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Administrative data

Description of key information

28- Day Repeated-dose Oral toxicity study in rats with 14 days recovery period.
91- Day Repeated-dose Oral toxicity study in rats with 28 day Recovery period

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Dose descriptor:
NOAEL
1 358 mg/kg bw/day
Study duration:
subchronic
Species:
rat

Additional information

Two oral toxicity repeated dose studies were conducted with FR-370 to evaluate any possible adverse effect implication, following subacute and subchronic exposure to the substance.

A 28 day Repeated dose Oral toxicity study in rats with 14 days recovery period was performed with FR-370. 4 groups of rats were exposed via diet to concentrations of 0, 266, 545 or 1361 mg/kg bw/day.

Oral administration of FR-370 to rats for 28 consecutive days produced no adverse effect up to the highest dose tested on body weights, body weight gain and food consumption were not. There were no deaths during the study. There were no differences in hematology or clinicl chemistry parameters that were attributed to administration of the test material. There were no statistically significant differences in organ weights or organ;brain ratios for brain, liver, kidneys, adrenal and testes, when comparing treated animals to control animals. There were no compound- related macroscopic or microscopic lesions noted during the histopathological evaluation. Therefore, under the conditions of this study, the No Observable Effect Level was 20,000 ppm in the diet (corresponding with an actual consumption of 1361-1959 (males) and 1691-2081 (females). The NOAEL was>1361mg/kg/day (lowest actual consumption in the highest dose group).

In a 90 day Repeated dose Oral toxicity study in rats with 28 days recovery period with FR-370, 4 groups of rats were exposed via diet to concentrations of 0, 137, 682 or 1358 mg/kg bw/day.

Following daily repeat dose (oral gavage) administration of FR-370 to Sprague Dawley rats, for up to 90 consecutive days at dose levels, no treatment-related deaths occurred. No treatment-related clinical signs were noted during the study. Mean body weights and body weight gains were significantly increased among males receiving 2000 ppm and greater during the study. These increases correlate to the statistically significant increases in food consumption which were noted among males receiving 2000 ppm and greater, and were not considered to be a toxicological effect of treatment. No significant differences in body weights, body weight gains or food consumption were noted among females when compared to controls.
No treatment-related ophthalmic lesions were noted during the terminal ophthalmic
examination. No treatment-related changes in any of the urinalyses parameters were noted when
comparing treated groups to controls. No treatment-related changes in any of the hematology or clinical chemistry parameters were noted when comparing treated groups to controls.
No treatment-related findings were noted during necropsy. No statistically significant
differences in absolute or relative organ weights were noted among males or females.
Dietary administration of PB-370 resulted in no treatment-related histomorphologic
tissue alterations.
Under the conditions of this study, the No Observed Adverse Effect Level (NOAEL) was 20,000 ppm (1358 and 1685 mg/kg/day for males and females, respectively). The actual NOAEL was>1358mg/kg/day (lowest actual consumption in the highest dose group).

Based on the information available it can be concluded that no effect due to increased exposure time is expected.

Justification for classification or non-classification

The substance should not be classified based on NOAEL> 1000mg/kg/day in both 28 day and 90 day oral repeated dose toxicity studies.