Reactive Blue F08-0170

Endpoint summary

Description of key information

Summary of repeated dose toxicity

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Dose descriptor:

NOAEL

150 mg/kg bw/day

Study duration:

subacute

Species:

rat

Additional information

In the combined repeated dose toxicity study with the reproduction/developmental toxicity screening test in rats (Kubaszky, 2011), REACTIVE Blue F08-0170 administered daily by oral gavage to Wistar rats did not result in test item related mortality or clinical adverse effects or changes in the body weight, food consumption, haematology, clinical chemistry, coagulation or urinalysis parameters at dose levels of 25, 150, or 1000 mg/kg bw/day during either the treatment or after a 14-day recovery period. On pathology evaluation of the Main animals, minimal focal reactive hyperplasia of the epithelium in the pyloric glands was noted in 6/12 male and 3/12 female Main High dose 1000 mg/kg bw/day Group 4, but not in 24/24 Mid dose and 8/24 Low dose Main animals, which were evaluated due to macroscopic findings or in the High dose Recovery animals. This microscopic observation was in correlation with dark, diffuse or multifocal, blue or purple, discoloration of the stomach mucosa recorded at these dose levels at necropsy. Following a 14 day recovery period, no test item-related macroscopic or microscopic findings were seen in the 1000 mg/kg bw/day High dose Recovery animals.

 

During the treatment period, dark blue discoloration of the faeces was noted in the High dose Main animals administered 1000 mg/kg bw/day Reactive Blue F08-0170 starting after the first treatment on Day 0. The discoloration of the faeces persisted in the 1000 mg/kg bw/Day Recovery animals for 3 days after the last dose administration (on Days 42-44); thereafter no test item-related effects were noted until completion of the 14-Day Recovery period. In addition, dark yellow urine was noted at 150 mg/kg bw/day in 5/5 male and 1/5 female Mid dose Main animals and dark blue urine, at 1000 mg/kg bw/day in all High dose Main animals, at urinalysis performed prior to necropsy. These changes were ascribed to elimination of Reactive Blue F08-0170 or its metabolites through faeces or urine and an expected staining effect. Staining of urine also indicates that renal excretion is a relevant pathway for the elimination of REACTIVE BLUE F08-0170.

 

Under the conditions of this study, the no observed adverse effect level (NOAEL) for REACTIVE BLUE F08-0170 for parental toxicity effects is considered to be 150 mg/kg bw/day based on histopathological changes in the glandular stomach. The effects on the glandular stomach are considered to be caused by adaptive changes in order to absorb and catabolise the dye substance.

Repeated dose toxicity: via oral route - systemic effects (target organ) digestive: stomach

Justification for classification or non-classification

The above study has been ranked reliability 1 according to the Klimisch et al system. This ranking was deemed appropriate because the study was conducted to GLP and in compliance with agreed protocols. Sufficient dose ranges and numbers are detailed; hence it is appropriate for use based on reliability and animal welfare grounds.The above results triggered no classification under the Dangerous Substance Directive (67/548/EEC) and the CLP Regulation (EC No 1272/2008). 

The effects on the glandular stomach at 1000 mg/kg bw/day are considered to be caused by adaptive changes in order to absorb and catabolise the dye substance. No classification for prolonged effects is therefore required.