Regulation and Risk Assessment of 1,4-Dioxane - Environmental Investigation and Remediation - page 293

result in a 1,4-dioxane residual concentration of up to 45 ppm if the methyl chloroform is stabilized
with 1,4-dioxane at a mass ratio of 3%.
Exposure to 1,4-dioxane from ingestion of pharmaceuticals is likely to be substantially less than
the permitted daily exposure, 3.8 ppm. No surveys of solvent residuals identifying 1,4-dioxane in
i nished pharmaceutical products have been published, possibly because (1) analysis of 1,4-dioxane
in pharmaceuticals presents difi cult analytical challenges and (2) the small mass and infrequent
consumption of pharmaceutical products are inherently unlikely to pose a risk of exposure.
An indirect indicator of the extent to which 1,4-dioxane may be present in current or previous
pharmaceutical products is the regulation of pharmaceutical manufacturers for 1,4-dioxane in plant
emissions and efl uent. USEPA (1998a) reported that 1,4-dioxane comprises 0.06% of overall phar-
maceutical manufacturing efl uent loading, or 24,422 pounds per year for all six plants included in
the review. To model the performance of pharmaceutical plant efl uent treatment works, USEPA
assumed a 1,4-dioxane concentration of 180 mg/L of efl uent. 1,4-Dioxane is certainly used in and
associated with the pharmaceutical industry; however, its presence in retail pharmaceutical prod-
ucts has not been documented and is indeterminate.
6.4.3 R EGULATION OF 1,4-D IOXANE IN C OSMETICS AND S HAMPOOS
1,4-Dioxane may be present at low levels in some cosmetics, shampoos, and other personal care
products because it occurs as a by-product during the production of ethoxylated surfactants used as
ingredients in such products. These ingredients include certain detergents, foaming agents, emulsi-
i ers, and solvents identii able by the prei x, word, or syllables “PEG,” “polyethylene,” “polyethylene
glycol,” “polyoxyethylene,” “-eth-,” or “-oxynol-” (FDA, 2007). 1,4-Dioxane is not used directly as
a cosmetic ingredient; it only occurs as a by-product. In shampoos, hair-care foaming agents such
as fatty alcohols and ether sulfates may contain 1,4-dioxane as an impurity (Wilkinson, 1989). The
FDA determines the levels at which a chemical is considered harmful; the levels depend on the
conditions of use. The FDA (2007) has concluded that the levels of 1,4-dioxane observed in moni-
toring of cosmetics do not present a hazard to consumers.
To examine the potential toxicity of cosmetic impurities, the FDA performed skin absorption
studies, which showed that 1,4-dioxane can penetrate animal and human skin when applied in cer-
tain preparations, such as lotions. However, studies determined that 1,4-dioxane evaporates readily
from the skin, diminishing the amount available for skin absorption, even in products that remain
on the skin for hours (Bronaugh, 1982). The FDA did not at i rst establish or recommend a specii c
limit on the level of 1,4-dioxane in cosmetics, but did provide guidance to manufacturers of ethoxy-
lated surfactant ingredients, alerting them to the health concerns over 1,4-dioxane and opportunities
to eliminate 1,4-dioxane by using vacuum stripping at the end of the polymerization process. The
guidance was included in the Cosmetic Handbook for Industry (FDA, 1992). The Cosmetic
Handbook includes 1,4-dioxane in the list of “explicitly prohibited ingredients.” Retail cosmetics
must list ingredients; however, 1,4-dioxane is a by-product and not an ingredient and has therefore
not been included in the list of ingredients in cosmetics (Title 21, Code of Federal Regulations,
Section 701.3). As reported by Pearl (2007), the FDA issued guidance in 2000 recommending that
cosmetic products should not contain 1,4-dioxane at concentrations greater than 10 ppm.
As proi led in Chapter 2, contamination of ethoxylated surfactants with dioxane was i rst reported
by the FDA in 1978 (FDA, 1981). Many of the raw materials analyzed since then have been found
to contain 1,4-dioxane; some contained as much as 100 ppm or more. The FDA reports that the
changes made in the manufacturing process have resulted in a signii cant decline in 1,4-dioxane
levels. A recent survey of 1,4-dioxane in personal care products reported that 1,4-dioxane remains
present in a number of shampoos and children's bubble bath products, some at levels in excess of
the FDA's 10 ppm guidance (Campaign for Safe Cosmetics, 2007). The analysis of cosmetics was
originally performed by David Steinman and published in the topic Safe Trip to Eden (Steinman,
2007). Results from Steinman's analysis of sundries are listed in Table 6.17 .