Environmental Engineering Reference
In-Depth Information
TABLE 5.5
Safe Drinking Water Concentrations for 1,4-Dioxane
Dose-Response Assessment
Method
Cancer
Risk
Concentration
(mg/L)
References
IRIS CSF—rat nasal tumors
1 × 10 -5
0.030
NCI (1978)
IRIS CSF—rat nasal tumors
1 × 10 -6
0.003
NCI (1978)
PBPK LMS model
1 × 10 -5
20 a
Reitz et al. (1990)
PBPK LMS model
1 × 10 -6
2 a
Reitz et al. (1990)
PBPK safety factor approach
NA
120
Reitz et al. (1990)
PBPK LMS model
1 × 10 -5
28 b
Leung and Paustenbach (1990)
PBPK LMS model
1 × 10 -6
2.8 b
Leung and Paustenbach (1990)
PBPK safety factor approach
NA
49 b
Leung and Paustenbach (1990)
Threshold approach
NA
3.5 c
Stickney et al. (2003)
Source: Adapted from Stickney et al., 2003, Regulatory Toxicology and Pharmacology 38: 183-195. With
permission.
Notes: IRIS = USEPA's Integrated Risk Information System; PBPK = physiologically based pharmaco-
kinetic; LMS = Linearized Multistage Model; NA = not applicable.
a
Calculated by assuming a linear relationship between risk level and the estimated cancer slope factor
(CSF).
b
Calculated from risk-specii c doses by assuming 70 kg body weight and 2 L per day ingestion rate.
c
Calculated by dividing the no observed adverse effect (NOAEL) of 10 mg/kg per day by an uncertainty
factor (UF) of 100 and by assuming 70 kg body weight and 2 L per day ingestion rate.
tumors. The CSF value can be used to estimate the cancer risk (i.e., the projected incidence of can-
cer associated with a specii ed dose), or it can be used to determine “safe” levels of a chemical in the
environment by making some assumptions regarding the acceptable level of cancer risk (e.g., 1 in
1 million or 1 × 10 -6 cancer risk). Stickney et al. (2003) provided an evaluation of safe drinking-
water concentrations of 1,4-dioxane that may be associated with different approaches to carcinogen
risk assessment (see Table 5.5). Factors that signii cantly affect the cancer risk assessment of 1,4-
dioxane include the following:
1. Determination of the human relevance of nasal and liver tumors
2. Elucidation of the mode of action for relevant tumor types
3. Identii cation of an appropriate internal dose metric (i.e., from PBPK modeling) for use in
quantii cation of human cancer risks
Each of these factors is subject to some degree of scientii c interpretation. Scientii c consensus
regarding cancer risk assessment is generally achieved through a peer review process.
ACKNOWLEDGMENTS
The insightful comments and questions provided by Heather Carlson-Lynch of SRC, Inc. are greatly
appreciated.
BIBLIOGRAPHY
Argus, M.F., Arcos, J.C., and Hoch-Ligeti, C., 1965, Studies on the carcinogenic activity of protein-denaturing
agents: Hepatocarcinogenicity of dioxane. Journal of the National Cancer Institute 35: 949-958.
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