TLV and BEI Committees:

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
Todays 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 (DI)
• 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 (Contd)

• 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 (Contd)

• 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 80s 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
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
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)

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?
• Nq 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 Nq

• 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 Nq (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 Nq
• EGME/EGMEA Nq
• EGEE/EGEEA 100 mg/g creatinine
• (based on TLV of 5 ppm)
• Is this a valid approach?
• Are Nq 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
GermanyThe BATs from the DFG
68
The HSE UK Biological monitoring guidelines
69
Guidance from WHO How to do biological
monitoring
70
Other GuidelinesNew 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
TLVPhysical 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

• Its 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/cm2, mW/cm2)

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
Not Accepted, or Considered Acceptable, by Any
Authority

• Power Limits for Various Exposures mW/cm2
• Electric and Magnetic Fields 170,000
• Radiofrequency/Microwave 1.0
• Infrared Light 10
• Blue Light 0.0001
• Ultraviolet Light 0.0012
• Ionizing Radiation 0.00000003
• Noise 0.00003
• Heat Stress 30

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
97
Energy Limits Within Bands
Emin
98
Limits by Band
Is the limit exceeded within one or more bands?
99
Sensitivity Curve
Sensitivity Energy Limit / Emin
100
Hazard Function
Hazard Function 1.0 / Sensitivity
101
Effective Exposure
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

• Altitude
• Impulse Noise
• ELF H-Fields

• HAL
• Lifting
• WMSDs
• Wide-Band RF

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

108
(No Transcript)
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 DispersalLinear
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

V D
Infectious Disease
RS
115
Infectious DiseaseTerminology

• Portal of entry
• Exposure vs. infection
• Clinical vs. subclinical or asymptomatic
  infection
• Carrier state
• Opportunistic infection
• Human pathogen vs. virulence
• Immunosuppression

116
Infectious DiseasePathways

• 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
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 SyndromeNon-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

125
No numeric criteria for interpreting environmental
measurements!
126
Why Not Scientifically Supportable?
Total Culturable or Countable Bioaerosols

• Not a single entity
• Human responses cover wide range
• No single sampling method exists
• No exposure/response relationships exist

127
Why Not Scientifically Supportable?
Specific Culturable or Countable Bioaerosols -
other than infectious

• Data are derived from indicators rather than
  actual effector agents
• Concentrations vary widely
• Low statistical power in cause-effect
  relationship studies

128
Why Not Scientifically Supportable?
Infectious Culturable or Countable Bioaerosols

• Dose-response data limited to a few agents
• Air sampling limited to research
• Administrative and engineering controls remain
  the primary defenses

129
Why Not Scientifically Supportable?
Assayable biological contaminants

• Some dose-response relationship data available
• Experimental studies
• Epidemiologic surveys
• Assay methods improving
• May be appropriate in the future

130
Questions?

• Pat Breysse
• Lisa Brosseau
• Larry Lowry
• Tom Bernard
• Ken Martinez