Reaction mass of 5,5'-[vinylenebis[(3-sulpho-p-phenylene)azo]]bis[3-methylsalicylic] acid, potassium salt, compound with 2,2',2''-nitrilotriethanol and potassium 5-amino-3-{[4-(2-{4-[(7-amino-1-hydroxy-3-sulfo-2-naphthyl)diazenyl]-2-sulfophenyl}vinyl)-3-sulfophenyl]diazenyl}-4-hydroxy-7-sulfonaphthalene-2-sulfonate - 2,2',2''-nitrilotriethanol (1:1) and 3,3'-[vinylenebis[(3-sulpho-p-phenylene)azo]]bis[5-amino-4-hydroxynaphthalene-2,7-disulphonic] acid, potassium salt, compound with 2,2',2''-nitrilotriethanol and 3,3'-[vinylenebis[(3-sulpho-p-phenylene)azo]]bis[6-amino-4-hydroxynaphthalene-2-sulphonic] acid, potassium salt, compound with 2,2',2''-nitrilotriethanol

Endpoint summary

Description of key information

The registered substance is an organic multi-constituent substance and can be characterized by its ionic nature. No experimental data on absorption, metabolism, distribution and excretion are available for the substance. Therefore, the toxicokinetic behavior was evaluated based on the structure and the physico-chemical properties of the substance as well as data from experimental in vivo toxicity studies. In accordance with the low log Pow value of ≤ -4, the components of the registered substance have a high water solubility. No bioaccumulation potential is to be expected based on the physico-chemical properties of the substance. In acute and repeated dose toxicity studies with oral application of the registered substance observations included grey discolorations in several organs. This finding indicates bioavailability and systemic distribution of components of the substance after oral uptake.

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Additional information

The registered substance is an organic multi-constituent substance and can be characterized by its ionic nature. In accordance with the low log P_owvalue, the target chemical is highly hydrophilic. According to the analytical investigations, the substance consists of the following main components:

Table 1: Composition of the target substance

CAS-No.	Typical concentration	Concentration range
85269-31-4	Ca. 25.5 % (w/w)	≥ 15 ≤ 35 % (w/w)
85283-47-2	Ca. 23 % (w/w)	≥ 15 ≤ 30 % (w/w)
85269-32-5	Ca. 19 % (w/w)	≥ 10 ≤ 25 % (w/w)
85269-33-6	Ca. 16 % (w/w)	≥ 10 ≤ 20 % (w/w)

Description of physico-chemical properties:

- Physical state (20°C): solid

- Colour: black

- Molecular weight: 1081 g/mol

- Relative density (20 °C): 1.369

- Log P_ow (23 °C): ≤ - 4

- Water solubility (20 °C): > 100 g to < 200 g/L (estimated)

- Boiling point: the substance decomposes before boiling

Toxicokinetic assessment:

No experimental data on absorption, metabolism, distribution and excretion are available for the substance. Therefore, the toxicokinetic behavior was evaluated based on the structure and the physico-chemical properties of the substance as well as data from experimental in vivo toxicity studies.

Absorption

The molecular weight of 1081 g/mol implies that the substance is less favourable for absorption after oral intake. As the target substance is ionized, it will not readily diffuse across biological membranes. However, according to the low log P_owin combination with the high water solubility (> 100 g to < 200 g/L) the substance is considered to be highly soluble in water, i.e. hydrophilic, and will readily dissolve into the gastrointestinal fluids. Due to the large molecule size and the high molecular weight, absorption by passive diffusion may be limited because substances with such properties are normally considered to be too large to cross biological membranes. However, small amounts may be transported into epithelial cells by pinocytosis or persorption. Regarding the structural properties, hydrolysis (e.g. in the stomach) is not expected. In the acute oral toxicity study available for Direct Black 18L NA active dye, a LD₅₀of > 2000 mg/kg bw was deduced. Clinical signs like impaired general state and piloerection were observed. Therefore, it is assumed that absorption has occurred. However, apart from that, no specific data concerning oral absorption of the test substance are available. Therefore, as a worst case an oral absorption of 100 % is assumed.

With regard to absorption after inhalation, the vapour pressure as well as the boiling point are not applicable, because the substance is a solid which decomposes before boiling and without melting, indicating that inhalation as a vapour will be negligible. If the substance reaches the respiratory tract, passive diffusion could occur due to the low log P_ow. Because of its good water solubility, the substance is likely to dissolve in the mucus of the upper respiratory tract, and consequently will at least partly be removed before reaching the lower respiratory tract. However, no specific data concerning absorption after inhalation are available.

The physical state of the substance is solid, therefore the substance will have to dissolve into the surface moisture of the skin before uptake can begin. Due to the high water solubility and low log P_owthe substance may be too hydrophilic to cross the lipid rich environment of the stratum corneum, therefore dermal absorption is likely to be low. Hence, dermal uptake for this substance is also suggested to be low. However, no specific data concerning dermal absorption of the test substance are available.

Distribution and Accumulative potential

Direct Black 18L NA active dye consists of a large molecules and therefore wide distribution of the systemically available part is not to be expected. Due to the high water solubility rapid diffusion through aqueous channels and pores is likely to occur and also limits its distribution. In an acute oral toxicity study as well as in an oral repeated dose toxicity study, observations included grey discolorations in several organs like e.g. forestomach, jejunum, colon, liver, mesenteric lymph nodes and kidneys. This finding gives evidence of the substances distribution. However, it does not provide any information on the amount of substance that has distributed. A bioaccumulation potential is not expected considering the physico-chemical properties of the substance. The estimated low log P_owvalue of equal to or less than – 4 (at 23 °C) confirms this assumption.

Metabolism and Excretion

Direct Black 18L NA active dye is assumed to be mainly excreted via feces as seen in both an acute toxicity study and a repeated dose toxicity study with oral application of the test material. Clinical signs included black discoloration of the feces of all animals, respectively, indicating that this discoloration is caused by the color of the substance.