PRINCIPLES OF TOXICOLOGY

19.5 RISK ASSESSMENT FOR ARSENIC 489
Cancer risks posed by exposure to soil are calculated using the lifetime average daily intake (LADI)
and the oral or inhalation slope factor. The oral slope factor for arsenic is 1.5 kg⋅mg/day. Thus, the
lifetime cancer risk for the child’s ingestion of arsenic in soil is calculated as 2.76 × 10 –5 mg/kg⋅day
× 1.5 kg⋅mg/day = 4 × 10 –5 (Note: Lifetime cancer risk estimates are expressed to only one significant
digit.) Lifetime cancer risks posed by dermal exposure are estimated by multiplying the dermal LADI
by the oral slope factor.
Inhalation lifetime cancer risks may be calculated using a unit risk factor (expressed in units of
m 3 /µg) or an inhalation slope factor (kg⋅day/mg). Since inhalation exposure is expressed in terms of
body weight (mg/kg⋅day), the inhalation slope factor should be used. If only an inhalation unit risk
factor is available, it can be converted to an inhalation slope factor by multiplying the unit risk factor
by (70 kg/20 m 3 ) × 1000 µg/mg. The inhalation slope factor for arsenic is 15 kg⋅day/mg. Multiplication
of the child’s inhalation LADI by this slope factor yields an estimated lifetime cancer risk of 1 × 10 –7
(9.05 × 10 –9 mg/kg⋅day × 15 kg⋅day/mg).
According to default USEPA policy, the cancer risks for adult and child residents are summed
together using the assumption that an individual will live at the affected residence from infancy until
30 years of age. The overall sum of calculated lifetime cancer risks from childhood and adult exposure
is 6 × 10 –5 .
The lifetime cancer risk associated with exposure to arsenic in soil is 6 × 10 –5 . This risk is within
the range of additional lifetime cancer risks considered acceptable by the USEPA (i.e., 1 × 10 –6 to 1
× 10 –4 ). However, many states have set the acceptable level of allowable added lifetime cancer risk at
1 × 10 –5 or even 1 × 10 –6 . In these cases the calculated lifetime cancer risk exceeds these targets by 6or
60-fold, respectively.
It is important to put the risks of site-related arsenic exposure and risk in perspective with
unavoidable arsenic exposures. For example, the USEPA estimated that daily inorganic arsenic intake
from food and water is approximately 0.018 mg/day. For a 70-kg individual, this amounts to 2.6 × 10 –4
mg/kg per day. Using the USEPA oral slope factor for arsenic (1.5 kg⋅day/mg), the lifetime cancer risk
for unavoidable ingestion of arsenic in food and water is 4 × 10 –4 , greater than the USEPAs upper
bound acceptable lifetime cancer risk level of 1 × 10 –4 . By placing site-related arsenic risk into context
with the higher risk from unavoidable sources of exposure, it may not be necessary to undertake action
to decrease site-related risks by limiting the residents exposure to arsenic in soil.
Furthermore, at the arsenic intakes from soil described in this example, default USEPA cancer risk
assessment methods may cause risk to be overestimated at low exposure levels. The default method
assumes that the carcinogenic response to arsenic intake is linear at low doses. However, according to
recent reviews of the possible carcinogenic mechanism of action in humans, a cancer threshold or
sublinear carcinogenic response may exist at lower doses such as those calculated in the residential
exposure scenario above.
The form of arsenic considered in this example is important consideration to the risk assessment.
Default risk assessment policy often assumes that organic chemicals in soil are absorbed to the same
extent as the form of the chemical studied in developing the oral RfD. Typically, these studies involve
exposure to the chemical in food or water. Studies in monkeys indicate that the oral bioavailability of
arsenic in soil or dust resulting from mining or smelting activities is only 10–28 percent that of sodium
arsenate in water. Mineralogic factors appear to control the solubility and therefore, the release of
arsenic from the soil impacted by smelting. Only soluble arsenic is available for absorption from the
gastrointestinal tract. This example stresses the need to consider the form the chemical in the
environment and the impact that chemical form may have on the bioavailability of the chemical. Use
of the default assumption that arsenic in soil is as bioavailable as arsenic in water would result in the
calculation of a hazard index above 1 and lifetime cancer risks in excess of 1 × 10 –4 in the preceding
example. Thus, even a change in one USEPA default exposure assumption (the bioavailability of
arsenic in soil) may greatly affect the degree to which regulatory action is taken.
Human exposure monitoring can be used as a check on calculated estimates of exposure to
arsenic in soil. Human arsenic exposure may be monitored by determining arsenic concentrations
in urine, hair, and nails. Although human exposure monitoring is not routinely conducted at most