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Administrative data

Description of key information

The NOAEL for the test substance was determined to be 1000 mg/kg bw in male and female animals after sub-acute repeated dose administration.

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
1 000 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

Mode of Action Analysis / Human Relevance Framework

Additional information

In a repeated dose toxicity study comparable to OECD guideline 407 (CIBA-GEIGY, 1982) a total of 80 RAIf (SPF) rats, 10 males and 10 females per dose group were used. The test substance was administered by oral gavage for 28 days at dosages of 0, 300, 1000 and 3000 mg/kg bw per day. The mean body weight gain, mean food consumption and mean water consumption of all treated male and female groups was similar to that of the respective control groups. Food conversion ratio of treated animals was similar to the control ratios. No death occurred during the 28 days test period. No clinical symptoms and no signs of local and/or systemic toxicity were observed. Hearing tests and ophthalmic inspections revealed no treatment related effects. A slight, but significant increase of absolute and relative liver weight was observed in male groups 3 and 4 (1000 and 3000 mg/kg bw) and in female group 4 (3000 mg/kg bw). Since the histopathological findings as well as the biochemical parameters were similar to those of the respective controls the experimental significance of this finding is in doubt. Histopathological examination revealed that the administration of the tested compound seems to be associated with the occurrence of spermatic granulomata in the epididymes. Although this change seems to be dose related it may, in fact, result from handling the test animals as similar changes may also occasionally be found in control male rats. Apart from this finding no other changes were observed that were considered to be due to the treatment with the test compound. It can be inferred from the observations made that a "no observable adverse effect level" for the test substance is 300 mg/kg bw in males and 1000 mg/kg bw in females.

In the course of another sub-acute study (OECD 407, GLP), the test item was administered orally by gavage to groups of 10 male Wistar rats at dose levels of 0 mg/kg body weight/day (mg/kg bw/d, test group 0) and 1000 mg/kg bw/d (test group 1) over a period of 4 weeks. The study was performed to determine the bioavailability of the test substance after oral administration at limit dose.

Clinical examination revealed orange discolored feces in all animals from study day 1 onwards.

Regarding pathology, an orange discoloration of contents in the glandular stomach, jejunum and cecum was observed. The discoloration was regarded to be treatment-related and corresponded to the color of the test substance. All other findings occurred either individually or were biologically equally distributed over control and treatment group. They were considered to be incidental or spontaneous in origin and without any relation to treatment. The increase in absolute and relative liver weight (as observed in a previous study) could not be confirmed. Thus, under the conditions of the study the no observed adverse effect level (NOAEL) is below 1000 mg/kg bw/d in male Wistar rats. Trace amounts of the applied substance could be detected in liver, spleen and kidney tissue of individual animals ranging from 0.94 - 15.3 ng/mg tissue. No test item could be detected in rat plasma samples. Thus, it could be concluded that the test item was bioavailable.

Justification for classification or non-classification

Classification, Labeling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. As a result the substance is not considered to be classified for repeated dose toxicity under Regulation (EC) No. 1272/2008.