PRINCIPLES OF TOXICOLOGY

24 GENERAL PRINCIPLES OF TOXICOLOGY
TABLE 1.9 Chemical Interactions with Ethanol
Agent Toxic Interaction Mode: Mechanism
Aspirin Increased gastritis Functional—both agents irritate the GI
tract
Barbiturates Increased barbiturate toxicity Functional/Dispositional—both agents are
CNS depressants; altered
pharmacokinetics and
pharmacodynamics of the barbiturates
Benzene Increased benzene-induced hematotoxicity Dispositional—enhanced benzene
bioactivation to toxic metabolites
Caffeine Caffeine antagonizes the CNS depressant Functional—both agents affect the CNS,
effects of ethanol
but one is a stimulant and one is a
depressant
Carbon disulfide Enhanced CS2 toxicity Dispositional—increased CS2
bioactivation and retention in critical
tissues
Chloral hydrate Increased CNS sedative effects of chloral Functional/dispositional—both agents are
hydrate
CNS depressants; ethanol also alters the
metabolism of chloral hydrate, leading
to greater trichloroethanol accumulation
Ethylene glycol Decreased ethylene glycol toxicity Dispositional—ethanol inhibits the
metabolism of ethylene glycol to its
toxic metabolites
Nitrosamines Increase in formation of extrahepatic Dispositional—ethanol alters the tissue
tumors induced by nitrosamines distribution of nitrosamines by
inhibiting hepatic metabolism
Source: Adapted from Calabrese (1991).
To help illustrate the ways in which chemical interactions are increased (additive, potentiation,
synergism) or decreased (antagonism), Tables 1.9 and 1.10, adapted from a textbook on chemical
interactions by Edward Calabrese, are provided. Table 1.9 summarizes a few of the chemical
interactions identified for drinking alcohol (ethanol) and other chemical agents that might be found in
home or occupational environments.
Like alcohol, smoking may also alter the effects of other chemicals, and the incidence of some
minor drug-induced side effects have been reported to be lower in individuals who smoke. For example,
TABLE 1.10 Aquatic Toxicity Interactions between Ammonia and Other Chemicals
Chemicals Toxic Endpoint Ratio of Chemical EC50s Interaction
Ammonia + cyanide 96-h LC50 1 : 1 Additive
Ammonia + sulfide 24-h LC50 1 : 2.2 Antagonism
Ammonia + copper 48-h LC50 1 : 1 Additive
48-h LC25 1 : 1 Synergism
48-hr LC10 1 : 1 Synergism
Ammonia + phenol 24-h LC50 1 : 0.1 Antagonism
1 : 0.7 Additive
Ammonia + phenol + zinc 48-h LC50 1 : 1 : 0.5 Additive
1 : 7 : 1 Synergism
1 : 1 : 6 Antagonism
Source: Adapted from Calabrese (1991).