PRINCIPLES OF TOXICOLOGY

18 GENERAL PRINCIPLES OF TOXICOLOGY
Figure 1.4 By plotting the cumulative dose–response curves (log dose), one can identify those doses of a toxicant
or toxicants that affect a given percentage of the exposed population. Comparing the values of LD50A to LD50B or
LD50C ranks the toxicants according to relative potency for the response monitored.
as coma or liver injury, and much lower doses than fatal exposures. This situation is shown in Figure
1.5, and it can be easily seen that understanding the relationship of the three dose–response curves
might allow the use of sentinel effects (represented in Figure 1.5 by the SD curve) to prevent
overexposure and the occurrence of more serious toxicities.
The difference in dose between the toxicity curve and a sentinel effect represents the margin of
safety. Typically, the margin of safety is calculated from data like that shown in Figure 1.5, by dividing
TD 50 by the SD 50 . The higher the margin of safety, the safer the chemical is to use (i.e., greater room
for error). However, one may also want to use a more protective definition of the margin of safety (for
example, TD 10 /SD 50 or TD 01 /SD 100 ) depending on the circumstances of the substance’s use and the
ease of identifying and monitoring either the sentinel response or the seriousness of the toxicity
produced. Changing the definition to include a higher percentile of the sentinel dose–response curve
(e.g., the SD 100 ) and correspondingly lower percentile of the toxic dose–response curve (e.g., the TD 10
or the TD 01 ) forces the margin of safety to be protective for the vast majority of a population.
TABLE 1.5 A Relative Ranking System for Categorization of the Acute Toxicity of a Chemical
Probable Oral Lethal Dose for Humans
Toxicity Rating or Class Dose (mg/kg) For Average Adult
1. Practically nontoxic > 15,000 > 1 quart
2. Slightly toxic 5000–15,000 1 pint to 1 quart
3. Moderately toxic 50–5000 1 ounce to 1 pint
4. Very toxic 50–500 1 teaspoonf ul to 1 ounce
5. Extremely toxic 5–50 7 drops to 1 teaspoonf ul
6. Supertoxic < 5 < 7 drops
Source: Reproduced with permission of the American Industrial Hygiene Association Journal.