1,4-Dioxane Chemistry, Uses, and Occurrence - Environmental Investigation and Remediation - page 101

The same two facilities reported larger quantities transferred for treatment at wastewater facili-
ties (4170 lb) and energy-recovery facilities such as cement kilns (47,916 lb) (USEPA, 1997c).
Following the Pollution Prevention Act of 1990, the pharmaceutical industry engaged in a large
effort to minimize solvent use and emissions; the industry developed alternative, solvent-free meth-
ods for producing pharmaceuticals. In earlier decades (i.e., the 1980s and earlier), pharmaceutical
facilities potentially released 1,4-dioxane from on-site handling of wastewater, burial of solvent-
laden sludge from the solid residues of botanical extraction processes (or landi lls that received such
sludge), and energy-recovery operations that handled solvents from pharmaceutical facilities.
An indirect means of establishing the use of 1,4-dioxane in the pharmaceutical industry is found
in the literature for analytical methods developed to detect organic volatile impurities (OVIs) in
i nished drug products. U.S. Pharmacopeia (USP) analytical method 467 for analysis of OVIs also
specii es the maximum permissible levels of i ve solvents of interest, including methylene chloride,
benzene, trichloroethylene, 1,4-dioxane, and chloroform. Literature from the commercial labora-
tory sector, the analytical instrument sector, peer-reviewed journals on laboratory analysis, and the
pharmaceutical industry literature all cite methods for improving the detection of 1,4-dioxane as an
OVI in i nished pharmaceutical products to ensure compliance with U.S. Food and Drug restric-
tions on residual solvents. For example, one gas chromatograph manufacturer's technical literature
notes that analysis of ascorbic acid (vitamin C) and acetaminophen (a common pain killer) showed
all solvents well below the regulated levels. Vitamin C had benzene at 35 ppb, and acetaminophen
had dichloromethane at 407 ppb; neither product had 1,4-dioxane above a method detection limit of
just less than 1 ppm (Rankin, 1996).
In the United States and Europe, the permitted daily exposure to 1,4-dioxane through consump-
tion of pharmaceuticals is 3.8 mg per person. The permissible concentration limit in the i nished
drug product is 380 ppm (FDA, 1997a; European Medicines Agency, 1998). The same levels are
considered permissible in U.S. veterinary medicinal products (FDA, 2001).

2.7 DETECTIONS OF 1,4-DIOXANE IN AMBIENT SURFACE WATER,
GROUNDWATER, AND AIR
There has not been a great deal of analysis for 1,4-dioxane in ambient environmental monitoring
samples. The most comprehensive monitoring program for ambient water quality in the United
States, the U.S. Geological Survey's National Ambient Water-Quality Assessment Program
(NAWQA), excluded 1,4-dioxane from its analyte list because of analytical challenges for quanti-
fying 1,4-dioxane by using the purge-and-trap GC methods preferred for the majority of the organic
compounds sought by the program. California's Groundwater Ambient Monitoring and Assessment
Program (GAMA) targeted 1,4-dioxane in a study of groundwater in the San Diego, California,
area. Groundwater samples were analyzed from 24 wells; at a reporting limit of 2 ppb, no 1,4-dioxane
was detected in any of the samples (Wright et al., 2004). Lawrence Livermore National Laboratory
conducted a similar GAMA study, using a reporting limit of 0.2 ppb, for groundwater in the
Sacramento, California, area; samples from 108 wells were analyzed for 1,4-dioxane. Three sam-
ples had detections below 1 ppb (Moran et al., 2003). Another aquifer-vulnerability assessment
tested 60 municipal wells in Santa Clara County, California (“Silicon Valley”), where widespread
solvent contamination of shallow aquifers had occurred. 1,4-Dioxane was included in the list of
analyses performed on the municipal well samples; however, none of the samples had detections
using a reporting limit of 0.15 ppb (J.E. Moran, personal communication, 2003).
Levels of 1,4-dioxane between 0.2 and 1.5 g/L were detected in tap water samples collected

during 1995 and 1996 in Kanagawa Prefecture, Japan, an 870-square-mile province adjacent to and
southwest of Tokyo (Abe, 1997). An additional comprehensive survey of the Kanagawa Prefecture
included multiple sampling events in three rivers and 20 wells and found 1,4-dioxane to be ubiquitous
at low levels; a few locations had relatively elevated levels. 1,4-Dioxane was detected in 90% of the
wells, with two-thirds of the detections falling below 1

μ

μ g/L, 20% between 1 and 10 μ g/L, and 10%