NIOSH 

RESEARCH AND DEMONSTRATION GRANTS 

FISCAL YEAR 1993 

NICl5M 

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES 

Public Health Service 

Centers for Disease Control and Prevention 

National Institute for Occupational Safety and Health 

Atlanta, Georgia 30333 

August 1994 
DISCLAIMER 

Mention of company names or products does not constitute endorsement by the National Institute for 

Occupational Safety and Health. 

DliHS(NIOSH} Publication No. 94-131 

ii 
FOREWORD 

The National Institute for Occupational Safety and Health (NIOSH) is mandated by the provisions of the 

Occupational Safety and Health Act of 1970 and the Federal Mine Safety and Health Amendments Act 

of 1977 to conduct research and demonstrations relating to occupational safety and health. Our overall 

goal is the prevention of illnesses, injuries, and deaths. Recognizing the valuable contributions of 

extramural scientists to this endeavor, NIOSH sponsors outstanding research through a grants program, 

which complements the lnstitute's intramural research program. The creativity and special resources 

available in the scientific community make the grants program a key component in achieving the Nation's 

goal to have safe jobs and healthy workers. We anticipate an expanded extramural research program in 

the coming years. 

To maximize the grants program's usefulness in protecting workers, NIOSH funds projects that are 

scientifically sound and related to program priorities. We are interested in funding grants that will 

ultimately be of practical value in solving workplace problems. 

This report provides a readily available source of information on the status and scope of the research 

grants program of NIOSH (all active grants during fiscal year 1993: October 1, 1992, to 

September 30, 1993). It is also intended to stimulate the submission of more proposals for high quality 

research on significant occupational safety and health concerns. We invite investigators in the biomedical 

sciences, engineering, and related disciplines to become partners in preventing United States workers 

from suffering adverse effects caused by occupational hazards. • 

111 

(%~ 

Linda Rosenstock, M.D. 

Director, National Institute for 

Occupational Safety and Health 

Centers for Disease Control and Prevention 
• 
TABLE OF CONTENTS 

FOREWORD ................................................................. iii 

INTRODUCTION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 

ACCESS TO LITERATURE ..................................................... 2 

GLOSSARY .................................................................. 3 

PROGRAM ANNOUNCEMENT ................................................... 4 

RESEARCH AND DEMONSTRATION GRANT SUMMARIES BY PROGRAM AREA ....... 11 

Occupational Lung Diseases 

Research Project Grants (ROI) 

(02277) Influence of Particles on Occupational Lung Disease ....................... 11 

(02421) Lung Disease in Chinese Textile Workers ............................... 12 

(02593) Airway Hyperresponsiveness Due to Cotton Dust .......................... 14 

(02761) Coal Dust Particle Size and Respiratory Disease .......................... 17 

(02772) Detecting Lung Overload by Magnetometry .............................. 18 

(02914) On-Site Enumeration of Fungal Spores and Bacteria in Air ................... 19 

(02987) Metal Fume Fever ................................................ 21 

(03044) Pulmonary Effects of Machining Fluid Aerosols .......................... 22 

(03168) Occupational Disease Among Carpenters ................................ 22 

Career Development Grants (KO]) 

(00079) Effects of Zinc Oxide Welding Fume Inhalation ........................... 24 

(00093) Asbestos-Induced Pleural Fibrosis and Lung Restriction ..................... 26 

(00134) Grain Dust Exposure: Physiologic & Biologic Correlates .................... 31 

Small Grants (R03) 

(02931) Radon, Bronchial Morphometry, and Occupational Health .................... 31 

(03061) Protein Damage Caused By Occupational Toxicants ........................ 33 

(03064) Role of Worksite-Associated Vanadium in Immunomodulation ................ 34 

Musculoskeletal Injuries 

Research Project Grants (ROI) 

(02434) Development of Models to Predict Optimal Lifting Motion ................... 36 

(02918) Cumulative Trauma Disorder: Skeletal Muscle Dysfunction .................. 37 

(02941) Ergonomic Risk Factors and Cumulative Trauma Disorders .................. 39 

Career Development Grants (KOJ) 

(00090) Unexpected Trunk Loading Following Seated Vibration ..................... 40 

(00098) Quantitative Assessment of Carpal Tunnel Syndrome ....................... 41 

(00107) Characterization of Posture, Force, and Repetitive Motion .................... 42 

(00121) Intracarpal Pressure During Hand Maneuvers ............................. 44 

(00132) Age & Cumulative Trauma Disorders in Garment Workers ................... 45 

(00135) Stochastic Model of Trunk Musculature During Lifting ..................... 46 

Small Grants (R03) 

(02765) Occupational Epidemiology of Carpal Tunnel Syndrome ..................... 47 

(03087) Effect of Load Asymmetry on Internal Loading of The Trunk ................. 49 

(03091) Occupational Physical Loads and Hip Osteoarthritis ....................... 49 

V 
Small Business Grants (R43, R44) 

(02907) Prevention of Cumulative Trauma Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . ... 50 

Occupational Cancers 

Research Project Grants (ROI) 

(02067) Occupational Cancer Surveillance: New Approaches ....................... 52 

(02647) Biological Monitoring/Risk Assessment In An Exposed Cohort ................ 54 

(02730) Case Control Study of Cancer in Synthetic Rubber Workers .................. 55 

(02820) Improved Magnetic Field Exposure Assessment ........................... 56 

(02953) Environmental Exposures and Risk Digestive Cancers ...................... 57 

Career Development Grants (KOJ) 

(00076) New Method for Occupational Cancer Surveillance ........................ 58 

(00081) Leukocyte DNA Adducts after Carcinogen Exposure ....................... 61 

(00110) Susceptibility to Genetic Damage from Butadiene ......................... 62 

(00125) General Mortality & Cancer Incidence in Florida Pesticide Applicators .......... 64 

Small Grants (R03) 

(02880) Molecular Dosimetry for Carcinogens .................................. 65 

(02972) Cocarcinogenic Particulates in Coculture System .......................... 66 

Traumatic Injuries 

Research Project Grants (ROI) 

(01122) Explosion Hazards Related to Combustible Dusts .......................... 68 

(02741) Case-Control Study of Sawmill Injuries in Maine .......................... 70 

(02743) Development of a Construction Injury Predictive Model ..................... 71 

(02794) Role of Postural Stability in Industrial Falls .............................. 72 

(02872) Workplace Assault-Related Injuries: Incidence and Risk .................... 73 

(02967) Vibration Oculomanual Coordination and Traumatic Injuries .................. 74 

(03079) Ergonomics of Task Performance On Slippery Surfaces ..................... 76 

Career Development Grants (KO]) 

(00115) Safety First: Fault Tree Expert System For Construction .................... 77 

Small Grants (R03) 

(03154) Analysis of Construction Tasks For Overexertion Injuries .................... 79 

Small Business Grants (R43, R44) 

(03099) Development of a Work Safety Scale .................................. 80 

Cardiovascular Diseases 

Career Development Grants (KOJ) 

(00108) Vascular Effects of Chelation In Lead Exposed Workers ..................... 82 

Disorders of Reproduction 

Research Project Grants (ROI) 

(00835) Occupational Risks of Pesticide Exposure for Females ...................... 84 

(02885) Menstrual Function and Physical and Mental Job Stress ..................... 85 

Small Grants (R03) 

(02966) Semen as a Biomarker of Effect Among Lead Exposed Men .................. 87 

(03000) Reproductive Health of Female Migrant Farm Workers ..................... 88 

Neurotoxic Disorders 

Research Project Grants (ROI) 

(00823) Occupational Neuropathies Due to Industrial Chemicals ..................... 90 

(02683) Neurologic Effects of Solvents and Age in Older Adults ..................... 93 

(02719) Central Nervous System Effects of PCE Exposure in Humans ................. 94 

(02767) Validity of Computerized Tests in Occupational Settings .................... 96 

(03078) A Computerized Tool to Screen Workers for Neurotoxicity ................... 97 

vi 
Career Development Grants (KOJ) 

(00123) Organophosphate Neuropathy and Biomarkers of Exposure ................... 98 

(00133) Neurological Effects of Organophosphates on Farmworkers .................. 99 

Noise-Induced Hearing Loss 

Research Project Grants (ROI) 

(01152) The Effects of Impulse Noise on the Auditory System ..................... I 00 

(02128) Functional Correlates of Cochlear Injury ............................... I 02 

(02317) Hearing Hazard Associated with Industrial Noise Exposure .................. I 05 

(03136) Preventing NIHL In Construction Workers ............................. 107 

Psychological Disorders 

Research Project Grants (ROI) 

(02571) Stress in One Occupational Group: Teachers ........................... 108 

Control Techniques 

Research Project Grants (ROI) 

(02611) Relative Health Risks of Diesel Emission Control Systems .................. 110 

(02710) Computer Simulation of Push-Pull Systems ............................. 112 

(02740) Application of Neural Networks for Process Fault Diagnosis ................. 112 

(02804) Emission Factor Development for Intermittent Workplace Sources ............. 114 

(02858) Computational Methods in Industrial Ventilation ......................... 115 

(02951) Permeation Mechanisms of Pesticides Through Materials ................... 115 

(03015) Encapsulating Protective Clothing: Work Tolerance ...................... 116 

(03021) Communication with Flat-Attenuation Hearing Protectors ................... 117 

(03033) Predictive Models of Solvent Permeation Through CPC .................... 118 

(03052) Transport Modeling of Industrial Ventilation ............................ 119 

(03157) Load Monitoring For Safe Construction ............................... 120 

Career Development Grants (KOJ) 

(00078) Field Study of Local Exhaust Ventilation Performance ..................... 121 

Small Business Grants (R43, R44) 

(03010) Smart, Safe Scaffolding ........................................... 122 

(03018) Active Seat Suspension to Control Low Back Injuries ..................... 123 

Respirator Research 

Research Project Grants (ROI) 

(02922) Evaluation of Respirators for Asbestos Fibers ........................... 124 

(02948) Performance of Surgical Masks ..................................... 125 

Career Development Grants (KOJ) 

(00085) Factors Affecting Respirator Leak Sites and Shapes ....................... 126 

(00087) Adsorption of Vapor Mixtures onto Activated Carbon ..................... 127 

Small Grants (R03) 

(02938) Aerosol Penetration Behavior of Respirator Valves ........................ 128 

Small Business Grants (R43, R44) 

(03011) Lighter Compact Respirators For Toxic Vapor Protection ................... 129 

Other Occupational Needs 

Research Project Grants (ROI) 

(02148) Effects of 27 MHz Radiation on Somatic and Germ Cells . . . . . . . . . . . . . . . . . . . 131 

(02149) Plasma Proteins: Markers of Chemical Exposure ......................... 133 

(02221) Dose/Response for Styrene Exposures ................................. 136 

(02391) Hydrocarbon Exposure and Chronic Renal Disease ........................ 138 

(02622) Biological Monitoring for Exposure to Coal Tar ......................... 139 

(02663) Selective Real-Time Detection of Olefin Gases and Vapors .................. 141 

(02664) A Dichotomous Sampler for TRIG Aerosol and Vapor ..................... 143 

vii 
(02666) Theory and Evaluation of a Workplace OP-FTIR Monitor ................... 144 

(02758) Minimizing Work Schedule Disruption with Bright Light ................... 146 

(02792) Measurement of Alkenyl/Epoxy DNA Adducts by GC-MS .................. 147 

(02945) Dosimetry for Workplace EMFs at Power-Line Frequencies ................. 148 

(03024) Biological Monitoring of Methanol Exposure ............................ 150 

(03056) Knowledge-Based Framework For Automating Hazop Analysis ............... 151 

(03073) Statistical Issues For Compliance to Exposure Standards .................... 153 

(03134) Physiologic Sampler For Airborne Health Hazards ........................ 154 

(03177) Evaluation of Controls Protecting Lead-Exposed Workers ................... 155 

Career Development Grants (KOJ) 

(00077) Microsensor Array for the Identification of Organic Vapors . . . . . . . . . . . . . . . . . 157 

(00103) Optical Remote Sensing and Computed Tomography in Industrial Hygiene ....... 158 

(00106) Measurement Errors in Occupational Epidemiology ....................... 159 

(00129) Generation of Fibrous Aerosols in Narrow Size Ranges .................... 161 

(00131) Health Care Worker Compliance with Hepatitis B Vaccine .................. 162 

(00137) Elevated Blood Leads in the Iowa Construction Industry .................... 164 

(00138) An Exposure Matrix For Construction Painters .......................... 165 

Small Grants (R03) 

(02932) TCD as a Screening Procedure for Exposures to Toxicants . . . . . . . . . . . . . . . . . . 166 

(02971) Dose-Response Assessment Issues in Occupational Studies .................. 167 

(03039) A Volatile Aerosol Sampler and Particle Size Analyzer .................... 167 

(03088) Training and Medical Surveillance Under the ETO Standard ................. 169 

Small Business Grants (R43, R44) 

(03009) Air Dispersion of Chemicals in Industrial Facilities ....................... 170 

(03102) Micromachined System For Selective Measurement of VOCs ................ 171 

(03103) Persona!' Monitor For Toxic Vapors .................................. 171 

FY93 GRANT AWARDS BY ACTIVITY .......................................... 173 

FY93 GRANT AWARDS BY PROGRAM AREA .................................... 174 

FY93 GRANT AWARDS BY STATE ............................................. 175 

GRANT NUMBER INDEX ...................................................... 176 

PRINCIPAL INVESTIGATOR INDEX ............................................. 179 

GRANTEE INSTITUTION INDEX ................................................ 182 

viii 
Page 1 

INTRODUCTION 

The organization of this annual report on the NIOSH research grants program is designed to facilitate the reader's 

understanding ofthe types of extramural research projects supported under the primary areas ofNIOSH's interest 

with respect to the leading work-related diseases and injuries. 

Summaries of the supported projects are grouped according to these major areas of interest, as indicated 

in the Table of Contents. 

Within each program area, projects are grouped by type of grant (e.g., research project grant, career 

development grant, and small grant). 

Note: See the program announcement beginning on page 4 for descriptions ol these 

grant types and other types that NIOSH awards. 

Each grant summary contains administrative information about the grant, followed by a synopsis of the project 

and any publications that have resulted to date. 

Principal investigators prepare the summaries for inclusion in this report. The synopsis is an explanation 

of the nature of the project and a discussion of results, with sections on Importance to Occupational 

Safety and Health, Objectives, Methodology, and Significant Findings. 

Publications are listed so that the reader may gain more information about the projects than is given in 

the brief summaries. Although some citations are not yet published or may not be retrieved easily, they 

have been included for the sake of providing maximum information. 

Note: Should there be an interest in more information, principal investigators should 

be contacted directly. 

Statistics on the number and amount of funds awarded by grant type, program area, and region/state are given 

in tabular form at the end of the report. Indices are included for ease in locating particular grants if the reader 

knows the grant number, the principal investigator, or the grantee institution. 

Note: See glossary on page 3 for an explanation of the components of a grant 

number. 

Suggestions on content or format of this report to make it more useful to the reader would be welcomed. The 

process of assembling the report begins in the fall of each year, so comments should be received at least by the 

end of September. 

Inquiries or ideas should be addressed to: NIOSH Grants Office 

1600 Clifton Road 

Building 1, Room 3053, MS - D30 

Atlanta, Georgia 30333 

404/639-3343 
Page 2 

ACCESS TO LITERATURE 

In addition to the publications listed after each grant summary, readers may wish to refer to NIOSH's 

Document Information Directory System (DIDS). 

What is DIDS? 

DIDS is a computerized data base of documents that are produced from NIOSH-sponsored research 

(intramural and extramural). This data file is maintained by the NIOSH Division of Standards 

Development and Technology Transfer to track the following types of NIOSH documents: Alerts, 

Current Intelligence Bulletins, criteria documents, control technology reports, hazard evaluation and 

technical assistance reports, industrywide study reports, contract reports, health and safety guides, Fatal 

Accident Circumstances and Epidemiology (FACE) reports, research grant publications and reports, 

training documents, testimony, and books, book chapters, and journal articles authored by NIOSH 

employees. 

What Specific Data does DIDS include? 

Each entry includes the document title, publication number, subject index terms, availability information, 

NIOSHTIC accession number, name of principal investigator for research grants, and complete citations 

for books, book chapters, and journal articles. Nearly 11,000 entries are currently maintained in the 

system. 

Who may use DIDS and What is the Cost? 

DIDS is used primarily by NIOSH personnel, but searches are often requested by persons from industries, 

unions, academic institutions, and the general public. Searches are free of charge. 

How can a Search be Requested? 

Contact NIOSH at the following address and telephone number: 

Technical Information Branch 

Division of Standards Development and Technology Transfer 

National Institute for Occupational Safety and Health 

4676 Columbia Parkway 

Cincinnati, Ohio 45226-1998 

Telephone: 513/533-8350 
GLOSSARY 

Grant Number - The identification number assigned to a grant application 

EXAMPLE: I ROI OH02183-0IAI 

1 ROI OH 02183 -01 Al 

[ 

I r Signifies a first resubmission 

I_ Year of funding 

quence number for NIOSH grants 

_ Institute with primary assignment 

_ Grant Activity 

_ Grant Type 

Typical Codes: 

Grant Type 

Page 3 

with modifications 

The first component of an application number which identifies the type of application that 

has been submitted. 

I New Competing application 

2 Competing renewal application 

5 Noncompeting continuation application 

7 Change of grantee institution 

Grant Activity 

Institute 

This three-digit code indicates the activity to which application is being made. 

RO l - Research Project Grant 

KOi - Special Emphasis Research Career Award (SERCA) Grant 

R03 - Small Grant 

R 13 - Conference Grant 

Rl8 -

R43 -

Demonstration Grant 

Small Business Innovation Research (SBIR) Grant 

This two letter code identifies the primary funding institution. 

OH - NIOSH 

Sequence Number 

Five-digit serial numbers are assigned in sequence. 

Year of Funding 

This 2-digit number identifies the budget period of a project. An 01 indicates the first year 

of the grant award and the series of years continues through succeeding renewals. 
Page 4 

A. Introduction 

Department of Health and Human Services 

Centers for Disease Control and Prevention (CDC) 

National Institute for Occupational Safety and Health 

Research and Demonstration Grants 

Occupational Safety and Health 

PA-94-021 

The Centers for Disease Control and Prevention (CDC), National Institute for Occupational Safety and Health 

(NIOSH), is soliciting grant applications for research and demonstration projects relating to occupational safety 

and health, including the construction industry (see "FUNDS AVAILABLE"). 

B. Authority 

This program is authorized under the Public Health Service Act, as amended, Section 301 (42 U.S.C. 241); the 

Occupational Safety and Health Act of 1970, Section 20 (a) (29 U.S.C. 669[a]); and the Federal Mine Safety and 

Health Amendments Act of 1977, as amended, Section 501 (30 U.S.C. 951). The applicable program regulations 

are in 42 CFR Part 52. 

C. Eligible Applicants 

Eligible applicants include domestic and foreign non-profit and for-profit organizations, universities, colleges, 

research institutions, and other public and private organizations, including State and local governments and small, 

minority and/or woman-owned businesses. 

D. Availability of Funds 

For fiscal year (FY) 1994, the budget for research grants is $9,250,000. Of that amount, about $5,500,000 is for 

non-competing continuation awards, and $3,750,000 is for new and competing renewal awards. Of the money 

for non-competing continuation awards, $1,200,000 is committed to provide ongoing support for construction 

grants that were started last year under a new initiative that was announced in a FY 1993 request for applications 

(OH-93-001 ). Of the money for new and competing renewal awards, $1,250,000 is for new construction grants, 

which is an expansion of the FY 1993 initiative. Note that construction grant applications must be received 

by the March 1, 1994, deadline in order to be considered for funding with this new money. 

The projected breakdown for the $3,750,000 in new and competing renewal awards by type of grant mechanism 

is as follows: ROI and Rl8 grants - 19 awards for $3,000,000 (total costs of these currently awarded grants range 

from $50,000 to $350,000 with the average of about $170,000); KO 1 grants - 4 awards for $200,000 (total costs 

are limited to $54,000 per award); and R03 grants - 14 awards for $550,000 (total costs are about $37,500 per 

award). 

E. Background 

The NIOSH is mandated to develop recommendations for protecting workers of the United States against diseases 

and injuries related to risks on the job. In 1983, NIOSH published a suggested list of ten leading work-related 

diseases and injuries as part of a national goal to improve the health of the American people through prevention 

activities. These are listed as the first ten entries in Section "H. Funding Priorities." To provide guidance on 

priorities for action, NIOSH sponsored the development of "Proposed National Strategies for the Prevention of 

Leading Work-Related Diseases and Injuries." Working groups composed ofNIOSH scientists drafted proposed 

national strategies for these ten areas of concern. These strategies were refined in a process involving two 

national meetings of health and safety professionals representing academia, management, organized labor, 

professional associations, and voluntary organizations. Implementation of the Prevention Strategies requires 
Page 5 

commitment from a broad array of organizations and scientific and professional disciplines. The extramural 

research program is an important means of facilitating progress in these preventive efforts. 

The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention 

objectives of "Healthy People 2000," a PHS-led national activity to reduce morbidity and mortality and improve 

the quality of life. This program announcement is related to the priority area "Occupational Safety and Health." 

Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0) or 

"Healthy People 2000" (Summary Report, Stock No. 017-001-00473-1) through the Superintendent ofDocuments, 

Government Printing Office, Washington, DC 20402-9325 (telephone 202-783-3238). 

F. Purpose 

The purpose of this grant program is to develop knowledge that can be used in preventing occupational diseases 

and injuries. NIOSH will support the following types of applied research projects: causal research to identify 

and investigate the relationships between hazardous working conditions and associated occupational diseases and 

injuries; methods research to develop more sensitive means of evaluating hazards at work sites, as well as 

methods for measuring early markers of adverse health effects and injuries; control research to develop new 

protective equipment, engineering control technology, and work practices to reduce the risks of occupational 

hazards; and demonstrations to evaluate the technical feasibility or application of a new or improved occupational 

safety and health procedure, method, technique, or system. 

G. Mechanisms of Support 

The types of grants NIOSH supports are described below. Applications responding to this announcement will 

be reviewed by staff for their responsiveness to the following program requirements. Grants are funded for 12-

month budget periods in project periods up to 5 years for research project grants and demonstration project grants; 

3 years for SERCA grants; and up to 2 years for small grants. Continuation awards within the project period are 

made on the basis of satisfactory progress and on the availability of funds. 

I. Research Project Grants (RO 1) 

A research project grant application should be designed to establish, discover, develop, elucidate, or confirm 

information relating to occupational safety and health, including innovative methods, techniques, and 

approaches for dealing with occupational safety and health problems. These studies may generate 

information that is readily available to solve problems or contribute to a better understanding of the causes 

of work-related diseases and injuries. 

2. Demonstration Project Grants (RI8) 

A demonstration project grant application should address, either on a pilot or full-scale basis, the technical 

or economic feasibility of implementing a new/improved innovative procedure, method, technique, or system 

for preventing occupational safety or health problems. The project should be conducted in an actual 

workplace where a baseline measure of the occupational problem will be defined, the new/improved 

approach will be implemented, a follow-up measure of the problem will be documented, and an evaluation 

of the benefits will be conducted. 

3. Special Emphasis Research Career Award (SERCA) Grants (KOi) 

The SERCA grant is intended to provide opportunities for individuals to acquire experience and skills 

essential to the study of work-related hazards, and in so doing create a pool of highly qualified investigators 

who can make future contributions to research in the area of occupational safety and health. SERCA grants 

are not intended either for individuals without research experience or for productive, independent 

investigators with a significant number of publications and of senior academic rank. Moreover, the award 
Page 6 

is not intended to substitute one source of salary support for another for an individual who is already 

conducting full-time research; nor is it intended to be a mechanism for providing institutional support. 

Candidates must: (1) hold a doctoral degree; (2) have research experience at or above the doctoral level; 

(3) not be above the rank of associate professor; (4) be employed at a domestic institution; and (5) be 

citizens or persons lawfully admitted to the U.S. for permanent residence (resident alien) at the time of 

application. 

This non-renewable award provides support for a three-year period for individuals engaged in full-time 

research and related activities. A wards will not exceed $50,000 per year in direct costs for salary support 

(plus fringe benefits), technical assistance, equipment, supplies, consultant costs, domestic travel, 

publications, and other costs. The indirect cost rate applied is limited to 8 percent of the direct costs, 

excluding tuition and related fees and equipment expenses, or to the actual indirect cost rate, whichever 

results in the lesser amount. 

A minimum of 60 percent time must be committed to the proposed research project, although full-time is 

desirable. Other work in the area of occupational safety and health will enhance the candidate's 

qualifications but is not a substitute for this requirement. Related activities may include research career 

development activities as well as involvement in patient care to the extent that it will strengthen research 

skills. Fundamental/basic research will not be supported unless the project will make an original 

contribution for applied technical knowledge in the identification, evaluation, and/or control of occupational 

safety and health hazards ( e.g., development of a diagnostic technique for early detection of an occupational 

disease). Research project proposals must be of the applicants' own design and of such scope that 

independent investigative capability will be evident within three years. At the completion of this three-year 

award, it is intended that awardees should be better able to compete for individual research project grants 

awarded by NIOSH. 

SER CA grant applications should be identified as such on the application form. Section 2 of the application 

(the Research Plan) should include a statement regarding the applicant's career plans and how the proposed 

research will contribute to a career in occupational safety and health research. This section should also 

include a Jetter of recommendation from the proposed advisor(s). 

4. Small Grants (R03) 

The small grant program is intended to stimulate proposals from individuals who are considering a research 

career in occupational safety and health; as such, the minimum time commitment is I 0%. It is expected that 

a recipient would subsequently compete for a career development grant (KOi - see section G.3.) or for a 

traditional research project grant (RO 1 - see section G .1.) related to occupational safety and health. The 

award is not intended to supplement ongoing or other proposed research; nor is it intended to be a 

mechanism for providing institutional support. 

The small grant investigators must be U.S. citizens or persons lawfully admitted to the U.S. for permanent 

residence (resident alien) at the time of application who are predoctoral students, post-doctoral researchers 

(within 3 years following completion of doctoral degree or completion of residency or public health 

training), or junior faculty members (no higher than assistant professor). If university policy requires that 

a more senior person be listed as principal investigator, it should be clear in the application which person 

is the small grant investigator. Except for applicants who are assistant professors, there must be one or more 

named mentors to assist with the project. A biographical sketch is required for the small grant investigator, 

as well as for the supervisor and other key consultants, as appropriate. 

This non-renewable award provides support for project periods of up to two years to carry out exploratory 

or pilot studies, to develop or test new techniques or methods, or to analyze data previously collected. 

Awards will not exceed $25,000 per year in direct costs for salary support (plus fringe benefits), technical 

assistance, equipment, supplies, consultant costs, domestic travel, publications, and other costs. The indirect 
Page 7 

costs will be based upon the negotiated indirect cost rate of the applicant organization. An individual may 

not receive more than two small grant awards, and then, only if the awards are at different stages of 

development (e.g., doctoral student, post-doctoral researcher, or junior faculty member). 

H. Funding Priorities 

The NIOSH program priorities, listed below, are applicable to all of the above types of grants listed under "G. 

Mechanisms of Support." These priority areas represent the leading diseases and injuries related to risks on the 

job, and NIOSH intends to ·support projects that facilitate progress in preventing such adverse effects among 

workers. The conditions or examples listed under each category are selected examples, not comprehensive 

definitions of the category. Investigators may also apply in other areas related to occupational safety and health, 

but the rationale for the significance of the research to the field of occupational safety and health must be 

developed. 

Potential applicants with questions concerning the acceptability of their proposed work are strongly encouraged 

to contact the "Technical Information Contact, Dr. Roy M. Fleming, listed in this announcement under "P. Where 

to Obtain Additional Information." 

The NIOSH Program Priorities are: 

Occupational lung diseases: related to agriculture, the mining industry, or exposure to fibers; occupational 

asthma; longitudinal pulmonary function assessment; eradication of silicosis. 

Musculoskeletal injuries: disorders of the back, trunk, upper extremities, neck, lower extremities; vibration 

white finger disease. 

Occupational cancers (other than lung): leukemia, mesothelioma, cancers of the bladder, nose, liver, and skin. 

Severe occupational traumatic injuries and fatalities: amputations, fractures, falls, eye loss, lacerations, and 

intentional and non-intentional fatal injuries. 

Cardiovascular disease: hypertension, coronary artery disease, acute myocardial infarction. 

Disorders of reproduction: congenital malformations, spontaneous abortion, and infertility. 

Neurotoxic disorders: peripheral neuropathy, toxic encephalitis, neuroses, extreme personality changes 

( exposure-related). 

Noise-induced hearing loss. 

Dermatologic conditions: dermatoses, bums (scalding), chemical bums, contusions (abrasions). 

Psychological disorders: affective disturbances such as anxiety, depression and job dissatisfaction; maladaptive behavior and lifestyle patterns; aggression; stress and post traumatic stress disorders; substance 

abuse. 

Control techniques: new technology performance evaluation, preconstruction review, equipment redesign, 

containment of hazards at the source, fundamental dust generation mechanisms, machine guarding/avoidance 

methods, explosion control, removal of emissions after generation, dispersion models, monitoring and 

warning techniques, technology transfer, safe work practices, personal protective equipment. 

Respirator Research: new and innovative respiratory protective devices including air-purifying respirators 

to protect against biological and/or infectious agents, developing active and passive end-of-service-life 

indicators, workplace protection and quantitative fit factors for powered air-purifying respirators, effectiveness 

of respiratory programs, physiologic and ergonomic factors, medical surveillance strategies, psychological 

and motivational aspects of respirator use, effectiveness of sorbents and filters (including chemical and 

physical properties), 

I. Inclusion of Minorities and Women in Study Populations 

Applicants are required to give added attention (where feasible and appropriate) to the inclusion of minorities 

and/or women study populations for research into the etiology of diseases, research in behavioral and social 

sciences, clinical studies of treatment and treatment outcomes, research on the dynamics of health care and its 

impact on disease, and appropriate interventions for disease prevention and health promotion. Exceptions would 

be studies of diseases which exclusively affect males or whenc: involvement of pregnant women may expose the 
Page 8 

fetus to undue risks. If minorities and/or women are not included in a given study, a clear rationale for their 

exclusion must be provided. 

J. Applications Submission Deadlines and Review Dates 

Applications are to be submitted on Form PHS-398 (revised 9/91). Forms should be available from the contacts 

listed under "P. Where to Obtain Additional Information," or from: 

Office of Grants Inquiries 

Division of Resel!,Tch Grants, NIH 

Westwood Building - Room 449 

5333 Westbard Avenue 

Bethesda, MD 20892 

The original and five copies of the PHS-398 or the original and two copies of the PHS 5161-1 application must 

be submitted to the iiddress below on or before the specified receipt dates also provided below. A mailing label 

is provided in the Form PHS-398 application package. 

Division of Research Grants 

National Institutes of Health 

Westwood Building - Room 240 

5333 Westbard Avenue 

Bethesda, MD 20892 

The timetable for receiving applications and awarding grants is given below. This is a continuous announcement, 

consequently, these receipt dates will be on-going until further notice. 

Research and Demonstration Project Grants: 

Receipt Initial Secondary 

Date* Review Review 

February 1 June/July September 

June 1 Oct/Nov January 

October I Feb/Mar May 

*Competing continuation deadlines are 1 month later. 

SERCA and Small Grants 

Receipt Initial Secondary 

Date Review Review 

March I June/July August 

July 1 Oct/Nov December 

November Feb/Mar April 

Earliest Possible 

Start Date 

December 

April 1 

August I 

Earliest Possible 

Start Date 

November 1 

March 1 

July 1 

Applications must be received by the above receipt dates. To guard against problems caused by carrier delays, 

retain a legible proof-of-mailing receipt from the carrier, dated no later than one week prior to the receipt date. 

If the receipt date falls on a weekend, it will be extended to Monday; if the date falls on a holiday, it will be 

extended to the following work day. The receipt date will be waived only in extenuating circumstances. To 

request such a waiver, include an explanatory letter with the signed, completed application. No request for a 

waiver will be considered prior to receipt of the application. 
Page 9 

K. Evaluation Criteria 

Applications received under this announcement will be assigned to an Initial Review Group (IRG). The IRGs, 

consisting primarily of non-Federal scientific and technical experts, will review the applications for scientific and 

technical merit. Notification of the review recommendations will be sent to the applicants after the initial review. 

Applications will also be reviewed for programmatic importance by NIOSH. Awards will be made based on 

results of the initial and secondary reviews, as well as availability of funds. 

I. The initial (peer) review is based on scientific merit and significance of the project, competence of the 

proposed staff in relation to the type of research involved, feasibility of the project, likelihood of its 

producing meaningful results, appropriateness of the proposed project period, adequacy of the applicant's 

resources available for the project, and appropriateness of the budget request. 

Demonstration grant applications will be reviewed additionally on the basis of the following criteria: 

• Degree to which project objectives are clearly established, obtainable, and for which progress toward 

attainment can and will be measured. 

Availability, adequacy, and competence of personnel, facilities, and other resources needed to carry 

out the project. 

Degree to which the project can be expected to yield or demonstrate results that will be useful and 

desirable on a national or regional basis. 

Documentation of cooperation from industry, unions, or other participants in the project, where 

applicable. 

SERCA grant applications will be reviewed additionally on the basis of the following criteria: 

The review process will consider the applicant's scientific achievements, the applicant's research 

career plan in occupational safety and health, and the degree to which the applicant's institution offers 

a superior research environment (supportive nature, including letter(s) of reference from advisor(s) 

which should accompany the application). 

Small grant applications will be reviewed additionally on the basis of the following criteria: 

The review process will take into consideration the fact that the applicants do not have extensive 

experience with the grant process. 

2. In the secondary review, the following factors will be considered: 

The results of the initial review. 

The significance of the proposed study to the mission of NIOSH. 

I) Relevance to occupational safety and health, by contributing to achievement of the research 

objectives specified in Section 20(a) of the Occupational Safety and Health Act of 1970 and 

Section 50 I of the Federal Mine Safety and Health Amendments Act of 1977, 

2) Magnitude of the problem in terms of numbers of workers affected, 

3) Severity of the disease or injury in the worker population, 

4) Potential contribution to applied technical knowledge in the identification, evaluation, and/or 

control of occupational safety and health hazards, and 

5) Program balance, and 

6) Policy and budgetary considerations. 

Questions regarding the above criteria should be addressed to the Technical Information Contact listed under "P. 

Where to Obtain Additional Information." 
Page 10 

L. Technical Reporting Requirements 

Progress reports are required annually as part of the continuation application (75 days prior to the start of the 

next budget period). The annual progress reports must contain information on accomplishments during the 

previous budget period and plans for each remaining year of the project. Financial status reports (FSR) are 

required no later than 90 days after the end of the budget period. The final performance and financial status 

reports are required 90 days after the end of the project period. The final performance report should include, at 

a minimum, a statement of original objectives, a summary of research methodology, a summary of positive and 

negative findings, and a list of publications resulting from the project. Research papers, project reports, or theses 

are acceptable items to include in the final report. The final report should stand alone rather than citing the 

original application. Three copies of reprints of publications prepared under the grant should accompany the 

report. 

M. Executive Order 12372 Review 

Applications are not subject to review as governed by Executive Order 12372, Intergovernmental Review of 

Federal Programs. 

N. Catalog of Federal Domestic Assistance Number 

The Catalog of Federal Domestic Assistance number is 93.262. 

0. Public Health System Reporting Requirements: 

This program is not subject to the Public Health System Reporting Requirements. 

P. Where to Obtain Additional Information 

When requesting information, please refer to "PA-94-021" program announcement. 

For Technical Information Contact: For Business Information Contact: 

Roy M. Fleming, Sc.D. Ms. Lisa Tamaroff 

Associate Director for Grants Grants Management Specialist 

National Institute for Occupational Grants Management Branch, PGO 

Safety and Health Centers for Disease Control and Prevention 

Centers for Disease Control 255 E. Paces Ferry Road, N.E. 

and Prevention Room 321, Mail Stop E-13 

1600 Clifton Road, N.E. Atlanta, Georgia 30305 

Building 1, Room 3053, Mail Stop D-30 Telephone: (404) 842-6796 

Atlanta, Georgia 30333 

Telephone: (404) 639-3343 
Influence of Particles on 

Occupational Lung Disease 

David Warshawsky, Ph.D. 

University of Cincinnati 

Department of Environmental Health 

3223 Eden Avenue 

Cincinnati, Ohio 45267-0056 

Program Area: Occupational Lung Diseases 

Grant Number: 5 ROI OH02277-03 

Start & End Dates: 09/30/89 - 03/31/94 

Funding Level: $0 ($479,651 Cum) 

Importance to Occupational Safety and Health 

Epidemiological and experimental studies 

indicate that particles and/or chemical carcinogens are 

important in the development of respiratory disease. 

Occupational exposure to silica often includes 

exposure to polycyclic aromatic hydrocarbons (PAH); 

silica has an enhancing effect on benzo(a)pyrene 

induced lung carcinogenesis. This study is designed 

to investigate the ability of pulmonary alveolar 

macrophage (AM) to metabolize BaP-coated silica. 

In the evaluation of occupational hazards that may 

lead to increased susceptibility to lung cancer, the 

cocarcinogenic potential of other factors in an 

exposure is an important consideration. This research 

will provide information on particulate modified BaP 

metabolism and will contribute to our understanding 

of the involvement of pulmonary alveolar macrophage 

in the mechanism of lung disease. 

Objectives 

The long-term objective of this research is to 

investigate the role that AM play in the 

particulate-dependent response of the lung to BaP via 

mechanisms involving BaP metabolism. Although the 

mechanism of cocarcinogenic action is unknown, 

several investigators have implicated BaP metabolism. 

An important biological response to inhaled particles 

is ingestion by AM and clearance from the lung. 

Since these cells have the capacity to metabolize BaP, 

it is possible that altered BaP metabolism leading to 

enhanced carcinogenic potential occurs in the AM 

following phagocytosis of silica particles and 

adsorbed BaP. 

Methodology 

Alveolar macrophages (AM) were isolated by 

tracheal lavage from male Syrian hamsters 

Occupational Lung Diseases - Page 11 

( 100-150 g, 8-9 wks old) and resuspended in 

RPMI-1640 medium containing 0.1% gentamicin, 

25 mM L-glutamine, 0.2% sodium bicarbonate and 

2 mg/ml bovine serum albumin (pH= 7.2) (BSA). 

Viability and the numbers of cells were determined 

by trypan blue staining procedure. The purity of AM 

was determined using cellular differential staining 

(Diff-Quik stain set Sci. Product Inc.). About lxl06 

cells in 2.5 ml RPMI-1640 were plated dish. The 

unattached cells were removed and the AM were 

incubated with various chemical treatments. Viability 

analyses were carried out at 24 and 48 hr time points. 

The remainder of the medium was extracted with 

ethyl acetate. The ethyl acetate extract was analyzed 

by HPLC to quantify metabolites and parent 

compound. Additional studies were conducted to 

compare the extent of binding to DNA to the release 

of metabolites from the cell. 

Significant Findings 

Determination of the Physical Characteristics of 

Particles. All of the particles were of respirable size 

with a particle size distribution of greater than 98% 

less than 5 microns. The count median diameters for 

aluminum oxide and amorphous silicas were less than 

0.36 microns while for crystalline silica the count 

median diameter was 0.83 microns and for ferric 

oxide it was 1.8 microns. The surface areas of the 

particles were consistent with the median diameters 

and the size distributions in that the values for the 

aluminum oxide and the amorphous silicas were large 

varying from 124.8 to 253.1 m2

/g. For crystalline 

silica and ferric oxide that had larger count median 

diameters, the surface areas were 4.3 and 10.8 m2

/g, 

respectively. Neither precipitated nor gelled silica 

contained any crystalline silica while fumed contained 

1.6% crystalline silica. The results indicated that 

crystalline silica had a smaller surface area and a 

larger count median diameter than any of the 

amorphous silicas. 

Determination of AM to Phagocytize Particles 

and the Cytotoxicity of Particles to AM. 

Comparative viability studies of the AM in the 

presence of ferric oxide, aluminum oxide, or silica 

(crystalline, and gelled, fumed, and precipitated) were 

undertaken to determine noncytotoxic doses during 

phagocytosis. Doses of particles ranged from 0.0 to 

0.5 mg. The viability of the hamster AM in the 

presence of aluminum oxide and ferric oxide up to 

the highest dose was similar to controls. After 24 and 

48 hours, the viability of the AM for aluminum oxide 

and ferric oxide was approximately 80 and 70%, 

respectively. In the presence of silica, the viability of 

the hamster AM was similar to controls up to 

0.0 I mg and at least 80 and 66% at 24 and 48 hours 

respectively with the exception of precipitated silica 

at 48 hours where the viability was 57%. At doses 
Page 12 - Occupational Lung Diseases 

of 0.05 mg and 0.1 mg of crystalline, precipitated or 

fumed silica, at 24 hours the viability dropped to 70 

and 45%, respectively, and at 0.5 mg the viability 

dropped to zero. With gelled silica the viability of 

the AM decreased to 27% at 0.05 mg and zero at 

0.1 mg at 24 hours. These data are consistent with 

the physical characteristics in that the particle with 

the largest surface area is the most cytotoxic i.e. 

gelled silica followed by the other forms of silica. 

The data indicate that the count median diameter of 

less than .38 microns is sufficient for AM silica 

cytotoxicity. It would appear that the dose, surface 

properties and particle size are all important in the 

cytotoxicity of AM to silica. 

Determination of Metabolic profiles from 

BaP-coated Particles. The data indicate that the 

major pathway is through the dihydrodiol formation. 

The 7 ,8-diol metabolite which is the precursor of the 

ultimate metabolite 7,8-diol-9,10-epoxide is higher 

in all of the particle associated BaP relative to BaP 

alone. This would suggest that BaP-coated particle 

is metabolized more readily through the active 

pathway than by BaP itself which would suggest a 

change in the metabolic pattern due to particle. Of 

the particles studied the values for the 7 ,8-diol were 

higher for the amorphous silicas than that of Fei03 or 

crystalline silica. 

The level of DNA-binding from BaP-coated 

particles. The BaP-coated particles were incubated 

with AM and after 24 hours the AM were isolated. 

The DNA was isolated using a phenol extraction 

method and analyzed by 32P-postlabeling techniques. 

The data indicate that both qualitatively and 

quantitatively that the BaP-adduct patterns have been 

altered by the presence of particles. In all cases, ppt, 

crystalline or Fe20 3 adduct #2 is the predominant 

adduct as opposed to the presence of all three adducts 

for BaP alone. These data are consistent with the 

metabolism data previously reported in that particles 

appear to alter both the metabolic pattern in the 

media and adduct pattern in AM. What is evident is 

that particle with the larger surface areas appears to 

have an increased alteration of the formation of BaP 

produced active metabolite intermediates. 

In summary, BaP-coated particles in comparison 

with BaP alone have an impact on the metabolism, 

DNA binding and the extent of adduction. 

Additionally, dose as well as surface area and surface 

characteristics of particles are important determinants 

in the metabolism, DNA binding and cytotoxicity 

parameters of particles and BaP-coated particles. 

Publications 

Warshawsky D, Reilman R, Cheu J, Ratlike M, 

Rice C: Influence of Dose, Particle Size and Surface 

Area of Crystalline and Amorphous Silica on the 

Cytotoxicity to Hamster and Rat Pulmonary Alveolar 

Macrophage. J Toxicol Environ Health 38 :399-417, 

1993 

Griefe A, Warshawsky D: Influence of Dose, 

Particle Size and Surface Area of Crystalline and 

Amorphus Silica on the Cytotoxicity to Hamster and 

Rat Pulmonary Alveolar Macrophage. J Toxicol 

Environ Health, accepted, 1993 

Lung Disease in Chinese Textile 

Workers 

David C. Christiani, MD. 

Harvard University 

School of Public Health 

Environmental Health 

665 Huntington Avenue 

Boston, Massachusetts 02115 

Program Area: Occupational Lung Diseases 

Grant Number: 5 ROI OH02421-04 

Start & End Dates: 07/01/91 - 06/30/95 

Funding Level: $139,344 ($423,931 Cum) 

Importance to Occupational Safety and Health 

This study is a longitudinal follow-up of cotton 

textile workers in Shanghai, China. The relevance of 

the knowledge gained from this work includes: the 

relative contributions of cotton dust and gram 

negative bacterial endotoxins in producing acute and 

chronic respiratory disease; the rate of annual decline 

in lung function after exposure to cotton dust; and the 

importance of acute, cross-shift change in FEV1 in 

predicting longitudinal loss of lung function. 

Determination of exposure-response for gram 

negative bacterial endotoxins is important not only for 

textile workers, but also for thousands of workers 

exposed to other organic dusts and environments rich 

in endotoxin. 

Objectives 

Briefly stated, the project objectives have been: 

1. To determine the 11-year incidence and 

rem1ss1on of byssinosis and non-specific 

respiratory symptoms among cotton textile 

workers, using silk workers for comparison, and 

to relate these findings to exposure to cotton dust 

and endotoxin. 

2. To determine the rate of annual decline in 

pulmonary function in cotton workers and silk 
referents and relate these outcomes to various 

estimates of current and historical work 

exposures. 

3. To explore the relative contributions of cotton 

dust and airborne gram negative endotoxin 

exposure in the development and progression of 

respiratory symptoms and pulmonary function 

change. 

4. To explore the assumption of a cross-shift 

change in FEY I at baseline screening and 

subsequent development of respiratory symptoms 

and loss of FEY 1• 

Methodology 

The study is a I I -year follow-up with surveys 

done at years 0, 5, and 11. Respiratory 

questionnaire, pulmonary function, and air sampling 

were performed at both surveys using identical 

techniques. Retirees and workers on leave were 

contacted and tested at years 5 and 11. The cause of 

death, as well as other reasons for loss from cohort, 

has been ascertained on all subjects. 

Significant Findings 

Significant findings of the 5-year follow-up 

study include: (1) a generally good dust-endotoxin 

correlation in the mill environments; (2) workers with 

both non-specific and work-related symptoms at the 

time of first survey had accelerated 5-year losses in 

lung function; (3) after appropriate adjustments for 

smoking, age, etc., cotton textile workers had an 

accelerated loss of FEY I over 5 years; 

(4) cotton-exposed workers, but not silk workers, 

with a greater than or equal to across-shift loss in 

FEY 1 at the time of first survey had significantly 

greater 5-year loss in FEV1 after appropriate 

adjustments. 

Data collection for the I I -year follow-up was 

completed by July, 1993. Ninety percent follow-up 

is expected. Data analysis on the 11-year follow-up 

has begun. 

Publications 

Christiani DC, Wegman DH, Ye TT, Eisen EA: 

Variability in Symptom Reporting, Across-shift Drop 

in FEY 1, and Longitudinal Change in Pulmonary 

Function in Cotton Textile Workers. Chest, in press, 

1994 

Hayes G, Ye TT, Lu PL, Dai HL, Christiani DC: 

Respiratory Disease in Chinese Textile Workers, III: 

Assessment of Small Airways Function. 

Environmental Research, in press, 1994 

Occupational Lung Diseases - Page 13 

Beckett WS, Pope CA, Xu XP, Christiani DC: 

Women's Respiratory Health in the Cotton Textile 

Industry: An Analysis of Respiratory Symptoms. 

Br Jour Ind Med 51:14-19, 1994 

Christiani DC, Velazquez AV, Wilcox M, 

Olenchock SA: Airborne Endotoxin Concentrations 

in Various Work Areas within A Cotton Mill in 

Central America. Environmental Research, in press, 

1993 

Christiani DC, Wegman DH, Ye TT, Eisen EA, 

Olenchock SA: Cotton Dust - Gram Negative 

Bacterial Endotoxin Correlations in Two Mills. Am 

Jour lndustr Med 23:333-343, 1993 

Christiani DC: Occupational Diseases in the 

Industrializing and Industrialized World: 

Commonalities and Contrasts. Measurement Tools. 

Tubercle and Lung Disease 73:7-13, 1992 

Velazquez AV, Christiani DC, McConnell R, 

Eisen EA, Wilcox M: Respiratory Disease in A 

Textile Factory in Nicaragua. Am Jour lndustr Med 

20:195-208, 1991 

Olenchock SA, Christiani DC, Ye TT, Lu PL: 

Airborne Dust and Endotoxin Concentrations in 

Various Work Environments within Two Cotton 

Textile Mills in the People's Republic of China. 

Biomedical & Environmental Sciences 3:443-51, 

1990 

Christiani DC, Wegman DH, Ye TT, Eisen EA, 

Lu PL: A Longitudinal Study of Pulmonary Function 

in Chinese Cotton Textile Workers. American 

Review of Respiratory Diseases A589, 1990 

Christiani DC, Wegman DH, Eisen EA, Ye Tt, 

Lu PL: Cotton Dust Exposure and Longitudinal 

Change in Lung Function. American Review of 

Respiratory Diseases 141:589, 1990 
Page 14 - Occupational Lung Diseases 

Airway Hyperresponsiveness Due to 

Cotton Dust 

E. Neil Schachter, MD. 

Mount Sinai 

Medical Center 

One Gustave L. Levy Place 

A24-30, Box 1232 

New York, New York 10029-6574 

Program Area: Occupational Lung Diseases 

Grant Number: 5 ROJ OH02593-04 

Start & End Dates: 09/01/89 - 08/31/95 

Funding Level: $147,561 ($556,714 Cum) 

Importance to Occupational Safety and Health 

Byssinosis remains a significant occupational 

health priority in the United States. Many textile 

workers exposed to cotton dust over several decades 

before the advent of the current environmental 

standards are at risk of impairment due to chronic 

airway disease. Younger workers are at a lower risk 

but the current prevalence is unknown. 

A growing body of evidence associates 

occupational and environmental pollutants with 

airway inflammation. The inflammation may be 

clinically reflected by non-specific airway 

hyperresponsivenss, a condition associated with the 

development of chronic airflow obstruction. By 

exploring the effects of cotton bract (a major 

component of cotton dust) extract (CBE) challenge on 

the development of airway responsiveness in our 

model of healthy volunteers, we hope to provide 

insight into the transition between the well 

characterized acute response to cotton dust and the 

often irreversible chronic airflow obstruction found in 

many older workers with byssinosis. Additionally, 

this study will help validate our in vivo model of 

byssinosis in healthy volunteers exposed to (CBE) 

and will extend our previous observations concerning 

the interaction of cigarette smoking and other risk 

factors with byssinosis. 

Objectives 

Our specific aims are: 

1. To investigate if cotton bract extract induces 

greater airway hyperresponsiveness in healthy 

smokers than in healthy non-smokers. The 

working hypothesis is that smokers have an 

asymptomatic, low-level airway inflammation 

that makes them more susceptible to in 

CBE-induced airway hyperresponsiveness. 

2. Examine the effect of repeated CBE exposures on 

non-specific bronchial hyperresponsiveness. The 

working hypothesis is that repeated exposures to 

CBE result in progressively greater inflammatory 

changes in the airway that will manifest 

themselves by airway hyperresponsiveness. 

3. To compare the bronchoconstrictor effect of CBE 

with a similarly prepared extract of cotton dust. 

The hypothesis is that the bronchoconstrictor 

agent(s) in cotton bract extract are the same or 

similar to those found in cotton dust and hence 

will provoke similar effects. 

4. To examine the effect of asymptomatic airway 

hyperresponsiveness on the airway response to 

methacholine following CBE. The hypothesis is 

that non-specific mild airway 

hyperresponsiveness, which is widely distributed 

in the healthy population, contributes to airway 

hyperresponsiveness to CBE. 

5. To examine the effect of atopic status on airway 

responsiveness following CBE. The hypothesis is 

that atopic status, in otherwise healthy individuals 

without airway symptoms may enhance 

CBE-induced airway hyperresponsiveness. 

Methodology 

Our laboratory has developed a clinical model for 

studying the effects of cotton dust on human airways. 

The model consists of measuring lung function 

changes resulting from aerosol challenge with CBE. 

Aerosol inhalation of CBE consists of a 10 minute 

challenge using tidal breathing for a total of 120 

inhalations. Lung function is measured following 

these exposures using maximal and partial expiratory 

flow volume (MEFV and PEFV) curves. The main 

parameter of interest is the MEF40%(P) (the flow 

rate on the PEFV curve measured at 60% of baseline 

vital capacity below TLC). 

In study 1 twenty-eight healthy non-smokers and 

fifty smokers were examined on two separate days. 

On the first day baseline airway reactivity to 

methacholine was established. On Day 2 the subjects 

first inhaled CBE following which lung function was 

measured for ninety minutes (at 15 minute intervals) 

and responsiveness to methacholine 

(PD20MEF40%(P)) was then determined. In 

study 2, 27 healthy non-smokers were examined on 

7 separate days. On the first day we measured 

airway reactivity to methacholine (MC). On five 

consecutive days following the screening the subjects 

were challenged with CBE and again after 2 days on 

the eighth day. MC reactivity was determined 

90 minutes after CBE challenge on days 1, 5 and 8. 

Study 3 compares airway responses to CBE and 

cotton dust extract (CDE) in 20 healthy subjects. 
Studies 4 and 5 using a protocol similar to study 2 

compares healthy subjects to subjects with atopy and 

with mild airway hyperresponsiveness. 

Significant Findings 

Studies I and 2 of this proposal have been 

completed and reported upon in full detail in the final 

report to NIOSH dated November 1992. The major 

significant findings of those studies were: CBE 

challenge caused significant drops (responders) in 

lung function (MEF40%(P) .2 20%) in 

9/28 non-smokers and 27 /50 smokers. Significant 

decreases in PD20MEF40%(P) were demonstrated 

for methacholine in smokers (p.:s 0.01) but not in 

non-smokers. When only responders were studied, 

MC responsiveness increased in non-smokers 

(p.:s .001) as well as smokers (p.:s 0.005). Repeated 

daily challenge with CBE in 27 non-smokers brought 

about accentuated lung function decline on day I and 

8 but not on days 2 through 5. 

We conclude that "naive" non-smoking subjects 

never exposed to cotton dust show characteristic 

bronchoconstrictor responses (Monday 

bronchoconstriction) when challenged daily with 

CBE. Airway hyperreactivity accompanies this 

response. Smoking is an independent cause for 

airway hyperreactivity and enhances the effect of 

CBE challenge. 

Work is now well under way on studies 3,4 and 

5. Data collection has been completed for study 

objective 3. Twenty subjects have been studied with 

CBE and CDE (obtained from NIOSH). In a 

preliminary analysis of 11 subjects there were 

8 responders (R) to CBE and 9 (R) to CDE. All 

CBE responders were CDE responders. The average 

maximal response to CBE was a fall in MEF40%(P) 

to 68 ± 9/1 % of baseline compared to 68 ± 6.8% for 

CDE (NS). All subjects R and non-responders (NR) 

enhanced their MC response following CBE and 

CDE. We conclude that both CBE and CDE exert 

similar physiologic effects in naive healthy adults. 

In studies 4 and 5 which investigate the role of 

pre-existing airway hyper- responsiveness and 

pre-existing atopy on the response to CBE we have 

completed data collection on 38 subjects. Analysis of 

this preliminary data is not yet available. 

Publications 

Schachter EN, Zuskin E, Rienzi N, Godbold J: 

In Vitro Pharmacologic Studies of Poultry Dust 

Extract. Proceedings of the 18th Cotton Dust 

Conference, San Diego, in press, 1994 

Schachter EN, Zuskin E, Buck M, Rienzi N, 

Godbold J, Castranova V, Whitner M, Siegel P: 

Comparison of the Airway Response To Cotton Dust 

Occupational Lung Diseases - Page 15 

And Cotton Bract Extracts. Proceedings of the 18th 

Cotton Dust Conference, San Diego, in press, 1994 

Zuskin E, Mustajbegovic J, Schachter EN: 

Follow-up Study of Respiratory Function in Hemp 

Workers. Am J Ind Med, in press, 1994 

Zuskin E, Mustajbegovic J, Schachter EN, Rienzi N: 

Respiratory Symptoms and Ventilatory Capacity in 

Workers in a Vegetable Pickling and Mustard 

Production Facility. Int Arch of Occupational and 

Environ Health, in press, 1993 

Zuskin E, Schachter EN, Kanceljak B, Witek TJ, Jr., 

Fein E: Organic Dust Disease of Airways. Int Arch 

Occup Env Health 65:135-140, 1993 

Schachter EN, Russomanno J, Siegal J, Fine E, 

Rienzi N, Witek TJ, Jr., Buck MG, Godbold J: Does 

Cotton Bract Extract Challenge Cause "Monday" 

Bronchospasm? Proc 17th Cotton Dust Conference, 

pp. 279-280, 1993 

Castranova V, Robinson VA, Borger MW, Siegel PD, 

Judy JD, Schachter EN, Frazer DG: Pulmonary 

Response of Guinea Pigs To Inhalation of Purified 

Cotton Bract Extract. Proc 17th Cotton Dust 

Conference, pp. 248-251, 1993 

Schachter EN, Tai A, Cardozo C, Zuskin E, 

Godbold J, Rienze N, Kesser M: Characterization of 

the Potentiation of Bradykinin-Induced Constriction 

By An Inhibitor of Endopeptidase 24.15. Am Rev 

Resp Dis 147:A851, 1993 

Fein E, Godbold J, Chusid E, Schachter EN: The 

Effect of High Dose Steroids or Sleep Patterns and 

Respiratory Function in Symptomatic Steroid 

Dependent Asthmatics. Amer Rev Resp Dis, 

147:A291, 1993 

Zuskin E, Mustajbegovic J, Schachter EN: 

Respiratory Function in Sewage Workers. Am J 

Indust Med 23:751-763, 1993 

Zuskin E, Butkovic D, Schachter EN, 

Mustajbegovic J: Respiratory Function in Workers 

Employed in the Glass Blowing Industry. Am J 

Indust Med 23:835-844, 1993 

Zuskin E, Schachter EN, Mustajbegovic J: 

Respiratory Function in Greenhouse Workers. Int 

Arch of Occup and Environ Health 64:521-526, 

1993 

Schachter EN: Byssinosis. In: Textbook of 

Clinical, Occupational and Environmental Medicine, 

WB Saunders, Philadelphia, PA, in press, 1993 
Page 16 - Occupational Lung Diseases 

Zuskin E, Kanceljak B, Schachter EN, Witek TJ, 

Maayani S, Goswami S, Marom Z, Rienzi N: 

Immunological Findings in Hemp Workers. Env Res 

59:350-361, 1992 

Zuskin E, Kanceljak B, Mustajbegovic J, 

Schachter EN: Immunological and Respiratory Status 

in Swine Workers. Allergy 12:251, 1992 

Zuskin E, Kanceljak B, Schachter EN, Witek TJ, 

Maayani S, Goswami S, Marom Z, Rienzi N: 

Immunological and Respiratory Changes in Animal 

Food Processing Workers. Am J Ind Med 

21: 177-191, 1992 

Zuskin E, Zagar Z, Schachter EN, lvankovic D: 

Respiratory Symptoms and Ventilatory Capacity in 

Swine Confinement Workers. Br J Ind Med 

49:435-440, 1992 

Schachter EN, ZuskinE, MustajbegovicJ, Buck MG, 

Maayani S, Marom Z, Goswami SK, Rienzi N: 

Pharmacologic Studies of Wool Dust Extract in 

Isolated Guinea Pig Trachea. Proc XVI Cotton Dust 

Research Conference, (Volume I), pp. 290-291, 

1992 

Zuskin E, Ranceljak B, Schachter EN, Witek TJ, 

Mustajbegovic J, Maayani S, Buck M, Rienzi N: 

Immunological Findings and Respiratory Function in 

Cotton Textile Workers. Int Arch Occup Env Health 

64:31-37, 1992 

Schachter EN, Marom Z, Goswami S, Gollub E, 

Rienzi N, Maayani S: Purified Macrophage Mucus 

Secretagogue is A Potent Bronchial Smooth Muscle 

Relaxing Agent In Vitro. Am Rev Resp Dis 

145:A374, 1992 (Abstract) 

Cabrera M, Rienzi N, Schachter EN: Patterns of 

Asthma Admissions to A Metropolitan Hospital. 

1990. Am Rev Resp Dis 145:A506, 1992 

Zuskin E, Kanceljak B, Stilinovic L, Schachter EN, 

Kopjar B: Immunological Status and Respiratory 

Findings in Furriers. Am J Industr Med 21 :433-442, 

1991 

Zuskin E, Ivankovic D, Schachter EN, Witek TJ: A 

Ten Year Follow-up Study of Cotton Textiles 

Workers. Amer Rev Resp Dis 143:301-305, 1991 

Russomanno J, Siegel J, Witek TJ, Rienzi N, 

Zuskin E, Buck M, Schachter EN: Does Smoking 

Status Influence Responsiveness to Cotton Bract 

Extract? Proc Beltwide Cotton Conference XV, 

pp 214, 1991 

Zuskin E, Kanceljak B, Witek TJ, Schachter EN: 

Acute Ventilatory Response to Green Coffee Dust 

Extract. Ann Allergy 66:219-224, 1991 

Zuskin E, Kanceljak B, Schachter EN, Witek TJ, 

Marom Z, Goswami S, Maayani S: Immunological 

and Respiratory Changes in Soybean Workers. Int 

Arch of Occup Env Health 63:15-20, 1991 

Zuskin E, Kanceljak B, Schachter EN, 

Mustajbegovic J, Goswami S, Maayani S, Marom Z, 

Rienzi N: Immunological and Respiratory Findings 

in Swine Farmers. Env Res 56:120-130, 1991 

Russomanno J, Siegel J, Fine E, Rienzi N, Witek TJ, 

Buck MG, Godbold J, Schachter EN: Does Cotton 

Bract Extract Challenge Cause "Monday" 

Bronchospasm? Amer Rev Resp Dis 

143:A428, 1991 (Abstract) 

Russomanno J, Siegel J, Fine E, Rienzi N, Witek TJ, 

Buck MG, GodboldJ, Schachter EN: The Interaction 

of Cotton Bract Extract and Methacholine in Smokers 

and Non-smokers. Amer Rev Resp Dis 143:A428, 

1991 (Abstract) 

Schachter EN, Marom Z: Erythromycin Reduces 

Airway Responsiveness to Methacholine. Amer Rev 

Resp Dis 143:A428, 1991 

Schachter EN, Zuskin E, Cardoza C, Godbold J, 

Rienzi N, Lesser M: Inhibitor of Endopeptidase 

24.15 Potentiates Bradykinin-induced Contraction of 

Guinea Pig Trachea. Amer Rev Resp Div 143:A616, 

1991 (Abstract) 

Goswami S, Gollub E, Slavin S, Schachter EN: 

Erythromycin Reduces Muscus Glycoprotein 

Secretion and Symptoms in Stable Chronic 

Bronchitis. Amer Rev Resp Dis 143:A669, 1991 

(Abstract) 

Fein E, Zuskin E, Rienzi N, Schachter EN: 

Prevalence of Chronic Respiratory Symptoms in 

Workers Exposed to Elevated Ambient Dust Levels. 

Fourth International Conference on Environmental 

Lung Disease, Montreal, p. 8, September 28, 1991 

Schachter EN: Occupational Airway Disease. Mount 

Sinai J Med 58(6):483-493, 1991 

Zuskin E, Kanceljak B, Porkrajac D, Schachter EN, 

Witek TJ: Respiratory Symptoms and Lung Function 

in Hemp Workers. Br J Ind Med 47:627-632, 1990 

Witek TJ, Schachter EN: Problems in Respiratory 

Care Volume 3: 1 and 2: Current Issues in 
Respiratory Public Health. Volumes I and II, JB 

Lippincott, Philadelphia, 1990 

Witek TJ Jr., Schachter EN: Multidisciplinary 

Approaches to Environmental Lung Disease. 

Investigations in Byssinosis and Inner City Asthma. 

In: Current Issues in Respiratory Public Health, (eds. 

TJ Witek, Jr., EN Schachter), Philadelphia: JB 

Lippincott Co. 3:206-219, 1990 

Witek TJ, Mazzara CA, Zuskin E, Beck GJ, 

Buck MG, Schachter EN: Bronchial Responsiveness 

After Inhalation of Cotton Bract Extract. Am Rev 

Resp Dis 183:1579-83, 1988 

Coal Dust Particle Size and 

Respiratory Disease 

Thomas G. Robins, MD., MP.H 

University of Michigan 

School of Public Health 

1420 Washington Heights 

Ann Arbor, Michigan 48109-2029 

Program Area: Occupational Lung Diseases 

Grant Number: 5 ROI OH02761-02 

Start & End Dates: 09/01190 - 08/31/93 

Funding Level: $0 ($229,614 Cum) 

Importance to Occupational Safety and Health 

Exposure to coal mine dust is strongly associated 

with the development of coal workers' 

pneumoconiosis (CWP) and chronic obstructive lung 

disease including emphysema and chronic bronchitis. 

The most important studies which demonstrate such 

effects use measurements of respirable coal mine 

dust, i.e., dust depositing in primarily in the terminal 

airways and alveoli, as the basis of their exposure 

assessment. There are, however, good reasons to 

hypothesize that chronic bronchitis may be more 

specifically associated with exposure to larger 

particles of dust which deposit in the 

tracheo-bronchial tree. This study is designed to 

examine the independent effects of respirable and 

tracheo-bronchial dust fractions in the development 

of obstructive lung disease. In addition, most 

quantitative exposure-response studies rely upon 

simple cumulative exposure as the primary dose 

metric. This study will utilize the time 

period-specific quantitative exposure estimates to 

examine the assumptions inherent in simple 

Occupational Lung Diseases - Page 17 

cumulative exposure and to define a more appropriate 

metric for exposure response analyses. 

Objectives 

1. Characterize the particle-size distribution of dusts 

in underground coal mining operations based on 

personal exposure data. 

2. Develop estimates of cumulative respirable and 

tracheobronchial dust exposures for a cohort of 

previously studied underground miners. 

3. Explore the exposure-response functions for 

these exposure measures and the development of 

airflow limitations and symptoms of chronic 

bronchitis. 

4. Explore the construction of simple cumulative 

exposure to identify an optimal exposure metric 

for the study of coal dust and obstructive lung 

disease. 

Methodology 

Particle-size distributions of dust exposure were 

characterized for a set of occupations identified from 

the work histories of miners participating in the 

National Study of Coal Workers' Pneumoconiosis. 

Four mines were visited and exposure to miners 

employed in the targeted occupations were monitored 

using a personal cascade impactor. Using a 

deposition model for pulmonary aerosols, the 

respirable and tracheo-bronchial dust fractions were 

calculated for each sample. The parameters were 

then compare . across occupations, proximity to the 

coal face and by mining technology. Analysis of 

variance was used to consider the possible effects of 

these factors while simultaneously considering 

differences between mines. The potential for using 

these ratios of tracheo-bronchial to respirable dust 

fractions in conjunction with previously developed 

estimates of respirable dust concentrations to estimate 

respirable and tracheo-bronchial dust cumulative 

doses would then be explored. Exposure response 

functions using the alternative dose metrics could then 

be compared. 

An alternative method for summar1zmg 

exposures over time was also developed that accounts 

for non-linear effects of exposure concentrations and 

time since exposure. 

Significant Findings 

Collection of particle size distribution data was 

accomplished at four underground Appalachian 

mines. The data included 180 valid samples obtained 

with the assistance of volunteer miners at each site 

using an 8-stage personal cascade impactor. 

Findings from this effort indicated little 

variability between occupations, or groups of 
Page 18 - Occupational Lung Diseases 

occupations in the particle size distributions, or the 

ratio of respirable to tracheo-bronchial dust fractions. 

There was some difference observed between mines, 

which may have resulted from the use of diesel 

transportation equipment in one mine. The findings 

are somewhat at deviance to observations of previous 

researchers, however all previous data were obtained 

by area samples placed in positions which may have 

accentuated the different distributions. 

The findings of this proposal made application of 

particle size-specific fractions to historical data 

infeasible so the original intent of estimating 

exposure-response relations using cumulative 

tracheo-bronchial dust exposures was not possible. 

However, the results also suggest that data collected 

as respirable exposure fractions should be equally 

predictive of obstructive disease, at least for historical 

reconstruction purposes. 

Additional analysis of the relationship between 

respirable dust exposures and obstructive disease, 

especially symptoms of bronchitis and pulmonary 

function variables, was conducted prospectively on 

the previously analyzed cohort of 977 underground 

miners attending Round 2 and Round 4 of the 

National Study of Coal Workers' Pneumoconiosis 

(NSCWP). These findings suggest a steep 

exposure-response relationship between dust 

exposure and the incidence of bronchitis symptoms 

within a few years of onset of exposure. Further, the 

data suggest a strong relationship between bronchitis 

symptoms and loss of pulmonary function. 

A further exploration of the dimensions of 

cumulative exposure resulted in a proposal to 

integrate time of exposure, dust concentration and 

exposure duration into a single flexible dose metric. 

The proposed metric uses exponents of the 

concentration and time of exposure components to 

estimate the optimal contribution of these factors in 

the development of disease. The metric was tested in 

the previously described cohort from the NSCWP, 

and the result suggested that the square root of 

concentration and the first power of time since 

exposure might be an optimal expression for 

cumulative exposure for low level coal dust exposure 

and decrements in forced expiratory volume in one 

second. For the incidence of wheezing, concentration 

and time since exposure squared may represent an 

improvement in a dose metric over simple cumulative 

exposure. The model is seen as experimental and 

application of this or similar models to other data sets 

will ultimately prove its utility. 

Publications 

Seixas NS, Robins TG, Becker M: A Novel 

Approach to the Characterization of Cumulative 

Exposure for the Study of Chronic Occupational 

Disease. Am J Epid 137:463-471, 1993 

Seixas NS, Robins TG, Becker M: Determination of 

an Optimal Exposure Metric for the Study of Coal 

Dust Exposures and Obstructive Lung Disease. Am 

J Epid, in press, 1992 

Detecting Lung Overload by 

Magnetometry 

Jura} J. Ferin, MD. 

University of Rochester 

School of Medicine and Dentistry 

Department of Environmental Medicine 

Box EHSC 

575 Elmwood Avenue 

Rochester, New York 14642 

Program Area: Occupational Lung Diseases 

Grant Number: 5 ROI OH02772-04 

Start & End Dates: 09101/90 - 08/31/94 

Funding Level: $144,299 ($832,522 Cum) 

Importance to Occupational Safety and Health 

The concept of lung overload is based on 

observations made in chronic inhalation exposures of 

rats to high concentrations of coal dust, iron oxide, 

titanium dioxide, diesel engine exhaust and polymer 

particles. The accepted indicator of lung overload is 

a significant decrease in the alveolar clearance rate of 

particles. Besides decreased alveolar clearance, lung 

overload is associated with inflammatory responses in 

the alveoli (influx of neutrophilic leukocytes, protein 

leakage), macrophage accumulation, fibrotic changes 

and even tumors. Extrapolation of data from rats 

suggests that decreased particle clearance may occur 

in humans at a mass burden of 1-3 mg/g lung when 

inhaling particles of density 1 g/cm3 and clearance 

could cease at 30 mg/g lung. Under reasonable 

assumptions for the deposition rate and clearance 

half-times in humans, the accumulated dust burden 

would exceed 3 mg/g lung after I 1/2 years of 

exposure to "nuisance" dusts at the concentration of 

5 mg/m3

, which is the present OSHA standard of 

exposure limit for respirable dusts. If pulmonary 

mass load in the range of 1-3 mg/g lung causes a 

decrement in clearance in humans, as it does in rats, 

then lung overload related effects might occur in 

humans inhaling concentrations of dust allowed by 

governmental regulations. 

Magnetometry is the non-invasive measurement 

of the amount of ferro- and ferri-magnetic materials 

in a sample. If this technique could be adapted for 

use in humans to assess particle retention and 
clearance, it would mean a great advancement to 

clarify questions regarding overload in humans. 

Objectives 

The long-term objectives of the proposed line of 

research are to characterize and clarify lung overload 

in rodents and to develop magnetometry to a level 

which makes assessment of overload in humans 

realistic. The overall aims of this project are to: 

(1) develop needed aerosol generation and 

magnetometry systems; (2) demonstrate that dust 

clearance rates can be measured reliably using 

magnetic aerosols, (3) test hypotheses which suggest 

that magnetometry may have unique capabilities to 

detect and characterize lung overload, and 

(4) compare results from two animal species to 

provide a broader information base for extrapolating 

to humans and for planning future human studies. 

Methodology 

The thorax of animals was placed in a strong DC 

magnetic field for a short time to align the magnetic 

moments of individual particles by both rotating 

particles and rotating magnetic domains within 

particles. After the magnetizing field was removed, 

the remanent field was measured by an array of 

8 fluxgate magnetometers arranged such that the 

magnetic moment and subsequent relaxation of as 

little as 0.1 mg of magnetite in the lungs of rats could 

be recorded. In addition to the 8 magnetometers, the 

system consists of shielding, analog signal processing 

hardware and a computerized digital signal processing 

system. Rats were exposed nose-only to magnetite 

or to a mixture of magnetite and Ti02 particles. 

When sacrificed the pulmonary tissue was analyzed 

chemically for iron and titanium in addition to a 

number of biological parameters ( determined from 

lavage, e.g., cells, proteins). 

Significant Findings 

Using multiple exposures, magnetometric results 

clearly show the increase in lung burden during 

exposure and also clearance of magnetite particles 

when the exposure was discontinued. However, 

post-exposure clearance of particles based on 

magnetometry measurements seemed to be 

unexpectedly fast (up to T 1/2 = -20 days) 

compared to clearance based on chemical analysis of 

magnetite (T 1/2 = -150 days). The results with 

respect to clearance were similar after single or after 

repeated exposures and between magnetite and Ti02 

particles determined chemically. The magnetic signal 

seemed to be affected by some post-exposure 

processes. We tested the lung contents using x-ray 

crystallography and concluded that neither solubility 

Occupational Lung Diseases - Page 19 

nor changes of magnetite into a different form 

(e.g. hematite) can explain the discrepancy. Results 

of other experiments indicate that rearrangement of 

particle agglomeration affects magnetometric 

measurements. It is conceivable that during particle 

translocation within the lung such rearrangement may 

occur. Presently, we are performing studies on 

particle agglomeration and its effects on 

magnetometry in the post-exposure phase. We 

believe that a clarification of the discrepancy between 

the magnetometric and chemical clearance 

determination may be decisive for the practicality of 

using magnetometry in human studies. 

In another experiments, rats were irradiated 

(thorax only) before particle exposure. The 

compromised AM may change the pulmonary tissue 

response at the time of exposure to magnetite which 

may show in the magnetometric results. 

Publications 

Ferin J, Oberdi:irster G, Soderholm SC: 

Magnetometric Analysis of Pulmonary Retention of 

Particles. Ninth Congress of the International Society 

for Aerosols in Medicine, J Aerosol Medicine 6, 

Supplement, pp 50, March 1993 

Ferin J, Soderholm S, Oberdorster G: Quantitative 

Analysis of Particle Translocation Within the Lung. 

Am Rev Respir Dis 145( 4):A801, 1992 (International 

Conference Supplement) 

On-Site Enumeration of Fungal 

Spores and Bacteria in Air 

H Kenneth Dillon, Ph.D. 

University of Alabama 

School of Public Health 

Department of Environmental Health Sciences 

UAB Station 

Birmingham, Alabama 35294 

Program Area: Occupational Lung Diseases 

Grant Number: 5 ROI OH02914-02 

Start & End Dates: 02/01192 - 01/31195 

Funding Level: $115,087 ($234,318 Cum) 

Importance to Occupational Safety and Health 

The sampling and analysis methodology is 

expected to yield a measure of exposure to viable and 

nonviable bioaerosols that have been implicated in the 

occurrence of many diseases of the lower airways 

(e.g., hypersensitivity pneumonitis, organic dust toxic 

syndrome, asthma, aspergillosis, and bronchitis) and 
Page 20 - Occupational Lung Diseases 

diseases of the upper airways (e.g., allergic rhinitis 

and sinusitis). The onset of acute HP symptoms have 

been observed upon repeated exposures to high 

concentrations of fungi and actinomycete spores, 

viable and nonviable. Allergy-related diseases are 

often associated with specific organisms; the 

developed method will yield information that will aid 

in the identification of fungal spores and bacteria. 

The method will, also, allow timely on-site analyses 

which will facilitate the correlation of currently 

observed symptoms with exposure conditions and the 

development and interpretation of comprehensive 

sampling strategies. Sampling sequentially with the 

sampling manifold will allow the development of time 

and spatial concentration profiles over extended time 

periods which will aid in locating sources of 

bioaerosols and in the correlation of environmental 

conditions or work activities that may induce or 

influence the release of bioaerosols to the indoor air 

environment. The filter catch can be used for the 

determination of other proposed indices of exposure 

to bioaerosols, including avian and animal serum 

proteins, proteases, antigens, and endotoxins. The 

determination of individual exposures, i.e., personal 

samples, will be possible by the use of individual 

filter holders. 

Objectives 

1. The overall objective of the proposed work is to 

develop an on-site screening method involving 

air sampling with membrane filter discs and 

subsequent analysis by brightfield and 

epifluorescent microscopy after supravitally 

staining collected spores and bacteria. 

2. The primary goal of the first phase of study was 

the development of an analysis protocol that can 

be used in the field and that will yield results 

within minutes of the cessation of air sampling. 

The developed sample preparation procedure 

should permit determinations of viability. The 

analysis method was developed and evaluated. 

3. In the second phase, an air sampling device was 

fabricated that provides sequential sampling with 

replicates. The evaluation of this device is 

underway. Test atmospheres of a nonbiological 

fluorescent aerosol and representative fungal 

spores and bacteria are being produced in the 

laboratory for the evaluation of the sampling 

device and for the evaluation of the total 

sampling and analysis procedure. 

4. The final phase of the proposed work, which will 

be undertaken in the third year, will be the field 

evaluation of the developed technique. 

Methodology 

For the development and evaluation of the 

analysis method, aliquots of aqueous suspensions of 

fungal spores and bacteria were deposited on Irgalan 

black-stained, track-etched polycarbonate filters with 

a pore size of 0.2 or 0.4 μ.m (Poretics, Bedford, MA), 

and the liquid was removed by vacuum. The levels 

of the bioparticles in suspensions were determined 

using a Coulter ZM counter. The bioparticles were 

stained without fixation with s2 mM acridine orange 

in neutral buffered saline; a coverslip was added and 

sealed with wax or clear nail polish. The slides were 

viewed with a binocular Leitz® Laborlux D 

fluorescent microscope with BP filter 450-490 nm, 

barrier filter 515 nm, and IOOx ( 1.25-0.60 Oel) oil 

immersion objective, and 12.5x eyepieces (Leica 

Mikroskopie und Systeme GmbH, D-6330, Wetzlar, 

Germany). For the ongoing evaluation of the 

sampling method, bioaerosols have been collected on 

13-mm diameter filters in the designed sampling 

manifold and prepared for viewing as specified 

above. 

The laboratory evaluation of the developed 

sampler is being carried out in a wind tunnel, which 

is a 10-ft (3.0-m) length of 22.8 in. (0.56 m) ID, 

26.0 in. (0.66 m) OD PVC pipe coated on the inside 

with a graphite-containing paint that renders the pipe 

conductive to ground. A high efficiency particulate 

air (HEPA) filter is installed at each end of the pipe 

to purify the inlet air and to remove the generated 

aerosol before exhausting air from the system. A 

centrifugal fan powered by a 1.5 hp (1750 rpm) 

motor is used to pull air through the system so that 

the tunnel is under negative pressure when being 

used. 

Significant Findings 

Mean bacterial counts >100 yielded CVs sl3% 

except for two out of 18 sets of replicates. Mean 

spore counts >100 yielded CVs sl2%. The 

conclusion was drawn that, if biases were small, 

counts of individual particles and aggregates with 

accuracies s25% could be obtained as long as counts 

were greater than l 00. The limit of quantitation 

(LOQ) was defined as l 00 particle counts for which 

the CV was sl3%. The limit of detection (LOD) 

was defined as a single particle count because blank 

polycarbonate filters were consistently found to be 

free of bacteria and fungal spores. Desiccation of 

osmotically fragile E. coli on filters exhibited no 

effects on morphology or the enumeration of the 

bacteria. Microscopic examination of fungal spores 

and of colonies grown as pure cultures demonstrated 

the utility of bright field and epifluorescent 

microscopy not only as useful tools in the 

enumeration of bioaerosols but also in the 
identification of fungi. A sampling system was 

designed with variable cutpoints to offer the 

opportunity for sampling thoracic-sized aerosols and 

larger particles when desired. One of the primary 

design features is a sampling manifold to allow the 

collection of replicate samples over sequential 

sampling periods. Laboratory and field tests are 

currently being conducted with the sampler. 

Metal Fume Fever 

William S. Beckett, MD. 

Yale University 

School of Medicine 

Department of Occupational Medicine 

333 Cedar Street CB 5039 

New Haven, Connecticut 06510 

Program Area: Occupational Lung Diseases 

Grant Number: 5 ROJ OH02987-02 

Start & End Dates: 09/30/92 - 09/29/95 

Funding Level: $218,211 ($477,442 Cum) 

Importance to Occupational Safety and Health 

Metal fume fever is a common occupational 

illness caused by inhalation of freshly generated zinc 

oxide and other metal fumes. This illness is 

characterized by fever, systemic symptoms, and mild 

lung inflammation with onset several hours after the 

acute exposure. Repeated exposure results in 

adaptation with reduction in symptoms and febrile 

response. There is little information regarding 

dose-response relationships in naive and chronically 

exposed individuals, the nature of adaptation to the 

acute response, or the mechanism by which zinc 

oxide exposure causes metal fume fever. 

Objectives 

Our laboratory has developed a quantitative zinc 

oxide fume generating, monitoring, and exposure 

system for animal and human subjects. Using this 

system, we have previously demonstrated: 

(1) systemic effects in humans at the current OSHA 

PEL of 5 mg/m3

; (2) induction of human 

zinc-binding protein (metallothionein) after exposure; 

(3) acute lung inflammation in animals exposed below 

the PEL; and (4) alterations in cytokine release from 

guinea pig lung inflammatory cells. To further 

understand acute and adaptive responses to zinc oxide 

exposure and to determine the mechanism by which 

it causes metal fume fever, the following hypotheses 

Occupational Lung Diseases - Page 21 

will be tested: (1) acute, febrile, and pulmonary 

responses to exposure in human subjects occur at and 

below the current OSHA PEL; (2) adaptive responses 

to chronic exposures in humans do not eliminate lung 

inflammatory changes; (3) adaption involves changes 

in nasal epithelial metallothionein gene induction; 

(4) mechanism of metal fume fever and adaption 

involves release of cytokines and a modulation of 

their response at a central or peripheral level in zinc 

oxide-exposed animals. 

Methodology 

Using a carefully controlled quantitative pure zinc 

oxide fume generating system, naive subjects and 

workers chronically exposed to zinc oxide fume will 

be exposed for two hours at concentrations below the 

current OSHA PEL. Symptoms, fever, peripheral 

blood indices of inflammation and nasal epithelial 

induction of metallothionein will be assessed. The 

ability for these low levels of zinc oxide fume to 

induce inflammatory changes in the lung will be 

assessed by lavage of lung lining fluid. These studies 

will be accomplished using an integrated 

multi-disciplinary approach and should yield 

important insights into the genesis and adaption of 

this debilitating occupational illness. 

Significant Findings 

Using this exposure system, we have 

demonstrated our ability to expose human subjects to 

zinc oxide fume for two hours at and below the 

current OSHA TL V in a blinded fashion. Subjects 

have developed characteristic symptoms of metal 

fume fever as well as symptoms in proportion to their 

exposure level. 

In related animal studies, we have found that 

mice which have previously received repeated daily 

exposure to zinc oxide fume at 5 mg/m3 have greater 

inducibility of lung metallothionein gene expression 

to a single zinc oxide exposure than naive mice. 

Additional human subjects are currently under 

study to test the hypotheses noted as objectives 

above. 

Publications 

Cosma GN, Chen LC, Currie D, Garte SJ, Gordon T: 

Metallothionein (MT) and Cytokine Gene Expression 

Following Single and Repeated Inhalation to Metal 

Fumes. The Toxicologist, in press, 1994 (Abstract) 

Gordon T, Fine J: Metal Fume Fever, In: 

Occupational Medicine, State of the Art Reviews. De 

novo Toxicants: Combustion Toxicology, Mixing 

Incompatibilities, and Environment Activation of 

Toxic Agents, (eds. DJ Shusterman, JE Peterson), 
Page 22 - Occupational Lung Diseases 

Philadelphia, Hanley and Belfus, Vol 8, pp. 505-518, 

1993 

Pulmonary Effects of Machining 

Fluid Aerosols 

Terry Gordon, Ph.D. 

New York University 

School of Medicine 

Department of Environmental Medicine 

Lanza Lab 

Long Meadow Road 

New York, New York 10987 

Program Area: Occupational Lung Diseases 

Grant Number: J ROJ OH03044-0JAJ 

Start & End Dates: 09/01193 - 08131/95 

Funding Level: $97,953 ($97,953 Cum) 

Importance to Occupational Safety and Health 

This research proposal will examine the acute 

and subchronic pulmonary effects of machining fluid 

aerosols - an occupational hazard for nearly 1 million 

workers in this country. Machining fluids/cutting oils 

are hypoosmolar, alkaline fluids which are frequently 

contaminated with a variety of microbial agents. 

Objectives 

The major goals of the proposed studies are to 

(1) determine the roles of contaminating endotoxin, 

hypotonicity, and alkalinity in the adverse pulmonary 

effects associated with occupational exposure to 

machining fluid aerosols; and (2) compare the 

potential of different classes of machining fluids to 

produce inflammatory and functional changes in the 

lung. The proposed studies will determine in an 

animal model whether subclinical inflammatory 

changes may persist in the lung after repeated 

exposure to machining fluid aerosols at exposure 

concentrations near the current TL V. The proposed 

experiments will help to provide a clearer 

understanding of the role of microbial contamination 

in the pulmonary effects of inhaled machining fluid 

aerosols. 

Methodology 

Adverse pulmonary effects after single and 

repeated exposures to machining fluid aerosols will 

be examined using functional, biochemical, and 

morphological techniques in a sensitive guinea pig 

model. Animals will be exposed to aerosols of water 

(the control atmosphere), used machining fluids, or 

unused machining fluids. During the single 

exposures, non-invasive measurements of airway 

resistance will be performed at hourly intervals. In 

the repeated exposure protocol, measurement of 

nonspecific airway responsiveness will be performed 

prior to initiation of, at 2 week intervals during, and 

at the end of exposure. 

Significant Findings 

None to date. 

Occupational Disease Among 

Carpenters 

John M Dement, Ph.D. 

Duke University Medical Center 

Department of Community 

& Family Medicine 

2200 W. Main Street, Suite 700 

Durham, North Carolina 27710 

Program Area: Occupational Lung Diseases 

Grant Number: J ROJ OH03168-0l 

Start & End Dates: 09/30/93 - 09/29/95 

Funding Level: $177,290 ($177,290 Cum) 

Importance to Occupational Safety and Health 

The National Institute for Occupational Safety and 

Health (NIOSH) has identified occupational lung 

diseases as one of the ten leading occupational health 

problems in the United States. The construction 

industry has been identified as one of the "Special 

Population Targets" in the Health People 2000 

document due to the high rate of work-related deaths 

and work related injuries among this population. 

Additionally, occupational respiratory disease 

surveillance data for 1973-1988, calculated from 

Bureau of Labor Statistics data, demonstrate annual 

incidence rates to range from 1.8 to 3.7 cases 

per 10,000 full-time workers for the construction 

industry. 

Surveillance is the first step in development of 

prevention strategies for leading work-related 

diseases and injuries. Unfortunately, no single 

comprehensive data base is available to study 

occupational illness/disease/injury. With no 

surveillance mechanism in place, a number of 

avenues have been explored including the use of 
pre-ex1stmg data bases such as state worker's 

compensation files and health insurance claims. 

The use of data bases for epidemiologic research 

that were developed for other purposes raises a 

number of issues. Morbidity information relative to 

occupational injuries and illness can be collected from 

worker's compensation data and from health 

insurance claims. Collectively, use of both of these 

data sources is necessary to fully characterize 

occupational morbidity and the interaction of 

occupational and other risk factors. This project will 

explore the use of medical claims data for study of 

occupational lung disease among carpenters in 

Washington State. 

Objectives 

The major objective of this proposed research 

project is to study work-related respiratory disorders 

among members of the United Brotherhood of 

Carpenters (UBC) international union. Specific aims 

are as follows: 

1. To integrate several existing databases in order 

to develop a comprehensive data system useful 

for study of work-related respiratory disorders 

among carpenters. These databases include: 

(a) medical claims data, (b) worker's 

compensation data, (c) UBC national 

membership file data, and (d) disability and 

pension data. This study will be conducted using 

data for Washington State. 

2. To develop epidemiological methods for analyses 

of medical claims data. This includes 

development of appropriate case definitions for 

purposes of surveillance and etiologic 

epidemiology of respiratory diseases. 

3. To analyze these integrated data with respect to 

incidence and prevalence of occupational lung 

diseases among carpenters in Washington State. 

These analyses will have the objective of 

identifying high risk industries and carpenter 

sub-trades. 

4. To conducted an asthma case-control study of 

carpenters for purposes of identifying possible 

etiologic associations with specific occupational 

exposures. 

Methodology 

Occupational lung diseases to be studied include 

malignant neoplasms (ICD-9 158, 162, 163), 

obstructive pulmonary diseases (IDC-9 406-496) and 

pneumoconioses (ICD-9 500-508). Case definition 

criteria using ICD-9 codes will be used to identify 

existing and new cases of each target lung disorder 

using both worker's compensation data and insurance 

data. In order to calculate rates, estimates of the 

Occupational Lung Diseases - Page 23 

populations covered will be derived from computer 

tapes of all eligible members covered by the 

insurance Funds for the chosen study years. 

Analyses will include generation of conventional 

descriptive statistics as well as more refined internal 

comparisons. Age, race and sex specific incidence 

and period prevalence rates with confidence limits 

based on Poisson statistics will be calculated for each 

target lung disease. For identification of high risk 

populations, further analyses will include calculation 

of age-adjusted incidence and period prevalence rates 

for each lung disease for various carpenter trades and 

industries in Washington. 

The proposed case definition of asthma for the 

case-control study will be a primary ICD-9 diagnosis 

code of 493. The case-control study will include 

newly diagnosed cases of asthma during 1988-1992 

(estimated to be 100-150) from the medical claims 

file or the State of Washington Worker's 

compensation files. Three controls for each case, 

group matched on age (within 2 years), sex and race 

will be randomly selected from the population of 

carpenters who do not file a medical or compensation 

claim for lung diseases of interest during the study 

period. 

Cases and controls will be contacted by mail and 

asked to complete a self-administered questionnaire 

soliciting information concerning respiratory 

symptoms as well as information concerning specific 

occupational exposures possibly associated with 

occupational asthma. The occupational/environmental 

exposure questionnaire will include questions 

concerning exposures to wood dusts, isocyanates, 

anhydrides, metals, soldering fluxes, paints, solvents 

plants, animal products and other biological and 

chemical materials. Stratified analyses will be used 

to control for possible confounders such as age, race, 

sex, smoking, etc. Multiple logistic regression will 

be used to analyze the association between asthma 

diagnosis, respiratory symptom data (and 

combinations of symptoms) and occupational 

exposures after adjustment for potential confounders. 

Significant Findings 

This research is just underway. Preliminary 

analyses of the medical claims data have shown the 

following number of persons filing claims for lung 

disorders of interest during 1988-92: 

Malignant Neoplasms (ICD-9 158, 162, 163) - 149 

Obstructive Pulmonary 

diseases 

Pneumoconioses 

(IDC-9 406-496) - 2796 

(ICD-9 500-508) - 58 
Page 24 - Occupational Lung Diseases 

Effects of Zinc Oxide Welding Fume 

Inhalation 

Paul D. Blanc, MD. 

University of California 

School of Medicine 

Division of Occupational 

and Environmental Medicine 

P. 0. Box 0924 

San Francisco, California 94143-0924 

Program Area: Occupational Lung Diseases 

Grant Number: 5 KOJ OH00079-03 

Start & End Dates: 09/28190 - 09/27/93 

Funding Level: $0 ($157,960 Cum) 

Importance to Occupational Safety and Health 

The self-limited systemic illness following zinc 

oxide fume inhalation consists of a flu-like illness: 

malaise, myalgia, and fever ranging from 38 to 

39 degrees. The mechanisms underlying zinc induced 

MFF have not previously been clearly elucidated. 

However, animal and limited previous human data 

suggest that zinc oxide fume inhalation leads to a 

marked pulmonary inflammatory cellular response. 

The lung may be more than merely a route of 

exposure, but instead may play an important role 

initiating the metal fume fever response. Although the 

syndrome of metal fume fever has been studied 

experimentally since the early 1900' s, explanations of 

its mechanism have remained speculative. The 

hypothesis of this study has been that the effects of 

zinc oxide fume inhalation are mediated by cytokines. 

To study this hypothesis, we have examined the 

exposure-response relationship between zinc oxide 

exposure and human health effects, providing data 

crucial to evaluating currently promulgated safety 

standards as well as assessing the health effects of 

real world conditions where higher exposures are 

frequent. 

Objectives 

Inhalation of zinc oxide fume causes a syndrome 

consisting of fever, malaise, and leukocytosis known 

as "Metal Fume Fever" (MFF). Study Hypotheses 

are: (1) MFF is a systemic response to zinc oxide 

fume inhalation that results from the synthesis and 

release of cytokines acting as chemotactic factors and 

as endogenous pyrogens. One manifestation of the 

zinc oxide mediated release of cytokines is a local 

inflammatory response in the lung. (2) The 

pulmonary macrophage, which may act in concert 

with other cells resident in the lung, is pivotal in 

response to zinc oxide fume inhalation. Elucidating 

the mechanism of zinc oxide's effect will address a 

group of illnesses representing an important clinical 

problem in occupational medicine. Furthermore, zinc 

oxide inhalation provides a useful model in which to 

study general mechanisms of cellular responses to 

inhaled toxins in the human lung together with their 

pulmonary function and systemic manifestations. 

Better understanding of these mechanisms may also 

provide the basis for therapeutic interventions aimed 

at preventing or ameliorating the effects of inhaled 

toxins. 

Methodology 

We have studied subjects who perform electric 

welding on galvanized materials. Exposures are 

carried out within a specially designed environmental 

chamber. Personal breathing zone air sampling data 

provides an assessment of the level of exposure 

experienced. We measure pulmonary function and 

airway responsiveness to methacholine at baseline and 

again 1 hour and either 6 or 20 hours following 

exposure. We then carry out bronchoscopy with 

bronchoalveolar lavage (BAL) at either 8 or 22 hours 

post exposure, analyzing cell numbers and types; and 

measuring by immunodetection the cytokines 

interleukin {IL)-1, IL-4, IL-6, IL-8 and TNF. In 

addition, we have carried out pilot in vitro studies 

with human pulmonary macrophages from normal 

subjects without zinc oxide exposure. We have 

exposed macrophages to low levels of zinc oxide in 

vitro, using titanium oxide as a negative control and 

lipopolysaccharide (LPS) as a positive control. 

Significant Findings 

We carried out 26 experimental welding 

exposures in 23 volunteer subjects, performing 

post-exposure bronchoalveolar lavage (BAL) 3 hours 

(n = 6), 8 hours (n = 11), or 22 hours (n = 9) after 

exposure. We initially analyzed the first 14 subjects. 

Subjects with the highest cumulative exposures all 

experienced typical MFF symptoms. We showed that 

overall, the changes in pulmonary function and 

reactivity at one, six and 20 hours were minimal. 

Moreover, there was no statistically significant 

correlation between cumulative zinc exposure and the 

minimal changes observed, including a 7% fall in 

DLco, the greatest change seen. Bronchoalveolar 

lavage fluid at 22 hours in the late follow-up group 

yielded numerous polymorphonuclear leukocytes with 

a strongly positive correlation between cumulative 

zinc oxide welding fume exposure and 

polymorphonuclear leukocyte concentrations both at 

8 and 22 hours follow-up. These initial data 

demonstrated that zinc oxide welding fume inhalation 
is associated with a dose-dependent, marked 

inflammatory cellular response in the lung whether or 

not clinical symptoms of metal fume fever were 

reported. We then carried out further analysis and 

have submitted for publication further analysis of 

cytokine analysis from all 26 exposures. We detected 

tumor necrosis factors (TNF), interleukin-6 (IL-6) 

and interleukin-8 (IL-8) varying in a time- and 

exposure-related manner. The concentration of TNF 

in the BAL fluid supernatant was significantly greater 

at 3 hours than at 8 or 22 hours after exposure 

(p<0.05), exhibiting a statistically significant 

exposure-response relationship to airborne zinc at 

each follow-up time period (p<0.05). TNF 

concentrations were statistically correlated with those 

of IL-6 in BAL supernatant obtained at 22 hours 

(r=0.78, p=0.01) and with concentrations of IL-8 in 

BAL 8 hours after exposure (r=0.85, p=0.001). IL-6 

displayed a significant exposure-response relationship 

to zinc (p<0.05) at 22 hours. IL-8 exhibited a 

significant exposure-response relationship to zinc 

(p<0.05) at 8 hours after exposure, a time at which 

IL-8 correlated with marked increases in BAL fluid 

polymorphonuclear leukocytes (PMNs) 

(r=0.7,p=0.01). Although we also detected 

interleukin-I (IL-1) in BAL samples, this cytokine 

did not demonstrate a statistically significant 

exposure-response. TNF, IL-6 and IL-8 in BAL 

fluid supernatant concentrations increased in a time 

and exposure-dependent fashion after zinc oxide 

welding fume exposure. The time course of 

increased cytokines, their correlations with one 

another and with PMNs in the BAL fluid, and the 

consistency of our findings with the known kinetics 

and actions of these cytokines support the hypothesis 

that a network of cytokines is involved in the 

pathogenesis of metal fume fever. 

We have also studied a "positive control" group 

consisting of exposures to moldy wood chips. This 

exposure is associated with a syndrome clinically 

similar to metal fume fever. Our studies in this area 

are preliminary, but also suggest a role for cytokines. 

In total we have studied six subjects after such 

exposures: four subjects at 22 hours follow-up; and 

one each at 3 and 8 hours. Among the 22 hour group 

we have observed a marked increase in PMN s in 

BAL; in three of these subjects control BAL without 

preceding exposure has been without any increased 

PMNs. 

Pilot in vitro exposure of human pulmonary 

macrophages has demonstrated an increase in TNF in 

supernatant media as early as three hours post 

initiation of exposure. A similar response has not 

been observed with titanium. We intend to continue 

this in vitro work, including study in other animal 

models and delineation of other cytokines relevant to 

potential interactions of interest ( cytokine 

networking). 

Occupational Lung Diseases - Page 25 

Publications 

Blanc PD, Schwartz DA: Acute Pulmonary 

Responses To Toxic Exposures. In: Textbook of 

Respiratory Medicine, 2nd edition, (eds. JF Murray, 

JA Nadel), WB Saunders, in press, 1993 

Blanc PD, Boushey HA, Wong H, Wintermeyer SF, 

Bernstein MS: Cytokines in Metal Fume Fever. Am 

Rev Respir Dis 147:134-139, 1993 

Wintermeyer SF, Wong H, Blanc PD: 

Bronchoalveolar Lavage Fluid lnterleukin-6 in 

Human Subjects Exposed To Organic Dust. Amer 

Rev Respir Dis 147:A527, 1993 

Wintermeyer SF, Wong H, Blanc PD: Lymphocyte 

Subsets in Bronchoalveolar Lavage Fluid After Zinc 

Oxide Welding Fume Inhalation in Human Subjects. 

Clin Res 41 :32A, 1993 

Blanc PD, Boushey HA: The Lung in Metal Fume 

Fever. Semin Respir Med, in press 1993 

Blanc PD, Boushey HA, Wintermeyer S, Wong H, 

Bernstein M: Bronchoalveolar Lavage Fluid Tumor 

Necrosis Factor After Zinc Oxide Fume Inhalation in 

Human Subjects. Am Rev Respir Dis 145:A795, 

1992 

Blanc PD, Boushey HA, Wintermeyer S, Wong H, 

Bernstein M: Bronchoalveolar Lavage Fluid 

Interleukin-8 After Zinc Oxide Welding Fume 

Inhalation in Human Subjects. Clin Res 40(1):67 A, 

1992 

Blanc P, Boushey HA: Metal Fume Fever: Specific 

Clues to Making the Diagnosis. J Respir Dis 

13: 15-26, 1992 

Conrad DJ, Warnock M, Blanc P, Cowan M, Golden 

JA: Microgranulomatous Aspergillosis after 

Shoveling Wood Chips. Am J Ind Med 22:411-418, 

1992 

Blanc P, Wong H, Bernstein MS, Boushey HA: An 

Experimental Model of Metal Fume Fever. 

Ann Int Med 114:930-936, 1991 
Page 26 - Occupational Lung Diseases 

Asbestos-Induced Pleural Fibrosis 

and Lung Restriction 

David A. Schwartz, MD., MP.H 

University of Iowa 

The Pulmonary Disease Division 

Department of Internal Medicine 

Room C33, GH 

Iowa City, Iowa 52242 

Program Area: Occupational Lung Diseases 

Grant Number: 5 KOJ OH00093-03 

Start & End Dates: 07/01/90 - 06/30/93 

Funding Level: $0 ($122,514 Cum) 

Importance to Occupational Safety and Health 

The overall goals of this project are to improve 

and advance the current criteria established by the 

International Labor Organization (ILO) to evaluate 

chest wall abnormalities and to understand the 

determinants of restrictive lung function in 

asbestos-induced pleural fibrosis. Together, 

circumscribed pleural plaques and diffuse pleural 

thickening are the most frequent radiographic 

abnormality among asbestos-exposed workers. The 

radiographic criteria established by the ILO to define 

and classify circumscribed pleural plaques and diffuse 

pleural thickening have not been adequately 

evaluated. Moreover, the association between pleural 

fibrosis and restrictive lung function were not 

considered when establishing these radiographic 

criteria. Although several groups have established a 

relationship between restrictive lung function and 

both circumscribed pleural plaques and diffuse pleural 

thickening, the determinants accounting for this 

association have not been adequately addressed. Our 

preliminary studies indicate that restrictive lung 

function among those with asbestos-induced pleural 

fibrosis is, in part, caused by sub radiographic 

inflammation and fibrosis of the lung parenchyma. 

These findings lead us to hypothesize that more 

sensitive indicators of parenchymal injury will allow 

us to fully understand the determinants of restrictive 

lung function in persons with asbestos-induced 

pleural fibrosis. The hypotheses put forth in this 

proposal are designed to investigate the accuracy of 

the diagnostic criteria established by the International 

Labor Organization, evaluate the anatomic and 

functional validity of these criteria, and identify the 

determinants of restrictive lung function among 

individuals with asbestos-induced pleural plaques and 

diffuse pleural thickening. 

Objectives 

1. Evaluate the anatomic and functional validity of 

the criteria established by the International Labor 

Organization to identify and classify pleural 

fibrosis and, using these findings, develop an 

improved classification system for pleural 

abnormalities. 

2. Use sensitive physiologic, radiographic, and 

biologic measures to control for the presence of 

parenchymal fibrosis while investigating the 

relationship between asbestos-induced pleural 

fibrosis and restrictive lung function. In addition, 

we will use computer-assisted methods to 

identify and quantify the extent of pleural disease 

on the CT scan. 

Methodology 

We will use a nested case-control study design 

with 120 subjects randomly selected from a large 

cohort (N=l,211) of sheet metal workers who have 

recently undergone a screening medical evaluation. 

Using chest x-rays, chest CT scans, and physiologic 

measures of lung function, we will evaluate the 

reliability and validity (anatomic and functional) of 

the current ILO criteria for pleural fibrosis. We will 

also use sensitive physiologic (progressive exercise 

ergometry and lung and chest wall compliance), 

radiographic (high resolution CT scans), and biologic 

(bronchoalveolar lavage cellularity) measures to 

control for the presence of parenchymal fibrosis 

while investigating the relationship between 

asbestos-induced pleural fibrosis and restrictive lung 

function. In addition, we will use computer-assisted 

methods to identify and quantify the extent of pleural 

and parenchymal disease on the CT scan. 

Significant Findings 

To further define the relationship between 

asbestos-induced pleural fibrosis and restrictive lung 

function, we investigated the pleural determinants of 

respiratory symptoms and restrictive physiology in 

1,211 sheet metal workers. We specifically evaluated 

the relationship between components of pleural 

fibrosis (costophrenic angle involvement, 

diaphragmatic plaques, width and length of pleural 

fibrosis, pleural calcifications, and the type of pleural 

fibrosis circumscribed pleural plaque or diffuse 

pleural thickening) and both forced vital capacity 

(FVC) and respiratory symptoms. After controlling 

for the appropriate confounding variables, we found 

that costophrenic angle involvement (p=.004), the 

width (p=.037) and length (p=.0001) of pleural 

fibrosis, and the presence of either circumscribed 

plaques (p=.0006) or diffuse pleural thickening 

(p=.0003) were each significantly associated with a 
lower forced vital capacity (FVC). No significant 

relationship was observed between FVC and either 

diaphragmatic plaques or pleural calcifications. 

However, since the pleural abnormalities are highly 

collinear, none of these abnormalities alone or in 

combination predicted the decline in FVC better than 

circumscribed plaques or diffuse pleural thickening. 

Next, we investigated the relationship of each 

component of pleural fibrosis with three respiratory 

symptoms: cough, dyspnea, and chest pain. After 

controlling for appropriate confounders, a marginally 

significant relationship was observed between 

increased width and length of pleural fibrosis and 

dyspnea. Otherwise these pleural abnormalities were 

not consistently related to any of the three respiratory 

symptoms. Our results indicate that although pleural 

plaques and diffuse pleural thickening and their 

components are independently associated with a lower 

FVC, these components of pleural fibrosis do not 

substantially improve the previously defined 

relationship between FVC and either circumscribed 

pleural plaques or diffuse pleural thickening. 

To identify the determinants of dyspnea and 

evaluate the validity of this subjective measure, we 

compared dyspnea assessments to objective measures 

of lung disease in workers exposed to asbestos. Our 

study population consisted of 78 asbestos-exposed 

workers, 23 with a normal chest radiograph (CXR), 

43 with pleural fibrosis, 27 with asbestos is, and 16 

with both pleural fibrosis and asbestos is. 

Assessments of dyspnea, by categorical 

measurements, were performed by one observer who 

was blinded to all other clinical information. 

Dyspnea classes ranged from I to V with class I 

being dyspnea at an activity level appropriate to elicit 

dyspnea in normal subjects and class V being dyspnea 

with minimal activity or at rest. Subjects had full 

pulmonary function tests (PFT), a complete 

cardiopulmonary exercise test, a measurement of lung 

compliance, a CXR, and a high resolution CT 

(HRCT) scan. In our study population 35 subjects 

had class I dyspnea, 21 subjects had class n dyspnea, 

6 subjects had class III dyspnea, 10 subjects had class 

IV dyspnea, and 6 subjects had class V dyspnea. 

Dyspnea classes were collapsed into fewer classes 

when needed to facilitate statistical analysis. PFT 

data showed significant associations between 

increases in dyspnea class and decreases in percent 

predicted total lung capacity (p=0.007), forced vital 

capacity (p=0.002), forced expiratory volume at 

1 second (p=0.002), and decreases in absolute 

maximum voluntary ventilation (MVV) (p=0.02). 

Increasing dyspnea was also found to be marginally 

associated with decreases in percent predicted 

diffusion capacity of carbon monoxide (p=0.06). 

Cardiopulmonary exercise data showed significant 

associations between increases in dyspnea class and 

both decreases in oxygen consumption per kilogram 

Occupational Lung Diseases - Page 27 

of body weight at maximum exercise (V02 Max/kg) 

(p=0.005) and increases in heart rate reserve at 

maximum exercise (p=0.02). In addition, increasing 

dyspnea was marginally associated with decreases in 

breathing reserve at maximum exercise (p=0.08). 

Decreased expiratory lung compliance at 60 percent 

of total lung capacity tended to be associated with 

increasing dyspnea (p=0.07). No consistent 

association was identified between dyspnea class and 

abnormalities on either the CXR or the HRCT scan. 

These results indicate that dyspnea is related to 

several objective measures of lung disease among 

workers exposed to asbestos. In particular, we found 

that dyspnea is associated with reduced lung volume 

and decreased exercise tolerance. These findings 

suggest that dyspnea is a valid measure of impaired 

lung function in asbestos-exposed workers. 

To assess the clinical significance of 

asbestos-induced pleural fibrosis on exercise 

physiology, we evaluated the relationship between 

radiographic evidence of pleural fibrosis and 

physiologic results from cardiopulmonary exercise 

testing in 90 asbestos-exposed subjects. A bicycle 

ergometer was used to measure the cardiac and 

pulmonary response to maximal exercise. Eight 

subjects were found to have an abnormal cardiac 

response to exercise (6 unstable blood pressure and 

2 ischemic electrocardiogram) and these individuals 

were excluded from further analysis. Of the 

remaining 82 subjects, 47 (57%) had pleural fibrosis. 

Of those with pleural fibrosis, 33 (70%) had 

circumscribed pleural plaques and 14 (30%) had 

diffuse pleural thickening involving the costophrenic 

angle. Interstitial fibrosis (ILO ~ 1/0) was present in 

40% of those with normal pleural, 39% of those with 

circumscribed pleural plaques, and 14% of those with 

diffuse pleural thickening. Pleural fibrosis was found 

to be significantly associated with older age, a lower 

baseline maximal voluntary ventilation, and a lower 

percent predicted total lung capacity. Although 

pleural fibrosis did not appear to be related to 

impaired respiratory function with exercise in our 

entire cohort, this finding was confounded by a 

higher proportion of interstitial fibrosis in subjects 

with normal pleura. In fact, among study subjects 

without asbestos is, significant decreases in gas 

exchange (higher VDNT and increased A-a 0 2 

difference) were observed at maximal exercise among 

subjects with pleural fibrosis. Interestingly, neither a 

high respiratory rate nor a lower VT/FVC ratio was 

observed among those with pleural fibrosis indicating 

that pleural fibrosis alone does not explain the 

increased VDNT. Using multi variate analyses to 

control for potential confounders (age, height, weight, 

smoking history, pack-years of smoking, and ILO 

profusion category), regression models demonstrated 

that pleural plaques and diffuse pleural thickening 

were independently associated with significant 
Page 28 - Occupational Lung Diseases 

increases in dead space ventilation (VDNT) with 

maximal exercise. These findings indicate that 

asbestos-induced pleural fibrosis is independently 

associated with decrements in gas exchange with 

maximal exercise and suggest that interstitial lung 

disease, not detected on the routine chest x-ray, may 

be responsible for this abnormal response to exercise. 

Traditional radiological methods to assess the 

extent and severity of interstitial lung disease have 

proved imprecise and unreliable. Moreover, 

considerable intra- and inter-observer variability 

exist using the ILO classification system to assess the 

interstitial changes on the chest x-ray. To improve 

the reliability of the radiographic assessment of 

interstitial lung disease, we developed and tested a 

computer assisted method to analyze the lung 

Abestos Exposed 

(n=60) 

parenchyma imaged on the high resolution CT 

(HRCT) scan. We have analyzed full chest HRCT 

scans of 60 subjects with extensive occupational 

asbestos exposure and 24 subjects with idiopathic 

pulmonary fibrosis (IPF). The images from the lung 

parenchyma were used to construct a gray scale 

histogram standardizing the density of air in the 

trachea to a value of -1000 and the column of blood 

in the aorta to a value of zero. The gray scale 

histogram in both groups of study subjects has a 

skewed, unimodal distribution. However, when 

compared to the asbestos-exposed subjects, the 

patients with IPF had a gray scale distribution that 

was shifted to the right and was flatter (lower 

kurtosis). 

IPF P Value 

(n=24) 

Gray Scale Intensity 

Mean -825.20±32.3 

Median -877.70±28.0 

Kurtosis 7.63±2.35 

Skewness 2.63±0.37 

Limiting the analysis to study subjects with 

category 1 ILO chest films, patients with IPF 

appeared to have more abnormal gray scale densities 

than those with asbestos is. However, in a multi 

variate analysis after controlling for age and cigarette 

smoking, we found that the mean and median gray 

scale density were independently related to total lung 

capacity, the concentration of eosinophils in the 

bronchoalveolar lavage fluid, the ILO category on 

chest x-ray, and the presence of moderate to severe 

dyspnea. Importantly, these factors accounted for 

65% of the variance of the mean and 63% of the 

variance of the median gray scale density. Moreover, 

once these factors were accounted for, no differences 

in gray scale measures were noted between IPF and 

asbestos is. These findings indicate that computer 

derived measures of interstitial lung disease appear to 

be clinically meaningful and may overcome the well 

documented problem of subjective radiological 

interpretation. We anticipate that this approach may 

provide useful information regarding interstitial lung 

disease which will complement the traditional 

measures currently used to assess disease extent and 

severity. 

To further assess the clinical significance of 

asbestos-induced pleural fibrosis, we used a computer 

algorithm to three-dimensionally reconstruct images 

from the high resolution computerized tomography 

-749.10±53.9 <0.001 

-811.60±53.7 <0.001 

2.56±2.01 <0.001 

1.57±0.46 <0.001 

(HRCT) scan of the chest in 60 asbestos-exposed 

study subjects. The study subjects had been 

occupationally exposed to asbestos at least 20 years 

prior to this investigation and were on average 62 

years of age. Pulmonary function tests, chest 

radiographs, and HRCT scans were performed on all 

study subjects. Thirty-five (58.3%) had pleural 

fibrosis and 19 (31. 7%) had asbestosis (ILO 2 2:': 1/0) 

identified on the chest radiograph. The volume of 

asbestos-induced pleural fibrosis was computed from 

the three-dimensional reconstruction of the HRCT 

scan and among those with pleural fibrosis identified 

on the HRCT scan (N=29), the volume of the pleural 

lesion varied from 0.5 ml to 260.4 ml or between 

0.01% and 7.11% of the total chest cavity. To assess 

the validity of these computer-derived estimates, we 

compared the computer derived estimates of 

parenchymal volume to those independently obtained 

by pulmonary function testing. Importantly, the 

three-dimensional computer-derived estimate of lung 

volume was found to be significantly associated with 

the independent measurement of total lung capacity 

(r=.46; P=0.0001). To investigate the relationship 

between asbestos induced pleural fibrosis and 

restrictive lung function, we compared the 

computer-derived estimate of pleural fibrosis to the 

total lung capacity and found that these measures 

were inversely related (r=-.40; P=0.002). After 
controlling for age, height, pack-years of cigarette 

smoking, and the presence of interstitial fibrosis on 

the chest radiograph, the volume of pleural fibrosis 

identified on the three-dimensional reconstructed 

image from the HRCT scan was inversely associated 

with the total lung capacity (P=0.03) and 

independently accounted for 9.5% of the variance of 

this measure of lung volume. These findings further 

extend the scientific data supporting an independent 

association between pleural fibrosis and restrictive 

lung function. 

To prospectively identify the determinants of 

progressive loss of lung function among workers 

occupationally exposed to asbestos and assess the 

relative contribution of cigarette smoking, 

asbestos-induced pleural fibrosis, and findings from 

bronchoalveolar lavage and the high resolution CT 

scan, we examined the determinants of lung function 

changes in 117 subjects occupationally exposed to 

asbestos. All subjects had been occupationally 

exposed to asbestos for at least one year in a high 

exposure setting and a minimum of 20 years was 

required between the first exposure to asbestos and 

entry into the study. Baseline studies included an 

independent assessment of dyspnea, lung volumes, 

diffusing capacity of carbon monoxide (Dlc0 ), a chest 

radiograph, a high resolution CT (HRCT) scan, and 

bronchoalveolar lavage. Our subjects were observed 

for an average of two years (range 0.5 years to 4.0 

years) and lung function was measured on at least 

two separate occasions (mean=4.1 separate tests). 

During the period of observation, there was an 

average 1.5% decrease (range=loss of 27% to an 

increase of 39%) in the total lung capacity (TLC) and 

a 2.5% decrease (range=loss of 30% to an increase of 

39%) in the diffusing capacity of carbon monoxide 

(Dlc0 ). After controlling for age, height, pack-years 

of cigarette smoking, and follow-up time, 

longitudinal declines in TLC were independently 

related to moderate to severe dyspnea (P=0.005), 

diffuse pleural thickening (P=0.007), and higher 

concentrations of fibronectin in the BAL fluid 

(P=O.O I). Interestingly, interstitial lung disease either 

on the chest radiograph or HRCT scan was not 

independently associated with longitudinal changes in 

TLC. After controlling for age, height, and 

follow-up time, longitudinal declines in Dlco were 

independently related to moderate to severe dyspnea 

(P=0.006), increased pack-years of cigarette smoking 

(P=0.00001), honeycombing on HRCT scan 

(P=0.0009), and higher concentrations oflymphocytes 

(P=0.0008), neutrophils (P=0.0005), eosinophils 

(P=0.03), and fibronectin (P=0.02) in the BAL fluid. 

These results indicate that among asbestos-exposed 

subjects, prognostically important risk factors include 

symptoms of dyspnea, cigarette smoking, diffuse 

pleural thickening, honeycombing on HRCT scan, and 

higher concentrations of inflammatory cells and 

Occupational Lung Diseases - Page 29 

fibronectin in the BAL fluid. Moreover, these risk 

factors could be used to identify high risk 

asbestos-exposed workers who would be ideal 

candidates for innovative, disease modifying drug 

regimens. 

Publications 

Hartley PG, Galvin JR, Hunninghake GW, Merchant 

JA, Yagla SJ, Speakman SB, Schwartz DA: High 

Resolution CT-derived Measures of Lung Density 

Are A Valid Index of Interstitial Lung Disease. 

J App Physiol, in press, 1993 

Shih JF, Wilson JS, Broderick A, Watt JL, Galvin JR, 

Merchant JA, Schwartz DA: Asbestos-Induced 

Pleural Fibrosis and Impaired Exercise Physiology. 

Chest, in press, 1993 

Schwartz DA, Helmers RA, Galvin JR, Van Fossen 

DS, Frees KL, Dayton CS, Burmeister LF, 

Hunninghake GW: Determinants of Survival in 

Idiopathic Pulmonary Fibrosis. Am Rev Respir Dis, 

in press, 1993 

Blanc PD, Schwartz DA: Acute Pulmonary Response 

to Toxic Exposure. In: Textbook of Respiratory 

Medicine, (eds. JF Murray, JA Nadel), W.B. 

Saunders Co., Philadelphia, in press, 1993 

Schwartz DA: Chemical Injury to the Lung. In: 

Textbook of Clinical Occupational and Environmental 

Medicine, (eds. L Rosenstock, M Cullen), W.B. 

Saunders Co., Philadelphia, in press, 1993 

Clapp WD, Thome PS, Frees KL, Zhang X, Lux CR, 

Schwartz DA: The Acute Effects of Inhalation of 

Grain Dust Extract and Endotoxin on Upper and 

Lower Airways. Chest 104:825-830, 1993 

Schwartz DA, Redlich CA: 

Occupational Lung Disease. 

14:167-180, 1993 

Biomarkers in 

Sem Respir Med 

Schwartz DA, Galvin JR, Frees KL, Dayton CS, 

Burmeister LF, Merchant JA, Hunninghake GW: 

The Clinical Relevance of Cellular Mediators of 

Inflammation in Workers Exposed to Asbestos. Am 

Rev Respir Dis 148:68-74, 1993 

Shih JF, Hunninghake GW, Goeken NE, Galvin JR, 

Merchant JA, Schwartz DA: The Relationship 

Between HLA-A, B, DR Antigens and 

Asbestos-induced Lung Disease. Chest 104:26-31, 

1993 

Schwartz DA, Galvin JR, Yagla SJ, Speakman SB, 

Merchant JA, Hunninghake GW: Restrictive Lung 
Page 30 - Occupational Lung Diseases 

Function and Asbestos-induced Pleural Fibrosis: A 

Quantitative Approach. J Clin Invest 91 :2685-2692, 

1993 

Pueringer RJ, Schwartz DA, Dayton CS, Gilbert SR, 

Hunninghake GW: The Relationship Between 

Alveolar Macrophage TNF, IL-1, and PG.Ei Release, 

Alveolitis, and Disease Severity in Sarcoidosis. 

Chest, in press, 1992 

Dayton CS, Schwartz DA, Helmers RA, Pueringer 

RJ, Gilbert SR, Merchant RK, Hunninghake GW: 

Outcome of Subjects with Idiopathic Pulmonary 

Fibrosis Who Fail Corticosteroid Therapy -

Implications for Further Studies. Chest, in press, 

1992 

Kline JN, schwartz DA, Monick MM, Floerchinger 

CS, Hunninghake GW: Relative Release of IL-lb 

and IL-IRA by Alveolar Macrophages in 

Asbestos-induced Lung Disease, Sarcoidosis, and 

Idiopathic Pulmonary Fibrosis. Chest, in press, 1992 

Schwartz DA, Landas SK, 

Hunninghake GW, Merchant JA: 

Swine Confinement Workers. 

116:630-635, 1992 

Burmeister LF, 

Airway Injury in 

Ann Intern Med 

Schwartz DA, Galvin JR, Dayton CS, Merchant JA, 

Hunninghake GW: The Influence of Cigarette 

Smoking on Bronchoalveolar Lavage Cellularity in 

Asbestos-induced Lung Disease. Am Rev Respir Dis 

145:400-405, 1992 

Broderick A, Fuortes LJ, Merchant JA, Galvin JR, 

Schwartz DA: The Pleural Determinants of 

Restrictive Lung Function and Respiratory Symptoms 

in an Asbestos-exposed Population. Chest 

101:684-691, 1992 

Schmidt LE, Thorne PS, Watt JL, Schwartz DA: Is 

an Abbreviated Bronchial Challenge with Histamine 

Valid? Chest 101:141-145, 1992 

Merchant RK, Schwartz DA, Helmers RA, 

Dayton CS, Hunninghake GW: Bronchoalveolar 

Lavage Cellularity: The Distribution in Normal 

Volunteers. Am Rev Respir Dis 146:448-453, 1992 

Hempel SL, Schwartz DA, Hunninghake GW: The 

Mast Cell and Idiopathic Pulmonary Fibrosis. Mayo 

Clin Proc 67:1009-1010, 19.92 

Broderick A, Schwartz DA: Halogen Gases, 

Ammonia, and Phosgene. In: Medical Toxicology of 

Hazardous Materials, (ed. JB Sullivan, Jr.), Williams 

& Wilkins, Baltimore, pp. 791-796, 1992 

Merchant JA, Schwartz DA: Classification of the 

Chest Radiograph and CT Scan for the 

Pneumoconioses. In: Environmental and 

Occupational Medicine, (ed. W Rom), Little, Brown, 

Boston, MA, pp. 215-225, 1992 

Schwartz DA: Effects of Dusts, Fumes, and Other 

Inhaled Substances. In: Foundations of Respiratory 

Care, (eds. DJ Pierson, CV Spearman, RM 

Kacmarek), Churchill Livingstone, Inc., pp. 365-369, 

1992 

Schwartz DA: Effects of Smoking on the 

Cardiorespiratory System. In: Foundations of 

Respiratory Care, ( eds. DJ Pierson, CV Spearman, 

RM Kacmarek), Churchill Livingstone, Inc., pp. 

359-364, 1992 

Schwartz DA: Asbestos-induced Lung Disease: A 

Model Approach to Pneumonoconioses. Immunology 

and Allergy Clinics of North America, (ed. EJ 

Bardana, Jr.), W.B. Saunders Co., Philadelphia, 

12:847-859, 1992 

Merchant JA, Schwartz DA: Occupational 

Parenchymal Disease. In: Textbook of Internal 

Medicine, (ed. WN Kelley), J.B. Lippincott Co., 

Philadelphia, pp. 1753-1759, 1992 

Schwartz DA: The Clinical Relevance of 

Asbestos-Induced Pleural Fibrosis. Ann N Y Acad 

Sci 643:169-177, 1991 

Landas SK, Schwartz DA: Mica-associated 

Pulmonary Interstitial Fibrosis: A Case Report. 

Am Rev Respir Dis 144:718-721, 1991 

Schwartz DA, Dayton CS, Hunninghake GW: The 

Clinical Utility and Reliability of Asbestos Bodies in 

Bronchoalveolar Fluid. Am Rev Respir Dis 

144:684-688, 1991 

Schwartz DA, Helmers RA, Dayton CS, Merchant 

RK, Hunninghake GW: Determinants of 

Bronchoaveolar Lavage Cellularity in Idiopathic 

Pulmonary Fibrosis. J Appl Physio 

71(5):1688-1693, 1991 

Schwartz DA, Merchant RK, Helmers RA, 

Gilbert SR, Dayton CS, Hunninghake GW: The 

Influence of Cigarette Smoking on Lung Function in 

Patients With Idiopathic Pulmonary Fibrosis. 

Am Rev Respir Dis 144:504-506, 1991 

Schwartz DA: 

Asbestos-Induced 

99:191-198, 1991 

New 

Pleural 

Developments in 

Disease. Chest 
Grain Dust Exposure: Physiologic 

& Biologic Correlates 

William D. Clapp, MD. 

University of Iowa 

College of Medicine 

Department of Internal Medicine 

200 Hawkins Drive 

Iowa City, Iowa 52242-1081 

Program Area: Occupational Lung Di;eases 

Grant Number: 1 KOJ OH00134-0l 

Start & End Dates: 08/01/93 - 07/31/96 

Funding Level: $54,000 ($54,000 Cum) 

Importance to Occupational Safety and Health 

Inhalation of grain dust is associated with acute 

and chronic airflow limitation, as well as 

inflammation of the lower respiratory tract. There 

are a large number of workers who are exposed to 

levels of grain dust that are considered to be harmful. 

Furthermore, there is evidence that a variety of host 

factors such as atopy, asthma, ethnic background, age, 

and smoking, modulate the physiologic (airflow) 

response to inhalation of grain dust. Little work has 

been done investigating the inflammatory response. 

By characterizing the physiologic as well as the 

inflammatory responses further, insight will be gained 

into the extent to which these host factors modulate 

the response to inhaled grain dust. Furthermore, the 

effects of a variety of interventions (physical 

manipulation of the environment to pharmacologic 

methods) can be explored. In this way, groups of 

workers at greater or lesser risk for disease, as well 

as preventive measures can be defined. 

Objectives 

l. Inhalation of aqueous grain dust extract causes 

inflammation primarily localized to the airways, 

and is associated with airflow obstruction. 

2. Host factors, such as age, ethnic background, 

gender, atopic status, asthma, and cigarette 

smoking modulate the duration, intensity and 

severity of these effects. 

3. Repeated exposure results in physiologic and 

biologic tolerance occurring within days of onset 

of exposure. This tolerance is modulated by one 

or several host factors which will be investigated 

in objective 2 above. 

Occupational Lung Diseases - Page 31 

Methodology 

Using aqueous extracts of grain dust, subjects will 

undergo inhalation challenge followed by pulmonary 

function testing to assess the physiologic effects of 

the inhalation of the extract, then bronchoscopy, to 

collect specimens from the airways and alveoli for 

examination of the inflammatory response. 

Specimens will be evaluated at the cellular, 

biochemical and molecular level, to find sensitive and 

specific markers of inflammation that can be used to 

characterize the inflammatory response. Subjects 

endowed with different host factors will then be 

tested and compared to control subjects. The 

presence of tolerance will be assessed using repeated 

inhalation challenge. 

Significant Findings 

None to date. 

Radon, Bronchial Morphometry, and 

Occupational Health 

David J. Brenner, Ph.D. 

Columbia University 

Center for Radiological Research 

630 West 168th Street 

New York, New York 10032 

Program Area: Occupational Lung Diseases 

Grant Number: 5 R03 OH02931-02 

Start & End Dates: 01/01/92 - 12/31/93 

Funding Level: $24,083 ($47, 769 Cum) 

Importance to Occupational Safety and Health 

The hazards of occupational exposure to radon 

daughters relative to environmental exposure is 

significant both for occupational and environmental 

health. Much attention has been paid to relative 

physical factors (bronchial epithelial dose/WLM) in 

the two situations, but almost no attention to the 

relative biological factors (risk/unit bronchial dose in 

miners vs. general public). These biological 

differences arise because of the (average) thicker 

mucosa! layers in the 70% of miners who smoke, 

compared to the - 70% of the general public who do 

not smoke. Preliminary calculations for a single 

biological endpoint suggest that this biological factor 

may differ by about a factor of two between miners 

and the general public, which would be larger than 
Page 32 - Occupational Lung Diseases 

any physical differences in dose per unit WLM 

exposure. 

Objectives 

The aim of this small grant pilot study is to 

produce evaluations of the relative biological hazards 

of radon daughters per unit lung dose, for pertinent 

biological endpoints, for miners vs. 

envirommentally-exposed home residents. 

Methodology 

In particular, it is proposed to (1) analyze 

previously-collected biological data to quantify how 

the relative biological hazard varies with LET (Linear 

Energy Transfer, or stopping pow or, dE/dx) and its 

microdosimetric correlate, lineal energy. Only 

biological measurements pertinent to risk estimation, 

namely oncogenic transformation, mutation, and 

chromosomal damage, will be considered; (2) use 

Monte-Carlo simulation of alpha-particle transport 

together with the best available data on mucosal and 

epithelial thicknesses in smokers and nonsmokers, to 

estimate the energy deposition characteristics of the 

radon-daughter alpha particles in the cells at risk in 

the bronchial epithelia of miners and the general 

public; (3) combine the data from (1) and (2) to 

obtain relative biological risk factors for occupational 

miners and the general public. 

Significant Findings 

A large body of new biophysical data, measured 

in our laboratory using the C3H10Tl/2 in vitro 

oncogenic transformation system, has been analyzed. 

This new data set is by far the most complete 

quantitative data set for an oncogenic transformation 

end point, as a function of LET and dose, currently 

available. The data consist of results at 12 LET Is 

varying from 3 to 475 keV/micron, and an average of 

8 low-dose points per LET. The lower curve in the 

Figure shows the resulting quality factor for radon 

daughters, as a function of depth from the 

radon-daughter sources, in the bronchial epithelium. 

We have drawn the following conclusions from 

the analysis of these data: 

1. The quality factor for radon is less than the 

values of 20-30 suggested by the ICRU and 

ICRP. This is because many of the energy 

depositions are taking place in the alpha-particle 

energy region where the biological effect is 

saturating, i.e. there is an "overkill" 

phenomenon. 

2. Specifically, if target cells are distributed 

throughout the whole bronchial epithelium, the 

doseweighted quality factor (biological weighting 

factor) would be about 15. If, on the other hand, 

the target cells are only basal cells, the mean 

quality factor would be 50% less, i.e. around 11. 

3. If miners have an extra mucosal layer of - 20 

microns in depth, and the target cells are basal 

cells, the quality factor would be expected to be 

around 9. 

The importance of these biological weighting 

factors is that they provide the link between radon 

risk estimates obtained from analysis of survivors at 

Hiroshima and Nagasaki, with risk estimates obtained 

from miner studies. When quality factors of 

-20-30 have been applied to A-bomb based risk 

estimates, the resulting risk estimates have been 

inconsistent with (higher than) those derived from 

miners. A basis for lower quality factors, provided 

here, would therefore tend to reconcile radon risk 

estimates from the two disparate sources. 

30.o ....... --------------, 

1-4 

0 

] 

:;rx. 

1-4 ~ 20.0 o .... ........ 

t) .cl :.~ Q) 

::::: 

~ ':j 11 0 10.0 

;:I .... O]I 

o .. .... 

IXI 

---------------- Q ,, ICRU ',, /1 

' I l ' I 

I 

I 

I 

I 

! 

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0.0 

Publications 

25.0 50.0 

Deoth (um) 

75.1 

Brenner DJ: The Significance of Dose Rate in 

Assessing the Hazards of Domestic Radon Exposure. 

Health Physics, accepted, 1993 

Brenner DJ, Hall EJ, Randers-Pehrson G, Miller RC: 

Model Considerations on the Dose-Rate/LET 

Dependence of Oncogenic Transformation by 

Charged Particles. Radiation Research 

133:3365-369, 1993 
Protein Damage Caused By 

Occupational Toxicants 

Randal J. Keller, Ph.D. 

University of Arkansas 

UAMS Division of & Toxicology 

4301 W Markham, MS 638 

Little Rock, Arkansas 72205 

Program Area: Occupational Lung Diseases 

Grant Number: 1 R03 OH03061-0l 

Start & End Dates: 06/01/93 - 05/31/95 

Funding Level: $34,640 ($34,640 Cum) 

Importance to Occupational Safety and Health 

Occupational toxicants are potentially capable of 

producing free radicals in biological systems which 

can lead to oxidative stress. There are numerous 

oxidants encountered in occupational environments 

which may lead to this damage. These include 

metals, pesticides, volatile organic compounds, ozone, 

and components of environmental tobacco smoke. 

One technique which is useful in the assessment of 

oxidative stress is the monitoring of protein oxidation. 

Oxidative damage to proteins has been shown to 

result in increased protein turnover, decreased 

enzymatic function, and has been associated with a 

number of pathological processes, including 

emphysema, atherosclerosis, and neurological 

diseases. 

We are utilizing protein oxidation as a biomarker 

for oxidant exposure. Levels of oxidized proteins 

are increased during conditions of oxidative stress, as 

occurs from occupational exposure to toxicants. This 

project addresses a significant gap in the literature 

because there are currently no antibody techniques 

available for the study of protein oxidation. This 

project will develop a method to selectively analyze 

oxidized proteins in a complex mixture of oxidized 

and non-oxidized proteins, and to assess oxidative 

stress in a reliable and noninvasive manner. The 

development of a sensitive measure of protein 

oxidation using polyclonal antibody techniques will be 

a major addition to the area of oxidative damage. 

This will be particularly important in the area of 

occupational exposure, due to the long _P~t~ntial 

exposure times to oxidants and the suscepttbtl~ty of 

lung to oxidant damage. The polyclonal antibody 

technique will be a powerful tool which will have 

tremendous applicability in exposure assessment. 

This project will provide information that may lead to 

development of a simple, inexpensive immunoassay 

Occupational Lung Diseases - Page 33 

that can be utilized to monitor the effects of exposure 

to oxidants in occupational environments. 

Objectives 

This project examines the hypothesis that certain 

occupational toxicants are capable of causing tissue 

damage by oxidatively modifying proteins and that 

these oxidized proteins can be detected using 

polyclonal antibody techniques to provide a measure 

of exposure assessment. The research plan includes 

the following two objectives: 

Objective I. To develop an immunochemical assay 

to detect oxidative protein damage using a polyclonal 

antibody assay and validate the assay by direct 

comparison with the established spectrophotomtric teclmiques. 

Objective 2. To test the utility of the immunoassay 

to detect oxidized proteins in animals exposed to 

oxidants found in occupational environments. 

Methodology 

These experiments to complete objective I will 

directly compare the spectrophotometric 

2,4-dinitrophenylhydrazine technique with the 

polyclonal antibody technique. Purified protein 

preparations and tissue fractions will be oxidized 

using three in vitro free radical generating systems. 

These include exposing the proteins to radiation 

damage, metal-ion-catalyzed free radical damage, 

and to an enzymatic free radical generating system 

consisting of xanthine/xanthine oxidase. In addition 

to validating the assay, we will determine a 

quantitative assessment of the sensitivity of the 

technique. Carbonyl content will be determined 

spectrophotometrically by reaction with 

2,4-dinitrophenylhydrazine and subsequent 

absorbance determination. 

An immunochemical assay will be developed to 

detect proteins oxidized by chemicals found in 

occupational environments. The general principle of 

the assay is similar to the spectrophotometric method 

for the detection of oxidized proteins except the 

dinitrophenol group will be detected using an specific 

antibody. Briefly, proteins from tissue homogenates 

or fractions will be separated using SDS/PAGE then 

transferred to nitrocellulose paper (Western blot). 

The separated proteins will be treated with 

2,4-dinitrophenylhydrazine. The nitrocellulose ~s 

immunochemically stained with polyclonal rabbit 

anti-dinitrophenol, and the staining intensity detected 

using an alkaline phosphatase based detection system 

or a system based on enhanced chemiluminescence. 

The experiments in objective 2 will test the utility 

of the immunoassay to detect oxidized proteins in 

animals exposed to oxidants found in occupational 
Page 34 - Occupational Lung Diseases 

environments, and we will use the model lung 

toxicant paraquat. We will determine both dose 

dependent and time course of carbonyl formation 

in vivo. 

Significant Findings 

We have successfully developed the 

immunochemical assay for the detection of carbonyl 

groups generated by in vitro methods on purified 

proteins. The technique has been shown to be 

significantly more sensitive than the 

spectrophotometric method. 

Role of Worksite-Associated 

Vanadium in lmmunomodulation 

Mitchell D. Cohen, Ph.D. 

New York University 

School of Medicine 

Department of Environmental Medicine 

Long Meadow Road 

Tuxedo, New York I 0987 

Program Area: Occupational Lung Diseases 

Grant Number: I R03 OH03064-0I 

Start & End Dates: 05/01/93 - 04/30/95 

Funding Level: $36,905 ($36,905 Cum) 

Importance to Occupational Safety and Health 

The knowledge gained from the proposed studies, 

while helping overall to clarify the mechanisms of 

vanadium-inducedimmunomodulation, will ultimately 

contribute to the determination (or revision) of 

minimal acceptable exposure levels for vanadium in 

the workplace. As macrophages represent the 

primary mediators of pulmonary immunocompetence, 

the mechanisms by which this particular pollutant (in 

both a soluble and insoluble form) alters macrophage 

biochemistry with respect to immunoregulating 

cytokines may also provide a model by which other 

potential workplace toxicants act in exposed workers. 

By defining the possible mechanism(s) by which 

immune responses can be affected by workplace 

contaminants, such as the vanadium oxides, more 

accurate assessments of their potential immunotoxicity 

can be made and proper steps can be taken to 

minimize the risk from exposure. 

Objectives 

Several epidemiological studies and our previous 

in vivo laboratory studies have indicated a marked 

increase in host susceptibility to bacterial/viral 

diseases after vanadium exposure. Our earlier work 

determined that following host exposure to vanadium, 

there is a failure in the ability of resident 

macrophages to become fully activated for 

participation in host antibacterial responses. We 

hypothesized that this reduction in the macrophage 

capacity to become fully activated is, in part, a result 

of altered macrophage production, binding, and/or 

processing of autocrine/lymphokine interferons (IFNa 

and y). The specific aims of this project are: (1) to 

assess the levels of inducible IFNa and IFNy 

produced by pulmonary macrophages (PAM) (and 

other lung accessory cells) found in the intact rat lung 

after inhalation of occupationally-relevant 

concentrations of vanadium (in soluble and insoluble 

forms), (2) to determine whether inhaled vanadium 

alters PAM surface IFN receptor expression and/or 

IFN binding, the intracellular delivery and subsequent 

dissociation of the receptor-IFN complex, and/or the 

recycling/de nova synthesis of surface IFN receptors, 

and (3) to relate any changes in these measured 

parameters to overall changes in PAM responsiveness 

to exogenous IFN, i.e., IFN-induced expression of 

Class II MHC surface antigens and enhanced 

production of reactive oxygen intermediates. 

Methodology 

Male Fisher 344 rats are exposed (nose-only) to 

atmospheres containing either soluble ammonium 

metavanadate (NH4 V03) or insoluble vanadium 

pentoxide (V 20 5) at concentrations found in work 

environments where vanadium levels are at OSHA 

permissible levels (0.05 mg V20/m3). Control rats 

receive either air only or inert latex particles of the 

same mass median diameter as the 

vanadium-generated particles. Respirable/penetrable 

( < 1 μm) V 20 5 atmospheres are generated using a 

Wright dust feeder, while soluble NH4V03 

atmospheres are generated with a Laskin aerosolizer. 

All rats are exposed for 8 hr/day for 4 days in order 

to approximate the maximal levels of exposure 

encountered by workers in an average workweek. 

One day after the final exposure, the rats are either 

inoculated intranasally with viable Sendai virus to 

induce IFN production, or sacrificed and the lung 

macrophages harvested (by serial lavage) for use in 

all IFN binding/processing/responsiveness 

experiments. 

IFN analyses: All harvested IFN (IFNa, 13, y 

mixture) are separated from one another by chemical/ 

physical removal prior to quantitation in a viral 
cytotox1c1ty reduction assay using rat kidney 

fibroblast cells. 

IFN Receptor Binding and Expression: To 

assess the levels and strengths of IFN receptor 

binding, radioiodinated IFN is used in both a 

saturation and competitive binding study with the 

harvested PAM. Scatchard analyses are used to 

estimate both the strength of binding (K.J) and the 

relative numbers of surface receptors present on the 

target cells. To more accurately assess IFN receptor 

expression, FACS analyses of the cells tagged with 

FITC-labeled anti-JPN-receptor monoclonal 

antibodies is performed. 

Receptor Internalization, IFN Release and 

Degradation: The kinetics of IFN-receptor complex 

internalization are determined using selective 

stripping of the non-internalized complexes from the 

surface of the PAM. To monitor changes in the 

release of the internalized IFN from its receptor 

complex, the cells are lysed at fixed intervals and the 

receptor proteins collected by immunoprecipitation. 

Subsequent separation over PAGE gels and analysis 

by differential densitometry allows determination of 

the disappearance of signal from the complex band, 

a measure of complex dissociation. To assess the 

status of the intracellular IFN, the lysate proteins are 

separated without prior modifications over PAGE gels 

and analyzed by autoradiography. The signal at the 

region for free IFN is measured (after accounting for 

the appearance of newly-released IFN by accounting 

for total free IFN and complex signals) and the 

kinetics of IFN breakdown determined. 

Receptor Recycling/Synthesis: PAM are treated 

with unlabeled IFN to induce maximal receptor 

expression and internalization. After stripping the 

surface of remaining complexes or unused receptors, 

half of the PAM are treated with cycloheximide to 

block de novo receptor synthesis. All cells are then 

incubated with radiolabeled IFN and harvested at 

fixed intervals to monitor IFN binding. The relative 

increases in binding by cycloheximide-treated cells 

are indicative of receptor recycling, while in 

untreated cells, the degree of binding above that 

accounted for by recycling are indicative of de novo 

synthesis. 

IFN-lnducibleResponses: PAM are treated with 

IFN for periods up to 48 hr and then analyzed by 

FACS for expression of Class II MHC antigens using 

standard protocols with anti-rat Class II antibodies. 

Reactive oxygen intermediate (i.e., superoxide anion 

and hydrogen peroxide) formation by IFN-treated 

macrophages are assessed using spectrophotometric 

measurements of the reduction of ferricytochrome c 

and the oxidation of phenol red by horseradish 

peroxidase, respectively. 

Occupational Lung Diseases - Page 35 

Significant Findings 

Difficulties with the proposed exposure system 

forced a redesign. The fully-functional 

newly-designed nose-only exposure system has been 

completed and, following quality assurance testing of 

sample delivery, initial exposures are now underway. 

In addition to the proposed endpoints, all tissues from 

the exposed rats will now be processed by our 

departmental histopathology core for determination of 

physical changes within the lung environment 

following vanadium exposures; attempts will be made 

to correlate any hystological changes with functional 

changes. Furthermore, a recently-developed rat lung 

macrophage line (NR8313.1) is currently being 

exposed to both vanadium compounds in order to 

provide possible correlative data for the information 

obtained in the in vivo studies. 
Page 36 - Musculoskeletal Injuries 

Development of Models to Predict 

Optimal Lifting Motion 

Mohamed M Ayoub, Ph.D. 

Texas Tech University 

Department of Industrial Engineering 

Mail Stop 3061 

Lubbock, Texas 79409 

Program Area: Musculoskeletal Injuries 

Grant Number: 5 ROI OH02434-05 

Start & End Dates: 01/01/88 - 04/30/95 

Funding Level: $76,357 ($354,531 Cum) 

Importance to Occupational Safety and Health 

Back injuries due to manual lifting are a serious 

problem in terms of human suffering and cost. An 

ergonomic approach to solve the problem is to 

redesign the lifting tasks to better fit human 

capabilities. Thus, biomechanical models serves a 

very useful purpose in analyzing the human motion 

patterns and estimating the stresses on the 

musculoskeletal system especially the lumbar spine. 

With the development of simulation lifting models, it 

is possible to provide an indirect means of 

performing the biomechanical analysis without 

collecting the displacement-time information. The 

model predicts the motion pattern based on the 

specified characteristics of anthropometry, of work 

station, and of lifting task, using optimization 

techniques. 

Objectives 

The goal of this study is to develop a 

biomechanical simulation model which can predict 

displacement time information for five selected joints 

during manual lifting. The six selected joints are 

wrist, elbow, shoulder, hip, knee, and ankle. 

Methodology 

To accomplish the objective, there are three 

general tasks to be undertaken. The first task is to 

generate the possible posture assumed by the joints at 

each time frame during the lifting course. The 

second task is to evaluate the kinematics and kinetics 

of the lifting generated from the first task. Within 

the two-dimensional space defined by the 

ankle-origin coordinate system, the lifting motion 

from the starting posture to the ending posture is 

computed and mathematically described. The third 

task is to improve the lifting motion by minimizing 

an objective function. By considering that different 

lifting motion patterns have different objective 

function values, the smallest objective function value 

within the feasible operation region indicates the best 

lifting motion pattern. 

Significant Findings 

The predictions and the actual displacement-time 

information were compared by closeness (average of 

the sum of squares of errors) and trend (average of 

the disconcordant pairs). The model, considering 

both kinematic and kinetic capabilities, provides 

promising results. In general, the envelope formed 

by the predicted motion patterns overlapped with the 

envelope formed by the actual motion patterns. In 

addition to the displacement-time plot comparison, 

model analyses were also carried out by comparing 

the box and joint trajectories using stick diagram and 

animated stick motion. Close examination of the 

predicted trajectory of the box revealed that in some 

cases the box penetrated through the table. Analyses 

using data collected on trained subjects showed a 

significant decreasing trend in the objective function 

during the training period, which was indicative of 

the optimization hypothesis of the model. Overall, 

the analyses showed: 

1. The prediction of the box and joint trajectories 

may violate physical constraints such as object 

avoidance. New constraints are being developed 

and evaluated to allow the model to better 

describe the motion responsible for object 

avoidance during the lifting course. 

2. Phase relationships, evaluated by the 

disconcordant pairs, can be found in the 

displacement-time plot comparisons. In most 

cases, actual displacement arose faster than the 

prediction in the early stage of the lift. The 

animated stick motion also showed that the model 

lagged behind the actual lift at the beginning of 

the lift. 

3. Training data showed that the decreasing trend in 

objective function was primarily due t o t h e 

decrease in total lifting time. This may have 

important implication in accounting for the lag of 

the prediction as described in 2. 

Publications 

Bernard TM, Lin CJ, Ayoub MM, Hsiang MS: 

Predicting the Optimal Lifting Motions Through 

Simulation, Proc of the M.M. Ayoub Occupational 

Ergonomics Symposium, pp 97-100, 

April 16-1 7, 1993 

Ayoub MM, Blair EL, Hsiang S, Chinnam B: 

Biomechanical Simulation of Lifting. Proc of the 
11th Congress of the International Ergonomics 

Association, Paris, pp 63-65, 1991 

Ayoub MM, Blair EL: From Biomechanical 

Modelling to Biomechanical Simulation. Proc of 

Human-Centered Design Technology for 

Maintainability Workshop. Air Force Human 

Resources Laboratory, Wright-Patterson Air Force 

Base, Ohio, September 13, 1990 

Lee YH: Toward Electronic Work Design. Proc of 

Human Factors Society, 32nd Annual Meeting, 

Volume 1, pp 622-626, 1988 

Cumulative Trauma Disorder: 

Skeletal Muscle Dysfunction 

William T. Stauber, Ph.D. 

West Virginia University 

School of Medicine 

Department of Physiology 

P.O. Box 9229 

Morgantown, West Virginia 26506-9229 

Program Area: Musculoskeletal Injures 

Grant Number: 5 ROI OH02918-02 

Start & End Dates: 01/01/92 - 12131/94 

Funding Level: $125,972 ($267,057 Cum) 

Importance to Occupational Safety and Health 

Chronic pain ongmating from the 

musculoskeletal system is a dominant cause of 

sick-leave in modem industry and can be very 

disabling and troublesome for the individual. The 

cause of this problem as it originates in skeletal 

muscle is unknown. However, one of the most 

common situations in which muscle pain is 

experienced is the cumulative trauma disorder (CTD) 

which results from repeated movements. One aspect 

of repeated movements is the necessity for muscles to 

decelerate the body or moving body part by eccentric 

muscle actions. During eccentric muscle actions, 

muscles act as shock absorbers and absorb strain 

energy. It is during these shock absorption activities 

that strain injuries occur. We have developed a 

laboratory model for repeated strain injury in order 

to study the tissue response and adaptation of muscles 

subjected to repeated strains. From our initial 

studies, it was apparent that the overall size of the 

muscles becomes larger but the individual 

components are smaller - perhaps in an attempt to 

distribute the strain over a greater number of 

Musculoskeletal Injuries - Page 37 

functional units. However, this response seems to be 

dependent on the rate of strain. In addition, the 

non-muscle tissue of some of these strained muscles 

proliferates as one might see in scar tissue or 

dystrophy. This additional non-muscle tissue may: 

(1) alter the action of muscles as motors decreasing 

their force or ability to shorten at maximal speeds; 

(2) decrease their compliance causing connecting 

structures (e.g., fascia, ligaments, tendons) to be 

injured. Therefore, the development and 

characterization of a rodent model of repeated strain 

injury is necessary for the understanding of the 

physiology or pathophysiology of cumulative trauma 

disorder in order to develop preventative strategies. 

Objectives 

The proposed experiments are designed to 

develop a reproducible technique for producing 

chronic overload injury to rat skeletal muscles as a 

model for cumulative trauma disorder (CTD) and to 

understand the functional outcome of repeated 

microtrauma in order to develop strategies and 

programs for its prevention. The objectives of the 

study are: (1) to design and build a rodent 

dynamometer which will control the velocity and 

range of movement of the rat foot during a strain 

overload and to test the functional outcome in terms 

of muscle strength, endurance, and stiffness in vivo; 

(2) to document changes in the extracellular matrix 

(ECM) and sarcolemma of skeletal muscles which 

could lead to microfibrosis, restricted movement or 

impaired nutrient flow through the interstitial space 

using morphological and immunochemical analysis; 

(3) to characterize the cellular responses of muscle 

and non-muscle cells following repeated injury in 

order to understand if the adaptation seen following 

repeated microtrauma is functional (regeneration and 

repair) or dysfunctional (fibrosis with myofiber 

atrophy); (4) to determine the parameters most 

critical to injury production such as velocity of strain, 

nature of loading (duration), magnitude of force, 

frequency of injury and rest periods; 5) to develop 

immunohistochemical markers for myofiber injury 

and repair. 

Methodology 

Cumulative microtrauma is administered three 

times a week for four weeks using our newly 

constructed rodent dynamometer to one leg of female 

rats. Muscle weights, myofiber counts and sizes are 

analyzed from control soleus muscles and injured 

(CTD) soleus muscles using the image analysis 

program, OPTIMAS and a unique technique we 

developed using Kodak Ektachrome slides as the 

source of the image. Accurate and reproducible fiber 
Page 38 - Musculoskeletal Injuries 

size distributions can now be made without missing 

very small fibers. 

Immunohistochemical markers have been 

developed to test for injury and repair as follows. 

Myofiber integrity is monitored by using dystrophin 

for plasma membrane, fibrinogen for extracellular 

protein entry, and desmin for cytoskeletal degradation 

an early response of injured muscles. 

Immunohistochemical localization of tenascin and fast 

myosin proved good indicators of regeneration and 

have become routine markers. 

The extracellular matrix outside that considered 

the basal lamina appears to proliferate following some 

types of repeated injury (CTD) - similar to that seen 

in dystrophic muscles. Increased amounts of 

proteoglycans, collagens I and III and fibronectin are 

localized with immunohistochemical techniques in 

injured muscles along with mast cell proliferation and 

degranulation. Quantitative ELISAs are midway 

through development for documenting the extent of 

this matrix expansion. A few samples have been 

studied with scanning electron microscopy to 

determine the nature of attachments between 

myofibers. These connections seem to have an 

ultrastructure similar to collagen fibers - absent from 

control samples. Because of the nature of the sample 

preparation, it is difficult to maintain the structural 

integrity and alignment of the fibrous skeleton of the 

muscle sample. However, the results are better and 

should be finished this year. It is very important to 

document these connections because they have 

tremendous implications for muscle mechanics and 

the energy cost of simple movements. 

In order to understand the physiological 

significance of the cellular and matrix changes, a 

dynamometer was needed for the measurement of rat 

hind-limb muscles in vivo. Dynamic movements can 

now be measured by a motor driven arm which 

moves the rat foot through a predetermined range of 

motion while measuring the force exerted on the 

dorsum of the foot opposing the movement. After 

much pilot investigation, a protocol for injury and 

muscle testing has been developed. Briefly, an 

isovelocity movement at 30 deg/sec is performed only 

using concentric muscle actions. This test does not in 

itself injure the muscle as we have demonstrated in 

humans as well. Subsequently, a series of sinusoidal 

movements are introduced to the active muscles 

which produce repeated damage. The isovelocity test 

is repeated to document any force decrement or 

material fatigue. Isometric tests are performed to 

correlate with the type of measurements used by 

NIOSH in evaluation of human performance. 

Significant Findings 

Muscle and non-contractile tissue proliferated 

following repeated strain injury but this response was 

dependent on the strain rate. If the strains were 

performed at fast speeds, the size of the myofibers 

was smaller and there was an increase in fiber 

number and extracellular matrix content - an 

appearance often seen in a dystrophic muscle. If the 

strains were repeated at slower speeds, the muscles 

hypertrophied with little matrix expansion as seen 

following exercise training. This unique observation 

has never been reported before and may provide a 

key towards prevention. Part of the increase in 

muscle size in muscles injured by fast strain rates 

could be accounted for by an increase in extracellular 

matrix (non-contractile tissue). Increased amounts of 

proteoglycans, collagens I and II and fibronectin were 

common features of the injured muscles with an 

increase of almost 40% as assessed by morphometric 

methods. In addition, preliminary evidence obtained 

with scanning electron microscopy revealed 

attachments between myofibers which were similar to 

collagen fibers. The implication of these connections 

is not clear but could result in greater muscle 

stiffness. 

The physiological outcome of such dramatic 

muscle changes can now be tested on a custom built 

dynamometer which has provided quantitative 

evidence for an increased material fatigue following 

muscle atrophy. Sinusoidal movements such as 

experienced while using vibrating tools can be applied 

to active rat muscles in vivo. The stretch-shortening 

cycle of muscles has never been investigated in 

relationship to the development of muscle damage 

and CTD. 

Publications 

Miller GR and Stauber WT: Use of ComputerAssisted Analysis For Myofiber Size Measurements 

of Rat Soleus Muscles From Photographed Images. 

J Histochem Cytochem, in press, 1993 

Stauber WT: Delayed Onset Muscle Soreness. In: 

Athletic Injuries and Rehabilitation, 

( eds. J Zachazewski, D Magee, W Quillen), Saunders, 

Philadelphia, in press, 1993 
Ergonomic Risk Factors and 

Cumulative Trauma Disorders 

Alfred Franzblau, MD. 

University of Michigan 

Department of Environmental 

and Industrial Health 

1420 Washington Heights 

Ann Arbor, Michigan 48109-2029 

Program Area: Musculoskeletal Injuries 

Grant Number: 1 ROJ OH02941-0l 

Start & End Dates: 09/30/92 - 01129/95 

Funding Level: $0 ($313,551 Cum) 

Importance to Occupational Safety and Health 

Cumulative trauma disorders (CTDs) are a large, 

growing and costly problem in industry. The 

National Institute for Occupational Safety and Health 

has identified CTDs as among the l O most significant 

occupational health problems in the United States. 

Prevention of occupational injury and disease relies, 

in part, on promulgation of standards which mandate 

limits of acceptable exposure to harmful agents in the 

work place. This approach has been applied 

successfully with regard to metals, solvents, 

carcinogens, and other toxins. In the realm of 

ergonomics, NIOSH has issued guidelines for manual 

lifting and prevention of low back disorders. Ideally, 

the foundations of such standards are a quantitative 

understanding of the relationship of exposure to risk 

of disease or injury. Generic work standards are 

needed for prevention of cumulative trauma disorders 

of the upper extremities, but current scientific 

knowledge does not permit precise quantification of 

risk of developing CTDs. The current study is 

intended to address that need. 

Objectives 

The overall objective of this cross-sectional 

investigation is to study jobs and perform medical 

screening of workers who are at risk of developing 

upper extremity cumulative trauma disorders (CTDs) 

with the goal of modeling quantitative dose-response 

relations between generic job exposures and medical 

outcomes. Specific objectives include: 

l. To identify jobs with at least three levels of 

repetition and with at least 20 workers in each 

category in the study plants. 

2. To quantitatively assess job exposures for 

repetitiveness and other factors which are known 

Musculoskeletal Injuries - Page 39 

to be potential risk factors for developing CTDs, 

including force, mechanical stress, posture, 

vibration, and temperature extremes. 

3. To perform medical screening of 

subjects/workers that would include: 

questionnaire surveys (demographic information, 

pertinent medical history, occupational history, 

discomfort/symptom survey), standardized 

physical examinations of the upper extremities, 

nonaversive quantitative sensory tests of the 

upper extremities, strength testing, and limited 

electrodiagnostic testing of the upper extremities. 

4. To model relationships between indices of job 

exposure ( e.g. quantitative rating of 

repetitiveness) and indices of medical outcomes 

( e.g. symptoms, physical examination findings, 

quantitative sensory test results, electrodiagnostic 

test results, and prevalence of specific CTDs) 

with the goal of developing quantitative, 

dose-response relationships between job 

exposures and medical outcomes. 

5. To compare the efficacy of the various medical 

screening techniques employed to detect CTDs 

(e.g. to compare the predictive value of 

quantitative sensory scores in the distal upper 

extremities to electrodiagnostic test results with 

regard to identification of possible carpal tunnel 

syndrome). 

6. To make specific recommendations to 

participating plants and workers about how to 

reduce ergonomic risk factors identified during 

the course of this investigation. (If this 

cross-sectional investigation is successful, then 

the plants/jobs/workers studied would form the 

basis of a possible follow-up, prospective study 

whereby one could assess the medical impact of 

ergonomic interventions made at the conclusion 

of the initial cross-sectional investigation). 

Methodology 

This study will use a cross-sectional design 

comparing the health of workers in jobs that are 

stratified on different levels of repetition. Jobs will 

be analyzed for repetitiveness, force, mechanical 

stress, posture, vibration, and temperature extremes. 

Workers in these jobs will undergo standardized 

medical evaluations that will include a questionnaire, 

physical examination of the upper extremities, 

quantitative sensory testing, and limited 

electrodiagnostic studies at the wrists. 

Exposure-response relationships will be examined 

through univariate and multivariate analyses. 

ANCOV A will be used to evaluate personal risk 

factors and multiple work factors that may be related 

to CTDs. 
Page 40 - Musculoskeletal Injuries 

Significant Findings 

The initial focus of this first year has been on 

identifying plant sites and jobs that meet the study 

requirements of having at least three levels of 

repetition and with at least 20 workers in each 

repetition category. Plant walk-throughs, job 

analyses, and medical surveys have been conducted at 

several locations, but additional ergonomic and 

medical surveys will need to be completed before 

analyses can be performed. 

Unexpected Trunk Loading 

Following Seated Vibration 

David G. Wilder, Ph.D. 

University of Vermont 

Department of Orthopaedics 

and Rehabilitation 

430B Stafford Building 

Burlington, Vermont 05405-0068 

Program Area: Musculoskeletal Injuries 

Grant Number: 5 KOi OH00090-03 

Start & End Dates: 07101/90 - 06/30/94 

Funding Level: $0 ($204,967 Cum) 

Importance to Occupational Safety and Health 

This work is studying in vivo, the effects of 

common loading environments on the mechanical 

response of the seated human. The eventual goal of 

this work is to evaluate and control the occupational 

health hazard of low back pain, a musculoskeletal 

injury, by establishing an "envelope" of loading 

conditions which should not be exceeded if the spine 

is not to experience mechanical damage. Proceeding 

from prior in vitro findings of short-column buckling 

in the lumbar spine following vibration exposure, this 

proposal is evaluating how the supporting trunk 

musculature responds to an unexpected load 

application after a 40-minute load intervention 

[seated vertical vibration, seated lateral vibration, 

seated lateral and vertical vibration or sitting still (as 

a control)]. This will simulate the sudden and 

unexpected shift of an object in the hands of the car 

or truck driver who has driven for 40 minutes. 

Normal walking (as a break) for ten minutes, prior to 

an unexpected load application, is also being tested to 

determine if it would be a reasonable control. This 

would allow lumbar discs to return, via creep 

behavior, to the upright posture orientation where the 

facets are more firmly engaged. 

Objectives 

These hypotheses will be tested using a repeated 

measures analysis of variance: 

1. There are significant differences in trunk muscle 

activity during unexpected load application 

between: 

a. subjects with "lumbar instability" and normal 

controls and 

b. subjects with different load exposure 

histories [ seated vertical vibration, seated 

lateral vibration, seated lateral and vertical 

vibration, or sitting still (as a control)]. 

2. There are significant differences in main and 

coupled mechanical driving point impedance 

characteristics during brief vibration exposures 

for mechanical response evaluation between: 

a. subjects with "lumbar instability" and normal 

controls and 

b. subjects with different load exposure 

histories [seated vertical vibration, seated 

lateral vibration, seated lateral and vertical 

vibration, or sitting still (as a control)]. 

3. A walking break for IO minutes "resets" the 

system. 

Methodology 

Trunk muscle activity (via surface 

electromyography) and main and coupled mechanical 

driving point impedance (via brief vertical vibration 

exposures for mechanical response assessment) of the 

subjects will be recorded and used as the outcome 

measures of the tests. Forty subjects will be tested: 

20 males and 20 females of whom 30 are normal 

controls and 10 are diagnosed with "lumbar 

instability". Outcome measures will be obtained 

before and after sustained exposure to specific 

loading environments. Trunk muscle activity will 

also be monitored during a sudden, unexpected flex 

ion load applied to the subject, performed before and 

after sustained exposure to the specific loading 

environments. 

Significant Findings 

None to date. 

Publications 

Pope MH, Wilder DG: Whole Body Vibration. In: 

Occupational Musculoskeletal Disorders: Assessment, 

Treatment and Prevention, (eds. M Nordin, MH 

Pope, GBJ Andersson), In Press: Mosby Year Book, 

1993/1994 
Wilder DG, Wasserman DE, Pope MH, Pelmear PL, 

Taylor W: Occupational Vibration Exposure, 

Measurement, Standards and Control. In: Physical 

and Biological Hazards of the Workplace, (eds. P 

Wald, G Stave), Van Nostrand Reinholdt, New York, 

NY, in press, June 1994 

Wilder DG: The Biomechanics of Vibration and Low 

Back Pain. American Journal of Industrial Medicine 

23(4):577-588, 1993 

Quantitative Assessment of Carpal 

Tunnel Syndrome 

Fredric E. Gerr, MD. 

Emory University 

School of Public Health 

Division of Environmental 

and Occupational Health 

1599 Clifton Road 

Atlanta, Georgia 30329 

Program Area: Musculoskeletal Injuries 

Grant Number: 5 KOJ OH00098-03 

Start & End Dates: 09/28190 - 09/27193 

Funding Level: $0 ($161,973 Cum) 

Importance to Occupational Safety and Health 

Carpal tunnel syndrome is a common nerve 

entrapment disorder. Increasing evidence indicates 

that occupational factors, especially hand force and 

repetition, are etiologically related to its development. 

Although electrophysiologic evaluation with nerve 

conduction testing and electromyography is 

considered the gold standard for confirmation of the 

diagnosis of carpal tunnel syndrome, it is seldom 

performed in epidemiologic studies of the 

occupational etiologies of this disorder. 

Electrophysiologic evaluations are not well suited for 

use in field studies of workers because they are 

noxious to the subject, take considerable time to 

perform, require careful control of testing conditions, 

utilize expensive equipment and require highly trained 

personnel to administer. The development of a 

quantitative, objective, and valid test for carpal tunnel 

syndrome that is nonaversive, easy to administer, 

rapid, and does not require sophisticated equipment 

would be of value in research into the occupational 

etiologies of carpal tunnel syndrome. 

The primary goal of this project is to determine 

the sensitivity and specificity of vibrotactile threshold 

testing for the detection of carpal tunnel syndrome. 

Musculoskeletal Injuries - Page 41 

Vibrotactile threshold testing has been used 

successfully in studies of other occupationally induced 

disorders of the peripheral nerves, including the 

hand-arm vibration syndrome and 

organophosphate-induced peripheral neuropathy. 

Objectives 

1. To determine the specificity and sensitivity of 

vibrotactile threshold testing for the diagnosis of 

carpal tunnel syndrome using a combination of 

characteristic signs, symptoms and 

electrophysiologic findings as the "gold standard" 

for the diagnosis. 

2. To compare the change in reporting of symptoms 

in patients after treatment for carpal tunnel 

syndrome to changes in both vibrotactile 

threshold measurement and electrophysiologic 

parameters. 

3. To determine the magnitude and variability in 

change of vibrotactile threshold parameters over 

time by measuring them serially in a group of 

asymptomatic subjects free of carpal tunnel 

syndrome. 

Methodology 

To determine the sensitivity and specificity of 

vibrotactile threshold testing for the diagnosis of 

carpal tunnel syndrome, disease positive and disease 

negative groups will be established using well defined 

"gold-standard" methodologies. In this context, both 

symptoms, signs and the results of electrophysiologic 

tests will be utilized to establish disease positive and 

disease negative groups. Specifically, three groups 

will be defined: Group 1 - those with clinical and 

electrophysiologic evidence of carpal tunnel 

syndrome, Group 2 - those with symptoms 

suggestive of carpal tunnel syndrome but free of 

electrophysiologic evidence of the disease, and 

Group 3 - those free of both symptoms and 

electrophysiologic evidence of disease. Test 

outcomes of 80, 90 and 95% specificity will be 

estimated from both Groups 2 and 3. Estimates from 

Group 3 will be considered best case estimates. 

To determine the relationship between change in 

symptoms following treatment and change in 

vibrotactile threshed and electrophysiological 

measures all Group 1 subjects, regardless of 

treatment, will be invited to undergo repeat testing 

7 months following entry into the study. The change 

in subjective symptomatology will be compared to 

changes in vibration threshold and 

electrophysiological parameters. 

To determine the change in the magnitude and 

variability of vibrotactile thresholds in disease-free 

subjects, Group 3 subjects will be asked to undergo 
Page 42 - Musculoskeletal Injuries 

symptom review and repeat vibrotactile threshold 

testing 7 months after the first evaluation. 

Significant Findings 

Objective I. At this time, 144 subjects have 

been evaluated. Analyses were performed separately 

for the dominant and non-dominant hands. For the 

dominant hand, 30 subjects met the criteria for 

Group I, 30 for Group 2, and 59 for Group 3. For 

the non-dominant hand, 27 subjects met the criteria 

for Group 1, 28 for Group 2, and 64 for Group 3. 

All thresholds are reported in log microns of 

peak-to-peak displacement of the vibration 

stimulator. 

The mean differences between digit 2 threshold 

and digit 5 threshold (2-5DIF) after the wrist flexion 

period for the dominant hand were 0.01 (SD=0.51) 

among Group 3 subjects, and 0.67 (SD=l.00) among 

Group 1 subjects (p=0.002). At a specificity of 80% 

(2-5DIF>0.29), the sensitivity of this measure for 

detection of dominant hand carpal tunnel syndrome 

was 55%. The mean change in 2-5DIF measured 

before and after the wrist flexion period (DELTA 

2-5DIF) was -0.16 (SD=0.58) for Group 3 subjects 

and 0.40 (SD=l.01) for Group I subjects (p=0.009). 

At a specificity of 80% (DELTA 2-5DIF>0.31), the 

sensitivity of this measure for detection of dominant 

hand carpal tunnel syndrome was 41 %. 

The 2-5DIF after the wrist flexion period for the 

non-dominant hand were -0.08 (SD=0.44) among 

Group 3 subjects, and 0.69 (SD=l.23) among 

Group I subjects (p=0.005). At a specificity of 80%, 

the sensitivity of this measure for detection of 

dominant hand carpal tunnel syndrome was 60%. 

The DELTA 2-5DIF was -0.05 (SD=0.37) for 

Group 3 subjects and 0.50 (SD=0.86) for Group I 

subjects (p=0.004). At a specificity of 80% (DELTA 

2-5DIF>0.24), the sensitivity of this measure for 

detection of dominant hand carpal tunnel syndrome 

was 52%. 

Objective 2. Very few of the Group I subjects 

were willing to undergo even limited repeat nerve 

conduction velocity testing. No analyses are possible 

at this time. 

Objective 3. Repeat vibrotactile threshold 

measurements were performed on Group 3 subjects 

seven months after the initial measurements were 

made. The mean change in 2-5DIF after wrist 

flexion over the seven month interval was -0.20 

(SD=0.58) for the dominant hand and 0.02 (SD=0.48) 

for the non-dominant hand. The mean change in 

DELTA 2-5DIF over the seven month interval was 

-0.01 (SD=0.86) for the dominant hand and 0.12 

(SD=0.70) for the non-dominant hand. 

Publications 

Letz R, Gerr F: Covariates of Human Peripheral 

Nerve Function: I. Nerve Conduction Velocity and 

Amplitude. Neurotoxicology and Teratology, 

in press, 1993 

Gerr F, Letz R: Covariates of Human Peripheral 

Nerve Function: II. Vibrotactile and Thermal 

Thresholds. Neurotoxicology and Teratology, 

in press, 1993 

Gerr F, Letz R: Covariates of Human Peripheral 

Nerve Function: III. Effects of Reported Drinking. 

Neurotoxicology and Teratology, in press, 1993 

Gerr F, Letz R: Vibrotactile Threshold Testing in 

Occupational Health: A Review of Current Issues 

and Limitations. Environmental Research 

60:145-159, 1993 

Gerr F, Letz R, Landrigan PJ: Upper-extremity 

Musculoskeletal Disorders of Occupational Origin. 

Annual Review of Public Health 12:543-566, 1991 

Gerr F, Letz R, Hershman D, Farraye J, Simpson D: 

Comparison of Vibrotactile Thresholds with Physical 

Examination and Electrophysiological Assessment. 

Muscle and Nerve 14:1059-1066, 1991 

Characterization of Posture, Force, 

and Repetitive Motion 

Robert G. Radwin, Ph.D. 

University of Wisconsin 

College of Engineering 

Department of Industrial Engineering 

1513 University Avenue 

Madison, Wisconsin 53706 

Program Area: Musculoskeletal Injuries 

Grant Number: 5 KOJ OHOOI07-03 

Start & End Dates: 09/01/91 - 08/31/94 

Funding Level: $53,681 ($160,578 Cum) 

Importance to Occupational Safety and Health 

Cumulative trauma disorders are caused, 

aggravated, and precipitated by repetitive exertions 

and movements that workers are routinely required to 

perform, as well as awkward postures they must 

assume. Currently, there are no quantitative 

standards available for protecting workers from 
excessive exposure to these hazards. But before 

dose-response relationships can be established leading 

to exposure standards for preventing these disorders, 

practical methods are needed for measuring and 

characterizing worker exposure to cumulative trauma 

stress factors. Applications of this theory include 

assessing exposure to physical stress in a manner 

analogous to the way sound level meters are used for 

measuring exposure to acoustic noise. 

Objectives 

This project is developing efficient analytical 

techniques for assessing physical stress and strain 

associated with hand-intensive tasks containing 

repetitive motion and forceful exertions. It is 

hypothesized that if the associated power spectrum 

magnitudes correspond to joint excursion angles and 

forces at a particular frequency of repetition, then the 

degree of stress and repetitiveness will be indicated 

by the spectrum frequency components. Capability 

for characterizing and reducing stress and strain 

associated with repetitive motion and exertions are 

being tested using both industrial tasks simulated in 

the laboratory and actual tasks performed in the 

workplace. This investigation further hypothesizes 

that frequency-weighted filters can be developed, 

corresponding to human exposure response 

characteristics as a function of frequency, in order to 

reduce the data in a single quantity while retaining 

the relationship between amplitude and frequency. 

Methodology 

Spectral analysis was investigated as a method 

for characterizing repetitive wrist motion and postural 

stress using a simple peg transfer task. Wrist posture 

was controlled by adjusting the pegboard location and 

by having subjects reach over an obstruction. Work 

pace was externally controlled using an auditory 

signal. Angular wrist flexion/extension and 

ulnar/radial deviation was recorded using a Penny and 

Giles strain gage electrogoniometer and sampling the 

analog signal at a 60 Hz sample rate. Wrist 

movement data was transformed into the frequency 

domain for determining the frequency and magnitude 

of repetitive motion and forceful exertions performed 

during manual work. Power spectra were computed 

by stratifying data segments into individual work 

elements, divided by break points associated with the 

task. This frequency domain approach was used for 

averaging elemental data from repetitive cycles. 

To test the feasibility of frequency-weighted 

filters, a psychophysical experiment was conducted 

for studying the effects of repetition rate (frequency) 

and repetitive motion (wrist flexion angle) on 

subjective discomfort. Low force repetitive wrist 

flexion was studied. A fixture was constructed for 

Musculoskeletal Injuries - Page 43 

limiting wrist flexion limits. Subjects grasped a 

handle and repetitively flexed and extended at the 

wrist. Two mechanical stops were adjustable so wrist 

flexion can be limited between 0° and ±90°. An 

electronic timer produced a tone indicating the pace. 

The full-factorial experiment consisted of five 

paces and two wrist flexion angles. The timer 

produced a brief tone indicating to the subject to 

perform a wrist flexion every I s, 2.5 s, 5 s, IO s, 

and 20 s. Wrist flexion was limited to 35° and 65°. 

The experiment was a repeated measures experiment 

where every subject received all treatments, and 

subjects was treated as a random effects blocking 

variable. Each experimental condition was performed 

for one hour. Five subjects were randomly recruited 

and paid on an hourly basis. All subjects were right 

handed females, ranging from 21 yr to 26 yr. 

Discomfort was measured using the cross-modality 

matching method. Subjects marked localized 

discomfort on a IO cm linear scale, anchored on the 

left as a no discomfort," and on the right as a very 

high discomfort." Localized forearm discomfort was 

assessed every fifteen minutes during a one minute 

break in the hour long experimental session. 

Significant Findings 

Peak spectral magnitudes and frequency 

components corresponded closely with Jomt 

displacement amplitudes and repetition rates. Power 

spectra fundamental frequencies corresponded to the 

cycle repetition frequency, within the frequency 

resolution of the spectrum. Spectrum fundamental 

frequency magnitudes were able to resolve 

differences in postural changes between different peg 

board rows. Therefore, this method was not only 

demonstrated useful for measuring the rate of 

repetition, but for indicating the magnitude of 

postural stress for movements at each repetition rate. 

Spectrum DC component magnitudes were directly 

related to sustained wrist postures. These 

components independently measured sustained posture 

while the AC components measured repetitive 

movements. Although eliminating the obstruction 

affected the DC component magnitude, due to the 

absence of sustained wrist flexion, ulnar/radial 

deviation DC components and the flexion/extension 

fundamental frequency magnitude were unaffected. 

A linear polynomial regression model for 

log-transformed discomfort was fitted against the log 

of wrist flexion angle and the log of frequency. 

Equal discomfort strata for wrist flexion were 

determined by solving the regression equation for 

flexion range at given frequencies for different 

discomfort levels. This equation was used for 

specifying attenuation levels needed for high pass 

filters that weigh repetitive wrist flexion in proportion 

to the discomfort function. This resulted in a 
Page 44 - Musculoskeletal Injuries 

high-pass filter having a slope of 10 dB/decade. A 

validation experiment resulted in good agreement 

between reported discomfort and frequency-weighted 

wrist movement. This investigation showed that 

frequency-weighted filters corresponding to 

discomfort responses associated with exertions and 

movements at specific frequencies can be developed. 

Publications 

Radwin RG: An Analytical Method for 

Characterizing Repetitive Motion and Postural Stress 

Using Spectral Analysis. Ergonomics 

36(4):379-389, 1993 

Radwin RG, Lin ML, Yen TY: Exposure 

Assessment of Biomechanical Stress in Repetitive 

Manual Work Using Spectral Analysis. Proc of the 

Human Factors and Ergonomics Society Annual 

Meeting, 1993 

lntracarpal Pressure During Hand 

Maneuvers 

David M Rempel, MD. 

University of California 

Center for Occupational 

and Environmental Health 

SFGH, Bldg. 30, 5th Floor 

San Francisco, California 94110 

Program Area: Musculoskeletal Injuries 

Grant Number: 5 KOJ OH00121-02 

Start & End Dates: 08/01/92 - 07/31195 

Funding Level: $54,000 ($108,000 Cum) 

Importance to Occupational Safety and Health 

Carpal tunnel syndrome is the most common 

entrapment neuropathy in humans and accounts for 

significant disability, suffering, and cost. There is 

strong evidence that it is related to occupations 

involving hand intensive work activity. Toe long 

term objective of this line of research is to use 

intracarpal pressure to specify hand maneuvers that 

can be safely performed in the workplace, which, if 

followed, will prevent carpal tunnel syndrome and 

wrist tendinitis. 

Objectives 

Toe specific aims are to (1) determine whether 

the relationships between CTP and elementary hand 

maneuvers are consistent between subjects and 

identify what those relationships are, (2) determine 

whether the CTP varies significantly within subjects 

performing typical work-related activities and 

identify the predictors of that variability, and 

(3) develop a mathematical model that will predict 

CTP as a function of elementary hand motions. 

Methodology 

Fifty normal subjects will be recruited from local 

newspapers to participate in this laboratory study. A 

blunt tipped 23-gauge catheter connected to a 

pressure transducer will be inserted at the wrist into 

the carpal space. Wrist motion will be tracked with 

a two-axes electronic goniometer. These outputs and 

the output of an electronic pinch meter will be 

sampled at 40 Hz and stored on a microcomputer. 

Toe hand maneuvers to be evaluated are: wrist 

extension/flexion angle and wrist ulnar/radial 

deviation angle, metacarpophalangeal joint angle, and 

pinch force. During the first phase, subjects will 

perform elementary hand maneuvers while data is 

collected. In the second phase, these results will be 

used to establish a mathematical relationship between 

hand maneuvers and ICP. During the third phase, 

subjects will perform simulated work activities while 

varying task rate and wrist angle. 

Significant Findings 

Twenty subjects without carpal tunnel syndrome 

have been tested to date. As observed by others, this 

normal population had mean baseline CTP of 

7.3 mmHg (s.d. 5.1). Toe CTP baseline was 

measured 8 times over a 4 hour period and did not 

vary: the estimated within-subject variance was 2.2 

and the between-subject variance was 22. 7. 

Subjects were asked to move their wrist and 

fingers to the one hand position associated with the 

lowest CTP. The group mean wrist position selected 

was -3 degrees ulnar deviation (s.d. 8) and 2 degrees 

of flex ion (s.d. 11). This position is similar to the 

"optimal - neutral" position suggested by ergonomists 

and industrial engineers for task design. 

Subjects moved their wrists slowly in 

extension/flexion and ulnar/radial deviation. CTP 

varied as some parabolic function of wrist position in 

all subjects. That is, the lowest CTP was near 

0 degrees extension/flexion and ulnar/radial deviation 

and then rose to its highest levels at extremes of 

extension and flexion, and ulnar and radial deviation. 

Toe highest CTPs were recorded at extremes of 

extension and radial deviation. Toe highest CTP 

measured was 220 mmHg. MP angle also modified 

CTP, but the relationship between MP and CTP 

remains to be analyzed. 
Subjects also pressed with their index finger on 

a pinch meter to four different load levels (0, 6, 9, 

and 12 Newtons). This experiment was repeated with 

the wrist in 10 different position by 15 subjects. 

Across all subjects and wrist angles, the CTP 

increased as a function of static load at the fingertip. 

CTP rose to a high of 80 mmHg in one subject. 

Publications 

Weiss ND, Gordon L, Bloom T, So Y, Rempel DM: 

Wrist Position of Lowest Carpal Tunnel Pressure and 

Implications for Splint Design. J of Hand Surgery, 

in press, 1994 

Weiss N, Bloom T, Gordon L, Rempel D: Wrist 

Position for Lowest Carpal Tunnel Pressure: A New 

Method to Measure Intracarpal Pressure as a 

Function of Wrist Position. Proc of 47th Annual 

Meeting of American Society for Surgery of the 

Hand, Phoenix, November 12, 1992 

Rempel D, Bloom T, Tai R, Hargens A, Gordon L: 

A Method of Measuring Intracarpal Pressure and 

Elementary Hand Maneuvers. Proc of International 

Scientific Conference on Prevention of Work-Related 

Musculoskeletal Disorders (PREMUS), Stockholm, 

1992 

Age & Cumulative Trauma 

Disorders in Garment Workers 

Jacqueline Agnew, Ph.D. 

Johns Hopkins University 

School of Hygiene & Public Health 

Department of Environmental Health 

Sciences, Rm. 7503 

615 North Wolfe Street 

Baltimore, Maryland 21205 

Program Area: Musculoskeletal Injuries 

Grant Number: 1 KOJ OHOOJ 32..,01 

Start & End Dates: 09101/93 - 08/31/96 

Funding Level: $54,000 ($54,000 Cum) 

Importance to Occupational Safety and Health 

Cumulative trauma disorders (CTD) constitute a 

significant occupational health problem in the United 

States and other industrialized nations. It is generally 

agreed that CTDs are of multifactorial etiology; 

work-related and individual characteristics have been 

implicated by various studies. Specific ergonomic 

Musculoskeletal Injuries - Page 45 

components of manual jobs are thought to be major 

risk factors for CTD. Although age has been 

included among the individual risk factors also 

thought to play a role in CTD incidence, the role that 

age plays in the etiology of CTDs among workers is 

relatively unexplored. Furthermore, it is unknown 

whether there is a potential interactive effect of 

increasing age and occupational ergonomic factors. 

The role of age as a risk factor for occupational 

injuries or illness is of particular concern in view of 

the steadily increasing age of the U.S. work force. 

The rise in average age of workers has especially 

been noted in older U.S. industries of the 

manufacturing sector, such as the apparel industry. 

This study will therefore examine the association 

between age and CTD prevalence in a garment 

worker population exposed on the job to varying 

levels of ergonomic stresses. Improved 

understanding of risk factors for CTD will be useful 

in defining intervention strategies for the prevention 

of this major cause of worker impairment in 

occupational settings. 

Objectives 

This study will examine the association between 

age and CTD prevalence in garment workers, an 

industrial population with documented levels of 

ergonomic stresses and a high incidence of CTD. 

Ergonomic factors will be analyzed and the 

interaction between age and these factors will be 

assessed, controlling for other important confounding 

or effect-modifying variables. 

The specific aims of this research are: 

1. determine the prevalence of symptoms consistent 

with cumulative trauma disorders in a garment 

worker population by a cross-sectional survey. 

2. perform observational analyses of individual 

workers' jobs to characterize ergonomic 

exposures. 

3. develop variables that describe ergonomic risk 

factors associated with each worker's job, 

including a quantitative cumulative exposure 

variable. 

4. evaluate potential interactive effects between age 

and ergonomic risk factors on CTD symptom 

prevalence. 

5. establish baseline data for this cohort of garment 

workers in preparation for a future follow-up 

study. 

Methodology 

This study will be a cross-sectional survey of 

apparel industry workers. Participants in this study 

will be workers in a rainwear manufacturing industry 
Page 46 - Musculoskeletal Injuries 

located in the Maryland-Virginia area. Workers of 

two plants, totalling 566, will be invited to participate 

voluntarily. Workers of an additional plant from the 

same company participated in a recent study at a 

participation rate of 85%. 

CTD symptom status, history of CTD diagnosis, 

age and other individual factors, as well as current 

ergonomic exposures will be determined concurrently. 

An on-site job analysis will be performed for each 

worker using a method of direct observation. An 

additional measure of ergonomic risk exposure, 

however, will incorporate retrospective work 

performance data to create a variable describing each 

worker's cumulative ergonomic stress experience. 

The relationships between CTD symptom prevalence, 

age, and measures of ergonomic exposure will be 

assessed. This will be done by stratifying data 

according to levels of ergonomic stressors and 

analyzing for interactive effects of age and ergonomic 

factors. 

Significant Findings 

None to date. 

Stochastic Model of Trunk 

Musculature During Lifting 

Gary A. Mirka, Ph.D. 

North Carolina State University 

College of Engineering 

Department of Industrial Engineering 

P. 0. Box 7906 

Raleigh, North Carolina 27695 

Program Area: Muscu/oske/etal Injuries 

Grant Number: J KOJ OH00135-0l 

Start & End Dates: 09/30/93 - 09/29/96 

Funding Level: $51,484 ($51,484 Cum) 

Importance to Occupational Safety and Health 

Traditionally, biomechanical models of the 

lumbar spine have assumed that the forces exerted by 

the trunk muscles in response to external loads are 

deterministic. That is, given a set of lifting 

conditions (torque, position, velocity, etc.) the 

activation of the trunk muscles is precisely 

determined such that equilibrium exists. However, 

because of the indeterminate nature of the 

biomechanical system, variability in the individual 

muscle forces is not only possible, it is likely. 

Variability in the individual muscle forces alters the 

loading patterns on the spine because each muscle has 

its own vector line of action which has a component 

in compression, anterior shear and lateral shear. 

Therefore, by omitting the stochastic nature of trunk 

muscle activation from the analysis, it is believed that 

deterministic biomechanical models are not capable of 

modelling the range of potential spine reaction forces 

and ultimately are underestimating risk of manual 

materials handling tasks. 

Objectives 

The objective of this research project is to 

develop a stochastic model of the lumbar trunk during 

lifting. This model will use stochastic principles to 

predict the activation levels of ten trunk muscles 

under occupational lifting conditions including varied 

weights, postures, dynamic components, and 

asymmetric lifting. This stochastic model will be 

developed in two phases. In the experimental phase, 

human subjects will be asked to perform highly 

controlled simulated lifting motions repeatedly. The 

electromyographic (EMG) activity of ten trunk 

muscles will be sampled and will be used to develop 

a database describing that particular lifting motion. 

In the modelling phase, this database will be used in 

a simulation model which will generate potential 

muscle activities. Multiple runs of the simulation 

model will generate possible time dependent EMG 

traces suitable for input into an EMG assisted 

biomechanical model which will then generate 

stochastic spine reaction forces. 

Methodology 

fhase I. EMG data from a sample of college 

undergraduate and graduate students will be collected 

as the subjects perform simulated lifting activities. 

These simulated lifting activities will be described by 

the following independent variables: sagittal trunk 

angle (5 and 40 degrees), angular velocity of the 

trunk (0, 20 and 40 degrees/second), angular 

acceleration of the trunk (0, 40 and 

80 degrees/second/second), trunk extension torque 

(40 and 80 Nm) and asymmetry of the bending 

posture (0 and 30 degrees). 

To control the levels of the independent variables 

an experimental apparatus will be used which will 

place the axis of rotation of a dynamometer in line 

with the L5/S 1 joint of the lumbar spine. The 

position, velocity, acceleration and torque during 

trunk extension will be controlled simultaneously by 

this device. Asymmetry will be controlled by the 

positioning of the subject in the apparatus. 

The dependent variables in this study will be the 

integrated EMG (IEMG) values for the ten trunk 

muscles: right and left erector spinae, right and left 

latissimus dorsi, right and left rectus abdominis, right 
and left external obliques and the right and left 

internal obliques muscles. The EMG signals will be 

sampled using surface electrodes. In hardware the 

EMG signals will be filtered (high pass 80, low pass 

1000), rectified and a moving average (20ms) will be 

taken. The EMG data will then be normalized with 

respect to the trunk angle specific resting and 

maximum EMG levels. 

Phase II. The EMG data collected and processed 

in Phase I will be used as a data base which will 

allow us to develop distributions of muscle activities. 

These distributions will then be used in the simulation 

model to predict potential EMG vales for each 

muscle. Our approach during the distribution 

development phase will be to construct a ten 

dimensional joint distribution structure. This ten 

dimensional joint distribution will include 40 

marginal distribution parameters ( 4 distribution 

parameters for each of the ten trunk muscles) and 45 

(10 choose 2) correlation parameters (one for each 

combination of trunk muscles). Corresponding to a 

particular lifting condition we will fit a 

ten-dimensional Johnson distribution to the vector of 

EMG coactivation responses for the ten muscles. The 

proposed distribution-fitting technique is a 

multivariate extension of the techniques for fitting 

univariate Johnson distributions which possess all of 

the advantages for statistical modelling and simulation 

of conventional multivariate Johnson distributions. 

The EMG generator model will then use these 

distributions as a database from which samples will 

be taken during the simulation. The result will be a 

time dependent trace of muscle activity for each of 

the ten trunk muscles. When the simulation model is 

run multiple times a probabilistic range of potential 

EMG activity for each muscle will result. The final 

step in quantifying the internal trunk forces will be to 

input these generated EMG traces into an 

EMG-assisted biomechanical model. This will allow 

one to evaluate the stochastic spinal stresses which 

would be generated due to the muscle activities 

predicted by the EMG generator model. It is hoped 

that this research project will show the pitfalls of 

using deterministic modelling approach on a system 

which is inherently probabilistic and give a illustrate 

a method of modelling risk of low back injury 

probabilistically. 

Significant Findings 

None to date. 

Musculoskeletal Injuries - Page 47 

Occupational Epidemiology of 

Carpal Tunnel Syndrome 

Hal Morgenstern, Ph.D. 

UCLA School of Public Health 

Department of Epidemiology 

10833 Le Conte Avenue 

Los Angeles, California 90024-1772 

Program Area: Musculoskeletal Injuries 

Grant Number: 5 R03 OH02765-02 

Start & End Dates: 09/28/90 - 09/27/93 

Funding Level: $0 ($44,442 Cum) 

Importance to Occupational Safety and Health 

Cumulative trauma disorders (CTDs) are one of 

the most commonly reported occupational health 

problems in today's working environment. Carpal 

tunnel syndrome (CTS) is the most commonly 

reported cumulative trauma disorder. Although CTS 

has been widely recognized as a clinical syndrome, 

there are few studies that have examined CTS 

utilizing rigorous epidemiologic methods. This 

research examines the magnitude of CTS among 

selected occupational groups ( office workers, court 

reporters, carpenters, and sprinkler fitters) that have 

received little epidemiologic attention. The 

information derived from this research will be useful 

in assessing the magnitude of CTS and for identifying 

occupational risk factors for CTS that can be 

addressed in the development of prevention strategies. 

Objectives 

The primary objective of this research is to 

provide epidemiologic information regarding the 

prevalence of CTS among occupational groups for 

which there is a paucity of epidemiologic data. Other 

objectives are to estimate the effects of other factors 

on CTS occurrence such as psychosocial factors, past 

medical history, and personal life style factors, and to 

evaluate diagnosis-related issues of CTS through a 

comparison of electrodiagnostic findings, objective 

clinical signs, and symptom reporting. 

Methodology 

The study design involves two phases: a 

cross-sectional survey and a nested case-control 

study of 75 cases and 75 controls selected from the 

cross-sectional survey population. In the 

cross-sectional phase, about 4,400 members from 

three selected unions, representing office workers, 
Page 48 - Musculoskeletal Injuries 

court reporters, carpenters, and sprinkler fitters, 

received a self-administered questionnaire. These 

members were randomly selected from union rosters 

provided by three Los Angeles area unions: Service 

Employees International Union (Local #660), the 

Carpenters Union (Local #409), and the Sprinkler 

Fitters Union (Local #709). 

The data in the cross-sectional survey 

questionnaire and the case-control interview include 

information on sociodemographic factors (age, race, 

sex, education, marital status), occupational history 

(current occupation, job task information, 

psychosocial factors of work), medical and physical 

information (history of traumatic injury, reproductive 

history, selected medical diagnoses and conditions, 

current height and weight, handedness), CTS 

symptoms and related factors (pain, numbness, 

tingling and weakness in hands and wrist, use of 

medical care for symptoms, symptoms' impact on 

work and leisure activities), other symptoms (pain in 

other areas of the body), and behavioral/leisure 

activities (smoking history, leisure activities). 

In the case-control phase, participants received 

electrodiagnostic testing ( distal sensory and motor 

latencies of the median nerve), clinical exams 

(Phalen' s test, Tinel' s test, and measurements of wrist 

size and dimensions), and a personal interview. The 

case-control interview included more extensive 

questions on CTS symptoms, medical history, and 

occupational work task information. Cases were 

selected on the basis of their reporting of CTS 

symptoms, controls were selected from those without 

CTS symptoms and matched by age, sex, and union. 

Significant Findings 

The analyses of the cross sectional survey data 

have been completed. Case-control data collection 

has also been completed and preliminary analyses are 

underway and will be available in December 1993. 

In the cross-sectional survey, we examined the 

prevalence of symptoms consistent with carpal tunnel 

syndrome ("CTS symptoms") among 529 county 

office workers, 667 active carpenters and sprinkler 

fitters, and 136 retired trade workers. For office 

workers, we estimated the effects on CTS symptoms 

for hours per day using computer keyboards and time 

involved in repetitive motion activities. For trade 

workers, we examined hours using power and hand 

tools, working above shoulder level, and hours 

involved in repetitive motion activities. We also 

evaluated the effects of medical conditions, previous 

injury, and reproductive factors. The adjusted 

prevalence odds ratios (POR) and 95% confidence 

intervals (95% CI) for keyboard use and repetitive 

motion exposures were 1.9 and ( 1.1, 3 .3) and 2 .2 and 

(LO, 4.9). The effects of hours of keyboard use 

varied across occupations and were higher among 

court reporters and data entry staff than among clerks 

and technical staff. Among trade workers, the POR 

and 95% CI for repetitive motion activities were 3.2 

and (1.6, 6.3). However, power and hand tool use 

were only modestly associated with CTS symptoms. 

For all occupations, CTS symptoms decreased with 

increasing length of employment suggesting 

healthy-worker selection bias. Several medical 

conditions and previous injuries were associated with 

CTS symptoms: rheumatoid arthritis, ganglionic 

cysts, nerve damage, tendinitis, wrist sprains, and 

previous hand/wrist injuries. However, these factors 

were not confounders for the effects of work task 

exposures on CTS symptoms. 

We also examined the relationships between 

psychosocial factors and hand/wrist symptoms, 

neck/shoulder pain, and low back pain. The 

prevalence of experiencing these musculoskeletal 

conditions in the past month was 20% for all 

hand/wrist symptoms (pain, tingling and numbness), 

59% for one or more of the hand/wrist symptoms, 

and 56% for neck/shoulder pain, and 52% for low 

back pain. Our study showed that a stressful 

psychosocial work environment was associated with 

increased prevalence of musculoskeletal disorders. 

Job demand and job satisfaction consistently show an 

independent effect on all four outcomes. The effect 

of high job demand appeared to be stronger in 

females than in males. In addition, the most stressful 

level of any two psychosocial factors acting together 

produce a greater combined effect compared to their 

component effects. 

Healthy-worker selection bias and low response 

rates limit the ability to estimate the effects of 

workplace exposures. However, these results suggest 

that, among trade workers, CTS symptoms are higher 

than what is indicated by studies of workers 

compensation data. They also suggest that, among 

office workers, keyboard use and duration of 

employment were associated with CTS symptoms and 

that providing a sound physical workplace and a 

health psychosocial work environment could help to 

prevent further increase in job-related 

musculoskeletal conditions. 

Publications 

Kelsh MA, Ke D, and Morgenstern H: The 

Importance of Non-occupational Risk Factors in the 

Assessment of Occupationally-related Carpal Tunnel 

Syndrome. Abstracts for the Society for 

Epidemiologic Research Annual Meetings, June, 1993 

Keystone, CO. Am J Epidemiol, in press, 1993 

Kelsh MA, Morgenstern H, and Ke D: A Crosssectional Study of Carpal Tunnel Syndrome 

Symptoms Among Trade and Office Workers. Proc 

of the Ninth International Symposium, Epidemiology 
in Occupational Health, Cincinnati, OH, September, 

1992 

Effect of Load Asymmetry on 

Internal Loading of The Trunk 

Ali Sheikhzadeh 

Hospital For Joint Diseases 

Occupational and Industrial 

Orthopaedic Center 

63 Downing Street 

New York, New York 10014 

Program Area: Musculoskeletal Injuries 

Grant Number: 1 R03 OH03087-01 

Start & End Dates: 08101/93 - 07131/95 

Funding Level: $35,900 ($35,900 Cum) 

Importance to Occupational Safety and Health 

In industry, carrying and lifting objects 

asymmetrically is the rule rather than the exception. 

This situation is hazardous to the musculoskeletal 

system due to an increase in coactivation of the 

musculature and an increase of the forces on the 

spine. 

Toe present study will provide a better 

understanding of the effect of asymmetrical lifting on 

mechanical and neuromuscular performance and on 

the risk of injury to the back. 

Objectives 

Toe aim of this study is to quantify the activities 

of ten trunk muscles by using the surface 

electromyography (EMG) during maximal and 

submaximal isometric exertion under pure and 

combined loading conditions of the trunk. Combined 

loading is defined as the vectorial sum of moments in 

the sagittal and transverse planes. These planes are 

selected based on their prevalence in industrial tasks 

and low back injuries. 

Methodology 

To calculate the effect of internal loading, the 

muscle parameters are calculated from CT -scan 

images of each individual participant and individual 

muscle forces are estimated using an EMG-driven 

model. Toe compression and shear forces are 

calculated under suggested conditions. Toe effects of 

planar exertion (pure exertion) and combined exertion 

Musculoskeletal Injuries - Page 49 

on the patterns of trunk muscle recruitment and 

compression and shear forces will be compared. 

The primary hypotheses of this study are: 

1. Toe peak EMG activity of trunk muscles will be 

higher during the maximal combined exertion 

than during pure maximal exertion. 

2. The mean of RMS-EMG of the ten selected 

trunk muscles will change significantly with the 

orientation of the net resultant moments of the 

trunk. 

3. The compression and shear forces will be 

changed significantly by the orientation of the 

resultant moment. 

Significant Findings 

None to date. 

Occupational Physical Loads and 

Hip Osteoarthritis 

Bradley Evanoff, MD. 

Washington University 

School of Medicine 

Occupational and Environmental Medicine 

660 South Euclid Avenue, Campus Box 8005 

St. Louis, Missouri 63110 

Program Area: Musculoskeletal Injuries 

Grant Number: 1 R03 OH03091-0l 

Start & End Dates: 09/01193 - 08/31/95 

Funding Level: $21,310 ($21,310 Cum) 

Importance to Occupational Safety and Health 

Osteoarthritis, a common degenerative joint 

disease, causes substantial morbidity with large 

attendant economic costs. Establishing an association 

between this disease and heavy physical loading may 

give further impetus to efforts aimed at reducing 

harmful physical exposures in the workplace. 

Objectives 

Occupational or recreational physical activities 

which lead to heavy static or dynamic physical 

loading of the hips may lead to osteoarthritis as a 

result of cumulative wear or microtrauma. This 

project will examine the relationship between lifetime 
Page 50 - Musculoskeletal Injuries 

occupational physical exposures and severe 

osteoarthritis of the hips. 

Methodology 

In this case-control study, both cases and 

controls will be recruited from a Health Maintenance 

Organization (HMO). Cases will be persons aged 

50-70 undergoing hip replacement surgery for 

symptomatic primary (or idiopathic) osteoarthritis. 

Controls will be HMO members matched by age, sex, 

geographic catchment area, and length of HMO 

enrollment. All subjects will complete a selfadministered exposure questionnaire which assesses 

lifetime recreational activities and physical activities 

at work. Telephone follow-up interviews will be 

performed with subjects unable to complete the 

questionnaire. Specific exposures which will be 

evaluated include lifting, jumping, climbing, 

whole-body vibration, and work postures. 

Recreational physical activities and subjects' body 

weight in different decades of life will be controlled 

for in analyzing the relationship between occupational 

physical exposures and hip osteoarthritis. 

Significant Findings 

None to date. 

Prevention of Cumulative Trauma 

Disorders 

Beth Ann Marcus, Ph.D. 

EXOS, Inc. 

2A Gill Street 

Woburn, Massachusetts 01801 

Program Area: Musculoskeletal Injuries 

Grant Number: 1 R43 OH02907-0l 

Start & End Dates: 09/30/91 - 11130/92 

Funding Level: $0 ($49,999 Cum) 

Importance to Occupational Safety and Health 

Cumulative Trauma Disorders (CTDs) currently 

account for more than one-half of this country's 

occupational illnesses, striking an estimated 185,000 

U.S. office and factory workers per year. The 

incidence of these injuries is rising, and currently cost 

$7 billion a year. Risk factors, including awkward 

posture, high repetition, forceful actions and vibration 

are well known. This knowledge however, is based 

primarily on qualitative data. What has not 

adequately been determined are the quantitative 

associations between CTDs and the cited risk factors. 

The ultimate goal of this research is to establish 

quantitative relationships between CTDs and work 

conditions. The end result will be the ability to: 

1. Identify work environments which have a high 

risk of CTDs, 

2. Quantify the risk factors thereby allowing a 

rational, scientific and systematic means of 

reducing the risk factors, and 

3. Verify that ergonomic changes are effective in 

reducing the risks of CTDs. 

The potential for technical innovation is 

significant because current techniques and technology 

focus on detecting CTDs after damage is significant. 

These technologies remain primarily an element of 

clinical practice and typically rely on advanced CTD 

symptoms for detection. While patients may already 

be experiencing significant symptoms of Carpal 

Tunnel syndrome - numbness and sensory loss in the 

hand due to compression of the median nerve, 

atrophy of the thenar eminence, and pain and loss of 

motor control - nerve conduction tests may remain 

normal. Some patients have normal nerve conduction 

results, yet require surgical intervention. 

Medical costs can be significantly reduced if 

CTD risk factors are recognized and corrected early. 

Therefore, prevention and early detection are of 

primary importance. This requires the technology 

used be compatible with both the medical and factory 

environment. Quantification, prevention, and early 

detection must be moved out of the research 

laboratory and medical facility and into the assembly 

plant, supermarket, and dental office. 

Objectives 

The first step in developing such quantitative 

relationships is the attainment of accurate 

measurements of the relevant risk factors. The 

GripMasterTM (GM) has the potential to be an 

ergonomic tool capable of measuring these 

parameters. This Phase I project was designed to 

validate the GM's measurement of wrist motion and 

finger and hand force, and to develop a strategy for 

advancing this technology to the point where it is 

accurate and viable in a field/factory environment. 

Methodology 

Two classes of experiments were performed; 

laboratory and field. The laboratory testing focused 

directly on comparing the GM to other measurement 

techniques: hand dynamometers and EMG for force 

measurement; video analysis and manual goniometry 

for angle measurement. The field testing was a pilot 
study designed to verify consistent operation of the 

GM between the laboratory and the field environment 

and to identify operational parameters influencing the 

functional capability of the GM. 

Laboratory experiments were conducted at 

University of Massachusetts, Amherst (UMASS). 

Three static grip force experiments were conducted. 

The GM's force measurements were compared to a 

hand dynamometer and EMG measurement 

techniques in static hook, power, and pinch grips. 

The GM's measurement of static wrist postures were 

also compared to video analysis techniques in the 

laboratory experiments. The reliability of the GM's 

force sensors was also tested. 

The field testing was conducted at a lock 

manufacturing facility over a period of two days. 

Data analysis of the laboratory and field experiments 

were conducted at both UMASS and EXOS, Inc. 

Significant Findings 

This Phase I project was designed to validate the 

measurements of wrist motion and finger and hand 

force provided by the GripMasterTM (GM) and to 

develop a strategy for advancing this technology to 

the point where it is accurate and viable in a 

field/factory environment. The GM tested in this 

study showed high correlation to more established 

techniques when the contact area was constant and 

sensors were new. Angle measurements were shown 

to be as accurate as current clinical techniques. It 

was demonstrated that it is feasible to use a tool like 

the GM in the field environment, but operational 

parameters identified in the field provide additional 

requirements for further development of this 

technology. 

Musculoskeletal Injuries - Page 51 
Page 52 - Occupational Cancers 

Occupational Cancer Surveillance: 

New Approaches 

G. Marie Swanson, Ph.D. 

Michigan State University 

Cancer Center 

A-211 East Fee Hall 

East Lansing, Michigan 48824 

Program Area: Occupational Cancers 

Grant Number: 5 ROI OH02067-09 

Start & End Dates: 09/28/84 - 09/29/94 

Funding Level: $0 ($1,233,788 Cum) 

Importance to Occupational Safety and Health 

Toe Occupational Cancer Incidence Surveillance 

System (OCISS) developed by this study will 

contribute to reduction of morbidity and mortality due 

to occupational risk factors for eleven types of 

cancer. It has developed both methodologic and 

substantive leads that contribute to prevention 

programs as well as to future research. Findings to 

date indicate that important new information is being 

gained regarding the occupational cancer risks of 

blacks and women, in particular. Toe significance of 

leads regarding occupational cancer risks among 

blacks and women cannot be overemphasized, as to 

date, more than 95% of occupational cancer 

epidemiology has included white males only. OCISS 

data have contributed to the methodology of 

occupational epidemiology, having demonstrated that 

occupational information derived from death 

certificates provides incomplete information about 

occupational cancer risk. Our studies als? have 

demonstrated that direct information about cigarette 

smoking histories is essential to occupational cancer 

studies. Data from OCISS and related studies will 

ultimately be utilized to develop cancer prevention 

programs in the workplace. 

Objectives 

Toe specific aims of this study are: 

1. To determine risks by occupation and industry 

for black and white males and females in 

conjunction with detailed tobacco smoking 

history, socioeconomic status, and age at 

diagnosis by cancer type. 

2. To determine cancer risk within specific 

occupations in major local industries, such as 

automobile manufacturing, construction, 

machinery manufacturing, and primary ferrous 

metals manufacturing. 

3. To investigate work-related cancer risk by race, 

gender, socioeconomic status, age at diagnosis, 

and cancer site among persons who have never 

smoked tobacco. 

4. To develop new methodologic approaches for 

occupational epidemiology. 

Methodology 

Detailed work histories, tobacco use histories, 

health history, and demographics have been obtained 

by telephone interview. Cancer cases were selected 

from a population-based registry; population 

referents were selected by random digit dialing. 

Eleven cancer sites are included in this study. A total 

of 16,888 cancer patients were interviewed, including 

6,349 with lung cancer, 2,443 with urinary bladder 

cancer, 3,211 withcoloncancer, 1,428 withcancerof 

the rectum, 1,111 with cancer of the esophagus, 795 

with stomach cancer, 540 with liver cancer, 570 with 

cutaneous melanoma, 178 with cancer of the salivary 

glands, and 127 with eye cancers. There were 3,913 

population referents interviewed. 

Significant Findings 

Analysis of usual occupation and industry among 

lung cancer cases revealed excess risks for farmers, 

excavating and mining workers, driver sales, furnace 

workers, armed services personnel, truck drivers, 

mechanics, and painters; excess risks also were seen 

in the mining, farming, and primary ferrous metals 

manufacturing industries. Five of these occupations 

have exposure to diesel exhaust. Assessment of these 

risks separately for black and white men revealed that 

the risk among mechanics was restricted to black 

males and that the risk among armed services 

personnel was considerably higher in black males 

than among white males. 

Analysis of urinary bladder cancer revealed 

excess risk among armed services personnel for white 

males and among automobile mechanics for black 

males. These data also reveal a higher attributable 

risk for cigarette smoking among bladder cancer than 

previously observed - 51 %. Industries with elevated 

risk among bladder cancer patients included wood 

manufacturing, drug manufacturing, hardware sales, 

and other transportation manufacturing. 

An important contribution of this project to the 

discipline of occupational cancer epidemiology is the 

clear demonstration that men and women and blacks 

and whites have different workplace cancer risks, 

even when employed in the same occupations or 

industries. Our analyses of cancer risks among black 

and white men show that Odds Ratios are different 

for these two groups in nearly every occupation and 
industry. This is an important finding, indicating not 

only that blacks must be included in occupational 

cancer epidemiology studies, but also that they must 

be evaluated separately from white men. 

A comprehensive analysis of occupational risks 

among women for each of the eleven cancer sites was 

conducted, with summary results presented to the 

International Conference on Women's Health: 

Occupation and Cancer in Baltimore on 

November 1, 1993. This conference was the first 

ever to focus upon occupational cancer risks among 

women and it was co-sponsored by the National 

Institute for Occupational Safety and Health, the 

National Cancer Institute, the National Institute of 

Environmental Health Sciences, and the NIH Office 

of Research on Women's Health. The OCISS results 

provided extensive information about specific 

methodologic issues that must be addressed in 

investigations of cancer risk in the workplace among 

women and provided new leads about several 

occupations and industries and their association with 

specific cancers. Methodologic issues include: (I) a 

large proportion of women in the age range of 

highest incidence of the cancers studied had a usual 

occupation of housewife (ranging from 54% among 

women diagnosed with cancer of the salivary gland to 

76% for women diagnosed with eye tumors and 63% 

for population controls); (2) the small number of 

categories of either occupations or industries with 

even IO cases or controls (there were IO or more 

cases in 1 to 14 occupation groups and O to 

12 industry groups across the eleven cancer sites); 

and (3) it is necessary to assess occupational risk 

among women ever employed in specific occupations 

or industries, as well as usual occupation and 

industry, since among those with housewife as usual 

occupation, 80% held some other job). These 

limitations are particularly striking, since OCISS 

includes much larger numbers of women than most 

occupational cancer studies--there are nearly 6000 

cancer cases and 2000 controls who are women. 

Even with these limitations, new leads regarding 

the association between specific occupations or 

industries and specific cancer sites were obtained. 

These include a four-fold increase among women in 

the computer manufacturing industry among those 

diagnosed with bladder cancer, a two-fold excess of 

women employed in restaurants among those 

diagnosed with cancer of the esophagus, a three-fold 

excess of women employed in hairdressing shops 

among those diagnosed with cancers of the salivary 

gland, an eight-fold elevation of women in the 

beverage manufacturing industry among those 

diagnosed with bladder cancer, a three-fold excess of 

women employed in food stores who were diagnosed 

with stomach cancer, and four-fold increases among 

both women employed in bus and truck services and 

in military service among those diagnosed with eye 

Occupational Cancers - Page 53 

cancers. Although not statistically significant, there 

was a large excess of women ever employed as tool 

and die workers who were diagnosed with cancers of 

the salivary gland (OR=8.5). 

Publications 

Swanson GM, Lin C-S, Bums PB: Diversity in the 

Association Between Occupation and Lung Cancer 

Among Black and White Men. Cancer Epidemiology, 

Biomarkers, and Prevention 2(4):313-320, 1993 

Bums PB, Swanson GM: Risk of Urinary Bladder 

Cancer Among Blacks and Whites: The Role of 

Cigarette Use and Occupation. Cancer Causes and 

Control 2:317-379, 1991 

Bums PB, Swanson GM: The Occupational Cancer 

Incidence Surveillance Study (OCISS): Risk of Lung 

Cancer by Usual Occupation and Industry in the 

Detroit Metropolitan Area. Am J Ind Med 

19:655-671, 1991 

Schade WJ, Swanson GM: A Comparison of Death 

Certificate Occupation and Industry Data with 

Lifetime Occupational Histories Obtained by 

Interview: Variations in the Accuracy of Death 

Certificate Entries. Am J Ind Med 14:121-136, 

1988 

Illis WR, Swanson GM, Satariano ER, Schwartz AG: 

Summary Measures of Occupational History. A 

Comparison of Latest Occupation and Industry with 

Usual Occupation and Industry. Am J Public Health 

77(12):1532-1534, 1987 

Swanson GM, Schwartz AG, Brown KL: 

Population-Based Occupational Cancer Incidence 

Surveillance - Utilization of the Telephone Interview. 

J Occup Med 27(6):439-444, 1985 

Swanson GM, Schwartz AG, Burrows RW: An 

Assessment of Occupation and Industry Data from 

Death Certificates and Hospital Medical Records for 

Population-Based Cancer Surveillance. Am J Public 

Health 74(5):464-467, 1984 
Page 54 - Occupational Cancers 

Biological Monitoring/Risk 

Assessment In An Exposed Cohort 

George P. Hemstreet, Ph.D. 

University of Oklahoma 

College of Medicine 

Department of Urology 

920 Stanton L. Young Blvd., 5SP330 

P.O. Box 26901 

Oklahoma City, Oklahoma 7 3190 

Program Area: Occupational Cancers 

Grant Number: 2 ROI OH02647-03 

Start & End Dates: 09/30189 - 04/30/98 

Funding Level: $267,940 ($840,908 Cum) 

Importance to Occupational Safety and Health 

Thousands of workers worldwide are at 

increased risk of bladder cancer because of previous 

exposure to aromatic a mines. These risks have been 

characterized in the past primarily by epidemiologic 

means, permitting assessment of risks associated with 

the cohort as a whole. If markers within the cancer 

process can be identified, individuals in the exposed 

cohorts might be differentiated according to risk and 

targeted for the appropriate intervention. In addition 

to occupational chemical exposure, other exogenous 

risk factors and endogenous risk factors influence the 

estimated relative risk or overall odds of the 

individual developing bladder cancer. Data on the 

prevalence of various risk factors and biological 

markers in exposed cohorts could be used to develop 

individual risk profiles which could be helpful for 

determining individual risk in other high-risk cohorts 

identified by epidemiologic means. 

Results of this study of identified high-risk 

cohorts in China could provide significant new data 

on early detection of bladder cancer, exogenous and 

endogenous risk factors associated with the disease, 

and biological intermediate endpoint markers 

indicative of bladder cancer risk. These findings 

could have profound implications for the development 

and initiation of bladder cancer screening programs 

in the large number of U.S. industries in which 

workers are or have been exposed to bladder 

carcinogens. 

Objectives 

The primary objectives of this research are to 

continue screening studies in a cohort of workers 

occupationally exposed to benzidine to both develop 

a bladder cancer screening approach as well as to 

reduce the number of deaths and serious morbidity 

associated with bladder cancer in this cohort. The 

ultimate aim is to devise a strategy that will detect 

persons likely to develop dangerous, invasive disease 

early enough to alter potentially unfavorable 

outcomes and release those at little elevated risk. 

The detection window during which this can be 

achieved with conventional screening techniques is 

very narrow, but can be widened with new tests 

based upon detecting the emerging malignant 

phenotype rather than waiting for frank cancer. The 

long-term goals are to develop a strategy based upon 

a combination of biochemical intermediate markers 

and clinical signs and symptoms, combined with 

assessments of various exposures to (I) assess the 

bladder cancer risk faced by an individual and 

(2) more effectively manage such individuals to 

minimize their risk. 

Methodology 

We propose to continue to screen and monitor a 

cohort of approximately 2,000 Chinese workers 

exposed to benzidine to identify confirmed and 

presumptive cases of bladder cancer and conduct a 

risk factor analysis. This large worker population is 

located in five cities -- Shanghai, Jilin, Tianjin, 

Chongqing, and Henan -- in the People's Republic 

of China. 

Significant Findings 

In a pilot study and the 2-year bladder cancer 

screening program which preceded the present study, 

we detected bladder cancer in its earliest stages prior 

to detection by conventional cytologic criteria using 

a biomarker profile consisting of G-actin, a marker 

for early differentiation changes, the p300 

tumor related antigen detected with M344 monoclonal 

antibody, and abnormal DNA ploidy detected by the 

presence of cells with >5C DNA. We have screened 

1686 exposed male workers and 388 unexposed male 

controls matched for age and smoking history. 

Preliminary statistical analysis of the results from 

workers in two of the cities using the previously 

defined panel of biomarkers using both x2 and 

Logistic Regression, identified highly significant 

correlations (p < 0.05 to 0.0001) with duration of 

benzidine exposure, pack-years smoked, and urinary 

stasis associated with benign prostatic hypertrophy, 

all of which are also risk factors for bladder cancer. 

The currently employed weighted exposure index and 

hematuria did not correlate with the biomarkers. The 

current study is designed to assess the bladder cancer 

risk of exposed individuals and validate using a panel 

of biomarkers for risk assessment. The original 

screening of this cohort has yielded three subject 

groups. From screening the worker groups in 
Shanghai and Chongqing, we estimate the numbers in 

each group (totals of exposed and controls) to be: 

Group 1 - negative for any biomarkers (about 

1500 subjects); Group 2 - positive for one marker 

(about 400 subjects); and Group 3 - positive for two 

or more markers (about 150 subjects). We plan to 

screen Group 1 every 3 years, Group 2 every year 

(or five times during the study), and Group 3, the 

highest risk group, every 6 months ( or 10 times 

during the study). Group 3 will include urological 

followup, and screening in Groups 2 and 3 will 

include additional, more specific markers to further 

stratify risk within the groups and to investigate the 

relationships among such markers in the carcinogenic 

process. 

Publications 

Bi WF, Rao JY, Hemstreet GP, Yin S, Asal NR, 

Zang M, Min KW, Ma Z, Fang P, Lee E, Li G, 

Hurst RE, Wu W, Bonner RB, Wang Y, Fradet Y: 

Field Molecular Epidemiology: Feasibility of 

Monitoring For The Malignant Bladder Cell 

Phenotype In A Benzidine-exposed Occupational 

Cohort. J Occup Med 35:20-27, 1993 

Rao JY, Hemstreet GP, Hurst RE, Bonner RB, 

Jones PL, Min KW, Fradet Y: Alterations In 

Phenotypic Biochemical Markers In Bladder 

Epithelium During Tumorigenesis. Proc Nat Acad 

Sci, USA 90:8287-8291, 1993 

Bonner RB, Hemstreet GP, Fradet Y, Rao JY, 

Min KW, Hurst RE: Bladder Cancer Risk 

Assessment With Quantitative Fluorescence Image 

Analysis Of Tumor Markers In Exfoliated Bladder 

Cells. Cancer 72(8):2461-2469, 1993 

Case Control Study of Cancer in 

Synthetic Rubber Workers 

Genevieve M Matanoski, MD., Dr.P.H 

Johns Hopkins University 

School of Hygiene and Public Health 

615 North Wolfe Street 

Baltimore, Maryland 21205 

Program Area: Occupational Cancers 

Grant Number: 5 ROI OH02730-02 

Start & End Dates: 06/01190 - 12/31/92 

Funding Level: $0 ($652,183 Cum) 

Occupational Cancers - Page 55 

Importance to Occupational Safety and Health 

Butadiene is the 36th most common chemical 

produced in the U.S. (IARC, 1986). It is used in the 

making of plastics, resins, rocket fuels, and rubber 

and rubber products. Animal studies suggest that the 

chemical is carcinogenic - at different sites 

depending on dose - and it also has the unusual 

property of activation of retroviruses. The Internal 

Agency for Research on Cancer considered the 

chemical to be "possibly carcinogenic." 

In the 1950s and 1960s, toxicologists tested some 

for the metabolic byproducts of 1,3-butadiene and 

found them to be carcinogenic in mice and rats. 

Species differences in metabolic pathways and in the 

rate of concentration may have played a role in the 

differences in incidence of cancers found in these 

animal studies. 

Although the risk of cancer associated with work 

in the rubber industry has been recognized for many 

years, few studies of health effects from rubber 

polymerization have been done. In the 1970s, 

concern about styrene-butadiene rubber polymer 

production centered primarily around the use of 

styrene. Results of studies in the late 1970s and 

early 1980s suggested that styrene might not be the 

chemical which was related to observed cancer risks. 

Some studies of humans have been done; 

however, more work is needed to identify human 

risks from butadiene and potential interactions 

between styrene and butadiene. Since animal data 

suggest effects at very low levels, human data are 

needed to help identify the appropriate level for a 

new industry standard. The differences in 

metabolism of the chemicals by species makes it 

important to have data on health effects related to 

dose in humans. This study emphasizes human 

effects from exposure to butadiene based on industrial 

monitoring measures. 

Objectives 

The goals of this research are to examine the risk 

of mortality from lympho-hematopoietic, and 

gastrointestinal cancers and sarcomas from 

occupational exposure to butadiene and styrene and to 

determine if a dose response exists. 

Methodology 

The study consists of three components: (1) A 

nested case-control study of selected cancers to 

determine the association between exposure to 

butadiene and styrene and risk of specific cancers. 

(2) An expansion of the original cohort of workers 

studied earlier to include short-term workers for 

mortality analysis and for addition to the nested 

case-control study. (3) A characterization of 
Page 56 - Occupational Cancers 

exposure by jobs using measured levels of butadiene 

and styrene, the comparison of these measured levels 

to the estimated relative ranks used in earlier studies, 

and the use of both the actual measures and the 

estimated measures in the case-control study. 

Significant Findings 

The study showed that even when using different 

methodologies such as choosing different types of 

controls, the risk of leukemia among workers in this 

industry remains high. Analysis of the case-control 

sets matched for duration worked have compared 

cases with gastrointestinal cancers and controls above 

and below the median butadiene exposure to subjects 

with no exposure in an exact analysis. Although 

some of the odds ratios are high for butadiene and 

styrene associated with esophagal cancers and there 

is a suggestive trend for increasing odds ratios with 

increasing butadiene exposure for colorectal cancers, 

none of the results are significant. These data need 

to be reexamined using measurement data and 

controls which are not matched for duration of 

exposure. 

Hospital records were sought for all cases of 

lymphohematopoietic and gastrointestinal cancers 

included in the study. Of those with a diagnosis of 

leukemia, a higher proportion were acute lymphocytic 

leukemia than would be expected based on SEER 

data. Unusual observations were also made when 

reviewing hospital records of patients with 

gastrointestinal cancers. Two of the soft tissue 

sarcomas are angiosarcomas (one of the liver, the 

other of the femur). According to SEER data, this 

cell type and the fibrosarcomas are occurring at a 

frequency much higher than expected. 

The inclusion of short-term workers (those with 

less than one year of employment) in the cohort 

analysis has increased the all cause mortality but 

remarkably did not increase the SMRs for cancer or 

circulatory diseases. For cancers of interest in the 

current research, the long-term workers have higher 

risks than short-term workers. This might suggest 

that those exposed in the industry the longest are at 

highest risk of cancer. The data indicate that 

inclusion of these short-term workers does not add to 

the risk of lymphohematopoietic and gastrointestinal 

cancers. 

Biologic importance of the work: In repeated 

analyses using different control groups, the risk of 

lymphohematopoietic cancers was increased in 

workers who had increased exposure to butadiene. 

This has important implications with regard to the 

present consideration of a safe standard to set for 

anyone exposed to butadiene. 

Methodologic importance of the work: Choosing 

new leukemia controls who were not matched for 

duration of employment resulted in a slightly lower 

odds ratio for butadiene. However, when duration 

was added to the model, the odds ratio for butadiene 

was higher than the original odds ratio using duration 

matched controls. The model with both butadiene 

and styrene is significant at p=.02. This may mean 

that the dose in a fixed time period is more important 

than total cumulative dose. This is very important 

since most occupational studies have used duration 

worked as the marker of "dose." 

The application of measurement data to describe 

dose in a population at risk is complicated and needs 

to be approached with caution. The job titles 

abstracted from the personnel records and the jobs on 

the samples may not be compatible. Not all job 

titles are sampled and the reason for sampling is not 

always clear. Samples used for a purpose other than 

that for which they were collected may have other 

short-comings which are not immediately obvious. 

Publications 

Matanoski GM, Francis M, Correa-Villasenor A, 

Elliott EA, Santos-Burgoa C, Schwartz L: Cancer 

Epidemiology Among Styrene Butadiene Rubber 

Workers. Accepted for publication. International 

Symposium on Health Hazards of Butadiene and 

Styrene, Espoo, Finland, April 1993. 

Santos-Burgoa C, Matanoski GM, Zeger S, 

Schwartz L: Lymhohematopoietic Cancer in 

Styrene-Butadiene Polymerization Workers. Am J 

Epidmiol 136:843-854, 1992 

Improved Magnetic Field Exposure 

Assessment 

David Kriebel, Sc.D. 

University of Lowell 

College of Engineering 

Department of Work Environment 

One University Avenue 

Lowell, Massachusetts 01854 

Program Area: Occupational Cancers 

Grant Number: 5 ROI OH02820-02 

Start & End Dates: 01/01/91 - 12/31/92 

Funding Level: $0 ($50, 700 Cum) 

Importance to Occupational Safety and Health 

The accurate assessment of magnetic field 

exposure is essential to the epidemiologic evaluation 

of the hypothesis that these fields contribute to 
increased cancer or reproductive risk. This 

investigation is evaluating methods for making 

appropriate exposure assignments to worker subjects 

in epidemiologic studies, and for choosing efficient 

measurement strategies. 

Objectives 

The objectives of the project are to improve the 

characterization of magnetic field exposures and their 

variability in the workplace and to evaluate 

alternative measurement strategies. Central to these 

objectives is the accurate assessment of the degree of 

exposure variability within given work locations 

(which is thought to be greater than for airborne 

hazards), and over time for given subjects. 

Methodology 

Exposure data from both a personal dosimeter 

and a hand-held "spot" magnetic field meter were 

available for these investigations. The data were 

collected at a large automobile transmission plant in 

the midwestern U.S. The dosimeters were worn by 

a representative group of 81 workers for 

approximately 200 minutes each, recording a 

measurement every 4 seconds. These data were 

reduced to series of 1 minute averages for further 

analysis of between-worker and temporal variability. 

Since there is little biological guidance on possible 

disease mechanisms, six different exposure metrics 

were computed for each worker, and these were 

compared with one another. 

The spot meter was also used to take multiple 

measurements at each of the work locations of the 

production and assembly workers among those 

wearing the dosimeter. Estimates were made of time 

spent at each of these locations, so that 'built-up' 

average exposure estimates could be made; these 

were then compared to average exposures derived 

from the dosimeter. Source identification and 

exposure falloff with distance were also evaluated 

with this spot meter. 

Significant Findings 

Background exposure at this heavy industrial 

plant was surprisingly low, less than 0.2 milliGauss 

(mG). This compares with a 25th percentile for 

home exposures of 0.4 mG in a large survey of 

electric utility workers who wore the same dosimeter 

at work and at home. The median of the workers' 

average exposures was also not particularly high, 

namely 1.3 mG, though 25 percent of the measured 

workers had exposures above 2.5 mG. Moment to 

moment exposure variability was very large, with 

some workers' 1 minute averages varying over four 

Occupational Cancers - Page 57 

orders of magnitude. The highest average exposure 

found was 46 mG. 

The "built-up" average exposures, which were 

calculated from spot measurements and time estimates 

at each locations, were compared to average magnetic 

field exposure as derived from the dosimeter records; 

correlations were found to be very high between the 

two averages. 

Little information was available prior to this 

survey about principal magnetic field sources in the 

metalworking industry. Our initial hypothesis was 

that electric motors would predominate, but other 

unexpected strong sources were found. Most 

important were demagnetizers, which in some cases 

strongly affected worker exposures as far away as 

12 meters. These devices are used to remove 

permanent magnetism which has been induced in 

some parts by grinding operations. 

With very limited biological guidance on how 

magnetic fields might contribute to cancer promotion, 

six different exposure metrics have been computed 

for each worker, reflecting several possible 

mechanisms of harm. These metrics included 

measures of central tendency, time spent above 

possible thresholds, and indicators of exposure profile 

irregularity. This last characteristic has recently been 

suggested to have biological significance in laboratory 

experiments. Correlations between some of these 

indices are moderately high, but not high enough to 

assume that exposure assignments for epidemiology 

would yield the same results with each of them. 

Environmental Exposures and Risk 

Digestive Cancers 

Ellen A. Eisen, Sc.D. 

University of Massachusetts 

College of Engineering 

Department of Work Environment 

450 Aiken Street 

Lowell, Massachusetts 01854 

Program Area: Occupational Cancers 

Grant Number: I ROI OH02953-0JAJ 

Start & End Dates: 09/01/93 - 08/31/95 

Funding Level: $123,282 ($123,282 Cum) 

Importance to Occupational Safety and Health 

The applicants have recently found excesses of 

several digestive cancers of a priori interest in a 

large cohort of automobile workers with exposure to 

metal working fluids. Since the previous application 
Page 58 - Occupational Cancers 

we have completed an exposure-response analysis 

based on internal comparisons in the full cohort of 

autoworkers. Based on results of Poisson regression 

models, statistically significant relative risks of up to 

three fold were found between esophagus cancer and 

increasing levels of exposure of machining fluids 

used in the course of grinding operations. Evidence 

of weaker associations, between 1.5 and 2.0, were 

observed between grinding and stomach and 

pancreatic cancer. Strong evidence was also observed 

for associations between straight machining fluids and 

rectal and larynx cancer. 

NIOSH has estimated that 1.2 million workers in 

the U.S. engaged in metal grinding or machining 

operations are exposed to these fluids, while over 

6 million workers are more generally exposed to the 

various components of the fluids. Better specification 

of the causal agents is necessary for an assessment of 

risk associated with metal working fluids in use 

today. 

Objectives 

This revised proposal requests funds to further 

examine the elevated risks for cancer of the 

esophagus, stomach, pancreas, colon and rectum in 

this cohort of autoworkers with exposure to 

machining fluids. A series of nested case-control 

analyses will be conducted. The objective of the 

study is to identify the specific agent(s) in the 

machining fluids which are causing the elevated 

cancers in this cohort. 

Methodology 

Conditional logistic regression models will be 

used to provide estimates of adjusted Odds Ratios for 

the major fluids types as well as specific components 

of the fluids such as sulfur, chlorine, selected metals, 

nitrosamines and biocides. Semi-quantitative 

estimates of exposure to sulfur and polycyclic 

aromatic hydrocarbones (PAH) will also be developed 

in the proposed study and included in the 

exposure-response models. 

Significant Findings 

None to date. 

New Method for Occupational 

Cancer Surveillance 

Paul W Brandt-Rauf Sc.D., MD. 

Columbia University 

School of Public Health 

Division of Environmental Sciences 

60 Haven Avenue, B-1 Level 

New York, New York 10032 

Program Area: Occupational Cancers 

Grant Number: 5 KOJ OH00076-03 

Start & End Dates: 07/15/89 - 01114/93 

Funding Level: $32,314 ($102,342 Cum) 

Importance to Occupational Safety and Health 

An important goal of occupational health is the 

prevention of occupational cancers. A critical step 

toward that goal is the development of biomarkers of 

exposure and response to workplace carcinogens. 

Such biomarkers should allow identification of those 

individuals who are at an early stage of developing 

neoplastic disease so that the disease process can be 

aborted. This research proposes to demonstrate the 

utility of a newly developed biomarker, based on the 

detection of oncogene-encoded proteins in serum, in 

contributing to the early detection of biological 

response to workplace carcinogen exposure. 

Objectives 

The overall aim of this research is to develop 

monoclonal antibody immunoblotting assays for the 

detection of oncogene protein products in serum. The 

assays could be used to screen for early neoplastic 

changes in occupational cohorts at risk for malignant 

disease due to workplace exposures. This approach 

is based on the hypothesis that many occupational 

carcinogen exposures presumably produce cancer via 

a pathway that includes oncogene activation at a 

relatively early stage, a hypothesis for which there is 

already considerable experimental support. 

Methodology 

The research consists of two parts. The first will 

involve validation of the serum oncogene protein 

assay in cohorts of cancer patients (including cancers 

of occupational concern such as lung cancer) with 

known oncogene activation and in matched controls. 

Sensitivity, specificity, and reproducibility of the test 

will be determined, and the sero prevalence of 

specific oncogene products among patients with 
various types and stages of cancer will be 

demonstrated. The second part will involve an 

attempt to estimate the predictive value of this assay 

in determining those individuals who will get cancer 

in occupational cohorts with potential carcinogen 

exposure and potential increased risk of malignancy 

(asbestos workers, firefighters) in a nested 

case-control study based on banked sera specimens. 

Significant Findings 

Results on cancer patients and controls indicate 

this assay to be highly sensitive (detecting 

sub-nanogram quantities of oncoprotein), specific and 

reproducible. Results in the serum of lung cancer 

patients appear consistent with studies of tumor 

tissue. In particular, a significant proportion of lung 

cancer patients (33-45%) exhibit elevation of the 

p2 l ras oncogene protein compared to low rates 

( <5%) in normal, health controls; in addition, a small 

percentage of lung cancer patients (<5%) exhibit 

point mutated forms of p2 l in their serum. Also, a 

significant proportion of colon cancer patients 

(30-35%) exhibit elevation of the p21 ras oncogene 

protein, as do a significant proportion of colonic 

polyp patients (15-20%); the highest proportions of 

serum positive cases were among those with large 

polyp (30%) and those with carcinoma in situ (65%), 

suggesting that serum p2 l may be a useful early 

marker of oncogenic change. Furthermore, analysis 

of results from occupationally exposed cohorts are 

consistent in that a significant proportion of 

asbestos-exposed workers who developed respiratory 

malignancies ( 45%) demonstrated elevated serum 

expression of p2 l , and this elevation was significant 

on the average of 16 months prior to the time of 

clinical diagnosis of disease. This confirms that 

serum p2 l can be a useful early marker of preclinical 

carcinogenic pulmonary response in persons with 

respiratory exposure to carcinogens. Analysis of the 

results for serum growth factors, such as PDGF and 

TGF-B, in this cohort and other asbestos-exposed 

groups further suggest that elevated serum growth 

factors correlate with severity and progression of 

non-malignant respiratory disease, in particular 

pneumocomos1s. Application of this approach to 

environmentally exposed cohorts in Eastern Europe 

show that populations exposed to high ambient levels 

of carcinogens have twice the rate of elevated serum 

p2 l protein expression as unexposed controls (10% 

in exposed vs 5% in controls). Analysis for point 

mutated forms of p2 l (Asp 13) in vinyl chloride 

exposed workers indicate that individuals who 

develop hemangiosarcomas have detectable protein in 

their serum and tumor tissue (with confirming 

mutations in tumor DNA), and that a high proportion 

(50%) of individuals with long-term, high exposure 

Occupational Cancers - Page 59 

also express the protein in their serum. Studies of 

effective, oncogene-specific chemo prophylactic 

intervention development for such cohorts are 

underway. Finally, the analytical approach is being 

applied to the detection of serum tumor suppressor 

gene proteins, such as p53, in similarly exposed 

cohorts. 

Publications 

Brandt-Rauf PW, Pincus MR, Carney WP: The 

C-erbB-2 Protein in Oncogenesis: Molecular 

Structure to Molecular Epidemiology. Critical 

Reviews in Oncogenesis, in press, 1993 

Brandt-Rauf PW, Luo JC, Carney WP, Smith S, 

DeVivo I, Milling C, Hemminki K, Koskinen H, 

Vainio H, Neugut AI: The Detection of Increased 

Amounts of the Extracellular Domain of the 

C-erbB-2 Oncoprotein in Serum During Pulmonary 

Carcinogenesis in Humans. International Journal of 

Cancer, in press, 1993 

Luo JC, Zehab R, Antilla S, Ridanpaa M, 

Husgafvel-Pursiainen K, Vainio H, Carney W, 

DeVivo I, Milling C, Brandt-Rauf PW: The 

Detection of Serum p53 Protein in Lung Cancer 

Patients. Journal of Occupational Medicine, in press, 

1993 

Breuer B, DeVivo I, Luo JC, Smith S, Pincus MR, 

Tatum AH, Daucher J, Minick CR, Miller DG, 

Novak EJ, Cody HS, Niman H, Carney WP, 

Brandt-Rauf PW: ErbB-2 and Myc Oncoproteins in 

Sera and Tumors of Breast Cancer Patients. Cancer 

Epidemiology, Biomarkers and Prevention, in press, 

1993 

Vineis P, Brandt-Rauf PW: Mechanisms of 

Carcinogenesis: Chemical Exposure and Molecular 

Changes. European Journal of Cancer 

29A:1344-1347, 1993 

Breuer B, Luo JC, DeVivo I, Pincus M, Tatum AH, 

Daucher J, Minick R, Osborne M, Miller D, 

Nowak E, Cody H, Carney WP, Brandt-Rauf PW: 

Detection of Elevated C-erbB-2 Oncoprotein in the 

Serum and Tissue in Breast Cancer. Medical Science 

Research 21:383-384, 1993 

Luo JC, Yu MW, Chen CJ, Santella RM, 

Carney WP, Brandt-Rauf PW: Serum C-erbB-2 

Oncopeptide in Hepatocellular Carcinogenesis. 

Medical Science Research 21 :305-307, 1993 

DeVivo I, Breuer B, Smith S, Milling C, Pincus M, 

Tatum AH, Daucher J, Niman H, Minick R, 

Osborne M, Miller D, Nowak E, Cody H, 
Page 60 - Occupational Cancers 

Brandt-Rauf PW: Detection of Serum C-myc 

Oncoprotein in cancer Patients by Immunoblot. 

Medical Science Research 21:345-347, 1993 

Brandt-Rauf PW, Smith S, Hemminki K, 

Koskinen H, Vainio H, Niman H, Ford J: Serum 

Oncoproteins and Growth Factors in Asbestosis and 

Silicosis Patients. International Journal of Cancer 

50:881-885, 1992 

Perera FP, Hemminki K, Gryzbowska E, 

Motykiewicz G, Santella RM, Young TL, Dickey C, 

Brandt-Rauf PW, De Vivo I, Blaner W, Tsai WY, 

Chorazy M: Molecular and Genetic Damage in 

Humans from Environmental Pollution in Poland. 

Nature 360:256-258, 1992 

Brandt-Rauf PW: Oncogenes and Oncoproteins in 

Occupational Carcinogenesis. Scandinavian Journal 

of Work, Environment and Health 18:27-30, 1992 

Brandt-Rauf PW: The Molecular Epidemiology of 

Oncoproteins. Scandinavian Journal of Work, 

Environment and Health 18:46-49, 1992 

Ford J, Smith S, Luo JC, Friedman-Jimenez G, 

Markowitz S, Garibaldi K, Niman H, 

Brandt-Rauf PW: Serum Growth Factors and 

Oncoproteins in Firefighters. Occupational Medicine 

42:39-42, 1992 

Perera FP, Santella R, Brandt-Rauf PW, Kahn S, 

Jiang W, Mayer J: Molecular Epidemiology of Lung 

Cancer. In: Origins of Human Cancers: A 

Comprehensive Review, (ed. H Hiatt), Cold Spring 

Harbor Laboratory, Cold Spring Harbor, 

pp. 219-236, 1991 

Perera FP, Santella RM, Brandt-Rauf PW, Kahn S, 

Jiang W, Tang D, Mayer J: The Role of Molecular 

Epidemiology in Cancer Prevention. In: Xenobiotics 

and Cancer: Implications of Chemical 

Carcinogenesis and Cancer Chemotherapy, (eds. L 

Ernster, H Esumi, Y Fujii, HV Gelboin, R Kato, 

T Sugimura), Japan Scientific Societies Press, Tokyo, 

pp. 339-350, 1991 

Brandt-Rauf PW: Advances in Cancer Biomarkers 

as Applied to Chemical Exposures: The ras 

Oncogene and p21 Protein and Pulmonary 

Carcinogenesis. Journal of Occupational Medicine 

33:951-955, 1991 

Luo JC, Neugut Al, Nieves J, Benson M, Niman H, 

Brandt-Rauf PW: lnt-1 Related Proteins in Serum 

of Prostate Cancer Patients and Controls. Medical 

Science Research 19:453-454, 1991 

Brandt-Rauf PW: Oncogene Proteins as Biomarkers 

in the Molecular Epidemiology of Occupational 

Carcinogenesis: The Example of the ras Oncogene 

Encoded p2 l Protein. International Archives of 

Occupational and Environmental Health 63: 1-8, 1991 

Perera F, Mayer J, Santella RM, Brenner D, 

Jeffrey A, Latriano L, Smith S, Warburton D, 

Young TL, Tsai WY, Hemminki K, Brandt-Rauf 

PW: Biologic Markers in Risk Assessment for 

Environmental Carcinogens. Environmental Health 

Perspectives 90:247-254, 1991 

Ford J, Smith S, Markowitz S, Brandt-Rauf PW: 

Increased Levels of TGF-B in Serum of Firefighters. 

American Review of Respiratory Disease 

143:A103,1991 (Abstract) 

Brandt-Rauf PW: Advances in Cancer Biomarkers 

as Applied to Chemical Exposures. Journal of 

Occupational Medicine 33:537, 1991 (Abstract) 

Perera FP, Jeffrey AM, Brandt-Rauf PW, Brenner D, 

Mayer JL, Smith SJ, Latriano L, Hemminki K, 

Santella R: Molecular Epidemiology and Cancer 

Prevention. Cancer Detection and Prevention 

14:639-645, 1990 

Perera F, Fischman HK, Hemminki K, 

Brandt-Rauf PW, Niman HL, Smith S, Toporoff E, 

O'Dowd K, Tang MX, Tsai WY, Stoopler M: 

Protein Binding, Sister Chromatid Exchange and 

Expression of Serum Oncogene Proteins in Patients 

Treated with Cisplatinum (cisDDP)-based 

Chemotherapy. Archives of Toxicology 64:401-406, 

1990 

Brandt-Rauf PW, Niman HL, Smith SJ: Correlation 

Between Serum Oncogene Protein Expression and the 

Development of Neoplastic Disease in a Worker 

Exposed to Carcinogens. Journal of the Royal 

Society of Medicine 83:594-595, 1990 

Brandt-Rauf PW: Oncogene Proteins as Molecular 

Epidemiologic Markers of Cancer Risk in Hazardous 

Waste Workers. Occupational Medicine: State of the 

Art Reviews 5:59-65, 1990 

Perera F, Jeffrey A, Santella RM, Brenner D, 

Mayer J, Latriano L, Smith S, Young TL, Tsai MY, 

Hemminki K, Brandt-Rauf PW: Macromolecular 

Adducts and Related Biomarkers in Biomonitoring in 

Epidemiology of Complex Mixtures. In: Complex 

Mixtures and Cancer Risk, (eds. H Vainio, M Sorsa, 

AJ McMichael), IARC Scientific Publications No. 

104, IARC, Lyon, pp. 164-180, 1990 
Brandt-Rauf PW, Smith S, Perera FP: Molecular 

Epidemiology and Environmental Carcinogenesis of 

the Lung. Problems in Respiratory Care 3:44-61, 

1990 

Brandt-Rauf PW, Smith S, Niman HL, Yohannan W, 

Hemminki K, Perera F, Santella R: Serum Oncogene 

Proteins in Foundry Workers. Journal of the Society 

of Occupational Medicine 40: 11-14, 1990 

Brandt-Rauf PW: Oncogenes and their Applications 

in Epidemiologic Studies. American Journal of 

Epidemiology 131: 1099-1100, 1990 (Letter) 

Brandt-Rauf PW: Serum Screening for Oncogene 

Proteins in Occupationally Exposed Workers. Journal 

of Cancer Research and Clinical Oncology 116:982, 

1990 (Abstract) 

Brandt-Rauf PW, Smith S, Niman HL, Goldstein 

MD: Serum Oncogene Proteins in Hazardous Waste 

Workers. Journal of the Society of Occupational 

Medicine 39:141-143, 1989 

Leukocyte DNA Adducts after 

Carcinogen Exposure 

Gerald N Levy, Ph.D. 

University of Michigan 

Department of Pharmacology 

6322 Medical Sciences Building I 

Ann Arbor, Michigan 48109-0626 

Program Area: Occupational Cancers 

Grant Number: 5 KOJ OH00081-03 

Start & End Dates: 03/01190 - 02/28/94 

Funding Level: $0 ($149,975 Cum) 

Importance to Occupational Safety and Health 

Humans are exposed to a wide variety of 

carcinogenic compounds, many of which are 

unidentified. Individuals within the same 

occupational environment receive different levels of 

exposure to chemicals depending on their specific 

tasks and personal habits. Even individuals receiving 

the same dose of carcinogen exposure will differ in 

their sensitivity to the chemical due to differences in 

metabolism and excretion based on genetics, sex, age, 

and nutritional and health status. The work supported 

by this grant seeks to develop a method for 

determining the actual dose of carcinogen received by 

individuals in order to set appropriate limits for such 

Occupational Cancers - Page 61 

exposures and to evaluate safety measures taken to 

reduce exposures. 

Objectives 

The major goal of this research is to determine if 

the measurement of DNA-carcinogen adducts in 

circulating white blood cells (WBC) can be used as a 

monitor of in vivo exposure to carcinogens. This 

determination will be made by developing methods of 

analyzing DNA adducts in white blood cells, 

investigating the dose-response relationship, and then 

comparing the levels of leukocyte DNA adducts with 

DNA-carcinogen adducts found in target tissues of 

various classes of carcinogens. A secondary goal of 

the research is to determine if white blood cells have 

the ability to activate environmental and occupational 

carcinogens to metabolites capable of forming DNA 

adducts. 

Methodology 

Inbred mice are used as an animal model of 

human exposure to the arylamine carcinogen 

2-aminofluorene (2-AF). The animal model allows 

for controlled exposure to known doses of a specific 

carcinogen for selected time periods. In addition, the 

animal model permits access to internal target tissues 

of the carcinogen. Thus, dose-response 

measurements comparing carcinogen exposure to 

DNA-carcinogen adduct production can be made in 

the bio-marker and in the target tissue. 

Acute exposure to 2-AF is achieved by 

intraperitoneal injection. Subchronic exposure is by 

addition of 2-AF to the drinking water. DNA is 

isolated from WBC, liver, and bladder of control and 

carcinogen treated mice. DNA-carcinogen adducts 

are detected and quantitated by 32P-postlabeling of 

nucleotides obtained by enzymatic hydrolysis of DNA 

followed by HPLC analysis of adducted nucleotides. 

The ability of white blood cells to activate 

carcinogens is examined by isolating mouse white 

blood cells and incubating them with carcinogen for 

12 to 24 hours under standard cell culture conditions. 

The cells are harvested, DNA prepared, and adducts 

analyzed by 32P-postlabeling followed by HPLC and 

scintillation counting. 

Significant Findings 

In mice, the formation of 2-aminofluorene-DNA 

adducts in the target tissues liver and bladder is 

dependent on a number of factors that can modify the 

metabolic activation of 2-aminofluorene. Among 

these are age at time of exposure, sex, and acetylator 

status. Studies of these variables have indicated that 

acetylator status is of major significance in hepatic 

DNA adduction, while age at time of exposure is 
Page 62 - Occupational Cancers 

particularly important in bladder adduct formation in 

male mice. Sex is a significant determinant of which 

tissue will be the major target of DNA damage (liver 

in females and bladder in males). In order to 

simplify initial comparisons between target tissues 

and WBC, we have examined C57BU6J (rapid 

acetylators) male mice at 7 weeks of age. 

The formation and disappearance of WBC DNA 

adducts for 24 hr after exposure to 2-aminofluorene 

was measured and compared with liver and urinary 

bladder DNA adducts. In general, adduction of DNA 

by 2-AF metabolites appeared similar in the three 

tissues. The highest level of 2-AF-DNA adducts 

were observed at 3 hr and decreased with time over 

the period studied. The decline in WBC adducts 

during the 24 hr period was parallel to the decline in 

liver adduct levels; WBC adducts were between 11 % 

and 14% of liver adduct levels for the period. A 

similar relationship between WBC and bladder 

adducts was only observed for the first 12 hr, during 

which WBC adducts were about 5% of bladder 

adduct levels. 

Seven day continuous exposure experiments 

demonstrated a clear dose response between the 

amount of 2-AF consumed and DNA adduct 

formation in both leukocytes and the target tissues. 

Increasing the concentration of 2-AF in the drinking 

water produced an almost linear increase in DNA 

adducts in all 3 tissues examined. 

The findings indicate that WBC are potentially 

useful as exposure indicators both for acute and 

chronic exposures to the arylamine carcinogen 2-AF 

and that WBC are worthy of further investigation as 

biological monitors of DNA damage in internal target 

tissues. The parallel decline in adduct levels in WBC 

and liver after acute exposure and the similar 

dose-response curves for WBC, liver, and bladder 

DNA adduct formation during continuous exposure 

indicate WBC may be very useful in determining 

individual carcinogen exposure levels. 

Cultured mononuclear leukocytes (MNL) 

demonstrated the ability to activate 2-AF and form 

DNA adducts. The extent of adduct formation was 

related to the genetically determined ability of MNL 

to activate 2-AF. Incubation of isolated MNL with 

carcinogen followed by DNA-carcinogen adduct 

measurement may give an indication of individual 

susceptibility to DNA damage. 

Publications 

Levy GN, Chung JG, Weber WW: 2-Aminofluorene 

Metabolism and DNA Adduct Formation by 

Mononuclear Leukocytes from Rapid and Slow 

Acetylator Mouse Strains. Carcinogenesis 15, 

in press, 1994 

Chung JG, Levy GN, Weber WW: The Distribution 

of 2-Aminofluorene and p-Aminobenzoic Acid 

N-Acetyltransferase Activity in Tissues of C57BU6J 

Rapid and B6.A-Naf Slow Acetylator Congenic 

Mice. Drug Metab Dispo 21, in press, 1993 

Levy GN: Ciculating Leukocytes as Indicators of 

Arylamine Carcinogen Exposure. Fund Appl Toxicol 

21:23-30, 1993 

Levy GN, Martell KJ, DeLeon JH, Weber WW: 

Metabolic, Molecular Genetic, and Toxicologic 

Aspects of the Acetylation Polymorphism in Inbred 

Mice. Pharmacogenetics, in press, 1992 

Levy GN: Circulating Leukocytes as Indicators of 

Arylamine Carcinogen Exposure. The Toxicologist 

12:189, 1992 (Abstract) 

Levy GN, Weber WW: 2-Aminofluorene-DNA 

Adducts in Mouse Urinary Bladder: Effect of Age, 

Sex, and Acetylator Phenotype. Carcinogenesis 

13:159-164, 1992 

Susceptibility to Genetic Damage 

from Butadiene 

Karl T. Kelsey, MD. 

Harvard University 

School of Public Health 

Occupational Health Program 

665 Huntington Avenue 

Boston, Massachusetts 02115 

Program Area: Occupational Cancers 

Grant Number: 5 KOJ OHOOJ 10-03 

Start & End Dates: 09/30191 - 09/29/94 

Funding Level: $54,000 ($162,000 Cum) 

Importance to Occupational Safety and Health 

In recent years there has been a growing interest 

in the application of biomarkers in cancer 

epidemiology. The current research is being 

conducted with an emphasis on genotoxic and 

mutagenic markers and the genetic modifiers of sister 

chromatid exchange induction. Such modifications 

will likely have relevance for the prevention of 

occupationally-induced cancers. 
Objectives 

The objectives of this research are to determine 

the extent of genotoxicity attributable to 

1,3-butadiene exposure in humans in the workplace 

and to test whether chromosomal sensitivity to 

diepoxybutane predicts individual susceptibility to 

genotoxic effects of butadiene exposure. 

Methodology 

Butadiene workers involved in monomer and 

polymer production were studied. Exposure was 

assessed by questionnaire, workplace walk-throughs 

and personal and area monitoring. 

Butadiene-exposed workers contributed a blood 

sample and chromosomal endpoints were analyzed. 

Individual sensitivity to the cytogenetic effects of 

diepoxybutane added in vitro was assessed. Analysis 

was completed to determine if individual cytogenetic 

sensitivity to diepoxybutane predicts the baseline level 

of chromosome damage induced by butadiene 

exposure. In this way, susceptibility to the 

chromosomal effects of butadiene was examined by 

looking at chromosomal sensitivity to the butadiene 

metabolite, diepoxybutane. 

Significant Findings 

The field portion of the study has been 

completed. Exposure to butadiene has been assessed 

with 8-hour time wait of average personal sampling 

as well as urine collection and metabolite 

determination. Significant data has been collected by 

questionnaire and blood has also been collected. 

Early analysis of the data reveals baseline cytogenetic 

changes in the exposed group to be unrelated to 

time-weighted average measurements of exposure. 

Urine was collected and there is no relationship 

between induced cytogenetic damage and urinary 

measures of exposure to butadiene. However, 

examination of high SCE frequency cells reveals that 

there is some relationship between length and the 

trade and high frequency SCE cells present in 

workers. Also, one individual who had previously 

been noted to have a very high hprt mutant fraction 

was also sensitive to diepoxybutane in vitro. 

Thus, our work indicates that acute exposure to 

1,3-butadiene was not associated with induction of 

chromosomal abnormalities. However, tenure in the 

trade was associated with production of high SCE 

frequency cells. Companion studies of molecular 

epidemiology are being carried out using these same 

techniques. These studies have shown that genetic 

damage, induced by exposure to radiation results in 

persistent genetic damage measured as sematic 

mutations. Further, we've noted that constitutional 

heterozygosity for the ataxia-telangiectasia gene 

Occupational Cancers - Page 63 

results in heterogeneity in the clastogenic response to 

x-rays in lymphocytes from these individuals. In 

addition, molecular determination of the 

heterozygosity in glutathione transferase class μ does 

not modify venodilatory potency of nitroglycerin in 

human veins. 

Publications 

Wieneke JK, Kelsey KT: Susceptibility To 

Chromosomal Damage Induction by Metabolites of 

1,3-Butadiene and Its Relationship To II Spontaneous 11 

Sister Chromatid Exchange Frequencies in Human 

Lymphocytes, IARC Monograph, (ed. M Sorsa), 

in press, 1993 

Wieneke JK, Kelsey KT: Susceptibility To Induction 

of Chromosomal Damage by Metabolites of 

1,3-Butadiene and Its Relationship To II Spontaneous 11 

Sister Chromatid Exchange Frequencies in Human 

Lymphocytes, IARC Scientific Publications No. 127, 

(eds. M Sorsa, K Pelionen, H Vainio, K Hemminki), 

Lyon, International Agency for Research on Cancer, 

1993 

Kelsey KT, Bechtold WE, Ward JB, Wieneke JK: 

Susceptibility to Genetic Damage From Occupational 

Exposure to Butadiene. Proceedings of the 

International Symposium on Health Hazards of 

Butadiene and Styrene, 1993 

Wieneke JK, Kelsey KT: Inter-Individual Sensitivity 

and Cytogenic Response to Diepoxybutane. 

Proceedings of the International Conference on the 

Health Hazards of Butadiene and Styrene, 1993 

Bechtold WE, Kelsey KT, Ward JB: Measurement of 

1,2-Dihydroxy-4-(N-Acetylcysteinyl-S)Butane In a 

Urine As a Biomarker of Exposure to 1,3-Butadiene. 

Proceedings of the International Conference on the 

Health Hazards of Butadiene and Styrene, 1993 

Haefeli WE, Srivastava N, Kelsey KT, Wieneke JK, 

Hoffman BB, Blaschke TF: Glutathione 

S-transferase Polymorphism Does Not Modify 

Venodilatory Potency of Nitroglycerin in Human 

Veins. Clinical Science, in press, 1992 

Cullen MR, Solomon L, Pace PE, Buckley P, 

Duffy T, McPhedran P, Kelsey KT, Redlich CA: 

Morphologic Biochemical and Cytogenetic Studies of 

Bone Marrow and Circulating Blood Cells in Painters 

Exposed to Ethylene Glycol Ethers. Environ Res, 

in press, 1992 

Smith CM, Kelsey KT, Christiani DC: Risk 

Assessment and Occupational Health Overview and 

Recommendations. New Solutions, in press, 1992 
Page 64 - Occupational Cancers 

Wieneke JK, Wara DW, Little JB, Kelsey KT: 

Heterogeneity in the Clastogenic Response to X-rays 

in Lymphocytes from Ataxia-Telangiectasia 

Heterozygotes and Controls. Cancer Causes and 

Control 3:237-245, 1992 

Caggana M, Liber HL, Coleman MD, Mauch PM, 

Clark JR, Kelsey KT: A Prospective Study of hprt 

Mutant and Mutation Frequency in Treated Cancer 

Patients. Cancer Epidemiology, Biomarkers and 

Prevention 573-580, 1992 

General Mortality & Cancer 

Incidence in Florida Pesticide 

Applicators 

Lora E. Fleming, MD.· 

University of Miami 

School of Medicine 

Department of Epidemiology & Public Health 

P.O. Box 016069 (R-669) 

Miami, Florida 33101 

Program Area: Occupational Cancers 

Grant Number: I KOJ OHOOJ25-0JAJ 

Start & End Dates: 09/30/93 - 09/29/96 

Funding Level: $53,832 ($53,832 Cum) 

Importance to Occupational Safety and Health 

Pesticides are chemicals used since ancient times 

to destroy or control pests. Although the primary 

hazard to humans associated with pesticide exposure 

is acute poisoning, there has been considerable 

concern surrounding the possibility of pesticide 

carcinogenicity and other chronic health effects in 

humans. The pesticides which have generated the 

greatest concern for possible carcinogenicity include 

the herbicides ( chlorophenoxy acids and 

chlorophenols), heavy metals (especially arsenicals), 

petroleum products (polyaromatic hydrocarbons), 

organochlorines, and fumigation agents (EDB, 

MethylBromide). This is important given the huge 

volume of pesticides now used throughout the world 

in agriculture, industry and in homes; in addition, 

. there is concern with regards to the environmental 

and food residue contamination from pesticides which 

could lead to mass chronic low-level exposure. 

Under EPA since 1970, the Federal Insecticide, 

Fungicide, and Rodenticide Act (FIFRA) has required 

that persons who buy or use restricted-use pesticides 

must be certified as competent pesticide applicators or 

must be directly supervised by a certified applicator. 

The State of Florida has computerized records of 

over 16,000 certified pest applicators for over 

10 years and paper records for up to 25 years. In 

addition, as a highly agricultural and tropical state, 

Florida is a major pesticide user. 

Objectives 

The proposed study will be retrospective cohort 

analyses of the cancer incidence and general 

mortality, with a nested (synthetic) case control study 

of cancer incidence, among a cohort of the Florida 

certified pesticide applicators with occupational 

pesticide exposure in Florida for at least 20 years. 

Because the greatest exposures to pesticides occur 

in the occupational setting, this study should add to 

the body of knowledge concerned with pesticides and 

their health effects in humans. Results from the study 

(i.e. specific cancer and other mortality rates, 

protective equipment use, and other risk factors) can 

be incorporated into existing mandatory educational 

programs of the Florida Department of Agriculture 

Bureau of Pesticides to prevent future illness in this 

and similar workforces. 

Methodology 

Cancer incidence since 1980 will be obtained by 

linking the data from the pest applicator licenses with 

the Florida Cancer Data System (FCDS). Mortality 

information will be obtained through the Florida Vital 

Statistics Death Linkage. In a nested (synthetic) case 

control study, exposure and relevant risk behavior 

data will be sought through the distribution of a 

questionnaire to selected cases of incident cases of 

cancer and a random sample of matched applicators 

as controls. Information concerning specific pesticide 

use, race/ethnic status, and possible confounding 

factors (such as tobacco use) will be obtained. 

Analyses will evaluate total cancer incidence and 

specific cancer incidences compared to age and sex 

adjusted state and national rates. In addition, risks 

for specific cancers associated with pesticide exposure 

will be evaluated, controlling for confounding 

variables such as tobacco use and using an internal 

cohort control group. Finally, cause specific 

mortality and cancer incidence experience of this 

cohort with national and internal comparisons will be 

evaluated. 

Significant Findings 

None to date. 
Molecular Dosimetry for 

Carcinogens 

Suresh P. Krishnan 

University of Cincinnati 

College of Medicine 

Department of Environmental Health 

3223 Eden Avenue 

Cincinnati, Ohio 45267-0056 

Program Area: Occupational Cancers 

Grant Number: 5 R03 OH02880-02 

Start & End Dates: 09/30/91 - 09/29/94 

Funding Level: $0 ($36,805 Cum) 

Importance to Occupational Safety and Health 

Airborne levels of contaminants will not always 

predict dermal absorption, and in some occupations, 

dermal absorption may be the main route of exposure 

for many carcinogens in the workplace. Exposure to 

complex mixtures containing polycyclic aromatic 

hydrocarbons e.g., benzo(a)pyrene (BaP) and 7,12 

dimethylbenzanthracene [DMBA]; N-heterocyclic 

aromatics e.g., 7H-dibenz[c,g]carbazole [DBC]; and 

aromatic amines e.g., 4-aminobiphenyl (4ABP), can 

cause tumors at the site for BaP, DBC and DMBA 

or at distant organs (as in the case of aromatic 

amine-caused bladder cancer or DBC induced liver 

cancer). Biomarkers sensitive to the effects of 

compounds absorbed dermally would increase our 

ability to predict significant exposure and early effect. 

The aims of our grant are to develop two such 

markers (DNA adducts and micronuclei (MN) 

frequencies) for proto-typical occupational 

carcinogens. This may help identify threshold levels 

of exposure for individual carcinogens that 

correspond to the limits of detection for combined 

adduct and MN measurements in the workplace. 

Objectives 

The kinetics of DNA adduct levels 

(32P-postlabeling assay) and MN frequencies 

(cytochalasin-B blocking method) will be determined 

in mouse skin and liver for BaP, DBC & 4ABP 

respectively. Dose-response relationships will be 

established between carcinogen-DNA adducts and 

cytogenetic damage as measured by MN frequencies. 

Finally, the mechanisms of clastogenicity will be 

evaluated by using centromere-specific antibodies for 

MN formation in mouse skin and liver. 

Occupational Cancers - Page 65 

Methodology 

The study has been divided into two main parts: 

1. Kinetics Study - The kinetics study has been 

divided into two parts: 

(a) Dose response study (b) Time course study 

This study will allow for observation of repair 

and determine the times of maximum DNA 

binding and maximum MN expression. 

2. Inhibitor study - An inhibitor of Cytochrome 

P-450 will be used to determine if MN formation 

could be inhibited. These experiments will 

enable us to understand the mechanism of MN 

formation. 

Keratinocytes from treated and control animals 

will be isolated under sterile conditions. They will be 

resuspended in low calcium minimum essential 

medium and plated in collagen coated microscope 

slides at a cell density of 4 x 106 cells/slide. Once 

these conditions are established, similar studies will 

be carried out on hepatocytes. Hepatocytes from 

treated and control mice will be isolated in a 

dissociation medium containing collagenase in Hepes 

buffer, resuspended in Leibowitz (L15) or Williams 

WE medium and plated at appropriate densities in 

tissue culture plates. DNA from keratinocytes 

(scraped epidermal fragments from the dermis and 

stored at -80 "C) and hepatocytes will be isolated 

using the phenol extraction procedure. DNA adduct 

levels will be determined by the 32P-postlabeling 

assay. Approximately 10,000 micronuclei/dose will 

be scored in cytokinesis blocked keratinocytes and 

hepatocytes. Kinetochores of micronuclei will be 

stained with the primary and secondary antibodies in 

order to distinguish micronuclei formed as a result of 

aneuploidy as opposed to those formed as a result of 

clastogenicity. 

Significant Findings 

Conditions have been established for the isolation, 

growth and maintenance of keratinocytes in collagen 

coated microscope slides and petri dishes. 

Methodology is currently being developed to 

isolate DNA and to improve its yield from epidermal 

fragments. Once the conditions are optimized, the 

DNA samples from treated and control animals will 

be used for 32P-postlabeling. Preliminary 

experiments indicate that carcinogen-DNA adducts 

are present at the 50 μg/mouse dose. 

Experiments were performed to optimize the 

conditions for obtaining maximal numbers of 

binucleate (BN) cells [MN are scored in 

1000 cytokinesis-blocked binucleate cells]. It has 

been found that mouse keratinocytes have to be 

cultured, in the presence of cytochalasin-B, for 
Page 66 - Occupational Cancers 

72 hours in order to obtain optimal numbers of 

binucleated cells. 

Conditions have been optimized for performing 

the micronucleus assay. The BN fraction and the 

number of MN in acetone treated controls, in vivo, 

were 22 +/- 8.7 % and 12.5 +/- 6.7 respectively. 

In vitro, the BN fraction and the number of 

micronuclei in the controls were 22 +/- 6.3 % and 

13.9 +/- 7.7 respectively. In vitro, the BN fraction 

and the number of micronuclei in the solvent 

(dimethyl sulfoxide) controls were 29.5 +/- 10.9 % 

and 10.5 +/- 2.4 respectively. 

At the doses ranging between 4.5-50 μg/mouse, 

BaP does not produce a significant increase in MN 

over acetone treated controls [in vivo]. In addition, 

this compound does not produce a significant increase 

in MN in vitro [12μg - 120μg/ml of media]. 

However, adriamycin (in vitro) produces a very 

significant dose dependent increase in MN when 

compared to controls [25 ng/ml 99MN/1000 BN 

cells; 50 ng/ml 165 MN/1000 BN cells; 100 ng/ml 

288 MN/1000 BN cells]. This indicates that mouse 

keratinocytes have the ability to express MN 

formation. This finding is further substantiated by 

the fact that DBC [in vitro], an equally significant 

environmental and occupational pollutant also induces 

a dose [0.01 - 2.5 μg/ml] dependent increase in MN 

[6.5-25.5 MN/1000 BN cells] over controls. Further 

experiments are underway to examine more closely 

the kinetics of MN formation by DBC and to 

determine if an association exists between adducts 

and MN for DBC as well as DMBA. 

The lack of a response in mouse keratinocytes 

for BaP indicates that negative results in the skin MN 

assay should be interpreted with caution. 

Cocarcinogenic Particulates in 

Coculture System 

Changhwa Jacob Cheu 

University of Cincinnati 

Medical Center 

Department of Environmental Health 

3223 Eden Avenue 

Cincinnati, Ohio 45267-0056 

Program Area: Occupational Cancers 

Grant Number: 5 R03 OH02972-02 

Start & End Dates: 08/01192 - 07/31/94 

Funding Level: $12,472 ($23,930 Cum) 

Importance to Occupational Safety and Health 

Pulmonary abnormalities are listed among the ten 

leading occupational diseases in the work place in the 

United States. Iron and aluminum compounds are 

widely encountered particles in the occupational 

settings. In addition to these particles, workers are 

frequently exposed to polycyclic aromatic 

hydrocarbons (PAH). Benzo(a)pyrene (BaP), a 

ubiquitous P AH has been well characterized over 

70 years. The adverse effects of BaP are linked to its 

active metabolites rather than to BaP itself. It has 

been shown that iron oxide, but not aluminum oxide, 

can enhance lung tumor formation in combination 

with BaP. The purpose of this study is to explore the 

role of particles in the induction of pulmonary 

disorders, in particular, lung cancer. Male Syrian 

Golden hamsters (6-8 wks old) will be used in this 

study based upon: (I) low spontaneous lung cancer 

rate; (2) higher resistance to pulmonary infection and ' 

inflammation; (3) resemblance to humans in terms of 

histogenesis and pathogenesis. Primary alveolar 

macrophages (AM) and tracheal epithelial cells (a cell 

line provided by Dr. Mossmon from University of 

Vermont, Burlington, Vermont) will be cocultured. 

The reasons are that (1) biological responses to 

inhaled particles include their ingestion by AM and 

clearance from the lung; (2) both AM and tracheal 

epithelial cells have the capability to metabolize BaP; 

(3) the target tissue in terms of pulmonary carcinoma 

is associated with epithelial origins. The main focus 

of this project is to study the effect of particles upon 

the alteration of BaP metabolism and DNA binding. 

The profile of BaP metabolites, the amount and types 

of DNA-adduct formation may provide us with some 

insights upon the role of particles in the mechanism 

of cocarcinogenicity. 

Objectives 

The overall objective of this study is to 

investigate the role of particles in potentiating 

pulmonary tumorigenicity. The proposed hypothesis 

is that cocarcinogenicity of particles with BaP is due 

to the enhancement of BaP metabolism in AM and 

potentiation of the binding of BaP metabolites to the 

DNA of target epithelial cells. The specific aims are 

as follows: (1) to determine the alteration of basal 

metabolic activities of AM in response to BaP or 

BaP-coated particles (Fe20 3 and Al20 3); (2) to 

determine the pattern and amount of BaP metabolites, 

in particular, 7,8-diol-BaP, the precursor of the 

ultimate carcinogen, in response to radiolabeled BaP 

or BaP-coated particles in AM; (3) To determine the 

level of DNA-binding in epithelial cells which have 

been cocultured with AM in response to BaP or 

BaP-coated particles; and (4) to identify the profile 

of DNA adducts in epithelial cells in response to 
cocultivation of AM which have been treated with 

BaP or BaP-coated particles. 

Methodology 

Cytochrome c reduction assay is used to measure 

the basal metabolic activity of AM. Ethyl acetate 

extraction and HPLC analysis are conducted to 

determine the pattern and amount of BaP metabolites 

in the cells. 32P-postlabelling is conducted to 

measure and identify DNA adducts in the cells. 

Significant Findings 

Viability ( erythosin B dye exclusion) data suggest 

that up to BaP(5ug) coated 2.0mg Fez03 or Al20 3 

particles /106 AM /plate revealed no signs of 

cytotoxicity. Within this dose range, metabolism 

studies were conducted with BaP(5ug) alone or 

BaP(5ug) coated particles (0.5,1.0,1.5 and 2.0mg). 

After 24 hr, metabolism data indicate that the release 

of dihydrodiols(9,10;4,5;7,8), phenols(9;3;7), 

quinones(4,5;3,6) and total BaP metabolites was 

significantly greater with Fe20 3 compared to Al20 3 or 

BaP alone. The formation of 7,8-dihyrodiol-BaP, 

the procarcinogen, was also consistent with the 

increase of Fe20 3 doses. Coadministration of 

7,8-benzo(a)flavone (a-NF,5uM), an inhibitor of 

cytochrome P-450s, significantly reduced the BaP 

metabolism in BaP-coated Fe20 3 and Al20 3 

treatments, 66% and 55%, respectively. These data 

suggest that particles enhance the metabolism of BaP 

in AM via the modulation of P-450s isozymes. 

Currently, cyclohexene oxide(CO), an inhibitor of 

epoxide hydrolase is also under investigation. The 

DNA from tracheal epithelial cells (HTE) which were 

coincubated with AM were isolated and quantitated. 

The treatments of these DNA samples include, 

BaP(5ug), BaP(5ug)-coated Fe20 3 (l .Omg)or Al20 3 

(2.0mg),BaP(5ug)/a-NF(5uM), 

BaP(5ug)/CO(O.OOIM) and BaP(5ug)-coated Fe20 3 

(l.Omg)or Al 20 3 (2.0mg)with a-NF(5uM). 32P-postlabeling assays are underway to identify the 

profiles of DNA adducts. 

Occupational Cancers - Page 67 
Page 68 - Traumatic Injuries 

Explosion Hazards Related to 

Combustible Dusts 

Charles W. Kauffman, Ph.D. 

University of Michigan 

Department of Aerospace Engineering 

2508 Patterson Drive 

Ann Arbor, Michigan 48109-2140 

Program Area: Traumatic Injuries 

Grant Number: 5 ROI OH01122-09SJ 

Start & End Dates: 01/01/81 - 12131/92 

Funding Level: $0 ($1,287,986 Cum) 

Importance to Occupational Safety and Health 

The safety hazard resulting from finely divided 

combustible material has to some extent been 

recognized, although it would appear that these 

materials are not treated with the same concern as 

flammable liquids and gases. In the grain industry in 

fiscal 1991, there were 16 dust explosions, 9 injuries, 

and I death. It is the grain and underground coal 

mining industries in which dust explosions are most 

prevalent. This situation is much improved from the 

late 1970's and early 1980's, in that in FY 1987 and 

FY 1990 there were no deaths as compared with the 

high for this decade of 11 in FY 198 l. Additionally, 

the number of injuries has declined steadily from a 

decade high of 59, also in FY 1981. Data collected 

under the research effort supported by this grant has 

had an influence upon safety regulations for the grain 

industry put into effect by OSHA on March 31, 1988 

and finally upheld by the U.S. Circuit Court. 

Objectives 

The purpose of this research project is to 

quantitatively characterize the explosion hazard 

represented by suspended and layered combustible 

dust. Using specially developed facilities, 

measurements are made which describe the 

fundamental aspects of dust combustion (laminar and 

turbulent burning velocities, denotation, velocity, 

reaction zone thickness, etc.) as a function of the 

parameters describing the initial conditions for the 

dust (chemical composition, size, shape, 

concentration, moisture content, premixedness, 

turbulence parameters including intensity and scale, 

etc.) This contrasts strongly with the traditional 

characterization of dust explosion hazards which 

employed "standard" testing apparatus in which well 

characterized dust was allowed to react under 

unknown and in some cases inappropriate conditions 

and where the results were characterized by 

parameters which may not be quantatively useful. 

Analytical efforts directed at the development of 

models which explain the observed phenomena have 

been productive. 

Methodology 

The suspended dust combustion studies are 

conducted in the Premixed Turbulent Combustion 

Bomb (PTCB) which is a spherical, one cubic meter 

jet-stirred reactor. The combustion process is 

initiated at the center of the well-characterized, 

uniform, turbulent dust cloud. During its propagation 

toward the vessel wall, appropriate measurements are 

made to characterize the burning process. The 

layered dust combustion studies are done in the 

extended Flame Acceleration Tube (FAT) which 

consists of seven continuous segments of 3000 psi 

working pressure steel tubing with a total length of 

231 ft. and an im.ide diameter of one foot. It is 

closed at one end and open at the other. A controlled 

thickness and width dust layer is placed along the 

bottom of the tube, and it is then ignited by the 

combustion of a presuspended dust cloud (primary 

explosion) in the first twelve feet of the closed end. 

The history of the resulting combustion process as it 

accelerates toward the open end is monitored using 

regularly spaced appropriate instrumentation. In both 

of these facilities, the burning velocity and the 

post-combustion thermodynamic conditions are 

measured as a function of parameters characterizing 

the dust and pre-combustion thermodynamic 

conditions. Additionally, a horizontal and a vertical 

detonation tube are being used. In the vertical tube, 

which is 20 feet long and has a square internal cross 

section of 2.5 inches, it is possible to create a 

uniform, suspended dust-air mixture and to introduce 

at the top end a blast wave which may initiate a 

detonation. In the horizontal tube, which is 23 ft. 

long and has a 1.5 inch by 2.5 inch internal 

rectangular cross section, it is possible to deposit a 

uniform layer of dust along the bottom or narrow 

surface, for the length of the tube and then allow a 

blast wave to propagate into the tube which may 

initiate a detonation. Both facilities are instrumented 

to monitor the decay of the initiating wave or its 

transition into a steady detonation. One additional 

piece of equipment is used which allows the 

suspension of a dust particle in a controlled 

environment where it may be ignited and its 

subsequent combustion observed. Analytical work is 

being continued with regard to the layered dust 

combustion problem within the framework initially 

established by the U.S. Bureau of Mines, although 

this has now been significantly improved upon. For 

the suspended dust, much of the analysis depends 

upon that done by Bradley at Leeds for turbulent 
premixed gas flames. Modelling of dust detonations 

has been based upon the heterogeneous models 

originally developed at the University of Michigan 

with appropriate modifications. The modelling of 

particulate combustion is similar to classic droplet 

combustion models and that done for coal particles. 

Significant Findings 

Using the particle on the fiber technique for 

cellosic particles, the volatile and char combustion 

rates have been established for both non and nearly 

spherical particles. Modification of the apparatus 

which allows multiple view imaging of the burning 

particle has been completed allowing the 

determination of a more accurate size shape history 

thus improving the burning rate data. The Premixed 

Turbulent Combustion Bomb has been modified to 

produce extremely high levels of nonsteady 

turbulence exhibiting some similarity to the more 

traditional dust explosion testing apparatus. The 

Laser Doppler Anemometer system has been adopted 

to acquire data under these transient conditions. The 

higher levels of turbulence have been verified as 

previously successful and strong ignition sources 

under these conditions do not lend to flame 

propagation. The layered dust experiments conducted 

in the Flame Acceleration Tube which was 

lengthened to seventy meters regularly produces 

deflagration to detonation transitions. The severity of 

the combustion process is indicated by overpressures 

varying from 30-60 atm, temperatures varying from 

1600-1800 K, and velocities bracketed by 

1120-1760 mis. The exact results depend upon the 

dust layer pattern, moisture content, type, and 

intensity of the ignition source. The multiheaded 

structure of the detonation wave is currently being 

resolved. Finally, an instrument based upon forward 

and back scattered light has been developed which 

gives the rate of entrainment of the layered dust, 

which is presumably the rate limiting process. The 

analytical modelling of the accelerating flame 

supported by the layered dust has shown that such 

flames can generate higher overpressures than 

constant velocity flames. In the deflagration to 

detonation transition, the peak pressure occurs where 

the detonation originates, and after a short distance, 

a steady detonation is established. The direct 

initiation of a detonation fueled by layered dust by a 

strong ignition source has proved to be more elusive. 

However, with a strong initiating blast wave in a pure 

oxygen environment with a high layered dust 

concentration, an accelerating detonation wave could 

be generated behind the initiating blast wave. It is 

apparently difficult to rapidly suspend the layered 

dust in the small characteristic time available. 

Traumatic Injuries - Page 69 

Publications 

Austin PJ, Kauffman CW, Sichel M: Combustion of 

Single Non-Spherical Cellulosic Particles. Dynamics 

of Heterogeneous Combustion and Reacting Systems, 

Progress in Astronautics and Aeronautics AIAA, 

Vol 152, pp 136-154, 1993 

Jarosinski J, Pu YK, Bulewicz EM, Kauffman CW, 

Johnson VG: Some Fundamental Characteristics of 

Cornstarch Dust Air Flames. Dynamics of 

Heterogeneous Combustion and Reacting Systems, 

Vol 152, Progress in Astronautics and Aeronautics, 

pp 119-135, AIAA, 1993 

Sheng J, Tonello N, Kauffman CW, Sichel M, 

Wolanski P: Enhancement and Generation of 

Detonations Using Dust Layers. Dynamic Aspects of 

Explosion Phenomena, Vol 154 Progress in 

Astronautics and Aeronautics, AIAA pp 185-194, 

1993 

Kauffman CW, Sichel M, Wolanski P: Research on 

Dust Explosions at The University of Michigan. 

Powder Technology, pp 119-134, v 71, 1992 

Sichel M, Kauffman CW: Dust Combustion. 

International Workshop on Heterogenous Combustion, 

Ministry of Science and Technology, The Dead Sea, 

Israel, January 6-10, 1992 

Sichel M: Numerical Modelling of Heterogenous 

Detonations. Numerical Approaches to Combustion 

Modeling, (eds. ES Oran, JP Boris), Progress in 

Astronautics and Aeronautics, Vol 135 AIAA 1991 

Sichel M: Numerical Modelling of Heterogenous 

Detonations. In Numerical Approaches to 

Combustion Modelling, (eds. ES Oran, J Boris), 

American Institute of Aeronautics and Astronautics, 

in press, 1989 

Leisch SO, Kauffman SW, Sichel M: The 

Smoldering Combustion of Cellulosic and Starch 

Dusts. Proc of the International Conference in the 

Physical and Chemical Processes Occurring in a 

Burning Cigarette, RJ Reynolds Tobacco Co., 

Winston Salem, NC, 1987 

Srinath SR, Kauffman CW, Nicholls JA, Sichel M: 

Secondary Dust Explosions. Industrial Dust 

Explosions, ASTM STP 958, Philadelphia, PA, 1987 

Kauffman CW: Recent Dust Explosion Experiences 

in the U.S. Grain Industry. Industrial Dust 

Explosions, ASTM STP 958, Philadelphia, PA, 1987 
Page 70 - Traumatic Injuries 

Case-Control Study of Sawmill 

Injuries in Maine 

Laura Punnett, Sc.D. 

University of Lowell 

Department of Work Environment 

One University Avenue 

Lowell, Massachusetts 01854 

Program Area: Traumatic Injuries 

Grant Number: 5 ROI OH02741-03 

Start & End Dates: 06/01190 - 08/31/94 

Funding Level: $48,493 ($167,775 Cum) 

Importance to Occupational Safety and Health 

Lumber and wood products processing (SIC 24) 

is the second largest industry in Maine, with an 

annual average employment of approximately 13,500 

workers, accounting for about 13% of the 

manufacturing work force. In 1987, the incidence of 

OSHA recordable injuries and illness in sawing and 

related mills, excluding logging (SIC 242-249) was 

29.1 cases per 100 workers, more than twice the 

average statewide rate. Preliminary analyses of cases 

recorded on the OSHA Form 200, as well as 

Workers' Compensation First Reports of Injury, 

suggested that about two-thirds of the lost-time 

injuries were acute traumatic incidents and one-third 

were musculoskeletal disorders. 

A number of specific safety and ergonomic 

hazards have been identified in Maine sawmills. 

These include unguarded platforms, stairways, and 

floor openings; dangerous and improperly guarded 

equipment; manual materials handling of logs and 

other heavy items; unshielded hot surfaces; excessive 

noise; and carbon monoxide from power equipment 

exhaust. Although these hazards are virtually 

ubiquitous, the conditions under which they actually 

result in energy transfer and injury have not been 

well defined by epidemiologic analysis. The sparse 

literature on injuries in this industry is primarily 

descriptive, with little insight into causal factors that 

could be preventable, particularly by means of 

ergonomic or safety engineering controls. 

Objectives 

The primary objective of the proposed research 

project is to identify the wood product processing 

activities, equipment, and working conditions that are 

associated with increased risk or severity of acute 

traumatic events and musculoskeletal injuries, to 

identify etiologic associations and the opportunity for 

preventive interventions. 

Methodology 

A case-control study is being conducted of risk 

factors in the work environment for occupational 

injury in the Maine wood products industry 

(SIC 242-249). A population based case-control 

study design is employed, in which cases are 

identified from employers' First Reports of Injury 

filed with the State Workers' Compensation 

Commission, collected for the U.S. Department of 

Labor Supplementary Data System. Controls are 

selected from employee lists provided by participating 

employers or from membership lists provided by 

participating union locals. 

All subjects are interviewed to obtain information 

on demographics, anthropometry, work history and 

medical history. The interview also obtains 

information on production tasks, characteristics of the 

equipment, tools and product, and other features of 

the work environment. For cases, this information is 

obtained regarding the specific activities performed 

on a typical work day and at the time of the injury. 

Controls are asked about their work activities on a 

typical work day and on the last day worked on the 

same day of the week as the index injury. Exposure 

items include specific ergonomic features and general 

working conditions, including tool weight, noise, 

thermal environment, illumination, work pace, heavy 

lifting, machine pacing, piece rate wages, overtime, 

shift work, and volume of production output. 

Subjects are also asked about the presence and 

activities of any workplace health and safety 

programs, such as worker training or 

labor-management committees. 

Some supplementary exposure data is being 

sought, to attempt to validate the interview 

information. Where possible, the plant mechanics in 

participating mills are contacted after the interviews 

for additional specific information on equipment, 

tools and machinery. For a small number of 

workplaces, the investigators have visited the plants 

in order to evaluate working conditions, using a 

standardized safety and ergonomic job analysis 

methodology modified to adapt it to this particular 

industry. All participating mills have been requested 

to provide any environmental data that might have be 

available for noise, heat, dust levels, etc., through 

in-house monitoring or OSHA inspections. 

Exposure odds ratios will be computed to 

estimate the risk associated with specific factors for 

each type of injury and body part. Some features of 

the work environment are hypothesized to affect the 

risk of injury in a manner that is not highly specific 

to the type of injury. Factors such as piece work vs. 

hourly wage, shift worked, work pace and production 
output, noise intensity, heat and humidity, and work 

on a temporary vs. usual job assignment may be 

associated with a general increase in injury rates 

because they cause generalized fatigue, difficulty in 

safely maintaining the required work pace, or 

unfamiliarity with safe operating procedures. 

In addition, a series of specific hypotheses will 

be examined regarding risk factors for different types 

of injuries. For example, strains and sprains of the 

back will be studied with respect to weight of loads 

in manual material handling and the trunk postures 

used to operate tools or machinery. Acute injuries 

(cuts, lacerations, contusions, etc.) of the upper 

extremity will be analyzed with respect to use and 

characteristics of gloves, non-neutral upper extremity 

postures, and the length of the exposed blade or 

cutting surface. Slips and falls will be studied in 

relation to heat and humidity, workload intensity, 

respirator use, weight of loads handled, and condition 

of the floor surface. 

Significant Findings 

None to date. 

Development of a Construction 

Injury Predictive Model 

Kweku K. Bentil, Ph.D. 

University of Washington 

Department of Building Construction 

116 Architecture Hall, Al-I 5 

Seattle, Washington 98195 

Program Area: Traumatic Injuries 

Grant Number: J ROI OH02743-0JA2 

Start & End Dates: 09/30/93 - 09129/95 

Funding Level: $106,833 ($106,833 Cum) 

Importance to Occupational Safety and Health 

Analysis of previous injury data has been used to 

prevent injuries in other industries (such as 

manufacturing and transportation) in the past. As 

asserted by the National Safety Council (1982): 

Job safety analysis has proven time and 

again to be an accident and occupational 

illness prevention tool in many industries 

over the past years. (p. 2) 

The ability to analyze accident data and predict 

the number of injuries that can be expected can make 

Traumatic Injuries - Page 71 

it possible for safety programs to be narrowly tailored 

to each specific construction project and contractor in 

order to make existing safety programs more 

effective in preventing injuries. Therefore the results 

of this study can greatly expand available knowledge 

about safety in the construction industry and lead to 

lower injury rates. Results of this research will be 

disseminated to the Occupational Safety and Health 

Administration (OSHA), the major construction 

contractor organizations (such as the Associated 

General Contractors, Associated Builders and 

Contractors, Mechanical Contractors Association and 

the National Electrical Contractors Association) for 

distribution to their membership, the Center for 

Excellence in Construction Safety, and the major 

insurance companies. The results of this study will 

be published in the relevant journals. (such as the 

"Constructor" and "Builder & Contractor"). 

The results of this research will provide the 

construction safety research community, contractors, 

insurance companies, risk managers, and OSHA a 

tool that can help measure the effectiveness of safety 

programs. Specifically, it will also enable OSHA to 

target projects with high risk factors for inspection 

and more aggressive prevention programs. Finally, 

the results will also serve as the basis for future 

research on developing injury predictive models for 

other categories of construction (residential, 

industrial, heavy and highway). 

Objectives 

The purpose of this research is to develop 

knowledge that can be used in preventing traumatic 

injuries at commercial construction sites. The main 

objective of this study is to develop a parsimonious 

empirical model that will have good capabilities of 

predicting the incidence of traumatic injuries 

requiring medical care among construction workers 

employed by commercial construction contractors. 

The first aim is to investigate and identify the most 

significant risk factors that can influence the 

occurrence of injuries at commercial construction 

sites. The general categories of risk factors to be 

addressed are characteristics of commercial 

construction contractors, projects and workers. The 

second aim is to analyze these categories of risk 

factors and understand the relationship between them 

and the number of traumatic injuries at commercial 

construction sites requiring medical treatment by a 

licensed caregiver. The third aim is to utilize these 

factors and their functions in a model that will have 

good capabilities of predicting the incidence of 

injuries at given construction sites before the 

commencement of that project. 
Page 72 - Traumatic Injuries 

Methodology 

The main outcome of interest will be the rate of 

traumatic injuries occurring at commercial 

construction sites that require medical treatment by a 

licensed caregiver. The injuries studied will be the 

same as those that are required to be reported by 

OSHA. Data will be collected for a minimum of 

I 00 commercial construction contractors and 

400 projects from commercial construction 

contractors and the State of Washington Department 

of Labor and Industries, and a data base created. 

Risk factors focussing on specific characteristics of 

construction contractors, projects and workers will be 

analyzed. 

Analysis will involve fitting Poisson regression 

models, with adjustment for overdispersion, and for 

shared contractor and project effects. Model fitting 

will be accomplished using the GLIM Computer 

Software, developed by the Royal Statistical Society. 

The characteristics of commercial construction 

contractors, projects, and workers will be investigated 

as explanatory variables in order to determine their 

significance in predicting injuries. Rates of injuries 

will be calculated as injuries/FTE. Relative risks and 

corresponding confidence intervals will be estimated 

for combined injuries, and for individual types of 

injury. Standard likelihood methods of generalized 

linear models will be used for testing the effect of 

each explanatory variable on the injury rate, both 

alone, and adjusted for the confounding effects of 

other explanatory variables. 

Significant Findings 

None to date. 

Role of Postural Stability in 

Industrial Falls 

Amit Bhattacharya, Ph.D. 

University of Cincinnati 

College of Medicine 

Department of Environmental Health 

3223 Eden Avenue 

Cincinnati, Ohio 45267-0056 

Program Area: Traumatic Injuries 

Grant Number: 5 ROJ OH02794-02 

Start & End Dates: 09/30191 - 09/29194 

Funding Level: $0 ($373,611 Cum) 

Importance to Occupational Safety and Health 

Falls have been found to be a significant 

contributor in causing lumbar spine injury, fracture of 

bones, and disability. A review of occupational 

injury data in U.S. industries and those in other 

countries indicates that the construction industry has 

the highest incidence rates of accidents, including 

fatalities, among major industries. As per literature 

review, various field studies have identified several 

risk factors as contributing to falls at the workplace. 

These are: Environmental (surface contamination and 

friction, standing surface firmness and lighting); 

Job-Task (blocking of peripheral vision due to poor 

work layout and workload); and Personal (age, sex, 

and physical fitness level) factors. 

This ongoing study will help identify and quantify 

the influence of individual and combination effects of 

Environmental, Job-Task and Personal risk factors on 

fall potential. The results from the proposed study 

will help develop a statistical model showing 

relationship between fall potential and the independent 

variables characterizing the Environmental, Job-Task 

and Personal risk factors. In future field studies, use 

of the statistical model to help evaluate the fall 

potential can be accomplished by measuring, in a 

walk-through evaluation, existing risk factors at the 

work site. The model can then be used to determine 

which of the risk factors need to be corrected to 

reduce the fall potential. Availability of such models 

will have significant impact in identifying risk factors 

and their reduction will help prevent fall-related 

injuries, disabilities, lost work days, and higher 

medical costs as well as increasing national 

productivity. 

Objectives 

1. To measure the upright postural balance (stability 

or sway) under different standing surface 

contamination conditions (dry/clean and oily), 

standing surface firmness (firm and compliant), 

environmental lighting (good and poor), and 

peripheral vision conditions (blocked and 

unblocked) after being exposed to different 

workloads (40 watts and 100 watts) in workers in 

the age range of 21 to 55 years. 

2. To investigate the age-associated differences in 

the maintenance of upright postural balance under 

above mentioned risk factors. 

3. To investigate the age-associated differences in 

postural corrective responses to: (a) sudden 

perturbation in the body segment movement; 

(b) forward reach and lifting; and (c) sudden 

external loading under all combinations of risk 

factors. 

4. To investigate the age-associated differences in 

the relationship between an objective measure of 
postural instability and the subjective perception 

of postural instability, under all combinations of 

risk factors. 

Methodology 

In this study, postural instability and fall potential 

of risk factors are being evaluated for industrial 

workers' performance (21 to 55 years of age) on 

32 test conditions which represent combinations of 

these risk factors. These tests simulate conditions 

which occur in industrial/occupational environments. 

The current pool of industrial subjects represent a 

wide range of occupations. Subjects are tested 

immediately after exposure to light and 

moderate-to-heavy workloads (bicycle ergometer) to 

quantitate their postural stability. Before and 

immediately after completion of a workload, the 

subject is tested for upright postural sway and 

postural corrective responses to simulated tasks which 

might occur in an industrial environment. Also, their 

subjective perception of postural balance is assessed 

immediately after each test using a subjective Scale of 

Rating of Perceived Sense of Fall. The postural 

stability is measured with a six-component force 

platform located inside our Fall/Stability Assessment 

Facility. Each subject's "Functional Stability 

Boundary" is also determined. This information is 

used for the calculation of the Index of Proximity to 

Stability Boundary (IPSB). The value of IPSB 

obtained during the postural stability tests is used to 

determine which of the test conditions pushed the 

body's center of pressure (CP) to or beyond its 

stability boundary and, therefore, had the potential to 

create an accident due to a fall or near fall. 

Significant Findings 

The data are still being collected from the 

subjects therefore the findings presented are 

preliminary in nature. A quantitative method of 

characterizing fall potential has been developed and 

is being used to determine the effectiveness of this 

technique with the data from this ongoing study. A 

preliminary analysis of the data collected from the 

38 subjects (complete data set from 46 subjects have 

been collected but all of them have not been analyzed 

yet) who have completed the testing protocol 

(providing data from 8,492 postural tests) has been 

performed. Despite the small sample, all conditions 

(workload,surface firmness, surface slipperiness, 

lighting and peripheral vision) already show a 

significantly (p<0.05) detrimental effect on postural 

balance as measured by the sway length parameter in 

a repeated measure analysis of variance. Each of 

these significant effects are consistent with our 

proposed hypotheses. Certain interactions among the 

experimental conditions or between age or gender and 

Traumatic Injuries - Page 73 

the within-subject conditions are also significant. 

For example, a significant lighting/surface firmness 

interaction indicated that subjects had even more 

difficulty while standing on a compliant surface in 

dim lighting than would be expected from either of 

these factors alone. 

Workplace Assault-Related Injuries: 

Incidence and Risk 

Jess F. Kraus, Ph.D. 

University of California 

School of Public Health 

Department of Epidemiology 

10833 Le Conte Avenue 

Los Angeles, California 90024-1772 

Program Area: Traumatic Injuries 

Grant Number: 5 ROI OH02872-03 

Start & End Dates: 09/30/91 - 09/29/94 

Funding Level: $193,325 ($547,337 Cum) 

Importance to Occupational Safety and Health 

The Occupational Safety and Homicide Act was 

created in order to "assure as far as possible every 

working man and woman .... safe and healthful 

working conditions and to preserve our human 

resources." Though occupational injury has changed 

significantly since the enactment of the OSHA Act by 

Congress, no specific portions of the act deal directly 

with intentional injury in the workplace. The 

potential for workplace violence, an increasing public 

health issue, threatens many employers and 

employees. 

Occupational homicides account for 7,000 to 

13,000 deaths per year, based on estimates from 

various data sources. In a recent NIOSH update, it 

was noted that occupational injuries affected minority 

groups in high-risk occupations disproportionately 

(19% black and 6% other races). Differences 

between men and women at work were also 

highlighted: while homicide at work accounted for 

10% of deaths among men, it was the leading cause 

of death for women at work (41%). 

Employees of high-risk industries previously 

Identified (convenience food stores, discount retail 

stores, gasoline service stations, eating and drinking 

establishments, and taxicab companies) continue to 

bear the brunt of assault-related injuries and 

fatalities. Most of the research in this area has 

focused on workplace homicides, yet the magnitude 

of non-fatal assault-related injuries has not been 
Page 74 - Traumatic Injuries 

assessed. Thus far, no specific risk factors or 

standards on preventive strategies for these industries 

have been developed. 

Objectives 

The overall objective of the proposed research is 

to understand the magnitude and identify the 

determinants of workplace assault-related injuries. 

To accomplish this objective, two specific aims are 

being undertaken: (1) to estimate the average 

incidence rates of fatal and nonfatal work-related 

assault injuries in seven California counties between 

January 1993 and June 1994; and (2) to identify 

individual occupational and environmental predictors 

of fatal and non-fatal assault-related injuries in 

selected high-risk occupations in the same seven 

California counties. 

Methodology 

The study design consists of two components: 

1. Incidence determination and rate estimation 

based on a number of sociodemographic, 

occupational, environmental and industrial group 

parameters; and 

2. A case-control study to identify risk factors for 

fatal and non-fatal assaultive injury. 

We have expanded the study to encompass most 

of the conurban areas within the counties of 

Sacramento, Alameda, Santa Clara, Los Angeles, 

Riverside, San Bernardino and San Diego, California. 

The scope of our collaborative network now includes 

police, sheriff and coroner's departments, Cal-OSHA, 

and State Compensation Insurance Fund. This 

network of data sources serves an important role in 

linking health information to allow more precise 

estimates of work-related assaults and homicides. 

We successfully piloted a detailed survey 

instrument for assessing factors surrounding 

assault-related violent incidents resulting in mild to 

severe injuries or fatalities. The survey is currently 

being implemented in all seven counties by field 

researchers, each of whom has received extensive 

training in survey administration and case- and 

control-finding protocols. Our field research staff 

has been equipped with a portfolio that contains 

letters of support from various members of the state 

legislature and from Cal-OSHA. 

Case ascertainment procedures have evolved with 

recognition of the budgetary crisis affecting state and 

federal agencies. Additionally, some unforeseen 

delays in case surveys have surfaced: irreparable 

damage to business establishments following some 

violent incidents, permanent closure of small 

businesses where the victim was the owner, language 

barriers, and refusals to participate. For control 

finding, we are utilizing a database of business 

names, addresses, phone numbers, and contact 

persons across an identical spectrum of industries. 

Significant Findings 

None to date. 

Vibration Oculomanual 

Coordination and Traumatic Injuries 

Bernard J. Martin, Ph.D. 

University of Michigan 

School of Engineering 

Center for Ergonomics 

1205 Beal Avenue, 156 JOE 

Ann Arbor, Michigan 48109-2117 

Program Area: Traumatic Injuries 

Grant Number: 5 ROI OH02967-02 

Start & End Dates: 05/01/92 - 04/30194 

Funding Level: $90,109 ($189,066 Cum) 

Importance to Occupational Safety and Health 

The focus on manual control perturbation 

resulting from vibration exposure as a potential risk 

factor is of particular importance. Indeed, 

performance of visually guided motor activities is an 

important factor of accidents involving falls, dropping 

objects and improper use of controls. Furthermore, an 

estimated 1.45 million workers use vibrating tools 

an? disabling injuries numbered 570,000 for mining, 

construction and manufacturing industries where 

vibrational hand-tools and vibrating machines are 

intensively used. Although one cannot blame 

vibration as a common denominator to those injuries, 

a significant number is likely to be related to manual 

control impairment resulting from vibration exposure. 

The aim of this project is to contribute to the 

reduction of risk of acute occupational traumatic 

injuries associated with vibration-induced alterations 

of oculo-manual coordination. The proposed work 

will model eye-hand performance and the withdrawal 

reflex responses as a function of vibration frequency, 

displacement amplitude and exposure time of 

vibration applied to the hand. 

The expected results will be used to estimate a 

vibration limit relevant to manual performance 

effects. Further disclosure of the importance of 

visual control of the limbs should lead to the 
formulation of safety and design recommendations 

concerning the placement of controls and handles. 

Objectives 

The overall objective is to emphasize the often 

ignored or neglected role of movement errors in 

accidents occurring in vibratory environments. The 

general hypothesis is that vibration-induced 

modification of sensory messages, used by the central 

nervous system to control and regulate sensorimotor 

activities, contribute to the alteration of both 

movement accuracy and oculo-manual coordination. 

The following hypotheses are tested: 

I. Involuntary motor activities, such as reflexes, are 

significantly affected during vibration, 

2. Sensory perception is significantly affected by 

vibration, 

3. Oculo-manual coordination is significantly 

affected during vibration, 

4. Vibration-induced alterations persist after 

exposure and vary with intensity, 

5. Permanent visual control of the upper limbs 

should compensate to some extent 

vibration-induced affection of other sensory 

modalities and contribute to performance 

improvement, 

6. Vibration displacement amplitude should exhibit 

a high correlation with performance decrement 

over the 80-200 Hz frequency range, 

7. Sensorimotor performance should be less 

affected by high frequency vibration(> 200 Hz) 

Methodology 

Withdrawal reflex 

This protective muscular response, elicited in the 

forearm flexor muscles by electrical stimulation of 

the radial nerve at the wrist is studied during low 

level grip exertion (at rest or 10% MVC). Electrical 

activity of the fingers and wrist flexor and extensor 

muscles are monitored using pairs of small cupular 

electrodes. Hand vibration (90, 150, 200 Hz, 

0.2 mm) is applied perpendicularly to a vertical 

handle held by the subject. Changes in the amplitude 

of both components of the reflex responses are 

quantified as a function of vibration parameters. 

Manual dexterity 

Manual movement prec1S1on and performance 

time are evaluated through a visuo-manual tracking 

task performed before and after long term hand 

vibration exposure (90, 150, 300 Hz, 0.2 mm and 

0.3 mm, IO min. duration). The alterations of 

tracking errors and tracking time are analyzed as a 

function of the vibration parameters. 

Traumatic Injuries - Page 75 

Oculo-manual coordination 

A pointing task consisting in a1mmg 

simultaneously with the hand and the eye at visual 

targets is performed before, during short term hand 

vibration exposure (200 sec) and after long term hand 

vibration exposure (10 min.). The vibration 

frequencies are 90, 150, 300 Hz, the amplitude is 

0.2 mm. Eye and hand position are measured to 

quantify ocular and manual performance. Eye 

movement pattern is analyzed to evaluate 

oculo-manual coordination. The influence of 

vibration parameters is analyzed. 

Significant Findings 

Withdrawal reflex 

Motor effects - Both components of the reflex 

response are facilitated by hand vibration and this 

facilitation increases with initial muscle contraction; 

however, each component is affected differentially by 

vibration frequency. For the early component, the 

facilitation is significantly less pronounced for a 

200 Hz vibration, while for the late component 

vibration frequency had no significant effect. 

Effects on perception - When the muscles were 

initially at rest, a decrease in perceived discomfort 

elicited by the electrical stimulus was indicated by 

7 /10 subjects during vibration exposure. When a 

moderate level of voluntary contraction was exerted 

the differentiation between pre and per-vibration 

sensation evoked by the electrical stimulus was not 

statistically significant. 

Manual dexterity 

Vibration induced a significant increase in errors 

and a significant decrease in tracking time. These 

impairments decay with time after vibration exposure. 

The recovery period is greater than 5 min. but less 

than 10 min. The subjective rating of the 

performance indicates that the subjects tend to 

perceive the task as being easier after vibration 

exposure. Thus, the results show that vibration 

affects precision and velocity control of visually 

guided hand movements and that performance 

decrements are not perceived. Vibration frequency 

and amplitude do not seem to have a strong influence. 

Both studies indicate that vibration-induced 

alterations of involuntary or voluntary motor activities 

are not consciously perceived. 
Page 76 -Traumatic Injuries 

Ergonomics of Task Performance 

On Slippery Surfaces 

Amit Bhattacharya, Ph.D. 

University of Cincinnati 

College of Medicine 

Department of Environmental Health 

3223 Eden Avenue 

Cincinnati, Ohio 45267-0056 

Program Area: Traumatic Injuries 

Grant Number: J ROI OH03079-0I 

Start & End Dates: 09/15193 - 09114/96 

Funding Level: $233,071 ($233,071 Cum) 

Importance to Occupational Safety and Health 

Previous studies have shown that the event which 

immediately led to injury was slip in about 50% of 

the cases. This type of underfoot "first event" has 

been the main contributor to falls. The proposed 

study provides an experimental design which has the 

potential for investigating the interaction between age, 

sex and other fall risk factors such as psychophysical 

aspects of slipperiness evaluation, objective measure 

of surface slipperiness, shoe wear/tear, and lighting, 

while performing simulated industrial tasks. The 

proposed study will provide dynamic coefficient of 

friction (DCOF) and the rate of change in DCOF as 

criteria for slip prevention for (1) dynamic task 

performance while standing on a slippery surface and 

(2) walking with and without a turning motion with 

a weight in hand. Additional information will be 

provided regarding the change in the above criteria 

when wearing a used shoe with a worn-out sole 

surface in a young and an older age groups of 

workers. The gait pattern characteristics can 

significantly influence the required DCOF demand 

which provides the necessary slip protection. This 

type of information will have significant impact on 

the development of better portable slip-testing 

devices which can be used in a more realistic manner 

at the worksite (such as, the use of worker shoes 

which were involved in a slip-related accident) and 

can measure appropriate variables which better 

predict slips at the workplace. The evaluation of any 

slip-testing device as described above is dependent 

on the assumption that human performance on 

slippery surfaces is influenced by only limited 

biomechanical factors without regard to 

environmental, psychophysical and personal risk 

factors. 

While slip potential is predicted by DCOF and 

rate of DCOF the fall potential is influenced by 

additional factors such as Job, Environmental and 

Personal factors. For example, Personal factors of 

age, postural muscle strength, reaction time, 

subjective ability to correctly assess slipperiness of 

surface (psychophysical aspect) and gait patterns can 

significantly dictate whether task performance on a 

slippery surface will produce a fall or not. 

Objectives 

1. To determine the relationship between subjective 

assessment of slipperiness and the objective 

measure of coefficient of friction under optimal 

environmental lighting, job-task, and shoe sole 

wear/tear conditions. Also, determine the 

age-associated influence on the above 

relationship. 

2. To determine the effect of nonoptimal conditions 

of environmental lighting, job-task, shoe sole 

wear/tear and the subject's age on her/his ability 

to correctly assess the slipperiness of a surface. 

3. To determine the effect of environmental lighting, 

job-task, shoe sole wear/tear conditions, and age 

on the subject's ability to perform tasks (of daily 

living and occupational nature) requiring demands 

on her/his static (upright balance) and dynamic 

(gait) postural balance while her/his shoe sole 

surfaces are in contact with a slippery surface. 

To determine the age-associated differences in 

postural balance and gait characteristics 

associated with task performance on a slippery 

surface. 

4. To identify and quantitate postural balance (for 

both static and dynamic tasks) variables relevant 

for assessing the fall potential associated with 

task (of daily living and occupational nature) 

performance on slippery surfaces under various 

combinations of environmental lighting,job-task, 

and shoe sole wear/tear conditions. 

5. To determine the characteristics of the required 

coefficient of friction values and body segment 

movement dynamics for performing tasks without 

slipping under various combinations of 

environmental lighting, job-task, and shoe sole 

wear/tear conditions. 

Methodology 

In the proposed study, gait and postural instability 

and fall potential of all risk factors will be evaluated 

for industrial workers' (21 to 59 years of age) task 

performance on a slippery surface. These tasks 

simulate conditions which occur in nonoccupational 

and occupational environments while standing or 

walking on a slippery surface. The upright postural 

sway test (stability) and tests of postural corrective 

responses to the testing of upright postural balance, 

rapid movement of body segment, and 
forward/upward reach during lifting will be 

administered under all combinations of the following 

test conditions. After the postural stability test, the 

subjects will undergo gait evaluation tests with and 

without a five pound weight in hand under all 

combinations of the following three test conditions. 

Condition I: Three levels of randomized slippery 

surface (low, medium and highly slippery). Subjects 

will know that the surface is slippery but will be 

without the knowledge of its degree of slipperiness. 

Condition 2: Under acceptable (good) or 

unacceptable (poor) environmental lighting as per 

American Illuminating Engineering Society guidelines 

for rough to moderately precise work. Condition 3: 

Shoe conditions will be not worn-out sole (new) and 

worn-out sole. The order of administration of 

postural stability and gait tests will be randomized. 

An initial baseline measure (standing on a dry, 

nonslippery surface) will be performed before the 

twelve randomized combinations of these conditions. 

All subjects will undergo the test of Estimated 

Maximum Displacement of Center of Pressure 

(EMAX) before initiating the series of Postural 

Balance Tests and Gait Tests. The results of the 

EMAX test will provide an estimate of each subject's 

stability boundary in the anterior direction and the 

"Functional Stability Boundary" will be quantified. 

After the EMAX tests, each subject will return to the 

laboratory for additional visits to perform postural 

stability and gait tests. Before initiating the postural 

balance and gait tests each subject will undergo 

subjective assessment of slipperiness test. During 

subjective slipperiness assessment test, postural 

stability test and gait test each subject's insole 

pressure distribution will be also measured. The 

postural balance will be quantitated with a six 

component strain gauge force platform and the three 

dimensional gait characteristics will be measured with 

a video-based motion analysis system. 

Significant Findings 

None to date. 

Traumatic Injuries - Page 77 

Safety First: Fault Tree Expert 

System For Construction 

Fabian C. Hadipriono, Dr.Eng. 

Ohio State University 

School of Engineering 

Department of Civil Engineering 

470 Hitchcock Hall 

2070 Neil Avenue 

Columbus, Ohio 43210 

Program Area: Traumatic Injuries 

Grant Number: 5 KOi OHOOl 15-02 

Start & End Dates: 09/30/92 - 09/29/95 

Funding Level: $54,000 ($108,000 Cum) 

Importance to Occupational Safety and Health 

The project develops a system to improve 

construction safety by emphasizing the engineering 

aspects, and further incorporates other aspects 

pertinent to the engineering control system (e.g., 

procedural, behavioral, social, and economic aspects) 

The importance of the work is as follows: 

I. The knowledge gained could have a great impact 

on the way occupational safety and health 

institutions perform an analysis of a construction 

accident. These institutions are constantly 

involved in promoting safety in construction and 

in performing investigations in the event of 

construction accidents. The product of our 

research can be used as an engineering control 

system and would be of an invaluable aid to these 

institutions in reaching their objectives. 

2. We expect that research results will affect 

existing procedures and will automate the 

processing of construction accident information 

When completed, our project produces a 

run-time version of a software for use in micro 

computers. The system can be stationed centrally 

or distributed to any construction site. The 

service life of the system is essentially unlimited. 

Objectives 

Our objective is to develop SAFETY FIRST, a 

fault tree expert system for investigating and avoiding 

construction accidents in the area of construction 

falls. It is expected that the system could be used to 

mm1m1ze construction accidents and improve 

construction safety. SAFETY FIRST will provide a 

heuristic yet systematic approach for investigating the 

causes of construction accidents and for reducing and 
Page 78 - Traumatic Injuries 

avoiding them, thereby increasing labor safety. The 

research is intended to accomplish the following: 

1. To provide the user a tool with which to 

investigate a construction accident that has 

already occurred. The fault tree models will 

establish all possible causes contributing to the 

accident (and any combination of these causes), 

and will rank them in order of importance. 

Based on evidence gathered from the accident 

site, the expert system will trace a particular 

cause and will explain to the user how and why 

the accident has occurred. The expert system 

will also recommend ways to avoid this accident 

in the future. 

2. To provide the user with consulting tool that will 

explain the contributing causes of potential 

construction accidents. The fault tree models 

will show graphically the relationships among 

these causes and will determine the potential 

"weak links" that could result in a construction 

accident. Simulation study by the user using the 

expert system models will establish which causes 

are potentially hazardous to the workers. Hence, 

the system will serve as a tool to warn the user 

of potential accidents and to suggest applicable 

precautions. 

Methodology 

In order to achieve the objectives of our 

proposed project, we will use and combine two 

innovative research methods: the fault tree system 

and the expert system. Fault tree models are 

employed to represent the knowledge obtained from 

experts and literature concerning the causal 

relationships among events/causes that contribute to 

a construction accident. In simulating the way 

experts determine the cause of the accident, the 

expert system accommodates the knowledge for use 

by safety investigators. The research encompasses 

the following four major tasks: (1) Knowledge 

acquisition, (2) Fault tree development, (3) Expert 

system development, and (4) Validation. 

During the knowledge acquisition process, we 

function as the knowledge engineer who communicate 

with the experts, gather information from literature, 

and build the knowledge base. We perform three 

phases of knowledge acquisition: preliminary 

discussion, detailed discussion, and organization. 

Expert knowledge are represented by fault tree 

models, which show the paths of knowledge an expert 

takes in reaching a conclusion. Development of fault 

tree models include fault tree logic evaluation, fault 

tree modeling, and analyses. The development of the 

expert system includes knowledge base development 

and system validation. The knowledge acquired from 

experts and literature is organized in each path. A 

piece of knowledge can be rewritten in IF-THEN 

statements, which represent the way an expert 

assesses the cause(s) of an accident-i.e., 

heuristically. These assessments are often based on 

an expert's rules-of-thumb, educated guesses, and 

assumptions based on the expert's experience in 

construction safety. Knowledge from research 

literature on safety, including codes, regulations, and 

construction safety practices, can also be represented 

by IF-THEN statements much the same way as that 

from experts. These statements will be compiled and 

translated into IF-THEN production rules using the 

production rule language The production rules will be 

accommodated in a knowledge base, an essential part 

of am expert system. Evidence or information 

furnished by a user will be matched with a rule to 

produce the basic causes of a fall. The knowledge 

base of SAFETY FIRST will be validated by the 

knowledge engineer, participating expert(s), and 

non-participating experts. 

Significant Findings 

To date, we have completed the knowledge 

acquisition and representation of SAFETY FIRST. 

The knowledge acquisition includes researching 

literature and selecting and meeting with experts Most 

articles we encountered during our study are brief 

reports or news releases of construction worker's 

accidents, statistics of such accidents, and regulations 

and codes to avoid these accidents. Although 

injuries, illnesses, and deaths during construction 

occur at a rate that is 54% higher than the rate for all 

industries, our literature study reveals that causes of 

construction worker's accidents, and in particular, 

construction falls are seldom discussed in detail. 

The knowledge acquisition also includes obtaining 

information about construction falls from experts, 

who because of their experience, are knowledgeable 

in this domain. Experts elaborated on specific causes 

and their experience in solving past fall cases. Our 

findings reveal that experts' knowledge provides a 

wealth of information concerning construction falls 

that is often unavailable in literature. 

We classified construction falls as falls from 

higher elevation, falls from same elevation, and slips 

(not fall). The platforms where falls could occur 

were categorized into floor openings, floor edges, 

wall openings, roofs, steel beams, top of walls, 

ladders, and scaffoldings. We analyzed all possible 

events that may cause the fall and represent them 

using fault trees. The results of our study confirm 

our earlier prognosis of using fault tree diagrams to 

best represent the structure of experts' knowledge. 
Analysis of Construction Tasks For 

Overexertion Injuries 

John G. Everett, Ph.D. 

University of Michigan 

Department of Civil 

& Environmental Engineering 

2352 G.G. Brown Lab 

Ann Arbor, Michigan 48109-2125 

Program Area: Traumatic Injuries 

Grant Number: 1 R03 OH03154-0l 

Start & End Dates: 09/30/93 - 09/29195 

Funding Level: $36,920 ($36,920 Cum) 

Importance to Occupational Safety and Health 

Overexertion injuries are the single largest 

classification of injury in construction, accounting for 

about 24% of all injuries. The Bureau of Labor 

Statistics and OSHA define overexertion injuries as 

"nonimpact cases in which the injury resulted from 

excessive physical effort, as in lifting, pulling, 

pushing wielding, or throwing the source of injury. 

Includes conditions resulting from repetitive motion 

in the use of hand tools". 

Overexertion injuries generally occur as a result 

of performing a given task as planned. While 

overexertion injuries are not intentional, the 

underlying causes of the injuries are built into the 

prescribed tools and work methods. If the causes can 

be identified, it should be possible to engineer them 

out of the work. Once afflicted with an overexertion 

injury, many construction craft workers can be 

excessively challenged by the physical demands of 

their jobs. If the worker has the requisite skills and 

if alternative less-demanding employment is 

available, the worker can seek a different job where 

demands are better matched to physical capacity and 

ability. If alternative work cannot be found, the 

injured worker faces the dilemma of continuing at a 

job that causes excess fatigue or discomfort, or 

perhaps dropping out of the workforce. 

Construction injuries have been categorized in 

many ways, including by trade (e.g. carpenters, 

electricians, laborers, etc.) but no attempt has been 

made to identify a causal relationship between 

specific tasks within a trade and the associated 

overexertion injuries. For example, carpenters 

account for 17% of all injuries and illnesses, but 

carpenters perform many fundamentally different 

tasks such as erecting concrete formwork, installing 

suspended ceilings, hanging drywall, etc. Carpenters 

Traumatic Injuries - Page 79 

who install formwork for concrete experience high 

rates of tendinitis in their elbows from banging the 

forms and connectors with hammers, carpenters who 

install suspended ceiling systems experience neck and 

shoulder problems from constantly looking and 

reaching up, and carpenters who hang drywall often 

suffer nerve damage in their hands from the vibration 

of the screwguns used to fasten the drywall to the 

framing system. All of these injuries fall into the 

general classification of overexertion injuries to 

carpenters, but the underlying causes are quite 

different and they call for fundamentally different 

types of workplace intervention. 

The goal of this project is to identify specific 

construction tasks which place craft workers at high 

risk for overexertion injuries and disorders. High 

risk tasks can then be identified so that ergonomic 

and administrative principles can be applied to modify 

the task or work environment to accommodate human 

capabilities and limitations. 

Objectives 

The objective of this project is to analyze 

construction tasks for the presence of seven generic 

risk factors for overexertion injuries and to identify 

high risk tasks for possible ergonomic or 

administrative intervention. The hypotheses to be 

tested are that it is possible to identify the underlying 

risk factors for overexertion injuries for many 

specific construction tasks and that it is technically 

and economically feasible on many construction tasks 

to reduce the level of physical demands placed on 

craft workers. 

Methodology 

Overexertion injury data are currently reported by 

construction trade. No attempt has been made to 

determine which specific tasks within each trade place 

workers at high risk. This study will analyze each 

specific construction task for the presence of seven 

generic risk factors for overexertion injuries: 

repetitive exertions, static exertions, forceful 

exertions, localized mechanical stresses, posture 

stresses, low temperature, and vibration. Ratings for 

each risk factor will be made on a three point scale: 

Insignificant - The job is free of potentially harmful 

ergonomic stresses in the risk factor of interest. No 

corrective actions are necessary; Moderate - The job 

has stresses in the risk factor of interest that could be 

problematic (i.e. cause fatigue and/or injury) for some 

workers. Additional analyses using more precise 

methods should be used to determine the necessity for 

intervention; and High - The job has significant 

stresses in the risk factor of interest that are likely to 

cause fatigue and/or injury in some workers. 

Additional analyses and interventions should be taken 
Page 80 - Traumatic Injuries 

at a high priority. This study will identify 

particularly high risk tasks for ergonomic or 

administrative intervention. The ratings will be 

shared with the participants to help establish priorities 

for intervention or more detailed analysis. 

Significant Findings 

None to date. 

Development of a Work Safety 

Scale 

Bob E. Hayes, Ph.D. 

Medical Consultants Northwest, Inc. 

901 Boren Avenue, Suite 1400 

Seattle, Washington 98104-3512 

Program Area: Traumatic Injuries 

Grant Number: 1 R43 OH03099-0l 

Start & End Dates: 09130/93 - 03/31194 

Funding Level: $49,225 ($49,225 Cum) 

Importance to Occupational Safety and Health 

The National Safety Council (NSC) estimated 

that the total cost of industrial accidents in 1990, 

including insurance administration costs, wage losses, 

and medical costs, was 63.8 billion dollars (NSC, 

1991 ). Millions of dollars annually could be saved if 

the number of accidents was decreased. 

Fewer work related accidents have been linked 

to employees who perceive their jobs as relatively 

safe. These same employees report experiencing less 

anxiety, stress, and exposure to environmental 

hazards, all of which have been linked to accident 

rates. Therefore, the perceptions of the work 

environment and safety are correlated. By assessing 

the perceptions of employees, companies can alter the 

workplace and decrease the likelihood of accidents. 

There are four existing measures of workplace 

safety perceptions: The Occupational Hazards Survey 

(Guastello & Guastello, 1988); Safety Climate Scale 

(Zohar, 1980); Physical Demands and Dangers scale, 

a sub-scale of the Job Stress Index (Sandman, 1992); 

and the Perceptions of Workplace Hazards Scale 

(Smith et al., 1992), though they are not 

comprehensive nor psychometrically sound. The 

reliability and validity of each instrument is not well 

established, and no measure adequately taps the 

domain of workplace safety. Thus, there is a need 

for a comprehensive and psychometrically sound 

instrument to assess issues of workplace safety. 

Objectives 

The aim of the present research is to complete 

Phase I of the development of a questionnaire 

assessing employees' attitudes toward workplace 

safety. The proposed instrument will: (a) possess 

adequate psychometric integrity - reliability and 

validity information; (b) comprehensively assess 

important dimensions of perceptions of workplace 

safety; and (c) be easy to complete. Scores on this 

measure will assist decision-makers in industrial 

settings to: (1) predict the extent of accidents; 

(2) determine the need for workplace safety 

programs; (3) help organizational officers design 

specific workplace safety programs to address 

specific employee concerns; and (4) determine the 

effect of such safety programs. 

The series of proposed studies is designed to 

develop and validate a measure of workplace safety, 

the Work Safety Scale (WSS). The WSS will be 

designed to assess five dimensions of work-related 

safety: perceptions of job safety; coworker safety; 

supervisor safety; management safety; and satisfaction 

with the safety program. This multidimensional 

approach to safety assessment is necessary because 

ample evidence exists that work safety is not a 

unidimensional construct. 

Methodology 

For each of the five scales of the WSS, 

descriptive adjectives or phrases will be written to tap 

into relevant content domains. For each item, 

respondents indicate the extent to which they agree 

that the item describes their job situation using a 

five-point Likert scale 1 - Strongly Disagree to 

5 - Strongly Agree). An attempt will be made to 

counterbalance the number of positively phrased 

items with negatively phrased items. Twenty-two to 

29 items have been written for each of the sub-scales 

being developed, with the expectation that, after item 

analysis, at least half of the items will be retained for 

the final form of the instrument. 

Two studies will be conducted. The first will 

assess the distribution of scores for each scale item, 

the factor structure of the items, item statistics 

(means, corrected item-total correlations) and the 

internal consistency of the subscales. This study will 

be used to retain items that possess good 

psychometric characteristics. The second study will 

be conducted to provide a cross-validation of the 

findings of the first study. Specifically, for the 

second study, retained scale items will be 

administered to an independent sample of subjects, 

and item statistics (item means and corrected 

item-total correlations) will be calculated. 

Additionally, a factor analysis will be conducted on 
all items in Study II and internal consistency 

estimates will be calculated for each subscale. 

The WSS will consist of 124 items, reflecting the 

five content areas described above. The respondents 

are to indicate, for each item, how strongly they 

agree that the word or phrase describes their job 

(I - Strongly Disagree to 5 - Strongly Agree). 

Approximately 700 patients seen at Medical 

Consultants Northwest, Inc. (MCN) will serve as 

subjects in the first sample. These patients will be 

seen at MCN for independent medical evaluations. In 

addition to the paperwork they normally complete, 

patients will also be given the WSS. Their responses 

on the WSS will remain anonymous. 

An independent sample of respondents will be 

used in Study II. The approach to obtaining subjects 

used in Study I will be used in Study II. The 

approximately 700 respondents will be asked to 

complete the initial items of the WSS, along with 

other information, including occupational title, 

educational status attained, shift work status, sleep 

complaints, physical complaints, and psychological 

complaints. The additional information will be used 

to provide evidence of the validity of the WSS. 

Significant Findings 

None to date. 

Traumatic Injuries - Page 81 
Page 82 - Cardiovascular Diseases 

Vascular Effects of Chelation In 

Lead Exposed Workers 

Michael J. Kosnett, MD. 

University of California 

Occupational Health Clinic 

SFGH, Building 9, Room 109 

San Francisco, California 94110 

Program Area: Cardiovascular Diseases 

Grant Number: 5 KO] OHOOJ08-02 

Start & End Dates: 09/30191 - 03/29/95 

Funding Level: $0 ($108,000 Cum) 

Importance to Occupational Safety and Health 

There is growing evidence from epidemiological 

and animal studies that low-level exposure to lead 

may result in increased blood pressure, a major risk 

factor in the development of cardiovascular, 

cerebrovascular, and renovascular disease. From 

both a physiologic and public health standpoint, black 

adults appear particularly susceptible to the 

hypertensive effects of lead, and constitute a key 

target group for initial clinical investigation. In our 

group's recent cross-sectional study of San Francisco 

busdrivers, a strong relationship between lead and 

blood pressure was found exclusively in black 

subjects. Other studies have found black 

hypertensives to have an elevated pressor response to 

infused catecholamines, and to have higher 

intracellular stores of calcium, the same mechanisms 

experimentally implicated in lead's blood pressure 

effects. Although black adults constitute a key 

susceptible group, large epidemiological evaluations, 

such as NHANES II, have found a positive 

association between lead and blood pressure in 

non-black subjects as well. 

Most investigations of the effect of lead on blood 

pressure and other health outcomes have relied on 

blood lead as a biomarker of exposure. However 

cumulative lead exposure may be better assessed by 

measurement of lead in bone, where greater than 

95% of the adult body lead burden occurs with a 

half-life of several years. The availability of K 

x-ray fluorescence as a noninvasive quantitative 

measurement of the lead concentration of cortical and 

trabecular bone may enhance the investigation of 

dose-response relationships in lead-associated 

disorders. In addition, the recent availability of the 

oral chelating agent 2,3 dimercaptosuccinic acid 

(DMSA) permits implementation of an outpatient 

chelation challenge test to investigate the relationship 

between bone lead stores and the"mobilizable" pool 

of lead that may be most closely associated with toxic 

effects on target tissues. 

Objectives 

The research objectives are to assess cumulative 

lead exposure by K x-ray fluorescence, and to 

elucidate the mechanism of lead's vascular effects in 

a subset of lead exposed subjects with borderline to 

moderate hypertension. The latter aim will be 

approached by determining whether a reduction in 

soft tissue lead burden by EDT A chelation will 

reduce the pressor response to infused 

norepinephrine. The relationship between chelatable 

lead and bone lead burden will be explored using an 

outpatient chelation challenge test. 

Methodology 

K x-ray fluorescence measurement of lead in 

bone is determined noninvasively with an Abiomed 

Body Lead Analyzer. In this technique, the tibia 

(representative of cortical bone) and the patella 

(representative of trabecular bone) are sequentially 

irradiated with low energy photons from a 109Cd 

source, and a germanium detector quantifies 

fluorescent x-rays with energy characteristic of lead 

K-shell electron transitions. The lead fluorescence 

signal is normalized to the elastic, or coherently 

scattered x-ray signal, yielding a measurement of 

bone lead concentration expressed as micrograms of 

lead per gram of bone mineral (ppm). 

To investigate the effect of lead chelation on 

vascular responsiveness, asymptomatic subjects with 

blood lead concentrations between 15 and 80 μg/dl, 

are recruited as subjects from industries, unions, and 

occupational and environmental health clinics. Black 

adult men are specifically targeted for recruitment. 

Subjects with diastolic blood pressure between 85 and 

I 05 mmHg on two consecutive screenings, indicative 

of borderline to moderate hypertension, are admitted 

to the UCSF General Clinical Research Center, 

concurrent with outpatient and inpatient stabilization 

of dietary sodium. In each of 2 intervention cycles, 

subjects receive a stepped-dose infusion of 

norepinephrine (NE), immediately before and after an 

experimental intervention, and the slope of the 

dose-response lines is assessed. In one cycle, the 

intervention consists of a 48-hour lead chelation with 

i.v. EDTA, in the other matched i.v. placebo. The 

order of the two cycles is assigned in a double 

blinded, balanced manner. For each subject, the 

change in slope between the pre- and 

post-intervention NE infusion, a measure of the 

change in pressor sensitivity, is compared between 

the chelation and placebo cycles. 

To assess the relationship between "chelatable" 

lead and bone lead, selected subjects with 
occupational lead exposure will collect urine 

specimens before and after an out-patient challenge 

dose of the new oral chelating agent, 

dimercaptosuccinic acid, (DMSA, succimer). The 

relationship of urinary lead to bone lead concentration 

measured by K x-ray fluorescence will be 

investigated using regression models. 

Significant Findings 

Normative data on K x-ray fluorescence 

measurement of bone lead concentration has been 

collected on l 00 subjects, age 11 to 78, with limited 

occupational lead exposure. Results revealed that 

log transformed tibia (cortical bone) and patella 

(trabecular bone) lead concentration were highly 

correlated with age (r = .71, p <0.0001; r = .65, 

p <0.0001). An age-sex interaction existed, resulting 

in higher bone lead concentrations in older males. 

Blood lead concentration (mean 5.72 ± 3.98 μg/dl), 

was not correlated with age. Log blood lead was 

weakly correlated with log of tibial lead (r = .23, 

p = .02) and patella lead (r = .33, p = 0.001). A 

piece-wise linear regression model in age and sex 

yielded R2 = .60 for tibia lead, and R2 = .55 for 

patella lead. An expanded model for tibia lead 

(R2 = .66) revealed that smoking history was 

significantly associated with an increased bone lead 

concentration, and among females, a history of ever 

having nursed an infant was associated with lower 

bone lead. These models may serve as a basis for 

determining whether a subject with a history of 

occupational lead exposure has elevated bone lead 

concentration compared to age and sex adjusted 

norms. 

Preliminary data has been analyzed on three 

hypertensive black male subjects who have completed 

the norepinephrine infusion protocol. The first 

subject was a 52 year old demolition worker with a 

blood lead concentration of 17.3 μg/dl, the second 

subject was a 57 year old scrap metal worker with a 

blood lead concentration of 56.6, and the third subject 

was a 53 year old machinist with a blood lead 

concentration of 38.1. In each subject, 

norepinephrine infusion resulted in a linear increase 

in blood pressure. After adjustment for the placebo 

cycle, the mean change in slope relating systolic and 

diastolic to norepinephrine infusion rate was 

consistent with a slight chelation induced decline in 

vascular responsiveness; however, critical assessment 

of the relationship awaits the analysis of data from 

additional subjects. 

The relationship between K x-ray fluorescence 

measurement of bone lead concentration and 

creatinine corrected urinary lead excretion after a 

single oral dose of DMSA dose has undergone 

preliminary investigation in 27 subjects, age 22 to 67, 

with a range of occupational lead exposures. Urine 

Cardiovascular Diseases - Page 83 

lead concentration after DMSA was significantly 

correlated with tibia lead concentration ( r = . 71, 

p < .0001), patella lead concentration (r = .63, 

p < .0001), and blood lead concentration (r = .86, 

p < .0001). Bone lead concentration in this cohort 

was not significantly correlated with age. 

Publications 

Kosnett MJ, Becker CE, Osterloh JD, Kelly TJ, 

Pasta DJ: Factors Influencing Bone Lead 

Concentration in a Suburban Community Assessed By 

Noninvasive K X-Ray Fluorescence. JAMA, 

in press, 1994 

Kosnett MJ, North W, Herzberg W, Wu P: Bone 

Lead Concentration After Delayed Intoxication From 

Retained Buckshot. Vet Hum Toxicol 35:354, 1993 

(Abstract) 

Kosnett MJ, Becker CE, Osterloh JD, Kelly TJ: 

Assessment of Body Lead Burden by K X-ray 

Fluorescence Measurement of Lead in Bone. Vet 

Hum Toxicol 34:355, 1992 (Abstract) 

Kosnett MJ: Unanswered Questions in Metal 

Chelation. Clin Toxicol 30:529-547, 1992 
Page 84 - Disorders of Reproduction 

Occupational Risks of Pesticide 

Exposure for Females 

William J. Swartz, Ph.D. 

Louisiana State University 

School of Medicine 

Department of Anatomy 

1901 Perdido Street 

New Orleans, Louisiana 70112-1393 

Program Area: Disorders of Reproduction 

Grant Number: 5 ROJ OH00835-14 

Start & End Dates: 09129/79 - 08/31194 

Funding Level: $82,973 ($1,256,842 Cum) 

Importance to Occupational Safety and Health 

Each year there is an increasing number of 

females entering the workplace. Women can no 

longer be discriminated against when applying for a 

position in which exposure to a hazardous agent is 

likely. This becomes a great concern when such 

women are of childbearing age. There is a need to 

critically evaluate the toxicity of hazardous chemicals 

on reproductive function of females both prior to and 

during pregnancy. 

Objectives 

This study will provide a comprehensive 

evaluation of the toxic effects of the estrogenic 

pesticide methoxychlor on the reproductive tract. 

Exposure of the non-pregnant and the pregnant 

female will provide the models to evaluate the 

relative risks of these individuals to impairment of 

morphological and physiological parameters of the 

reproductive tract. This study will examine 

functional outcomes such as effects on fertility and 

pregnancy and correlate these with the observed 

anatomic and metabolic alterations within the 

reproductive tract as measured through the use of 

biological markers. It is anticipated that critical use 

of these biomarkers will allow the development of a 

means of identifying women to be at reproductive 

risk following exposure to a toxic agent. 

Methodology 

Adult non-pregnant mice (7-10 weeks old) were 

exposed to specific doses of the pesticide 

methoxychlor for five consecutive days/week for four 

consecutive weeks. Animals were sacrificed either 

immediately following exposure or allowed to mate 

in order to ascertain whether the observed toxicity 

was reversible once exposure ceased. Morphometric 

measurements of the height of the cells lining the 

uterine cavity were taken. These endometrial cells 

were also examined with the electron microscope in 

order to observe alterations in cellular organelles 

indicative of alterations in metabolic activity of these 

cells. Radioimmunoassays were also done to 

determine circulating estrogen levels in serum 

following exposure. Additionally, assessments of the 

fertility of these mice were conducted following the 

exposure period. In the second part of the study, an 

evaluation of the effects of methoxychlor on the 

implantation process was conducted on pregnant 

mice. 

Significant Findings 

Non-Pregnant Females 

Experiments in which mice were exposed for four 

weeks to specific doses of methoxychlor revealed a 

dose-dependent increase in the heights of uterine 

epithelial cells which line the uterine lumen. Cell 

heights of the two groups treated with the highest 

doses of methoxychlor (2.5 and 5.0 mg) were similar 

to that of the group treated with estradiol-I 7p. This 

appears to be an estrogenic response induced by 

methoxychlor. Electron microscopy revealed 

increased vacuolization and swelling of mitochondria, 

dilated rough endoplasmic reticulum and Golgi 

complexes and fewer microvilli in uterine epithelial 

cells. These alteration in cellular organelles were not 

observed in the estradiol-treated group, and thus, 

appear to be a result of the toxicity of methoxychlor 

directed toward the uterine lining. Rough 

endoplasmic reticulum and Golgi complexes are 

actively engaged in protein synthesis and in packaging 

of such protein for secretion. Morphologic alterations 

in these organelles may result in changes in protein 

secretion within the uterus of methoxychlor-treated 

mice. It appears that in light of the overall 

appearance of the cells of the uterine lining and the 

condition of the organelles in these cells, it is unlikely 

that such a uterus could accept a fertilized egg for 

successful implantation. Radioimmunoassay studies 

performed immediately after a four-week exposure to 

methoxychlor have revealed increased serum levels of 

estrogen. 

It does appear though that these effects are 

reversible once exposure ceases. When methoxychlor 

exposure ceases after four weeks, animals are able to 

mate, become pregnant and deliver what appear to be 

normal young. Therefore, even though a constant 

exposure of an adult results in reproductive toxicity, 

removal of the individual from the exposure restores 

the reproductive integrity of the individual. 
Pregnant Females 

Exposure of pregnant females on Days 4, 5 

and 6 of pregnancy to either 5.0 or 10.0 mg 

methoxychlor resulted in a decrease in survivability 

of embryos when examined on Day 7, twenty-four 

hours following the final exposure. Animals exposed 

to lower doses of methoxychlor (1.25 or 2.5 mg) 

exhibited no deleterious effects on implanting 

embryos on the day examined. This time is critical, 

since implantation is occurring during this period. 

Whether the uterus is the target site for the action of 

methoxychlor as reported in the studies with 

non-pregnant mice or whether the embryo is the 

target cannot be ascertained as of yet. Histological 

and histochemical evaluations of these tissues will be 

performed to confirm the target site and attempt to 

elucidate the mechanism for this toxic action. What 

effect such an exposure might have on future 

pregnancies is not known. 

Publications 

Swartz WJ, Wink CS, Johnson WD: Response of 

Adult Murine Uterine Epithelium to 50% 

Methoxychlor. Reproductive Toxicology, in press, 

1994 

Swartz WJ, Wink CS, Johnson, WD: Response of 

Adult Murine Uterine Epithelium to Methoxychlor 

Exposure. Anatomical Record Suppl., I: 109, 1993 

(Abstract) 

Swartz WJ, Corkern M: Effects of Methoxychlor 

Treatment of Pregnant Mice on Female Offspring of 

the Treated and Subsequent Pregnancies. 

Reproductive Toxicology 6:431-437, 1992 

Martinez EM, Swartz WJ: Effects of Methoxychlor 

on the Reproductive System of the Adult Female 

Mouse. II. Ultrastructural Observations. 

Reproductive Toxicology 6:93-98, 1992 

Martinez EM, Swartz WJ: Effects of Methoxychlor 

on the Reproductive System of the Adult Female 

Mouse. I. Gross and Histological Observations. 

Reproductive Toxicology 5:139-147, 1991 

Swartz WJ, Corkern M: Reproductive Alterations 

Induced by Exposure of Mice to Methoxychlor 

During Pregnancy. Anat Rec, 229:87A, 1991 

(Abstract) 

Swartz WJ, Mall GM: Chlordecone-Induced 

Follicular Toxicity in Mouse Ovaries. Reproductive 

Toxicology 3:203-206, 1989 

Disorders of Reproduction - Page 85 

Martinez EM, Swartz WJ: Response of the Murine 

Ovary to Methoxychlor Exposure. Anat Rec, 

223:75A, 1989 (Abstract) 

Swartz WJ, Eroschenko VP, Schutzmann RL: 

Ovulatory Response of Chlordecone (Kepone)-

Exposed Mice to Exogenous Gonadotropins. 

Toxicology 51:147-153, 1988 

Menstrual Function and Physical 

and Mental Job Stress 

Maureen C. Hatch, Ph.D. 

Columbia University 

School of Public Health 

Division of Medicine 

600 West 168th Street 

New York, New York 10032 

Program Area: Disorders of Reproduction 

Grant Number: 5 ROJ OH02885-03 

Start & End Dates: 08/01191 - 07131/94 

Funding Level: $207,513 ($792,277 Cum) 

Importance to Occupational Safety and Health 

The menstrual cycle is a marker of female 

reproductive physiology and can serve to monitor 

female workers who never attempt or achieve a 

pregnancy, but whose reproductive function and risk 

of hormone-related chronic disease may nonetheless 

be affected by the work environment. This project is 

investigating menstrual function in women workers, 

in relation to physical and mental job stress, and 

stress-related behaviors like caffeine consumption. 

Both cycle characteristics and ovarian hormone 

patterns will be studied. Stress is a pervasive 

occupational exposure and one that potentially can be 

prevented or reduced. It may be a particular problem 

for women whose added responsibility for the 

so-called "second shift" does not readily allow for 

recovery from job stress during nonwork hours. 

Objectives 

This project addresses two important issues: 

(1) job stress in females - an exposure whose effect 

needs rigorous investigation both on its own merits 

and to help disentangle stress effects from effects of 

other workplace agents; and (2) the need to develop 

biological markers of ovarian function in order to 

identify and prevent work-related disorders among 
Page 86 - Disorders of Reproduction 

nonpregnant women (much as semen analysis has 

served to monitor male occupational exposures). 

Methodology 

We have followed 100 female nurses from 

Memorial Sloan-Kettering Cancer Center (MSKCC) 

for three consecutive menstrual cycles. Nurses were 

selected as the target population because previous 

research has shown them to have high job stress 

levels. To maximize the range of job stress levels, 

subjects were recruited from areas of the hospital 

judged to be "high" and "low" stress on the basis of 

archival material and discussions with administrators. 

Subjects were asked to record basal body 

temperature, collect a small aliquot of urine daily, and 

maintain a structured menstrual diary. To evaluate 

ovulatory and luteal function, urine samples are being 

analyzed for estrone-3-glucuronide (E1G), 

pregnanediol-3-glucuronide (PdG), luteinizing 

Age !! 

(in years) (in cycles) 

22-27 47 

28-33 103 

34-39 78 

40-45 57 

46-52 12 

Age was also found to be significantly correlated 

with social support and smoking; younger women 

smoked more cigarettes on average and received 

more social support on average than older women 

(r=-0.11, p= .05, and r=-0.14, p= .02 respectively). 

As expected, social support was found to be inversely 

proportionate to stress (r= -0.31, p= .0001). 

The data also show a tendency for cycle length 

to be 2 to 3 days shorter among heavier smokers; 

however, this trend is based on a small number of 

heavy smokers (20+ cigarettes per day). Caffeine 

consumption did not appear to have an appreciable 

effect on cycle length. Preliminary analyses of job 

stress and work-related social support also did not 

show clear and consistent effects on cycle length. 

Future analyses incorporating the hormone assay 

results will complement the data on cycle 

characteristics. 

hormone (LH) and creatinine (CR). Salivary samples 

have been collected for measurement of cortisol, a 

physiologic indicator of stress. 

Using a similar design and translations of our 

data collection instruments, collaborators in Rome, 

Italy have conducted an investigation of nurses at the 

3,000-bed University hospital. 

Significant Findings 

Data collection is now complete. Information 

from the daily diaries has been coded and entered. 

As hormone assays are still pending, the initial 

analyses have utilized the diary data on cycle 

characteristics. Cycle length has been studied in 

connection with age, self-reported work stress, social 

support, smoking levels, and caffeine consumption. 

In general, there was little variability across cycles in 

the exposures of interest or in cycle characteristics. 

The data show the expected relationship between 

age and cycle length; mean cycle length and 

variability decrease with increasing age (r=-0.27, 

p=.0001). 

Mean Cycle Length Standard Deviation 

(in days) 

31.47 8.33 

29.44 4.71 

27.15 3.37 

27.49 2.85 

26.67 3.06 

Publications 

X Shu, Brinton L, Zheng W, Swanson C, Hatch M, 

Gao Y-T, Frauneni J: Relation of Obesity and Body 

Fat Distribution to Endometrial Cancer in Shanghai, 

China. Cancer Res, in press, 1992 

Hatch M: The Epidemiology of Electric and 

Magnetic Field Exposures in the Power Frequency 

Range and Reproductive Outcomes. Paed Peri 

Epidemiol 6:198-214, 1992 
Semen as a Biomarker of Effect 

Among Lead Exposed Men 

Harvey Checkoway, Ph.D. 

University of Washington 

School of Public Health 

and Community Medicine 

Department of Environmental Health 

SC-34 

Seattle, Washington 98195 

Program Area: Disorders of Reproduction 

Grant Number: 5 R03 OH02966-02 

Start & End Dates: 04/01/92 - 03/31/94 

Funding Level: $22,380 ($45,208 Cum) 

Importance to Occupational Safety and Health 

This study will provide information on the 

reproductive consequences of occupational lead 

exposure, and will serve as a model for evaluating the 

effects of occupational and environmental exposures 

on male reproductive function. 

Objectives 

The overall objective of this project is to use 

semen quality as a biomarker of effect on the male 

reproductive system resulting from occupational and 

environmental exposures. Occupational exposure to 

lead will be the focus of this study. 

Methodology 

The study design is a cross-sectional survey 

comparing semen quality parameters, serum 

reproductive hormone levels, and reproductive 

histories among men occupationally exposed to lead. 

The men in the study population are workers 

employed at a large lead-zinc smelter in British 

Columbia. The workers have blood lead levels 

ranging from less than 15 μg/dl to greater than 

55 μg/dl. Study participants were recruited from the 

entire male employee population by the means of a 

postal questionnaire. The questionnaire documents 

reproductive histories, socio-demographic 

characteristics, personal habits, such as tobacco and 

alcohol use, current and past illness, and a range of 

symptoms potentially related to lead exposure. Of the 

2469 male employees contacted (2156 current 

employees and 340 employees laid-off in 1992) 922 

returned questionnaires, 148 provided blood and urine 

samples; 121 of the latter 148 workers also provided 

Disorders of Reproduction - Page 87 

semen samples. Nine repeated semen samples were 

obtained. 

Recent lead exposure was determined by 

measuring blood lead and zinc protoporphyrin levels. 

A first A.M. void urine sample was obtained for 

measurement of urinary porphyrins. Aliquots of 

blood, urine, and semen were frozen for future 

analysis for metals other than lead. Information on 

past lead exposure was obtained from company 

employment and health records for all individuals 

who participated in the study. These data include the 

work histories of all employees and blood lead 

monitoring data from the worker health program. 

The exposure assessment will include data on length 

of employment, work area, job task, and routine 

blood lead screening values. Summary values were 

obtained for all currently employed workers to 

compare the study participants with the 

non-participants. 

Semen samples were collected at home or on site 

and delivered to the field laboratory within one hour 

of collection. The semen samples were processed 

according to standard protocol recording the sperm 

concentration, count, motility, morphology, and 

viability. Further analysis was done using computer 

assisted sperm analysis (CASA) techniques for 

motility and morphometry. Aliquots of semen were 

cryopreserved for a flow cytometric assay of sperm 

chromatin structure and a sperm penetration assay 

which will be conducted at a later date. Plasma 

levels of testosterone, follicle stimulating hormone, 

and luteinizing hormone were measured to evaluate 

the effect of lead exposure on the hormonal control of 

the male reproductive system. 

The effects of acute and chronic lead exposure on 

the semen quality parameters and reproductive 

hormones will be assessed by comparing these 

measures of reproductive health between subjects 

with high, moderate, and low lead exposure. 

Dose-response models will be derived for the various 

semen quality parameters and reproductive hormones 

with respect to current and long-term lead exposures. 

Significant Findings 

None to date. 
Page 88 - Disorders of Reproduction 

Reproductive Health of Female 

Migrant Farm Workers 

Marc B. Schenker, MD. 

University of California 

Institute of Environmental Health Research 

Department of Occupational 

& Environmental Medicine 

Davis, California 95616 

Program Area: Disorders of Reproduction 

Grant Number: 5 R03 OH03000-02 

Start & End Dates: 09/30/92 - 09/29/94 

Funding Level: $17,835 ($35,670 Cum) 

Importance to Occupational Safety and Health 

Migrant farmworkers, especially female 

farmworkers, have been one of the most underserved 

and understudied occupational populations in the 

United States. Occupational risks and hazards 

associated with agricultural work are ranked among 

the highest in the United States. Among adverse 

health outcomes due to occupational exposures, 

adverse reproductive health outcomes among women 

in the migrant farm labor force have been studied 

very little. Female farmworkers experience potential 

occupational hazards, such as prolonged standing and 

bending when working at conveyor belts or 

harvesting, long shifts, overexertion, and fatigue, as 

well as potential exposure to pesticides, climatic 

extremes, and insufficient toilet facilities in the fields 

(which may lead to infrequent use of the toilet 

facilities and thus may in tum result in urinary 

infections that can lead to adverse reproductive 

outcomes). In addition, the low socio-economic 

status, poor access to health care, and migratory 

lifestyle of these workers, as well as their often 

undocumented stay, contribute to the fact that high 

quality data about the health of farmworkers, 

specifically female farmworkers and their offspring, 

are almost non-existent. 

Objectives 

The primary objective of this cross-sectional 

hypothesis-generating pilot study is to investigate the 

reproductive health of a sample of minority, largely 

Hispanic, women (aged 18-45), living in a California 

farmworker community, and to evaluate and improve 

study tools and methods for future research purposes 

for studying adverse effects in this population. The 

specific aims of this study are: (l) to conduct a 

survey of women living in a California farmlabor 

community, using a questionnaire covering 

demographic and health characteristics, the 

availability and the use of basic health care for and 

by the target population, and occupational activities 

and exposures; (2) to determine and compare the 

prevalence of gynecologic and reproductive health 

problems between women who work as farmworkers 

as compared to women who do not perform such 

work; (3) to determine the prevalence of specific 

gynecologic and reproductive health problems in 

female farmworkers engaged in different specific 

farmwork activities and compare them to women who 

are not performing farmwork; (4) to determine the 

prevalence of pregnancy complications at birth, 

experienced by the study women and their newborns, 

to compare the prevalences to those women not 

engaged in farmwork, and to determine any 

relationship to specific occupational farmwork 

activities; (5) to review and refine the study design, 

study instruments, and community approach for 

future studies in farmworker communities in different 

agricultural regions of California and other states. 

Methodology 

A pilot study has been carried out, as a necessary 

step to characterize the population, to develop 

acceptable and appropriate approaches for community 

cooperation, to develop the correct sampling 

methodology, to determine the community response 

and learn about the bi-cultural setting, all of which 

will ultimately aid the researchers in developing the 

most accurate, acceptable and comprehensible 

bilingual, bicultural approach. 

Parlier, an agricultural community in Fresno 

county, California, was chosen to serve as the target 

community for the pilot study. Once chosen, the 

area, which encompassed the zip code district of 

Parlier, was divided into enumeration parcels, 

including both urban and rural areas. After random 

sampling of several enumeration blocks, the dwelling 

units on each block were mapped out for each parcel 

of land for later enumeration of the target population. 

From each sampled and mapped block, dwellings 

were randomly chosen and their occupants 

enumerated for further interviewing purposes. After 

the enumeration, female occupants were randomly 

sampled, and an extensive interview using a pretested 

questionnaire was administered by bicultural, 

bilingual interviewers in the homes of respondents. 

After the interviews were administered and reviewed 

for completeness, the answers were coded and 

entered into a computerized data base. In addition, 

limited physical examinations of participants were 

conducted in the community clinic to determine 

weight, height, pulmonary function, as well as limited 

blood tests to assess hematocrit and other hematologic 

values, and urinalysis. Each study participant who 
completed both the questionnaire and the limited 

physical exam was monetarily compensated 

($20/participant). 

Statistical data analyses of the interview-based 

and the lab-based findings are now being performed 

and are nearing completion. The analysis is focusing 

on the association of reproductive health outcomes 

with exposure to farming activities. Women not 

employed as farmworkers will serve as the 

comparison group. Specific outcome variables of 

interest are menstrual cycle irregularities, pregnancy 

and birth complications, as well as spontaneous 

abortions. The final results of the pilot study will 

be used to plan and implement a full-scale study in 

several agricultural regions of California, which is 

planned to begin in spring of 1994. 

Significant Findings 

In the community-based pilot study in Parlier, 

60 women, aged 18 to 44 years (a subsample of 

150 adults interviewed), were enrolled to participate 

in a cross-sectional assessment of reproductive and 

gynecological health outcomes among others. The 

response rate was fairly high (75%) for this 

population which works long hours and lives in 

crowded conditions. Preliminary results show that: 

more than 90% of the women were of Hispanic 

origin, 67% were born in Mexico; 83% were married 

or living as married; 91 % had at some point 

performed agricultural work, and 65% had worked in 

agriculture the previous year; 31 % described 

themselves migrant farmworkers, and 18% moved for 

work purposes. In terms of reproductive outcomes: 

80% had been pregnant (n=48); the miscarriage rate 

per pregnancy was 11 % and low birth weight rate 

7% (both of which are comparable to general 

population rates); the pregnancy and delivery 

complication rate, however, was 34% and the 

premature labor rate was I 0%. 

Disorders of Reproduction - Page 89 
Page 90 - Neurotoxic Disorders 

Occupational Neuropathies Due to 

Industrial Chemicals 

Mohamed B. Abou-Donia, Ph.D. 

Duke University 

School of Medicine 

Department of Pharmacology 

Box 3813 

Durham, North Carolina 27710 

Program Area: Neurotoxic Disorders 

Grant Number: 5 ROI OH00823-12 

Start & End Dates: 08/01182 - 08/31/93 

Funding Level: $0 ($1,567,389 Cum) 

Importance to Occupational Safety and Health 

Occupational exposure to one or multiple 

chemicals may cause neuropathies. Studies in this 

project are aimed to develop methods for screening 

or monitoring biological workers for over-exposure 

to neurotoxicants. The industrial solvents n.-hexane 

and carbon disulfide (CS2) were selected because of 

their potential to produce neurotoxicity and the 

potential for occupational exposure. Assay of 

biomarkers for exposure to chemicals can improve 

the assessment of exposure, dose-response, and 

comparison of dose between species. Such studies in 

experimental animals using defined exposures to 

neurotoxic chemicals can assist in the interpretation 

of neurological disorders in workers. 

Objectives 

The overall objective of this project is the 

prevention of occupational neurodegenerative 

disorders following exposure to industrial chemicals. 

Biological markers will be developed for early 

detection of exposure to n-hexane/metabolites and 

CS2• 

Methodology 

The principle in developing biomarkers for 

exposure to n.-hexane and CS2 is based on the 

reactivity of the n.-hexane metabolite, 

2,5-hexanedione (2,5-HD), and CS2 that allows them 

to react with specific proteins in the body, thus 

providing a long-term dosimeter. 2,5-HD reacts 

with amino groups of lysine residues to form 

protein-bound pyrroles. CS2 reacts with lysyl amino 

groups to yield dithicarbamates. We have developed 

monoclonal and polyclonal antibodies to bovine serum 

albumin (BSA)-pyrrole derivative of 2,5-HD. 

Studies on antibodies for BSA-bound CS2 have 

started. We have demonstrated that serum 

protein-bound pyrroles are not suitable biomarkers 

for 2,5-HD since they may undergo autoxidation 

resulting in crosslinked proteins that do not react with 

the protein-pyrrole antibodies following exposure to 

2,5-HD. Furthermore, the rapid turnover of the 

circulating serum proteins might result in the 

replacement of modified proteins, leading to a 

decreased titer so that they may not be detected. This 

is consistent with our results that neither monoclonal 

nor polyclonal antibodies reacted with serum from 

2,5-HD-treated rats. In contrast, antibodies against 

BSA-pyrrole derivatives gave positive reactions with 

hair protein-bound pyrroles from 2,5-HD treated 

rats. Our preliminary results indicated that polyclonal 

antibodies to BSA-pyrrole derivative of 2,5-HD 

reacted positively with protein-bound pyrrole 

compounds, both in the intact hair and in the 

solubilized hair of 2,5-HD-treated rats. Similar 

studies are being conducted on CS2 • In addition, we 

have been studying 2,5-HD pyrrole derivatives in the 

urine as a biomarker for 2,5-HD and 

n-hexane-treated rats. We plan to develop 

biomarkers for n-hexane/metabolites and CS2 to 

provide a means of assessing exposure to these 

chemicals and of comparing internal dose between 

species including man, resulting from short- to 

long-term exposure, and from low- to high-dose. 

Significant Findings 

During the initial phase of this project, we have 

established the following two important findings: 

(1) protein-pyrrole derivatives of 2,5-HD in blood 

are not suitable markers for detecting exposure to 

2,5-HD since they may undergo autoxidation and 

crosslinking that drastically change their 

immunoreactivity to monoclonal and polyclonal 

antibodies for protein pyrroles, (2) the finding of hair 

protein-bound pyrroles, which can act as sensitive 

and accurate biomarkers for exposure to n-hexane 

and metabolites. Furthermore, the protein-bound 

pyrrole derivatives formed in the hair are 

time-dependent and their longitudinal accumulation 

a reflection of the duration and level of exposure to 

n-hexane/metabolite. This would make the hair an 

accurate dosimeter that would give a good 

approximation of the duration and level of exposure. 

A significant advantage of the proposed studies is that 

hair protein-bound chemicals can be detected and 

quantified in early preneurotoxic conditions and 

correlated with subsequent neurologic deficits to 

determine their temporal relationship to development 

of neurotoxicity. We plan to carry out these studies 

on rats exposed via inhalation to n-hexane or oral 

administration or injection of 2,5-HD. Similar 

studies will be carried out following inhalation of 
CS2• Since the neurotoxicity of both !!-hexane and 

CS2 is increased with concurrent exposure to methyl 

isobutyl ketone (MiBK), a situation that occurs in 

some occupational environments, we plan to carry out 

studies on the effect of simultaneous exposure to 

MiBK in the formation of these biomarkers. 

Correlations will be made between these biomarkers 

and kinase activity in red blood cells and in nervous 

tissues. Protein-bound pyrroles will be investigated 

as biomarkers in human hair transplants in the nude 

mouse. Integration with other results will be essential 

for human hazard identification and exposure 

response characterization. 

Publications 

Lanning CL, Wilmarth KR, Abou-Donia MB: 

In Vitro Binding of 2,5[14C]hexanedione to 

Cytoskeletal Proteins. Neurochem Int, in press, 1994 

Jensen KF, Wilmarth KR, Olin JK, Abou-Donia MB: 

lmmunohistochemical Characterization of Carbon 

Disulfide (CS2) Induced Cytoskeletal Alterations in 

the Central Nervous System. Toxicologist, 1994 

(Abstract) 

Wilmarth KR, Viana ME, Abou-Donia MB: 

Evidence for Crosslinking of Neurofilament (NF) 

Proteins in Rat Spinal Cord Following Inhalation 

Exposed to Carbon Disulfide (CS2). Toxicologist, 

1994 (Abstract) 

Johnson DJ, Lack L, Abdel-Rahman SM, 

Abou-Donia MB: Hair as a Target Tissue for 

Protein Binding Following Subchronic lntraperitoneal 

Injection of 2,5-Hexanedione. Toxicologist, 1994 

(Abstract) 

Wilmarth KR, Viana ME, Abou-Donia MB: Carbon 

Disulfide Inhalation Increases 

Ca2+/Calmodulin-dependent Kinase Phosphorylation 

of Cytoskeletal Proteins in the Rat Central Nervous 

System. Brain Res 628:293-300, 1993 

Johnson DJ, Lack L, Abou-Donia MB: Hair As A 

Target Tissue for Developing A Biological Marker 

for Precursors to 2,5-hexanedione. IN: Biomarkers 

of Human Exposure to Pesticides, (eds. MA Saleh, 

JN Blancato, CH Nauman), American Chemical 

Society, Washington, DC, pp. 125-132, 1993 

Knoth-Anderson J, Veronesi B, Jones K, 

Lapadula DM, Abou-Donia MB: Triphenyl 

Phosphite-induced Ultrastructural Changes in Bovine 

Adrenomedullary Chromaffin Cells. Toxicol Appl 

Pharmacol 112:110-119, 1992 

Neurotoxic Disorders - Page 91 

Anderson JK, Abou-Donia MB: Adrenomedullary 

Chromaffin Cells: A Well Characterized Model 

System for Toxicological Studies. In: In Vitro 

Biological Models, (eds. Tyson and Frazier), 

Academic Press, (Vol I of Methods in Toxicology), 

San Diego, CA, 1992 

Abou-Donia MB: Triphenyl Phosphite: A Type II 

Organophosphorus Compound Induced Neurotoxic 

Agent. In: Organophosphate: Chemistry, Fate, 

Effects. ( eds. J Chambers, PE Levi), Academic 

Press, San Diego CA, 327-351, 1992 

Abou-Donia MB, Hu Z, Lapadula DM, Gupta RP: 

Mechanisms of Joint Neurotoxicity of !!-hexane, 

Methyl Isobutyl Ketone, and 0-ethyl 

Q-4-nitrophenyl Phenylphosphonothioate (EPN) in 

Hens. J Pharmacol Exper Thera 257:282-289, 1991 

Lapadula DM, Habig C, Gupta RP, Abou-Donia MB: 

Induction of Cytochrome P-450 lsozymes by 

Simultaneous Inhalation Exposure of Hens to 

!!-hexane and Methyl lso-butyl Ketone (MiBK). 

Biochem Pharmacol 41:877-883, 1991 

Somkuti SG, Lapadula DM, Chapin RE, 

Abou-Donia MB: Light and Electron Microscopic 

Evidence of Tri-Q.-cresyl Phosphate 

(TOCP)-mediated Testicular Toxicity in Fischer 344 

Rats. Toxicol Appl Pharmacol 107:35-46, 1991 

Gupta RP, Lapadula DM, Abou-Donia MB: 

Purification and Characterization of Cytochrome 

P-450 lsozymes from Phenobarbital-induced Adult 

Hen Liver. Comp Biochem Physiol 96C: 163-176, 

1990 

Gupta RP, Lapadula DM, Abou-Donia MB: 

Purification and Characterization of Cytochrome 

P-450 Isozymes from ~-naphthoflavone-induced 

Hen Liver. Arch Biochem Biophys 282: 170-182, 

1990 

Abou-Donia MB, Nomeir AA, Bower JH, 

Makkawy HA: Absorption, Distribution, Excretion, 

and Metabolism of A Single Oral Dose of [ l 4C]TriQ-cresyl Phosphate (TOCP) in the Male Rat. 

Toxicology 65:61-74, 1990 

Somkuti SG, Abou-Donia MB: Disposition, 

Elimination, and Metabolism of Tri-Q-Cresyl 

Phosphate Following Daily Oral Administration in 

Fischer 344 Male Rats. Arch Toxicol 64:572-579, 

1990 

Abou-Donia MB, Suwita E, Nomeir A: Absorption, 

Distribution, and Elimination of A Single Oral Dose 
Page 92 - Neurotoxic Disorders 

of [14C]Tri-Q-cresyl Phosphate in Hen. Toxicology 

61:13-25, 1990 

Suwita E, Abou-Donia MB: Pharmacokinetics and 

Metabolism of A Single Neurotoxic Oral Dose of 

Tri-Q-cresyl Phosphate in Hens. Arch Toxicol 

64:237-241, 1990 

Abou-Donia MB, Lapadula DM: Mechanisms of 

Organophosphorus Ester-induced Delayed 

Neurotoxicity: Type I and Type II. Annu Rev 

Pharmacol Toxicol 30:405-440, 1990 

Abou-Donia MB, Lapadula DM: Cytoskeletal 

Proteins and Axonal Neuropathies. Comme Toxicol 

3:427-444, 1989 

Abou-Donia MB, Lapadula DM: Studies on the 

Molecular Pathogenesis of Organophosphorus 

Compound-induced Delayed Neurotoxicity (OPIDN). 

In: Insecticide Action (eds. T Narahashi, 

JE Chambers), Plenum Publishing Corporation, 

pp. 205-216, 1989 

Lapadula DM, Suwita E, Abou-Donia MB: Evidence 

for Multiple Mechanisms Responsible 

2,5-hexanedione-induced Neuropathy. Brain Res 

458:123-131, 1988 

Carrington CD, Abou-Donia MB: Triphenyl 

Phosphite Neurotoxicity in the Hen: Inhibition of 

Neurotoxic Esterase and Prophylaxis by 

Phenylmethylsufonyl Fluoride. Arch Toxicol 

62:375-380, 1988 

Carrington CD, Abou-Donia MB: Variation Between 

Three Strains of Rat: Inhibition of Neurotoxic 

Esterase and Acetylcholinesterase by Tri-o-Cresyl 

Phosphate. J Tox Env Health 25:255-264, 1988 

Carrington CD, Brown HR, Abou-Donia MB: 

Histopathological Assessment of Triphenyl Phosphite 

Neurotoxicity on the Hen. 9(2):233-234, 1988 

Abou-Donia MB, Lapadula DM, Suwita E: 

Cytoskeletal Proteins as Targets for 

Organophosphorus Compound and Aliphatic 

Hexacarbon-induced Neurotoxicity. Toxicology 

49:469-477, 1988 

Somkuti SG, Tilson HA, Brown HR, Campbell GA, 

Lapadula DM, Abou-Donia MB: Lack of Delayed 

Neurotoxic Effect after Tri-Q-Cresyl Phosphate 

Treatment in Male Fischer 344 Rats: Biochemical, 

Neurobehavioral, and Neuropathological Studies. 

Fund Appl Toxicol 199-205, 1988 

Somkuti SG, Lapadula RE, Chapin JC, Lamb IV, 

Abou-Donia MB: Reproductive Tract Lesions 

Resulting from Subchronic Administration (63) days 

of Tri-Q-cresyl Phosphate in Male Rats. Toxicol 

Appl Pharmacol 89:49-63, 1987 

Somkuti SG, Lapadula RE, Chapin JC, Lamb IV, 

Abou-Donia MB: Time Course of the Tri-Q-cresyl 

Phosphate-induced Testicular Lesion in F-344 Rats: 

Enzymatic, Hormonal, and Sperm Parameter Studies. 

Toxicol Appl Pharmacol 89:64-72, 1987 

Somkuti SG, Lapadula RE, Chapin JC, Lamb IV, 

Abou-Donia MB: Testicular Toxicity Following 

Oral Administration of Tri-Q-cresyl Phosphate 

(TOCP) in Roosters. Toxicol Lett 37:279-290, 1987 

Suwita E, Nomeir AA, Abou-Donia MB: 

Disposition, Pharmacokinetics, and Metabolism of a 

Dermal Dose of [1 4

C] 2,5-Hexanedione in Hens. 

Drug Metab Disp 15:779-785, 1987 

Lapadula DM, Tilson HA, Campbell G, 

Abou-Donia MB: Neurotoxic Effects of Combined 

Treatment of 2,5-Hexanedione and Trithyllead 

Chloride. J Toxicol Environ Health 21 :483-492, 

1987 

Lapadula DM, Irwin RD, Suwita E, 

Abou-Donia MD: Crosslinking of Neurofilament 

Proteins of Rat Spinal Cord In vivo after 

Administration of 2,5-hexanedione. J Neurochem 

46:1843-1850, 1986 

Abou-Donia MB, Lapadula DM, Campbell GA, 

Timmons PR: The Synergism of n-Hexane-Induced 

Neurotoxicity by Methyl Iso-butyl Ketone Following 

Subchronic (90 days) Inhalation in Hens: Induction of 

Hepatic Microsomal Cytochrome P-450. Toxicol 

Appl Pharmacol 81: 1-16, 1985 

Abou-Donia MB, Lapadula DM, Campbell GA, 

Abdo KM: The Joint Neurotoxic Action of Inhaled 

methyl Butyl Ketone Vapor and Dermally Applied 

Q-Ethyl, Q-4-Nitrophenyl Phenylphosphonothioate 

in Hens: Potentiating Effect. J Toxicol Appl 

Pharmacol 79:69-82, 1985 

Abou-Donia MK, Makkawy HM, Campbell GM: 

The Pattern of Neurotoxicity Produced by Dermal 

Application of n-hexane, Methyl n-butyl Ketone, 

2,5-hexanediol, and 2,5-hexanedione Alone and In 

Combination with Q-ethyl Q-4-nitrophenyl 

Phenylphosphonothioate in Hens. J Toxicol Environ 

Health 16:85-100, 1985 

Nomeir AA, Abou-Donia MB: Analysis of 

n-hexane, 2-hexanone, and 2,5-hexabedione, and 
Related Chemicals by Capillary Gas Chromatography 

and High-Pressure Liquid Chromatography. Anal 

Biochem 151:381-388, 1985 

Neurologic Effects of Solvents and 

Age in Older Adults 

William Daniell, MD., MP.H 

University of Washington 

Occupational Medicine Program 

SC-34 

Seattle, Washington 98195 

Program Area: Neurotoxic Disorders 

Grant Number: 5 ROI OH02683-02 

Start & End Dates: 09/30/89 - 09/29/92 

Funding Level: $0 ($391,937 Cum) 

Importance to Occupational Safety and Health 

A number of cross-sectional epidemiologic 

studies have demonstrated functional abnormalities of 

the central nervous system among solvent-exposed 

working populations. However, the differences have 

generally been subclinical, and their long-term 

significance has not been characterized. There is 

evidence that aging-related processes may latently 

interact with the effects of subclinical central nervous 

system injury, such as former solvent exposure, to 

result in neurologic dysfunction that is clinically 

significant and disproportionately greater than that 

which might result from either variable alone. Older, 

retired adults who were routinely exposed to solvents 

during working years may therefore be at increased 

risk for significant neurologic problems attributable 

to their former work, even though such problems may 

have been inapparent during the periods of solvent 

exposure. 

Objectives 

The study addressed the following questions: 

I. Are there decrements in neurologic function 

among the retired painters relative to the control 

population? 

2. Does neurologic function show any biologically 

plausible, adverse relationship to measures of 

recalled past solvent exposure, and can any such 

relationships be explained by latency or threshold 

effects? 

Neurotoxic Disorders - Page 93 

3. Is there any evidence that alcohol consumption 

interacts with solvent exposure to influence 

neurologic function? 

4. Secondarily, are there intergroup differences 

among selected non-neurologic areas of function? 

Methodology 

The study used a cross-sectional design to 

examine neurologic function (subjective, 

neurosensory, neuropsychological, and psychiatric 

parameters) among 89 retired, formerly solventexposed workers (67 Painters; 22 Aerospace painters 

and fuel cell sealers) in comparison to 126 retired 

Carpenters, who had relatively minimal prior 

occupational solvent exposures. Neurologic function 

was also evaluated relative to semiquantitative indices 

of recalled past solvent exposure. Non-neurologic 

parameters, including respiratory symptoms, 

spirometry, blood tests of liver function, and urine 

proteins were also examined as outcomes of 

secondary interest. 

Subjects were identified systematically through 

pension funds. The proportions of invited retirees 

who responded to approach materials (47-52%) and 

who were willing and eligible to participate 

(25-31 % ) were relatively low but uniform across the 

study groups. Surveys of non-respondent retirees in 

each study group revealed similar distributions of 

reasons for non-response. By design, all subjects 

were male, with ages 62-74 years and at least I year 

since retirement (average 5 years). The exposed 

subjects on average had 25-30 years experience in 

solvent-exposed occupations. 

Significant Findings 

Lifetime cumulative alcohol use was 1.5-2.5 

times greater among current and former drinkers, 

respectively, for Painters in comparison to Carpenters 

and Aerospace Workers. It is plausible that the 

history of heavier alcohol consumption in Painters 

represents a direct or indirect consequence of solvent 

exposure, as speculated previously in other reports. 

However, this is not supported by the absence of such 

a pattern in the Aerospace Workers. 

The Aerospace Workers showed significantly 

worse mean performance on neuropsychological tests 

of memory and visual-motor speed, and to lesser 

degree motor and attention/concentration abilities. 

The total number of individual tests on which 

Aerospace Workers scored worse than 90% of 

Carpenters ("total outlier number") was more 

commonly relatively "high" compared to the 

Carpenters; however, their highest total outlier 

numbers were still lower than the Carpenters' worst 

90th percentile value. This suggests that this 
Page 94 - Neurotoxic Disorders 

probable solvent effect is singularly of less magnitude 

than contributory factors unrelated to solvents. 

Among ~e (non-aerospace) Painters, neurologic 

and depressive symptoms were significantly more 

common than either Carpenters or Aerospace 

Workers. However, even with lower mean 

vocabulary test scores and higher cumulative alcohol 

consumption, the (non-aerospace) Painters showed 

little evidence of relative dysfunction on 

ne~ropsycholog~cal testing. Neurosensory testing 

(vibratory tactile perception and color visual 

discrimination abilities) showed no clear evidence of 

relative dysfunction possibly attributable to prior 

solvent exposure, in either Painters or Aerospace 

Workers. The absence of such findings on 

neuropsychological testing of Painters and on 

neurosensory testing of both exposed groups stands in 

strong contrast to ( and calls into question the 

lon~-:-term c!inic~ relevance ot) the repeatedly 

pos1t1ve findmgs m multiple previous studies of 

pre-retirement workers with similar occupational 

exposures. 

The average, cumulative and era-specific solvent 

exposure indices in numeric form showed no 

significant association with any major outcome 

variables. However, when exposed subjects were 

categorized into index tertiles, the Aerospace Workers 

with relatively moderate or high cumulative solvent 

exposure showed greatest evidence of adverse 

association between exposure and neuropsychological 

test performance. There was also no evidence that 

tempo.ral phen~mena, such as latency or recency, 

were mvolved m the observed associations between 

prior solvent exposure and neuropsychological test 

performance. There were no significant associations 

between test performance and either solvent-alcohol 

or solvent-age interactive terms (within the narrow 

sample age range), beyond those observed for the 

individual variables. 

The Painters, but not the Aerospace Workers, 

showed increased risk for possible restrictive 

ventilatory dysfunction (by spirometry), consistent 

with probable long-term adverse pulmonary effects 

of occupational exposures, speculatively either paint 

or asbestos exposures. 

There were no significant differences on liver 

function tests or on urinary excretion of total protein 

or NAG enzyme, providing no evidence of persistent 

effect by long-term solvent exposure on liver or 

renal excretory function. 

Central Nervous System Effects of 

PCE Exposure in Humans 

Diana Echeverria, Ph.D. 

Batte/le Human Affairs Research Center 

4000 NE. 41st Street 

Seattle, Washington 98105 

Program Area: Neurotoxic Disorders 

Grant Number: 5 ROI OH02719-03 

Start & End Dates: 02/01/90 - 01/31/94 

Funding Level: $0 ($594,962 Cum) 

Importance to Occupational Safety and Health 

This study examines for the first time the 

relationship between chronic exposure to 

perchloroethylene (PCE) and the prevalence of 

symptoms, neurobehavior, and neurophysiologic 

central nervous system (CNS) effects in workers. 

These effects are being evaluated in dry cleaners 

occupationally exposed to different levels of PCE 

using never-exposed laundry workers as a reference 

pop~lation. The study documents a possible 

contmuum from subclinical to clinical CNS effects 

following exposure to PCE in one of the few 

industrial populations frequently exposed to high 

levels above 40 ppm. At completion of the study, the 

prevalence of chronic CNS effects will be thoroughly 

characterized between O and I 00 ppm, and the lower 

threshold of adverse symptoms, behavior, and 

physiologic effects will be known at the OSHA PEL 

of 25 ppm. 

Objectives 

Based on a pilot study, a frontal/limbic system 

behavioral hypothesis is offered as the site of 

underlying pathology for subclinical PCE effects. 

The behavioral hypothesis posits that functions such 

as the ability to alternate between tasks and other 

tests requiring integration of complex attention and 

visuo-spatial skills, primarily frontal lobe functions, 

should be more affected by exposure to PCE. In 

contrast, simple attention, motor speed, and verbal 

ability should be affected by PCE exposure to a 

lesser extent. In addition, solvent exposures are 

known to affect memory and mood, associated with 

the limbic system. 

Methodology 

The cross-sectional CNS evaluation is being 

conducted on 84 never-exposed laundry workers, 
42 low, 42 moderate, and 84 highly exposed dry 

cleaner employees in the Western Washington area. 

To control for acute exposure effects, the symptom 

and behavioral evaluations are conducted over 

3 sessions; on the afternoon of their day off; 36 hours 

post-exposure in the morning at their work site, and 

again after the workshift. The core behavioral 

battery is presented in Table 1. A pre- and 

post-exposure alveolar breath sample is measured to 

control for variation in PCE body burden, 

supplementing 8 hr air monitoring for each exposed 

and for one out of eight non-exposed workers. 

Exposure zones will be based on (1) distance form 

PCE source, (2) PCE air levels, (3) PCE breath 

levels. Full-shift continuous PCE peak sampling 

(Bruel and Kjaer 1302) is being conducted on 

operators with fluctuating exposures. These exposure 

measures are used to construct lifetime indices of 

cumulative exposure. The 2-hour neurophysiologic 

assessment occurs at least 24 hours post-exposure on 

a separate day. Paid volunteers must have at least 

1 year on the job, are older than 18 years old, english 

speaking, and have had no history of CNS disorders. 

No subjects will be excluded on the basis of alcohol 

or drug consumption since interaction between PCE 

and alcohol is a research interest. The immediate 

influence of caffeine and alcohol will be controlled. 

To evaluate the exposure-effect within each stop, 

volunteers from each exposure zone will be tested. 

Potential confounding effects of age and education 

will be controlled by measures of stratification and 

multiple regression. 

The analysis will be conducted in two phases. 

First, within each separate category of health 

outcomes, efforts will be made to identify reliable 

measures. Two methods will be compared to reduce 

the number of variables resulting in a set of more 

reliable and uncorrelated composite variables. The 

first way is to group variables into clinically 

consistent categories. This approach is to be 

compared with a principal factor analysis (RxT). The 

same factor analysis will be repeated for the zero, 

low, moderate, high, and previously exposed PCE 

exposure categories, identifying the number of 

underlying dimensions corresponding to the 

hypothesis. The analysis of an a priori hypothesis 

eliminates the concern cumulative alpha error being 

responsible for positive results. The difference in 

relationships between symptoms, neurobehavior, and 

physiological measures will be examined for zero, 

low, moderate, and high acute and chronic exposure 

categories. The CNS data would be reanalyzed using 

these factors as new outcome variables in regression 

models to increase the statistical strength of the 

exposure-effect relationship. The second step is to 

model the potential exposure-effect relationships. 

Neurotoxic Disorders - Page 95 

Table l. The Test Battery 

Function 

Motor: 

Attention: 

Cognitive 

Flexibility: 

Reasoning: 

Memory 

Short Term: 

Mood 

Basic Skill 

Add ons 

Mode 

MD 

vs 

VB 

vs 

VB 

vs 

VB 

vs 

vs 

vs 

VB 

vs 

VB 

vs 

vs 

vs 

vs 

C Computerized 

Test 

One Hole 

NES Digit Span 

Oral Digit Span 

Trial Making 

PASAT 

Similarities 

Wisconsin card sort 

Pattern Memory 

Pattern Recognition 

Visual Reproduction 

Cal Verb Learn Test 

POMS 

POMS 

Vocab 

Arith 

Switch 

, Color Hue 

MD Manual Dexterity 

P = Paper and Pencil 

VB Verbal 

VS = Visual 

Significant Findings 

Method 

C 

C 

p 

p 

p 

p 

p 

C 

C 

p 

p 

p 

p 

C 

C 

C 

p 

Data collection and analysis is in progress. 

However a preliminary study evaluating how to 

interpret the ability to switch between tasks, the 

L' Anthony Color Hue Test, and the Stroop Test has 

been completed. Unexposed production workers at 

two facilities (n=I04), between the ages of 18 and 70 

were stratified into 5 age groups and tested pre- and 

post-shift. The effect of age, sex, repetition, and 

when possible ethanol consumption, was assessed to 

establish their use in chronic and acute solvent studies 

and to estimate psychometric properties. 

Performance on all tests was affected by age. 

Repetition improved performance on the switching 

task and the Stroop Test, but not the Color Hue Test. 

Ethanol consumption significantly affected the ability 

to switch, but was examined for the other two tests. 

Gender did not affect performance. The switching 

task and the Color Hue Test were added to the core 

behavioral battery. 

Exposure to PCE in commercial shops were 

quantified by 8 hour time weighted average personal 

dosimetry, real time area sampling indicating peak 

exposures, and the amount of PCE in alveolar breath. 

As expected there was a statistically significant 

association between all measures. Analysis of 

variance determined that the type of process and job 

title were associated with each measure of exposure. 

The personal badge samples accounted for .88 of the 
Page 96 - Neurotoxic Disorders 

variance in breath whereas the area samples only 

accounted for .84 of the total variance. Peale 

exposures were experienced by wet transfer operators 

15% of the time above 50 ppm whereas dry-to-dry 

operators were exposed to this level less than 1 % of 

their shift. Lastly wet-transfer operations ranged 

between .2 to 86 ppm. 

Publications 

Echeverria D, Heyer N, Toutonghi G, Ronhovde N, 

Bittner A: The Stroop Test: The Effect of Age, Sex, 

and Color Confusion on Selective Attention Among 

Unexposed Workers. Advances in Industrial 

Ergonomics and Safety IV, 1992 

Ronhovde N, Heyer N, Toutonghi G, Echeverria D: 

Color Hue Impairment as An Indicator of CNS 

function. Advances in Industrial Ergonomics and 

Safety IV, 1992 

Toutonghi G, Echeverria D, Bittner A, Ronhovde N: 

The Use of Switching Ability to Assess Central 

Nervous System Function. Advances in Industrial 

Ergonomic and Safety III, 1991 

Ronhovde N, Heyer N, Toutonghi G, Echeverria D: 

The Effect of Age on Color Vision. Advances in 

Ergonomics and Safety III, Elsevier, Denver, CO, 

1991 

Echeverria D, Heyer N, Ronhovde N, Toutonghi G: 

The Effect of Adverse Color Vision of the Stroop 

Test. Advances in Ergonomics and Safety III, 

Elsevier, Denver, CO, 1991 

Validity of Computerized Tests in 

Occupational Settings 

Roberta F. White, Ph.D. 

Boston University 

School of Medicine 

Department of Neurology 

720 Harrison Avenue, Suite 801A 

Boston, Massachusetts 02118 

Program Area: Neurotoxic Disorders 

Grant Number: 5 ROI OH02767-03 

Start & End Dates: 05/01/91 - 04/30/94 

Funding Level: $176,762 ($560,772 Cum) 

Importance to Occupational Safety and Health 

This study represents an attempt to validate a 

computerized neurobehavioral test battery which can 

then be used in research studies to investigate CNS 

dysfunction secondary to neurotoxicant exposure in a 

valid and theoretically meaningful way. If the battery 

proves valid as an indicator of CNS function, it will 

also have utility in clinical examination of patients 

with suspected encephalopathy secondary to exposure. 

Objectives 

To examine the relationship between specific 

types of brain damage (white matter lesions in 

multiple sclerosis, basal ganglia dysfunction in 

Parkinson's disease, focal cortical lesions in stroke) 

and performance on Neurobehavioral Evaluation 

System (NES) tests. 

Methodology 

Subjects from each of three neurological groups 

will be tested with the NES battery and compared to 

age- and gender-matched controls. The neurological 

groups include multiple sclerosis, early Parkinson's 

disease, and focal stroke (the 4 stroke subgroups 

include left and right anterior, left and right 

posterior). 

Significant Findings 

As of 11/23/93, 226 subjects have been tested. 

Subgroups of patients enlisted were Parkinson's 

Disease (PD; N=68), multiple sclerosis (MS; N=60), 

focal lesion (FL; N=31) and normal controls (NC; 

N==67). We have confirmed that most neurologic 

patients meeting the exclusion criteria used in the 

study can complete all of the tests in the battery and 

that the remainder can complete the majority of tests. 

A preliminary analysis of results has been carried 

out for the PD, MS, and NC groups. Correlations 

between NES tests were estimated for each of the 

three groups separately. These correlations were 

generally small in magnitude, suggesting that the 

battery taps distinct functions in addition to functions 

common to the several tests. This held for the 

neurological patient groups as well as for the 

controls, indicating sensitivity of these tasks to 

specific deficits rather than merely to degree of 

overall impairment. 

Linear regression models were fit to the data to 

estimate associations between disease and test 

performance, adjusting for differences in age, gender, 

educational level, and a measure of native cognitive 

ability. The two disease groups differed from 

controls in distinct ways. For the PD sample there 

was an association between disease and tests of motor 
speed, hand-eye coordination, visual memory, and a 

measure of fatigue, all of which had been predicted. 

In the MS group, significant associations with disease 

were more widespread. MS patients were impaired 

on tasks assessing motor speed, hand-eye 

coordination, psychomotor speed, attention, 

concentration, verbal memory, visual discrimination, 

and visual memory. These patients also reported 

more fatigue than did controls. The contrast between 

the two disease groups suggests that the present NES 

battery is more sensitive to the neuropathological 

consequences of MS (especially white matter lesions) 

than to those of PD (dysfunction of the basal ganglia, 

especially the substantia nigra). 

The results indicate that the NES subtests are 

most effective in measuring the expected motor 

deficits in PD and MS. However, they failed to 

detect deficits in complex attention, visuospatial 

function, and verbal encoding in PD patients, and 

deficits in verbal functioning and memory in MS 

patients, which have been identified in past studies 

using traditional neuropsychological tests. These 

limitations have suggested that if the NES is to be 

effective in detecting CNS dysfunction (especially at 

the subclinical levels to be expected in working 

populations exposed to neurotoxicants) the battery 

requires expansion and further validation. 

A Computerized Tool to Screen 

Workers for Neurotoxicity 

Richard E. Letz, Ph.D. 

Emory University 

School of Public Health 

1599 Clifton Road, NE 

Atlanta, Georgia 30329 

Program Area: Neurotoxic Disorders 

Grant Number: 1 ROI OH03078-0l 

Start & End Dates: 09/15/93 - 09/14/94 

Funding Level: $136,688 ($136,688 Cum) 

Importance to Occupational Safety and Health 

Exposure to chemicals that can cause effects on 

the nervous system is common, and neurotoxic 

disorders are one of NIOSH's IO leading diseases and 

mJunes. Many epidemiologic studies of workers 

have demonstrated neurobehavioral effects of 

chemical exposures. However, screening of 

individuals for early signs of neurotoxicity from 

workplace exposures is currently rarely performed. 

Screening of individuals is rare due to the cost of 

Neurotoxic Disorders - Page 97 

full-scale clinical neuropsychological testing 

(averaging over $700 per patient nationally), the 

limited availability of qualified personnel, and the 

absence of efficient screening tools. Currently 

available neurobehavioral instruments are optimized 

for efficient collection of epidemiologic outcome 

information on groups of workers, not for screening 

of individuals among exposed workers who may 

require follow-up examinations. 

The present project concerns the first phase of a 

two-phase effort, development of the new 

computer-based testing instrument. Successful 

completion of the proposed project work will lead to 

the second phase of the overall research program, 

which includes: (I) assembling a network of clinics 

to use the neurobehavioral screening system, 

(2) performing a normative data collection project, 

and (3) performing a validation study. The system 

could be adapted to allow its effective use in other 

countries and in populations potentially most 

susceptible to effects of neurotoxic exposure such as 

the elderly and children. 

Objectives 

The main goal of this effort is to produce a new 

computer-based neurobehavioral testing system to 

screen workers for early signs of occupational 

neurotoxicity. The results of this screening test 

would provide information to help decide whether 

individual workers exposed to potential 

neurotoxicants should be referred for more expensive 

full-scale clinical neuropsychological assessment. 

This tool is intended for widespread use in clinics and 

workplaces. The aims of the present project are to 

create a set of computer-based neurobehavioral tests 

specifically for screening of individuals exposed to 

potentially neurotoxic agents, to pilot test the 

instrument for feasibility of use, to develop training 

materials to instruct potential users of the 

computer-based testing system, and to evaluate those 

training materials. 

Methodology 

The project employs new hardware and software 

technology to accomplish these aims. A pen-based 

notebook computer with a speech production device 

is employed. This hardware represents improvements 

over that used by existing computer-based batteries 

by allowing both auditory presentation of the tests 

and recording of responses in a manner equivalent to 

paper-and-pencil neuropsychological tests. The set 

of tests to be implemented in this project includes 

tests of a range of behavioral functions: orientation, 

verbal learning, spatial memory, visual and cognitive 

tracking. The screening instrument is to be pilot 

tested for feasibility of use among 50 outpatients at 
Page 98 - Neurotoxic Disorders 

an occupational medicine clinic. In addition, training 

materials are to be developed to instruct potential 

users of the computer-based testing system. 

Multi-media capabilities of the hardware/software 

development environment will be utilized to develop 

the training materials. A pilot test of these training 

materials using students in an occupational and 

environmental health training program will be 

performed. 

Significant Findings 

None to date. 

Organophosphate Neuropathy and 

Biomarkers of Exposure 

Rob McConnell, MD. 

Mount Sinai 

School of Medicine 

One Gustave L. Levy Place 

New York, New York 10029-6754 

Program Area: Neurotoxic Disorders 

Grant Number: 5 KOJ OHOOJ23-02 

Start & End Dates: 07/01/92 - 06/30/95 

Funding Level: $54,000 ($107,987 Cum) 

Importance to Occupational Safety and Health 

Poisoning with methamidophos and certain other 

organophosphate insecticides, including chlorpyrifos, 

has been reported to cause neuropathy. Recent 

studies suggest that mild and subclinical neuropathy 

may affect over 25% of all individuals poisoned with 

methamidophos, an insecticide used widely by 

hundreds of thousands of farmers throughout the 

world. Experimental studies suggest that inhibition of 

the activity of neuropathy target esterase, which can 

be measured in lymphocytes, is predictive of 

subsequent neuropathy and that autoantibodies to 

neurofilament triplet protein are increased in serum of 

animals with experimentally induced organophosphate 

induced neuropathy. We propose to validate these 

assays among a poisoned population. These assays 

are potentially of use for screening workers exposed 

to organophosphate neurotoxins, for predicting the 

clinical sequela among individuals poisoned with 

methamidophos, chlorpyrifos, and other 

organophosphate neurotoxins, and as the basis for 

further exploration of the mechanism of 

organophosphate neuropathy. 

Objectives 

The biological hypothesis under study is that 

there exists a syndrome of persistent subclinical 

peripheral neuropathy caused by methamidophos or 

chlorpyrifos, and that this syndrome can be reliably 

detected by electrophysiologic assessment of sensory 

and motor function coupled with assessment of serum 

autoantibodies to nervous system tissue and 

assessment of exposure through measurement of NTE 

activity in circulating lymphocytes. 

Specific Aims are: 

1. Whether inhibition of lymphocyte neuropathy 

target esterase (NTE) measured in peripheral 

lymphocytes is a sensitive and specific index of 

peripheral neurotoxicity and of serum 

autoantibodies to peripheral nervous system 

proteins. 

2. Whether previous poisoning with methamidophos 

or chlorpyrifos results in diminished motor and 

sensory function, as reflected in 

electrophysiologic studies, pinch strength, and 

elevated vibrotactile threshold. 

3. Whether a dose-response relationship exists 

between lymphocyte NTE inhibition and motor or 

sensory function, or serum autoantibodies. 

4. Whether there exist threshold levels of 

methamidophos or chlorpyrifos exposure, below 

which either sensory or motor neuropathy is no 

longer evident. 

Methodology 

The study population consists of 50 patients 

previously poisoned with neuropathic 

organophosphates and treated at two teaching 

hospitals in Nicaragua plus two control groups: 

(I) patients poisoned with other organophosphates not 

known to be neurotoxins, and (2) unexposed cattle 

rancher controls. At the time of acute poisoning, 

inhibition of neuropathy target esterase (NTE), the 

putative target enzyme for organophosphate 

neuropathy, and serum autoantibodies to 

neurofilament triplet proteins, are measured in 

peripheral lymphocytes. Severity of poisoning also is 

evaluated clinically. Before hospital discharge (and 

before neuropathy is likely to have occurred), 

vibrotactile threshold, thermal sensory threshold, 

dynamometric grip and pinch strength, nerve 

conduction studies, and clinical evaluations are 

conducted among poisoned and never poisoned 

patients (cattle rancher controls). Exposure is 

characterized by patient interview and field visit to 

the site of poisoning, and by analysis of residue in 

dermal wipe samples or in field samples, where 

necessary, to confirm the pesticide responsible for 
poisoning. All patients are re-examined 6 weeks to 

3 months after poisoning, long enough for peripheral 

neuropathy to develop. Convalescent autoantibodies 

are measured, and baseline neuropathy target esterase 

is measured at the time of followup. Neuropathy 

target esterase will be validated against clinical 

outcome and serum autoantibodies, and 

dose-response relationships and possible thresholds of 

inhibition of NTE, necessary for the development of 

neuropathy, will be examined by measuring acute and 

subsequent baseline (percent depression) of 

neuropathy target esterase. All workers will be 

re-examined two years after poisoning to evaluate the 

persistence of neuropathy. 

Significant Findings 

Of the thirty-five acutely poisoned patients 

recruited to date to this cohort, twenty have been 

poisoned with the peripheral neurotoxins chlorpyrifos 

or methamidophos. All thirty-five poisoned patients 

have been re-examined between 6 weeks and 

3 months. In addition, 12 not poisoned cattle 

ranchers have had two examinations at similar 

intervals to the controls. In the poisoned cohort, we 

have identified one case of profound neuropathy who 

had markedly depressed neuropathy target esterase at 

the time of acute poisoning. 

Publications 

McConnell R, Keifer M, Rosenstock L: Elevated 

Quantitative Vibrotactile Threshold Among Workers 

Previously Poisoned With Methamidophos and Other 

Organophosphate Pesticides. Am J of Indust Med, 

in press, 1993 

Neurological Effects of 

Organophosphates on Farmworkers 

Matthew C. Keifer, MD. 

University of Washington 

School of Medicine 

Department of Medicine 

& Environmental Health 

325 Ninth Avenue, ZA-66 

Seattle, Washington 98104 

Program Area: Neurotoxic Disorders 

Grant Number: I KOJ OH00133-01 

Start & End Dates: 09/01/93 - 08/31/96 

Funding Level: $50,470 ($50,470 Cum) 

Neurotoxic Disorders - Page 99 

Importance to Occupational Safety and Health 

The World Health Organization (WHO) estimates 

that 600 million people world wide are exposed to 

pesticides on a regular basis, much of this exposure 

is to organophosphate pesticides (OP). Past studies 

have documented persistent neurological effects in 

previously OP poisoned workers and some with 

chronic OP exposure. This study will focus on 

identifying persistent neurobehavioral deficits which 

may result from chronic long-term pesticide 

exposure. The results of this study will have direct 

bearing on the occupational health of the 

approximately 5 million people in the U.S. who 

derive some part of their income from agricultural 

work. The results will also have bearing on the 

pesticide application industry as structural pesticide 

applicators use many of the same products. 

Objectives 

The goal of this clinical epidemiological study is 

to determine whether farmworkers chronically 

exposed to OP pesticides in field work have 

quantifiable nervous system abnormalities after an 

exposure season and whether these changes are 

persistent after a several month period of 

non-exposure. 

Methodology 

This cross-sectional study with a follow-up 

component will compare 60 female orchard farm 

workers with chronic low-level OP exposure to age, 

education, and language matched unexposed referents. 

Exposure estimates will be based on orchard spray 

logs, work questionnaires of subjects, and biological 

monitoring (cholinesterase testing). A neurological 

battery including the WHO Neurobehavioral Core 

Test Battery, vibratory threshold, color discrimination 

testing, nerve conduction and repetitive stimulation 

studies, and pattern reversal visual evoked potentials 

will be applied to both groups, both at the end of an 

exposure season and again following a 5-6 month 

period of non-exposure. Several biological markers 

which may serve as markers of susceptibility, 

physiological effect, or dose will also be evaluated: 

cholinesterase, paraoxonase, chlorpyrifos oxonase 

levels, and muscarinic receptor density in 

lymphocytes. 

Significant Findings 

None to date. 
Page 100 - Noise-Induced Hearing Loss 

The Effects of Impulse Noise on the 

Auditory System 

Donald Henderson, Ph.D. 

State University of New York 

School of Social Sciences 

Communicative Disorders and Sciences 

215 Parker Hall 

Buffalo, New York 14214 

Program Area: Noise-Induced Hearing Loss 

Grant Number: 5 ROJ OH01152-12 

Start & End Dates: 07/01/80 - 03/31/96 

Funding Level: $233,677 ($1,840,031 Cum) 

Importance to Occupational Safety and Health 

Impulse and impact noise found in industry 

constitutes a special hazard to workers' hearing. For 

equivalent amounts of acoustic energy, impulse and 

impact noise may cause significantly more hearing 

loss than exposure to continuous noise. There is 

consensus that current noise standards are completely 

inadequate for protecting workers from exposure to 

impulse and impact noise. Our research is trying to 

understand the biological basis of impulse 

noise-induced hearing loss. From a practical 

perspective, the research is directed at learning the 

range of parameters of impulse and impact noise that 

contribute to making an exposure hazardous. The 

results of this research will serve as part of the 

scientific foundation of more comprehensive noise 

standards. 

Objectives 

The research program has three complementary 

objectives: (I) to understand the relation between the 

parameters of impulse/impact noise (peak pressure, 

duration, number, repetition rate, exposure duration, 

spectrum) and the effects on hearing; (2) to 

understand the anatomical and physiological changes 

in the inner ear following traumatic exposures; and 

(3) to explore the possibility that "toughening" 

exposures to non-traumatic noise can reduce the 

amount of hearing loss from a dangerous noise 

exposure. 

Methodology 

An electrical-mechanical system is used to 

produce realistic noise impacts. The hearing of the 

experimental animals tested, is before and after 

exposure for twenty days. Routine data collection 

consists of measurements of hearing sensitivity, 

auditory discrimination, and cochlear histology. 

More detailed studies of certain experimental groups 

will include scanning Electron Microscopy, as well as 

more discriminating psychoacoustic measures of 

hearing. 

Significant Findings 

Since the inception of this project, we have 

reported a number of findings. (I) Certain 

combinations of impulse and continuous noise 

constitute an especially hazardous situation. 

(2) Exposures above a certain "critical" level cause 

direct mechanical damage. This project has begun to 

document how the critical level varies with the 

parameters of the impact/impulse. In addition, 

microscopic studies have elucidated the complicated 

series of changes that occur in the inner ear following 

exposure to traumatic levels of impulse and impact 

noise. (3) The project has developed a number of 

psychoacoustic tests that better characterize the 

hearing impairment caused by dangerous noise. 

(4) The project has shown the damaging effects of 

noise can be exacerbated with other agents, i.e., 

vibration and certain drugs. (5) In the last few years 

we have shown that certain low level exposures 

protect the auditory system from future higher level 

exposures. During the last year we have found that 

these prophylactic exposures are effective in reducing 

the hearing loss produced by high level impact and 

impulse noise. All of these results have direct 

implications for the management of workers in noisy 

environments. 

Publications 

Subramaniam M, Salvi RJ, Spongr V, Henderson D, 

Powers NL: Changes in Distortion Product 

Otoacoustic Emissions and Outer Hair Cells 

Following Interrupted Noise Exposures. Hearing 

Research, in press, 1993 

Salvi RJ, Henderson D, Clock AE: Effects of Noise 

Exposure on the Auditory System. In: Handbook of 

Neurotoxicology Vol. 2, Effects of Mechanisms, (eds. 

L Chang, R Dyer), Marcell Decker Inc., New York, 

in press, 1993 

Henderson D, Salvi RJ, Boettcher FA, Clock AE: 

Neurophysiological Correlates of Sensorineural 

Hearing Loss. Handbook of Clinical Audiology, 4th 

Edition (ed. J Katz), in press, 1993 

Salvi RJ, Henderson D, Clock AE: Effects of Noise 

Exposure on the Auditory System. In: Handbook of 

Neurotoxicology Vol 2: Effects and Mechanisms 

(eds. L Chang, R Dyer), in press, 1993 
Subramaniam M, Henderson D, Spongr V: 

Protection from Noise Induced Hearing Loss: Is 

Prolonged "Conditioning" Necessary? Hearing 

Research 65:234-239, 1993 

Henderson D, Subramaniam M, Boettcher F: 

Individual Susceptibility to Noise Induced Hearing 

Loss: An Old Topic Revisited. Ear and Hearing 

14:152-168, 1993 

Subramaniam M, Henderson D, Campo P, Spongr V: 

The Effect of Low Frequency Conditioning on 

Hearing Loss from High Frequency Noise. J Acoust 

Soc Am 93:952-956, 1992 

Henderson D, Mills J, Colletti V: Psychophysical 

Limits of Auditory Performance: Implications for the 

Diagnosis of Hearing Loss. Otolaryngology ( ed. M 

Paparella), Saunders, pp 255-268, 1992 

Henderson D, Campo P, Subramaniam M, Fiorino F: 

Development of Resistance to Noise. Noise Induced 

Hearing Loss (eds. Dancer A, Henderson D, Salvi RJ, 

Hamernik R), Mosby Year Book, 

pp 476-488, 1992 

Salvi RJ, Henderson D, Boettcher FA, Powers NL: 

Functional Changes in Central Auditory Pathways 

Resulting From Cochlear Diseases. Mosby Year 

Book, pp 47-60, 1992 

Subramaniam M, Henderson D, Campo P, Spongr V: 

The Effect of "Conditioning" on Hearing Loss From 

A High Frequency Traumatic Exposure. Hearing 

Research 58:57-62, 1992 

Danielson R, Henderson D, Gratton MA, Bianchi L, 

Salvi RJ: The Importance of "Temporal Pattern" in 

Traumatic Impulse Noise Exposures. J Acoust Soc 

Am 90:209-218, 1991 

Campo P, Subramaniam M, Henderson D: The 

Effect of "Conditionaling" Exposures on Hearing 

Loss from Traumatic Exposure. Hearing Research 

55:195-200, 1991 

Subramaniam M, Campo P, Henderson D: The 

Effect of Exposure Level on the Development of 

Progressive Resistance to Noise. Hearing Research 

52:181-188, 1991 

Subramaniam M, Campo P, Henderson D: 

Development of Resistance to Hearing Loss from 

High Frequency Noise. Hearing Research 56:65-68, 

1991 

Henderson D, Subramaniam M, Gratton MA, 

Saunders SS: Impact Noise: The Importance of 

Noise-Induced Hearing Loss - Page 101 

Level, Duration, and Repetition Rate. J Acoust Soc 

Am 1350-1357, 1991 

Henderson D, Farzi F, Danielson R: The Concept of 

Critical Level and Impulse Noise. Environmental 

International Vol 16 353-361, 1990 

Fiorino F, Gratton MA, Subbanna M, Bianchi L, 

Henderson D: Physiological Mechanism Underlying 

the Progressive Resistance to Noise Induced Hearing 

Loss. Valsalva 54(Suppl 1):36-41, 1989 

Boettcher FA, Henderson D, Gratton MA, Byrne C, 

Bancroft B: Recent Advances in the Understanding 

of Noise Interactions. Archives of Complex 

Environmental Studies I (I): 15-21, 1989 

Byrne C, Henderson D, Saunders S, Powers N, Farzi 

F: Interaction of Noise and Whole Body Vibration. 

Recent Advances in Research on the Combined 

Effects of Environmental Factors, (ed 0. Manninen), 

Pk-Paino Oy Printing House, Tampere, Finland, pp 

239-254, 1988 

Henderson D, Hamernik RP: A Parametric 

Evaluation of the Equal Energy Hypothesis. In: 

Basic and Applied Aspects of Noise-Induced Hearing 

Loss, (eds. R Salvi, D Henderson, RP Hamernik), 

Plenum Press, New York, 1988 

Henderson D, Colletti V, Sittoni V: The Role of the 

Acoustic Reflex in Noise-Induced Hearing Loss. In: 

Clinical Measurement of Acoustic Impedance, ( ed. V 

Colletti), Amplaid, Milano, 1987 

Henderson D, Hamernik RP, Salvi RJ: A Parameter 

Evaluation of the Equal Energy Hypothesis. In: 

Noise Induced Hearing Loss: Basic and Applied 

Aspects, (eds. RJ Salvi, RP Hamernik, D Henderson, 

V Colletti), Plenum Press, 1985 

Henderson D, Hamernik RP, Salvi RJ: Impulse 

Noise Repetition Rate: Implication for the Equal 

Energy Hypothesis. J Acoust Soc Am 78, 

Supple 1-55, 1985 

Henderson D, Hamernik RP: Assessing the Hazards 

of Impulse Noise Superimposed on Background 

Noise. J Acoust Soc Am 78:S5, 1985 

Salvi RJ, Henderson D, Hamernik RP, Colletti V: 

Basic and Applied Aspects of Noise-Induced Hearing 

Loss. Plenum Press, NY, 1985 

Henderson D, Salvi RJ, Hamernik RP, Ahroon WA: 

Neural Correlates of Sensorineural Hearing Loss. 

Ear and Hearing 4:115-129, 1983 
Page 102 - Noise-Induced Hearing Loss 

Henderson D, Salvi R, Hamernik R: Is the Equal 

Energy Rule Applicable to Impact Noise? J of the 

Acoust Soc of Am Supplement 1, Vol 71, S50, 1982 

Hamernik RP, Henderson D, Salvi RJ: New 

Perspectives on Noise-Induced Hearing Loss. Raven, 

Press, New York, NY, 1982 

Functional Correlates of Cochlear 

Injury 

William W. Clark, Ph.D. 

Central Institute for the Deaf 

818 South Euclid 

St. Louis, Missouri 63110 

Program Area: Noise-Induced Hearing Loss 

Grant Number: 5 ROI OH02128-08 

Start & End Dates: 09/01/84 - 05/31194 

Funding Level: $0 ($1,063,373 Cum) 

Importance to Occupational Safety and Health 

The laboratory studies of noise-induced hearing 

loss in animal subjects and the relation with cochlear 

pathology directly address the long-term research 

goals described by the NIOSH prevention document. 

They will help to establish damage-risk criteria for 

human noise exposures, delineate the mechanisms of 

noise-induced hearing loss, determine the role of 

degenerative and recuperative processes, and 

determine the relative hazard of different schedules of 

noise exposure to help develop noise descriptors for 

workers exposed on an irregular basis. In addition, 

they address the interaction between aging and noise 

induced hearing loss. 

Measures of hearing sensitivity obtained by 

positive-reinforcement operant conditioning 

techniques provide accurate assessment of hearing 

sensitivity in appropriately trained subjects. 

Combined with morphometric evaluation of cochlear 

damage produced by noise exposure, these laboratory 

studies provide important information about the 

precise relation between specific noise exposure 

parameters, i.e., level, duration, schedules, pattern, 

and the resultant histopathology that is not attainable 

in human subjects. 

Acoustic measures made from ear canals of 

unanesthetized chinchillas ( acoustic inter modulation 

distortion products and otacoustic emissions) before 

and after noise exposure will help elucidate cochlear 

mechanisms and may lead to an objective test for 

cochlear function. 

Field studies of noise exposure and hearing levels 

of workers exposed at levels below a time-weighted 

average of 85 dBA provide important baseline data 

for comparison of groups of exposed individuals to 

determine the relative contribution of occupational 

noise exposure to the hearing levels of the groups. 

Objectives 

The major goal of this project is to determine 

with behavioral and anatomical studies how the 

magnitude, pattern, and growth of hearing loss and 

structural damage are altered as the parameters of 

noise exposure are varied. Secondary objectives 

include evaluating hearing loss and cochlear damage 

as a function of age in a group of chinchillas that 

have never been exposed to noise and comparing the 

effects of noise exposure in young and old animals. 

In addition, acoustic measures of spontaneous 

otacoustic emissions and acoustic distortion products 

are being made from the ear canals of all subjects. 

Finally, an attempt is being made to develop a 

national II Annex B II comparison database for U.S. 

industry, for use with the new International Standard 

R 1999. 

Methodology 

Hearing thresholds are obtained by behavioral 

methods in chinchillas before, during, and after noise 

exposure; the ears of all animals are then prepared 

for microscopic examination of the cochlea. 

Behavioral measures of thresholds and discrimination 

ability are controlled by newly-developed virtual 

instrumentation software which is programmed on a 

Macintosh II computer system. Acoustic measures 

are made with small probe microphones and receivers 

positioned in the ear canal of the unanesthetized 

animal. Audio metric data from industry are 

accumulated in a large database on a Macintosh 

computer, and statistical software packages are used 

for data selection and analysis. 

Significant Findings 

Some of the significant findings of the project 

include: 

1. Asymptotic threshold shifts appear to set an 

upper bound on permanent threshold shifts. 

Animals exposed continuously for the equivalent 

of a working lifetime of noise (9 years 

continuously) do not suffer additional hearing 

losses as the exposure continues; even after very 

long exposures some recovery is always observed 

after cessation of the noise, indicating a persisting 

temporary component to the hearing loss. 

Animals exposed for long periods, allowed to 
recover, and then re-exposed lose hearing much 

more slowly than they did on the initial 

exposure, indicating that the surviving sensory 

cells are "toughened" by long-term exposure to 

noise and become much more resistant to 

subsequent exposures. 

2. Interrupting an exposure with rest is protective. 

Exposures with quiet periods interspersed 

produce less hearing loss and less cochlear 

damage than equal-energy continuous exposures. 

These data suggest that a 3-dB time-intensity 

tradeoff for equating hazardous effects of 

interrupted noise is overly protective; a 5-dB 

trading relation provides a better fit to the data. 

3. Under some schedules of interrupted exposure, 

hearing sensitivity recovers even though the 

exposure continues. That is, some of the sensory 

elements of the inner ear can "toughen" 

themselves against further insult by noise. 

Physiological evaluation of auditory nerve fiber 

thresholds confirmed that recovery of up to 

30 dB of sensitivity can occur, and the locus of 

the phenomenon is peripheral, probably at the 

level of the hair cell. 

4. The mechanism of the recovery phenomenon 

differs, depending upon the primary site of 

stimulation of the cochlea. Low-frequency 

exposures ( octave band of noise centered at 

0.5 kHz, 95 dB SPL, 15 minutes per hour) result 

in considerably more recovery than high 

frequency exposures ( octave band of noise 

centered at 4.0 kHz, 86 dB SPL, l 5 minutes per 

hour). These findings suggest different 

mechanisms of recovery with different time 

constants. 

5. Sensory cell damage from noise exposure 

precedes measurable hearing loss; individuals 

may sustain substantial cochlear damage before 

there is any measurable elevation of hearing 

sensitivity. 

6. Chinchillas raised in quiet environments for 

periods of up to 19 years show anatomical signs 

of age-related hearing loss (presbycusis), but the 

hearing ability of old chinchillas is not 

significantly worse than that of young animals. 

This is in stark contrast to the findings from 

humans which show that 25% of Americans over 

65 years of age have material impairment in 

hearing and suggest that much of what is 

typically called presbycusis in humans is caused 

by environmental factors, principally noise 

exposure. 

7. Distortion product otacoustic em1ss1ons 

(DPOAE) measured during and after interrupted 

noise exposure behave differently than 

behaviorally-measured threshold shifts. DPOAE 

continue to deteriorate during interrupted noise 

exposure even when thresholds are recovering; 

Noise-Induced Hearing Loss - Page 103 

after noise exposure DPOAES continue to 

recover for as long as 90 days after noise 

exposure, even though threshold recovery is 

complete by l O days. Finally, correlation 

between DPOAE shifts and outer hair cell loss is 

poor, implying that the DPOAE may not be a 

sensitive indicator of hearing function or outer 

hair cell integrity. 

Publications 

Bohl CD, Clark WW: The Effect of Hand Held 

Radio Operation on Audio Dosimeters. Am Ind Hyg 

AssocJ 54:127-134, 1993 

Clark WW: Hearing: 

Otolaryngology Head 

l 06:669-676, 1992 

Effects of Noise. 

and Neck Surgery 

Clark WW, Bohl CD: Corrected Values for Annex B 

of ISO 1999. J Acoust Soc Am 91 :3064-3065, 1992 

Clark WW: Noise Exposure and Hearing Loss in 

Children and Youths. ASHA 34:93, 1992 (Abstract) 

Cherow E, Clark WW, Berger E: A National Noise 

Abatement Strategy for the United States. ASHA 

34:187, 1992 (Abstract) 

Clark WW: The ASA's Role in Preventing 

Nonoccupational Hearing Loss in the United States. 

J Acoust Soc Am 92:2357, 1992 (Abstract) 

Clark WW: Noise Exposure in Children and Youths. 

J Acoust Soc Am 91:2375, 1992 (Abstract) 

Royster L, Lipscomb D, Clark WW, Dobie R, Jayne 

T: The Expert Witness in Heating Loss Claims and 

Other Hearing Related Actions. Proceedings of the 

1992 Hearing Conservation Conference, sponsored by 

the National Institute for Occupational Safety and 

Health and the National Hearing Conservation 

Association, Cincinnati, OH, p. 3, 1992 (Abstract) 

Clark WW, Bohne BA: Hearing Loss and Cochlear 

Damage from Interrupted Exposure to Noise. In: 

Noise-Induced Hearing Loss, (eds. A Dancer, D 

Henderson, R Salvi, R Hamernik), Mosby, St. Louis, 

pp. 445-455, 1991 

Clark WW: Recent Studies of Temporary Threshold 

Shift (TTS) and Permanent Threshold Shift (PTS) in 

Animals. J Acoust Soc Am 90:155-163, 1991 

Clark WW: Noise Exposure and Hearing Loss from 

Leisure-time Activities: A Review. J Acoust Soc 

Am 90:175-181, 1991 
Page 104 - Noise-Induced Hearing Loss 

Clark WW: A Head Start on Hearing Loss. 

Spectrum: The National Hearing Conservation 

Association Newsletter 8:1-6, 1991 

Clark WW: Effect of Amplified Music on Hearing 

of Children. In: Hearing Before the U.S. House 

Select Committee on Children, Youth, and Families., 

"Tum it Down: Effects of Noise on Hearing Loss in 

Children and Youth. July 22, 1991. US Government 

Printing Office, Washington pp. 54-67, 1991 

Clark WW, Lambert PR: Hearing Loss: 

Occupational and Nonoccupational. In: Combatting 

Noise in the 90's: A National Strategy for the United 

States. American Speech-Language Hearing 

Association, Washington, pp 29-31, 1991 

Clark WW: Amplified Music from Stereo Headsets 

and Its Effect on Hearing. Hearing Instruments 

41(10):29-30, 1990 

Bohne BA, Clark WW: Studies of Noise-Induced 

Hearing Loss Using an Animal Model. Hearing 

Instruments 41(10):13-16, 1990 

Clark WW, Popelka GR: Response to Dr. Kryter's 

Letter Concerning the Article, "Hearing levels of 

Railroad Trainmen". Laryngoscope 100: 1136-113 8, 

1990 

Clark WW: Role of Non-occupational Exposure in 

Diagnosing Occupational NIHL. Proceedings of the 

1992 Hearing Conservation Conference, sponsored by 

the National Institute for Occupational Safety and 

Health and the National Hearing Conservation 

Association, Cincinnati, OH, p. 167, 1991 (Abstract). 

Clark WW: Noise and Leisure Activities. 

Proceedings of the NIH National Consensus 

Conference of Noise. Office of Medical Applications 

of Research and National Institute on Deafness and 

Other Communication Disorders, 1990 

Clark WW, Popelka GR: Hearing Levels of Railroad 

Trainmen. Laryngoscope 99: 1151-1157, 1989 

Clark WW, Bohne BA, Reilly TJ: Effects of Periodic 

Rest on Hearing Loss and Cochlear Damage 

Following Interrupted Exposure to High-Frequency 

Noise. Abstracts of the 12th Midwinter Meeting of 

the Association for Research in Otolaryngology, 

pp. 218-219, 1989 

Clark WW, Bohne BA, Reilly TJ: Effects of Periodic 

Rest on Hearing Loss and Cochlear Damage 

Following Interrupted Exposure to High-Frequency 

Noise. J Acoust Soc Am 84:S75-S76, 1988 

(Abstract) 

Bohne BA, Clark WW: Hazardous Effects of Noise 

on Hearing. Proc. International Conference on Noise 

Control Engineering, Vol II, pp 905-908, 1987 

Sinex DG, Clark WW, Bohne BA: Effect of Periodic 

Rest on Physiological Measures of Auditory 

Sensitivity Following Exposure to Noise. J Acoust 

Soc Am 82:1265-1273, 1987 

Clark WW, Bohne BA, Boettcher F: Effect of 

Periodic Rest on Hearing Loss and Cochlear Damage 

in the Chinchilla. J Acoust Soc Amer 84: 1253-1264, 

1987 

Clark WW, Bohne BA: Attenuation and Protection 

Provided by Ossicular Removal. J Acoust Soc Amer 

81: 1093-1099, 1987 

Clark WW, Solomonson M: Spontaneous Otacoustic 

Emission from a Chinchilla Ear Following Exposure 

to Noise. J Acoust Soc Am 82:S 117 A, 1987 

(Abstract) 

Clark WW, Bohl CD, Davidson LS, Melda KA: 

Evaluation of a Hearing Conservation Program at a 

Large Industrial Company. J Acoust Soc Am 

82:Sl 13, 1987 (Abstract) 

Bohne BA, Clark WW: Hazardous Effects of Noise 

on Hearing. Proc. International Conference on Noise 

Control Engineering, Vol II, pp 905-908, 1987 

Bohne BA, Bozzay DG, Harding GW: Inter Aural 

Correlations in Normal and Traumatized Cochleas. 

J Acoust Soc Amer 80:1729-1736, 1986 

Sinex DG, Havey DC: Neural Mechanisms of 

Tone-On-Tone Masking: Patterns of Discharge Rate 

and Discharge Synchrony Related to Rates of 

Spontaneous Discharge in the Chinchilla Auditory 

Nerve. J Neurophysiology 56: 1763-1780, 1986 

Clark WW, Bohne BA: Temporary Threshold Shifts 

from Attendance at a Rock Concert. J Acoust Soc 

Am 79, Supp 1, S48, 1986 (Abstract) 

Clark WW, Bohne BA: Cochlear Damage: 

Audiometric Correlates, In: Sensorineural Hearing 

Loss, Mechanisms, Diagnosis, Treatment, (eds. E 

Harford, T Glattke), Univ of Iowa Press, pp 59-82, 

1986 

Clark WW: Spontaneous Otacoustic Emissions and 

Acoustic Intermodulation Distortion Products as 

Indicators of Hearing Loss and Cochlear Pathology. 

In: Sensorineural Hearing Loss: Mechanisms, 

Diagnosis, Treatment, (eds. E Harford, T Glattke), 

Univ of Iowa Press, pp 209-232, 1986 
Clark WW, Bohne BA: The Effects of Noise on 

Hearing and the Ear. Resident and Staff Physician 

31:6-19, 1985 

Bohne BA, Marks JE, Glasgow GP: The Delayed 

Effects of Ionizing Radiation on the Ear. 

Laryngoscope 95:818-828, 1985 

Bohne BA, Carr CD: Morphometric Analysis of 

Hair Cells in the Chinchilla Cochlea. J Acoust Soc 

Amer 77:153-158, 1985 

Clark WW, Bohne BA: The Effects of Noise on 

Hearing and the Ear. Medical Times 112: l 7-22fm, 

1984 

Clark WW, Kim DO, Zurek PM, Bohne BA: 

Spontaneous Otacoustic Emissions in Chinchilla Ear 

Canals: Correlation with Histopathology and 

Suppression by External Tones. Hearing Research 

16:299-315, 1984 

Hearing Hazard Associated with 

Industrial Noise Exposure 

Roger P. Hamernik, Ph.D. 

State University of New York 

Department of Physics/Speech & Hearing 

107 Beaumont Hall 

Plattsburgh, New York 12901 

Program Area: Noise-Induced Hearing Loss 

Grant Number: 2 ROI OH02317-09 

Start & End Dates: 08/01/90 - 08/31/98 

Funding Level: $198,536 ($198,536 Cum) 

Importance to Occupational Safety and Health 

The noise research supported by this continuing 

grant began in August 1993 after concluding a 

previous three-year project. Thus the summary 

descriptions that follow reflect the results of two 

different but related kinds of noise studies. Industrial 

noise environments are typically characterized by 

high levels of impact noise that are superimposed on 

a continuous noise background producing a complex 

temporal signal. These high kurtosis noise 

environments pose an unusually high risk of hearing 

loss to the repeatedly exposed individual. Current 

noise measurement practice relies upon a time 

averaged energy metric (e.g., Leq) which has been 

shown to be inadequate to characterize a long-term 

noise exposure. Alternatives to such metrics that are 

Noise-Induced Hearing Loss - Page 105 

highly correlated with the magnitude and frequency 

specificity of hearing loss are desirable for industrial 

hearing conservation practice. Furthermore, hearing 

Joss in industrial workers accumulates from repeated 

daily (interrupted) exposures to excessive noise over 

a long period of employment. Most strategies 

designed to estimate hearing loss rely either upon 

extrapolations from experimental data acquired from 

short-term acute exposures or from noninterrupted 

long-term noise exposures or from epidemiological 

data with its typically 70 dB or more across-subject 

variability. Recent discoveries show that the 

peripheral auditory system can modulate the effects of 

noise exposure as much as 40 dB. These effects are 

believed to be partially medicated by the outer hair 

cell motor system which can be activated by a 

low-level noise exposure that precedes a hazardous 

noise exposure, or by interrupting a daily noise 

exposure regime. The outer hair cell bi-directional 

transduction system is also responsible for generating 

cochlear emissions which are now being intensively 

studied because of their potential use as a noninvasive 

and objective diagnostic test for noise-induced 

changes in outer hair cell function. Although 

exposure to high-level impact noise continues to pose 

a problem to hearing in many industrial 

environments, there is virtually no experimental data 

on the accumulation of hearing loss from interrupted 

high-level impact noise and relatively little data 

available on the relation between cochlear emissions 

and noise-induced sensory cell pathology. Similarly, 

our knowledge of how low-level noise outside the 

work place affects hearing loss acquired in the work 

environment is inadequate. 

Objectives 

Our noise research program is designed to study 

the types of issues that are summarized above in an 

animal (chinchilla) model. The objectives of this 

research are: (I) to extract metrics from a complex 

noise environment that correlate with the magnitude 

and frequency specificity of the hearing loss resulting 

from prolonged exposure to such noise environments; 

(2) to characterize the hearing loss and cochlear 

pathology resulting from interrupted impact and 

complex noise (i.e., non-Gaussian, high kurtosis 

noise) in order to determine the extent to which 

temporal factors of an exposure affect trauma; and 

(3) to develop correlations among the cubic distortion 

product emissions (3DPE), permanent threshold shift 

and sensory cell pathology in an effort to determine 

the extent to which the 3DPE can be used as a 

diagnostic or screening tool for persons at risk of 

acquiring noise-induced hearing loss. 
Page 106 - Noise-Induced Hearing Loss 

Methodology 

The chinchilla is being used as an animal model. 

Hearing thresholds and 3DPE input/output functions 

are obtained prior to exposure and at regular intervals 

following exposure up to 30-days postexposure. 

After the effects of the acoustic insult have stabilized, 

surface preparation histology is used to quantify the 

sensory cell population. The exposure paradigms 

include interrupted and noninterrupted noise 

presentations for either 5 or 20 days. Exposures are 

balanced for total energy so that comparisons based 

upon energy can be made. The noise stimuli are 

computer generated and consist of: (a) narrow band 

(400 Hz) impacts with center frequencies between 0.5 

and 8.0 kHz. These frequencies were chosen to 

characterize the cochlear protective (toughening) 

mechanisms across a broad extent of the basilar 

membrane; (b) broad band impacts; and (c) various 

complex high kurtosis noises all having the same Leq 

and spectrum but differing in their statistical 

properties. 

Significant Findings 

1. A series of five noise exposures each having the 

same Leq = 100 dB and long-term spectrum, but 

varying statistical properties i.e., from Gaussian 

where the time domain kurtosis P(t) = 3 through 

various increasing values of P(t). The impulsive 

components of the non-Gaussian noises had 

various spectral configurations, while the peak 

pressures and the inter impulse intervals were 

controlled though probability functions. Despite 

equivalent energies and spectra in each of the 

five exposures, the resulting permanent threshold 

shifts and sensory cell losses varied in magnitude 

and frequency specificity in a manner that was 

not predictable on the basis of conventional 

measurements or P(t). However, computation of 

the frequency domain kurtosis P(t) for each of 

the exposures using various algorithms showed 

that P(t) could be used to predict the relative 

magnitude and frequency specificity of the 

hearing loss and outer hair cell loss. Taken 

together these experiments show that while the 

temporal structure of a continuous, uninterrupted 

exposure is an important variable in determining 

trauma, conventional measures of an exposure 

such as Leq are not sufficient to predict the 

nature of trauma. The P(t) metric however, 

shows a high correlation with trauma and may be 

a useful measure in industrial noise assessment. 

2. Exposure of chinchillas to broad band, 

high-level (107, 113, 119, or 125 dB peak SPL) 

impact noise (1/s) on an interrupted 6h daily 

schedule over 20 days has shown that pure tone 

thresholds measured immediately following each 

daily exposure improve as much as 30 dB despite 

the continuing noise exposure. The time constant 

of this recovery effect (toughening) and the 

magnitude of the effect are related to test 

frequency (impact spectrum) and the exposure 

energy. The trauma, quantified by permanent 

threshold shifts and sensory cell losses, produced 

by the interrupted exposure paradigm is generally 

less than that produced by an equal-energy 

uninterrupted exposure. The wide variations in 

the temporal pattern of threshold shift across 

similarly exposed animals suggest that the 

toughening effect reflects the underlying 

susceptibility of that animal to noise trauma. 

Publications 

Ahroon WA, Davis RI, Hamernik RP: The Role of 

Tuning Curve Variables and Threshold Measures in 

the Estimation of Sensory Cell Loss. Audiology 

32:244-259, 1993 

Davis RI, Hamernik RP, Ahroon WA: Frequency 

Selectivity in Noise-Damaged Cochleas. Audiology 

32:110-131, 1993 

Ahroon WA, Hamernik RP, Davis RI: Complex 

Noise Exposures: An Energy Analysis. J Acoust 

Soc Am 93:997-1006, 1993 

Hamernik RP, Ahroon WA, Hsueh KD, Lei SF, 

Davis RI: Audiometric and Histological Differences 

between the Effects of Continuous and Impulsive 

Noise Exposures. J Acoust Soc Am 93:2088-2095, 

1993 

Hamernik RP, Ahroon WA, Davis RI, Lei SF: 

Hearing Threshold Shifts from Repeated Six-hour 

Exposure to Impact Noise. J Acoust Soc Am 94, in 

press, 1993 

Ahroon WA, Lei SF, Davis RI, Hamernik RP: The 

Use of Frequency Domain Kurtosis in the Assessment 

of Industrial Environments for Hearing Conversation 

Purposes. J Acoust Soc Am 91 (A):2381, 1992 

RP: Performance 

Domain Approach to 

J Noise Control 

Hsueh KD, Hamernik 

Characteristics of a Phase 

Random Noise Synthesis. 

Engineering 36(1):18-32, 1991 
Preventing NIHL In Construction 

Workers 

Sally L. Lusk, Ph.D. 

University of Michigan 

School of Nursing 

Department of Health Promotion 

& Risk Reduction 

400 N. Ingalls, Room 3180 

Ann Arbor, Michigan 48109-0482 

Program Area: Noise-Induced Hearing Loss 

Grant Number: 1 ROJ OH03136-0l 

Start & End Dates: 09/30/93 - 09/29/96 

Funding Level: $177,840 ($177,840 Cum) 

Importance to Occupational Safety and Health 

The purpose of this project is to prevent 

noise-induced hearing loss (NIHL), an irreversible 

impairment with significant monetary and personal 

costs, in construction workers through improved 

training in use of hearing protection (HP). The 

training will be based on a conceptual model, the 

Health Promotion Model (HPM) and specific to 

construction workers (CWs). 

The Department of Public Health has estimated 

that one quarter of the five million CWs in the U.S. 

are exposed to average daily noise levels above 

85 dBA (USDPH, 1988); yet no data regarding 

prevalence of NIHL or level of use of HP by CWs 

has been reported. While it is preferable to reduce 

this noise exposure through engineering controls, it is 

not feasible to eliminate all harmful noise. However, 

consistent use of HP equipment prevents NIHL. 

CWs represent a diverse and mobile population, 

exposed to various types of noise in conjunction with 

other safety hazards, on multiple and variable job 

sites. Therefore, knowledge of the predictors of these 

workers' use of HP is essential to the design of more 

effective training programs. 

This study will provide needed data covering five 

different areas: (1) the degree of hazardous noise 

exposure as perceived by CWs; (2) the frequency of 

use of HP by CWs; (3) the strongest predictors of use 

of HP by CWs; (4) recruitment of CWs into research 

studies through their training programs; and 

(5) worker behavior related to personal involvement 

in safety precautions within a comprehensive health 

promotion framework. 

Additionally, the proposed study will result in a 

customized training program for the prevention of 

NIHL in CWs through the increased use of personal 

HP. By developing the individual worker's consistent 

Noise-Induced Hearing Loss - Page 107 

use of protective equipment, safety measures can be 

transported from construction site to construction site, 

despite the limited options for environmental control. 

Objectives 

This project has four specific aims: (I) identify 

the most important predictors of CW's use of hearing 

protection, specifically for carpenters, operating 

engineers, and plumbers/pipefitters; (2) use the 

identified predictors of CW's use of HP to adapt the 

training program already developed for factory 

workers to the needs of CWs; (3) assess the effect of 

the training program on CWs' use of HP; and 

(4) revise the training program as indicated and make 

it available for general use in training CWs. 

Methodology 

This study will be conducted with two distinct 

samples, a regional sample and a national sample, in 

three phases: (I) a cross-sectional correlational 

study will identify predictors of selected CWs' use of 

HP (carpenters, operating engineers, and 

plumbers/pipefitters); (2) the trammg program 

prepared for factory workers will be revised to 

incorporate the predictors of CWs' use of HP and 

pilot-tested with CWs in this region; (3) the effect of 

the training program on the use of HP will be 

measured in both the regional and national samples 

through random assignment of workers to a Solomon 

Four-Group experimental design. 

Significant Findings 

None to date. 
Page 108 - Psychological Disorders 

Stress in One Occupational Group: 

Teachers 

Irvin Schonfeld, Ph.D. 

City College of CUNY 

School of Education 

Convent Avenue and 138th Street 

New York, New York 10031 

Program Area: Psychological Disorders 

Grant Number: 5 ROI OH02571-06 

Start & End Dates: 06/01188 - 09/29194 

Funding Level: $114,399 ($599,479 Cum) 

Importance to Occupational Safety and Health 

Little longitudinal research has been devoted to 

effects adverse working conditions exert on mental 

health and job-related morale. Teaching is an apt 

context in which to study these effects because the 

working conditions teachers encounter vary widely. 

An innovative feature of this study is that it follows 

newly appointed teachers through three years of 

work-force experience. Because the study begins 

before the women teachers entered the work force 

and includes a nonteacher comparison group, 

selection-based effects could be assessed. The study 

is also important because of the profession's critical 

role in our nation's social and economic life. 

Objectives 

l. To compare the mental health (e.g., depressive 

symptoms) of recent women college graduates 

who enter the teaching profession with that of 

similar graduates who enter other occupations. 

2. To identify job conditions that affect the mental 

health, health behaviors (e.g., psychophysiologic 

symptoms--headaches, etc.), and morale (e.g., 

job satisfaction) of newly appointed women 

teachers. 

3. To ascertain the effects of different types of 

resources, including personal dispositions (e.g., 

locus of control--an individual's belief about the 

degree to which people control their 

circumstances), social support, and coping 

behaviors, on health outcomes in teachers. 

4. To study the formation of one social resource, 

social support from colleagues. 

Methodology 

The project recruited subjects from two types of 

senior-year college classes: education classes that 

students typically attend enroute to teacher 

certification and psychology classes that are largely 

taken by students with little intention of entering the 

teaching profession. Education and psychology 

students tend to be similar on a number of social 

demographic characteristics (e.g., predominance of 

females). The colleges were selected because they 

have had a record of supplying teachers to New York 

area school districts. Subjects were part of the 

classes of 1987, 1988, 1989, and 1990. 

Participants completed specially constructed 

survey instruments in the summer following 

graduation (Time 0), the fall (Time 1 ), and the 

following spring (Time 2). They also completed 

instruments during a second summer (Time 3), a 

second fall (Time 4), a second spring (Time 5), a 

third fall (Time 6), and a third spring (Time 7). 

With the Time-0 survey, the project collected critical 

preemployment data on the various outcome measures 

(e.g., depressive symptoms) including expected job 

satisfaction. Outcome data and data on working 

conditions were collected during Times 1 and 2, and 

Times 4 to 7. 

Significant Findings 

The findings presented here include women 

teachers who met two criteria: they taught full-time 

during two consecutive data collection periods and 

did not change schools between those two periods. 

For the purpose of examining women with maximal 

exposure histories, women who taught part-time and 

women who changed from one school to another 

between assessment periods were excluded. 

1. In a comparison of the women who went on to 

obtain positions in the "best" schools, the "worst" 

schools, and schools of intermediate levels of 

adversity, there were no differences in 

preemployment levels of depressive symptoms. 

These women also did not differ from control 

women who obtained full-time nonteaching jobs. 

This finding is important because it indicates that 

self-selection or selection by administrative 

gatekeepers did not account for later differences. 

2. Once the women obtained full-time jobs, those 

who went on to obtain jobs with the most adverse 

working conditions (e.g., student violence, 

administrator insensitivity) had the highest levels 

of depressive symptoms in the fall and spring. 

The women who obtained jobs in the best run 

schools had the lowest levels of depressive 

symptoms. The women who obtained jobs in the 

schools of intermediate adversity and the women 

who obtained nonteaching jobs showed 

intermediate symptom levels. 
We conducted lagged regression analyses in 

which we predicted future problems (e.g., fall of 

the teacher's third year) from working conditions 

measured during the prior data collection period 

(e.g., the spring to the teacher's second year). 

Preemployment factors, social demographic 

characteristics, and nonwork stressors were 

controlled statistically. The results indicated that 

adverse school conditions were generally related 

to future depressive symptoms, satisfaction with 

work, motivation to remain in teaching, and 

psychophysiologic symptoms. 

3. These analyses also tended to show that social 

support from nonwork sources was related to 

fewer depressive and psychophysiologic 

symptoms and better self-esteem during the first 

year. After year one, however, nonwork social 

support was related only to better self-esteem. 

Over time, job satisfaction was the main outcome 

to which social support from colleagues was 

related. The most important factor predicting 

colleague support was social support from 

outside sources. The personality factor locus of 

control was not related to the outcomes. 

4. Individual coping behaviors tended not to be 

related to reduced problems. The effects of 

coping behaviors were swamped by the quality 

of working conditions. 

Conclusions. The factors that adversely affect 

teachers' well-being are preventable. They include 

student violence and disrespect as well as 

disrespectful behavior on the part of administrators. 

The findings underline the relative importance of 

efforts aimed at "environmental protection" in 

comparison to more purely "personal solutions." The 

findings indicate that private solutions in the teacher's 

coping repertoire ( e.g., use of discipline, advice 

seeking, etc.) are at best of limited efficacy. What 

was clear, however, was that the teachers fortunate 

enough to obtain jobs in safe, well-run schools had 

fewer depressive symptoms than their colleagues in 

worse-run schools. Moreover, the symptom picture 

of teachers who obtained jobs in the better-run 

schools compared favorably to those same women's 

preemployment symptom picture. In order to ensure 

the supply of well-functioning teaching professionals, 

it is important to make every school safe and well 

run. 

Publications 

Schonfeld IS, Rhee J, Xia F: Some Methodologic 

Issues in Occupational Stress Research: Examples 

From Research in One Occupational Group. In: Job 

Stress 2000: Emerging Issues, (eds. GP Keita, 

S Sauter), Washington, DC, American Psychological 

Association, in press, 1994 

Psychological Disorders - Page 109 

Schonfeld IS: Burnout in Teachers: Is It Burnout or 

Is It Depression? Human Stress: . Current and 

Selected Research, in press, 1994 

Schonfeld IS: Assessing Stress in Teachers: 

Depressive Symptoms Scales and Neutral 

Self-reports on the Work Environment. In: Work 

and Well-being: Assessments and Instruments for 

Occupational Mental Health, ( eds. J Quick, 

L Murphy, J Hurrell, Jr.), Washington, DC: 

American Psychological Association, pp 270-285, 

1992 

Schonfeld IS: A Longitudinal Study of Occupational 

Stressors and Depressive Symptoms in First-year 

Teachers. Teaching and Teacher Education 

8:151-158, 1992 

Schonfeld IS: Dimensions of Functional Social 

Support and Psychological Symptoms. Psychological 

Medicine 21: I 051-1060, 1991 

Schonfeld IS, Ruan D: Occupational Stress and 

Pre-employment Measures: The Case of Teachers. 

Journal of Social Behavior and Personality 6:95-114, 

1991 

Schonfeld IS: Coping with Job-Related Stress: The 

Case of Teachers. Journal of Occupational 

Psychology 63: 141-149, 1990 

Schonfeld IS: Distress in a Sample of Teachers. 

Journal of Psychology 123:321-338, 1990 

Schonfeld IS, Shaffer D, Barmack JE: Neurological 

Soft Signs and School Achievement: The Mediating 

Effects of Sustained Attention. Journal of Abnormal 

Child Psychology 17:575-596, 1989 

Schonfeld IS, Shaffer D, O'Connor P, Portnoy S: 

Conduct Disorder and Cognitive Functioning. 

Testing Three Causal Hypotheses. Child 

Development 19:993-1007, 1989 

Trautman C, Erickson D, Shaffer D, Correra A, 

Schonfeld IS: Prediction of Intellectual Deficits in 

Children with Acute Lymphocytic Leukemia. Journal 

of Developmental and Behavioral Pediatrics 

19:122-128, 1989 
Page 110 - Control Techniques 

Relative Health Risks of Diesel 

Emission Control Systems 

Susan T. Bagley, Ph.D. 

Michigan Technological University 

College of Sciences and Arts 

Department of Biological Sciences 

1400 Townsend Drive 

Houghton, Michigan 49931-1295 

Program Area: Control Techniques 

Grant Number: 2 ROI OH0261 l-04 

Start & End Dates: 01/01/89 - 10/31/93 

Funding Level: $0 ($352,307 Cum) 

Importance to Occupational Safety and Health 

Whole diesel exhaust is regarded as a potential 

occupational carcinogen by the National Institute for 

Occupational Safety and Health (NIOSH) but the risk 

of cancer to exposed workers has not been 

quantitatively defined. One problem encountered in 

defining risk is the chemical complexity of diesel 

exhaust, making it difficult to define exposure. 

Michigan Technological University (MTU) and the 

Bureau of Mines (BOM) are working together to 

define key aspects of the chemical nature and 

biological activity of diesel particulate matter (DPM) 

collected in underground mines with and without 

diesel emissions control devices and DPM and 

semi-volatile organics collected from a heavy-duty 

diesel engine operated with and without emission 

control devices in the laboratory. Together, these 

data will help evaluate the potential health effects of 

diesel exhaust and the impact of emission control 

Objectives 

The overall objectives of this project were: 

(1) to obtain estimates of diesel pollutant levels in 

underground coal mines when DPM emission control 

devices are not in use, to include polynuclear 

aromatic hydrocarbons (PAH) and biological activity; 

(2) to assess the effects of using DPM emission 

control systems on these pollutants in laboratory tests; 

and (3) to obtain estimates of the effectiveness of 

using various DPM emission control devices on these 

same pollutants in a metal mine and in a coal mine. 

Methodology 

Samples from four dieselized underground coal 

mines without DPM control devices were collected by 

BOM personnel using Hi-volume samplers equipped 

with inertial impactors to collect size-differentiated 

particle samples. Particles :;;; l um in size were 

considered to be primarily of diesel origin. 

Samplers were located at the section intake and in the 

haulageway near where diesel shuttle cars turned 

around to dump their loads. The soluble organic 

fraction (SOF) was removed from the particles on 

the filters by Soxhlet extraction with dichloromethane. 

The daily extracts from all filters at each sampling 

location in a mine were pooled to reflect average 

levels over each day's sampling period. 

Samples were also collected and analyzed using 

similar techniques from (1) a dieselized metal mine 

where a catalyzed diesel particle filter (CDPF) and an 

oxidation catalytic converter (OCC) were used 

together and (2) a dieselized underground coal mine 

where a disposable diesel exhaust filter (DDEF) was 

used. 

Laboratory samples for DPM and semi-volatile 

organics were also collected at the BOM in two 

separate studies: (1) with and without a CDPF; and 

(2) with and without an OCC. Both filter (DPM) 

and XAD-2 resin (XAD-2 resin organic component 

or XOC) samples were collected, with organic 

material removed from both types of media by 

Soxhlet extraction with dichloromethane. The CDPF 

studies were conducted using a low sulfur (0.039 wt. 

percent) fuel. The OCC studies were conducted with 

six different fuels varying in sulfur and aromatic 

levels and cetane number. 

PAH and nitro-PAH fractions of the SOF and 

XOC were obtained from a two-column clean-up 

procedure and analyzed by HPLC with fluorescence 

detection. The compounds chosen for quantification 

due to their known or suspected health effects 

included fluoranthene, chrysene, benz[a]anthracene, 

benzo[a]pyrene, 1-nitropyrene, 2-nitrofluorene, and 

3-nitrofluoranthene. Sulfate levels were determined 

by ion chromatography of aqueous extracts from the 

filters following their Soxhlet extraction for SOF 

removal. Unfractionated SOF and XOC and some 

fractions were tested for biological activity using the 

microsuspension version of the Ames assay. 

Significant Findings 

Estimates of Diesel Pollutant Levels in 

Underground Coal Mines - The DPM, PAH, and 

mutagenic activity levels represented potential highest 

in-mine values that would occur when diesel 

equipment was operating in a given area. The DPM 

values (mean/mine range of 0.9 - 1.9 mg/m3

) were 

typically at the upper end of values obtained with 

other, more personal-type sampling methods. In most 

cases, the mine atmosphere levels of DPM, SOF, 

PAH, and mutagenicity were statistically similar for 

all four underground coal mines, thus providing a 

range of values that might be expected to occur when 
diesel vehicles without DPM emission control devices 

are operating. Use of the DDEF in another coal 

mine resulted in at least 50 percent reductions in all 

diesel emissions' concentrations in the haulageways. 

The differences in levels between the mines were 

likely related to differences in parameters such as 

vehicle type, mine ventilation efficiencies, fuel 

composition, and engine design, operation, and 

maintenance, with engine operation and maintenance 

probably being the major factor. The lowest levels 

of SOF and associated PAH were found at the mine 

with well-maintained engines operating at high loads; 

the highest levels of these parameters were found at 

the mine with relatively poorly maintained vehicles 

spending a considerable amount of time idling. 

Laboratory Studies with DPM Emission Control 

Devices - Laboratory-generated data were found to 

be reliable for estimating in-mine levels in dieselized 

underground mines. When making such comparisons, 

it is particularly important that the laboratory data 

have been generated from engine operating conditions 

that closely resemble the diesel engine operation in 

the comparison mines. The data obtained from a 

transient cycle designed to simulate haulage vehicle 

operation closely resembled the coal mine data where 

such haulage vehicles operate. The data from a 

steady-state cycle designed to simulate operation of 

load-haul-dump vehicles, such as would be used in 

metal mines, did not as closely resemble the actual 

data from the coal mines. 

When used in conjunction with a low sulfur 

(<0.05 wt percent) fuel, it was estimated that use of 

the tested CDPF in underground mines could result 

in at least 90 percent reductions in DPM levels, with 

comparable effects on other diesel exhaust 

components. The CDPF was slightly less effective in 

reducing XOC compared to SOF (99 percent versus 

89 percent, respectively), although both reductions 

were significant. The CDPF removal efficiency for 

DPM-associated PAH was c::98 percent for both 

transient and steady-state operation. Only 

fluoranthene and pyrene were found with the XOC 

with or without the CDPF. Over the transient cycle, 

the CDPF reduced the DPM-associated mutagenicity 

levels by 75 percent and the vapor phase 

organics-associated levels by 80 percent. The 

steady-state weighted cycle produced an average 

69 percent reduction in SOP-associated mutagenicity 

levels. This difference between reductions in 

organics (up to 99 percent) and mutagenicity levels 

(up to 80 percent) was related to presence of active 

compounds such as nitro-PAH. 

When used in conjunction with a low sulfur fuel, 

use of the tested OCC in underground mines could 

also have a significant impact on reducing D PM 

levels as well as other emission components. Using 

a transient test cycle simulating potentially worst case 

operation of the OCC, from 30 to 60 percent 

Control Techniques - Page 111 

reductions were found in all measured em1ss10ns. 

Some differences in emissions due to fuel 

composition were also noted. 

Effects of a CDPF and an OCC in an 

Underground Metal Mine - Use of a combined 

CDPF/OCC in an underground metal mine resulted 

an approximately 50% reductions in DPM, SOF, and 

P AH concentrations. These less-than-expected 

reductions (based on data from the laboratory studies) 

may have been due to the fact that the area being 

sampled was heavily impacted by air from areas in 

the mine where dieselized vehicles without this 

combined control devices were in use. Mutagenic 

activity concentrations (revertants/m3

) increased by 

about 250% with CDPF/OCC use, reflecting over 

500% increases in activity on a mass basis 

(revertants/ug SOF). This increase appeared to be due 

to increases in nitro-PAH with use of the CDPF 

component of the control device. 

Publications 

Cantrell BK, Rubow KL, Watts WF Jr, Bagley ST, 

Carlson DJ: Pollutant Levels in Underground Coal 

Mines Using Diesel Equipment. Proc of the 6th US 

Mine Ventilation Symposium, Society for Mining, 

Metallurgy, and Exploration, Inc, Salt Lake City, 

Utah, in press, June 21-23, 1993 

Bagley ST, Baumgard KJ, Gratz LD: Polynuclear 

Aromatic Hydrocarbons and Biological Activity 

Associated with Diesel Particulate Matter Collected 

in Underground Coal Mines. Proc of Bureau of 

Mines Information and Technology Transfer Seminar 

on Diesels in Underground Mines: Measurement and 

Control of Particulate Emissions, Bloomington, 

Minnesota, pp. 40-48, September 29-30, 1992 

McClure BT, Bagley ST, Gratz LD: The Influence 

of an Oxidation Catalytic Converter and Fuel 

Composition on the Chemical and Biological 

Characteristics of Diesel Exhaust Emissions. SAE 

Technical Paper Series No 920854, 1992 

Bagley ST, Baumgard KJ, Gratz LD, Bickel KL, 

Watts WF Jr: Effects of a Catalyzed Diesel Particle 

Filter on the Chemical Biological Character of 

Emissions from a Diesel Engine Used in 

Underground Mines. SAE Transactions 

I00:1578-1589, (SAE Technical Paper Series No 

911840), 1991 

Bagley ST, Baumgard KJ, Gratz LD: Comparison of 

IN-mine and Laboratory-generated Diesel Particulate 

Matter, Biological Activity, and Polynuclear Aromatic 

Hydrocarbon Levels. Proc of 3rd Symposium on 

Respirable Dust in the Mineral Industries, Pittsburgh, 

Pennsylvania, 61-70, October 17-19, 1990 
Page 112 - Control Techniques 

Computer Simulation of Push-Pull 

Systems 

Michael R. Flynn, Sc.D. 

University of North Carolina 

School of Public Health 

Environmental Sciences and Engineering 

CB 7400 Rosenau Hall, Room 118 

Chapel Hill, North Carolina 27599-7400 

Program Area: Control Techniques 

Grant Number: 5 ROI OH02710-02 

Start & End Dates: 09/01190 - 12/31/92 

Funding Level: $0 ($154,156 Cum) 

Importance to Occupational Safety and Health 

This research seeks to improve the design of 

local exhaust ventilation systems that are augmented 

by the use of push jets. These systems are used to 

control worker exposure to toxic airborne 

contaminants from numerous industrial processes eg, 

open surface tank operations. 

Objectives 

The specific objectives are to (I) develop a 

computer code to solve the three-dimensional 

continuity and Navier-Stokes equations governing the 

flow of a hood, jet and crossdraft; and (2) validate 

the computer predictions of velocity, capture 

efficiency, and contaminant distribution with wind 

tunnel tracer studies. 

Methodology 

An upwind finite element algorithm employing a 

penalty approximation has been used to approximate 

the three-dimensional velocity field. Experimental 

validations of the predictions are made with hot-film 

anemometry, smoke wire flow visualization 

techniques, and hood capture efficiency using sulfur 

hexafluoride as the tracer and infrared 

spectrophotometry as the detection method. 

Significant Findings 

Computer velocity predictions are in good 

agreement with values measured using hot-film 

anemometry. Flow visualization of this simple 

push-pull flow has been achieved by using a smoke 

wire in the plane of the cross draft. The resulting 

estimate of the jet trajectory is in excellent agreement 

with computer simulations. Turbulence kinetic 

energy is not well predicted by the code particularly 

in the vicinity of the hood reflecting either an 

inadequate turbulence model or insufficient gris 

resolution. 

Application of Neural Networks for 

Process Fault Diagnosis & Safety 

Venkat Venkatasubramanian, Ph.D. 

Purdue University 

School of Chemical Engineering 

Laboratory for Intelligent Process Systems 

West LaFayette, Indiana 47907 

Program Area: Control Techniques 

Grant Number: 5 ROI OH02740-02 

Start & End Dates: 01/01/92 - 12/31193 

Funding Level: $82,901 ($161,706 Cum) 

Importance to Occupational Safety and Health 

The study of fault detection and diagnosis is 

concerned with designing systems that can assist 

human operators in detecting and diagnosing process 

failures in order to prevent accidents. As modem 

chemical plants are extremely complex they are more 

vulnerable to failures, as witnessed by the recent 

chemical plant related accidents. Because of this 

complexity, modem plants are also more difficult to 

diagnose thus raising serious occupational safety 

related problems. We are also dealing more with 

toxic substances, and with the advent of 

biotechnology and genetic engineering industries, the 

results of an industrial accident can be quite 

devastating. Occupational safety and health hazards 

pose a serious threat to an estimated 80 million 

workers in the United States. Industrial statistics 

show that even though major catastrophies and 

disasters of chemical plants are infrequent, minor 

accidents are very common, occurring on a day to 

day basis, resulting in many occupational injuries, 

illnesses, and costing the society billions of dollars 

every year. During 1983 the Bureau of Labor 

Statistics has reported over 3,000 job-related deaths 

and estimated 4.9 million job-related injuries and 

illnesses. It is also estimated that the annual cost to 

society of work-related injuries, illnesses, and deaths 

has nearly tripled from $11.5 billion in 1972 to $33.0 

billion in 1984. 

The proposed project is aimed at the prevention 

and control of such frequent, day to day, accidental 

events in the industry. The proposed research would 

lead to a better understanding of the complexities that 
are involved in the design of intelligent computer 

systems that can effectively monitor, diagnose, and 

control chemical plants. In this project, we propose 

a neural network-based methodology that has 

considerable potential in the development of such 

intelligent systems. 

Objectives 

The major goal of this proposal is to research 

and demonstrate a novel approach based on Neural 

Networks for the design of chemical process hazard 

detection, prevention, and control systems. Fault 

detection and diagnosis using neural networks is 

achieved by exploiting their non-linear pattern 

classification properties. This diagnostic ability 

crucially depends upon the discrimination of decision 

regions corresponding to various fault classes. The 

delineation of decision regions for a given number of 

fault classes, in tum, hinges on several factors, such 

as the number of input and hidden nodes, the type of 

activation function employed, noise in sensor 

measurements, the extent and nature of training, etc. 

Further, it is also important to examine the ability of 

neural nets in detecting and diagnosing faults during 

process transients by extracting key qualitative 

features of the underlying process trend. In this 

project, we propose to examine these central issues. 

Methodology 

We have built a dynamic simulator of a chemical 

reactor-distillation column system which is used to 

simulate a wide variety of faults and dynamic process 

trends. Using this as a test bed, we have been 

investigating a variety of neural network architectures 

to analyze their classification characteristics, their 

ability to deal with dynamic and noisy sensor data, 

and so on. 

Significant Findings 

In the first year of the project, we developed a 

hierarchical representation framework that can model 

process trends at different levels of detail to address 

the problem of extracting key qualitative features 

from noisy data to aid in fault diagnosis. We also 

demonstrated the superiority of ellipsoidal neural nets 

for representing bounded fault classes. 

In the second year of the project, the following 

important contributions have been made following up 

on our hierarchical framework: 

Fault diagnosis during dynamic process 

transients using the hierarchical trend 

analysis framework through the use of 

moving window schemes. 

Control Techniques - Page 113 

We have demonstrated that a properly trained 

network can detect abnormal process conditions soon 

after they appear, thus facilitating early diagnosis and 

supervisory control actions. 

Evaluation of the neural network approach in 

the presence of noisy and uncertain sensory 

data. 

This is a very important issue from the industrial 

perspective. Much progress was made here with the 

aid of a distillation column-reactor case study. We 

have shown that neural nets are quite noise-tolerant 

and can diagnose successfully in the presence of 

considerable random noise. We are currently 

exploring the performance of the neural nets for a 

more complex industrial case study under a variety of 

dynamic transients in the presence of process 

uncertainties and noise to quantify their performance. 

Explore further the use of ellipsoidal nets 

and investigate issues concerning the design 

of the ellipsoids, network decomposition 

strategies etc. 

We have developed a network and problem 

decomposition scheme to reduce the complexity in 

large-scale fault diagnosis problems. The technique 

involves input space reduction through the use of 

principal component analysis and hidden nodes 

specialization. The results have been very 

encouraging so far. We are currently focusing on the 

issue of ellipsoids design to incorporate a priori 

probabilities and predefined error bounds. 

Publications 

Kavuri S, Venkatasubramanian V: Neural Network 

Decomposition Strategies for Large Scale Fault 

Diagnosis. (Eds. Morari and Morris), Special Issue 

of Intl J Control, in press, 1994 

Kavuri S, Venkatasubramanian V: Using Fuzzy 

Clustering and Ellipsoidal Units in Neural Networks 

to Improve Fault Classification. Computers and 

Chemical Engineering 17(8):765-784, 1993 
Page 114 - Control Techniques 

Emission Factor Development for 

Intermittent Workplace Sources 

Richard A. Wadden, Ph.D. 

University of Illinois at Chicago 

School of Public Health 

Environmental & Occupational 

Health Sciences 

P. 0. Box 6998 

Chicago, Illinois 60680 

Program Area: Control Techniques 

Grant Number: 5 ROI OH02804-03 

Start & End Dates: 12101/90 - 11/30/94 

Funding Level: $35,515 ($177,423 Cum) 

Importance to Occupational Safety and Health 

The conceptual thrust of this proposal is to 

develop a method for generalizing the design of 

engineering control of workplace hazards. In 

particular, we are developing emission factors, based 

on field observations, for four types of commonly 

encountered, hazardous, open-tank processes: vapor 

degreasing, electroplating ( chromium and copper 

plating), offset printing, and wave soldering. 

Objectives 

The value of the emission factor approach is that 

the effect of the particular interior space in which the 

data are collected is removed. The factors are 

developed from the area concentration pattern 

surrounding each device while production is taking 

place, using mathematical models describing a mass 

balance for the contaminant in order to transform this 

pattern for a particular source to an emission rate. 

To systematically describe the variability of 

emissions, the release rate is related to measures of 

source activity, process conditions, and equipment 

geometry. A total of 11 source tests have been 

carried out consisting of 12 I-hour sampling periods 

which also include measurements of general and local 

exhaust ventilation. The results of this study will 

provide: (1) A compilation of activity-based 

emission factors for Cr and Cu electroplating, vapor 

degreasing, wave soldering, and offset printing; (2) A 

measure of the variability in emissions which can be 

expected from such processes; (3) Actual 

determinations, based on an emission mass balance, 

of control device performance for each of the 

processes studied; (4) A generalized basis for 

estimating workplace concentrations from these types 

of sources; and (5) A mass-balance basis for 

evaluating control design alternatives. 

Methodology 

Field tests under production conditions have been 

carried out on: (1) Three methyl chloroform 

degreasers in a microcircuit production facility; 

(2) Four Pb wave soldering lines of different designs 

in two plants making electronic circuit boards; (3) Cu 

emissions from an electrolytic copper plating line; 

(4) Two decorative chrome-nickel electroplating 

lines; (5) A methylene chloride degreaser; (6) A 

terpene degreaser using limonene; and (7) Three 

different offset printing .Plants using, respectively, 

sheetfed offset, offset web, and heatset web offset 

printing processes. 

Significant Findings 

Average total emissions from three uncontrolled 

methylchloroform degreasing were determined to be 

between 0.39 kg/hr and 0.74 kg/hr depending on the 

model used. The approximate usage inventory value 

for the same time period was 0.62 kg/hr. Emissions 

were related to uncovered tank conditions, dragout, 

and type of parts, and 80% were identified as coming 

from a single line. Total uncontrolled emissions from 

three Pb wave soldering lines averaged 50.4 mg 

Pb/hr. Total lead bath scrapings and dedrossings 

appeared to be the most important source activity 

variable with an emission factor of 

11 mg/solder cleaning. Average copper emissions 

and emission factor from electroplating were 

29 mg/hr and 0.25 mg/amp•hr; and for sulfur were 

59 mg/hr and 0.54 mg/amp•hr. Total emissions from 

a terpene degreaser were 0.68 kg limonene/hr with an 

emission factor of 2.2 g limonene/circuit board 

cleaned. Average uncontrolled emissions from a 

sheet-fed offset print shop were 0.4 kg VOC/hr; with 

an emission factor of 30-38 g VOC/press cleaning. 

Additional printing and wave soldering emission 

factors are still being developed as well as those for 

methylene chloride, and chrome electroplating. 
Computational Methods in Industrial 

Ventilation 

Michael R. Flynn, Sc.D. 

University of North Carolina 

School of Public Health 

Environmental Sciences and Engineering 

CB 7400 Rosenau Hall, Room 118 

Chapel Hill, North Carolina 27599-7400 

Program Area: Control Techniques 

Grant Number: 5 ROJ OH02858-03 

Start & End Dates: 07/01/91 - 06/30/94 

Funding Level: $59,540 ($183,386 Cum) 

Importance to Occupational Safety and Health 

This project is designed to bring the methods of 

computational fluid mechanics to bear on the problem 

of estimating worker exposure. At the present time 

the inability to estimate exposure remains a serious 

deficiency in the design process for contaminant 

control ventilation systems. 

Objectives 

The specific objectives are: (1) expand an 

existing computer code based on discrete vortex 

methods to predict airflow patterns around a worker 

and a nearby obstacle; (2) develop predictions of 

exposure using particle tracking methods; and 

(3) conduct wind tunnel simulations to validate 

computer predicted flow patterns and exposure 

estimates. 

Methodology 

Significant improvements in parallel and serial 

algorithms for discrete vortex methods continue to 

appear in the fluid mechanics literature. These 

improvements are being integrated into an existing 

algorithm to improve speed and flexibility. Sulfur 

hexafluride tracer gas studies using infrared 

spectrophotometry are used to validate exposure 

estimates. Smoke wire techniques are used to explore 

flow patterns around mannequins and objects in the 

wind tunnel. 

Significant Findings 

A discrete vortex code (DVM) has been 

developed employing a boundary integral potential 

flow solver, for prediction of the time dependent flow 

around a worker and object. Testing continues to 

Control Techniques - Page 115 

evaluate the stability and convergence of the 

algorithm. In addition a particle tracking algorithm 

for estimating concentration fields has been 

incorporated into the code. Several wind tunnel 

studies to collect data for model validation are 

complete. Predictions of concentration are in 

reasonable agreement with measured values, but 

further work is needed to specify small-scale 

turbulent time and length scales. Experimental 

studies confirm predicted air flow patterns around a 

worker and obstacle and the algorithm correctly 

identifies worker orientations leading to reduced 

exposure. 

Permeation Mechanisms of 

Pesticides Through Materials 

Shane Que Hee, Ph.D. 

University of California 

School of Public Health 

Department of Environmental Health Sciences 

10333 Le Conte Avenue 

Los Angeles, California 90024-1772 

Program Area: Control Techniques 

Grant Number: 5 ROJ OH02951-02 

Start & End Dates: 09/30/92 - 09/29/94 

Funding Level: $122,129 ($239,760 Cum) 

Importance to Occupational Safety and Health 

While permeation characteristics of single specific 

solvent chemicals through gloves and garments are 

well documented, those for specific pesticides and for 

pesticides in their emulsion concentrate forms 

(regarded as the most hazardous forms to handle), 

have not been intensively investigated. Emulsion 

concentrates consist of the active ingredient, organic 

solvents, surfactants, and other adjuvants, and thus 

constitute a multi component chemical exposure on 

inhalation, dermal or ingestion exposure. This is 

important during spraying, on worker field reentry, 

and when formulating. When several pesticides are 

coformulated in blends under small shop conditions, 

permeation characteristics through gloves and 

garments may be influenced by the prior and 

concurrent handling of the other formulary 

components. 

Objectives 

The hypothesis is: the most permeating 

constituent of the challenge medium containing a 
Page 116 - Control Techniques 

pesticidal emulsion concentrate regulates the 

permeation of the pesticide through glove and 

garment materials. 

The studies will allow selection of the 

appropriate permeation method, the most protective 

gloves and garments for these formulations, and 

development of a predictive model. 

Methodology 

The initial studies will involve the identification 

and quantification of the inert components and 

surfactants/adjuvants in the selected emulsion 

concentrates. The latter are: cap tan, chlorpyrifos, 

2,4-D (three forms), endosulfan, malathion, 

methomyl, methyl parathion, and trifluralin. The 

selected glove materials are: Butyl, Nitrite, Silver 

Shield, and Viton. The g.μment materials are: 

Barricade, two-ply Saranex-Laminated Tyvek 23-P, 

Chemrel Max, and Teflon/Nomex/Teflon. 

Eight-hour screening studies with two 

ASTM-type permeation techniques will be 

performed. One technique involves a I-PTC 

ASTM-type permeation cell and liquid collection 

system. The other method utilizes a solid silicone 

sheet collection method. Challenges will be to the 

neat chemical if liquid, the neat chemical in the major 

solvent of the formulation in the presence/absence of 

surfactant/adjuvant, the emulsion concentrate, and to 

the aqueous emulsion diluted to its highest spraying 

concentration. Kinetics studies over two-hour 

periods at three different temperatures will then lead 

to measurement of breakthrough times, and steady 

state rates. Shelf-life studies for materials aged 0.5 

and 1.0 years after acquisition will also be performed. 

A predictive permeation model will be developed. 

Significant Findings 

Work has been initiated with two malathion 

emulsion concentrates. The liquid malathion neat 

chemical behaves like a nonpolar ester and thus 

permeates Nitrile (lag time 50-85 minutes· 2 ' 0.41-.37 mg/cm /min) and penetrates Latex (causes 

holes within minutes). The permeation is enhanced 

by the presence of xylene inert component. 

Challenge of malathion as aqueous emulsion 

formulations has necessitated optimization of mixing 

conditions and selection of an inert collection solvent 

that also permits solubilization of the malathion. 

Permeation was still observed at much lower steady 

state rates and about the same breakthrough times 

relative to challenges with formulations alone. 

Initial studies with formulations containing 

endosulfan, chlorpyrifos, and methomyl have shown 

that Nitrile is protective for at least two hours. 

Lannate had the highest steady state rate. Whereas 

the formulations having endosulfan and chlorpyrifos 

contained mesitylene inert components, those for 

lannate were methanol and propanols. The latter 

were responsible for the faster breakthrough times 

and higher steady state rates for methomyl. 

Encapsulating Protective Clothing: 

Work Tolerance 

Phillip A. Bishop, Ed.D. 

University of Alabama 

College of Arts and Science 

Box 870312 

Tuscaloosa, Alabama 35487-0312 

Program Area: Control Techniques 

Grant Number: J ROI OH03015-0JAJ 

Start & End Dates: 09/15/93 - 09/14/95 

Funding Level: $153,499 ($153,499 Cum) 

Importance to Occupational Safety and Health 

This is the initiation period of a two-year study 

of the efficacy, stability and generalizability of a 

prediction model for work tolerance of workers 

wearing encapsulating protective clothing (PC) in 

moderate to warm environments. The project will 

test and refine a recently developed prediction model 

and determine the generalizability of this approach to 

prediction in simulated industrial situations. 

Successful completion of this project will 

contribute to managing personnel engaged in labor 

requiring encapsulating protective clothing in 

moderate to warm temperatures. Worker safety will 

be enhanced, and more efficient worker scheduling 

can be utilized. Workers currently are required to 

self monitor, which increases risk and impedes 

effective work management. Current American 

Conference of Government Industrial Hygienists 

TLVs provide little help in this situation (1988-89 

ACGIH, 1990). Additionally this proposed project 

addresses, in part, 5 of the 12 research needs listed in 

NIOSH Criteria for a Recommended Standard for 

Occupational Exposure to Hot Environments, Revised 

Criteria, 1986. Current guidance for worker safety 

in PC is limited. The results of this study could be 

immediately useful in maximizing work productivity 

while minimizing safety risks. 

Objectives 

The purposes of the proposed study are to (1) test 

the generalizability, stability, and validity of, and 

refine the multiple regression equations developed in 
the previous study, (Bishop et al, 1994) and 

(2) Derive new equations as needed for other 

environments and work conditions. 

Both purposes of this study lead to development 

of a technique for predicting physical work capacity 

of workers in these situations based upon field 

measurements gathered in a short-term work task 

performed in protective clothing in a mild ambient 

environment. This work will build upon recent work 

done in our laboratory (Bishop et al., 1994). This 

prior study extended earlier work of Kenny et al. 

(1986), and Shvartz et al. (1977) and showed that the 

work tolerance of 15 subjects wearing protective 

clothing could be predicted from simple performance 

measures obtained during bench stepping in a 21 °C 

environment. 

Methodology 

After medical screening, 50 subjects will be 

measured during a bench step test of less than 

20 minutes duration at room temperature 

(WBGT = l 8°C). Simple data (i.e duration, comfort 

rating, etc.) from this bench step test will then be 

used to predict performance on a generic work 

protocol consisting of 15 min. of treadmill walking at 

3 mph followed by 5 min. of arm curls with 14.6 kg 

of weight referred to as "work" hereafter), with this 

work sequence repeated on separate days in 

counterbalanced order under these four conditions: 

Environment 

(WBGT 0C) 

18 

18 work, 18 rest 

26 work 

26 work, 26 rest 

Workload 

(Umin) 

V02= 1.0, continuous 

V02=1.8 for 30 min, rest 

30 min (1.8 +.0.2 @ rest 

yields 1.0) 

V02= 1.0 continuous 

V02= 1.8 for 30 min, rest 

30 min (1.8 +.0.2 @ rest) 

Models will be derived and tested for 

generalizability and stability by comparisons of 

models across subgroups and treatments. 

Significant Findings 

None to date. 

Control Techniques - Page 117 

Communication with 

Flat-Attenuation Hearing Protectors 

Tomasz R. Letowski, HD., Ph.D. 

Pennsylvania State University 

Department of Communication Disorders 

5 Moore Building 

University Park, Pennsylvania 16802 

Program Area: Control Techniques 

Grant Number: 1 ROJ OH03021-0JAJ 

Start & End Dates: 09/30/93 - 09/29/94 

Funding Level: $114,330 ($114,330 Cum) 

Importance to Occupational Safety and Health 

The results of this study are expected to 

determine noise spectra and ranges of noise levels 

which are appropriate environments for wearing 

flat-attenuation hearing protection devices (HPDs). 

Collected data will also be used to assess efficacy of 

various speech communication measures for 

assessment of HPDs. 

Objectives 

The proposed study is designed to evaluate the 

relationship between noise attenuation and speech 

communication effectiveness resulting from wearing 

flat-attenuation HPDs in several simulated work 

environments. Various objective and subjective 

measures will be compared to assess the amount of 

noise attenuation by the protectors as well as the 

effectiveness of speech communication between 

workers wearing the protectors. 

Methodology 

Sixty subjects will participate in the study. The 

following measures will be directly obtained or 

calculated in the study: (I) real-ear attenuation at 

threshold, (2) sound pressure level reduction, 

(3) word recognition score, (4) speech intelligibility 

rating, (5) double-task performance effectiveness, 

(6) speech level adjustment, and (7) vocal effort. 

Significant Findings 

None to date. 
Page 118 - Control Techniques 

Predictive Models of Solvent 

Permeation Through CPC 

Edward T. Zellers, Ph.D. 

University of Michigan 

School of Public Health 

Department of Environmental 

and Industrial Health 

1420 Washington Heights 

Ann Arbor, Michigan 48109-0292 

Program Area: Control Techniques 

Grant Number: J ROI OH03033-0I 

Start & End Dates: 12/01192 - 11/30/95 

Funding Level: $116,453 ($116,453 Cum) 

Importance to Occupational Safety and Health 

Dermatological disease arising from contact with 

chemicals historically has accounted for a 

disproportionately large percentage of all cases of 

chronic occupational illness. Dermal absorption of 

systemic toxicants is also known to be important for 

several classes of chemicals and is likely 

underreported. The use of chemical protective 

clothing (CPC) is often the only feasible means of 

protecting workers from dermal contact with toxic 

chemicals. Yet, our current understanding of the 

factors affecting the permeation resistance of CPC 

materials to solvents is very rudimentary. As a 

result, the protection afforded by a given type of CPC 

in workplace applications, particularly those involving 

organic solvents, is rarely known with certainty. The 

research proposed here entails a comprehensive 

investigation of solvent permeation through CPC and 

the development and validation of semi-empirical 

predictive permeation models for solvents and solvent 

mixtures. 

Objectives 

The broad goals of this project are to gain 

improved understanding of the physicochemical 

factors affecting the permeation of organic solvents 

through CPC and to develop broadly applicable and 

easily implemented models for industrial hygienists to 

use in selecting CPC when experimental data are not 

available. More specifically, the project focuses on 

the development and validation of new models for 

predicting the equilibrium solubilities and the 

diffusion coefficients in common CPC materials of a 

wide range of individual organic solvents and solvent 

mixtures as a function of the type of solvent and CPC 

material; temperature; CPC production variables such 

as the degree of polymer crosslinking; and the nature 

and concentration of co-solvents. This information 

will then permit accurate prediction of breakthrough 

times and steady-state permeation rates as a function 

of these variables. 

Methodology 

Permeation and immersion tests are being 

performed on four types of commercial polymeric 

CPC materials (i.e., butyl, natural, nitrile and 

neoprene rubbers) challenged with several organic 

solvents from each of 14 chemical classes. Binary 

mixtures are being examined for a representative 

subset of these solvents. These experimental data 

will serve as the basis for the models of equilibrium 

solubilities, diffusion coefficients and permeation 

rates. Solubility models based on 

(I) three-dimensional solubility parameters, 

(2) solvatochromic indices in conjunction with linear 

solvationfree-energy relationships, and (3) molecular 

group contribution methods are being investigated. 

Models for diffusion coefficients rely on empirical 

correlations of measured values with the physical 

properties and CFC-interaction strengths of the 

solvents. Modeled solubility and diffusion coefficient 

values will be used in Fickian models to obtain 

estimates of solvent breakthrough times and 

steady-state permeation rates. 

Significant Findings 

Over 1,300 immersion tests have been performed 

to date, representing duplicate or triplicate tests of 

solubility of each of 53 solvents in each of the four 

types of glove samples at each of three temperatures 

(25, 35, and 45 0C). Results show that solubility 

generally increases with increasing temperature as 

expected, however, decreases in solubility as well as 

solubility maxima at the intermediate temperature 

have also been observed. The development of the 

solubility models is currently in progress. Immersion 

testing of selected binary mixtures is also in progress. 

Permeation tests are being performed with two 

automated test systems, each of which can analyze 

two CPC samples simultaneously. Analyses are 

performed by gas chromatography using 

computer-controlled sampling, data acquisition, 

integration and management functions. A total of 80 

permeation tests have been completed. All tests are 

performed in duplicate and proper calibration and 

quality control procedures are being followed. 

Breakthrough times ranging from <5 min to > 10 days 

have been measured. The data set is too small at 

present for the implementation/validation of the 

permeation models. 
Transport Modeling of Industrial 

Ventilation 

Kyle D. Squires, Ph.D. 

University of Vermont 

Mechanical Engineering Department 

209B Votey Building 

Burlington, Vermont 05405-0156 

Program Area: Control Techniques 

Grant Number: I ROI OH03052-01 

Start & End Dates: 09/30193 - 09/29/96 

Funding Level: $152,013 ($152,013 Cum) 

Importance to Occupational Safety and Health 

Accurate, robust computational models must play 

an integral role in any plan directed towards 

significantly improving the design and development 

of ventilation systems. An area in which improved 

predictive methods are especially critical is 

contaminant transport in unsteady turbulent flow 

fields in which the contaminant is comprised of dense 

particulates. Because dense particles cannot follow 

the fluctuations of gas-phase turbulence, the range of 

interactions between the turbulent gas flow and 

suspended particles are very complex and not 

particularly well understood at the present time. It is 

not surprising, therefore, that design of ventilation 

hoods for applications of particulate removal is for 

the most part empirical. Consequently, there is no 

well developed rationale for current design practices 

and design techniques applicable to large classes of 

ventilation systems are lacking. Improved predictive 

capabilities are especially important because the 

complex interactions between the turbulent gas flow 

and suspended particles may pose greater risk to 

industrial workers than is currently accounted for by 

present day design practices. . 

Thus, given the complex nature of gas-particle 

interactions in turbulent flow fields and their impact 

on industrial ventilation, new predictive 

methodologies are needed to improve the design and 

development of these systems. The long-range goal 

of this research program is therefore development of 

a new generation of predictive methods for 

contaminant removal in industrial ventilation 

applications. 

Objectives 

The principal objective of the present study is 

model development for prediction of turbulent flow 

fields laden with small, dense particles. Specifically, 

Control Techniques - Page 119 

in this work models of particle transport appropriate 

for large-eddy simulation (LES) of the 

Navier-Stokes equations is being addressed. A major 

emphasis of the work is model development in the 

framework of the most promising approach to 

turbulence modeling developed within at least the last 

IO years: dynamic sub grid-scale modeling. 

Because of the complex nature of gas-particle 

flow fields in industrial ventilation applications, it is 

unrealistic at this stage to attempt development a 

general computational methodology suitable for 

arbitrary ventilation systems. Thus, this effort is 

directed towards model development in canonical 

flows containing the essential physics present in 

actual ventilation systems, viz.\ particle-laden free 

shear layers. 

Methodology 

Traditionally, predictive techniques for turbulent 

gas-particle flows have been limited by deficiencies 

in not only the particle transport models but also the 

turbulence models employed in the Navier-Stokes 

equations. This difficulty has been alleviated in the 

present work by employing large-eddy simulation of 

the Navier-Stokes equations as the solution technique 

for the gas-phase turbulent flow. 

Filtering of the Navier-Stokes equations in LES 

introduces turbulent stresses which cannot be resolved 

by the computational grid. One of the novel features 

of this work is parameterization of the subgrid-scale 

stresses using dynamic subgrid-scale modeling. The 

novel feature of dynamic modeling is that the 

subgrid-scale stresses are modeled using information 

from the resolved scales. This approach has yielded 

extremely accurate descriptions of several canonical 

flows. Its application to turbulent two-phase flows 

represents an important step in furthering the use of 

LES for engineering applications. The dispersed 

phase of solid particles is treated in this work using 

a Lagrangian approach, i.e., the equation of motion is 

integrated along discrete trajectories for a large 

ensemble of particles. 

Significant Findings 

As this work has been recently initiated, the 

majority of our efforts have been devoted to 

establishing the foundation for the research. 

Specifically, we are implementing the nu~eri~al 

methods to be employed in the work and contmumg 

our efforts in further refining dynamic subgrid-scale 

modeling. Notable in this effort has been application 

of the dynamic model to rotating turbulent flows; 

providing yet another example of a class of flows in 

which the dynamic model correctly accounts for the 

effect of system rotation on turbulence structure. 

This is extremely positive from the standpoint of 
Page 120 - Control Techniques 

industrial ventilation applications since the 

complicated, three-dimensional, time-dependent flow 

fields are not easily amenable to prediction by 

traditional methods. 

Load Monitoring For Safe 

Construction 

Dryver R. Huston, Ph.D. 

University of Vermont 

College of Engineering & Mathematics 

Department of Mechanical Engineering 

Votey Building, Room 201E 

Burlington, Vermont 05405-0156 

Program Area: Control Techniques 

Grant Number: I ROI OH03157-0l 

Start & End Dates: 09/30/93 - 09/29196 

Funding Level: $218,678 ($218,678 Cum) 

Importance to Occupational Safety and Health 

This project addresses the problem of 

occupational safety on construction sites. The 

specific problem addressed in this study is the 

prevention of the unexpected collapse of partially 

constructed facilities, in particular multistory 

reinforced concrete structures which are built using 

falsework and shoring structures. Over the past 

25 years at least 85 such collapses have been 

documented and reported. The effects of such a 

collapse can be catastrophic as evidenced by the 1987 

collapse of the L' Ambiance Plaza in Bridgeport, CT 

in which 28 construction workers were killed. 

At present there is little detailed guidance in the 

construction building codes regulating the design and 

construction of shoring systems for the construction 

of reinforced concrete buildings. There are also, at 

present, very few instruments available that can 

detect, document and provide a warning for 

dangerous loading conditions on the shoring systems. 

The overall results of this project will be the 

acquisition of load data on shoring systems during 

construction which can be used in the development of 

rational design codes. A subsidiary result will be the 

development and testing of equipment that can 

possibly be used to provide a real-time early warning 

and data logging capability for dangerous loading 

conditions. 

Objectives 

The overall goals of this project are to develop 

and implement real-time load and deflection 

monitoring instrumentation for buildings during 

construction, to develop an improved understanding 

of critical construction loading conditions, and to 

develop guidelines for safe construction practices 

specifically associated with multistory reinforced 

concrete construction. The fundamental hypotheses 

for this work are (1) that the primary cause of 

construction failures is inadequacy of the temporary 

support elements such as vertical shores and lateral 

bracing, (2) that an investigation of load and 

deflection histories during actual projects can 

contribute greatly to our understanding of critical 

loading conditions, and (3) that this improved 

understanding and invaluable information can be used 

as the basis for improved construction procedures and 

guidelines for safe design and construction. 

Methodology 

The research plan for this project contains two 

distinct portions. The first involves taking shoring 

load data at two or three building sites. The load 

data will be measured with an array of eight or more 

three-axis load cells. The three axis load cells will 

enable the measurement of side loads as well as 

vertical loads. Side loads have been implicated in a 

number of collapses that involved a loss of lateral 

stability. The data will be gathered and stored on an 

optical disk drive for further analysis. The second 

phase will involve a detailed analysis of the data 

coupled with computer models of the load distribution 

in curing concrete structures. The data and structural 

analysis will then be used with various 

reliability-based techniques to develop proposed 

guidelines for shoring design. The proposed 

guidelines will be presented to the cognizant bodies 

for comment and possible adoption. 

Significant Findings 

None to date. 
Field Study of Local Exhaust 

Ventilation Performance 

Lorraine M Conroy, Sc.D. 

University of Illinois 

School of Public Health 

EOHS (MIC 922) 

P. 0. Box 6998 

Chicago, Illinois 60680 

Program Area: Control Techniques 

Grant Number: 5 KOJ OH00078-03 

Start & End Dates: 09/28/89 - 09/29/93 

Funding Level: $0 ($138,046 Cum) 

Importance to Occupational Safety and Health 

A model which can be used to predict capture 

efficiency of flanged slot hoods exhausting area 

sources in the presence of a uniform crossdraft has 

been developed and validated under controlled 

laboratory conditions. This project will field validate 

the capture efficiency model for vapor degreasers 

exhausted with exterior type hoods, quantify industrial 

crossdrafts, and correlate process and worker 

activities with capture efficiency and crossdraft 

measurements. 

The research will lead to (1) an improved 

method for predicting hood capture efficiency and 

improved hood design methods; and (2) a better and 

more systematic evaluation of industrial crossdrafts, 

including the turbulence characteristics of these 

crossdrafts. Improved hood design methods, 

combined with a better understanding of the 

characteristics of industrial crossdrafts, will result in 

improved air quality in plants using vapor degreasers, 

lower probability of health hazards and safety hazards 

associated with air concentrations of halogenated 

solvents, and possibly lower operating costs if the 

solvent is recovered from the local exhaust system. 

Objectives 

The broad long-term objective of this research 

is to answer the question: Can exterior hood design 

be improved to adequately control emissions from 

open surface tanks? The specific aims of the 

research are to answer the following questions: 

(I) Can laboratory validated capture efficiency 

models be used to predict capture efficiency of local 

exhaust hoods in industrial settings? (2) Can 

industrial crossdrafts be quantified and characterized? 

(3) Can activity parameters be correlated with 

measured crossdrafts and capture efficiencies? 

Control Techniques - Page 121 

Methodology 

Measurements were conducted over two days at 

each of seventeen locations. Local exhaust and 

general ventilation flow rates, as well as the physical 

dimensions of the workspace and the degreaser were 

measured. Solvent concentrations at several locations 

in the workspace and in the local exhaust duct were 

measured in one-hour intervals. Crossdraft velocity 

was measured simultaneously with concentration in 

two-minute intervals. The concentration results and 

the ventilation characteristics of the space were used 

to determine the rate of solvent emission into the 

workspace using several mass balance models. The 

local exhaust emission rate was calculated from the 

duct flow rate and concentration. The ratio of duct 

emission rate to total emission rate is the hood 

capture efficiency. The measured crossdrafts, local 

exhaust hood flow rate, and the area of the tank 

surface were used in the predictive capture efficiency 

model for each sampling interval. These were 

compared with the measured capture efficiencies. 

Activities involving the degreaser and activities in the 

vicinity of the degreaser were recorded during each 

hour that sampling was conducted. Recorded 

activities were correlated with measured crossdrafts 

and capture efficiencies to determine how specific 

activities are related to crossdrafts and capture 

efficiencies. 

Significant Findings 

Measured crossdrafts ranged from near O to more 

than 2 fps. Measured workspace emission rates 

averaged l 0.0 g/min and ranged from O to 254 g/min. 

Measured capture efficiencies averaged 0.83 and 

ranged from 0.08 to 1.00. Predicted capture 

efficiencies averaged 0.77 and ranged from 0.55 to 

0.85. 

Using overall averages, there appears to be 

reasonably good agreement between measured and 

predicted capture efficiency (0.83 measured vs. 0.77 

predicted). However, examining the daily averages 

for each degreaser showed poor agreement between 

predicted and measured efficiency. This could be due 

to several factors: (I) turbulence was inadequately 

accounted for in the predictive model; (2) the effects 

of the cooling condenser were not considered; and 

(3) solvent was carried out of the degreaser to areas 

where the hood could not be expected to capture 

contaminants. 

The ACGIH recommended flow rate for vapor 

degreasers is 50 cfm/ft2 of tank surface.<1

> The 

measured hood flow rates ranged from 72% to 162% 

of the recommended flow rate. The recommended 

flow rate appeared to be adequate for some conditions 

but inadequate for other conditions. An increase in 
Page 122 - Control Techniques 

flow, above design recommendations, did not 

necessarily improve hood performance. 

Smart, Safe Scaffolding 

Peter J. Kajenski, Ph.D. 

Vermont Sensing 

RD2, Box 978 

Underhill, Vermont 05489 

Program Area: Control Techniques 

Grant Number: 1 R43 OH03010-0l 

Start & End Dates: 09130/92 - 06/29/93 

Funding Level: $0 ($49,650 Cum) 

Importance to Occupational Safety and Health 

Over the past 25 years there have been more 

than 85 collapses of structures under construction that 

have been directly attributable to formwork failure. 

We have proposed to develop sensing systems and 

techniques applicable to the monitoring of 

construction site shoring and scaffolding. It is 

anticipated that this sensor network will provide 

significant information about the load distribution on 

shoring systems that is currently not available. This 

information will allow dangerous situations to be 

quickly identified so that corrective action can then be 

taken. Thus the risk of injury or loss of life at a 

construction site can be reduced, possibly leading to 

lower liability insurance costs. Furthermore, this 

information may also be used to formulate new 

construction codes that will further enhance 

construction work safety. 

Objectives 

The overall objective of this effort is the 

development of sensing systems and techniques 

applicable to the monitoring of construction site 

shoring and scaffolding. This work was demonstrated 

at our in-house laboratory facilities as well as at a 

"real-world" major construction site. The resultant 

sensor systems will have the inherent robustness and 

ease of use to be readily used on real construction 

sites while providing the dangerous situation 

identification necessary for increased construction site 

safety. 

Methodology 

This study, whose ultimate object is to design, 

develop, test, and evaluate methods to increase 

shoring and scaffolding safety at real-world 

construc!ion sites, incorporates sensing system design 

along with laboratory and field testing. During the 

first phase of this study, a set of laboratory studies 

were .. undertaken to determine if unsafe loading 

conditions could be detected with scale model 

instrumented shoring systems. Three potentially 

dangerous loading conditions were examined: 

(I) overload; (2) soft footing; and (3) uplift. These 

situations were simulated using a test frame 

strain-gage-based load cells, a data acquisitio~ 

system, and model shoring. The next phase of the 

study involved taking shoring load measurements on 

a real construction site during a concrete pour and 

during the following cure cycle. Data were gathered 

using strain-gage-based load cells, a PC-based 

digital data acquisition system and a supplemental 

power supply. The field data were analyzed off-site. 

Significant Findings 

The laboratory studies indicated that overload 

soft footing and uplift conditions could be detected o~ 

shoring systems with a proper interpretation of the 

load data. However, overload causes excessive loads 

to be measured, whereas soft footings involve an 

inability to carry a high load and uplift involves an 

initial load that reduces to zero. The identification of 

these situations requires the proper interpretation of 

the load data. 

The field studies indicated that shoring loads 

could be readily monitored in the field. Construction 

sites are very rugged and required ruggedized 

equipment. The measured load data indicated that 

nothing out of the ordinary occurred at the site. The 

curing of the concrete was monitored from the load 

data by interpreting the loads with a simple 

exponentially-decaying load sharing model. The 

results calculated from the model agreed quite well 

with the measured data. 

Publications 

Huston DR, Ambrose TP, Fuhr PL, Devino E, 

Werner M: Construction Load Monitoring Using 

Instrumented Shoring. Proc. SPIE Conf. on Smart 

Materials and Structures, Orlando, FL, Paper 

No. 2191-48, in press, February, 1994 

Ambrose TP, Huston DR, Fuhr PL, Devino E, 

Werner M: Shoring Systems for Construction Load 

Monitoring, Smart Materials and Structures, in press, 

1993 
Active Seat Suspension to Control 

Low Back Injuries 

Christopher C. Johnson 

Rehabilitation Technology Inc. 

J South Prospect Street 

Burlington, Vermont 05401 

Program Area: Control Techniques 

Grant Number: J R43 OH03018-0l 

Start & End Dates: 09/30/92 - 03/29/93 

Funding Level: $0 ($32,613 Cum) 

Importance to Occupational Safety and Health 

The operation of vehicles, e.g. trucks, has been 

demonstrated to be highly correlated with the 

occurrence of low back pain and herniated discs. 

Truck drivers and other vehicle operators typically 

report two to four times the number of low back ~ain 

problems and disabilities as the normal pop~l~tl?n. 

The economic and human costs of lower back mJunes 

are enormous. Vehicle-related lower back injuries 

have been attributed in large part to 

vibration-induced stresses in the lumbar spine, 

especially vibration at the 4-5 Hz fundamental 

resonance of seated humans. The development and 

use of a seat suspension in trucks that suppresses 

most of the injury-causing vibrations would 

significantly reduce the number of back injuries and 

related disabilities. In addition, such a seat would 

have the added benefit of reducing operator fatigue 

and possibly accident rates. 

Objectives 

The overall objective of this work is to produce 

a vehicle seat suspension system that is capable of 

significantly reducing the vibrations experienced by 

a vehicle operator. Such a seat will be capable of 

preventing the occurrence and reocc?r~e~ce of 

vibration-induced fatigue and lower back mJunes and 

disabilities. This seat must be relatively inexpensive 

and be capable of new or retrofit installation. The 

aim of this first phase of the project was to prove the 

feasibility of the concept. 

Methodology 

This study involved three major phases. These 

were: 

1. A hydraulically damped commercially available 

truck seat was thoroughly tested on a vibration 

Control Techniques - Page 123 

platform to analyze its response to a previously 

recorded truck cab input signal. Seat 

accelerations, velocities, and displacements were 

all recorded and analyzed to help in designing a 

semi-active suspension system. 

2. A prototype was built based on the design from 

phase l. This involved retrofitting a seat with a 

prototype computer controlled variable orifice 

hydraulic damper. A linear displacement 

transducer was fitted between the seat and base to 

provide relative position and velocity information 

for the control equation. 

3. To test this seat a pseudo-human 

(spring-mass-dashpot system) with similar 

primary dynamic properties (resonance at 

approximately 4-5 Hz) was designed and built. 

This allowed for objective comparisons between 

this new actively controlled seat and existing 

passive seat suspension systems. Accelerometers 

were attached to the pseudo-human base and to 

the seat base in order to determine the vibration 

damping characteristics of the system. The seat 

was tested and compared in two modes; 

(1) damper orifice in active control, and 

(2) damper orifice fixed (passive) to provide 

approximately 0.7 critical damping. 

Significant Findings 

In the 4 to 5 Hz range the active seat reduced 

vibration to 77% of the amount for the passive seat. 

The fact that vibration at the human' s natural 

frequency of 4-5 Hz was reduced as much as 23.3% 

is very important. Damage to the spine due to 

vibration most likely occurs from the work performed 

on the body by the kinetic energy from the vibration. 

Since kinetic energy is proportional to the square of 

acceleration, a reduction to 77% of the original 

acceleration is equivalent to a reduction to 59% of 

work done to the driver. This represents a significant 

improvement in the occupational health environment 

of the driver. 
Page 124 - Respirator Research 

Evaluation of Respirators for 

Asbestos Fibers 

Yung-Sung Cheng, Ph.D. 

Lovelace Biomedical & Environmental 

Research Institute 

Inhalation Toxicology Research Institute 

Aerosol Science Group 

P. 0. Box 5890 

Albuquerque, New Mexico 87185 

Program Area: Respirator Research 

Grant Number: 5 ROI OH02922-02 

Start & End Dates: 09/30/92 - 09/29194 

Funding Level: $179,833 ($357,145 Cum) 

Importance to Occupational Safety and Health 

Results from this research will provide 

quantitative information for determining the 

performance of respirators against asbestos and 

manmade fibers. The information can then be used 

as a basis to evaluate the current NIOSH procedures 

for certification of respirators for protecting workers 

exposed to fibers. Improved designs of the 

respirators and test procedures for NIOSH 

certification will help to reduce occupational 

exposures to asbestos and manmade fibers. 

Objectives 

The goal of this research is to quantify the 

performance of respirator filters used to protect 

workers in environments where they are at risk of 

exposure to asbestos and manmade fibers. Current 

OSHA guidelines require the use of respirators fitted 

with high efficiency filters. These filters must be 

approved under NIOSH certification criteria based on 

penetration tests using spherical aerosols. Fiber 

aerosols are known to have different aerodynamic 

behaviors than spherical particles and usually carry 

higher electrostatic charges. Because the 

carcinogenicities of asbestos and other fibers are 

known to be due, in part, to fiber dimensions, the 

efficiency of the respirator filters in relation to fiber 

dimension is very important. It is difficult to predict 

how fiber aerosols will penetrate respirator filters 

based on the NIOSH testing results using spherical 

particles. 

The specific objectives of this study are: (1) to 

elucidate effects of fiber size, electrostatic charge, 

and flow rate on fiber aerosol penetration of filter 

cartridges, (2) to develop a mathematical model for 

predicting the penetration of fiber aerosols in 

respirator filters, and (3) to determine the fiber 

aerosol penetration through leaks in the face seal. 

Methodology 

Three asbestos fibers with mean diameters 

ranging from 0.04 to 0.5 μm and aspect ratios from 

3 to 60 will be used. Both overall and size-specific 

penetration of fiber aerosols through filters will be 

determined. Based on size-specific fiber penetration 

information, the effects of particle diameter, length, 

and flow rate will be examined and the filtration 

mechanisms identified. We will then determine the 

dimensions of fibers that will most likely penetrate 

the respirator filter. We also hypothesize that 

electrostatic collection is the main reason for the 

inconsistent filter performance reported in the 

literature. This hypothesis will be tested by 

investigating the effects of electrostatic forces on 

fiber collection. Filtration models will be established 

to predict the penetration of fiber aerosols of given 

size distributions and electrostatic charges. Filter 

penetration efficiencies for spherical particles and 

fibers under these conditions will be compared to 

provide a scientific basis for evaluating the adequacy 

of current NIOSH guidelines, and for recommending 

possible improvements. The penetration of fiber 

aerosols through leaks in a respirator face seal will 

also be measured, and the effects of mass loading of 

fiber aerosols on flow resistance and fiber aerosol 

penetration will be determined. These studies can 

provide important information in determining 

respiratory fit factors for field use. 

Significant Findings 

I . The surface charge measurements on the 

respirator filters showed that some filters 

including those used in disposable respirators are 

charged to enhance the collection efficiency. Our 

data also showed that the surface charges 

decreased in a high-temperature and 

high-humidity environment and disappeared in a 

relatively short time. The deposition of spherical 

particles in the charged disposable filter was 

enhanced, as compared to the deposition of the 

same aerosol in the same filter after the charges 

were removed. On the other hand, for filter 

cartridges that did not carry electrostatic charges, 

collection efficiency was not enhanced. Our 

results suggested that the electrostatic charge in 

some filter cartridges was the major factor for 

increased collection efficiency. However, the 

efficiency enhancement due to these electrostatic 

charge effects may not be long-lasting when used 

in certain environments. 

2. The mathematical filtration model for fiber and 

spherical aerosols showed increased filter 
collection efficiency for elongated fibers due 

mainly to the interception mechanism. Because 

of the long axis, an elongated particle contacted 

the filter material and was collected. Our model 

showed that this interception effect increased 

with the aspect ratio. However, the interception 

effect was only effective for fiber aerosols with 

a volume equivalent diameter greater that1i 

0.5 μm. For fibers smaller than 0.5 μm, the 

diffusion deposition mechanism dominates, and 

the filtration efficiency for fiber aerosols was not 

enhanced. 

3. Preliminary results on the penetration of amosite 

fibers in a disposable filter showed that smaller 

and thinner fibers had higher penetration. We 

are analyzing the data. This preliminary result 

suggested that both the diameter and length 

distributions of a fiber aerosol change after filter 

penetration. 

Publications 

Chen BT, Irwin R, Cheng YS, Hoover MD, Yeh HC: 

Aerodynamic Behavior of Fiber and Disk-Like 

Particles in a Millikan Cell Apparatus. J Aerosol 

Science 24: 181-195, 1993 

Performance of Surgical Masks 

Klaus Willeke, Ph.D. 

University of Cincinnati 

College of Medicine 

Department of Environmental Health 

Kettering Laboratory 

3223 Eden Avenue 

Cincinnati, Ohio 45267-0056 

Program Area: Respirator Research 

Grant Number: 5 ROI OH02948-02 

Start & End Dates: 09/01/92 - 08/31/94 

Funding Level: $147,152 ($287,049 Cum) 

Importance to Occupational Safety and Health 

Results of this study will extend our ability to 

protect both patients and operating teams from 

airborne and dispersed bloodborne pathogens. This 

concern is encouraging the examination of existing 

respiratory protective devices and the consideration of 

modifying devices used in industrial settings for use 

in health-care environments. About 6.9 million 

health care and other workers in the U.S. are at risk 

for blood contact at the worksite. The number at risk 

Respirator Research - Page 125 

from aerosol transmission has not been accurately 

estimated; however, given the variance in mask 

collection efficiencies, the continued use of new 

technologies, and the potential for disease 

transmission, ascertaining the value of current mask 

protection is important. 

Objectives 

The objective of this research is to study the 

performance of masks currently used or considered 

for use in the health care industry. Specific aims are: 

(I) To study the currently used bacterial filtration 

efficiency test as to the particle size distribution of its 

spray. (2) To develop a method for simultaneously 

counting airborne test bacteria by physical and 

biological means on the masks being tested. This 

method is to be used to evaluate the collection 

efficiency of health care masks and to determine to 

what degree the collection efficiencies obtained with 

bacteria differ from those obtained by the use of 

inert, non-viable test particles currently used to 

evaluate industrial masks and respirators. 

Methodology 

Viable bacteria and inert particles are generated 

in the laboratory for testing a wide range of available 

masks. The masks are exposed in a test chamber 

specifically designed for studies of respiratory 

protective devices. The aerosols are analyzed 

physically by aerosol size spectrometry and 

biologically by sampling the bacteria into bioaerosol 

samplers. Pseudomonas fluorescens A TCC 13525 is 

used as the initial challenge bacterium. It is grown in 

tryptic soy agar at 25°C for 25 hours, washed and 

dispensed in deionized water. The size of this 

bacterium is approximately 0.5 μm in width and 

1.5 μm in length, i.e. it is physically similar to the 

tuberculosis bacterium. The size-dependent 

penetration efficiencies of inert and biologically active 

test aerosols are compared with each other. 

Significant Findings 

Experiments with inert particles have shown a 

considerable range in collection efficiency values 

depending on the mask used. Penetration is highest 

for submicrometer-sized aerosols, approaching I 00% 

for some masks used.Some industrially used 

dust-mist-fume respirators have less penetration than 

the best currently used surgical mask. However, in 

the presence of a large face-seal leak, the 

dust-mist-fume mask may not provide any more 

protection than a surgical mask with a lower filtration 

efficiency. Due to the higher pressure drop across 

the dust-mist-fume mask it may even perform worse 

than the surgical mask, because considerable aerosol 
Page 126 - Respirator Research 

flow may be directed through the leak site. Thus, it 

is concluded that improvements in filtration efficiency 

in health care masks may necessitate quantitative fit 

testing to ensure proper fit of the mask to the health 

care worker's face. 

Experiments with bacteria have shown that the 

penetration of bacteria is lower than that of inert, 

spherical corn oil. The difference is difficult to 

quantitate because it depends on the definition of 

particle size used for the complex shape of the 

bacterium. Further development of the test procedure 

is being performed before proceeding to the testing 

with bacteria of different physical and/or 

microbiological characteristics. 

Publications 

Weber A, Willeke K, Marchioni R, Myojo T, 

McKay R, Donnelly J, Liebhaber F: Aerosol 

Penetration and Leakage Characteristics of Masks 

used in the Health Care Industry. Am Journal 

Infection Control 21:167-173, 1993 

Chen CC, Willeke K: Aerosol Penetration Through 

Surgical Masks. Am Journal Infection Control 

20:177-184, 1992 

Willeke K, Chen CC, Myojo T, Weber A, 

Krishnan U, Juozaitis A, Marchioni R, Lehtimaki M: 

Filtration, Loading and Faceseal Leakage 

Characteristics of Filtering Facepieces. J Aerosol 

Science 23:S749-S752, 1992 

Factors Affecting Respirator Leak 

Sites and Shapes 

Riedar K. Oestenstad, Ph.D. 

University of Alabama 

School of Public Health 

Department of Environmental Health Sciences 

UAB Station 

Birmingham, Alabama 35294 

Program Area: Respirator Research 

Grant Number: 5 KOJ OH00085-03 

Start & End Dates: 09/28/90 - 01/27/94 

Funding Level: $0 ($160,373 Cum) 

Importance to Occupational Safety and Health 

Results of this study will expand our knowledge 

of where respirator faceseals leak and how those leak 

sites are related to such critical factors as facial 

dimensions, the brand of respirator, and if the leak 

sites vary between different fittings and fit test 

exercises. This information will be useful to persons 

designing respirator facepieces and to those 

responsible for selecting and testing respirators for 

individual users. It will also permit more accurate 

modelling of respirator leakage by determining the 

size and one-dimensional shape of faceseal leaks on 

human subjects. The study will also provide 

additional information on the phenomenon of airflow 

streamlining inside respirator facepieces. 

Objectives 

The specific objectives of the study are to: 

(I) determine if leak sites and shapes change between 

the exercises of a quantitative fit test, (2) determine 

the variation of leak sites and shapes for multiple 

fittings of the same respirator on the same subject, 

(3) determine the distribution of leak sites and shapes 

for different respirators being worn by the same 

sample of subjects, (4) more accurately define the 

characteristics of subjects who show evidence of 

aerodynamic streamlining under the respirator 

facepiece, and (5) determine the effect of increased 

breathing rates on the development of air flow 

streamlining patterns. 

Methodology 

The first four objectives will be accomplished by 

performing respirator fit tests on human subjects 

using an aerosol of an fluorescent whitening agent. 

Faceseal leak sites will be identified by observation 

of fluorescence of the aerosol deposited at the site(s) 

when illuminated by ultraviolet light. Anthropometric 

facial dimensions of the subjects will also be 

measured. The fifth objective will be accomplished 

by performing the same tests on a mannequin fitted 

with a respirator using a breathing simulator. Data 

will be analyzed by conditional logistic regression, 

multiple linear regression and ANOV A. 

Significant Findings 

Activities completed to date include the selection 

and toxicological evaluation of an alternative 

fluorescent aerosol which could be nebulized in 

aqueous solutions, the construction and evaluation of 

a larger generation and exposure system, and 

mannequin tests at various inspiratory flow rates. 

Tests on human subjects have commenced and are 

partially complete. 

Tinopol CBS-X has been used as the test agent 

in this study. This compound is water soluble, 

non-mutagenic, non-carcinogenic, and of low 

toxicity. It has a much higher fluorescent efficiency 

than the coumarin-type used in our previous studies, 
and has provided better definition of leak sites and 

identification of streamlined air flow patterns. An 

aerosol generating and exposure system including 

three Liu nebulizers, aerosol conditioning system and 

exposure chamber been installed and evaluated. The 

aerosol size distribution has a MMAD of 1.2 μm and 

a geometric standard deviation of 1.4, and chamber 

concentration has been measured at "" 20 mg/m3

• 

Aerosol size distribution and concentration have been 

stable throughout the testing period. 

Testing human subjects has progressed slowly 

because of a less than anticipated number of 

volunteers, loss of enrolled subjects from the study, 

and frequent turnover of research assistants. The 

tests on the mannequin showed that strong aerosol 

deposition patterns at low inspiratory flow rates did 

not persist at higher flow rates. This would indicate 

that air flow streamlining, and thus sampling bias, 

would be more likely to occur at low breathing rates 

characteristic of quantitative fit testing protocols. 

Publications 

Oestenstad RK, Graffeo JB: Determination of 

Respirator Fit by an Aerosol Method and a Negative 

Pressure Method. J Internat Soc Resper Prot, 

accepted for publication, 1993 

Oestenstad RK, Perkins LL: An Assessment of 

Critical Anthropometric Dimensions for Predicting 

the Fit of a Half-Mask Respirator. Am Ind Hyg 

Assoc J 53:639-644, 1992 

Oestenstad RK, Zwissler AM: A Comparison of Fit 

Provided by Natural and Silicone Rubber of the Same 

Brand of Half-Mask Respirator. Appl 0cc Env Hyg 

6:785-789, 1991 

Oestenstad RK, Perkins JL, Rose VE: Identification 

of Faceseal Leak Sites on A Half-Mask Respirator. 

Am Ind Hyg Assoc J 51:280-284, 1990 

Oestenstad RK, Dillon HK, Perkins LL: Distribution 

of Faceseal Leak Sites on A Half-Mask Respirator 

and Their Association with Facial Dimensions. Am 

Ind Hyg Assoc J 51 :285-290, 1990 

Rose JC, Oestenstad RK, Rose VE: A Comparison 

of Respirator Fit Factors Determined by Portable 

Nuclei Counting and Forward Light-Scattering 

Methods. Appl 0cc Env Hyg 5:792-797, 1990 

Respirator Research - Page 127 

Adsorption of Vapor Mixtures onto 

Activated Carbon 

Patrick N Breysse, Ph.D. 

Johns Hopkins University 

School of Hygiene and Public Health 

Department of Environmental Health Sciences 

615 North Wolfe Street 

Baltimore, Maryland 21205 

Program Area: Respirator Research 

Grant Number: 5 KOJ OH00087-03 

Start & End Dates: 09/28190 - 05/27194 

Funding Level: $54,000 ($162,000 Cum) 

Importance to Occupational Safety and Health 

Complex industrial environments typically contain 

numerous organic vapors and a range of relative 

humidities. It is not possible to experimentally 

determine respirator breakthrough performance for 

every possible combination of vapor mixtures. A 

fundamental understanding of the physicochemical 

interaction of adsorption of vapor mixtures is needed 

in order to properly understand and model activated 

carbon bed behavior. Data generated by this proposal 

will be used to evaluate and modify existing 

respirator service-life models. 

Objectives 

The purpose of this investigation is to evaluate 

adsorption of organic vapor mixtures onto activated 

carbon. Experiments are designed to measure 

parameters associated with adsorption kinetics and 

equilibria. Binary vapor mixtures containing a 

variety of different polarities and functional groups at 

different humidities will be selected and tested. 

Adsorption studies using silica gel are also to be 

conducted. Adsorption onto silica gel, a polar 

adsorbent, will help to determine the role of polar 

forces in adsorption and to evaluate the suitability of 

silica gel as an adsorbent. 

Successful completion of this project will provide 

a more fundamental understanding of adsorption of 

complex organic vapor mixtures onto activated 

carbon and silica gel. 

Methodology 

Experimental data will be analyzed using 

parameters of the Dubinin Equilibrium Model and the 

Wheeler Kinetic Model. These parameters include 

equilibrium adsorption affinity coefficients and 
Page 128 - Respirator Research 

capacities and kinetic rate constants and capacities. 

Equilibrium and kinetic behavior of vapor mixtures 

will be evaluated using gas chromatography (GC). 

Mixed vapor analysis will be conducted using a GC 

equipped with flame-ionization and photo-ionization 

detectors in series. The photo-ionization detector 

(PID) will be used with two different ionization 

potential lamps, 8.4 and 9.6 eV. Vapor pairs are 

selected such that the PID will respond to only one of 

the vapors in the mixture. 

Significant Findings 

The first phase of this investigation involved the 

development of the GC/two-detector system. The 

photo-ionization detector (PIO) was installed on the 

GC. Different ionization potentials were evaluated in 

order to provide sufficient analytical sensitivity. 

Vapor pairs to be used to evaluate component 

polarity effects have been selected and the adsorption 

system has been tested and calibrated. 

Kinetic experiments using paired organic vapors 

onto activated carbon are complete. Experiments 

were designed to pair each of two test vapors, 

p-xylene and pyrrole, with polar and non-polar 

vapors (toluene and p-dichlorobenzene are non-polar 

and o-dichlorobenzene and p-fluorotoluene are 

polar). To account for any boiling point effects, each 

test vapor is also paired with vapors having a higher 

and a lower boiling point (the dichlorobenzene 

isomers have boiling points greater than p-xylene or 

pyrrole, while toluene and p-fluorotoluene have 

boiling points less than either test vapor). 

Comparison of the kinetic adsorption capacities of 

p-xylene and pyrrole for the different mixtures 

indicates that the adsorption space occupied by each 

vapor is reduced based on it's mole fraction in the 

mixture. The data do not indicate that there are any 

differences based on whether p-xylene and pyrrole 

are paired with polar or non-polar vapors. 

Furthermore the boiling point of the paired vapor 

does not seem to effect the kinetic adsorption 

capacity. 

Collection of equilibrium adsorption data is 90% 

complete. Preliminary analysis indicates, similar to 

the kinetic experiments, that the overall adsorption 

space is conserved when isotherms are determined for 

paired vapors. 

Aerosol Penetration Behavior of 

Respirator Valves 

Lisa M Brosseau, Sc.D. 

University of Minnesota 

Box 807 UMHC 

420 Delaware Street SE 

Minneapolis, Minnesota 55455 

Program Area: Respirator Research 

Grant Number: 5 R03 OH02938-02 

Start & End Dates: 06/01/91 - 11/30/93 

Funding Level: $13,096 ($31,198 Cum) 

Importance to Occupational Safety and Health 

Properly fitted air purifying respirators must have 

functioning valves (exhalation and inhalation)in order 

to provide the protection expected. Inhalation valves 

open during inhalation and close on exhalation, thus 

ensuring that all expired air exits through the 

exhalation valve. The exhalation valve, which is the 

more important of the two in providing protection, 

closes during inhalation, thus ensuring that all 

inspired air passes through the filters before being 

breathed. 

The adequate functioning of respirator valves is 

not often easy to evaluate. Respirators can be 

visually checked for malfunctioning valves; 

qualitative checks of their function are also possible. 

Neither of these methods is done often enough by 

respirator wearers, and neither guarantees adequate 

valve functioning. Only by quantitative measurement 

can the protection of a used respirator be determined, 

and this is rarely if ever done. 

There is not, at present, any easy method by 

which valve replacement can be predicted. This 

research will lead to the development of an empirical 

model derived from experimental results which can 

be used to predict how often and when respirator 

valves must be replaced before they fail, given their 

particular use conditions. This model will be 

validated by comparison with measurements of used 

valve behavior. 

Objectives 

The objectives of this research include: 

I. Evaluation of three respirator manufacturers' new 

exhalation and inhalation valves for particle 

size-related penetration as valves are stressed by 

a breathing cycle over an 8-hr period; 
2. Evaluation of used valves for particle 

size-related penetration; 

3. Comparison of predictions by an empirical 

model ( developed from experimental data) to 

measurements of penetration made with used 

valves; 

4. Evaluation of local companies' respirator 

maintenance practices, particularly as they relate 

to valve replacement. 

Methodology 

The experimental portion of this research will 

stress inhalation and exhalation valves using a 

breathing machine with humidified and heated 

exhalation air over an 8-hr period. Periodic 

measurements of aerosol penetration upstream and 

downstream of each valve type are made during the 

test period and recorded by computer, which also 

controls exhalation air conditions. Measurements of 

aerosol penetration will be made at several particle 

sizes, starting at 0.3 μm and extending to I μm. 

Two different work rates will be evaluated. The 

survey of respirator users has been completed by 

thirty local companies. Local companies have 

received new valves, which will used for a time 

equivalent to 8 hr before evaluation of particle size 

penetration in the laboratory. A model to describe 

particle-size related penetration for a given work rate 

over time will be developed. Model predictions will 

be compared with results of experiments with used 

valves. 

Significant Findings 

Of the 28 companies surveyed on respirator 

maintenance practices, 60% had workers wearing 

respirators on a daily basis for a range of aerosol and 

gas and vapor exposures. All but two of the 

companies had a formal, written respiratory 

protection program. In half of the companies the 

employee was responsible for inspecting the 

respirator on a daily basis prior to use, for 

maintaining the respirator as needed, and for 

replacing valves and filters or cartridges as needed. 

In all but three of the companies the person 

responsible for maintenance received formal training 

in repair methods. During inspection and 

maintenance, almost all companies indicated that 

inspection included a visual check of the harness, face 

piece, valves, and filters or cartridges; respirators 

were stored in a bag when not in use. In 60% of the 

companies cleaning and sanitization were 

accomplished by wiping or manually washing the 

respirator. A majority of the companies indicated the 

service life of their respirators as being about three to 

four years. Almost all companies indicated that 

worker training included inspection, cleaning and 

Respirator Research - Page 129 

sanitization, maintenance, storage, and negative and 

positive pressure tests. Most companies indicated that 

these items were demonstrated by a trainer, while 

only half of the companies show videos and have 

workers practice the items during training Sessions. 

For the experiments of valve leakage, two of four 

conditions have been evaluated to date: high and low 

flow with a small diameter (0.31 μm) aerosol. While 

the data have not been completely analyzed, initial 

evaluation shows that, under high flow conditions, the 

smaller aerosol may experience penetration up to 

20% through exhalation valves and up to 5% through 

inhalation valves. Under low flow conditions 

penetration is much less, as expected. For exhalation 

valves penetration averages about 0.02% and for 

inhalation valves the 0.31 μm particles experience 

about 0.005% penetration. Experiments are presently 

underway for low and high flow conditions with a 

larger particle size (0.84 μm). 

Lighter Compact Respirators For 

Toxic Vapor Protection 

Clinton E. Brown 

Dynajlow, Inc. 

72 IO Pindell School Road 

Fulton, Maryland 20759 

Program Area: Respirator Research 

Grant Number: 2 R44 OH03011-02 

Start & End Dates: 09/30/93 - 09/29/95 

Funding Level: $164,458 ($164,458 Cum) 

Importance to Occupational Safety and Health 

Lighter and more compact respirators can 

improve work place safety and health by providing 

greater comfort and ease of use. Worker acceptance 

and adherence to safety rules is enhanced when 

respirators are less cumbersome, easily and quickly 

donned and provide for unstrained breathing. The 

present research effort focuses on a system using 

two-way breathing through an absorbent medium so 

that valving may be eliminated to simplify and lighten 

the respirators. This system will also permit reuse of 

the absorbent elements by flushing and thus reduce 

cost. 

Objectives 

The goal of the research is to develop technology 

for lighter and more compact respirators using 
Page 130 - Respirator Research 

alternating flow and absorbent materials insensitive to 

the presence of water vapor. 

The project will identify suitable absorbent 

polymer and toxic gas pairs or groups that will allow 

reduction of the weight and size of respirator 

elements relative to activated charcoal elements in 

common use today. These materials will be used in 

a two-way flow breathing mode. Predictive codes 

for estimating the performance of various absorbent 

materials relative to selected toxic gases when 

incorporated in a filter design of specified geometry 

will be developed and validated. Experiments to 

assess performance will be conducted in a test 

apparatus simulating human breathing. Finally, an 

engineering study will be made to design two-way 

flow respirators and assess the practical issues of 

wearer comfort, face seal leakage and methods of 

mass production. 

Methodology 

A combined experimental and numerical 

modeling approach is being utilized to evaluate the 

influence of various parameters and materials on 

respirator performance. The predictive numerical 

code developed will compute mass and heat transfer 

in the absorbent materials using well grounded 

fundamental physical and chemical relations. Effects 

of temperature variation will be included where they 

affect the local thermal and mass diffusities as well as 

the solubility coefficients of the absorbents. 

The experimental program provides for testing 

filter elements of reduced flow through area but of 

essentially full scale geometry otherwise. The test 

apparatus simulates the human breathing cycle and 

provides for concentration measurements using flame 

ionization detection in two-way oscillating flow with 

return flow matched in temperature and humidity to 

human breath. 

Significant Findings 

During the first phase of the research, the 

feasibility of the two-way flow concept was 

demonstrated. Experiments were conducted with a 

high boiling point vapor typical of many toxic vapors 

found in industrial work places in an experimental 

loop which simulates the human breathing cycle and 

includes a small section of an absorbent polymer. 

Measurements were made of the concentrations of the 

toxic gas simulant exiting the module as a function of 

time. Comparison of results for operation with 

two-way oscillatory flow with those of conventional 

one-way flow show a dramatic increase in the 

breakthrough time and a large decrease in the 

concentrations following breakthrough. These 

experiments demonstrated the feasibility of the new 

concept and its potential for superior performance 

relative to conventional respirators such as those 

using charcoal. Results of the numerical simulation 

model developed show similar significant 

improvements in respirator performance using 

two-way oscillatory flow over conventional one-way 

flow. A parametric study conducted with the 

numerical simulation model determined the influence 

of various factors such as partition coefficient, 

diffusivity and flow velocity on respirator 

performance. 
Effects of 27 MHz Radiation on 

Somatic and Germ Cells 

Stephen F. Cleary, Ph.D. 

Virginia Commonwealth University 

Medical College of Virginia 

Department of Physiology, Box 551 

Richmond, Virginia 23298-0551 

Program Area: Other Occupational Needs 

Grant Number: 5 ROI OH02148-07 

Start & End Dates: 09/27/85 - 09/29/93 

Funding Level: $0 ($913,524 Cum) 

Importance to Occupational Safety and Health 

Current guidelines to protect workers from 

effects of radio frequency radiation exposure are based 

upon the premise that adverse health effects are due 

to tissue heating. It is of primary importance for 

occupational safety and health to determine the 

validity of this premise. Studies are being conducted 

of the effects of continuous wave (CW) and 

pulse-modulated (PM) 27-MHz and 2450-MHz RF 

electromagnetic radiation on mammalian cells in vitro 

to determine the validity of this premise. 

Studies conducted to date provide firm evidence 

that these RF radiation frequencies affect cell mitotic 

activity under conditions that simulate occupational 

exposure. It has been determined that RF radiation 

directly affects cells in the absence of heating. These 

results indicate the need for detailed characterization 

of cellular effects of RF radiation to provide insight 

regarding: (a) the adequacy of the basis for pn~sent 

occupational exposure guidelines, and (b) mechanisms 

of direct RF-induced cellular alterations. 

Objectives 

The principal objective is to determine dose 

thresholds and dose-response relationships for effects 

of continuous wave (CW) and pulse-modulated (PM) 

27-MHz and 2450-MHz RF radiation on mammalian 

cell proliferation in vitro. By comparing effects of 

27-MHz RF with effects of exposure to 2450 MHz 

the role of RF frequency is being investigated. 

Precise control of exposure conditions, such as 

temperature, permit testing hypotheses regarding ~he 

mechanisms of RF-induced alteration of mammalian 

somatic and germ cells. 

The principal objective is to determine dose 

thresholds and dose-response relationships for effects 

of continuous wave (CW) and pulse-modulated (PM) 

27-MHz and 2450-MHz RF radiation on mammalian 

Other Occupational Needs - Page 131 

cell proliferation in vitro. By comparing effects of 

27-MHz RF with effects of exposure to 2450 MHz 

the role of RF frequency is being investigated. 

Precise control of exposure conditions, such as 

temperature, permit testing hypotheses regarding the 

mechanisms of RF-induced alteration of mammalian 

somatic and germ cells. 

Methodology 

Cell suspensions are exposed for 2 hours to CW 

or PM 27-MHz or 2450-MHz radiation under 

isothermal conditions in vitro. Viability and 

morphology are assayed immediately after exposure. 

Cells are cultured for 1-, 3-, or 5 days and 

functional assays (i.e., cell proliferation, mitogenesis, 

DNA, RNA, protein synthesis, sperm viability, and 

motility, in vitro fertilization) are conducted. 

Cytofluorimetry and dielectric spectroscopy are used 

to investigate the interaction of RF radiation with the 

cell cycle using synchronized populations of Chinese 

hamster ovary (CHO) and HeLa cells. 

Significant Findings 

A single 2h isothermal (37 ± 0.2°C) exposure to 

either 27- or 2450 MHz RF radiation induces 

biphasic dose-dependent alterations in human 

lymphocyte mitogenesis 3d after exposure, or in 

DNA and RN A synthesis in glioma (LN7 l) cells l, 

3, or 5d after exposure. The threshold for RF effects 

on lymphocytes and glioma is being investigated. 

Exposure of either cell type to SARs in the range 

5-50 W /kg stimulated biosynthetic processes, 

whereas exposure at >50W/kg suppressed cellular 

activity. Comparison of the effects of CW versus 

PM (duty cycle 0.377) 27 MHz RF radiation indicate 

similar biphasic effects on human lymphocyte 

activation and glioma proliferation. RF exposure of 

lymphocytes or glioma in vitro at elevated 

temperature (39°C) altered proliferation relative to 

exposure at 37°C. This finding is potentially 

significant since in vivo RF exposures in the w~rk 

place are known to involve radiation-induced heatmg 

in some instances. 

Exposure of lymphocytes to either CW or PM 

2450-MHz at SARs of 0.5- or 5 W/kg resulted in 

consistent suppression of lymphocyte proliferation 

3 days postexposure. Mean suppression resulting 

from CW exposure was 8%. Exposure at 5 W /kg 

resulted in statistically significant suppression (p=0.05 

for logarithmic transformed data), whereas 

suppression following exposure at 0.5 W/kg was not 

statistically significant. Exposure to PM 2450 MHz 

at SARs of either 0.5- or 5 W/kg resulted in 

statistically significant suppression (p values 0.0001 

and 0.002, respectively). Exposure to PM 27-MHz 

RF radiation at 0.5- or 5 W /kg resulted in 
Page 132 - Other Occupational Needs 

statistically significant suppression with the exception 

of PM exposure at 0.5 W/kg. 

Exposure of glioma to 0.5 or 5 W/kg CW or PM 

27- or 2450-MHz RF radiation resulted in 

statistically significant, time-dependent increases in 

proliferation. Three days after exposure to CW or 

PM 2450-MHz RF radiation at 5 W /kg, glioma 

proliferation was increased 42- or 380%, 

respectively. Exposure to CW or PM 27-MHz 

resulted in statistically significant 14- or 50% 

increases in proliferation respectively. Three days 

following exposure of glioma to CW or PM 

2450-MHz RF radiation at a SAR of 0.5 W/kg there 

was an 18% mean increase in proliferation, whereas 

CW or PM 27-MHz exposure, at this same SAR, 

caused a statistically significant (p=0.001) 119% 

mean increase in 3H-TdR uptake. 

Dose-dependent RF-induced shifts in the cycle 

of synchronized CHO and HeLa cells indicate that the 

biphasic response results from cycle-specific effects 

on DNA/RNA synthesis. Maximum sensitivity for 

RF-induced cycle phase shifts appear to occur during 

Go/G 1 phase. 

A statistically significant reduction in the ability 

of mouse spermatozoa to fertilize mouse ova occurred 

following a 1 h exposure of sperm at 37 ± 0.2°C. 

Recent studies of the effect of 27- or 2450-MHz RF 

radiation on human spermatozoa, using hamster ova 

penetration as the dependent variable indicate that 

human spermatozoa are less sensitive to RF exposure 

than mouse spermatozoa. 

A novel helical coil RF exposure system has 

been designed and constructed to permit long-term 

exposure of mammalian cells in vitro. In contrast to 

other in vitro RF exposure systems which are limited 

to exposure durations of 2-4 hours, the helical coil 

system permits continuous exposure of mammalian 

cells to uniform RF fields under controlled 

conditions. This system was used to investigate the 

effect of a 24 h exposure of Chinese hamster ovary 

cells to 30 MHz RF radiation at a SAR of 0.5 W/kg. 

RF exposure caused a statistically significant increase 

in CHO cell proliferation. 

A mathematical model has been used to calculate 

cellular level RF energy absorption in a mammalian 

cell model exposed to 27- or 2450 MHz RF 

radiation. Comparison of the distribution of absorbed 

energy in a simple cell model with absorption in a 

model incorporating a 2nm thick layer of bound 

(vicinal) water at the inner and outer membrane 

surfaces indicates significant frequency-dependent 

differences. Approximately 40 times greater 

absorption occurs in the bound water layer at 

2450 MHz compared to 27 MHz. This finding 

suggests frequency-dependent differences in 

membrane related physiological processes. 

Publications 

Cleary SF: Biophysical Mechanisms of Interaction of 

Electromagnetic Fields. URSI Review of Radio 

Science, 1990-1992, in press, 1992 

Cleary SF, Liu LM, Cao G: Cellular Effects of 

Extremely Low Frequency (ELF) Electromagnetic 

Fields. In: Charge and Field Effects in Biosystems, 

Boston, MA, Vol 3 Birkhauser, pp. 203-216, 1992 

Cleary SF, Liu LM, Cao G: Radiofrequency Power 

Absorption in Mammalian Cells. In: Biological 

Effects and Safety Aspects of Nuclear Magnetic 

Resonance Imaging and Spectroscopy. Annals N.Y. 

A cad Science 649: 166-175, 1992 

Cao G, Liu LM, Cleary SF: Modified Method of 

Mammalian Cell Synchronization Improves Yield and 

Degree of Synchronization. Exptl Cell Res 

193:405-410, 1991 

Cleary SF: In Vitro Studies: Low Frequency 

Electromagnetic Fields. Proceedings of the Scientific 

Workshop on the Health Effects of Electromagnetic 

Radiation on Workers. U.S. DHHS, PHS, CDC, 

(NIOSH), Publication No. 91-11:17-43, 1991 

Cleary SF, Liu LM, Cao G: Functional Alteration of 

Mammalian Cells by Direct High Frequency 

Electromagnetic Field Interactions. In: Charge and 

Field Effects in Biosystems, Vol 2, Plenum Press, 

N.Y., pp. 211-221, 1990 

Cleary SF, Liu LM, Merchant RE: Lymphocyte 

Proliferation Modulated In Vitro by Isothermal 

Radiofrequency Radiation Exposure. 

Bioelectromagnetics 11:47-56, 1990 

Cleary SF, Liu LM, Merchant RE: Glioma 

Proliferation Modulated In Vitro by Isothermal 

Radiofrequency Radiation Exposure. Radiation 

Research 121:38-45, 1990 

Cleary SF: Biological . Effects of Radiofrequency 

Electromagnetic Radiation. In: Biological Effects 

and Medical Applications of Electromagnetic Fields, 

Chapter 10, (ed. 0 Gandhi), Prentice Hall, 

Englewood Cliffs, New Jersey, 1990 

Cleary SF: Cellular Effects of Radiofrequency 

Electromagnetic Radiation. In: Biological Effects 

and Medical Applications of Electromagnetic Fields, 

Chapter 14, (ed. 0 Gandhi), Prentice Hall, 

Englewood Cliffs, New Jersey, 1990 
Cleary SF, Liu LM, Cao G: Functional Alteration of 

Mammalian Cells by Direct High Frequency 

Electromagnetic Field Interactions. In: Charge and 

Field Effects in Biosystems. Vol 2, Plenum Press, 

New York, pp 211-221, 1990 

Cleary SF, Liu LM, Graham R, East J: In Vitro 

Fertilization of Mouse Ova by Spermatozoa Exposed 

Isothermally to Radiofrequency Radiation. 

Bioelectromagnetics 10:361-370, 1989 

Cleary SF: Biological Effects of Non-ionizing 

Electromagnetic Radiation: An Overview. In: 

Electromagnetic Biointeraction: Mechanisms, Safety 

Standards, Protection Guides, ( eds. G Franceschetti, 

OP Gandhi, M Grandolfo), Plenum Press, New York, 

pp 59-79, 1989 

Liu LM, Cleary SF: Effects of 2.45 GHz Microwave 

and 100 MHz Radio frequency Radiation on Liposome 

Permeability at the Phase Transition Temperature 

Bioelectromagnetics 9:249-257, 1988 

Cleary SF: Biological Effects of Non-ionizing 

Electromagnetic Radiation. In: Encyclopedia of 

Medical Devices and Instrumentation, (ed. JG 

Webster), J Wiley & Sons, New York, pp 274-303, 

1988 

Plasma Proteins: Markers of 

Chemical Exposure 

Ghulam A.S. Ansari, Ph.D. 

University of Texas Medical Branch 

Department of Human Biological 

Chemistry and Genetics 

Galveston, Texas 77550-2774 

Program Area: Other Occupational Needs 

Grant Number: 5 ROJ OH02149-06 

Start & End Dates: 01/01/86 - 08/31/93 

Funding Level: $0 ($721,590 Cum) 

Importance to Occupational Safety and Health 

The purpose of this study is to develop biological 

markers of chemical exposure. The chemical and 

biological assays thus developed to measure changes 

in plasma proteins can be used to monitor 

occupationally-exposed populations. Correlation 

between the changes in plasma proteins and the 

medical histories of the occupationally-exposed 

Other Occupational Needs - Page 133 

individuals can be used for medical surveillance as 

well as for risk assessment. 

Objectives 

A significant number of people are exposed to a 

variety of chemicals at work sites which may be 

responsible for toxic manifestation. Such exposure(s) 

can bring about changes in plasma proteins in terms 

of their function, concentration, or covalent 

modification. These changes, which may be 

responsible for toxic effects, can be used as markers 

of chemical exposure. The intent of this research is 

to develop method(s) which can identify the changes 

in plasma proteins caused by chemical exposure. 

Methodology 

Effects of chemical exposure on plasma proteins 

were studied in terms of their biological activity, 

concentration, and covalent modification. These 

changes were measured by using bio- and 

immunoassays and electrophoretic and 

chromatographic techniques. Covalent modification 

was further characterized by peptide mapping and 

compositional and sequential amino acid analysis. 

The structure of the modified amino acid(s) was 

determined by spectral techniques. 

Significant Findings 

Covalent binding of acrolein to albumin 

We have studied the covalent binding of acrolein 

to human serum albumin. Amino acid analysis 

showed four new ninhydrin positive peaks. These 

were identified as lysine and histidine adducts 

utilizing methods we developed earlier. 

The adducts formed as a function of increasing 

concentration of acrolein was dose dependent between 

1 to 10 mM range. The lowest concentration of 

acrolein used to quantitate the adducts was 1 μ mM at 

an albumin concentration of 1 mg/ml. The effects of 

acrolein on the ultraviolet absorption and the 

biological function of the protein to bind fatty acid or 

bromocresol green were also studied. At acrolein 

concentrations of 2.5 to 10 mM, we observed an 

increased absorption at 280 nm by about 80%. This 

data suggest that more tyrosine and/or tryptophan 

residues were exposed due to the unfolding of the 

protein as a result of covalent modification of the 

lysyl and histidyl residues. In spite of significant 

numbers of modified lysyl and histidyl residues in 

albumin, the serum protein did not lose the ability to 

bind either palmitic acid or bromcresol green. 

Apparently, the alteration in the secondary or higher 

ordered structure (unfolding) of albumin did not 

affect its capacity to bind these ligands. These 
Page 134 - Other Occupational Needs 

studies indicate that even substantial covalent 

modification may not result in the loss of biological 

activity of albumin. 

Rapid Ouantitation of Acrolein and Crotonaldehyde 

Modified Albumin 

We developed a rapid and sensitive method for 

the estimation of acrolein adduct of albumin which 

can subsequently be used as a marker of acrolein 

exposure. 

In Vitro Studies: Human plasma albumin 

samples were incubated with increasing 

concentrations of acrolein (0.025 to 10 mM) at 37°C 

in 0.1 M phosphate buffer, pH 7.2, for 2 hr. After 

exhaustive dialysis, the modified protein was treated 

with [

3

H]-NaBH4 to reduce the aldehyde adduct to 

corresponding alcohol. The radioactivity was 

measured after exhaustive dialysis and nmoles of 

carbonyl function/mg protein calculated. The 

response was found to be linear. This method is 

about four fold more sensitive compared to the amino 

acid analysis method in detecting covalent binding of 

acrolein to albumin. Although not as reactive, 

crotonaldehyde (a metabolite of butadiene) had a 

similar capacity to bind covalently with albumin as 

acrolein. 

In Vitro Studies: Rats were treated with acrolein 

by gavage (13 mg kg-1

) and killed at 1,2,4, and 6 hr. 

Blood samples were collected and analyzed for 

adducts of plasma proteins and hemoglobin as 

described above. The adducts of both plasma 

proteins and hemoglobin were found to be 

significantly higher than in the controls. 

The efficacy of this method needs to be 

established in humans before it can be used for 

molecular dosimetry. 

Susceptibility to Degradation of Covalently Modified 

Albumin 

In Vitro Studies: Albumin which was covalently 

modified by acrolein or crotonaldehyde as described 

above was incubated with elastase. Proteolysis in 

both cases occurred at a faster rate than with the 

native protein. Albumin treated with elastase 

degraded between 20 - 25% while covalently 

modified albumin with 5 mM acrolein or 

crotonaldehyde degraded 98 and 91 % respectively. 

A dose response was observed between 0.025 -

5 mM range in both cases. 

In Vitro Studies: Biosynthetically [

3

H]-lysine 

labeled rat albumin was incubated with 5 mM 

acrolein in 0.1 M phosphate buffer pH 7.2 in order to 

prepare radioactively labeled protein adducts. The 

acrolein-adducted albumin and native albumin were 

injected intravenously into a group of rats. The 

disappearance of radioactivity was followed in 

plasma. In contrast to that of native albumin (t 1/2 of 

12 hr), the corresponding estimated half-life of the 

adducted-protein was about 6 hr. Moreover, at the 

end of 33 hr after injection only 6.26% (5.5%, TCAinsoluble, and 0.9%, TCA-soluble) remained in the 

plasma vs. 20.4%, (19.4% TCA-insoluble; 1.1 %, 

TCA-soluble) with native protein. Thirty-three hrs 

after the injection only 4.4% of the radioactive dose 

was associated with plasma albumin in the adducted 

protein, while 16.2% remained in the plasma when 

native albumin was used. The radioactivity data from 

the liver indicates that more degradation is occurring 

with the adducted protein (4.5%, in TCA-soluble 

function) than in the native protein (1.5%, 

TCA-soluble). 

These studies show that chemically modified 

proteins may be degraded at faster rates than native 

proteins. Further studies are needed to substantiate 

this observation using several other protein adducts. 

Publications 

Trieff NM, Ficklen D, Gan J: In Vitro Inactivation 

of Glucose-6-Phosphate Dehydrogenase from Human 

Red Cells by Acrolein: A Possible Biomarker of 

Exposure. Toxicol Letters 69:121-127, 1993 

Khan MF, Kaphalia BS, Boor PJ, Ansari GAS: 

Subchronic Toxicity of Aniline Hydrochloride in 

Rats. Arch Environ Contam Toxicol 24:368-374, 

1993 

Ahmad F, Kaphalia BS, Khan MF, Ansari GAS: 

Fatty Acid Anilides: A New Conjugation Pathway of 

Aniline. Biochem Arch 9:111-118, 1993 

Awasthi S, Srivastava SK, Ahmad F, Ahmad H, 

Ansari GAS: Interactions of Glutathione 

S-Transferase-i\ with Ethacrynic Acid and Its 

Glutathione Conjugate. Biochim Biophys Acta 

1164:173-178, 1993 

Thakore K, Gan JC, Oandasan A, Ansari GAS: 

Quantitation of Blood Protein Adducts of Acrolein by 

Tritiated Bromohydride Reduction. Toxicol Methods 

2:295-305, 1992 

Kanz MF, Kaphalia L, Kaphalia BS, Romagnoli E, 

Ansari GAS: Methylene Dianiline: Acute Toxicity 

and Effect on Biliary Function. Toxicol Appl 

Pharmacol 117:88-97, 1992 

Kaphalia BS, Ansari GAS: Covalent Binding of 

Ethylene Dibromide and Its Metabolites to Albumin. 

Toxicol Lett 62:221-230, 1992 

Kaphalia BS, Bhat HK, Khan MF, Ansari GAS: 

Tissue Distribution of Monochloroacetic Acid and Its 
Binding to Albumin in Rats. Toxicol Ind Hlth 

8:53-61, 1992 

Gan JC, Oandasan A, Ansari GAS: In Vitro 

Covalent Modification of Serum Albumin by 

Acrolein. Toxicologist 11: 133, 1991 (Abstract 

#458); Chemosphere 23:939-947, 1991 

Bhat HK, Asimakis GK, Ansari GAS: Uncoupling of 

Oxidative Phosphorylation in Rat Liver Mitochondria 

by Chloroethanols. FASEB J 5:A55 l, 1991 (Abstract 

#1950); Toxicol Lett 59:203-211, 1991 

Bhat HK, Kanz MF, Campbell GA, Ansari GAS: 

Ninety-day Toxicity of Chloroacetic in Rats. Fund 

Appl Toxicology 17:240-253, 1991 

Kanz MF, Bhat HK, Ansari GAS: Alterations in 

Hepatocellular Ultrastructure Following Oral 

Exposure to Chloroacetic Acids. Toxicologist 

11:349, 1991 (Abstract #1371) 

Gan JC, Ansari GAS: Inactivation of Plasma 

a,-proteinase Inhibitor by Aldehydes Found in 

Cigarette Smoke. SAAS Bull Biochem Biotech 

3:32-36, 1991 

Gan JC, Ansari GAS: Inactivation of Plasma 

a 1-proteinase Inhibitor by Acrolein: Adduct 

Formation with Lysine and Histidine Residues. Mol 

Toxicol 2:137-145, 1989 

Ahmad H, Medh RD, Singh SV, Caccuri AM, Ansari 

GAS, Awasthi YC: Anionic Glutathione 

S-transferases of Human Erythrocytes, Placenta and 

Lung: Evidence for Structural Differences. Enzyme 

42:129-135, 1989 

Sanduja R, Ansari GAS, Boor PJ: 

3-Hydroxypropyl-mercapturic Acid: A Biological 

Marker for Exposure to Allylic and Related 

Compounds. J Appl Toxicol 9:235-238, 1989 

Britt SG, Ansari GAS: Formation of Lipid Adducts 

by Carbon Tetrachloride. Clin Chem Enzyme 

Comms 1 :305-311, 1989 

Ahmad H, Singh SV, Medh RD, Ansari GAS, 

Kurosky A, Awasthi YC: Differential Expression of 

a, μ, and 7t Classes of lsozymes of Glutathione 

S-transferase in Bovine Lens, Cornea, and Retina. 

Arch Biochem Biophys 266:416-426, 1988 

Ansari H, Gan JC, Barton BK: In Vitro Inactivation 

of Plasma a,-proteinase Inhibitor by Epoxides and 

1,2-dihaloethanes. Arch Environ Contam Toxicol 

17:537-542, 1988 

Other Occupational Needs - Page 135 

Ansari GAS, Gan JC, Barton BK: Synergistic 

Activation of Plasma a 1-proteinase Inhibitor by 

Aldehydes of Cigarette Smoke with Styrene Oxide 

and 1,2-dichloroethane. Arch Environ Contam 

Toxicol 17:533-536, 1988 

Ahmad H, Singh SV, Medh RD, Ansari GAS, 

Kurosky K, Awasthi YC: Glutathione S-transferases: 

Tissue Specific Expression in Lens, Cornea, and 

Retina. Arch Biochem Biophys 266:416-426, 1988 

Ansari GAS, Kaphalia BS, Boor PJ: Selective 

Pancreatic Toxicity of Palmitoylpentachlorophenol. 

Toxicol 46:57-63, 1987 

Singh SV, Leal T, Ansari GAS, Awasthi YC: 

Purification and Characterization of Glutathione 

S-transferases of Human Kidney. Biochem J 

246: 179-186, 1987 

Ansari GAS, Singh SV, Gan JC, Awasthi YC: 

Human Erythrocyte Glutathione S-transferase: A 

Possible Marker of Chemical Exposure. Toxicol Lett 

37:57-62, 1987 

Boor PJ, Sanduja R, Nelson TJ, Ansari GAS: In 

Vivo Metabolism of the Cardiovascular Toxin, 

Allylamine. Biochem Pharmacol 24:43L!7--4353, 

1987 

Gan JC, Ansari GAS: Plausible Mechanism of 

Inactivation of a 1-proteinase Inhibitor by Acrolein. 

Res Commun Chem Path Pharmacol 55:419-422, 

1987 

Kaphalia BS, Ansari GAS: 2-Chloroethylstearate: 

An In Vivo Fatty Acid Conjugate of 2-chloroethanol. 

Bull Environ Contam Toxicol 39:835-842, 1987 

Upreti RK, Farooqui MYH, Ahmed AE, Ansari GAS: 

Toxicokinetics and Molecular Interaction of 

[

14C]-formaldehyde in Rats. Arch Environ Contam 

Toxicol 16:263-273, 1987 

Farooqui MYH, Upreti RK, Ahmed AE, Ansari GAS: 

Influence of Intraperitoneally Administered 

Formaldehyde on Bile Production and Glutathione 

Levels in Rats. Res Commun Chem Path Pharmacol 

53:233-236, 1986 

Gan JC, Ansari GAS: Non-oxidative Inactivation of 

Plasma a,-proteinase Inhibitor by Carbonyl 

Compounds Found in Cigarette Smoke. Res 

Commun Subs Abuse 7:59-69, 1986 

Singh SV, Ansari GAS, Awasthi YC: Anion 

Exchange High Performance Liquid Chromatography 

of Glutathione S-transferases: Separation of the 
Page 136 - Other Occupational Needs 

Minor Isozymes of Human Erythrocytes, Heart, and 

Lung. J Chromatogr 361:337-345, 1986 

Dose/Response for Styrene 

Exposures 

Stephen M Rappaport, Ph.D. 

University of North Carolina 

School of Public Health 

Department of Environmental 

Sciences & Engineering 

CB #7400 - Campus 

Chapel Hill, North Carolina 27599-7400 

Program Area: Other Occupational Needs 

Grant Number: 5 ROI OH02221-05 

Start & End Dates: 09/29186 - 12127/93 

Funding Level: $0 ($838,329 Cum) 

Importance to Occupational Safety and Health 

The project represents one of the first 

comprehensive applications of biochemical 

epidemiology to an occupational cohort. The 

extensive exposure assessment, performed 

longitudinally, allows for the correction of biases in 

any dose-response relationships which are derived 

from the work. This study design has allowed us to 

detect elevated levels of SCEs at styrene 

concentrations below those which had heretofore been 

reported, even after adjustment for cigarette smoking. 

The development and application of methods for 

detecting styrene-7,8-oxide (SO) adducts of DNA 

(SO-DNA) and the blood proteins, hemoglobin 

(SO-Hb) and albumin (SO-Alb) will produce 

important new information concerning the 

bioavailability of SO in humans exposed to styrene. 

Objectives 

This study is investigating the linkages between 

exposure, uptake, and genotoxic response resulting 

from occupational exposure to styrene in the 

reinforced-plastics industry. A longitudinal 

assessment of exposure was completed in which 

48 subjects were monitored in a single facility where 

fiberglass boats were manufactured. The primary 

purpose of the study is to accurately estimate the 

airborne exposure and uptake of each individual in 

the cohort for comparison with several indices of the 

dose of SO measured in blood samples, i.e., 

sister-chromatid exchanges (SCEs) in peripheral 

lymphocytes and the adducts, SO-Hb, SO-Alb and 

SO-DNA. This would allow exposuredose-response relationships to be established for 

styrene and for SO arising from metabolism of 

styrene in vivo. A secondary objective is to correlate 

the above indices of styrene uptake and genotoxicity 

with each other in a common pool of samples where 

exposure had been carefully documented. 

Methodology 

Each individual's airborne exposure was 

measured 7 times (shift-long sampling), his/her blood 

was collected 4 times, and his/her exhaled air was 

collected up to 25 times over a 12-month period. 

Exposures were measured with passive monitors. 

Measurement of styrene in the exhaled air employed 

a new device which collects styrene from 3 L of 

mixed exhaled air in a tube containing 200 mg of 

coconut carbon. Both types of samples were 

analyzed by solvent desorption/gas chromatography. 

Blood styrene was measured via the head space 

technique using standard addition and gas 

chromatography. SCEs were measured by the 

standard method. Styrene glycol was measured in the 

blood by extraction followed by derivitization and gas 

chromatography with electron-capture detection. 

SO-DNA is being measured by a modification of the 32P post-labeling technique developed in this study. 

A new technique has been developed for measuring 

SO-Hb and SO-Alb, which takes advantage of a 

metal catalyst (Raney-nickel) to selectively cleave 

SO-cysteine adducts to yield 1- and 2-phenylethanol, 

which are subsequently derivitized and measured by 

gas chromatography with negative-ion mass 

spectrometry. 

Significant Findings 

The exposure assessment was completed with 

analysis of styrene in all samples of air, exhaled air, 

and blood. Individual mean exposures ranged 

between 0.2 and 55 ppm for the 48 subjects with an 

overall mean of 15.1 ppm. A correlation matrix 

revealed that all of the biomarkers were significantly 

correlated with exposure to styrene. The strongest 

correlation with exposure to styrene was observed for 

exhaled air (r=0.91, n=48) followed by styrene in 

blood (r=0.74, n=48), styrene glycol in blood 

(r=0.73, n=48), SCEs (r=0.35, n=46), albumin 

adducts (r=0.42, n=48), and DNA adducts (r=0.33, 

n=47). All of these exposure-biomarker relationships 

were significant (p<0.05). Interestingly, a significant 

relationship was not found between hemoglobin 

adducts and exposure to styrene. The only biomarker 

which was found to be significantly correlated with 

SCEs was styrene in exhaled air (r=0.45, n=46). The 

correlations between SCEs and both exposure to 

styrene and styrene in exhaled air were still 
significant after accounting for the number of 

cigarettes smoked per day by multiple regression 

analysis. This indicates that styrene exposure below 

50 ppm, the current OSHA PEL, contributed to 

elevated SCEs; such findings of SCEs at these levels 

of styrene exposure have not been reported before. 

We have successfully applied the 32P postlabeling 

technique to in vitro modified samples of nucleosides, 

DNA, and cells and in samples of human DNA 

obtained from this study. The results clearly show 

that five SO-DNA adducts have been detected. 

Recent work has confirmed the identities of these 

adducts in the in vitro modified samples as products 

of reaction of SO at N2-, 0 6-, N-7-, and C-8-

positions of guanine. Application of the method to 

the human samples has confirmed the presence of the 

SO-N2

- adduct of guanine and of an 

as-yet-unknown adduct associated with styrene 

exposure. 

The methods for measurement of SO-Hb and 

SO-Alb were first applied to samples of blood which 

had been modified with SO in vitro, and following 

administration of both SO and styrene to rats in vivo. 

The in vivo results suggest that only about 2% of the 

styrene dose was bioavailable as SO in the blood of 

rats. Application of the methods to the human 

samples has shown significant correlation with 

styrene exposure with SO-Alb but not with SO-Hb 

as noted above. 

Publications 

Rappaport SM, Symanski E, Kupper L: The 

Relationship Between Environmental Monitoring and 

Biological Markers in Exposure Assessment. Environ 

Health Perspectives, in press, 1994 

Yager J, Paradisin W, Rappaport SM: Sister 

Chromatid Exchanges in Lymphocytes are Increased 

in Relation to Longitudinally Measured Occupational 

Exposure to Low Concentrations of Styrene. Mut 

Research, in press, 1993 

Rappaport SM, Ting D, Jin ZL, Yeowell-O'Connell 

K, Waidyanatha S, McDonald T: Application of 

Raney Nickel To Measure Adducts of Styrene Oxide 

with Hemoglobin and Albumin. Chem Res Toxicol 

6(2):238-244, 1993 

Rappaport SM, Dionne L, Woodlee J, Yager J: The 

Relationship between Exposure to Styrene, 

Biomarkers of Exposure and Cytogenetic Response: 

(Abstract from the Proc of the 8th International 

Symposium of Epidemiology in Occupational Health, 

Paris, France, Sept. 10-12, 1991) Revue 

d'epidemiologie et de Sante Publique 40:S80-S8 l, 

1992 

Other Occupational Needs - Page 137 

Pongracz K, Kaur S, Burlingame AL, Bodell WJ: 

Iden ti f i cation o f N2 - subs ti tut e d 

2 '-deoxyguanosine-3 '-phosphate Adducts Detected 

by 32P-postlabeling pf Styrene-Oxide-treated DNA. 

Carcinogenesis 13(3):315-319, 1992 

Compton PJE, Jensen RH, Bigbee WL, Langlois RG, 

Smith MT, Rappaport SM: Workers Exposed to 

Styrene Studied with the Glycophorin A Human 

Mutation Assay. Environmental Health Perspectives, 

in press, 1992 

Rappaport SM, Kure E, Petreas M, Ting OT, 

Woodlee J: A Field Method for Measurement 

Vapors In Exhaled Air - Application To Styrene 

Exposure. Scand J Work Environ Health 

17:195-204, 1991 

Ting D, Smith MS, Doane-Setzer P, Rappaport SM: 

Analysis of Styrene Oxide-Globin Adducts Based 

Upon Reaction With Raney Nickel. Carcinogenesis 

I I :755-760, 1990 

Yager JW, Paradisn W, Symanski E, Rappaport SM: 

Sister-Chromatid Exchanges Induced in Peripheral 

Lymphocytes of Workers Exposed to Low 

Concentrations of Styrene. Proc of the Fifth 

International Conference on Environmental Mutagens, 

(eds. ML Mendelsohn, RJ Albertini), pp 3470-356, 

1989 

Bodell WJ, Pongracz SK, Burlingame AL, Liu SF, 

Rappaport SM: Investigation of Styrene Oxide-DNA 

Adducts and Their Detection in Workers Exposed To 

Styrene. In: Mutation and the Environment, Part C: 

Somatic and Heritable Mutation, Adduction, and 

Epidemiology, ( eds. ML Mendelsohn, RJ Albertini), 

pp 271-282, 1989 

Selvin S, Rappaport SM: A Note On The Estimation 

of The Mean From a Lognormal Distribution. Am 

Ind Hyg Assoc J 50:627-630, I 989 

Rappaport SM, Spear RC: Physiological Dampening 

of Exposure Variability During Brief Periods. Ann 

Occup Hyg 32:21-33, 1988 

Liu SF, Rappaport SM, Pongracz K, Bodell W: 

Detection of Styrene-Oxide DNA Adducts in 

Lymphocytes of a Worker Exposed to Styrene. In 

Methods for Detecting DNA-Damaging Agents in 

Humans, Appl in Cancer Epidemiology and 

Prevention ( eds. H Bartsch, K Hemminki, IK 

O'Neill), IARC Sci, Puhl #89, Lyon, pp 2 I 7-222, 

1988 
Page 138 - Other Occupational Needs 

Lui SF, Rappaport SM, Rasmussen J, Bodell WJ: 

Detection of Styrene-Oxide-DNA Adducts by 

32P-Postlabeling. Carcinogenesis 9: 1401-1404, 1988 

Hydrocarbon Exposure and Chronic 

Renal Disease 

Nabih R. Asal, Ph.D. 

University of Oklahoma 

Health Sciences Center 

801 NE 13th Street 

Oklahoma City, Oklahoma 73190 

Program Area: Other Occupational Needs 

Grant Number: 5 ROI OH02391-03 

Start & End Dates: 09/15/89 - 09/14/93 

Funding Level: $0 ($544,420 Cum) 

Importance to Occupational Safety and Health 

Occupational exposure to nephrotoxins has for 

many years been suggested as an important etiological 

factor in chronic renal failure. However, only a few 

epidemiologic studies have attempted to clarify this 

suspicion. There is little doubt that chronic 

tubulointerstitial nephropathy may result from heavy 

metal toxicity; however, this is a relatively rare cause 

of chronic renal failure. In contrast, although 

hydrocarbons have been clearly implicated as a cause 

of chronic renal disease, there are reports suggesting 

that these ubiquitous agents may be associated with 

the development of a variety of chronic 

glomerulopathies. 

Because of an ever increasing number of end 

stage renal disease patients (ESRD)(i.e.- those 

requiring dialysis or having had a renal transplant), 

they have become a major factor in Medicare 

expenditures. Elucidating the processes leading to 

ESRD and finding ways to control them are the most 

valid ways to reduce the personal, social, and 

economic hardships produced by this condition. 

Objectives 

The objective of this study was to investigate the 

role of chronic exposure to hydrocarbons in causing 

chronic renal disease. 

Methodology 

This population-based case-control study utilized 

patients and controls identified from the major 

counties in Oklahoma. Cases included all adult 

patients between the ages of 18 and 79 with chronic 

renal disease (both those with ESRD and those not 

yet at that stage) having a confirmed diagnosis of 

idiopathic chronic glomerulopathy (ICG) as their 

primary disease and patients with chronic renal 

failure who have an unknown primary disease. 

Minimum criteria for diagnosis of ICG included 

either a histologic diagnosis or the presence of 

unexplained proteinuria exceeding 2 gms/24 hrs. 

New cases diagnosed between January 1, 1985 and 

July 31, 1992 meeting these criteria were included in 

the study. 

A general population-based control group 

matched to the cases by sex and age (±5 yrs) was 

selected from the same communities by a Random 

Digit Dialing technique. 

A detailed questionnaire was administered to 

cases and controls. The questionnaire included 

information on medical history, family history of 

chronic renal disease, medication history, smoking 

and beverage use, life-time occupational history 

specific for hydrocarbon exposure, demographics and 

other pertinent data. 

A lifetime hydrocarbon exposure score was 

determined and expressed as average exposure in 

parts per million (PPM). This process included the 

following steps: (1) Development of a database of 

subjects' occupational histories which were given SIC 

(Standard Industrial Classification) and SOC 

(Standard Occupational Classification) codes by 

decade, (2) Formation of an expert panel of Industrial 

Hygienists to provide hydrocarbon exposure estimates 

for each SIC/SOC/decade combination, 

(3) Supplementation of exposure estimates by an 

extensive search of the literature and through the 

Occupational Safety and Health Administration 

Computerized Information System database located in 

Salt Lake City, and (4) Cross-matching of the 

SIC/SOC/decade combinations with the 

SIC/SOC/decade and length of employment for each 

job reported by each subject to determine the final 

estimate of lifetime hydrocarbon exposure. 

Significant Findings 

321 matched pairs were obtained. The subjects 

were mainly male (58%), white (79%) and married 

(71 % ) with about 54% never going to college. The 

cases were significantly less educated than controls 

and consisted of significantly more non-white 

subjects (Black, Hispanic, Native American and 

others). Significantly more controls drank diet soda 

and used artificial sweeteners. There was no 

difference in their smoking history and usage of 

coffee, tea, beer, wine and distilled spirits. The 

occurrence of a relative (parents, siblings, children, 

aunts, uncles or grandparents) with chronic renal 

disease was not significantly different between cases 
and controls. Prescription and over-the-counter drug 

use was the same in both groups. Cases had 

significantly higher occurrence of high cholesterol, 

arteriosclerosis, heart attacks, fast heartbeats, angina, 

gout, frequent headaches and gallstones. Controls had 

a significantly higher occurrence of sinus conditions. 

No significant difference was found between 

cases and controls regarding lifetime hydrocarbon 

exposure. No or low exposure (0-50 ppm) was seen 

in 51 % of the cases and 52% of the controls. The 

exposure distribution was similar for all categories. 

Those with high exposure (500+) made up 8% of the 

cases and 9% of the controls. When matched pairs 

were compared, the case score was greater than the 

control in 122 pairs, but less than the control in 

119 pairs. The case and control score were the same 

(if scores were within 10 ppm of each other they 

were considered equal) in 80 pairs. The odds ratio 

(using 100 ppm as the cutoff between exposure and 

no exposure) was significant when looking only at 

males over 30 years of age and for the subgroup of 

92 cases with an unclassified diagnosis. When 

analyzing the subgroup of cases with creatinine levels 

over 4.0 mg/di a significant OR (3.50) was also 

found. However, the unclassified subgroup consisted 

mostly of patients with high creatinine levels. 

When analyzing the data by the extended 

Mantel-Haenszel test for matched analysis, a 

chi-square test which takes into account the actual 

dosage exposure for each pair, no significance was 

found overall or for any subgroups. No difference 

was found after controlling for possible confounding 

factors. 

Biological Monitoring for Exposure 

to Coal Tar 

Regina M Santella, Ph.D. 

Columbia University 

Division of Environmental Science 

650 West I 68th Street 

New York, New York 10032 

Program Area: Other Occupational Needs 

Grant Number: 5 ROI OH02622-03 

Start & End Dates: 01101/89 - 12/31/92 

Funding Level: $0 ($651,727 Cum) 

Importance to Occupational Safety and Health 

A major goal of biological monitoring for 

exposure to genotoxic agents is to identify 

occupations as well as individuals at elevated risk for 

Other Occupational Needs - Page 139 

cancer development. Methods for the detection of 

carcinogen-DNA and protein adducts have been 

established. These methods require the collection of 

blood or tissue samples and are not practical for 

routine occupational monitoring. In this proposal, 

methods have been developed for the determination 

of exposure to benzo(a)pyrene (BP) by measurement 

of BP and its metabolites in urine. Since urine is 

much more readily collected than blood, this method 

should simplify workplace screening. 

Objectives 

The major objective of this work is the 

development of a new technique to monitor human 

exposure to BP, a polycyclic aromatic hydrocarbon 

(P AH), by measurement of its urinary excretion. An 

immunoassay for measurement of BP and its 

metabolites in urine was developed utilizing 

monoclonal antibodies recognizing these compounds. 

This new assay was validated in a model population, 

crude coal tar treated psoriasis patients and controls. 

Blood and urine were collected from patients and 

controls. Exposure to BP was also measured by a 

panel of previously developed assays including 

quantitation of white blood cell DNA adducts by 

immunoassay and [

32P] postlabeling and measurement 

of BP-albumin adducts and serum antibodies to 

BP-DNA adducts by immunoassay. Urines were 

analyzed for mutagens with the Salmonella 

typhimurium assay, for 1-hydroxypyrene by HPLC 

with fluorescence detection and with the new 

immunoassay developed in this project. The levels of 

different biological markers were correlated to each 

other and to exposure. 

Methodology 

To develop an immunoassay for the measurement 

of urinary BP, monoclonal antibodies were developed 

from animals immunized with BP covalently coupled 

to carrier protein and characterized in terms of 

sensitivity and specificity by competitive 

enzyme-linked immunosorbent assay (ELISA). An 

ELISA was developed for the sensitive detection of 

BP and its metabolites in urine. To validate the 

ELISA, urine from mice treated with radiolabeled BP 

was analyzed by ELISA and values correlated with 

those determined by radioactivity. 

Blood and urine was collected from 50 crude coal 

tar treated psoriasis patients and 50 controls. Blood 

was separated into plasma, white blood cell and red 

blood cell fractions, and frozen. DNA was isolated 

from the white blood cells and adducts were 

determined by ELISA utilizing a previously 

developed antiserum recognizing BP diol epoxide 

modified DNA. This antiserum recognizes a number 

of structurally related PAH diol epoxide adducts and 
Page 140 - Other Occupational Needs 

thus provides a general marker of exposure to this 

class of chemicals. Total hydrophobic adducts were 

quantitated with the [

32P] postlabeling assay. BP 

protein adducts were measured in an ELISA with an 

antiserum recognizing these adducts. Plasma were 

tested for the presence of antibodies to BP-DNA 

adducts by noncompetitive ELISA as an alternate 

marker of exposure to BP. 

In addition to quantitation of urinary levels of BP 

and its metabolites by ELISA, 1-hydroxypyrene was 

measured by HPLC and mutagens determined with 

the Salmonella typhimurium mutagenesis assay. 

Creatinine levels were determined to standardize the 

data to urine concentration. 

In a small subset of patients, skin biopsies were 

obtained at the time of treatment. PAH-DNA 

adducts were visualized in frozen sections by 

immunohistochemical staining with the adduct 

specific antiserum used in the ELISA followed by 

fluorescent labeled secondary antiserum. This 

allowed visualization of adducts in specific cell types. 

Adducts were also quantitated on DNA isolated from 

the biopsies by [

32P] postlabeling. 

Significant Findings 

In a competitive ELISA 50% inhibition of 

antibody 4D5 binding is at 4 pmole of BP/well. 

There is significant crossreactivity with a number of 

BP metabolites and several other PAHs, including 

pyrene, 1-0H-pyrene 1-aminopyrene and 

1-nitropyrene. To validate the ELISA, mice were 

treated with radiolabeled BP and urine collected. 

Metabolites, isolated by chromatography on Sep-pak 

C 18 cartridges were counted for radioactivity and 

analyzed by competitive ELISA. The values by 

ELISA, determined with a standard curve of BP, 

were about one third those determined by 

radioactivity. Although unmetabolized BP is not 

excreted in the urine, it is used as the standard since 

the metabolite ratio in the urine is unknown. Thus, 

the assay will provide a relative measure of 

metabolites present. 

The ELISA has been validated in humans by 

application to coal tar-treated psoriasis patients and 

controls. Urine samples were analyzed for the 

presence of PAH metabolites by ELISA, for 

1-hydroxypyrene by HPLC with fluorescence 

detection and for mutagenicity by the Salmonella 

typhimurium mutagenesis assay. Urinary excretion of 

PAH metabolites, measured by competitive ELISA 

with a monoclonal antibody (4D5), were elevated in 

patients (mean 730±1370 μmol/mol creatinine) 

compared to untreated volunteers (110±90 μmol/mol 

creatinine, p<0.0001). 1-Hydroxypyrene was also 

elevated in patients (mean 547±928 μmol/mol 

creatinine) compared to volunteers 

(mean 0.14±0.17 μmol/mol creatinine, p<0.0001). 

While mutagenicity was elevated in patients compared 

to controls the difference was not statistically 

significant (p=0.134). There was a good correlation 

between the ELISA and 1-hydroxypyrene data 

(r=0.717, p<0.0001). These results demonstrate that 

the ELISA which can easily be carried out on large 

numbers of samples can detect exposure to P AH in 

treated patients. 

PAH diol epoxide-DNA adducts in white blood 

cells, PAH-albumin adducts and measurement of 

serum levels of antibodies recognizing BP diol 

epoxide-DNA adducts were measured by ELISA. 

PAH-DNA adducts were elevated in patients 

(mean 6.77±12.05/108 ) compared to controls 

(4.90±8.81/108

). There was no difference in albumin 

adducts (mean 0.61±0.31 fmol/μg in patients and 

0.63±0.30 fmol/μg in controls). About 30% of both 

patients and controls had measurable titer of 

antibodies recognizing BPDE-I-DNA adducts. In 

these studies, measurement of white blood cell DNA 

adducts was the most sensitive method for detecting 

exposure in coal tar treated psoriasis patients. 

An immunofluorescence method has also been 

developed for the localization of PAH-DNA adducts 

in specific cell types. Initial application was to skin 

biopsies from treated patients and controls. Staining 

of fixed tissues with adduct specific antiserum was 

followed by fluorescein labeled secondary antiserum 

and indicated specific nuclear staining in biopsies of 

treated patients but not controls. Results agreed with 

quantitation of adducts by [

32P]postlabeling. The 

immunohistochemical method should be applicable to 

detection of adducts in biopsy material since small 

amounts of tissue are required. 

The development of an immunoassay for PAH 

exposure which uses urine samples should greatly 

simplify biological monitoring of workplace exposure. 

Publications 

Santella RM, Nunes MG, Blaskovic R, Perera FP, 

Tang D, Beachman A, Lin JH, DeLeo V: 

Quantitation of Polycyclic Aromatic Hydrocarbons, 

1-hydroxypyrene, And Mutagenicity in Urine of Coal 

Tar Treated Psoriasis Patients and Untreated 

Volunteers. Cancer Epi, Biomarkers & Prevention, 

in press, 1993 

Santella RM, Perera FP, Zhang YJ, Chen CJ, Young 

TL: Immunologic Methods for Monitoring 

Carcinogen Exposure. European Optical 

Society/International Society for Optical Engineering, 

in press, 1993 

Santella RM, Grinberg-Funes R, Perera FP, 

Zhang YJ, Chen CJ, Young TL: Molecular 

Epidemiology: Measurement of DNA Adducts. 

Advances in Cancer Research, in press, 1993 
Santella RM, Gomes M, Zhang YJ, Young TL, 

Perera FP: Immunologic Methods for Detection of 

Human Exposure to Polycyclic Aromatic 

Hydrocarbons, Proceedings of Symposium on Health 

Risk Assessment and Surveillance in the Industrial 

Setting, Taipei, Taiwan, pp 81-94, 1992 

Santella RM, Zhang YJ, Young TL, Li Y, Toor M, 

Lee BM, Stefanidis M, Warburton D, DeLeo V, 

Perera FP: Biological Monitoring of Exposure to 

Polycyclic Aromatic Hydrocarbons. In: 

Anticarcinogenesis and Radiation Protection: 

Strategies in Protection from Radiation and Cancer, 

(ed OF Nygaard), Plenum Press, New York, 

pp 155-169, 1991 

Santella RM: DNA Adducts in Humans as 

Biomarkers of Exposure to Environmental and 

Occupational Carcinogens. Environ Care Reviews 

C9(1):57-81, 1991 

Gomes M, Santella RM: Immunologic Methods for 

the Detection of Benzo(a)pyrene Metabolites in 

Urine. Chemical Research in Toxicology 3:307-310, 

1990 

Santella RM, Li Y, Zhang YU, Young TL, 

Stefanidis M, Lu XQ, Lee BM, Gomes M, Perera FP: 

Immunologic Methods for the Detection of Polycyclic 

Aromatic Hydrocarbons-DNA and Protein Adducts. 

In: Genetic Toxicology of Complex Mixtures, (ed 

MD Waters) Plenum Publishing Corporation, New 

York, in press, 1990 

Zhang YJ, Li Y, DeLeo VA, Santella RM: Detection 

of DNA Adducts in Skin Biopsies of Coal Tar 

Treated Psoriasis Patients: Immunofluorescence and 32P Postlabeling. J Skin Pharm 3: 171-179, 1990 

Other Occupational Needs - Page 141 

Selective Real-Time Detection of 

Olefin Gases and Vapors 

Edward T. Zellers, Ph.D. 

University of Michigan 

School of Public Health 

Department of Environmental 

and Industrial Health 

1420 Washington Heights 

Ann Arbor, Michigan 48109-2029 

Program Area: Other Occupational Needs 

Grant Number: 5 ROI OH02663-03 

Start & End Dates: 09101/89 - 11/30192 

Funding Level: $0 ($269,506 Cum) 

Importance to Occupational Safety and Health 

This project has focused on the development of a 

prototype instrument employing coated 

surface-acoustic-wave (SAW) sensor technology for 

real-time measurement of several olefins and dienes 

that have been associated with carcinogenic, 

neurotoxic, and/or adverse-reproductive health 

effects. Due to the presence of other organic vapors 

in industrial settings where these chemicals are used, 

real-time measurement of these contaminants with 

current portable direct-reading instruments is often 

not possible. The sensitivity and selectivity provided 

by the proposed instrument should permit the 

collection of more accurate personal exposure data. 

Objectives 

The goal of this research has been to develop and 

perform laboratory performance testing of SAW 

sensors and associated instrumentation for monitoring 

several olefin and diene gases and vapors in the 

presence of common olefin and non-olefin industrial 

co-contaminants. The response of the SAW sensor, 

which is a function of change of mass that occurs in 

a chemically sensitive surface coating upon exposure 

to gas-phase analytes, has been tested for exposure to 

styrene, ethyl acrylate, acrylonitrile, 1,3-butadiene, 

vinyl chloride, and 13-chloroprene, as well as other 

olefin and non-olefin gases and vapors. Selectivity 

for a given target olefin or diene has been achieved 

by coating the sensor with one of several novel 

trapping reagents. 

Methodology 

A large number of reagents have been 

synthesized and tested as sensor coatings for detection 
Page 142 - Other Occupational Needs 

of each of the target analytes. The reagents comprise 

Pt-olefin coordination compounds of the general 

formula trans-PtCli{amine)(olefin) designed to react, 

via substitution of the initially bound olefin, with 

certain olefin(s) and dienes. The steady-state rate of 

mass change accompanying the olefin substitution 

reaction is detected by the underlying SAW sensor, 

permitting real-time measurement of olefin/diene 

concentrations. By altering the electronic and steric 

properties of the ligands in the reagent, it has been 

possible to adjust the selectivity and sensitivity of the 

sensor. The sensor has been incorporated into a 

compact prototype instrument and tested in the 

laboratory over a range of operating conditions. 

Significant Findings 

Real-time measurement of styrene, ethyl 

acrylate, vinyl acetate and several butene isomers at 

low-ppm concentrations in the presence of each of 

several non-olefin solvent vapors has been achieved 

using a 30-MHz SAW sensor coated with a mixture 

of trans-PtCl 2 (ethylene)(pyridine) and 

poly{isobutylene). In all cases post-exposure 

regeneration of the reagent has been possible by 

treatment with ethylene, in situ. A high degree of 

selectivity for the target olefins in the presence of 

other olefin gases and vapors was achieved and could 

be attributed to steric and electronic factors favoring 

reaction with the target olefins. 

A systematic investigation of steric factors 

affecting the olefin-substitution reactions showed a 

remarkably high degree of selectivity for unhindered 

olefins. For example, ethyl acrylate could be 

monitored without interference from its more 

hindered isomers methylmethacrylate and 

methylcrotonate. Similarly, the response to styrene 

was about 8-10 times higher than that to 

a-methylstyrene and indene. Testing of various 

butene isomers showed that I -butene could be 

monitored without interference from isobutylene. 

The effect thus appears to be quite general and 

similar selectivity would be expected for other 

less-hindered olefins in the presence of their more 

hindered structural analogues. 

1,3-butadiene could not be measured with the 

Pt-ethylene reagent coating. However, use of the 

related reagent PtCli 1-hexene )(pyridine) permitted 

selective measurement of 1,3-butadiene with a limit 

of detection (LOD) of 100 ppb. In this case there is 

a 2-for-l ligand exchange involved, with formation 

of the bridged Pt:butadiene complex 

[PtCl2(pyridine) Mbutadiene ), which effectively 

amplifies the sensor response. No interference was 

observed from several industrially relevant non-olefin 

gases and vapors, and repeated regeneration of the 

reagent was possible by brief exposure to 1-hexene. 

Certain olefins could also be measured with this 

reagent, but only at concentrations higher than that of 

butadiene. For example, acrylonitrile could be 

detected above 2 ppm using the Pt-(1-hexene) 

reagent whereas it could not be measured using the 

corresponding Pt-ethylene reagent. Chloroprene 

could also be measured but only at concentrations 

above I 00 ppm. Vinyl chloride gave measurable 

responses above about 30 ppm. Vinylidene chloride, 

dichloroethylene and trichloroethylene neither reacted 

nor interfered with the responses of the other 

analytes. 

Replacing the pyridine ligand with 

2,6-dimethylpyridine in the reagent precluded 

reaction with styrene but still allowed sensitive 

detection of acrylonitrile and butadiene. Use of a 

60-MHz sensor instead of a 30-MHz sensor 

increased the sensitivity to butadiene by a factor of 

four {LOD = 24 ppb). Interestingly, ethyl acrylate 

did not react with the Pt-(1-hexene) reagent but it 

reacted quite rapidly with the Pt-ethylene reagent. 

Thus, it has been possible to achieve significant 

changes in the sensor response through subtle changes 

in the molecular design of the coating reagent. 

A prototype battery-powered dual-SAW 

instrument has been designed and constructed. The 

instrument can provide real-time output of olefin and 

diene vapor concentrations as well as datalogging and 

coating-regeneration capabilities. 

Publications 

Zhang GZ, Zellers ET: The Influence of Substituent 

Electronic Factors on the Measurement of Gas Phase 

Olefins Using a Surface-Acoustic-Wave Oscillator 

Coated with trans-PtCliolefin)(amine) Complexes. 

Analytica Chimica Acta 280: 1-13, 1993 

Zhang GZ, Zellers ET: A Coated Surface Acoustic 

Wave Sensor Employing A Reversible Mass 

Amplifying Ligand Substitution Reaction for 

Real-Time Measurement of 1,3-Butadiene at Lowand Sub-ppm Concentrations. Anal Chem 

65: 1340-1349, 1993 

Zellers ET, Zhang GZ: Steric Factors Affecting the 

Discrimination of Isomeric and Structurally Related 

Olefin Gases and Vapors with a Reagent-Coated 

Surface Acoustic Wave Sensor. Anal Chem 

64:1277-1284, 1992 

Zellers ET, Patrash SJ, Zhang GZ: Selective 

Measurement of Organic Vapors Using SAW Sensors 

with Reactive or Sorptive Coatings: Steric, 

Electronic, and Solubility Factors. Proc 6th Int Conf 

Solid-State Sensors and Actuators Transducers '91, 

San Francisco, pp 998-1001, 1991 
Zellers ET, White RM, Rappaport SM: Use of 

Surface-Acoustic-Wave Sensor to Characterize the 

Reaction of Styrene Vapor with a Square-Planar 

Organoplatinum Complex. Anal Chem 

62:1222-1227, 1990 

Zellers ET, Noralynn H, White RM, Rappaport SM: 

Selective Real-time Measurement of Styrene Vapor 

Using a Surface-Acoustic-Wave Sensor with a 

Regenerable Organoplatinum Coating. Anal Chem 

62:1227-1232, 1990 

A Dichotomous Sampler for TRIG 

Aerosol and Vapor 

Roy Rando, Sc.D. 

Tulane University Medical Center 

Section of Environmental Medicine/SL] 5 

1430 Tulane Avenue 

New Orleans, Louisiana 70112 

Program Area: Other Occupational Needs 

Grant Number: 5 ROJ OH02664-02 

Start & End Dates: 02/01192 - 01131/94 

Funding Level: $98,493 ($209,735 Cum) 

Importance to Occupational Safety and Health 

The isocyanates are an important class of 

commercial chemicals used in the production of 

polyurethanes and certain pesticides. Exposure may 

result in occupational asthma, hypersensitivity 

pneumonitis, and accelerated decline in lung function. 

The compounds are highly reactive, and some have a 

high affinity for surfaces and relatively low vapor 

pressures at ambient temperatures. These properties 

result in a tendency for some isocyanates to partition 

into gaseous and particulate phases in the atmosphere. 

The physical state of the compound will affect its site 

of deposition/adsorption in the respiratory tract, as 

well as dictate the appropriate sampling techniques 

and engineering control methods. This project entails 

the development of a dichotomous sampler for total 

reactive isocyanate group (TRIG) vapor and 

particulate which will be used to characterize TRIG 

in workplace atmosphere in polyurethane foam plants 

and in isocyanate manufacturing plants. This work 

will result in a better understanding of the 

fundamental behavior of TRIG in the atmosphere and 

will offer a powerful tool for future studies of the 

toxicology of vapor and condensed phase isocyanate. 

Other Occupational Needs - Page 143 

Objectives 

A critical laboratory comparison of the 

selectivity, sensitivity, accuracy, and precision of 

analysis of the methoxy-phenylpiperazine (MOPIP), 

methyamino-methylanthracene (MAMA), and 

tryptamine (TR YP) methods will be performed using 

a series of model aliphatic and aromatic isocyanate 

monomers and oligomers. The best of these 

techniques will be adapted for use in an annular 

denuder for dichotomous sampling of condensed and 

vapor phase TRIG. After a thorough evaluation of 

the performance of the dichotomous sampler in the 

laboratory, it will be used in a survey of TRIG in 

representative workplace atmospheres, including 

isocyanate manufacture and flexible polyurethane 

foam production. 

Methodology 

Analytical derivatives of eleven isocyanate 

monomers with MAMA, MOPIP, and TRYP were 

synthesized in the laboratory. The isocyanates 

included methyl-, butyl-, phenyl-, benzyl-, o-tolyl-, 

and p-tolyl-isocyanate, and 

1,6-hexamethylenediisocyanate, 

2,4-toluenediisocyanate, 2,6-toluenediisocyanate, 

methylene-bis-( 4 ,4' -cyclohexylisocyanate) (HMD I), 

and methylene-bis-( 4,4 '-phenylisocyanate) (MDI). 

The analytical response of each of the derivatives 

was compared for consistency within derivatizing 

agent. Equimolar amounts of each derivative based 

on isocyanate content were analyzed by 

reversed-phase HPLC using three detection modes: 

MAMA derivatives were analyzed using fluorescence, 

and UV absorbance at two wavelengths; MOPIP 

derivatives were analyzed with electrochemical 

detection and with UV absorbance at two 

wavelengths; TRYP derivatives were analyzed with 

fluorescence, with electrochemical detection, and with 

UV absorbance. For each analysis, a response factor 

was calculated as the ratio of the integrated 

chromatographic peak area to the sample 

concentration in terms of isocyanate equivalence. 

From the above work, MAMA was chosen as the 

derivatizing agent and was applied to quantitation of 

TRIG content in a series of oligomers of MDI and 

HDI in comparison to a reference titration procedure. 

Testing of the dichotomous sampler for TRIG 

aerosol and vapor was also begun. The dichotomous 

sampler consisted of an impactor inlet, annular 

diffusional denuder (University Research Glassware) 

and treated filter, coated with derivatizing agent for 

isocyanates. Sampling of test atmospheres of vapor 

and condensation aerosol of MDI, vapors of HDI and 

TDI, and aerosols of HDl-biuret was accomplished 

with the sampler. 
Page 144 - Other Occupational Needs 

Significant Findings 

Statistically significant intra-group differences 

were found across isocyanates for each of the three 

derivatizing agents and their three associated 

detection modes. The variabilities as measured by 

relative standard deviations of the mean response 

factors were as follows: MAMA derivatives; 

fluorescence, 55%; UV at 245 nm, 14%; UV at 

370 nm, 8.6%; for MOPIP derivatives 

electrochemical, 26%; UV at 242 nm, 50%; UV at 

277 nm, 35%; for TRYP derivatives 

electrochemical, 55%; fluorescence, 24%; UV at 

280 nm, 24%. The MAMA derivatives were clearly 

the most consistent when detected by UV absorbance. 

The ratio of absorbance at 254 to that at 370 nm 

averaged 10.46 with a RSD of only 8.3%. These 

results led to the choice of MAMA for use in the 

TRIG technique. Assay of three oligomeric 

isocyanate materials based on MDI monomer using 

MAMA reagent resulted in average recovery of 

100.6 ± 4.7% of TRIG content in comparison to a 

reference assay utilizing titration with 

di-n-butylarnine. Several TRIG containing peaks 

were identified during chromatography, including the 

parent MDI monomer. Two HDI based oligomeric 

materials were also assayed resulting in a recovery of 

103.2 ± 1.1 %. HDI monomer and HDI-biuret were 

easily identified in these samples along with an 

unknown TRIG containing compound. 

The dichotomous sampler clearly separated test 

atmospheres of MDI ranging from 24 to 355 μg/m3 

into vapor and aerosol fractions. Aerosols of MDI 

began to penetrate the diffusional denuder and collect 

on the backup filter at an MDI level of 75 μg/m3

, 

very near the saturated vapor pressure of MDI at 

26°C. The overall performance of the device for 

both vapor and aerosol matched theoretical 

predictions closely. 

Little penetration past the denuders was noted 

when sampling test atmospheres of HDI and TDI, 

indicating that these materials were in the vapor 

phase. HDl-biuret aerosols were found only on the 

impactor and back-up filter. Interestingly, the small 

amount of HDI monomer contained in the 

HDI-biuret was evenly distributed among the 

components of the dichotomous sampler, an indication 

of partitioning between aerosol and vapor phases. 

Publications 

Rando RJ, Poovey HG, Lefante JJ, Esmundo FR: 

Evaluation of 9-Methylarnino-Methylanthracene as 

a Chemical Label for Total Reactive Isocyanate 

Group: A Comparison of Mono- and Di-Isocyanate 

Monomers. Journal of Liquid Chromatography, in 

press, 1993 

Rando RJ, Poovey HG: Dichotomous Sampling of 

Vapor and Aerosol of Methylene-Bis-

(Phenylisocyanate) [MDI] with an Annular 

Diffusional Denuder. American Industrial Hygiene 

Association Journal, accepted for publication, 1993 

Theory and Evaluation of a 

Workplace OP-FTIR Monitor 

Steven P. Levine, Ph.D. 

University of Michigan 

School of Public Health 

Department of Environmental 

& Industrial Health 

1420 Washington Heights 

Ann Arbor, Michigan 48109-2028 

Program Area: Other Occupational Needs 

Grant Number: 5 ROI OH02666-04 

Start & End Dates: 09/01/89 - 08/31195 

Funding Level: $211,324 ($699,299 Cum) 

Importance to Occupational Safety and Health 

This project has allowed advancement in the 

strategies, hardware, and software associated with the 

evaluation and use of remote sensing optical 

instrumentation in the workplace. Remote sensing 

systems need no sampling and pumping manifolds, 

are very fast, and can detect labile and polar air 

contaminants in situ. Quantitative results can be 

obtained for multi-component mixtures at 

concentrations of a fraction of the TL V. Full scale 

profiles of concentration fields of air contaminants 

can be determined. In addition, the presence of an 

active FTIR-air monitoring group allowed the 

concurrent development and evaluation of an FTIR 

system for biological monitoring of methanol via 

breath analysis. 

Objectives 

1. Design, construction, and pilot scale evaluation of 

open path-FTIR system hardware and software. 

2. Completion of pilot scale test room, modeling of 

flow conditions, and strategy for optimal beam 

placement. 

3. Field testing of fixed beam open path-FTIR 

system. 

4. Modeling and pilot scale testing of "gamma" and 

time-series modeling concepts using fixed beam. 

5. Field testing of "gamma" and time-series 

modeling concepts. 
6. Design of system for rapid beam movement. 

7. Modeling and pilot scale testing of "gamma", 

"optimbeam" and "tomography" concepts using 

rapid beam movement. 

8. Field testing using system for rapid beam 

movement. 

Methodology 

Mathematical frameworks were developed for the 

relationship of beam averaged air contaminant 

concentrations to a critical volume of contaminated 

air that moves along with the worker as the worker 

moves through the workplace. The framework and 

software were also developed for optimizing the 

placement of a beam system for monitoring of 

exposures of workers in a concentration gradient. 

We then collaborated in the development of a 

OP-FTIR system with the capability of rapidly 

moving the beam. A new series of pilot experiments 

were then performed. Field tests are planned to 

parallel the pilot tests and evaluate the mathematical 

framework. 

Significant Findings 

1. During pilot scale evaluations, an open 

path-FTIR system, including newly designed 

hardware and software, operated in a manner 

suitable for use in the workplace. 

2. A pilot scale test room was modeled and built 

for the open path-FTIR, and found to be suitable 

for evaluation of the instrument and for 

development of strategies for optimal beam 

placement in the workplace. 

3. The open path-FTIR system was found to yield 

both quantitative and qualitative information 

regarding organic vapor and inorganic gas 

contaminants in workplace air during field 

testing at Abbott Pharmaceutical Laboratories. 

4. Modeling strategies developed for this project 

have been found in pilot scale testing to be 

useful for determination of the relationship of 

open path-FTIR data to real time decisions of 

required levels of respiratory protection. 

5. Software-based strategies have been developed 

and found to be useful for the analysis of data 

obtained from the OP-FTIR system in cases in 

which there is no source of clean air with which 

to obtain a background spectrum. 

6. Time series analysis was found to be a useful 

method of determining when a statistically 

significant departure from normal airborne 

contaminant concentrations occurred during field 

testing at Monsanto Chemical Company. 

7. Tomographic reconstruction of air contaminant 

profiles was demonstrated for full room-sized 

chambers. 

Other Occupational Needs - Page 145 

8. Initial work performed in support of methanol 

exposure experiment resulted in reconsideration 

of ACGIH BEi, and in several publications (listed 

below). 

Publications 

Yost MG, et al.: Imaging Indoor Tracer-Gas 

Concentrations With Computed Tomography: 

Experimental Results With a Remote Sensing FTIR 

System. Amer Ind Hyg Assoc J, in press, 1994 

Yost MG: Imaging Indoor Tracer-Gas 

Concentrations With Computed Tomography: 

Experimental Results With a Remote Sensing FTIR 

System. Amer Ind Hyg Assoc J, in press, 1994 

Franzblau A, et al.: Absence of Formic Acid 

Accumulation in Urine Following Five Days of 

Occupational Methanol Exposure. Appl Occup 

Environ Hyg 8:883-888, 1993 

Xiao HK, Levine SP: Application Of Computerized 

Differentiation Technique to Remote Sensing Fourier 

Transform Infrared Spectrometry for Analysis of 

Toxic Vapors. Anal Chem 65:2262-2269, 1993 

Xiao H, Levine SP, Nowak J, Puskar M, Spear RC: 

Analysis of Organic Vapors in the Workplace by 

Remote Sensing Fourier Transform Infrared 

Spectroscopy. Am Ind Hyg Assoc J 54(9):545-556, 

1993 

Yost MG, Spear RC, Xiao HK, Levine SP: 

Comparative Testing of A Remote Sensing Optical 

System with Area Samplers in A Controlled 

Ventilation Chamber. Amer Ind Hyg Assoc J 

53:611-616, 1992 

Xiao HK, Levine SP, Nowak J, Puskar M, Spear R: 

Analysis of Organic Vapors in the Workplace by 

Remote Sensing Fourier Transform Infrared 

Spectroscopy. Amer Ind Hyg Assoc J, accepted, 

1992 

Wythoff B, et al.: Computer-Assisted IR ldent of 

Vapor-Phase Mixture Components. J Chem Info 

Comp Sci, 31:392-399, 1991 

Xiao HK, Levine SP, Herget WF, D' Arey JB, Spear 

R, Pritchett T: A Transportable Remote Sensing 

Infrared Air Monitoring System. Amer Ind Hyg 

Assoc J 52:449-457, 1991 

Franzblau A, et al.: The Use of A Transportable 

FTIR Spectrometer for the Direct Measurement of 

Solvents in Breath & Ambient Air: Methanol. Amer 

Ind Hyg Assoc J 53:221-227, 1991 
Page 146 - Other Occupational Needs 

Levine SP, et al.: FTIR Least Squares Method for 

the Quantitative Analysis of Multi-Component 

Mixtures of Airborne Vapors. IN: Measurement of 

Toxic and Related Air Pollutants, Air Waste Manage. 

Assoc., Pittsburgh, PA, pp 895-900, 1990 

Minimizing Work Schedule 

Disruption with Bright Light 

Scott S. Campbell, Ph.D. 

New York Hospital - Cornell Medical Center 

Institute of Chronobiology 

Department of Psychiatry 

21 Bloomingdale Road 

White Plains, New York 10605 

Program Area: Other Occupational Needs 

Grant Number: 5 ROI OH02758-02 

Start & End Dates: 05/01/92 - 04/30/94 

Funding Level: $142,120 ($295,783 Cum) 

Importance to Occupational Safety and Health 

It is generally acknowledged that almost 

three-quarters of the 20 million shift workers in the 

United States suffer from a variety of symptoms 

associated with the maladjustment of their circadian 

rhythms to an ever-changing work schedule. The 

cost of shift work due to accidents, loss of 

productivity, and increased health care demands is 

staggering. Recently, the aggregate social cost was 

estimated at approximately 70 billion dollars annually. 

Despite the magnitude of the problem, traditional 

approaches to reducing the impact of shift work have 

been largely unsuccessful. The traditional use of 

hypnotics to treat sleep disturbance in shift work 

populations is complicated by a number of factors, 

the most problematic of which are hangover effects 

on waking function and the potential for abuse. 

Attempts to implement behavioral strategies that 

address more closely the etiology of the disturbance 

have been largely unsuccessful due to compliance 

problems. 

Objectives 

In contrast, the use of bright light offers a safe 

and viable alternative to hypnosis. The approach 

offers rapid action without the drawbacks associated 

with pharmacological interventions. There is 

substantial evidence that exposure to bright light is 

effective in modifying both the phase and the 

amplitude of circadian rhythms, which in tum, can 

improve sleep quality and waking function. This 

knowledge has already been applied successfully in 

clinical circadian disorders, but surprisingly, it has 

not been used to address the problems associated with 

circadian adaptation to shift work. Because night 

shift workers are awake, and thus available, to 

receive light during intervals in which the most 

robust physiological effects have been demonstrated, 

they constitute an ideal population for such an 

approach. 

Methodology 

In previous studies, we have shown that two 

distinct components of bright light exposure are 

effective in alleviating sleep and/or performance 

deficits associated with rotating shift work. Timed 

exposure to a 4-hour pulse of very bright light 

(>6000 lux) on the first night of shift work facilitates 

adaptation by rapidly shifting circadian phase by up 

to five hours. Such re-setting of the biological clock 

improves daytime sleep quality and subsequent onshift performance. In addition, exposure to ambient 

light of less intensity (approximately 1000 lux) 

throughout the night shift results in an immediate 

enhancement of alertness and performance efficiency. 

This effect is probably not the consequence of 

changes in the circadian timing system, but rather the 

result of a direct cortical activating effect of bright 

light exposure. 

The current study seeks to examine the effects of 

a light regimen that combines these two components 

during a simulated shift work protocol. Because 

middle-aged shift workers suffer most from shift 

work maladaptation, it is these individuals who are 

likely to benefit most from the implementation of 

bright light interventions. As such, we are comparing 

rates of physiological and behavioral adaptation in 40 

to 60 year old subjects in the combined bright light 

condition and a control conditions. It is expected that 

these important and necessary laboratory-based, 

simulated night shift studies will form the basis for 

subsequent investigations to evaluate the efficacy of 

such interventions in applied settings. 

Significant Findings 

Data acquisition is ongoing. The results reported 

here are from a group of subjects whose data have 

been fully analyzed. As such, the findings should be 

considered preliminary. 

Bright light had the expected result on the 

circadian timing system. By the third night of shift 

work the Active group showed a mean delay in the 

course of body core temperature of over seven hours, 

whereas, the Control group exhibited a mean delay of 

less than four hours. Despite this, there was no 

significant difference between the Active and Control 
groups in any measure of sleep quality following light 

exposure, with both groups exhibiting substantial 

reductions in the ability to sleep relative to Baseline. 

Post-hoc t-tests revealed significant reductions in 

sleep efficiency and significant increases in 

wakefulness after initial sleep onset. In addition, in 

the Active group, total sleep time declined by an 

hour. Similarly, analyses revealed that by the third 

night of shift work, no differences in performance 

were evident between the Active and Control 

subjects. 

These results suggest that bright light treatment 

in middle-aged subjects may be less effective than 

equivalent interventions in younger subjects. It is 

essential that the issue of possible differential age 

effects be clarified if bright light interventions are to 

be of maximum benefit in the applied setting. 

Publications 

Campbell SS: Effects of Bright Light Exposure on 

Shift Work Adaptation in Middle-aged Subjects. 

Sleep Research, in press, 1994 

Campbell SS, Dawson D and Zulley J: When The 

Human Circadian System Is Caught Napping: 

Evidence For Endogenous Rhythms Close To 

Twenty-four Hours. Sleep 16(7):638-640, 1993 

Campbell SS: Alerting/activating Effects of Light. 

Sleep, in press, 1993 

Campbell SS and Broughton RJ: Declining Body 

Temperature Prior To Sleep Initiation: Fluffing The 

Physiological Pillow? Chronobiology International, 

in press, 1993 

Campbell SS: Effects of Sleep and Circadian 

Rhythms on Performance. In: Handbook of Human 

Performance, Volume 3, (eds A Smith, D Jones) New 

York, Academic Press, pp. 195-216, 1992 

Other Occupational Needs - Page 147 

Measurement of Alkenyl/Epoxy DNA 

Adducts by GC-MS 

Roger W. Giese, Ph.D. 

Northeastern University 

Pharmaceutical Sciences Department 

360 Huntington Avenue 

122 Mugar Building 

Boston, Massachusetts 02115 

Program Area: Other Occupational Needs 

Grant Number: 5 ROI OH02792-03 

Start & End Dates: Ol/01/91 - 12131/93 

Funding Level: $136,446 ($401,386 Cum) 

Importance to Occupational Safety and Health 

DNA is an ultimate target in the body for 

carcinogenic and mutagenic chemicals. 

Measurements of DNA adducts therefore can help to 

sort out some of the uncertainties in exposure and 

risk assessment arising from exposure of individuals 

to chemicals. Our understanding of the biological 

significance of chemical damage to DNA is 

dependent on our ability to measure it. 

Objectives 

New analytical methodology is being developed 

to measure DNA adducts arising from occupational 

human exposure to ethylene, ethylene oxide, 

butadiene, styrene, and propene. These chemicals 

were selected since they are widely used and 

genotoxic. Also, they are anticipated to give similar 

types of DNA adducts. 

Methodology 

The proposed methodology basically comprises 

four steps: (I) isolate the DNA from a biological 

sample; (2) separate the DNA adducts from the bulk 

of the DNA; (3) derivatize the adducts with an 

electrophoric reagent; and (4) detect the electrophoric 

products by gas chromatography-electron capture 

negative ion-mass spectrometry (GC-ECNI-MS). 

Significant Findings 

For the N7 ethylene oxide adduct of guanine 

(N7-EO-G), we have developed a procedure that 

detects 1 picogram (5 femtomoles) of a standard of 

this adduct. We are now extending the method so 

that it will detect this adduct derived from a DNA 

sample. 
Page 148 - Other Occupational Needs 

Both solid phase extraction and HPLC are 

important sample cleanup techniques for the kind of 

methodology that we are developing. We compared 

their performance for the second derivatization 

reaction (a penafluorobenzylation) of the N7-EO-G 

and found that HPLC has a carryover problem. This 

problem was found to be due to the injector. We 

demonstrated that the use of two injectors overcomes 

the carryover problem. 

We have begun work on the detection of the 

corresponding Q6 -G ethylene oxide adduct. A novel 

chemical transformation reaction was required for this 

adduct that would retain the Q6

-hydroxyethyl group. 

This has been achieved by converting the exocyclic 

amino to fluoro. 

Some of the trace contamination in our 

methodology was found to derive from the Teflon 

liner and plastic cap employed to seal the reaction 

vial. This was overcome by introducing an all-glass 

vial. A patent application has been submitted by 

Northeastern University for this invention. 

Our work is significant in two general respects. 

First, is the general significance of detecting DNA 

adducts in humans as biomonitors for exposure to 

chemicals. Second, is the broader methodological 

significance of the new chemical and physical 

techniques that we have developed to date for the 

N7-G and .Q6-G ethylene oxide adducts. 

Publications 

Giese RW, Saha M, Abdel-Baky S, Allam K: 

Measuring DNA Adducts by GC-EC-MS: An 

Example of Trace Organic Analysis. Meth Enzymol, 

in press, 1993 

Saha M, Giese RW: HPLC vs Solid Phase 

Extraction for Post-Derivatization Cleanup Prior to 

GC-ECNI-MS for N l ,N3-Bis-(pentafluorobenzyl)-

N7-(2-[pentafluorobenzyloxy }-ethyl)xanthine, A 

Product Derived from an Ethylene Oxide DNA 

Adduct. J Chromatogr 629:35-40, 1993 

Saha M, Giese RW: Primary Contribution of the 

Injector to Carryover of a Trace Analyte in HPLC. 

J Chromatogr 631:161-163, 1993 

Saha J, Saha M, Giese RW: 

4-(Trifluoromethyl)-2,3,5,6-Tetrafluorobenzyl 

Bromide: A New Electrophoric Derivatizing 

Reagent. J Chromatogr 641 :400-404, 1993 

Chiu CS, Saha M, Abushamaa A, Giese RW: 

Chemical Transformation/Derivation of 0 6-Methyland 0 6

-(Hydroxyethyl)guanune for Detection by GCEC-MS. Anal Chem 65:3071-3075, 1993 

Abdel-Baky S, Allam K, Giese RW: Derivatization 

in Trace Organic Analysis: Use of an All-Glass 

Conical Reaction Vial. Anal Chem 64:2882-2884, 

1992 

Abdel-Baky S, Giese RW: Gas 

Chromatography/Electron Capture Negative-Ion 

Mass Spectrometry at the Zeptomole Level. Anal 

Chem 63(24):2986-2989, 1991 

Dosimetry for Workplace EMFs at 

Power-Line Frequencies 

Om P. Gandhi, Sc.D. 

University of Utah 

College of Engineering 

Department of Electrical Engineering 

3280 Merrill Engineering Building 

Salt Lake City, Utah 84112 

Program Area: Other Occupational Needs 

Grant Number: I ROI OH02945-0l 

Start & End Dates: 05/01192 - 11/30/94 

Funding Level: $0 ($118,188 Cum) 

Importance to Occupational Safety and Health 

There is an increasing concern that 

electromagnetic fields (EMFs) at power frequencies 

may have health effects. A key research need, 

therefore, is to establish the mechanisms of bioeffects 

of these EMFs. An important aspect of this is to 

understand the coupling of the EMFs to the tissues in 

the human body. Knowledge in this area is relatively 

poor, since, in the past, only simple saline-filled and 

metal-coated idealized models have been used. 

Objectives 

The focus of our project is to obtain internal 

electric fields and induced current densities in 

heterogeneous, anatomically based models of the 

human body for a variety of worker exposure 

conditions encountered in occupational situations. 

Another objective is to develop two new instruments, 

namely the contact-current meter and the 

stored-energy meter, which may be used to assess the 

potential for shock and bums in the EMF workplace. 

Using an equivalent circuit as the human surrogate, 

the contact-current meter will measure the current 

that will flow for different conditions of contact such 

as finger or grasping contact, with or without 

rubber-soled shoes, and with or without safety 
gloves. Likewise, the stored-energy meter will 

measure the open-circuit voltage and short-circuit 

current for various locations of possible worker 

contact, allowing an evaluation of the stored energy 

which is related to the possibility of spark discharge 

for transient contacts. 

Methodology 

The accomplishments of the O l year of the 

project are as follows: 

l. We have developed a new high-resolution model 

of the human body based on the magnetic 

resonance imaging scans of a male volunteer that 

were taken with a resolution of 3 mm along the 

height of the body and 1.875 mm for the 

cross-sectional planes. For this model we have 

incorporated the an isotropic conductivities of the 

various tissues such as the skeletal muscle and 

heart that are important for power-frequency 

EMFs. We have started to use this model to 

calculate induced electric-field and 

current-density distributions for exposure of the 

human body to incident vertical electric fields 

(up to l O kV /m) and horizontal magnetic fields 

(up to 50 μT) associated with high-voltage 

power transmission and distribution lines. 

2. We have developed computer graphical methods 

to obtain color pictures of the spatial variations 

of the calculated electric-field and current 

density distributions for the various cross 

sections of the body. Because of the fairly high 

electrical conductivity associated with regions of 

the cerebrospinal fluid (CSF), the highest current 

densities are calculated for these regions. We 

are also examining the current densities and 

E-fields induced for the region of the pineal 

gland, since alterations in the melanonin levels 

have been observed in laboratory animals 

exposed to EMFs at power frequencies. 

3. We have started to calculate the induced currents 

in the human body for exposure to EMFs 

encountered in the workplace. To date we have 

calculated currents induced in the human arm 

and the body by the spatially varying magnetic 

fields of an electric drill and for linemen exposed 

to magnetic fields of high-voltage power 

transmission lines. 

4. We have fabricated prototype contact current and 

stored energy meters to assess the potential for 

electrical and for hazardous transient spark 

discharges in the EMF workplace situations. 

The specifications for the contact-current meter 

are 0-50 mA and for the stored energy meter 

are 0-15 kV open circuit voltage and 0-50 mA 

short circuit current, respectively. 

Other Occupational Needs - Page 149 

Significant Findings 

l. The highest induced electric fields and current 

densities for a hand drill are for the front half of 

the right arm and for the sections of the torso 

that are in proximity to the hand drill. For a 

power drill with a maximum magnetic field of 

500 μT the section-averaged current densities for 

the hand are as high as 2.5 mA/m2 and the 

highest local current densities are on the order of 

8.5 mA/m2. 

2. For linemen working on high-voltage power 

transmission lines the magnetic fields may be as 

high as S Gauss (500μT). Since these repairmen 

are often in a horizontal position parallel to the 

high-voltage line, they are subjected to these high 

magnetic fields that are fairly uniform over the 

extent of the body and are generally in the 

direction of arm to arm of the body. For such 

exposures we calculate a maximum induced 

current density of 1.0 mA/m2 and a maximum 

induced electric field of 7.3 mV/m. 

We have surveyed the magnetic fields at the 

power generation facilities of a utility company. The 

highest magnetic fields on the order of 0.5 - 0.7 

Gauss were found close to the output leads of the 

power generators. These magnetic fields were 

generally vertical and the highest magnetic fields 

occurred for the region of the floor above these leads 

or else underneath the leads on the primary side of 

the voltage step-up transformer. Using the 

millimeter resolution model of the human body we 

are presently calculating the induced current densities 

and electric fields for such occupational 

environments. 
Page 150 - Other Occupational Needs 

Biological Monitoring of Methanol 

Exposure 

Alfred Franzblau, MD. 

University of Michigan 

School of Public Health 

Department of Environmental 

& Industrial Health 

1420 Washington Heights 

Ann Arbor, Michigan 48109-2029 

Program Area: Other Occupational Needs 

Grant Number: J ROI OH03024-0I 

Start & End Dates: 02/01/93 - 01/31195 

Funding Level: $176,191 ($176,191 Cum) 

Importance to Occupational Safety and Health 

Methanol has been selected by the U.S. 

government as a primary candidate for promotion as 

an alternative automotive fuel. Usage as an 

automotive fuel would involve vastly greater 

opportunities for chronic low-level exposure of 

workers and consumers to methanol than have existed 

in the past. Human health effects related to chronic, 

low-level methanol exposure are largely unknown. 

There have been no human epidemiological studies 

focused on the effects of chronic low-level methanol 

exposure, and results of animal studies are difficult to 

extrapolate to humans because of significant 

differences in the metabolism and toxicity of 

methanol in most animal models. An essential 

component of any human epidemiological 

investigation of the effects of chronic low-level 

methanol exposure will be exposure assessment of 

subjects. Methanol is quite well absorbed via all 

major routes of exposure (gastrointestinal, inhalation, 

and dermal), so biological indicators of methanol 

exposure would provide more accurate assessment of 

the total absorbed dose, in comparison to routine 

measurements of the airborne concentration of 

methanol that are usually applied in the industrial 

setting. Although two approaches to biological 

monitoring of occupational methanol exposure have 

been endorsed by the ACGIH, the published data 

supporting these methods are limited, and in some 

areas, are contradicted by more recent reports. The 

data and analyses from this study will permit 

separate, quantitative examination of the major factors 

which are believed to influence biological indicators 

of methanol exposure in the occupational setting: 

airborne concentration of exposure; duration of 

exposure; level of pulmonary ventilation; and 

cutaneous exposure. 

Objectives 

The goal of this research is to identify valid, 

reproducible, and noninvasive methods for 

biologically monitoring occupational methanol 

exposure, and to assess quantitatively the impact of 

exercise and cutaneous methanol exposure on such 

indices. The underlying approach will be to perform 

a series of controlled experiments with volunteer 

subjects. Specific aims are to investigate the: 

1. Use of formic acid (formate) in urine as a 

quantitative biological exposure indicator for 

exposure of humans to methanol via the 

inhalation route and via the cutaneous route; 

2. Use of methanol in urine as a quantitative 

biological indicator for exposure of humans to 

methanol via the inhalation route and via the 

cutaneous route; 

3. Use of methanol in end-expired (alveolar) air as 

a quantitative biological exposure indicator for 

exposure of humans to methanol via the 

inhalation route and via the cutaneous route; 

4. Effect of exercise, as measured by the ventilation 

rate, on formic acid in urine, methanol in urine 

and methanol in end-expired air when humans 

are exposed to methanol via the inhalation route. 

Methodology 

The study will involve two sets of separate 

human experiments. In the first, paid volunteer 

subjects will undergo controlled exposures to 

methanol vapor in an exposure chamber. Each 

subject will have 10 separate chamber exposure 

sessions consisting of 5 different methanol exposure 

levels, and two levels of exercise/pulmonary 

ventilation. This is a complete block design 

experiment in that each subject will under each 

combination of 'treatments' (5 levels of methanol 

exposure and 2 levels of exercise/pulmonary 

ventilation). Exposure sessions will last 

approximately 8 hours. Breath, blood and urine 

specimens will be collected before, during and after 

exposures. It is our goal to have 12 subjects 

complete this entire protocol. Methanol in urine and 

blood, and formic acid in urine will be assayed using 

gas chromatography. Methanol in breath will be 

measured using Fourier transform infrared 

spectroscopy. Minute ventilation at rest and during 

controlled exercise will be quantitated using standard 

pulmonary function methods. 

The second set of experiments will address 

dermal methanol exposure and absorption. Each paid 

volunteer subject will have 5 separate exposure 

sessions consisting of different durations of controlled 

dermal exposure to methanol. Again, this is a 

complete block design experiment. Each level of 
exposure is a 'treatment', and each subject will 

complete each 'treatment'. Dermal exposure of one 

hand to methanol will vary from zero to 8 minutes, 

and possibly up to 16 minutes. Baseline breath, 

blood and urine specimens will be collected before 

exposure begins, and will then be repeated at timed 

intervals for up to 8 hours following cessation of 

exposure. The goal is for 12 subjects to complete 

this entire protocol. Methanol in urine and blood, 

and formic acid in urine will be assayed using gas 

chromatography. Methanol in breath will be 

measured using Fourier transform infrared 

spectroscopy. 

Significant Findings 

The project started on 2/1/93. The focus of the 

first year of the project has been on writing and 

validating laboratory protocols for analyses of blood, 

urine and breath specimens, recruitment of volunteer 

subjects, and initiation of human experiments. 

The first cycle of inhalation exposures was 

completed in October of 1993. This experiment 

involved 4 volunteer subjects. Exposure sessions 

generally involved all four subjects simultaneously. 

During each exposure session 2 subjects remained 

sedentary, and the other two subjects performed 

intermittent exercise on a bicycle ergometer. The 

minute ventilation of all subjects was quantitated both 

at rest and during exercise. The methanol exposures 

lasted approximately 8 hours. Subjects did not report 

any odor or irritant effects. Blood, urine and breath 

specimens were obtained before, during and 

immediately after cessation of exposure to methanol. 

The first round of inhalation exposures has 

generated a large quantity of data. Preliminary 

analyses of these data indicate the following: 

(1) Methanol levels in urine and blood rapidly rise 

following exposure and approach a steady state level 

after an exposure period of approximately 5 hours; 

(2) Uptake and metabolic rates calculated from blood 

and urine data are in rough agreement with results of 

multicompartment models using parameters obtained 

from the literature; (3) concentrations of methanol in 

breath very rapidly approach equilibrium with 

chamber air, and do not reflect alveolar air, as 

demonstrated by very significant drops in 

concentrations of methanol in breath upon leaving the 

exposure chamber; ( 4) blood and urine concentrations 

of methanol appear roughly proportional to the 

methanol exposure level at steady-state; 

(5) inter-subject variability can be high, especially 

for methanol concentrations in urine and blood levels; 

(6) In some cases, e.g., low exposure experiments, 

several pre-exposure tests are needed to determine 

the absolute level and trend of background levels. 

The first cycle of dermal methanol exposures 

was initiated in October of 1993, and will be 

Other Occupational Needs - Page 151 

completed in January of 1994. This· experiment 

involves 4 subjects during each experimental session. 

Dermal exposures consist of putting one hand into a 

beaker of methanol (up to the distal wrist crease) for 

varying periods of time (from zero minutes up to 8 or 

16 minutes). Two sessions (4 minutes and 8 minutes) 

have been completed. Blood, urine and breath 

specimens were/will be obtained before exposure, and 

at timed intervals up to 8 hours following cessation of 

exposure. 

Publications 

Franzblau A, Lee EW, Schreck RM, D' Arey JB, 

Santrock J, Levine SP: Absence of Formic Acid 

Accumulation in Urine Following Five Days of 

Methanol Exposure. Applied Occup Environ Hyg, 

in press, I 993 

Franzblau A: I 993-I 994 Threshold Limit Values for 

Chemical Substances and Physical Agents and 

Biological Exposure Indices. ACGIH, Cincinnati, 

OH, 1993 

Knowledge-Based Framework For 

Automating Hazop Analysis 

Venkat Venkat, Ph.D. 

Purdue University 

School of Engineering 

Department of Chemical Engineering 

West LaFayette, Indiana 47907 

Program Area: Other Occupational Needs 

Grant Number: I ROI OH03056-0JAJ 

Start & End Dates: 09/15/93 - 09/14196 

Funding Level: $213,908 ($213,908 Cum) 

Importance to Occupational Safety and Health 

Occupational safety and health hazards pose 

threats to an estimated 20 million workers in the 

manufacturing sector in the United States. Industrial 

statistics show that even though major catastrophies 

and disasters of chemical plants may be infrequent, 

minor accidents are very common, occurring on a day 

to day basis, resulting in many occupational injuries, 

illnesses, and costing the society billions of dollars 

every year [CMA, 1991]. For example, in 1983 

alone over 3,000 job related deaths and an estimated 

4.9 million job-related injuries and illnesses occurred 

[Bureau of Labor Statistics, 1985]. It is also 

estimated that the annual cost to society of 
Page 152 - Other Occupational Needs 

work-related injuries, illnesses, and deaths has nearly 

tripled from $11.5 billion in 1972 to $33.0 billion in 

1984 [National Safety Council, 1985; McGraw-Hill 

Economics, 1985]. 

The occurrence of several catastrophic accidents 

in the refining and chemical industries during the 

1980s has intensified public concern about process 

safety. The chemical industry, the federal 

government, and many state governments have 

responded to address these concerns in the form of 

new guidelines and requirements. The recently 

published final Occupational Safety and Health 

Administration (OSHA) standard on process safety 

management, Rule 29 CFR 1910.119 [OSHA, 1992], 

requires the use of a process hazards analysis (PHA) 

technique for the Identification of hazards for process 

systems containing toxic substances and/or flammable 

process materials above specified threshold quantities. 

OSHA estimates that such a process hazards analysis 

will be required at approximately 25,000 existing 

plant sites in the U.S. and for all the new ones that 

are built or retrofitted in the future [Freeman et. al., 

1992]. At a typical plant site, five to ten different 

PHA studies will be needed to comply with the 

OSHA standard. This comprehensive mandatory 

review of process hazards will directly impact on the 

safety of about one million workers who are 

employed in the chemical industry, and many millions 

of people residing in the neighboring communities 

surrounding chemical plants [CMA, 1991]. It is 

estimated that about I 00 million person-hours and 

IO billion dollars might have to be spent using the 

current PHA approaches to meet this new regulation 

[Freeman et. al., 1992]. This project proposes to 

develop a novel computer-based framework that has 

a great potential to decrease this massive effort and 

also increase the productivity by providing for a fast, 

systematic, thorough, and detailed analysis of routine 

process hazards. 

Objectives 

HAZOP analysis is the study of systematically 

identifying every conceivable deviation, finding all 

the possible abnormal causes, and the adverse 

hazardous consequences of that deviation in a 

chemical plant (Kletz, 1991, McCluer and Whittle, 

1992). This is a very difficult, labor-intensive and 

time-consuming process. Such an analysis is often 

carried out by a group of experts poring over the 

process P&IDs for weeks or months, applying a set 

of 'guide words' to the process variables associated 

with each process line and equipment, and finding the 

causes and consequences for those process variable 

deviations. This is a major labor- and knowledge 

intensive problem that can benefit from automation 

using Artificial Intelligence (AI) techniques. An 

automated HAZOP system can cut down on the time 

and effort involved in performing a HAZOP review, 

make the review more thorough, complete, and 

detailed, and minimize or eliminate human errors. 

The main goal of this proposal is to develop a 

knowledge-based system for automating certain 

aspects ofHAZOP analysis and demonstrate its utility 

and performance on complex, industrial-scale, 

HAZOP case studies. Related subgoals involve the 

solution of various problems such as process 

knowledge representation, search and inference, 

HAZOP models development, system modification, 

validation and maintenance, graphical user interfaces, 

information overload 

Methodology 

The automation of HAZOP analysis demands the 

solution of a number of important problems as listed 

below: 

Ability to represent different types of 

knowledge such as if-then heuristics, 

cause-and-effect relationships, procedures, 

default reasoning, etc. 

Recognizing and representing that certain 

types of knowledge are the same for 

different process plants and certain other 

types of knowledge are unique to the process 

at hand 

Dealing with the propagation of causes and 

effects due to abnormal deviations through 

out the process plant, both in the forward 

and the reverse directions of material flow 

Handling loops and recycles in the plants 

Developing a convenient graphical 

user-interface that facilitates the use of the 

automated system for inputting knowledge, 

to perform HAZOPs on various sections of 

the plant, to generate explanations about 

what is going on, etc. 

Have interfaces to download information 

about the plant from P&ID diagrams and 

plant databases 

In our proposed framework, we address all these 

problems and some other related issues by utilizing 

several novel techniques as listed below: 

A generalized object-oriented framework is 

used as the backbone of the system that will 

be able to represent and organize all kinds of 

knowledge including heuristics, causal 

models, procedures etc. This is a very 

powerful framework that will facilitate 

default reasonings, reasoning with composite 

objects, provide flexibility of control, 

facilitate inter-object communications etc. 
The problem of representing knowledge in 

HAZOP expert systems can be tackled if we 

divide the knowledge required for HAZOP 

into "process general" and "process 

specific" knowledge and allow for 

interactions between these two tiers of 

knowledge. This way, the general, basic 

knowledge required for performing HAZOP 

can be kept in the process general 

knowledge base, which remains fixed 

irrespective of the process plant under 

consideration and the process specific 

knowledge can be created separately for 

each process plant. 

The 'process general' knowledge would be 

stored as a library of causal models that 

capture all the generic features of the 

process equipments and their behavior, 

represented as objects accessible through 

icons of the graphical user-interface. 

The 'process specific' knowledge would 

consist of the type of the process materials, 

properties of process materials, the 

knowledge about the reactions and the type 

of the reactions (exothermic, endothermic, 

etc.), and the topology of the process units 

in the process plant under consideration. 

The process specific knowledge will be 

supplied n the user for each process plant. 

A sophisticated 'message-passing' inference 

mechanism that provides for reasoning about 

the causes or abnormal deviations all the 

way to their root and to propagate the 

consequences all the way to the end. Thus, 

it can make the knowledge-based system 

reason forward and backward of material 

flow in the plant. 

An object-oriented graphical user-interface 

to attend to the needs of the developer and 

the user. 

Significant Findings 

None to date. 

Other Occupational Needs - Page 153 

Statistical Issues For Compliance to 

Exposure Standards 

Michael J Symons, Ph.D. 

University of North Carolina 

School of Public Health 

Department of Biostatistics, CB #7 400 

Chapel Hill, North Carolina 27599-7400 

Program Area: Other Occupational Needs 

Grant Number: 1 R18 OH03073-01 

Start & End Dates: 09/15/93 - 09/14/95 

Funding Level: $68,139 ($68,139 Cum) 

Importance to Occupational Safety and Health 

NIOSH's Occupational Exposure Sampling 

Strategy Manual (Manual) contains industrial hygiene 

and statistical guidelines for sampling occupational 

environments and analyzing exposure data. The 

consequence of selecting high risk employees, namely 

those with maximum exposures, however, is not 

recognized in the analysis of this sampling for 

compliance to an environmental standard in a 

workplace. The application of extreme value theory 

will be explored. 

Objectives 

Three areas of statistical investigation are 

proposed: (I) to apply the theory of extreme values 

in the analysis of exposure measurements obtained by 

compliance sampling; (2) to examine alternative 

assumptions about the distribution of exposures by 

comparing a nonparametric procedure with fitting of 

a Burr XII distribution to exposure measurements; 

(3) to address the time series sampling of 

occupational environments by incorporating serial 

correlation into the analysis models. 

Methodology 

Applying the sampling theory of extreme values 

is the major objective. Specifically, the distribution 

of a maximum deals with the Manual's sampling of 

high risk employees and selection of the greatest 

exposure sites for evaluating ceiling standards. The 

basics of compliance sampling is to document the 

maximum exposures. The exact distribution of the 

maximum in samples from a specific distribution and 

the limiting Gumbel distribution of extremes are two 

aspects of the approach. And, knowing the number 

of workers/sites at lower exposures should be 

informative. 
Page 154 - Other Occupational Needs 

The concern for the distribution of exposure 

measurements will be addressed in two ways. First, 

a Bayesian nonparametric approach to compliance 

classification is provided and will be compared with 

parametric procedures. Second, an empirical feel for 

the relevance of normal, lognormal, Weibull and 

gamma distributions will be gained by plotting a 

variety of occupational exposure data on a 

moment-ratio diagram. Since the relevant portion of 

the skewness-kurtosis plane is covered by the Burr 

XII distribution, the fit of this distribution to a variety 

of exposure data will be explored. 

The effect on compliance decisions of correlated 

exposures will also be examined. Short, partial-shift 

samples collected on a maximum risk employee 

during a single shift are likely to exhibit higher serial 

correlation than a sequence of 8-hour samples. 

First-order autoregressive models will appropriately 

increase estimates of variance, for example of mean 

exposures. Consequently, not incorporating 

autocorrelation may result in anti-conservative 

inferences. 

Significant Findings 

None to date. 

Physiologic Sampler For Airborne 

Health Hazards 

Michael G. Yost, Ph.D. 

University of Washington 

School of Public Health 

Department of Environmental Health 

Mail Stop SC-34 

Seattle, Washington 98195 

Program Area: Other Occupational Needs 

Grant Number: I ROI OH03134-0l 

Start & End Dates: 09/30/93 - 09/29/96 

Funding Level: $119,762 ($119,762 Cum) 

Importance to Occupational Safety and Health 

Inhalation exposures are typically assessed by 

personal breathing zone air monitoring using a 

constant flow sampling device. Although breathing 

zone sampling accounts for spatial and temporal 

variability in the air concentrations, it does not take 

into account spatial and temporal variability in the 

uptake of contaminants due to changes in pulmonary 

ventilation rate. This may well represent an 

important source of variability in exposure to 

inhalation hazards, since many common work tasks in 

construction generate exposures coupled with 

increased physical activity which alters breathing 

rates. 

Furthermore, efforts to measure body burden of 

volatile organic compounds (VOC) have employed 

several methods, including breath sampling, to 

estimate the contaminant concentration in blood. 

Interpretation of these readings in complicated by the 

pharmacokinetics of VOC in humans, which can vary 

widely for different compounds. Single time-point 

measurements have limited value when attempting to 

estimate body burden from breath samples; multiple 

time course (washout) measurements however, can 

provide the basis for estimating decay rates and, in 

many cases, body burden. The difficulty with 

multiple measurements is the additional time they 

impose on workers, and increased analytical costs to 

employers. A simple and rapid breath analysis 

method, particularly one that employs a direct reading 

instrument and a repeated measures sampling strategy 

optimized to account for the wide range of VOC 

excretion rates, could provide a cost effective method 

for breath monitoring. 

Objectives 

The hypothesis of this project is that a personal 

air sample whose volume is proportional to the 

construction worker's inhaled air volume will yield a 

measure of inhalation exposure which is better 

correlated with the body burden, estimated through 

biological monitoring, than a constant flow air sample 

taken in the traditional way. If supported, this 

hypothesis will lead to significant improvement in the 

estimates of construction worker exposure to VOC 

using personal air sampling. 

The specific aims of this study are: 

I. to develop a physiologic sampling device, which 

samples at a rate proportional to an individual's 

pulmonary ventilation rate, and which can be 

worn as a free ranging personal monitor suitable 

for construction workers. Data on VOC 

concentration and exposure rate collected with 

this sampler from active subjects Wider 

laboratory conditions will be compared to 

conventional personal samples and to breath 

samples. 

2. to use a novel instrument, the Rapid Exhaled 

Breath Analyzer (REBA), for monitoring expired 

air from solvent exposed construction workers. 

This direct reading instrument employs a 

customized Fourier Transform Infrared (FTIR) 

spectrometer to measure VOC mixtures in breath 

samples. Existing pharmacokinetic data for 

several target voe will be used to develop a 

repeated measures sampling strategy aimed at 
providing an estimate of body burden and hence 

absorbed dose, to be compared with the two 

measures of inhalation exposure. 

3. to conduct a field pilot study using the 

physiologic sampler and REBA to analyze air 

and breath samples from solvent-exposed 

construction workers. The field pilot study will 

provide data to explore both the analytical 

sensitivity and sampling strategy that is most 

appropriate for voe exposures in the 

construction industry. 

Methodology 

The sampling pump will use an input signal, 

derived from either heart rate or thoracic dimensions 

to alter the air flow rate. Thus the amount of 

contaminant collected during the sampling period will 

be proportional to the mass inhaled by the worker. 

This contrasts with the traditional constant flow 

sampling methods which give a result proportional to 

the average ambient concentration of contaminant. 

The sampler will first be validated in laboratory 

experiments in which volunteers will wear the 

sampler while exercising on a bicycle at rates chosen 

to simulate work rates on construction jobs. Once 

validated in the controlled setting, the device will be 

placed on selected workers at local construction sites 

where exposure to paint solvents occurs. 

Performance of the sampler will be evaluated by 

taking breath samples from the workers at the start of 

the next shift to estimate absorbed dose. A high 

correlation between absorbed dose from breath 

samples and the physiologic sampler measurement 

will demonstrate the effectiveness of the new method. 

Significant Findings 

None to date. 

Other Occupational Needs - Page 155 

Evaluation of Controls Protecting 

Lead-Exposed Workers 

Lewis D. Pepper, MD. 

Boston University 

School of Public Health 

Department of Environmental Health 

80 E. Concord Street, T3-C 

Boston, Massachusetts 02118 

Program Area: Other Occupational Needs 

Grant Number: I ROI OH03177-0l 

Start & End Dates: 09/30/93 - 09/29196 

Funding Level: $236,680 ($236,680 Cum) 

Importance to Occupational Safety and Health 

The study is a response to the persistent reports 

of elevated blood and air lead levels in bridge 

construction and maintenance activities and it 

represents an attempt to determine why high blood 

levels continue to occur despite government 

regulations and industry recommendations. It is 

designed to evaluate which work processes controls 

and practices contribute most to 'the lead 

overexposures and to determine whether and why the 

recommendations that have been made are or are not 

being implemented. Air and surface sampling as well 

as blood lead and changes in blood lead over a 

2-week period will be done as measures of the 

effectiveness of the lead exposure control programs 

in use at each job site. The lead exposure control 

programs will be evaluated through examination of 

background on the company; the controls in place at 

the work site; the processes and work practices used 

on the work site; and the knowledge and attitudes of 

the workers themselves. 

The investigators will provide the results of the 

blood lead tests to each study subject, and upon 

request, their physician. All blood test results will be 

reviewed by an occupational physician who will send 

a letter informing the individual of the health 

significance of the results and the recommended 

medical follow-up. Subjects will also be provided 

with a fact sheet describing the health effects of lead 

exposure. 

Project participants will be provided a project 

summary at the end of the study. Information to be 

included will be summary blood lead levels, 

environmental sampling data, study conclusions, and 

recommendations. The final report, which will be 

completed at the end of the study, will be provided to 

appropriate agencies and institutions, e.g., OSHA and 

EPA. 
Page 156 - Other Occupational Needs 

This study is one of the first evaluations of 

structural steel paint abatement activities following 

the extension of OSHA' s Lead Standard to the 

construction industry. The study, which uses 

innovative evaluation methods including the 

measurement of lead particle exposure in three 

particle size fractions, the creation of an ordinal index 

variables representing containment, ventilation, 

personal protection and similar variables using 

structured observations of work practices and the use 

of personal protective devices and control 

technologies, the use of blood lead observations over 

a defined interval, the use of ethnographic techniques 

(observation, questionnaires and semi-structured 

interviews) to assess worker and management 

awareness of lead poisoning issues associated with 

bridge repair work practices at each site, and the 

development of predictors of blood lead and air 

concentrations using industrial hygiene controls, work 

practice, training and company and worker attitude 

variables, will permit an early assessment of the 

impact of federal regulatory requirements and the 

barriers to optimal worker protection. 

Objectives 

The overall objective of this project is to 

determine why high blood levels continue to occur in 

bridge construction workers despite government 

regulations and industry recommendations. The 

project objective will be met through the following 

specific aims: 

1. Perform a set of structured observations of work 

practices and the use of personal protective 

devices and control technologies at times 

coinciding with the exposure measurements. 

These observations will be combined into ordinal 

index variables representing containment, 

ventilation, personal protection and similar 

variables. 

2. Measure lead particle exposure in three particle 

size fractions and perform surface wipe 

measurements for 150 Massachusetts bridge 

construction workers working in a variety of 

state Highway Department sites; there will be 

three to five exposure measurements during a 

two week study period at each site. 

3. Per for n a project baseline blood lead on this 

group, followed by a second measurement 

14 days later. 

4. Use ethnographic techniques (observation, 

questionnaires and semi structured interviews) to 

assess management and worker awareness of 

lead poisoning issues associated with bridge 

repair work practices at each site. 

5. Develop predictors of blood lead and air 

concentrations using industrial hygiene controls, 

work practice, training and company and worker 

attitude variables. 

Methodology 

This project is a cross-sectional survey of bridge 

repair and maintenance workers at work sites in 

Massachusetts. It is anticipated that project staff will 

visit fifteen work sites, and assess five workers at 

each site each year for two years. This will result in 

a total sample of 150 bridge workers in the survey. 

Workers will be interviewed in person using a 

questionnaire used in a previous study; they will also 

be asked to keep a work task diary during a 

two-week period. In addition, blood samples and air 

samples will be taken to determine individual-level 

exposures and biological markers of effect. Other 

information on environmental conditions and work 

practices will be gathered by project staff and used to 

construct a personal exposure score which will be 

used in the analysis. Blood lead levels at the 

beginning of the two week observation period will be 

compared with levels at the end. This is primarily to 

note whether biological measures changed 

significantly during the time period and, if so, to 

examine changes in job assignments or work tasks 

that might be associated with the changes. The mean 

blood levels for all workers involved in a particular 

task will be compared at the beginning and at the end 

of the two week observation period. The analysis of 

the data collected over the two year period will be 

focused on associations between specific work 

activities and environmental factors and blood lead 

levels and airborne lead levels for bridge repair and 

maintenance workers. The basic method of analysis 

will be analysis of variance (ANOV A) and analysis 

of covariance (ANCOV A). 

Significant Findings 

None to date. 
Microsensor Array for the 

Identification of Organic Vapors 

Edward T. Zellers, Ph.D. 

University of Michigan 

School of Public Health 

Department of Environmental 

and Industrial Health 

1420 Washington Heights 

Ann Arbor, Michigan 48109-2029 

Program Area: Other Occupational Needs 

Grant Number: 5 KOi OH00077-03 

Start & End Dates: 07/15/89 - 03/14193 

Funding Level: $0 ($90,878 Cum) 

Importance to Occupational Safety and Health 

This project was motivated by the need for 

improved sensor technology in compact 

direct-reading industrial-hygiene monitoring 

instruments for organic vapors. The high-cost, 

complexity, and/or poor selectivity of currently 

available direct-reading instruments preclude their 

use in routine personal exposure monitoring 

applications. Instruments employing SAW sensor 

arrays can provide rapid identification and 

quantification of a wide range of organic vapors of 

occupational health concern. The small size, 

versatility, and potential low cost of instruments 

based on SAW sensor technology promise 

improvements in the quality and quantity of data used 

to guide industrial hygiene exposure assessment and 

control efforts. 

Objectives 

This project has entailed a series of laboratory 

investigations of several performance parameters 

relevant to the deployment of instrumentation 

employing rnicrofabricated surface-acoustic-wave 

(SAW) chemical sensor arrays for the measurement 

of organic solvent vapors in the occupational 

environment. The primary goal was to develop 

arrays of coated SAW sensors and pattern recognition 

methodologies to provide optimal sensitivity and 

selectivity for each of a wide range of organic vapors 

when present alone or in simple mixtures. In 

addition, semi-empirical predictive models of sensor 

responses were developed and the effects of 

environmental variables were characterized. 

Other Occupational Needs - Page 157 

Methodology 

The prototype instrument tested here included an 

array of four 158-MHz quartz SAW oscillators, each 

having approximate dimensions 0.5 cm2

• The 

instrument was not optimized for field use. 

Sensitivity to organic vapors was achieved by coating 

each of the sensors with a polymer or high-boiling 

liquid into which the vapors would reversibly 

partition: vapor sorption increases the mass and 

decreases the elastic stiffness of the surface coating 

film which causes a commensurate shift in the 

oscillation frequency of the sensor. Responses from 

SAW sensors overlayed with each of 16 different 

isotropic polymer coatings were collected following 

exposure to each of up to 40 organic vapors 

representing 12 different chemical classes. Various 

binary vapor mixtures were also tested. Certain 

coatings were found to be unstable and were 

eliminated from further consideration. Response 

patterns for each vapor or vapor mixture were 

obtained from all possible combinations of four 

coated sensors in the data set. Pattern recognition 

analysis was used to decode the multidimensional 

sensor array output and to select optimal sets of 

coated sensors for inclusion in the array for a given 

set of vapor analytes. Subsets of coated sensors and 

vapors were examined at different temperatures and 

relative humidities. Semi-empirical predictive sensor 

response models were also developed. 

Significant Findings 

Limits of detection were typically in the range of 

1-80 ppm. Lower detection limits were generally 

obtained for the less volatile and more polar vapors. 

Measurement of most vapors below their 

ACGIH-TLV values was demonstrated. Recent 

improvements in SAW sensor design promise a 

reduction in detection limits of up to an order of 

magnitude. Sensor responses are dependent on 

temperature and, in certain cases, on relative 

humidity, indicating a need for compensation for, or 

control of, these variables. The sensors provide 

stable, reproducible responses for periods of at least 

eight months indicating minimal recalibration 

requirements. 

A new pattern recognition method was developed 

for determining which coated sensors would 

maximize the selectivity and accuracy of detection of 

a given subset of vapor contaminants. Using this 

method in conjunction with a Monte Carlo simulation 

procedure, optimal subsets of coated sensors can be 

selected for inclusion in the array for any potential 

exposure situations. This approach to coating 

selection allows the assessment of sensor array 

performance in terms of correct vapor identification 

rates, quantification accuracy, and the influence of 
Page 158 - Other Occupational Needs 

potential interferences. With proper design, a single 

array can identify and quantify a wide range of 

different vapors when present individually or in 

simple mixtures. 

Also developed during this project were several 

predictive models of sensor responses. Models based 

on vapor boiling points, coating/vapor solubility 

parameters, and coating/vapor salvation parameters 

used in conjunction with linear salvation energy 

relationships (LSER) were examined. The LSER 

model provided the most accurate correlation of 

modeled and experimental responses. Use of this 

model, together with the pattern recognition method 

described above permits the selection of optimal 

coatings and the estimation of array performance 

without the need for experimental calibrations. 

These investigations showed that with a simple 

four-sensor array it is possible to identify and 

quantify each of a large number of organic vapors. 

Using optimized arrays, errors in identification are 

generally restricted to cases of mixtures where one 

component is present at concentrations near the 

detection limit and the mixture is identified as the 

dominant component alone. In addition, while 

surprisingly good discrimination between vapors both 

between and within chemical classes is possible, 

identification errors are observed for some vapors of 

similar structure. A preliminary investigation of 

liquid crystals as sensor coatings shows that this class 

of sensor coatings can enhance discrimination by 

virtue of subtle size and shape differences between 

otherwise similar (e.g., isomeric) vapors. 

Publications 

Patrash SJ, Zellers ET: An Investigation of Nematic 

Liquid Crystals as Surface Acoustic Wave Sensor 

Coatings for Discrimination Between Isomeric 

Aromatic Vapors. Analytica Chimica Acta, in press, 

1993 

Zellers ET, Pan TS, Patrash SJ, Han M, Batterman 

SA: Extended Disjoint Principal-Components 

Regression Analysis of SAW Vapor Sensor-Array 

Responses. Sensors and Actuators B 

12(2):123-133, 1993 

Patrash SJ, Zellers ET: Characterization of 

Polymeric Surface Acoustic Wave Sensor Coatings 

and Semiempirical Models of Sensor Responses to 

Organic Vapors. Anal Chem 65:2055-2066, 1993 

Zellers ET, Patrash SJ, Zhang G: Selective 

Measurement of Organic Vapors Using SAW Sensors 

with Reactive or Sorptive Coatings: Steric, 

Electronic, and Solubility Factors. Proc 6th Int Conf 

Solid-State Sensors and Actuators - Transducer '91, 

San Francisco, pp 998-1001, June 1991 

Optical Remote Sensing and 

Computed Tomography in Industrial 

Hygiene 

Lori A. Todd, Ph.D. 

University of North Carolina 

School of Public Health 

Department of Environmental Sciences 

and Engineering 

CB #7400 Rosenau Hall 

Chapel Hill, North Carolina 27599-7400 

Program Area: Other Occupational Needs 

Grant Number: 5 KO] OHOOJOJ-03 

Start & End Dates: 07101/91 - 06/30/94 

Funding Level: $53,936 ($160,355 Cum) 

Importance to Occupational Safety and Health 

Current methods for sampling and evaluating air 

concentrations of gases and vapors involve the use of 

integrated samplers or direct-reading instruments. 

The integrated sampling devices result in a 

time-weighted average result; fluctuations in 

concentrations are smoothed out resulting in poor 

temporal resolution of chemical concentrations. 

Although direct-reading instruments do not suffer 

from the temporal resolution problem, both methods 

are essentially point samplers and give poor spatial 

resolution of concentrations. Currently, there are no 

methods which can give both good spatial and good 

temporal resolutions of chemical concentrations for 

an area. 

This research is investigating an air sampling and 

evaluation system that does not suffer from these 

problems. This method combines the techniques of 

optical remote sensing with computed tomography to 

determine the concentration distribution of a gas or 

vapor in a workplace. Chemicals would be detected 

over large areas remotely, non-invasively, and in 

real-time; the system would produce a topographical 

map of the distribution with both good spatial and 

good temporal resolution. 

The optical remote sensing/computed tomography 

system would have wide application in industrial 

hygiene work. It could be used for routine 

monitoring of chemical vapors in a workplace, 

evaluation of ventilation systems by using tracer gases 

or monitoring airflow of chemicals, and detection of 

leaks from an operation. 
Objectives 

This research proposes to combine the techniques 

of optical remote sensing with computed tomography 

to determine the concentration distribution of a gas or 

vapor in a room, non-invasively and in real-time. 

The aims of the research are to develop and test 

theoretical designs for a remote sensing/computed 

tomography system in a workplace, and to evaluate 

them by constructing a prototype system. 

Methodology 

Specific goals of this research involve: 

(I) designing and testing feasible optical remote 

sensing geometries for the placement of light sources 

and detectors in a room; (2) developing image 

reconstruction algorithms and computer code to 

produce the maps of concentration distributions; and 

(3) validating the remote sensing/computed 

tomography system in a controlled chamber and using 

a calibration cell using a tracer gas to create test 

concentrations. 

Successful completion of this work will 

demonstrate the feasibility of the proposed technique. 

The next step in the research program, following 

completion of the work proposed here, will be field 

evaluation of the system. 

Significant Findings 

A systematic method has been developed to 

compare the effectiveness of different algorithms, and 

different optical remote sensing geometries for 

tomographically reconstructing chemical 

concentrations in air from an optical remote sensing 

system. The underlying assumption is that the 

performance of an algorithm, and usefulness of a 

configuration cannot be accurately assessed without 

thorough testing using a wide variety of possible 

concentration maps under ideal and non-ideal 

sampling conditions. Four different algorithms, and 

ten configurations have been evaluated in numerical 

studies using 120 different test concentration maps, 

and six different sampling conditions. 

The algebraic reconstruction algorithms, ART 

and ART3 were found to be superior to other 

algorithms tested. In terms of resolution, the equal 

angle configuration is optimal because it floods the 

room with contiguous parallel rays; however, it is 

hardware intensive. An alternative configuration, that 

provides reasonable reconstructions, but introduces 

more artifacts, is the scan configuration. Four 

sources, one in each comer must be used for 

adequate reconstructions. Reconstruction quality was 

related to the number of detectors, the location of 

detectors in the room, and the complexity of the test 

concentration maps. 

Other Occupational Needs - Page 159 

The performance of an infrared optical remote 

sensing device was evaluated using an exposure 

chamber, and a five-compartment calibration cell 

placed directly in the optical path. Open-path 

measurements of SF1

, were compared with point 

sample measurements taken along the beam and 

analyzed using a GC-ECD or a MIRAN IR 

spectrophotometer. The open-path measurements 

were in close agreement, within 10-12'Y.,. with 

path-averaged concentrations calculated from the 

point samples. There was no significant difference 

found in measurement accuracy for a variety of path 

lengths, between the experiments performed using the 

chamber or calibration cell, homogeneous or 

heterogeneous tracer gas concentrations, and single or 

reflected-beam configurations. 

Publications 

Todd LA, Ramachandran: Evaluation of Algorithms 

for Tomographic Reconstruction of Chemicals in 

Indoor Air. AIHA Journal, in press, 1993 

Todd LA: Optical Remote Sensing/Computed 

Tomography Systems for Workplace Exposure 

Assessments. Proceedings Optical Remote Sensing: 

Applications to Environmental and Industrial Safety 

Problems SP-81 :356-360, 1992 

Todd LA: Optical Remote Sensing/Computed 

Tomography Beam Geometries for Monitoring 

Workplace Gases and Vapors. Proceedings Optical 

Remote Sensing: Applications to Environmental and 

Industrial Safety Problems, SP-81 :390-393, 1992 

Measurement Errors in Occupational 

Epidemiology 

Donna Spiegelman. Sc. D. 

Harvard University 

School of Public Health 

Deparlment of Epidemiology 

677 Hunfingf(m Avenue 

Boston. Massachusetts 02115 

Program Area: Other Occupational Needs 

Grant Number: 5 KOJ OHOOJ06-04 

Start & End Dates: 07101/91 - 06130/94 

Funding Level: 554,000 ($161,872 Cum) 
Page 160 - Other Occupational Needs 

Importance to Occupational Safety and Health 

Nearly all occupational studies face problems 

measuring the exposure variable. Although other 

types of epidemiology are also faced with this 

problem, the necessity of retrospective exposure 

assessment in most cohort studies and the cost of 

detailed personal exposure sampling even in 

prospective and cross-sectional studies makes this a 

particularly difficult attribute of occupational safety 

and health research. It is quite possible that many 

occupational studies which have been interpreted as 

negative have in fact failed to detect important 

exposure-response relationships due to substantial 

exposure measurement error or misclassification. I 

propose to contribute to a resolution of these 

problems through the development of statistical 

methods to adjust point and interval estimates of 

relative risk for bias due to measurement error. By 

illustrating these procedures with examples from 

important occupational data sets, it is hoped that the 

use of these methods of design and analysis will 

become standard practice in occupational 

epidemiology. 

Objectives 

1. To develop new simple measurement error 

methods for l) retrospective cohort studies, 

2) case-control studies, and 3) cross-sectional 

studies of occupational exposure-disease 

relationships 

2. To illustrate the use of these methods through 

the analysis of important occupational data sets, 

including: ( a) the GM/UAW study of respiratory 

and digestive cancer mortality and cumulative 

machining fluids exposure, (b) the New Mexico 

uranium miners' study of exposure to radon 

progeny and lung cancer mortality, (c) the 

GM/UAW study of acute respiratory effects and 

components of current machining fluids 

exposure, and (d) the ACE study of between 

health and occupational exposure to anti-cancer 

drugs 

3. To develop user-friendly computer software to 

implement those methods which appear to be 

most useful in practical settings. 

Methodology 

All methods require a small validation substudy 

in which the usual method of exposure assessment is 

validated against a more accurate method. Then, a 

measurement error model is developed empirically 

from these data. This is used explicitly in maximum 

likelihoods methods to obtain an unbiased estimate of 

effect, which takes into account measurement error as 

modeled through the validation substudy. 

Measurement error models appropriate for cumulative 

exposure variables are a special focus of this 

research. 

Significant Findings 

Current work involves investigating parametric 

full maximum likelihood methods for a constant 

prevalence ratio model with a realistic exposure 

measurement error model, such as based on the 

gamma or log-normal distribution. It appears that 

the gamma family of distributions for XIZ fit these 

data well, and leads to a closed form likelihood for 

the main study distribution of symptom prevalence 

conditional on exposure. Using the validation study 

data, we fit a gamma measurement error model to the 

distribution of XIZ with parameters μ(Z,U)=aμ + bμZ 

+ cμ'Uμ for the mean of XIZ,U and with shape 

parameter v(Z,U)=av + bvZ + c.'Uv, where Uμ and U, 

are arbitary dimensional vectors of covariates which 

may or may not be the same. Using a constant 

prevalence ratio model, Pr(D=l) = exp{a + pz + 

y'UJ for symptom prevalence, where UY is an 

arbitrary dimensional vector of covariates which may 

or may not be idential to Uμ and U, used for the 

measurement error model, we derive the distribution 

Pr(D=llZ,U) = J Pr(D=llX,Uy) f(XIZ,Uμ, U,U) dx = 

e a.+y'Uv [ v(Z,U,) r<Z,Uv) 

v(Z,U)-μ(Z,Uμ) p1 

We then maximize the likelihood 

L(P, 8) = L h(DIZ; p,6) + L .ftDIX; P) 

and obtain an estimate of the variance-covariance of 

the parameter estimates as the inverse of the observed 

information matrix at the maximum likelihood 

estimates. 

Detailed analysis of two symptoms, chest pain 

(CHEST) and loss of appetite (APPETITE), has 

progressed nicely. In this analysis, the exposure of 

interest was defined as number of doses of 

antineoplastics mixed per week. It was self-reported 

by memory (Z) in the main study, and measured 

through a 1-2 week written log (X) in the validation 

study. The correlation between these two methods of 

measurement was estimated at 0.42. For the 

purposes of illustration, I present the results of the 

analysis for chest pain. Using stepwise regression 

techniques and likelihood ratio testing procedures, we 

discovered empirically that Uμ = current smoking 

status, Uv = age, and UY = (stress, body mass index 

and age). With these model covariates, we then 
estimated the effect of number of drugs mixed per 

week using several strategies and compared the 

Other Occupational Needs - Page 161 

results. 

The relationship between the prevalence of chest pain, and number of doses of anti-neoplastics mixed per 

week, among hospital pharmacists and pharmacists' assistants 

Methodology (X 103

) POR [I SD(X) ll 1

] p-value, p-value, 

(95% CI) Wald test LRT2 

uncorrected logistic 1.60 0.807 1.02 (1.00-1.04) 0.048 n/a 

regression 

Rosner et al. 3 correction 10.84 6.4 1.16 (0.98-1.37) 0.093 n/a 

uncorrected constant 1.00 0.745 1.0 I (0.99-1.03) 0.180 0.033 

prevalence ratio model 

constant prevalence ratio 40.54 61.59 1. 73 (0.34-8.88) 0.512 0.532 

model, validation study 

only 

maximum likelihood 6.80 32.5 l.J O (0.46-2.60) 0.834 0.045 

estimate 

1 SD(Z) = 128.7, SD(X) = 13.54 

2 Likelihood ratio test 

3 Rosner B, Spiegelman D, Willett W. Correction of logistics regression relative risk estimates and confidence 

intervals for measurement error: the case of multiple covariates measured with error". Am J Epidemiol 1990; 

132:732-745. 

As expected, the logistic regression estimate 

over-estimates the prevalence ratio in analyses both 

corrected and uncorrected for exposure measurement 

error. The estimated log prevalence odds ratio ( ) 

for a one dose/week increment increases 7-10 fold 

after correction for measurement error, when using 

both the constant prevalence odds model with the 

Rosner et al. correction, and using the maximum 

likelihood measurement (ML) error model. With ML 

methods but not with the Rosner et al. correction 

procedure, the association remained statistically 

significant (p=0.045) after adjustment for 

measurement error. This is not surprising, as ML 

methods are maximally efficient assuming the model 

is correct. 

Because they obviate the need to make 

distributional assumptions about the measurement 

error process, semi-parametric models are also being 

considered. 

Generation of Fibrous Aerosols in 

Narrow Size Ranges 

Ching-Ping Fang, Ph.D. 

New York University 

Medical Center 

Department of Environmental Medicine 

550 First Avenue 

New York, New York 10016 

Program Area: Other Occupational Needs 

Grant Number: 1 KOJ OH00129-0JAJ 

Start & End Dates: 08/01/93 - 07131/96 

Funding Level: $53,811 ($53,8.J J Cum) 

Importance to Occupational Safety and Health 

It has long been recognized that durable fibrous 

materials (asbestos and Man-Made Mineral Fibers 

(MMMF)) can become carcinogenic when 
Page 162 - Other Occupational Needs 

aerosolized. It has also been accepted that the 

physical properties of the fibers can be more 

important determinants of injury than its chemical 

ones. Due to the fibers' elongated geometries, the 

efficiencies of lung deposition and clearance for 

fibers can be significantly different from those of 

compact particles. Many studies have reported that 

shorter fibers are removed more effectively from 

lung than the longer ones. A review of published 

literature sources by HEI-AR (1991) demonstrates 

the critical importance of fiber dimensions and 

durability in tissues to the biological responses. 

However, there are still insufficient reliable 

experimental results to fully support the fiber size 

criteria and toxicity ranges. The difficulties of 

interpreting results from prior experimental animal 

and in vitro studies of responses to fiber exposures 

have been due, in part, to the wide-spread ranges of 

diameter and length of the administered fibers. The 

first aim of this study is to develop techniques for 

generating fibrous aerosols with various fibrous 

materials (asbestos and MMMF) in narrow size 

ranges for laboratory use. The generated fibers 

could be used directly in in vitro, in vivo instillation, 

or in vivo implantation studies, or could be 

resuspended (with some losses) for inhalation 

studies. With these high quality fibrous particles, 

the research on quantitative assessment of the 

inhalation hazard from aerosolized fibrous materials 

(asbestos and MMMF) can be conducted more 

definitively. 

Objectives 

Quantitative assessment of the inhalation hazard 

from aerosolized fibrous materials (asbestos and 

MMMF) requires geometrically defined fibers. The 

primary objective of the current proposal is to 

develop techniques for generating relatively 

monodisperse fibrous aerosols for laboratory use. 

The specific aims of the project are: 

1. To develop a system for generating relatively 

monodisperse fibrous aerosols for a variety of 

fiber types, both natural and man-made. It will 

consist of an inertial impactor, a virtual 

impactor and Nuclepore filters in cascade. The 

collected fibrous particles, which will have 

geometric standard deviations less than 1.50 for 

both diameter and length, will be used in future 

work to determine the inhalation hazard from 

fibers of various lengths, diameters, and fiber 

types. 

2. Experimental and theoretical determination of 

the extent of influence of factors which affect 

collection characteristics of fibrous particles 

within sampling systems and lung airways. 

Methodology 

Polydisperse fibrous aerosols will first be 

generated by a fluidized bed fibrous generator 

(FBG) with number concentrations of 102-103/cc. 

The polydisperse fibrous aerosols will then be 

classified by an inertial impactor-virtual impactor 

system in diameter ranges of interest for subsequent 

biological effects testing, e.g., <0.15, 0.3-0.5, 

2-3 μm. The fibrous aerosol in each diameter range 

then will be sorted by fiber length using Nuclepore 

filters under conditions where collection by 

interception is the dominant collection mechanism. 

Length cuts could be made at 2.5, 5, IO and 20 μm. 

The system could be operated in cascade, collecting 

fractions with lengths <2.5, 2.5-5, 5-10, 10-20 and 

>20 μm. Our goal is to select fractions having 

narrow distributions of both fiber diameter and 

length, e.g., geometric standard deviation for both 

parameters will be less than 1.50. 

Significant Findings 

None to date. 

Health Care Worker Compliance 

with Hepatitis B Vaccine 

Bradley N Doebbeling, MD. 

University of Iowa 

College of Medicine 

Department of Internal Medicine 

200 Hawkins Drive 

Iowa City, Iowa 52242 

Program Area: Other Occupational Needs 

Grant Number: I KOi OHOOl31-01 

Start & End Dates: 04/01193 - 03/31/96 

Funding Level: $50,956 ($50,956 Cum) 

Importance to Occupational Safety and Health 

The overall goal of this study is to evaluate the 

distribution and determinants of hepatitis B vaccine 

use and compliance in Iowa hospitals and among 

Iowa health care workers. This study is designed to 

identify institutional, occupational, and behavioral 

variables among health care workers that impact on 

their practice of effective preventive health measures, 

using compliance with the hepatitis B vaccine as the 

paradigm. 
Objectives 

We propose to test the following specific 

hypotheses: 

1. that institutional levels of HBV vaccine 

compliance are directly related to the type of 

vaccine implementation program; 

2. that high levels of institutional compliance with 

OSHA's Bloodborne Pathogens Rule will have 

indirect benefits on the frequency of sharps 

injuries, cutaneous exposures to blood, TB 

exposures, and PPD conversions 

3. that the frequency of educational programs is 

unimportant in determining compliance in 

individual hospital workers; 

4. that institutional factors including provision of 

the vaccine at the work site, increased access 

(availability), and documented informed refusal 

are more important than individual factors in 

determining individual compliance; 

5. that compliance with universal precautions will 

predict compliance with HBV vaccination; 

6. that social influence and facilitating conditions 

are extremely important in behavioral models of 

HCW vaccination behavior. 

Methodology 

In the first stage, a longitudinal survey of Iowa 

health care institutions will be performed over a 

two-year period to define the rates and distribution of 

hepatitis B vaccine compliance following 

implementation of a federal mandate for vaccination. 

Levels of institutional compliance with OSHA's 

Bloodborne Pathogens Rule will be categorized and 

their effect on vaccine compliance and occupational 

exposures measured. Vaccine compliance rates 

among health care workers in different job categories 

will be determined in institutional assessments at 12 

and 24 months after the initial survey. In the second 

stage of the study, a stratified random sample of 15 

health care workers in each of three occupational 

categories at 30 general hospitals will be studied to 

investigate attitudes about vaccination, the 

effectiveness of different types of vaccination 

programs, as well as the effect of OSHA's 

Bloodborne Pathogens Rule. Data from individual 

interviews will be used to evaluate the relative utility 

of two theoretical behavioral models in predicting 

health care worker vaccine compliance. Multi variate 

models will be developed to predict individual and 

institutional compliance. Additionally, the relative 

importance of institutional versus individual factors in 

determining individual hepatitis B vaccine compliance 

will be evaluated. In the third year of the study, 

these models will be validated prospectively in a 

second sample of health care workers and unstudied 

Other Occupational Needs - Page 163 

hospitals and used to identify an effective vaccine 

implementation program for hospitals and other 

health care facilities. 

Significant Findings 

Study 1: Hepatitis B Vaccination: Independent 

Predictors of Health Care Worker Compliance: We 

evaluated a 20% random sample of HCWs at risk for 

exposure to blood and body fluids at our tertiary care 

teaching center in Spring 1992; 908 of 1,018 (89%) 

questionnaires were returned. Only 54% had 

completed the HBV vaccine series, although 70% had 

received one or more doses. Significant univariate 

predictors of vaccination (1 or more doses) included: 

occupational category (p<0.0001), age (p=0.0001), 

previous influenza vaccination (p=0.003), and clinical 

setting (p=0.0052). The importance of reasons for 

vaccination (N= 13) or vaccine refusal (N=l5) 

suggested by the literature and from our pilot testing 

of the questionnaire was assessed on a 7-point Likert 

scale and combined using factor analysis. The 

internal consistency (reliability) of each scale in this 

data (Cronbach's alpha statistic) in SPSS 

demonstrated an alpha of 0.72 for the reasons for 

refusal, and an alpha of 0.82 for the reasons for 

vaccination. The final logistic model for vaccine 

compliance included: occupational category 

(p<0.0001) and sharps injury (p=0.0008, Tables 3 

and 4). The maximum likelihood ratio demonstrated 

the model fit the data well (Chi-Square=5.0, 5 DF, 

p=O .416). These data suggest that future vaccine 

implementation efforts must target specific 

occupational categories at risk, as well as HCWs 

during evaluation for sharps injury and possibly, 

cutaneous exposure. It is not certain that these 

determinants of individual HCW vaccination apply to 

HCWs in community hospitals and chronic care 

facilities. Final revision of the final structured 

interview form for the health care worker study is 

underway. Study 2: Hepatitis B Vaccination: 

Institutional Predictors: The Iowa Statewide 

Surveillance System (ISSS) is composed of 

representatives from all hospitals (N=128) and the 

largest chronic care facilities (N = 13) in Iowa with 

trained infection control practitioners and ongoing 

surveillance for nosocomial infections. We developed 

a questionnaire to evaluate current HBV vaccine 

implementation programs in Iowa hospitals prior to 

OSHA's Bloodborne Pathogens Rule becoming law. 

The questionnaire was pilot tested, then administered 

to infection control practitioners (ICPs) at the 128 

hospitals and 13 chronic care facilities in the ISSS. 

Two serial mailings were performed, with 133 of 141 

(94%) returned. Telephone interviewing was 

performed to verify the data and complete missing 

items. Hospitals were stratified by their location in 

an urban versus rural county, based upon census data. 
Page 164 - Other Occupational Needs 

Counties were divided into urban/rural quartiles, 

based upon the proportion of the population of the 

county residing in a single incorporated place of more 

than 2,500 inhabitants. Mean rates of vaccination 

(three or more doses) in different occupational groups 

in urban versus rural counties ranged from 63% to 

54% among housekeepers, 46% to 52% among 

physicians, and from 70% to 65% among laboratory 

workers. Data regarding rates of vaccination among 

physicians are limited in that most are not considered 

hospital employees and records were not available. 

· Vaccine implementation programs also differ red 

considerably by size of the institution and whether it 

was located in an urban versus a rural county. 

Regression analysis to predict vaccination rates 

demonstrates that a variety of program characteristics 

are significantly associated with vaccination rates 

among workers. Data collection for the follow-up 

study of vaccine provision program characteristics 

and rates of vaccination among health care workers 

at 18 months after OSHA' s guidelines becoming 

enforceable is currently underway. 

Elevated Blood Leads in the Iowa 

Construction Industry 

Stephen J. Reynolds, Ph.D. 

University of Iowa 

College of Medicine 

Department of Preventive Medicine 

& Environmental Health 

JOO Oakdale Campus - 136 AMRF 

Iowa City, Iowa 52240-5000 

Program Area: Other Occupational Needs 

Grant Number: 1 KOJ OHOOJ 37-01 

Start & End Dates: 09/30193 - 09/29196 

Funding Level: $54,000 ($54,000 Cum) 

Importance to Occupational Safety and Health 

Sentinel data from case reports and surveillance 

systems strongly indicate that workers in selected 

construction trades are significantly exposed to lead, 

are inadequately monitored, and are sustaining serious 

illness from exposure. Although OSHA's new lead 

standard for the construction industry should help 

provide a framework for evaluation and control of 

lead exposures, there remains an acute need to 

determine the true scope of the problem and identify 

contributing risk factors. The results of this study 

will be useful for developing intervention strategies, 

and prioritizing prevention activities. 

Objectives 

The objectives of this project are to: characterize 

the prevalence of blood lead concentrations in 

selected high risk construction trades in the State of 

Iowa; identify and evaluate risk factors that may 

contribute to occupational exposure to lead in 

construction; evaluate the utility of using the Iowa 

Department of Public Health's (IDPH) Adult Blood 

Lead Surveillance Project for identification and 

mitigation of lead poisoning cases in construction; 

evaluate compliance with the new OSHA construction 

lead standard; collect, organize, and disseminate 

information concerning lead hazard and controls via 

the National Hazard Communication Resource Center 

(NHCRC) and presentations to construction workers; 

develop intervention strategies and future projects to 

quantitatively evaluate lead exposure in construction. 

Methodology 

This project involves a cooperative effort between 

the University of Iowa and the Eastern Iowa 

Construction Alliance, a labor management 

organization representing approximately 100 

construction contractors and more than 3,400 union 

members. A sample of 500 workers will be 

randomly selected from the total population of all 

union members, using union records. 100 workers 

will be selected from each of the following high risk 

trade groups: painters, plumbers and pipe fitters, 

ironworkers, laborers, and electricians. Venous blood 

samples will be collected from each participant and 

analyzed for lead using atomic absorption 

spectroscopy. Information on demographics, 

symptoms, occupational history, work practices, 

personal protective equipment, training, other 

potential risk factors and confounders will be 

gathered using questionnaires at the same time that 

blood samples are collected. Awareness of, and 

compliance with OSHA's construction lead standard 

will also be ascertained. The primary objectives of 

data analysis will be to describe the distribution of 

blood lead concentrations, test the null hypothesis that 

there are no significant differences between the blood 

lead concentrations of workers in different trade 

groups, and evaluate the relationships between risk 

factors, symptoms, and blood lead concentrations. 

Results will also be used to evaluate the efficacy of 

the ID PH's Adult Blood Lead Surveillance Program, 

and the University of Iowa Hospital and Clinics' data 

base for identification and control of occupational 

exposure to lead in the Iowa construction industry. 

Upon completion of the prevalence study, and using 

the resources of the NHCRC, focus groups will be 

conducted with construction workers to present the 

findings and explore methods for reducing exposure. 
Significant Findings 

None to date. 

An Exposure Matrix For 

Construction Painters 

Philip L. Bigelow, Ph.D. 

Colorado State University 

Department of Environmental Health 

110 Veterinary Science Building 

Fort Collins, Colorado 80523 

Program Area: Other Occupational Needs 

Grant Number: 1 KOJ OHOOJ 38-01 

Start & End Dates: 09/30/93 - 09/29/96 

Funding Level: $53,535 ($53,535 Cum) 

Importance to Occupational Safety and Health 

Construction painters are exposed to a wide 

variety of substances that may cause acute and 

chronic adverse health effects. Relatively little work 

has focused on this occupational group despite the 

extent of exposure, the large population of workers, 

and the potential for severe effects -neurotoxicity, 

increased accident rates, cancer, reproductive 

disorders, and respiratory disease. The investigation 

will provide much needed quantitative information on 

exposures in construction painting. By focusing on 

specific work tasks, a new methodology will be 

developed in which exposures can be accurately 

estimated on the basis of self reports of work activity. 

This exposure assessment technique will be valuable 

when dealing with workers who perform tasks at 

different jobsites or who perform a variety of 

activities. The new technique will enhance the 

capabilities of health scientists in the assessment of 

exposure of individuals that in the past have been 

difficult to characterize. 

Objectives 

The major hypothesis of the study is that by 

studying specific job tasks, a construction painter's 

overall occupational exposure can be estimated. In 

order to test this hypothesis, methods are under 

development to standardize the measurement of 

organic vapor exposures during specific construction 

painting tasks. Another importan~ obj~ctive of the 

study is to determine the relationships betw~en 

occupational exposures and variables that ch~actenze 

the work environment. Through the analysts of data 

Other Occupational Needs - Page 165 

collected during this investigation a method will be 

developed that will allow the prediction of overall 

occupational exposures based on descriptions of work 

tasks and characteristics of the occupational 

environment. 

Methodology 

Measurements of exposures during specific work 

tasks will be evaluated for 200 construction painters 

in Colorado. The focus of the exposure assessments 

will be organic vapors. Collection and analytical 

techniques will vary depending on the expected 

contaminants in the work environment and the 

expected durations of exposure. Gas chromatography 

and IR spectrophotometry will be extensively used 

methods of analysis. Video taping of the work tasks 

will be undertaken to assist in the collection and 

interpretation of data. 

A database of tasks and exposure levels will be 

developed for later use in the characterization of 

exposure on the basis of information from 

self-reported activities. Self-reported work activities 

will be obtained through the administration of a task 

history questionnaire. The statistical relationships 

between variables that characterize the work (tasks 

and environment) and exposure levels will be 

determined. Information obtained at the job sites will 

be used to develop and modify the task history 

questionnaire, and statistical analyses will be 

performed to assess its' utility in developing overall 

exposure profiles. A short questionnaire will be 

administered before and after each workshift in order 

to assess the relationship of painting exposures on the 

incidence of specific symptoms. The statistical 

associations between peak and time weighted average 

exposure levels and symptom scores will be 

determined. 

Significant Findings 

None to date. 
Page 166 - Other Occupational Needs 

TCD as a Screening Procedure for 

Exposures to Toxicants 

Michael E. Drues 

Iowa State University 

Department of Biomedical Engineering 

1146 Veterinary Medicine 

Ames, Iowa 50011 

Program Area: Other Occupational Needs 

Grant Number: 5 R03 OH02932-02 

Start & End Dates: 09/30/91 - 09/29/93 

Funding Level: $0 ($16,507 Cum) 

Importance to Occupational Safety and Health 

Each year, thousands of new chemicals are 

developed and many eventually come into contact 

with people on the job or simply through everyday 

activities. Although every effort is made to ensure 

that each chemical is safe for human exposure, any 

new testing procedure that may potentially detect 

subtle changes occurring prior to observing clinical 

symptoms would certainly be worth further 

investigation. If subtle changes can be detected early 

enough, perhaps the chance of permanent damage 

occurring could be reduced or even eliminated 

completely. 

Objectives 

The purpose of this experiment was to use 

transcranial Doppler sonography (TCD) in the dog to 

noninvasively measure changes in cerebral blood flow 

(CBF) resulting from a low-level exposure to the 

commonly used pyrethroid insecticide deltamethrin. 

TCD has been well established as a noninvasive and 

cost effective means of measuring CBF in man. 

Although the use of TCD in animals has been limited, 

pilot work indicated that CBF can be measured in 

normal greyhound dogs. Further, it was shown that 

manipulations of CBF (using CO2) can be detected 

using TCD. Deltamethrin has previously been shown 

to increase CBF in rats as determined by other 

techniques. 

Methodology 

In this experiment, deltamethrin was dissolved in 

glycerol-formal solvent and administered 

intravenously at dosage levels of 5% and 10% of the 

LD50 value to 12 adult dogs 48 hours apart. It was 

expected that vascular changes resulting from these 

low-level deltamethrin exposures would be subtle and 

occur over several minutes (rather than beat-to-beat 

changes). To test this hypothesis, mean blood flow 

velocity (MBFV) in the middle cerebral artery, mean 

arterial blood pressure (MAP) in the aorta, end tidal 

CO2 (pC02), mean heart rate (MHR) and 

concentration of deltamethrin in the blood were 

measured during control, glycerol-formal and 

exposure (deltamethrin in glycerol-formal) periods 

according to a randomized block factorial design. In 

addition to the aforementioned parameters, 

systolic-to-diastolic ratio (SDR), Pourcelout 

pulsatility index (PPI), Gosling pulsatility index (GPI) 

and systolic upstroke (SU) were calculated using the 

blood flow velocity waveform. 

Significant Findings 

An analysis of variance was performed on each 

parameter to determine if there were significant 

differences among the three treatment groups. With 

respect to control levels, glycerol-formal alone did 

not exhibit significant effects on any of the 

physiological parameters measured. However, there 

was a significant decrease in SDR, PPI and GPI 

associated with the administration of glycerol-formal. 

This suggested that the shape of the blood flow 

velocity waveform changed in the presence of 

glycerol-formal without any corresponding changes 

in the measured physiological parameters. Following 

the administration of deltamethrin, there was a 

significant increase in MBFV lasting 10 minutes post 

exposure, a significant increase in MAP and decrease 

in MHR lasting 20 minutes post exposure and a 

significant increase in pC02 lasting 30 minutes post 

exposure. The increase in MBFV was expected and 

corroborates the increase in CBF previously observed 

in rats. These changes indicate that the deltamethrin 

was having systemic effects on the cardiovascular and 

cerebrovascular systems. Further, this data agrees 

with circulating deltamethrin concentrations in the 

blood which peaked approximately 5 minutes post 

exposure. SDR, PPI and GPI returned to control 

levels following the administration of deltamethrin. 

TCD seems to have significant potential as a 

screening methodology, however, to date, it has not 

been used with animals nor has it been applied in the 

field of toxicology. In this research, it has been 

shown that TCD is sensitive to alterations in CBF 

caused by deltamethrin in the greyhound dog. 

Publications 

Drues ME, Hopper DL, Lange DN: Transcranial 

Doppler Sonography: A New Noninvasive Method 

for Measuring Toxicant-Induced Alterations in 

Cerebral Blood Flow. Journal of Ultrasound in 

Medicine and Biology, 1992 (publication pending) 
Drues ME, Hopper DL, Lange ON: A System for 

Detecting Chemically-induced Changes in Cerebral 

Blood Flow Using Transcranial Doppler Sinography 

in A Dog Model. Proc of the Fifth Annual IEEE 

Symposium on Computer-based Medical Systems. 

Duke University, Durham, North Carolina, 

pp. 477-485, June 14-17, 1992 

Dose-Response Assessment Issues 

in Occupational Studies 

Irva Hertz-Picciotto, Ph.D. 

University of North Carolina 

School of Public Health 

Department of Epidemiology 

CB# 7400 McGavran-Greenberg Hall 

Chapel Hill, North Carolina 27599-7400 

Program Area: Other Occupational Needs 

Grant Number: I R03 OH02971-0JAI 

Start & End Dates: 09/30/92 - 09/29194 

Funding Level: $0 ($19,363 Cum) 

Importance to Occupational Safety and Health 

Dose-response assessment is used as a criterion 

in establishing causality on the basis of observational 

studies, and is used to improve understanding of 

biologic mechanisms. Additionally, it is used to set 

exposure standards in occupational and environmental 

settings. Biases in dose-response assessment can 

occur due to competing risks from morbidity and 

mortality that manifest as a healthy worker survivor 

effect. This project is examining the use of a job 

instability index as a surrogate for job- and 

dose-related morbidity. Results from this project 

may be used to increase the sensitivity of analyses of 

occupational studies that utilize quantitative exposure 

measures, and hence to improve the ability to set 

appropriate regulatory standards. 

Objectives 

The objective of this project is to determine ways 

to detect and quantify biases that may alter 

dose-response relationships in occupational studies. 

Methodology 

Exposure-related morbidity is being assessed 

using as a surrogate, gaps in employment. The 

association between exposure and this index of job 

instability is characterized using Cox hazard 

Other Occupational Needs - Page 167 

regression with time-dependent exposure variables 

(cumulative exposure, as well as current exposure), 

controlling for other variables such as age and date of 

hire. Relationships between gaps in employment and 

pre-retirement job leaving are also characterized by 

means of similar proportional hazards regression 

models, with gaps in employment representing an 

additional time-dependent variable. The association 

of this surrogate for exposure-related morbidity and 

respiratory cancer mortality is analyzed. Competing 

risks from other causes of death may also be related 

to exposure and will be analyzed as outcomes in their 

own right, using hazard regression models. 

Significant Findings 

Empirical findings indicate a strong association 

between gaps of 30 days or more and the following 

variables: age-at- hire; year-of-hire; cumulative 

exposure up to one year previously; current exposure 

in the preceding year. Younger age at hire, later 

year of hire, higher cumulative exposure, and lower 

current exposure were all associated with the risk of 

a 30-day gap. Three of these variables also show an 

interaction with time since hire. In particular, as time 

since hire increases, the positive association with 

cumulative exposure declines, the negative association 

with current exposure increases in absolute 

magnitude, and the positive association with year of 

hire increases. 

Gaps in employment are positive predictors of 

early job- leaving, i.e., termination prior to 

retirement age. This association continues to hold 

after controlling for exposure and age and year of 

hire. Given the predictiveness of gaps in 

employment, it appears to be a useful index of job 

instability. 

A Volatile Aerosol Sampler and 

Particle Size Analyzer 

Judy Q. Xiong, Ph.D. 

New York University 

Medical Center 

Department of Environmental Medicine 

Long Meadow Road 

Tuxedo, New York 10987 

Program Area: Other Occupational Needs 

Grant Number: 5 R03 OH03039-02 

Start & End Dates: 09/30/92 - 09/29/94 

Funding Level: $28,100 ($50,595 Cum) 
Page 168 - Other Occupational Needs 

Importance to Occupational Safety and Health 

Assessment of worker exposure to a volatile 

organic chemical (VOC) requires measuring the 

airborne concentration of the vapor phase and the 

coexisting particle phase separately, because the 

resulting inhalation dose can differ substantially. 

American Conference of Governmental Industrial 

Hygienists (ACGIH) has suggested establishing dual 

Threshold Limit Values (TLVs) for the two phases of 

a volatile substance. However, due to particle 

evaporation and vapor absorption by the particle 

surface in the sampling process, air samplers 

presently in use are not adequate for efficient 

separation of the VOC vapor and particles; and 

currently, there are no simple field sampling methods 

to measure the size distribution of particles that 

contain VOCs. The proposed VPS sampler and the 

MVPS particle size analyzing system will be 

appropriate for monitoring the airborne 

concentrations of VOCs in the industrial spray work 

environment, such as the reinforced plastic industry 

and the paint spray booth. They are relatively simple 

and inexpensive field sampling devices and will 

provide essential data for the assessment of worker 

exposure to the vapor and particle phases of a VOC 

and important reference data for establishing dual 

Threshold Limit Values (TL Vs) for both phases. The 

same principle may also be applied for sampling and 

size classifying the particles that contain volatile, or 

semi-volatile components that are traditionally 

sampled with other sorbent collectors (silica gel, 

porous polymer, etc.). 

Objectives 

The first goal of this work is to develop a 

prototype Vapor/Particle Sampler (VPS) for rapid 

anisokinetic separation of the vapor phase and 

coexisting particle phase of an airborne VOC 

substance into gaseous and particulate fractions 

according to their differential inertia. Our second 

goal is to develop a prototype Multiple Vapor/Particle 

Sampler (MVPS) system, which not only can separate 

vapor and particles, but also can provide the size 

classification of the particles that contain VOCs. The 

aerodynamic cut-off sizes of the MVPS system will 

be designed to I, 2, 4, IO and 20 μm aerodynamic 

diameters, where, 4 and 10 μm are the ACGIH 

defined particle cut sizes for respirable and thoracic 

particulate mass fractions, respectively. 

Methodology 

The VPS sampler is designed for anisokinetic 

separation of the vapor molecules and particles into 

two identifiable fractions due to their differential 

inertia. The MVPS sampler system is designed to 

measure the particle size distribution of voe 

containing particles by using a series of single-stage 

virtual impactors of designed cut-off size. 

Experimental studies are carried out to determine the 

optimum sampler geometric parameters, flow 

conditions and sampling time for efficient (>90%) 

separation of vapor and particles with reasonable 

sensitivity. 

Laboratory-generated vapors and aerosols are 

used for sampler calibration and performance 

evaluation. A vibrating orifice aerosol generator is 

employed to produce monodisperse 

fluorescein-tagged oleic acid particles in the particle 

size range greater than I μm. Monodisperse 

submicron fluorescein particles are obtained from a 

system that includes a Collison nebulizer, an 

electrostatic classifier (DMA), and a condensation 

particle counter. The mass concentrations of 

fluorescein-tagged oleic acid particles or fluorescein 

particles are quantitatively analyzed by fluorometry. 

The sampling efficiencies will be measured at various 

inlet flow rates and various ratios of the dichotomous 

flow rates. The vapor collection efficiencies are 

tested in a chamber equipped with a vapor generating 

device and particle-free dilution air. Toluene, xylene 

and styrene are chosen as the test materials. The 

intersampler comparison tests are also carried out by 

comparing: (I) the VPS measurements of 

monodisperse particle concentration from the 

glassfiber filters; (2) the VPS measurements of 

airborne vapor concentration from charcoal sorbent 

tubes and 3M diffusion monitors; (3) the MVPS 

measurements of particle size distribution from a 

Climet Particle Size Analyzer and a multi-stage 

Mercer Cascade impactor. 

Significant Findings 

The preliminary design of the prototypes of VPS 

sampler and MVPS sampler system has been 

completed. A prototype VPS Sampler has been 

designed and fabricated. The sampler is designed to 

operate at a sample inlet flowrate 1.8 LPM, which 

can be conveniently and reliably provided by 

lightweight, commercial personal sampling pumps. 

The optimum sample geometrical parameters, such as 

nozzle diameter and length, distance of nozzle to 

filter, have been examined. The experimental tests 

and calibration of the VPS sampler have been carried 

out. The particle cut-off diameter (D50) of the VPS 

sampler is 0.95 μm, which is determined from the 

particle collection efficiency as a function of particle 

aerodynamic diameter. Intersampler comparison 

results showed a good agreement between the mass 

concentration data of monodisperse particles 

measured by VPS sampler and the 37 mm Glassfiber 

filters (GF) with a correlation of (CvrsfCGF) = 0.96 
± 0.06 (95% confidence interval, n=l3). An average 

wall loss of the VPS sampler is 2.2%. 

The experimental tests and calibration of the 

MVPS system will be completed in the second year 

of the two year grant. 

Training and Medical Surveillance 

Under the ETO Standard 

Anthony D. Lamontagne 

Harvard School of Public Health 

Occupational Health Program 

Department of Environmental Health 

665 Huntington Avenue 

Boston, Massachusetts 02115-9957 

Program Area: Other Occupational Needs 

Grant Number: 1 R03 OH03088-0l 

Start & End Dates: 08101/93 - 07/31/95 

Funding Level: $17,281 ($17,281 Cum) 

Importance to Occupational Safety and Health 

Broadly speaking, this study addresses the 

implementation of training and medical surveillance. 

Historically, training and medical surveillance have 

been emphasized and studied less than other 

preventive measures, such as engineering controls and 

exposure monitoring, which focus more directly on 

the source of exposure. Training and medical 

surveillance are generally assumed to occur and to 

have some preventive impact; however, systematic 

evaluation of these areas is only recently becoming 

recognized as a research need. Systematic study will 

help to develop untapped preventive potential of 

training and medical surveillance, fostering the 

development of a more integrated and balanced 

approach to hazard control at all levels. 

The general aim of this study is to critically 

evaluate the implementation of the training and 

medical surveillance (MS) provisions of the 

Occupational Safety and Health Administration's 

(OSHA) 1984 Ethylene Oxide (EtO) Standard in the 

hospital setting. The broader goal of this research is 

to identify strengths and weaknesses of training and 

MS implementation in substance-specific OSHA 

standards in order to provide for more effective 

practice, enforcement strategies, and policy-making 

in these areas. 

Other Occupational Needs - Page 169 

Objectives 

The following three specific hypotheses, derived 

directly from the implementation strategies of 

exposure monitoring-driven substance-specific health 

standards will be tested: Hypothesis (1) Exceedance 

of trigger exposure levels is positively associated with 

implementation of EtO training, and 

Hypothesis (2) exceedance of trigger exposure levels 

is positively associated with implementation of EtO 

medical surveillance. Two EtO exposure levels are 

specified to trigger training and MS requirements: 

the Action Level of 0.5 ppm Time-weighted Average 

(TWA) and the Excursion Limit of 5 ppm TWA per 

15 period. We are asking to what extent employers 

are in compliance with these requirements and to 

what extent exposure monitoring specifically guides 

employers in the implementation of EtO training and 

MS. Hypothesis (3): the implementation of training 

is positively associated with the implementation of 

medical surveillance. As stated in current OSHA 

policy, part of the intent of training is to make 

workers aware of their rights under a standard, which 

in tum is presumed to make workers more likely to 

exercise those rights. We will test for an association 

which would be consistent with such a causal 

relationship between training and MS. 

Methodology 

To achieve the specific aims, our approach 

integrates theory and principles from occupational 

health, health education, and the social sciences with 

survey research methodology. All Massachusetts 

hospitals were contacted by mail and surveyed for the 

use of EtO. To date, 93 have responded as EtO 

users, 63 as non-users. Only 4 of the 160 hospitals 

in the state have not responded. EtO users are then 

administered a 15 minute standardized telephone 

interview, followed by a standardized 1-2 hour 

face-to-face interview with the sterilization 

department supervisor. The telephone and face to 

face interviews are still in progress. Response rates 

to date are between 80 and 90% of EtO users. Brief 

questionnaires on health and safety support 

(professionals on staff, etc.) are also mailed to 

hospital health & safety departments, and brief 

questionnaires on the process and findings of EtO 

medical surveillance exams are mailed to providers 

wherever EtO medical surveillance has been 

provided. 

Significant Findings 

None to date. 
Page 170 - Other Occupational Needs 

Air Dispersion of Chemicals in 

Industrial Facilities 

Stephen G. Zemba, Ph.D. 

Cambridge Environmental, Inc. 

58 Charles Street 

Cambridge, Massachusetts 02141 

Program Area: Other Occupational Needs 

Grant Number: 1 R43 OH03009-0l 

Start & End Dates: 09/30/92 - 07/31193 

Funding Level: $0 ($49,680 Cum) 

Importance to Occupational Safety and Health 

Direct measurement is the traditional approach 

used to investigate exposure to airborne chemicals in 

the workplace. Modeling techniques can complement 

monitoring studies and provide a new tool for 

assessing air quality in workplaces. The ability to 

predict the behavior of chemicals may aid _in ~e 

identification of causes of hazardous concentrations m 

indoor air and provide an opportunity to avoid such 

hazardous conditions prospectively. Modeling may 

also serve as a cost-effective screening tool that can 

be used in conjunction with monitoring to examine an 

environment more rigorously and to suggest optimal 

locations at which measurements should be taken. 

Objectives 

The overall goal of this work is to develop 

user-friendly software for modeling the 

concentrations of hazardous chemicals in indoor air. 

The aim of the Phase I study was to develop an 

approach to predict the dispersion of che~c:i-ts in 

indoor settings in which pollutants are not distnbuted 

uniformly. Subsequent research (if unde~aken) wi_ll 

extend modeling capabilities to include flmd dynamic 

simulation and other predictive tools for assessing 

indoor air quality. 

Methodology 

Most models available for assessing indoor air 

quality are designed to simulate poll~tant behav_ior in 

well-mixed regions throughout which contammants 

are distributed uniformly. Such models are 

inappropriate, however, in industrial settings in which 

pollutants may be introduced or removed at numerous 

locations, thus leading to gradients in pollutant 

concentrations. The Phase I research study utilized 

an interactive software package called SIMULINKTM to 

develop a user-friendly modeling environment to 

simulate the behavior of pollutants in large, open 

indoor settings in which contaminant concentrations 

may vary greatly. A set of modeling elements were 

developed that can be used as building blocks to 

simulate pollutant dispersion. The physical processes 

considered include pollutant emission, transport, 

chemical reactions, local ventilation, and deposition to 

surfaces. Volume elements are used to represent 

subregions of the workplace that can reasonably be 

assumed to be well-mixed, and Exchange elements 

serve as linkages that specify pollutant transport 

between adjacent Volume elements. The modeling 

approach is demonstrated in the final Phase I report 

for a number of illustrative benchmark problems. In 

addition, two detailed examples illustrate practical 

applications of the modeling approach. In the first 

application, the simulation of ozone concentrations in 

a commercial setting suggests that both internal and 

external sources may contribute to exposure to ozone 

indoors, and that exposures may vary with 

significantly with proximity to sources. The second 

application was a retrospective study of toluene 

diisocyanate in a polyurethane manufacturing facility 

that was the focus of a detailed industrial hygiene 

survey. Using limited measurements of air flow 

velocities, the modeling simulation reproduced the 

pattern of toluene diisocyanate concentrations 

measured throughout the factory. In its current 

formulation, the modeling approach requires the 

specification of air flow data. Future research efforts 

(if undertaken) will investigate predictive tools for 

simulating air flow patterns in the absence of detailed 

empirical data. 

Significant Findings 

SIMULINKTM, an interactive software package for 

modeling dynamic systems, has been used to develop 

a set of indoor air modeling elements. These 

elements can be used to simulate the time-dependent 

behavior of pollutants in indoor environments. 
Micromachined System For 

Selective Measurement of voes 

Stuart W. Wenzel 

Berkeley Microinstruments, Inc. 

1301 South 46th Street, Bldg. 164 

Richmond, California 94804 

Program Area: Other Occupational Needs 

Grant Number: 1 R43 OH03102-0l 

Start & End Dates: 09115/93 - 08/14194 

Funding Level: $49,975 ($49,975 Cum) 

Importance to Occupational Safety and Health 

Vapor-phase chemical detection is important in 

industrial hygiene and indoor air quality assurance. 

However, existing chemical-sensing technologies do 

not . meet the needs in these areas adequately, 

particularly for portable air-quality instrumentation. 

Sensors for personal chemical-exposure monitors 

must be reliable, have sufficient sensitivity to detect 

~ fr~ction of the OSHA-dictated permissible exposure 

hmit, and have high selectivity to the target chemical 

in the presence of interferents. They should also be 

small, inexpensive, fast-responding, and 

energy-efficient so that they can operate on batteries 

for extended periods. Existing sensor technologies do 

not meet these requirements, either because they are 

too expensive and complicated to use, or too limited 

in their capabilities. The sensing technology we 

propose is designed to overcome these limitations, so 

that it can be widely employed in occupational health 

and safety and in other applications. 

Objectives 

The goal of this research is to make a chemical 

measurement system for real-time detection of 

volatile organic compounds (VOCs) using a silicon 

micromachined system of components, such as 

ultrasonic flexural-plate-wave sensors. This system 

will be designed for use in personal 

chemical-exposure monitors. It will be small, 

inexpensive, robust, battery-operated, sensitive 

enough to detect VOCs at a fraction of the OSHA 

permissible exposure level, and selective enough to 

identify toxic chemicals in a realistic environment. 

Methodology 

Work in this phase focuses on three interrelated 

tasks: (I) design and fabrication of prototype 

chemical-identification chips that incorporate 

Other Occupational Needs - Page 171 

micro~a':hi~ed chemical-sensing components; 

(2) optimization of computer-based algorithms that 

control and coordinate the function of these 

components and analyze output data; (3) tests of the 

abilit~ of the ~icromachined system to sense specific 

~olatile organic compounds in the presence of 

mterferants, including water vapor. The 

first-generation chip includes an ultrasonic 

flexural-plate-wave sensor and a preconcentrator 

with its associated heater. 

Significant Findings 

We have designed, built and tested a 

first-:generat_ion chemical-identification chip, 

associated dnve circuitry and a data acquisition and 

control system. Electrical testing shows that the 

individual chip components function as designed: the 

preconcentrator temperature can be pulsed to 150 °C 

for over 1,000 cycles with no noticeable degradation 

or drift; the flexural-plate-wave sensors operate 

stably and respond to organic vapors; the 

computer-based control system allows us to 

coordinate the action of the micromachined 

components and the vapor-generation system, and to 

process, display and log data in real time. 

Initial vapor-sensing tests show that attention 

must be paid to physical interaction between the 

system components. Changes are being made to the 

vapor generation system, and to the design of the chip 

in order to improve performance. 

Personal Monitor For Toxic Vapors 

N. L. Jarvis, Ph.D. 

Microsensor Systems, Inc. 

62 Corporate Court 

Bowling Green, Kentucky 42103 

Program Area: Other Occupational Needs 

Grant Number: 1 R43 OH03103-0l 

Start & End Dates: 09115/93 - 08/14/94 

Funding Level: $49,616 ($49,616 Cum) 

Importance to Occupational Safety and Health 

There is a need in the industrial workplace for 

small, sensitive, rugged, and easy-to-use personal 

monitors for toxic organic vapors. Many existing 

methods, e.g. electrochemical detectors, are not well 

suited for many toxic organic compounds and other 

methods such as dosimeter badges do not offer 

real-time response. The Surface Acoustic Wave 

(SAW) microsensor devices being developed in this 
Page 172 - Other Occupational Needs 

program are well suited for the real-time monitoring 

of high molecular weight, low volatility, toxic 

organics that are difficult to detect by other 

techniques. 

Objectives 

The objective of this program is to develop a 

miniature SAW vapor detection system with the size, 

sensitivity, reliability and power requirement 

appropriate for a pocket size Personal Monitor for 

Toxic Vapors. The aim of the Phase I effort is to 

develop a laboratory, or "breadboard" unit that 

demonstrates sensitivity to glutaraldehyde, a 

hazardous chemical used as a disinfectant for a 

number of medical applications, such as endoscope 

sterilization, and is very difficult to monitor by 

present detection technologies. In Phase II the 

detection capability of the Personal Monitor for Toxic 

Vapors will be extended to other hazardous vapors 

that are also difficult to detect by other means, such 

as the isocyanate!3. Also in Phase II, small, 

lightweight demonstration models of the Personal 

Monitor for Toxic Vapors will be designed, built, and 

evaluated. 

Methodology 

The work being conducted in this phase I study 

is intended to show feasibility of the SAW 

microsensor approach. SAW vapor microsensors are 

surface mass sensitive micro-chip devices that can be 

made sensitive to organic vapors by the application of 

a suitable sorbent coating. Specific tasks in this 

program include development of a calibrated system 

to generate glutaraldehyde vapor, fabrication of a 

sensor electronic test system, coating of the SAW 

devices with a variety of sensitizing films, and 

evaluation of the sensor responses when challenged 

by known concentrations of glutaraldehyde vapor. 

Significant Findings 

None to date. 
Activity 

ROI 

KOl 

R03 

Other 

Total 

FY93 Grant Awards by Activity 

Percentage of Total Budget 

R03 

New 

Awards 

No. Amount 

19 $3,089,086 

9 $476,088 

6 $182,956 

4 $313,274 

38 $4,061,404 

Other 

6% 

Continuation 

Awards 

No. Amount 

25 $3,329,535 

8 $431,617 

6 $117,684 

I $130,863 

40 $4,009,699 

Page 173 

TOTAL 

Awards 

No. Amount 

44 $6,418,621 

17 $907,705 

12 $300,640 

5 $444,137 

78 $8,071, I 03 
Page 174 

FY93 Grant Awards by Program Area 

Competing and Total Dollars 

a Competing Awa,ds I 

$2,000,000 

$1,800,000 

$1,600,000 

$1,400,000 

$1,200,000 

$1,000,000 

+-----------_____, • Total Awards J'--· _____ _ 

$800,000 

$600,000 

$400,000 

$200,000 

$0 

= CJ 

~ 

= 

~ 

Program Area 

Lung 

Musculoskeletal 

Cancer 

Trauma 

Cardiovascular 

Reproductive 

Neurotoxic 

Noise 

Dermatological 

Psychological 

Control Techniques 

Respirator 

Other 

TOTAL 

0 

I,, 

= 

~ 

z 

Competing Awards 

Number Amount 

5 $400,788 

4 $162,694 

3 $445,054 

4 $426,049 

0 $0 

0 $0 

2 $187,158 

2 $376,376 

0 $0 

0 $0 

5 $754,973 

1 $164,458 

12 $1,143,854 

38 $4,061,404 

I,, 

.... 

C 

0 

u 

Total A wards 

Number Amount 

11 $1,189,373 

8 $472,704 

5 $511,526 

8 $811,976 

0 $0 

4 $330,701 

4 $417,920 

3 $610,053 

0 $0 

1 $114,399 

9 $1,055,058 

5 $558,257 

20 $1,999,136 

78 $8,071,103 
State Amount 

Alabama $399,449 

Arkansas $34,640 

California $437,264 

Colorado $53,535 

Connecticut $218,211 

Florida $53,832 

Georgia $136,688 

Iowa $158,956 

Illinois $35,515 

Indiana $296,809 

Kentucky $49,616 

Louisiana $181,466 

Massachusetts $986,288 

Maryland $272,458 

FY93 Grant Awards by State 

78 Totaling $8,071,103 

% State 

4.9 Michigan 

0.4 Minnesota 

5.4 North Carolina 

0.7 New Mexico 

2.7 New York 

0.7 Ohio 

1.7 Oklahoma 

2.0 Pennsylvania 

0.4 Texas 

3.7 Vermont 

0.6 Washington 

2.2 Wisconsin 

12.2 West Virginia 

3.4 

Page 175 

Amount % 

$808,837 10.0 

$12,814 0.2 

$410,389 5.1 

$179,833 2.2 

$1,518,857 18.8 

$446,695 5.5 

$267,940 3.3 

$114,330 1.5 

$76,357 1.0 

$370,691 4.6 

$369,980 4.6 

$53,681 0.6 

$125,972 1.6 
GRANT NUMBER INDEX - Page 176 

FY93 

Grant Number Principal Investigator Funding Page 

Research Proiect Grants (ROI) 

5 ROI OH00823-12 Mohamed B. Abou-Donia, Ph.D. $0 90 

5 ROI OH00835-14 William J. Swartz, Ph.D. $82,973 84 

5 ROI OH01122-09Sl Charles W. Kauffman, Ph.D. $0 68 

5 ROI OHOl 152-12 Donald Henderson, Ph.D. $233,677 100 

5 ROI OH02067-09 G. Marie Swanson, Ph.D. $0 52 

5 ROI OH02128-08 William W. Clark, Ph.D. $0 102 

5 ROI OH02148-07 Stephen F. Cleary, Ph.D. $0 131 

5 ROI OH02149-06 Ghulam A.S. Ansari, Ph.D. $0 133 

5 ROI OH02221-05 Stephen M. Rappaport, Ph.D. $0 136 

5 ROI OH02277-03 David Warshawsky, Ph.D. $0 11 

2 ROI OH02317-09 Roger P. Hamernik, Ph.D. $198,536 105 

5 ROI OH02391-03 Nabih R. Asal, Ph.D. $0 138 

5 ROI OH02421-04 David C. Christiani, M.D. $139,344 12 

5 ROI OH02434-05 Mohamed M. Ayoub, Ph.D. $76,357 36 

5 ROI OH02571-06 Irvin Schonfeld, Ph.D. $114,399 108 

5 ROI OH02593-04 E. Neil Schachter, M.D. $147,561 14 

2 ROI OH0261 l-04 Susan T. Bagley, Ph.D. $0 110 

5 RO I OH02622-03 Regina M. Santella, Ph.D. $0 139 

2 ROI OH02647-03 George P. Hemstreet, Ph.D. $267,940 54 

5 RO 1 OH02663-03 Edward T. Zellers, Ph.D. $0 141 

5 RO 1 OH02664-02 Roy Rando, Sc.D. $98,493 143 

5 ROI OH02666-04 Steven P. Levine, Ph.D. $211,324 144 

5 ROI OH02683-02 William Daniell, M.D., M.P.H. $166,820 93 

5 ROI OH02710-02 Michael R. Flynn, Sc.D. $0 112 

5 ROI OH02719-03 Diana Echeverria, Ph.D. $0 94 

5 ROI OH02730-02 Genevieve M. Matanoski, M.D., Dr.P.H. $0 55 

5 ROI OH02740-02 Venkat Venkatasubramanian, Ph.D. $82,901 112 

5 ROI OH02741-03 Laura Punnett, Sc.D. $48,493 70 

I ROI OH02743-01A2 Kweku K. Bentil, Ph.D. $106,833 71 

5 ROI OH02758-02 Scott S. Campbell, Ph.D. $142,120 146 

5 ROI OH02761-02 Thomas G. Robins, M.D., M.P.H. $0 17 

5 ROI OH02767-03 Roberta F. White, Ph.D. $176,762 96 

5 RO I OH02772-04 Juraj J. Ferin, M.D. $144,299 18 

5 ROI OH02792-03 Roger W. Giese, Ph.D. $136,446 147 

5 ROI OH02794-02 Amit Bhattacharya, Ph.D. $0 72 

5 ROI OH02804-03 Richard A. Wadden, Ph.D. $35,515 114 

5 ROI OH02820-02 David Kriebel, Sc.D. $0 56 

5 ROI OH02858-03 Michael R. Flynn, Sc.D. $59,540 115 

5 RO 1 OH02872-03 Jess F. Kraus, Ph.D. $193,325 73 

5 ROI OH02885-03 Maureen C. Hatch, Ph.D. $207,513 85 

5 ROI OH02914-02 H. Kenneth Dillon, Ph.D. $115,087 19 

5 ROI OH02918-02 William T. Stauber, Ph.D. $125,972 37 

5 ROI OH02922-02 Yung-Sung Cheng, Ph.D. $179,833 124 

I ROI OH02941-0l Alfred Franzblau, M.D. $0 39 

I ROI OH02945-0l Om P. Gandhi, Sc.D. $0 148 

5 ROI OH02948-02 Klaus Willeke, Ph.D. $147,152 125 

5 ROI OH02951-02 Shane Que Hee, Ph.D. $122,129 115 

I ROI OH02953-01Al Ellen A. Eisen, Sc.D. $123,282 57 
GRANT NUMBER INDEX - Page 177 

FY93 

Grant Number Principal Investigator Funding Page 

5 ROI OH02967-02 Bernard J. Martin, Ph.D. $90,109 74 

5 ROI OH02987-02 William S. Beckett, M.D. $218,211 21 

I ROI OH03015-01Al Phillip A. Bishop, Ed.D. $153,499 116 

1 ROI OH03021-01Al Tomasz R. Letowski, H.D., Ph.D. $114,330 117 

I ROI OH03024-0l Alfred Franzblau, M.D. $176,191 150 

1 ROI OH03033-0l Edward T. Zellers, Ph.D. $116,453 118 

I ROI OH03044-01Al Terry Gordon, Ph.D. $97,953 22 

I ROI OH03052-0l Kyle D. Squires, Ph.D. $152,013 119 

I ROI OH03056-0IAI Venkat Venkatasubramanian, Ph.D. $213,908 151 

I Rl8 OH03073-0l Michael J. Symons, Ph.D. $68,139 153 

I ROI OH03078-0l Richard E. Letz, Ph.D. $136,688 97 

I ROI OH03079-0l Amit Bhattacharya, Ph.D. $233,071 76 

I ROI OH03134-0l Michael G. Yost, Ph.D. $119,762 154 

I ROI OH03136-0I Sally L. Lusk, Ph.D. $177,840 107 

I ROI OH03157-0l Dryver R. Huston, Ph.D. $218,678 120 

1 ROI OH03168-0l John M. Dement, Ph.D. $177,290 22 

I ROI OH03177-0l Lewis D. Pepper, M.D. $236,680 155 

Career Development Grants (KOi) 

5 KO 1 OH00076-03 Paul W. Brandt-Rauf, Sc.D., M.D. $0 58 

5 KOI OH00077-03 Edward T. Zellers, Ph.D. $0 157 

5 KOI OH00078-03 Lorraine M. Conroy, Sc.D. $0 121 

5 KOI OH00079-03 Paul D. Blanc, M.D. $0 24 

5 KOi OH00081-03 Gerald N. Levy, Ph.D. $0 61 

5 KOi OH00085-03 Riedar K. Oestenstad, Ph.D. $0 126 

5 KOI OH00087-03 Patrick N. Breysse, Ph.D. $54,000 127 

5 KOi OH00090-03 David G. Wilder, Ph.D. $0 40 

5 KOI OH00093-03 David A. Schwartz, M.D., M.P.H. $0 26 

5 KOI OH00098-03 Fredric E. Gerr, M.D. $0 41 

5 KOI OH00103-03 Lori A. Todd, Ph.D. $53,936 158 

5 KOi OH00106-04 Donna Spiegelman, Sc.D. $54,000 159 

5 KOI OH00107-03 Robert G. Radwin, Ph.D. $53,681 42 

5 KOI OH00108-02 Michael J. Kosnett, M.D. $0 82 

5 KOI OHOOI 10-03 Karl T. Kelsey, M.D. $54,000 62 

5 KOi OHOOI 15-02 Fabian C. Hadipriono, Dr.Eng. $54,000 77 

5 KOI OH00121-02 David M. Rempel, M.D. $54,000 44 

5 KOi OH00123-02 Rob McConnell, M.D. $54,000 98 

1 KOl OH00125-01Al Lora E. Fleming, M.D. $53,832 64 

1 KOl OH00129-01Al Ching-Ping Fang, Ph.D. $53,811 161 

1 KOl OH00131-01 Bradley N. Doebbeling, M.D. $50,956 162 

1 KOl OH00132-0l Jacqueline Agnew, Ph.D. $54,000 45 

1 KOl OH00133-0l Matthew C. Keifer, M.D. $50,470 99 

1 KOl OH00134-0l William D. Clapp, M.D. $54,000 31 

1 KOl OH00135-0l Gary A. Mirka, Ph.D. $51,484 46 

1 KOi OH00137-0l Stephen J. Reynolds, Ph.D. $54,000 164 

1 KOl OH00138-0l Philip L. Bigelow, Ph.D. $53,535 165 
GRANT NUMBER INDEX - Page 178 

FY93 

Grant Number Principal Investigator Funding Page 

Small Grants (R03) 

5 R03 OH02765-02 Hal Morgenstern, Ph.D. $0 47 

5 R03 OH02880-02 Suresh P. Krishnan $0 65 

5 R03 OH02931-02 David J. Brenner, Ph.D. $24,083 31 

5 R03 OH02932-02 Michael E. Drues $0 166 

5 R03 OH02938-02 Lisa M. Brosseau, Sc.D. $13,096 128 

5 R03 OH02966-02 Harvey Checkoway, Ph.D. $22,380 87 

1 R03 OH02971-01Al Irva Hertz-Picciotto, Ph.D. $0 167 

5 R03 OH02972-02 Changhwa Jacob Cheu $12,472 66 

5 R03 OH03000-02 Marc B. Schenker, M.D. $17,835 88 

5 R03 OH03039-02 Judy Q. Xiong, Ph.D. $28,100 167 

1 R03 OH03061-01 Randal J. Keller, Ph.D. $34,640 33 

1 R03 OH03064-01 Mitchell D. Cohen, Ph.D. $36,905 34 

1 R03 OH03087-0l Ali Sheikhzadeh $35,900 49 

1 R03 OH03088-0l Anthony D. Lamontagne $17,281 169 

1 R03 OH0309 l-O 1 Bradley Evanoff, M.D. $21,310 49 

1 R03 OH03154-0l John G. Everett, Ph.D. $36,920 79 

Small Business Grants (R43, R44) 

1 R43 OH02907-01 Beth Ann Marcus, Ph.D. $0 50 

1 R43 OH03009-0l Stephen G. Zemba, Ph.D. $0 170 

1 R43 OH03010-0l Peter J. Kajenski, Ph.D. $0 122 

1 R43 OH03018-0l Christopher C. Johnson $0 123 

1 R43 OH03099-0l Bob E. Hayes, Ph.D. $49,225 80 

1 R43 OH03l02-01 Stuart W. Wenzel $49,975 171 

1 R43 OH03103-0l N. L. Jarvis, Ph.D. $49,616 171 

2 R44 OH0301 l-02 Clinton E. Brown $164,458 129 
PRINCIPAL INVESTIGATOR INDEX - Page 179 

Principal Investigator Area Grant Number Page 

Research Proiect Grants (RO I) 

Abou-Donia, Mohamed B., Ph.D. Neurotoxic Disorders 5 ROI OH00823-12 90 

Ansari, Ghulam A.S., Ph.D. Other Occupational Needs 5 ROI OH02149-06 133 

Asal, Nabih R., Ph.D. Other Occupational Needs 5 RO I OH0239 I -03 138 

Ayoub, Mohamed M., Ph.D. Musculoskeletal Injuries 5 ROI OH02434-05 36 

Bagley, Susan T., Ph.D. Control Techniques 2 ROI OH0261 l-04 110 

Beckett, William S., M.D. Occupational Lung Diseases 5 ROI OH02987-02 21 

Bentil, Kweku K., Ph.D. Traumatic Injuries I ROI OH02743-0IA2 71 

Bhattacharya, Amit, Ph.D. Traumatic Injuries I ROI OH03079-0l 76 

Bhattacharya, Amit, Ph.D. Traumatic Injuries 5 RO I OH02794-02 72 

Bishop, Phillip A., Ed.D. Other Occupational Needs I ROI OH03015-0IAI 116 

Campbell, Scott S., Ph.D. Other Occupational Needs 5 RO I OH02758-02 146 

Cheng, Yung-Sung, Ph.D. Respirator Research 5 ROI OH02922-02 124 

Christiani, David C., M.D. Occupational Lung Diseases 5 ROI OH02421-04 12 

Clark, William W., Ph.D. Noise-Induced Hearing Loss 5 ROI OH02128-08 102 

Cleary, Stephen F., Ph.D. Other Occupational Needs 5 ROI OH02148-07 131 

Daniell, William, M.D., M.P.H. Neurotoxic Disorders 5 RO I OH02683-02 93 

Dement, John M., Ph.D. Occupational Lung Disease I ROI OH03168-0I 22 

Dillon, H. Kenneth, Ph.D. Occupational Lung Diseases 5 ROI OH02914-02 19 

Echeverria, Diana, Ph.D. Neurotoxic Disorders 5 ROI OH02719-03 94 

Eisen, Ellen A., Sc.D. Occupational Cancers I ROI OH02953-0IAI 57 

Ferin, Juraj J., M.D. Occupational Lung Diseases 5 RO I OH02772-04 18 

Flynn, Michael R., Sc.D. Control Techniques 5 ROI OH02710-02 112 

Flynn, Michael R., Sc.D. Control Techniques 5 ROI OH02858-03 115 

Franzblau, Alfred, M.D. Musculoskeletal Injuries I ROI OH02941-0I 39 

Franzblau, Alfred, M.D. Other Occupational Needs I ROI OH03024-0I 150 

Gandhi, Om P., Sc.D. Other Occupational Needs I RO I OH02945-0 I 148 

Giese, Roger W., Ph.D. Other Occupational Needs 5 ROI OH02792-03 147 

Gordon, Terry, Ph.D. Occupational Lung Diseases I ROI OH03044-0IAI 22 

Hamernik, Roger P., Ph.D. Noise-Induced Hearing Loss 2 ROI OH02317-09 105 

Hatch, Maureen C., Ph.D. Disorders of Reproduction 5 ROI OH02885-03 85 

Hemstreet, George P., Ph.D. Occupational Cancers 2 ROI OH02647-03 54 

Henderson, Donald, Ph.D. Noise-Induced Hearing Loss 5 ROI OHOl 152-12 100 

Huston, Dryver R., Ph.D. Control Techniques I ROI OH03157-0l 120 

Kauffman, Charles W., Ph.D. Traumatic Injuries 5 ROI OHOI 122-09Sl 68 

Kraus, Jess F., Ph.D. Traumatic Injuries 5 ROI OH02872-03 73 

Kriebel, David, Sc.D. Occupational Cancers 5 RO I OH02820-02 56 

Letowski, Tomasz R., H.D., Ph.D. Control Techniques I ROI OH03021-0IAI 117 

Letz, Richard E., Ph.D. Neurotoxic Disorders I ROI OH03078-0I 97 

Levine, Steven P., Ph.D. Other Occupational Needs 5 RO I OH02666-04 144 

Lusk, Sally L., Ph.D. Noise-Induced Hearing Loss I ROI OH03136-0I 107 

Martin, Bernard J., Ph.D. Traumatic Injuries 5 ROI OH02967-02 74 

Matanoski, Genevieve M., M.D., Dr.P.H. Occupational Cancers 5 RO I OH02730-02 55 

Pepper, Lewis D., M.D. Other Occupational Needs 1 ROI OH03177-0I 155 

Punnett, Laura, Sc.D. Traumatic Injuries 5 RO 1 OH0274 l-03 70 

Que Hee, Shane, Ph.D. Other Occupational Needs 5 RO I OH0295 l -02 115 

Rando, Roy, Sc.D. Other Occupational Needs 5 RO 1 OH02664-02 143 

Rappaport, Stephen M., Ph.D. Other Occupational Needs 5 ROI OH02221-05 136 

Robins, Thomas G., M.D., M.P.H. Occupational Lung Diseases 5 ROI OH02761-02 17 

Santella, Regina M., Ph.D. Dermatological Conditions 5 RO I OH02622-03 139 
PRINCIPAL INVESTIGATOR INDEX - Page 180 

Principal Investigator Area Grant Number Page 

Schachter, E. Neil, M.D. Occupational Lung Diseases 5 ROI OH02593-04 14 

Schonfeld, Irvin, Ph.D. Psychological Disorders 5 ROI OH02571-06 108 

Squires, Kyle D., Ph.D. Control Techniques 1 ROI OH03052-0l 119 

Stauber, William T., Ph.D. Musculoskeletal Injures 5 ROI OH02918-02 37 

Swanson, G. Marie, Ph.D. Occupational Cancers 5 ROI OH02067-09 52 

Swartz, William J., Ph.D. Disorders of Reproduction 5 ROI OH00835-14 84 

Symons, Michael J., Ph.D. Other Occupational Needs 1 Rl8 OH03073-0l 153 

Venkatasubramanian, Venkat, Ph.D. Control Techniques 5 ROI OH02740-02 112 

Venkatasubramanian, Venkat, Ph.D. Other Occupational Needs 1 ROI OH03056-01Al 151 

Wadden, Richard A., Ph.D. Control Techniques 5 ROI OH02804-03 114 

Warshawsky, David, Ph.D. Occupational Lung Diseases 5 ROI OH02277-03 11 

White, Roberta F., Ph.D. Neurotoxic Disorders 5 ROI OH02767-03 96 

Willeke, Klaus, Ph.D. Respirator Research 5 ROI OH02948-02 125 

Yost, Michael G., Ph.D. Other Occupational Needs 1 ROI OH03134-0l 154 

Zellers, Edward T., Ph.D. Other Occupational Needs 5 ROI OH02663-03 141 

Zellers, Edward T., Ph.D. Control Techniques 1 ROI OH03033-0l 118 

Career Development Grants (KO 1) 

Agnew, Jacqueline, Ph.D. Musculoskeletal Injuries 1 KOl OH00132-0l 45 

Bigelow, Philip L., Ph.D. Other Occupational Needs 1 KOl OH00138-0l 165 

Blanc, Paul D., M.D. Occupational Lung Diseases 5 KOl OH00079-03 24 

Brandt-Rauf, Paul W., Sc.D., M.D. Occupational Cancers 5 KOl OH00076-03 58 

Breysse, Patrick N., Ph.D. Respirator Research 5 KOl OH00087-03 127 

Clapp, William D., M.D. Occupational Lung Diseases 1 KOl OH00134-0l 31 

Conroy, Lorraine M., Sc.D. Control Techniques 5 KOl OH00078-03 121 

Doebbeling, Bradley N., M.D. Other Occupational Needs 1 KOl OH00131-0l 162 

Fang, Ching-Ping, Ph.D. Other Occupational Needs 1 KOl OH00129-01Al 161 

Fleming, Lora E., M.D. Occupational Cancers 1 KOl OH00125-01Al 64 

Gerr, Fredric E., M.D. Musculoskeletal Injuries 5 KOl OH00098-03 41 

Hadipriono, Fabian C., Dr.Eng. Traumatic Injuries 5 KOl OHOOl 15-02 77 

Keifer, Matthew C., M.D. Neurotoxic Disorders 1 KOl OH00133-0l 99 

Kelsey, Karl T., M.D. Occupational Cancers 5 KOl OHOOll0-03 62 

Kosnett, Michael J., M.D. Cardiovascular Diseases 5 KOl OH00108-02 82 

Levy, Gerald N., Ph.D. Occupational Cancers 5 KOl OH00081-03 61 

McConnell, Rob, M.D. Neurotoxic Disorders 5 KOl OH00123-02 98 

Mirka, Gary A., Ph.D. Musculoskeletal Injuries 1 KOl OH00135-0l 46 

Oestenstad, Riedar K., Ph.D. Respirator Research 5 KOl OH00085-03 126 

Radwin, Robert G., Ph.D. Musculoskeletal Injuries 5 KOl OH00107-03 42 

Rempel, David M., M.D. Musculoskeletal Injuries 5 KOl OH00121-02 44 

Reynolds, Stephen J., Ph.D. Other Occupational Needs 1 KOl OH00137-0l 164 

Schwartz, David A., M.D., M.P.H. Occupational Lung Diseases 5 KOl OH00093-03 26 

Spiegelman, Donna, Sc.D. Other Occupational Needs 5 KOl OH00106-04 159 

Todd, Lori A., Ph.D. Other Occupational Needs 5 KOl OH00103-03 158 

Wilder, David G., Ph.D. Musculoskeletal Injuries 5 KOl OH00090-03 40 

Zellers, Edward T., Ph.D. Other Occupational Needs 5 KOl OH00077-03 157 

Small Grants (R03) 

Brenner, David J., Ph.D. Occupational Lung Diseases 5 R03 OH0293 l-02 31 

Brosseau, Lisa M., Sc.D. Respirator Research 5 R03 OH02938-02 128 
PRINCIPAL INVESTIGATOR INDEX - Page 181 

Principal Investigator Area Grant Number Page 

Checkoway, Harvey, Ph.D. Disorders of Reproduction 5 R03 OH02966-02 87 

Cheu, Changhwa Jacob Occupational Cancers 5 R03 OH02972-02 66 

Cohen, Mitchell D., Ph.D. Occupational Lung Diseases 1 R03 OH03064-01 34 

Drues, Michael E. Other Occupational Needs 5 R03 OH02932-02 166 

Evanoff, Bradley, M.D. Musculoskeletal Injuries l R03 OH0309 l-O l 49 

Everett, John G., Ph.D. Traumatic Injuries l R03 OH03154-0 l 79 

Hertz-Picciotto, Irva, Ph.D. Other Occupational Needs l R03 OH02971-01Al 167 

Keller, Randal J., Ph.D. Occupational Lung Diseases 1 R03 OH0306 l -O l 33 

Krishnan, Suresh P. Occupational Cancers 5 R03 OH02880-02 65 

Lamontagne, Anthony D. Other Occupational Needs l R03 OH03088-0 l 169 

Morgenstern, Hal, Ph.D. Musculoskeletal Injuries 5 R03 OH02765-02 47 

Schenker, Marc B., M.D. Disorders of Reproduction 5 R03 OH03000-02 88 

Sheikhzadeh, Ali Musculoskeletal Injuries l R03 OH03087-0l 49 

Xiong, Judy Q., Ph.D. Other Occupational Needs 5 R03 OH03039-02 167 

Small Business Grants (R43, R44) 

Brown, Clinton E. Respirator Research 2 R44 OH03011-02 129 

Hayes, Bob E., Ph.D. Traumatic Injuries l R43 OH03099-0 l 80 

Jarvis, N. L., Ph.D. Other Occupational Needs l R43 OH03 l 03-0 l 171 

Johnson, Christopher C. Control Techniques l R43 OH03018-0 l 123 

Kajenski, Peter J., Ph.D. Control Techniques l R43 OH030 l 0-0 l 122 

Marcus, Beth Ann, Ph.D. Musculoskeletal Injuries l R43 OH02907-0l 50 

Wenzel, Stuart W. Other Occupational Needs l R43 OH03 l 02-0 l 171 

Zemba, Stephen G., Ph.D. Other Occupational Needs l R43 OH03009-0 l 170 
GRANTEE INSTITUTION INDEX - Page 182 

Grantee Institution Principal Investigator 

Research Proiect Grants (ROI) 

Alabama, University of 

Alabama, University of 

Battelle Human Affairs Research Center 

Boston University 

Boston University 

California, University of 

California, University of 

Central Institute for the Deaf 

Cincinnati, University of 

Cincinnati, University of 

Cincinnati, University of 

Cincinnati, University of 

City College of CUNY 

Columbia University 

Columbia University 

Duke University 

Duke University 

Emory University 

Harvard University 

Illinois, University of 

Johns Hopkins University 

Louisiana State University 

Lovelace Biomedical & Environmental Res Institute 

Lowell, University of 

Lowell, University of 

Massachusetts, University of 

Michigan State University 

Michigan Technological University 

Michigan, University of 

Michigan, University of 

Michigan, University of 

Michigan, University of 

Michigan, University of 

Michigan, University of 

Michigan, University of 

Michigan, University of 

Michigan, University of 

Mount Sinai 

New York Hospital - Cornell Medical Center 

New York University 

North Carolina, University of 

North Carolina, University of 

North Carolina, University of 

North Carolina, University of 

Northeastern University 

Oklahoma, University of 

Oklahoma, University of 

Pennsylvania State University 

Purdue University 

H. Kenneth Dillon, Ph.D. 

Phillip A. Bishop, Ed.D. 

Diana Echeverria, Ph.D. 

Lewis D. Pepper, M.D. 

Roberta F. White, Ph.D. 

Jess F. Kraus, Ph.D. 

Shane Que Hee, Ph.D. 

William W. Clark, Ph.D. 

Amit Bhattacharya, Ph.D. 

Klaus Willeke, Ph.D. 

Amit Bhattacharya, Ph.D. 

David Warshawsky, Ph.D. 

Irvin Schonfeld, Ph.D. 

Maureen C. Hatch, Ph.D. 

Regina M. Santella, Ph.D. 

Mohamed B. Abou-Donia, Ph.D. 

John M. Dement, Ph.D. 

Richard E. Letz, Ph.D. 

David C. Christiani, M.D. 

Richard A. Wadden, Ph.D. 

Genevieve M. Matanoski, M.D., Dr.P.H. 

William J. Swartz, Ph.D. 

Yung-Sung Cheng, Ph.D. 

David Kriebel, Sc.D. 

Laura Punnett, Sc.D. 

Ellen A. Eisen, Sc.D. 

G. Marie Swanson, Ph.D. 

Susan T. Bagley, Ph.D. 

Bernard J. Martin, Ph.D. 

Charles W. Kauffman, Ph.D. 

Alfred Franzblau, M.D. 

Edward T. Zellers, Ph.D. 

Sally L. Lusk, Ph.D. 

Steven P. Levine, Ph.D. 

Edward T. Zellers, Ph.D. 

Alfred Franzblau, M.D. 

Thomas G. Robins, M.D., M.P.H. 

E. Neil Schachter, M.D. 

Scott S. Campbell, Ph.D. 

Terry Gordon, Ph.D. 

Michael J. Symons, Ph.D. 

Stephen M. Rappaport, Ph.D. 

Michael R. Flynn, Sc.D. 

Michael R. Flynn, Sc.D. 

Roger W. Giese, Ph.D. 

Nabih R. Asal, Ph.D. 

George P. Hemstreet, Ph.D. 

Tomasz R. Letowski, H.D., Ph.D. 

Venkat Venkatasubramanian, Ph.D. 

19 

116 

94 

155 

96 

73 

115 

102 

76 

125 

72 

11 

108 

85 

139 

90 

22 

97 

12 

114 

55 

84 

124 

56 

70 

57 

52 

110 

74 

68 

39 

141 

107 

144 

118 

150 

17 

14 

146 

22 

153 

136 

115 

112 

147 

138 

54 

117 

112 
Grantee Institution 

Purdue University 

Rochester, University of 

State University of New York 

State University of New York 

Texas Tech University 

Texas, University of 

Tulane University Medical Center 

Utah, University of 

Vermont, University of 

Vermont, University of 

Virginia Commonwealth University 

Washington, University of 

Washington, University of 

Washington, University of 

West Virginia University 

Yale University 

Alabama, University of 

California, University of 

California, University of 

California, University of 

Colorado State University 

Columbia University 

Emory University 

Harvard University 

Harvard University 

Illinois, University of 

Iowa, University of 

Iowa, University of 

Iowa, University of 

Iowa, University of 

Johns Hopkins University 

Johns Hopkins University 

Miami, University of 

Michigan, University of 

Michigan, University of 

Mount Sinai 

New York University 

North Carolina State University 

North Carolina, University of 

Ohio State University 

Vermont, University of 

Washington, University of 

Wisconsin, University of 

Arkansas, University of 

California, University of 

GRANTEE INSTITUTION INDEX - Page 183 

Principal Investigator 

Venkat Venkatasubramanian, Ph.D. 

Juraj J. Ferin, M.D. 

Donald Henderson, Ph.D. 

Roger P. Hamernik, Ph.D. 

Mohamed M. Ayoub, Ph.D. 

Ghulam A.S. Ansari, Ph.D. 

Roy Rando, Sc.D. 

Om P. Gandhi, Sc.D. 

Dryver R. Huston, Ph.D. 

Kyle D. Squires, Ph.D. 

Stephen F. Cleary, Ph.D. 

Kweku K. Bentil, Ph.D. 

Michael G. Yost, Ph.D. 

William Daniell, M.D., M.P.H. 

William T. Stauber, Ph.D. 

William S. Beckett, M.D. 

Career Development Grants (KOi) 

Riedar K. Oestenstad, Ph.D. 

Paul D. Blanc, M.D. 

David M. Rempel, M.D. 

Michael J. Kosnett, M.D. 

Philip L. Bigelow, Ph.D. 

Paul W. Brandt-Rauf, Sc.D., M.D. 

Fredric E. Gerr, M.D. 

Donna Spiegelman, Sc.D. 

Karl T. Kelsey, M.D. 

Lorraine M. Conroy, Sc.D. 

Bradley N. Doebbeling, M.D. 

William D. Clapp, M.D. 

Stephen J. Reynolds, Ph.D. 

David A. Schwartz, M.D., M.P.H. 

Jacqueline Agnew, Ph.D. 

Patrick N. Breysse, Ph.D. 

Lora E. Fleming, M.D. 

Gerald N. Levy, Ph.D. 

Edward T. Zellers, Ph.D. 

Rob McConnell, M.D. 

Ching-Ping Fang, Ph.D. 

Gary A. Mirka, Ph.D. 

Lori A. Todd, Ph.D. 

Fabian C. Hadipriono, Dr.Eng. 

David G. Wilder, Ph.D. 

Matthew C. Keifer, M.D. 

Robert G. Radwin, Ph.D. 

Small Grants (R03) 

Randal J. Keller, Ph.D. 

Marc B. Schenker, M.D. 

151 

18 

100 

105 

36 

133 

143 

148 

120 

119 

131 

71 

154 

93 

37 

21 

126 

24 

44 

82 

165 

58 

41 

159 

62 

121 

162 

31 

164 

26 

45 

127 

64 

61 

157 

98 

161 

46 

158 

77 

40 

99 

42 

33 

88 
GRANTEE INSTITUTION INDEX - Page 184 

Grantee Institution 

California, University of 

Cincinnati, University of 

Cincinnati, University of 

Columbia University 

Harvard School of Public Health 

Hospital For Joint Diseases 

Iowa State University 

Michigan, University of 

Minnesota, University of 

New York University 

New York University 

North Carolina, University of 

Washington University 

Washington, University of 

Principal Investigator 

Hal Morgenstern, Ph.D. 

Changhwa Jacob Cheu 

Suresh P. Krishnan 

David J. Brenner, Ph.D. 

Anthony D. Lamontagne 

Ali Sheikhzadeh 

Michael E. Drues 

John G. Everett, Ph.D. 

Lisa M. Brosseau, Sc.D. 

Judy Q. Xiong, Ph.D. 

Mitchell D. Cohen, Ph.D. 

Irva Hertz-Picciotto, Ph.D. 

Bradley Evanoff, M.D. 

Harvey Checkoway, Ph.D. 

Small Business Grants (R43, R44) 

Berkeley Microinstruments, Inc. 

Cambridge Environmental, Inc. 

Dynaflow, Inc. 

EXOS, Inc. 

Medical Consultants Northwest, Inc. 

Microsensor Systems, Inc. 

Rehabilitation Technology Inc. 

Vermont Sensing 

tr U.S. GOVERNMENT PRINTING OFFICE: 1994: 550-147/00027 

Stuart W. Wenzel 

Stephen G. Zemba, Ph.D. 

Clinton E. Brown 

Beth Ann Marcus, Ph.D. 

Bob E. Hayes, Ph.D. 

N. L. Jarvis, Ph.D. 

Christopher C. Johnson 

Peter J. Kajenski, Ph.D. 

47 

66 

65 

31 

169 

49 

166 

79 

128 

167 

34 

167 

49 

87 

171 

170 

129 

50 

80 

171 

123 

122