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Description of key information

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential

Additional information

The toxicokinetic properties of metal laked 2B pigments are derived from acute and subacute toxicity studies and physico-chemical data.

Pigment Red 53:1 (D&C Red No 9) is of very low solubility and tends to re-agglomerate in aqueous solution. Experimental data on inorganic Barium salts indicates that the solubility increases in the acidic environment of the stomach as Barium chloride is of high solubility in water. To what extent this happens depends on the actual pH in the stomach. Dissolved Ba2+is detected rapidly in the blood after ingestion. It is eliminated to a higher extent in the feces than in the urine and is also incorporated into the bone and detected in tissues.

In the course of an in vitro skin penetration study, the percutaneous absorption of D & C Red No. 9 through human skin was found to be very low. With all four vehicles, total absorption was less than 0.1% of the applied dose and the maximum flux rate achieved was less than 0.1 mug/cm2/24 hours. The vast majority of the unabsorbed material remained on the surface of the skin and was found in the skin wash. This amount varied from 85-103 %. Very little colorant was found in the epidermis or dermis, less than 0.3% in all cases. Total drug recovery averaged 83-103% of the applied dose.

Regarding the inhalation route, only acute data is available. After inhalation of PR 53:1, all animals survived until scheduled necropsy. Hunched posture, wet and stained fur and noisy respiration were observed. All effects, unless staining, resolved within 2-3 days and animals appeared to be normal.

Subacute, subchronic and chronic repeated dose toxicity data are available for Pigment Red 53:1 Ba salt. In the majority of this studies, changes in red blood count, hemosiderosis in liver and spleen as well as fibrosis in and discoloration of the spleen were observed. These effects indicate that metabolites of the test article (1-amino-2-naphthol) cause methemoglobinamia leading to disturbances of iron metabolism and subsequently increased iron deposition in liver and spleen (hemosiderosis). Moreover, the substance or metabolites are attached at methemoglobin and transported via red blood cells into the spleen which acts as a filter for old or damaged erythrocytes. During degradation of methemoglobin, the substance or metabolite is released and affects spleenic mesenchymal tissue leading to fibrosis and promotion of tumor formation (sarcomas).

The substance was examined in several in vitro and in vivo genotoxicity assays. A mutagenic potential could not be detected in bacteria or mammalian cells. Likewise cytogenicity studies failed to detect a clastogenic potential. Furthermore, the pigment did not induce formation of micronuclei or unscheduled DNA synthesis in vivo. Gene mutation in vivo was also not observed. Thus, Pigment Red 53:1 has no genotoxic potential and does not interact with DNA or genetic material.

In conclusion, the absorption of the pigment via skin is very low. In the course of the acute inhalation study neither stained urine nor specific toxic effects or mortalities were observed indicating a very limited uptake of the substance via the respiratory system. The poor solubility of the test item and the property to stick together in aequeous solution support this assumption. Repeated dose toxicity tests revealed some effects which suggest a cleavage of the azo bond and a subsequent release of amino-naphthol. However, the substance was not considered to be genotoxic. Amino-naphthol might cause met-hemoglobin formation and be responsible for hematotoxicity and damage of the splenic tissue. Uptake of small amounts of barium after dissociation in gastric acid is likely. Effects on CNS, kidney, GIT or other target organs were not observed.