Regulation and Risk Assessment of 1,4-Dioxane - Environmental Investigation and Remediation - page 296

other reproductive harm. Chemicals may also be listed if other organizations, including USEPA,
FDA, National Institute for Occupational Safety and Health (NIOSH), National Toxicology Program
(NTP), and International Agency for Research on Cancer (IARC), list a compound in any of these
categories. If a chemical on the list is present in a product, businesses must post a warning unless
exposure is low enough to pose no signii cant risk of cancer or is signii cantly below levels observed
to cause birth defects or other reproductive harm.
For carcinogens, the No Signii cant Risk Level (NSRL) is the level of exposure that would result
in not more than one excess case of cancer in 100,000 individuals exposed to the chemical over a
70-year lifetime. For chemicals that are listed as causing birth defects or reproductive harm, the No
Observable Effect Level (NOEL) for the chemical is divided by 1000 to provide a large margin of
safety. If a product or workplace would cause exposures to chemicals listed as causing birth defects
or reproductive harm that exceed 1/1000th of the NOEL, businesses are required to provide a warn-
ing to consumers or employees.
To help businesses determine when they are subject to the rules of Proposition 65, Cal EPA's
OEHHA publishes “safe harbor numbers,” below which businesses are exempt from the Proposition
65 warning requirements. California's safe harbor numbers consist of NSRLs for chemicals listed
as causing cancer and Maximum Allowable Dose Levels (MADLs) for chemicals listed as causing
birth defects or other reproductive harm.
1,4-Dioxane i rst appeared on the California Proposition 65 list of chemicals “known to the state
to cause cancer” on January 1, 1988. The NSRL for 1,4-dioxane, that is, the 1:100,000 excess cancer
risk level, is 30 μg/d (Cal EPA, 2007b). Because 1,4-dioxane causes neither birth defects nor repro-
ductive toxicity, an MADL has not been established.
6.5 RISK ASSESSMENTS OF 1,4-DIOXANE
Risk assessments determine the likelihood and severity of harm to human health and environmental
receptors that may result from exposure to a chemical substance. Risk assessments include four
components: source or release assessment, exposure assessment, dose-response assessment, and
risk characterization. Source assessment includes monitoring and modeling to estimate the magni-
tude of the release and the potential for chemical exposure resulting from the release. Exposure
assessments evaluate the chemical concentrations to which populations are exposed by identifying
toxic contaminants present in the release, quantifying the magnitude of exposure, determining the
routes of exposure, and assessing the known or potential duration of exposure. Exposure assessment
may include biomonitoring, that is, the sampling of l uid or tissue samples, as well as modeling, to
estimate exposure levels.
6.5.1 O VERVIEW OF R ISK -A SSESSMENT P ROCESS AND D ATA R EQUIREMENTS
Dose-response assessment is the quantitative evaluation of toxicity as a function of exposure. The
relationship between the dose of a chemical and the incidence of adverse health effects forms the
basis for the quantitative dose response. Toxicity values (i.e., RfDs and slope factors) are derived
from these relationships and can be used to estimate the incidence or potential for adverse effects in
an exposed population. For carcinogens, the process of dose-response assessment involves the use
of modeling to determine a point of departure followed by low-dose extrapolation. The method of
low-dose extrapolation is dependent on the mode of action for the chemical; linear methods are used
for chemicals that cause genotoxicity, and nonlinear approaches are suggested for chemicals that
produce cancer via a nongenotoxic mode of action. For noncarcinogens, the point of departure may
be the NOAEL or a benchmark dose level that is determined by modeling. UFs are applied to these
values to derive RfDs and acceptable or tolerable daily intakes (TDIs).
Risk characterization integrates source assessment, exposure assessment, and dose-response
assessment into a statement of the types and magnitudes of adverse effects that the contaminant may