66 BIOLOGICAL EFFECTS OF LOW LEVEL EXPOSURES
Figure 4.2. Structures of carbon tetrachloride, bromotrichloromethane, and chloroform
as examples of halomethane solvents. Hepatotoxicity and lethality of these
solvents is remarkably amplified by the pesticide chlordecone.
4.3, Table 4.3) is not potentiated 104 except after exposure to high levels of
chlordecone.105 This remarkable capacity to potentiate halomethane hepato
toxicity does not appear to be related to chlordecone-induced cytochrome
P-450 or associated enzymes,55" 106 enhanced bioactivation of
CC14,41’42’54’86’104 increased lipid peroxidation,55 104 105 or decreased glu
tathione.107 Several candidate mechanisms were considered carefully until a
novel mechanism was discovered (Table 4.4).
Mechanism of the Interactive Toxicity of Chlordecone and CCI 4These findings led to some very basic studies concerning the progression
of the hepatotoxicity during a time course following CC1 4 administration to
either normal or chlordecone pretreated rats. The histochemical and histo-
morphometric experiments revealed that suppressed hepatocellular regener
ation and tissue repair might explain the remarkable amplification of CC1 4
toxicity by prior exposure to chlordecone.55 108 109 Similar time-course studies
on Ca2+ levels in the liver mitochondria, microsomes, and cytosol fractions
revealed a possible association of increased Ca2+ accumulation and sup
pressed hepatocellular regeneration.110111 Despite some reports that chlorde
cone interferes with Ca2+ uptake mechanisms in extrahepatic tissues,112 even
at toxic doses, chlordecone does not cause disruption of hepatocellular
Ca2+,113 while the chlordecone + CC1 4 interaction does remarkably so.110114