- Email: [email protected]
Dermal exposure assessment
PII: S0003-4878(00)00048-X
Ann. occup. Hyg., Vol. 44, No. 7, pp. 493–499, 2000 2000 British Occupational Hygiene Society Published by Elsevier Science Ltd. All rights reserved Printed in Great Britain. 0003-4878/00/$20.00
Dermal Exposure Assessment THOMAS SCHNEIDER†*, JOHN W. CHERRIE‡, ROEL VERMEULEN§ and HANS KROMHOUT§ †National Institute of Occupational Health, Lersø Parkalle 105, DK 2100, Copenhagen, Denmark; ‡University of Aberdeen and Institute of Occupational Medicine, Edinburgh, UK; §Environmental and Occupational Health Group Utrecht University, Utrecht, The Netherlands
Assessing dermal exposure is a complex task. Even the most commonly used methods face fundamental problems and there are large gaps in the documentation and validation of sampling methods. Still larger uncertainties exist regarding strategies for measurement. We propose a strategy based on a conceptual model and which draws on the considerable insight gained for airborne contaminants, including EN 689 for assessing exposure by inhalation. The vast amount of air sampling data has provided good insight into the statistical properties of short-term and long-term exposure levels, which is essential for designing cost-effective exposure studies. For surface and skin contaminants an understanding of the distribution types and parameter values is only beginning to emerge. Transport rates away from the skin contaminant layer determine the ‘memory’ of a dermal sample and measurement principles are proposed depending on these rates. It is argued that uptake is the ultimate dermal exposure metric for risk assessment and should be the basis for devising dermal occupational exposure limits. 2000 British Occupational Hygiene Society. Published by Elsevier Science Ltd. All rights reserved. Keywords: dermal exposure
IMPORTANCE OF DERMAL EXPOSURE
Exposure to hazardous substances may occur by inhalation, ingestion, or dermal contact. Occupational hygiene has traditionally focused on the inhalation exposure pathway because it was considered to be the most important route of exposure with the exception of exposure to pesticides and certain solvents. Many methods have been developed to measure inhalation exposure levels and there is a clear understanding of how such levels should be interpreted as part of a risk reduction strategy. As a result, exposure by inhalation has been reduced over the years, and some authors have suggested that dermal exposure therefore might be, relatively, more important. Recent results from a longitudinal exposure study in the rubber manufacturing industry showed, however, that reduction of contaminant source strength concurrently reduced dermal exposure (Vermeulen et al., 2000a). Contamination of the skin leading to uptake may arise in many different ways and several methods have been developed
Received 26 April 2000. *Author to whom correspondence shoud be addressed. Tel.: +45-39-16-5200; Fax: +45-39-16-5201; E-mail: [email protected]
for assessing dermal exposure. However, compared with inhalation exposure it is less clear how the measured levels should be interpreted. It is possible for hazardous substances to deposit or adsorb onto the skin directly from the air, to be transferred to the skin on contact with contaminated surfaces or by submersion of part of the body into the substance. In addition, a contaminant may be lost from the skin without being taken up into the body, either by evaporation or some other mechanisms such as washing or abrasion. Finally, the presence of clothing or protective garments may modify the rate at which hazardous substances come into contact with the skin. Given these factors, it is a complex but challenging task to quantitatively assess dermal uptake. THE CONCEPTUAL MODEL
A simple conceptual model of the processes leading to uptake via the dermal route has been postulated (Schneider et al., 1999). The model describes uptake as a result of transport of mass between compartments (Fig. 1). The identified compartments are: source, air, surface contaminant layer, outer and inner clothing contaminant layer separated by the fabric having a
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Fig. 1. The conceptual model. Adapted from Schneider et al. (1999). Overview of the conceptual model, compartments and transport processes. (E=Emission (———), Dp=Deposition (— — —), L=Resuspension/Evaporation (–··–), T=Transfer (- - -), R=Removal (– · –), Rd=Redistribution (· · ·), D=Decontamination (-·-·-), P=Penetration/Permeation (······).
buffer capacity, and skin contaminant layer. The skin contaminant layer is separated from perfused tissue by the stratum corneum, which acts as a rate-limiting barrier having a certain buffer capacity. The proposed transport processes are: Emission of substances by splashing, spilling and ejection of particles into the air and onto surfaces, outer clothing, and skin contaminant layer. Deposition of substances from the air to surfaces, outer clothing, and the skin contaminant layer. Resuspension or evaporation of substances from surfaces, outer clothing, and the skin contaminant layer to the air, as particulate, vapours, or both.
Transfer of substances by direct contact between surface, skin and outer respectively inner clothing contaminant layers in a direction towards the worker. Removal is the corresponding transport in a direction away from a worker. Redistribution of substances between compartments of the same type, e.g. redistribution of contaminants from one part of the skin contaminant layer to another as a result of touching the face with contaminated fingers. Decontamination, which is the deliberate transport of contamination away from the entire system (e.g. ventilation of room air, cleaning of room surfaces
Dermal exposure assessment
and outer clothing or washing off skin contaminant layer). Brushing dust off clothing is resuspension. Penetration and permeation, which both involve transport of substances through the rate-limiting barriers, clothing and stratum corneum. Hazardous substances in the dermal contaminant layer will be taken up continuously into the body through the stratum corneum, driven by the concentration gradient between the dermal surface and the perfused tissue. The risk arising from dermal exposure is thus firstly related to the time-dependent concentration of a substance on the dermal surface. However, the skin contaminant layer compartment has conventionally been represented as a two-dimensional layer giving concentration as mass per surface area without specifying concentration of the hazardous agent in the layer itself. This has contributed to the confusion regarding choice of measurement principles for, and interpretation of, dermal contamination in terms of dermal uptake, see e.g. Schneider et al. (1999). Particles complicate the concept of concentration since they are discrete entities. Uptake can, for example, be limited by the rate of dissolution and not by the diffusion through the stratum corneum. For these reasons existing measurement methods can be criticised because they determine directly or indirectly the mass of contaminant either depositing on the skin or retained on the skin at the end of the exposure period. MEASUREMENT METHODS TO ASSESS DERMAL EXPOSURE
Practical measurement methods have been developed to assess dermal exposure directly or indirectly. Table 1 presents a list of selected methods that cover a range of approaches (adapted from Schneider et al., 1999). The conceptual model stresses the difference in mass in compartment and transport of mass between compartments. In Table 1 we indicate for which of these two purposes the methods have been used. A clear distinction has not always been made in the literature resulting in confusion regarding determination and interpretation of sampling efficiencies. As an example, measurement methods intended to assess compartment mass should aim to have 100% sampling efficiency. On the other hand, a 100% sampling efficiency for a wipe test to quantify the transfer to skin upon contact with a surface is not necessarily desirable (Fenske, 1993). Even the most commonly used among the methods listed in Table 1 are faced with fundamental problems, such as: 앫 the behaviour of a tracer in the transport process may differ from the behaviour of the substance of interest; 앫 transfer of mass depends on the amount of mass already present in the skin contaminant layer;
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앫 skin stripping or washing with solvents cannot recover what has already penetrated to perfused tissue. Solvents influence the characteristics of the skin and can therefore not be used for repeated sampling; 앫 adherence of contaminants to patch sampler and real skin differs. Thus the amount on the patch sampler does not represent the amount actually present for uptake on the skin. Uptake is driven by concentration in the skin contaminant layer, not mass per skin surface area; 앫 patch samplers sample over small areas and therefore errors can occur when results have to be extrapolated to the whole exposed area; 앫 sampling efficiency of micro vacuuming is strongly dependent on sampling geometry and air flow rate. It is not an imperative that a method has to result in an unbiased determination of dermal uptake if the purpose of the measurement is to gain information on the location of a source in the form of contaminated surfaces, on surface concentrations and trends, or to determine the effectiveness and maintenance of control measures. For such tasks it will suffice that the methods are simple and gives reproducible results for the compartments or transport processes in question. The papers by Brouwer et al. (2000a), Soutar et al. (2000), Byrne (2000) and Cherrie et al. (2000) in this issue address key measurement techniques, their performance in relation to various measurement tasks and needs for development. APPROACHES TO DERMAL EXPOSURE ASSESSMENT
While there are large gaps in the documentation and validation of sampling methods for dermal exposure, still larger gaps exist regarding strategies for measurement. The following discussion of strategies for dermal exposure assessment draws on the considerable insight gained for airborne contaminants. By analogy with EN 689 for assessing exposure by inhalation for comparison with limit values (CEN, 1995) a measurement strategy based on a tiered approach is proposed. Following this approach, the first step would consist of identifying potential exposure, meaning the preparation of a list of all chemical substances in the workplace and appropriate toxicological information. The second step would be to evaluate workplace factors, including tasks, work patterns and techniques, production processes, sources of direct skin contact, spilling, splashing, and emission to air, safety precautions and procedures (including protective clothing and gloves). The purpose would be to gauge the potential for dermal exposure to the chemical agents. The third step would consist in using a structured
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Table 1. Measurement methods. Modified from Schneider et al. (1999) Method
Principle of sampling
Measured compartment mass
u.v. Fluorescence
In situ
Portable X-ray fluorescence monitor
In situ
Skin, surface, inner and outer clothing Surface
Wet wipe
Manual wiping
Surface, skin
Wet wipe
Mechanised wiping
Surface
Gelatine foil Fixed pressure dislodgeable residue sampler Dislodgeable foliar residue sampling Adhesive tape
Surface dust lifting Surface Mechanical transfer in Surface situ Surface removal
Surface
Skin stripping
Skin
Hand wash
Wash with water or alcohol
Skin
Patch
Passive
Skin
Whole body
Passive
Skin
SMAIR
–
FLEC
Resuspension by air jet Resuspension by impact Resuspension by suction Evaporation by airflow
TEWL
Evaporation
–
STEPP Microvacuuming
Measured transport process All processes
Ref.
Cherrie et al. (2000)
All processes related Dost (1995) to the surface contaminant layer Transfer from surface Anon (1990) to skin and to outer clothing Removal from skin to surface, inner and outer clothing Wheeler and Stancliffe (1998) Schneider et al. (1996) Ness (1994, pp. 191– 194) Iwata et al. (1977) Removal from skin to Rougier et al. (1987) surface, inner and outer clothing. Deposition on skin Removal from skin to Brouwer et al. (2000a) surface, inner and outer clothing. Decontamination of skin Transfer from surface, Soutar et al. (2000) outer and inner clothing to skin. Deposition on skin
–
Royster and Fish (1967) Kildesø et al. (1999)
Surface
Byrne (2000)
–
approach to assess exposure. It would begin with an initial appraisal. All intermediate compartments and transport processes should be included with reference to Fig. 1. Emphasis should be given to the individuals own work practices and which body locations may get contaminated. If as a result dermal uptake of hazardous substances cannot be ruled out a basic survey should be made. The purpose of the basic survey would be to provide quantitative information about the distribution and level of dermal exposure. Had the perfect dermal uptake monitor with corresponding dermal occupational exposure limits (DOEL) been available, the basic survey would have included results obtained by such monitors from earlier measurements, plus measurements from comparable installations or work processes. If the information was
Resuspension from surface
Evaporation from Wolkoff (1996) surface Evaporation from skin Morrison and Scala (1996)
insufficient to decide that conditions were acceptable according to a given DOEL, it would have to be supplemented by workplace measurements. If it still was insufficient to decide that conditions were well below or clearly above any DOEL, a detailed survey would have to be made, aimed at narrowing the prediction interval. However, at present we do not have accepted DEOLs and a proxy-strategy has to be applied. One possibility would be to use existing dermal sampling methods and estimate uptake following a correction scheme taking into consideration all the limitations (Jackson, 1999). Another possibility would be to use criteria targeted at compartment mass or transport. The actual values could be obtained from cross-industry measurements showing what is reasonably practi-
Dermal exposure assessment
cable (i.e. benchmarks) (Kromhout et al., 1994; de Cock et al., 1998). WORKPLACE MEASUREMENTS
It is not possible to specify in detail a procedure for selection of workers to be measured regarding exposure by inhalation (CEN, 1995), and thus much less so for dermal exposure. Rather a set of options can be given. One approach is to subdivide the exposed population in subgroups within each of which the exposure is supposed to be similar and consequently to draw a random sample from each subgroup (i.e. stratified random sampling). For air contaminants fixed point measurements in the vicinity of workers can be used to monitor general concentration levels and trends. The analogue for dermal exposure would be to monitor hazardous substances in surface layer compartments with which the worker has frequent contact. Obviously the industrial hygienist can monitor any of the compartments or transport processes and use the conceptual model (Fig. 1) to interpret the results. Worst-case measurements for air contaminants are used to direct measurement efforts to problem areas. Ideally, worst-case measurements represent episodes where high exposures occur (CEN, 1995). It has been shown that it can be difficult to identify such episodes (Olsen and Jensen, 1994). An alternative approach is to use a task-based exposure model, such as proposed by Nicas and Spear (1993). A task-based approach to dermal exposure would assess dermal uptake caused by each individual task and combine these uptakes into a long-term uptake using task time weights. This approach assumes that concentration in the skin contaminant layer during each task and duration of tasks are equally important determinants of long-term uptake. However, randomly taken shift long measurements with simultaneously collected information on tasks and conditions offer the opportunity to statistically unravel exposure-affecting factors for dermal exposure (Kromhout et al., 1994). The large amount of air sampling data has provided good insight into the statistical properties of shortterm and long-term concentrations. The distribution (except extreme values) can be modelled satisfactorily by the log-normal distribution which is completely characterised by the geometrical mean and geometrical standard deviation. Concentrations are thus usually log-transformed prior to statistical analysis. Measurements on different exposure groups, on random samples of workers within groups and repeated measurements on individual workers have provided a database from which typical values of the within-worker, within-group (i.e. between-worker) and between-group variance components have been estimated (Kromhout et al., 1993, 1996; Rappaport et al., 1993). It has become evident that it is not easy to give criteria for grouping a priori workers in uniform
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exposed groups. Within-worker variability in exposure concentrations has been shown to be predominantly larger than within-group variability in exposure concentrations and within-group variability can be larger than between-group differences in average exposure. This has important implications for the design of cost-effective exposure studies. So, repeated measurement designs are needed to give the researcher the opportunity to optimise grouping schemes (Kromhout and Heederik, 1995; Kromhout et al., 1997). For surface and skin contaminants an understanding of the distribution types and parameter values is only beginning to emerge. Spatial distribution on surfaces in offices has been found to be log-normal and there was correlation between close sampling positions (Schneider et al., 1990). A database called ‘DERMDAT’ with dermal exposure measurements primarily collected with surrogate skin samplers, has recently been compiled. By focussing on repeated measurement series, between-body location, betweenworker, and within-worker variance components have been estimated, as well as correlation patterns between body locations and between total estimated dermal exposure and exposure of individual body locations. Results of this database are presented in a paper currently under consideration (Kromhout and Vermeulen, personal communication). TEMPORAL ASPECTS
The amount of hazardous substances in the skin contaminant layer at any given time depends on the time variable transport of mass to and from the skin. A basic question is how much ‘memory’ of past exposure incidents there is in a sample of the skin contaminant layer, e.g. a hand rinse sample. This will depend on the rate of transport of the substance from the skin contaminant layer. Suppose that the rate of transport away from the skin contaminant layer is given by a single time constant τ and that a given mass is transferred to the layer by an event occurring at time t=0. Then the fraction of mass remaining at time t will be exp(⫺t/τ). Obviously effective decontamination events represent step changes and define natural boundaries for sampling time intervals. The transport from the skin contaminant layer can be divided into two pathways: penetration/permeation, and removal+resuspension/evaporation (neglecting redistribution). By dichotomising each of the transport rates, four types of sampling tasks are defined (Fig. 2). In the lower left corner, the skin contaminant layer has a long memory, in the upper right corner the memory is short. This diagram can assist in selecting a proper sampling method. If both transport rates (or rather if the amount of mass transported in time periods between decontamination events) are low then a removal technique or fluorescence technique applied immediately before a decontamination can be used to
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Fig. 2. Proposed sampling methods. The sampling conditions are characterised by the transport rates away from the skin contaminant layer; *u.v. tracers will have a low permeation/penetration rate.
estimate uptake. If the removal+resuspension/evaporation rate is low but penetration/permeation rate is high, a surrogate skin sampler would give a good measure of dermal uptake. Since u.v. tracers have a low permeation/penetration rate, a fluorescence technique could also be used. If the removal+resuspension/ evaporation rate is high and penetration/evaporation rate is low, a surrogate skin sampler would greatly overestimate uptake. In this case biological monitoring would be preferable and also in the case of both transport rates being high. DISCUSSION
The papers byVermeulen et al. (2000b), Brouwer et al. (2000b) and Kromhout et al. (2000) in this issue describe how currently available sampling techniques incorporated in a model driven exposure assessment strategy can be used to determine exposure scenarios and exposure pathways and to develop hazard control strategies. Fogh and Andersson (2000) have added transport rate constants to the conceptual model and used it to quantify exposure risk in a specific scenario. Dermal uptake is the ultimate dermal exposure metric. It offers a scientifically justifiable approach to measuring and controlling the risks from dermal exposure to hazardous substances. Existing dermal sampling methodologies do not measure dermal uptake directly and in order to quantify dermal uptake from results of measurements several assumptions and corrections would have to be made, as evidenced in the previous sections. We consider that rather than devising a system of DOELs based on present day measurement methods further development should be
undertaken to improve the measurement methodology. The novel dermal sampler concept for quantifying dermal uptake proposed by Cherrie and Robertson (1995) could be a promising way forward. A dermal exposure metric describing dermal uptake has the further advantage that it provides some of the necessary conditions for deriving total uptake limits, which would enable exposure by inhalation and dermal uptake to be controlled simultaneously. Acknowledgements—This work was facilitated by the Dermal Exposure Network, supported by European Commission Contract SMT4-CT96-7502 (DG12-RSMT).
REFERENCES Anon (1990) Sampling for Surface Contamination. Industrial Hygiene Technical Manual. Occupational Safety and Health Administration. Brouwer, D. H., Boeniger, M. F. and van Hemmen, J. J. (2000a) Hand wash and manual skin wipes. Annals of Occupational Hygiene 44, 501–510. Brouwer, D. H., Lansink, C. M., Cherrie, J. W. and van Hemmen, J. J. (2000b) Assessment of dermal exposure during airless spray painting using a quantitative visualisation technique. Annals of Occupational Hygiene 44, 543–549. Byrne, M. A. (2000) Suction methods for assessing contamination on surfaces. Annals of Occupational Hygiene 44, 523–528. CEN (1995) Workplace atmospheres—guidance for the assessment of exposure by inhalation to chemicl agents for comparison with limit values and measurement strategy, EN 689. CEN, European Committee for Standardization, Brussels. Cherrie, J. W. and Robertson, A. (1995) Biologically relevant assessment of dermal exposure. Annals of Occupational Hygiene 39, 387–392. Cherrie, J. W., Brouwer, D. H., Roff, M., Vermeulen, R. and Kromhout, H. (2000) Use of qualitative and quantitative
Dermal exposure assessment fluorescence techniques to assess dermal exposure. Annals of Occupational Hygiene 44, 519–522. de Cock, J., Heederik, D., Kromhout, H., Boleij, J. S. M., Hoek, F., Wegh, H. and Tjoe Ny, E. (1998) Determinants of exposure to captan in fruit growing. American Industrial Hygiene Association Journal 59, 166–172. Dost, A. A. (1995) Monitoring inorganic airborne and surface contamination by a portable XRF spectrometer. Epidemiology 6, 547. Fenske, R. A. (1993) Dermal exposure assessment techniques. Annals of Occupational Hygiene 37, 687–706. Fogh, C. L. and Andersson, K. G. (2000) Modelling of skin exposure from distributed sources. Annals of Occupational Hygiene 44, 529–532. Iwata, Y., Knaak, J. B., Spear, R. C. and Foster, R. J. (1977) Worker re-entry into pesticide-treated crops: I: procedure for the determination of dislodgeable residues on foliage. Bulletin of Environmental Contamination Toxicology 10, 649– 655. Jackson, J. R. (1999) Issues relating to the risk assessment of dermal exposures. An output of the EU Dermal Exposure Network. Report, University of Surrey, December. Kildesø, J., Vinzents, P., Kloch, N. P. and Schneider, T. (1999) A simple method for measuring the potential re-suspension of dust from carpets in the indoor environment. Textile Research Journal 69, 169–175. Kromhout, H. and Heederik, D. (1995) Occupational epidemiology in the rubber industry. Implications of exposure variability. American Journal of Industrial Medicine 27, 171–185. Kromhout, H., Symanski, E. and Rappaport, S. M. (1993) A comprehensive evaluation of within- and between-worker components of occupational exposure to chemical agents. Annals of Occupational Hygiene 37, 253–270. Kromhout, H., Swuste, P. and Boleij, J. S. M. (1994) Empirical modelling of chemical exposure in the rubber manufacturing industry. Annals of Occupational Hygiene 38, 3–22. Kromhout, H., Tielemans, E., Preller, L. and Heederik, D. (1996) Estimates of individual dose from current exposure measurements. Occupational Hygiene 3, 23–39. Kromhout, H., Loomis, D. P., Kleckner, R. C. and Savitz, D. A. (1997) Sensitivity of the relation between cumulative magnetic field exposure and brain cancer mortality to choice of monitoring data grouping scheme. Epidemiology 8, 442–445. Kromhout, K., Hoek, F., Uitterhoeve, T., Huijbers, R., Overmars, R. F., Anzion, R. and Vermeulen, R. (2000) Postulating a dermal pathway for exposure to anti-neoplastic drugs among hospital workers. Applying a conceptual model to the results of three workplace surveys. Annals of Occupational Hygiene 44, 551–560. Morrison, B. M. and Scala, D. D. (1996) Comparison of instrumental measurements of skin hydration. Journal of Toxicology, Cutaneous Ocular Toxicology 15, 305–314.
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Ness, S. A. (1994) Surface and Dermal Monitoring for Toxic Exposuresy. Van Nostrand Reinhold, New York. Nicas, M. and Spear, R. C. (1993) A task-based statistical model of a worker’s exposure distribution: Part I—description of the model. American Industrial Hygiene Association Journal 54, 211–220. Olsen, E. and Jensen, B. (1994) On the concept of the ‘normal’ day: quality control of occupational hygiene measurements. Applied Occupational and Environmental Hygiene 9, 245– 255. Rappaport, S. M., Kromhout, H. and Symanski, E. (1993) Variation of exposure between workers in homogeneous exposure groups. American Industrial Hygiene Association Journal 54, 654–662. Rougier, A., Lotte, C. and Dupuis, D. (1987) An original predictive method for in vivo percutaneous absorption studies. Journal of the Society of Cosmetics Chemistry 38, 397–417. Royster, G. W. and Fish, B. R. (1967) Techniques for assessing removable surface contamination. In Surface Contamination, Proceedings of a Symposium held at Gatlingsburg, Tennessee, ed. B. R., Fish, pp. 201–207. Pergamon Press, New York. Schneider, T., Petersen, O. H., Aasbjerg Nielsen, A. and Windfeld, K. (1990) A geostatistical approach to indoor surface sampling strategies. Journal of Aerosol Science 21, 555–567. Schneider, T., Kildesø, J., Petersen, O. H., Kloch, N. P. and Løbner, T. (1996) Design and calibration of a simple instrument for measuring dust on surfaces in the indoor environment. Indoor Air 6, 204–210. Schneider, T., Vermeulen, R., Brouwer, D. H., Cherrie, J. W., Kromhout, H. and Fogh, C. L. (1999) Conceptual model for assessment of dermal exposure. Occupational and Environmental Medicine 56, 765–773. Soutar, A., Semple, S., Aitken, R. J. and Robertson, A. (2000) Use of patches and whole body sampling for the assessment of dermal exposure. Annals of Occupational Hygiene 44, 511–518. Vermeulen, R., de Hartog J., Swuste, P. and Kromhout, H. (2000a) Trends in exposure to inhalable particulate and dermal contamination in the Rubber Manufacturing Industry: effectiveness of control measures implemented over a nineyear period. Annals of Occupational Hygiene 44, 343–354. Vermeulen, R., Heideman, J., Bos, R. P. and Kromhout, H. (2000b) Identification of dermal exposure pathways in the rubber manufacturing industry. Annals of Occupational Hygiene 44, 533–541. Wheeler, J. P. and Stancliffe, J. D. (1998) Comparison of methods for monitoring solid particulate surface contamination in the workplace. Annals of Occupational Hygiene 42, 477–488. Wolkoff, P. (1996) An emission cell for measurement of volatile organic compounds emitted from building materials for indoor use—the field and laboratory emission cell FLEC. Gefahrstoffe-Reinhaltung der Luft 56, 151–157.
Ann. occup. Hyg., Vol. 44, No. 7, pp. 493–499, 2000 2000 British Occupational Hygiene Society Published by Elsevier Science Ltd. All rights reserved Printed in Great Britain. 0003-4878/00/$20.00
Dermal Exposure Assessment THOMAS SCHNEIDER†*, JOHN W. CHERRIE‡, ROEL VERMEULEN§ and HANS KROMHOUT§ †National Institute of Occupational Health, Lersø Parkalle 105, DK 2100, Copenhagen, Denmark; ‡University of Aberdeen and Institute of Occupational Medicine, Edinburgh, UK; §Environmental and Occupational Health Group Utrecht University, Utrecht, The Netherlands
Assessing dermal exposure is a complex task. Even the most commonly used methods face fundamental problems and there are large gaps in the documentation and validation of sampling methods. Still larger uncertainties exist regarding strategies for measurement. We propose a strategy based on a conceptual model and which draws on the considerable insight gained for airborne contaminants, including EN 689 for assessing exposure by inhalation. The vast amount of air sampling data has provided good insight into the statistical properties of short-term and long-term exposure levels, which is essential for designing cost-effective exposure studies. For surface and skin contaminants an understanding of the distribution types and parameter values is only beginning to emerge. Transport rates away from the skin contaminant layer determine the ‘memory’ of a dermal sample and measurement principles are proposed depending on these rates. It is argued that uptake is the ultimate dermal exposure metric for risk assessment and should be the basis for devising dermal occupational exposure limits. 2000 British Occupational Hygiene Society. Published by Elsevier Science Ltd. All rights reserved. Keywords: dermal exposure
IMPORTANCE OF DERMAL EXPOSURE
Exposure to hazardous substances may occur by inhalation, ingestion, or dermal contact. Occupational hygiene has traditionally focused on the inhalation exposure pathway because it was considered to be the most important route of exposure with the exception of exposure to pesticides and certain solvents. Many methods have been developed to measure inhalation exposure levels and there is a clear understanding of how such levels should be interpreted as part of a risk reduction strategy. As a result, exposure by inhalation has been reduced over the years, and some authors have suggested that dermal exposure therefore might be, relatively, more important. Recent results from a longitudinal exposure study in the rubber manufacturing industry showed, however, that reduction of contaminant source strength concurrently reduced dermal exposure (Vermeulen et al., 2000a). Contamination of the skin leading to uptake may arise in many different ways and several methods have been developed
Received 26 April 2000. *Author to whom correspondence shoud be addressed. Tel.: +45-39-16-5200; Fax: +45-39-16-5201; E-mail: [email protected]
for assessing dermal exposure. However, compared with inhalation exposure it is less clear how the measured levels should be interpreted. It is possible for hazardous substances to deposit or adsorb onto the skin directly from the air, to be transferred to the skin on contact with contaminated surfaces or by submersion of part of the body into the substance. In addition, a contaminant may be lost from the skin without being taken up into the body, either by evaporation or some other mechanisms such as washing or abrasion. Finally, the presence of clothing or protective garments may modify the rate at which hazardous substances come into contact with the skin. Given these factors, it is a complex but challenging task to quantitatively assess dermal uptake. THE CONCEPTUAL MODEL
A simple conceptual model of the processes leading to uptake via the dermal route has been postulated (Schneider et al., 1999). The model describes uptake as a result of transport of mass between compartments (Fig. 1). The identified compartments are: source, air, surface contaminant layer, outer and inner clothing contaminant layer separated by the fabric having a
493
494
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Fig. 1. The conceptual model. Adapted from Schneider et al. (1999). Overview of the conceptual model, compartments and transport processes. (E=Emission (———), Dp=Deposition (— — —), L=Resuspension/Evaporation (–··–), T=Transfer (- - -), R=Removal (– · –), Rd=Redistribution (· · ·), D=Decontamination (-·-·-), P=Penetration/Permeation (······).
buffer capacity, and skin contaminant layer. The skin contaminant layer is separated from perfused tissue by the stratum corneum, which acts as a rate-limiting barrier having a certain buffer capacity. The proposed transport processes are: Emission of substances by splashing, spilling and ejection of particles into the air and onto surfaces, outer clothing, and skin contaminant layer. Deposition of substances from the air to surfaces, outer clothing, and the skin contaminant layer. Resuspension or evaporation of substances from surfaces, outer clothing, and the skin contaminant layer to the air, as particulate, vapours, or both.
Transfer of substances by direct contact between surface, skin and outer respectively inner clothing contaminant layers in a direction towards the worker. Removal is the corresponding transport in a direction away from a worker. Redistribution of substances between compartments of the same type, e.g. redistribution of contaminants from one part of the skin contaminant layer to another as a result of touching the face with contaminated fingers. Decontamination, which is the deliberate transport of contamination away from the entire system (e.g. ventilation of room air, cleaning of room surfaces
Dermal exposure assessment
and outer clothing or washing off skin contaminant layer). Brushing dust off clothing is resuspension. Penetration and permeation, which both involve transport of substances through the rate-limiting barriers, clothing and stratum corneum. Hazardous substances in the dermal contaminant layer will be taken up continuously into the body through the stratum corneum, driven by the concentration gradient between the dermal surface and the perfused tissue. The risk arising from dermal exposure is thus firstly related to the time-dependent concentration of a substance on the dermal surface. However, the skin contaminant layer compartment has conventionally been represented as a two-dimensional layer giving concentration as mass per surface area without specifying concentration of the hazardous agent in the layer itself. This has contributed to the confusion regarding choice of measurement principles for, and interpretation of, dermal contamination in terms of dermal uptake, see e.g. Schneider et al. (1999). Particles complicate the concept of concentration since they are discrete entities. Uptake can, for example, be limited by the rate of dissolution and not by the diffusion through the stratum corneum. For these reasons existing measurement methods can be criticised because they determine directly or indirectly the mass of contaminant either depositing on the skin or retained on the skin at the end of the exposure period. MEASUREMENT METHODS TO ASSESS DERMAL EXPOSURE
Practical measurement methods have been developed to assess dermal exposure directly or indirectly. Table 1 presents a list of selected methods that cover a range of approaches (adapted from Schneider et al., 1999). The conceptual model stresses the difference in mass in compartment and transport of mass between compartments. In Table 1 we indicate for which of these two purposes the methods have been used. A clear distinction has not always been made in the literature resulting in confusion regarding determination and interpretation of sampling efficiencies. As an example, measurement methods intended to assess compartment mass should aim to have 100% sampling efficiency. On the other hand, a 100% sampling efficiency for a wipe test to quantify the transfer to skin upon contact with a surface is not necessarily desirable (Fenske, 1993). Even the most commonly used among the methods listed in Table 1 are faced with fundamental problems, such as: 앫 the behaviour of a tracer in the transport process may differ from the behaviour of the substance of interest; 앫 transfer of mass depends on the amount of mass already present in the skin contaminant layer;
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앫 skin stripping or washing with solvents cannot recover what has already penetrated to perfused tissue. Solvents influence the characteristics of the skin and can therefore not be used for repeated sampling; 앫 adherence of contaminants to patch sampler and real skin differs. Thus the amount on the patch sampler does not represent the amount actually present for uptake on the skin. Uptake is driven by concentration in the skin contaminant layer, not mass per skin surface area; 앫 patch samplers sample over small areas and therefore errors can occur when results have to be extrapolated to the whole exposed area; 앫 sampling efficiency of micro vacuuming is strongly dependent on sampling geometry and air flow rate. It is not an imperative that a method has to result in an unbiased determination of dermal uptake if the purpose of the measurement is to gain information on the location of a source in the form of contaminated surfaces, on surface concentrations and trends, or to determine the effectiveness and maintenance of control measures. For such tasks it will suffice that the methods are simple and gives reproducible results for the compartments or transport processes in question. The papers by Brouwer et al. (2000a), Soutar et al. (2000), Byrne (2000) and Cherrie et al. (2000) in this issue address key measurement techniques, their performance in relation to various measurement tasks and needs for development. APPROACHES TO DERMAL EXPOSURE ASSESSMENT
While there are large gaps in the documentation and validation of sampling methods for dermal exposure, still larger gaps exist regarding strategies for measurement. The following discussion of strategies for dermal exposure assessment draws on the considerable insight gained for airborne contaminants. By analogy with EN 689 for assessing exposure by inhalation for comparison with limit values (CEN, 1995) a measurement strategy based on a tiered approach is proposed. Following this approach, the first step would consist of identifying potential exposure, meaning the preparation of a list of all chemical substances in the workplace and appropriate toxicological information. The second step would be to evaluate workplace factors, including tasks, work patterns and techniques, production processes, sources of direct skin contact, spilling, splashing, and emission to air, safety precautions and procedures (including protective clothing and gloves). The purpose would be to gauge the potential for dermal exposure to the chemical agents. The third step would consist in using a structured
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Table 1. Measurement methods. Modified from Schneider et al. (1999) Method
Principle of sampling
Measured compartment mass
u.v. Fluorescence
In situ
Portable X-ray fluorescence monitor
In situ
Skin, surface, inner and outer clothing Surface
Wet wipe
Manual wiping
Surface, skin
Wet wipe
Mechanised wiping
Surface
Gelatine foil Fixed pressure dislodgeable residue sampler Dislodgeable foliar residue sampling Adhesive tape
Surface dust lifting Surface Mechanical transfer in Surface situ Surface removal
Surface
Skin stripping
Skin
Hand wash
Wash with water or alcohol
Skin
Patch
Passive
Skin
Whole body
Passive
Skin
SMAIR
–
FLEC
Resuspension by air jet Resuspension by impact Resuspension by suction Evaporation by airflow
TEWL
Evaporation
–
STEPP Microvacuuming
Measured transport process All processes
Ref.
Cherrie et al. (2000)
All processes related Dost (1995) to the surface contaminant layer Transfer from surface Anon (1990) to skin and to outer clothing Removal from skin to surface, inner and outer clothing Wheeler and Stancliffe (1998) Schneider et al. (1996) Ness (1994, pp. 191– 194) Iwata et al. (1977) Removal from skin to Rougier et al. (1987) surface, inner and outer clothing. Deposition on skin Removal from skin to Brouwer et al. (2000a) surface, inner and outer clothing. Decontamination of skin Transfer from surface, Soutar et al. (2000) outer and inner clothing to skin. Deposition on skin
–
Royster and Fish (1967) Kildesø et al. (1999)
Surface
Byrne (2000)
–
approach to assess exposure. It would begin with an initial appraisal. All intermediate compartments and transport processes should be included with reference to Fig. 1. Emphasis should be given to the individuals own work practices and which body locations may get contaminated. If as a result dermal uptake of hazardous substances cannot be ruled out a basic survey should be made. The purpose of the basic survey would be to provide quantitative information about the distribution and level of dermal exposure. Had the perfect dermal uptake monitor with corresponding dermal occupational exposure limits (DOEL) been available, the basic survey would have included results obtained by such monitors from earlier measurements, plus measurements from comparable installations or work processes. If the information was
Resuspension from surface
Evaporation from Wolkoff (1996) surface Evaporation from skin Morrison and Scala (1996)
insufficient to decide that conditions were acceptable according to a given DOEL, it would have to be supplemented by workplace measurements. If it still was insufficient to decide that conditions were well below or clearly above any DOEL, a detailed survey would have to be made, aimed at narrowing the prediction interval. However, at present we do not have accepted DEOLs and a proxy-strategy has to be applied. One possibility would be to use existing dermal sampling methods and estimate uptake following a correction scheme taking into consideration all the limitations (Jackson, 1999). Another possibility would be to use criteria targeted at compartment mass or transport. The actual values could be obtained from cross-industry measurements showing what is reasonably practi-
Dermal exposure assessment
cable (i.e. benchmarks) (Kromhout et al., 1994; de Cock et al., 1998). WORKPLACE MEASUREMENTS
It is not possible to specify in detail a procedure for selection of workers to be measured regarding exposure by inhalation (CEN, 1995), and thus much less so for dermal exposure. Rather a set of options can be given. One approach is to subdivide the exposed population in subgroups within each of which the exposure is supposed to be similar and consequently to draw a random sample from each subgroup (i.e. stratified random sampling). For air contaminants fixed point measurements in the vicinity of workers can be used to monitor general concentration levels and trends. The analogue for dermal exposure would be to monitor hazardous substances in surface layer compartments with which the worker has frequent contact. Obviously the industrial hygienist can monitor any of the compartments or transport processes and use the conceptual model (Fig. 1) to interpret the results. Worst-case measurements for air contaminants are used to direct measurement efforts to problem areas. Ideally, worst-case measurements represent episodes where high exposures occur (CEN, 1995). It has been shown that it can be difficult to identify such episodes (Olsen and Jensen, 1994). An alternative approach is to use a task-based exposure model, such as proposed by Nicas and Spear (1993). A task-based approach to dermal exposure would assess dermal uptake caused by each individual task and combine these uptakes into a long-term uptake using task time weights. This approach assumes that concentration in the skin contaminant layer during each task and duration of tasks are equally important determinants of long-term uptake. However, randomly taken shift long measurements with simultaneously collected information on tasks and conditions offer the opportunity to statistically unravel exposure-affecting factors for dermal exposure (Kromhout et al., 1994). The large amount of air sampling data has provided good insight into the statistical properties of shortterm and long-term concentrations. The distribution (except extreme values) can be modelled satisfactorily by the log-normal distribution which is completely characterised by the geometrical mean and geometrical standard deviation. Concentrations are thus usually log-transformed prior to statistical analysis. Measurements on different exposure groups, on random samples of workers within groups and repeated measurements on individual workers have provided a database from which typical values of the within-worker, within-group (i.e. between-worker) and between-group variance components have been estimated (Kromhout et al., 1993, 1996; Rappaport et al., 1993). It has become evident that it is not easy to give criteria for grouping a priori workers in uniform
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exposed groups. Within-worker variability in exposure concentrations has been shown to be predominantly larger than within-group variability in exposure concentrations and within-group variability can be larger than between-group differences in average exposure. This has important implications for the design of cost-effective exposure studies. So, repeated measurement designs are needed to give the researcher the opportunity to optimise grouping schemes (Kromhout and Heederik, 1995; Kromhout et al., 1997). For surface and skin contaminants an understanding of the distribution types and parameter values is only beginning to emerge. Spatial distribution on surfaces in offices has been found to be log-normal and there was correlation between close sampling positions (Schneider et al., 1990). A database called ‘DERMDAT’ with dermal exposure measurements primarily collected with surrogate skin samplers, has recently been compiled. By focussing on repeated measurement series, between-body location, betweenworker, and within-worker variance components have been estimated, as well as correlation patterns between body locations and between total estimated dermal exposure and exposure of individual body locations. Results of this database are presented in a paper currently under consideration (Kromhout and Vermeulen, personal communication). TEMPORAL ASPECTS
The amount of hazardous substances in the skin contaminant layer at any given time depends on the time variable transport of mass to and from the skin. A basic question is how much ‘memory’ of past exposure incidents there is in a sample of the skin contaminant layer, e.g. a hand rinse sample. This will depend on the rate of transport of the substance from the skin contaminant layer. Suppose that the rate of transport away from the skin contaminant layer is given by a single time constant τ and that a given mass is transferred to the layer by an event occurring at time t=0. Then the fraction of mass remaining at time t will be exp(⫺t/τ). Obviously effective decontamination events represent step changes and define natural boundaries for sampling time intervals. The transport from the skin contaminant layer can be divided into two pathways: penetration/permeation, and removal+resuspension/evaporation (neglecting redistribution). By dichotomising each of the transport rates, four types of sampling tasks are defined (Fig. 2). In the lower left corner, the skin contaminant layer has a long memory, in the upper right corner the memory is short. This diagram can assist in selecting a proper sampling method. If both transport rates (or rather if the amount of mass transported in time periods between decontamination events) are low then a removal technique or fluorescence technique applied immediately before a decontamination can be used to
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Fig. 2. Proposed sampling methods. The sampling conditions are characterised by the transport rates away from the skin contaminant layer; *u.v. tracers will have a low permeation/penetration rate.
estimate uptake. If the removal+resuspension/evaporation rate is low but penetration/permeation rate is high, a surrogate skin sampler would give a good measure of dermal uptake. Since u.v. tracers have a low permeation/penetration rate, a fluorescence technique could also be used. If the removal+resuspension/ evaporation rate is high and penetration/evaporation rate is low, a surrogate skin sampler would greatly overestimate uptake. In this case biological monitoring would be preferable and also in the case of both transport rates being high. DISCUSSION
The papers byVermeulen et al. (2000b), Brouwer et al. (2000b) and Kromhout et al. (2000) in this issue describe how currently available sampling techniques incorporated in a model driven exposure assessment strategy can be used to determine exposure scenarios and exposure pathways and to develop hazard control strategies. Fogh and Andersson (2000) have added transport rate constants to the conceptual model and used it to quantify exposure risk in a specific scenario. Dermal uptake is the ultimate dermal exposure metric. It offers a scientifically justifiable approach to measuring and controlling the risks from dermal exposure to hazardous substances. Existing dermal sampling methodologies do not measure dermal uptake directly and in order to quantify dermal uptake from results of measurements several assumptions and corrections would have to be made, as evidenced in the previous sections. We consider that rather than devising a system of DOELs based on present day measurement methods further development should be
undertaken to improve the measurement methodology. The novel dermal sampler concept for quantifying dermal uptake proposed by Cherrie and Robertson (1995) could be a promising way forward. A dermal exposure metric describing dermal uptake has the further advantage that it provides some of the necessary conditions for deriving total uptake limits, which would enable exposure by inhalation and dermal uptake to be controlled simultaneously. Acknowledgements—This work was facilitated by the Dermal Exposure Network, supported by European Commission Contract SMT4-CT96-7502 (DG12-RSMT).
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Dermal exposure assessment fluorescence techniques to assess dermal exposure. Annals of Occupational Hygiene 44, 519–522. de Cock, J., Heederik, D., Kromhout, H., Boleij, J. S. M., Hoek, F., Wegh, H. and Tjoe Ny, E. (1998) Determinants of exposure to captan in fruit growing. American Industrial Hygiene Association Journal 59, 166–172. Dost, A. A. (1995) Monitoring inorganic airborne and surface contamination by a portable XRF spectrometer. Epidemiology 6, 547. Fenske, R. A. (1993) Dermal exposure assessment techniques. Annals of Occupational Hygiene 37, 687–706. Fogh, C. L. and Andersson, K. G. (2000) Modelling of skin exposure from distributed sources. Annals of Occupational Hygiene 44, 529–532. Iwata, Y., Knaak, J. B., Spear, R. C. and Foster, R. J. (1977) Worker re-entry into pesticide-treated crops: I: procedure for the determination of dislodgeable residues on foliage. Bulletin of Environmental Contamination Toxicology 10, 649– 655. Jackson, J. R. (1999) Issues relating to the risk assessment of dermal exposures. An output of the EU Dermal Exposure Network. Report, University of Surrey, December. Kildesø, J., Vinzents, P., Kloch, N. P. and Schneider, T. (1999) A simple method for measuring the potential re-suspension of dust from carpets in the indoor environment. Textile Research Journal 69, 169–175. Kromhout, H. and Heederik, D. (1995) Occupational epidemiology in the rubber industry. Implications of exposure variability. American Journal of Industrial Medicine 27, 171–185. Kromhout, H., Symanski, E. and Rappaport, S. M. (1993) A comprehensive evaluation of within- and between-worker components of occupational exposure to chemical agents. Annals of Occupational Hygiene 37, 253–270. Kromhout, H., Swuste, P. and Boleij, J. S. M. (1994) Empirical modelling of chemical exposure in the rubber manufacturing industry. Annals of Occupational Hygiene 38, 3–22. Kromhout, H., Tielemans, E., Preller, L. and Heederik, D. (1996) Estimates of individual dose from current exposure measurements. Occupational Hygiene 3, 23–39. Kromhout, H., Loomis, D. P., Kleckner, R. C. and Savitz, D. A. (1997) Sensitivity of the relation between cumulative magnetic field exposure and brain cancer mortality to choice of monitoring data grouping scheme. Epidemiology 8, 442–445. Kromhout, K., Hoek, F., Uitterhoeve, T., Huijbers, R., Overmars, R. F., Anzion, R. and Vermeulen, R. (2000) Postulating a dermal pathway for exposure to anti-neoplastic drugs among hospital workers. Applying a conceptual model to the results of three workplace surveys. Annals of Occupational Hygiene 44, 551–560. Morrison, B. M. and Scala, D. D. (1996) Comparison of instrumental measurements of skin hydration. Journal of Toxicology, Cutaneous Ocular Toxicology 15, 305–314.
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