WORKING FOR A HEALTHY FUTUREEstimating Dermal Exposure toChemicalsJohn CherrieINSTITUTE OF OCCUPATIONAL MEDICINE . Edinburgh . UK www.iom-world.org
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 1
Growing interest in dermal exposure… Publications in Scopus by year 2
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? 3
Dermal uptake…J = kpdC - where kp is the permeability constantImportant factors:• Concentration of contaminant• Mass on skin• Area exposed From Wikipedia.com• Duration of exposure 4
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 5
Dermal exposure to metals…EASE CaCO3 Zn Pb Sb Ni Source: http://www.herag.net / 6
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 7
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 8 Hygiene;50(1):85-94.
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 9
Schneider et al conceptual model Surface contamination layer Air compartment Source Clothing outer layer Clothing inner layer Skin contamination layer Schneider et al. (1999) Conceptual model for assessment of dermal exposure. Occup Environ Med vol. 56 (11) pp. 765-73. 10
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 11 Hyg.;44(7):533-541.
Different process – different pathways Curing Pre-treatment 12
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- 13 120.
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) 14
DREAMExposure Assessors estimate exposure from each ofthe three pathways of dermal exposure: • Emission • Surface Contact • Deposition Number of Skin area Substance exposure events exposed characteristics 15
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 OccupHyg 2001;45:137–43. 16 Scheeperset al.Scan J Work, Environ Health 2009;35:212–221.
Adaption of DREAM for PPE…• We argue that the biomonitoring data are more reliable indicators of protection 18
DART…• Dermal Advanced Dermal exposure database REACH Tool from DART deterministic the ART Consortium model Similarity module to• Combine mechanistic select data model (DREAM?) Bayesian process and to combine data and model output• Exposure data using• A Bayesian process Exposure estimates for risk assessment 19
News…• The WHO IPCS will publish an Environmental Health Criteria Monograph (EHC) on Dermal Exposurelater this year.• This is a companion to the earlier volume on Dermal Absorption, published 2006. 20
Questions and thanks…My collaborators…Melanie Gorman Ng1, Mark Stenzel2, Richard Kwok3,Berna van Wendel de Joode4,Patricia Stewart51 IOM, Centre for Human Exposure Science2 Exposure Assessment The work was partly funded by… Applications, LLC3 National Institute of Environmental Health Sciences4 Universidad Nacional de Costa Rica5 Stewart Exposure Assessments, LLC 21