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THE DOSE MAKES THE POISON

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1 THE DOSE MAKES THE POISON
“All substances are poisons; there is none that is not a poison. The right dose differentiates a poison and a remedy.” Paracelsus ( ) 1

2 What amount causes harm?
Some chemicals are good in small amounts, but toxic in large amounts Example: botulinum toxin Small amount → Large amount → 2

3 What amount causes harm?
Some chemicals are good in small amounts, but toxic in large amounts Example: botulinum toxin Small amount → prevents wrinkles (BOTOX) Large amount → paralysis, death 3

4 TOXIC EFFECTS Rank the following in order of least toxic (1) to most toxic (6) based on LD50 data: TOXICANT TOXICITY Sugar Salt Herbicide Arsenic Nicotine Botulism 4

5 TOXIC EFFECTS Rank the following in order of least toxic (1) to most toxic (6) based on LD50 data: TOXICANT TOXICITY Sugar 1 Salt 2 Herbicide 3 Arsenic 4 Nicotine 5 Botulism 6 5

6 TOXIC EFFECTS Approximate Lethal Doses of Common Chemicals
(Calculated for a 160 lb. human based on data on rats) Chemical Lethal Dose Sugar 3 quarts Alcohol (ethyl alcohol) Salt (sodium chloride) 1 quart Herbicide (2,4-D) ½ cup Arsenic (arsenic acid) 1-2 teaspoons Nicotine ½ teaspoon Food poison (botulism) microscopic Source: NIH Curriculum, Chemicals, the Environment, and You Videodiscovery, 2000 6

7 Terms used to refer to different durations of exposure:
TOXIC EFFECTS Terms used to refer to different durations of exposure: ACUTE EXPOSURE CHRONIC EXPOSURE Refers to single exposure or a very limited exposure Example: breathing fumes from chlorine spill Refers to a prolonged or repeated exposure Example: breathing polluted air over a lifetime 7

8 Chemical Interactions
Antagonistic Reaction - One material interferes with the effects, or stimulates the breakdown, of other chemicals. Additive Reaction - Effects of each chemical are added to one another. Synergistic Reaction - One substance exacerbates the effect of the other.

9 MECHANISMS FOR MINIMIZING TOXIC EFFECTS
Most chemicals have a safe threshold under which their effects are insignificant. Metabolic Degradation the liver is the primary site of detoxification of both natural and introduced poisons Excretion Breathing Kidneys Urine

10 MECHANISMS FOR MINIMIZING TOXIC EFFECTS
Tissues and organs often have mechanisms for damage repair. Any irritating agent can be potentially carcinogenic Tissues (skin) have the highest cell replacement and are most likely to develop cancer

11 MEASURING TOXICITY Animal Testing
Most commonly used and widely accepted toxicity test is to expose a population of laboratory animals to measured doses of specific toxins. Sensitivity differences pose a problem.

12 EXPOSURE Dose Response Curves
The toxicity of a chemical can be expressed by a dose-response curve Shows the relative effect of a chemical on an organism(s) Allows scientists to determine a threshold dose Point above which all response can lead to death LD 50 12

13 Dose Response Curves EXPOSURE 13 13

14 PROBLEM Who took the largest dose of Tylenol?
An adult woman who weighs 125 lb and took 300 mg of Tylenol B. An adult man who weighs 180 lb and took 300 mg of Tylenol C. A teenage boy who weighs 135 lb and took 600 mg of Tylenol D. A baby who weighs 20 lb and took 100 mg of Tylenol 14

15 PROBLEM A. 300mg/125lb = mg/lb B. 300mg/180lb = mg/lb
Who took the largest dose of Tylenol? Answer: To calculate dose, divide the amount of the hazard by the body weight A. 300mg/125lb = mg/lb B. 300mg/180lb = mg/lb C. 600mg/135lb = mg/lb D. 100mg/20lb = mg/lb 5.0 2.4 1.7 4.4 The concentration of the chemical in the small body is much higher than in the larger bodies.

16 Toxicity Ratings Moderate toxin takes about (1) g/kg of body weight to produce a lethal dose. Very toxic materials require about 10% of that amount. Extremely toxic materials require 1% of that amount. Supertoxic chemicals can be lethal in a dose of a few micrograms. Many carcinogens, mutagens, and teratogens are dangerous at levels far below their direct toxic effect because abnormal cell growth exerts a form of biological amplification.

17 RISK ASSESSMENT AND ACCEPTANCE
Risk - Possibility of suffering harm or loss. Risk Assessment - Scientific process of estimating the threat that particular hazards pose to human health. Risk Identification Dose Response Assessment Exposure Appraisal Risk Characterization

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19 Understanding Risks Factors influencing risk perception:
Personal preferences and logic agendas and experiences Exaggerated view of ability to control our fate Irrational fears Media sensationalizing rare events

20 Accepting Risks Most people will tolerate a higher probability of occurrence of an event if the harm caused by that event is low. Harm of greater severity is acceptable only at low levels of frequency. Level of risk in which people will change behavior: 1 /100,000 EPA generally assumes 1 / 1 million is acceptable risk for environmental hazards.

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22 ESTABLISHING PUBLIC POLICY
It is difficult to separate the effects of multiple hazards and evaluate their risks accurately, especially when exposures are near the threshold of measurement and response. May not be reasonable to mandate protection, no matter how small the risk, from every potentially harmful contaminant in our environment. Different people have different degrees of susceptibility


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