Registration Dossier

Administrative data

Description of key information

Data from a 14-day dietary dose range finding study and a subsequent 90-day subchronic dietary toxicity study with the substance in male and female Sprague-Dawley rats (GLP) are available.

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
500 mg/kg bw/day
Study duration:
subchronic
Species:
rat
Quality of whole database:
RL 1

Mode of Action Analysis / Human Relevance Framework

Additional information

Based on a 14-day palatability study in adult Sprague-Dawley rats (5/sex/group) conducted with diets containing 0, 140, 3500, or 14,000 ppm of the test item, target dose levels of 30, 100, and 500 mg/kg bw/day were selected for the 90-day toxicity study. In the palatability study including only a limited set of parameters, no test substance-related or other mortalities, no adverse clinical observations, no effects on body weight, body weight gain, food consumption or food efficiency, and no gross findings that were considered a result of test substance administration were observed.

In the 90-day subchronic toxicity study, four groups of adult Sprague-Dawley rats (10/sex/group) were maintained on diets prepared to contain 0, 30, 100, or 500 mg/kg bw/day of the test item. The diets were calculated to provide an average daily intakes of 29.4, 97.5, and 489.5 mg/kg bw/day for males and 29.4, 98.6, and 492.2 mg/kg bw/day for females, respectively, over the course of the study.

There were no mortalities, clinical observations or findings in the functional observational battery or motor activity, ophthalmological or clinical pathological changes (hematology, clinical chemistry or urianlysis), effects on body weight, body weight gain, food consumption or food efficiency, organ weights, pathological or histopathological changes attributable to treatment with the test item.

Under the conditions of the study and based on the toxicological endpoints evaluated, the no-adverse- effect level (NOAEL) for administration of the test item in the diet was determined to be 500 mg/kg bw/day (highest dose level tested) for both males and females.


Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:
No adverse effects observed at the highest dose tested (500 mg/kg bw/d)

Justification for classification or non-classification

No classification for specific target organ toxicity after repeated exposure (STOT-RE) following the oral route is required according to the CLP criteria, because no primary target organs of toxicity were identified in the 90-day dietary toxicity study with the substance up to a dose level of 500 mg/kg bw/d. The identified NOAEL of 500 mg/kg bw/d is clearly above the guidance values for classification into Category 1 (< 10 mg/kg bw/d) and Category 2 (< 100 mg/kg bw/d) for oral toxicity in rat.