Chapter 8 Toxicology: Poisons and Alcohol “All substances are poisons. There is none which is not. The right dose differentiates a poison and remedy.”---Paracelsus (1495-1541). Swiss physician and chemist. Was Paracelsus Right? *_________________—refers to the concept promoted by Paracelsus: that substances that kill at high doses are actually beneficial at low doses--________________________ -This appears to be true for many substances: ____________________________ Historical Perspective of Poisoners *____________________--a famous Greek poisoner *____________________--personal poisoner of Emperor Nero *_________________________--father was Pope Alexander VI *____________________________--committed over 600 successful poisonings, including two Popes. *_________________________--formed a society to teach women how to murder their husbands *_________________________________________________--French poisoners AND many others through modern times. People of Historical Significance *_____________________--known as the father of __________________________, published in 1814, “___________________________” which described the first systematic approach to the study of the chemistry and physiological nature of poisons. Toxicology *___________________--the study of the adverse effects of chemicals or physical agents on living organisms. *Types: 1. ___________________________--air, water, soil 2. ___________________________--foods, cosmetics, drugs 3. __________________________________--prescription medication 4. ____________________________--use of toxicology to aid in the investigation of death, poisoning and drug use. Forensic Toxicology *____________________--medical examiner or coroner *___________________--motor vehicle accidents (MVA) *___________________--drug testing *___________________--human and animal *___________________--industrial, catastrophic, terrorism Toxins *Toxin—a substance that causes ____________________________________ on contact or absorption, typically by interacting with enzymes and receptors. (Usually a naturally produced substance that kills rapidly in small quantities) Toxic Substances *Toxic substances may: 1. ________________________________ 2. ________________________________ 3. ________________________________ 4. ________________________________ Elements of Toxicity 1. _________________: many substances are only lethal in high doses 2. The _________________________________ of the substance Ex: Arsenic is not very poisonous in its natural form (metal); but arsenic trioxide or arsenic gas is very poisonous 3. The ______________________ into the body: some substances are most poisonous if _____________________; others must be ________________________________ 4. _______________________ and physiological conditions of the victim, including age and sex Ex: Blood alcohol content is directly _______________________________ Infants and elderly are more __________________________________ 5. The ________________________________ -Sometimes ________________________________________ create a tolerance for the toxin -_______________________ (larger amounts over time) can create serious medical problems -_______________________--very large dose causing immediate problems, including death 6. The presence of _____________________________________ or in the dose. -_______________________: combination of two chemicals increases the effects of both in the system Ex: antihistamine and alcohol -_______________________: combination of two chemicals decreases the effects of both in the system Ex: Chelating agent and arsenic Lethal Dose *_______--refers to the dose of a substance that _______________________________, usually within _______________ (Note: test population is usually mice or rats) *Expressed in ____________________________________________________________. A correlation is then made to humans based on the body weight data. *However, estimating lethal doses for humans is often complicated by the fact that resistance to certain chemicals __________________________ between species. Toxicity Classes LD50 (rat, oral) <1mg/kg 1-50 mg/kg 50-100 mg/kg 500-5000 mg/kg 5-15 g/kg Over 15 g/kg Correlation to Ingestion by 150lb Adult Human a taste to drop to a teaspoon to an ounce to a pint to a quart more than 1 quart Toxicity LD50 Update *Because a single test may kill as many as ___________________, the U.S. and other members of the Organization for Economic Cooperation and Development agreed in December 2000 to phase out the LD50 test in favor of alternatives that ____________ _____________________________________________________________________ Federal Regulatory Agencies *To ensure public safety, the federal government has created several regulatory agencies related to toxic substances: 1. __________________________________--deals with pharmaceuticals, food additives, and medical devices 2. __________________________________--works with agricultural and industrial chemicals released to the environment 3. _________________________________--concerned with toxins in consumer products 4. ________________________________ --watches shipment of toxic chemicals 5. ____________________________________________--concerned with exposure to chemicals in the workplace Symptoms of Various Types of Poisoning Type of Poison Symptom/Evidence Characteristic burns around the lips and mouth of the victim Red or pink patches on the chest and thighs, unusually bright red lividity Black vomit Greenish-brown vomit Yellow vomit Coffee brown vomit. Onion or garlic odor Burnt almond odor Pronounced diarrhea Nausea and vomiting, unconsciousness Possibly blindness Critical Information on Poisons Form Common color Characteristic odor Solubility Taste Common sources Lethal dose Mechanism Possible methods of administration Time interval of onset of symptoms Symptoms resulting from an acute exposure Symptoms resulting from chronic exposure Disease states mimicked by poisoning Notes relating to the victim Specimens from victim Analytical detection methods Known toxic levels Notes pertinent to analysis of poison List of cases in which poison was used To Prove a Case *Prove a _______________________________ *__________________ *__________________ *Access to __________________ *Access to __________________ *Death was _____________________________ *Death was ______________________ Forensic Autopsy *Look for: 1. _________________________ 2. Characteristic _____________ 3. ______________________--single transverse white bands on nails *Order toxicological screens 1. ____________________________ should be done at the scene for comparison 2. No realistic calculation of dose can be made from a _______________________ Human Specimens for Analysis *___________________________ *___________________________ *___________________________ *___________________________ *___________________________ *_________________________ *_________________________ *_________________________ *_________________________ Alcohol—Ethyl Alcohol (C2H5OH) *_____________________________ in America *About ______________________________ are alcohol related *__________--affecting the ____________________________, especially the ________ *Colorless liquid, generally diluted in water *Acts as a _____________________ *Alcohol ___________________________________ of consumption: 30-90 minutes for full absorption *__________________--about 90% is done in the liver at a rate of about 0.015% per hr. *About _____________________ unchanged in breath, perspiration and urine Rate of Absorption *Depends on: 1. _______________ of alcohol consumed 2. the _______________________ of the beverage 3. __________________________________ 4. __________________________________ present in the stomach 5. _____________________ of the consumer BAC Blood Alcohol Content *Expressed as ___________________________________________________ *Legal limits in all states is ___________ (0.08 grams of pure alcohol for every 100 ml of blood) *Parameters influencing BAC: 1. ___________________________ 2. ___________________________ 3. _____________________________________ 4. _____________________________________ BAC *Burn off rate of 0.015% per hour but can vary: *Male: BAC male = *Female: BAC female = Sample Problem: What would be the approximate BAC of a 185 pound man who has consumed three shots (1.5 oz. each) of Jack Daniels (80 proof = 40% alcohol) in an hour? Henry’s Law *Henry’s Law provides ______________________ for the breath test check for sobriety. *When a volatile chemical is dissolved in a liquid and is brought to equilibrium with air, there is a fixed ratio between the concentration of the volatile compound in the air and its concentration in the liquid; this ratio is constant for a given temperature. *THEREFORE, ____________________________________________________________ *This ratios of alcohol in the blood to alcohol in the alveolar air is approximately 2100 to 1. In other words, 1 ml of blood will contain nearly the same amount of alcohol as 2100ml of breath. Field Tests *_________________________--used to determine the degree of suspect’s physical impairment and whether or not another test is justified. *_______________________________--3 Basic Tests 1. _____________________________________: follow a pen or small flashlight, tracking left to right with one’s eyes. In general, wavering at 45 degrees indicates 0.10 BAC 2. _____________________________________: comprehend and execute two or more simple instructions at one time 3. _____________________________________: maintain balance, comprehend and execute two or more simple instructions at one time. The Breathalyzer *Invented in _____________ *More ____________________________ *Collects and __________________________________________________________ *Breath sample mixes with _______________________________________________ *Potassium dichromate is yellow, as concentration decreases its light absorption diminishes so the breathalyzer indirectly measures alcohol concentration by ____________________________________________________________________ ____________________________________________________________________ Generalizations *During absorption, the concentration of alcohol in _______________________ will be higher than in ________________________ *Breath tests reflect alcohol ________________________________________________ *The breathalyzer also can react with acetone (as found with diabetics), acetaldehyde, methanol, isopropyl alcohol, and paraldehyde, but these are toxic and their presence means the person is in serious medical condition. *Breathalyzers _______________________________ absorption device with a _____________________. Prints out a card for a permanent record.