Benzoic acid, 4-[2-(2-hydroxy-6-sulfo-1-naphthalenyl)diazenyl]-, strontium salt (2:1)

Endpoint summary

Description of key information

Organic pigments have shown no indication for systemic uptake unless they contain groups susceptible to acid-catalysed hydrolysis (Stratmann et al 2020). For Pigment Orange 79, none of the experimental data gives an indication for systemic update.

A mechanistic study was performed in 2021 to investigate the potential of pigment particles to cause local affects during the clearance by macrophages in the lung.

Pigment Orange 79 (Strontium Salt) was administered to the NR8383 cells as a well dispersed suspension. While the uptake of few larger particles (<10 μm) was obvious from micrographs, the degree of internalization of the small diffusible particle fraction could not be estimated and appeared incomplete. Under these conditions Pigment Orange 79 (Strontium Salt) elicited neither cytotoxic (LDH), activating (GLU) nor oxidative effects (H2O2). A minimal pro-inflammatory effect (TNFα) was noted at the highest concentration only.

Taking into account the BET value of 20.3 m²/g and the active/passive classification criteria of Wiemann et al. 2016m  Pigment Orange 79 (Strontium Salt) was classified as passive.

Reference

H. Stratmann, M. Hellmund, U. Veith, N. End and W.Teubner: Indicators for lack of systemic availability of organic pigments. Regulatory Toxicology and Pharmacology (2020), Vol 115, 104719

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Additional information

Toxicokinetic Assessment

The substance is the strontium salt of an aryl-azo-aryl compound of a molecular weight of about 416.161g/mol that does not necessarily preclude absorption.

Some insights into possible toxicokinetic behaviour can be made from the chemical structure. The substance is a non-volatile powder (vapour pressure of less than 1.3 x 10e-5 Pa at 25 °C, BASF SE, Testing Lab.: Safepharm Laboratories Ltd., 1235/053, 1999) with only a small proportion of particles of respirable particle size (< 10µm, 11.7 %, BASF SE, Testing Lab.: Safepharm Laboratories Ltd., 1235/051, 1999), so significant inhalation exposure is not anticipated. It is not prone to hydrolysis but metabolism is predicted including bacterial metabolism in the gut so exposure to these metabolites could occur.

 

ABSORPTION

Acute oral and dermal toxicity studies and a repeated dose toxicity study on a structural analogue (also a strontium comlex), showed no systemic effects and, therefore, provide no evidence of absorption. No effects have been observed in a screening study for reproductive toxicity (OECD 421) with the substance itself (BASF 2012).

The substance had a low log pow value (log pow: -1.37, BASF SE, Testing Lab.: Safepharm Laboratories Ltd., 1235/001, 1998), so absorption by passive diffusion would not occur readily, although it does contain ionisable groups so absorption could be affected by pH. The putative metabolites are also ionisable and could be available for absorption under appropriate pH conditions.

Nevertheless, the study results indicate either very low toxicity or limited absorption.

 

DISTRIBUTION

There is no experimental evidence of distribution but the low log Pow value suggests that wide distribution and bioaccumulation would not occur. Furthermore, biotransformation is expected, producing water-soluble metabolites that would probably be rapidly eliminated. A contact sensitisation study was negative so the substance may not become bound to proteins, although this result may be affected by low bioavailability. 

 

METABOLISM

There is no experimental evidence of metabolism but 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. The resulting metabolites would be 2-hydroxynaphthylamine-6-sulphonate and p-aminobenzoic acid.

Subsequent conjugation reactions could also occur. 

 

EXCRETION

Again, there is no experimental evidence to indicate a route of excretion for any absorbed substance. The substance is moderately water-soluble (7.23 x 10 e-3, BASF SE, Testing Lab.: Safepharm Laboratories Ltd., 1235/001, 1998) and could be eliminated unchanged but biotransformation would be expected, with elimination of metabolites either in urine or bile. The parent substance is non-volatile and could not be eliminated via the lungs in expired air. During the screening study for reproductive toxicty, stained/discolored red feces were recorded in most or all test item treated animals of both genders from the start of dosing until necropsy. This indicates passage through the gastrointestinal tract of the intact chromophore for at least some fraction of the ingested orange pigment.