REACTIVE BLUE FC 75311

Endpoint summary

Description of key information

Summary of repeat-dose data

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Dose descriptor:

NOAEL

200 mg/kg bw/day

Study duration:

subacute

Species:

rat

Additional information

The only effects attributed to the substance in a 28-day subacute oral toxicity caused gastritis with increased mucus production in the glandular stomach and hyperkeratosis at the limiting ridge between forestomach and glandular stomach. The latter finding was still present in one male animal at the end of the recovery period.At 40mg/kg there were no effects on the stomach.

However it is proposed that gastritis with increased mucus production of all dose groups could be considered as reversible, following further evaluation of the pathological data associated with the substance and the effects seen following the recovery period. This is based on the fact that a number of parameters associated with being a permanent toxicological effect are not noted within the study groups. Hematological, clinico-chemical, organ-gravimetric, gross pathological and histopathological investigations produced no evidence of damage to the other organs or tissues.

Therefore it is considered that the effects may be considered an adaptive response rather than a toxicological effect of the test substance. A NOEL of 200 mg/kg/day will be applied to the substance.

Furthermore, it is considered that the substance is unlikely to be inhaled and the physicochemical and toxicological properties suggest low potential for significant rate of absorption through the skin. Furthermore the results of laboratory animal studies show negligible acute dermal toxicity. In the 28 - days repeated dose study via oral gavage, administration does not exacerbate systemic toxicity effects which suggest bioavailability is low, thereby there is low toxicity potential. This intrinsic property/toxicity potential can therefore be extrapolated to repeated dermal and inhalation routes of administration. Further studies for these endpoints are therefore not appropriate both on predictive toxicology and animal welfare grounds.

The test substance seems not to be absorbed from the gastrointestinal tract and therefore a significant bioaccumulation potential can most probably be excluded due to the marked hydrophilic properties and lack of solubility in fat. From the mutagenicity assays it appears that the test substance is not metabolised toward genotoxic structures. Review of the available data indicates that the substance does not exhibit a conspicuous toxicokinetic behaviour. The results from all studies with dermal exposure indicate that the test substance has insignificant or no dermal absorptive potential. Bioaccumulation of the test substance can therefore most probably be excluded.

Due to this fact, and the fact that exposure to the test substance is expected to be very low, based on its granular form and its identified uses, further animal testing such as a 90-day sub-chronic toxicity study is considered not to be justified.

The following information is taken into account for any hazard / risk assessment:

Assessment of subacute exposure by oral route is discussed below.

Value used for CSA (route: oral):

NOAEL: 200 mg/kg bw/day (subacute; rat)

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

Justification for classification or non-classification

The above studies have all been ranked reliability 1 according to the Klimish et al system. This ranking was deemed appropriate because the studies were conducted to GLP an 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. As the effects are considered adaptive rather than toxicological, no classification is proposed.

The above results triggered no classification under the Dangerous Substance Directive (67/548/EEC) and the CLP Regulation (EC No 1272/2008). No classification for prolonged effects is therefore required.