Dermal exposure measurement and modelling

WORKING FOR A HEALTHY FUTURE

INSTITUTE OF OCCUPATIONAL MEDICINE . Edinburgh . UK www.iom-world.org

Dermal exposure assessment

John Cherrie

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Outline…

• Measurement methodology• Metals• ISO and CEN standards• Novel approaches

• Schneider et al• Rubber dust and fume

• Inhalation and dermal exposure• Isocyanates and jet fuel (JP-8)

• The effectiveness of protective equipment• Exposure models• Where next?

Health concerns from skin exposure…

• Local effects in the skin• Cancer• Allergic contact dermatitis• Irritant contact dermatitis

• Contribution to systemic exposure

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Growing interest in dermal exposure…

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How do we measure?

• Interception (e.g. patches)• The mass of chemical that lands on

the skin over the sampling time (integrated flux)

• Removal (e.g. wipe/wash)• The mass of contaminant left

on the skin

• In-situ (e.g. fluorescence)• The mass of a surrogate

compound retained on the skin

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Interception sampling…

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‘Generic’ protocols that prescribe sizes, numbers, location and method of attachment of patches are given by WHO, US-EPA, OECD

Possible to use whole suit, gloves, hood, socks…

“actual” and “potential” exposure

Removal sampling…

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Removal sampling…

• Hand washing or rinsing• Use water (+surfactant), solvent (e.g. ethanol)• Use of bags to hold the washing liquid• Main limitation is that it can only be used on hands

• Wiping• Moist wipes (commercial hand wipes or manufactured)• Fixed area wiped or whole hands• May require multiple wipes to get acceptable recovery

• Tape stripping• Adhesive tape to remove (successive) layers of stratum

corneum

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Tape stripping…

• Evaluation of a tape-stripping for measuring dermal exposure to pyrene and benzo(a)pyrene

91.Kammer R, Tinnerberg H, Eriksson K. Evaluation of a tape-stripping technique for measuring dermal exposure to pyrene and benzo(a)pyrene. J. Environ. Monit. 2011.

Tape Glass Skin

Pyrene 97% 88% 70%

Benzo(a)pyrene

93% 76% 63%

Recovery efficiency…

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Fluorescent tracers…

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European and International “Standards”

• CEN/TC 137 - Assessment of workplace exposure to chemical and biological agents• Workplace exposure - Strategy for the evaluation of

dermal exposure (CEN/TR 15278:2006)• Workplace exposure - Measurement of dermal exposure

- Principles and methods (CEN/TS 15279:2006)

• ISO TC146 SC2 WG8 - Assessment of contamination of skin and surfaces from airborne chemicals• TR 14294 – accepted 3rd May 2011

Dermal exposure to metals…

CaCO3 CaCO3 ZnZn PbPb SbSb NiNi

Source: http://www.herag.net /

13Hughson 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.

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Schneider et al conceptual model

Surface contamination layer Air compartment

Clothing outer layer

Skin contamination layer

Source

Clothing inner layer

Schneider et al. (1999) Conceptual model for assessment of dermal exposure. Occup Environ Med vol. 56 (11) pp. 765-73.

What we measure…

• Dermal exposure mass (mg)• Dermal exposure loading = Mass loading (mg/cm2) • Mass flux onto the skin (mg/cm2/hr)• Surface area exposed (cm2)• Exposure period (hr)

• However, we don’t measure the concentration of the substance in the skin contamination layer

15Kissel JC. (2010) The mismeasure of dermal absorption. J Expos Sci Environ Epidemiol;21(3):302–309.

Biologically-relevant samplers…

• An interception sampler that mimics the skin• with a diffusion membrane, ideally chosen with similar uptake

characteristics to the skin• adsorbent material• impervious backing

• Prototype IOM dermal sampler

Lindsay FE, Semple S, Robertson A, Cherrie JW. (2006) Development of a biologically relevant dermal sampler. Annals of Occupational Hygiene;50(1):85-94.

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• NIOSH POD• 5-layer Passive

Organic Dermal sampler

Field trials of the IOM sampler

• Two companies using toluene• Factory A - a specialist printing blankets

and rubber coated fabrics• Factory B - pigment mixing process and

coating process

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Factory A

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IOM dermal sampler v ACC

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IOM sampler v air concentration

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Design difficulties…

• Range of membranes tested but none completely suitable• more permeable than skin

• Adsorbent more easily saturated than we would have wished

• Need to correct for air concentration

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The IOM wet-work sampler and irritation

2222

Time

Threshold

after Malten/van der Walle

Dermatitis

Sub

-clin

ical

Dam

age

The design…

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• Sensor based on two thermocouples

• Difference in temperature indicates wetness

• Can be used to estimate the duration of wetness and the number of events

Cherrie JW, Apsley A, Semple SE. (2007) A new sampler to assess dermal exposure during wet working. Ann Occup Hyg.;51(1):13-18.

The IOM wet-work sampler…

• The difference between the temperature readings provides an indicator of wet events and duration hands wet

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Why do we measure dermal exposure?

• Dermal exposure not routinely undertaken to control risk

• Main focus is research• Understanding exposure routes (for health impact

assessments)• Assessing the effectiveness of protective clothing• Epidemiological studies

• Regulatory approval• Under the REACH Regulations• In other regulatory systems

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The relationship between exposure routes

• Understanding the association between inhalation and dermal exposure is one of the key research issues to be investigated:• How best to control exposure• Whether it is important to have exposure limits

for skin exposure

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Vermeulen et al (2000)

• Identified the exposure pathways in rubber manufacturing

• They measured…• Air concentration – both near and far-field• Dermal exposure loading

• They showed that…• Hand (wrist) contamination was on average highest• Strong correlation between hand (wrist) and whole

body contamination

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.

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Different process – different pathways

Curing Pre-treatment

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Inhalation and dermal exposure…

• Searching Scopus database for entries since 2000• Search query: (inhalation) AND (dermal) AND

(exposure) AND (occupational OR worker)

• 271 papers• Screening on title gave 46 possibly informative

papers• Screening on abstract gave identified about half of

these as uninformative

• Final assessment based on 21 papers

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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

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Spraying paint…

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For spraying of low-volatility agents there seems to be a fairly strong association between inhalation and dermal exposurePhoto from Dhmiter Bello

Correlation between measures…

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.

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%33

Creosote impregnation…

• 34 employees classified into three exposure groups

• Spot urine samples analysed for 1-OHP• Air samples for PAH

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.

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JP-8 and fuel cell maintenance…

• Personnel in six US Air Force bases

• Dermal tape strip samples for naphthalene

• Air concentration of naphthalene and exhaled breath

• PBTK model

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.

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Protective clothing and gloves…

• Measurements made on top of and under clothing, usually with interception samplers

• Biomarker studies with and without the protective clothing

• Search query:   (dermal exposure) and ("protective clothing" or gloves) and (effectiveness) - only 13 papers since 2000

• Level of protection may be quite variable• Protection factor may change with the duration

of wearing

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Protection factor paradign

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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.

Modelling exposure…

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Tools for estimating exposure…

• ConsExpo (by RIVM) • Estimates dermal exposure to consumer products• http://www.rivm.nl/en/healthanddisease/productsafety/ConsExpo.js

p

• ECETOC TRA (Targeted Risk Assessment for REACH), variant of EASE• http://www.ecetoc.org/tra

• RISKOFDERM (TNO, task-based approach relying on similar dermal exposure operation units)

• DREAM (DeRmal Exposure Assessment Method)• Derived from Schneider’s conceptual model• Generates a relative index of exposure

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Tools for estimating uptake…

• NIOSH Skin Permation Calculator• http://www.cdc.gov/niosh/topics/skin/skinPermCalc.html

• IH SkinPerm• http://www.aiha.org/

insideaiha/volunteergroups/

Pages/EASC.aspx

• Models based on area of skin exposed not mass load

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Issues with current research…

• Little progress towards measuring biologically relevant exposure

• Little connection between measurement and modelling

• Poor understanding of the effectiveness of PPE• Insufficient collaboration within and between our

constituent research groups• We haven’t really convinced our colleagues of

the importance of dermal exposure measurements

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News…

• The WHO IPCS will publish an Environmental Health Criteria Monograph (EHC) on Dermal Exposure later this year

• This is a companion to the earlier volume on Dermal Absorption, published 2006

• Slides from this talk will be available at… www.slideshare.net/johncherrie

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