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Description of key information

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
88 mg/kg bw/day
Study duration:
subacute
Species:
rat
Quality of whole database:
Two studies were performed according to the respective OECD guideline under GLP conditions and evaluated with a Klimisch score 1.

Additional information

A reproduction/ developmental toxicity screening test was carried out in order to assess the test material in accordance with the standardised guidelines OECD 421 and EPA OPPTS 870.3550 under CLP conditions.

Four groups of ten male and female Wistar Han rats were exposed by oral gavage to the test material at 0, 88, 300 and 1000 mg/kg bw/day in carboxymethylcellulose. Males were exposed for 28 days ( 2 weeks prior to mating, during mating, and up to termination) and females were exposed for up to 55 days ( 2 weeks prior to mating, during mating and gestation and during at least 4 days of lactation).

Animals were evaluated for mortality/ viability, clinical and functional observations, body weights and food consumption, clinical pathology, macroscopy at termination, organ weights and histopathology on a selection of tissues.

No clinical signs directly related to the test item were observed in any group.

Under the conditions of this study, the NOAEL for general systemic toxicity was 300 mg/kg bw/day in males based on decreased food consumption and body weights/ body weight change at 1000 mg/kg bw/day. For females the NOAEL was 88 mg/kg bw/day as they showed decreased absolute and relative thymus weights at 300 mg/kg bw/day.  There was reduced cellularity in the thymus of females at 1000 mg/kg bw/day only. At 1000 mg/kg bw/day, there were also signs of chronic nephropathy and hypertrophy of the kidney tubules as well as hepatocellular hypertrophy in female animals only.

In a second 28 day study following OECD guideline, Wistar rats were exposed to 0, 100, 300, and 1000 mg/kg bw/day of the test substance. Animals were evaluated for mortality/ viability, clinical and functional observations, body weights and food consumption, clinical pathology, macroscopy at termination, organ weights and histopathology on a selection of tissues. The only effects were reduced body weight likely due to reduced food intake as well as an increase in alkaline phosphatase in the high dose group, but no histological effects were found. The NOAEL for this study was 1000 mg/kg bw/day.


Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:
Two 28 day studies were performed according to the respective guideline under GLP conditions and evaluated with a Klimisch score 1. The lowest NOAEL was chosen based on the study data.

Justification for classification or non-classification

Based on the available data no classification or labelling is required.

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