Nickel bis(2-ethylhexanoate)

Endpoint summary

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.

 

Repeated dose toxicity

No repeated dose toxicity study with nickel bis(2-ethylhexanoate) is available, thus the repeated dose toxicity will be addressed with existing data on the dissociation products as detailed in the table below. 

 

Table: Summary of repeated dose toxicity 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)
repeated dose, oral toxicity	NOAEL(rat,104weeks) = 2.23 mg Ni/kg bw/day	NOAEL(rat; 90d) = 300 mg/kg bw/day   NOAEL(mice; 90d) = 200 mg/kg bw/day	No data
repeated dose, inhalation toxicity	NOAEc = 0.027 mg Ni/m^3	No data	No data

 

 

Nickel

ORAL: A 2-year oral carcinogenicity study reported a NOAEL of 10 mg/kg body weight/day (2.2 mg Ni/kg b. w. /day) and a LOAEL of 30 mg/kg body weight/day (6.7 mg Ni/kg b. w. /day) (Heim et al. 2007). The LOAEL of 6.7 mg Ni/kg bw/day based on reduced body weight and increased mortality together with a NOAEL of 2.2 mg Ni/kg bw/day is taken forward to the risk characterisation. 

INHALATION: Chronic lung inflammation including lung fibrosis results from long-term exposure via inhalation to a concentration of 0.056 mg Ni/m³or 0.25 mg nickel sulphate hexahydrate/m³. A NOAEC of 0.12 mg/m³ (0.027 mg Ni/m³, MMAD = 2.5 µm) was identified for these effects (Dunnick et al., 1995).

DERMAL: It was not possible to determine a NOAEL/LOAEL for the dermal route based on the available information.

 

2-Ethylhexanoic acid

In a 90-day repeated dose toxicity study in rats and mice with 2-ethylhexanoic acid, a diet containing 0.5% 2-ethylhexanoic acid caused no adverse effect in rats in a 13 week feeding study (dose levels were 0, 0.1, 0.5, or 1.5%, calculated NOAEL ca. 300 mg/kg bw/day). No adverse effect was observed in mice receiving a diet containing 0.5 % 2-ethylhexanoic acid in a 13 week feeding study (dose levels were 0, 0.1, 0.5, or 1.5%). The NOAEL was calculated to be 200 mg/kg bw/day. Both NOAELs were based on reduced food consumption and a decreased rate of body weight gain in the high dose groups. For further information on the toxicity of 2-ethylhexanoic acid, please refer to the relevant sections in the IUCLID and CSR.

Justification for classification or non-classification

Repeated toxicity by inhalation: Nickel 2-ethylhexanoate is legally classified as STOT RE 1 (or T, R 48/23).