Registration Dossier

Administrative data

Link to relevant study record(s)

Description of key information

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential

Additional information

Data on the bioaccessibility of Ni fluoride in biological fluids as a surrogate for bioavailability can be found in Section 7.1.1 of this IUCLID file (Bioaccessibility Data, KMHC 2010). This document demonstrates that Nickel fluoride can be grouped in the class of soluble Nickel Compounds, represented by Nickel sulfate whcih is the most extensively examined.

In the following table, highest values for both salts are reported:

   Time

 % Nickel release /Nickel content

Nickel fluoride

Average of two replicates

 % Nickel release /Nickel content

Nickel sulfate

Average of two replicates

 Simulated Gastric fluid  72h  86.4  100 (5 hours)
 Simulated Alveolar Fluid  72 h  42.1  48.2
 Artificial Perspiration  72 h  99.3  101
 Lysosomal Fluid  2 h  109.4  94.6
Simulated Interstitial Fluid  72 h  50.25  57.4
 Simulated Intestinal Fluid  5 h  77.4  46

All values are very similar, with nickel release from nickel sulfate always higher. The only value where nickel sulfate seems significantly lower than nickel fluoride is in the Simulated Intestinal fluid.

Being less bioavailable than Nickel sulfate, most of the data collected for this substance can used in read-across in a conservative way, as nickel fluoride is less bioavailble.

ENDPOINT SUMMARY INFORMATION FROM THE 2008/2009 EU NICKEL SULPHATE RISK ASSESSMENT.

ABSORPTION:

The available data on nickel sulphate indicate that the absorption of nickel following inhalation might be as high as up to 97-99%; it should be noted that the fraction absorbed apparently depends on the concentration of the nickel compound in the inhaled air as well as on the duration of exposure. The available data indicate that the absorption of nickel following administration in the drinking water to fasting individuals might be as high as up to about 25-27% and about 1-6% when administered to non-fasting individuals and/or together with (or in close proximity to) a meal. Absorption of nickel following dermal contact to various nickel compounds can take place, but to a limited extent with a large part of the applied dose remaining on the skin surface or in the stratum corneum. The data are too limited for an evaluation of the absorbed fraction of nickel following dermal contact to nickel sulphate. The in vitro study of soluble nickel compounds (nickel sulphate, nickel chloride, nickel nitrate, and nickel acetate) using human skin (Tanojo et al. 2001) showed about 98% of the dose remained in the donor solution, whereas 1% or less was found in the receptor fluid and less than 1% was retained in the stratum corneum.

DISTRIBUTION AND ELIMINATION:

Absorbed nickel is excreted in the urine, regardless of the route of exposure. Most ingested nickel is excreted via faeces due to the relatively low gastrointestinal absorption. In humans, nickel excreted in the urine following oral intake of nickel sulphate accounts for 20-30% of the dose administered in drinking water to fasting subjects compared with 1-5% when administered together with food or in close proximity to a meal. From biological monitoring in small groups of electroplaters exposed to nickel sulphate and nickel chloride, the half-life for urinary elimination of nickel has been estimated to range from 17 to 39 hours. Inhaled nickel particles can be eliminated from the respiratory tract either by exhalation, by absorption from the respiratory tract, or by removal due to mucociliary elimination.

FOR AN EXTENSIVE DISCUSSION, REFER TO THE NICKEL SULFATE DOSSIER WHICH IS BASED ON THE CONCLUSIONS EXPLAINED IN THE 2008/2009 EUROPEAN UNION EXISITING SUBSTANCE RISK ASSESSMENT OF NICKEL (EU RAR) (EEC 793/93)

Discussion on bioaccumulation potential result:

ENDPOINT SUMMARY INFORMATION FROM THE 2008/2009 NICKEL SULPHATE RISK ASSESSMENT

Two inhalation studies in rats (Benson et al. 1988, NTP 1996) indicate that lung nickel burdens increase with increasing concentrations of nickel sulphate (at least up to around 0.8 mg Ni/m3) in the inhaled air as well as with duration of exposure. The study by Benson et al. (1988) indicates that the lung nickel burden may rise to a steady state level as the lung nickel burdens were almost similar in rats exposed to 15 or 30 mg/m3. A third study (Dunnick et al. 1989) found similar concentrations of nickel in the lungs of rats and mice after 4, 9, and 13 weeks of inhalation to nickel sulphate (0.02 to 0.4 mg Ni/m3). Of nickel remaining in the body after 96 hours following a single dose of nickel sulphate administered by intratracheal administration, over 50% was in the lungs. The deposition of nickel in the lungs of rats is apparently greater than in the lungs of mice. No human data have been located.

Generally, nickel tends to deposit in the lungs of workers occupationally exposed to nickel compounds and in experimental animals following inhalation or intratracheal instillation of nickel compounds. The tissue distribution of nickel in experimental animals does not appear to depend significantly on the route of exposure (inhalation/intratracheal instillation or oral administration) although some differences have been observed. Low levels of accumulation in tissues are observed (generally below 1 ppm). A primary site of elevated tissue levels is the kidney. In addition, elevated concentrations of nickel are often found in the lung, also after oral dosing, and in the liver. Elevated nickel levels are less often found in other tissues. Limited information exists on tissue distribution in humans.

Absorbed nickel is excreted in the urine, regardless of the route of exposure. Most ingested nickel is excreted via faeces due to the relatively low gastrointestinal absorption. In humans, nickel excreted in the urine following oral intake of nickel sulphate accounts for 20-30% of the dose administered in drinking water to fasting subjects compared with 1-5% when administered together with food or in close proximity to a meal. From biological monitoring in small groups of electroplaters exposed to nickel sulphate and nickel chloride, the half-life for urinary elimination of nickel has been estimated to range from 17 to 39 hours.

Inhaled nickel particles can be eliminated from the respiratory tract either by exhalation, by absorption from the respiratory tract, or by removal due to mucociliary elimination.

In addition to this summary from the EU Risk Assessment, data on the bioaccessibility of Ni sulfate in biological fluids as a surrogate for bioavailability are reported within Section 7.1.1 of this IUCLID file.