1. Toxicology 23 March 2015

2. Drugs, Poisons, Toxins Drug - a substance that when taken into the body produces a physiological or psychological effects, usually by interfering with the body’s normal chemical reactions Poison – a substance that when taken into the body produces death or physical harm, usually by interfering with the body’s normal chemical reactions Toxin – a naturally produced substance that when taken into the body at very low doses causes death or physical harm, usually by interfering with the body’s normal chemical reactions Ricin – a by product of castor beans

3. Drugs, Poisons, Toxins How are they similar? Must be taken into the body (inhaled, swallowed, absorbed, or injected) for effect Causes changes to the body by interfering with normal chemical reactions All can be poisons in the right dose How are they different? Drugs produce desired effects Toxins are naturally produced, and cause damage at very low doses

4. Examples? “All substances are poisons. There is none which is not. The right dose differentiates a poison and a remedy” – Paracelsus 16 th c. physician

5. Examples? All drugs will become poisons at high doses. ● Tylenol, multivitamins, codeine, alcohol, etc. “All substances are poisons. There is none which is not. The right dose differentiates a poison and a remedy” – Paracelsus 16 th c. physician

6. Examples? All drugs will become poisons at high doses. ● Tylenol, multivitamins, codeine, alcohol, etc. Moreover, things that are typically considered toxins are sometimes therapeutic in the right dose. ● Arsenic is used to treat certain types of leukemia ● Botulin is used for botox, muscle spasms, crossed eyes, etc. “All substances are poisons. There is none which is not. The right dose differentiates a poison and a remedy” – Paracelsus 16 th c. physician

7. Determining Toxicity There are 5 main things which determine the toxicity (adverse effects) of a poison: 1)The chemical form of the substance 2)How it enters the body 3)The victim’s age, weight, gender, and condition 4)Time period of exposure 5)Presence of other chemicals

8. Determining Toxicity There are 5 main things which determine the toxicity (adverse effects) of a poison: 1)The chemical form of the substance 2)How it enters the body 3)The victim’s age, weight, gender, and condition 4)Time period of exposure 5)Presence of other chemicals Example: Arsenic, the metal, is not absorbed by the body, and so is not poisonous. Arsenic compounds, such as As 2 O 3 and As 2 O 5, however, are readily absorbed and very toxic.

9. Determining Toxicity There are 5 main things which determine the toxicity (adverse effects) of a poison: 1)The chemical form of the substance 2)How it enters the body 3)The victim’s age, weight, gender, and condition 4)Time period of exposure 5)Presence of other chemicals Poisons can enter the body through inhalation, swallowing, absorption through skin or mucus membranes, or injection.

10. Determining Toxicity There are 5 main things which determine the toxicity (adverse effects) of a poison: 1)The chemical form of the substance 2)How it enters the body 3)The victim’s age, weight, gender, and condition 4)Time period of exposure 5)Presence of other chemicals Fetuses, the very young, the very old, and individuals in poor condition experience greater toxicity. The greater the body weight, the less toxicity. Women typically experience greater toxicity than men.

11. Determining Toxicity There are 5 main things which determine the toxicity (adverse effects) of a poison: 1)The chemical form of the substance 2)How it enters the body 3)The victim’s age, weight, gender, and condition 4)Time period of exposure 5)Presence of other chemicals Chronic exposure – toxin exposure occurs over a long period of time. Acute toxicity – toxin exposure that is large enough to cause immediate serious problems People with chronic exposure build up some tolerance to the poison, but will still experience ill effects

12. Determining Toxicity There are 5 main things which determine the toxicity (adverse effects) of a poison: 1)The chemical form of the substance 2)How it enters the body 3)The victim’s age, weight, gender, and condition 4)Time period of exposure 5)Presence of other chemicals Synergist - drugs are synergistic if their combined effects are greater than the sum of their individual effects (e.g. alcohol + some antihistamines) Antagonists – drugs are antagonistic if taking them together reduces their individual effects

13. Measuring Toxicity The toxicity of substances can be measured in animal trials. The poison is introduced to test animals at different dosages. The dose of poison that kills half of the animals exposed within a short time frame is LD 50 (50% leathal dose).

14. Measuring Toxicity Which substance is most toxic? Why? Botulin is most toxic because it is deadly in the smallest doses.

15. Measuring Toxicity Which substance is most toxic? Why? Not an easy question! Green has the lowest LD 50, and is the most toxic at high doses. Red is most toxic at low doses.

16. Measuring Toxicity Which substance is most toxic? Why? Not an easy question! Green has the lowest LD 50, and is the most toxic at high doses. Red is most toxic at low doses. Doses where green is most toxic Doses where red is most toxic

17. LD 50 problem 1.Determine the LD50 for each drug. 2.Compare the toxicity of the two drugs.

18. Calculating Dose Levels Tylenol LD 50 rat = 3000 mg/kg Recommended maximum daily dose for adults: 4000 mg 1)What dose would be fatal for 50% of rats, if an average rat is 300g? 2)How much tylenol would a 150 lb person have to take to equal the LD 50 dose (calculated for rats)? (Hint 1 kg = 2.2lb) 3)How many tylenol capsules would a 150 lb person have take to equal the LD 50 ? (Hint 1 capsule = 500 mg)

19. Calculating Dose Levels Tylenol LD 50 rat = 3000 mg/kg Recommended maximum daily dose for adults: 4000 mg 1)What dose would be fatal for 50% of rats, if an average rat is 300g? 90 mg 2)How much tylenol would a 150 lb person have to take to equal the LD 50 dose (calculated for rats)? (Hint 1 kg = 2.2lb) 20,000 mg 3)How many tylenol capsules would a 150 lb person have take to equal the LD 50 ? (Hint 1 capsule = 500 mg) 40 capsules

20. Calculating Dose Levels Caffeine LD 50 rat = 192 mg/kg 1)What dose would be fatal for 50% of rats, if an average rat is 325g? 2)How much caffeine would a 125 lb person have to take to equal the LD 50 dose (calculated for rats)? (Hint 1 kg = 2.2lb) 3)How many No-Doz capsules would a 125 lb person have take to equal the LD 50 ? (Hint 1 capsule = 100 mg)

21. Calculating Dose Levels Caffeine LD 50 rat = 192 mg/kg 1)What dose would be fatal for 50% of rats, if an average rat is 325g? 62.4 mg 2)How much caffeine would a 125 lb person have to take to equal the LD 50 dose (calculated for rats)? (Hint 1 kg = 2.2lb) 13100 mg 3)How many No-Doz capsules would a 125 lb person have take to equal the LD 50 ? (Hint 1 capsule = 100 mg) 131 capsules

22. Problems with LD 50 Although LD 50 trials are still used today, their use has declined over the last 20-30 years. Many people and organizations criticize LD 50 trials both for their cruelty and their effectiveness. Why might LD 50 not be a useful measure of toxicity? Animal studies have limited relevance to humans We care about harmful effects, not just lethality The toxicity of a substance varies greatly according to all the factors discussed before (age, gender, condition, method, timing, other drugs, etc.)

23. Exit Ticket 1.Name 4 factors that affect the toxicity of a drug. 2.Estimate the LD 50 of the drug shown below. 3. The LD 50 of ricin is 0.02 mg / kg. What does that dose correspond to in a 140 lb person? (1 kg = 2.2 lbs).

24. Homework Toxicity Homework due next class Bring materials to work on poisoner project next class – that project will be due 3/27

25. Closure What were our objectives, and what did we learn? What was our learner profile trait and how did we demonstrate it? How does what we did today tie to our unit question?