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By F. Sherwood Taylor

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For example, bacteria do not absorb folic acid but synthesize it from p-aminobenzoic acid, glutamic acid, and pteridine, whereas mammals cannot synthesize folic acid but have to absorb it from the diet. Thus, sulfonamide drugs are selectively toxic to bacteria because the sulfonamides, which resemble p-aminobenzoic acid in both charge and dimensions, antagonize the incorporation of p-aminobenzoic acid into the folic acid molecule—a reaction that humans do not carry out. Species Differences Although a basic tenet of toxicology is that “experimental results in animals, when properly qualified, are applicable to humans,” it is important to recognize that both quantitative and qualitative differences in response to toxic substances may occur among different species.

Individual, or Graded, Dose–Response Relationships Individual dose–response relationships are characterized by a doserelated increase in the severity of the response. The dose relatedness of the response often results from an alteration of a specific biochemical process. For example, Fig. 2-3 shows the dose– response relationship between different dietary doses of the organophosphate insecticide chlorpyrifos and the extent of inhibition of two different enzymes in the brain and liver: acetylcholinesterase and carboxylesterase.

Comparison of effective dose (ED), toxic dose (TD), and lethal dose (LD). The plot is of log dosage versus percentage of population responding in probit units. to elicit the desired therapeutic response. Similarly, an index of comparative toxicity is obtained by the ratio of doses of two different materials to produce an identical response or the ratio of doses of the same material necessary to yield different toxic effects. The most commonly used index of effect, whether beneficial or toxic, is the median dose—that is, the dose required to result in a response in 50 percent of a population (or to produce 50 percent of a maximal response).

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A History Of Industrial Chemistry by F. Sherwood Taylor


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