A mixture of isomers of: 1,1'-[(3,5(or 2,4 or 4,6 or 2,6)-dihydroxy-o(or m or p)-phenylene)bis(azo-meta-phenyleneazo{1-[3-(dimethylamino)propyl]-1,2-dihydro-6-hydroxy-4-methyl-2-oxopyridine-5,3-diyl})]dipyridinium-dichloride-dihydrochloride; 1-(1-[3-(dimethylamino)propyl]-5-{3-[x-(4-{1-[3-(dimethylamino)propyl]-1,6-dihydro-2-hydroxy-4-methyl-6-oxo-5-pyridinio-3-pyridylazo}phenylazo)-2,4(or 2,6 or 3,5 or 4,6)-dihydroxyphenylazo]phenylazo}-1,2-dihydro-6-hydroxy-4-methyl-2-oxo-3-pyridyl)pyridinium-dichloride-dihydrochloride (where x is variable)

Endpoint summary

Description of key information

Based on high molecular weight of the test item which is close to 1000 g/mol, on low logP value which is -1 at 20 °C and the effects observed in skin sensitisation test, in acute oral and acute dermal toxicity studies as well as in oral subacute toxicity study, it can be postulated that this material has very little bioavailability by the oral and dermal routes.

Key value for chemical safety assessment

Bioaccumulation potential:

low bioaccumulation potential

Additional information

Oral absorption

This test item will readily dissolve into the gastrointestinal fluids due to the high water solubility (1000 g/l). However, since the molecular weight is high (close to 1000 g/mol) the unchanged substance may not pass through aqueous pores or may not be carried through the epithelial barrier by the bulk passage of water.

Absorption via inhalation

Due to the very low vapour pressure, inhalation exposure is only possible via aerosols of solid particles or dissolved material.

The mass median diameter of test substance is 37.0 µm and less than 5 % of particles is < 10 µm. By evaluating the particle size distribution in terms of fractions as defined in EN481 (1993), i.e. inhalable (10 -100 µm), thoracic (4 -10 µm) and respirable (< 4 µm) fractions, only a very small amount of particles, less than 5 %, might be be able to pass the larynx and possibly reach the alveoli and be absorbed. Most of particles remain in the high part of the respiratory tract, where they can be cleared out or enter the gastrointestinal tract. Moreover, the substance has high water solubility, a low partition coefficient and a relatively high molecular weight (close to 1000 g/mol), thus bioavailability via this route is expected to be very low.

 

Dermal absorption

As for oral absorption, the high molecular weight of the dye may prevent dermal uptake. In addition, the substance is too hydrophilic (logP = -1) to cross the lipid rich environment of the stratum corneum. The surface tension of 73.2 mN/m of aqueous solution prevents the compound uptake as well. Since the molecule contains heterocyclic ammonium ions and acid chlorides it could result the binding to skin and uptake of the compound can be slowed. In the Guinea pig maximisation test the molecule has been identified as a skin sensitiser (Daamen, 1989). Since the challenge application was to intact skin, some uptake must have occurred.

Distribution / metabolism

Due to the high water solubility and the low partition coefficient accumulation in fatty tissues is very unlikely. Metabolism prior to absorption may occur by gut microflora or enzymes in the gastrointestinal mucosa. In this molecule four diazo binding could undergo reduction by azoreductase to yield respectively two amine fragments. Further N-glucuronidation for these cleavage products may occur. The hydroxyl groups could as well conjugate with glucuronide or sulfate to facilitate the excretion of the substance. Since the skin sensitisation test was positive (Daamen, 1989) it could be assumed that substance binds to proteins.

Excretion

As the substance registered is highly water soluble it might be excreted via bile or via urine, where the former is more probable due to the relative high molecular weight of the compound.