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Description of key information

Based on its physicochemical properties and study observations systemic systemic uptake of Butanamide 2-[2-(2-methoxy-5-nitrophenyl)diazenyl]-N-(2-methoxyphenyl)-3-oxo- is unlikely but cannot be excluded. The insolubility in water and poor solubility in octanol do not favor passage of biological membranes. The logPOW and the molecular weight are however in a range for which systemic uptake is assumed. The substance contains functional groups known to be susceptible to enzyme-catalysed transformations. Both conjugating reactions as well as hydrolysis are in theory possible. Hydrolysis would reduce the conjugated sytem and result in non-coloured substances.

The fact that the substance was found to be non-hazardous up to the limit dose upon subacute oral studies is strongly in favour of absence of systemic uptake or hydrolysis. Theoretical hydrolysis products would have an aromatic amine core and therefore any uptake and hydrolysis would have been resulted in adverse effects. Conjugated Phase II-metabolites would keep the yellow colour and are expected to be non-toxic.

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential

Additional information

Toxicokinetic analysis of Butanamide 2-[2-(2-methoxy-5-nitrophenyl)diazenyl]-N-(2-methoxyphenyl)-3-oxo-

The test substance is a solid yellow powder at room temperature with a molecular weight (MW) of 386.36 g/mol. It is almost insoluble in water (19.0 µg/L at 20 °C, pH 6) as well as in organic solvent (n-octanol, 4.05 mg/L) and has a log Pow of 2.3 (at 23 °C, pH 5). The molecule is a conjugated system of rigid shape.

 

Absorption

A screening study for reproductive/developmental toxicity according to OECD 421 reported a transient discoloration of the fur as well as urine and faeces (BASF SE, 2011). As the substance was applied via the diet, coloration of the fur is related to external contamination from the colorant in the feed. Yellow discoloration of feces indicates passage through the intestine without destruction of the chromophore. Whether yellow coloration of urine is indicator of uptake is questionable since urine is naturally yellow and the intensity of the color is related to its concentration.

According to the solid state of Butanamide 2-[2-(2-methoxy-5-nitrophenyl)diazenyl]-N-(2-methoxyphenyl)-3-oxo-, exposure to the test substance as vapor is very limited if handled at room temperature (vapour pressure < 1.0E -6 hPa). Considering the MMD of the test substance (66.0 µm) it is very unlikely that inhaled particles reach the tracheal, bronchial or alveolar region of the respiratory tract. If inhaled, the low water soluble test substance will not dissolve in the mucus of the respiratory tract. However, particles inhaled or deposited in the oropharynx could be coughed out and swallowed into the GI tract, possibly leading to intestinal absorption. These assumptions are based on the physico-chemical properties of the test substance, since no repeated-dose data of inhalation studies were available.

Particles of the test substance will have to dissolve into the surface moisture of the skin before absorption. Considering the non-hydrophilic character and the low solubility, the test substance will dissolve hardly in the surface moisture.

Dermal uptake of substances < 100 g/mol is favored. The MW of the test substance of 386.36 g/mol hinders dermal absorption. According to the solubility (19.0 µg/L) a minimal dermal uptake can be anticipated. Furthermore, the log Pow of 2.3 and the poor solubility in organic solvents (4.05 mg/L in n-octanol) will limit penetration into the stratum corneum and hence dermal absorption. It can be assumed that dermal absorption of the test substance is limited.

Distribution

In the oral studies, no discoloration of organs and absence of target organ toxicity was observed.

Metabolism

No data on metabolism is available. The structure contains a number of functional groups that are in theory known to be susceptible to enzymatic transformations. These include both hydrolytic and non-hydrolyic type transformations.

Excretion

The available data shows that at least a major fraction is eliminated via the feces.