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EC number: 224-699-9 | CAS number: 4454-16-4
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Endpoint summary
Administrative data
Description of key information
The key value is exclusively based on the presence of nickel in the substance. Main studies selected were conducted according to or were similar to OECD guidelines no 406. Other studies concerned open epicutaneous application tests or modified Draize. Nickel and nickel containing substances are considered to cause dermal sensitization in humans. Exposure to the nickel salts of sulphate and chloride caused significant sensitization in treated patients with a NOEL of 45 mg Ni/L. Permeation rate of the nickel ion depends on the solubility of the salt. Although the water solubility of nickel bis(2-ethylhexanoate) is relatively low , the fact that 2-ethylhexanoic acid is readily absorbed by the skin may facilitate the absorbtion of nickel. Hence, the key value based on the study data of other nickel salts than nickel bis(2-ethylhexanoate) is probably also valid for this substance.
Key value for chemical safety assessment
Skin sensitisation
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed (sensitising)
- Additional information:
Read-across approach
Selected endpoints for the human health hazard assessment are addressed by read-across, using a combination of data on the metal cation and the organic acid anion. This way forward is acceptable, since metal carboxylates are shown to dissociate to the organic anion and the metal cation upon dissolution in aqueous media. No indications of complexation or masking of the metal ion through the organic acid were apparent during the water solubility and dissociation tests (please refer to the water solubility and dissociation in sections 4.8 and 4.21 of IUCLID). Once the individual transformation products of the metal carboxylate become bioavailable (i.e., in the acidic environment in the gastric passage or after phagocytosis by pulmonary macrophages), the “overall” toxicity of the dissociated metal carboxylate can be described by a combination of the toxicity of these transformation products, i.e., the metal cation and carboxylate anion according to an additivity approach.
Nickel bis(2-ethylhexanoate) is the nickel salt of 2-ethylhexanoic acid, which readily dissociates to the corresponding divalent nickel cation and monovalent 2-ethylhexanoate anions. The nickel cation and the 2-ethylhexanoate anion are considered to represent the overall toxicity of nickel bis(2-ethylhexanoate) in a manner proportionate to the free acid and the metal (represented by one of its readily soluble salts).
A detailed justification for the read-across approach is added as a separate document in section 13 of IUCLID.
Sensitisation
No skin sensitisation study with nickel bis(2-ethylhexanoate) is available, thus the skin sensitisation potential will be addressed with existing data on the dissociation products as detailed in the table below.
Table: Summary of skin sensitisation data of nickel bis(2 -ethylhexanoate) and the individual constituents.
nickel ion
2-ethylhexanoic acid
(CAS# 149-57-5)
nickel bis(2 -ethylhexanoate)
(CAS# 4454-16-4)
Skin sensitisation
sensitising
not sensitising
sensitising
(read-across)
In five well-performed maximalization tests the results showed a potential skin sensitisation of Ni applied as NiSO4 (FDRL et al., 1986, Goodwin et al., 1981, Lamminausta et al., 1985, Maurer et al., 1979 and Rohold et al., 1991). In addition, in three well documented open or occlusive epicutaneous tests (Lammintausta et al., 1985, Maurer et al., 1979 and Nielsen et al., 1992), authors showed that application of NiSO4 did cause dermal contact sensitization in female albino guinea pigs. Furthermore, two studies were included, which exhibited no skin sensitization. Although performed in compliance with OECD guideline 406, results from these animal studies should be interpreted with caution when extrapolating to humans.
A patch test on 430 patients showed that exposure to NiCl2 concentrations of 0.1 to 2.0% resulted in an average response of 9% of the patients exposed with a min. of 6% and a maximum of 12%. Exposure of 430 patients to 5% NiSO4 resulted in 11% response. Exposure to 2% NiCl2induced irritation in 6% of the patients, whereas this was 2% for NiSO4. A higher permeation rate for Ni in NiCl2exposed skins appeared to be related with a higher risk of irritation. NOEL for sensitization corresponds with 0.01% NiCl2.
For 2-ethylhexanoic acid, in a guinea pig maximization assay (Berol Kemi AB, 1979), 0/10 female Dunkin-Hartley guinea pigs exhibited a response 48 h after induction and challenge with 5 % (w/w) and 2 % (w/w) aqueous 2-ethylhexanoic acid solution, respectively. The intracutaneous injections were performed with 1 % (w/w) aqueous 2-ethylhexanoic acid solution. In summary, there is no evidence of a notable sensitization potential of 2-ethylhexanoic acid.
Since nickel bis(2-ethylhexanoate) is already classified as sensitizing based on the presence of nickel, there is no need for further testing.
Justification for classification or non-classification
Skin sensitisation:
Concerning 2-ethylhexanoic acid, no data is available. But Nickel compounds and Nickel bis(2-ethylhexanoate) are legally classified as dermal sensitizers. So Nickel bis(2-ethylhexanoate) was classified as a dermal sensitizer.
Respiratory sensitisation:
Nickel bis(2-ethylhexanoate) is legally classified as Respiratory Sensitisation 1.
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