Dose - Response Relationships

Understand the quantitative relationship between toxicant exposure and induced effects. • Describe frequently encountered toxic effects. • Interpret frequency (normal distribution) and dose response curves. • Understand threshold effects with dosage increase.
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Dose - Response Relationships Principles of Environmental Toxicology Learning Objectives • Understand the quantitative relationship between toxicant exposure and induced effects. • Describe frequently encountered toxic effects. • Interpret frequency (normal distribution) and dose - Dose - Response Relationships response curves. • Understand threshold Principles of Environmental Toxicology effects with dosage increase. Instructor: Gregory Möller, Ph.D. University of Idaho 2 Principles of Environmental Toxicology Principles of Environmental Toxicology Learning Objectives, 2 What is a Dose?• Understand effective dose, margin-of-safety and • The amount of a substance administered at the relationship of effective vs. toxic dose. one time.• Examine the use of actual data for no observed • Dosage is the amount per unit weight of the effect and lowest observed exposed individual. effect in risk assessments. • Exposure is characterized• Summarize effective, lethal by and toxic doses. – Number of doses – Frequency of dosing• Understand a linearized – The total period of time multi-stage model for for the exposure. non-threshold responses.3 4 Principles of Environmental Toxicology Principles of Environmental Toxicology Quantifying the Dose Key Concepts • Dosage - response mathematical relationship• Gram (g) is the standard unit but mg is typical of most exposures in toxicology. (positive slope).• Dosage: mg (dose) / kg (bw) / day (duration) • Causal relationship. – mg/kg/d • Observable responses.• Exposures are quantified in relation to the • Statistical management of variability media. of individual responses. – mg/L in water. – Species, genetics, age, sex. – mg/kg in food. – mg/m3 in air.• Variation in units common (ppm, ppb).5 6 1 Principles of Environmental Toxicology Principles of Environmental Toxicology Responses (Toxic Effects) Responses (Toxic Effects), 2• Inflammation. • Lethal synthesis. – Local or systemic response. – Toxicant incorporation into a biochemical pathway.• Necrosis. • Lipid peroxidation. – Cell or tissue death. – Free radical oxidation of fatty acids leading to cell death.• Enzyme inhibition. • Covalent binding. – Biochemical pathway interruption. – Of electrophilic reactive – Competitive; non-competitive. metabolites to nucleophillic• Biochemical uncoupling. macromolecules. – Interference with phosphate molecule synthesis (ATP) 8 Ballantyne7 Principles of Environmental Toxicology Principles of Environmental Toxicology Responses (Toxic Effects), 3 Responses (Toxic Effects), 4• Receptor interac ...