3-Pyridinecarbonitrile, 4-methyl-2,6-bis[(4-methylphenyl)amino]-5-[2-[2-(trifluoromethyl)phenyl]diazenyl]-

Endpoint summary

Description of key information

In a GLP-compliant subacute toxicity study, the test item as described in section 1.2 was administered daily by oral gavage to SPF-bred Wistar rats of both sexes at dose levels of 50, 200 and 1000 mg/kg bw/day for a period of 28 days according to OECD guideline No. 407. 1000 mg/kg bw/day of the test item was considered to be the no-observed-effect-level (NOEL) (RCC 2004)

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:

subacute

Species:

rat

Additional information

In a GLP-compliant subacute toxicity study, the test item was administered daily by oral gavage to SPF-bred Wistar rats of both sexes at dose levels of 50, 200 and 1000 mg/kg body weight/day for a period of 28 days according to OECD guideline No. 407 (version of July 27, 1995). A control group was treated similariy with the vehicle, PEG 300, only. The groups comprised 5 animals per sex which were sacrificed after 28 days of treatment. Additional 5 rats per sex and group were used at 0 and 1000 mg/kg bw/day. These animals were treated for 28 days and then allowed a 14-day treatment-free recovery period after which they were sacrificed. Clinical signs, outside cage observation, food consumption and body weights were recorded periodically during pretest, the treatment and recovery periods.

Functional observational battery, locomotor activity and grip strength were performed during week 4. At the end of the dosing and the treatment-free recovery period, blood samples were withdrawn for hematology and plasma chemistry analyses. Urine samples were collected for urinalyses. All animals were killed, necropsied and examined post mortem. Histological examinations were performed on organs and tissues from all control and high dose animals, and all gross lesions from all animals.

Treatment with the test item for 28 days resulted in no lethality, no clinical signs of toxicological relevance during daily or weekly (at weeks 1-3) observations, no effects upon the parameters of the functional observational battery (at week 4, including mean fore- and hindlimb grip strength or locomotor activity), no changes in mean food consumption or mean body weights, no effects of toxicological relevance on the parameters of hematology, clinical biochemistry or urinalysis, no differences in mean absolute or relative organ weights, or macroscopicaI/microscopical findings. Test item-related findings were restricted to passive findings (discoloration of the feces at all dose levels and discoloration at 1000 mg/kg/day). These findings are frequently seen in gavage studies with dyestuffs and are not considered to represent an adverse effect. Based on the results of this study, 1000 mg/kg body weight/day of the test item was considered to be the no-observed-effect-level (NOEL).

Justification for classification or non-classification

Based on the available data, the test item does not need to be classifiied or labelled for repeated-dose oral toxicity according to Directive 67/548/EEC (DSD) and 1272/2008 EC (CLP).