Regulation and Risk Assessment of 1,4-Dioxane - Environmental Investigation and Remediation - page 298

Young et al. (1977) to derive the 2 ppm acute inhalation MRL. In a 2-year inhalation bioassay in rats
exposed intermittently to 111 ppm 1,4-dioxane, no adverse effects were observed (Torkelson et al.,
1974). ATSDR used the 111 ppm NOAEL to derive the chronic-duration inhalation MRL of 1 ppm
for 1,4-dioxane.
Risk estimates for ingested 1,4-dioxane are usually based upon oral rat or oral mouse studies for
which an NOAEL was established. For cancer risks, the CSF is the key index for evaluating expo-
sure risk. The noncancer toxic effects of 1,4-dioxane drinking water exposure in a 2-year rat study
included severe effects on the nasal cavity, lungs, liver, and kidneys; the NOAEL was equivalent to
10 mg/(kg d) (ECB, 2002).
ATSDR's draft Toxicological Proi le for 1,4-dioxane derives MRLs for different durations of
exposure to 1,4-dioxane. The MRL is dei ned as the daily human exposure to a substance that is
likely to be without an appreciable risk of adverse noncarcinogenic effects over a specii ed duration
of exposure. MRLs are based only on noncancerous health effects and do not consider carcinogenic
effects. The MRL does not account for delayed health effects or those resulting from repeated high-
dosage exposures; such effects include hypersensitivity reactions, asthma, or chronic bronchitis
from acute inhalation exposure (ATSDR, 2004).
ATSDR determined an acute-duration (14 days or less) MRL of 4 mg/(kg d) oral exposure to 1,4-
dioxane, based on an NOAEL of 370 mg/(kg d) for nasal effects in the 1998 Japan Bioassay Research
Center (JBRC) rat study summarized in Chapter 5 (JBRC, 1998; Yamazaki et al., 1994; ATSDR,
2004). For intermediate-duration oral exposure (15-364 days), ATSDR developed an MRL of 0.6 mg/
(kg d), based on an NOAEL of 60 mg 1,4-dioxane per kilogram of body weight per day for liver
effects in rats (JBRC, 1998). ATSDR's determination of the chronic-duration oral-exposure (365 days
or more) MRL for 1,4-dioxane, 0.1 mg/(kg d), used the NOAEL of 9.6 mg 1,4-dioxane per kilogram
of body weight per day for liver effects in male rats from the study by Kociba et al. (1974).
A number of comprehensive risk assessments have been published by various government agen-
cies. The key risk summaries reviewed for this topic are listed in Table 6.19.
Risks associated with 1,4-dioxane exposure may occur through the occupational and domestic use
of products containing varying amounts of 1,4-dioxane. Inhalation is the most common route of expo-
sure to chemicals used in the workplace, but occupational exposure can also lead to dermal absorption
of 1,4-dioxane, as described in the next section. Chapter 2 provides a detailed description of 1,4-di-
oxane occurrence in various manufacturing settings, and Table 2.7 lists the industrial processes
in which 1,4-dioxane emissions may occur. Table 6.20 lists the leading occupations with potential

TABLE 6.19
Key Review Reports on 1,4-Dioxane Exposure by Ingestion, Inhalation, and
Dermal Exposure
Year Title Publishing Agency

2005 “1,4-Dioxane in Drinking-Water” WHO

2004 “Draft Toxicological Proi le for 1,4-Dioxane” ATSDR, USA

2002 “European Union Risk Assessment Report:

1,4-Dioxane”

European Union Institute for Health and Consumer Protection

1999 “Risk Assessment: 1,4-Dioxane” Netherlands (VROM and several other Dutch government

agencies)

1998 “Priority Existing Chemical No. 7—1,4-Dioxane” National Industrial Chemicals Notii cation and Assessment

Scheme (NICNAS)—Australian National Occupational
Health and Safety Commission, and Environment Australia

1991 “1,4-Dioxane BUA Report 80” Committee on Existing Chemicals of Environmental

Relevance, German Chemical Society