home edit2 whole TSD November 2002 PDF format - OEHHA

studies of smelter workers in Anaconda, Montana by Welch et al. (1982), Higgins et al. (1985) and
Lee-Feldstein (1986), and in Tacoma, Washington by Enterline et al. (1987a).
Oral
US EPA (1995) conducted a review of the available literature and identified the studies by Tseng et al.
(1968, 1977) as the key references for quantifying ingested arsenic cancer potency. US EPA stated
that these studies demonstrate a causal association between arsenic ingestion and an elevated risk of
skin cancer. These data were considered reliable for the following reasons: 1) the study and control
populations (40,421 and 7,500, respectively) were large enough to provide reliable estimates of the skin
cancer incidence rates; 2) a statistically significant elevation in skin cancer incidence in the exposed
population compared to the control population was observed many years after first exposure; 3) a
pronounced skin cancer dose-response by exposure level was demonstrated; 4) the exposed and
control populations were similar in occupational and socioeconomic status, with ingestion of arseniccontaminated
drinking water the only apparent difference between the two groups, and 5) over 70% of
the observed skin cancer cases were pathologically confirmed.
Methodology
Inhalation
Data from the Anaconda and Tacoma smelters show nonlinear relationships between cumulative dose
and the relative risk (or SMR) for death from lung cancer. These dose-response curves are concave
downward (their slopes remain positive but decrease as exposure increases). Notwithstanding this
observation, the staff of DHS used linear models for this risk assessment. In these models, the dose of
arsenic was measured as cumulative µg/m 3 -years; the response was measured as the relative increase in
risk over the background (risk ratio). In addition, the models assume that the mechanism of
carcinogenesis is a nonthreshold process.
The data from Enterline et al. (1987a), Higgins et al. (1985), and Lee-Feldstein (1986) were fitted to
the model. The regression model used to achieve a linear extrapolation is described by the equation:
E[obs i ] = [α + β(d i )] × Exp i
where E[⋅] represents the expectation of a random variable, d i represents the average cumulative dose
of arsenic (in µg/m 3 -years) for exposure group i, obs i represents the observed number of deaths in
exposure group i, Exp i represents the expected number of deaths in group i based on the standard
population, α represents the risk ratio predicted for a cumulative dose (d) of zero, and β is the slope
parameter (in [µg/m 3 -years] -1 ).
To calculate unit risk, the staff of DHS selected the MLE (maximum likelihood estimate) slope and
upper 95% confidence limit (UCL) based on use of the four lowest exposure groups from the Enterline
et al. (1987a) analysis.
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