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such as chlorpyrifos by CYP2B6 and CYP3A4, could have higher or lower risk factors
in some proportion of the exposed population dependent upon the distribution of the
relevant polymorphisms (
Dai et al., 2001; Hodgson and Rose, 2007; Tang et al., 2001
).
TOLERANCE AND RESISTANCE
The terms resistance and tolerance refer to a relative lack of susceptibility of a popula-
tion of organisms to the effects of a toxicant. If the genetic trait pre-exists in a popu-
lation so that it is obvious when the population is first exposed to the toxicant, this
should be regarded as tolerance rather than resistance, the latter term being reserved
for those cases in which the trait is brought to an observable level only through selec-
tion brought about by exposure to the toxicant. It is clear that many instances of resis-
tance are based on differences in toxicant metabolism that distinguish the resistant from
the nonresistant population.
Tolerance
Tolerance to a compound is often the result of an organism's increased ability to
metabolize the chemical subsequent to an initial exposure. This is true, for example,
in connection with the pesticides nicotine (
Werle and Uschold, 1948
) and dieldrin
(
Wright et al., 1972
).
In a few instances, it has been shown clearly that the increased metabolism respon-
sible for tolerance was mediated by higher activity of the microsomal enzymes of the
liver. It seems likely that the same explanation will hold in connection with some
other instances of tolerance. As recorded in Chapter 7, pesticides frequently act as
inducers of microsomal enzymes. Because activity of these enzymes usually leads to
detoxication, it seems likely that many of the compounds listed as inducers are capable
of producing tolerance under suitable conditions.
Tolerance also may exist in situations in which it has been impossible to demon-
strate any increased ability to metabolize the toxicant; finally, there are instances of tol-
erance for which the mechanism is not only unknown but unexplored. For example,
rodents may develop true tolerance, as distinguished from bait shyness, to a number of
rodenticides including arsenic oxide, zinc phosphide, strychnine, sodium fluoroacetate,
ANTU, and norbormide (
Lund, 1964, 1967
). Certain populations of pine mice sub-
jected to control with endrin lost susceptibility to the compound, but sublethal expo-
sure conferred a degree of tolerance regardless of the past history of the population
(
Webb and Horsfall, 1967
).
Resistance
Resistance in the toxicological sense is better known in insects and a variety of other
pest species than in vertebrates. Many insect species with public health importance
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