 mg/kg/day group presented a gastric submucosal edema. These changes were most likely local effects caused by the corrosive nature of the test article and do not reflect systemic organ toxicity. Therefore, classification for repeated dose toxicity is not warranted.

In conclusion, based on these results and under the described experimental conditions, the No observed effect level was estimated to be 60 mg/kg body weight per day for both sexes.


Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:
guideline study

Repeated dose toxicity: via oral route - systemic effects (target organ) digestive: stomach

Justification for classification or non-classification

The effects observed in the 28d-repeated dose study were most likely local effects caused by the corrosive nature of the test article and do not reflect systemic organ toxicity. Therefore, classification for repeated dose toxicity is not warranted under Regulation (EC) No.1272/2008.