WORKING FOR A HEALTHY FUTURE

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

Dermal exposure assessment: Progress and Pitfalls

John Cherrie

2

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• Pitfalls (lack of progress)• Where next?

Growing interest in dermal exposure…

3

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

4

5

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 /

6Hughson 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.

7

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

8Kissel 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.

9

• NIOSH POD• 5-layer Passive

Organic Dermal sampler

The IOM wet-work sampler…

• Sensor based on two thermocouples

• Difference in temperature indicates wetness

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

10Cherrie JW, Apsley A, Semple SE. (2007) A new sampler to assess dermal exposure during wet working. Ann Occup Hyg.;51(1):13-18.

Why do we measure?

• 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

11

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.

12

Different process – different pathways

Curing Pre-treatment

13

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

14

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

15

Correlation between measures…

• For spraying of low-volatility agents there seems to be a fairly strong association between inhalation and dermal exposure

• Isocyanate data from Fent et al

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%17

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.

18

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.

19

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

20

Protection factor paradign

21

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.

Interest in exposure measurement…

22

23Dermal + exposure + measurement + (work or occupational) 23

Pitfalls…

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

the importance of dermal exposure measurements

24

The way forward…

• Define a clear research agenda for dermal exposure measurement

• Look for ways to increase collaboration between groups and disciplines

• Figure out the importance of dermal exposure to risk

25

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

26