Penetration of industrial chemicals across the skin: A predictive model

The recently reported dermal absorption and toxicity potential of industrial chemicals is reconsidered using an alternative physicochemically based model of skin penetration. In this model, the outermost, and least permeable, component of the skin [namely, the stratum corneum (SC)] is considered to provide only a lipoidal transport pathway into the body for chemicals that come into contact with the skin. The predictive algorithm of the model is biophysically compatible with known SC properties, and is based on experimental determinations of permeability coefficients through human skin in vitro for nearly 100 compounds of widely divergent physicochemical properties. This simpler prediction results in significantly lower estimates of maximum percutaneous penetration fluxes. © 1993 Wiley-Liss, Inc.     

Dermal absorption potential of industrial chemicals: criteria for skin notation

A dermal penetration rate (flux), predicted from physical properties of 132 chemicals, is suggested as an index of the dermal absorption potential of industrial chemicals. The prediction is designed for organic nonelectrolytes. Two reference values are recommended as criteria for skin notation: 1) dermal absorption potential, which relates to dermal absorption raising the dose of nonvolatile chemicals or biological levels of volatile chemicals 30% above those observed during inhalation exposure to TLV-TWA only--dermal absorption of chemicals belonging to this category should be considered when data obtained by biological monitoring are interpreted; and 2) dermal toxicity potential, which relates to dermal absorption that triples biological levels as compared with levels observed during inhalation exposure to TLV-TWA only. Chemicals belonging in this category should carry a skin notation. The toxicity criteria may not be valid for chemicals whose TLVs are based on preventing irritation and discomfort.     

Absorption of chemicals through compromised skin

Skin is an important route of entry for many chemicals in the work place. To assess systemic uptake of a chemical in contact with the skin, quantitative information on dermal absorption rates of chemicals is needed. Absorption rates are mainly obtained from studies performed with intact, healthy skin. At the work place, however, a compromised skin barrier, although not necessarily visible is common, e.g. due to physical and chemical damage. As reviewed in this article, there are several lines of evidence that reduced integrity of the skin barrier may increase dermal absorption of chemicals in the occupational setting. An impaired skin barrier might lead not only to enhanced absorption of a specific chemical, but also to entrance of larger molecules such as proteins and nanoparticles which normally are not able to penetrate intact skin. In addition to environmental influences, there is increasing evidence that some individuals have an intrinsically affected skin barrier which will facilitate entrance of chemicals into and through the skin making these persons more susceptible for local as well for systemic toxicity. This review addresses mechanisms of barrier alteration caused by the most common skin-damaging factors in the occupational settings and the consequences for dermal absorption of chemicals. Furthermore, this review emphasizes the importance of maintained barrier properties of the skin.     

Estimation of the percutaneous absorption of styrene in an industrial situation

This field study was designed to compare the level of styrene absorbed percutaneously with that absorbed by inhalation in a real situation in the fiberglass-reinforced polyester industry. Methods: The study protocol consisted of comparisons of the patterns of urinary excretion of styrene metabolites by four groups of workers, all of whom performed the same task at the same time in the same workshop but wore the following different protective equipment: total protection with an insulating suit and mask, respiratory equipment only, percutaneous protection only, and no protection. Results: The urinary excretion level of the group with total protection did not significantly differ from that of the group with respiratory protection only. Conclusions: Precutaneous absorption is not a particularly important pathway for styrene absorption during stratification work in the polyester industry. Completely insulating personal protective equipment provides no greater level of protection than does a respirator at positive pressure alone. Received: 14 April 1998 / Accepted: 4 August 1998     

Percutaneous penetration of benzene in hairless mice: an estimate of dermal absorption during tire-building operations

Repeated skin contact with solvents containing as much as 0.5% benzene is common in workers building regular bias passenger tires. To estimate the amount of benzene absorbed through the skin of these workers, a series of in vivo studies was conducted in hairless mice. Percutaneous absorption, following single dermal applications of 14C-benzene contained in rubber solvent at a concentration of 0.5% (v/v), was calculated directly from the sums of radioactivity found in excreta, expired breath, and the carcass. Data from the study, together with observations made during tire-building operations, suggest that a worker could absorb 4-8 mg of benzene daily through the skin. This compares to 14 mg per day via inhalation at the NIOSH recommended standard of 1 ppm. Thus dermal absorption could contribute from 20-40% of the total benzene dose of these workers.     

A Meta-analytic Review of the Effectiveness of Single-Layer Clothing in Preventing Exposure From Pesticide Handling

This review summarizes available information on the penetration of pesticides through single-layer clothing by pesticide handlers and introduces epidemiological and observational studies on pesticide exposure. The data for this report were taken from peer-reviewed articles, publicly available government reports, and publicly available government reviews of registrant-submitted data and information. The arithmetic mean of calculated clothing penetration was obtained for various parts of the body (upper arm, lower arm, chest/torso, back/torso, upper leg, and lower leg) that were exposed to pesticide. The range of pesticide penetration to the various parts of the body through single-layer clothing during mixing, loading, and application (MLA) activities was found to be 6.2% ± 5.7% to 21.4% ± 6.7%, which demonstrates a potential for increased and unintentional pesticide exposures. Based on this evaluation, some accepted default values for protection against pesticide exposure may be overestimated.     

Distribution of lost-work-time claims for skin disease in California agriculture: 1978-1983

In order to identify California agricultural workers at high risk for occupational skin disease, we evaluated the distribution of 2,722 claims for lost-work-time skin conditions reported between 1978 and 1983 by Standard Industrial Classification (SIC) and source of illness. In the overall work force, cases were most frequently attributed to plants (52.1%), chemical exposures (20.4%), and food products (12.5%), but considerable variation occurred in the distribution of cases among the subdivisions of agriculture. The forestry subdivisions (SICs 081, 082, 084, and 085) had the highest rate (given as cases/10,000 employed) of claims for skin disease attributed to plants (53.5), but no cases due to other exposures. For chemical exposures, the highest rate of claims occurred in the horticultural specialities (SIC 018) subdivision (5.1), but this group also had a significant claims rate for plant-related skin disease (15.9). The highest claims rate for cases attributed to food products occurred in the vegetables/melons subdivision (4.7), but this group had claims rates for exposure to plants (3.8) and chemicals (2.8) that were nearly as high. Efforts to evaluate and prevent skin disease in agricultural workers should recognize the complex range of exposures to which this work force is subject.     

Biological surveillance of workers exposed to dimethylformamide and the influence of skin protection on its percutaneous absorption

Summary Two studies were carried out among workers exposed to dimethylformamide (DMF) in an acrylic fiber factory. The first study involved 22 exposed workers and 28 control workers. Blood was examined at the beginning and at the end of a working week for the presence of biological signs of liver dysfunction. Pre- and post-shift urine samples were also collected during 1 week for determination of N-methylformamide (NMF) concentration. The airborne concentration of DMF was determined at different work places during the same period. On prevention of direct skin contact with DMF solution a significant correlation was found on a group basis between the concentration of DMF vapor and the NMF concentration in post-shift urine samples. When the concentration of NMF in post-shift urine samples from a group of workers does not exceed 30 mg/g creatinine, then their integrated exposure is probably below 60 mg/m³ × h (10 mg/m3 for 6 h). This exposure appears to be safe with regard to the risk of liver damage but does not necessarily preclude episodes of alcohol intolerance in some workers.During a second study, NMF concentrations in pre- and post-shift urine samples were followed-up in seven workers during three weeks when different personal protective devices were used. In an acrylic fiber factory, skin absorption was found to be more important than inhalation in the overall exposure to the solvent when no personal protective devices were used. The use of impermeable gloves with long sleeves appears to be the best method of preventing skin absorption of DMF. Silicone or glycerol barrier creams are less effective and should not be recommended.Part of this work was presented at the First International Congress on Toxicology in Toronto 1977     

A real-time in-vivo method for studying the percutaneous absorption of volatile chemicals

Realistic estimates of percutaneous absorption following exposures to solvents in the workplace, or through contaminated soil and water, are critical to understanding human health risks. A method was developed to determine dermal uptake of solvents under non-steady-state conditions using real-time breath analysis in rats, monkeys, and humans. The exhaled breath was analyzed using an ion-trap mass spectrometer, which can quantitate chemicals in the exhaled breath stream in the 1-5 ppb range. The resulting data were evaluated using physiologically-based pharmacokinetic (PBPK) models to estimate dermal permeability constants (Kp) under various exposure conditions. The effects of exposure matrix (soil versus water), occlusion versus non-occlusion, and species differences on the absorption of methyl chloroform, trichloroethylene, and benzene were compared. Exposure concentrations were analyzed before and at 0.5-hour intervals throughout the exposures. The percentage of each chemical absorbed and the corresponding Kp were estimated by optimization of the PBPK model to the medium concentration and the exhaled-breath data. The method was found to be sufficiently sensitive for animal and human dermal studies at low exposure concentrations over small body surface areas, for short periods, using non-steady-state exposure conditions.     

Effects of arsenic on human keratinocytes: morphological,physiological, and precursor incorporation studies

Measurement of in vitro percutaneous absorption of As(III) and As(V) by artificial human skin shows a strong affinity of arsenic for the human keratinocytes, with 1-10% of the applied arsenic dose retained by the artificial skin per hour. The inordinate retention of arsenic by the skin is a risk factor for As toxicity. The calculated permeability constant (K(p)) averaged about 4.3 x 10(-5) cm/h for As(V) and 10.1 x 10(-5) cm/h for As(III). A facile calculation suggests that dermal absorption during showering and hand washing can be an important exposure route if the water contains more than 100 microg/L As(III) or As(V). The effects of the absorbed arsenic in artificial skin were evaluated in terms of morphological characteristics, integrity of the cell membrane (by means of lactate dehydrogenase and MTS assays), and rates of DNA, RNA, and protein synthesis estimated by incorporation of radioactive precursors. We found significant morphological changes, cytotoxicity associated with disruption of the cell membrane, and inhibition of DNA and protein syntheses at As(III) exposure doses as low as 10 microg/L.     

In vitro evaluation of the efficacy of skin barrier creams and protective gloves on percutaneous absorption of industrial solvents

OBJECTIVES: The aim of the experiments was to evaluate the efficacy of skin barrier creams (SBCs) and protective gloves and its potential for reduction of percutaneous absorption of industrial solvents. METHODS: We assessed percutaneous absorption of ethylene glycol (EG), isopropyl alcohol (IA) and 1,2,4-trimethylbenzene (TMB), using static diffusion cells. These solvents were applied neat (EG, TMB) as well as in 10% and 50% aqueous solution (EG, IA) or in 10% and 50% ethanol-diluted solution (TMB). Furthermore, we tested the percutaneous absorption of IA mixed in one cleaning agent (CA), used in newspaper printing shops to clean the rollers of printing machines. Additionally, the penetration behaviour of 10% and 50% solutions of EG, IA and TMB was tested. The experiments were carried out on untreated and on SBC-treated excised human skin from one donor, and on protective gloves. Saline was used as receptor fluid for EG and IA, and neat ethanol for TMB. RESULTS: The penetration of 50% EG, IA and TMB solutions through SBC-treated skin was higher than in untreated skin (factor 3.9 for EG, 0.32 for IA and 0.06 for TMB). The penetration of IA in the IA-CA mixture was five-times higher through untreated skin as for the single compound in 10% aqueous solution. In skin, treated with SBC, we found a 17-fold penetration enhancement of IA in the IA-CA mixture. No appreciable penetration of EG and IA was observed through nitrile rubber gloves. CONCLUSIONS: Our in vitro experiments could not demonstrate an efficacy of SBC to protect skin penetration for the tested solvents. The percutaneous absorption of all solvents in 50% solution was increased through skin treated with SBCs. Furthermore, SBCs enhance the penetration rates of solvents from complex mixtures compared with the single solvents. The tested gloves showed sufficient protection for the hydrophilic solvents, but not for TMB.     

In vitro percutaneous absorption of cobalt

Objectives To evaluate skin absorption of cobalt powder in an in vitro system. Experiments with volunteers show that cobalt powder can permeate through the skin, but there are no data with regard to the mechanism or the amount of permeation.Methods Skin permeation was calculated by the Franz diffusion cell method with human skin. A physiological solution was used as receiving phase and the cobalt powder was dispersed in synthetic sweat. The amount of metal passing through the skin was analysed by electro-thermal atomic absorption spectrometry (ETAAS). Parallel polarographic analysis (differential pulse polarography—DPP) allowed evaluation of cobalt present as ions (Co²⁺) in donor and receiving phases. Measurements of cobalt skin content were also performed.Results Evaluation of metal in the receiving phase allowed us to demonstrate the permeation of cobalt through the skin. Steady-state flow of percutaneous cobalt permeation was calculated as 0.0123±0.0054 g cm^–2 h^–1, with a lag time of 1.55±0.71 h.Conclusions The experiments show that cobalt powder can pass through the skin when applied as a dispersion in synthetic sweat, oxidising metallic cobalt into ions, which permeate the skin. These experiments show for the first time how cobalt can permeate the skin.     

Guttate psoriasis: a case of unusual evolution of an occupation-related skin chemical burns

Introduction:Chemical burns are a risk in domestic and occupational accidents due to the common use of caustic agents. Long-term sequelae are normally due to the amount of skin and underlying tissues damaged. We describe a case of work-related chemical burns with unusual evolution in guttate psoriasis.Case Report:A 36 years-old man was admitted to the Emergency Department (ED) three-hours after a work accident. During the cleaning of an industrial hydraulic system, a jet of hydrochloric acid 20% injured his face and upper limbs. At ED admission, he presented first and second-degree skin burns on the frontal region, on the scalp, on the right forearm, and earlobe. Plastic surgery management consisted in wound topical dressing with silver sulfadiazine and paraffin gauze twice a week for one month. Forty-eight hours after the latter topical treatment (45-days after the work accident), in the same anatomical regions of the previous burn scars, he developed a skin reaction with itchy erythema. The application of topical products was suspended without improvement, excluding an allergic reaction. Within few days, a generalized guttate psoriasis was evident on the whole body.Discussion:Despite many prevention actions, work-related burns are a relatively common cause of hospitalization and may involve up to 80% of patients admitted to a burn unit. Guttate psoriasis has not been described as a sequelae of chemical burns. In our case, the others most frequent factors causing guttate psoriasis have been ruled out. Considering the temporal link between the development of guttate psoriasis and the work accident, hydrochloric acid skin burns might have promoted the systemic inflammatory mediators’ mechanism involved in the development of guttate psoriasis lesion’s after the dermal injury.     

Occupational lead poisoning: Who should conduct surveillance and training?

This commentary challenges the current employer-controlled model for delivering occupational health services. Problems emanating from traditional employer-based medical surveillance and worker education programs for occupational lead poisoning are identified. A new public health model for delivering these services is proposed. This model utilizes a case-based and hazard-based method for bringing workplaces and employers into the program and features direct delivery of surveillance and training services by public health agencies.     

化学品刺激性组织工程皮肤检测模型的构建

目的构建检测化学品刺激性的组织工程皮肤模型。方法利用组织工程学方法,以牛胶原为支架,以人皮肤角质形成细胞和成纤维细胞为细胞来源,构建检测用组织工程皮肤模型。选用10种化学品为检测物质。在刺激性检测实验中,10种化学品(固体10 mg、液体10μL)局部接触检测模型表面15 min,用MTT方法测定细胞活力。结果以相对细胞活力值为判定刺激性的依据,在10种化学品中,构建的检测模型能够分辨7种化学品的刺激性。结论构建的组织工程皮肤模型能判定化学品的刺激性,可以尝试用于化学品刺激性的检测。     

Summary of "Proposed national strategies for the prevention of leading work-related diseases and injuries, Part 1"

Strategies for the prevention of leading occupational health problems have been proposed by the National Institute for Occupational Safety and Health (NIOSH). NIOSH prepared these strategies following publication in 1983 of its suggested list of ten leading work-related diseases and injuries. At a national symposium in 1985, occupational health experts from academia, organized labor, management, professional associations, and voluntary organizations conducted an in-depth evaluation of the prevention strategies for the first five conditions on the list: occupational lung diseases, musculoskeletal injuries, occupational cancers, severe occupational traumatic injuries, and occupational cardiovascular diseases. The strategies were then revised to incorporate improvements suggested at the symposium and were published in booklet form. A summary of the revised strategies is provided.