DS-2920A-E

Endpoint summary

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, showed no systemic effects and, therefore, provide no evidence of absorption.

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.