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Description of key information

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
50

Additional information

Oral exposure: Reliable data have been obtained on repeated dose toxicity of three members of the category of derivatives of 4,4’-bis(1,3,5-triazinyl-2-yl)amino)stilbene-2,2’-disulfonic acid, each with one anilino and one alkyl amino moiety: EC 432-690-8, EC 476-900-6 and EC 416-640-2.

Dermal exposure: The test material is a highly polar salt with a poly-anion of high molecular weight. It is used exclusively in aqueous solutions and completely ionised. Therefore, a significant skin penetration (bioavailability) and adverse effects via dermal exposure are not expected. Additionally the test material did show adverse systemic effects only after high doses (500-750 mg/kg bw) by oral gavage for prolonged periods and a structurally closely related substance did not cause skin irritation or sensitisation. Thus, no adverse effects are expected after dermal exposure with low bio-availability and no in vivo study (animal use) is justified.

Inhalation: The test material is produced and handled in industry exclusively in aqueous solutions. There are no spraying operations. Thus neither exposure nor risks are expected via the inhalation route.

 

EC 432-690-8:
Subchronic toxicity after repeated oral exposure (gavage) was evaluated
 on the basis of a 90 day study according to OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity in Rodents) in rats (Sprague-Dawley; male/female) with daily exposure.The dose range was: 5 mg/kg bw/day (actual ingested), 50 mg/kg bw/day (actual ingested) and 750 mg/kg bw per day (reduced to 500 mg/kg bw/day on day 56 due to severe effects).Parameters examined were: Mortality, clinical signs, FOB, body weights, food consumption, clinical chemistry, haematology, necropsy, histopathology

The broad and unspecific spectrum of findings in a large number of organs indicate an unspecific distribution of well being of the animals by the application of high doses of the substance over an extended period of time. The main targets most probably are liver and kidneys as these organs handle and excrete xenobiotic material. Most of the other changes can be interpreted as secondary effects of the reduced performance of these organs. As no effects were detected at the mid and low dose levels the effects in the high dose group are seen as an effect of metabolic overload of the rat organism. The NOAEL (90 d) is 50mg/kg bw.

 

EC 476-900-6:

Subacute toxicity after repeated oral exposure was evaluated on the basis of a 28-day (feeding) study according to OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity in Rodents) in rats (Wistar rats; male/female) with daily exposure of the test substance registered. Five animals per sex and dose were tested. The dose ranges tested were 0, 50, 200 and 1000 mg/kg bw/day (nominal in diet). Concentration, homogeneity and stability of test item in the feed were determined. The 28 day treatment resulted in no test item related deaths, no clear test item related clinical signs during daily or weekly observations, no test item related findings during functional observation battery, no differences in mean daily food consumption or mean bodyweights upon mean absolute or relative organ weights, no macroscopical and no microscopical findings. The target dose levels were largely attained. The missing of any adverse findings in the 28-day repeated dose (feeding) study performed with the test substance up to the highest dose tested (i.e. 1000 mg/kg bw/day) provides indication that the toxic potential after prolonged treatment is low.

EC 416-640-2:
Subacute toxicity after repeated oral exposure was evaluated on the basis of a 28-day (feeding) study according to OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity in Rodents) in rats (Sprgue-Dawley; male/female) with daily exposure of the test substance registered. Five animals per sex and dose were tested. The dose ranges tested were 0, 15, 150 and 1000 mg/kg bw/day (nominal in diet). Oral administration of the test material for a period of 28 consecutive days, at dose levels up to 1000 mg/kg bw/day, resulted in treatment related changes at dose levels of 150 and 1000 mg/kg bw/day. No such effects were demonstrated in animals treated with 15 mg/kg bw/day and the NOEL is, therefore, considered to be 15 mg/kg bw/day. The changes observed at a dose level of 150 mg/kg bw/day were considered not to be indicative of serious damage to the health of the animals and not sufficient to warrant classification.

Justification for classification or non-classification

Dangerous Substance Directive (67/548/EEC)

The available studies are considered reliable and suitable for classification purposes under 67/548/EEC. As a result the category members are not considered to be classified for repeated toxicity under Directive 67/548/EEC, as amended for the 28th time in Directive 2001/59/EC.

 

Classification, Labelling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. As a result the category members are not considered to be classified for repeated toxicity under Regulation (EC) No. 1272/2008.