Document ID: chunk:federal_register_of_legislation:F2013C00288:reg:1:p5
Version: federal_register_of_legislation:F2013C00288
Segment Type: reg
Provision Reference: reg 1 (pt 5/10)
Character Range: 2747748–2750895

battery to derive a comprehensive conclusion. However, the metabolites that have been tested, particularly DCVC, have predominantly resulted in positive data, supporting the conclusion that these compounds are genotoxic.

The MoA relevant to specific target organs in laboratory animals has been reviewed by US EPA.  Only in the case of the kidney is it concluded that the data is sufficient to support a particular MoA being operative. For the kidney, the predominance of positive genotoxicity data in the database of available studies of TCE metabolites, together with toxicokinetic data, supports the conclusion that a mutagenic MoA is operative in TCE-induced kidney tumours.  Hence a linear (non-threshold) approach is recommended for the quantification of carcinogenic effects.

There is some evidence that certain populations may be more susceptible to exposure to TCE. Because the weight of evidence supports a mutagenic MoA being operative for TCE carcinogenicity in the kidney, and there is an absence of chemical-specific data to evaluate differences in carcinogenic susceptibility, early-life susceptibility is recommended by US EPA to be assumed and the age-dependent adjustment factors (ADAFs) should be applied.

On the basis of the above, it is reasonable to consider a non-threshold approach for the assessment of carcinogenicity in relation to TCE. It is noted that a number of guidelines (such as WHO 2011) have been derived on the basis of both carcinogenic and non-carcinogenic end points, with non-carcinogenic end points noted to be more sensitive for at least oral intakes. Hence both non-threshold and threshold reference values available have been noted in the following.

The following quantitative values are available for TCE from Level 1 Australian and International sources:
Source                        Value                          Basis/Comments
Australian
ADWG (NHMRC 2011)             No health-based value derived  Not derived due to insufficient data.
International
WHO (2011)                    SF = 0.00078 (mg/kg/day)-1     The WHO guideline of 0.02 mg/L is based on the lower value derived from carcinogenic and non-carcinogenic end points. It is noted that the guideline derived on the basis of reproductive/developmental (threshold) effects was most conservative.
                              TDI = 0.00146 mg/kg/day        The oral slope factor adopted is from Health Canada (range of values derived) and based on combined tubular cell adenomas and adenocarcinomas of the kidneys in rats following oral exposure to TCE for 103 weeks and a linear multistage model.
                                                             The oral TDI derived from a BMDL10 of 0.146 mg/kg/day associated with reproductive/developmental effects in rats, and an uncertainty factor of 100.
WHO (2000 and 2010)           UR = 4.3x10-7 (g/m3)-1        Inhalation unit risk derived on the basis of Leydig-cell tumours in the testes of rats and a linear multistage model. Inhalation unit risk from rat study is supported by a similar unit risk of 9 x10-7 (g/m3)-1 derived from increased incidence of hepatic tumours in