Soil ingestion 50, (100), [100] mg/day Central tendency for outside soil. (Reasonable maximum, outside soil) [Central tendency outside soil + indoor dust]. (Section 4.5.3) Incidental water ingestion while swimming 50 (~ average) 150 (~ upper estimate) mL/hr Section 4.6.3 Inhalation exposure parameters Inhalation rate 8.0 (12.8) m3/day Section 5.1.3. For specific inhalation rates by activity or for short term exposures, see Section 5.1;Table 5.1.2 Activity patterns Frequency of hand to mouth 20 (63) (indoors) Section 6.1.1.3 14 (42) (outdoors) Mouthing duration Varies hr/d Mean and maximum values differ by object mouthed (Section 6.1.1.3) Time spent indoors 22.6 (total) hr/d Upper estimate not available (Section 6.1.2.3) 17.8 (24) (at home) hr/d Section 6.1.2.3 Time spent outdoors 1.4 hr/d Average. Upper estimates not available (Section 6.1.2.3) Playing on sand/gravel 0.7 hr/d Playing on grass 1.1 hr/d Playing on dirt 0.9 hr/d Time spent swimming 21 hr/year Average value. Upper estimate not available (Section 6.2.4.3) Footnotes for Tables 8a and 8b a See . For screening risk assessments and establishing guidelines the most sensitive receptor is assumed to be a (Table 8a) or a 1–2-year-old (Table 8b). b The references to sections and tables refer to those in the Australian exposure factors guidance document.
Table 9: Summary of non-age-dependent exposure factors Note: Values are average or 95th percentile (in parenthesis) Parameter Suggested value Units Comment Anatomical and physiological parameters Life expectancy 82 yrs Male and female combined (Section 2.4.1) 79 Male (Section 2.4) 84 Female (Section 2.4) Dermal exposure parameters Soil adherence 0.5 (1.7) mg soil/cm2 skin Applicable for outdoor and indoor residential child and adult exposures (Section 3.3.1). For specific activities and body parts see Tables 3.3.3, 3.3.4, and 3.3.5. Dermal bioavailability Organics: 1 Inorganics: 0.0001 Unitless Chemical-specific. These table values are to be used only when other reasonable information is not available. Bioaccessibility of inorganics from soil or other media can be approximated with experimental tests (Sections 3.4 and 4.0). Dermal bioaccessibility Organics: 1 Inorganics: No default Shower and bath frequency 1 (2) #/day Central estimate (upper estimate) for adults and children (Section 3.5.5) Shower duration 8 (16) mins Section 3.5.5 Shower volume 72 L Volume and flow rate of non-water saving shower (Section 3.5.5). Upper estimates not available. Shower flow rate 9 L/min Bath duration 21 mins Bath duration for adults and children combined (Section 3.5.5). Upper percentile not available. Bath volume Insufficient data L Insufficient data (Section 3.5.4).
Oral exposure parameters Oral bioavailability Organics: 1 Inorganics: No default Unitless Chemical-specific. These table values are to be used only when other reasonable information is not available. Bioaccessibility of inorganics from soil or other media can be approximated with experimental tests (Sections 3.4 and 4.0). Oral bioaccessibility Organics: 1 Inorganics: No default Inhalation exposure parameters Building air exchange rate Residential: 0.6 Commercial: no recommendation #/hr The residential value is midpoint of range for ‘closed’ Australian dwellings. Air changes will be higher with open doors/windows, ceiling fans and air conditioning. A single value is not suggested for commercial buildings. Ur estimates not available (Section 5.2.4). Indoor particle deposition rate No recommendation #/hr Markedly differs from house to house. No suggested value (Section 5.3.1). Floor area of residential dwelling Houses: 190 Other: 120 All: 180 m2 Average values. There is a wide range of values for houses and other types of dwellings (Section 5.4.1). Upper estimates not available. Air volume of residential dwellings Houses: 460 Other: 280 All: 420 m3 Average values. Assumed ceiling height is 2.4 m. There is a wide range of values for houses and other types of dwellings (Section 5.4.1). Upper estimates not available. Uptake (product of retention and absorption) of inhaled contaminants Default 100% unitless Chemical-specific value should be used if available (Section 5.5). Background particulate PM10; 17 (39) PM2.5; 7 (16) µg/m3 [unitless] National average of all urban monitoring sites – 50th percentile, (95th percentile).
The CSF is used in EHRA to estimate the upper-bound probability that cancer will develop over a lifetime of exposure to a chemical at a specific level of intake. It is the slope of a linear extrapolation from the estimate of a POD dose to zero. The URF can be derived directly from inhalation or drinking-water studies depending on which media is being assessed. Where such data is not directly available, these unit risks can be derived by converting an oral CSF with units of mg/kg/d–1 to a concentration of the substance in air, water or other media. These extrapolations often assume default intake rates for the specified media (e.g. an inhalation rate of 20m3 per day of air, or ingestion of 2 L/day of water and a body weight of 70 kg). The conversion equation most commonly used is: Inhalation URF (µg/m3)–1 = (BW = body weight) Where different default values are used (e.g. those recommended in the Australian exposure factor guidance document – see Chapter 4), it may be necessary to adjust CSFs derived by the US EPA or in Integrated Risk Information System (IRIS) databases. Recent US EPA (2009a) guidance (RAGS-F) indicates that inhalation risks should be assessed by calculating an exposure-adjusted air concentration, which is then used in EHRA risk characterisation equations. This means that exposure estimates are no longer adjusted based on inhalation rate or body weight, and the only difference in risk estimates between a child and an adult is the exposure time. The application of these risk factors is to calculate the probability of a finite increase in cancer risk over a lifetime, according to the equation: Increased lifetime cancer risk (ILCR) = chronic daily intake (mg/kg/d) × CSF (mg/kg/d)–1 or Increased lifetime cancer risk (ILCR) = exposure concentration × URF bound
Has the report been peer reviewed or is it being audited? 7.9 A checklist of points that should be considered in the overall presentation of the report and an assessment of its quality is provided below. Report structure and data presentation Have all tables and figures been referred to correctly in the text of the report? Is the presentation of results consistent with the units for which the standards are written (e.g. using milligrams/m3 instead of nanograms/m3 when sampling ambient air)? Have SI units been used correctly throughout the report (Thompson & Taylor 2008)? Is there a map of testing sites that enables ready identification of sampling sites in relation to relevant environmental sources? Does the presentation format enable easy cross-referencing of results to maps and between different parts of a report? Are results presented in linear geographic sequence (e.g. either going downstream or upstream, or towards or away from a point source)? Has the report been presented in a suitable format to enable ‘track changes’, comments and cutting and pasting into a Word document? PDF formats hinder rapid transcription and can create the potential for transcription errors. Issues of data quality Has the nature of the analyte been specified? This may be important when the valency (e.g. chromium) or chemical form (e.g. organic arsenic versus inorganic arsenic in fish; haem iron versus non-haem iron in animal samples) may be relevant for health risk assessment. Has the level of reporting (LOR) been specified for each analyte and for each batch of results? Have the laboratories involved in the assays been identified, along with their QA/QC procedures? When there have been several sampling periods, have the results been collated into a single table to enable efficient appraisal of results and trends to be readily detected?
non-diseased (controls) identified and measured they may be addressed may incorporate biases; cannot derive rates Recall bias is a major problem quick; particularly useful for studying rare diseases Time-series study Large community (several million people); susceptible groups such as asthmatics Current (e.g. daily) changes in exposure Current (e.g. daily) variations in mortality Often difficult to sort out; e.g. effects of influenza Many confounding factors; often difficult to measure Useful for studies on acute effects Historical (retrospective) cohort study Special groups; workers, patients, insured persons Records of past measurement Records of past or current diagnosis Often difficult because of retrospective nature; depends on availability of previously obtained data Need to rely on records that may not be accurate Less expensive and quicker than a prospective study; can be used to study exposures that no longer exist Prospective cohort study Community or special groups; exposed versus non-exposed Defined at outset of study (can change during study) To be determined during study Usually easy to measure Expensive and time consuming; exposure categories can change; high dropout rate possible Can estimate incidence and relative risk; can study many diseases in one study; can describe associations that suggest cause–effect relationships Experimental study Community or special groups Controlled or already known To be measured during study Can be controlled by randomisation of subjects Expensive; ethical considerations; study subjects compliance required Well accepted results; strong evidence for causality or efficacy of intervention Adapted from: WHO (1991). Epidemiological studies are rarely definitive, and a single epidemiological study cannot establish causality. Any such study is necessarily a sample of the total population of interest, so there will always be questions about being able to generalise from an individual study sample to the total population. Moreover, undetected methodological biases can only be overcome by having numerous studies by different investigators with
methodologies and the reliance on establishment of a policy-driven ‘target risk’ for the evaluation of the EHRA outcomes. While there has been some movement towards accepting a threshold approach for carcinogenic responses associated with some non-genotoxic modes of action, the dominant method of dose–response assessment in Australian EHRA practice and regulatory requirements remains the non-threshold approach taken in US regulatory agencies. The detailed critique of quantitative cancer risk assessment provided in Hrudey (1998) is quite informative and still relevant. The continued use of a non-threshold approach for most carcinogenic risk assessments results in quite conservative, and potentially costly outcomes in many types of EHRA processes. 11.7 While there is strong precedent for both Australian and international regulatory systems to expect application of a non-threshold approach to risk assessment of carcinogens, in 1999 the National Health and Medical Research Council (NHMRC), acting on advice from a specialist working party, endorsed a set of guidelines for risk assessment of carcinogens on contaminated sites, which was based on a modified threshold approach, or modified benchmark dose (mBMD) methodology (NHMRC 1999a). While the NHMRC document has since been rescinded, it did outline an approach that could harmonise the HRA of cancer and non-cancer toxicological endpoints by moving away from the need to calculate or estimate a finite risk level for carcinogens alone, and the need to establish a ‘target risk’ with which this could be compared. The essential features of this alternative approach, deriving a POD for carcinogenic risk assessment were: use of a range of mathematical models to explore the data ‘fit’ to a derived dose–response relationship estimation of a BMD at the 5 per cent excess risk level (BMD05) to serve as a ‘point of departure’ (POD) for further risk assessment application of a range of modifying factors to the BMD05 dose estimate, in order to derive a ‘guideline dose’ (GD), which should be protective of human health. The NHMRC mBMD methodology has many similarities with the BMD methodology used by the US EPA to derive a POD for its carcinogen risk assessments, but there are also some important differences. The NHMRC advocates estimation of a mean BMD05 from all the curve-fitting data, after discarding those models which
powers of TEFs for dioxins and dioxin-like PCBs (Walker et al. 2005; NTP 2006), ternary mixtures of TCDD, PeCDF and PCB 126 were administered at dose levels representing the four TEF-equivalent doses used for TCDD alone in previous NTP studies. While the dioxin mixtures produced a range of cellular proliferative and carcinogenic responses comparable to that seen with TCDD alone, the dose–response relationships were not identical. Therefore, while this NTP study provided some support for the TEF concept, it did show that the numerical values for TEFs may not be applicable across the full range of toxicological outcomes (Gray et al. 2006). On the other hand, Smialowicz et al. (2008) were able to validate the US EPA dioxin-like TEFs to predict immunotoxic endpoints, based on their CYP inductive effects. A more comprehensive review of the methodologies and databases used to establish dioxin TEFs has been published by Haws et al. (2006). 12.4 This approach is the one most commonly used in health risk assessments. The contribution of an individual mixture component is calculated as a ratio of predicted exposure compared with a health-based benchmark (ADI, TDI). This derived ratio is termed a hazard quotient (HQ). To derive an overall estimate of risk across all components of the mixture, the individual HQs are summed to derive a hazard index (HI) (Herzberg & Teuschler 2002). Ej = exposure level of chemical j RfDj = RfD of chemical j HQj = HQ for chemical j (dimensionless) RfD is US terminology equivalent to the ADI or TDI While this pragmatic approach may be a useful screening tool, is used quite extensively in HRA practice and is generally accepted, or even required, by Australian regulatory authorities, it is based on a potentially flawed premise. As noted above, additive risk estimates imply a common MoA, or at least a common toxicological outcome. Where the toxicity of individual components does not satisfy such an assumption, the contributions to risk are theoretically independent.
Table 23: Chemicals regulation in Australia Agency National Industrial Chemicals Notification and Assessment Scheme (NICNAS) Australian Pesticides and Veterinary Medicines Authority (APVMA) Therapeutic Goods Administration (TGA) Food Standards Australia New Zealand (FSANZ) Portfolio Health and Ageing Agriculture, Fisheries and Forestry Health and Ageing Health and Ageing Scope Assessment and review, not registration based Assessment, product registration and review Assessment and product registration Assessment and standard-setting Relevant legislation Industrial Chemicals (Notification and Assessment)Act 1989 Agricultural and Veterinary Chemicals Code Act 1994 and Veterinary Chemicals Administration Act 1994 Therapeutic Goods Act 1989 Australia New Zealand Food Authority Act 1994. Food Standards Code About the chemicals Industrial chemicals are varied and include dyes, solvents, adhesives, plastics, laboratory chemicals, paints and coatings, chemicals used in cleaning products, cosmetics including some sunscreens. Agricultural products, including chemicals that destroy/repel pests or plants. Veterinary products are used to prevent, diagnose or treat disease in animals. Therapeutic goods, including prescription medicines and medicines available over the counter (OTC). OTCs include complementary medicines (herbal, vitamin and homeopathic preparations); some sterilants and disinfectants and cosmetic-type products that make therapeutic claims. Food additives and processing aids used in food to assist with preservation, flavouring, colouring, or modifying its functions; permitted levels of some environmental contaminants are also controlled via the Food Standards Code. What follows is a brief synopsis of the roles and methods of operation of the two agencies listed in Table 23 that have main responsibility for chemicals likely to be released into the environment (industrial chemicals, AgVets and consumer product chemicals). Note that the agencies and responsibilities are current at 2011, but may change according to future government reorganisations.