TLV ® and BEI ® Committees: The Decision Making Process Presented at AIHce May 13, 2003, Dallas, TX Bill Wells PhD, CI

1. 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. MembershipApril 2003 Government & Academia Private Industry & Others

6. Membership by Profession, 2003

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 (C1-C4) • 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 C5 - C15 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/m3 (respirable) • 10 mg/m3 (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. ProposedNew 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. ProposedNew 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. ProposedNew 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® CommitteeLarry 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. BEI® development • 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

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

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 • Nq- Nonquantitative • Biol. monitoring recommended, no BEI® • Ns- Non-Specific • Needs confirmation • Sq 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)