Toxicology Toxicology—the study of the adverse effects of chemicals or physical agents on living organisms Types: Environmental—air, water, soil Consumer—foods, cosmetics, drugs Medical, clinical, forensic

Forensic Toxicology Postmortem—medical examiner or coroner Criminal—motor vehicle accidents (MVA) Workplace—drug testing Sports—human and animal Environment—industrial, catastrophic, terrorism

Toxicology Toxic substances may: Be a cause of death Contribute to death Cause impairment Explain behavior

Historical Perspective of Poisoners Olympias—a famous Greek poisoner Locusta—personal poisoner of Emperor Nero Lucretia Borgia—father was Pope Alexander VI Madame Giulia Toffana—committed over 600 successful poisonings, including two popes Hieronyma Spara—formed a society to teach women how to murder their husbands Madame de Brinvilliers and Catherine Deshayes—French poisoners.

People of Historical Significance Mathieu Orfila—known as the father of forensic toxicology, published in 1814 Traité des poisons which described the first systematic approach to the study of the chemistry and physiological nature of poisons

Aspects of Toxicity Dosage The chemical or physical form of the substance The mode of entry into the body Body weight and physiological conditions of the victim, including age and sex The time period of exposure The presence of other chemicals in the body or in the dose

Lethal Dose LD50 refers to the dose of a substance that kills half the test population, usually within four hours Expressed in milligrams of substance per kilogram of body weight

Toxicity Classification LD50 (rat,oral) Correlation to Ingestion by 150-lb Adult Human Toxicity <1 mg/kg a taste to a drop extreme 1–50 mg/kg to a teaspoon high 50–500 mg/kg to an ounce moderate 500–5,000 mg/kg to a pint slight 5–15 g/kg to a quart practically nontoxic Over 15 g/kg more than 1 quart relatively harmless

Federal Regulatory Agencies Food and Drug Administration (FDA) Environmental Protection Agency (EPA) Consumer Product Safety Commission Department of Transportation (DOT) Occupational Safety and Health Administration (OSHA)

Summary Questions: Read p. 208-214 What is Clostridium botulinum commonly used for today? Explain hormesis? How was Socrates poisoned? What were the common poisons during the European Renaissance? What was the importance of Mathieu Orfila’s 1814 book “Traite des poisons”? Explain how the Marsh test was used in the 1840 trial of Marie Lafarge. Define chronic exposure. Define acute toxicity. How does synergism affect a substance? How does antagonism affect a substance? A lady is lying in bed & she is dead. Beside her is a pool of liquid & two pieces of wood. How did she die? Why is estimating lethal doses in humans very difficult? What is the lethal dose of nicotine in humans? Dogs? In Dec. 2004, how was Viktor Yushchenko (Ukranian Presidential candidate) poisoned? What is the LD50 in humans for Clostridium botulinum? Explain how Aleksandr Litvinenko was poisoned KGB operatives. What are some of the influences on the effect of poisons and toxins on the body? Why does arsenic accumulate in hair and fingernails? What is the LD50 of table salt for a 180-lb man? What would it be for MgCl2 (epson salt)? For NiCl2? Why is there such a difference? What is LD100?

Lead Poisoning: Lead compounds are not highly poisonous. But chronic exposure to lead poses a real health problem. Most common exposure is contact with lead-based paints (Banned in 1978). Lead-based paints taste sweet. A teething child will often lick and chew the paint.

Symptoms of Various Types of Poisoning Type of Poison Symptom/Evidence Caustic Poison (lye) Burns around lips & mouth of victim Carbon monoxide Red or pink patches on chest & thigh, unusually bright red lividity Sulfuric acid Black vomit Hydrochloric acid Greenish-brown vomit Nitric acid Yellow vomit Phosphorus Coffee-brown vomit, onion or garlic odor Cyanide Burnt almond odor Arsenic, mercury Extreme diarrhea Methyl (wood) or isopropyl (rubbing) alcohol Nausea & vomiting, unconsciousness, blindness

Critical Information Form Symptoms resulting from an acute exposure 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 crime was committed Motive Intent Access to poison Access to victim Death was homicidal Death was caused by poison

Forensic Autopsy Look for: Irritated tissues Characteristic odors Mees lines—single transverse white bands on nails Order toxicological screens Postmortem concentrations should be done at the scene for comparison. No realistic calculation of dose can be made from a single measurement.

Human Specimens for Analysis Blood Urine Vitreous humor of eyes Bile Gastric contents Liver tissue Brain tissue Kidney tissue Hair/nails

Summary Questions: Read p. 214-219 How can you determine whether there is lead in paint? What are three other sources of lead in the everyday environment? Describe how Georgi Markov was killed? What did his autopsy reveal? Some elements are naturally radioactive; that is they have either no stable isotopes or have one or more radioactive isotopes. List three common ones. What are the three types of particles emitted by radioactive substances? Which one is stopped most easily? Why? Would Litvinenko have died if he had merely spilled tea laced with Po-210 on his shirt?

Alcohol - Ethyl Alcohol (C2H5OH) Most abused drug in America About 40 percent of all traffic deaths are alcohol-related Toxic—affecting the central nervous system, especially the brain Colorless liquid, generally diluted in water Acts as a depressant Alcohol appears in blood within minutes of consumption; 30–90 minutes for full absorption Detoxification—about 90 percent in the liver About 5 percent is excreted unchanged in breath, perspiration, and urine

Rate of Absorption Depends on: Amount of alcohol consumed The alcohol content of the beverage Time taken to consume it Quantity and type of food present in the stomach Physiology of the consumer

BAC: Blood Alcohol Content Expressed as percent weight per volume of blood Legal limit in all states is 0.08 percent Parameters influencing BAC: Body weight Alcohol content Number of beverages consumed Time since consumption

BAC Calculation Burn-off rate of 0.015 percent per hour, but can vary: Male BAC = 0.071  (oz)  (% alcohol) body weight Female BAC = 0.085  (oz)  (% alcohol)

Henry’s Law 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, the concentration of alcohol in breath is proportional to that in the blood. This ratio of alcohol in the blood to alcohol in the alveolar air is approximately 2,100 to 1. In other words, 1 ml of blood will contain nearly the same amount of alcohol as 2,100 ml of breath.

Field Tests Preliminary tests—used to determine the degree of suspect’s physical impairment and whether or not another test is justified Psychophysical tests—three basic tests:

Horizontal gaze nystagmus (HGN): follow a pen or small flashlight, tracking left to right with one’s eyes. In general, wavering at 45 degrees indicates 0.10 BAC.

Nine-step walk and turn (WAT): comprehend and execute two or more simple instructions at one time

One-leg stand (OLS): maintain balance; comprehend and execute two or more simple instructions at one time

The Breathalyzer More practical in the field Collects and measures alcohol content of alveolar breath Breath sample mixes with 3 ml of 0.025 percent K2Cr2O7 in sulfuric acid and water: 2K2Cr2O7 +3C2H5OH + 8H2SO4  2Cr2(SO4)3 + 2K2SO4 + 3CH3COOH + 11H2O Potassium dichromate is yellow; as concentration decreases, its light absorption diminishes, so the breathalyzer indirectly measures alcohol concentration by measuring light absorption of potassium dichromate before and after the reaction with alcohol.

During absorption, the concentration of alcohol in arterial blood is higher than in venous blood. Breath tests reflect alcohol concentration in the pulmonary artery. The breathalyzer also can react with acetone (as found in diabetics), acetaldehyde, methanol, isopropyl alcohol, and paraldehyde, but these are toxic and their presence means the person is in serious medical condition. Breathalyzers now use an infrared light-absorption device with a digital readout. Prints out a card for a permanent record.

Summary Questions: Read p. 220-225. Define DUI? What is the rate of absorption of alcohol dependent upon? What is the BAC limit for alcohol? How much alcohol is metabolized in the liver? What is alcohol’s average rate of removal from the body? How do you calculate BAC for a male? Female? Define Henry’s Law. What would be the BAC of a 160-lb male who has consumed 2 pints (16 oz each) of beer (5% alcohol) in 1 hour? What is the distribution of alcohol between blood and air expelled deeply from the lungs? What does the Nystagmus test show for an intoxicated person? About how much total alcohol would you expect to find in the blood of a 110-lb woman with a BAC of 0.04? Calculate how much blood the woman above has in her body. Show your work. What would be the BAC of a 136-lb woman who has consumed three vodka tonics (2 oz. of vodka each, with vodka at 80 proof) during her lunch hour? If she forgets the time and talks for two more hours with her friend without having another drink, what will her BAC be when she gets back to work? A 165-lb man was involved in a car accident at 10 PM. His BAC was measured at the time at 0.08, which he said was impossible because he had only two beers (pint-size, 5% alcohol) just after work at 6 PM. How many beers did he actually have?