Linear dose-response relationship defined

In general, the relationship between dose and response can be represented by a variety of functional forms. At low doses of substances that cause stochastic effects, the dose-response relationship usually is assumed to be linear and, thus, can be expressed as a single probability coefficient. This coefficient is frequently referred to as a risk (or potency factor or unit risk factor or slope factor) in the literature. However, it is really the response (consequence) resulting from a dose of a hazardous substance, and it should not be confused with risk as defined and used in this Report. 

The boundaries between different waste classes would be quantified in terms of limits on concentrations of hazardous substances using a quantity called the risk index, which is defined in Equation 6.1. The risk index essentially is the ratio of a calculated risk that arises from waste disposal to an allowable risk (a negligible or acceptable risk) appropriate to the waste class (disposal system) of concern. The risk index is developed taking into account the two types of hazardous substances of concern substances that cause stochastic responses and have a linear, nonthreshold dose-response relationship, and substances that cause deterministic responses and have a threshold dose-response relationship. The risk index for any substance can be expressed directly in terms of risk, but it is more convenient to use dose instead, especially in the case of substances that cause determinstic responses for which risk is a nonlinear function of dose and the risk at any dose below a nominal threshold is presumed to be zero. The risk index for mixtures of substances that cause stochastic or deterministic responses are given in Equations 6.4 and 6.5, respectively, and the simple rule for combining the two to obtain a composite risk index for all hazardous substances in waste is given in Equation 6.6 or 6.7 and illustrated in Equation 6.8. The risk (dose) that arises from waste disposal in the numerator of the risk index is calculated based on assumed scenarios for exposure of hypothetical... 

Lutz WK. 2001. Susceptibility differences in chemical carcinogenesis linearize the dose-response relationship threshold doses can be defined only for individuals. Mutat. Res. 482 71-76... 

The Association for Official Analytical Methods (AOAC) has approved the mouse bioassay [183] as a standard method for the screening of PSTs in seafood. It involves the intraperitoneal injection of 1 ml acid extract into a 20 g mouse, and the recording of symptoms and time to death. One mouse unit (MU) is defined as the toxin amount that kills a 20 g mouse in 15 min, which is equivalent to 0.18 mg saxitoxin. An obvious drawback of this method is animal cruelty. In addition, this method is not specific for PSTs, and it is prone to interference from substances that are imrelated to PSTs. Also the dose-response relationship is not always linear. 

The basis of this model is the experimental fact that most agonist dose-response curves are hyperbolic in nature. The reasoning for making this assumption is as follows. If agonist binding is governed by mass action, then the relationship between the agonist-receptor complex and response must either be linear or hyperbolic as well. Response is thus defined as... 

Therapeutic Efficacy. The therapeutic efficacy of risperidone for schizophrenia has been well established in several controlled trials conducted worldwide ( 74, 75). The clinical efficacy trials performed to support approval of risperidone by regulatory agencies have all been published. Therefore, it is appropriate to combine these data using meta-analytic techniques to explore the efficacy of risperidone compared with neuroleptics. For most drugs, the relationship of dose and response is defined by the classic sigmoidal curve. Thus, as the dose (or plasma level) increases beyond a threshold and reaches the linear portion of the curve, response increases. Once the dose is high enough to produce maximal clinical response, the dose-response curve then levels off. 

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