Document ID: chunk:federal_register_of_legislation:F2013C00288:reg:4:p4
Version: federal_register_of_legislation:F2013C00288
Segment Type: reg
Provision Reference: reg 4 (pt 4/8)
Character Range: 2131855–2135043

recommended inhalation TRV in air (also considered as an international target in the DEC document). Background levels for cadmium in air can be conservatively assumed to comprise 20% of the recommended inhalation TRV.

4.4              Identification of Toxicity Reference Values

    4.4.1         Classification
IARC (2012) has classified cadmium and cadmium compounds as a Group 1 agent (i.e. carcinogenic to humans) based on additional evidence of carcinogenicity in humans and animals. It is noted that there is limited evidence of carcinogenicity in experimental animals following exposure to cadmium metal.

    4.4.2         Review of Available Values/Information
The following has been summarised from the review of cadmium presented by MfE (2011):
    * Cadmium is primarily toxic to the kidney, especially to the proximal tubular cells where it accumulates over time and may cause renal dysfunction. Loss of calcium from the bone and increased urinary excretion of calcium are also associated with chronic cadmium exposure. Recent studies have reported the potential for endocrine disruption in humans as a result of exposure to cadmium. Notably, depending on the dosage, cadmium exposure may either enhance or inhibit the biosynthesis of progesterone, a hormone linked to both normal ovarian cyclicity and maintenance of pregnancy. Exposure to cadmium during human pregnancy has also been linked to decreased birth weight and premature birth.
    * While cadmium has been classified as a known human carcinogen (based on inhalation data from occupational inhalation data), there is no evidence of carcinogenicity via the oral route of exposure.
    * There is conflicting data on the genotoxicity of cadmium. Some studies indicate that chromosomal aberrations occur as a result of oral or inhalation exposures in humans, while others do not (ATSDR 2008). Studies in prokaryotic organisms largely indicate that cadmium is weakly mutagenic. In animal studies, genetic damage has been reported, including DNA strand breaks, chromosomal damage, mutations and cell transformations (ATSDR 2008). IARC (2012) concluded that several mechanisms have been identified that potentially contribute to cadmium-induced carcinogenicity. Direct binding to DNA appears to be of minor importance and mutagenic responses are weak. Based on the weight of evidence, MfE considered there to be weak evidence for the genotoxicity of cadmium.
On the basis of the available information TRVs relevant for oral (and dermal) intakes and inhalation intakes have been considered separately.

    4.4.3         Oral (and Dermal) Intakes
Insufficient data is available to assess carcinogenicity via oral intakes and therefore the oral TRV has been based on a threshold approach with renal tubular dysfunction considered to be the most sensitive end point. The following are available for oral intakes from Level 1 Australian and International sources:
Source              Value                                                       Basis/Comments
Australian
ADWG(NHMRC 2011)    TDI = 0.0007 mg/kg/day                                      The threshold oral value available from the ADWG (NHMRC 2011) of 0.0007