Sodium 4-[(9,10-dihydro-4-hydroxy-9,10-dioxo-1-anthryl)amino]toluene-3-sulphonate

Endpoint summary

Description of key information

According to the key studies results (Klimisch 1, GLP compliant study, OECD Guideline 408 method), the main adverse effect was an increase of Activated Partial Thromboplastine. Hence the No Observed Adverse Effect Level was defined as 200 mg/kg bw/day in rats exposed to the test item Jarocol Violet 43, according CLP classification.

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:

subchronic

Species:

rat

Additional information

Two subchronic ( 90 days) studies were availables for repeated dose toxicity by oral routes on rats. They were considered as Klimisch 1 and key studies (GLP compliant, OECD Guideline 408 method).

-In the first key study (1994, Goldfain, Klimisch 1, GLP) rats received the test item by gavage at 0, 50, 200 or 800 mg active dye/kg/day in 5 ml/kg for 13 weeks. Evaluations and measurements included mortality, daily clinical observations, weekly body weight and food intake, ophthalmoscopy, haematology, blood clinical chemistry and urinalysis. At the end of the dosing period, surviving animals were killed and subjected to macroscopic examination, selected organs were weighed, and organs/tissues were preserved. Microscopic examination was performed for specified tissues/organs from all decedent rats, control and high dose rats killed at the end of the study, as well as for gross anomalies, lungs, liver and kidneys from all animals in each key study.

Acid Violet 43 induced ptyalism at all dose levels and increase in activated partial thromboplastin time at 800 mg/kg/day. Colouration of different tissues and/or organs were also noted at all dose levels and attributed to the staining properties of the test substance. The No Observed Adverse Effect Level of the Acid VIolet 43 was defined as 200 mg/kg/day in rats treated by oral gavage in this study.

-In the second key study (Hamman, Klimisch 1, GLP, 2000) rats received the test item by gavage at 0 (vehicle, 1% aqueous solution of carboxymethylcellulose), 100, 300 or 1000 mg/kg/day at a dosing volume of 10 ml/kg for 13 weeks.Under the experimental conditions of this study, the No Observed Adverse Effect Level (NOAEL) of test substance Jarocol Violet 43 was defined as 300 mg of test material/kg/day on repeated toxicity (gavage) on rats for 90 day period of treatment according to the APTT Activated Partial Thromboplastin Time increased activity in the high dose level group.

-Two other studies were available in order to assess the potential dermal dose toxicity of the Acid Violet 43(Klimisch 3, no GLP-compliant, no guideline followed, Shaffer, 1965 and 1966). In one study, guinea pig were exposed to the test item dermally during three weeks and in the second, rabbit were exposed dermally during three months at 0.1% and 1% of the substance in formulation. However, the two methods had some significant deficiencies and did not follow standard method. This studies cannot be used for classification.

Justification for classification or non-classification

According the two key studies results (Klimisch 1, GLP compliant study, OECD Guideline 408 method), the main adverse effect was an increase of Activated Partial Thromboplastine Time in high doses levels (1000 mg/kg/day and 800 mg/kg/day). Hence the No Observed Adverse Effect Level (NOAEL) was defined as 200 mg/kg bw/day in rats exposed to the registered item Jarocol Violet 43. No STOT classification was applied.