p-[4,5-dihydro-4-[[2-methoxy-5-methyl-4-[[2-(sulphooxy)ethyl]sulphonyl]phenyl]azo]-3-methyl-5-oxo-1H-pyrazol-1-yl]benzenesulphonic acid, sodium salt

Endpoint summary

Description of key information

Absorption

According to ECHA Guidance R.7c (ECHA (2017c)), the smaller the molecule the more easily it may be taken up via oral route. Generally, oral absorption is favoured for molecular weights below 500 g/mol. As the Substance is a large molecule (> 500 g/mol), it will therefore be taken up at a very low rate following the oral route. This assumption is supported by the results of the acute oral toxicity study in rats, where no deaths and no clinical signs were noted at the limit dose of 5000 mg dye/kg bw. Yellow discolouration of faeces for 48 hours followed treatment. No discolouration of urine, organs or tissues were seen in the repeat-dose study in surviving animals

For dermal absorption, molecular weights below 100 g/mol favours dermal uptake, molecules with a weight above 500 g/mol may be too large to be absorbed (ECHA 2017c). Hence, with a molecular weight of the substance above 500 g/mol, the molecule is too large to allow absorption through skin. The high water solubility of the substance, would favour the dermal absorption rates under normal circumstances, as the substance must be sufficiently soluble in water to partition from the stratum corneum into the epidermis; however, the poor lipophilicity (log Kow < -1) will hinder penetration through the lipid rich environment of the stratum corneum and therefore dermal absorption is limited. Single dermal application of 500 mg test substance to intact or abraded skin of rabbits produced no deaths or symptoms of systemic toxicity. Testing for sensitising properties was performed in guinea pigs according to the method of Magnusson & Kligman. Intradermal induction was done at 5% test substance concentration and dermal induction and challenge treatment at 25%. No signs of toxicity or evidence of skin sensitising properties was found in the guinea pig maximisation test, confirming a low dermal penetration rate of the substance.

As the substance has a low volatility (melting point above 300°C), it is not available for inhalation as a vapour. Should particles of the solid form of the substances be inhaled, absorption through the respiratory tract epithelium is not expected due to the molecule sizes.

Distribution

In general, the smaller the molecule, the wider the distribution. Based on their molecular weight distribution and the hydrophilicity it is assumed, that if absorbed, the substance is distributed within the aqueous compartment of the organism. Furthermore, an accumulation within adipose tissue can be excluded based on the low log Kow of the substance. Neither at macroscopical nor at microscopical examination any discoloration of inner tissues or organs were found further proving that the test substance has not been distributed into organs or tissues.

Metabolism

The substance is not expected to be bioavailable following oral, inhalative or dermal exposure at a relevant level as a result of their properties. Based on the results of in-vitro genotoxicity studies, it can be assumed that the substance is not enzymatically activated (toxified) during metabolism as the metabolic activated test substance showed no higher genotoxicity compared to the test substance without metabolic activation. Available data indicate that the substance is susceptible to hydrolysis.

Excretion

According to the physico-chemical properties of the substances, molecular weight and hydrophilic characteristics the main route of excretion is expected to be via faeces, as substances that are excreted in the urine tend to be water-soluble and of low molecular weight (below 300 g/mol in the rat).

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential