毒物毒性作用的主要概念及基本.pptx

毒物毒性作用的主要概念与基本机制;;Dose 剂量;Dose II;Dose-response curve;;NOEC and LOEC;;联合毒性作用joint toxic effect;Antagonism拮抗作用;毒性作用的机制;其他毒性作用的机制;影响毒性作用的因素;;比较;物理性质与毒性;机体状况;接触条件;环境因素;联合作用类型评定(一）;K与联合作用类型;Models of joint toxic effectII- Toxic unit approach ;Models of joint toxic effect;Toxic unit approach based on Concentration Additivity浓度相加性 - after adjustment for relative potency, concentrations of toxicants can be added together to predict effects under the assumption of additivity. However, toxicant concentration (or dose) is often related to lethal effect by a sigmoid, not a linear relationship. Some relationships are pseudolinear over a range of concentrations of interest and concentration additivity can be used to approximate effects. ;To progress to a more involved treatment of mixtures, the distinction must be made between toxicants that act independently or similarly. Similar joint action they act by the same mechanism (i.e., have identical modes of action) and “one component can be substituted at a constant proportion for the other … toxicity of a mixture is predictable directly from that of the constituents if their relative proportions are known” Independent joint action Exists if each toxicant produces an effect independent of the other and by a different mode of action. Quantifying joint “mixtures whose constituents act independently, the mortalities, not the doses, are additive.” ;Effect Additivity Sum of the predicted effects could be compared to the observed effect of the actual combination of the two concentrations of A and B in order to assess conformity to or deviations from effect additivity. For example, the separate effects of 2 toxicants on the proportion of exposed individuals dying (PA and PB) are estimated with the equations:;Two Independently Acting Toxicants;Two Similarly Acting Toxicants;;