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Description of key information

Key value for chemical safety assessment

Bioaccumulation potential:
low bioaccumulation potential
Absorption rate - oral (%):
50
Absorption rate - dermal (%):
50
Absorption rate - inhalation (%):
100

Additional information

The substance is a mono-constituent having a molecular weight >500. The extent of water solubility is greater than 125 g/L. This implies that the partition coefficient (log Kow) is low. Taking into account the low log Kow and high water solubility, bioaccumulation of the substance is considered to be unlikely. Further, the high molecular weight implies low dermal absorption of the substance.

Based on the results of the in vivo studies with the test and the read-across substance, the following evaluation of toxicokinetic properties can be made:

Absorption:

After oral gavage, the substance is anticipated to be at least partially absorbed. This can be concluded from the data obtained in the repeated dose study with the read-across substance, in which clinical signs occurred at a dose of 1000 mg/kg bw/day, and the blood serum, urine and several organs and tissues of high- and/or mid-dose animals were discoloured reddish, confirming the presence of the test substance in these tissues. Therefore, the default value of 50% oral absorption will be used for the risk assessment.

The physico-chemical properties of the substance suggest little or no dermal absorption. This is in accordance with the evidence from the skin irritation study with the test substance and the skin sensitization study with the read-across substance which shows absence of systemic effects. Therefore, in the absence of any toxicokinetic data on the substance, a conservative value of 50% dermal penetration will be used for the risk assessment.

As no data is available for inhalation exposure, the default value of 100% absorption was selected for risk assessment.

Metabolism:

As the substance is a dye with an azo bond, a partial metabolic cleavage by bacterial azo-reductases in the intestine resulting in two hydrophilic amines is likely. This is confirmed by QSAR study of the possible metabolic fate of both the substance and its read-across (OECD QSAR Toolbox v3.4). According to this prediction, the first metabolic reaction for target and source substances is either the cleavage of the N=N bond or dealkylation.

Accumulation and elimination:

Owing to the physico-chemical properties of the substance (high water solubility and predicted low log Kow), an accumulation in the fatty tissues is unlikely. Moreover, it can be assumed that the elimination of the substance and/or its metabolites is very efficient. This is supported by the results obtained from the clinical chemistry examination done as part of the repeated dose toxicity study. In the recovery group, these changes were no longer found at the end of the recovery period of 14 days, indicating that the substance was already eliminated at the time of examination. It was further confirmed by the appearance of the serum, organs and tissues after the cessation of exposure, as the serum, organs and tissues of the recovery animals were not stained.

Although substances with molecular weight above 300 g/mol are preferentially excreted via faeces in rats, the red discolouration of the kidneys and urine of the mid- and high-dose animals support the hypothesis that the absorbed dye was excreted via the kidneys and urine.