1. { Lethal Dose LD50 APES – Chapter 8

2. Toxicology  Toxicology is the study of the adverse physico-chemical effects of chemical, physical or biological agents on living organisms and the ecosystem.  Includes the prevention and treatment of disease.  Toxicology, ancient in practice, came to be known simplistically as the science of poisons.

3.  “The dose makes the poison.”– almost everything is toxic at some level. (According to Swiss scientist Paracelsus 500 years ago.) (According to Swiss scientist Paracelsus 500 years ago.)  How do you determine if a drug or chemical is safe to use…lab testing! Laboratory Investigations to Measure Toxicity

4. Animal Studies  Populations of lab animals usually rodents  Measured doses under controlled conditions  Takes two to five years  Costs $200,000 to $2,000,000 per substance  Newer methods Laboratory Investigations

5. Newer methods  Bacteria (Transgenic experiments)  Cell and tissue culture  Appropriate tissue  Stem cells  Chicken egg membrane Laboratory Investigations

6.  Love Canal Part I Love Canal Part I Love Canal Part I  Love Canal Part 2 Love Canal Part 2 Love Canal Part 2 Biohazards / Superfund Site

8.  Epidemiology is the study of distribution and determinants of health problems in specified populations. a) applying the learned information to control a) applying the learned information to control the health problems. the health problems. It is the scientific method of problem solving disease—epidemiologists, laboratory scientists, statisticians, physicians and other health care providers, and public health. Epidemiology

9.  Determine severity of health concern…is it an epidemic or an outbreak?  Identify the cause.  Identify if it is a small cluster or larger population  Geographic location(s) Criteria used to measure concerns

10.  Epidemic--refers to a contagious, infectious or viral illness that spreads to many people in one geographic region that occurs in excess of the numbers of cases that would usually be expected.  Pandemic refers to a contagious, infectious or viral illness that spreads, and may include millions of people in many areas across the globe, according to the World Health Organization's description. according to the World Health Organization's description according to the World Health Organization's description

11.  Laboratory testing on different drugs or chemicals are done by looking at a dose response curve.  To determine the toxicity of a chemical, look at dose to which 50% of the test population is sensitive. Which dose is right?

12. Fig. 8.16, p. 171 100 75 50 25 0 24 6 8 10 12 14 16 Percentage of population killed by a given dose Dose (hypothetical units) LD 50 In case of lethal dose (LD), this is called LD50.

13. LD-50 Dose Response  LD50 =individual dose required to kill 50% of test population (e.g., rats, fish, mice, cockroaches).  Standard to compare relative toxicities of chemicals.  The lower the LD50 dose, the more toxic the pesticide.  A pesticide with an LD50 value of 10 mg/kg is 10 times more toxic than a pesticide with an LD50 of 100 mg/kg

14. Fig. 8.15, p. 171 Very Sensitive Majority of Average Population low Sensitivity 020406080 Dose (hypothetical units) Number of individuals affected Different sensitivities to toxin to specific populations. Low Sensitivity

15.  Validity Challenged  Human physiology is different  Different species react different to same toxins  Mice die with aspirin  Species can be selected depending on physiological area  Pigs circulatory very similar to humans Laboratory Investigations

16. Toxicity ToxicityLD50Lethal DoseExamples Super < 0.01less than 1 drop dioxin, botulism mushrooms Extreme <5less than 7 drops heroin, nicotine Very 5-507 drops to 1 tsp. morphine, codeine Toxic50-5001 tsp. DDT, H 2 SO 4, Caffeine Moderate 500-5K1 oz.-1 pt. aspirin, wood alcohol Slightly5K-15K 1 pt. ethyl alcohol, soaps Non-Toxic>15K>1qt. water, table sugar (LD50 measured in mg/kg of body weight)

17. Why so little is known of toxicity  Only 10% of at least 75,000 commercial chemicals have been screened  ~ 2% determined to be carcinogen, teratogen or mutagen  >1000 new synthetic chemicals added per year  >99.5% of US commercial chemicals are NOT regulated

18. Dose-Response Curves Nonlinear dose-response Linear dose-response Threshold level Effect Dose Nonlinear dose-response Linear dose-response No threshold Effect Threshold Dose Fig. 16.6, p. 401