Regulation and Risk Assessment of 1,4-Dioxane - Environmental Investigation and Remediation - page 301

monkeys showed little dermal penetration from skin lotion. The primary effects of dermal exposure
to 1,4-dioxane are irritation, dermatitis, eczema, and dried skin. As noted in Section 2.3.3, 1,4-
dioxane is preferred in histology labs as a tissue preservative because it dehydrates tissues; there-
fore, avoiding direct skin contact with 1,4-dioxane in pure form is advisable. 1,4-Dioxane readily
penetrates animal and human skin (Gosselin et al., 1984); however, most of the dioxane applied to
the skin evaporates and thus may not be available for skin absorption (FDA, 2007).
Direct dermal exposure to 1,4-dioxane is primarily caused by a risk of incidental contact by
workers handling 1,4-dioxane in laboratories, manufacturing facilities, and chemical production
facilities. Signii cant dermal exposure to 1,4-dioxane probably occurred in earlier decades, when
dioxane-stabilized methyl chloroform was widely used in vapor degreasing, and worker health and
safety protective measures were less comprehensive than current standards. Occupational exposure
regulations and enforcement, together with worker training and use of personal protective
equipment, now minimize the potential for dermal exposure, and the number of industries in which
1,4-dioxane is routinely used is relatively limited. The general population may have skin contact
with low concentrations of 1,4-dioxane while bathing in water contaminated by 1,4-dioxane (see
Table 6.3 ). Dermal exposure may also occur from use or application of shampoos, lotions, and cos-
metics containing 1,4-dioxane as a residual in the ethoxylated surfactant ingredients, as described
in Section 2.4 and Table 6.17 .
Incidental contact with solutions or cosmetic products containing 1,4-dioxane may result in
absorption by diffusion through the outermost layer of skin (the dead stratum corneum) and tra-
versal of the living epidermis, where metabolic processes may be involved. Unlike the stratum
corneum, the cutaneous tissue is primarily an aqueous medium into which hydrophilic compounds
like 1,4-dioxane will partition. Some of the chemical in contact with the skin will be absorbed,
while some may be subject to evaporation. Many of the measured values of dermal permeability for
chemicals are obtained by percutaneous absorption studies conducted by covering the site of appli-
cation with an occlusive wrap to prevent loss of the compound. Values obtained by this approach
may overestimate skin permeability for volatile compounds. Up to 3.2% of applied 1,4-dioxane
(dissolved in lotion) was absorbed under occlusion for 3.5 h, whereas 0.3% absorption occurred
under nonoccluded conditions (Bronaugh, 1982). The difference is due to the relative volatility of
dioxane (USEPA, 2002).
Skin absorption is dominated by passive diffusion; the rate of absorption is inversely propor-
tional to the thickness of the barrier layer (USEPA, 1992a). Skin permeation by diffusion follows
Fick's i rst law and assumes steady-state conditions, that is, the volumes of solutions on either side
of the skin membrane must be much greater than the effective volume of the membrane, solutions
are well mixed, skin composition and properties are homogeneous, and concentration of the com-
pound at the membrane surface is constant (USEPA, 1992a).
Skin penetration may also occur via skin appendages such as hair follicles, sebaceous glands,
and sweat glands, which may allow dioxane to diffuse through otherwise rate-limiting barriers.
Less than 1% of the human skin surface is composed of these appendages; therefore, this route of
dermal exposure is negligible for lipophilic compounds such as the chlorinated solvents. 1,4-Dioxane
is expected to diffuse slowly through the stratum corneum; therefore, skin appendages may play a
more important role than diffusion for 1,4-dioxane passage through the skin. Polar compounds such
as 1,4-dioxane are generally poorly absorbed through the skin, whereas nonpolar compounds are
more readily absorbed (USEPA, 1992a). A different view is presented by the Danish EPA, which
notes that 1,4-dioxane is a “fat solvent,” and 1,4-dioxane can cause eczema upon prolonged or
repeated contact (Danish EPA, 2005).
Rates of chemical permeation of the skin vary in humans by gender, skin type, skin condition,
skin hydration, skin temperature, circulation of blood to the skin, capacity of the compound to bind
to keratin, and the anatomic region exposed. For example, absorption of hydrocortisone through
skin on the forehead is six times greater than through skin on the forearm, and the dermis of
the scrotum absorbs hydrocortisone six times more than on the forehead, because of substantial