Registration Dossier

Administrative data

Description of key information

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

Data for C.I. Pigment Green 50 (spinel pigment based on cobalt (II)/nickel (III)/zinc titanate) are not available. Thus read across was performed with 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 skin sensitisation. Because both pigments contain nickel titanate as impurity, surrogate data from other nickel species were used to cover the endpoint. Bridging to nickel oxide was performed.

Data characterizing sensitization were limited to two skin sensitization studies; no studies evaluating respiratory sensitization were identified. No relevant or reliable human studies were identified for skin irritation.

Key studies

Two skin sensitization studies conducted according to OECD guideline 406 indicated that nickel oxide was not a contact sensitizer in guinea pigs. Both studies relied on an initial sensitization phase followed by a challenge phase, and collectively evaluated skin sensitization following both dermal and intradermal exposures. The most recently conducted study (Nickel Consortium, 2009) used the Buehler Methods to evaluate the sensitization potential of repeated topical applications of a nickel oxide sinter (composed of 98 % Nickel oxide and 1.5 % Cobaltous oxide), also described as dark grey nickel oxide green, in a preliminary test and a main test (induction, challenge and rechallenge). For the preliminary test, the highest non-irritating concentration (HNIC) of 68 % w/w was determined following a single 6-hour exposure of 0.4 g of 90 %, 68 %, 45 % or 23 % w/w mixture, and thus was used as the challenge dose in the main test. During the induction phase of the main test, a 90 % w/w mixture of the test substance in mineral oil (0.4 g) was topically applied to 20 healthy test guinea pigs, once each week for a three-week induction period. Twenty-seven days after the first induction dose, a challenge dose (0.4 mL of 68 % w/w mixture in mineral oil) was applied to a naive site on each surviving guinea pig. Approximately 24 and 48 hours after each induction and challenge dose, the animals were scored for erythema. Three and five animals (of twenty) had positive responses (incidence) at 24 and 48 hours, respectively; the severity was 0.53 and 0.50, respectively. However, because of higher than expected irritation scores in the naive control animals after the challenge dose, study authors could not determine if a sensitization response had occurred and thus conducted a rechallenge phase using a lower concentration. Seven days after the primary challenge, 0.4 mL of a 45 % w/w mixture of the test substance in mineral oil was applied to a naïve site in the test animals; a new group of naive control animals (n=10) was also exposed. In the rechallenge phase, no test animals had an incidence of positive response at 24 or 48 hours, and severity was 0.15 and 0.10, respectively. Thus, the study report concluded that under the current test conditions, Nickel oxide green was not considered to be a contact sensitizer. It should be noted that the Buehler Method, as with other animal models for evaluating potential dermal sensitizers, may not be sufficient for assessing nickel-containing compounds. Therefore, the results of this study should be interpreted with caution.

Similar findings were also reported by the Cyanamid Company (1986) several years prior. In this evaluation using the guinea pig maximization test (GPMT), guinea pigs were sensitized to nickel via intradermal injection with 0.1 mL 1 % (w/v) nickel sulfate in distilled water and 0.1 mL Freund’s complete adjuvant. Eight days later, each site was further sensitized by a topical exposure to nickel sulfate (0.3 mL 5 % w/v) and occluded for 48 hr. On day 22 after the initial sensitization injections, virgin sites and original injection sites were challenged and occluded for 24 hr with nickel sulphate, 0.2 g NiO moistened with propylene glycol, or plain propylene glycol. The challenge sites were scored for erythema and edema via the Draize method at 24 and 48 hr after removal. The erythema scores in animals challenged with NiO were 0 at 24 and 48 hr for animals previously sensitized with nickel sulfate or vehicle controls. The authors concluded that under the conditions of this study, NiO failed to cause sensitization in female albino guinea pigs.

Collectively, these two studies provide sufficient data to characterize skin sensitization potential following dermal or intradermal exposure to nickel oxide. The available data indicate that nickel oxide does not present a skin sensitization health hazard in guinea pigs under the conditions evaluated.

Conclusions

Pigments can be regarded as physiologically inert due to their very low water solubility. The leachable fraction of metals incorporated in the spinel lattice of the pigment C.I. Green 50 can be regarded as neglible (please refer to IUCLID section 7.9.3). Furthermore in both studies conducted with the read across substance nickel oxide no sensitising potential was observed. Together with the inert character of C.I. Pigment Green 50, skin sensitisation can most likely be excluded.

Migrated from Short description of key information:
No sensitising effects were observed in two studies with guinea pigs (Nickel Consortium, 2009; Cyanamid Company, 1986).

Justification for selection of skin sensitisation endpoint:
GLP and guideline compliant study.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Dangerous Substance Directive (67/548/EEC)

The available studies are considered reliable and suitable for classification purposes under 67/548/EEC. As a result the substance is not considered to be classified for skin sensitization under Directive 67/548/EEC.

                               

Classification, Labeling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. As a result the substance is not considered to be classified for skin sensitization under Regulation (EC) No. 1272/2008.