PRINCIPLES OF TOXICOLOGY

8 GENERAL PRINCIPLES OF TOXICOLOGY
TABLE 1.1 Cross-Matching Exercise: Comparative Acutely Lethal Doses
The 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 the
answer table at the end of the chapter.
A B
N LD50 (mg/kg) Toxic Chemical Correct Order
1 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 the
pesticide 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 these
substances 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 the
substance is per unit of exposure. Review the correct answers in the table found at the end of this
chapter.
Defining Dose and Response
Because 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 for
estimating the safe exposure level for a chemical. A dose–response relationship is said to exist when
changes in dose produce consistent, nonrandom changes in effect, either in the magnitude of effect or
in the percent of individuals responding at a particular level of effect. For example, the number of
animals dying increases as the dose of strychnine is increased, or with therapeutic agents the number
of patients recovering from an infection increases as the dosage is increased. In other instances, the
severity of the response seen in each animal increases with an increase in dose once the threshold for
toxicity has been exceeded.
The Basic Components of Tests Generating Dose–Response Data
The design of any toxicity test essentially incorporates the following five basic components:
1. The selection of a test organism
2. The selection of a response to measure (and the method for measuring that response)
3. An exposure period