DERMAL EXPOSURE TO CHEMICALS IN THE WORKPLACE: JUST HOW IMPORTANT IS SKIN ABSORPTION?

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1 376 DERMAL EXPOSURE TO CHEMICALS IN THE WORKPLACE: JUST HOW IMPORTANT IS SKIN ABSORPTION? HOW Correspondene to: Dr S Semple, Department of Environmental & Oupational Mediine, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK; sean.semple@abdn.a.uk T SSemple Oup Environ Med 2004; 61: doi: /oem he study of oupational and environmental exposure to hemials has traditionally foussed on the quantity of dust, aerosol, or vapour inhaled. This has been driven by the high histori prevalene of respiratory illness among those in mining and manufaturing industries. The large proportion of respiratory physiians working in oupational mediine reflets this. Other exposure routes are often overlooked when evaluating the impat of hemials on health. It is important to remember that in addition to inhalation, hemials may enter the body by ingestion, by injetion, or by uptake through the unbroken skin (dermal absorption). Often dermal exposure is viewed purely in terms of perutaneous uptake of hemials. There are however three types of hemial-skin interations, and an understanding of these is required to haraterise the nature of any dermal exposure taking plae. Firstly, the hemial may pass through the skin and ontribute to the systemi load. Alternatively, the hemial an indue loal effets ranging from irritation through to burns or degradation of the barrier properties of the skin. Lastly, the hemial an evoke allergi skin reations through omplex immune system responses that an subsequently trigger responses in the skin at both the point of ontat and at skin sites remote to the ontat. There is also onern that skin ontat may ause respiratory sensitisation. In any given exposure senario there may be interations between these modes of ation. For example, a hemial an irritate the skin surfae leading to inreased perutaneous penetration of that, or other, hemials. However, in eah ase the substane must diffuse through the outer layers of the skin before any adverse effet is possible. This artile aims to highlight the importane of the dermal exposure and absorption route in oupational settings, identify some of the fators that influene exposure and absorption, and desribe methods urrently used for the measurement and assessment of dermal exposure. IMPORTANT IS DERMAL EXPOSURE? The ability of organi materials suh as tetra-ethyl lead to enter the blood after ontat with the skin was reognised as early as the 1920s. However, muh of the urrent understanding of dermal exposure and uptake has ome from researhers investigating the health effets of pestiides. The importane of dermal exposure has been reently highlighted by a speial edition of the journal Annals of Oupational Hygiene 1 and an international onferene on oupational and environmental exposures of skin to hemials held by the US National Institute of Oupational Safety and Health ( Dermal exposure to hemials ours in a wide variety of oupations spanning agriulture, manufaturing, and servie setors. Jobs where dermal exposure may be signifiant are as diverse as degreasers, painters, hairdressers, and fruit pikers. The degree of exposure may vary from small quantities of dilute material deposited aidentally on small areas of skin through to repeated immersion of the hands and forearms in onentrated solutions. Environmental and onsumer exposures also take plae from bathing and swimming in water ontaining hemials and from handling or touhing surfaes ontaminated with pestiides or bioides. Pestiides, solvents, and polyyli aromati hydroarbons (PAHs) are some of the main hemial groups that have been reognised as posing health problems by dermal absorption. Pestiides generally have a very low volatility and the amount of material inhaled is likely to be low unless a partiularly vigorous appliation results in signifiant aerosol formation. Workers in market gardens and greenhouses an experiene high dermal exposures during appliation or harvest or re-entry proesses where handling of vegetation oated with pestiide residues takes plae. 2 Pestiides are also used in industrial and domesti settings to prevent plant growth or remove insets or fungi. Infants and hildren playing in environments treated with pestiides have been the subjet of reent dermal exposure researh. 3 The use of organophosphate based sheep-dips has been impliated in the onset of a range of illnesses suh as hroni fatigue syndrome. It is believed that a signifiant proportion of the Oup Environ Med: first published as /oem on 18 Marh Downloaded from on 16 August 2018 by guest. Proteted by opyright.

2 Figure 1 Worker using solvents to lean sludge from barrel. biologial dose reeived during sheep dipping omes via the dermal route with the primary determinant of exposure being the handling or mixing of sheep dip onentrate rather than the amount of ontat with diluted sheep-dip. 4 There is growing interest in the dermal uptake of organi solvents. Solvents are used as thinners, degreasants, de-iers, and paint oatings. In Britain an estimated two million workers have regular ontat with solvents, and approximately one in three workers report having worked in a job where they were exposed to these hemials at some stage in their working lives. Several hundred million tonnes of solvents are used worldwide per year; the vast majority of use involves ethanol, isopropanol, aetone, toluene, xylene, or mixtures of these. Organi solvents used more ommonly in the past inlude benzene and arbon tetrahloride. Despite their widespread use, solvents are known to be toxi to a number of target organs within the body inluding the kidneys, liver, and nervous system. In terms of neurotoxiity, high exposures are known to ause aute symptoms inluding dizziness and nausea. They may produe long term irreversible damage to the entral nervous system ausing behavioural and personality hanges. As solvents tend to be volatile, measurement of exposure has primarily foused on inhalation of vapour. However, the highly lipophili nature of Table 1 Seletion of ommon hemials with signifiant perutaneous absorption Arylamide Carbon disulphide Cresols Dihloromethane Dimethyl sulphate Hydrazine Isoyanates Metalli merury Paraquat PCBs Toluene White spirit Benzene Carbon tetrahloride Diazinon Dihlorvos Ethylene glyols Hydrogen yanide Malathion Niotine Parathion Tetraethyllead Xylene This list is not exhaustive. There are over 160 hemials that have a skin notation assigned by the ACGIH. 8 Figure 2 Worker in overall washing spray lane. most solvents an also result in dermal uptake when deposited on the skin. Skin absorption has also been shown to be a primary determinant of the internalised dose of PAHs in many irumstanes. 5 Many other materials may also be absorbed through the skin in signifiant amounts. These inlude merury, isoyanates, polyhlorinated biphenyls (PCBs), arylates, and pharmaeutial produts suh as steroids and niotine. 6 Table 1 lists some hemials where dermal uptake an signifiantly inrease body burden. EXPOSURE LIMITS AND SKIN NOTATION Unlike inhalation exposure there are no oupational exposure limits (OELs) for dermal exposure. Instead various national regulatory authorities assign a skin notation for a variety of substanes. The intention of the skin notation is to identify substanes that an ontribute substantially to total body burden by uptake via the unbroken skin and ause serious systemi health effets. Bos and olleagues 7 have reently proposed the onept of quantitative dermal oupational exposure limits (DOELs) to replae the qualitative skin notations. This work investigates the onept of a limit related to the total dose deposited on the skin during a working shift. Diffiulties in alulating absorption rate or absorption perentage, a lak of a standardised measurement method for most hemials, and limited information on the likely health effets that an our from dermal exposure and uptake have prevented this onept from being further developed. The qualitative skin notation is defined by the Amerian Conferene of Governmental Industrial Hygienists (ACGIH) 8 as applying where there is potential signifiant ontribution to the overall exposure by the utaneous route, inluding muous membranes and the eyes, either by ontat with vapours or, of probable greater signifiane, by diret skin ontat with the substane. A review of the use of the skin notation employed by many of the world s health and safety authorities identified inonsistenies. 9 The UK Health and 377 Oup Environ Med: first published as /oem on 18 Marh Downloaded from on 16 August 2018 by guest. Proteted by opyright.

3 378 Safety Exeutive (HSE) urrently assigns a skin notation to over 120 hemials, while the ACGIH apply the skin note to over 160 substanes. These inonsistenies are due to a lak of information on dermal absorption rates of hemials and the absene of learly defined riteria to determine the signifiane of dermal absorption. Other investigators have argued for standardised guidelines for assigning skin notations. 10 For example, the Netherlands use the riteria that dermal exposure to the hands and forearms for one hour must lead to uptake exeeding 10% of that reeived by inhalation for eight hours at the oupational exposure limit. This raises the potential problem of assigning an overprotetive skin notation in the situation where the oupational limit value has been assigned to protet against respiratory irritation rather than any systemi effet. UNDERSTANDING DERMAL ABSORPTION The skin is omposed of two layers. The outer dead layer of squamous keratinoytes is a thin layer alled the epidermis or the stratum orneum. This layer is highly hydrophobi and provides the protetive barrier funtion of skin. Beneath the epidermis is a muh thiker living layer of ells inluding blood vessels, nerves, hair folliles, and sweat glands. The uptake of hemials through these two skin layers is ontrolled by diffusion. There are no ative transport mehanisms. Chemials deposited on the outside of the skin set up a onentration gradient between the outer skin onentration and the onentration within the rihly perfused dermis. This gradient produes a mass transfer that is dependent on the physial properties of the skin at that site and also the hemial properties of the substane. Diffusion aross the omplex membrane of the skin is therefore regulated by Fik s law, whih states that the rate of diffusion aross a barrier will be diretly proportional to the onentration gradient. The intensity of exposure from inhalation hazards is the airborne onentration (mg.m 23 or ppm) and, as desribed earlier, the driving fore for dermal uptake is similarly the onentration of the substane on the skin surfae (mg.m 23 ). Unfortunately the methods developed to measure dermal exposure have generally used mass as an exposure metri and this an lead to diffiulties when we try to use these measures to alulate or estimate the absorption into the body. A large mass of dilute material splashed on the hands may leave a higher mass residue than a small quantity of onentrated liquid spilled over a smaller area, but the diffusion rate aross the skin of the onentrated material will, by Fik s law, be greater. Many studies fous on the quantity of material deposited on the workers skin as the fator regulating dermal uptake. This measurement is a skin loading (mg.m 22 ) and is not a onentration, and while it is true that dermal absorption annot physially exeed the mass of material on the skin, it is the onentration of the substane that drives the diffusive proess. The fat that the flux through the skin is determined not by the mass but by the onentration of material on the skin is desribed in work by Cherrie and Robertson. 11 The transfer of a hemial substane through the skin an therefore be defined by two measurements. The lag-time is the time taken from initial ontat with the skin until the material enters the blood supply, while the flux is the steady state diffusion rate of the material when the lag-time is omplete. The flux (J) is measured in units of mass per unit area per time period (mg.m 22.h 21 ). The flux is diretly proportional to the onentration gradient and the rate is regulated by the hemial speifi permeability onstant (k p ). The equation to alulate dermal uptake for a steady state diffusion proess is thus: U sk =k p.c.a.t where: U sk is the mass of hemial absorbed through the skin (mg) k p is the permeability oeffiient (m.h 21 ) C is the onentration on the skin (mg.m 23 ) A is the area exposed (m 2 ) t is the duration of exposure (h). To examine the potential impat of dermal exposure, we an onsider an example of a painter who is spray painting in a room with a paint ontaining 300 mg.m 23 xylene. The task lasts 10 minutes and the average airborne onentration is 100 ppm (441 mg.m 23 ). If about 10 m 2 of the painter s skin is overed by paint, the paint droplets take 10 minutes to dry, and the xylene onentration in the deposited paint is the same as the initial mix, then the approximate dermal uptake is likely to be about 6 mg. U sk = m.h mg.m m h U sk = 5.8 mg When ompared with the inhalation uptake of 110 mg over the same time period it is evident that the dermal route is not ontributing a signifiant additional body burden. The omparable uptake by inhalation is alulated by multiplying the exposure level in mg.m 23 (C) by the breathing rate in m 3.h 21 (B) and the duration of exposure in hours (t). U inh = C.B.t U inh = 441 mg.m m 3.h h U inh = 110 mg If however the painter also washes his or her hands in neat xylene thinners (with a xylene onentration of 900 mg.m 23 ) for one minute at the end of the task, this will add a further 130 mg of xylene to her internalised amount. This would now mean that the dermal route had ontributed more than one-half of the painter s xylene uptake. U sk = m.h mg.m m h U sk = 130 mg FACTORS AFFECTING ABSORPTION The passage of a hemial through the skin barrier is dependent on many fators. The skin is not uniform in terms of thikness, epidermis to dermis ratio, density of hair folliles, and many other parameters that will affet permeability. The amount of material that may be absorbed will, as a onsequene, vary depending on the anatomial site of the exposure. For example, exposure to highly permeable sites suh as srotal skin an result in uptake some 50 times greater than the same exposure applied to the thiker, less permeable skin of the legs and abdomen. 12 Another important influene on uptake is olusion. This an our when liquid beomes trapped between the skin and lothing. It is often apparent in workers who wear gloves that allow fluid to spill over the uff and into the spae between the skin and the inside of the glove. The olusive proess results in the liquid being unable to evaporate from the skin surfae, and the quantity of material absorbed may be as Oup Environ Med: first published as /oem on 18 Marh Downloaded from on 16 August 2018 by guest. 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4 Table 2 Fators affeting the amount of hemial that is absorbed through the skin Exposure fators Type of task Duration Area of skin exposed Use of protetive lothing Conentration of the hemial Hygiene: washing and wearing of ontaminated lothing Chemial fators Moleular weight Solubility in water Solubility in oils Struture Irritany Presene of other hemials Skin fators Skin thikness Skin type and ondition Anatomial loation of exposure Temperature and humidity Olusion Skin perfusion Hairiness, pore density and sweating Skin metabolism muh as five times that from a similar non-oluded exposure. 12 Other fators that an play an important role in determining the degree of uptake inlude temperature and the presene of other materials on the skin. The omplex effet of mixtures of substanes, and the effets of the vehile that a substane is ontained within, are poorly understood, but a ommon example is the greatly inreased uptake of one hemial due to the skin irritation aused by another hemial. For example, Brand and o-workers 13 have arried out work investigating how the ative ingredients of sunsreens may promote the penetration of herbiides through the skin of agriultural workers. The hierarhy of ontrol priniple entral to oupational hygiene states that personal protetive equipment should only be used as a last resort to manage worker exposure. Despite this the use of hemial protetive lothing and gloves is ommon aross a wide range of oupations handling hazardous liquids. While gloves and protetive overalls an offer a degree of protetion, their seletion and use is typially poorly managed. It is also worth noting that urrent standards for testing gloves and overalls do not take into aount how the lothing will perform in workplae onditions nor the influene of hemial mixtures, temperature, and physial stresses. 14 Protetive lothing an also onfer a false sense of seurity on a worker and may lead to behaviours that an result in inreased exposure. For example, an ungloved worker washing parts in degreasing solvent may use a tool to remove parts from the degreasing bath. Wearing gloves, however, may ause the worker to beome omplaent and dip his or her hands in the bath. A final issue in using gloves or protetive lothing to redue dermal exposure is that of proper removal. Studies have illustrated the importane of instrution and training on how to use and remove gloves to redue the amount of material deposited on the worker s skin. 15 Table 2 provides a omprehensive listing of fators that should be onsidered when evaluating uptake. DERMAL EXPOSURE ASSESSMENT Just like any assessment of exposure to airborne hazards there are a number of exposure parameters that should be measured to haraterise dermal exposure and to determine uptake. The exposure intensity and the surfae area exposed together with the duration of skin ontat and frequeny of skin leaning or repeated exposure are all required to understand the mass of substane likely to be absorbed. Measurement of dermal exposure has developed in a pieemeal and often hemial or use speifi manner with muh of the methodology entred around measurement of pestiide residues on the skin. Current methods an be divided into five main types. 16 Surrogate skin and path methods use whole body suits or representative pathes to apture the potential exposure. Removal methods use washing, wiping, or skin stripping tehniques to determine the amount of material on the skin at a given time point. Visualisation uses fluoresene to determine the area of exposure and quantify the mass deposited on the skin. Biomonitoring an be used to indiretly determine the amount of dermal uptake and from this provide an estimate of the amount of atual exposure. Dermal exposure modelling utilises statistial or deterministi methods to help estimate the amount of hemial likely to be deposited on the skin. A review by Soutar and o-workers 17 desribes the range of surrogate skin and path methods in use for the assessment of dermal exposure. The two most ommonly used sampling protools are published by the World Health Organisation (WHO) and the Organisation for Eonomi Cooperation and Development (OECD). Eah type of surrogate skin sampling tehniques has a variety of advantages and disadvantages and eah measures a different fration of exposure. For example, pathes measure the amount of material deposited over a seleted area and, by proportion, an be used to provide an estimate of the total dermal exposure. Differenes in the type of material used for path samplers, the body loations sampled, and the pathsubstane interation will all inrease the variability of any measurement made. Removal tehniques aim to sample the mass of material remaining on a worker s skin at a partiular point in time. Wipe sampling and washing tehniques an show a high degree of variability in reovery effiieny and are also of limited use when the substane under study is either highly volatile or likely to be rapidly absorbed by the skin. 18 Tape stripping involves the physial removal of outer layers of the epidermis and an be used to provide a piture of the quantity of material that has already been absorbed into the skin. Others have reported this tehnique for the measurement of jet fuel, isoyanates, and arylate exposure. 19 Visualisation of workers exposure an be ahieved by the addition of fluoresent traer to the material being handled or proessed. 20 The Fluoresent Interative Video Exposure System (FIVES) or similar Video Imaging Tehnique to Assess Dermal Exposure (VITAE) system allow uniform illumination of the body surfae and an provide information on both the amount of surfae area exposed and, by orrelation with the image intensity, a quantifiation of the mass of hemial on the skin. All of these dermal measurement proesses tend to provide data on the mass sampled rather than the onentration of material present on the skin. Lindsay and olleagues 21 have reported the development of a novel sampler that measures 379 Oup Environ Med: first published as /oem on 18 Marh Downloaded from on 16 August 2018 by guest. Proteted by opyright.

5 380 Figure 3 The oneptual model of dermal exposure (see Shneider et al 23 for full desription). Oup Environ Med: first published as /oem on 18 Marh Downloaded from solvent exposure using a surfae membrane designed to reflet the uptake of solvent through the skin. This onept of ombining measurement of exposure and uptake holds signifiant promise for the future and would address many of the problems assoiated with measuring surfae mass ontamination. Biomonitoring for hemials or their metabolites in the breath, blood, or urine of workers is another option for the assessment of dermal exposure. Using hamber experiments researhers are able to expose given areas of skin to liquids. 22 By separating the subjet from the material and ensuring that his or her inhaled atmosphere is solvent free, biologial monitoring an be used to determine how muh material is absorbed dermally. While biomonitoring an provide valuable information on dermal uptake in ontrolled onditions it must be used with are in assessing the amount of exposure in the workplae where the internalised material may be additionally absorbed by the inhalation or ingestion exposure routes. Observation of the worker and work praties is important in determining the routes of exposure to understand results from biologial monitoring. Knowledge of the hemial half-life and metabolism is also required and inter-worker variability in metabolism an make it diffiult to ompare exposures from biologial monitoring data. MODELLING EXPOSURE AND UPTAKE A oneptual model of dermal exposure has been reated to help those involved in ontrolling and evaluating the importane of this route to identify the key transport proesses. 23 This model divides the worker s environment into six ompartments: the soure, the air (Air), the surfae ontaminant layer (Su), the outer lothing layer (CloOut), on 16 August 2018 by guest. Proteted by opyright.

6 Key points Many hemials an ross the unbroken skin. Workers exposed to pestiides or solvents an reeive most of their body burden via the dermal route. Uptake is ontrolled by hemial onentration, area of skin exposed, and duration of exposure. Skin site, temperature, humidity, and other hemials an all influene dermal uptake. Dermal exposure assessment an be done by surrogate skin method removal tehniques, visualisation, biomonitoring, or modelling. the inner lothing layer (CloIn), and the skin (Sk). Movement of a hemial within the environment is then haraterised by the following transport proesses: emission (E), deposition (Dp), resuspension/evaporation (L), transfer (T), removal (R), deontamination (D), penetration/permeation (P), and re-distribution (Rd). Figure 3 illustrates the ompartments and transfer proesses of the oneptual model. This oneptual model has been utilised to identify pathways of dermal exposure among workers employed in the rubber manufaturing industry. 24 Others have also used the oneptual model to develop a omputer based questionnaire to provide the user with data on how to ontrol dermal exposure. 25 Quantifying the variability in a measurement is an important part of any modelling proess. Kromhout and Vermeulen have used their DERMDAT database of 6400 observations to show that total, within-worker, and betweenworker variability in dermal exposure measurements aross 20 surveys from a wide range of industries was very similar to that found for inhalation exposure. 26 Modelling of uptake of hemials through the skin is also important. Work by Wilshut and o-workers 27 reviews five mathematial models used to predit the skin permeation of hemials based on their physial and hemial properties. Others have further advaned these methods, and Patel and olleagues 28 have published work on the optimal physiohemial parameters to employ in a quantitative strutureativity relation (QSAR) approah to predit skin permeation rates. THE FUTURE There is evidene that oupational physiians, hygienists, and epidemiologists are beoming more aware of the importane of dermal exposure and uptake when taking a history or evaluating the effet of hemials on health. Our understanding of the fators ontrolling dermal exposure and the perutaneous uptake of hemials is inreasing, and there is great potential for new developments in dermal measurement methodologies. Some reent work has suggested that a onentration gradient may not be the sole driving fore in perutaneous uptake. Experimental findings that aqueous solutions of 2-butoxyethanol may be absorbed more rapidly than onentrated solutions, 29 and other work indiating that fine powdered solids may penetrate the skin without first entering an aqueous phase 30 are of partiular interest. The mehanisms involved in these experiments pose serious questions for those involved in determining the uptake of hemials through skin and require further exploration. The importane of dermal exposure in respiratory sensitisation and the development of hroni beryllium disease has also been hypothesised. Reent work has suggested a mehanism where fine and ultrafine metal partiles may pass through the epidermis and into the dermis to generate an immune response. 31 Dermal exposure and uptake of hemials through the skin is fast beoming one of the most interesting and hallenging aspets of environmental and oupational mediine and epidemiology. Great strides have been made in our understanding of the determinants of exposure and the fators driving uptake, but there is still muh for us to learn and apply. REFERENCES 1 Fenske R. Dermal exposure: a deade of real progress. Ann Oup Hyg 2000;44: Editorial outlining reent advanes and introduing a series of important papers in a speial issue devoted to dermal exposure. 2 Tielemans E, Louwerse E, de Cok J, et al. Exposure to fungiides in fruit growing: re-entry time as a preditor for dermal exposure. Am Ind Hyg Asso J 1999;60: Cohen Hubal E, Sheldon L, Burke J, et al. Children s exposure assessment: a review of fators influening hildren s exposure, and the data available to haraterize and assess that exposure. Environ Health Perspet 2000;108: Tahmaz N, Soutar A, Cherrie J. Chroni fatigue and organophosphate pestiides in sheep farming: a retrospetive study amongst people reporting to a UK pharmaovigilane sheme. Ann Oup Hyg 2003;47: Van Rooij J, Van Lieshout E, Bodelier-Bade M, et al. Effet of the redution of skin ontamination on the internal dose of reosote workers exposed to polyyli aromati hydroarbons. Sand J Work Environ Health 1993;19: Grandjean P. Skin penetration: hazardous hemials at work. London: Taylor & Franis, Comprehensive guide to hemials that penetrate the skin with a detailed desription of how penetration takes plae. 7 Bos P, Brouwer D, Stevenson H, et al. Proposal for the assessment of quantitative dermal exposure limits in oupational environments: part 1. Development of a onept to derive a quantitative dermal oupational exposure limit. Oup Environ Med 1998;55: Amerian Conferene of Governmental Industrial Hygienists. TLVs and BEIs. Cininnati, OH: ACGIH, Fiserova-Bergerova V, Piere J, Droz P. Dermal absorption potential of industrial hemials: riteria for skin notation. Am J Ind Med 1990;17: Czerzak S, Kupzewska M. Assignment of skin notation for maximum allowable onentration (MAC) list in Poland. Appl Oup Environ Hyg 2002;17: Cherrie J, Robertson A. Biologially relevant assessment of dermal exposure. Ann Oup Hyg 1995;39: Important paper highlighting that onentration and not mass drives dermal uptake. 12 Bowman A, Maibah H. Perutaneous absorption of organi solvents. Int J Oup Environ Health 2000;6: Brand R, Spalding M, Mueller C. Sunsreens an inrease dermal penetration of 2,4-dihlorophenoxyaeti aid. J Toxiol Clin Toxiol 2002;40: Evans P, MAlinden J, Griffin P. Personal protetive equipment and dermal exposure. Appl Oup Environ Hyg 2001;16: Rawson B, Wheeler J, Roff M, et al. The routes and onsequenes of internal ontamination of gloves. Presented at the International Conferene on Oupational and Environmental Exposure of Skin to Chemials: Siene and Poliy, Washington DC, 8 11 September, Vermeulen R, Stewart P, Kromhout H. Dermal exposure assessment in oupational epidemiologi researh. Sand J Work Environ Health 2002;28: Reent review of methods of dermal exposure assessment used in epidemiology. 17 Soutar A, Semple S, Aitken R, et al. Use of pathes and whole body sampling for the assessment of dermal exposure. Ann Oup Hyg 2000;44: Brouwer D, Boeniger M, van Hemmen J. Hand wash and manual skin wipes. Ann Oup Hyg 2000;44: Nylander-Frenh L. A tape stripping method for measuring dermal exposure to multifuntional arylates. Ann Oup Hyg 2000;44: Cherrie J, Brouwer D, Roff M, et al. Use of qualitative and quantitative fluoresene tehniques to assess dermal exposure. Ann Oup Hyg 2000;44: Lindsay F, Cherrie J, Robertson A. Development of a method to assess biologially relevant dermal exposure. Contrat Researh Report RR117, HSE Books, Sudbury, UK. Available online at rrhtm/rr117.htm. 22 Kezi S, Monster A, van de Gevel I, et al. Dermal absorption of neat liquid solvents on brief exposures in volunteers. Am Ind Hyg Asso J 2001;62: Oup Environ Med: first published as /oem on 18 Marh Downloaded from on 16 August 2018 by guest. Proteted by opyright.

7 Shneider T, Vermeulen R, Brouwer D, et al. A oneptual model for assessment of dermal exposure. Oup Environ Med 1999;56: Important paper outlining the mehanisms by whih dermal exposure takes plae. Attempt to standardise the language used in dermal exposure assessment. 24 Vermeulen R, Heideman J, Bos R, et al. Identifiation of dermal exposure pathways in the rubber manufaturing industry. Ann Oup Hyg 2000;44: van-wendel-de-joode B, Brouwer D, Vermeulen R, et al. DREAM: a method for semi-quantitative dermal exposure assessment. Ann Oup Hyg 2003;47: Kromhout H, Vermeulen R. Temporal, personal and spatial variability in dermal exposure. Ann Oup Hyg 2001;45: Wilshut A, ten Berge W, Robinson P, et al. Estimating skin permeation. The validation of five mathematial skin permeation models. Chemosphere 1995;30: Patel H, ten Berge W, Cronin M. Quantitative struture-ativity relationships (QSARs) for the predition of skin permeation of exogenous hemials. Chemosphere 2002;48: Jakasa I, Mohammadi N, Kruse J, et al. Perutaneous absorption of neat and aqueous solutions of 2-butoxyethanol in volunteers. Int Arh Oup Environ Health 2004;77: Sun C, Wong T, Hwang T, et al. Perutaneous absorption of inorgani lead ompounds. Am Ind Hyg Asso J 2002;63: Tinkle S, Antonini J, Rih B, et al. Skin as a route of exposure and sensitisation in hroni beryllium disease. Environ Health Perspet 2003;111: QUESTIONS (see answers on p 288) Please indiate if the following statements are true or false. (1) Dermal uptake (a) Tends to be greater from vapours than from onentrated fluids (b) Refers to the transfer of ontamination from the hands to the mouth () Is an ative transport proess (d) Ours only through the sweat glands (e) Is ontrolled by dermal oupational exposure limits (2) Measurement of dermal exposure (a) Involves pumped samples set at 2.0 litres per minute (b) Can be ahieved by stripping the outer epidermis () Is advisable when assessing workers exposure to solvents (d) Is best done using biomonitoring results (e) Is not neessary when the airborne levels are very low (3) The skin notation (a) Is assigned only to substanes that are skin irritants (b) Requires workers handling that substane to wear gloves () Has the same riteria aross the EU (d) Indiates the material an penetrate unbroken skin (e) Is ommonly assigned to solvents and pestiides (4) Fators influening the amount of hemial that will be absorbed through the skin inlude (a) Temperature (b) Skin ondition () The presene of polarised light (d) Humidity (e) Other hemials on the skin surfae (5) Dermal exposure is likely to be a signifiant exposure route among (a) Call entre employees (b) Market gardeners () Painters (d) Hairdressers (e) Rubber manufaturing employees Oup Environ Med: first published as /oem on 18 Marh Downloaded from on 16 August 2018 by guest. Proteted by opyright.