Pentasodium bis{7-[4-(1-butyl-5-cyano-1,2-dihydro-2-hydroxy-4-methyl-6-oxo-3-pyridylazo)phenylsulfonylamino]-5'-nitro-3,3'-disulfonatonaphthalene-2-azobenzene-1,2'-diolato} chromate (III)

Endpoint summary

Description of key information

NOAEL (oral, 28 d) = 200 mg/kg/day

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

NOAEL

200 mg/kg bw/day

Study duration:

subacute

Species:

rat

System:

urinary

Organ:

kidney

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

The repeated dose toxicity of the substance was evaluated in a subacute 28-day toxicity study, according to the OECD Guideline 407 (1981) and the method B.7 of the Directive 92/69/EEC. The substance 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. A control group was treated similarly with the vehicle only (bidistilled water). Each dose-group 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. These animals were treated for 28 days and then observed for further 15-day treatment-free period after which they were sacrificed.

Clinical signs, mortality, food consumption, body weights and ophtalmoscopic examinations were recorded during the treatment and recovery periods.

At the end of the dosing and the treatment-free recovery period, blood samples were withdrawn for haematology and biochemistry analyses. Urine samples were collected for urinalyses.

All animals were killed, necropsied and examined post mortem; histological examinations were performed on organs and tissues.

The treatment with the test substance caused some effects in the kidneys at all dose levels which was indicated by higher kidney weights, some changes in urinalytical parameters (occult blood score, urine discoloration, urine volume) and histopathological findings (tubular degeneration associated with exogenous pigment deposition In kidneys). Regarding the histopathological and urinanalytical findings a dose-relationship was evident.

Based on these results the NOAEL of the substance was established as 200 mg/kg body weight for male and female rats.

Justification for classification or non-classification

According to the CLP Regulation (EC 1272/2008), classification in Category 1 for repeated dose toxicity applies to substances that have produced significant toxicity in humans or that, on the basisof evidence from studies in experimental animals, can be presumed to have the potential to produce significant toxicity in humans following repeated exposure. Substances are classified in Category 1 for target organ toxicity (repeat exposure) on the basis of:

— reliable and good quality evidence from human cases or epidemiological studies; or

— observations from appropriate studies in experimental animals in which significant and/or severe

toxic effects, of relevance to human health, were produced at generally low exposure concentrations.

Classification in Category 2 applies to substances that, on the basis of evidence from studies in experimental animals, can be presumed to have the potential to be harmful to human health following repeated exposure. Substances are classified in Category 2 for target organ toxicity (repeat exposure) on the basis of observations from appropriate studies in experimental animals in which significant toxic effects, of relevance to human health, were produced at generally moderate exposure concentrations. If classification is based on results obtained from studies conducted in experimental animals, the dose/concentration guidance values that classify refer to effects seen in a standard 90-day toxicity study conducted in rats. These guidance values are presented in the CLP Regulation (EC 1272/2008) in Annex I, Part 3, Table 3.9.2 for classification in Category 1 and in Annex I, Part 3, Table 3.9.3 for classification in Category 2. For a 28-day study the guidance values is increased by a factor of three: classification in category 1 applies when toxicity by oral route is seen at concentrations below 30 mg/kg/d, while category 2 applies for toxicity at doses between 30 and 300 mg/kg/d.

Based on the results of Repeated Dose 28-Day Oral Toxicity Study OECD 407, the lowest dose of the substance inducing significant/severe target organ toxicity can be established to be 1000 mg/kg b.w./day. Thus, no classification for repeated dose toxicity is warranted under the CLP Regulation (EC 1272/2008).