1. TLV and BEI Committees: TLV ® and BEI ® Committees: The Decision Making Process Presented at AIHce May 13, 2003, Dallas, TX Bill Wells PhD, CIH, CSP, Moderator Dennis Casserly, PhD, CIH & Marilyn Hallock, CIH Monitors

2. Forum Overview Pat Breysse: Introduction Lisa Brosseau: TLV ® -CS Committee Larry Lowry: BEI ® Committee Tom Bernard: TLV ® -PA Committee Ken Martinez: Bioaerosols Committee

3. ACGIH, ® the TLVs ® and BEIs ® Patrick N. Breysse, PhD, CIH Johns Hopkins University Bloomberg School of Public Health Chair, ACGIH ®

4. What Is ACGIH ® ? Membership Society (founded in 1938) Not-for-profit, Non-governmental Association (501(c)(6) organization) Multi-Disciplinary Membership Traditionally Neutral on Public Positions

5. Membership April 2003 Government & Academia Private Industry & Others

6. Membership by Profession, 2003 Industrial Hygienist39% Administrator/Manager12% OH&S Professional6% Environmental Professional4% Safety Professional3% Other (Engineer, Scientist, Toxicologist, Professor, etc.) ~36%

7. Technical Committees Committees provide the creativity, initiative, and technical expertise that has made ACGIH ® what it is today and what it will be tomorrow..

8. Core Mission

9. ACGIH ® Statement of Position ® ACGIH ® is not a standards setting body. ®® TLVs ® and BEIs ® – Are an expression of scientific opinion. Are not consensus standards. ®®Are based solely on health factors; it may not be economically or technically feasible to meet established TLVs ® or BEIs ®.

10. ACGIH ® Statement of Position ®® TLVs ® and BEIs ® – Should NOT be adopted as standards without an analysis of other factors necessary to make appropriate risk management decisions. ® ®Can provide valuable input into the risk characterization process. The full written Documentation for the numerical TLV ® or BEI ® should be reviewed.

11. Conflict of Interest Basis for Conflicts of Interest: –Employment –Financial benefit –Personal –Professional Avoid perceived as well as real conflict of interest

12. Conflict of Interest Committee members serve as individuals –they do not represent organizations and/or interest groups Members are selected based on expertise, soundness of judgement, and ability to contribute

13. COI Process at ACGIH ®

14. Today’s Roundtable Chemical Substances - TLV Biological Exposure Indices (BEI) Physical Agents – TLV Bioaerosols Committee

15. ACGIH ® TLVs ® for Chemical Substances Committee Update Chair: Lisa M. Brosseau, ScD, CIH Associate Professor University of Minnesota School of Public Health

16. Overview TLV ® -CS Committee has 20 members and 3 member-candidates, who volunteer time towards developing scientific guidelines and publications –Primary goal is to serve the scientific needs of industrial hygienists –Committee expenses (travel) are supported by ACGIH ® –Time is donated by the members

17. Committee Structure Chair and Vice Chair Three Subcommittees, Chair and Co-Chair –Dusts & Inorganics (D&I) –Hydrogen, Oxygen & Carbon Compounds (HOC) –Miscellaneous Compounds (MISCO) Administrative Subcommittees –Communications and Outreach –Membership –Notations –Chemical Substance Selection Staff Support –Liaison, Clerical, Literature Searching

18. Chemical Substance Subcommittees Approximately 10 members on each Membership from academia, government, unions, industry Membership represents four key disciplines: –Industrial hygiene –Toxicology –Occupational Medicine –Occupational Epidemiology

19. Core TLV ® Principles Focus on airborne exposures in occupational settings Utilize the “threshold” concept Primary users are industrial hygienists Goal is towards protection of “nearly all” workers Technical, economic, and analytic feasibility are NOT considered

20. Committee Actions in 2003 Adopted TLVs ® for 22 substances Proposed 6 new TLVs ® – (listed on the Notice of Intended Changes (NIC)) Revised 7 adopted TLVs ® (listed on the NIC) Proposed withdrawing TLVs ® for methane, ethane, propane, butane and liquified petroleum gas. (Will also withdraw iso-butane.) –All to be replaced with a proposal for Aliphatic Hydrocarbon Gases, Alkane (C 1 -C 4 ) Revised 3 proposals for TLVs ® and retained on the NIC

21. Committee Actions in 2003 (Cont’d) Adopted a new Appendix E for Particulates (Insoluble or Poorly Soluble) Not Otherwise Specified (PNOS) Developed new Documentation for 2 substances (no change in values) Changed the name of one TLV ® and kept on the NIC with revised recommendations Retained 4 proposed TLVs ® on the NIC Withdrew 2 proposed TLVs ® from the NIC

22. Committee Actions in 2003 (Cont’d) Proposed withdrawal of Appendix B: Substances of Variable Composition Proposed revision of Appendix C: Threshold Limit Values for Mixtures Proposed a new Appendix F: Commercially Important Tree Species Identified as Inducing Sensitization

23. Substances and Issues Under Study in 2003 115 chemical substances currently under study Issues under study include: –Ceiling limits, excursions, and STELs –Notations for reproductive effects –Skin notation –Reciprocal Calculation Procedure, Group Guidance Values for refined C 5 - C 15 aliphatic and aromatic hydrocarbon solvents and constituent chemicals

24. Particulates (Insoluble or Poorly Soluble) Not Otherwise Specified The recommendations are guidelines (not TLVs ® ) for limiting exposure to insoluble particles: –3 mg/m 3 (respirable) –10 mg/m 3 (inhalable) Apply to particles that: –Do not have a TLV ® –Are insoluble or poorly soluble in water or lung fluid –Have low toxicity (not genotoxic, cytotoxic, etc.) –Only toxic effects are inflammation or “lung overload” mechanisms

25. Proposed New Appendix C: TLVs ® for Mixtures In the absence of other information, assume additivity of substances having similar effects –Same outcomes, same target organs or systems the TLV ® for the mixture has been exceeded.

26. Proposed New Appendix C: TLVs ® for Mixtures Recommends using the TLV ® Documentation, as well as the TLV ® Basis information in the book Where possible, only combine TLVs ® having a similar time basis –Table showing appropriate combinations of different types of TLVs ®

27. Proposed New Appendix C: TLVs ® for Mixtures Limitations and Special Cases –Do not use when suspect inhibition or synergism –Take care when considering mixtures of A1, A2, or A3 carcinogens –Not appropriate for complex mixtures with many different components (e.g., gasoline, diesel exhaust)

28. Committee Activities Notations –Complete re-write of Introduction to the TLV ® -CS section of the book –Improved definition and categorization of TLV ® Basis Communications –Symposia on substances under study Membership –Recruitment, especially of physicians and epidemiologists –Bill Wagner Award & member recognition Chemical Substance Selection –Refining the selection process

29. Committee Activities Sponsored symposium on TDI (Spring 2002) Attended ACGIH ® symposium on oil mists and metalworking fluids (Fall 2002) Plenary talk on TLVs ® at AIOH in Australia (Winter 2002) Co-sponsored a colloquium on Workplace Chemical Exposure Standards with IRSST in Montreal (Spring 2003)

30. Committee Plans Co-sponsor symposium on enzymes (Spring 2004) Roundtables on TLVs ® at other professional meetings (SOT, ACOEM) Joint meetings with ACGIH ® BEI ® and AIHA WEEL Committees

31. Questions?

32. Scheduled Break Take a minute to stretch!

33. Biological Exposure Indices (BEIs ® ) Process and Use Larry K. Lowry, Ph.D. Chair, ACGIH ® BEI ® Committee The University of Texas Health Center at Tyler

34. Where are we going today ? Current definitions of the BEI ®, 2002 The development of BEIs ® The key – Documentation Examples Biomonitoring without limits Current and future issues Resources

35. Biological monitoring. Why? Assess exposure and uptake by all routes –TLV ® not protective – skin –Includes workload –More closely related to systemic effects Assess effectiveness of PPE Legal or ethical drivers –Regulations –Control workers’ compensation costs

36. “Guidelines” for biological monitoring – The BEIs ®

37. The BEIs ® – 2003 BEIs ® are intended for use in the practice of industrial hygiene as guidelines or recommendations to assist in the control of potential workplace health hazards and for no other use.

38. The BEI ® – Definition Biological monitoring … entails measurement of the concentration of a chemical determinant in the biological media of the exposed and is an indicator of the uptake of the substance. The BEI ® determinant can be the chemical itself; one or more metabolites; or a characteristic reversible biochemical change induced by the chemical.

39. BEIs ® Represent levels of determinants that are most likely to be observed in specimens collected from a healthy worker who has been exposed to chemicals to the same extent as a worker with inhalation exposure to the TLV ® -TWA. Generally indicate a concentration below which nearly all workers should not experience adverse health effects.

40. Current basis for BEIs ® Bio-equivalent to TLV ® (traditional) –“BEIs ® represent levels of determinants that are most likely to be observed in specimens collected from a healthy worker who has been exposed to chemicals to the same extent as a worker with inhalation exposure to the TLV ® -TWA.” Most of the BEIs ® are based on TLVs ®

41. Current basis Indicators of early, reversible health effect –Approach developed in late 80’s as relationships did not always exist between airborne exposure and biomonitoring determinant. Examples: –CO, Acetyl cholinesterase inhibiting pesticides, Cd, Pb, Hg, Hexane-MnBK

42. The BEI ® Committee Larry Lowry, Ph.D., U TX Health Center at Tyler – Chair Phil Edelman, MD, CDC – Vice Chair Mike Morgan, Sc.D, CIH, U. of WA – Past Chair Joe Saady, Ph.D., VA Division of Forensic Science Leena Nylander-French, Ph.D, CIH, UNC, Chapel Hill John Cocker, Ph.D., HSE, UK K. H. Schaller, Dipl. Ing., Univ Erlangen, Germany M. Ikeda, Ph.D., Kyoto Ind Health Assoc, Japan Gary Spies, CIH, Pharmacia Glenn Talaska, Ph.D., CIH, Univ of Cincinnati Jan Yager, Ph.D., EPRI

43. Volunteer assigned document Prepares draft Documentation Sources of data –Human laboratory & workplace data Limited use of animal data –Simulation modeling with verification –Published peer-reviewed data Draft Documentation discussed in committee meetings, e-mail BEI ® development

44. Development Process Select Chemical Review Data Assign Author Select Determinant Discuss Justification Develop Feasibility Prepare Draft BEI ® ? Review Draft Return to Author Revise Final Document Yes No Yes

45. How are chemicals selected? Chemicals with human data Potential for dermal absorption Availability of adequate lab methods Recommendations by others Interest/experience of committee member

46. The Documentation Who is the audience? –The practicing occupational hygienist or other practicing occupational health professional What the Documentation is –Justification supporting the BEI ® –Practical information on sampling, background, etc. What the Documentation is not –An extensive review of toxicological data –A novel research approach to setting guidelines

47. The Documentation – contents Basis of the BEI ® Uses and properties Absorption Elimination Metabolic pathways & biochemical interactions Possible non-occupational exposure Summary of toxicology

48. For each index or BEI ® Analytical methods, sampling, and storage Levels without occupational exposure Kinetics Factors affecting interpretation –Analytical procedures and sampling –Exposure –Population Justification – the key Current quality of database Recommendations and references

49. The notations B - Background levels expected N q - Nonquantitative –Biol. monitoring recommended, no BEI ® N s - Non-Specific –Needs confirmation S q Semiquantitative (but specific) –Screening test –Confirmatory tests

50. Practical applications Bioavailability of metals – Chromium –Chromium VI (water soluble) fume Specificity and Sensitivity – Benzene biomonitoring –t,t-Muconic acid in urine (t,t-MA) –S-Phenylmercapturic acid in urine (SPMA)

51. Bioavailability of metals – Chromium Physical properties and solubility –Cr (III), very insoluble particulates –Cr (VI) insoluble particulate – the lung carcinogen –Cr (VI) water soluble Fume as generated in MMA arc welding Mist as generated in electroplating Health effects of Cr (VI) water soluble –Fume – lung irritant –Mist – chrome ulcers on skin, mucus membranes

52. Biological monitoring of Cr exposure Cr (III) inappropriate – not bioavailable Cr (VI) insoluble – not bioavailable Cr (VI) water soluble –If fume, use BEI ® based on welding studies –If mist, bioavailability less See chrome ulcers at “acceptable” BEI ® values

53. Biomonitoring of benzene

54. Biomonitoring at the current TLV ® t,t-Muconic acid in urine (t,t-MA) –Good sensitivity (to 0.1 ppm benzene) –HPLC methodology –Considerable variability in populations S-Phenylmercapturic acid in urine (SPMA) –Ultimate sensitivity (to 0.01 ppm benzene) –GC/MS methodology –Good data base, but expensive

55. Biological monitoring without limits What about substances absorbed through the skin and with chronic systemic health effects that occur after a long lag time such as cancer?

56. The traditional approach Cannot relate to airborne limits, TLVs ® –Irrelevant Cannot relate to skin absorption –Difficult to quantitate dermal dose Cannot relate to health effect –Often wrong timeline What to do?

57. The BEI ® approach Rationale –Biological monitoring is essential to assess dermal exposure –How do you correlate dermal dose with a biomarker of exposure? N q Approach –“Biological monitoring should be considered for this compound based on the review; however, a specific BEI ® could not be determined due to insufficient data.”

58. Criteria for an N q Dermal route of exposure significant Good measurement methods Good qualitative data on human exposure and biomarker concentration Poor quantitative data relating exposure & biomarker Long lag time, exposure to health outcome Low or no background in general population

59. If criteria are met, then Develop full Documentation Describe sampling and analysis Define background levels Describe justification for biomonitoring Note the lack of quantitative data Cite guidance values from literature Publish BEI ® as N q (no value)

60. Examples – MBOCA Principal route of exposure – dermal Alleged health effect in humans – cancer Good methods and human data on exposure-response Industry practice guidance from the HSE

61. Health and Safety Executive, UK Scientific basis to justify guidance values Use "yardstick or benchmark" approach Issues –Results – no "safe" or "unsafe" exposure levels –Results – estimates of exposure areas and allow intervention to reduce exposures –No legal status Examples – MBOCA and MDA

62. The “yardstick or benchmark” approach Good analytical methods All specimens analyzed by one laboratory or with a single method Establish "best industry practice" using an upper 90% confidence limit of the "best" industries Benchmarks – guidance value to provide users with assessment of their results

63. Current issues Carcinogens? –Is there a safe level of exposure? –The German EKA approach Mixtures and interactions –Metabolism/toxicokinetics on pure chemical –Workers exposed to mixtures –How does this effect BEI ® ? Biomarkers of effect – irreversible effects? Data gaps – lack of human data Animal data – should this be used?

64. Skin absorption Justification for BEI ® –Existing BEIs ® for substances with substantial skin absorption MBOCA – N q EGME/EGMEA – N q EGEE/EGEEA – 100 mg/g creatinine –(based on TLV ® of 5 ppm) –Is this a valid approach? Are N q notations appropriate? Should a chemical without a “skin” notation have a BEI ® ?

65. The future As TLVs ® drop, BEIs ® based on TLVs ® drop –Cannot distinguish exposure at TLV ® from background What do we do for substances that have no human data? What is the future of modeling techniques? –Can these modeling techniques be validated? Should animal data be used? What about mixtures?

66. Other guidelines

67. Germany The BATs from the DFG

68. The HSE – UK Biological monitoring guidelines

69. Guidance from WHO – How to do biological monitoring

70. Other Guidelines New edition, 2001

71. Your questions please Thank you for your attention

72. Scheduled Break Take a minute to stretch!

73. ACGIH ® TLVs ® for Physical Agents Committee Update Vice-Chair: Thomas Bernard University of South Florida College of Public Health

74. TLV ® Physical Agents Committee Process for Hazardous Agent Selection and Decision Making

75. Mission To foster, solicit, collect and evaluate data on potential health hazards of exposures to physical agents. When appropriate, recommend ACGIH ® Threshold Limit Values ® for physical agents.

76. 2002 PAC Harry Mahar Maurice Bitran Thomas Bernard Gerald Coles Anthony Cullen Daniel Johnson John Leonowich William Murray Bhawani Pathak Robert Patterson Thomas Tenforde Carla Treadwell Consultants: Thomas Adams Thomas Armstrong Gregory Lotz Martin Mainster Gary Myers

77. Overview Physical Agents Process –Committee Activities –TLV ® Development Future –Format –Agents

78. Disclaimer The opinions expressed here are those of the author and not of his employer, the Physical Agents Committee or the ACGIH ® Worldwide.

79. Physical Agents It’s the Movement of Energy

80. Risk of Health Effects What is the nature of the energy? How much energy? What is the interaction with tissue?

81. Nature of Energy Electric and Magnetic Fields Photons Kinetic Energy –Pressure –Vibration –Mechanical Heat

82. Amount of Energy Total Amount of Energy Absorbed –What does it take to raise water temperature? Rate of Absorption (Power or Intensity) –How fast does the temperature rise? Normalized to Surface Area (e.g., mJ/cm 2, mW/cm 2 )

83. Interactions Electric and Magnetic Fields –Induce Currents –Align Molecules –Vibrate Molecular Bonds Photons –Vibrate Molecular Bonds –Disrupt Molecular Bonds

84. More Interactions Mechanical Disruption of Tissue –Pressure –Vibration –Force Applications Loss of Tissue Function –Thermal: Gain or Loss of Heat

85. Bernard Watt-O-Meter Power Limits for Various Exposures [mW/cm 2 ] Electric and Magnetic Fields170,000 Radiofrequency/Microwave1.0 Infrared Light10 Blue Light0.0001 Ultraviolet Light0.0012 Ionizing Radiation0.00000003 Noise0.00003 Heat Stress30 {Not Accepted, or Considered Acceptable, by Any Authority}

86. Exposure Energy Distribution in the Immediate Environment The distribution is usually described as Power or Intensity (directly or through a surrogate) versus Frequency or Wavelength in Bands

87. Exposure Threshold Total Energy –Ability to Absorb Energy Rate of Energy (Power or Intensity) –Ability to Dissipate Absorbed Energy In a Band Integrated Over All Bands

88. Process Committee Activities Development of TLVs ®

89. Representation Usually one or two members with an expertise for a particular agent (e.g., a small portion of the electromagnetic spectrum) Small committee to maintain a working and collegial group. We meet as a whole. Leverage with outside experts

90. Updating TLVs ® PAC meets with outside experts Members bring recommendations to the PAC for discussion Consideration of actions taken by national and international committees or agencies

91. New TLVs ® Quintessential Example: Hand Activity Formed a cadre of consultants Convened a conference Developed recommendation and Documentation Presented to PAC and discussed PAC voted after internal deliberations

92. Future Format Agents

93. Format TLV ® Book –Use of Flow Charts –Evolving (see Heat Stress and RF/MW) Training Documentation –Expanded and Focused (see HAL and Lifting) –Health Effects and Exposure Indices –Guidance (see Heat Stress)

94. Form Physical agents have their own history and character with respect to measurement and exposure assessment There is an underlying similarity among the physical agents that may be introduced

95. Example Set Radiofrequency / Microwave Radiation Optical Radiation (IR, Visible and UV) Vibration (Hand-Arm and Whole Body) Noise

96. Energy Distribution 0.01 0.1 1 10 100 1000 0.0010.010.11101001000 Energy Bands

97. Energy Limits Within Bands 1 10 100 1000 10000 100000 1000000 0.0010.010.11101001000 Energy Limit Bands E min

98. Limits by Band Is the limit exceeded within one or more bands? 0.01 0.1 1 10 100 1000 10000 100000 1000000 0.0010.010.11101001000 Energy Bands PDExp Lmt

99. Sensitivity Curve Sensitivity = Energy Limit / E min 0.1 1 10 100 1000 0.0010.010.11101001000 Sensitivity Bands

100. Hazard Function 0.001 0.01 0.1 1 0.0010.010.11101001000 Filter Multiplier Bands Hazard Function = 1.0 / Sensitivity

101. Effective Exposure 0.00001 0.0001 0.001 0.01 0.1 1 10 100 1000 0.0010.010.11101001000 Energy Bands EDE-eff Effective Exposure = Energy Distribution x Hazard Function

102. Total Energy Multiplying –Energy Limits by Band –Hazard Function by Band and Integrating (Summing) Yields a Constant Value: A Total Energy Limit

103. Limit by Total Energy Total Energy –In One Band –Under the Effective Energy Curve Compared to Total Energy Limit

104. In Summary TLVs ® –Limit Power (Ability to Dissipate) –Limit Total Energy (Ability to Absorb) Limit by –Band –Total

105. Agents Under Review Lasers Vibration Cold Stress HAL Lifting WMSDs Wide-Band RF Altitude Impulse Noise ELF H-Fields

106. Scheduled Break Take a minute to stretch!

107. Biologically Derived Airborne Contaminants: Bioaerosols and TLVs ® Kenneth F. Martinez, MSEE, CIH Chair, ACGIH ® Bioaerosols Committee NIOSH

109. Where ?

110. Microorganisms Obligate parasites (must have a living host) –viruses –bacteria –rickettsia Facultative saprophytes (will utilize dead organic material) –fungi –bacteria

111. Size Ranges of Microorganisms

112. Mechanisms for Microbial Dispersal Linear Distances

113. Microbiological Concerns Infections Immunologic Reactions Toxic Effects

114. Infectious Disease Pathogenicity Virulence Relationship between virulence (V), numbers of pathogens or dosage (D), and resistant state of the host (RS) Colonization Invasiveness Infectious Disease = V * D RS

115. Infectious Disease Terminology Portal of entry Exposure vs. infection Clinical vs. subclinical or asymptomatic infection Carrier state Opportunistic infection Human pathogen vs. virulence Immunosuppression

116. Infectious Disease Pathways Respiratory Oral (via ingestion) Contact Penetration Vectors (via insect bite)

117. Allergic Disease Allergic rhinitis Allergic asthma Allergic bronchopulmonary aspergillosis Extrinsic allergic alveolitis (hypersensitivity pneumonitis)

118. U.S. Disease Prevalence 1 of 5 Americans suffer from allergic disease Indoor allergens responsible for significant share Environmental control reduces disease severity Source: NHLBI, 1991

119. Allergen Exposure Dust Mites Molds Animal Dander Pollen Allergenic Chemicals Other Exposures Viruses Air Pollution Tobacco Smoke Genetic Predisposition or Susceptibility Immunologic Sensitization Allergic Disease MildModerateSevere (Death) Source: Pope AM, et al., eds., 1993

120. Important Mycotoxins

121. Where Are We?

122. Classification of Occupant Complaints Sick Building Syndrome Building-Related Disease Occupant Discomfort

123. Sick Building Syndrome Non-specific Symptoms Headache Eye, nose, throat irritation Sneezing Fatigue and lethargy Skin irritation Dizziness and nausea Cough Chest tightness

124. Building-Related Disease Known etiologies Related to identifiable exposure Legionnaires Disease Pontiac Fever Humidifier Fever Hypersensitivity Pneumonitis Anthrax

126. Why Not Scientifically Supportable? Not a single entity Human responses cover wide range No single sampling method exists No exposure/response relationships exist Total Culturable or Countable Bioaerosols

127. Why Not Scientifically Supportable? Data are derived from indicators rather than actual effector agents Concentrations vary widely Low statistical power in cause-effect relationship studies Specific Culturable or Countable Bioaerosols - other than infectious

128. Why Not Scientifically Supportable? Dose-response data limited to a few agents Air sampling limited to research Administrative and engineering controls remain the primary defenses Infectious Culturable or Countable Bioaerosols

129. Why Not Scientifically Supportable? Some dose-response relationship data available –Experimental studies –Epidemiologic surveys Assay methods improving May be appropriate in the future Assayable biological contaminants

130. Questions? Pat Breysse Lisa Brosseau Larry Lowry Tom Bernard Ken Martinez