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Description of key information

Based on the physico-chemical properties and the absence of findings in toxicity studies, the substance is considered to be non bioavailable.

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential

Additional information

Assessment of the Toxicokinetic Behaviour of

3-[(4-chloro-2-nitrophenyl)azo]-2-methylpyrazolo[5,1-b]quinazolin-9(1H)-one (CAS-No.74336-59-7)

There were no studies available in which the toxicokinetic properties of the substance were investigated.

The substance (molecular weight of 382.77 g/mol) is an odourless, orange powder at room temperature with an extremely low water solubility (measured water solubility: < 10 µg/L at 20°C and pH 6.1-6.3 (BASF 2011, see chapter "water solubility"). The substance is not prone to hydrolysis. Additionally, due to the structure of the molecule and the extremely low water solubility of the substance biodegradation is not expected. The log Po/w is 2 at 23°C and pH = 6.2 (BASF 2011, see chapter "partition coefficient"), indicating that accumulation of the substance is not expected.

ABSORPTION

No indication of a substance specific systemic toxicity can be found in an acute toxicity study in rats with oral administration by gavage (see chapter „acute toxicity“) as well as in a subacute toxicity study and reproductive toxicity screening study in rats with oral application (see chapter „repeated dose toxicity“ and "reproductive toxcity"). Therefore absorption and bioavailability of the test substance after oral administration is not expected (BASF 1981, see chapter "acute oral toxicity" and chapter "repeated dose toxicity").

There are no data available about dermal and inhalative absorption. Nevertheless, due to the low water solubility dermal uptake is likely to be very low. Based on the log Po/wof 2, penetration into the stratum corneum may occur, but due to the limited transfer rate into the epidermis, systemic absorption is expected to be low (ECHA guidance document 7c, 2008).

The test substance is a non-volatile powder at room temperature (vapour pressure of less than 1 x 10e-6 hPa at 20 °C, BASF 2011, see chapter "vapour pressure"), with only a very small proportion of particles of inhalative and respirable particle size (< 100 µm: 7.4% and < 10 µm: 0.3% BASF 2011, see chapter "particle size distribution"), thus significant inhalation exposure is not anticipated.

Based on the physico-chemical properties and the absence of systemic toxicity in acute and repeated-dose studies, absorption of the test substance is unlikely.

DISTRIBUTION

There is no experimental evidence of distribution.

 

METABOLISM

There is no experimental evidence of metabolism. In theory the chemical structure indicates that the most likely route of biotransformation is by reductive cleavage of the azo bond either by bacterial enzymes in the gut or by microsomal azo reductase in the liver. However, azo reduction products typically cause adverse effects on liver and blood and such (or any) effects were not observed for this substance. So metabolism is not expected due to lack of absorption after oral administration of the test substance. Studies on genetic toxicity (bacterial reverse mutation assay (Ames-Test), in vitro mammalian cell gene mutation and chromosome aberration test) see chapter "genetic toxicity") were negative and gave no indications of a reactivity of the test substance or its metabolites under the test conditions (i.e. no increased mutagenicity or cytotoxicity in treatments with and without metabolic activation).

 

EXCRETION

The observation of orange faeces in the acute and repeated oral study is assessed as indication of intestinal passage of the pigment. The extremely low water solubility of the test substance makes absorption from the gastro-intestinal tract unlikely and the substance is expected to be eliminated unchanged (ECHA guidance document 7c, 2008).