Occupational chemicals, dermal absorption

Drug and chemical dermal absorption typically involves experiments conducted using single chemicals, making the mechanisms of absorption of individual chemicals extensively studied (the subject of most chapters in this volume). Similarly, most risk assessment profiles and mathematical models are based on the behavior of single chemicals. A primary route of occupational and environmental exposure to toxic chemicals is through the skin however, such exposures are often to complex chemical mixtures. In fact, the effects of coadministered chemicals on the rate and extent of absorption of a topically applied systemic toxicant may determine whether... 

Workers in industrial facilities manufacturing or using hexachloroethane as an intermediate in the manufacture of other products may be exposed to the chemical by inhalation or dermal absorption. In addition, military or civilian personnel working with smoke or pyrotechnic devices may be exposed. Based on information collected for the National Occupational Exposure Survey, the National Institute for Occupational Safety and Health (NIOSH) estimates that 8,515 workers were potentially exposed to hexachloroethane (NOES 1991). 

The detection of PBBs and PBDEs in the serum and fat of people who were occupationally exposed to these chemicals indicates that PBBs and PBDEs can also be absorbed by the lungs and skin in humans. Although no specific methods to reduce absorption of dermally applied or inhaled PBBs or PBDEs were located, multiple washings of contaminated skin with soap and water immediately following exposure have been suggested to reduce the dermal absorption of PCBs (HSDB 1992). Studies with monkeys showed that soap and water was as effective as or better than such solvents as ethanol, mineral oil, or trichlorobenzene in removing PCBs from skin (Wester et al. 1990). 

As an alternative to the assumption of a one-time exposure for 1,000 h at the time of facility closure, permanent occupancy of a disposal site following loss of institutional control could be assumed (see Section 7.1.3.4). The assumption of chronic lifetime exposure would affect the analysis for hazardous chemicals that induce deterministic effects only if estimated intakes due to additional pathways, such as consumption of contaminated vegetables or other foodstuffs produced on the site, were significant. Based on the results for lead in Table 7.8, an intake rate from additional pathways of about 50 percent of the assumed intake rate by soil ingestion, inhalation, and dermal absorption would be sufficient to increase the deterministic risk index above unity. The importance of additional pathways was not investigated in this analysis, but they clearly would warrant consideration. The increase in exposure time during permanent occupancy does not otherwise affect the analysis for chemicals that induce deterministic effects, provided RfDs are appropriate for chronic exposure, because chronic RfDs incorporate an assumption that the levels of contaminants in body organs relative to the intake rate (dose) are at steady state. 

Okrent and Xing (1993) estimated the lifetime cancer risk to a future resident at a hazardous waste disposal site after loss of institutional control. The assumed exposure pathways involve consumption of contaminated fruits and vegetables, ingestion of contaminated soil, and dermal absorption. The slope factors for each chemical that induces stochastic effects were obtained from the IRIS (1988) database and, thus, represent upper bounds (UCLs). The exposure duration was assumed to be 70 y. Based on these assumptions, the estimated lifetime cancer risk was 0.3, due almost entirely to arsenic. If the risk were reduced by a factor of 10, based on the assumption that UCLs of slope factors for chemicals that induce stochastic effects should be reduced by this amount in evaluating waste for classification as low-hazard (see Section 7.1.7.1), the estimated risk would be reduced to 0.03. Either of these results is greater than the assumed limit on acceptable risk of 10 3 (see Table 7.1). Thus, based on this analysis, the waste would be classified as high-hazard in the absence of perpetual institutional control to preclude permanent occupancy of a disposal site. 

No quantitative data were located regarding absorption of CDDs in humans following dermal exposure. However, based on data from studies with structurally related chemicals it is reasonable to assume that CDDs are absorbed by this route. Furthermore, data on levels of CDDs in blood from populations with above-background exposures (i.e., occupational, accidental) also suggest that dermal absorption occurs in humans. Due to the relatively low vapor pressure and high lipid solubility, dermal uptake of 2,3,7,8-TCDD in the workplace may be a significant source of occupational exposure (Kerger et al. 

USEPA (2004). In vitro Dermal Absorption Rate Testing of Certain Chemicals of Interest to Occupational Safety and Health Administration, Federal Register, 69(80), 22402-22441, April 26, Washington, DC, USA. 

To protect patients and health care workers, it is essential to determine the responsible hazardous chemical as early in the decontamination process as possible. Based on previous experience with hazardous exposures, the National Institute of Occupational Safety and Health (NIOSH) and the Environmental Protection Agency (EPA) recommend level B protection as a minimal precaution (see Table 3.1) before the offending substance is identified (11). However, if available evidence suggests that the substance involves the skin as a route of exposure or is dangerous by dermal absorption or corrosion, health care workers and others coming in contact with victims require the additional skin protection of Level A PPE (9). 

Occupational exposures to 2-butoxyetlranol and 2-butoxyethanol acetate also occur primarily via inhalation or dermal absorption. Estimates from the National Occupational Exposure Survey (NOES) conducted by the National Institute of Occupational Safety and Health (NIOSH) indicate that from 1981 to 1983 more than 2 million workers were potentially exposed to 2-butoxyethanol, and more than 150,000 workers were potentially exposed to 2-butoxyethanol acetate (NIOSH 1989b). In addition to occupational exposures related to the production, processing, or handling of these chemicals, workers may be exposed to 2-butoxyethanol and 2-butoxyethanol acetate in a wide variety of occupations in which products containing these compounds are used. These occupations include janitors and cleaners, painters, mechanics, nurses and health aids, construction workers, printing machine operators, and furniture and wood finishers. 

Occupational studies indicate that humans absorb elemental selenium dusts and other selenium compounds, but quantitative inhalation toxicokinetic studies in humans have not been done. Studies in dogs and rats indicate that following inhalation exposure, the rate and extent of absorption vary with the chemical form of selenium. Studies in humans and experimental animals indicate that, when ingested, several selenium compounds including selenite, selenate, and selenomethionine are readily absorbed, often to greater than 80% of the administered dose. Although a study of humans did not detect evidence of dermal absorption of selenomethionine, one study of mice indicates selenomethionine can be absorbed dermally. There is little or no information available on the absorption of selenium sulfides, but selenium disulfides are not believed to be absorbed through intact skin. 

Toxicity can occur secondary to exposure to treated fields since many of these compounds may be easily absorbed across the skin. The potential for dermal absorption is compound dependent and varies from 2-70% of the applied dose. These compounds may also be metabolized while being absorbed across the skin, and the environmental conditions during exposure (temperature, relative humidity) drastically modify absorption. Similarly, solvent effects and coapplication of other pesticides may modify the amount absorbed, making risk assessment from single-chemical data difficult. This is a primary reason that occupational exposure, and not food residues, should be the primary focus of pesticide toxicology. 

The objective of the work described here was to examine whether a similar approach can be used to assess chemical uptake into the skin in vivo from contaminated soil. It is now well recognized that human skin contact with contaminated soil can represent an important route of exposure to toxic compounds in occupational, environmental, and recreational settings. Data on the dermal uptake of chemicals from soil, especially in vivo, are limited, however, and those that do exist may underrepresent the true risk. This is because the amount of soil applied to skin in these experiments (1) greatly exceeds the mass of soil adhering to skin during a typical exposure (U.S. Environmental Protection Agency, 2001) and (2) may have provided multiple soil layers that do not contribute equally to dermal absorption (Bunge and Parks, 1998). 

Local skin effects are not the only consideration for dermal toxicity. The role of the skin as a barrier preventing the free penetration of exogenous chemicals into the systemic circulation is equally important. Indeed, it is becoming apparent that the dermal route of exposure is in many cases comparable to inhalation and oral absorption as a potential source of potentially toxic chemicals in the body and forms an integral part of many multi-media multi-pathway risk assessments. In this context, for example, the (US) National Institute of Occupational Safety and Health is currently revising its current skin notations (which identify chemicals likely to present dermal hazards in the workplace) to take into account a... 

Semple, S. (2004). Dermal exposure to chemicals in the workplace Just how imptnlant is skin absorption. Occup. Envimn. Med. 6,376-382. 

The problem of dermal mixture absorption is conceptually similar to that of dermatologieal formulations in the pharmaceutical arena. The primary difference is that most pharmaceutical formulation components are added for a specific purpose relative to the delivery, stability, or activity of the active ingredient. In the environmental and oecupational scenarios, additives are a function of either their natural occurrence or presence in a mixtore for a purpose related to uses of that mixture (e g., a fuel performance additive, stability) and not for their effects on absorption or toxicity of the potential toxicant. Unlike pharmaceutical formulation additives in a dermal medication, chemical components of a mixture are not classified on how they could modulate percutaneous absorption of simultaneously exposed topical chemicals. They are either present functionally for specific purposes (e.g., performance additives, lubricants, modulators of some biological activity), sequentially because they wae applied to the skin indepradently at different times for unrelated purposes (cosmetic followed by topical insect repellent, sunscreens), accidentally because they were disposed of simultaneously as waste, or coincidentally associated as part of a complex occupational or environmental exposure. 

Occupational disease, caused by skin contact with toxic substances, represents a major health problem In the United States (1). Dermal exposure of agricultural workers to pesticide agents, of course. Is a particularly pertinent example of this problem. Prediction of the detrimental toxic effects of hazardous chemical exposure Is difficult, however, because of the complexity of the percutaneous absorption process in man and a lack of any consistently Identifiable relatlonshlp(s) between transport rate and chemical properties. In addition, the very diverse approaches, which have been used to measure skin penetration, further complicate the situation since the extrapolation of results to man In his workplace may Involve questionable, non-valldated assumptions. Our specific aim Is to predict accurately the toxicokinetics of occupationally-encountered molecules (e.g., pesticides) absorbed across human skin In vivo. We present... 

Albeit individuals can be exposed to toxic chemicals in many ways, industrial exposures usually occur via the dermal and/or the respiratory routes. Theoretically, gastrointestinal absorption of chemicals may result from contaminated hands or handling of foods [53]. Direct skin contact with the hazardous substance undoubtedly represents the most important and common route of exposure for occupational skin disorders. Cutaneous site and total area of exposure are significant factors in skin penetration of substances [54, 55] and, consequently, in determining the degree of local -and also systemic - toxicity of chemical agents. 

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