Document ID: chunk:federal_register_of_legislation:F2013C00288:reg:11:p5
Version: federal_register_of_legislation:F2013C00288
Segment Type: reg
Provision Reference: reg 11 (pt 5/9)
Character Range: 2277689–2280540

0.005 mg/kg/day  The ADWG (NHMRC 2011) derived a health-based guideline of 0.02 mg/L based on NOEL of 5 mg/kg/day associated with organ-to-body-weight ratios in a 2-year rat study and an uncertainty factor of 1000. An additional factor of 10 was not included to address carcinogenicity as this was only relevant for inhalation exposures, not oral exposures.
International
WHO (2011)          TDI = 0.012 mg/kg/day  The current WHO DWG (2011), based on a review conducted in 2005, derived a guideline of 0.07 mg/L based on a TDI of 0.012 mg/kg/day derived from a LOAEL of 0.012 mg/day established from a study associated with hand eczema in nickel-sensitised volunteers who had fasted prior to administration of the nickel salt (Nielsen et al. 1999). This study (using fasted patients) was considered conservative and an uncertainty factor of 1 was adopted.
                                           The review also noted that a general guideline value of 0.13 mg/L could also be derived from a TDI of 0.022 mg/kg/day on the basis of a two-generation study in rats where a NOAEL of 2.2 mg/kg/day could be determined for all end-points studied and an uncertainty factor of 100.
RIVM (2001)         TDI = 0.05 mg/kg/day   TDI derived on the basis of a NOAEL of 5 mg/kg/day (same study considered in the ADWG) and an uncertainty factor of 100.
EA (2009b)          TDI = 0.012 mg/kg/day  Adopted the WHO evaluation presented in the WHO DWG (2011).
TERA (1999)         RfD = 0.008 mg/kg/day  RfD derived for soluble nickel salts on the basis of a LOAEL of 7.6 mg/kg/day associated with kidney effects in rats and an uncertainty factor of 1000. The value derived was in addition to the diet rather than total intake.
ATSDR (2005)        No oral MRL derived
US EPA (IRIS 2012)  RfD = 0.02 mg/kg/day   RfD (last reviewed in 1991) based on a NOAEL of 5 mg/kg/day (same study as considered in the ADWG (NHMRC 2011)) and an uncertainty factor of 300.

11.4.2.2     Inhalation
Inhalation exposures to nickel are complex, with the toxicity dependent on the form of nickel present. The most recent review of nickel toxicity by EA (2009b) indicates the following with respect to the consideration of inhalation exposures:
    * Nickel and compounds are established carcinogens via the inhalation route with tumours of the respiratory tract a consequence of occupational exposure to both soluble and insoluble nickel salts.
    * Nickel compounds are generally considered to be genotoxic; however the mechanism of action associated is not well understood. The lack of understanding has resulted in a conservative approach that genotoxicity is critical in the development of tumours and that a non-threshold may be appropriate.
    * Non-threshold assessments of inhalation cancer risk have relied on occupational studies to derive a quantitative value (unit risk).