Benzenesulfonic acid, 4-chloro-2-[2-[4,5-dihydro-3-methyl-5-oxo-1-(3-sulfophenyl)-1H-pyrazol-4-yl]diazenyl]-5-methyl-, ammonium salt (1:2)

Endpoint summary

Description of key information

There were no studies about metabolism and kinetic of the test substance performed. However, the available studies and properties indicate that the test substance is not absorbed after oral or dermal application. There is also no evidence for systemic distribution.

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Additional information

No studies regarding toxicokinetic properties of the test substance were performed. Subsequently, assumptions on ADME were based on physico-chemical data and the available toxicity studies. Taking all information into account, experimental studies and physico-chemical properties indicate that the test substance is not absorbed after oral, respiratory or dermal application. There is also no evidence for systemic distribution.

Absorption

Absorption – oral

The test substance has three ionizable groups, namely hydroxyl group (OH) and two sulfonate groups, thus, being favorable for absorption. However, due to the high molecular weight (> 500 g/mol) gastrointestinal absorption is assumed to be very limited. Water solubility is suggested to be moderate (1.2 g/L). The Log P value of -1.43 indicates oral absorption to be unlikely as well. Furthermore, experimental studies indicate no oral absorption due to the absence of effects and the observation of discolored feces.

Absorption – respiratory

Particles of the test substance have an aerodynamic diameter of 47.5 μm, which have the potential to be inhaled (< 100 μm). Particle size distribution was determined, and particle size fractions were as follows:

< 4 μm = 4 %

< 10 μm = 10 %

< 100 μm = 83 %

Following inhalation, the particles are assumed to behave like inert dusts as due to the high molecular weight and the log P value absorption is expected to be unlikely.

As the test substance is a solid vapor pressure is not applicable. Experimental data on the toxicity after inhalation are not available for the test substance itself.

Absorption – dermal

Dry particulates are not taken up readily. In addition, the molecular weight of the test substance (520.975 g/mol) indicates that the molecule is too large to be taken up dermally. The water solubility of 1.2 g/L points to a moderate absorption. However, the log P of -1.43 suggests that the test substance is not likely to be sufficiently lipophilic to cross the stratum corneum, thus, dermal absorption is likely to be low. This assumption is confirmed by experimental data from a dermal acute toxicity study. Herein, no adverse effects were observed. Furthermore, the substance does not possess a skin irritating or corrosive potential, that would damage the skin surface and enhance skin penetration.

Distribution

Since absorption of the test substance is assumed to be very limited, distribution is not relevant. However, in the unlikely case of absorption, distribution may be limited due to molecular weight of above 500 g/mol. Diffusion through aqueous channels and pores is considered to be low.

Accumulative potential

Considering the log P value being below 3, an accumulative potential is suggested unlikely in adipose tissue. In addition, accumulation potential in bone and stratum corneum is considered unlikely as well.

As mentioned above, particles of the test substance can be inhaled. As only about 4 % of the particles are below 4 μm the amount of particles reaching the alveoli is small. In the unlikely case of respiration, the particles are likely to undergo phagocytosis by alveolar macrophages.

Metabolism

As no experimental data regarding metabolism is available, possible metabolites were identified with OASIS TIMES (version 2.27.19) and the metabolism simulator “in vivo rat 07.08”.

Bacterial or enzymatic cleavage of the azo group may lead to the formation of 3-(4-amino-3-methyl-5-oxo-4H-pyrazol-1-yl)benzenesulfonic acid (metabolite 1) and 2-amino-4-chloro-benzenesulfonic acid (metabolite 2). Concerning metabolite 1, limited information is available. However, studies with a test substance lacking the amine group at position 4 (m-(4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzenesulfonic acid, CAS 119-17-5) were performed. This analogue metabolite was without pathological findings in an acute toxicity study and did not induce mutations in an Ames test. In addition, based on results obtained from several in vitro genetic toxicity studies, it can be assumed that the test substance is not enzymatically activated (toxified) during metabolism as the parent compound showed no higher toxicity compared to the metabolic activated substance.

In conclusion, the test substance has a molecular weight greater than 500 g/mol indicating limited gastrointestinal absorption and systemic availability which is supported by the observation of yellow stained feces after repeated application and the absence of any treatment related effects. Thus, it could be demonstrated that, at least in part, the chromophore of the test substance is preserved.

Excretion

Based on experimental data and physico-chemical properties, the test substance is expected to be excreted mainly unchanged via feces. Discolored feces observed in experimental animals after oral application of the substance supports this assumption.

Hydrolysis products

The test substance will hydrolyze slowly in contact with water. No significant hydrolysis was observed at pH 4, 7 and 9 at 50°C over 5 days.

In general, the substance does not contain functional groups that are susceptible to pH-dependent hydrolysis at environmentally relevant pH.