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Administrative data

Description of key information

Repeat dose oral toxicity study in rats to test guideline OECD422 standard. Animals were treated daily at dose levels of 1, 3 and 10 mg/kg/day for a total of 35 days for males and 43 days for females.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
NOAEL
3 mg/kg bw/day
Study duration:
subchronic
Species:
rat
Quality of whole database:
Klimisch 1 rated study (reliable without restrictions)

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 the general toxicity part of this OECD422 repeat dose toxicity and reproductive toxicity screening study, the high dose level of 10 mg/kg/day demonstrated signs of systemic toxicity principally in the form of reduced mobility and increased urination. In addition, haematology investigations revealed changes in the erythrocyte parameters of the male and female rats (Reduced haemoglobin content and cell count, with increases in reticulocyte count) and clinical biochemistry revealed a decreased protein concentration in the plasma of the male rats. At termination, increased liver and spleen weights were noted in female rats and a tendency towards an increased spleen weight was also noted in the male animals. The animals treated at 3 and 1 mg/kg/day showed no similar effects. The occurrence of gastric pathological lesions in rats treated at 3 or 10 mg/kg/day were considered to be local irritant effects and not indicative of systemic toxicity.


Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:
A single guideline study (OECD422) conducted in accordance with GLP

Justification for classification or non-classification

There were no severe signs of toxicity at doses up to 10 mg/kg/day. However, increases in liver and spleen weight were suggestive of minor target organ toxicity which was associated with reductions in circulating erythrocytic parameters at this dose level. Despite these changes there were no pathological changes suggestive of organ malfunction observed in the liver or spleen at the high dose level of 10 mg/kg/day. Consequently, these effects are considered not to support classification for specific organ toxicity following repeated exposure.