Disodium 4,4'-bis[[4-anilino-6-[(2-carbamoylethyl)(2-hydroxyethyl)amino]-1,3,5,-triazin-2-yl]amino]stilbene-2,2'-disulphonate

Carcinogenicity

Description of key information

Oral NOAEL: 542 mg/kg bw/day (chronic; rat)

Dermal chronic mouse: the test substance does not contribute to carcinogenicity induced by UV-irradiation

Key value for chemical safety assessment

Carcinogenicity: via oral route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

542 mg/kg bw/day

Study duration:

chronic

Species:

rat

Carcinogenicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Carcinogenicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Study duration:

chronic

Species:

mouse

Justification for classification or non-classification

According to the CLP Regulation (EC 1272/2008), 3.6 Carcinogenicity section, carcinogen means a substance, which induce cancer or increase its incidence. Substances, which have induced benign and malignant tumours in well performed experimental studies on animals are considered also to be presumed or suspected human carcinogens unless there is strong evidence that the mechanism of tumour formation is not relevant for humans. For the purpose of the classification for carcinogenicity, substances are allocated to one of two categories (known or presumed human carcinogens and Suspected human carcinogens) based on strength of evidence and additional considerations (weight of evidence). In certain instances, route-specific classification may be warranted, if it can be conclusively proved that no other route of exposure exhibits the hazard.

The combined chronic/carcinogenicity studies available did not provide any evidence of carcinogenicity.

In conclusion, the available experimental data are adequate for classification and labelling and the substance is not classified for carcinogenicity according to the CLP Regulation (EC 1272/2008).

Additional information

The substance under registration (OB 5-A) belongs to the category of Stilbene Fluorescent Whitening Agents.

Based on the metabolic pathway profiled using the OECD Toolbox, it can be expected that the same conclusions drawn for OB 3a-MSA and OB 3a-A (free acid) can be applied to OB 5 -A. The three substances differ in the fact that the substitution on the triazino moiety is a carbamoyl/hydroxyethyl for the substance under registration, while the substitution for both the analogous is dihydroxyethyl. The carbamoyl derivative is less reactive, from a biological point of view based on OECD Toolbox metabolism liver simulator.

In two combined chronic/carcinogenicity studies (Bomhart 1978), the analogue substances were administered to Wistar rats/sex/dose in diet at dose levels of 0, 100, 1000, 10000 ppm for 24 months. There were no compound related effects in mortality, clinical signs, body weight, food consumption, haematology, clinical chemistry, urinalysis, organ weights, or gross and histological pathology.

In the test with OB 3a-A(free acid), the acid form of the disulphonated derivative dihydroxyethyl derivative, the haematological investigations performed during and at the end of the test showed no dose of injuries. The clinical chemical analysis, sections and histopathological examinations revealed no evidence for treatment-related damage to the liver. Urinalysis, urea and creatinine concentrations in serum as well as macroscopic and histopathological organ findings did not indicateany influence. The No Observed Effect Level was set at 779 mg/kg bw/day (actual dose received) for females and at 542 mg/kg bw/day for males (Bomhard E. and Löser E., 1978).

In the test conducted on the analogous dihydroxyethyl derivative tetrasulphonated sodium salt (OB 3a-MSA), appearance, behaviour, feed intake, body weights and mortality were not influenced in male and female animals of doses up to and including 10000 ppm. The animals in the dose groups to 10000 ppm did not show during the entire experimental period any treatment-related symptoms. The growth of the rats was not affected and the haematological investigations performed showed no dose of injuries; also the clinical chemical analysis, sections and histopathological examinations revealed no evidence for treatment-related damage to the liver. Furthermore, the from nature, localization, abundance and time of occurrence of the identified benign and malignant tumours was no evidence of a carcinogenic effect of the test item. The NOAEL was set at 709 mg/kg bw/day (actual dose received) for females and at 521 mg/kg bw/day (actual dose received) for males (Bomhard et al., 1978). The substance tested has the same organic functionalities than the CAS 4193 -55 -9, with a higher sulphonation degree.

A further study was done in order to investigate whether the test substance has a carcinogenic effect onto skin under light exposure (Strinhoff D. 1979). Photocarcinogenesis testing involved pretreating hairless mouse skin with the test compounds, 8 -methoxypsoralen (8 -MOP; known phototoxic agent), or solvent only before each daily exposure to simulated solar ultraviolet light. In terms of tumour yield and tumour development time, photocarcinogenesis was enhanced by 8 -MOP, but not by test substances.

Based on the similarities in toxicological behaviour for all members of the category, the results of the described studies can be considered as a reference also for the substance under registration.