Equivalent dose, estimation

When using animal inhalation e.xpcrimcnts to estimate lifetime human risks for partially soluble vapors or gases, the air concentration (ppm) is generally considered to be the equivalent dose between species based on cqui alcnt c.xposure times (measured as fractions of a lifetime). For inhalation of particulates or completely absorbed gases, the amount absorbed per unit of body surface area is considered to be the equivalent dose between species. 

Indoor air radon concentrations measured in a randomly selected sample of 220 Irish houses have been found to range from about 20 Bq/nr to as high as 1740 Bq/nr with a median value of 61 Bq/nr. Using current dose estimation methods the estimated effective dose equivalents due to radon daughter inhalation in these houses are 1.6 mSv/year (median value) and 46 mSv/year (maximum value). 

For products intended for operation at elevated temperatures it would be expected that the temperatures would be known. Where the operating temperature is cyclic, the maximum might be used or an equivalent temperature dose estimated on the basis of the Arrhenius relation. 

Data from epidemiological studies, of sufficient quality, are generally preferred for estimating risks. When the evaluation is based on animal studies, the estimation of a human-equivalent dose should utilize toxicokinetic data for cross-species dose scaling if adequate data are available. Otherwise, a default procedure should be applied. The aim of the cross-species dose scaling is to define exposure levels for humans and animals that are expected to produce the same degree of effect, taking into account differences in scale between test animals and humans, such as size and life span. 

In December 1997, Secretary of Defense William Cohen announced a departmentwide anthrax immunization program for high-risk military personnel. Implementation began in March 1998. On May 18, 1998, the Secretary authorized the vaccination of all military forces (Cohen, 1998). Almost 2.5 million troop-equivalent doses of vaccine were required to implement the Secretary s decision, much more than had ever been produced by the licensed manufacturer in its entire history. Prior to Desert Storm, the primary vaccine users had been veterinary, laboratory, and industrial workers at risk of infection, for whom an estimated 60,000 doses of Anthrax Vaccine Absorbed (AVA) were distributed between 1974 and 1989, an average of 4,533 doses per year (foellenbeck et al., 2002). During Desert Storm, approximately 150,000 troops received 300,000 doses of AVA, without accurate recording of recipients or adverse reactions. 

A fundamental difference between radionuclides and hazardous chemicals in regard to dose-response assessment is the following. Estimates of responses from exposure to radionuclides can be based on estimates of absorbed dose and equivalent dose in all organs and tissues, and the dose-response relationships for different organs or tissues obtained from human or animal studies can be applied to any radionuclide and any exposure situation. Separate studies of responses from exposure to each radionuclide of concern are not needed. For hazardous chemicals, however, quantities analogous to absorbed dose and equivalent dose have not been developed i.e.,... 

It is now usual to calculate the effective dose equivalent (Appendix 1.2). The dose equivalent measured in Sieverts (Sv), takes into account the relative biological efficiency of different radiations. For gamma and beta radiation, the conversion factor is unity, but for alpha radiation it is 20. The effective dose equivalent allows also for the relative importance of irradiation of various organs to the risk of cancer. To convert thyroid dose from beta particles, measured in Gy, to effective dose equivalent, a factor 0.03 is applied. Thus the maximum thyroid doses estimated by Loutit et al. correspond to effective dose equivalents of 4.8 mSv (child) and 1.2 mSv (adult). Adding the external whole body gamma radiation, for which the conversion factor is unity, gives 5.4 mSv (child) and 1.8 mSv (adult). 

For radionuclides with half-lives zero to 3 months the equivalent dose is equal to the armual dose of the year of intake (Harley, 2001). It is often convenient to estimate the fraction of the committed equivalent dose which remains. For a radionuchde with a half-life of 3 months, after 1 year of exposure, it had undergone the passage of four half-fives so tfiat fraction of dose delivered was (1 /2 ) 94% of... 

In the RPF method (eqn (1)), the user must identify the constraints of the application of a set of RPFs. For example, the health effect, dose range of component doses, route(s) of exposure, and dura-tion(s) of exposure for which the RPFs can be applied must be specified (e.g., a set of RPFs may be constrained to oral exposures and not be used for exposures to the same mixture through the inhalation route). To apply the method, an RPF is estimated for each mixture component the RPF estimates the toxicity of the component relative to that of the IC. RPFs commonly are estimated from a ratio of equally toxic doses of the individual dose-response functions for the component and the IC. For example, the quotient of the effective dose at which ten percent of a test population exhibits an effect (EDio) of the IC and the component could serve as a value for the component s RPF obviously, the RPF for the IC equals 1. The index chemical equivalent dose of an individual component is the product of the component dose and the RPF of the component. These equivalent doses are summed across all components. The risk posed by the mixture is estimated by comparing the summed index chemical equivalent doses of the mixture to the dose-response function of the IC ... 

Acute lethal concentrations (LC5°s) of airborne gasoline in experimental animals have not been reported. The acute oral LDsofor gasoline in rats has been reported to be 18.8 mL/kg, or approximately 14,063 mg/kg (Becketal. 1983 Vernot et al. 1990). This is higher than the approximate lethal dose estimated for humans cited above (12 ounces, which is equivalent to approximately 5 mL/kg, or 3,740 mg/kg). The lethal dose of gasoline following dermal exposure has not been determined in animals, but it does exceed 8.0 mL/kg, or 6,000 mg/kg, indicating that it is relatively nontoxic by the dermal route (Beck et al. 1983). Linder the exposure conditions expected to be present at hazardous waste sites, it is not expected that lethal air or water concentrations of gasoline will be achieved. 

Schlosser, P. M., Patrick, D. L., Conolly, R. B., Janszen, D. B., and Kimbell, J. S. (2003). Benchmark dose risk assessment for formaldehyde using airflow modeling and a single-compartment, DNA-protein cross-link dosimetry model to estimate human equivalent doses. Risk Analysis 23, 473-487. 

The Food and Drug Administration (FDA) develops standards for radioactive material concentrations in food (FDA 1998), and medical devices used in radiation therapy (FDA 1997). The FDA recently updated its guidance document that presents recommended action levels for radionuclides in foods, both domestic and imported (FDA 1998). These derived intervention levels (DILs) are estimated levels in food that could lead to individuals receiving a radiation equivalent dose equal to the FDA protection action guide (PAG) that is set as the more limiting of either 0.5 rem (5 mSv) for committed effective dose or 5 rem (50 mSv) committed dose equivalent to any individual tissue or organ. Table 8-2 presents the most restrictive DILs for strontium. 

The tumor incidence model is then used to estimate a safe ED defined as that equivalent dose which yields a negligible increase in risk for the tumor over the background risk. For the purposes of risk estimation, it is assumed that this safe ED represents the safe ED in humans. It remains only to convert this safe ED in humans into a safe human exposure level. As before, a model relationship is assumed between the ED and exposure dose in humans (usually the same conceptual model as was used in the animal species) and parameter estimates are obtained. In addition to obtaining parameter estimates from the fields previously mentioned, a considerable number of parameters are estimated as simple allometric formulae of parameters which are easily obtained in animals, such as body weight. The complexity of these models, the number of parameters and the number of experiments used to estimate the parameters contribute to the overall uncertainty in the safe dose estimates. 

---