Benzenesulfonic acid, 2-[2-[5-(aminocarbonyl)-1-ethyl-1,6-dihydro-2-hydroxy-4-methyl-6-oxo-3-pyridinyl]diazenyl]-4-[[4-chloro-6-[[4-[[2-(sulfooxy)ethyl]sulfonyl]phenyl]amino]-1,3,5-triazin-2-yl]amino]-, sodium salt (1:2)

Endpoint summary

Description of key information

Summary of 28-day repeated dose oral toxicity

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

The 28-day toxicity study was conducted in order to characterise the toxicological profile of the test substance after repeated oral exposure no detectable adverse effects in male and female Wistar rats when administered 28 times during 29 days. With regard to the present study the 'no observed adverse effect level' is 1000 mg/kg bodyweight per day.

 

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. In addition 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: 1000 mg/kg bw/day (subacute; rat)

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.