Monitoring dermal exposure to chemicals


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Slides from a keynote presentation at the Occupational and Environmental Exposure of Skin to Chemicals (OEESC) conference.

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  • Thank you and my thanks to the organisers for inviting me to give this Keynote address. It is always an interesting and informative exercise to try to review work in a specific area and try to draw out some lessons, and I hope that you will find this talk a helpful beginning to our discussions about exposure measurement.
  • Dermal exposure measurement is a broad field and I have had to limit the scope somewhat. I have chosen to look only at occupational studies, although I suspect that much of what I have to say will also be relevant to environmental exposure, and I have mostly kept to the last ten years. The brief version of the talk is that we have made progress but that it is slow and if we are to really improve things we are going to have to work differently in the future.
  • Over the last 40 years interest in dermal exposure has grown enormously or at least as measured by the number of published scientific papers with the term in the title or abstract. Interest in dermal exposure measurement has also grown since with a significant number of papers being published since the start of the 1990s. However, interest in measurement has not grown as fast as other aspects of occupational dermal exposure and we are still a very small scientific field publishing 20 – 30 papers per annum.
  • The methods that we have available have been around for a long time and they are all very practical pragmatic techniques. We can either reply on interception, removal or in-situ assessments (Questionnaires, which one might reasonably include here are going to be dealt with by Dr Bello in the next talk). Not all techniques are applicable in all situations. Clearly relying on washing or wiping for materials that are either rapidly transferred into the body or are lost to the environment would not be sensible. A lot of work has been done on sampling recovery, the distribution of exposure across the body, the appropriateness of sampling only part of the skin. For wiping and washing there are also issues about the number and timing of samples collected.
  • Important developments in the last ten years are the “Standards” describing the measurement methods and strategies, the latest of these being finally agreed just last month. Fortunately these documents summarise the key knowledge. relating to these methods. They also attempt to standardise the terminology used by researchers and others.
  • Over the last ten years there has been increasing interest in dermal exposure to metals, mainly from the perspective of risk assessment. These data show the exposure loading on the hands and forearms, which tend to be the most highly exposed, for 19 different scenarios for four metals and CaCo3. The data span almost four orders of magnitude with substances where there is greater use of engineering control measures. We have looked at estimates of the maximum likely loading from immersing your hand in powder and concluded that it is around 10 mg/cm2, i.e. at the top of this scale.
  • The Schneider et al conceptual model, which was developed as part of a European capacity building initiative, was intended as a way of understanding what was going on in relation to exposure processes and it can be used as a tool to guide the development of research questions. It comprises a series of compartments that are linked and may exchange contaminant (this is a simplified schematic of the published model). Importantly we underline that it is not the mass on the skin contamination layer that determines uptake but rather the concentration of the substance.
  • In fact we measure the Dermal exposure mass, or the dermal exposure mass loading, or … However, we don’t measure the concentration. Often we don’t even report the concentration in the source.
  • We developed a prototype sampler to measure Something more biologically relevant, particularly for volatile agents although the concept is applicable to all substances of interest. It’s based on a diffusion membrane and an adsorbent material. The IOM sampler worked well but suffered because the permeability of the available membranes was higher than the skin and so it was necessary to adjust the results for uptake of vapour. The device needs further development. NIOSH have independently developed a POD for PAH sampling for asphalt workers, although the details are not yet published.
  • Another attempt to measure exposure in a biologically relevant manner is the wet-work sampler that we developed. This is based around measuring the difference in temperature from two thermocouples – one located on the skin and the second about a millimeter above the skin. By counting the spikes in the measurement and the duration the reading is above the baseline we can assess both duration of wetness and number of wet events. Some further measurements using this device will be reported in the next session at this conference.
  • Dermal exposure not routinely undertaken to control risk. The main focus is research, for example to: Understanding exposure routes (for health impact assessments) Assessing the effectiveness of protective clothing Epidemiological studies Increasingly in Europe industry is undertaking work to develop datasets for use in regulatory approval Under the REACH Regulations In other regulatory systems
  • Vermeulen and colleagues carried out a study in the rubber industry to investigate the importance of different pathways in relation to the Schneider et al model. They measured air concentration, dermal exposure loading. They showed that; Hand (wrist) contamination was on average highest Strong correlation between hand (wrist) and whole body contamination
  • In addition they looked at the correlation between the measured values in different compartments by the stage of the production process. They found that this differed by process stage. For example, in curing there was a moderate correlation between near-field air concentration and the load in the skin contamination layer but no association between surface levels and the load in the SCL. However, in pre-treatment the reverse was the case, with moderate correlation between surface load and SCL load, but no association between air concentrations and the load in the SCL.
  • A more systematic look at the published literature identified 271 papers that were potentially relevant, and screening these got it down to 21 for review.
  • In fact there were only seven that had data on the correlation between inhalation and dermal exposure measures. These danged from 0.79 in spray painters to no correlation for greenhouse workers. Not surprising but we need to better understand these associations so that we can decide when we might expect to find some benefits in reduced dermal exposure from intervening to reduce inhalation exposure.
  • The paper by Fent shows a strong correlation between the inhalation exposure (concentration x duration spent painting) and dermal dermal loading. This is probably because the spraying process is the main source of contamination in the workplace.
  • There were 10 paper that provided some information about the relative contribution from dermal exposure to overall exposure. Sometimes based on an analysis of biological monitoring information in relation to air and dermal exposure data, sometimes on estimates of intake using models. One paper used a PBTK model to relate the various measures and estimate the contributions form different pathways. Interestingly these show that for many of the more volatile agents the proportion from dermal exposure was relatively small.
  • The paper from Borak et al shows data from 34 workers involved in impregnating timber with creosote. In this case they estimated that more than 90% of the uptake was from skin contact.
  • The data from Kim and colleagues and a second paper by Chao et al show that the majority of naphthalene uptake was by inhalation. Kim used a PBPK model to link the various measurements made.
  • There are very few research studies that have looked at the effectiveness of PPE – just 13 since 2000 on glove of clothing protectiveness.
  • Monitoring dermal exposure to chemicals

    1. 1. Dermal exposure assessment: Progress and Pitfalls <ul><li>John Cherrie </li></ul>WORKING FOR A HEALTHY FUTURE INSTITUTE OF OCCUPATIONAL MEDICINE . Edinburgh . UK
    2. 2. Outline… <ul><li>Measurement methodology </li></ul><ul><ul><li>Metals </li></ul></ul><ul><ul><li>ISO and CEN standards </li></ul></ul><ul><ul><li>Novel approaches </li></ul></ul><ul><li>Schneider et al </li></ul><ul><ul><li>Rubber dust and fume </li></ul></ul><ul><li>Inhalation and dermal exposure </li></ul><ul><ul><li>Isocyanates and jet fuel (JP-8) </li></ul></ul><ul><li>The effectiveness of protective equipment </li></ul><ul><li>Pitfalls (lack of progress) </li></ul><ul><li>Where next? </li></ul>
    3. 3. Growing interest in dermal exposure…
    4. 4. How do we measure? <ul><li>Interception (e.g. patches) </li></ul><ul><ul><li>The mass of chemical that lands on the skin over the sampling time (integrated flux) </li></ul></ul><ul><li>Removal (e.g. wipe/wash) </li></ul><ul><ul><li>The mass of contaminant left on the skin </li></ul></ul><ul><li>In-situ (e.g. fluorescence) </li></ul><ul><ul><li>The mass of a surrogate compound retained on the skin </li></ul></ul>
    5. 5. European and International “Standards” <ul><li>CEN/TC 137 - Assessment of workplace exposure to chemical and biological agents </li></ul><ul><ul><li>Workplace exposure - Strategy for the evaluation of dermal exposure (CEN/TR 15278:2006) </li></ul></ul><ul><ul><li>Workplace exposure - Measurement of dermal exposure - Principles and methods (CEN/TS 15279:2006) </li></ul></ul><ul><li>ISO TC146 SC2 WG8 - Assessment of contamination of skin and surfaces from airborne chemicals </li></ul><ul><ul><li>TR 14294 – accepted 3 rd May 2011 </li></ul></ul>
    6. 6. Dermal exposure to metals… Source: / Hughson GW, Cherrie JW. (2005) Comparison of measured dermal dust exposures with predicted exposures given by the EASE expert system. Annals of Occupational Hygiene;49(2):111–123. CaCO 3 Zn Pb Sb Ni
    7. 7. Schneider et al conceptual model Schneider et al. (1999) Conceptual model for assessment of dermal exposure. Occup Environ Med vol. 56 (11) pp. 765-73. Surface contamination layer Air compartment Clothing outer layer Skin contamination layer Source Clothing inner layer
    8. 8. What we measure… <ul><li>Dermal exposure mass (mg) </li></ul><ul><li>Dermal exposure loading = Mass loading (mg/cm 2 ) </li></ul><ul><li>Mass flux onto the skin (mg/cm 2 /hr) </li></ul><ul><li>Surface area exposed (cm 2 ) </li></ul><ul><li>Exposure period (hr) </li></ul><ul><li>However, we don’t measure the concentration of the substance in the skin contamination layer </li></ul>Kissel JC. (2010) The mismeasure of dermal absorption. J Expos Sci Environ Epidemiol;21(3):302–309.
    9. 9. Biologically-relevant samplers… <ul><li>An interception sampler that mimics the skin </li></ul><ul><ul><li>with a diffusion membrane, ideally chosen with similar uptake characteristics to the skin </li></ul></ul><ul><ul><li>adsorbent material </li></ul></ul><ul><ul><li>impervious backing </li></ul></ul><ul><li>Prototype IOM dermal sampler </li></ul>Lindsay FE, Semple S, Robertson A, Cherrie JW. (2006) Development of a biologically relevant dermal sampler. Annals of Occupational Hygiene;50(1):85-94. <ul><li>NIOSH POD </li></ul><ul><ul><li>5-layer Passive Organic Dermal sampler </li></ul></ul>
    10. 10. The IOM wet-work sampler… <ul><li>Sensor based on two thermocouples </li></ul><ul><li>Difference in temperature indicates wetness </li></ul><ul><li>Can be used to estimate the duration of wetness and the number of events </li></ul>Cherrie JW, Apsley A, Semple SE. (2007) A new sampler to assess dermal exposure during wet working. Ann Occup Hyg.;51(1):13-18.
    11. 11. Why do we measure? <ul><li>Dermal exposure not routinely undertaken to control risk </li></ul><ul><li>Main focus is research </li></ul><ul><ul><li>Understanding exposure routes (for health impact assessments) </li></ul></ul><ul><ul><li>Assessing the effectiveness of protective clothing </li></ul></ul><ul><ul><li>Epidemiological studies </li></ul></ul><ul><li>Regulatory approval </li></ul><ul><ul><li>Under the REACH Regulations </li></ul></ul><ul><ul><li>In other regulatory systems </li></ul></ul>
    12. 12. Vermeulen et al (2000) <ul><li>Identified the exposure pathways in rubber manufacturing </li></ul><ul><li>They measured… </li></ul><ul><ul><li>Air concentration – both near and far-field </li></ul></ul><ul><ul><li>Dermal exposure loading </li></ul></ul><ul><li>They showed that… </li></ul><ul><ul><li>Hand (wrist) contamination was on average highest </li></ul></ul><ul><ul><li>Strong correlation between hand (wrist) and whole body contamination </li></ul></ul>Vermeulen R, Heideman J, Bos RP, Kromhout H. (2000) Identification of dermal exposure pathways in the rubber manufacturing industry. Ann Occup Hyg.;44(7):533-541.
    13. 13. Different process – different pathways Curing Pre-treatment
    14. 14. Inhalation and dermal exposure… <ul><li>Searching Scopus database for entries since 2000 </li></ul><ul><ul><li>Search query: (inhalation) AND (dermal) AND (exposure) AND (occupational OR worker) </li></ul></ul><ul><li>271 papers </li></ul><ul><ul><li>Screening on title gave 46 possibly informative papers </li></ul></ul><ul><ul><li>Screening on abstract gave identified about half of these as uninformative </li></ul></ul><ul><li>Final assessment based on 21 papers </li></ul>
    15. 15. Inhalation and dermal exposure Authors Substance Workplace Corr Comment Fent et al (2008) HDI Spray painters 0.79 Log transformed data Day et al (2007) Beryllium Cu-Be alloy plant 0.63 McClean et al (2004) PAH Asphalt workers 0.59 Based on pyrene analysis Hughson et al (2010) Nickel Various Ni production 0.48 Log-transformed hand data Sobus et al (2009) PAH Asphalt workers 0.32 Not statistically significant Cocker et al (2009) MbOCA Polyurethane elastomers None Aprea et al (2009) Imidacloprid Greenhouse None
    16. 16. Correlation between measures… <ul><li>For spraying of low-volatility agents there seems to be a fairly strong association between inhalation and dermal exposure </li></ul><ul><li>Isocyanate data from Fent et al </li></ul>Fent K, Jayaraj K, ball LM, Nylander-French L. (2008) Quantitative monitoring of dermal and inhalation exposure to 1,6-hexamethylene diisocyanate monomer and oligomers. J. Environ. Monit.;10(4):500-507.
    17. 17. Contribution of skin to total exposure… Authors Substance Workplace % skin Comment Borak et al (2002) PAH Creosote impregnation >90% Aprea et al (2009) Imidacloprid Greenhouse work >78% Est. absorbed dose Sheenan et al (2008) Benzene Cleaning ≈ 50% Low levels Bader et al (2008) NMP Simulation 47% Vapour uptake at rest Chen et al (2008) PAH Metal machining 37% Lindsay et al (2006) Toluene Coating work <9% Kim et al (2007) Jet fuel Fuel cell maintenance 4% PBTK model Chao et al (2006) Jet fuel Fuel cell maintenance 3% Xing et al (2011) PCB Recycling 0% Diet main source Vermeulen (2006) Benzene Shoe manufacture 0%
    18. 18. Creosote impregnation… <ul><li>34 employees classified into three exposure groups </li></ul><ul><li>Spot urine samples analysed for 1-OHP </li></ul><ul><li>Air samples for PAH </li></ul>1.Borak J, Sirianni G, Cohen H. et al (2002) Biological versus ambient exposure monitoring of creosote facility workers. Occup. Env. Med.;44: 310-319.
    19. 19. JP-8 and fuel cell maintenance… <ul><li>Personnel in six US Air Force bases </li></ul><ul><li>Dermal tape strip samples for naphthalene </li></ul><ul><li>Air concentration of naphthalene and exhaled breath </li></ul><ul><li>PBTK model </li></ul>Kim D, Andersen ME, Chao YE, Egeghy PP, Rappaport SM, Nylander-French LA. (2007) PBTK Modeling Demonstrates Contribution of Dermal and Inhalation Exposure Components to End-Exhaled Breath Concentrations of Naphthalene. Environ Health Perspect.;115(6): 894-901.
    20. 20. Protective clothing and gloves… <ul><li>Measurements made on top of and under clothing, usually with interception samplers </li></ul><ul><li>Biomarker studies with and without the protective clothing </li></ul><ul><li>Search query:   (dermal exposure) and (&quot;protective clothing&quot; or gloves) and (effectiveness) - only 13 papers since 2000 </li></ul><ul><li>Level of protection may be quite variable </li></ul><ul><li>Protection factor may change with the duration of wearing </li></ul>
    21. 21. Protection factor paradign Simulated data Cherrie JW, Semple S, Brouwer D. (2004) Gloves and dermal exposure to chemicals: Proposals for evaluating workplace effectiveness. Annals of Occupational Hygiene;48(7):607–615.
    22. 22. Interest in exposure measurement…
    23. 23. Dermal + exposure + measurement + (work or occupational)
    24. 24. Pitfalls… <ul><li>Little progress towards measuring biologically relevant exposure </li></ul><ul><li>Little connection between measurement and modelling </li></ul><ul><li>Poor understanding of the effectiveness of PPE </li></ul><ul><li>Insufficient collaboration within and between our constituent groups </li></ul><ul><li>We haven’t really convinced our colleagues of the importance of dermal exposure measurements </li></ul>
    25. 25. The way forward… <ul><li>Define a clear research agenda for dermal exposure measurement </li></ul><ul><li>Look for ways to increase collaboration between groups and disciplines </li></ul><ul><li>Figure out the importance of dermal exposure to risk </li></ul>
    26. 26. News… <ul><li>The WHO IPCS will publish an Environmental Health Criteria Monograph (EHC) on Dermal Exposure later this year </li></ul><ul><li>This is a companion to the earlier volume on Dermal Absorption , published 2006 </li></ul><ul><li>Slides from this talk will be available at… </li></ul>