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Administrative data

Description of key information

The NOAEL for systemic toxicity in rats is considered to be > 600 mg/kg bw/day as there were no adverse effects observed in any parameters up to the highest dose tested.

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
600 mg/kg bw/day
Study duration:
subacute
Species:
rat
Quality of whole database:
In accordance to OECD guideline 422 and in compliance with GLP regulations.

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

For this endpoint there is one recent key study available with data on toxicity after repeated dosing.

This Combined Repeated Dose Toxicity Study with the Reproduction/ Developmental Toxicity Screening Test in Wistar Rats was performed in accordance to OECD guideline 422 and in compliance with GLP regulations.

The test item was suspended in corn oil and administered orally at the dose levels of 65, 200 and 600 mg/kg bw/day as low, mid and high dose/ high dose recovery group rats, respectively. A concurrent control and a control recovery group of rats received vehicle (corn oil) alone. The dose volume administered was 5 mL/kg body weight. The main groups consisted of 10 male and 10 female rats per group and recovery groups consisted of 5 male and 5 female rats per group. The prepared dose formulations were administered once daily to specific group of rats prior to mating, during mating and post mating periods (for males), during pregnancy and up to lactation day 4 (for females). In the control and high dose recovery groups, the treatment period was followed by a 14-day no treatment (recovery) period. The recovery period of the study was started from the day of sacrifice of the first littered animals.

All animals were observed for clinical signs, physical abnormalities and mortality. The body weight and food consumption were measured at periodic intervals. The functional observation battery was done shortly before sacrifice for randomly selected 5 males and 5 females from each group. For recovery groups the functional observation battery was performed prior to sacrifice.

Laboratory investigations such as haematology and clinical chemistry were performed in randomly selected 5 males and 5 females from each group at the end of the premating period for main groups and at the end of recovery period from all animals of recovery groups.

The animals were subjected to detailed necropsy at sacrifice after overnight fasting and study plan specified tissues were collected. Tissues collected from randomly selected 5 males and 5 females in the control and high dose groups (including reproductive organs) were examined microscopically for histopathological changes.

There were no test item-related changes observed at high dose group; hence, histopathological evaluation was not carried out for lower (65 and 200 mg/kg bw/day) and recovery dose groups. Gross lesion was examined microscopically.

Under the experimental conditions, the following results were obtained:

• No clinical signs or mortality was observed during the course of the study

• No treatment-related neurological abnormalities /dysfunctions were observed at all the doses tested

• The body weights and food consumption were unaffected by the treatment at all the doses tested

• The test item administration did not reveal any treatment related changes in the hematology, coagulation and clinical chemistry parameters of both males and females

• There were no test item related changes in the terminal body weights, organ weights and organs weight ratios in both males and females

• There were no test item related gross and microscopic changes in both males and females

No Observed Adverse Effect Level:

The NOAEL for systemic toxicity in parental rats is considered to be > 600 mg/kg bw/day as there were no adverse effects observed in any parameters up to the highest dose tested.

Justification for classification or non-classification

In section 3.9.2 of the EU regulation No. 1272/2008 on the Classification, Labelling and Packaging of Substances and Mixtures (CLP), the criteria are depicted for the classification of a substance for

repeated exposure.

Based on the available information obtained on the substance there was no specific target organ toxicity nor were there compound-related effects after 28 days of dosing.

No Observed Adverse Effect Level:

The NOAEL for systemic toxicity in parental rats is considered to be > 600 mg/kg bw/day as there were no adverse effects observed in any parameters up to the highest dose tested.

Therefore the substance is not considered to be classified.