PRINCIPLES OF TOXICOLOGY - Biology East Borneo

8 GENERAL PRINCIPLES OF TOXICOLOGYTABLE 1.1 Cross-Matching Exercise: Comparative Acutely Lethal DosesThe chemicals listed in this table are not correctly matched with their acute median lethal doses(LD50’s). Rearrange the list so that they correctly match. The correct order can be found in theanswer table at the end of the chapter.ABN LD50 (mg/kg) Toxic Chemical Correct Order1 15,000 Alcohol (ethanol) ____________2 10,000 Arrow poison (curare) ____________3 4,000 Dioxin or 2,3,7,8-TCDD ____________4 1,500 (PCBs)—an electrical insulation fluid ____________5 1,375 Food poison (botulinum toxin) ____________6 900 Iron supplement (ferrous sulfate) ____________7 150 Morphine ____________8 142 Nicotine ____________9 2 Insecticide (malathion) ____________10 1 Rat poison (strychnine) ____________11 0.5 Sedative/sleep aid (phenobarbital) ____________12 0.001 Tylenol (acetaminophen) ____________13 0.00001 Table salt (sodium chloride) ____________the pain killer morphine compare to the acutely lethal potency of a poison such as strychnine or thepesticide malathion?Now take the allowable workplace chronic exposure levels for the following chemicals—aspirin,gasoline, iodine, several different organic solvents, and vegetable oil mists—and again rank thesesubstances going from the highest to lowest allowable workplace air concentration (listed in Table 1.2).Remember that the lower (numerically) the allowable air concentration, the more potently toxic thesubstance is per unit of exposure. Review the correct answers in the table found at the end of thischapter.Defining Dose and ResponseBecause all chemicals are toxic at some dose, what judgments determine their use? To answer this,one must first understand the use of the dose–response relationship because this provides the basis forestimating the safe exposure level for a chemical. A dose–response relationship is said to exist whenchanges in dose produce consistent, nonrandom changes in effect, either in the magnitude of effect orin the percent of individuals responding at a particular level of effect. For example, the number ofanimals dying increases as the dose of strychnine is increased, or with therapeutic agents the numberof patients recovering from an infection increases as the dosage is increased. In other instances, theseverity of the response seen in each animal increases with an increase in dose once the threshold fortoxicity has been exceeded.The Basic Components of Tests Generating Dose–Response DataThe design of any toxicity test essentially incorporates the following five basic components:1. The selection of a test organism2. The selection of a response to measure (and the method for measuring that response)3. An exposure period