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incidence data on male rats for three exposures beyond controls. CDHS (1990) chose to develop
cancer risk estimates for VC using both the human and animal data described above.
Methodology
Human-derived risk estimates
The review of the epidemiological studies strongly suggests a causal association between vinyl chloride
and several different types of cancer, including liver, lung, and brain. However, none of the
occupational cohort studies presented exposure data for a large enough cohort to derive a
dose-response curve; so the CDHS (1990) analysis used historical industrial hygiene data to reconstruct
a range of likely exposures, from which risk estimates can be extrapolated.
This risk analysis proceeds by selecting the Waxweiler et al. (1976) study of 1294 workers who
experienced high sustained exposures to vinyl chloride and who were followed long enough (10 years)
to develop substantial numbers of cancers that appeared to be related to the exposure. The
retrospective estimates of Barnes et al. (1976) for the relevant industrial processes furnished
concentrations of the exposures of vinyl chloride, having an overall average value of 647 ppm. The
analysis converts these annual average exposure estimates to a lifetime daily equivalent tissue exposure
of 3.6 ppm on the assumption of a saturable metabolic process (Michaelis-Menten) leading to active
carcinogens. This is based on extrapolated measurements of binding rates to macromolecules (Gehring
et al. 1977). The seven liver cancer deaths reported for that cohort project to a lifetime risk of .039
(.089 upper confidence limit) per worker for liver cancers. That risk divided by the overall lifetime daily
equivalent of effective exposure yields unit risk estimates for that malignancy.
The calculations provided the following upper confidence limits (UCL) on unit risks: 2.5 × 10 -5 ppb -1 for
liver cancers, and 4.5 × 10 -5 ppb -1 for three sites of cancer combined, liver, lung and brain. Each of
these three sites of cancer had a significantly elevated SMR when calculated for a 15-year follow up
time. The unit risks calculated in this manner are about six times greater than would be calculated by
using actual exposures instead of the effective exposures that take account of the metabolic saturation in
the tissue.
Animal-derived risk estimates
The animal bioassay-based quantitative risk assessment analyses performed by CDHS (1990) used the
computer program GLOBAL86 to calculate potential risks using a linearized multistage procedure that
were associated with vinyl chloride exposure. Significant trends for liver angiosarcoma dominated the
results of the modeling. All three analyses of female rats and two of the three analyses of male rats met
the statistical criterion (p > 0.05) for goodness of fit of the dose-dependent response of liver
angiosarcoma (LAS) to vinyl chloride. In addition, the following experimental groups met that criterion:
lung carcinoma in the Swiss mice of Drew et al. (1983), lung angiosarcoma in the Wistar rats of Bi et
al. (1985), and mammary tumors in both the Sprague Dawley rats of Maltoni et al. (1984) and the
F-344 rats of Drew et al. (1985).
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