INTRODUCTION TO TOXICOLOGY Background Information for “Toxicity Testing with California Blackworms and Alcohol” Created by Stefani D. Hines with modifications by Debbie Gevirtzman, SWEHSC, University of Arizona

Toxicology What is it? How is it used?

Toxicology The study of harmful effects of chemicals on living systems The chemicals are called toxicants. (Toxins are toxicants produced by living organisms, ie. Snake venom.) Chemicals may be man-made or naturally-occurring. ~9 million patented chemicals millions of non-patented chemicals in perfumes and cosmetics even more are naturally occurring in the environment

Toxicology Biology Chemistry Physiology Physics Statistics Immunology Ecology Forensic Medicine Clinical Treatments Drug Development Public Health Industrial Hygiene Veterinary Science Agriculture Environmental Science

You are already toxicologists! CONGRATULATIONS! You are already toxicologists! You didn’t pour Drano into your cereal this morning. You only took 2 Tylenol for your headache instead of the whole bottle. You didn’t stand by the bus’s tailpipe and inhale the fumes. You have have already learned a lot about toxicology on your own through life’s lessons.

Hazard A chemical substance, physical agent, or biological agent that can harm the health of people

Exposure Contact with a hazard The hazard must enter the body! ie. A pack of cigarettes in a man’s shirt pocket does not cause him harm because nothing from the cigarettes has entered his body. Once he smokes a cigarette, the smoke has now entered his body through his lungs and can cause harm.

Routes of Entry

Routes of Entry Ingestion – chemicals can enter the body by eating or drinking Inhalation – chemicals can be breathed into the lungs Absorption - chemicals can enter the body by moving through the skin Ingestion – From digestive tract, to liver and lymphatic system to bloodstream – ie. Alcohol, drugs Inhalation – the inside surface area of the lungs is very large and is a poor chemical barrier; many inhaled chemicals can easily and quickly enter the bloodstream from lung tissue – ie. smoke Absorption – the skin is a good barrier and protects the body from many hazards, but some substances can penetrate the skin, then enter the bloodstream and be carried to all parts of the body – ie. insect repellent used by the military can be sprayed on clothing, but not on skin

Dose Dose is the amount of a chemical that gets inside of your body. Measured in mg of chemical/kg or lb of weight

Dose: A Visual Explanation

Who took the largest dose of Tylenol? Weight: 125 lb 135 lb 20 lb 5 lb Tylenol: 300 mg 600 mg 100 mg 50 mg

Calculating Dose: 50 mg  5 lb = 10 mg/lb 300 mg  125 lb = 2.4 mg/lb

The Dose Makes The Poison “What is it that is not a poison? All things are poisons and nothing is without poison. It is the dose only that makes a thing not a poison.” Paracelsus, 1493-1541 Paracelsus is considered “the father of modern toxicology”. Ie. 2 Tylenol are ok, but not a whole bottle; 2 Tylenol are ok for an adult, but not for a baby; small amounts of salt or sugar are ok, but a whole pound at once can kill a person.

Most hazardous substances exhibit a “dose-response” relationship Most hazardous substances exhibit a “dose-response” relationship. What does this mean? A. The harm caused by the hazard increases as the amount of hazard entering the body (dose) increases. B. It does not matter how big a dose you receive, you will always have the same amount of harm/sickness. C. Exposure to the hazard always results in harm. A At low doses - there will be no detectable affect Mid-range – damage increases as dose increases High doses – maximum level of damage is reached

Dose-Response Curve for Alcohol Death Labored breathing Unconscious Deep sleep Response Sleep Giddy Absorption from the digestive tract is very rapid with peak blood levels attained 30-60 minutes after ingestion. Typically, it takes one drink an hour to burn off. 1 glass of wine = 1 shot = 1 beer No effect No effect Dose

Dose-Response Curve for Vitamin D Toxic Healthy Response Unhealthy Dose

Exposure Exposure Frequency – how often Exposure Duration – how long Exposure Concentration – how much Exposure Frequency – a person exposed only once is likely to have a lower dose than a person exposed many times. Exposure Duration - a person exposed for a short time will have a lower dose than a person exposed for a long time. Exposure Concentration – a higher concentration of a hazard generally means a higher dose because there is more of the hazard to enter the body.

For a Chemical to Affect You Exposure Dose

Toxicity Acute Toxicity – a high toxicant dose over a short period of time Chronic Toxicity – a small dose of a toxicant over a long period of time Acute Toxicity – ie. A chemical spill; drugs or alcohol ingested in a short period of time Chronic Toxicity – ie. Hazardous material in the air at a factory at which you work; smoking

Factors Affecting Toxicity Extrinsic Factors – occur outside the body Intrinsic Factors – occur within an individual organism Extrinsic Factors – ie. Temperature, barometric pressure

Intrinsic Factors Age Genetic Difference Body Size Age – the old and the very young are more likely to be adversely affected. Genetic Difference – can increase or decrease the tolerance to a toxicant. Body Size – the larger the body size, the less response to a toxicant; this is because the dose is smaller when compared to someone who weighs less but ingested the same amount of toxicant.

Control Our biggest chemical risks are with things we have control over

Control Food Exposure to Known Hazards in Daily Lifestyle Cigarettes Alcohol Preventable Poisonings

Factors Contributing to Cancer Risk in the U.S. Diet ~35% Tobacco ~30% Occupational exposures & pollution ~5% Infection (viruses) ~10% Other ~20% Genetic susceptibility Sun/radiation Alcohol Make wise choices throughout your life and be at lower risk!

And now, let’s do the blackworm lab!