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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Description of key information

Value used for CSA (read-across from Nickel sulphate):

NOAEL (oral, systemic, animal): 10 mg Ni sulphate hexahydrate /kg bw/day (or 2.2 mg Ni/kg bw/day) (Heim et al. 2007)

NOAEC (inhalation, local, animal): 0.12 mg Ni sulphate hexahydrate /m³ air ( or 0.027 mg Ni/m3 air) (Dunnick et al., 1995)

LOAEC(inhalation, local, animal): 0.25 mg nickel sulphate hexahydrate/m3 (or 0.056 mg Ni/m3) (Dunnick et al., 1995)

Key value for chemical safety assessment

Toxic effect type:
dose-dependent

Additional information

Oral data

Four animal studies have been found which describe toxicity in relation to repeated oral exposure during 28 days, 77 days, 92 days, or 25 weeks. In two of these studies nickel chloride was given in drinking water, in one study nickel chloride was added to the food, and in one study dosing was by gavage. All of these studies suffer from various limitations in design and reporting. The most comprehensive study was the 91-day gavage study, which however suffered from a high mortality and a high number of fatalities caused by gavage errors. Furthermore, gavage dosing may in this case be less relevant than exposure via drinking water or food in relation to human exposure. In addition to mortality, the animals exhibited salivation, lethargy, and irregular breathing, and decreased body weight. The LOAEL was 5 mg Ni/kg bw/day based on mortality. This was the lowest dose level in the study. In the 25-week drinking water study no toxicity was observed at the single dose level studied, 10.2 mg Ni/kg bw/day, however, only a limited number of endpoints were studied. In the 77-day dietary study, no general toxic effects were found at 10 or 20 mg Ni/kg bw/day, however the group size was only 6, and the number of endpoints studied was limited. At 20 mg/kg bw/day, effects in an operant task were observed, thus the NOAEL was 10 mg/kg bw/day. In the 28-day drinking water study, body weight gain was reduced at all dose levels with a LOAEL of 0.01 mg Ni/kg bw/day, however, the limitations in reporting makes it difficult to interpret the findings in terms of biological significance. In conclusion, although several studies of repeated dose oral toxicity of nickel chloride have been found, none are considered adequate for the determination of a NOAEL.

Data regarding repeated toxicity of Ni chloride via oral exposure are read-across from Ni sulphate. In addition, a summary document on the read-across assessment and systemic oral toxicity of nickel compounds can be found as a background document in Appendix B1 of the CSR (Section 7.5.1 of IUCLID). In a 2- year OECD 451 carcinogenicity study, decreased body weight gain ranging from 4% to 12% was recorded (male and female rats combined) following oral gavage of 2.2 to 11 mg Ni/kg bw/day. A dose-related reduced survival achieving statistical significance at the two highest dose levels was seen in females (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 are taken forward to the risk characterisation for oral repeated dose toxicity. These data are considered relevant for the risk assessment of nickel chloride and are taken forward to the Risk Characterisation.

 

Inhalation data

Inhalation of nickel chloride (0.2-0.6 mg Ni/m3 for up to 8 months) causes adverse effects on lung macrophages in rabbits. The LOAEC for local lung effects is 0.2 mg Ni/m3, which corresponds to roughly 0.8 mg NiCl2.6H2O/m3.

No animal studies of systemic effects following repeated inhalation of nickel chloride have been found. A single occupational study has been found, indicating kidney effects in humans at high exposure levels, however, the exposure information is insufficient for risk characterisation.

From the background document on nickel compounds it appears that long-term inhalation of insoluble as well as soluble nickel compounds results in adverse effects on the lungs including chronic inflammation and fibrosis. Read-across to other nickel compounds shows that the rabbit LOAEC identified for nickel chloride is higher than the lowest LOAEC which has been found for nickel sulphate in studies in rats. Nickel chloride has not been studied in a comprehensive chronic toxicity study.

Data for repeated-dose toxicity via inhalation exposure are read-across from Ni sulphate. Chronic lung inflammation including lung fibrosis results from long-term exposure (2 year) via inhalation to a concentration of 0.056 mg Ni/m3 or 0.25 mg nickel sulphate hexahydrate/m3 (NTP, 1996a; Dunnick et al., 1995). Nickel sulphate fulfils the criteria for classification as STOT RE 1; H372 since chronic lung inflammation including lung fibrosis results from long-term exposure via inhalation to a concentration of 0.056 mg Ni/m3. A LOAEC for repeated dose toxicity via inhalation of 0.056 mg Ni/m3 for lung inflammation and fibrosis, and a NOAEC of 0.027 mg Ni/m3 for these effects based on the chronic study of nickel sulphate by NTP, are used in the risk characterization of nickel chloride.

Chronic lung inflammation and lung fibrosis are serious and potentially irreversible effects. Based on data from other nickel compounds, supported by the nickel chloride-specific data on macrophage effects in rabbits, nickel chloride is classified as STOT RE 1; H372 with a specific concentration limit of ≥ 1% in the 30th ATP.

The following information is taken into account for any hazard / risk assessment:

ORAL: Data are read-across from Ni sulphate. 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). 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. A summary document on this topic is provided as a background document in section 7.5.1 of IUCLID and in Appendix B1of the CSR.

INHALATION: Data are read-across from Ni sulphate. Chronic lung inflammation including lung fibrosis results from long-term exposure via inhalation to a concentration of 0.056 mg Ni/m3 or 0.25 mg nickel sulphate hexahydrate/m3 (LOAEC). Nickel sulphate fulfils the criteria for classification as STOT RE 1; H372. A concentration of 0.027 mg Ni/m3 (MMAD = 2.5 µm) corresponding to the NOAEC for respiratory toxicity effects in rats is taken forward for the risk characterisation.

DERMAL: There was no available information to determine a NOAEL/LOAEL for the dermal route. Testing by the dermal route has been waived as described in IUCLID Section 7.5.3.

Justification for classification or non-classification

Ni chloride is classified as STOT RE 1; H372 according to the 1st ATP to the CLP. Background information on this topic can be found in the discussion section.