Dermal exposure to dangerous substances
Peter Paszkiewicz, Karl Buchwald, Institut for Occupational Safety and Health of the German Social Accindent Insurance (IFA), Germany
- 1 Introduction
- 2 About dermal exposure
- 3 Anatomy and functions of the skin
- 4 Health effects
- 5 Occupations at risk
- 6 Determination of dermal exposure
- 7 Risk assessment - models for exposure and risk estimation
- 8 Control and prevention
- 9 References
- 10 Links for further readings
European statistics report 5,778 cases of occupational contact dermatitis within the EU in 2005 . These work-related dermatosis, in particular hand dermatitis, are among the most prevalent occupational diseases. Due to the lack of scientific methods to measure the level of the body’s exposures to dangerous substances via dermal contact, no dermal exposure limit values are set. This increases the importance of recognising risk factors and developing methods of assessing and controlling them. This article will deal with the risk of dermal exposure to hazardous substances. Depending on the nature of the substance and the working conditions the quantification of the extent of exposure and their potential reduction by protective measures will be described.
About dermal exposure
Acids, bases, cooling lubricants, greases, pesticides, cleaning agents and frequent contact with water – the skin is exposed to many risks at the workplace. Workers are therefore exposed not only to risks from inhaled and ingested substances, but also to the effects of agents acting on the skin, i.e. dermal exposure. A distinction is therefore made between agents acting primarily on the surface (local irritants and/or allergens) and those that penetrate the layers of the human skin, enter the blood and lymph vessels of the human body (percutaneous absorption) and can thus act systemically. The combined effect of irritation of the top layer of skin and penetration of the skin has been observed in many cases. However, dermal exposure is often only comprehended as the effect of health-hazardous gases/vapours, liquids, aerosols and solid particles, and particularly nanoparticles, on the skin’s surface, inclusive of their accumulation and deposition, while the absorption of substances in deeper layers of the skin is in many cases not considered.
Methods for measuring and assessing inhalation exposure at the workplace became established early on (in “traditional” sectors such as the mining and manufacturing industry) and are well documented. However, the degree of dermal exposure can only be quantified to a limited extent by measurement. Factors such as the skin-relevant properties of the substances (e.g. irritant, sensitizing, corrosive, abrasive, resorptive) used, the type of activity and handling of the substance, and the duration and extent of possible skin contamination (skin contact) at the workplace are important to assess dermal exposure. In order to carry out a proper workplace risk assessment as per Directive 98/24/EC on the protection of workers from the risks related to chemical agents at work , these determinants of dermal exposure should be ascertained with suitable measurements or, in certain circumstances, with a rough estimate. On this basis, the effects of the skin-relevant hazardous substances on human health can be assessed. Based on the results of the risk assessment process, adequate protective measures can then be selected and put in place. Models for describing and estimating the degree of dermal exposure due to the associated activities at the workplace, e.g. RISKOFDERM, EASE, DREAM, ECETOC TRA (see Chapter “Risk assessment - models for exposure and risk estimation”), which have been developed in recent years, have proven helpful. There are not yet any specific occupational limit values for dermal exposure to hazardous substances on the European level. Under REACH, certain hazardous substances have been assigned DNELs (Derived No-Effect Levels) as guide values for dermal exposure limits for workers, beneath which a substance ought not to impair health.
Anatomy and functions of the skin
With a surface area of 1.5 to 2 m² and roughly a sixth of the body’s weight, the skin is the biggest and functionally most versatile sense organ of the human body. Serving as the interface with the surroundings, it protects the human body from all manner of aggression. It consists of three different layers: the epidermis with the stratum corneum, the dermis beneath it, and the subcutis or hypodermis with the subcutaneous fatty tissue.
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The extremely thin horny layer (stratum corneum) of the epidermis serves as the immediate protective barrier of the skin’s surface vis-à-vis the outside world. As such, it not only has to fend off chemical and physical aggression from outside, but also limit water uptake and release by the epidermis. It does this additionally with a hydrolipid film on the surface of the stratum corneum. This protective film constantly replenishes itself, keeps the skin supple and is composed of lipids (fats) from the sebaceous gland secretions, water, proteins and salts from the sweat glands. The cells of the epidermis are held together with flexible adhering spots. The epidermis is thus internally cohesive and connected to the dermis. The tiny gaps between the epidermis cells are flushed with lymphatic fluid only and are not supplied with blood. Injuries confined to the epidermis do not therefore bleed, but weep.
The dermis consists of firm and strong connective tissue. This structure gives it its high tensile and dimensional strength. Its collagen fibres also bind water. Numerous blood and lymph capillaries, heat/cold receptors and touch receptors are embedded in the dermis along with sweat glands, hairs and sebaceous glands.
The hypodermis or subcutaneous tissue is composed of clusters of fat cells and connective tissue. It serves as a connective and sliding layer between the dermis and the body’s muscle and organ tissue beneath. It also serves as thermal insulation, is pressure-elastic and stores nutrients and water. The properties and vitality of this skin layer depends greatly on gender, age, the region of the body, state of nutrition and to a large extent on degeneration by physical load.
In addition to its function of protecting the interior of the body from external effects, the skin regulates body temperature, identifies changes in temperature and pressure with the numerous nerve endings and specialized cells on its surface, and reports injury or disease with pain stimuli. In interaction with the body’s own immune system, the skin is an active organ providing protection against pathogens. If the above-mentioned aggression overcomes the barrier of the layers of skin and they are no longer capable of regenerating, skin disease is the result. Depending on the individual’s skin constitution and exposure (type, duration and concentration) to substances, fatty acids are removed from the upper layers of skin and water-binding structures are deactivated. The barrier function particularly of the stratum corneum is weakened, and harmful substances can increasingly penetrate into the organism. In the event of prolonged contact with water, changes in the skin may also arise, resulting in impairment of the barrier function. Sweating in liquid-tight protective clothing and work performed in wet or damp conditions cause the stratum corneum to swell by maceration and can increase the skin’s tendency to admit chemical agents or microorganisms.
Chemicals can either act locally, and are capable of acutely irritating or burning the skin and, after repeated exposure, may chronically damage the skin or they can act systematically, after percutaneous absorption, and cause poisoning or even cancer. Sensitising substances may cause allergic reactions due to skin contact, such as from activities in the health service (e.g. disinfectants in general and methacrylates in dental laboratories) and in the construction area (e.g. dichromate, cobalt, nickel of cements and epoxy resins) . In the EU, attention is drawn to these effects by the classification and labelling of substances and products (risk assessment). Regulation (EC) No. 1272/2008 on the Classification, Labelling and Packaging of Substances and Mixtures (CLP Regulation ) lists skin-relevant chemical agents in hazard categories and hazard classes with associated hazard statements.
Local skin effects
A chemical can remain on the skin surface and induce local effects. A brief contact with a corrosive substance, e.g. strong acids, wet cement and alkalis can lead to severe skin damage (burns) and skin scarring  .
If the skin comes into repeated contact with skin-stressing substances, this can cause contact dermatitis. Such non-infectious inflammations are usually manifested by reddening of the skin with blistering, swelling, flaking or cracking, and in some cases with cornification. A distinction is made between two important, frequently occupational forms: allergic contact dermatitis (ACD) and irritant contact dermatitis (ICD). Both can result in developing eczema.
Irritant contact dermatitis (ICD) arises after exposure to corrosive and irritant substances (such as acids, lyes and thinners), mostly as a result of an accident or the grossly negligent handling of concentrated and mostly liquid substances and products. But also dilute acids and bases, cooling lubricants, dishwashing detergents, soaps, shampoos, phototoxic and photosensitising substances, particularly plant constituents and even water itself are capable over a prolonged period, due to repeated contact, of weakening the skin’s protective function to cause cumulative-subtoxic contact eczema. This condition is also known as degenerative dermatosis. Particularly at risk are people who tend naturally to have dry skin, including people with an inherited high risk of allergy (sufferers of neurodermitis or atopic dermatitis).
If the skin’s protective function and especially that of the cornified layer breaks down, sensitising substances (reactive, mostly low-molecular compounds such as preservatives and fragrances, metal ions, rubber auxiliaries, epoxy resin ingredients and many more besides) can penetrate more readily into the living upper layers of the skin and skin cells and induce allergic contact eczema (ACD). The latter is attributable to an exaggerated immune response, whose visible symptoms (reddening, swelling and blistering) are usually associated with pronounced itching. Allergic contact eczema occasionally spreads beyond the regions of the skin directly affected into other regions of the body. For instance, isocyanates are suspected of causing allergic reactions of the air passages (asthma) after skin contact. Conversely, sensitising substances that enter the body by inhalation or ingestion are also readily capable of causing allergic skin reactions. Even where adequate protective measures of a technical and organisational nature are taken, once a worker has suffered an occupational allergy a change of workplace is therefore often necessary .
For microorganisms (bacteria, fungi or viruses), damaged skin can be a point of entry. Animal bites, thorns and splinters can thus cause local infection. Hands that are often damp become susceptible to chronic disease such as mycosis. Among workers that frequently immerse and wash their hands in water or soap and detergent solutions (e.g. cooks, barkeepers, cake bakers, fish sellers and hair dressers), this disease manifests itself as an inflammation of the nail wall and bed. Yeasts and bacteria are the cause of this. A small group of viruses cause “butcher’s warts” (specific cutaneous condition) on the hands of people who professionally handle meat and meat juices. Parapox viruses can affect animal breeders, milkers, shepherds, veterinary surgeons and animal keepers who come into contact with cattle, sheep and goats .
Another skin disease due to dermal exposure to chemicals are contact urticaria. This is a skin condition that typically shows as an immediate skin swelling surrounded by areas of redness. Skin irritants or allergens may cause it. It is different from ICD and ACD in that it quickly follows skin contact and disappears again within hours.
Dermal exposure may also lead to skin cancer. Skin cancer is one of the most common types of cancer. Skin tumours can result from exposure to ionizing radiation, some metals, arsenicals, Polycyclic Aromatic Hydrocarbons (PAHs), etc. The most widespread cause of skin cancer in light-skinned populations is exposure to sunlight, specifically to its UV component.
Acne is an inflammatory disease of the sebaceous glands and hair follicles in the skin. Acne can result from exposures to various chemical and environmental factors (physical or mechanical), usually encountered at the workplace, but occasionally in non-occupational settings as well. Different forms of acne have been associated with exposure to petroleum and its derivatives (i.e. crude oil, metalworking and cutting oils), certain coal tar products and halogenated aromatic compounds  
Dermal penetration / absorption
After contact with the skin, certain chemical substances at the workplace have not only a superficial effect, but can also under certain circumstances enter the body by penetrating the layers of the skin via the blood and lymph vessels and cause systemic damage of the inner organs. This mode of uptake is termed “percutaneous absorption”. Not only liquids, but also gases can be absorbed via the skin. However, even assuming that no effective personal protective equipment (PPE) is used, the uptake by inhalation is about ten times higher than via the skin . There is currently controversy over the extent to which ultrafine solid particles and nanoparticles (particles with a diameter of less than 100 nm) or coarser dusts can be absorbed via the skin.
The speed with which a substance penetrates the skin is known as “flux” or the “dermal penetration rate”. The rate of penetration depends to a large degree on the affected region of the skin and its condition. The permeability of the sole of the foot, for example, is much lower than the insides of the lower arms which only have a very thin cornified layer. Genetic predisposition, gender, age, temperature and the skin’s moisture content also affect absorption behaviour. Substances can also be stored in the upper skin layers and be released into the organism over a long period of time (depot effect), in particular, if the skin has already been damaged by disease or by chemical or mechanical aggression.
The scientific criteria for the specific classification and designation of substances that are readily absorbed by the skin often lack the desired clarity. Skin notation  is not always based on a comprehensible quantitative analysis of absorption behaviour. International harmonisation of the criteria would be desirable. The Scientific Committee on Occupational Exposure Limits (SCOEL) issues a skin notation indicating a possible significant uptake through the skin. A skin notation also alerts risk assessors and occupational hygienists in the interpretation of workplace air monitoring results that may not reflect the total uptake of the substance if skin contact or gut uptake occurs due to workplace practices or usage. Usually, SCOEL issues a skin notation when it can be assumed that dermal exposure may contribute to about 10 % or more of the body burden by inhalation exposure at the occupational exposure limit .
Occupations at risk
Occupational skin disease is still a frequent occurrence in the working environment. Virtually all branches of industry and commerce, from crafts & trades through to the service sector, are affected. Prominent here are occupations in the health, social and nutritional services, hairdressers, the metalworking sector, the retail trade and the construction trades. Work performed in wet areas, designated as wet work, can seriously impair the skin’s barrier function. In the EU member states, occupationally induced skin disease occupies second place behind musculoskeletal disease . The most frequently and directly affected regions of the skin are on the hands and upper arms. From there the contamination can easily be transferred to other parts of the body. The cost of occupational skin disease is immense. This includes not only expenditure on compensation, retraining and skin disease prevention amounting to several hundred millions of euros within the EU economy, but also the social consequences. In many cases, particularly in the event of repeated recurrence, an occupational disease of the skin can force the worker to give up his task and/or his occupation.
Determination of dermal exposure
Dermal exposure is an estimate of the amount of substance contacting the exposed surfaces of the skin. Dermal exposure is highly variable and often unpredictable. It is often made up of splashes and smears and not an idealised evenly spread layer on the skin, or it may occur from spraying an aerosol that generates a high concentration which is then deposited widely on the exposed skin and clothing. Dermal exposure may occur through direct skin contact or indirectly, through contact with surfaces that have been previously contaminated. Although direct handling and application to the skin should be considered as the most direct source of dermal exposure, also indirect pathways of dermal exposure (e.g. contact with substances being deposited on or adsorbed onto surfaces) have to be considered as well. Examples are the re-entering of a field after pesticide application, contact with contaminated materials, contact with contaminated surfaces such as workbenches, cleaning equipment, work tools, contaminated hands, clothes and protective equipment (e.g. gloves). Indirect contact can also expose co-workers or family members.  .
When the inhalation exposure of workers is monitored at the workplace, the hazard potential is relatively easy to estimate, either by measuring the hazardous substance in the air with a directly indicating instrument at the workplace or by collecting the substance with sample carriers and subsequent analysis. The results also usually show high reproducibility, even independently of the measuring method. There is also the risk of the measurement being uninformative if it is not certain that the conditions during measurement are representative for the workplace. However, estimating the quantitative risk to the skin is much more difficult. Specific factors have to be taken into account here: mass and/or concentration of the substance on the skin, extension of the exposed area, localisation of the substance’s effect on the body, and duration of exposure. The measurement techniques currently under discussion are based on very different methods and yield different measurement results.
Most promising are those methods that allow the hazardous substances deposited on the skin to be measured . These methods pursue a variety of goals. While those exploiting the principle of adsorption permit the quantification of deposition, those using fluorescence are primarily concerned with localising contaminated regions of the skin, e.g. on the hands or face, during a work shift. None of the usual methods for estimating dermal exposure allow determining realistically how much of the potentially hazardous, skin-resorptive or skin-sensitising substance is actually taken up via the skin. The skin’s transport mechanisms, the substance behaviour with increasing skin damage, the difference in behaviour between liquid and vaporous substances on the skin, the level of moisture on the skin’s surface and the effects of work clothing on substance uptake can only be gauged to a limited extent. Pragmatic approaches in combination with other measurement principles, e.g. biological monitoring, yield models permitting an approximate estimate of dermal exposure.
Surrogate skin methods (adsorption)
These adsorption methods make use of collection media (adsorber pads) attached to the skin that are removed after a certain exposure time so that the accumulated hazardous substance can be subsequently analysed. The adsorption and absorption behaviour and recovery rate are affected not only by the chemical collection and retention properties, but also by the physical properties of the collection materials consisting of cellulose paper, polystyrene or polyisoprene. Gloves or complete disposable suits can also serve as the collection medium . With these methods, measurements at the same workplace or at comparable workplaces often yield divergent results. This may be because the splashes of liquids are randomly distributed, meaning that the skin regions exposed may vary at different times even within a same workplace. In case adsorber pads are used, only the exposure of a very small surface area is determined, while the result is used for calculating the exposure of a much larger area (up to whole-body exposure) by extrapolation. If collection media are selected solely on the basis of their (good) adsorption behaviour, positively biased assessments are probable. Results are expressed in mass per unit area. These methods are also of interest for the stationary monitoring of workplaces or, in a modified form, for checking the effectiveness of personal protective equipment.
Removal techniques (wash and wipe techniques)
With these methods, potentially affected areas of the skin are washed with water/or suitable solvents and the solutions obtained are analysed . Results can be expressed, for example, in mass per body part. Variation can arise solely due to differences in the mechanical force applied during the washing process. Another method involves using adhesive tape (tape stripping), by which hazardous substances are removed from the skin. This method also shows large spread in the measurement results due not only to the type of adhesive film, but also to the pressing force and action time until the tape is stripped.
Imaging methods (fluorescence method)
Fluorescent substances, e.g. polycyclic aromatic hydrocarbons (PAHs), or substances containing fluorescent compounds (tracers) can be localised and quantified by measuring the intensity of the fluorescent radiation. In the case of quantitative analysis, again only the defined area of a representative region of the skin can be used for measurement and assessment of dermal exposure . Like most of the methods already described, the fluorescence method is also susceptible to measurement error due to uneven exposure, e.g. splashes. The fluorescence method gives rise to special problems when exposed to sunlight, e.g. fading of the tracer, and due to differences in behaviour of the hazardous substance and the tracer on the skin.
Estimation of dermal penetration
A variety of methods is available for the experimental determination of the dermal penetration rate. These may yield very different results .
Studies on living humans yield the most informative results. After controlled application on a defined area of the skin, the uptake of substances and their products of degradation can be quantitatively determined in the blood or urine. A modern but invasive method is microdialysis in which a small cuvette with a semi-permeable membrane is implanted under the skin. A physiological solution is pumped through the cuvette and collected for subsequent analysis.
With these methods, living tissue removed from the organism is isolated and analysed in laboratory conditions. When preparing such tissue, care must be taken that the skin’s natural ability to metabolise penetrating substances is not significantly impaired.
In-vitro methods The in-vitro models include studies on porcine ears, bovine udders or also on small pieces of human skin. The blood vessels of these biopsies are perfused with a physiological fluid in a temperature-controlled test cell. After external application of the test substance, the perfused fluid serves as an uptake medium and analysis matrix for determining the share of the test substance that has penetrated the skin. The advantage of such models is that percutaneous absorption shows relatively quickly how the substance is transported.
Risk assessment - models for exposure and risk estimation
The factors affecting dermal exposure are as varied as the working conditions and emission sources themselves . The worker’s personal hygiene also affects the extent of skin contact of skin-stressing substances at work far more than would be the case with purely inhaled substance. Investigations performed in the context of the RISKOFDERM project  funded by the EU show that the statistical variation in dermal exposure during activity with a certain substance for an occupational group is relatively low, while the measurement results vary considerably from one worker to the next. This is because the substances may be distributed randomly on the different regions of the body and therefore do not necessarily touch the sampler at their specific locations. A precise toxicological assessment based on surveys of the exposure of the surface of the body calls for a wide range of information: the mass concentration of the substance on the stratum corneum, the size of the affected parts of the body and exposed area, and the duration of contact (which is also challenging to determine as volatile substances may vaporise!). Measuring methods (see Section "Estimation of dermal penetration") supply information on the deposited mass (dermal exposure mass) and, in the best case, on the mass per unit area (dermal loading). Collection and washing techniques merely ascertain exposure at a certain moment in time. The relatively slim body of data derived from highly different measuring methods and the considerable individual spread in the results make it difficult to develop accurate methods for estimating dermal exposure and the associated risk. Various models have become established in the last few years, using different approaches and with only limited exposure assessment comparability. Most of them are based on the Control banding approach which is a semi-quantitative and practical approach to controlling hazardous exposures at work. It includes a risk assessment and management process of assigning a compound to a hazard category that corresponds to a range of exposure scenarios – and the engineering controls, administrative controls, and personal protective equipment – needed to ensure safe handling. Often, practical experience in the assessment of exposure of the skin at a certain workplace is more valuable than the results obtained from existing exposure models.
The computer-aided expert system Estimation and Assessment of Substance Exposure (EASE) of the British Health and Safety Executive (HSE) and Health and Safety Laboratory (HSL) is a method for estimating exposure to inhaled substances which has been extended to include a module for dermal exposure. It can be used to predict exposures using task- and situation-specific information about the substance and the methods of control. The tool presents the user with a series of choices that are used to identify the appropriate exposure estimate. It predicts the potential exposure to the hands and forearms expressed as a mass per unit area of exposed skin per day. However, the effect of work clothing, skin cleansing or volatile substances is disregarded by the EASE model. Validation studies show that the model sometimes considerably overestimates the quantity of substance that reaches the skin in the recorded workplace conditions . Manufacturer and importer of chemicals often use the ECETOC (European Centre for Ecotoxicology and Toxicology of Chemicals) TRA (Targeted Risk Assessment) model for dermal exposure . This method is based on the EASE model, which is divided into an inhalation model and a model for potential dermal exposure. The TRA in its current version assumes no personal protection equipment being in place as a risk management measure. The tool should be used assuming no local exhaust ventilation (LEV), as it has been found that the tool underestimates the dermal exposure when the presence of local exhaust ventilation is assumed.
The DREAM model (Dermal Exposure Assessment Method) is a structured method with a scoring system for determining and assessing exposure that can be used universally in occupational hygiene and supplies semi-quantitative results. DREAM consists of two elements: an inventory of the present situation and subsequent evaluation. The inventory is supported by a computer-based questionnaire, which gathers information on the company and department, substance, workplace/activity, time period and exposure. The last point includes questions about the work clothing, working methods and distance from the exposure source. The documented data can be weighted with the aid of a scoring system for 33 different variables. The scores for the different variables are added together to yield the Total Actual Dermal Exposure at Job Level. The method supplies relative estimates of contamination of both the clothing and the skin. DREAM is a highly meticulous and hence time-consuming estimation method.
The EU-funded project RISKOFDERM (Risk Assessment for Occupational Dermal Exposure to Chemicals) was designed to produce a validated prediction model for estimating dermal exposure . The method is the outcome, firstly, of results of systematic qualitative workplace observations in various European countries and, secondly, an extensive measurement programme for dermal exposure during certain activities. On the basis of the qualitative data, six activity classes, Dermal Exposure Operation Units (DEO), have been identified, making it possible to classify all activities with dermal exposure. The method takes account of the possible local effect on the skin as well as the risk of systemic effect after percutaneous absorption and brings together the effect and exposure parameters in a decision-support matrix (to estimate the potential dermal exposure rate see “RISKOFDERM Potential Dermal Exposure Model” that indicates the action that can be taken to protect the skin.
The acceptance of the DREAM model and RISKOFDERM varies within the EU. In some member states, simple systems of measures based on the British Controls of Substances Hazardous to Health Regulations (COSHH Essentials  are applied as an alternative to the complex control banding approaches .
Control and prevention
For activities with skin-stressing substances at work or even where the onset of skin disease is suspected, a risk assessment is to be carried out. The outcome may call for measures to prevent skin disease. If skin contact cannot be totally excluded consideration should be given to substitute for a less toxic chemical or to re-designing the work process to avoid splashes, immersion or the contact duration with chemicals as an organisational measure . Where that is not feasible, the use of personal protective equipment (PPE) becomes particularly important as the last resort. Depending on the substance, how it is handled and the activity of the worker at the workplace, it may be necessary to use tight chemical protection gloves covering the skin, protective boots, a chemical protection suit and possibly skin agents (skin protection agent, skin cleanser, skin care cream). Although barrier creams and moisturizing creams protect the skin, they must be viewed as supplements only. They do not replace good personal hygiene or the use of chemical protective gloves where appropriate. Protective clothing and particularly protective gloves of different models and sizes and made of a variety of materials are used in industrial practice. Factors that affect glove selection include:
- type of chemical(s) to be handled (or used)
- frequency and duration of chemical contact (often to rarely)
- nature of contact (total immersion, splash, mist, contaminated surfaces)
- concentration and temperature of the chemical
- abrasion, puncture, tear resistance requirements of the job or task
- length to be protected (hand only, forearm, arm)
- dexterity requirements of the job or task
- grip requirements (dry grip, wet grip, oily)
- glove features (e.g. cuff edge, lining, color (to show contamination))
- thermal protection and
- size and comfort requirements (ergonomic factors).
The primary goal in the use of protective clothing and skin agents is to keep the skin’s barrier effect intact with as little impairment as possible for the function of the upper skin layers. For this reason, protective clothing and particularly the skin agents must satisfy certain requirements in terms of effectiveness”.
- European Occupational Diseases Statistics (EODS), Eurostat Metadata in SDDS format: Base Page, Eurostat, 2005
- Semple, S.: Dermal exposure to chemicals at the workplace: just how important is skin absorption? Occup. Environm. Med. 61 (2004), S. 376-382. Available at: 
- Council Directive 98/24/EC of 7 April 1998 on the protection of the health and safety of workers from the risks related to chemical agents at work (fourteenth individual Directive within the meaning of Article 16(1) of Directive 89/391/EEC). Available at: 
- Regulation (EC) No 1907/2006 of the European Parliament and of the Council of 18 December 2006 concerning the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH), establishing a European Chemicals Agency, amending Directive 1999/45/EC and repealing Council Regulation (EEC) No 793/93 and Commission Regulation (EC) No 1488/94 as well as Council Directive 76/769/EEC and Commission Directives 91/155/EEC, 93/67/EEC, 93/105/EC and 2000/21/EC. Available at: 
- Packham, C.L., ‘Essentials of Occupational Skin Management, a practical guide to the creation and maintenance of an effective skin management system’, The Limited Edition Press, 1998.
- Van Hemmen, J.J., ‘Dermal Exposure to Chemicals’. The Annals of Occupational Hygiene, 48 (2004) No. 3, pp. 183-185
- EU-OSHA – European Agency for Safety and Health at Work‘Occupational skin diseases and dermal exposure in the European Union (EU-25): policy and practice overview’, , European Risk Observatory Report 6, 2008. Available at: 
- Regulation (EC) No 1272/2008 of the European Parliament and of the Council of 16 December 2008 on classification, labelling and packaging of substances and mixtures, amending and repealing Directives 67/548/EEC and 1999/45/EC, and amending Regulation (EC) No 1907/2006. Available at: 
- WHO – World Health Organisation, Dermal exposure, International programme on chemical safety, Environmental Health Criteria 242, 2014. Available at: 
- HSE – Health and Safety Executive, Managing skin exposure risks at work, 2015. Available at: 
- Dicke, W., Funk-Stendel, I., Marschner, B., Zuther, F. , ‘Alles über Hautschutz, Hautreinigung, Hautpflege’. Wirtschaftsverlag NW, Bremerhaven 2005.
- Bunge, A.L.; Ley, E.E., Dermal Exposure to powdered solids and aqueous solutions: are the risks different? Proceedings of the International Conference on Occupational & Environmental Exposures of Skin to Chemicals: Science & Policy. Hilton Crystal City 2002. Available at: 
- Fiserova-Bergerova, V., Pierce, T., Droz, P.O., ‘Dermal absorption of industrial chemicals: Criteria for skin notation. Am. J. Ind. Med. 15 No. 5, pp. 617-635.
- EU Commission, ECHA, Joint Task Force ECHA Committee for Risk Assessment (RAC) and Scientific Committee on Occupational Exposure Limits (SCOEL) on Scientific aspects and methodologies related to the exposure of chemicals at the workplace. Available at: 
- Karjalainen, A., Niederlaender, E., ‘Occupational Diseases in Europe in 2001, Statistics in focus, POPULATION AND SOCIAL CONDITIONS, 15/2004.
- ECHA – European Chemicals Agency, Guidance on Information Requirements and Chemical Safety Assessment, Chapter R.14: Occupational exposure assessment, 2016. Available at: 
- Fenske, R.A., ‘Dermal exposure assessment techniques’, Ann. Occup. Hyg. 37 (1993) No. 6, pp. 687-706.
- Soutar, A., Semple, S., Aitken, R.J., Robertson, A., Use of patches and whole body sampling for the assessment of dermal exposure. Ann. Occup. Hyg. 44 (2000) No. 7, pp. 511-518.
- Lindsay, F.E., Semple, S., Robertson, A.; Cherrie, J.W.: Develepment of a biologically relevant dermal sampler. Ann. Occupat. Hyg. 50 (2006), Vol 1, pp. 85-94.
- Brouwer, D.H., Boeniger, M.F., van Hemmen, J.J., ‘Hand wash and manual skin wipes’. Ann. Occup. Hyg. 44 (2000) No. 7, pp. 501-510.
- Cherrie, J.W., Brouwer, D.H., Roff, M., Vermeulen, R., Kromhout, H., ‘Use of qualitative and quantitative fluorescence techniques to assess dermal exposure’. Ann. Occup. Hyg. 44 (2000) No. 7, pp. 519-522.
- Riviere J.E. (ed.), Dermal absorption models in toxicology and pharmacology, Taylor & Francis, Boca Raton London, New York, 2005.
- Eickmann, U., Ermittlung dermaler Expositionen und deren Einflussgrößen: Technische Aspekte, IVSS-Workshop skin@work, Dresden, 16. – 18. April 2008. Available at: 
- van Hemmen, J.J., Auffarth, J., Evans, P.G., Rajan-Sithamparanadarajah, B., Marquardt, H., Oppl, R., RISKOFDERM: ‘Risk assessment of occupational dermal exposure to chemicals. An introduction to a series of papers on the development of a toolkit’, Ann. Occup. Hyg. 47 (2003), pp. 595-598.
- Creely, K.S., Tickner, J., Soutar, A.J., Hughson, G.W., Pryde, D.E., Warren, N.D., Rae, R., Money, C., Phillips, A., Cherrie, J.W., ‘Evaluation and further development of EASE Model 2.0’. Ann. Occupat. Hyg. 49, 2005, pp. 135-145.
- Targeted risk assessment tool TRA, version 3, ECETOC, April 2012. Available at: 
- van Wendel de Joode, B., An occupational DREAM: Development, evaluation, and application of a Dermal Exposure Assessment Method, Dissertationsschrift, Univ. Utrecht 2004
- Health and Safety Executive (no date). COSHH essentials. Retrieved on 11 June 2013, from: 
- Health and Safety Executive, Technical basis for COSHH essentials: Easy steps to control chemicals, 09/09. Available at: 
- Garrod, A. N. I., and Rajan-Sithamparanadarajah, R., ’Developing COSHH Essentials: Dermal Exposure, Personal Protective Equipment and First Aid’, Ann. Occup. Hyg. 47 (2003) No. 7, pp. 577–588.
- ECHA: ‘Guidance on information requirements and chemical safety assessment, Part D: Exposure Scenario Building’. October 2012, version 1.2. Available at: 
Links for further readings
EU-OSHA – European Agency for Safety and Health at Work, Dangerous substances e-tool. Available at: 
EU-OSHA - European Agency for Safety and Health at Work, Occupational skin diseases and dermal exposure in the European Union (EU-25): policy and practice overview. Available at: 
Kanerva, L., Elsner, P., Wahlberg, J.E., Maibach, H.I.,’Condensed Handbook of Occupational Dermatology. Springer, Berlin, 2004.
HSE - Health and Safety Executive, Managing skin exposure risks at work, 2009. Available at: 
Electronic Library of Construction Occupational Safety and Health (eLCOSH.org; 2013). A Safety & Health Practitioner's Guide to Skin Protection. Retrieved on 10 June 2013. From: