NIOSH HEALTH HAZARD EVALUATION REPORT:

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Centers for Disease Control and Prevention

National Institute for Occupational Safety and Health

HETA #99-0260-2906

Marx Industries, Inc.

Sawmills, North Carolina

June 2003

This Health Hazard Evaluation (HHE) report and any recommendations made herein are for the specific facility evaluated and may not be universally

applicable. Any recommendations made are not to be considered as final statements of NIOSH policy or of any agency or individual involved.

Additional HHE reports are available at http://www.cdc.gov/niosh/hhe/reports

This Health Hazard Evaluation (HHE) report and any recommendations made herein are for the specific facility evaluated and may not be universally

applicable. Any recommendations made are not to be considered as final statements of NIOSH policy or of any agency or individual involved.

Additional HHE reports are available at http://www.cdc.gov/niosh/hhe/reports

applicable. Any recommendations made are not to be considered as final statements of NIOSH policy or of any agency or individual involved.

Additional HHE reports are available at http://www.cdc.gov/niosh/hhe/reports
ii

PREFACE

The Hazard Evaluations and Technical Assistance Branch (HETAB) of the National Institute for

Occupational Safety and Health (NIOSH) conducts field investigations of possible health hazards in the

workplace. These investigations are conducted under the authority of Section 20(a)(6) of the Occupational

Safety and Health (OSHA) Act of 1970, 29 U.S.C. 669(a)(6) which authorizes the Secretary of Health and

Human Services, following a written request from any employer or authorized representative of employees,

to determine whether any substance normally found in the place of employment has potentially toxic effects

in such concentrations as used or found.

HETAB also provides, upon request, technical and consultative assistance to Federal, State, and local

agencies; labor; industry; and other groups or individuals to control occupational health hazards and to

prevent related trauma and disease. Mention of company names or products does not constitute endorsement

by NIOSH.

ACKNOWLEDGMENTS AND AVAILABILITY OF REPORT

This report was prepared by Josh Harney, Jeffrey Nemhauser, Chris Reh, and Doug Trout of HETAB,

Division of Surveillance, Hazard Evaluations and Field Studies (DSHEFS), and Steve Schrader of the

Division of Applied Research and Technology (DART). Field assistance was provided by Greg Burr, Aaron

Sussell, and Dino Mattorano of HETAB. Paul Dowdy, Registered ElectroDiagnostic Technician, performed

our nerve conduction studies. Interpretation of nerve conduction studies was performed by Mark J. Goddard,

MD, University of Cincinnati Department of Physical Medicine and Rehabilitation. Analytical support was

provided by Datachem Laboratories. Desktop publishing was performed by Ellen Blythe, David Butler, and

Pat McGraw. Review and preparation for printing were performed by Penny Arthur.

Copies of this report have been sent to employee and management representatives at Marx Industries, Inc.

and the OSHA Regional Office. This report is not copyrighted and may be freely reproduced. Single copies

of this report will be available for a period of three years from the date of this report. To expedite your

request, include a self-addressed mailing label along with your written request to:

NIOSH Publications Office

4676 Columbia Parkway

Cincinnati, Ohio 45226

800-356-4674

After this time, copies may be purchased from the National Technical Information Service (NTIS) at

5825 Port Royal Road, Springfield, Virginia 22161. Information regarding the NTIS stock number may be

obtained from the NIOSH Publications Office at the Cincinnati address.

For the purpose of informing affected employees, copies of this report shall be

posted by the employer in a prominent place accessible to the employees for a period

of 30 calendar days.
iv

Highlights of the NIOSH Health Hazard Evaluation

Evaluation of Exposure to Spray Adhesive 

(1-bromopropane [1-BP])

This Health Hazard Evaluation was requested by the North Carolina Department of Labor to address concerns

about possible health problems related to working with a spray adhesive that contains the chemical 1-

bromopropane [1-BP]. We also checked to see if Marx employees were exposed to arsenic.

What NIOSH Did

# We checked the air for 1-BP levels.

# We took air, water, hand wipe, and surface dust

samples to try to find any arsenic source.

# We asked employees to fill out a questionnaire

and participate in a medical survey.

# We conducted a medical survey to see if

exposure to 1-BP at Marx was causing

problems with blood counts, nerve problems,

and, for men, reproductive problems.

What NIOSH Found

# Employees on the spray lines were exposed to

high levels of 1-BP.

# The wall fans near spray tables don’t lower

1-BP levels enough.

# Some Marx workers were having symptoms of

headache and feeling “drunk” that might have

been related to overexposure to 1-BP.

# We did not find evidence that 1-BP exposure

caused nerve or reproductive problems, or

problems with blood counts.

# Many spray line employees had increased

levels of arsenic in their urine, but we did not

find any exposure to arsenic at Marx.

What Marx Managers Can Do

# Lower worker exposures to 1-BP by switching

to water-based spray glue, or by making

ventilated spray booths that enclose the spray

tables and exhaust the 1-BP to the outdoors.

# Make sure glue sprayers are protected from skin

contact with the glue.

# Train employees on health and safety issues

related to 1-BP and on proper use of equipment

so that exposure to 1-BP can be minimized.

# Re-evaluate employee exposures to 1-BP after

attempts to decrease 1-BP exposure have been

made.

What Marx Employees Can Do

# Attend all training and education sessions given

by the management

# Follow instructions on proper use of the

adhesive spray equipment and any equipment

designed to decrease exposure to 1-BP,

including spraying only the smallest amount of

glue that still makes a good cushion.

Highlights of the HHE Report

What To Do For More Information:

We encourage you to read the full report. If you

would like a copy, either ask your health and

safety representative to make you a copy or call

1-513-841-4252 and ask for

 HETA Report #99-0260-2906

Health Hazard Evaluation Report 99-0260-2906
v

Marx Industries, Inc.

Sawmills, North Carolina

June 2003

Joshua M. Harney, MS

Jeffrey B. Nemhauser, MD

Christopher M. Reh, PhD, CIH

Douglas Trout, MD, MHS

Steve Schrader, PhD

SUMMARY

In April 1999, the North Carolina Department of Labor (NCDOL), Occupational Safety and Health Division,

responded to reports that four employees of Marx Industries, Inc., in Sawmills, North Carolina, had been treated

at a local hospital. All four had been evaluated for neurologic symptoms of an unclear cause. Hospital laboratory

testing reportedly revealed each to have had elevated levels of bromide ion (Br) in blood and arsenic in urine. A

NCDOL investigation found no evidence of occupational exposure to arsenic at Marx. Because of concern that

worker exposure to 1-bromopropane (1-BP) (and/or possibly arsenic) at Marx was related to observed health

effects, NCDOL submitted a request to the National Institute for Occupational Safety and Health (NIOSH) for a

health hazard evaluation (HHE). 

On November 16-17, 1999, NIOSH investigators conducted an initial site visit, and measured 1-BP

and 2-bromopropane (2-BP, also known as isopropyl bromide, found as a contaminant of 1-BP formulations)

inhalation exposures to employees working in and near the adhesive spray operations. An additional inhalation

exposure assessment was conducted on January 29, 2001. A medical evaluation was performed in

January/February 2001 and consisted of (1) a questionnaire survey, (2) collection of blood for a complete blood

count (CBC) and to measure whole blood and serum Br concentrations, (3) collection of urine to measure urine Br

and arsenic concentrations, (4) nerve conduction testing, and (5) an evaluation of the male reproductive system.

NIOSH representatives further investigated potential sources of arsenic exposure at Marx on May 23, 2001.

Data from 16 full-shift personal breathing zone (PBZ) samples for 1-BP during the November 1999 exposure

assessment (geometric mean [GM] 81.2 ppm; range 18 - 254 ppm) and from 13 full-shift PBZ samples during the

January 2001 assessment (GM 45.7 ppm; range 7 - 281 ppm) revealed that most spray-line workers were exposed

to 1-BP at concentrations above proposed 25 ppm exposure guidelines during both exposure assessments. PBZ

concentrations of 1-BP were lower in January 2001 compared to November 1999, although the difference was not

statistically significant. Among unexposed workers (assessed only during the January 2001 survey), none had 1-BP

exposures exceeding 5 ppm (GM 1.1 ppm; range 0.1 - 4.9 ppm). Area air sampling in areas adjacent to the spray

lines during both surveys found low concentrations of 1-BP, indicating that 1-BP vapors were migrating from the

spraying operations. 2-BP concentrations in air were found to be low in both exposure assessments. 

Forty-three (72% of the 60 workers) persons participated in the questionnaire survey, including 13 workers exposed

to 1-BP and 30 workers unexposed. Among these 43, end-of-week and start-of-week serum and urine Br and whole

blood Br concentrations were statistically significantly greater among the exposed group compared to the

unexposed group, and all were correlated with individual PBZ 1- BP air concentrations. 
vi

Among the symptoms assessed in the questionnaire survey were symptoms consistent with nonspecific effects of

exposure to bromine and/or solvents. Headache was the symptom reported by the most workers (22 workers). We

found that symptoms of anxiety (nervousness), feeling drunk, and headache were associated with exposure to 1-BP.

Other evaluated symptoms (such as trouble concentrating) were not related to exposure.

Forty workers had blood samples analyzed for a CBC. All measures of red blood cells, hemoglobin, and platelets

were within the normal ranges provided by the laboratory; one person (unexposed to 1-BP) had a white blood cell

count slightly below the lower end of the normal range provided by the laboratory. There were no statistically

significant differences in the medians of these parameters between the exposed and unexposed workers and we

found no statistically significant relationships between exposure (increasing 1-BP PBZ air or urine Br

concentrations) and individual cell counts or hemoglobin concentration. 

None of the workers completing the questionnaire responded that they had a doctor-diagnosed reproductive or

infertility problem. Nine men (50% of the 18 male participants) participated in the laboratory evaluation of male

reproductive function, including three exposed workers. Five of the nine men had an abnormal semen analysis; four

of these five were unexposed to 1-BP. Analyses to evaluate relationships between measures of exposure (including

1-BP PBZ air concentration and end-of-week urine Br concentration) and the three sperm indices (shape, motility,

and number) revealed no evidence of a statistically significant correlation.

Forty-two (98%) of the forty-three participants had nerve conduction studies performed. The one worker who did

not have nerve conduction testing was unexposed. Of the 42, five (12%) were abnormal. Among the 5 workers

with abnormal tests, 2 were among the 13 workers exposed to 1-BP, although neither were sprayers. The

prevalence ratio (PR) for an abnormal nerve conduction test among exposed workers was 1.5 (95% confidence

interval 0.3 - 7.9). PBZ exposure to 1-BP and end-of-week urine Br concentration were higher among persons with

normal nerve conduction testing, although the differences were not statistically significant.

Forty-one participants provided urine specimens that were analyzed for total inorganic arsenic. Twelve workers

had levels of inorganic arsenic above 25 :g/g creatinine; ten (83%) of those twelve workers had jobs near or on the

Springs and Glue Lines. As a result of these data and previous concern about arsenic exposure at Marx, in May

2001 NIOSH investigators conducted a thorough examination of the Marx workplace for a source of arsenic. No

arsenic was detected in any of the air, bulk adhesive, or drinking water samples collected during that evaluation.

Of the 30 surface wipe samples collected from around the plant, one (collected on the concrete surface of the

loading dock) had a detectable quantity of arsenic on it.

In this HHE we found inadequate controls of 1-BP exposure and a potential health hazard among employees

exposed to 1-BP. Most workers on the adhesive application lines were exposed to 1-BP at concentrations above

25 ppm, and some were exposed to much higher concentrations. These results suggest that the spray-line exhaust

fans in place at Marx at the time of the HHE were not adequately capturing the 1-BP vapors generated during the

spray adhesive operations. Data from the questionnaire survey suggest that excessive exposure to 1-BP among

HHE participants may be related to acute symptoms (such as anxiety [nervousness], feeling drunk, and headache)

that have been associated with excessive exposure to bromine or to other types of solvents. We found no evidence

for other health effects related to occupational exposure to 1-BP among persons working at Marx during the time

of our evaluation.

Where NIOSH has conducted surveys in other foam fabrication facilities, implementation of recommended

engineering controls has successfully reduced inhalational exposure to 1-BP. Recommendations are made in this

report to assist Marx Industries in accomplishing similar results.
vii

We found no source of arsenic at Marx and conclude that occupational exposures at Marx are not likely to account

for the elevated urinary arsenic levels found among employees.

KEYWORDS: SIC Code 2392 (House furnishing, Except Curtains and Draperies) 1-bromopropane, 1-BP, npropyl bromide, 2-BP, 2-bromopropane, isopropyl bromide, arsenic, nerve conduction tests, bromine, reproductive

problems, semen analysis, sperm analysis, complete blood count, solvent. 
TABLE OF CONTENTS

Preface . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ii

Acknowledgments and Availability of Report . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ii

Highlights of the HHE Report . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . iii

Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . iv

Introduction ......................................................................... 1

Background ......................................................................... 1

Review of Medical Records . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1

Workplace Description ............................................................. 2

Methods ........................................................................... 3

Environmental exposure assessment ................................................... 3

1-BP and 2-BP . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3

Arsenic . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3

Medical Assessment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4

Questionnaires ................................................................ 5

Complete Blood Count .......................................................... 5

Serum Chemistry . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6

Serum, Whole Blood, and Urine Bromide Ion ......................................... 6

Semen Samples . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6

Nerve Conduction Studies ........................................................ 6

Urinary Arsenic Levels . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7

Evaluation Criteria . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7

1-BP and 2-BP Evaluation Criteria . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7

Bromine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9

Urinary Arsenic . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10

Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10

November 1999: Initial 1-BP and 2-BP Exposure Assessment and Medical Evaluation . . . . . . . . . . . . 10

January 2001: Second 1-BP and 2-BP Exposure Assessment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11

January 2001: Medical Survey . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11

Serum, Urine, and Whole Blood Br . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11

Questionnaires - Questions Concerning Possible Excessive Exposure to Solvent . . . . . . . . . . . . . . 12

Complete Blood Count . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12

Serum Chemistry . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13

Reproductive Issues . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13

Questionnaire . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13

Semen Samples . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13

Nerve Conduction Studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14

Urinary Arsenic Concentrations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14

May 2001: Arsenic Investigation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14
ix

Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15

1-BP Industrial Hygiene Exposure Assessment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15

1-BP Medical Survey . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16

Markers of Exposure to 1-BP . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16

Bromism and Questionnaire Assessment of Solvent-Related Symptoms . . . . . . . . . . . . . . . . . . . . 17

CBC . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17

Reproductive Issues . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17

Nerve Conduction Tests . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17

Survey Limitations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17

Arsenic . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18

Recommendations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18

References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20
Health Hazard Evaluation Report No. 99-0260-2906 Page 1

INTRODUCTION

In April 1999, the North Carolina Department of

Labor (NCDOL), Occupational Safety and Health

Division responded to reports of four employees of

Marx Industries, in Sawmills, North Carolina, who

had been treated at local hospitals in March 1999.

All four had been evaluated for neurologic

symptoms of uncertain etiology. Hospital laboratory

testing revealed each to have had elevated levels of

bromide ion (Br) in blood and arsenic in urine.

Based on these findings, an investigator from

NCDOL visited Marx Industries to collect air, wipe,

water, and bulk samples for arsenic. No arsenic was

detected in any sample collected by NCDOL.

Because of concern that workers may have had

occupational exposures to Br and/or arsenic in their

work at Marx Industries, in June 1999 NCDOL

submitted a request to the National Institute for

Occupational Safety and Health (NIOSH) for a

health hazard evaluation (HHE). In the request,

NCDOL was specifically concerned about

occupational exposures to the solvent

1-bromopropane (1-BP, also known as n-propyl

bromide) during the spray application of adhesives.

1-BP is a solvent recently introduced for use in the

United States and is the primary solvent vehicle for

the adhesive used in the manufacturing processes at

Marx Industries.

On November 16-17, 1999, NIOSH investigators

conducted an initial site visit to Marx Industries. At

that time, the plant had been using adhesives

formulated with 1-BP for approximately one year.

NIOSH investigators spoke with management and

employee representatives, reviewed the company’s

Occupational Safety and Health Administration

(OSHA) Log and Summary of Occupational Injuries

and Illnesses (“200 Logs”), and interviewed

available employees whose names appeared on the

OSHA log as having had an “adhesive exposure

related illness” within the previous year. In addition,

NIOSH investigators measured 1-BP and

2-bromopropane (2-BP, also known as isopropyl

bromide) exposures to workers in and near the

adhesive spray operations. An additional inhalation

exposure assessment was conducted on January 29,

2001, in conjunction with a medical survey. The

medical evaluation was performed in

January/February 2001 and consisted of a

questionnaire survey; collection of blood and urine to

determine complete blood counts (CBC), serum,

urine, and whole blood Br concentrations, and urine

arsenic concentrations; nerve conduction testing; and

an evaluation of the male reproductive system.

Because urine arsenic concentrations collected

during the medical evaluations raised concerns

regarding the presence of an unidentified source of

arsenic within the plant, investigators from NIOSH

returned to Marx Industries on May 23, 2001, to

further investigate potential sources of arsenic

exposure within the workplace.

A letter summarizing the results of the November

1999 industrial hygiene data was distributed to

management and employee representatives on

February 1, 2000. In April 2001 employees were

notified of their individual urinary arsenic levels

from the tests performed during the week of January

29, 2001. In a letter to management and employee

representatives dated April 16, 2001, NIOSH also

provided a summary of the results of that arsenic

testing. Letters to individual employees presenting

the remaining results of their medical tests were

distributed in June 2001. A letter to management

and employee representatives summarizing the May

23, 2001, site visit to Marx was distributed on

October 3, 2001. The North Carolina State

Department of Health and the NCDOL were advised

by telephone of data concerning potential arsenic

exposure immediately after data were analyzed.

BACKGROUND

Review of Medical Records

A review of available medical records for the

hospitalized Marx Industries employees (two of

whom were working at Marx at the time of the initial

site visit) revealed that all four had been hospitalized

in March 1999 for similar neurological complaints:

lightheadedness and/or dizziness, lower extremity

weakness, varying degrees of difficulty standing or

walking (ataxia), and varying degrees of bilateral
Page 2 Health Hazard Evaluation Report No. 99-0260-2906

lower extremity numbness or paresthesias. Each

employee had had these symptoms for variable

lengths of time (ranging from approximately two

weeks to two months) prior to their hospital

admission. One employee also described visual

hallucinations at that time. Three of the four had

worked at Marx Industries for at least three years as

foam cushion fabricators; the fourth had only

recently been hired at the facility as a foam cushion

fabricator. Each attributed their symptoms to an

occupational exposure. 

On admission, all four hospitalized employees were

found to have elevated serum Br concentrations (77

milligrams per deciliter [mg/dL]; 53 mg/dL; 100

mg/dL; 24 mg/dL). Three of four employees also

had elevated urinary arsenic concentrations identified

at admission (224 micrograms per liter [:g/L]; 200

:g/L; 318 :g/L); the fourth employee was

subsequently identified as having an elevated urinary

arsenic level following discharge from the hospital

(224 :g/L). Ultimately, all four of the hospitalized

Marx Industries employees carried a diagnosis of

(and were treated for) both Br and arsenic

intoxication.

Workplace Description

At the time of the initial NIOSH site visit (November

1999), Marx Industries employed approximately 80

workers in the manufacture of foam cushions for

sofas and other upholstered seating furniture. At the

time of the return site visit in January/February 2001,

there were approximately 60 persons working at the

plant. Cushion manufacture is also referred to as

foam fabrication. Workers apply a spray adhesive to

variously-shaped pieces of flexible foam and then

press the pieces together by hand. The adhesive is

applied to the foam by means of a siphon-cup feed,

compressed air spray gun. The solvent vehicle for

the spray adhesive is 1-BP. Although 1-BP is the

primary solvent constituent, small amounts of 2-BP

are found in many 1-BP formulations.*

Marx Industries employs workers on two separate

foam fabrication lines where the 1-BP-containing

adhesive is spray applied: the Springs Line and the

Glue Line. The Springs Line consists of four spray

tables. Three of these tables are designed to

accommodate two sprayers, while the fourth table is

designed for only one sprayer. A mechanical

conveyor belt, on which assembled cushions are

placed, runs alongside the spray tables and separates

the tables from an outside wall. Completed cushions

are placed on the conveyor belt by Springs Line

employees and are then collected by a doffer who

bundles the cushions into a complete order in

preparation for shipping. Four exhaust fans are

located in the outside wall along which the conveyor

belt runs. These fans were installed in the late

winter/early spring of 1999 to facilitate vapor

removal after some employees on the foam

fabrication lines had begun to experience adverse

health effects. At one time, the Springs Line

included an extra spray table (designed for two

sprayers) located in the same area but away from the

conveyor belt. By January 2001 this table was no

longer in use.

The Glue Line, similar in design to the Springs Line,

is located in a different room. The Glue Line has

five spray tables, with three being designed to

accommodate two sprayers, and two designed for a

single sprayer. As on the Springs Line, a conveyor

belt separates the spray tables from an outside wall.

The three exhaust fans on the wall opposite the spray

tables on the Glue Line were installed at the same

time as were the fans on the Springs Line.

METHODS

Environmental exposure

assessment

*

Bulk sampling of the two adhesive formulations

used at Marx during the course of the HHE revealed

that the formulations contained (by weight): 58 % 1-BP

and 0.135 % 2-BP (Imperial Adhesive); and 68.5 % 1-

BP and 0.0265 % 2-BP (Mid-South Adhesive). The

current (ASTM) International standard for 2-BP

contamination of neat 1-BP is 0.1%; the industry

average, however, ranges from 0.02% to 0.03%.
Health Hazard Evaluation Report No. 99-0260-2906 Page 3

1-BP and 2-BP

In the course of the two exposure assessments, all

workers on the Springs and Glue Lines were targeted

for full-shift 1-BP and 2-BP personal breathing zone

(PBZ) air sampling. Worker participation in this

study was voluntary. Area air sampling was

conducted at operations near these lines to determine

the extent of 1-BP and 2-BP vapor migration. Air

sampling was conducted using a NIOSH draft

analytical method for 1-BP and 2-BP. In this

method, air is drawn through a standard charcoal tube

(SKC Anasorb® CSC) at a nominal flowrate of 50 to

100 milliliters per minute (mL/min) using a

calibrated personal sampling pump. For the PBZ air

sampling, the sampling pumps and sample trains

were worn by the subjects for the entire work-shift;

the sample media (charcoal tubes) were placed in the

subjects’ breathing zones. 

After sampling, the charcoal tubes were capped and

shipped refrigerated to the analytical laboratory. The

front and back sections of the charcoal tubes were

placed in glass vials, and each section was desorbed

for 30 minutes with one mL of carbon disulfide.

Each sample was analyzed for 1-BP and 2-BP using

gas chromatography with a flame ionization detector.

For the bromopropane exposure assessment

conducted during November 1999, the 1-BP limit of

detection (LOD) and limit of quantification (LOQ)

for the draft NIOSH method were 0.9 micrograms

per sample (:g/sample) and 3 :g/sample,

respectively. The LOD and LOQ for 2-BP were 2

and 6 :g/sample, respectively. LODs and LOQs are

values determined by the analytical procedure used

to analyze the samples, and are not dependent on

sample volume. Minimum detectable concentrations

(MDCs) and minimum quantifiable concentrations

(MQCs) are determined by dividing the LODs and

LOQs by air sample volumes appropriate for the

given set of samples. In determining the MDC and

MQC for these exposure data, the NIOSH industrial

hygienist used the highest sample volume collected

during this survey (24.7 liters[L]). This results in a

1-BP MDC and MQC of 0.007 and 0.02 parts per

million (ppm), and a 2-BP MDC and MQC of 0.02

and 0.05 ppm. The MDC and MQC reflect the

sensitivity of the air sampling and analysis protocol,

that is, the lowest 1-BP and 2-BP exposure

concentrations that could be reliably detected and

quantified by the procedures used in this study.

The purpose of the follow-up bromopropane

exposure assessment in January 2001 was to provide

current exposure information for those workers

participating in the medical survey. Additionally, the

second exposure assessment was more

comprehensive in that it included employees working

on the spray lines as well as employees working

away from the spray lines. During this second

bromopropane exposure assessment, the personal

sampling pumps were calibrated at 100 mL/min.

The LOD and LOQ for 1-BP were 1 :g/sample and

3 :g/sample, respectively. This translates into an

MDC and MQC of 0.004 ppm and 0.01 ppm,

respectively, when using a sample volume of 50.6 L,

the highest sample volume collected during this

exposure assessment. The LOD and LOQ for 2-BP

were 0.8 :g/sample and 3 :g/sample, respectively.

This yields an MDC of 0.003 ppm and an MQC of

0.01 ppm, based upon the same sample volume.

Arsenic

The May 2001 site visit was conducted specifically

to evaluate the potential for arsenic exposure among

Marx employees. During this site visit, NIOSH

representatives collected 18 air samples, 30 wipe

samples (Ghost Wipes®) of many work surfaces, 17

bulk samples of materials used during the workday,

and four drinking water samples from different

sources within the plant. The air, wipe, and bulk

samples were analyzed according to NIOSH Method

7300, with modifications made for each respective

matrix.1

The air samples were collected onto mixed cellulose

ester filters in 37 mm cassettes using air sampling

pumps calibrated at a nominal flow rate of 3 L/min.

The LOD and LOQ, were 0.9 :g/sample and 3

:g/sample, respectively. Based on a sample volume

of 1400 L, this yielded a minimum detectable arsenic

concentration of 0.6 micrograms per cubic meter of

air (:g/m3

). 
Page 4 Health Hazard Evaluation Report No. 99-0260-2906

Among the 18 air samples for arsenic were three PBZ

samples and 15 general area samples. A Springs

Line sprayer, a Glue Line sprayer, and a utility

worker each provided a PBZ sample. The area

samples were collected from the following locations:

the break room, Springs Line (3 samples), pattern

cutting, near the shredder, foam cutting (2 samples),

Glue Line (2 samples), ‘hand cutting’ area near the

Glue Line, at the cutting table, outside the north side

of the Marx Industries building near the veneer

building, ‘blow & fill,’ and outside near the loading

dock. 

Thirty wipe samples were collected for arsenic. The

LOD and LOQ were 8 :g/sample and 30 :g/sample,

respectively. Morning and afternoon hand wipe

samples were collected from five workers at the Glue

Line, and three workers at the Springs Line. Two

NIOSH investigators submitted hand wipe samples

at the same times for comparison purposes. Ten

wipe samples were collected from the following

areas: Springs Line spray table, Springs Line saw

table, Glue Line spray table; exhaust fan near Glue

Line Parabound M-295 silicone release agent, Husky

525 lotion from Glue Line, vending room table top,

settled dust from gas heater near Glue Line, sewing

department break table, and the loading dock near the

Glue Line.

Bulk samples of solid and liquid materials present in

the workplace were also collected and submitted for

arsenic analysis. The solid bulk sample analysis had

an LOD and LOQ of 3 micrograms per gram (:g/g)

and 10 :g/g, respectively. For the liquid bulks, the

LOD and LOQ were 80 :g/L and 300 :g/L,

respectively. Solid and liquid bulk samples included

the following: Mid South #6464 adhesive (from Glue

Line supply barrel and a spray gun); Mid South

#6464 adhesive (from Springs Line supply barrel and

a spray gun); red kerosene-based spray gun cleanser;

white battening material; foams P180-27, P180-33,

1122B (blue), P1545, H1A80-27, and P1530;

Loshun yellow hand cream; brown paper from spray

table coverings; and TACC T-285 Hi Yield spray

adhesive (an adhesive used in the past at Marx).

Drinking water samples from the sewing bags room

drinking fountain, the drinking fountain by the ramp

down to the Springs Line, the sink by the four

bathrooms in the rear loading dock between the

Springs and Glue Lines, and the office water cooler

were also collected for arsenic analysis. The samples

were cooled and shipped overnight to be analyzed by

US Environmental Protection Agency (EPA) method

6010.2

 The LOD and LOQ for this method were 2

:g/L and 7 :g/L, respectively.

Medical Assessment

As part of the initial survey conducted in November

1999, a NIOSH medical officer reviewed the OSHA

200 Log and spoke with 4 of the 10 employees

whose names appeared in the logs as having had

illness related to their exposure to the adhesive

containing 1-BP. 1-BP is a solvent which has has

had increasing use for industrial applications in

recent years; there is limited published information

concerning potential health effects related to

occupational exposure to 1-BP. The primary goal of

the overall medical assessment was to evaluate

workers for health effects potentially related to

occupational exposure to 1-BP. We included an

assessment of exposure to arsenic in our protocol to

provide follow-up information to the 1999 NCDOL

survey. The protocol for this evaluation was

approved by the NIOSH Human Subjects Review

Board.

Based on job title and description of duties, we

identified those Marx employees who regularly work

on or near the lines where spray adhesive was

applied (the Springs and Glue Lines). For the

purposes of this investigation, those workers were

classified as being exposed to 1-BP. The

environmental and biological sampling results of this

group of workers were compared to those from the

group of workers who do not regularly work on or

near the Springs and Glue Lines. This second group

of workers was classified as being unexposed to

1-BP. PBZ air concentrations of 1-BP from the

January 2001 industrial hygiene assessment were

used as measures of personal exposure for many of

the analyses of the medical and biologic monitoring

data.
Health Hazard Evaluation Report No. 99-0260-2906 Page 5

Data analyses were done with SAS version 8.12.

The prevalence of symptoms among the exposed and

unexposed workers was assessed by the prevalence

ratio (PR); a 95% confidence interval (95% CI)

which excluded one, or a significance level of p #

0.05, indicates a statistically significant finding. The

PR represents the prevalence of the symptom in the

exposed group (workers on or near a foam

fabrication line) relative to the prevalence in the

unexposed group (other workers). A PR of one

means there is no association between the

symptom/illness and exposure. A PR of greater than

one indicates that there is evidence of an association.

For example, a PR of two would mean that a person

in the exposed group may be twice as likely to have

reported the symptom than a person in the unexposed

group. The assessment of the differences between

two groups of data was done with the t-test (for

normally distributed data) and the Wilcoxon twosample test (for data not normally distributed).

Correlation between the various biologic measures of

exposure was assessed by using the Spearman

correlation coefficient.

Questionnaires

Participants were recruited from the 60 employees at

Marx Industries during meetings conducted by

NIOSH representatives on the morning of Thursday,

January 25, 2001. Following an orientation session

that described the NIOSH HHE program and

provided basic information about 1-BP, employees

were asked to sign a consent form signifying their

agreement to participate in the HHE. The orientation

and consent process for the employees of Marx

Industries was conducted both in English and in

Spanish. All questions regarding participation were

answered prior to obtaining signed consent. Workers

received instruction that they could choose to

participate in all, some, or none of the HHE without

penalty.

On Tuesday, Wednesday, and Thursday of the

following week (January 30, January 31, and

February 1, 2001) workers completed

questionnaires. Spanish language questionnaires and

a Spanish-speaking interpreter were available for any

worker who requested them. The questionnaires

included questions about current work activities and

practices, length of employment at Marx Industries,

previous and additional employment, and personal

medical history information. The questionnaire

included questions that dealt specifically with issues

of reproductive and neurological health. Some of the

questions regarding neurologic health dealt with the

known acute narcotic (central nervous system

depressant) effects of solvents.3

Complete Blood Count

Participants in the HHE had a blood sample

collected both at the beginning of the work week and

again at the end. One of the tests performed on the

end-of-week blood was a CBC. This test measures

several different components within the blood: total

number of red blood cells (RBCs) and the amount of

hemoglobin (Hgb) inside them, total number of white

blood cells (WBCs), and total number of platelets.

Since blood cells are produced within the bone

marrow, the CBC can be used as a measure of the

health of the bone marrow, and has been used to

evaluate other types of occupational exposures.4

Because bone marrow is known to be poisoned by

some chemicals and there is evidence that

bromopropanes may cause bone marrow damage, we

collected a CBC to identify if 1-BP might be

affecting the blood-forming system among Marx

employees.

Serum Chemistry

The concentration of several different chemical

components in the blood was measured for HHE

participants. Serum chemistry levels measure the

concentrations of sodium, potassium, chloride,

carbon dioxide, blood urea nitrogen (BUN), and

creatinine. Alterations in some or all of these values

may serve as a marker for toxicity to the kidneys or

other body organs.

Serum, Whole Blood, and Urine

Bromide Ion

The concentration of Br in the serum (that portion of

the whole blood after blood cells are removed) and in
Page 6 Health Hazard Evaluation Report No. 99-0260-2906

the urine was measured for workers at both the

beginning and end of the work week. This test was

performed to determine whether Br concentrations

are elevated in the blood or urine of persons known

to be exposed to 1-BP, and also to determine whether

the measurement of Br concentrations in the serum or

urine can be used as an accurate marker for exposure

to 1-BP. At the end of the work week, a sample of

whole blood was also collected to be tested for Br

concentration. The whole blood Br concentration

was also compared to other data to determine its

suitability as a marker for exposure to 1-BP.

Semen Samples

Because 2-BP has been associated with effects on the

male reproductive system, we collected semen

samples from male Marx workers. Male volunteers

who consented to provide specimens of semen for

laboratory analysis were each given one insulated

specimen container. Each participant also received

both written and verbal instructions (in English or in

Spanish) detailing how semen specimens were to be

collected for optimal laboratory analysis.

Participants were responsible for delivering

specimens within 30 minutes of collection to an offsite laboratory during hours after work.

Semen samples were analyzed by NIOSH

investigators at a local, off-site laboratory for (1)

sperm count (the total number of sperm per cubic

centimeter of semen) and (2) sperm motility (the

percentage of sperm seen under a microscope to be

moving normally). A portion of each semen sample

was also sent to an outside contract laboratory for

analysis of sperm morphology (shape). Normal

ranges for each of these three measures (sperm

count, motility, and shape) were used as comparative

values. Based on these three measures, NIOSH

investigators made a semi-quantitative assessment

concerning whether each semen sample was normal

or abnormal.

Nerve Conduction Studies

Because there is evidence that bromopropanes can

cause neurological damage in laboratory animals, we

performed nerve conduction testing in order to

identify if 1-BP might be causing damage to the

peripheral nervous system (i.e., those parts of the

nervous system outside of the brain and spinal cord)

of Marx workers. Nerve conduction testing is

thought to be a sensitive indicator of damage to

peripheral nerves (it may detect abnormalities in

sensory nerves prior to the person being able to

detect a sensory loss).5

 On January 31, 2001, and

February 1, 2001, participating Marx Industries’

employees underwent nerve conduction studies.

These studies were conducted by a contractor to

NIOSH using a standardized method at an air

temperature of at least 32 degrees Centigrade.

Nerve conduction tests are done by placing wires on

the skin, giving a slight electrical stimulation, and

measuring how fast electricity passes through

specific nerves. These tests measure nerve

conduction velocity and were performed in two

nerves in the leg and one in the arm, by measuring

the speed of the electrical impulse (in meters per

second). The faster the nerve conduction velocity,

the better. Nerve conduction tests also measure the

number of nerve fibers stimulated by the impulse

(called amplitude). The more nerve fibers

stimulated, the better. There can be many causes of

abnormal results in nerve conduction studies.

Although this test can accurately measure delays in

normal nerve conduction velocity, it cannot tell us

why the nerve conduction velocity is slowed. In

some situations, some amount of slowing may be

normal while in other cases it may be pathological (a

sign that something is wrong).

Urinary Arsenic Levels

As discussed above, occupational exposure to

arsenic had been raised as concern in the HHE. At

the end of the work week a sample of urine was

collected and analyzed for the presence of inorganic

arsenic and the two main metabolites of inorganic

acid (monomethylarsonic acid and dimethylarsinic

acid). For this HHE the total concentration of these

three substances in urine is referred to as the total

inorganic arsenic. Urine samples were collected in

acid washed specimen cups and were shipped to the

contract laboratory for analysis. Results were
Health Hazard Evaluation Report No. 99-0260-2906 Page 7

reported as micrograms of inorganic arsenic per gram

of creatinine (:g/g creat). 

EVALUATION CRITERIA

As a guide to the evaluation of the hazards posed by

workplace exposures, NIOSH field staff employ

environmental evaluation criteria for the assessment

of a number of chemical and physical agents. These

criteria are intended to suggest levels of exposure to

which most workers may be exposed up to 10 hours

per day, 40 hours per week for a working lifetime

without experiencing adverse health effects. It is,

however, important to note that not all workers will

be protected from adverse health effects even though

their exposures are maintained below these levels. A

small percentage may experience adverse health

effects because of individual susceptibility, a preexisting medical condition, and/or a hypersensitivity

(allergy). In addition, some hazardous substances

may act in combination with other workplace

exposures, the general environment, or with

medications or personal habits of the worker to

produce health effects even if the occupational

exposures are controlled at the level set by the

criterion. These combined effects are often not

considered in the evaluation criteria. Also, some

substances are absorbed by direct contact with the

skin and mucous membranes, and thus potentially

increase the overall exposure. Finally, evaluation

criteria may change over the years as new

information on the toxic effects of an agent become

available.

The primary sources of environmental evaluation

criteria for the workplace are: (1) NIOSH

Recommended Exposure Limits (RELs),6

 (2) the

American Conference of Governmental Industrial

Hygienists’ (ACGIH®) Threshold Limit Values

(TLVs®),7

 and (3) the U.S. Department of Labor,

OSHA Permissible Exposure Limits (PELs).8

Employers are encouraged to follow the NIOSH

RELs, the ACGIH TLVs, or the OSHA limits,

whichever is the more protective criterion.

OSHA requires an employer to furnish employees a

place of employment that is free from recognized

hazards that are causing or are likely to cause death

or serious physical harm [Occupational Safety and

Health Act of 1970, Public Law 91–596, sec.

5(a)(1)]. Employers should understand that not all

hazardous chemicals have specific OSHA exposure

limits such as PELs and short-term exposure limits

(STELs). However, an employer is still required by

OSHA to protect their employees from hazards, even

in the absence of a specific OSHA PEL.

A time-weighted average (TWA) exposure refers to

the average airborne concentration of a substance

during a normal 8- to 10-hour workday. Some

substances have recommended STEL or ceiling

values which are intended to supplement the TWA

where there are recognized toxic effects from higher

exposures over the short-term.

1-BP and 2-BP Evaluation

Criteria

As with other solvents, occupational exposure to 1-

BP is thought to occur via both inhalation and skin

absorption. Potential health effects related to

overexposure to 1-BP (and many other solvents) may

include irritation of the eyes, mucous membranes,

upper respiratory tract, and skin. At higher levels of

exposure, central nervous system depression

(characterized by headache and dizziness, and

possibly leading to loss of consciousness) may occur.

Animal studies and case studies of human exposure

to 1-BP have suggested that excessive exposure may

be associated with hematologic (blood forming),

reproductive, and neurologic toxicity.9

 Several

studies have attempted to evaluate the effects of 1-BP

exposure on peripheral blood indices (blood cell

counts). In those studies of chronic exposure to 1-BP

in which blood cell counts and red blood cell

parameters were measured, each employed a

different exposure protocol, making comparability

among the study results difficult. Results reported by

different authors did not appear to be consistent at

comparable levels of exposure. The major study of

the effects of chronic inhalational exposure of 1-BP

on the male organs of reproduction was conducted by

Ichihara and colleagues.10 In this study, researchers
Page 8 Health Hazard Evaluation Report No. 99-0260-2906

divided male rats into 4 groups and exposed them to

1-BP at concentrations of 0, 200, 400 or 800 ppm for

8 hours a day for 12 weeks. The researchers

identified several effects potentially related to 1-BP

exposure. Although the results of the Ichihara paper

are potentially of concern, it should be recognized

that there is not always a direct correlation between

specific targets in animal species when compared to

humans. Since spermatogenesis and spermiation

differ among species, the most sensitive sperm

measures in one species may not be the same in

another. This complicates extrapolating the results of

this study to humans. Nonetheless, given the results

of this paper, the following effects on the human

organs of male reproduction might be expected to

occur: (1) a decrease in the number of mature sperm

or sperm with normal motility and/or morphology

and (2) a decrease in semen volume as the seminal

vesicles in exposed rats were found to be smaller in

size than in controls (about 90% of semen volume

comes from the seminal vesicles). Of interest, a

different study showed that male rats exposed to

concentrations of 1-BP at 1800 ppm had increases in

testicular weights as compared to control animals

(contradicting the findings discussed earlier).11 A

review of the literature relevant to neurotoxicity and

occupational exposure to 1-BP and 2-BP is presented

in Appendix 1. 

Currently, there are no NIOSH, ACGIH, or OSHA

exposure evaluation criteria for 1-BP. After a review

of available exposure data and human and animal

toxicologic data, but based primarily on data from

animal studies (including effects on the male

reproductive system [sperm motility]), a contractor

for the EPA has proposed an Acceptable Industrial

Exposure Limit (AEL) for 1-BP of 25 ppm.12 This

AEL currently exists only in draft form and may be

subject to further revision following public comment.

Others have reviewed the literature and suggested

that an occupational exposure limit of 60-90 ppm

would be appropriate.9

 The conclusions from this

latter literature review were in part based on

preliminary interpretation of data from a previous

NIOSH HHE.13

Albemarle Corporation (a producer of 1-BP) has

recommended an occupational exposure guideline

for 1-BP, based on data from a two generation

reproductive study in rats.14 In that study, young

male and female rats received a daily 6-hour

inhalation exposure to a known concentration of 1-

BP for a minimum of 70 days. After this period, the

animals were paired for mating, and the daily

exposures continued through the 14-day mating

period, and through day 20 of gestation. No litters

were observed in the 750 parts per million (ppm)

exposure group, and a significant decrease was

observed in the number and size of litters in the 500

ppm exposure group. A slight (insignificant)

decrease was observed in the mean number of pups

born and live pups per litter for the 250 ppm

exposure group. Based on these results and a 10-fold

safety factor, Albemarle set their 1-BP

recommended exposure guideline at 25 ppm as an 8-

hour TWA exposure.15

The South Korea Ministry of Labor is the only

government agency to develop an occupational

exposure level (OEL) for 2-BP. In 1998, the

Ministry issued a 2-BP OEL of 1 ppm as an 8-hour

TWA.16 This standard is based on a limited number

of workplace epidemiological studies and

toxicological (animal) studies which found that 2-BP

exposure produces reproductive effects in both males

(low sperm count) and females (ovarian

dysfunction), and also affects the hematologic

system.17,18,19,20,21,22

Bromine

Br-containing medications were widely used

beginning in the late 1800s until the 1940s to prevent

seizures and as sedatives.23 Br toxicity, resulting

from the chronic use (and abuse) of Br-containing

drugs, was first recognized in the 1920s.24 Beginning

in the late 1920s, reports in the medical literature

described the signs and symptoms of Br toxicity, and

the levels of Br in the blood necessary to produce

them.

More recently, measurement of serum Br

concentrations (the amount of Br dissolved in the

blood) has been used to monitor for exposures to

brominated compounds (for example, methyl

bromide) in the workplace.25 In the case of 1-BP, it
Health Hazard Evaluation Report No. 99-0260-2906 Page 9

is known that the metabolism (breakdown by the

body) of this chemical involves the debromination

(removal of Br from) the parent molecule.26

Measuring Br levels among workers chronically

exposed to 1-BP could serve as an indication of

levels of exposure.27

Br is cleared from the body such that approximately

half the body burden is excreted (passed in the urine)

within about 12 days. For example, if, following an

exposure, a person has a Br level measured in the

blood at 10 mg/dL, that level will fall to 5 mg/dL

within about two weeks, provided there are no

additional exposures. Treatment with intravenous

fluids containing chloride will reduce the time

required to excrete half the body burden of Br to

approximately 3 days.23

Patients with chronic Br intoxication may present

with a variety of signs and symptoms.24,28 In general,

however, the earliest symptoms of Br toxicity are

increasing agitation and irritability.23,24 Subsequent

clinical signs of Br toxicity vary depending upon the

concentration of Br in the body and the time course

of intoxication. Patients who are early in the course

of Br toxicity may complain of drowsiness,

weakness, confusion, agitation, slurring of speech,

loss of interest in normal activities, decreased

memory, and a decreased appetite.23,24,28 As the

intoxication becomes more chronic and as Br levels

increase, patients may have more slurring of speech

and increasing difficulty with their ability to speak

clearly (dysarthria).23,28,29 Persons with severe Br

intoxication may ultimately develop a psychosis

similar to schizophrenia, seizures, and stupor,

delirium or coma.23,24,28,29 Apart from the signs

mentioned above, neurological findings may vary

from patient to patient without a consistent pattern of

dysfunction.23 Abnormalities with gait, reflexes, and

the eye examination have been reported. Skin rash,

described as one of the classic findings of Br

toxicity, occurs in 25-30% of cases of Br

intoxication.23,28 This rash, which is described as

“acneiform” (similar to acne in appearance) may

appear on the face, trunk, or legs.23,24,28 However,

high levels of Br have been observed in the absence

of any rash.28

In the general, unexposed population, Br levels (in

whole blood and in serum) range from 0.35 mg/dL to

0.49 mg/dL and typically do not exceed 0.5

mg/dL.24,28 Reports in the medical literature reveal

that the therapeutic range of Br concentrations in

patients prescribed Br-containing medications is

from 48-96 mg/dL.24 Although cases of Br toxicity

have been reported at blood levels as low as 4

mg/dL,25 this is distinctly unusual. More typically,

levels less than 40-50 mg/dL are considered to be

relatively safe,23,28 and even levels less than 80 mg/dL

may not manifest obvious clinical effects.24 There is

not, however, uniform agreement as to the levels at

which clinical symptoms become apparent. Based on

a review of the literature, correlations between Br

levels in the blood and expected symptoms cannot be

readily made. Potentially fatal blood Br levels range

from 200 mg/dL to 300 mg/dL and above.24,25,29

Urinary Arsenic

Arsenic is an element which is found naturally in low

levels in our environment, but which is a poison

when too much is taken up in the body. Arsenic has

many uses in industry. When it is used in industry,

arsenic is most often in its inorganic form. Low

levels of inorganic arsenic, occurring naturally, can

also be found in well water in many places in the

United States and around the world. If a person has

an increased level of inorganic arsenic in their body,

it is likely that that person is being exposed to arsenic

from some source –possible routes of exposure could

include ingestion (food, water, contaminants from

some other source) and inhalation (airborne).

Although the concentration of inorganic arsenic in

the urine of persons not exposed to arsenic in the

workplace is variable,30 persons who have no unusual

exposures to arsenic frequently have levels of

inorganic arsenic in the urine of less than

approximately 20-25 :g/L.31 For this HHE, we are

considering an elevated level of inorganic arsenic in

the urine to be 25 :g/g creat or more, indicating

possible environmental or occupational exposure to

arsenic (:g/g creat of a substance in urine is often

similar to :g/L of urine [1 L urine often contains

approximately 1 g creat]). The ACGIH recommends

a biological exposure index (BEI) for arsenic (as

inorganic arsenic) in urine of 35 :g/L.7
Page 10 Health Hazard Evaluation Report No. 99-0260-2906

RESULTS

November 1999: Initial 1-BP

and 2-BP Exposure

Assessment and Medical

Evaluation

A total of 17 workers participated in the air

monitoring. One of these workers left work early,

allowing us to gather full-shift exposure data only for

the remaining 16 workers. Of these workers, seven

were Glue Line sprayers, and five were Springs Line

sprayers. In addition, there was a doffer and

supervisor/set-up person from both the Glue and

Spring Lines.

The data from the complete 1-BP and 2-BP

inhalation exposure determinations are located in

Table 1, and summary results based on the 16

full-shift 1-BP exposure measurements are in Table

2. The geometric mean (GM) 1-BP exposure for all

16 full-shift exposure measurements was 81.2 ppm

(range: 18.1 to 253.9 ppm). The GM 1-BP

concentrations for workers on the Springs Line (98.6

ppm) and on the Glue Line (69.8 ppm) were

significantlly different (p=0.4). The GM 1-BP

concentration for sprayers on the Springs Line (139.1

ppm) and on the Glue Line (88.4 ppm) were also

significantlly different (p=0.1). The GM 1-BP

exposure for all sprayers was 107.6 ppm (range 57.7

to 253.9 ppm).

Summary data based on the 16 full-shift 2-BP

inhalation exposure measurements are in Table 3.

The GM 2-BP exposure was 0.24 ppm, and the

exposures ranged from 0.08 to 0.68 ppm. The GM

2-BP concentration for workers on the Springs Line

was 0.28 ppm; that of workers on the Glue Line was

0.22 ppm. The GM 2-BP concentration for sprayers

on the Springs Line was 0.38 ppm; that of sprayers

on the Glue Line was 0.26 ppm.

Two area air samples were collected in areas

adjacent to the Glue and Springs Lines. The purpose

of these air samples was to determine if 1-BP and

2-BP vapors were migrating to other areas. The

airborne 1-BP and 2-BP concentrations measured in

the sample from the Focus Saw Area near the

Springs Line were 8.7 ppm and 0.06 ppm,

respectively. The airborne 1-BP concentration

measured in the sample from the cutting area

adjacent to the Glue Line was 5.3 ppm.

Unfortunately, 2-BP could not be determined in this

second sample due to the presence of an unknown

interference (not present in other samples).

A review of the company’s OSHA 200 Logs for

1997, 1998, and 1999 revealed that recordable

illnesses due to adhesive exposure were confined to

1999. Ten employees were listed as having illnesses

reported to be due to adhesive exposure. In addition

to the 10 listed employees, NIOSH investigators

learned that an additional 11 employees had also

undergone blood testing to evaluate for the presence

of elevated serum Br levels. The results of that

testing was not available for review. Following

review of the OSHA logs, the NIOSH medical

officer held confidential interviews with 4 of the 10

employees who were listed as having illnesses

reported to be due to adhesive exposure, 2 of whom

were among the 4 index cases. At the time of the

interviews, 2 of the 4 persons noted persistent

headaches. All four employees described a

numbness or a “pins and needles” sensation in both

legs and feet. The employees reported that this

sensation had been present for a variable length of

time, but all reported that it was slowly improving.

January 2001: Second 1-BP

and 2-BP Exposure

Assessment 

Table 4 shows the bromopropane exposures of the

Marx workers considered unexposed to 1-BP

(personnel not working near the adhesive spray

lines), while exposures for exposed workers

(personnel working near the spray adhesive lines) are

listed in Table 5. Summary statistics for the data in

these two tables are presented in Tables 6 and 7. The

GM 1-BP exposure for unexposed workers was 1.1

ppm (range: 0.1 – 4.9 ppm). All 2-BP exposures for
Health Hazard Evaluation Report No. 99-0260-2906 Page 11

unexposed workers were below the MQC of 0.01

ppm. The GM 1-BP exposure for exposed workers

was 45.8 ppm (range: 7.2 – 280.5 ppm), significantly

greater than the 1-BP exposure among unexposed

workers (p<0.01). The GM 2-BP exposure for

exposed personnel was 0.07 ppm (range: ND [nondetectable]–0.52 ppm). As during the initial

exposure monitoring survey in November, Springs

Line sprayers had higher full-shift 1-BP exposure

(GM = 162.2 ppm) than did the Glue line sprayers

(GM = 58 ppm), although the difference was not

statistically significant (p=0.2). Two sprayers rotated

between the Springs Line and the Glue Line during

the day. The GM exposure for 1-BP of these two

sprayers was 116 ppm.

January 2001: Medical Survey

Forty-three (72% of the 60 workers) persons

participated in the questionnaire survey. Among

those, 41 provided job title information, including the

following: 7 saw operators, 4 hand cutters, 1 baler

operator, 5 sprayers on the Springs Line (also called

gluers) and 5 sprayers on the Glue Line, 4 sewers, 3

fiber handlers, and 12 in the category of ‘other’

(which included a variety of job tasks including

supervisors). All the sprayers except one were

considered to be exposed to 1-BP during their usual

job tasks based on observation of their work

practices (one person had a job title of sprayer but

actually did not perform spraying activities). Four

other persons, including one saw operator and three

listed as ‘other,’ were also considered to be exposed

to 1-BP based on job tasks. Therefore, there were a

total of 13 persons considered exposed to 1-BP based

on knowledge of job tasks. A description of survey

participants is provided in Table 8. Among the total

respondents there were 24 females and 18 males (one

participant did not provide demographic

information). The mean age was 34 years and the

median time working at Marx Industries was 29

months. As presented in Table 8, workers

considered to be exposed to 1-BP had a significantly

higher mean exposure (GM 46 ppm [range 7 ppm -

281 ppm]) as measured by January 2001 PBZ air

sampling compared to workers unexposed (GM 1.1

ppm [range 0.1 - 5 ppm]). Workers exposed to 1-BP

were more likely to be female, younger, and

Hispanic. Current cigarette smoking was similar

among the two groups. Among all respondents, only

one said they wore gloves when handling foam

cushions, one said they wore a respirator at work,

and three said they wore protective clothing at work.

Serum, Urine, and Whole Blood

Br

Appendix 2 contains all data for the serum, urine,

and whole blood Br testing. Table 9 provides

summary data for these analyses by exposure status.

Forty-two participants had start-of-week serum Br

concentrations tested and thirty-nine had end-ofweek serum Br concentrations tested; thirty-nine

completed both tests. The GM serum Br

concentration for the end-of-week testing was 4.8

mg/ (range 1.7 to 43.5). The average difference

between the end-of-week and the start-of-week

serum Br concentrations was 1.0 mg/dl; this varied

between the exposed (2.3 mg/dl, range -3.2 to 7.5)

and the unexposed (0.3 mg/dl, range -0.9 to 1.9).

Overall, 12 of the 39 (three among exposed workers,

and 9 among unexposed workers) cross-week

differences were negative numbers; a cross-week

difference less than zero indicates a drop in serum Br

concentration during the week.

Forty-two participants had start-of-week urine Br

concentrations tested and 40 had end-of-week urine

Br concentrations tested; 40 completed both tests.

The GM Br concentration for the end-of-week

testing was 46.5 mg/dl (range 15.4 to 595.4). The

average cross-week difference in urine Br

concentrations was 41.9 mg/dl; this varied between

the exposed (131.1 mg/dl, range -20.1 to 496.6) and

the unexposed (3.6 mg/dl, range -29.5 to 77.2).

Overall 13 of the 40 (two among exposed workers,

and 11 among unexposed workers) differences were

negative numbers; a cross-week difference less than

zero indicates a drop in urine Br concentration during

the week.

Forty participants had whole blood Br concentrations

tested. The GM whole blood Br concentration was

4.7 mg/dl (range 1.9 - 32.6).
Page 12 Health Hazard Evaluation Report No. 99-0260-2906

All measures of exposure (Br in serum, urine, and

whole blood) were statistically significantly greater

among the exposed group compared to the

unexposed group. Additionally, all five measures of

exposure (end-of-week and start-of-week serum and

urine Br, and whole blood Br) were correlated with

individual PBZ 1- BP air concentrations (Table 10);

all the correlations (coefficients ranged from 0.37 to

0.88) were statistically significant. The relationships

with the highest correlation coefficient (r=0.88) were

between 1-BP air concentration and end-of-week

serum and whole blood Br concentrations. The

cross-week differences of both serum and urine Br

concentrations were also correlated with the air

measure (although the correlation coefficients were

lower). 

Questionnaires–Questions

Concerning Possible Excessive

Exposure to Solvent

One of the purposes of the questionnaire was to

assess the prevalence of symptoms (occurring in the

30 days prior to the survey) that could be consistent

with excessive exposure to brominated solvents.

Included among these were questions concerning

anxiety (nervousness), feeling drunk, headache,

trouble concentrating, unusual fatigue (sleepiness),

paresthesias (numbness and tingling) in hands or

feet, and tremor. Among these symptoms, headache

was the symptom reported by the most workers (22

workers). The prevalence of these seven symptoms

among the 13 exposed workers (compared to the

unexposed workers) is reported in Table 11. Anxiety

(nervousness) was the only symptom reported

significantly more frequently among the exposed

workers compared to those unexposed.

Analyses of PBZ 1-BP exposure among employees

by presence or absence of these symptoms are

reported in Table 12. Employees reporting anxiety

(nervousness), headache, and feeling drunk had

statistically significantly higher PBZ concentrations

of 1-BP compared to those not reporting those

symptoms.

Complete Blood Count

Of the 43 participants in the questionnaire survey, 3

responded that they had a doctor-diagnosed history

of anemia; all 3 were among the unexposed group.

Forty workers had blood samples analyzed for a

CBC. All of the measures of RBC, hemoglobin, and

platelets were within the normal ranges provided by

the laboratory. One person (unexposed to 1-BP), had

a WBC count of 3,700 cells per cubic millimeter

(mm3

), slightly below the lower end of the normal

range for WBC (normal range: 3,900 - 11,400

cells/mm3

). The remainder of the WBC measures

were within the normal range. Table 13 presents the

median values for the CBC parameters; there were no

statistically significant differences in the medians of

these parameters between the exposed and

unexposed workers. Complete CBC data is

presented with exposure information in Appendix 2.

Linear regression was performed to evaluate possible

sub-clinical effects of exposure to 1-BP on the

peripheral blood indices (which were all within

laboratory normal ranges [one exception noted

above]). Exposure was assessed by both PBZ 1-BP

concentrations and by end-of-week urine Br

concentration. We found no statistically significant

relationships between exposure (increasing 1-BP

PBZ air or urine Br concentrations) and individual

cell counts or hemoglobin concentration (Table 14).

Serum Chemistry

Concentrations of sodium, potassium, chloride,

carbon dioxide, BUN, and creatinine for the

participants were compared to the normal ranges for

clinical specimens provided by the laboratory. The

concentrations of all these substances in the serum

were within, or close to, the normal ranges. There

was no pattern of abnormality suggesting any workrelated affect on the concentrations of these

substances.

Reproductive Issues

Questionnaire
Health Hazard Evaluation Report No. 99-0260-2906 Page 13

Of the 42 persons who completed the reproductive

questions on the questionnaire, none responded that

they had a doctor-diagnosed reproductive or

infertility problem. The 18 men participating in our

survey represented 67% of the 27 men employed at

Marx Industries at the time of this HHE; 17 of the

men provided answers to questions pertaining to

male reproductive history. Of the 17 respondents,

one answered that he had tried but failed to father a

child, and a different worker responded that he had

difficulty with having or maintaining an erection.

The first of these workers was considered unexposed

to 1-BP (by evaluation of job duties), had low

measures of exposure to 1-BP (PBZ 1-BP air and

urine Br concentrations), and did not take part in the

male reproductive evaluation. The second worker

was considered exposed to 1-BP based on evaluation

of job duties, although his PBZ air concentration of

1-BP was similar to those levels found among the

unexposed group. Semen analysis of this worker fell

within or close to the normal range and he was

determined by NIOSH investigators not to have any

evidence at the time of the survey of damage to the

sperm-forming system. No other respondents

reported difficulties in having or maintaining an

erection. No respondents reported a history of

miscarriage or wives/partners with difficulty

becoming pregnant in the year prior to the NIOSH

survey.

Twenty-four (73%) of the thirty-three women

employed at Marx Industries at the time of this HHE

completed the health survey questionnaire. Not all

women answered all questions concerning

reproductive health; the questionnaire included some

questions that were not applicable to all participants.

There was no increase in reports of abnormal

menstruation (unusual menstrual cycle or heavy

bleeding), inability to become pregnant, or

miscarriage among women exposed to 1-BP

compared to women not exposed. 

Semen Samples

Nine (50% of the 18 male participants) men

participated in the laboratory evaluation of male

reproductive function. Three of the nine participants

were among the thirteen exposed workers (the other

ten exposed workers were female). The PBZ air

concentrations of 1-BP for the three men were 10.4,

18.8, and 79.5 ppm. Equipment difficulty in the field

during the survey delayed analyses for sperm

motility. Because of potential effects of lowered

temperature on sperm motility, these types of

evaluations are usually performed within 90 minutes

of collection. In this HHE, some of the analyses

were not performed until almost 120 minutes after

collection. However, percent motility of sperm in the

semen samples and sample age were not correlated,

suggesting that adverse effects of increased time prior

to analysis on sperm motility were not observed with

these samples.

After reviewing all three components of the semen

analyses for the nine men, the NIOSH investigators

determined that five of the nine men had an

abnormal semen analysis. Four of these five with

abnormal semen analyses were unexposed to 1-BP

and one was exposed (Table 15). In particular, two

participants had notable abnormalities in the sperm

heads. The first of these two persons had two types

of unusual sperm shapes–this person was unexposed

to 1-BP and had 1-BP exposure measures (1-BP PBZ

air concentration and end-of-week urine Br

concentration) close to the GM for the unexposed

group. The second of the two had one type of

unusual sperm shape – this person was exposed to 1-

BP and had a PBZ air concentration of 10.5 ppm

(less than the GM of air concentrations among the

exposed) and an end-of-week urine Br concentration

of 109.8 mg/dL (less than the GM urine Br

concentrations among the exposed).

Analyses to evaluate relationships between measures

of exposure (including 1-BP PBZ air concentration

and end-of-week urine Br concentration) and the

three sperm indices revealed no evidence of

statistically significant correlation (Table 16).

Nerve Conduction Studies

Forty-two (98%) of the forty-three participants had

nerve conduction studies performed. The one

worker who did not have nerve conduction testing

done was unexposed. Of the 42, 29 (69%) studies

were complete and judged by the consulting
Page 14 Health Hazard Evaluation Report No. 99-0260-2906

physician to be normal, 4 (10%) were incomplete

tests but without an identifiable abnormality, and 4

(10%) were complete, not abnormal, but considered

to be borderline by the consulting neurologist. Thus,

37 (88% of the 42) tests were classified as normal or

borderline. Four tests were determined by the

consulting physician to be abnormal and one was

‘probably abnormal;’ these five (12% of the 42) were

classified as abnormal. Among the five workers with

abnormal tests, two were among the thirteen workers

exposed to 1-BP, although neither were sprayers.

This yielded a PR for an abnormal nerve conduction

test among exposed workers of 1.5, with a 95%

CI=0.3 - 7.9. PBZ exposure to 1-BP or end-of-week

urine Br concentration were higher among persons

with normal nerve conduction testing although the

differences were not statistically significant (Table

17).

To determine if there might be some effect not

apparent due to the borderline nature of four of the

tests, the four borderline nerve conduction tests were

alternatively grouped with the abnormal tests (so that

there were a total of 9 abnormal tests and 33 normal

tests). Among the nine workers with abnormal tests

by this alternate grouping, two were exposed to 1-BP

and seven were unexposed (all four of the persons

with borderline tests were unexposed). The same

analyses as those done above were done with this

alternate grouping; the results were consistent with

those presented above.

Urinary Arsenic Concentrations

Forty-one participants provided urine specimens that

were analyzed for total inorganic arsenic. Twelve

workers had levels of inorganic arsenic above 25

:g/g creat; ten (83%) of those twelve workers had

jobs near or on the Springs and Glue Lines. In

personal letters sent to all participants, it was

recommended to all 12 that they follow up with their

physicians concerning the finding of arsenic in their

urine. Eight of these workers had levels that were

above 35 :g/g creat; levels of inorganic arsenic

above 35 :g/liter are above the ACGIH BEI. As a

result, NIOSH investigators conducted a thorough

examination of the Marx workplace for a source of

arsenic, the results of which are summarized below.

May 2001: Arsenic

Investigation

No arsenic was detected in any of the 18 air or 17

bulk samples collected during the May 2001

environmental evaluation. The minimum detectable

concentration for airborne arsenic was 0.6 :g/m3

,

well below both the ACGIH TLV and the OSHA

PEL of 10 :g/m3

. The drinking water samples also

did not have detectable levels of arsenic; the

analytical limit of detection for the method used for

drinking water analysis was 2 :g/L, well below the

legal limit of 10 :g/L (10 parts per billion of arsenic

in drinking water).32 One of the 30 surface wipe

samples, collected on the concrete surface of the

loading dock, had a detectable quantity of arsenic on

it. This indicated that a very small amount of arsenic

was present on the Marx Industries property, but was

not likely to account for the elevated urinary arsenic

levels found among employees. During the site visit,

NIOSH investigators looked for other possible

common sources of arsenic exposure among

employees. No epidemiological links other than

assigned work tasks (for example, persons with both

high and low urinary arsenic levels socialized and

took breaks and ate lunch together) were found. 

DISCUSSION AND

CONCLUSIONS

1-BP Industrial Hygiene

Exposure Assessment

During the initial exposure assessment (November

1999), the 1-BP exposure data indicated that 15 of 16

foam fabrication line personnel had inhalation

exposures in excess of the 25 ppm exposure criteria

recommended in draft form by the US EPA and by

the Albermarle Corporation. Seven workers had

1-BP exposures exceeding 100 ppm; all seven were

sprayers (three from the Glue Line and four from the

Springs Line). Area air sampling identified low

concentrations of 1-BP in areas adjacent to the foam

fabrication lines, indicating that 1-BP vapors were
Health Hazard Evaluation Report No. 99-0260-2906 Page 15

migrating from the spraying operations. None of the

2-BP exposure measurements from the November

1999 survey exceeded the exposure guideline of 1

ppm. Based on these data, in the February 2000

interim letter, NIOSH representatives recommended

to Marx that efforts be made to reduce exposure of

spray line personnel to 1-BP. NIOSH investigators

were not aware of any substantial changes in

engineering or administrative controls, or in the

employee use of personal protective equipment, to

reduce exposure to 1-BP at Marx during the time

interval between the November 1999 and January

2001 surveys.

During the January 2001 exposure assessment, we

found that overall 1-BP exposures among employees

on or near a foam fabrication line decreased,

although the decrease was not statistically significant

(45.7 ppm [GM] versus 81.2 ppm [GM]; p=0.14).

This observed decrease was primarily among the

sprayers on the Glue Line; the 1-BP exposure among

the sprayers on the Springs Line was similar in the

two surveys. In the January 2001 survey, exposed

workers had greater exposure to 1-BP than did

unexposed workers. Eight of thirteen foam

fabrication line personnel had 1-BP exposures in

excess of 25 ppm; all were sprayers (range: 38 - 281

ppm). Four of the eight sprayers had 1-BP exposures

exceeding 100 ppm. The exposed employees also

had the highest serum Br levels (range = 2.7 - 43.5

mg/dL, end-of-week serum bromide levels). Among

the unexposed workers, none had 1-BP exposures

exceeding 5 ppm (range: 0.1 - 4.9 ppm). Although

levels of measured exposure were low, the data from

the unexposed workers, as well as the area sampling

in the areas away from the foam fabrication lines,

indicate that 1-BP vapor migrates into non-spraying

areas of the plant. Regarding 2-BP, none of the

workers considered to be exposed to 1-BP had 2-BP

exposures above 1 ppm; only trace amounts of 2-BP

were found in non-spraying areas of the plant.

Considering the above findings, the NIOSH

investigators believe there is convincing evidence

that the foam fabrication line exhaust fans are not

adequately capturing the 1-BP vapors generated

during the spray adhesive operations. Most workers

on the two foam fabrication lines are exposed to 1-

BP at concentrations above 25 ppm, and some are

exposed to much higher concentrations.

Additionally, 1-BP vapors are migrating (albeit at

low levels) to nearby areas.

Whenever there is a potential for a hazardous

exposure in a workplace, traditional industrial

hygiene practice dictates that the following hierarchy

of controls, in decreasing order of desirability and

effectiveness, be implemented to protect worker

health:

1. Elimination of the toxic substance from the

workplace.

2. Substitution of the toxic substance with a

less toxic substance. 

3. Installation of engineering controls designed

to reduce exposure.

4. Use of administrative controls to reduce

exposure.

5. Use of personal protective equipment to

reduce exposure.

In many instances, it is not possible to eliminate or

substitute a chemical or material from a production

process without altering the integrity of the desired

product. Thus, many strategies for reducing

hazardous exposures center on the use of engineering

controls such as process isolation and/or local

exhaust ventilation. The NIOSH investigators

believe the 1-BP vapors can be controlled using a

spray booth at each work station, with each booth

containing a local exhaust ventilation system that

discharges the captured air and vapors outside the

building. In two other facilities that use spray

adhesives where NIOSH has conducted HHEs, the

combination of partial enclosure and local exhaust

ventilation has been highly successful in lowering

sprayer exposures to 1-BP and 2-BP.13,33 PPE is

frequently used to protect workers from hazardous

exposures. PPE should only be used when

engineering controls are not feasible, in the interim

when engineering controls are being installed or

repaired, or when engineering controls have not

sufficiently reduced exposures.

Regarding 2-BP, NIOSH investigators believe it is

prudent to use a spray adhesive formulation with the

lowest concentration of 2-BP.
Page 16 Health Hazard Evaluation Report No. 99-0260-2906

1-BP Medical Survey

Markers of Exposure to 1-BP

Our survey demonstrated that airborne 1-BP

concentrations were correlated with start-of-week

and end-of-week urine and serum Br concentrations,

as well as with end-of-week whole blood Br

concentration. Based on the fact that previous

studies have used urine Br as a marker of exposure,34

we chose to use end-of-week urine Br as a marker of

exposure for some of the analyses in this report.

Both the urine and the serum testing cross-week

difference (end-of-week minus start-of-week) yielded

negative results for some participants (both exposed

and unexposed), indicating a decrease in Br

concentration during the week. There are several

possible explanations for the decreasing Br

concentration at the end of the week that we

observed among exposed workers. It may be that

exposure to 1-BP in the time period prior to our

survey was greater than that during our survey,

leading to declining Br levels (reflecting the

decreased exposure); alternatively, it may be that

random variation among individuals’ Br levels are

reflected in our testing. Other aspects of 1-BP

metabolism which were not evaluated may also be

important. We conclude that serum, urine, and

whole blood Br concentrations may all be good

indicators of 1-BP exposure. There is evidence that

1-BP excreted unchanged in the urine may be, in

some instances, a more suitable choice of a

biomarker.34 However, urinary 1-BP detection

requires gas chromatography-mass spectrometry

(GC-MS) instrumentation and the specimen must be

analyzed immediately after collection. The financial

and logistical costs of this test may make its

performance difficult to implement on a widespread

basis. Conversely, most clinical laboratories can

perform analysis for Br, and analysis may be delayed

without serious degradation of specimen quality.

Therefore, cost constraints would be a main reason

why Br analysis might be chosen over 1-BP anlaysis

by GC-MS analysis as a marker of 1-BP exposure.

Further research is needed to learn more about the

most appropriate use of biologic markers of exposure

to 1-BP.

Bromism and Questionnaire

Assessment of Solvent-Related

Symptoms

Of the four Marx workers who had been hospitalized

prior to the HHE, one had a serum Br level

(measured during hospitalization) of 24 mg/dL; the

remaining three had serum Br levels in excess of 50

mg/dL (77 mg/dL; 53 mg/dL; 100 mg/dL). It should

be noted that one of the four (serum Br = 77 mg/dL)

did not have this level checked until the third hospital

day (and after receiving intravenous fluids), and

therefore could have had substantially higher levels

on admission to hospital. Among current Marx

workers at the time of the NIOSH survey, the highest

measured serum Br level was 43.5 mg/dL.

A review of the medical literature (see Evaluation

Criteria) indicates that serum Br levels in excess of

0.5 mg/dL are considered elevated. Br levels of less

than 40-50 mg/dL in the serum are generally not

associated with toxicity, although the range of serum

Br levels associated with symptoms has been

reported to vary widely. Analysis of symptom

information collected from the questionnaires reveals

that exposure to 1-BP was associated with symptoms

that could potentially be due to early bromide

toxicity (including feeling drunk or anxious

[nervous]) and/or symptoms that could be due to

general solvent toxicity (including headache). It

must be noted that all the symptoms used in our

questionnaire to assess possible acute solvent-related

health effects are nonspecific symptoms which could

have many potential causes.

Separately, the four workers who had been

hospitalized all described both problems walking and

painful tingling/numbness/pins and needles feeling in

the feet as among their most prominent symptoms.

While problems walking (ataxia) has been identified

in the literature as occurring as a result of bromide

toxicity, painful tingling/numbness/pins and needles

feeling (paresthesias) have not.
Health Hazard Evaluation Report No. 99-0260-2906 Page 17

Our findings suggest that excessive exposure to 1-BP

may be related to some acute symptoms that have

been associated with excessive exposure to Br.

However, the limitations of our HHE (described

below) and the fact that we did not see a consistent

association of 1-BP exposure with similar symptoms

(e.g., differing results for feeling drunk and trouble

concentrating) indicate that further work is needed to

confirm these findings.

CBC

Our CBC testing found no clinically relevant

abnormalities in the cell or platelet counts, and we

found no differences in the hemoglobin

concentrations and cell or platelet counts between the

exposed and unexposed workers. Our statistical

analyses of the individual cell and platelet counts and

hemoglobin concentrations by exposure to 1-BP

revealed no statistically significant correlations

within the normal ranges of the CBC indices.

Reproductive Issues

Nine male workers took part in the semen analysis

portion of the medical survey, and of those nine, only

three were among the exposed workers. Among this

small number of participants, we found no evidence

of decreases in sperm number, shape, or motility

related to 1-BP exposure.

Nerve Conduction Tests

We conducted nerve conduction testing on 42 of the

43 HHE participants, and identified five persons with

abnormal nerve conduction tests; however, we found

no relationship between abnormal nerve conduction

and 1-BP exposure.

Survey Limitations

The ability of this survey to detect potential

associations between 1-BP exposure and health

effects was limited by several factors. The first

limitation was the small number of participants in

each group, which decreases our ability to detect

differences between the exposed and unexposed

groups. A second limitation was the moderate

participation rate (72%) for our HHE; because not all

the Marx workers participated, our findings may be

subject to selection bias (persons who participated

may not be representative of all the workers). A

third limitation involves the possibility that some

workers may be more likely than others to have

health effects related to occupational exposure to 1-

BP, and the possibility that those workers may have

removed themselves from the workplace (due to

those health effects) prior to our HHE. Of the ten

employees (including the four workers treated at the

hospital) identified in the November 1999 OSHA

200 log review as having illnesses reported to be due

to adhesive exposure, only one was still working at

Marx Industries at the time of the medical survey in

January 2001; that employee did not fully participate

in the survey. And lastly, as mentioned in Results, a

limitation in the reproductive portion of the HHE

involved delays in analyzing sperm motility.

Although we did not see an obvious effect of this

delay, an effect cannot be ruled out.

Arsenic

Arsenic intoxication represents another potential

explanation for the findings of ataxia and paresthesias

among the four Marx workers hospitalized prior to

the HHE (ataxia and paresthesias in the legs can

occur 5 to 10 days following large acute arsenic

intoxication and also after chronic but more moderate

arsenic exposures). All four workers had total

(organic and inorganic) urinary arsenic levels of at

least 200 :g/L (224 :g/L; 200 :g/L; 318 :g/L; 224

:g/L) measured either during or shortly after their

hospital stays in March 1999. The percentages of

organic (non-toxic) and inorganic (toxic) arsenic in

the samples collected from these 4 individuals is

unknown. In this HHE (nearly two years after the

workers were hospitalized), NIOSH investigators

collected spot urine samples from 41 employees at

Marx Industries and analyzed for the presence of

inorganic (toxic) arsenic separately from that of

organic (non-toxic) arsenic. Inorganic arsenic levels

in these samples ranged from 6 - 215 :g/g creatinine

(5 - 271 :g/L).
Page 18 Health Hazard Evaluation Report No. 99-0260-2906

Previous research has shown that levels of urinary

arsenic of approximately 35 :g/L typically occur

when airborne concentrations are on the order of 10

:g/m3.

35 Such concentrations of arsenic in air were

not found during either the NCDOL investigation of

April 1999 or during the thorough investigation

undertaken as part of this HHE. No arsenic was

found in bulk samples of materials from Marx, and

only a trace amount of arsenic was found in one of

30 wipe samples. NIOSH investigators concluded

from these data that the elevated urinary inorganic

arsenic concentrations of Marx workers which we

found as part of our HHE were not due to workplace

exposures at Marx. Individual follow-up of

employees with their personal physicians is indicated

to determine the clinical significance, and potentially

the source of, these elevated urine arsenic

concentrations. Regarding the four workers treated

at the hospital prior to the HHE, review of medical

records (including electrophysiological testing [nerve

conduction studies and electromyography]) revealed

that none of the four had a history of or displayed

other physical or laboratory findings consistent with

a diagnosis of acute or chronic arsenic toxicity;**

therefore, NIOSH investigators do not believe that

arsenic intoxication (as reflected by elevated total

urinary arsenic levels alone) sufficiently explains the

presence of ataxia and paresthesias among those four

workers. 

RECOMMENDATIONS

There are very few published data on human health

effects associated with 1-BP exposure, and a limited

amount of toxicologic data from studies in animals

(see Appendix 1). The exposure criteria of 25 ppm

discussed in this report is based on preliminary

evaluations of limited data. Considering the lack of

data concerning 1-BP exposure and possible human

health effects, and while further data are being

collected, NIOSH investigators believe that

occupational exposure to 1-BP should be minimized.

As more data are gathered concerning recommended

exposure guidelines for 1-BP, it is reasonable to use

the 25 ppm guideline for inhalation exposure that has

been suggested by some in industry and by the EPA.

The following recommendations, some of which

were made in the NIOSH letter of February 1, 2000,

are made with the goal of minimizing both inhalation

and dermal 1-BP exposure among Marx workers.

1. Marx should continue investigating the use of

non-hydrocarbon solvent (water-based) adhesives.

This may require experimentation with the flow of

cushion parts within the fabrication areas, since the

water-based adhesives do not set up as quickly as

does the current adhesive used at Marx Industries.

For example, instead of spraying a cushion piece

with the 1-BP-based adhesive and then immediately

affixing the next piece to the cushion as is done now,

with a water-based adhesive it may be necessary to

spray several cushion pieces with adhesive, wait a

short time, and then add the next cushion piece once

the adhesive achieves the desirable tackiness.

2. Marx should install engineering controls to

effectively reduce air concentrations of 1-BP (and

therefore exposure) in the workplace. As previously

mentioned, spray booths with local exhaust

ventilation that is discharged to the outside have been

shown to adequately reduce 1-BP exposures.

Design specifications for such spray booths and

ventilation systems can be found in the book

Industrial Ventilation, A Manual of Recommended

Practice, 22nd Edition by the ACGIH.36 After

equipment such as spray booths are installed, it is

important to note the following:

a. A routine maintenance program is necessary

for engineering controls to function properly.

b. Marx should reevaluate employee exposures

to 1-BP in the spray line areas after measures have

been taken to reduce exposures.

**Signs and symptoms of acute arsenic intoxication

include gastrointestinal upset (nausea, vomiting,

diarrhea, abdominal pain); findings of kidney, liver, and

heart damage; a brown peeling rash on palms and soles;

appearance of Mee’s lines on the nails; bone marrow

damage; and unusual appearance of red blood cells

under a microscope (basophilic stippling). Signs and

symptoms of chronic arsenic intoxication include

mucosal irritation; darkening and thickening of the

skin; liver injury; and peripheral vascular disease.
Health Hazard Evaluation Report No. 99-0260-2906 Page 19

1. NIOSH [1994]. Elements by ICP: Method

7300. In: Eller PM, Cassinelli ME, eds. NIOSH

manual of analytical methods. 4th ed. Cincinnati,

OH: U.S. Department of Health and Human

Services, Public Health Service, Centers for

Disease Control and Prevention, National Institute

for Occupational Safety and Health, DHHS

(NIOSH) Publication No. 94-113.

2. EPA Method 6010. World Wide Web.

http://www.epa.gov/epaoswer/hazwaste/test/6xx

x.htm. (August 30, 2001).

3. Axelson O and Hogstedt C [1994]. Chapter

52 - The health effects of solvents. In: Zenz C,

Dickerson OB, and Horvath EP, eds.

Occupational Medicine, 3rd Edition. Mosby

Publishers, St. Louis, MO. pp. 764-778.

4. Ward E, et al [1996]. Risk of low red or

white blood cell count related to estimated

benzene exposure in a rubberworker cohort (1940-

1975). AJIM 29:247-257.

5. Bleecker ML [1998]. Chapter 47 - Toxic

peripheral neuropathy. In Rom WN, ed.,

Environmental and Occupational Medicine, 3rd

Edition. Lippincott-Raven Press, Philadelphia,

PA. Pp 697-707.

6. NIOSH [1992]. Recommendations for

occupational safety and health: compendium of

policy documents and statements. Cincinnati, OH:

U.S. Department of Health and Human Services,

Public Health Service, Centers for Disease Control

and Prevention, National Institute for

Occupational Safety and Health, DHHS (NIOSH)

Publication No. 92-100.

7. ACGIH [2002]. 2002 TLVs® and BEIs®:

threshold limit values for chemical substances and

physical agents. Cincinnati, OH: American

Conference of Governmental Industrial

Hygienists.

8. CFR [1997]. 29 CFR 1910.1000. Code of

Federal Regulations. Washington, DC: U.S.

Government Printing Office, Office of the Federal

3. Marx should educate and train employees

concerning possible health problems associated with

1-BP exposure and the importance of proper use of

all equipment so that exposure to 1-BP is minimized.

4. In general, PPE is the least desirable method of

exposure control. Engineering controls (# 2 above)

are recommended to decrease inhalation exposure of

Marx employees to 1-BP. However, in some

instances, manufacturers have used respiratory

protection in workplaces where 1-BP is being used.

If respirators are used for protection from inhalation

exposures to 1-BP, NIOSH-approved air-purifying

respirator with organic vapor cartridges should be

used. Respirators should only be used in the context

of a comprehensive respiratory protection program.

This program should be consistent with the NIOSH

recommendations and the enforceable requirements

set forth in the OSHA Safety and Health

Standards.37,38

5. For protection from dermal (skin) exposures to

1-BP, gloves and aprons made from flexible

laminates (e.g. VitonTM, 4HTM (PE/EVAL), Silver

ShieldTM) should be used.39,40 

6. Marx should consider the extent of 2-BP

contamination when selecting a 1-BP-based

adhesive. If 1-BP-based adhesives are used, those

adhesives which have the minimum level 2-BP

contamination should be selected for use.

7. Marx should remain up-to-date with ongoing

development of guidelines concerning occupational

exposure to 1-BP, and also with any regulatory

activities occurring that concern the bromopropanes.

8. The findings of our medical survey do not by

themselves indicate that medical follow-up is needed

for any specific employees or groups of employees.

However, employees who are experiencing health

effects potentially related to the workplace should be

evaluated by a healthcare provider who has

experience with occupational or environmental

health issues.

REFERENCES
Page 20 Health Hazard Evaluation Report No. 99-0260-2906

Register.

9. Rozman KK and Doull J [2002]. Derivation

of an occupational exposure limit (OEL) for npropyl bromide using an improved methodology.

Applied Occup and Environ Hygiene 17(10):711-

716.

10. Ichihara G, Yu X, Kitoh J, Asaeda N,

Kumazawa T, Iwai H, Shibata E, Yamada T,

Wang H, Xie Z, Maeda K, Tsukamura H,

Takeuchi Y [2000]. Reproductive Toxicity of 1-

BP, a Newly Introduced Alternative to Ozone

Layer Depleting Solvents, in Male Rats. Tox Sci

54:416-423.

11. Kim H-Y, Chung Y-H, Jeong J-H, Lee Y-M,

Sur G-S, Kang J-K [1999]. Acute and Repeated

Inhalation Toxicity of 1-Bromopropane in

Sprague Dawley Rats. J Occup Health 41:121-

128.

12. EPA [2002]. Unpublished draft document:

Acceptable Industrial Exposure Limit for NPropyl Bromide. 

13. NIOSH [2002]. Hazard Evaluations and

Technical Assistance report: Custom Products,

Inc., Mooresville, NC. Cincinnati, OH: U.S.

Department of Health and Human Services, Public

Health Service, Centers for Disease Control and

Prevention; National Institute for Occupational

Safety and Health, DHHS (NIOSH) Publication

No. 98-153.

14. Stump D [2001]. An inhalation twogeneration reproductive toxicity study of

1-bromopropane in rats. Study No. WIL-380001.

Ashland, OH: WIL Research Laboratories.

Unpublished. (Study sponsored by Brominated

Solvents Consortium [BSCO]).

15. Smith RL [2000]. Presentation titled “NPropyl Bromide” which was given on November

6, 2000, at a meeting between the U.S.

Environmental Protection Agency and the

Brominated Solvents Consortium.

16. Korean Ministry of Labour [2002]. Regulation

on threshold limit values for chemical substances

and physical agents. Announcement No. 2002-8.

Korean Ministry of Labour, Seoul, Korea.

17. Park JS, Kim Y, Park DW, et al. [1997]. An

outbreak of hematopoietic and reproductive

disorders due to solvents containing 2-

bromopropane in an electronic factory, South

Korea: epidemiological survey. J Occup Health

39:138–143.

18. Kim Y, Jung K, Hwan T, et al. [1996].

Hematopoietic and reproductive hazards of South

Korean electronics workers exposed to solvents

containing 2-bromopropane. Scand J Work

Environ Health 22:387–391.

19. Ichihara G, Aseda N, Kumazawa T, et al.

[1997]. Testicular and hematopoietic toxicity of

2-bromopropane, a substitute for ozone layer

depleting chlorofluorocarbons. J Occup Health

39:57–63.

20. Kamijima M, Ichihara G, Yu X, et al. [1997].

Disruption of ovarian cyclicity due to

2-bromopropane in the rat. J Occup Health

39:3–4.

21. Yu IJ, Chung YH, Lim CH, et al. [1997].

Reproductive toxicity of 2-bromopropane in

Sprague Dawley Rats. Scand J Work Environ

Health 23:281–288.

22. Lim CH, Maeng SH, Lee JY, et al. [1997].

Effects of 2-bromopropane on the female

reproductive function in Sprague Dawley rats. Ind

Health 35:278–284.

23. Trump DL, Hochberg MC [1976]. Bromide

Intoxication. Johns Hopkins Med J. 138(4):119-

23.

24. van Leeuwen FX, Sangster B [1987]. The

toxicology of bromide ion. Crit Rev Toxicol.

18(3):189-213.

25. Eldan M, Carel RS, Factor-Litvak P,

Goldsmith JR, Weitzman S [1996]. Biological
Health Hazard Evaluation Report No. 99-0260-2906 Page 21

Monitoring of Workers’ Exposure to Bromine.

JOEM. 38(10):1026-31.

26. Jones AR, Walsh DA [1979]. The oxidative

metabolism of 1-bromopropane in the rat.

Xenobiotica. 9(12):763-72.

27. Kawai T, Takeuchi A, Miyama Y, Sakamoto

K, Zhang Z-W, Higashikawa K, Ikeda M [2001].

Biological monitoring of occupational exposure to

1-bromopropane by means of urinalysis for 1-

bromopropane and bromide ion. Biomarkers.

6(5):303-12.

28. Hanes FM, Yates A [1938]. An Analysis of

Four Hundred Instances of Chronic Bromide

Intoxication. South Med J. 31(6):667-71.

29. Ryan RP, Terry CE, Leffingwell SS.

Toxicology Desk Reference. The Toxic Exposure

and Medical Monitoring Index. 5th edition.

Volume 1: 1999-2000.

30. Lauwerys RR and Hoet P [2001]. Industrial

Chemical Exposure: guidelines for biological

monitoring. 3rd Edition. CRC Press LLC, Boca

Raton, Florida. pp. 202-218.

31. Smith TJ, Crecelius EA, and Reading JC

[1977]. Airborne arsenic exposure and excretion

of methylated arsenic compounds. Env Health

Persp 19: 89-93.

32. EPA [2002]. EPA Announces Arsenic

Standard For Drinking Water of 10 Parts per

Billion. Available at

http://www.epa.gov/epahome/headline_110101.

htm ; accessed February 18, 2003.

33. NIOSH [2002]. Hazard Evaluations and

Technical Assistance report: STN Cushion

Company, Thomasville, NC. Cincinnati, OH:

U.S. Department of Health and Human Services,

Public Health Service, Centers for Disease Control

and Prevention; National Institute for

Occupational Safety and Health. DHHS (NIOSH)

Publication No. 2000-410.

34. Kawai T, Takeuchi A, Miyama Y, Sakamto

K, Zhang ZW, Higashikawa K, Ikeda M [2001].

Biological monitoring of occupational exposure to

1-bromopropane by means of urinalysis for

1-bromopropane and bromide ion. Biomarkers

6(5):303–312.

35. ACGIH [2001]. Documentation of threshold

limit values and biological exposure indices for

chemical substances and physical agents.

Cincinnati, OH: American Conference of

Governmental Industrial Hygienists. 

36. ACGIH [1996]. Industrial Ventilation. 22nd

ed., A Manual of Recommended Practice.

Cincinnati, OH: American Conference of

Governmental Industrial Hygienists.

37. NIOSH [1987]. NIOSH guide to industrial

respiratory protection. Cincinnati, Ohio: U.S.

Department of Health and Human Services, Public

Health Service, Centers for Disease Control and

Prevention, National Institute for Occupational

Safety and Health, Publication No. 87-116.

38. OSHA [1998]. Respiratory protection.

Title 29 Code of Federal Regulations Part

1910.134. Washington, DC. U.S. Department

of Labor, Occupational Safety and Health

Administration.

39. Ensolv MSDS. World Wide Web

[URL=www.ensolv.com. ], August 27, 2001. 

40. Albemarle MSDS. World Wide Web [URL=

www.albemarle.com/abzuserman.htm ], June 21,

2002. 
Page 22 Health Hazard Evaluation Report No. 99-0260-2906

TABLE 1

Inhalation Exposure1 and Area Air Sampling Data for 1-BP and 2-BP,

Marx Industries, Inc., HETA 99-0260-2906, November 17, 1999

Job Title/Sample Type Location Sample Volume (L) 1-BP (PPM) 2-BP 

Adhesive Sprayer Glue Line 24.4 105.9 Adhesive Sprayer Glue Line 24.5 89.2 Adhesive Sprayer Glue Line 24.7 77.3 Adhesive Sprayer Glue Line 24.2 131.4 Adhesive Sprayer Glue Line 24.2 115.0 Adhesive Sprayer Glue Line 24.6 66.3 Adhesive Sprayer Glue Line 24.1 57.7 

Doffer Glue Line 23.4 51.8 

Supervisor/Set-up Glue Line 23.1 18.1 

Adhesive Sprayer Springs Line 23.1 86.1 Adhesive Sprayer Springs Line 23.6 160.0 Adhesive Sprayer Springs Line 23 121.0 Adhesive Sprayer Springs Line 22.7 253.9 Adhesive Sprayer Springs Line 22.6 123.1 

Foam Set-up Springs Line 22.5 38.0 

Doffer Springs Line 22.1 45.9 

Area Air Sample Focus Saw Area- Spring 21.8 8.7 Area Air Sample Cutting Area-Glue 21.2 5.3 

Minimum Detectable Concentration 0.007 0.0Minimum Quantifiable Concentration 0.02 0.0

1Time weighted average exposures; 2 Result not available
Health Hazard Evaluation Report No. 99-0260-2906 Page 23

TABLE 2

Descriptive Statistics for 1-BP Exposure Data

Marx Industries, Inc., HETA 99-0260-2906, November 17, 1999

Sample Set (Number1) 1-BP Concentration2 Data

GM 3 Range 

All Exposure Data (16) 81.2 18.1 - 253.9

Glue Line Workers (9) 69.8 18.1 - 131.4

Glue Line Sprayers (7) 88.4 57.7 - 131.4

Springs Line Workers (7) 98.6 38.0 - 253.9

Springs Line Sprayers (5) 139.1 86.1 - 253.9

All Sprayers (12) 107.6 57.7 - 253.9

1

Number of full-shift, time-weighted average exposures in the given sample set. 2

The numbers in these columns represent the geometric mean and range (minimum value - maximum value) for the 1-BP

exposure concentrations in the given sample set. The concentration data are in units of parts per million (ppm). 3

Geometric mean
Page 24 Health Hazard Evaluation Report No. 99-0260-2906

TABLE 3

Descriptive Statistics for 2-BP Exposure Data

Marx Industries, Inc., HETA 99-0260-2906, November 17, 1999

Sample Set (Number1) 2-BP Concentration2 Data

GM Range 

All Exposure Data (16) 0.24 0.08 - 0.68

Glue Line Data (9) 0.22 0.08 - 0.35

Glue Line Sprayers (7) 0.26 0.19 - 0.35

Springs Line (7) 0.28 0.11 - 0.68

Springs Line Sprayers (5) 0.38 0.24 - 0.68

All Sprayers (12) 0.31 0.19 - 0.68

1

Number of full-shift, time-weighted average exposures in the given sample set. 2

The numbers in these columns represent the geometric mean and range (minimum value - maximum value) for the 1-BP.

exposure concentrations in the given sample set. The concentration data are in units of parts per million (ppm).

3

Geometric mean.
Health Hazard Evaluation Report No. 99-0260-2906 Page 25

TABLE 4

1-BP and 2-BP Exposures1 for Unexposed Workers2

Marx Industries, Inc., HETA 99-0260-2906, January 29, 2001

Job Title/Work Location Sample # Sample time (min) Sample volume (L) 1-BP (ppm) 

Maintenance m-6 430 21.6 3.1 

Office - cust. service m-35 461 46.7 3.0 Office - cust. service m-39 463 46.9 3.3 Office - accountant m-49 344 34.7 0.2 Sew & cut m-15 462 46.4 0.7 Sew & cut m-18 461 47.6 1.0 Sew & cut m-19 459 46.1 0.5 Sewing m-20 356 35.6 0.4 Supervisor - cut & sew m-11 438 44.3 0.4 Fiber cutting - glue area m-45 467 46.7 4.6 Fiber cutting - glue area m-43 492 24.7 4.5 Blowing m-9 425 42.9 0.1 Blowing m-10 440 44.5 0.1 Blowing m-13 441 44.4 0.5 Blowing m-14 448 45.1 0.5 Fiber cutting m-44 466 46.8 3.8 Foam cutting m-30 467 47 1.3 Foam cut above springs m-38 495 50.1 4.9 Foam cutting m-31 470 47.3 1.0 Foam cutting m-8 408 40.9 1.0 
 TABLE 4 Continued

 1-BP and 2-BP Exposures1 for Unexposed Workers2 Marx Industries, Inc., HETA 99-0260-2906, January 29, 2001

Job Title/Work Location Sample # Sample time (min) Sample volume (L) 1-BP (ppm) 

Page 26 Health Hazard Evaluation Report No. 99-0260-2906

Foam cutting m-27 464 46.8 0.9 Foam cutting m-25 477 47.5 2.0 Foam cutting m-28 466 46.8 0.9 Foam cutting m-33 439 44.1 1.2 Foam cutting m-4 399 40 2.5 Foam cutting m-34 477 48 3.0 Foam cutting m-29 488 49.1 1.1 Minimum Detectable Concentration 0.004 Minimum Quantifiable Concentration 0.01 

1Time-weighted average exposures.2Unexposed workers defined by qualitative assessment of job duties as discussed in text.3nd = ‘not detected’; for 2-BP nd exposures are below 0.003 ppm.4trace = 2-BP was detected but not in quantifiable amounts; trace exposures for 2-BP fall between 0.003 - 0.01 ppm.
Health Hazard Evaluation Report No. 99-0260-2906 Page 27

TABLE 5

1-BP and 2-BP Exposures1 for Unexposed Workers2

 Marx Industries, Inc., HETA 99-0260-2906, January 29, 2001

Job Title/Sample Type Location Sample # Sample time

(minutes)

Sample volume (L) 1-BP (ppm

Springs area - no spraying Springs Line m-48 497 24.9 10.7 

Supervisor Springs Line m-40 503 50.6 21.4 Adhesive sprayer Springs Line m-42 499 24.9 215.8 Adhesive sprayer Springs and

GlueLine

m-26 484 24 77.7 

Adhesive sprayer Springs Line m-41 496 24.9 280.5 Adhesive sprayer Springs Line m-37 426 25 70.6 Adhesive sprayer Springs and

GlueLine

m-47 500 25.1 173.2 

Adhesive sprayer GlueLine m-21 477 24 115.2 Adhesive sprayer GlueLine m-5 412 20.7 44.5 Adhesive sprayer GlueLine m-32 481 24.1 38.0 Supervisor GlueLine m-22 483 24 7.2 

Baler GlueLine m-24 267 26.4 10.5 Baler GlueLine m-46 493 49.3 19.9 Minimum Detectable Concentration 0.004 Minimum Quantifiable Concentration 0.01 

1time-weighted average exposures.2Exposed workers defined by qualitative assessment of job duties as discussed in text.3nd = ‘not detected’; for 2-BP nd exposures are below 0.003 ppm.4trace = 2-BP was detected but not in quantifiable amounts; trace exposures for 2-BP fall between 0.003 - 0.01 ppm.
Page 28 Health Hazard Evaluation Report No. 99-0260-2906

TABLE 6

Descriptive Summary Statistics for 1-BP Exposure (Tables 4 and 5)

Marx Industries, Inc., HETA 99-0260-2906, January 29, 2001

Sample Set (Number1) 1-BP Concentration2

Geometric Mean 

All Monitoring Data (40) 3.7 Unexposed Workers (27) 1.1 Exposed Workers (13)3 45.7 

 Glue Line Sprayers (3) 58.0  Springs Line Sprayers (3) 162.2  Spring/Glue Line Sprayer (2) 116.1  All Sprayers (8) 101.4 

1Number of full-shift, time-weighted average exposures in the given sample set.2The numbers in these columns represent the geometric mean and range (minimum value - maximum value) for the 1-BP exposur

given sample set. The concentration data are in units of parts per million (ppm). 3Exposed workers included 8 sprayers and 5 other workers who were not actively spraying.
Health Hazard Evaluation Report No. 99-0260-2906 Page 29

TABLE 7

Descriptive Statistics for 2-BP Exposure

Marx Industries, Inc., HETA 99-0260-2906, January 29, 2001

Sample Set (Number1) 2-BP Concen

Geometric Mean 

All Exposure Data (40) n/a3 

Unexposed Workers (27) n/a Exposed Workers (13)5 0.066 

Glue Line Sprayers (3) 0.10 Springs Line Sprayers (3) 0.31 

Spring/Glue Line Sprayer (2) 0.19 

All Sprayers (8) 0.18 

1Number of full-shift, time-weighted average exposures in the given sample set.2The numbers in these columns represent the geometric mean and range (minimum value - maximum value) for the 1-BP exposur

given sample set. The concentration data are in units of parts per million (ppm). 3value not calculated.

4nd=not detected (concentration < 0.003 ppm); trace (concentration between 0.003 - 0.01 ppm). 6Spray line personnel included 8 sprayers and 5 other workers who were not actively spraying.
Page 30 Health Hazard Evaluation Report No. 99-0260-2906

TABLE 8

Description of Survey Participants by Qualitative Exposure Status 1

 Marx Industries, Inc., HETA 99-0260-2906

# (%)

Female

Age (Median) Median Time

(months) at

Current Job

Race # (%) # (%)

Reporting

Past Use of

Alcohol2

# (%)

Reporting

Current

CigaretteSmoking

White Hispanic

Exposed

(N=13)

10 (77) 25 17 5 (38) 8 (62) 7 (54) 4 (31) 

Unexposed

(N=30)

14 (50) 37 27 19 (68) 9 (32) 13 (46) 8 (29) 

1All percentages are based on number of actual respondents.2# (%) of respondents reporting at least one drink of alcohol in month prior to the survey.3Geometric mean 1-bromopropane personal breathing zone concentrations in parts per million from sampling peHHE; statistically significant difference in 1-BP exposure between exposed and unexposed workers (p-value <
Health Hazard Evaluation Report No. 99-0260-2906 Page 31

TABLE 9

 Summary of Exposure Assessments by Exposure Status

Marx Industries, Inc., HETA 99-0260-2906

1-BP Air

Concentration

GM1 (range), in

ppm

End-of-week Serum

Br

GM (range), in mg/dl

Cross-week Serum

Br difference

Mean (range)

End-of-week Urine

Br

GM (range), in

mg/dl

Cross-week Ur

Br difference

Mean (range

Exposed

(Qualitative)

45.8 (7, 281) 14.9 (3, 43.5) 2.3 ( - 3.2, 7.5) 151.8 (27,595) 131 ( - 20, 497

Unexposed

(Qualitative)

1.1 (0.1, 5) 2.7 (1.7, 11) 0.3 ( - 0.9, 1.9) 28.5 (15,151) 3.6 ( - 30, 77) 

Total 3.6 (0.1, 281) 4.8 (1.7, 43.5) 1.0 (-3.2,

7.5)

46.5 (15,

595)

41.9 (-30

497)

1Geometric Mean.
Page 32 Health Hazard Evaluation Report No. 99-0260-2906

TABLE 10

Correlation of Biologic Measures of Exposure with Personal Breathing Zone 1-BP Air Conce

Marx Industries, Inc., HETA 99-0260-2906

Start-of-WeekSerum Br

End-of-WeekSerum Br

Serum BrCross-WeekDifference 

Start-of-WeekUrine Br

End-of-WeekUrine Br

Urine BrCross-WeeDifferenc

CorrelationCoefficient

0.78 0.88 0.37 0.61 0.67 0.55 

# Observations 40 38 38 39 38 37 p Value <0.01 <0.01 0.02 <0.01 <0.01 <0.01 

1Biologic measures of Br with 1-BP air concentration using the Spearman correlation coefficient.

TABLE 11

Number of Participants with Specific Symptoms Grouped by Exposure Category, With Prevalence Ratio and 95% 

Marx Industries, Inc., HETA 99-0260-2906

Exposure category Painful Tingling1

# (%) Yes

Tremor2

 # (%) Yes

Headache3

# (%) Yes

Felt “Drunk”4

# (%) Yes

Excessive Fatigue5

# (%) Yes

Trouble

Concentrating 

# (%) Yes

Exposed (N=13)6 4 (31) 2 (15) 9 (69) 4 (36) 4 (31) 1 (8) 

Unexposed (N=30) 8 (30) 0 (0) 13 (45) 2 (7) 2 (7) 3 (11) 

Prevalence Ratio7

(95% CI)

1.0 (0.4 - 2.8) - 1.5 (0.9 - 2.7) 4.9 (1.0 - 23.0) 4.2 (0.9 - 19.9) 0.7 (0.1 - 6.3) 

1Numbness (pins and needles feeling) in hands or feet within last 30 days.2Tremor or shakiness within last 30 days.3Headache within last 30 days.4Felt “drunk or high” in the last 30 days (even if not using alcohol or drugs).5Sleeping too much in the last 30 days.6Qualitative assessment of exposure to 1-BP.7Prevalence ratio and 95% CI for prevalence of symptom among those exposed versus those unexposed.
Health Hazard Evaluation Report No. 99-0260-2906 Page 33

TABLE 12

Mean PBZ 1-BP Exposure Among Persons Reporting Presence/Absence of Symptoms in 30 Days Prior t

Marx Industries, Inc., HETA 99-0260-2906

Symptom Response (Number) GM 1-BP (ppm) 

Headache No (N=20) 2.1 

Yes (N=19) 7.9

Abnormal Fatigue No (N=32) 3.3 

Yes (N=5) 12.8

Problem Concentrating No (N=34) 3.7 

Yes (N=4) 8.9

Feel “Drunk”2 No (N=29) 2.1 

Yes (N=6) 25.8

Painful tingling in your hands or feet No (N=26) 4.3 

Yes (N=11) 3.9

Tremor (shakiness) No (N=35) 3.5 

Yes (N=2) 49.7

Anxiety, nervousness No (N=27) 2.4 

Yes (N=12) 12.2

1Two-sample t-test, two sided.2Positive response to the question: “Have you felt “drunk” when you have not been drinking?”
Page 34 Health Hazard Evaluation Report No. 99-0260-2906

TABLE 13

Median Value for Blood Count Test Results Among Participants in the Medical Survey, By Exposure Category

 Marx Industries, Inc., HETA 99-0260-2906

Exposure Status1 RBC2

(106 per mm3

)

Hemoglobin3

(grams per deciliter)

WBC4

(103 per mm3

)

Exposed (N=13) 4.9 14.3 6.6 

Unexposed (N=27) 5 14.7 8.5 

1Qualitative assessment of exposure status.2Red blood cells; Normal range: 3.8 - 5.8 106/mm3

3Normal range: 11.6 - 17.1 grams per deciliter

4White blood cells; Normal range: 3.9 - 11.4 103/mm35Normal range: 140 - 400 103/mm3

TABLE 14

Exposure Measures and Individual Components of CBC, $ (slope)1 and p-value from Linear Regression

 Marx Industries, Inc., HETA 99-0260-2906

Exposure Measure RBC2 Hemoglobin3 WBC4 

$ p-value

$ p-value

$ p-value

$ 

1-BP PBZ

Concentration 6

-0.03 0.23 -0.005 0.95 -0.37 0.10 -7.

End-of-Week Urine Br -0.019 0.7 0.03 0.9 -0.67 0.08 -11

1

$ = parameter estimate (slope) from linear regression model. 2Red blood cells; Values adjusted for age, gender, and race.

3Values adjusted for age, gender, and race.4White blood cells adjusted for age.5Adjusted for age.61-BP personal breathing zone concentration.
Health Hazard Evaluation Report No. 99-0260-2906 Page 35

TABLE 15

1-BP Exposure and Determination of Semen Analyses Among Participants in the Male Reproducti

Marx Industries, Inc., HETA 99-0260-2906

Exposure Status1 1-BP Exposure

(GM, range [ppm])

End-of-Week Urine Br

GM (range mg/dL)

# with Abnormal2

Semen Evaluation

# 

Se

Exposed (n=3) 19.9 (10.5, 70.6) 54.1 (27, 110) 13 

Unexposed (n=6) 1.6 (0.5, 4.5) 30.3 (15.4, 151) 44 

1Qualitative assessment of exposure status.2Qualitative assessment of semen analyses performed by NIOSH reproductive scientist.3Including one person with decreased percentage of sperm with normal shape.4Including one person with decreased sperm motility and three persons with decreased sperm motil

percentage of sperm, and normal sperm shape.

TABLE 16

Exposure Measures and Individual Components of Sperm Analyses Among Participants in the Male 

Evaluation

$ (slope)1 and p-value from Linear Regression

Marx Industries, Inc., HETA 99-0260-2906

Exposure Measure Sperm Number Sperm Shape Sperm 

$ p-value

$ p-value

$ 

1-BP PBZ

Concentration2

15.6 0.4 0.97 0.6 2.8 

End-of-Week Urine Br 49.1 0.1 5.5 0.1 9.8 

1

$ = parameter estimate (slope) from linear regression model. 21-BP personal breathing zone concentration.
Page 36 Health Hazard Evaluation Report No. 99-0260-2906

TABLE 17

1-BP Exposure and End-of-week Urine Br Concentrations by Status of Nerve Conduction T

Marx Industries, Inc., HETA 99-0260-2906

Nerve Conduction Testing1 PBZ 1-BP Exposure

(GM, range [ppm])

End-of-week urine 

(GM, rang

Abnormal (n=5) 2.6 (0.1 - 21.4) 35.5 (17

Normal (n=37) 4.22 (0.2 - 280.5) 48.83 (15

1Nerve conduction testing determined by the consulting physician to be normal (including 4 tests 

“borderline,” 4 tests which were incomplete or with a minor technical difficulty, and 29 completdetermined to be normal without qualification) or abnormal (including 1 determined to be ‘probab

2p-value = .07, t-test.3p-value = .09, Wilcoxon two-sample test.

TABLE 18

Summary of Urinary Inorganic Arsenic by Exposure Category1

Marx Industries, Inc., HETA 99-0260-2906

Exposure category Arsenic Concentration Geometric Mean

(range)

:g/g creat2

 # (%) 

Concentrati

c

Exposed (N=12) 62.8 (13, 215) 1

Unexposed (N=29) 12.9 (6, 81) 

1Exposure category refers to qualitative exposure to 1-BP.2Micrograms arsenic per gram of creatinine.325 

:g/g creat is the concentration of arsenic in urine used for this HHE as a cutoff above whic

occupational or environmental exposure is suspected.
Health Hazard Evaluation Report No. 99-0260-2906 Page 37

APPENDIX 1

1-BromopropaneBackgroundBromopropanes are a class of brominated hydrocarbons that exist in 2 isomeric forms: 1-bromopropane (1-BP; CAS No. 106-94-5) and isopropyl Br; CAS No.75-26-3). Both isomers are volatile and believed to be less destructive to the ozone layer than chlorinated hy

as 1,1,1-trichloroethane.Although each compound possesses useful solvent properties, 2-BP has not been used commercially in the United States. Workplace and animal toxicological studies conducted in South Korea, Japan, and China identified that 2-BP affects the organs of reproduction in and females (ovarian dysfunction), and also the hematopoietic (blood-forming) system.41,42,43,44,45,46,47,48 1-BP is currently marketed d

considered by the Environmental Protection Agency (EPA) as an alternative to chlorofluorocarbons (CFCs), a class of chemicals 

agreement for protection of the ozone layer.49

Workers exposed to 1-BP may be exposed to small (but measurable) quantities of 2-BP since the latter isomer is generated as a contamof the former. However, the percentage of 2-BP contamination in neat 1-BP has steadily decreased from 1-2% to 0.1% and below.50

Safety and Health Administration (OSHA) analysis of several commercial samples of 1-BP found them to contain 2-BP in concentr

0.2%.52 A voluntary consensus standard (D6368-02) published by ASTM International (formerly the American Society for Testing 

vapor degreasing and general grade 1-BP specifies that the content of 2-BP in these solvent grades remain below 0.1%.53

The three industrial sectors currently using 1-BP that fall under the regulations of the EPA’s Significant New Alternatives Policy progra(1) non-aerosol solvent cleaning; (2) aerosols; and (3) adhesives, coatings, and inks. Within these sectors, 1-BP has a variety of en

cleaning, precision cleaning, electronics cleaning, aerosol solvents, and adhesives. Previous NIOSH Health Hazard Evaluations (HH

in workplaces where employees have been exposed to 1-BP while using a cold vapor degreaser for the precision cleaning of electronplants where 1-BP was formulated as a solvent vehicle for spray adhesives.54,55,56 1-BP may also be found as an intermediate in closed 

synthesis of pharmaceuticals, insecticides, quaternary ammonium compounds, flavors, or fragrances.57

In 1998, 645 tons of 1-BP were sold for use in Japan.58 An article published in 1999 suggests that at that time more than 100,000 to

of brominated solvents were being produced annually in the United States alone.59 This likely represents an overestimation of both 

least one order of magnitude. By contrast, in a report issued by the National Toxicology Program’s Center for the Evaluation of Risks (NTP-CERHR), citing data provided by EnviroTech International, Inc., 1.5 million pounds per year of 1-BP were produced in the Uni
Page 38 Health Hazard Evaluation Report No. 99-0260-2906

and 2000.57 During that same time, 2.8 million pounds of this chemical were imported into the US. More recently, the Brominat

(BSOC) provided estimates of the annual global sales and emissions of 1-BP for solvent and adhesive applications: 10.6 million pou

pounds in 2001, and 8.2 million pounds in 2002. The United Nations Environment Program n-Propyl Bromide (nPB) Task Force estimannual use and emissions of 1-BP at 11-22 million pounds.57

At present, there is no domestic production of 1-BP. Industry estimates are that between 2-2.5 million pounds are imported annually East Asia.51 The EPA reported that 6-8 million pounds per year are used as cleaning solvents or in cold vapor degreasers and betwe

per year are used in the formulation of adhesives.50

Most of the toxicologic information available concerning 1-BP is based on the results of laboratory animal studies. For example, the a producer of 1-BP, has developed its own recommended occupational exposure guideline for this chemical upon completion of a stu

exposure on reproduction in rats. As a result of their study, Albemarle proposed to other manufacturers and end-users a voluntary reco

of 25 ppm as an 8-hour TWA exposure.60 A contractor hired by the US EPA, using a mathematical model, has similarly dev

occupational exposure limit of 25 ppm. This value was also based on the results of studies evaluating reproductive health effects in 

the various organ systems reported to be affected by 1-BP, it has been suggested that the organs of reproduction may be the most s

The HHE at Marx Industries, however, was requested by the North Carolina Department of Labor as a result of reported neurologi

Marx Industries. Because of the nature of the HHE request and, since the reproductive and developmental effects of 1-BP expcomprehensively reviewed by the NTP-CERHR,57 this appendix will focus on reports concerned with the neurological toxicity of 1-BP 

will attempt to summarize available published English-language literature focusing on the effects of 1-BP exposure on the nervous s

animals and humans. Unpublished studies concerning the toxicological effects of 1-BP exposure on laboratory animals were BioResearch (CTBR) and WIL Research Laboratories, Inc. These included a 28-day acute exposure, and a 13-week subchronic CTBR), and a 2-generation toxicity study (by WIL Research Labs). Together, these three studies provide somewhat contradictory inf

neurological effects of exposure to 1-BP. The 13-week study identified impairment of gait and microscopic lesions to the brain and 

reproduced in the subchronic study. Similarly, the study conducted by WIL did not identify neurological effects that could be attri

These studies will not be addressed further within this appendix but will be integrated into an upcoming NIOSH Current Intelligen

Effects of Acute and Chronic Exposure to 1-BP on Laboratory AnimalsAn early study of the effects of 1-BP looked at both acute and chronic exposures to rats at varying levels of exposure. In a study of acu

two groups of rats (20 male and 20 female) were subdivided into four groups of five rats each and exposed to 1-BP at doses of 11,

17,000 and ppm.59 In addition, five male and five female rats served as “control” animals and were not exposed to 1-BP.

Within an hour after experiment onset, the animals exposed to 1-BP developed lacrimation (watery eyes), piloerection (hair standing o

with balance and walking), “decreased activity,” and a decreased response to auditory stimuli. Thus, early on, there was an indicatio
Health Hazard Evaluation Report No. 99-0260-2906 Page 39

some neurotoxic properties. Two of five male rats that were exposed to 1-BP at 15,000 ppm died within 6 hours following exposure

exposed to the same concentration of 1-BP were dead within 24 hours following exposure. The authors reported no deaths of rats ex

ppm. In addition, there were no reports of seizure activity among the test animals.The same research group also studied the effects of chronic 1-BP exposure on rats. For this part of the study, Kim and colleagues su

groups of rats (40 male and 40 female) into four groups of 10 rats each. Each subgroup inhaled 1-BP at doses of 0, 50, 300, or 180

5 days a week for 8 weeks. Effects were noted only in those rats exposed to 1800 ppm of 1-BP and included “mild ataxia,” and “de

effects were neither permanent nor particularly long-lasting, resolving each day within approximately 1 hour following terminatio

In another study of the effects of chronic inhalational exposure, Ichihara and colleagues divided male rats into four groups and e

concentrations of 0, 200, 400, or 800 ppm for 8 hours a day for 12 weeks.61 Those rats exposed to airborne concentrations of 0, 200 

no difficulties with their balance or their ability to walk. Those rats exposed to airborne concentrations of 800 ppm developed wea

and consequently could not maintain their position on an inclined surface. The authors of this study did not, however, clearly state wh

appeared relative to the initiation of the experiment.

Effects of Acute and Chronic Exposure to 1-BP on the Peripheral Nervous System AnimalsLimb StrengthIn the study of chronic inhalational exposure to 1-BP described above, Ichihara and colleagues exposed male rats to 1-BP at concent

800 ppm for 8 hours per day for 12 weeks.61 During the course of the 12 weeks, the rats were monitored for clinical signs of neurologica

rats exposed to 1-BP at 200 ppm exhibited a decrease in hind limb grip strength that then resolved spontaneously. By the end of the rats exposed to 1-BP at 400 ppm were reported to exhibit a significant decrease in hind limb strength (as compared to controls). The 8

showed a transient increase in hind limb grip strength at 4 weeks before exhibiting a significant decrease in hind limb grip strength at 

limb grip strength was also reported to decrease during the exposure period. Beginning at 8 weeks of exposure, rats exposed to conc

greater exhibited a statistically significant dose-dependent fore limb weakness (as compared to controls) that became progressively w

period.Yu and colleagues identified neurological effects in their animals similar to those of Ichihara.49,62

In the study by Yu of chronic inhalational toxicity, male rats were either unexposed to 1-BP or were exposed at a dose of 1000 ppm period up to 7 weeks. (Rats were also exposed to 2-BP at 100 and 1000 ppm in this study.) During the fifth week of exposure, six to 1-BP at 1000 ppm began to walk with a “paddle-like” gait. This was described as a dragging of the animal’s hind limbs along the 

surface of the hind paw turned upwards. The most severely affected animals moved by using their forelimbs despite the paralysis of 

the remaining three out of nine rats exposed to 1-BP showed the same signs of hind limb paralysis. As compared to the Ichihara stud
Page 40 Health Hazard Evaluation Report No. 99-0260-2906

exposure, no forelimb weakness was reported. This may possibly be due to the overall length of exposure; the animals studied by Ich

of statistically significant forelimb weakness until 8 weeks of exposure, although weakness of forelimb grip strength was evident b

Nerve Conduction StudiesIchihara and colleagues, and Yu and colleagues also measured motor nerve conduction velocity (MCV) and distal latency (DL) in 

exposed to 1-BP. Both teams found evidence of demyelination (slowing of the MCV and a lengthening in the DL) with increases in 

of or duration of exposure to 1-BP. Ichihara reported that the effects on MCV and DL were not seen in either group of animals expoor 400 ppm, but became evident among animals exposed at 800 ppm.61

Yu and colleagues found MCV values slowed considerably and DL values became significantly prolonged as compared to control 

exposure to 1-BP at levels of 1000 ppm.49,62 This same research group noted that the onset of decrease in MCV and prolongation in DL 

rats exposed to 1-BP at 1000 ppm than in those exposed to 2-BP at 1000 ppm.49

Zhao and colleagues conducted a study in which male rats received daily subcutaneous injections of 1-BP (5 days a week for 4 wee

the authors to correspond to inhalational exposure levels of 300 and 1000 ppm.63 Although it is unclear that these injections a

inhalational exposures, the results of this study also showed slowing of MCV and prolongation of DL. Beginning at 2 weeks after expbegan to slow (non-significantly) in a dose-dependent fashion. At 4 weeks after experiment onset, the observed differences between cexposed to 1-BP at the inhalational equivalent of 1000 ppm became statistically significant. The MCV of those animals exposed to 

equivalent of 300 ppm did not slow significantly as compared to the control population. The DL in the peripheral nerves of rats exhibidependent prolongation as compared to controls. These results were consistent with those reported by Ichihara and Yu.

Studies of Microscopic PathologyIchihara and Yu also conducted light microscopic examinations of various peripheral nerves in animals with chronic inhalational ex

identified changes to the myelin sheaths of the peripheral nerves (“ovoid or bubble-like debris”) and also to the arrangement of striated 

of the lower limb (soleus muscle).61 These changes were found only in the group with the highest level of exposure to 1-BP (800 pp

400 ppm. Yu reported similar changes to the myelin sheaths of the peripheral nerves of the rats in his study. The animals in the study bof 1000 ppm.49,62

Ichihara and colleagues also examined peripheral nerve and muscle tissue under the electron microscope in rats chronically exp

resolution, they confirmed the findings made using the light microscope. Alterations in the structure of the myelin sheath and in the rmuscle fibers was seen in animals exposed to 1-BP at 800 ppm.61
Health Hazard Evaluation Report No. 99-0260-2906 Page 41

As with the previous studies, Sohn and colleagues also exposed rats to increasing levels of 1-BP: 200, 500, and 1250 ppm for 6 hou

for 13 weeks.64 Following exposure, animals were sacrificed and tissues from the central (brain and spinal cord) and peripheral (sac

nervous systems were examined by light and electron microscopy. Unlike Ichihara and Yu, however, Sohn and colleagues found n

differences between a control group of rats (no exposure to 1-BP) and any of the experimental groups in terms of weight gain, food 

or activity. In addition, they found no evidence of neuronal damage in the cerebral gray matter, or demyelination in the white mabnormal findings of the myelin that characterized the microscopy studies of Ichihara and Yu. Sohn and colleagues reported that th

study groups displayed uniform thickness throughout the length of the nerve.

Effects of Acute and Chronic Exposure to 1-BP on the Central Nervous System of LaboStudies of Microscopic PathologyThe studies conducted by Ichihara and colleagues and by Yu and colleagues provided evidence that chronic exposure to high doses 

result in central nervous system pathology. Both authors report swelling and other cellular changes in the gracilis nucleus, locat

Ichihara’s findings were made both under the light microscope and the electron microscope. Examination of the gracilis nucleus un

revealed an accumulation of “mitochondria, myelin-like debris, various sized vesicles, vacuolated mitochondria, and amorphous de

colleagues also reported finding “shrinkage” of cells within the cerebellum, and Ichihara noted a decreased cerebral weight as compar

Studies of Biochemical PathologyTwo additional studies reported on the findings of biochemical alterations in the nervous system of rats exposed to 1-BP. In th

colleagues measured levels of gamma-enolase and beta S-100 proteins in rats exposed to 1-BP for 7 days, 8 hours per day at 200, 400

enolase is a protein specifically located within nerve cells (neurons) and beta S-100 protein is found only outside the nerve cells, with

provide support to the nerve cells.) In addition to gamma-enolase and beta S-100, the authors measured creatine kinase, glutathione, an

groups in various regions of the central nervous system including the cerebrum, cerebellum, brain stem, and lumbar enlargement oexposed to 1-BP at 400 ppm for 7 days, there was a decrease in measured gamma-enolase levels in both the cerebrum and cereb

glutathione, nonprotein sulfhydryl groups, and gamma-enolase levels decreased in those same regions of the brain. The other measurbeta S-100 protein) either did not change significantly or showed an inconsistent pattern throughout the central nervous system follow

authors postulate that the decrease in gamma-enolase may be due to one of two causes: either a decrease in total amounts of the enzym

in the total number of neurons. The authors further conjecture that the decreases in gamma-enolase levels are specific for exposurindicate a mechanism of putative neurotoxicity, and that they occur sooner than do any obvious morphological changes within the Of interest is the concomitant decrease of glutathione and nonprotein sulfhydryl groups within the cerebrum and cerebellum of the 

Glutathione helps in the detoxification of various chemicals that enter the body. Conjugation with glutathione (and, possibly oth

molecules) represents a potential pathway of metabolism for 1-BP.66 Wang and colleagues, in their discussion of this research, sugge
Page 42 Health Hazard Evaluation Report No. 99-0260-2906

body burden of 1-BP, one might expect to see a concomitant decrease in glutathione concentration as metabolism exceeds the body’s molecule. In the absence of glutathione, then, the rat brain may be at risk for chemical injury.In the second paper published by Wang concerning the biochemical changes in the nervous system of rats exposed to 1-BP, the authof a more prolonged duration of exposure.67 In this second study, rats were exposed to 1-BP for 12 weeks, 7 days per week, 8 hour

800 ppm. The same biochemical parameters were measured in the same regions of the central nervous system as were described in 

In rats exposed to 1-BP for 12 weeks at 400 and 800 ppm there was a decrease in measured gamma-enolase levels in the cerebrcerebellum as was the case in the short-term exposure study. Wang and colleagues hypothesize that the decrease in cerebellar gam

the 7-day study may have represented only a transient effect of 1-BP in that area of the brain. Following 12 weeks of exposure to 1-BP levels decreased significantly in the cerebrum, cerebellum, and brainstem. And, as in the initial 1-week exposure study conducted 

measured markers either did not change significantly or showed an inconsistent pattern throughout the central nervous system foll

Studies of NeurochemistryThree articles published by Fueta and colleagues concern the effects of 1-BP exposure on the neurochemistry of the rat brain, specif

hippocampus.68,69,70 In the first two studies, rats were divided into groups that were exposed to 1-BP at 1500 ppm for 6 hours a day, 5 

4 weeks. In the final study, rats were exposed to 1-BP at 700 ppm for 6 hours a day, 5 days a week for 8 weeks. Taken together, thbeginning at 1 week post-exposure to 1-BP, there is a decrease in levels of inhibitory neurotransmitters around the hippocampus. Inhare responsible for regulating the flow of neurological impulses in the brain; in the absence of inhibitory neurotransmitters, abnorm

disorders, and seizures may result. Fueta and colleagues are conducting studies to further elucidate the cellular and biochemical mechan

neurotransmitter levels may decrease in response to 1-BP exposure; they are beyond the scope of this review.Case Reports of Occupational Exposure to 1-BPIn a case report by Sclar,71 a 19 year old male developed multiple medical complaints following a two-month exposure to an industri

for degreasing parts, the solvent mixture contained 1-BP as the primary component but also contained butylene oxide, 1,3-dioxolane, components.” The worker was responsible for dipping parts, by hand, into the solvent mixture and consequently had repeated daildominant (right) hand. Quantification of exposure (dermal or inhalational) was not available. Over the course of his two month exposu

weakness to both lower extremities as well as to his right hand. In addition, it is reported that he developed “numbness,” dysphagia 

and unspecified urinary difficulties. Although the worker underwent an MRI scan and extensive nerve conduction studies, the nadysphagia, and urinary difficulties was not well characterized in the report.Nerve conduction studies did, however, show evidence of a primary, symmetric, demyelinating polyneuropathy. The worker exhibmotor nerve conduction velocities and prolongation of the distal motor latencies in his lower extremities (legs). This finding is cons

animal studies described previously. Electromyelography of muscles in the legs revealed denervation and muscular wasting. In add
Health Hazard Evaluation Report No. 99-0260-2906 Page 43

found in the motor nerves, this man also showed “marked slowing” of the lower extremity sensory nerve conduction velocities. Ba

of the study results, the pathological process appeared to be located in the myelin sheath of the nerve as opposed to the nerve axon. 

and sensory nerves of the upper extremities in this gentleman revealed that they were apparently spared. Nerve conduction velocitiesamplitudes and measures of the time required for a nerve impulse to travel from the periphery to spinal cord and back were all within no

extremities.Finally, this worker also had evidence (by MRI scan and somatosensory evoked potential studies) of lesions to the myelinated are

system (brain and spinal cord). The animal studies by Ichihara showed evidence of myelin pathology in the central nervous system of 

to 1-BP. It should be noted that other components of the industrial solvent mixture used by this worker have been reported as putativoxide and nitromethane).72, 73 Moreover, without adequate characterization of the nature of this worker’s exposure, it is difficult to a

specifically to 1-BP. Nonetheless, when considered in light of the results of the previously described animal studies, this report suggepotent neurotoxic effects at sufficiently elevated levels of exposure.In a second case report,74 the authors describe clinical syndromes of three women who worked for companies producing foam cushions 

in North Carolina. All three applied spray adhesive to foam cushions using a compressed air spray gun; the primary solvent vehicle in t

to be 1-BP. Although a unique constellation of symptoms was reported for each of the workers, their clinical syndromes had some simiof staggering gait, numbness and paresthesias in the lower extremities (and in two workers extending to the perineum, hips, and ba

and a variety of other symptoms. Two of the three workers developed peak symptoms consisting primarily of inability to walk, on thThe third worker was also reported to have peak symptoms (including reported staggering gait) in June 2000, although the date waexaminations of the workers were essentially normal except for the following: (1) unsteady gait noted in one of the three workers (

have a normal gait and the gait examination was not reported for the third worker) and (2) decreased sensation to pin prick and decall three workers, with differing distributions for each worker. Notable portions of the physical examinations for the three workers inclu

normal reflex examinations, and normal muscle strength. Only one of the three workers had objective measures of peripheral neurotesting was reported as within normal limits.This case report included an assessment of exposure to 1-BP for one of the three workers, consisting of passive 1-BP sampling over a 6after the worker presented with the reported clinical syndrome. That exposure assessment revealed an average TWA airborne expo

(range: 60 - 261 ppm). The work histories of the three workers is not described completely in the paper. It was noted that the worke

of time working with 1-BP-based glue – 11 months, 4 months, and 5 months. In summary, this second case report describes clinical sy

a component of neurologic symptoms, among three workers in a manufacturing facility that appears to be similar to Marx Industrinformation which would be necessary to reach a conclusion concerning the nature of the reported clinical syndromes for these work

case report.

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Subchronically Exposed to a Substitute for Chlorofluorocarbons, 1-Bromopropane Vapor. J Occup Health 44:156-65.

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activated protein kinase in the hippocampus of rats exposed to 1-bromopropane. Life Sciences 72:521-9.

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Health Hazard Evaluation Report No. 99-0260-2906 Page 47

APPENDIX 2

TABLE 1

Data by Participant 

–Time-Weighted Average Personal Breathing Zone Air Concentrations o

Concentrations in Serum/Urine (start-and end-of-week samples) and Whole Blo

HETA 99-0260-2906, Marx Industries, Inc.

January/February 2001

Subject 1-BP

(ppm)1

Start-of-Week

Serum Br2

End-of-Week

Serum Br

Start-of-Week

Urine Br

End-of-Wee

Urine Br

1 3.1 1.7 -3 5.3 18.9 2 3.0 2.2 2.7 27 33.9 3 3.3 1.7 2.0 30.5 18.6 4 0.2 2.3 - 43.7 33.3 5 0.7 1.4 3.3 1.2 34.6 6 1.0 1.8 2.3 26 32.9 7 0.5 2.5 2.4 51.3 42.2 8 0.4 2.0 2.0 17.2 17.4 9 0.4 2.4 2.0 64 34.5 

10 4.6 2.3 2.9 25.5 37.9 11 4.5 10.8 11.1 73.7 150.9 12 0.1 1.5 2.1 13.3 35.4 13 0.1 1.4 1.7 14.0 21.4 14 0.5 1.4 2.0 22.9 35.3 15 0.5 2.2 2.0 17 15.4 16 3.8 3.3 3.0 43.4 40.8 
Page 48 Health Hazard Evaluation Report No. 99-0260-2906

17 1.3 1.6 2.3 17.1 28.7 18 4.9 3.6 4.6 51.8 34.4 

19 - 3.7 2.8 26.7 15.4 

1parts per million2all Br concentrations were milligrams per deciliter3- indicates data not collected for that participant.
Health Hazard Evaluation Report No. 99-0260-2906 Page 49

Table 1 - Appendix 2 - cont.

Subject 1-BP

(ppm)1

Start-ofWeek Serum

Br2

End-of-Week

Serum Br

Start-ofWeek Urine

Br

End-of-We

Urine B

20 0.9 2.6 2.2 27.3 28.6 21 -3 - - 20.1 29.2 

22 3.0 2.2 3.1 28.6 29.3 23 0.9 2.9 2.3 13.6 17.5 24 1.1 1.9 3.0 19.4 35.8 25 1.0 2.1 2.4 31.1 18.4 26 1.2 3.6 3.6 25.9 34.7 27 2.0 4.4 3.9 8.4 - 28 2.5 2.7 2.6 19.4 16.2 29 - 2.0 - 24.0 17.7 30 1.0 1.8 2.5 27.0 33.6 

314 70.6 10.1 14.7 19.2 53.1 

32 10.7 2.3 2.7 31.7 27.1 33 77.7 14.9 16.9 55.3 204.3 34 215.8 22.2 26.6 159.9 507.9 35 19.9 9.0 9.3 66.1 46 36 21.4 7.3 9.4 39 58.4 
Page 50 Health Hazard Evaluation Report No. 99-0260-2906

37 7.2 5.7 5.6 59.7 - 38 173.2 44.2 43.5 52.8 364.2 39 38.0 13.3 17.3 174 238.9 40 10.5 8.3 10.0 90.4 109.8 41 44.5 20.7 28.0 225.5 332 42 280.5 20.3 27.8 98.8 595.4 43 115.2 36.7 33.5 149.4 197.9 

1Parts per million2All Br concentrations were milligrams per deciliter3 -Indicates data not collected for that participant.4Shaded area represents data from workers exposed to 1-BP (qualitative assessment)
Health Hazard Evaluation Report No. 99-0260-2906 Page 51

Appendix 2 - cont.

Table 2 - Data by Participant –Complete Blood Count Indices

HETA 99-0260-2906, Marx Industries, Inc.

January/February 2001

Subject RBC1 HGB2 WBC3 

1 4.95 14.9 7.76 2 4.92 16.4 7.88 3 5.04 13.6 10.65 4 -5 -- 

5 5.06 14.7 10.52 6 4.50 13.6 9.02 7 4.53 13.8 9.48 8 4.44 13.5 4.88 9 4.76 13.9 9.94 

10 4.25 13.0 6.79 11 5.49 15.9 6.36 12 4.39 12.7 3.68 13 4.10 12.3 8.91 14 5.06 14.6 5.58 15 5.26 15.9 11.78 16 4.96 15.9 8.5 17 5.07 15.2 8.73 
Page 52 Health Hazard Evaluation Report No. 99-0260-2906

18 4.39 13.0 5.10 19 5.04 14.9 8.11 20 5.32 15.9 6.34 

1red blood cells, 106 per cubic millimeter 2hemoglobin, grams per deciliter3white blood cells, 103 per cubic millimeter 4platelets, 103 per cubic millimeter 5- indicates data not collected for that participant.
Health Hazard Evaluation Report No. 99-0260-2906 Page 53

Appendix 2 - cont.

Subject RBC1 HGB2 WBC3 

21 - - - 22 4.78 14.0 9.20 23 5.20 14.4 10.90 24 5.03 15.1 5.91 25 5.27 15.6 6.37 26 5.58 15.7 6.48 27 4.94 14.6 10.5 28 5.25 15.5 9.28 29 - - - 30 5.04 15.4 12.20 

316 4.92 15.5 5.51 

32 5.49 16.1 4.3 33 4.45 13.1 10.20 34 4.54 12.9 8.56 35 4.91 14.0 9.46 36 4.89 14.9 6.55 37 4.59 12.8 10.16 38 5.26 15.4 7.04 
Page 54 Health Hazard Evaluation Report No. 99-0260-2906

39 5.10 14.7 10.89 40 5.06 14.3 6.07 41 4.86 13.5 6.27 42 4.27 13.0 3.91 43 5.00 14.6 6.53 

1Red blood cells, 106 per cubic millimeter 2Hemoglobin, grams per deciliter3White blood cells, 103 per cubic millimeter 4Platelets, 103 per cubic millimeter 5-Indicates data not collected for that participant6Shaded area represents data from workers exposed to 1-BP (qualitative assessment)
Health Hazard Evaluation Report No. 99-0260-2906 Page 55

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