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Description of key information

Most pigments behave like inert dusts and thus oral, dermal and inhalative adsorption can be considered as not very likely. This is also supported by the low water solubility and the results of the leaching studies. The heavy metal oxides are absorbed by the spinel lattice and thus lose their chemical, physical, and physiological properties. If the substance is inhaled, it will be cleared without being absorbed due to the effective clearance capacity of the lung. Based on the low water solubility and the results from the comprehensive toxicity testing, it is unlikely that the test substance become systemically available. If any, there might be only a very small proportion for metabolisation and biotransformation available. The practically insoluble pigment is most likely be excreted via faeces. Bioaccumulation is unlikely due to the neglible bioavailability of the test substance.

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential

Additional information

Data for C.I. Pigment Green 50 (spinel pigment based on cobalt (II)/nickel (II)/zinc titanate) are not available. Thus read across was performed based on C.I. Pigment Yellow 53 (nickel antimony titanium yellow). The two Nickel-containing pigments belong to a family of spinel and rutile pigments that have been tested for ion leaching (please refer to IUCLID section 7.9.3) and have been exempted from classification based on non-availability of ion toxicophores. The heavy metal oxides (used for Pigment manufacturing) are absorbed by the spinel resp. rutile lattice and thus lose their chemical, physical, and physiological properties. Both pigments show a very low water solubility (< 0.05 mg/L) being practically physiologically inert. Thus, it can be concluded, that the chemical behaviour towards the different toxicological endpoints is similar for both pigments. Therefore all toxicological endpoints were addressed with C.I. Pigment Yellow 53. No data was available for repeated dose inhalation and skin sensitisation. Because both pigments contain nickel titanate as impurity, surrogate data from other nickel species were used to cover both endpoints. Bridging to nickel oxide was performed to cover the worst case for repeated dose inhalation. Due to the inert character the exposure towards fine dust is the most relevant health concern for pigments. As most pigments behave like inert dusts, oral, dermal and inhalative adsorption can be considered as not very likely.

C.I. Pigment Green 50 is a practically insoluble spinel pigment based on cobalt (II)/nickel (III)/zinc titanate. The heavy metal oxides are absorbed by the spinel lattice and thus lose their chemical, physical, and physiological properties. The substance has a very low water solubility of below 0.01 mg/L. Other Data for C.I. Pigment Green 50 are not available, thus read-across with analogue substances were performed.

Absorption

Following oral administration, the likelihood of systemic absorption through the walls of the intestinal tract depends on several physicochemical substance properties. Generally, the smaller the molecule the more easily it may be absorbed through the walls of the gastrointestinal tract. As the molecular weight of C.I. Pigment Green 50 is 230.9 g/mol, an uptake of the compound into the systemic circulation via the gastro-intestinal (GI) tract is likely (ECHA, 2014). But C.I. Pigment Green 50 has a very low water solubility of <0.01 mg/L. Due to the insolubility in water, the pigment can be regarded as not bioavailable.

Since very little data are available for the test substance, read- across with the rutile pigment C.I. Pigment Yellow 53 (Nickel antimony titanate yellow) was performed. The two nickel-containing pigments have been tested for ion leaching and have been exempted from classification based on non-availability of ion toxicophores.

Administered to rats via gavage in two acute oral toxicity studies, C.I. Pigment Yellow 53 led to LD50 values of greater than 2000 mg/kg bw and above 10000 mg/kg bw without any clinical signs or mortality. Furthermore, the results of two long-term toxicity studies in rats (90d: NOAEL >= 450 mg/kg bw/d; 46 [males]/41-45 d [females]: NOAEL >=1000 mg/kg bw/d) confirmed the results of the in vitro leaching studies that organ translocation of ions from the crystal lattice could not be demonstrated. Accordingly, C.I. Pigment Green 50 is also not expected to be orally absorbed.

In a subacute inhalation study, male Wistar rats were exposed for 5 days to 60 mg/m³ of C.I. Pigment Yellow 53. The observation period was 0, 3, 10, 31 and 60 d (BASF 1994). Nickel and antimony levels in the lung declined following first-order kinetics with a clearance of 50 d. In liver and kidneys, antimony and nickel were present in the range of the limit of quantification or below. In conclusion, study results indicate a negligible bioavailability of Ni and Sb after inhalation of the test substance.

The dermal exposure pathway is assessed as not relevant, because no leaching of metal ions was detected in a leaching study with C.I. Pigment Yellow 53. Furthermore, the substance must be sufficiently soluble in water to partition from the stratum corneum into the epidermis. Because the Pigment is nearly insoluble, dermal uptake is likely to be low.

 

Distribution

Based on the low water solubility and the results from the comprehensive toxicity testing, it is unlikely that the test substance becomes systemically available. If metal ions are absorbed they will probably be bound to carrier proteins and transported to the target location via bloodstream. This only happens to a very small degree because organ translocation of ions from the crystal lattice could also not be demonstrated in the repeated-dose studies.

Three leaching studies with C.I. Pigment Green 50 and read across substance C.I. Pigment Yellow 53 were performed under different pH conditions (pH 1, 8.5 and 6.5). These pigments showed leaching concentrations significantly below the prescribed threshold level for EN 1811 (0.5 µg/m³/week). Since the test covers the pH extrema in the human organs and for dermal contact, the leaching fraction of metals can be regarded as of no concern for all exposure pathways.

Metabolism

As already described above, due to its insolubility in water and inert character, if any only very low amounts of the test substance may be absorbed and become available for metabolisation. Metal ions are not metabolised in the body but are bound to carrier proteins and are transported to the target location.

Excretion

Chemicals can be excreted via various routes and mechanisms. The excretion depends on the physical and chemical properties of the compound. The inert pigment will most likely be excreted via faeces as can be seen in the several oral repeated dose studies conducted with the read across pigment. Faeces of all treated animals showed a yellow colour. Due to the lack of adsorption, urinary excretion will not occur and bioaccumulation can most likely be excluded due to the neglible bioavailability of the test substance.

 

References

ECHA (2014) Guidance on information requirements and chemical safety assessment, Chapter R.7c: Endpoint specific guidance.

Marquardt H. & Schäfer S. (2004): Toxicology. Academic Press, San Diego, USA, 2nd Edition.