Quantitative risk assessment for developmental neurotoxic effects.
Developmental neurotoxicity concerns the adverse health effects of exogenous agents acting on neurodevelopment. Because human brain development is a delicate process involving many cellular events, the developing fetus is rather susceptible to compounds that can alter the structure and function of the brain. Today, there is clear evidence that early exposure to many neurotoxicants can severely damage the developing nervous system. Although in recent years, there has been much attention given to model development and risk assessment procedures for developmental toxicants, the area of developmental neurotoxicity has been largely ignored. Here, we consider the problem of risk estimation for developmental neurotoxicants from animal bioassay data. Since most responses from developmental neurotoxicity experiments are nonquantal in nature, an adverse health effect will be defined as a response that occurs with very small probability in unexposed animals. Using a two-stage hierarchical normal dose-response model, upper confidence limits on the excess risk due to a given level of added exposure are derived. Equivalently, the model is used to obtain lower confidence limits on dose for a small negligible level of risk. Our method is based on the asymptotic distribution of the likelihood ratio statistic (cf. Crump, 1995). An example is used to provide further illustration.
Razzaghi
Mehdi
M
Bloomsburg University, Bloomsburg, PA 17815, USA. razzaghi@bloomu.edu
Kodell
Ralph
R
D015085:2,4,5-Trichlorophenoxyacetic Acid / Q000633:toxicity; D015084:2,4-Dichlorophenoxyacetic Acid / Q000633:toxicity; D000818:Animals; D001921:Brain / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D006540:Herbicides / Q000633:toxicity; D006801:Humans; D016013:Likelihood Functions; D015233:Models, Statistical; D020258:Neurotoxicity Syndromes; D009498:Neurotoxins / Q000633:toxicity*; D051381:Rats; D012306:Risk; D018570:Risk Assessment; D012307:Risk Factors
D006540:Herbicides; D009498:Neurotoxins; D015084:2,4-Dichlorophenoxyacetic Acid; D015085:2,4,5-Trichlorophenoxyacetic Acid