Skin as a Route of Exposure to Beryllium

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1 Skin as a Route of Exposure to Beryllium Gregory A. Day, Ph.D. National Institute for Occupational Safety and Health Division of Respiratory Disease Studies Morgantown, WV, USA International Beryllium Research Conference Montréal, Québec, Canada March 8-11, 2005

2 Controlling exposure Efforts to prevent sensitization and chronic beryllium disease (CBD) have historically focused on controlling inhalation exposures Lack of a clear relationship between airborne exposure and sensitization suggests other exposure pathways, such as the dermal route, may be relevant

3 Beryllium Source Air breathing zone Surfaces clothing hands clothing neck and face hands hands shoes

4 Skin exposure stratum corneum epidermis dermis Tinkle et al Skin as a Route of Exposure and Sensitization in Chronic Beryllium Disease. Env Health Perspect 111(9):

5 4 µm beads do not penetrate intact skin

6 Particles go through torn skin

7 Sally Tinkle s work Laboratory experiments in mice tested the hypothesis that skin exposure to insoluble beryllium oxide particles provides a route by which beryllium sensitization may occur Sensitization evidenced by increased ear thickness after challenge with soluble beryllium salt Sensitization also detected from pooled lymphocytes in a mouse LPT

8 Beryllium oxide particle Micrometer-scale aggregate Primary particles 0.2 µm (200 nm) Not easily broken apart Composition Homogeneous, single component Day et al Bioavailability of Beryllium Oxide Particles: An In Vitro Study in the Murine J774A.1 Macrophage Cell Line Model. Exp Lung Res (In Press).

9 Copper-beryllium particles Micrometer-scale agglomerates Nanometer-scale primary particles More easily broken apart Composition Heterogeneous, multicomponent material Stefaniak et al Differences in Dissolution Behavior in a Phagolysosomal Simulant Fluid for Single-component and Multicomponent Materials Associated with Beryllium Sensitization and Chronic Beryllium Disease. Toxicol Sci (In Review).

10 Case study: Copper-beryllium alloy strip and wire finishing facility Objectives to evaluate beryllium migration pathways by observing beryllium: 1. In workplace air, 2. On work surfaces, and 3. On the skin of production and office area employees.

11 Why this facility? Semi-finished copper-beryllium alloy strip and wire (~2% beryllium by mass) converted into finished strip, wire, and rod Historically low beryllium air concentrations Prevalences of sensitization and CBD comparable to those found in other facilities associated with higher average beryllium exposures* *Schuler et al Process-Related Risk of Beryllium Sensitization and Disease in a Copper-Beryllium Alloy Facility. Am J Ind Med (In Press).

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17 Approach General area air samples (n=10) collected continuously for 6 days Surface wipe samples (n=252) collected from 12 work surfaces in each of 21 separate areas Cotton gloves (n=113 pair) worn over nitrile gloves by each of 27 employees (21 production or production support, 6 office area) for first 2 hours in each of 6 work shifts

18 Approach (continued) Skin wipe samples collected from necks (n=109) and faces (n=109) of the same employees at the end of 6 work shifts Evaluated relationships between beryllium concentration on work surfaces and beryllium on workers gloves and skin

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23 Results: Air Beryllium mass concentrations in general area air samples were extremely low minimum = µg/m 3 maximum = 0.02 µg/m 3 arithmetic mean = µg/m 3 geometric mean = µg/m 3

24 Results: Surfaces (µg/100 cm 2 ) Number Min Max Med AM SD GM GSD Production Production Support Office

25 Results: Gloves (µg) Number Min Max Med AM SD GM GSD Production Production Support Office 6 <LOD

26 Results: Necks (µg) Number Min Max Med AM SD GM GSD Production 87 <LOD Production Support Office 6 <LOD <LOD <LOD <LOD 1.3

27 Results: Faces (µg) Number Min Max Med AM SD GM GSD Production 87 <LOD Production Support Office 6 <LOD <LOD <LOD <LOD 1.5

28 Log beryllium on cotton gloves (µg) 9 7 r = Log beryllium on surfaces (µg/100 cm 2 ) clothing Air breathing zone neck and face Beryllium Source hands hands Surfaces hands clothing shoes Log beryllium on necks (µg) 0-1 r = Log beryllium on cotton gloves (µg) Log beryllium on faces (µg) r = Log beryllium on cotton gloves (µg)

29 Beryllium transfer pathways Necks 10 1 Faces Surfaces Average Be 0.1 Gloves 0.01 Rod & wire production Production support Strip production Administration

30 Conclusions 1. Particulate exposures occur by the dermal route 2. Physicochemical properties must be considered 3. Bioavailability influenced by those properties 4. Case study: positive relationships between concentration of beryllium on surfaces and level of beryllium on exposed skin supports the importance of dermal exposure in terms of health outcome

31 Acknowledgements NIOSH Mark Hoover Kathleen Kreiss William Miller Christine Schuler Marcia Stanton Aleksandr Stefaniak NIEHS Sally Tinkle Brush Wellman Inc. David Deubner Michael Kent McGill University André Dufresne Los Alamos National Laboratory Robert Dickerson Ronald Scripsick