2,4,6-tris(2,4,6-tribromophenoxy)-1,3,5-triazine

Endpoint summary

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

1 000 mg/kg bw/day

Study duration:

subchronic

Species:

rat

Additional information

Two oral toxicity repeated dose studies were conducted on FR-245 to evaluate any possible adverse effect implication, following subacute and subchronic exposure to the substance.

A 28- Day Oral (gavage) Toxicity test in rats, with 14 days recovery period was performed with FR-245. The test material was administered to 3 groups (of 50, 250, 1000mg/kg/day), each of six male and six female rats. A control of six male and six female rats was dosed with vehicle alone. Two recovery groups, each of six male and six females, were treated with the high dose (1000mg/kg/day) or the vehicle for twenty eight consecutive days and then maintained without treatment for further fourteen days.

Oral administration of FR-245 to rats for 28 consecutive days at dose level of 1000 mg/kg/day produced no adverse effect on body weights, food consumption, hematology, blood biochemistry, urinalysis, organ weight, gross pathological and histopathological results. The No-Observed Effect Level (NOEL) was determined as>1000mg/kg/day (the highest dose level tested). Any statistically significant differences noted in hematology, blood chemistry, organ weight, clinical signs, gross pathology and histopathology were not considered treatment related since there was no dose response relationship.

A 91 Day Oral (gavage) Toxicity test in rats with 28 days recovery period was performed with FR-245. The test material was administered to 3 groups (of 100, 350 and 1000mg/kg/day), each of 10 male and 10 female rats, for 91 consecutive days. A control of 10 male and 10 female rats was dosed with vehicle alone.  Two recovery groups, each of five male and five females, were treated with the high dose (1000mg/kg/day) or the vehicle for 91 consecutive days and then maintained without treatment for further 28 days. Several endpoints of reproduction and Neurotoxicity were investigated in addition to the standard study protocol.

Daily repeat dose (oral gavage) administration of FR-245 to Sprague Dawley rats, for up to 91 consecutive days at dose levels, did not result in any adverse effects on body weights, food consumption, hematology, blood biochemistry, urinalysis, organ weight, gross pathological and histopathological results, following observation and examination throughout the in-life phase of the study, at necropsy or following histological assessment. The no-observed effect level (NOEL) was determined as >1000mg/kg/day (the highest dose level used). 

No treatment related changes in sperm count and motility were observed (data are attached in Tables 45 and 46 in section 7.8.1 of the IUCLID). Vaginal lavages which were taken early morning during the 3 week period from all females, prior to termination of the animals showed no treatment related changes in the oestrus cycle (data are attached as Appendix 40 in section 7.8.1 of the IUCLID). In addition, there were no dose related changes in organ weight of ovaries, seminal vesicles, testis, ureter, uterus, vagina in comparison to control animals.

In summary, from the results of the oral toxicity repeated dose studies it can be concluded that prolonged exposure to FR-245, which is hardly absorbed (outcome of the ADME study), is not likely to have adverse effect, nor cause systemic toxicity effect.

Justification for classification or non-classification

The substance should not be classified based on NOAEL> 1000 in both 28 day and 91 day of oral repeated dose exposure.