Document ID: chunk:federal_register_of_legislation:F2013C00288:reg:1:p8
Version: federal_register_of_legislation:F2013C00288
Segment Type: reg
Provision Reference: reg 1 (pt 8/10)
Character Range: 2756373–2759316

extrapolation from an inhalation study.
                                                             RfC based on route-extrapolation from and oral studies for the critical effects of heart malformations in rats and immunotoxicity in mice, and incorporation of uncertainty factors ranging from 10 to 100.

For TCE the health end points associated with carcinogenic (non-threshold) and non-carcinogenic (threshold) effects are similar in sensitivity. Hence it is appropriate that the derivation of a guideline consider all relevant end points to ensure that the value derived is adequately protective of all effects.

Many of the reviews conducted by WHO (2011), CCME (2007), RIVM (2001) and ATSDR (1997) have considered limited and dated databases of information (as noted). The most recent comprehensive review of TCE toxicity has been conducted by US EPA (2011), where the most recent studies and health end points have been addressed. The more recent review by WHO (2010), in relation to inhalation toxicity, considered some of the more recent studies, though the review has not considered non-carcinogenic end points, and the key studies considered by US EPA (2011) for the derivation of the inhalation unit risk were not considered in the WHO (2010) review. On this basis it is considered appropriate that the more recent evaluation conducted by US EPA (2011) be used for the purpose of establishing soil vapour Interim HILs.

The US EPA review has concluded that there is sufficient weight of evidence that TCE operates through a mutagenic mode of action (MoA) for kidney tumours and there is a lack of TCE-specific quantitative data in relation to early lifetime susceptibility. Hence it is appropriate to consider increased susceptibility associated with early lifetime exposures through the adjustment of exposure factors. This adjustment, however is noted to be relevant to the kidney cancer component of the total risk (note the inhalation unit risk includes a factor of 4-fold to address the risk of tumours at multiple sites). The effect of considering theses age-adjusted exposure factors to only the kidney cancer portion of the unit risk has been evaluated by US EPA and determined to be of minimal impacts to the total cancer risk, except when exposure only occurs during early life (if these effects occur). In addition to this evaluation, a number of uncertainties have been identified in relation to applying the age adjustment factors for a more complex carcinogenic MoA, as identified for TCE. Hence, for the purpose of deriving HILs where long-term exposures are considered, no further adjustments to account for potential early lifetime susceptibility have been incorporated.

    1.5.3         Recommendation
In relation to TCE, only soil vapour Interim HILs have been derived. Hence only the inhalation pathway has been quantified in the development of these HILs. On the basis of the discussion above, the following