tetrasodium 3-amino-4-{[4-({4-fluoro-6-[phenyl(2-{[2-(sulfonatooxy)ethyl]sulfonyl}ethyl)amino]-1,3,5-triazin-2-yl}amino)-2-sulfonatophenyl]diazenyl}-5-hydroxynaphthalene-2,7-disulfonate

Endpoint summary

Description of key information

The test substance is expected to have partial oral absorption, low dermal absorption and no bioaccumulation in the body.

Excretion will occur via urine and predominantly via faeces.

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Additional information

The assessment of the toxicokinetic properties of Reactive Red F00-0314 given below is based on the results obtained for the following toxicological end-points with simultaneous reference to physico-chemical data such as solubility in various solvents and log Kow:

• acute oral toxicity
• acute dermal toxicity
• skin irritation
• eye irritation
• skin sensitization
• subacute (28 day) oral toxicity
• developmental screening (structural analogue)
• bacterial reverse mutation test
• chromosome aberration test in vitro

Reactive Red F00-0314 has a molecular weight of 1010 g/mol, a water solubility of 325/L (corrected for purity) and a log Kow of <-2. The medial lethal dose (LD50) of Reactive Red F00-0314, and its structural analogue, after oral or dermal administration to rats is above 2000 mg/kg body weight. Testing for skin irritating properties in rabbits showed no signs of irritation. After administration into the conjunctival sac of New Zealand White rabbits signs of irritation were noted up to 24 hours after start of treatment. Persistent discoloration of the conjunctiva, nictitating membranes and iris was noted in the eye of one rabbit. As this did not cause impairment of sight, no classification for severe eye effects was necessary. Testing for sensitizing properties according to the method of Magnusson & Kligman showed no evidence for skin sensitization properties. In the 28-day study, a NOAEL of 1000 mg/kg bw/day was determined for systemic toxicity for both dyes. The discoloration of urine, serum and various tissues and organs was proof of absorption of the test substances and/or its metabolites. The reversibility of these effects showed that bioaccumulation does not occur. In the Ames Test both substances did not cause any relevant increases in the number of revertant colonies with any of the tester strains and is assessed to be non-mutagenic. In the chromosome aberration study in vitro with Reactive Red F00-0314 in V79 Chinese hamster cells no relevant reproducible enhancement of metaphases with aberrations outside the range of the solvent control was found with any of the concentrations used, either with or without metabolic activation by S9-mix indicating that the substance is not clastogenic in this in vitro test system.

The data of the acute dermal toxicity, dermal irritation and skin sensitization test indicate little or low dermal absorption, owing to the fact that neither systemic, nor irritating or sensitizing effects were observed with Reactive Red F00-0314 or its structural analogue. This is in accordance with the physico-chemical properties of both dyes. Oral resorption of the substances is probably also restricted due to the high molecular weight, high number of H-bond acceptors and low log Kow since most substances with a molecular weight > 500, H-bond acceptors >10 and log Kow < -0.5 are only marginally resorbed. However, after oral gavage the substance is at least partially absorbed as can be seen by the discoloration of urine, serum and various tissues and organs. The reversibility of these effects showed that bioaccumulation does not occur. As Reactive Red F00-0314 and its structural analogue are azo dyes, partial metabolic cleavage by bacterial azo reductases in the intestine resulting in more hydrophilic amines seem to be likely. After resorption following repeated oral administration in high doses, temporarily distribution in kidneys, skin, testes, epididymides and or rectum is possible as demonstrated by test substance related discolorations. Reddish discoloured faeces and urine after oral administration indicated that the test compound can be eliminated both via kidneys and via intestine as confirmed by corresponding organ discolorations in both cases.

In summary, the results of basic toxicity testing give no reason to anticipate unusual characteristics with regards to the toxicokinetics of Reactive Red F00-0314. The data indicate that there is little or no dermal absorption. No signs of a significant systemic toxicity associated with absorption through skin have been observed. Based on exposure model from AG Textilien des Bundesinstituts fur Risikobewertung (BfR), the dermal penetration rate for dyes through the skin was found to be less than 2%. Based on physico-chemical data and the results of oral toxicity studies, Reactive Red F00-0314 has a limited oral bioavailability.

The substance is considered to have low volatility as evident from the vapour pressure measurement and the calculated melting point of > 300°C, so the potential for the generation of inhalable forms is low. The molecular weight is higher than 500 g/mol and the chromophore is negative charged. This together with the high water solubility and low partition coefficient value, indicate the substance is not able to cross the mucous layer of the respiratory tract. Due to the high water solubility, vapours if generated/inhaled, will be trapped in the mucus of the respiratory tract, thereby further limiting the absorption. Hence, the main route of exposure of the substance, if inhaled, will be due to swallowing of particles deposited in the nose/mouth. Therefore, the bioavailability for inhalation is considered the same as for oral intake.

Bioaccumulation of Reactive Red F00-0314 can most probably be excluded due to the available data. Based on the results of genotoxicity assays, a metabolisation towards genotoxic metabolites can also be excluded for mammalian species.

The substance is therefore not considered to be of concern for ADME related effect.