Lecture Outline ( September 30, 2011)

1. Lecture Outline(September 30, 2011) * Definitions: • Toxicology • Poison * Areas of Toxicology: 1) Forensic toxicology 2) Clinical toxicology 3) Environmental toxicology 4) Others * Classification of Toxic agents * Factors affecting the Toxicity: 1) Route of exposure 2) Duration of exposure (acute vs chronic) 3) Frequency of exposure (single vs multiple) 4) age (new born vs adult)

2. Toxicology Definitions Toxicology: * the science of poisons (toxicants). The study of adverse effects resulted from the exposure to xienobiotics (foreign substances) * Relatively new academic discipline PHA 4530 Fall 2011 (Dr. M. Kolta)

3. Toxicology Poison: * Any substance that can produce adverse effects on biological systems - which could lead to injury OR destruction of life. * Almost any substance can be toxic or poisonous. Paracelsus (1493-1541), a Swiss/ German/ Austrian physician, scientist reported that, “All things are poison and nothing (is) without poison. Only the dose determines that a substance is not a poison.” • Even water and sugar are toxic in large quantities. • The concentration or dose of a substance determines its toxicity • It is a quantitative rather than qualitative relationship

4. Areas of Toxicology Major areas: • Forensic toxicology • Clinical toxicology • Environmental toxicology • Others (i.e., experimental, regulatory, Neuro, hepato, ocular, molecular, nephro) All Branches correlate and depend upon each other

5. Areas of Toxicology • Forensic toxicology(Analytical Chemistry + fundamental Toxicology)   Deals with the detection of poisoning from a legal point of view • Finding applications due to law enforcement (identify the cause of death), (FDLP, Crime Lab) • Examples: • Drug overdose • Homicides • Rx abuse • Suicides

6. Areas of Toxicology 2). Clinical toxicology (MD, emergency medicine + poison management) • Uses an application of knowledge • Bring all the information from all areas • Deals with detection/identification of poison in Human – (Hospital ER, Poison Control Centers) • Concerns with treating patients who have been poisoned • §   Managing • §   Identify • §   Prevention/treatment

7. Areas of Toxicology 3) Environmental toxicology (advanced knowledge of toxicology + biological systems), • Deals with the effects of environmental toxicants on the health of living organisms in the Eco. System • Examples:        * The poisoning of human, animals and plants (Academia, ATSDR, EPA) * The purity of the air (respiration) and water (EPA)        * Concerns with the conditions in manufacturing plants (occupational) (OSHA)

8. Classification of Toxic Agents • Target tissue or organ: (i.e., liver, kidney, lung, CNS,…) • Their use: (i.e., pesticides, medical, food additives) • Their sources (i.e., animal, plant, or synthetics) • Their effects: (i.e., Cancer, liver damage, kidney failure, …) • Their physical status: (i.e., powder, liquid or gas) • Their chemistry: (i.e., aromatic amines, halogenated hydrocarbons, …) • Labeling requirements: (i.e., flammable, corrosive, for handling, transporting, storage, ..) • Poisoning potential: (i.e. , extremely toxic, very toxic, slightly toxic)

9. Factors affecting the Toxicity • 1.      Rout of exposure • 2.      Duration (acute vs chronic) • 3. Frequency of exposure • 4.     Age (new born vs adult)

10. Factors affecting the Toxicity 1. Route of exposure: * GI tract (ingestion, PO): (In real life, PO from drug over dose, suicides, accidental poising-contamination, high incidence in toddlers ) * Lung (inhalation) & * Topical:(skin, mucous membrane): (poisoning in the work place, occupational , terrorist chemical warfare) * Other (Parenteral, injection): (IV most rapid effect, drug over dose, suicides, homicidal, animal bites snake, spider, bees, scorpions, jelly fish) (IV> Inhalation> IP> SQ> IM> ID> PO> Topical)

11. Factors affecting the Toxicity Route of exposure can affect the degree of toxicity, i.e., if a toxic agent is detoxified in the liver → will have much less toxic effect when is given PO vs IV or inhalation (example: snake bite)

12. Factors affecting the Toxicity 2. Duration of exposure: * Acute vs Chronic *Acute: single exposure/24 hr (PO, IP, IV, SQ, dermal), life threatening crises, of accidentals overdose or suicidal attempt) * Chronic: daily exposure >3 months (PO, SQ, IV), in life, accumulation of daily intake of food additives, agricultural chemical in food

13. Factors affecting the Toxicity 2. Duration of exposure: * The degree of toxicity for the same agent is varies between acute vs chronic exposure; i.e., Benzene Acute: CNS depression Chronic: Leukemia

14. Factors affecting the Toxicity • 3. Frequency of exposure: • Single dose vs multiple doses • The degree of Toxicity depends on the rate of * metabolism • * elimination • * accumulation (storage) • i.e., Methamphetamine • ** Single dose (20mg/kg)—death • ** Divided dose (4x @ 5mg/kg)---mild hyperthermia, but no death

15. Factors affecting the Toxicity • 4. Age (new born vs adult): * New born, infants and toddlers are more susceptible to the toxicity of an agent (same dose) than an adult: * Morphine: 3x more toxic in new born vs adult * Pb: causing encephelo-myelo-pathy in new born (Pubs) rats but not in adult rats ** In new born, infants and toddlers, the BBB and some physiological systems are not completely developed