Toxicology of Industrial Compounds

1,1,2-Trichloroethylene
N.P.E.VERMEULEN ET AL. 27
The solvent properties of 1,1,2-trichloroethylene (TRI) have resulted in its
widespread use in metal degreasing and a wide variety of other industrial
applications. TRI has now been in common use for more than 50 years.
During this period of time, workers have been exposed to a wide range of
concentrations, in some cases for periods of 25 years or longer. This has
allowed the compilation of a great data base about the effects of TRI on
human health. Moreover, information has been supplemented by
numerous studies in experimental animals.
Epidemiological studies on more than 15000 individuals with a followup
of more than 25 years have shown no evidence of an association
between human exposure to TRI and increased incidence of cancer or
cancer mortality. However, several of these studies had more or less serious
shortcomings. A summary of effects related to TRI and/or TRI-related
metabolism is given in Table 2.3. These and other data are taken from
Goeptar et al., 1995a.
An increased incidence of lung tumors has been reported in female
B 6C 3F 1 and male Swiss mice exposed to TRI by inhalation. The effect was
not observed in male B 6C 3F 1 nor in female Swiss mice nor in rats. This
apparent strain-, sex- and lung-specific response fails to resolve the issue of
whether or not TRI is a carcinogenic hazard to man. Mechanistic studies
on mouse lung tumor formation have explained the sex and species
differences. In this context, chloral formation (Figure 2.10) in Clara cells,
containing relatively high cytochrome P-450 concentrations, has been
identified to be responsible for the development of mouse lung tumors.
Importantly, lung tumors have not been found in humans after long-term
occupational exposure in TRI.
TRI causes an increase in the incidence of liver cancer in both sexes of
B 6C 3F 1 and Swiss mice following either gavage or inhalatory exposure, but
not in NMRI and Ha: ICR mice nor in rats. A rodent specific link between
peroxisome proliferation, DNA synthesis, inhibition of intercellular
communication and cancer (Table 2.3) suggests that these responses are the
basis of the hepatocarcinogenicity induced by TRI. The identification of
TCA in cancer bioassays as the responsible metabolite for these effects
confirmed this hypothesis. However, when TCA was administered to both
rats and mice, liver cancer was only observed in mice and not in rats. The
reason for this species selectivity in liver effects is explained by the kinetic
behavior of TRI and TCA in rodents. Both rats and mice have a considerable
capacity to metabolize TRI to TCA and TCE, the maximal capacities being
closely related to the relative surface areas rather than to their body
weights. Oxidative metabolism of TRI in rats is linearly related to dose at
lower dose levels, but it becomes saturated at higher dose levels. Thus, an
important difference between rats and mice is the lower saturation