Dose-Response Relationships organ differences

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.,... 

Dose-response relationship A description of changes in effect (response) of an organism due to differing levels of exposure (dose) to a stressor such as a chemical or dosages of a drug. 

For purposes of health protection, the dose-response relationships for deterministic effects from exposure to radionuclides and hazardous chemicals are assumed to have a threshold. For either type of substance, the assumed thresholds are based on data for the most sensitive organ or tissue. However, there are potentially important differences in the way these thresholds are estimated and then applied in health protection of the public. 

Establishing Allowable Doses of Substances That Cause Deterministic Responses. The risk index for substances that cause deterministic responses normally should be expressed in terms of dose, rather than risk, given the assumption of a threshold dose-response relationship. The allowable dose of substances that cause deterministic responses in the denominator in Equation 6.3 should be related to thresholds for induction of deterministic responses in different organs or tissues. 

The use of MLEs of probability coefficients for radionuclides but UCLs for chemicals that induce stochastic responses is the most important issue that would need to be resolved to achieve a consistent approach to estimating risks for the purpose of waste classification. For some chemicals, the difference between MLE and UCL can be a factor of 100 or more. The difference between using fatalities or incidence as the measure of response is unlikely to be important. Use of the linearized, multistage model to extrapolate the dose-response relationship for chemicals that induce stochastic effects, as recommended by NCRP, should be reasonably consistent with estimates of the dose-response relationship for radionuclides, and this model has been used widely in estimating probability coefficients in chemical risk assessments. The difference in the number of organs or tissues that are taken into account, although it cannot be reconciled at the present time, should be unimportant. 

This type of correlative approach is widespread, as only a few marine studies involving inducible defenses (and none with mobile invertebrates) have directly demonstrated that the induction results in a decrease in the susceptibility of the organism to predation.71,72 Statistically significant differences in shell thickness or concentrations of defensive chemicals may or may not meaningfully affect predator preferences in ecologically relevant field situations. For chemical defenses, compound dose-response relationships may be nonlinear, and threshold levels of defense could be sufficient to deter predators so that further induction has little additional benefit. Thus, future studies should focus on directly demonstrating whether an induced response reduces predation on prey organisms. 

Hazard characterization consists of qualitative or quantitative evaluation of the adverse health effects associated with different agents, whether they are chemicals or microorganisms. This step comprises several elements, like toxicokinetics (absorption, distribution, metabolism, and excretion of the toxic agent), mechanism of toxic action, dose-response relationships, target organs and different end points, like acute or chronic toxicity, teratogenicity, neoplastic manifestations, and so forth. 

Carcinogens, such as organic and inorganic chemicals with various biological actions, can act similarly to other toxic substances, with similar dose-response relationships but several distinct differences. 

Results from this extensive effects testing demonstrates that PDMS has a relatively low toxicity to freshwater, marine and terrestrial organisms. As a result, in most cases no dose/response relationships or toxicity differences between species exist. The toxicity test methods that most realistically simulate PDMS exposure in the environment produce the most reliable measure of potential PDMS environmental effects. For example, sediment-bound PDMS will be the primary route of exposure in the aquatic environment, because PDMS has not been measured in overlying water (due to its negligible water solubility and potential for sorption onto sediments). Therefore, studies in which PDMS was dosed as a component of sediment are the most realistic exposure... 

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