The effects of perchlorate on thyroidal gene expression are different from the effects of iodide deficiency.

Perchlorate (ClO₄⁻), which is a ubiquitous and persistent ion, competitively interferes with iodide (I) accumulation in the thyroid, producing I deficiency (ID), which may result in reduced thyroid hormone synthesis and secretion. Human studies suggest that ClO₄⁻ presents little risk in healthy individuals; however, the precautionary principle demands that the sensitive populations of ID adults and mothers require extra consideration. In an attempt to determine whether the effects on gene expression were similar, the thyroidal effects of ClO₄⁻ (10 mg/kg) treatment for 14 d in drinking water were compared with those produced by 8 wk of ID in rats.

A review of transcriptomics in cutaneous chemical exposure.

Monitoring gene expression profiles in the skin using microarrays has become a useful approach to enhance the understanding of dermal function, toxicologic mechanisms, and risk assessment. With respect to cutaneous chemical exposure, there are few transcriptomic studies in the published literature, and these often differ in experimental design and availability of raw data. An assessment of multiple microarray data sets could be advantageous for identifying potential redundant biological mechanisms or genes associated with dermal responses to chemical exposure.

Transcriptional changes in porcine skin at 7 days following sulfur mustard and thermal burn injury.

Severe cutaneous injuries continue to result from exposure to sulfur mustard [bis(2-chloroethyl)sulfide; HD] and thermal burns. Microarray analysis was utilized in this study to evaluate transcriptional changes in porcine skin assessing the underlying repair mechanisms of HD and thermal injury involved in wound healing. Four ventral abdominal sites on each of 4 weanling swine were exposed to 400 microL undiluted HD or a heated brass rod (70 degrees C) for 8 minutes and 45-60 seconds, respectively.

Transcriptional responses associated with sulfur mustard and thermal burns in porcine skin.

In military and civilian environments, serious cutaneous damage can result from thermal burns or exposure to the blistering agent sulfur mustard [bis (2-chloroethyl) sulfide; HD]. Similar therapies have historically been used to treat cutaneous thermal and HD injuries; however, the underlying molecular mechanisms of tissue damage and wound healing may differ between the types of burns. Using microarray analysis, this study assessed the transcriptional responses to cutaneous HD and thermal injury at 48 hours post-exposure to identify molecular networks and genes associated with each type of skin injury.

Gene expression analysis of bromine-induced burns in porcine skin.

Bromine is an industrial chemical that is irritating to the skin and causes cutaneous burns. An important factor in selecting or developing an effective treatment is to understand the underlying molecular mechanisms of tissue damage and wound healing. This study used a weanling swine burn model and microarray analysis to evaluate the effect of exposure length and sampling times on the transcriptional changes in response to cutaneous bromine injury.

In vitro dermal absorption rate testing of certain chemicals of interest to the Occupational Safety and Health Administration: summary and evaluation of USEPA's mandated testing.

In 2004, the United States Environmental Protection Agency (USEPA) published a final test rule in the US Federal Register requiring in vitro dermal penetration rate testing for selected industrial chemicals. The test rule described procedures for determining a permeability coefficient (Kp) and two short-term dermal absorption rates at 10 and 60min using human cadaver skin mounted in an in vitro diffusion cell model. According to the USEPA announcement, the selected chemicals were to be spiked with their radiolabeled form and tested in either water, isopropyl myristate (IPM) or neat depending on their physical character at room temperature, their aqueous solubility, their potential to damage the skin and their ability to achieve the study endpoints as prescribed.

Skin penetration and lag times of neat and aqueous diethyl phthalate, 1,2-dichloroethane and naphthalene.

Cutaneous exposures to occupational chemicals may cause toxic effects. For any chemical, the potential for systemic toxicity from dermal exposure depends on its ability to penetrate the skin. Most laboratory studies measure chemical penetration from an aqueous solution through isolated human or laboratory animal skin, although most exposures are not from pure aqueous solutions.

Gene expression and target tissue dose in the rat epidermis after brief JP-8 and JP-8 aromatic and aliphatic component exposures.

Exposures of jet propulsion fuel 8 (JP-8) to human and laboratory animal skin have resulted in skin irritation. JP-8 is a mixture of aromatic and aliphatic hydrocarbons, which in some cases have also been shown to be irritating to the skin. In an attempt to determine if aromatic or aliphatic components could mimic the JP-8-induced gene expression response, we exposed rats to JP-8, undecane (UND), tetradecane (TET), trimethylbenzene (TMB), and dimethylnaphthalene (DMN) for 1 h and examined the epidermis to characterize the gene expression response.

Effects of brief cutaneous JP-8 jet fuel exposures on time course of gene expression in the epidermis.

The jet fuel jet propulsion fuel 8 (JP-8) has been shown to cause an inflammatory response in the skin, which is characterized histologically by erythema, edema, and hyperplasia. Studies in laboratory animal skin and cultured keratinocytes have identified a variety of changes in protein levels related to inflammation, oxidative damage, apoptosis, and cellular growth. Most of these studies have focused on prolonged exposures and subsequent effects.

Characterization of the skin penetration of a hydrocarbon-based weapons maintenance oil.

Break-Free CLP is a commercial petroleum-based liquid used for cleaning, lubricating, and protecting firearms that is used in the United States by military personnel, police, and individual gun owners for maintaining a wide variety of firearms. According to its material safety data sheet (MSDS), Break-Free CLP is predominately polyalphaolefin oil but also contains dibasic ester and isoparaffinic hydrocarbons; all of these ingredients are known to induce skin irritation in laboratory animals. Studies completed in our labs found that repeated topical application of Break-Free CLP to the backs of CD-1 mice produced evidence of systemic effects.

Local and systemic toxicity of JP-8 from cutaneous exposures.

Jet propellant-8 (JP-8) jet fuel is a version of commercial jet fuel, Jet A, and is a complex mixture of primarily aliphatic (but also aromatic) hydrocarbons that varies in composition from batch to batch. There is potential for dermal exposure to jet fuels with personnel involved in aircraft refueling and maintenance operations as well as ground personnel. Cutaneous exposures have the potential to cause skin irritation, sensitization or skin cancer.

The cytotoxicity of volatile JP-8 jet fuel components in keratinocytes.

In vitro models are being used to evaluate the toxic and irritating effects of JP-8, a kerosene-based jet fuel. JP-8 components are volatile, which makes in vitro studies difficult to evaluate dose-response relationships due to changes in chemical dosimetry caused by evaporation from the exposure medium. An in vitro approach testing volatile chemical toxicity that we have recently developed was used to evaluate the toxicity of the JP-8 components m-xylene, 1-methylnaphthalene (1-MN), and n-nonane in keratinocytes.

Gene expression in rat skin induced by irritating chemicals.

Occupational skin disease is the second most significant cause of occupational disease, after accidents. Irritation from occupational chemicals such as solvents, hydrocarbons, and surfactants are one cause of this disease. Gene expression studies provide useful information about normal processes in the skin and responses of the skin to exogenous chemicals.

The effect of m-xylene on cytotoxicity and cellular antioxidant status in rat dermal equivalents.

Exposure of the skin to volatile organic chemicals (VOCs) can lead to irritation, inflammation and cytotoxicity. Since VOCs are used in industrial, commercial and military applications, concern is mounting with respect to VOC safe exposure limits. Although traditional toxicological assessment of VOCs has utilized animal models, the use of alternative in vitro models is becoming more widespread.

Molecular and histological responses in rat skin exposed to m-xylene.

Solvents, surfactants, cutting fluids, hydrocarbons, and oils cause skin irritation by incompletely understood mechanisms. This study examined histological and molecular changes in rodent skin caused by brief topical exposures to m-xylene. At 0, 1, 2, 4, and 6 h after 1-h exposure, skin samples were removed and analyzed for histopathological changes and interleukin-1 alpha (IL-1 alpha) and inducible nitric oxide synthase (iNOS) protein levels.

Improved method for in vitro assessment of dermal toxicity for volatile organic chemicals.

Cell culture methods are being developed to assess the dermal toxicity (irritancy and corrosion) of chemicals. These in vitro methods are being validated to categorize chemicals as irritating or non-irritating to humans. Currently, these cell culture tests are useful to assist in the ranking of chemicals for irritancy, but they are not useful for quantitative risk assessment for two reasons.

Methods for assessing risks of dermal exposures in the workplace.

The skin as a route of entry for toxic chemicals has caused increasing concern over the last decade. The assessment of systemic hazards from dermal exposures has evolved over time, often limited by the amount of experimental data available. The result is that there are many methods being used to assess safety of chemicals in the workplace.

Skin absorption and human risk assessment.

A common practice is to assume that percutaneous absorption does not significantly contribute to total bioavailability and therefore, absorption through other routes is more important to human risk assessment. The skin can represent a significant barrier to absorption, but some substances are absorbed to a significant extent. Since there is a potential for percutaneous penetration that is not consistent between species or substances, the assessment of the potential contribution of total body burden from dermal exposures should be considered.

Assessment of dermal absorption and penetration of components of a fuel mixture (JP-8).

Occupational and environmental multi-chemical exposures are extremely common. Methods for assessment of the risks from dermal exposures to complex mixtures vary depending on the information available. The composition of a volatile mixture (such as JP-8 jet fuel) can change radically, depending on the phase of the mixture - vapor, liquid or aerosol.