Risk assessment protective factors

In a more detailed risk assessment, other factors will need to be considered such as the effect of personal protective equipment and psychosocial factors in the work organization. The following points my need to be assessed ... 

EPA, Radiation Exposure and Risks Assessment Manual (RERAM) Risk Assessment Using Radionuclide Slope Factors, EPA 402-R-96-016, U.S. Environmental Protection Agency, Washington, D.C., 1996. 

The Swedish National Chemicals Inspectorate (KEMI) has published an extensive review on human health risk assessment with focus on the application of assessment factors in risk assessments for plant protection products, industrial chemicals, and biocidal products within the European Union (KEMI 2003). 

Gronlund (1992) has investigated methods used for quantitative risk assessment of non-genotoxic substances, with special regard to the selection of assessment factors. Gronlund found that humans, in most cases, seem to be more sensitive to the toxic effects of chemicals than experimental animals, and that the traditional 10-fold factor for interspecies differences apparently is too small in order to cover the real variation. It was also noted that a general interspecies factor to cover all types of chemicals and all types of experimental animals cannot be expected. It was concluded that a 10-fold factor for interspecies variability probably protects a majority, but not all of the population, provided that the dose correction for differences in body size between experimental animals and humans is performed by the body surface area approach (Section 5.3.2.2). If the dose correction is based on the body weight approach (Section 5.3.2.1), the 10-fold factor was considered to be too small in most cases. 

Gronlund (1992) has investigated methods used for quantitative risk assessment of non-genotoxic substances, with special regard to the selection of assessment factors. Gronlund found that the 10-fold factor suggested for interindividual variability probably protects a majority but not all of the population. 

FIGURE S.6 Schematic illustration of the traditional setting of an acceptable level of exposure (ADI) by dividing the NOAEL from an animal study by an assessment factor (AF). The two dose-response relationships have identical NOAEL. If a uniform assessment factor is applied, there will be an adequate MOS at the ADI for effect b but not for effect a. (Modified from KEMI, Human health risk assessment. Proposals for the use of assessment (uncertainty) factors. Application to risk assessment for plant protection products, industrial chemicals and biocidal products within the European Union. Report No. 1/03, Solna, Sweden, 2003. 

The question of an extra assessment factor in the hazard and risk assessment for chemicals of concern for children is specifically addressed in Section 5.2.1.13. The U.S. Food Quality Protection Act (FQPA) (US-EPA 1996) directed the US-EPA to apply an extra safety factor of 10 in assessing the risks of pesticides to infants and children. The US-EPA (2002) noted the overlap of areas covered by the FQPA factor and those addressed by the traditional UFs, and it was concluded that an additional UF (children-specific) is not needed in the setting of reference values because the currently available UFs (interspecies, intraspecies, LQAEL-to-NOAEL, subchronic-to-chronic, and database-deficiency) were considered sufficient to account for uncertainties in the database from which the reference values are derived. Renwick et al. (2000) concluded that the available data did not provide a scientific rationale for an additional 10-fold UF for infants and children and pointed out that when adequate reproduction, multigeneration, or developmental studies are conducted, there will be no need for an additional 10-fold factor. 

There are of course many mathematically complex ways to perform a risk assessment, but first key questions about the biological data must be resolved. The most sensitive endpoint must be defined along with relevant toxicity and dose-response data. A standard risk assessment approach that is often used is the so-called divide by 10 rule . Dividing the dose by 10 applies a safety factor to ensure that even the most sensitive individuals are protected. Animal studies are typically used to establish a dose-response curve and the most sensitive endpoint. From the dose-response curve a NOAEL dose or no observed adverse effect level is derived. This is the dose at which there appears to be no adverse effects in the animal studies at a particular endpoint, which could be cancer, liver damage, or a neuro-behavioral effect. This dose is then divided by 10 if the animal data are in any way thought to be inadequate. For example, there may be a great deal of variability, or there were adverse effects at the lowest dose, or there were only tests of short-term exposure to the chemical. An additional factor of 10 is used when extrapolating from animals to humans. Last, a factor of 10 is used to account for variability in the human population or to account for sensitive individuals such as children or the elderly. The final number is the reference dose (RfD) or acceptable daily intake (ADI). This process is summarized below. 

Determining whether the objective of the risk assessment is to provide the most accurate assessment of risk or a protective assessment resulting from the inclusion of conservatively biased uncertainty factors... 

Irrespective of the risk, assumptions and decisions will have to be made because of uncertainty. Implications of attempting to characterize all variability and uncertainty in the risk assessment need to be considered. For example, exaggerating uncertainties can obscure the scientific basis of risk management decisions, leaving the impression that the decision has been arbitrary in nature (NRC 1989). The purpose of the uncertainty factor together with the type of assessment (e.g., deterministic or probabilistic, protective or best estimate) must be clearly communicated. Uncertainty factors can be described in 3 categories ... 

California Air Resources Board/Office of Environmental Health Hazard Assessment, Benzol a] pyrene as a Toxic Air Contaminant (1994) Office of Environmental Health Hazard Assessment/California Environmental Protection Agency, Air Toxics Hot Spot Program Risk Assessment Guideline, Part II Technical Support Document for Describing Available Cancer Potency Factors (1998) Collins et al. (1998). 

Office of Environmental Health Hazard Assessment, California Environmental Protection Agency, Air Toxics Hot Spot Program Risk Assessment Guideline Part II Technical Support Document for Describing Available Cancer Potency Factors, 1998. 

Risk assessments for anionic surfactants are obtained by comparing environmental exposure concentrations to effect levels (the quotient method). A protection factor that reflects the environmental safety of the material is calculated by dividing the exposure level by the effect concentration. If the protection factor is greater than 1, the material is deemed safe. Although this approach to assessing risk yields a numerical value that could be interpreted as the relative safety of a compound, comparisons of protection factors for different compounds should be avoided. The risk assessment for each material must be considered separately because of differences in chemical properties and differences in the database used to obtain the protection factor. In addition, the degree of uncertainty in the exposure and effect... 

Most extrapolations from animal experimental data in the risk assessments require the utilization of uncertainty factors. This is because we are not certain how to extrapolate across species, with species for the most sensitive population, and across duration. To account for variations in the general population and to protect sensitive subpopulations, an uncertainty factor of 10 is used by EPA and ATSDR. The value of 10 is derived from a threefold factor for differences in toxicokinetics and for threefold factor for toxicodynamics. To extrapolate from animals to humans and account for interspecies variability between humans and other mammals, an uncertainty factor of 10 is used by EPA and ATSDR, and as with intraspecies extrapolations, this 10-fold factor is assumed to be associated with in toxicodynamics and toxicokinetics. An uncertainty... 

The 1996 Food Quality Protection Act (FQPA) now requires that an additional safety factor of 10 be used in the risk assessment of pesticides to ensure the safety of infants and children, unless the EPA can show that an adequate margin of safety is assured with out it (Scheuplein, 2000). The rational behind this additional safety factor is that infants and children have different dietary consumption patterns than adults and infants, and children are more susceptible to toxicants than adults. We do know from pharmacokinetics studies with various human pharmaceuticals that drug elimination is slower in infants up to 6 months of age than in adults, and therefore the potential exists for greater tissue concentrations and vulnerability for neonatal and postnatal effects. Based on these observations, the US EPA supports a default safety factor greater or less than 10, which may be used on the basis of reliable data. However, there are few scientific data from humans or animals that permit comparisons of sensitivities of children and adults, but there are some examples, such as lead, where children are the more sensitive population. It some cases qualitative differences in age-related susceptibility are small beyond 6 months of age, and quantitative differences in toxicity between children and adults can sometimes be less than a factor of 2 or 3. 

NORTH ATLANTIC TREATY ORGANISATION, COMMITTEE ON THE CHALLENGES of MODERN SOCIETY. International Toxicity Equivalency Factor (I-TEF) method of risk assessment for complex mixtures of dioxins and related compounds. Pilot study on international information exchange on dioxins and related compounds . CCMS Report Number 176, Environmental Protection Agency, Washington D.C., 1988. 

This option does not appear to be advantageous for either radionuclides or chemicals that cause stochastic responses. In radiation protection, total detriment is used mainly to develop the tissue weighting factors in the effective dose (see Section 3.2.2.3.3), but ICRP and NCRP have continued to emphasize fatal responses as the primary health effect of concern in radiation protection and radiation risk assessments. Since total detriment is based on an assumption that fatalities are the primary health effect of concern, the same difficulties described in the previous section would occur if this measure of response were used for chemicals that induce stochastic responses. Other disadvantages of using total detriment include that detriment is not a health-effect endpoint experienced by an exposed individual and the approach to weighting nonfatal responses in relation to fatalities is somewhat arbitrary. Furthermore, total detriment is not as simple and straightforward to understand as either incidence or fatalities. 

---