Revival: Biological Effects of Low Level Exposures to Chemical and Radiation (1992)

64 BIOLOGICAL EFFECTS OF LOW LEVEL EXPOSURES

Table 4.1. Amplification of Lethal Effects of Several Halomethanes by Dietary
Exposure of Rats to Subtoxic Contaminants

Dietary
Pretreatment Halomethane

48-hr LD50

(mL/kg)

Increase

in Toxicity

(-fold)

Female rats
Control CCI4 1.25 —
Chlordecone (10 ppm) CCI4 0.048 26

Male rats
Control CCI4 2.8 —
Chlordecone (10 ppm) CCI4 0.042 67
Phenobarbital (225 ppm) CCI4 1.7 1 .6a
Control BrCCI3 0.119 ___
Chlordecone (10 ppm) BrCCI3 0.027 4.5

Source: Adapted from Mehendale.16
aNot significant at P < 0.05.

production of *CC1 3 and CC1 302 radicals leads to increased lipid peroxida­
tion, culminating in increased liver injury.12

Interactive Toxicity of Chlordecone and CCI 4

From a perspective of public health, a major toxicological issue is the

possibility of unusual toxicity due to interaction of two or more toxic chem­
icals at individually harmless levels upon environmental or occupational
exposures. While some laboratory models exist for such interactions for the
simplest case of only two chemicals, progress in this area has suffered for

want of models where the two interactants are individually nontoxic. One
such model is available, where prior exposure to nontoxic levels of the
pesticide Kepone (chlordecone) results in a 67-fold amplification of CC1 4
lethality in rats (Table 4.1). The mechanism of the remarkable interactive
toxicity is of interest in the assessment of risk from exposure to combina­
tions of chemicals.
Prior exposure to nontoxic level of chlordecone (10 ppm in diet for 15
days) results in a marked amplification of CC1 4 hepatotoxicity 55 98 and
lethality.56’98 " Neither the close structural analogs of chlordecone (mirex
and photomirex) nor phenobarbital (Figure 4.1) exhibit this property.55 56
Plaa and associates 100101 have demonstrated the capacity of chlordecone to
potentiate CHC1 3 hepatotoxicity in mice. These observations have been
extended to demonstrate that in addition to the hepatotoxic effects, lethal
effect of CHC1 3 is also potentiated by exposure to 10-ppm dietary chlorde­
cone 102 (Table 4.2) and that this may be associated with suppressed repair of
the liver tissue.103 Chlordecone also potentiates the hepatotoxicity and
lethality of BrCCl3.9192 While the toxicity of these closely related halome­
thanes is potentiated by such low levels of chlordecone (Figure 4.2), the
toxicity of structurally and mechanistically dissimilar compounds (Figure