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: 1040371–1043380

ingestion of 2 L of water per day) and body weight (for example, 70 kg). When a theoretical upper-bound cancer risk estimate is calculated using a URF instead of a CSF, it is often termed the unit risk.
Unit risk factors can be converted to slope factors as follows:
    CSFinh = URinh x 1000 x 70/20
    where
    CSFinh = inhalation cancer slope factor (mg/kg-day)-1
    URFinh = inhalation unit risk factor (reported as per µg/m3), which is converted to a CSF assuming 70 kg body weight and 20 m3/day inhalation volume.
Benchmark doses are typically calculated for carcinogenic substances that are considered to be non-genotoxic (that is, threshold compounds). A benchmark dose is defined as the dose that corresponds to a specified change in adverse response compared to the response in untreated animals (Crump 1995).

The dose is associated with a given incidence (for example, 1%, 5% or 10% incidence) of effect, the benchmark risk, based on the best fitting doseresponse curve in the region of the doseresponse relationship where biologically observable data are available (Filipsson et al. 2003; enHealth 2012a). Although the benchmark dose has mainly been used for risk assessment of non-cancer end-points, this approach can also be applied for cancer end-points. When selecting benchmark doses, recent Australian guidance recommends adopting a 10% incidence (NEPC 2011).

Increasingly, the benchmark dose approach for cancer risk assessment is being adopted globally in recognition of the identified difficulties and uncertainties associated with the low-dose extrapolation method (that is, generation of cancer slope factors). A benchmark dose is applied in the same way as a threshold TRV.

There is often a choice to be made in selection of doseresponse data for carcinogens. Recommendations are summarised below.
    * Benchmark dose data, where available from the listed sources, should be adopted in preference to cancer slope factors or unit risks.
    * Where appropriate benchmark dose data is not available, cancer slope factors (for genotoxic carcinogens) and threshold TRVs (for non-genotoxic carcinogens) should be used. When using threshold TRVs for a substance with an IARC classification of group 1, 2A or 2B, care should be taken to check that the carcinogenic effects were considered in the derivation of the threshold TRVs.
    * In the event that the threshold TRV does not consider carcinogenic effects, and no other cancer toxicity criterion is available, the substance should be assessed using the available threshold TRV, noting the potential additional cancer risk as a weight-of-evidence factor for decision-making purposes.
For a more detailed treatment of the methodologies applied to assessing cancer risks, refer to the review of cancer risk methodologies in the ASC NEPM Toolbox at http://www.scew.gov.au/archive/site-contamination/asc-nepm.html.

5.4              Other considerations in toxicity assessment

    5.4.1          Absence of information
It will not