Aluminum cobalt oxide

Endpoint summary

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (sensitising)

Additional information:

There are no data available on skin sensitisation for cobalt aluminium oxide. However, there are reliable data for various cobalt and aluminium compounds considered suitable for read-across using the analogue approach. For identifying hazardous properties of cobalt aluminium oxide, the existing forms of the target substance at very acidic and physiological pH conditions are relevant for the assessment of human health effects. As cobalt aluminium oxide is a metal-organic salt, which is insoluble in water at pH 6, it is probable that the target substance has also a low degree of solubility at the physiological pH of 7.4. At acidic pH conditions, however, the study of Stopford et al. (2003) showed that water-insoluble cobalt compounds release cobalt ions. Thus, it can be assumed that cobalt aluminium oxide dissociates at acidic pH in the human body resulting in bioavailable cobalt and aluminate ions. Due to the fact that the toxicological effects of cobalt aluminium oxide are mainly caused by exposure to the cobalt ion, the use of data on soluble cobalt compounds is justified for toxicological endpoints as a worst case scenario. In addition, various aluminium compounds are used within the read-across approach. For further details, please refer to the analogue justification attached in section 13 of the technical dossier.

 

Cobalt compounds

Cobalt(II)chloride hexahydrate caused positive reactions in a modified guinea pig maximization test (GMPT) (Wahlberg and Boman, 1978). The test substance sensitised 100% of the test animals at the highest challenge dose (1% cobalt(II)chloride hexahydrate) tested 25 h after removal of the Finn chambers. The percutaneous absorption rate of the test substance through normal skin is obviously sufficient to induce contact allergy.

Ikarashi et al. (1992) showed a sensitising potential of cobalt(II)chloride hexahydrate in a local lymph node assay (LLNA) conducted similar to OECD 429. Repeated exposure to 5% of the test substance for three consecutive days induced an increase of LNC proliferative response in the draining lymph node of mice and resulted in a total stimulation index of 4.33.

In conclusion, reliable studies using different protocols, either GPMT or LLNA, demonstrated that cobalt(II)chloride hexahydrate is a skin sensitiser in guinea pigs and mice.

In humans, dermal exposures have been also observed to result in sensitisation reactions to soluble cobalt salts. Contact allergy was reported in 22 of 223 (9.9%) nurses who were tested with a patch test of 1% cobalt(II)chloride (Kiec-Swierczynska and Krecisz, 2000), as well as 16 of 79 (20.3%) of examined dentists (Kiec-Swierczynska and Krecisz, 2002). Numerous human data also showed that soluble cobalt(II)salts are skin sensitisers (for example Kanerva et al., 1988; Goh et al., 1986; Alomar et al., 1985).

References not cited in the IUCLID:

Kiec-Swierczynska M and Krecisz B, 2002, Allergic contact dermatitis in dentists and dental nurses. Exogenous Dermatology. 1(1): 27-31

Kanerva L et al., 1988, Occcupational skin disease in Finland, International Archives of Occupational and Environmental Health, 60: 89-94

Goh et al., 1986, Occupational dermatitis in a prefabrication construction factory. Contact dermatitis, 15: 235-240

Alomar A et al., 1985, Occupational dermatosis from cutting oils. Contact dermatitis, 12: 129-138

 

Aluminium compounds

The skin sensitisation potential of two samples aluminium oxide, namely aluminium oxide TBH: AK 43/79 and aluminium oxide TOF: AK 44/79, was assessed in guinea pigs (male albino SPF, 8 animals in each group) using the Landsteiner/Draize method (Central Institute for Nutrition and Food Research, Germany) at the request of Degussa AG, Germany (1979). Both compounds were administered by intra-dermal injections. A 33.3% aqueous suspension was used in both the induction and challenge phases. During the induction phase, the test animals received 10 intra-dermal injections of the test suspension, 3 times per week over a 3 week period. The test suspensions were administered to different shaved spots on the right flank of the animals within an area of 3 x 4 cm. The injected volume was 0.05 mL for the first injection and 1.0 mL for subsequent. The control group received a single injection during this phase. The injection sites were examined 24 hours after the injection and the diameter, colour and thickness of any lesions were used as criteria for the intensity of the reaction. In the induction phase, following 1 to 7 injections of AK 43/79, all animals showed mild reactions. Two animals showed moderate reactions after the 8th injection, an additional 2 animals showed moderate reactions after the 9th injection and all 8 animals showed a moderate reaction after the 10th injection. Data were provided on any skin reactions on the single injection received by the control animals. For AK 44/79, all reactions were mild until after the 6th injection when 5 animals showed a moderate reaction. All animals showed moderate reactions after the 7th to 10th injections.  Two weeks after the last injection, guinea pigs from both test groups and the control group received the challenge dose in the amount of 0.05 mL per animal. The reaction sites were examined 24 hours after the injection. After the challenge dose of AK 43/79, all animals exposed during the induction period developed a mild skin reaction. A mild reaction was also found in 7 and a moderate reaction in 1 of the animals in the control group. The challenge dose of AK 44/79 provoked a mild reaction in 6 animals and moderate reaction in 2 animals exposed during the induction period. In the control animals, 7 mild reactions and 1 moderate reaction were observed. No significant differences were observed between the test and control animals with respect to the degree and incidence of erythema and oedema. Under the conditions of this test, aluminium oxide AK 43/79 and aluminium oxide AK 44/79 are not skin sensitizers (Landsteiner/Draize test, guinea pig).

 

Migrated from Short description of key information:
Read-across with cobalt and aluminium compounds:
Cobalt(II)chloride hexahydrate was sensitising in the guinea pig maximization test as well as in the local lymph node assay. Numerous human data also showed that soluble cobalt(II)salts are skin sensitisers. Aluminium oxide was not found to be a skin sensitiser.
Based on a worst case scenario, cobalt aluminium oxide is expected to be a skin sensitiser due to the data on soluble cobalt compounds.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (sensitising)

Additional information:

There are no data available on respiratory sensitisation for cobalt aluminium oxide. However, there are reliable data for various cobalt and aluminium compounds considered suitable for read-across using the analogue approach. For identifying hazardous properties of cobalt aluminium oxide, the existing forms of the target substance at very acidic and physiological pH conditions are relevant for the assessment of human health effects. As cobalt aluminium oxide is a metal-organic salt, which is insoluble in water at pH 6, it is probable that the target substance has also a low degree of solubility at the physiological pH of 7.4. At acidic pH conditions, however, the study of Stopford et al. (2003) showed that water-insoluble cobalt compounds release cobalt ions. Thus, it can be assumed that cobalt aluminium oxide dissociates at acidic pH in the human body resulting in bioavailable cobalt and aluminate ions. Due to the fact that the toxicological effects of cobalt aluminium oxide are mainly caused by exposure to the cobalt ion, the use of data on soluble cobalt compounds is justified for toxicological endpoints as a worst case scenario. In addition, various aluminium compounds are used within the read-across approach. For further details, please refer to the analogue justification attached in section 13 of the technical dossier.

 

Cobalt compounds

The available case reports revealed that soluble cobalt(II) salts are capable of inducing hypersensitive reactions in the respiratory tract after inhalation exposure. These hypersensitive reactions include e. g. respiratory irritation, bronchial asthma, wheezing and pneumonia.

Shirakawa et al. (1989) reported that inhalation of cobalt(II)chloride aerosols can provoke an asthmatic attack in sensitised individuals. Inhalation exposure to cobalt(II)salts among glass bangle workers resulted in decreases in ventilatory function relative to the control workers (Rastogi et al., 1991). In the cross-sectional study of Nemery et al. (1992), 194 workers (166 men and 28 women) in the diamond polishing industry were exposed to cobalt dusts. A significant increase in the prevalence of eye, nose, and throat irritation and reduced lung function compared to 59 unexposed control workers (46 men and 13 women) were observed. Cobalt exposure groups were defined based on air measurements at the time of the study, and exposure was confirmed by measurement of cobalt in urine. The duration of employment was not discussed. In another cross-sectional study, workers in a cobalt refinery who were exposed to cobalt metal, salts and oxides for up to 39 years at an average concentration of 0.125 mg Co/m3 had increased dyspnoea and wheezing, and decreased lung function compared to unexposed controls (Swennen et al., 1993). Linna et al (2003) also found that asthma symptoms were more prevalent in workers in a cobalt plant who were exposed to cobalt compounds. However, many of the epidemiological studies on inhalation exposure to cobalt have been conducted on workers in the hard metal industry where subjects are co-exposed to elemental cobalt and other substances such as tungsten carbide. It is difficult to assess the effects of cobalt alone from these studies as the toxicity of cobalt metal is increased in the presence of tungsten carbide, and it has been proposed that a mixture of cobalt and tungsten carbide behaves as a unique entity (IARC 2006).

 

References not cited in the IUCLID:

Roto P, 1980, Asthma, symptoms of chronic bronchitis and ventilatory capacity among cobalt and zinc production workers. Scand J Work Environ Health 6: 1-49

Kusaka Y et al., 1996a, Epidemiological study of hard metal asthma. Occup Environ Med 53: 188-193

Kusaka Y et al., 1996b, Decreased ventilatory function in hard metal workers. Occup Environ Med 53: 194-199

Ruokonen EL et al., 1996, A fatal case of hard-metal disease. Scand J Work Environ Health 22: 62-65

IARC (International Agency for Research on Cancer). 2006. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Volume 86. Cobalt in hard metals and cobalt sulphate, gallium arsenide, indium phosphide and vanadium pentoxide.

Aluminium compounds

Ichinose et al. (2008) studied allergic inflammation after intratracheal instillation of Asian sand dust, and dust, amorphous silica and Al₂O₃in 6-week old male ICR mice. Four instillations were performed at 2-week intervals. There were ten groups of animals (n=16 in each). One of these groups received Al₂O₃ (particle size 1~5 µm), a dose of 0.1 mg suspended in saline. The control group received saline only (0.1 mL). The animals were killed one day after the last instillation. Eight out of 16 animals in each group were used for pathologic examination. The lung samples were stained with haematoxylin and eosin to evaluate the degree of infiltration of eosinophils or lymphocytes in the airways, and with periodic acid-shiff to evaluate the degree of proliferation of goblet cells in the bronchial epithelium. The other 8 mice were used for examination of free cell counts (total and differential), determination of levels of lactate dehydrogenase (LDH), cytokines (Interleukins – IL-5, IL-6, IL-12, IL-13, interferon-IFN-g and tumor necrosis factor- TNF-a) and chemokines in bronchoalveolar lavage fluids (BALF), and also total IgE in serum using enzyme-linked immunosorbent assays (ELISA). In the group of mice exposed to Al₂O₃, the levels of eosinophil and lymphocyte infiltration in the submucosa and proliferation of goblet cells in the airways, the level of LDH, chemokines and interleukins, number of cells in BALF and the level of IgE in serum were not significantly different from those in the control mice. The results suggest that intratracheal administration of Al₂O₃ does not produce allergic inflammatory effects in the lungs of mice.

Migrated from Short description of key information:
Read-across with cobalt and aluminium compounds:
Case reports evidenced respiratory sensitisation reactions by soluble cobalt(II)salts in humans. Aluminium oxide was not identified as respiratory sensitiser.
Based on a worst case scenario, cobalt aluminium oxide is expected to be a respiratory sensitiser due to the data on soluble cobalt compounds.

Justification for classification or non-classification

Based on the analogue approach, the available data on skin sensitisation meet the criteria for classification as Category 1 (H317) according to Regulation (EC) 1272/2008 and as R43 according to Directive 67/548/EEC.

Based on the analogue approach, the available data on respiratory sensitisation meet the criteria for classification as Category 1 (H334) according to Regulation (EC) 1272/2008 and as R42 according to Directive 67/548/EEC.