Reaction mass of isomers disodium 8-(2-{4-[benzyl(ethyl)amino]-2-methylphenyl}diazen-1-yl)-5-(2-{2,5-dimethyl-4-[2-(3-sulfonatophenyl)diazen-1-yl]phenyl}diazen-1-yl)naphthalene-2-sulfonate, disodium 5-(2-{4-[benzyl(ethyl)amino]-2-methylphenyl}diazen-1-yl)-8-(2-{2,5-dimethyl-4-[2-(3-sulfonatophenyl)diazen-1-yl]phenyl}diazen-1-yl)naphthalene-2-sulfonate

Endpoint summary

Description of key information

NOAEL (oral) ≥ 300 mg/kg bw/day

Key value for chemical safety assessment

Toxic effect type:

dose-dependent

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

NOAEL

300 mg/kg bw/day

Study duration:

subchronic

Species:

rat

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 test item was tested for subchronic toxicity using the OECD Test Guideline No. 407, Repeated Dose 28-day Oral Toxicity Study in Rodents.
The oral administration of the test substance to rats by gavage for a period of 28 consecutive days did not cause mortality related with the test item treatment.
No effect of the test item on the body weight, food consumption and water consumption were recorded during the study. Slight changes of these parameters were without toxicological importance.
At a daily oral dose of 1000 mg/kg, test item lead to an increased serum concentration of total bilirubin, increased reticulocyte formation and – in female – decreased mean corpuscular hemoglobin concentration. Histopathological evaluation indicated in the spleen, an increase in the incidence and mean severity grade of multifocal extramedullary hemopoiesis in males and females treated at 1000 mg/kg/day. In addition, in females of this dose group, only, the incidence and mean severity grade of multifocal golden-brown pigment (interpreted as hemosiderin) was also increased. There was recovery for the extramedullary hemopoiesis, but not for the occurrence of golden-brown pigment. Moreover, spleen weight was increased at the end of the recovery period. In view of the changes in hematological parameters noted in this study group, an adverse character of the spleen effect cannot be completely discounted.
Furthermore, treatment with test item caused alteration in liver weight in males and female at almost all dose levels associated with minimal or mild centrilobular hepatocellular hypertrophy which was noted in females of all dose groups and one single male at 1000 mg/kg/day.
The liver changes recovered completely during the recovery period. Minimal diffuse follicular cell hypertrophy of the thyroid gland observed at 1000 mg/kg/day is considered to be secondary to the liver change. Liver hypertrophy was interpreted as a minor adaptive change of the liver, probably involving the induction of hepatic microsomal enzymes, and as being non-adverse.
A test item-relationship of a minimal multifocal vacuolation of the inner cortex in the adrenal gland at 1000 mg/kg/day could not be excluded.
Based on these findings, the red blood cell system is considered to be a target system of test item. Based on histopathological findings in the spleen that failed to show complete recovery, the NOAEL for this study was established at 300 mg/kg bw/day.

Justification for classification or non-classification

For the classification of the substance as STOT-RE the dose in which significant toxic effects are observed is taken into consideration. If this dose is in the range of the guidance values indicated in the CLP Regulation (EC) No. 1272/2008 Annex I: 3.9.2.9.6 and Annex I: 3.9.2.9.7 then the substance is classified in Category 1 or Category 2 respectively.
Based on the available repeated dose toxicity studies, the substance is not classified for STOT-RE according to the CLP Regulation (EC) No. 1272/2008.