Registration Dossier

Administrative data

Description of key information

Oral, subacute 4 weeks (Rat-Wistar, GLP, OECD TG 407): NOAEL = 8 mg/kg bw/day; the findings at 50 mg/kg bw/day (LOAEL) were considered as of minor toxicological relevance; the dose of 200/100 mg/kg bw led to severe organ damage and deaths

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Study duration:

Additional information

In a 4 week oral toxicity study on 10 male and 10 female rats per group the daily oral administration of the test substance in doses of 8 and 50 mg/kg bw was well tolerated. The findings (increased sialorrhea; increased incidences of porphyrin deposits in the Harderian gland of male and female animals) in the 50 mg/kg bw dose group were judged as of minor toxicological relevance.

Signs of severe intolerance including deaths were found after 7 days of treatment with 200 mg/kg bw, whereafter the dose was reduced to 100 mg/kg bw. The signs of intolerance were reduced after reduction of dose, however, the animals still showed signs of toxicity such as reduced body weight, changes in blood parameters, atrophy of male sexual organs and changes in the lymphatic system.

Microscopic lesions were noted in the stomach, thymus, spleen, lymph nodes and bone marrow of both sexes and in the male sexual organs.

Severe forestomach lesions were observed in some animals which died or were sacrificed during administration of the high dose which may be caused by local irritation. It is suggested by the author of the report that the other substance related effects are secondary to these lesions and the subsequently degenerating status of the animals.

The NOAEL was established in this study with 8 mg/kg bw/day, while the findings at 50 mg/kg bw (LOAEL) were considered as of minor toxicological relevance. The daily dose of 200 mg/kg bw, reduced on day 8 to 100 mg/kg bw, led to severe organ damage and deaths in males and females.

Justification for classification or non-classification

Based on the study results a classification according to Directive 67/548/EEC or Regulation (EC) No. 1272/2008 (CLP) is recommended as follows:

R48/22 (Harmful: danger of serious damage to health by prolonged exposure if swallowed)

STOT Rep. Exp. 2 (H373: May cause damage to organs through prolonged or repeated exposure.)