Reaction mass of aluminium fluoride and aluminium oxide and chromium (III) oxide and nickel dichloride

Endpoint summary

Description of key information

Although physico-chemical data tend to indicate that Mélange impregné is a non-reactive inert substance and that its size and structure can not allow its absorption by skin or airway, a worst case approach has been chosen by considering the data for nickel chloride contained at a content of at least 13%.
Nickel was tested under a soluble form (nickel sulphate hexahydrate) in rats following oral administration for 2 years and in rats and mice following inhalation for 16 days, 13 weeks or 2 years. Oral administration mainly resulted in decreased survival rates (females) and reduced body weight gain (both genders) at the LOAEL. Inhalation exposure mainly resulted in local respiratory effects, with lung inflammation and fibrosis at all concentration levels.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Dose descriptor:

NOAEL

2.2 mg/kg bw/day

Study duration:

chronic

Species:

rat

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion

Dose descriptor:

LOAEC

0.06 mg/m³

Study duration:

chronic

Species:

rat

Additional information

The repeated-dose toxicity of nickel was mainly assessed using a soluble form of the metal, nickel sulphate hexahydrate (NiSO4.6H2O).

 

By oral route, nickel sulphate hexahydrate was administered to rats for 2 years at 0, 10, 30 or 50 mg Ni sulphate/kg/day (equivalent to 2.2, 6.7 or 11.2 mg Ni/kg). Based on decreased survival rate (females) and reduced body weight gain (both genders) at higher dose levels, a NOAEL of 2.2 mg Ni/kg was identified.

 

By inhalation, rats and mice were exposed for up to 2 years to nickel sulphate hexahydrate at concentrations of 0, 0.12, 0.25 or 0.5 mg Ni sulphate/m3 (equivalent to 2.2, 6.7 or 11.2 mg Ni/m3) and 0, 0.25, 0.5 or 1 mg Ni sulphate /m3 (equivalent to 2.2, 6.7 or 11.2 mg Ni/m3), for rats and mice, respectively. The lung was clearly a target organ of nickel sulfate hexahydrate toxicity, with inflammation and fibrosis findings. Based on organ weight and microscopic changes in lungs and respiratory tract, no NOAEC was identified in 2-year studies. Following chronic exposure in rats for 2 years (6 hours a day, 5 days a week), the concentration of 0.25 mg Ni sulphate /m3 (equivalent to 0.06 mg Ni/m3) can be considered as a LOAEC based on the increased incidence of chronic active inflammation, macrophage hyperplasia, alveolar proteinosis, and fibrosis in the lungs of male and female rats.

 

Biochemical, morphometric and electron microscopy studies were conducted on the lungs of rabbits exposed to various forms of nickel by inhalation. Morphometric and ultrasructural analyses showed significant increases in the volume density of type II cells of alveolar epithelium, with no visible ultrastructural alteration, likely related to an overproduction of pulmonary surfactant. Repeated inhalation exposure of rabbits to metallic or ionic nickel dusts produced a typical pattern of lung lesions, characterized by accumulation of surfactant in alveolar spaces, impaired function of alveolar macrophages, and decreased lysozyme levels. Following repeated inhalatory exposure of rabbits to nickel dichloride, a significant decrease in the lysozyme activity in the lung lavage fluid as well as in the alveolar macrophages was observed, whereas the fibronectin content was unchanged in the lavage fluid and significantly increased in the macrophages.

Repeated dose toxicity: inhalation - systemic effects (target organ) respiratory: lung

Justification for classification or non-classification

Physico-chemical data tend to indicate that Mélange impregné is a non-reactive inert substance and that its size and structure can not allow its absorption by skin or airways. Nevertheless by a conservative approach, the criteria for classification following the Directive 67/548/EEC or 1272/2008/EC will be applied.

Chronic lung inflammation and lung fibrosis are serious and potentially irreversible effects. According to Annex I of Directive 67/548/EEC, nickel chloride (CAS No.: 7718 -54 -9) present in Mélange impregné at more than 13%, is classified as T; R48/23, with a specific concentration limit of 1% for T; R48/23 classification. Mélange impregné should therefore be classified as T; R48/23 (Directive 67/548/EEC) or STOT RE cat. 1 (H372) (Directive 1272/2008/EC).