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Description of key information

Based on the physicochemical properties, particularly molecular weight, water solubility and log Kow, absorption via the gastrointestinal tract is likely to occur. This assumption was further supported by the results of the oral toxicity studies. If the substance becomes available as vapour it is plausible that the substance will also be absorbed after exposure via the inhalation route. Uptake of relevant amounts following dermal exposure cannot be excluded but seems less likely. After absorption, it is conceivable that the molecule distributes into cells. Bioaccumulation is not to be expected. Results of the Ames tests indicate that the test substance will be metabolised. In the Ames test the observed cytotoxicity of the test substance was lower with metabolic activation system (S9 mix) than without. As first step of the metabolism breaking of the azo-bound might occur. Further metabolisation via Phase I (functionalization) and Phase II (conjugation) enzymes is likely. Excretion of water soluble metabolites will occur via urine.

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential

Additional information

Toxicokinetic Assessment

The test substance is a white powder at room temperature with a molecular weight of 280.28 g/mol. It decomposes at > 75 °C without melting and is well soluble in water as indicated by the measured water solubility value of 9.3 g/L at 20 °C at a pH 9.2. The experimentally determined partition coefficient between octanol and water (log Kow) value of the test substance is low with 0.8. The soil adsorption coefficient (log Koc) was calculated to be 1.76 at 25 °C.

Absorption

Oral route

Following oral administration, the likelihood of systemic absorption through the walls of the intestinal tract depends on several physicochemical substance properties. In order to obtain a conclusive judgement of a substance’s potential to be able to reach the systemic circulation, important physicochemical factors such as molecular weight, water solubility and the log Kow need to be considered. According to ECHA Guidance Document R.7c, the smaller the molecule the more easily it passes through the walls of the gastrointestinal tract (GI). Furthermore, ionisable groups can limit the passive absorption across biological membranes. With a molecular weight of 280.28 g/mol, a low log Kow of 0.8 and a well water solubility of 9.3 g/L the test substance seems to be able to be absorbed. Uptake of the test substance into the systemic circulation via gastro-intestinal (GI) tract might be limited due to the ionisable groups (e.g. two carboxy acid groups), which are present within the structure of the molecule. Taken together the physiochemical properties indicate that the test substance will become bioavailable following the oral route. This assumption is confirmed by the results of the oral toxicity studies in rats. In an acute oral as well as in a combined repeated dose toxicity study no mortality occurred up to the highest doses tested of 2000 mg/kg bw and 1000 mg/kg bw/d, respectively. However, in both studies soft to liquid faeces was observed and in the acute oral toxicity study furthermore clinical signs of reaction to treatment such as piloerection, hunched posture, waddling/unsteady gait, dark colouring to eyes, ungroomed appearance and protruding eyes were observed indicating that the substance was absorbed following oral intake. 

Inhalation route

Since the vapour pressure of the test substance is not known the volatility potential cannot be predicted. Thus, inhalation as a vapour cannot be excluded even though no high vapour pressure is expected for a solid substance. The mass median parameter of the test item particles is 96 µm and less than 0.1% by mass of particles is smaller than 10 µm. Therefore, the test substance has the potential to be inhaled. Reaching the alveolar region is not expected. The low log Kow of 0.8 indicates that absorption directly across the respiratory tract epithelium could occur via passive diffusion. The systemic toxicity observed in the acute oral toxicity study showed that the test substance can be absorbed following ingestion. It is likely that the substance will also be absorbed if it is inhaled.

Dermal route

To assess the potential of a substance to cross the skin, basic physicochemical properties of the substance, i.e. molecular weight and lipophilicity (log Kow), should be taken into account. In general, dermal absorption is favoured for substances with a molecular weight < 100 g/mol. The molecular weight of the substances is above 100 g/mol, but < 500 g/mol and therefore still small enough to be absorbed by skin. Generally, oral absorption is favored with a log Kow in the range of 1 to 4. With a log Kow of 0.8, it is still conceivable that the test substance is able to passes biological membranes. Absorption is anticipated to be moderate to high if water solubility is between 100 and 10000 mg/L. The test substance has a water solubility of 9.3 g/L, therefore not supporting dermal absorption. An acute dermal toxicity study did not indicate that absorption occurred since no mortality or signs of systemic toxicity were observed.

Distribution

As mentioned above, the physicochemical properties and toxicological data revealed that the test substance can become systemically available following exposure. Once absorbed, it is conceivable that the molecule distributes into cells due to its slightly lipophilic properties (log Kow = 0.8). This applies especially for fatty tissues. The test item is unlikely to have a bio-accumulative potential, because it is not highly lipophilic (log Kow is not greater than 4) and there are no other physic-chemical properties indicating bio-accumulating properties. As a combined repeated dose toxicity study in rats did not reveal any signs of target organ toxicity or other indications for an accumulation in any organ or tissue, there is also no evidence for an accumulative property of this compound.

Metabolism

The test substance showed no genetic toxicity in a bacterial reverse mutations assays (Ames test), a mammalian cell HPRT and an in vitro micronucleus assay. In the Ames test, cytotoxicity was observed with and without metabolic activation (S9 mix). The cytotoxicity was lower with metabolic activation (S9 mix) than without. This indicates that the test substance will be metabolised (deactivated) by metabolsing enzymes. As part of the metabolism of the test substance, breaking of the azo-bound could occur. The resulting cleavage compounds might be transformed by Phase I (functionalisation) and Phase II (conjugation) enzymes to enhance the hydrophilicity and to facilitate the elimination.

Excretion

Excretion can occur via the urine especially for small (below 300 g/mol) and water-soluble substance and/or via biliary excretion predominately for larger molecules. With a molecular weight of 280.28 g/mol the test substance is small and has with 9.8 g/L a well water solubility.Excretion via urine is likely to occur for the test substance and for water soluble metabolites of the test substance. Excretion of the unmetabolised test substance via faeces is also conceivable.