WORKING FOR A HEALTHY FUTURE

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

Estimating Dermal Exposure to Chemicals

John Cherrie

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Outline…

• Consider what we mean by dermal exposure

• How do chemicals enter the body?• Available measurement methods• Modelling exposure• DREAM

• Efforts to improve models• The GuLF study• DART

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Growing interest in dermal exposure…

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Publications in Scopus by year

Exposure…

• Ideally, we would like to know there is an exposure-response relationship

• For inhalation exposure• Concentration x Duration (mg/m3.hr)

• Uptake• Cumulative exposure x Breathing rate (mg)

• What should we use for dermal exposure?

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Dermal uptake…

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J = kp dC

- where kp is the permeability constant

Important factors:• Concentration of contaminant• Mass on skin• Area exposed• Duration of exposure

From Wikipedia.com

How can 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 (area) of a surrogate compound retained on the skin

• Tape stripping• The mass of contaminant in the upper layers of

the stratum corneum

• Biological monitoring

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Dermal exposure to metals…

CaCO3 Zn Pb Sb Ni

EASE

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

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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

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 • NIOSH POD• 5-layer Passive

Organic 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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Problems with the IOM sampler…

• A range of membranes tested but none completely suitable• All more permeable than skin

• Adsorbent more easily saturated than we would have wished

• Need to correct for air concentration

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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.

Vermeulen et al (2000)

• Identified the exposure pathways in rubber manufacturing

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

• Based on Schneider et al model • Estimates from descriptive task information• Assessments are reproducible between

assessors• Estimates exposure in

“Dream Units” - DU• Validation study showed

reasonable correlation with measurement data

van Wendel de Joode et al. (2005) Occup Environ; 62(9): 623-32.van Wendel de Joode et al. (2005) J Expo Anal Environ Epidemiol; 15(1): 111-120.

The GuLF Study…

• A large epidemiological study to investigate potential health risks for clean-up workers involved with the Deepwater Horizon oil spill

• Using an updated version of DREAM for dermal exposure assessment

• Need to assess exposure to • Residues, (e.g. VOCs, PAHs, BTEX)• Dispersants (e.g. 2-butoxyethanol,

propylene glycol)

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DREAM

Exposure Assessors estimate exposure from each of the three pathways of dermal exposure:

• Emission• Surface Contact• Deposition

€

DermalExposure =Frequency x Intensity x Intrinsic Emission

ClothingProtectionFactor

Substance characteristic

s

Skin area exposed

Number of exposure

events

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Personal protective equipment…

• Studies of exposure often show a high degree of protection.• Creely & Cherrie found >99% reduction in contaminant inside

gloves

• Available biomonitoring studies suggest gloves are less effective

• Scheepers and colleagues found…• With polyethylene gloves median reduction of 51% excretion

of 1-hydroxypyrene in urine

• Vinyl gloves and Tyvek sleeves showed a 97% reduction in skin contamination with pyrene and benzo(a)pyrene and a lowering in urinary excretion of 1-hydroxypyrene by 57%

Creely KS, Cherrie JW. Ann Occup Hyg 2001;45:137–43.

Scheepers et al. Scan J Work, Environ Health 2009;35:212–221.

Asphalt exposure…

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Adaption of DREAM for PPE…

• We argue that the biomonitoring data are more reliable indicators of protection

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DART…

• Dermal Advanced REACH Tool from the ART Consortium

• Combine mechanistic model (DREAM?)

and• Exposure data

using• A Bayesian process

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DART deterministic model

Dermal exposure database

Similarity module to select data

Bayesian process to combine data

and model output

Exposure estimates for risk assessment

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.

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Questions and thanks…

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My collaborators…

Melanie Gorman Ng1, Mark Stenzel2, Richard Kwok3, Berna van Wendel de Joode4,

Patricia Stewart5

1 IOM, Centre for Human Exposure Science

2 Exposure Assessment Applications, LLC

3 National Institute of Environmental Health Sciences

4 Universidad Nacional de Costa Rica

5 Stewart Exposure Assessments, LLC

The work was partly funded by…