Nickel bis(sulphamidate)

Endpoint summary

Additional information

Information characterizing the toxicokinetics of nickel sulphamate was limited to in vitro studies evaluating the dissolution rates of nickel sulphamate in different synthetic fluids. Data on the bioaccessibility of Ni sulphamate in six biological fluids as a surrogate for bioavailability are reported within Section 7.1.1 of this IUCLID file (KMHC, 2010). The read across approach for oral exposure is described in Henderson et al. (2012a).

Additional information regarding the toxicokinetic properties of Ni sulphamate are read across from Ni sulphate.

Inhalation Absorption

ENDPOINT SUMMARY INFORMATION FROM THE 2008/2009 EUROPEAN UNION RISK ASSESSMENT FOR NICKEL SULPHATE:

The deposition of particles in the respiratory tract depends on the particle sizes (MMADs) as well as on other characteristics of the particles, and the absorption of nickel from the respiratory tract into the blood stream depends on the solubility of the nickel compound inhaled. Soluble nickel compounds, such as nickel sulphamate, are expected to be absorbed from the respiratory tract following inhalation exposure.

One study of nickel sulphate in rats (Medinsky et al. 1987) using intratracheal instillation of nickel sulphate (as a solution in saline) showed that 50 to 80% of a dose (dependent on the dose) of nickel sulphate can be absorbed from the respiratory tract. Studies in rats using intratracheal instillation of nickel chloride (Carvalho & Ziemer 1982, English et al. 1981, Clary 1975) showed that up to approximately 97% of a dose of nickel chloride can be absorbed from the respiratory tract. By assuming that the absorption of nickel following inhalation exposure to nickel chloride is similar to absorption following intratracheal instillation, the absorption of nickel from the respiratory tract following inhalation of nickel chloride might be as high as about 97%. Furthermore, an inhalation study on nickel sulphate (Benson et al. 1995) showed that clearance of nickel sulphate from the lungs of rats and mice is extensive (up to 99% in rats and 80 to 90% in mice). By assuming that the clearance of nickel sulphate particles (respirable particles, MMADs ranging from 2.0 to 2.4 μm) from the lungs in the inhalation study is due to absorption rather than to deposition or by mucociliary action, the absorption of nickel from the lungs following inhalation of nickel sulphate might be as high as up to 99% (at concentrations up to 0.11 mg Ni/m3 in rats and up to 0.22 mg Ni/m3 in mice).

In conclusion, the available data on nickel sulphate and nickel chloride indicate that the absorption of nickel following inhalation of these nickel compounds 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. For the purpose of risk characterisation, a value of 100% will be taken forward to the risk characterisation for the absorbed fraction of nickel from the respiratory tract following exposure by inhalation of nickel nitrate for particulates with an aerodynamic diameter below 5 μm (respirable fraction). For nickel particulates with aerodynamic diameters above 5 μm (non-respirable fraction), the absorption of nickel from the respiratory tract is considered to be negligible as these particles predominantly will be cleared from the respiratory tract by mucociliary action and translocated into the gastrointestinal tract and absorbed. Hence, for the non-respirable fraction, 100% clearance from the respiratory tract by mucociliary action and translocation into the gastrointestinal tract is assumed and the oral absorption figures can be taken.

For the purpose of risk characterisation, as described in the 2008/2009 European Union Risk Assessment for Nickel Sulphate a value of 100% (respirable fraction, 100% deposition) is taken forward for the risk characterisation as the absorbed fraction of nickel from the respiratory tract following inhalation exposure to nickel sulphamate in rats.

Oral Absorption:

ENDPOINT SUMMARY INFORMATION FROM THE 2008/2009 EUROPEAN UNION RISK ASSESSMENT FOR NICKEL SULPHATE:

A study on volunteers (Nielsen et al., 1999), in which the nickel compound administered was not specified, showed that 25.8% of the administered dose was excreted in the urine following administration of nickel in drinking water to fasting individuals compared with 2.5% when nickel was mixed into a meal. Based on experimental data from various human studies, Diamond et al. (1998) have used a biokinetic model to estimate nickel absorption; the results showed that estimated nickel absorption ranged from 12-27% of the dose when nickel was ingested after a fast, to 1-6% when nickel was administered either in food, in water, or in a capsule during (or in close proximity to) a meal.

For the purpose of risk characterisation, as described in the 2008/2009 European Union Risk Assessment for Nickel Sulphate, a value of 30% is taken forward for the risk characterisation as the absorbed fraction of nickel from the gastrointestinal tract following oral exposure to nickel ion under fasting conditions. Therefore, this same value is used for Ni sulphamate based on similar nickel ion release as described inthe read across approach for oral exposure in Henderson et al. (2012a). For absorption of nickel from food, soil, dust and from water consumed with food, a value of 5% will be used. When extrapolating rat exposures from the oral route to the inhalation route, a value of 11% is used for absorption by the oral route (Ishimatsu et al., 1995) and 100% for the inhalation route (respirable fraction, 100% deposition).

Dermal absorption

ENDPOINT SUMMARY INFORMATION FROM THE 2008/2009 EUROPEAN UNION RISK ASSESSMENT FOR NICKEL SULPHATE:

When considering dermal absorption, a distinction should be made between penetration of nickel into skin and percutaneous transport, where nickel is transported through the skin and into the blood stream. For further details, the reader is referred to the Background document in support of the individual Risk Assessment Reports.

No in vivo studies providing specific information about the absorbed fraction of nickel in humans or experimental animals following dermal contact to nickel nitrate have been located. In an in vitro study (Tanojo et al. 2001) using human skin (stratum corneum from cadaver leg skin), about 82.5% of the dose was recovered in the donor solution after 96 hours, with about 0.5% in the receptor fluid and 1% in the stratum corneum.

Recent human in vivo studies of nickel sulphate and nickel metal (Hostýnek et al. 2001a, 2001b) has shown that a large part of the administered dose remained on the surface of the skin after 24 hours or had penetrated into the stratum corneum. For further details, the reader is referred to the Risk Assessment Reports on nickel sulphate and nickel metal.

In vitro studies using human skin support the findings in the human in vivo studies as most of the dose remained in the donor solution and only minor amounts were found in the receptor fluid; the in vitro studies also indicate that absorption following dermal contact may have a significant lag time. For further details, the reader is referred to the Background document in support of the individual Risk Assessment Reports.

In conclusion, the available data indicate that 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 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. According to the revised TGD, the amount absorbed into the skin, but not passed into the receptor fluid, should also be included in the estimate of dermal absorption.

For the purpose of risk characterisation, a value of 2% will be taken forward to the risk characterisation for the absorbed fraction of nickel from nickel sulphamate.