Document ID: chunk:federal_register_of_legislation:F2013C00288:reg:5:p6
Version: federal_register_of_legislation:F2013C00288
Segment Type: reg
Provision Reference: reg 5 (pt 6/7)
Character Range: 1026735–1029719

groups in the population
    * the reliability of the available information.

    5.2.3          Chronic cancer effects
Chemicals may cause cancer in a wide variety of ways, termed modes of action. There is flexibility in defining modes of action, which can be described at almost any level of complexity, reflecting the extent of chemical-specific information available and the needs of the risk assessment (Clewell 2005; Lambert & Lipscomb 2007). It is now known that several modes of carcinogenic action exist, including mutagenicity, mitogenesis, inhibition of cell death, cytotoxicity with reparative cell proliferation, and immune suppression (US EPA 2005a; Butterworth 2007). Although it represents a simplification, for the purposes of risk assessment, cancer-causing chemicals (carcinogens) are generally divided into two types, genotoxic and non-genotoxic.

Genotoxic carcinogens are defined as chemicals for which there is adequate evidence of the potential to interact with and/or modify the functions of genetic material and which has the ability to induce tumours via a mechanism involving direct damage to DNA (Butterworth 1990; IARC 2006). For genotoxic carcinogens, it is assumed that no level of exposure is entirely safe and even at extremely low levels some damage to the genetic material may increase the chance of developing cancer.

This is known as a non-threshold (or linear) dose-response relationship and the application of a threshold — based on 'no observable adverse effect level' (NOAEL) — is not considered appropriate.

Non-genotoxic carcinogens are chemicals that induce tumours via a mechanism which does not involve direct damage to genetic material (IARC 2006). For non-genotoxic carcinogens, it is assumed that a threshold dose can be determined below which no toxic or carcinogenic effects are seen (that is, a non-linear dose-response relationship can be established). A common approach for determining a safe dose for chemicals that exhibit a threshold or non-linear dose-response relationship is the selection of a NOAEL (or other point of departure) from relevant animal or human studies.

Complexity is added by the uncertainty in whether some chemicals are carcinogenic or not, leading to difficulty for the risk assessor in deciding which approach to consider. Different sources of information may provide different views on whether a substance is a carcinogen or not. The US EPA in particular regards a wide range of chemicals as potential carcinogens and this view is not always shared by health authorities in other countries. The IARC classification is summarised in Table 5.

For contaminated land health risk assessment, it is recommended that the IARC classification (IARC 2006) should be applied as follows:
    * categories 1, 2A and 2B should be treated as carcinogens
    * category 3 substances can only be treated as non-carcinogens, given the paucity of information, but it should be recognised that this classification does