Disodium [2,4-dihydro-4-[(2-hydroxy-5-nitrophenyl)azo]-5-methyl-2-phenyl-3H-pyrazol-3-onato(2-)][3-hydroxy-4-[(2-hydroxy-1-naphthyl)azo]-7-nitronaphthalene-1-sulphonato(3-)]chromate(2-)

Endpoint summary

Description of key information

No bioaccumulation potential

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Additional information

Acid Brown 282 (ABr282) is a brown organic solid, used in powdered form.

ABr282 is not toxic/harmful for short-term exposures and it is not skin/eye irritating. It may cause an allergic skin reaction. No CMR activity was observed.

 

Considering the molecular size and the hydrophilic behaviour of ABr282, it is probable that dermal absorption does not occur. The metabolites simulation proposes possible reduction of azo bound and/or reduction of nitro group and the possible cleavage of azo bounds, with eventual formation of the phenyl-pyrazole moiety.

The dermal adsorption is expected as negligible, based on physical-chemical substance characteristics and estimated data. Furthermore, in the short-term toxicity studies available no substance-related effects were observed and at necropsy no abnormalities were recorded. Only the sensitisation assay showed that substance is able to cause a systemic effect as a contact allergen.

 

ABr282 is characterized by particles that are expected to remain in the upper respiratory tract, which is characterized by efficacious defence mechanisms able to remove them; therefore inhalation is expected to be an unlikely route of absorption of ABr282.

 

The high water solubility suggests that ABr282 is a hydrophilic substance, thus it is expected that only a small rate of substance as such could be absorbed by oral route.

No abnormalities were recorded in the acute toxicity studies available, by oral route.

In the Combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening test, substance-related effects were observed mainly on haematology and biochemistry: ABr282 may impact the white blood cells (leukocytes, granulocytes), bilirubin and ALP. Reversible increased weight of kidneys was reported and the gross necropsy in all dosed animals demonstrated reversible changes of colour of the digestive tract, mesenteric lymph nodes and pancreas. Microscopical evaluation showed effects in large intestine and caecum (brown cytoplasm of enterocytes) and pigmentophages with light-brown cytoplasm in mesenteric lymph nodes.

Furthermore, the number of females achieving pregnancy, sperm parameters and microscopical structure of reproductive organs parental males and females, number of post-implantation and post-natal losses of mothers were adversely affected by the test substance treatment.

 

The fact that some organs resulted coloured may suggest that the substance is not completely metabolised: the colouration is due to chromophore that is probably not impacted. Nevertheless, it has to be taken into account that the organ colourations observed in not necessarily an indicator of the dye distribution, thus it may be due to the ABr282 compound or it may be determined by the presence of ABr282 metabolites, which preserve intact their chromophores.

The nitrophenyl diazo phenhylpyrazole moiety can be often found in yellow dyes; furthermore it is known that 3-hydroxy-4-[(E)-(2-hydroxynaphthalen-1-yl)diazenyl]-7-nitronaphthalene-1-sulfonic acid (named as Eriochrome Black T) can be of dark colours (black-blue) or red, if salificated with calcium. Mordant Black 011, which is the dinaphthalen salificated with sodium, is dark.

Except in the case of different specification, it is expected that the colouration retrieved in the organs during the experiment is visually ascribable to the ABr282. 

In any cases, on the basis of the available information, the absorption rate of ABr282 is not known and cannot be estimated.

 

On the contrary, in the combined study is reported that the "test substance-coloured" excrements were observed in all treated animals; this fact suggests that part of ABr282 may be excreted by faeces.

 

Considering the complex dye chemistry, changes in the complex coordination and in the bounds with the chromate coordination centre can be expected and it can be supposed that ABr282 may have different steric hindrances, which may influence the substance absorption.

 

As mentioned, carcinogenicity and genotoxicity are the critical health effects of potential concern for Aromatic Azo and Benzidine-based Substances. The mechanism by which Aromatic Azo and Benzidine-based Substances exert toxicity involves the reductive cleavage of the azo bonds and the subsequent release of free aromatic amines. These aromatic amines are, in turn, converted to reactive electrophilic intermediates through metabolic oxidation. However, the studies available bring to the conclusion that ABr282 is not genotoxic and the available information of possible metabolites do not engender particular concern.

Furthermore, a recent study by Deb et al. (2011) showed that azo substances that are bound by metal ions such as chromium are much less reactive than their metal complex–free counterparts. In this study, 2 hydroxyphenyl-azo-2′-naphthol caused significant changes in the cell morphology of lung carcinoma cells in addition to deoxyribonucleic acid (DNA) fragmentation, while no significant change was observed with its cobalt(II) complex, even at high concentrations.