Regulation and Risk Assessment of 1,4-Dioxane - Environmental Investigation and Remediation - page 308

developing a more complex, probabilistic approach that accounts for the range of values encoun-
tered; for example, the distribution of droplet sizes produced by a shower nozzle, starting and i nal
air temperature, etc. (Giardino et al., 1992).
The MADEP shower model results suggest that inhalation cancer risk can be limited if the
1,4-dioxane level in shower water is maintained below 3 μg/L. As discussed in Chapter 5, 1,4-dioxane
exposure studies by Torkelson et al. (1974) on inhalation and by Kociba et al. (1974) on ingestion i nd
that cancer potency of 1,4-dioxane is greater by the oral route of exposure. This i nding suggests that
1,4-dioxane toxicity is related to metabolism, which is not involved with inhalation exposure; there-
fore, people should be less vulnerable to 1,4-dioxane toxicity from the inhalation route than from the
ingestion route. However, ATSDR's 2004 draft Toxicological Proi le of 1,4-dioxane states that expo-
sure to 1,4-dioxane in tap water through inhalation during showering or other indoor activities can
result in higher exposures to 1,4-dioxane compared to ingestion of drinking water (ATSDR, 2004).
Health risk assessments should carefully consider shower exposure to address inhalation exposure.
6.5.6 R ISK OF 1,4-D IOXANE O RAL I NGESTION IN D RINKING W ATER , F OOD , AND D RUGS
USEPA's IRIS previously listed the oral CSF value of 0.011 (mg/kg d) −1 based on linear extrapola-
tion to low doses from the 1978 National Cancer Institute study of nasal tumors in rats. As of
February 9, 2004, 1,4-dioxane is being reassessed under the IRIS Program. IRIS lists the 1 in
1,000,000 risk level for 1,4-dioxane in drinking water as 3 μg/L, on the basis of the previously listed
slope factor of 0.011 (mg/kg d) −1 (USEPA, 2007 h). The previous IRIS risk level used the LMS
extrapolation procedure, which has been questioned because a nonlinear dose-response curve is
observed for 1,4-dioxane. Alternative derivations of safe drinking water concentrations for 1,4-
dioxane using PBPK modeling range from 2 to 120 mg/L (Stickney et al., 2003), as presented in
Table 5.5 in Chapter 5.
The World Health Organization (WHO) established a 50 μg/L advisory level for 1,4-dioxane.
The WHO selected the LMS model to estimate cancer risk because studies they reviewed indicated
that 1,4-dioxane induces multiple tumors including hepatic and nasal cavity tumors in rodents in
most long-term oral studies conducted and tumors in peritoneum, * skin, and mammary glands
observed in rats given a high dose (WHO, 2005). By using the 1 in 100,000 cancer risk for hepatic
tumors observed in a 2-year study of rats and mice by Yamazaki et al. (1994) for the JBRC, the
WHO determined the drinking water equivalency level at 54 μg/L. For the noncarcinogenic end-
point, the WHO used the TDI approach, which, like the MCLG, is an estimate of the amount of a
substance that can be ingested or absorbed over a specii ed period of time without appreciable
health risk. The long-term study of 1,4-dioxane in drinking water supplied to rats by Kociba et al.
(1974) was used for the noncarcinogenic NOAEL of 16 mg/(kg d), coupled with a 1000-fold UF for
inter- and intraspecies variation, to obtain a TDI of 16 μg/(kg d). The equivalent concentration in
drinking water is calculated to be 48 μg/L. Taken together with a 54 μg/L TDI calculated from the
Kociba study, the WHO set the Drinking Water Quality Guideline at 50 ppb (WHO, 2005).
The drinking water standards development process discussed in Section 6.1 provides the basic
framework used by several American states to determine the risk threshold for ingestion of 1,4-
dioxane in drinking water. Exposure to 1,4-dioxane from ingesting food or drugs containing residual
1,4-dioxane is likely to be very low and possibly inconsequential, as discussed in Section 6.4.2 .
6.5.7 R ELATIVE R ISKS OF S OLVENT S TABILIZERS
The relative risk of exposure to stabilizer compounds can be discerned by comparing the key acute
and subchronic toxicity indicators for the major routes of exposure. The key indicators are the
* The peritoneum is the abdominal cavity lining.