Criteria for a Recommended Standard Occupational Exposure to
Polychlorinated Biphenyls (PCBs)
National Institute for Occupational Safety F* Health, Cincinnati,
September 1977
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[BIBLIOGRAPHIC DATA
SHEET
1. Report No.
NIOSH-77-225
2.
PB 276 849
[<»»Tiile and Subtitle
CRITERIA FOR A RECOMMENDED STANDARD....
OCCUPATIONAL EXPOSURE TO POLYCHLORINATED BIPHENYLS
(PCBs) __
S. Report Date
Sept. 1977
I 7. Author(s)
8. Performing Organization Repc.
No.
19. Performing Organization Name and Address
National Institute for Occupational Safety and Health
4676 Columbia Parkway
Cincinnati, Ohio 45226
10. Project/Task/Worlc Unit No.
11. Contract/Grant No.
jl2. Sponsoring Organization Name and Address
13. Type of Report It Period
Covered
14.
IS. Supplementary Notes
116. Abstracts
According to the recommended standard compiled by NIOSH, occupational exposure
to polychlorinated biphenyls, or PCBs, shall be controlled so that no worker is exposed
to PCBs at a concentration greater than 1.0 microgram per cubic meter of air, deter-
mined as a time-weighted average concentration, for up to a 10-hour workday, 40-hour
workweek. This recommended level of exposure was determined to be the lowest reliably
detectable limit by the sampling and analytical methods recommended in the document.
Criteria are outlined for the medical examination of all employees subject to occupatio-
nal exposure to PCBs, labeling and posting, personal protective eguipment and clothing
employee information, work practices and engineering controls, sanitation practices,
monitoring and recordkeeping.
17. Key Words and Document Analysis. 17a. Descriptors
Industrial hygiene
Industrial atmospheres
Toxicology
Chlorine organic compounds
Environmental surveys
Atmosphere contamination control
Air pollution
Preventive medicine
Safety engineering
Protective clothing
117b. Identifiers/Open-Ended Terms
Air quality measurement
Sampling methods
Analytical methods
Exposure limits
17c. COSATI Field.'Croup
06/J
|18. Availability Statement
I Release unlimited
19.. Security Class (This
Report)
UNCI A
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1
criteria for a recommended standard....
OCCUPATIONAL EXPOSURE
TO
POLYCHLORINATED BIPHENYLS
(PCBs)
U.S. DEPARTMENT OF HEALTH, EDUCATION, AND WELFARE
Public Health Service
Center for Disease Control
National Institute for Occupational Safety and Health
SEPTEMBER 1977
10L
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PREFACE
The Occupational Safety and Health Act of 1970 emphasizes the need
for standards to protect the health and safety of workers exposed to an
ever-increasing number of potential hazards at their workplace. The
National Institute for Occupational Safety and Health has projected a
formal system of research, with priorities determined on the basis of
specified indices, to provide relevant data from which valid criteria for
effective standards can be derived. Recommended standards for occupational
exposure, which are the result of this work, are based on the health
effects of exposure. The Secretary of Labor will weigh these recommen-
dations along with other considerations such as feasibility and means of
implementation in developing regulatory standards.
It is intended to present successive reports as research and epide-
miologic studies are completed and as sampling and analytical methods are
developed. Criteria and standards will be reviewed periodically to ensure
continuing protection of the worker.
I am pleased to acknowledge the contributions to this report on
polychlorinated biphenyls by members of the NIOSH staff and the valuable,
constructive comments by the Review Consultants on polychlorinated
biphenyls, by the ad hoc committees of the Society for Occupational and
Environmental Health and the American Occupational Medical Association, and
iii
Preceding pa» WanK
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by Robert B. O'Connor, M.D., NIOSH consultant in occupational medicine.
The NIOSH recommendations for standards are not necessarily a consensus of
all the consultants and professional societies that reviewed this criteria
document on polychlorinated biphenyls. A list of Review Consultants
appears on page vi.
¦John/?, rinklea, M.D.
Director, National Institute for
Occupational Safety and Health
iv
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The Division of Criteria Documentation and Standards
Development (DCDSD), National Institute for Occupational
Safety and Health, had primary responsibility for the
development of the criteria and recommended standard for
polychlorlnated blphenyls. From DCDSD, John M. Fajen served
as criteria manager and developed the basic information with
the assistance of John A. Wass, Ph.D. Personnel from other
NIOSH Divisions that assisted In the development of this
document were Robert H. Hill Jr., Ph.D., Alan K. Gudeman,
and Dennis M. O'Brien (Division of Physical Sciences and
Engineering); Mark W. Jones (Division of Surveillance,
Hazard Evaluations and Field Studies); and Trent R. Levis,
Ph.D. (Division of Biomedical and Behavioral Science).
The DCDSD review of this document was provided by Richard A.
Rhoden, Ph.D., Chairman; J. Henry Wills, Ph.D.; and Howard
L. McMartin, M.D., with A. Blair Smith, M.D. (Division of
Surveillance, Hazard Evaluations and Field Studies), and
James H. Sterner, M.D.
The views expressed In this document, the conclusions
reached, and the recommendations for a standard are those of
NIOSH after review of the evidence and consideration of the
comments of reviewers. These views and conclusions are not
necessarily those of the consultants, other federal
agencies, and professional societies that reviewed the
document.
v
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NIOSH REVIEW CONSULTANTS ON POLYCHLORINATED BIPHENYLS
Mary Bell, Ph.D.
Department of Environmental Health
University of Cincinnati
Cincinnati, Ohio 45267
Eula Bingham, Ph.D.
Department of Environmental Health
University of Cincinnati
Cincinnati, Ohio 45267
Rudolph J. Jaeger, Ph.D.
Department of Physiology
School of Public Health
Harvard University
Boston, Massachusetts 02115
Carl C. Smith, Ph.D.
Department of Environmental Health
University of Cincinnati
Cincinnati, Ohio 45267
James R. Allen, DVM, Ph.D.
Department of Pathology
University of Wisconsin Medical School
Madison, Wisconsin 53706
Paul E. Brubaker, Ph.D.
Mobil Oil Corporation
Paulsboro, New Jersey 08066
Renate D. Kimbrough, M.D.
Bureau of Laboratories
Center for Disease Control
Atlanta, Georgia 30333
David Kotelchuck, Ph.D.
United Electrical, Radio,
and Machine Workers of America
New York, New York 10007
Charles E. Lawrence, Ph.D.
New York State Department of Health
Albany, New York 12237
William B. Papageorge
Monsanto Industrial Chemicals Company
St. Louis, Missouri 63166
vi
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CRITERIA DOCUMENT: RECOMMENDATIONS FOR AN OCCUPATIONAL
EXPOSURE STANDARD FOR POLY CHLORINATED BIPHENYLS
Table of Contents
PREFACE 111
NIOSH REVIEW CONSULTANTS vi
I. RECOMMENDATIONS FOR A POLY CHLORINATED BIPHENYLS (PCBs)
STANDARD 1
Section 1 - Environmental (Workplace Air) 3
Section 2 - Medical 3
Section 3 - Labeling and Posting 5
Section 4 - Personal Protective Equipment and Clothing 6
Section 5 - Informing Employees of Hazards from PCBs 8
Section 6 - Work Practices and Engineering Controls 10
Section 7 - Sanitation Practices 14
Section 8 - Monitoring and Recordkeeping Requirements 15
II. INTRODUCTION 19
III. BIOLOGIC EFFECTS OF EXPOSURE 21
Extent of Exposure 21
Metabolism and Mechanism of Action 27
Historical Reports 31
Effects on Humans 33
Epidemiologic Studies 54
Animal Toxicity 66
Correlation of Exposure and Effect .105
Carcinogenicity, Mutagenicity, Teratogenicity, and 116
Effects on Reproduction
IV. ENVIRONMENTAL DATA AND BIOLOGIC EVALUATION 126
Environmental Concentrations 126
Control of Exposure 132
Environmental Sampling and Analytical Methods 133
Biologic Evaluation 144
V. WORK PRACTICES 145
vli
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Table of Contents (Continued)
VI. DEVELOPMENT OF STANDARD 148
Basis for Previous Standards 148
Basis for the Recommended Standard 152
VII. RESEARCH NEEDS 164
VIII. REFERENCES 166
IX. APPENDIX I - Sampling Procedure for Collection
of Polychlorlnated Biphenyla 191
X. APPENDIX II - Analytical Method for
Polychlorlnated Blphenyls 196
XI. APPENDIX III - Material Safety Data Sheet 208
XII. TABLES 218
vlil
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I. RECOMMENDATIONS POR A POLY CHLORINATED BIPHENYLS (PCBs) STANDARD
The National Institute for Occupational Safety and Health (NIOSH)
recommends that employee exposure to polychlorlnated blphenyls (PCBs) In
the workplace be controlled by adherence to the following sections. The
standard Is designed to protect the health and provide for the safety of
employees for up to a 10-hour workday, 40-hour workweek, over a normal
working lifetime. The standard Is measurable by techniques that are valid,
reproducible, and available to Industry and governmental agencies.
Compliance with the standard should substantially reduce any risk of
reproductive or tumorlgenlc effects of PCBs and prevent other adverse
effects of exposure In the workplace. Employees should regard the
recommended workplace environmental limit as the upper boundary for exposure
and make every effort to keep exposure as low as possible.
Evidence Indicates adverse reproductive and tumorlgenlc effects In
experimental animals exposed to certain commercial PCB preparations.
Currently available information Is not adequate to demonstrate that other
commercial PCB preparations do not have these effects. Should sufficient
Information become available to indicate that the standard offers greater
or lesser protection from some chlorobiphenyl Isomers or commercial
preparations than Is needed, It will be considered for revision.
The Toxic Substances Control Act of 1976 (Public Law 94-469) required
the US Environmental Protection Agency (EPA) to prescribe marking and
disposal regulations for PCBs by July 1, 1977 (Federal Register 42:26563-
77, May 24, 1977), By this Act, the manufacture, processing, distribution
1
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in commerce, or use of PCBa In any but totally enclosed systems Is to be
banned, effective 1 year after the date of its enactment, October 11, 1976.
Two years after the enactment date PCB manufacture is to be banned, and
processing and distribution in commerce are to be banned 2.5 years from
that date. However, the Act allows the Administrator of EPA to rule
otherwise if he finds that manufacture, processing, distribution in
commerce, or use in other than totally enclosed systems will not present an
unreasonable risk of injury to health or to the environment. The Act does
not affect use of equipment already containing PCBs in totally enclosed
systems, so that a potential for occupational exposure to PCBs will
continue to exist for many years as a consequence of their transportation,
installation, use, and disposal. The part of the Act specific for PCBs is
presented in Figure 1-1.
"PCBs" are defined for this recommended standard as commercial
preparations of chlorinated biphenyl compounds, including those
preparations which may be described as single Isomers or classes of
isomers, such as Decachlorodiphenyl. Biphenyl and its monochlorinated
derivatives occurring in commercial preparations of PCBs shall be measured
along with the polychlorinated derivatives, and shall be treated in this
standard as the polychlorinated components of the preparations.
"Occupational exposure to PCBs," is defined as working with PCBs or with
equipment containing PCBs that can become airborne or that can spill or
splash on the skin or into the eyes, or the handling of any solid products
that may result in exposure to PCBs by skin contact or by inhalation. The
term "PCB work area" is defined as an area where there is occupational
exposure to PCBs. In areas where no occupational exposure to PCBs occurs,
2
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but where PCBs are present in equipment in the workplace, adherence is
required only to Section 8(a).
Section 1 - Environmental (Workplace Air)
(a) Concentration
Occupational exposure to polychlorinated biphenyla (PCBs) shall be
controlled so that no worker is exposed to PCBs at a concentration greater
than 1.0 microgram total PCBs per cubic meter of air (1.0 jig/cu m),
determined as a time-weighted average (TWA) concentration, for up to a 10-
hour workday, AO-hour workweek.
(b) Sampling and Analysis
The recommended TWA occupational exposure limit for PCBs has been
determined to be the lowest reliably detectable limit by the sampling and
analytical methods recommended in this document. Environmental samples
shall be collected and analyzed as described In Appendices I and II, or by
any methods shown to be at least equivalent in accuracy, precision, and
sensitivity to the methods specified.
Section 2 - Medical
Medical surveillance shall be made available to all employees subject
to occupational exposure to PCBs.
(a) Preplacement or initial medical examinations for workers shall
include:
(1) Comprehensive medical and work histories with special
emphasis on hepatic function, skin condition, and reproductive history.
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(2) Comprehensive physical examination with particular
attention to the akin and to hepatic function including determinations of
serum glutamic-oxaloacetic transaminase (SGOT) and serum glutamic-pyruvic
transaminase (SGPT) activities. The responsible physician may also wish to
obtain measurements of serum triglyceride concentrations or of other
indices of fat metabolism.
(3) A Judgment of the employee's ability to use positive
pressure respirators.
(b) During examinations, applicants or employees having medical
conditions that could be directly or indirectly aggravated by exposure to
polychlorinated biphenyls or formulations containing polychlorinated
biphenyls shall be counseled on the increased risk of impairment of their
health that might result from working with these substances.
(c) Women in the work force who are of child-bearing age shall be
advised of the potential adverse effects of PCBs on the unborn child.
Those who bear children while working with PCBs shall be counseled
concerning the advisability of nursing their babies.
(d) Initial medical examinations shall be made available to all
workers as soon as practicable after promulgation of a standard based on
these recommendations.
(e) Periodic examinations shall be made available at least
annually and include: (1) interim medical and work histories, and (2)
physical examinations as outlined in paragraphs (a)(1) and (a)(2) of this
section.
(f) If evidence of adverse effects of exposure to PCBs is
suspected or confirmed, appropriate medical care shall be made available to
the affected worker(s).
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(g) Pertinent medical records shall be maintained for all
employees exposed to PCBs in the workplace. Such medical records shall be
maintained for the period of employment plus 30 years. These records shall
be made available to the designated medical representatives of the
Secretary of Health, Education, and Welfare, of the Secretary of Labor, of
the employer, and of the employee or former employee.
Section 3 - Labeling and Posting
All labels and warning signs shall be printed both in English and in
the predominant language of non-English-reading workers. Illiterate
workers and workers reading languages other than those used on labels and
posted signs shall be otherwise Informed regarding hazardous areas and
shall be informed of the Instructions printed on labels and signs,
(a) Labeling
The following warning label shall be affixed In a readily visible
location on PCB-processlng or other equipment, and on PCB-storage tanks or
containers:
POLYCHLORINATED BIPHENYLS
(PCBs)
DANGER! CONTAINS POLYCHLORINATED BIPHENYLS
CANCER SUSPECT AGENT
Use only with adequate ventilation.
Do not get in eyes, or on skin or clothing.
First Aid: In case of skin or eye contact, flush with running water.
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(b) Posting
Warning placards shall be affixed in readily visible locations in or
near PCB work areas. The information contained thereon shall be arranged
as in the following example.
POLYCHLORINATED BIPHENYLS
(PCBs)
danger:
CANCER SUSPECT AGENT
AUTHORIZED PERSONNEL ONLY
Do not enter unless area is adequately ventilated.
Do not get in eyes, or on skin or clothing.
First Aid: In case of skin or eye contact, flush with running water.
Section 4 - Personal Protective Equipment and Clothing
(a) Protective Clothing
In any operation where workers may come into direct contact with
PCBs, protective clothing impervious to PCBs shall be worn. Gloves, boots,
overshoes, and bib-type aprons that cover boot tops shall be provided when
necessary. Protective apparel shall be made of materials which most
effectively prevent skin contact with PCB9 where it is most likely to
occur. Employers shall ensure that all personal protective clothing is
inspected regularly for defects and that it is in a clean and satisfactory
condition.
(b) Eye Protection
Chemical safety goggles, face shields (8-inch minimum) with goggles,
or safety glasses with side shields shall be provided by employers and
shall be worn during any operation in which PCBs are present. If liquid or
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solid PCBs contact the eyes, the eyes shall be Irrigated immediately with
large quantities of water and then examined by a physician or other
responsible medical personnel. (A drop of vegetable oil on the eye has
been found to reduce the resultant Irritation.) Eye protection shall be In
accordance with 29 CFR 1910.133 and ANSI Z 87.1-1968.
(c) Respiratory Protection
(1) Engineering controls shall be used when needed to keep
concentrations of airborne PCBs at or below the recommended TWA
*
occupational exposure limit. The only conditions under which compliance
with the permissible exposure limit may be achieved by the use of
respirators are:
(A) During the time necessary to Install or test the
required engineering controls.
(B) For nonroutlne maintenance or repair activities.
(C) During emergencies when concentrations of
airborne PCBs may exceed the permissible limit.
(2) When the use of respirators Is permitted by paragraph
c(l) of this section, respirators shall be selected and used in accordance
with the following requirements:
(A) The employer shall establish and enforce a
respiratory protection program meeting the requirements of 29 CFR 1910.134.
(B) The employer shall provide respirators in
accordance with Table 1-1 and shall ensure that employees properly use the
respirators provided. The respirators shall be those approved by NIOSH or
the Mining Enforcement and Safety Administration. The standard for
approval is specified in 30 CFR 11. The employer shall ensure that
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respirators are properly cleaned, maintained, and stored when not In use.
TABLE 1-1
RESPIRATOR SELECTION GUIDE
Concentration
of PCBs
Greater than 1.0 ;ig/cu m (1)
or Emergency (entry into
area of unknown concentra-
tion)
(2)
Respirator Type Approved under
Provisions of 30 CFR 11
Self-contained breathing apparatus
with full faceplece operated in
pressure-demand or other positive
pressure mode.
Combination Type C supplied-air
respirator with full faceplece
operated in pressure-demand or other
positive pressure mode and an
auxiliary self-contained breathing
apparatus operated in pressure demand
or other positive pressure mode.
Section 5 - Informing Employees of Hazards from PCBs
(a) All new and present employees in any area in which PCBs are
used shall be informed of the hazards, relevant symptoms, and effects of
overexposure to PCBs, and the precautions to be observed for safe use and
handling of these materials.
(b) All employees involved with the manufacture, use, transport,
or storage of PCBa shall be informed that PCBs have been found to induce
tumors in experimental animals after repeated oral ingestion and that
because of these findings it is concluded that PCBs are potential human
carcinogens; employees shall also be informed that adverse reproductive
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effects may result from occupational exposure to PCBs.
(c) The employer shall Institute a continuing education program,
conducted by Instructors qualified by experience or training, to ensure
that all employees occupatlonally exposed to PCBs have current knowledge of
job hazards, proper maintenance and cleanup methods, and proper use of
protective clothing and equipment, Including respirators. The Instructions
shall Include a general description of the medical surveillance program and
of the advantages to the employee of participation. Special attention
shall be given to women In the workplace. They shall be made aware of the
potential adverse effects of PCBs on the unborn child, and of the known
transport of PCBs to breast milk. Elements of the program shall also
Include:
Emergency procedures and drills;
Instruction In handling spills and leaks;
Decontamination procedures;
Flreflghtlng equipment location and use;
First-aid procedures, equipment location, and use;
Rescue procedures;
Confined space entry procedures;
Low warning (odor) properties of PCBs.
(d) The Information explaining the hazards of working with PCBs
shall be kept on file and be readily accessible to workers at all places of
employment where PCBs are manufactured, used, stored, or transported.
Required information shall be recorded on the "Material Safety Data Sheet"
shown In Appendix III, or similar form approved by the Occupational Safety
and Health Administration, US Department of Labor.
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Section 6 - Work Practicea and Engineering Controls
(a) Regulated Areas
Access to PCB work areas shall be regulated and limited to authorized
persons. A dally roster shall be kept of persons entering such areas.
(b) Handling of PCBs and General Work Practices
(1) Operating instructions shall be formulated and posted
where PCBs are handled or used.
(2) Transportation and use of PCBs 9hall comply with all
applicable local, state, and federal regulations.
(3) PCBs shall be stored in tightly closed containers in
well-ventilated areas.
(4) When PCB storage containers are being moved, or when
they are not in use and are disconnected, valve protection covers shall be
in place. Containers shall be moved only with the proper equipment and
shall be secured to prevent dropping or loss of control during transport.
(5) Storage facilities shall be designed to contain spills
completely within surrounding dikes and to prevent contamination of
workroom air.
(6) Ventilation switches and emergency respiratory
equipment shall be located outside storage areas in readily accessible
locations which will remain minimally contaminated with PCBs in an
emergency.
(7) Process valves and pumps shall be readily accessible
and shall not be located in pits or congested areas.
(8) Containers and systems shall be handled and opened with
care. Approved protective clothing as specified in Section 4 shall be worn
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by employees engaged In opening, connecting, and disconnecting PCB
containers and systems. Adequate ventilation shall be provided to minimize
exposures of such employees to airborne PCBs.
(9) PCB-operatlng and storage equipment and systems shall
be Inspected dally for signs of leaks. All equipment, Including valves,
fittings, and connections shall be checked for leaks Immediately after PCBs
are Introduced therein.
(10) When a leak Is found, It shall be repaired or otherwise
corrected Immediately. Work shall resume normally only after necessary
repair or replacement has been completed, the area has been ventilated, and
the concentration of PCBs has been determined by monitoring to be at or
below the recommended TWA concentration limit.
(c) Control of Airborne PCBs
(1) Suitable engineering controls, designed to maintain
exposure to airborne PCBs at or below the limit prescribed In Section 1(a),
shall be used. Complete enclosure of processes is the recommended method
for control of PCB exposure. Local exhaust ventilation may also be
effective, used alone or in combination with process enclosure. When a
local exhaust ventilation system is used, It shall be so designed and
operated as to prevent accumulation or recirculation of airborne PCBs in
the workplace environment and to effectively remove PCBs from the breathing
zones of employees. Exhaust ventilation systems discharging to outside air
must conform to applicable local, state, and federal regulations and must
not constitute a hazard to employees or to the general population. Before
maintenance work on control equipment begins, the generation of airborne
PCBs shall be eliminated to the extent feasible.
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Enclosures, exhaust hoods, and ductwork shall be kept in good repair
so that designed airflows are maintained. Airflow at each hood shall be
measured at least semiannually and preferably monthly. Continuous airflow
indicators are recommended, such as water or oil manometers properly
mounted at the juncture of fume hood and duct throat (marked to indicate
acceptable airflow). A log shall be kept showing design airflow and the
results of semiannual airflow measurements.
(2) Forced-draft ventilation systems shall be equipped with
remote manual controls and shall be designed to shut off automatically in
the event of a fire in the PCB work area.
(d) Special Work Areas
(1) PCB Hazard Areas
A hazard area shall be considered as any space having physical
characteristics and containing sources of PCBs, such as transformers, that
could result in PCB concentrations in excess of the recommended airborne
PCB exposure limit. Exits shall be plainly marked, conveniently located,
and open outwardly into areas which will remain minimally contaminated in
an emergency.
(2) Confined or Enclosed Spaces
Entry into confined or enclosed spaces, such as tanks, pits,
process vessels, and tank cars where there is limited egress, shall be
controlled by a permit system. Permits shall be signed by an authorized
representative of the employer and shall certify that appropriate measures
have been taken to prevent adverse effects on the worker's health as a
result of his or her entry into such space.
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Confined or enclosed spaces which have contained PCBs shall be
thoroughly ventilated to assure an adequate supply of oxygen, tested for
PCBs and other contaminants, and inspected for compliance with these
requirements prior to each entry. Adequate ventilation shall be maintained
while workers are in such spaces. Leakage of PCBs into such confined or
enclosed spaces while work is in progress shall be prevented by
disconnecting and blanking the PCB supply lines. Each individual entering
such confined or enclosed space shall be furnished with appropriate
personal protective equipment and clothing and be connected by a lifeline
harness to a standby worker stationed outside of the space. The standby
worker shall also be equipped for entry with approved personal protective
equipment and clothing and have contact with a third person. The standby
person shall maintain communication (visual, voice, signal line, telephone,
radio, or other suitable means) with the employee inside the confined or
enclosed space. -
(e) Emergency Procedures
For all PCB work areas where there Is a potential for the occurrence
of emergencies, employers shall take all necessary steps to ensure that
employees are Instructed in, and follow, the procedures specified below as
well as any others appropriate to the specific operation or process.
(1) If PCBs leak or are spilled, the following steps shall
be taken:
(A) All nonessential personnel shall be evacuated
from the leak or spill area.
(B) The area of the leak of spill shall be
adequately ventilated to prevent the accumulation of vapors.
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(C) If the PCBs are in liquid form, they shall be
collected for reclamation or sorbed in vermiculite, dry Band, earth, or
similar nonreactive material.
(2) Personnel entering the spill or leak area shall be
furnished with appropriate personal protective equipment and clothing. All
other personnel shall be prohibited from entering the area.
(3) Only personnel trained in the emergency procedures and
protected against the attendant hazards shall shut off sources of PCBs,
clean up spills, control and repair leaks, and fight fires, in areas where
PCBs are used.
(4) All wastes and residues containing PCBs shall be
collected in PCB-resistant containers and appropriately disposed of
(Federal Register 42:26563-77, May 24, 1977).
(5) Safety showers, eyewash fountains, and washroom
facilities "shall be provided, maintained in working condition, and located
so as to be readily accessible to workers in all area9 where the occurrence
of skin or eye contact with PCBs is likely. If liquid or solid PCBs are
splashed or 9pilled on an employee, contaminated clothing shall be removed
promptly and the skin washed thoroughly with soap and water for at least 15
minutes. Eyes shall be irrigated immediately with copious quantities of
running water for at least 15 minutes if liquid or solid PCBs get into
them. A drop of vegetable oil may be applied to the eye to relieve the
irritating effect of PCBs.
Section 7 - Sanitation Practices
(a) Employees occupationally exposed to PCBs shall be provided
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with separate lockers or other storage facilities for street clothes and
for work clothes.
(b) Employees occupatlonally exposed to PCBs shall not wear work
clothing away from their place of employment.
(c) Employees occupatlonally exposed to PCBs shall be provided
clean work clothing dally, and cleaning establishments shall be Informed as
to the hazards of handling PCBs and proper disposal procedures for PCB-
contamlnated waste water.
(d) Facilities for shower baths shall be provided for employees
occupatlonally exposed to PCBs. Workers should shower before changing Into
street clothes.
(e) Employees exposed to PCBs shall be advised to wash their hands
and exposed skin before eating, drinking, smoking or using toilet
facilities during the work shift.
(f) Food, drink, or smoking materials shall not be permitted In
areas where PCBs are handled, processed, or stored.
Section 8 - Monitoring and Recordkeeping Requirements
(a) Monitoring
(1) As soon as practicable after the promulgation of a
standard based on these recommendations, each employer who manufactures,
processes, handles, stores or otherwise uses PCBs shall determine by an
Industrial hygiene survey whether occupational exposure to PCBs may occur.
Surveys shall be repeated at least once every year and within 30 days of
any process change likely to result in occupational exposure to PCBs.
Records of these surveys, including the basis for any conclusion that there
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may be no occupational exposure to PCBs, shall be retained until the next
survey has been completed.
(2) If occupational exposure to PCBs is determined to be
possible, a program of personal monitoring shall be instituted to measure
or permit calculation of the exposures of all employees.
(A) In all personal monitoring, samples
representative of the employees' breathing zones shall be collected.
(B) For each TWA concentration determination, a
sufficient number of samples shall be taken to characterize each employee's
exposure during each work shift. Variations in work and production
schedules and in employees' locations and job functions shall be considered
in choosing sampling times, locations, and frequencies.
(C) Each operation in each work area shall be
sampled at least once every 3 months.
(3) If an employee is found to be exposed to PCBs in excess
of the recommended TWA concentration limit, control measures shall be
initiated, the employee shall be notified of the exposure and of the
control measures being implemented to correct the situation, and the
employee shall be monitored every 30 days. Such monitoring shall continue
until two such consecutive determinations indicate that the employee's
exposure no longer exceeds the recommended TWA concentration limit.
Routine monitoring may then be resumed.
(b) Recordkeeping
Environmental monitoring records shall be maintained for at least 30
years after the employee's last occupational exposure to PCBs. These
records shall include the dates and times of measurements, job function and
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location of employees within the worksite, methods of sampling and analysis
used, types of respiratory protection In use at the time of sampling, TWA
concentrations found, and identification of exposed employees. Each
employee shall be able to obtain Information on his or her own
environmental exposures. Dally rosters of authorized persons who enter
regulated areas shall be retained for 30 years. Environmental monitoring
records and entry rosters shall be made available to designated
representatives of the Secretary of Labor and of the Secretary of Health,
Education, and Welfare.
Pertinent medical records for each employee shall be retained for 30
years after the employee's last occupational exposure to PCBs. Records of
environmental exposures applicable to an employee should be included in
that employee's medical records. These medical records shall be made
available to the designated medical representatives of the Secretary of
Labor, of the Secretary of Health, Education, and Welfare, of the employer,
and of the employee or former employee.
17
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PUBLIC LAW 94-469—OCT. 11, 1976
90 STAT. 2025
(e) Polychlorinated Biphenyls.— (1) Within six months after Rules,
the effective date of this Act the Administrator shall promulgate
rules to—
(A) prescribe methods for the disposal of polychlorinated
biphenyls, and
(13) require polychlorinated biphenyls to be marked with clear
nnd adequate warnings, and instructions with respect to their
processing, distribution in commerce, use, or disposal or with
respect to any combination of sucli activities.
Requirements prescribed by rules under this paragraph shall be con-
sistent with the requirements of paragraphs (2) and (3).
(2) (A) Except as provided under subparagraph (B), effective one
year after the effective date of this Act no person may manufacture,
process, or distribute in commerce or use any polychlorinated biphenyl
in any manner other than in a totally enclosed manner.
(B) The Administrator may by rule authorize the manufacture,
processing, distribution in conunerce or use (or any combination of
such activities) of any polyclilorinated biphenyl in a maimer other than
in a totally enclosed manner if the Administrator finds that such manu-
facture, processing, distribution in commerce, or use (or combination
of such activities) will not present an unreasonable risk of injury to
health or the environment.
(C) For the purposes of this paragraph, the term "totally enclosed "Totally enclosed
manner" means any manner which will ensure that any exposure of manner."
human beings or the environment to a polychlorinated biphenyl will
be insignificant as determined by the Administrator by rule.
(3) (A) Except as provided in subparagraphs (B) and (C) —
(i) no person may manufacture any polychlorinated biphenyl
after two years after the effective date of t his Act, and
(ii) no pei-son may process or distribute in commerce any poly-
chlorinated biphenyl after two and one-half yeai-s after such date.
(B) Any person may petition the Administrator for an exemption Petition for
from the requirements of subparagraph (A), and the Administrator exemption,
may grant by rule such an exemption if the Administrator finds
that—
(i) an unreasonable risk of injury to health or environment
would not result, and
(ii) good faith efforts have been made to develop a chemical
substance which does not present an unreasonable risk of injury
to health or the environment and which may bo substituted for
such polychlorinated biphenyl.
An exemption granted under this subparagraph shall be subject to Terms and
such terms and conditions as the Administrator may prescribe and conditions,
shall be in effect for such period (but not more than one year from
the date it is granted) as the Administrator may prescribe.
(C) Subparagraph (A) shall not apply to the distribution in com-
merce of any polychlorinated biphenyl if such polychlorinated
biphen3'l was sold for purposes other than resale before two and one
half years after the date of enactment of this Act.
(4) Any rule under paragraph (1), (2)(B), or (3)(B) shall be
promulgated in accordance with paragraphs (2), (3), and (4) of sub-
section (c).
(5) This subsection does not limit the authority of the Adminis-
trator, under any other provision of this Act or any other Federal law,
to take action respecting any polychlorinated biphenyl.
FIGURE 1-1. SECTION 6(e) OF THE TOXIC SUBSTANCES CONTROL ACT
18
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II. INTRODUCTION
This report presents the criteria and the recommended standard based
thereon which were prepared to meet the need for preventing occupational
disease and Injury arising from workplace exposure to PCBs. The criteria
document fulfills the responsibility of the Secretary of Health, Education,
and Welfare, under Section 20(a)(3) of the Occupational Safety and Health
Act of 1970, to "...develop criteria dealing with toxic materials and
harmful physical agents and substances which will describe...exposure
levels at which no employee will suffer impaired health or functional
capacities or diminished life expectancy as a result of his work
experience."
The National Institute for Occupational Safety and Health (NIOSH),
after a review of data and consultations with others, formalized a system
for the development of criteria upon which standards can be established to
protect the health and to provide for the safety of employees exposed to
hazardous chemical and physical agents. Criteria and recommended standards
should enable management and labor to develop better engineering controls
resulting in more healthful work environments. Mere compliance with the
recommended standard should not be used as a final goal.
These criteria for a standard for PCBs are part of a continuing
series of criteria developed by NIOSH. The recommended standard applies to
the processing, manufacture, and handling of PCBs as applicable under the
Occupational Safety and Health Act of 1970. The standard was not designed
for the population-at-large, and any application to situations other than
occupational exposures is not warranted. It is intended to (1) protect
19
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against acute and chronic PCB poisoning, (2) be measurable by techniques
that are available to industry and official agencies, and (3) be attainable
with existing technology.
The standard is designed to substantially reduce the risk of
development of carcinogenic, adverse reproductive, hepatotoxic, and
dermatologic effects. Since 1970, PCBs have been one of the more
thoroughly investigated environmental and occupational hazards.
Nevertheless, there are important gaps in the knowledge of chronic exposure
effects in man at low concentrations of PCBs. Important research needs
include studies on the reproductive histories of women who have been
exposed to PCBs, and quantitation of the dermal and respiratory absorption
of different mixtures of PCBs. A better understanding is needed of the
contaminants in commercial PCB preparations, particularly studies to
determine the extent to which any chlorinated dibenzofurans in tissues of
PCB-exposed American workers result from direct absorption or are derived
from PCBs in the body. Another need is for an assessment of the hazards
associated with the mobilization, during fasting or in other abnormal
physiologic states, of PCBs stored in the body.
20
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III. BIOLOGIC EFFECTS OF EXPOSURE
Extent of Exposure
Biphenyl (C 12H 10), diagrammed in Figure III-l, can be chlorinated
by replacing any or all of its hydrogen atoms with chlorine [1],
3 2 6' 5*
5 2' 3'
Figure III-l. BIPHENYL MOLECULE AND RING NUMBERING SYSTEM
Specific chlorobiphenyl molecules are designated by reference to the
positions of the chlorine atoms according to the numbering scheme depicted
in Figure III-l. The lowest possible numbers are assigned, and the phenyl
moiety with the fewest chlorine atoms is assigned prime numbers [1,2].
Examples of the nomenclature used here are shown in Figure III-2.
C1 C1 C1 C1
3-chlorobiphenyl 2,21,3,4',5-pentachlorobiphenyl
Figure III-2. EXAMPLES OF NOMENCLATURE SYSTEM OF CHLOROBIPHENYL COMPOUNDS
There are three monochlorobiphenyl compounds, 2-, 3-, and 4-
chlorobiphenyl. The 5- and 6-monochlorobiphenyls are identical to 3- and
2-monochlorobiphenyl, respectively. There are 18 dichlorobiphenyl
21
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compounds. The number of possible chlorobiphenyl isomers and the
corresponding weight-percents of chlorine are presented in Table III-l.
TABLE III-l
NUMBER OF ISOMERS AND PERCENT CHLORINE
FOR THE 10 CHLOROBIPHENYL (PCB) CLASSES
Chlorobiphenyl
Empirical
No. of
Weight %
Formula
Isomers
CI
mono
C
12H9C1
3
18.79
di
C
12H8C1 2
12
31.77
tri
C
12H7C1 3
24
41.30
tetra
C
12H6C1 4
42
48.56
penta
C
12H5C1 5
46
54,30
hexa
C
12H4C1 6
42
58.93
hepta
C
12H3C1 7
24
62.77
octa
C
12H2C1 8
12
65.98
nona
C
12HC1 9
3
68.73
deca
C
10C1 10
1
71.18
Adapted from reference 1
In the commercial synthesis of chlorobiphenyls,- biphenyl is
catalytically chlorinated with anhydrous chlorine; either iron filings or
ferric chloride may be used as the catalyst [1]. The commercial
preparations, commonly referred to as "PCBs," are isomeric mixtures. The
weight-percent chlorine in commercial mixtures has generally varied between
21 and 68% and has been used to designate grades of commercial products.
Commercial PCB products manufactured in the US, Great Britain, and Japan
have been marketed under the trade name "Aroclor" [1-3], Several grades of
Aroclor have been designated by numbers such as 1221, 1242, 1254, and 1260,
where the last two digits represent the percent by weight of chlorine in
22
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the mixtures. Another grade of Aroclor, 1016, made primarily of tri- and
tetrachlorobiphenyl compounds and containing 41% chlorine by weight, was
introduced In 1971 to replace Aroclor 1242 [2,4,5]. Other PCB products
manufactured In Japan were marketed as "Santotherm" [1], and "Kanechlors"
300, 400, 500, and 600, containing approximately 42%, 48%, 54%, and 60%
chlorine, respectively [6]. In Germany, products marketed as "Clophens"
A50 and A60 contained 54 and 60% chlorine, respectively [7], In France,
PCBs were marketed as "Fhenoclors" and "Pyralenes;" Phenoclor DP6 contains
60% chlorine [8]. Other countries reported to have produced PCBs are
Italy, Spain, Czechoslovakia, Poland, Argentina, Brazil, the USSR, and
India [1,9,10].
The chloroblphenyl constituents of several commercial PCB products
have been studied [6-8,11-16], Some data, both qualitative and
quantitative, rented In Table XII-2, About half the 209 possible
chloroblphenyls do not occur In any of the commercial preparations. Among
those compounds which do not occur, or which occur In trace amounts only,
are 3-chloroblphenyl, all of the trl- to pentachloro compounds that are
chlorinated In only one ring, the penta-, hexa-, and heptachloro compounds
that are completely chlorinated in one ring, and the penta- and hexachloro
compounds that are chlorinated In four positions In one ring.
Commercial PCBs are Insoluble in water, but are soluble in oil and
many organic solvents. Some other physical and chemical properties of
certain Aroclor products are presented in Table XII-1 [1],
In addition to chlorinated biphenyls, the commercial mixtures with
20-40% chlorine contained biphenyl from about 11% to traces, respectively,
by weight. Many commercial PCB products also contain chlorinated
23
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dibenzofurans [17-23] and naphthalenes [18,19]. Concentrations of
chlorinated dibenzofurans In various commercial PCB products are presented
In Table III-2.
TABLE III-2
CHLORODIBENZOFURAN TYPES AND CONCENTRATIONS (#ig/g)
IN COMMERICAL PCB PREPARATIONS
Chlorodibenzofurans
Mixture*
di tri
tetra
penta
hexa
hepta
Total
Ref.
(1) 1016
0.5
0.5
**
(1) 1016
<0.001
<0.001
<0.001
21
(1) 1248
0.5
1.2
0.3
2.0
21
(1) 1254
0.1
0.2
1.4
1.7
21
(1) 1254
0.2
0.4
0.9
1.5
21
(1) 1260
0.1
0.4
0.5
1.0
21
(1) 1260
0.2
0.3
0.3
0.8
21
(2) A-60
1.4
5.0
2.2
8.4
21
(3) DP-6
0.7
10.0
2.9
13.6
21
(4) K300
(a)
(a)
1-1.5
20
(4) K400
(c)*** (e)
(e)
(c)
17-18
20
(4) K500
(a)
(c)
(a)
2.5-4
20
(4) K600
(a)
(a)
(b)
(b)
3-5
20
*(1) Aroclor, (2) Clophen, (3) Phenoclor, (4) Kanechlor
**(I Pomerantz, written communication, January 1977)
*** (a), (b), (c), Cd), (e) represent relative amounts In increasing order
Some commercial preparations that were marketed under the trade name
Aroclor contained chlorinated terphenyls in addition to chlorinated
biphenyls. Aroclors 2565 and 4465 contained 75% and 60% chlorinated
biphenyl compounds and 25% and 40% chlorinated terphenyl compounds,
respectively. Both mixtures contained 65% chlorine [1],
A broad class of nonflammable synthetic chlorinated hydrocarbon
insulating liquids used in electrical capacitors, transformers, nuclear
24
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reactors, and accessory equipment is designated by the generic tern
"askarel" [4,5,24,25]. PCBs have been major components of most askarels
used in the US since 1932. Two general classes of PCB-containing askarels
are "capacitor"-grade and "transfonner"-grade [4,5]. Aroclor 1242 was the
major capacitor impregnant in the US before 1971; subsequently, Aroclor
1016 has been used mainly for this purpose [4]. Transformer-grade askarels
manufactured in the US Include those marketed under trade names including
"Asbestol," "Chlorextol," "Inerteen," "No-Flamol," "Pyranol," and "Saf-T-
Kuhl" [4]. Transformer-grade askarels are usually mixtures of
trichlorobenzene and more highly chlorinated (42-60%) blphenyls [5,24].
Some typical compositions are: 100% Aroclor 1242; 70% Aroclor 1254 and 30%
trichlorobenzene; 60% hexachloroblphenyl and 40% trichlorobenzene; 45%
hexachlorobiphenyl and 55% trichlorobenzene; and 70% pentachlorobiphenyl
and 30% trichlorobenzene. Another type of transformer-grade askarel
contains 45% polychlorinated biphenyl (54% chlorine) and 55% of a mixture
f trl- and tetrachlorobenzenes. Transformer-grade askarels also contain
stabilizers such as glycidyl phenyl ether and 3,4-epoxycyclohexylmethyl-3,
i-epoxycyclohexane carboxylate [24].
Exposure to commercial preparations of PCBs in the work environment
may involve many different chlorinated biphenyl compounds, and also
substantial amounts of biphenyl, tri- and tetrachlorobenzenes, and small
amounts of many different chlorinated dibenzofurans, chlorinated
naphthalenes and in special uses, chlorinated terphenyls.
Commercial production of PCBs in the US began in 1929 and reached 85
million pounds in 1970 when the major producer began selling PCBs only for
use in "closed" systems. Since 1972, only those Aroclors designated 1016,
25
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1221, 1242, and 1254 have been produced in the US, and total annual
production has been around 40 million pounds [26],
Imported PCBs amounted to about a half-million pounds in 1972 and
19-73 [26,27], A decacHlorobiphenyl produced in Italy and imported by one
company for use in investment casting waxes accounted for 80-90% of the
total PCB imports [26], The other 10-20% was imported from France for use
in semiclosed heat transfer applications [27]. Occupational exposure to
decachlorobiphenyl could occur in the manufacture of the investment casting
waxes as well as in the preparation of the investment casting molds in the
25 US foundries which use the decachlorobiphenyl wax [26],
Most of the PCBs produced in the US since 1971 have been used in
electrical capacitors (70%) and transformers (30%). About 95% of the 100
million capacitors produced annually in the US contain PCBs [27], There is
potential occupational exposure to PCBs in the plants of the 17 reported
companies that manufacture capacitors in the US. Capacitors are generally
classified into two categories for disposal purposes. "Small" capacitors
contain less than 2 pounds of PCBs; those incorporated into electrical
equipment such as television sets, home air conditioners, and light
fixtures contain 2-340 ml of PCBs and have service lives of at least 10
years [26,28], "Large" capacitors may contain about 25 liters of PCBs [26]
and have a service life of 15-20 years [26,27], Potential occupational
exposures exist in the servicing of appliances and in the disposal of used
capacitors or equipment.
Transformers that contain PCBs are used mainly in or near inhabited
buildings where fire hazards from cheaper oil-filled transformers are
greatest. The estimated 135,000 PCB-containing transformers represent
-------
about 5X of all transformers in the US [27]. Occupational exposure to
various askarels used for transformers may occur in their manufacture,
servicing, and transportation, or as a result of leaks [29].
Other potential occupational exposures to PCBs exist through losses
in storage [30], shipment [29], manufacture and use of heat exchange units
[27,31], and in use of previously manufactured items which contain PCBs,
such as hydraulic systems, vacuum pumps, and gas transmission turbines
[30,31]. The past use of PCBs in carbonless copying papers may result in
exposure of workers currently engaged in paper reclamation [30]. Workers
in plants that previously used PCBs may have current exposure in their
working environments because PCBs have been shown to remain in the
workplace air and on surfaces for years after PCB use has been discontinued
[32,33]. Several occupations that may have Involved exposure to PCBs were
tabulated in a 1966 publication [34]. NIOSH estimates that 12,000 workers
have potential occupational exposure as a result of current uses of PCBs in
their working environments [35].
In addition to their occupational exposures, PCB workers may be
exposed to PCBs carried into their homes from the workplace [36], from
general contamination of the ambient air [26,37,38] and water [26,37], and
to PCBs and their metabolites in their diets [39-46].
Metabolism and Mechanism of Action
A study of the metabolism of 4-chlorobiphenyl was reported in 1959 by
Block and Cornish [47]. In this experiment, 1 gram of 4-chlorobiphenyl was
fed to rabbits in a single dose and 41-chloro-4-biphenylol and its
27
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glucuroniside were recovered from the urine in amounts that accounted for
24 and 50%, respectively, of the administered dose.
Subsequently, a substantial number of metabolic studies of individual
chlorobiphenyl compounds [41-43,48-84], mixtures [85,86], and metabolites
[48,49,87] were reported, and a comprehensive review was published in 1976
[88]. These reports collectively demonstrate through many study methods
that some aspects of metabolism are of special significance to the toxicity
of PCBs and that some Isomers are more toxic, or have different effects,
than others [89-94].
Chlorinated biphenyl compounds are readily absorbed from the
digestive tract, regardless of the degree or pattern of chlorine
substitution [50,51,95,96]. It seems likely that similar absorptive
characteristics apply to the respiratory system since chlorobiphenyl
mixtures in air are rapidly absorbed [97], as is decachlorobiphenyl
[98,99]. Varying amounts of chlorobiphenyls, depending on degree and
pattern of chlorination, are excreted in the feces [42,50,53-56,100], milk
[41-44,51,101], and hair [102] of animals, but no more than trace amounts
are excreted in the urine [42,51-55,57-62,103-105].
Metabolites of chlorobiphenyl compounds have been found in the urine
of mammals including mice [52], rats [48,53-56,58-60,63,64,66,71,85],
rabbits [65,67-69], monkeys [51,61,74,75], swine [72], goats [73], and cows
[41,73], as well as in feces [48,50-54,56,58-65,76-80], and milk [41]. The
metabolites excreted in urine [53,54,58,59,61,63,64,66,67], bile
[50,51,53,81], feces [52-54,58,63,76], and milk [41] are, to varying
degrees, conjugated with glucuronic or sulfuric acids. Differences in
metabolism of PCBs among the aforementioned species are more quantitative
28
-------
than qualitative [51,73]; however, metabolism in birds and fish may differ
qualitatively from that in mammals [55,77]. Among mammals there are also
quantitative differences in PCB metabolism and in effects related to age
and sex [50,93,106]. Metabolites identified in mammals Include mono- to
polyhydroxylated derivatives [41,48,49,51-56,58-81,85], and methoxy
[59,60], hydroxymethoxy [64,65,68,70,76,87], dihydrodihydroxy
[51,53,54,69,74,75,81], hydroxydihydrodihydroxy [51,74], and dechlorinated
derivatives [48,65,70,77].
The lower-chlorinated biphenyl compounds are more readily metabolized
than are the more highly chlorinated ones [41,50,51,55,61-64,66,82-
84,96,107-109], with no metabolism having been demonstrated for
decachlorobiphenyl [66]. As a consequence, some of the more highly
chlorinated compounds persist in the tissues for years after Intake has
been discontinued [51,83,103,110].
The presence of at least two adjacent, unsubstituted hydrogen atoms,
particularly In positions 3, 4, and 5, or 3', 4', and 5', is required for
rapid metabolism of chloroblphenyls [79,83,84], All mono- di-, and
trlchloroblphenyls, and all tetrachloroblphenyls except 3,3',5,5'-
tetrachlorobiphenyl meet this requirement. The latter compound, 3,3',5,5'-
tetrachloroblphenyl, was found to be particularly toxic to monkeys, and it
was suggested that the chlorinated dibenzofuran derivative may have been
involved [94]. While dibenzofuran derivatives have not been demonstrated
to exist as mammalian metabolites, they may have been identified as PCB
metabolites in chickens [111] and Curley et al [22] reported the excretion
of dibenzofurans in urine of rats. In the latter case, however,
dibenzofurans were also identified in the administered PCB [22].
29
-------
Dibenzofurans are of concern because they may be many times more toxic than
PCBs [19,112].
Metabolites found in urine [48,51,53,56,60,61,64,66-74,85], bile
[81], feces [51-53,56,58,60,61,64,66,76,79,80,113], and milk [41] include
hydroxy derivatives. Such compounds have been demonstrated to be more
toxic than their respective parent chlorobiphenyl [41,114] and their
presence in milk [41] is of special concern.
Hydroxylation may be direct through hydroxylating enzyme systems, or
through formation of arene oxide intermediates [48,51,53,68,75,81,87,115].
This latter process is of particular concern because of potential
carcinogenesis and mutagenesis as a result of covalent binding of arene
oxides to nuclear components of the cell [51,68,74,82,86,116]. Such
binding has been demonstrated both in vivo [51,86] and in vitro
[51,82,86,116,117]. Additional evidence of hydroxylation through arene
oxide intermediates included findings of metabolites in which chlorine,
dueterium, or tritium were at different molecular locations than in the
administered compound [68,115,116,118], and transdihydrodiols as mammalian
metabolites [51,69,74,75,81].
Although adjacent unsubstituted hydrogen atoms are necessary for
rapid metabolism of chlorinated biphenyls, it has been demonstrated that
2,2',4,4',5,5'-hexachlorobiphenyl, which does not have this characteristic,
can be hydroxylated [70,79], and oxidatively dechlorinated [65,70]. It has
been proposed that the metabolism of this compound may also involve arene
oxide formation [65] , and chronic exposure to potential carcinogenic
activity of resulting arene oxides [86] may result from the metabolism of
this and similar compounds [75].
30
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Historical Reports
Smyth [119], in a paper read October 28, 1930, presented the results
of his studies with biphenyl, 2- and 4-chlorobiphenyl, and two unidentified
polychlorobiphenyl mixtures. He reported the oral minimum lethal doses for
rabbits and guinea pigs as 4+, 2.5, 3.5, 4+, and 4+ g/kg, respectively.
Health problems associated with the manufacture of PCBs were the
subject of a report by Jones and Alden [120] in 1936. The case history was
presented of a man whose employment, from April 1930 to the end of 1933,
involved the distillation of chlorobiphenyl. In May 1933 he developed
chloracne, a specific type of acne known to be caused by some chlorinated
hydrocarbon compounds [121,122]. Jones and Alden [120] stated that the
manufacturing process was not enclosed, that a different source of benzene
(a starting ingredient) had been used from the summer of 1932 through
October 1933, and that from March to October 1933, the dielectric qualities
of the PCBs produced had been substandard. Of 24 men working In the
manufacturing process during the period beginning in the summer of 1932, 23
developed chloracne. The first indication of chloracne in the workers
appeared in January 1933. Following another change In the source of
benzene, enclosure of the distillation apparatus and installation of
ventilation fans, a gradual improvement in the acneiform eruptions was
noted.
In 1936, Schwartz [123] reported digestive disturbances, burning of
the eyes, and impotence in men working with chlorobiphenyls. He also noted
that nonachlorobiphenyl was used as an insulator for automobile electric
wires, in capacitors, and as a delusterer of rayon.
31
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An early use of PCBs was for incorporation along with
chloronaphthalenes into synthetic waxes [124-128]. These waxes contained
10-20% PCBs [124-126] and were used to insulate electrical wire and cable.
There were several reports that chloracne [125-128] developed in workers
involved in the manufacture and use of these waxes, which were associated
with at least one fatality in 1936 [125,127],
The fatal case was described by Drinker et al [125] in 1937. The
patient, who had been exposed to low concentrations of tetra- and
pentachloronaphthalenes (90%) and chlorinated biphenyls (10%) developed
chloracne, followed by jaundice. He was hospitalized with abdominal pain
and distention. At autopsy, cirrhosis of the liver with superimposed acute
yellow atrophy was found. Two other fatal cases were described where the
exposures had been to mixtures of penta- and hexachloronaphthalenes [125].
According to the authors, no similar cases had been reported in the
literature. As a result of these fatalities, estimates of the airborne
concentrations of chlorinated hydrocarbons in 30 different factories were
made and animal experiments were performed to study the effects of exposure
at such concentrations.
Rats were exposed 16 hours/day, 6 days/week to trichloronaphthalenes
at 1.31 mg/cu m, to a mixture of penta- and hexachloronaphthalenes at 1.16
mg/cu m, to a mixture of penta- and hexachloronaphthalenes (90%) and
chlorinated biphenyls (10%) at 1.37 mg/cu m, and to a chlorinated biphenyl
mixture containing 64% chlorine at 0.57 mg/cu m. The authors [125] stated
that higher concentrations had frequently been found in the factories, and
that except for trichloronaphthalenes, they did not consider that it would
be safe to expose workers to any of the mixtures at the concentrations
32
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studied [125]. Further details of the animal experiment were reported by
Bennett et al [129] in 1938. These investigators [129] found morphologic
changes in the livers of two groups of rats exposed at the 0.57-mg/cu m
concentration and also at 0,93 mg/cu m for 8 hours/day. These animal
experiments reported by Drinker et al [125] and by Bennett et al [129] have
continued to be erroneously cited [130,131] even though Drinker [132]
reported in 1939 that the "chlorinated biphenyl" was actually a mixture of
chlorinated blphenyls and chlorinated terphenyls. Drinker [132] stated
that a followup inhalation experiment with chlorinated blphenyls containing
68% chlorine showed them to be of low toxicity and he recommended
permissible limits for workroom air of 0.5 mg/cu m for mixtures of
chlorinated blphenyls and terphenyls and 10 mg/cu m for chlorinated
blphenyls.
The first indication in the literature that PCBs might be embryotoxic
or have teratogenic effects was the report by McLaughlin et al [133] in
1963, 5 years prior to the recognition of PCBs as an environmental
pollutant. The authors evaluated the toxicity of Aroclor 1242 by injecting
it into the yolk sac of fertilized eggs prior to incubation, and then
observing the effects on embryonic development. None of the eggs hatched
after injection with 25 mg of PCBa/egg; with injection of 10 mg/egg, one
chick hatched out of 20 injected egg9, but it died 2 day9 later. Some of
the embryos examined showed beak deformities, edema, and retarded growth.
Effects on Human3
(a) Effects from General Environmental Contamination
In the United States, PCBs are present in ambient air [26,37,38],
33
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water [26,37], and in many foods [39,45,461. A common dietary intake of
10-20 /ug/day has been estimated for teenage males in the US [46]. PCBg
frequently have been found in various tissues and body fluids of the US
population, eg, at ppm concentrations in adipose tissue [7,36,134-136], ppb
concentrations in blood [137,138,140,141], and in milk [143,144] at ppm or
ppb concentrations in the milk fat or whole milk, respectively.
The Environmental Protection Agency's Human Monitoring Survey has
analyzed human adipose tissue samples collected since late 1968 for PCB
content [134], According to this 1972 report, 637 •samples had been
analyzed, and 198 of these contained more than 1 ppm of PCBs. Positive
findings were made in tissues from each of the 18 participating states.
A detailed analysis of two samples collected in the Human Monitoring
Survey was made by gas-liquid chromatography (GLC) and mass spectrometry
(MS) and reported by Biros et al [135] in 1970. The samples contained at
least 14 isomers ranging from penta- to decachlorobiphenyls. Price and
Welch [36] stated that of more than 4,000 human adipose tissue samples
examined by the Michigan State Department of Health Pesticides, none had
chromatograms that exactly matched those of standard Aroclor solutions.
Their data show relative accumulation in adipose tissue of the more highly
chlorinated compounds, and relative dilution or absence of the less highly
chlorinated compounds originally present in Aroclors 1254 and 1260, They
[36] described the analyses of tissue samples at autopsy of a 77-year-old
man in which PCB concentrations of 100-250 ppm (fat basis) were found. The
highest PCR concentration was in the liver. The authors [36] found about
55% of adipose tissue samples in the general population contained PCUs at
<1.0 ppm, about 36% at 1-2 ppm, and the remainder at more than 2 ppm.
-------
During July 1972 through June 1974, 2,324 fat samples were analyzed
by the Human Monitoring Survey, 1,277 in the first year and 1,047 in the
second [136], In the 2 years, respectively, PCBs were not detected in 24.5
and 9.1Z, were present at <1 ppm in 40.2 and 50.6%, were present at >2 ppm
in 5.5 and 4.9Z, and were present at 1-2 ppm in the remainder of the
samples. Penta-, hexa-, and heptachlorobiphenyl were the PCBs most
frequently present.
A complete analysis of PCB compounds in a composite sample of adipose
tissues from patients at the University Hospital in Lund, Sweden, was
reported by Jensen and Sundstrom [7] in 1974. Forty-five compounds,
accounting for the total PCB content of the adipose tissues, were found and
identified by comparison with known PCB isomers. The biphenyl compounds
included three tetrachloro isomers, many penta-, hexa-, hepta-, octa-, and
nonachloro isomers, and decachlorobiphenyl. By comparison with Clophens
A50 and A60, which had compositions similar to Aroclors 1254 and 1260,
respectively, the authors [7] found the relative concentration of several
compounds with chlorine substitution in the 4,4' positions of the biphenyl
ring to have occurred, as did many compounds without vicinal, unsubstituted
positions. Most of the compounds which underwent relative dilution to the
greatest extent had either vicinal, unsubstituted 3,4-positions or two
pairs of vicinal, unsubstituted positions.
Blood sera of 616 residents of urban and rural areas of South
Carolina were analyzed for PCBs and the results were presented by Flnklea
et al r137] In 1972. Analysis was accomplished by GLC with a Ni-63
electron capture detector after basic dehydrochlorination. The amounts of
PCBs present were estimated by integration of five peak areas associated
35
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with Aroclors 1254 and 1260. PCBs were not present in samples from all
individuals in quantities measurable by the technique used (Table III-3).
Analysis of the data indicated that measurable serum PCB concentrations
were not related to the age (<5 to >60 years) or sex (305 females, 311
males) of the donor, but that the concentrations associated with race and
residence (Table III-3) were statistically different.
TABLE III-3
PCB CONCENTRATIONS IN BLOOD SERUM BY RACE AND RESIDENCE
Race and No. in PCBs Measureable In PCB Concentrations
Residence Sample No. % Ave* Max
ppb ppb
Rural black 107 5 4.67 9.45 20.6
Urban black 151 57 37.75 5.22 29.0
Rural white 192 119 61.98 5.12 16.6
Urban white 166 89 53.61 4.38 22.0
*Average of measureable concentrations
Adapted from reference 137
Maternal and cord blood samples collected in Tokyo, Japan from
December 1973 through February 1974 were reported in 1975 by Akiyama et al
[138] to contain PCBs at mean concentrations of 2.8 and 1.1 ppb,
respectively (on a whole blood basis). The maximum concentrations found
were 7.6 ppb in maternal blood and 3,3 ppb in cord blood. Quantitatively,
significant correlations of PCB concentrations in 21 pairs of maternal and
cord blood samples were.not found. Qualitatively, pairs of maternal and
cord bloods had identical PCB patterns resembling those of Kanechlors 500
36
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and 600. The data suggested nonselective in utero transfer of PCB
compounds from mother to fetus. Concentrations of PCBs in human embryonic
and fetal tissues were reported by Shiota et al [139] in 1973 to not exceed
those found in postnatal individuals who died accidentally. The
concentrations, found in 19 embryos 5-8 weeks old, were reported as <2 ppb.
The concentrations found in 5 second trimester and 2 third trimester
fetuses are presented in Table III-4, expressed on the bases of both whole
tissue and on the fat content of the tissue.
TABLE III-4
CONCENTRATIONS (ppb) OF PCBs IN TISSUES OF HUMAN FETUSES
Tissue Analyzed
Age of Placental Basis Cerebrum Liver Kidney Skin
Contents
2nd trimester Whole
Fat
3rd trimester Whole
Fat
*0ne sample
Adapted from reference 139
PCB concentrations in the venous blood of nine patients hospitalized
with severe wasting diseases were reported by Hesselberg and Scherr [140]
in 1974. The investigators were concerned with the release of stored
organo-halide pesticides and PCBs during mobilization of body fat. They
were unable to detect any PCBs in the blood of 15 apparently healthy
2-23 2-33 6-20 17-83
150-60 230-800 60-1,900 550-1,300
2* 25-90 6-10 48-769
270* 1,000-1,300 420-470 880-1,400
37
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control subjects. PCB concentrations found in the patients' blood
(uncorrected for efficiency of recovery) ranged from 10 to 100 ppb.
Information was not presented on the patients' occupations etc prior to
their having become ill.
PCB concentrations in blood plasma and in adipose tissue samples
obtained from 28 people during routine abdominal sections had a correlation
coefficient of 0.74 according to Inoue et al [141], The average
concentration of PCBs was 6.1±3.52 ppb in blood plasma, and in the adipose
tissue (fat basis) it was 2.6+1.9 ppm. These investigators [141] also
evaluated the effect of emaciation on PCB concentrations in blood plasma of
these and other patients; they found an average of 8.4+4.26 ppb iq 19
emaciated patients and 4,7+2,17 ppb in 30 unemaciated patients.
Hair samples collected from a college barber shop were reported by
Matthews et al [102] in 1976 to contain PCBs at 0.34-0.76 ppm. The samples
were composites from five or more individuals collected on two occasions, 4
months apart. Hair was collected from the barber shop aprons, and care was
taken to avoid possible contamination. Five commercial preparations of
hair sprays, shampoos, and hair clipper lubricating oil were negative for
PCBs. Blood samples were not collected for comparison.
PCBs were reported in 1966 to have been found in hair samples from
three members of a Swedish family [142], but no concentration data were
given. It was speculated that one of the family members, a 5-year-old
girl, had acquired PCBs from her mother's milk.
""A correlation was found between the quantities and compositions of
PCBs in samples of adipose tissue collected from four women during
Caesarean deliveries and in milk samples collected 3-5 days later [143] .
38
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There were differences in chromatographic patterns between individuals, but
for each individual the chromatographic patterns for the adipose tissue and
trte milk were qualitatively the same. PCBs in all samples contained
principally 4-8 chlorine substitutions. Although the basis (fat or whole
milk) for expressing the concentration of PCBs in the milk was not stated,
comparisons with PCB concentrations found in adipose tissue and milk by
other investigators indicate that the whole milk basis was used [136,144]
(EP Savage, written communication, February 1977). Concentration data are
summarized in Table III-5.
TABLE III-5
PCBS IN MILK AND ADIPOSE TISSUE OF FOUR WOMEN
PCB Concentrations, ppm
Subject Adipose Tissue Milk
a 0.62 0.008
b 0.75 0.015
c 1.6 0.032
d 3.1 0.036
Adapted from reference 143
Concentrations of PCBs measured in milk samples from 39 women living
in two small cities in Colorado were presented by Savage et al [144] in
1973. Two samples contained PCBs at concentrations of 0.05 and 0.1 ppm.
Six other samples contained PCBs at 0.04 pom, the lower limit of detection
for the analytical method, or less. The time postpartum at which the
samples were collected and the basis (fat or whole milk) for expressing the
concentrations were not mentioned. (Comparison with data in the following
39
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paragraph suggests that the whole milk basis was used.)
Results of analyses of 384 human milk samples from 40 states for PCBs
were presented In a written communication by EP Savage In February 1977.
All positive samples that contained PCBs at less than 50 ppb on a whole
milk basis were recorded as a "trace." Samples with 50 ppb or more of PCBs
were reported as ppm in milk fat on the basis of 2.8£ milk fat. Only five
samples were not positive for PCBs, and 112 samples from 27 states
contained measurable amounts (up to 12.6 ppm on a fat basis). Of the total
number of samples, 141 were analyzed during December 1976 and January 1977.
The time postpartum when the samples were collected was not stated.
While no adverse effects have been associated with PCBs at the
concentrations found in adipose tissue, blood, or milk of individuals whose
only known exposures were from general environmental contamination
[7,36,102,136-144], knowledge of these concentrations is important to the
evaluation of reports on occupational exposures. That is, the data provide
a basis for evaluating body burdens of PCBs added by occupational exposure
and indicate that workers may have substantial body burdens before the
added insult of occupational exposure.
(b) Effects from Consuming PCB Contaminated Rice Bran Oil
An episode of poisoning associated with PCB ingestion occurred in
Japan in 1968, and was the subject of a special issue of the journal
Fukuoka Acta Medica in June 1969 [145-159], These reports dealt primarily
with the situation in Fukuoka prefecture where 325 poisoning cases had been
identified through January 20, 1969. The episode resulted from consumption
of a particular brand of rice bran oil [160] and ultimately involved
persons in 22 prefectures [161]. About equal numbers of cases
40
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(approximately 450 each) were registered in Fukuoka and Nagasaki
prefectures as of September 1973 [161]. In the prefectures of Hiroshima,
Kochi, and Yamaguchi, there were 80, 45, and 40 cases, respectively, at
that time. In each of the other 17 prefectures there were 1-25 registered
cases. The total number of cases registered by March 1970 was 1,015; by
September 1973, the number had increased to 1,200, and by May 1975 to 1,291
[161.162], The disease became known as "Yusho," or rice oil disease
[145.163]. The outstanding signs of the poisoning were acnelform eruptions
and eye discharges (a peculiar secretion from the meibomian glands) [146],
Chloracne was suspected [164], Hyperplgmentatlon of the skin, nails, and
mucous membranes, swelling of the upper eyelids, and hyperemia of the
conjunctivae were other common signs [146,165],
Studies of the rice oils consumed by the patients Indicated that the
oil associated with Yusho was produced mainly during February 1968
[147,148]. The source of the contamination was determined to be a heat
exchange unit containing PCBs that leaked through clny holes when rice bran
oil was heated at low pressure to remove odorous constituents [163,165],
By intensive chemical analyses, including Infrared spectrophotometry and
GLC, the major contaminant in the rice bran oil was found to be Kanechlor
400 [147], PCB concentrations in the oil varied, depending on the date of
production or shipment. The highest concentration of PCBs, based on the
chlorine content of the oil, was about 3,000 ppm which was found in canned
oil shipped on February 5. GLC data were not quantitated. In oils shipped
thereafter, PCB concentrations decreased rapidly, and only traces were
found in oils produced after February 19, 1968 [147,148], Minor
contaminants in the rice oil included polyehlorinated dibenzofurans at
41
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about 1/200 of the PCB concentration [20,160], traces of chlorinated
naphthalenes, and bromine at about 2% of the chlorine content [14?].
Recent analyses of some of the oil samples indicate that there may have
been other chlorinated organic contaminants (F Cordle, written
communication, November 1976),
In one study [148], the contaminated rice bran oil was found to have
been used largely for frying food (which may have altered the
constituents). The oil was consumed for various periods during the spring
through Octoblr 1968 [148]; the first reported clinical examination of a
Yusho patient had occurred on June 7, 1968 [163], Studies through January
1969 of patients in Fukuoka prefecture indicated that onsets of Yusho began
as early as February and as late as December 1968, and first involved the
eyes [146], Onset occurred in most patients in June, July, and August
[146],
Some attempts were made to estimate the amounts of rice oil and PCBs
consumed by the patients [166,167], Maximum consumption of oil was
estimated at 4,4 liters [166], Isono and Fujiwara [167] estimated that two
Yusho cases may have resulted from the ingestion of PCBs at a daily rate of
67 Mg/kg body weight for 3 months. For 146 Yusho patients who lived in
homes known to have used oil shipped on February 5-6, the estimated average
total oil consumption was 800 ml, a volume that contained an estimated 2 g
of PCBs [166], It was estimated that the maximum volume of oil consumed by
an individual was 2.7 liters. Of 21 patients who had consumed more than
1,400 ml (3-4 g of PCBs), 18 were considered to have had major signs of
Yusho. Among 80 patients estimated to have consumed less than 720 ml of
the oil, 31 were thought to have had maior signs of Yusho. From the same
-------
data, the minimum PCB ingestion among the 146 patients was estimated at 0,5
g [165]. Estimates of the amount of contaminated oil consumed by 13
pregnant women during the ingestion period ranged from 300 to 2,600 mg
[167], but estimates of their PCB consumption were not made. Of the 13
babies born to these women, 8 had jaundice, 3 had marked dermal chromopexy,
and 9 had excess secretion of tears [167],
Several studies of PCBs in the tissues and body fluids of Yusho
patients were made at various Intervals after Ingestion of the contaminated
oil [146,147], The samples taken closest to the time of ingestion were
collected in October and November 1968 [146,147]. Samples from discharges
of the acnelform eruptions of two patients contained PCBs at 32 and 45 ppm,
and samples of subcutaneous fat from the face and abdomen of an 18-year-old
man contained PCBs at about 75 and 13 ppm, respectively. PCBs with GLC
patterns similar to those of the contaminated oil were found in these
samples as well as in placental and fetal tissues [147]. Preserved tissues
from a baby that had been stillborn In October 1968 were later analyzed and
PCB concentrations of 1.8, 1.2, and 0.1 ppm in fat were found in the liver,
skin, and fat, respectively [168], The baby's mother had been classified
as a severe case of Yusho with onset about mid-June, but the amount of oil
consumed, the period of pregnancy during which it was consumed, and the
body burden of the mother were not reported f 149] . PCBs were found in all
sputum samples from 13 patients collected between December 1969 and May
1970 [169,170]. PCB concentrations were highest in December and detection
was less common by May.
Other data on concentrations of PCBs were obtained from body fat and
other tissues taken from five Yusho patients at autopsy [168,171], The
-------
dates of death were between July 1969 and May 1972. Cause of death was
heart failure in four cases and a ruptured liver in another case [171].
Estimates of contaminated oil consumed by two of the dead patients were
about 0.3 g and 1.6 g, respectively [171], One PCB, probably a hexa- or
heptachlorobiphenyl from the contaminated oil, was especially concentrated
in the tissues. The peaks associated with tetrachlorobiphenyls were very
low by comparison, suggesting that total PCBs in the body had been
substantially decreased within a year after the end of exposure. The
mesenteric fat contained PCBs at 0.9-15.1 ppm, and the liver contained 1.3-
10.4 ppm in its fat. PCB concentrations in fattv tissues obtained during
11 control autopsies averaged 2.6 ppm. Of the organs examined (liver,
heart, kidney, brain, and skin), the liver and heart usually contained the
highest concentrations of PCBs [168,171],
In an additional ca9e, the subcutaneous fat obtained on autopsy of a
woman who died in September 1972 (about 2 years after consuming
contaminated oil) contained PCBs at 2.9 ppm [168],
Polychlorinated dibenzofurans (PCDFs), mainly penta- and hexachloro
compounds, were found in tissues obtained on autopsy of two Yusho patients
who died in 1969 and of one who died in 1972 [160], No chlorinated
dibenzofurans were found in tissues obtained on autopsy of two controls,
although PCB concentrations of about 1-1.5 ppm were found in adipose tissue
and liver fat. The findings from the Yusho patients are summarized in
Table III-6.
kU
-------
TABLE II1-6
PCBs AND PCDFs (pptn) IN FAT FROM THREE YUSHO PATIENTS AT AUTOPSY
Year of PCBs PCDFs
Death Adipose Liver Adipose Liver
1969 3.4 4.7 0.03 2.3
1969 8.5 5.6 0.04 1.1
1972 2.1 3.5 0.01 0.3
Adapted from reference 160
The ratio of PCRs to PCDFs In the rice bran oil was about 200, as In
the adipose tissues obtained at autopsy. However, in the liver, ratios of
2, 5, and 12 indicate that considerable concentration of PCDFs had
occurred.
Information on PCBs [146,147,168,171] and PCDFs [160] in tissues
indicates some shifts in concentrations during the 3 years after ingestion
of the contaminated oil was discontinued. Maauda et al [168] reported that
a year after ingestion stopped, the concentrations of tetrachloroblphenyl
components had decreased and were near those found in persons who had not
ingested the contaminated oil. The more highly chlorinated PCB compounds
were still retained in the fatty tissue 4 years after ingestion had stopped
[168].
Blood from Yusho patients was first examined for PCBs 5 years after
ingestion of the contaminated oil ceased. Three distinct GLC patterns were
found among blood samples from 49 patients [172-175]. Two patterns (A and
B) were peculiar to the Yusho patients, and the third pattern (C) was
45
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similar to that of controls. Patterns A and B were characterized by peaks
corresponding to those of certain penta- and hexachlorobiphenyl compounds
that were present in the contaminated rice bran oil. Patterns A and B
differed, however, as to the relative amounts of these compounds [172,173].
These patterns became diagnostic for Yusho [ 161 ]. The average
concentrations of PCBs in the blood serum were 9, 4, and 2 ppb for patients
with patterns A, B, and C, respectively, and 3 ppb for 27 control subjects
[173]. The maximum blood serum PCB concentration found among 72 Yusho
patients examined between April 1973 and March 1974 was 26 ppb [174]. Of
these patients, 43 had pattern A, 26 had pattern B, and 3 had pattern C.
Similar patterns were reported in 1975 by Abe et al [176] in a 1974
study of 18 female Yusho patients and their 30 children. Concentrations of
PCBs in blood samples from mothers ranged from 3 to 33 ppb during 1974;
PCBs in samples from their children ranged from 1 to 20 ppb, and in samples
from 14 control children, from 1 to 8 ppb. PCB concentrations tended to be
higher in the blood samples from children nursed by Yusho mothers. A
sample of milk from a Yusho mother was reported in 1974 to contain PCBs
with a GLC pattern similar to those in samples of fatty tissue from other
Yusho patients [168]. Concentrations of PCBs in the mother's milk were
0.06 ppm on postpartum days 0-2, 0.04 ppm on days 3 and 4, and 0.03 ppm on
day 5. The respective concentrations in the milk fat were 4.5, 3.0, and
2.6 ppm.
In addition to the skin and eye conditions manifested by most people
who consumed the contaminated rice bran oil [146,151-153,162], there was
pigmentation of the nails [146] and of the oral mucosa [154J. A
substantial array of clinical and laboratory findings were published on
-------
patients with Yuaho [150,152,155,156,177-180], including alight increases
in activity of serum alkaline phosphatase, reduced serum Iron
concentrations [155], changes in the microanatomy of liver cells that were
considered Indicative of microsomal enzyme stimulation [156], symptomatic
and functional changes indicative of neuropathy [150,177], respiratory
Involvement [170,178], a decreased concentration of bilirubin in the serum
[179], and, in many patients, an elevation of the concentration of
triglycerides in the serum [155,157,158,175,179-181],
Babies born to women with Yusho, both during and after the period of
ingestion of the contaminated rice bran oil, were the subject of several
investigations [149,159,176,182,183]. Babies of mothers who had Ingested
the contaminated oil became known as "black" or "cola" babies because of
the abnormal skin pigmentation that tended to persist for several months
after their birth [176,182,183]. Infants born up to 5 years after their
mothers' last ingestion of contaminated rice oil were still affected to
some extent [182], In one study of four babies, other clinical and
anatomical abnormalities (retarded intrauterine growth In three, edematous
face and exophthalmic eyes in three, dentition in two, calcification on
skull and wide, open sagital suture of skull in three) were seen at birth
[183], These were not permanent, and postnatal body and mental development
appeared normal in these and other Yusho children [160,176,183]. In at
least one case, an Investigator concluded that a baby had developed Yusho
from nursing [182],
The period of ingestion of contaminated rice bran oil was only a few
months, but the effects have persisted for several years
[160,161,174,175,179,180,184,185]. The skin lesions and hypersecretion
-------
from meibomian glands remained unchanged for long periods in many patients
[174,184,185]; their magnitudes in 1974 appeared to be related to blood PCB
concentrations [174], In addition, complaints of generalized fatigue, and
symptoms referable to the peripheral nervous system and to the respiratory
system became more prominent. In 1974 these complaints and symptoms were
established as part of the diagnostic criteria for Yusho 11611. These
additional Bymptoms were not related to the PCB concentrations in the blood
[174].
Elevated serum triglyceride concentrations were found to be related
to the concentration of PCBs in the blood serum [175], and inversely
related to the bilirubin concentrations in the serum [179]. The average
serum triglyceride concentrations measured annually in 14 Yusho males from
1969 through 1974 ranged from 159 mg/100 ml in 1969, to 174 mg/100 ml in
1972, to 160 mg/100 ml in 1974 without any significant changes from year to
year. In 29 Yusho females, the concentrations initially (1964) averaged
153-161 mg/100 ml, but decreased in 1973 and 1974 to 129 and 111 mg/100 ml,
respectively [180].
The Yusho population of about 1,300 persons has been followed closely
and records indicate that as of May 1975, 29 of them had died [162],
Deaths have been due to a variety of causes such as accidents, suicides,
cardiac problems, and cancers. Malignant neoplasms were found in at ]east
nine cases [161], from which Kuratsune et al [160] concluded that there was
a suggestion of excess deaths but that no more could be said because
information essential for analysis was not available.
The relevance of the Yusho episode to occupational PCB exposure is
compromised because: (1) the oil was ingested; and (2) it contained large
48
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concentrations of dibenzofurans compared with those in the PCBs to which
workers generally have been exposed in their occupations. Its relevance is
further compromised because the effects observed from daily ingestion of 1-
15 mg of PCBs [165,167] were peculiar and excessive compared to those
observed in workers exposed by inhalation to PCBs at 1-5 mg/cu m [120,125],
notwithstanding that the amounts absorbed may have been similar.
Nevertheless, information obtained from the Yusho episode is relevant
to the study of PCB toxicology and occupational exposure. The information
establishes that PCBs can be transmitted from mother to fetus, and, in the
milk, from mother to child. It also establishes that some PCB compounds
are eliminated from the body relatively rapidly, and that others may
require years for elimination.
(c) Occupational Exposures
Chloracne was among the earliest reported effects associated with
worker exposure to PCBs [125-128]. It was not clear in some early reports
that PCBs were contributing to the chloracne because PCBs usually
constituted 10-20% of mixtures containing 80-90% chloronaphthalenes, a
previously known cause of chloracne [121,122], An early report that
associated chloracne with PCBs in the absence of chloronaphthalenes was
that of Jone9 and Alden [120] in 1936. The manufacturing process was
largely an open one and the workers were also exposed to benzene, biphenyl,
and other compounds incidental to PCB manufacture. Over the years, cases
of chloracne associated with occupational exposure to PCBs have continued
to appear [186-196],
Other effects associated with PCBs in early reports included
digestive disturbances, eye irritation, liver injury, and impotence
49
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[123,125]. Elkins [130] reported in 1950 that the average concentrations
of PCBs in the workroom air of several plants in Massachusetts ranged from
0.1 to 5.8 mg/cu m. Maximum concentrations ranged from 0.2 to 10.5 mg/cu
m. No evidence of immediate toxic effects was observed except at PCB
concentrations approaching 10 mg/cu m, which the workers found to be
unbearably irritating.
Three cases of severe chloracne were described by Puccinelli [186] in
1954. The affected employees worked in a factory that produced capacitors
impregnated with Aroclor 1254. The workroom was 24 x 9 x 5 meters.
Capacitors were heated to about 100 C in a 3-cu m autoclave to remove
moisture, and then impregnated with the Aroclor while in the autoclave.
The temperature in the autoclave was reduced about 12 hours later. When
the autoclave was opened, the temperature of the Aroclor was 70-80 C. The
capacitors were removed and carried to another location for finishing.
Originally, one autoclave was used, but eventually eight were in operation,
and PCB emissions to the workroom air occurred almost continuously.
Concentrations of PCBs in 500-liter samples of air were found to vary from
5.2 mg/cu m in the center of the room, to 6.4 mg/cu m around the finishing
operation, to 6.8 mg/cu m near the autoclave during removal of the
capacitors. The three chloracne cases were in men, 18-24 years of age.
They had worked in the factory for 2-4 years, and developed the first signs
of chloracne 4-8 months after their exposures began. Other than chloracne,
the men appeared healthy, and all findings, including liver function tests
were reported as normal.
Eight other cases of chloracne associated with PCB exposure during
the manufacture of radio capacitors were described by Hofmann and Meneghini
50
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[187] in 1962. In the process, PCB vapors were generated by heat. The
cases included one man and seven women, 20-37 years of age, who were
exposed to PCBs 2.5-4 months before onset of signs of chloracne. The face
was involved in six cases; other Involved areas varied, but Included the
arms, neck, upper torso, pubes, buttocks, and thighs. The case of a 21-
year-old woman was described in detail. The first signs of chloracne
appeared on her face 4 months after she began work, and she was observed by
the authors [187] 4 months later. On the face, a dirty brown coloring
appeared. A hyperplgmented spot with shaded areas was present on the
forehead. Subsequently, her buttocks and pubes became involved. Exposure
concentrations were not mentioned.
Severe chloracne was described by Birmingham [188] in 1964 in 13 of
15 workers exposed to an Aroclor which was a mixture of bl- and terphenyls
(65% chlorine content). An enamel containing the Aroclor was painted onto
glass and then baked In an oven. Faulty ventilation caused contamination
by chlorinated hydrocarbon vapors. Exposure concentrations and duration of
exposure were not given.
An additional case history published in 1969 involved a 43-year-old
man exposed to PCBs in an electrical component factory [189]. He developed
chloracne on the forehead, face, arms, and thighs within 3 months after
beginning work handling racks of electrical parts that had been dipped in
hot PCBs. Exposure concentrations and actual durations of exposure were
not stated, but it was reported that the man had put his hands in the
mixture without skin protection for a long time, and that his clothes often
became impregnated with the PCBs. On examination 8 months after transfer
to another Job in the same room, papules, comedones, and pustules were
51
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found on his forehead, scalp, face, and arms. Although the man had been
removed from direct exposure to PCBs, their odor was present in the man's
new work area. It was reported that this was the first case of chloracne
in the plant, where more than 100 workers had been engaged in the process
for more than 20 years.
A company that used PCBs at two manufacturing facilities provided
testimony on employee health in 1975 (In the Matter of General Electric
Company, File No. 2833, New York State Department of Environmental
Conservation). Examination of records submitted as testimony indicated
that exposures were to an askarel [25] containing, by weight, about 60% of
Aroclor 1254, 40% trichlorobenzene, and 0.0115-0.135% diepoxide scavengers.
From the records submitted, it was not possible to determine the precise
numbers of male and female workers. The exact occupations of the workers
could not be determined either but a substantial number of "crimpers" was
indicated.
The records showed that employees had reported to the dispensary
complaining of skin rashes and dermatitis on 49 occasions during the
previous 15 years. Only the fingers and hands were involved in 21
complaints, only the arms and hands in 5, and only the face and legs in 1.
In 7 other complaints the face, neck, and legs were mentioned in 4, 2, and
1 cases, respectively, in addition to the upper extremities. Associated
with the complaints of skin rashes and dermatitis were some complaints of
itching of the face (2), neck (1), eyes (1), arms (2), and hands (1). A
generalized skin rash was the basis of 14 additional complaints. One
worker developed the generalized rash on exposed parts of his body after
only 2 days of working with the askarel.
-------
The company physicians attributed the rashes to allergic or contact
dermatitis caused by exposure to the askarel. Treatment Included the use
of creams, and temporary or permanent removal from exposure. Of the 49
complaints, 22 were second episodes, and In these cases the workers were
removed permanently from exposure to askarels. One female employee who had
dermatitis of the fingers was removed from exposure for 12 days. Within 2
days of reexposure she again reacted to the askarel and was permanently
removed from such work.
Over% the same IS years, other kinds of complaints were made by the
workers on 16 occasions. These complaints Included burning sensations of
the eyes (7), nose (1), and face (1); dry throat (1); asthmatic bronchitis
(3); nausea (1); dizziness (1); and aggravation of acne (1). In most of
these cases, the company physicians recommended permanent removal from
exposure.
The health status of eight laboratory workers who routinely analyzed
dielectric fluids containing PCBs was reported by Levy et al [197] in 1977.
The men were 25-49 years of age and had been employed 2.5-18 years.
Breathing zone, point source, and general work area air samples were
collected on magnesium silicate at 50 ml/minute over the workday on three
occasions. The breathing zone samples contained PCBs at 0.014-0.073 mg/cu
m. Samples taken near an oven contained 0.042-0.264 mg/cu m, and general
room area samples contained PCBs at 0.013-0.15 mg/cu m. The blood PCB
concentrations in the workers were 36-286 ppb. The most common complaint
of the workers (6 of 8) was dry or sore throat. Other complaints were skin
rash (3 of 8), gastrointestinal disturbances (3 of 8), eye irritation and
headache (each, 2 of 8). Findings on examination of the eight workers were
53
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skin rash (1), nasal irritation (2), rales (1), and elevated blood pressure
(4). No liver, spleen or neurologic abnormalities were found by physical
examination. There were no cases of chloracne. Serum alkaline
phosphatase, SGOT, SGPT, and total bilirubin, measured in seven subjects,
were all within normal limits. In addition, medical records of 40 other
exposed employees were examined, revealing two cases of slightly increased
SGOT, two elevated serum triglycerides, and one case each of increased
serum alkaline phosphatase (SAP) activity, total serum bilirubin, and serum
uric acid.
Epidemiologic Studies
An outbreak of dermatitis among workers in a Connnecticut chemical
plant was described in 1954 by Meigs et al [190], PCBs had been
substituted for molten salt in a heat exchange unit without modification of
the system. There were slight, but obvious, vapor leaks under certain
conditions, and the concentration of PCBs in the workers' breathing zones
was determined to be 0.1 mg/cu m. No employee worked regularly at points
of leakage, and the operations, as described, continued for 19 months.
Mild to moderate chloracne on the face, forehead, and ears developed
in 7 of 14 exposed workers; the mastoid region of one worker also was
affected. The duration of exposure before the initial signs occurred
ranged upward from 5 months and averaged 14 months. The average length of
exposure was 11 months for those who did not develop chloracne, with one
worker showing no signs after 19 months. Liver function tests were
performed on the seven workers who had developed chloracne. Clinical tests
included direct and total serum bilirubins, 24- and 48-hour cephalin
54
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flocculations, thymol turbidity, and SAP activity. Findings were normal in
six workers, and borderline increases in cephalin flocculation and thymol
turbidity were found in the seventh worker with chloracne. Thirteen months
later, the thymol turbidity test had improved, but cephalin flocculation
had not changed. All cases of chloracne were stated to have cleared up
after an unspecified treatment. Control of vapor emissions by welding all
Joints in the heat exchange unit prevented recurrence [190],
Exposures of workers to PCBs In six industrial plants were discussed
by Hasegawa et al [19f] in 1972. The concentrations of PCBs found are
summarized in Table III-7.
TABLE II1-7
RANGE OF PCB CONCENTRATIONS (jig/cu m) IN WORKROOM AIR
Factory
Function
No.
PCB
Concentrations
Samples
Vapors
Particulates
A
PCB manufacture
6
26-163
19-37
B
Capacitor manufacture
3
120-350
20-125
C
Biphenyl recovery
2
13-15
4*
D
Capacitor manufacture
2
350-540
U8-6,270**
E
ft
3
95-965
73-650
*1 sample
**6,270 due to spillage
Adapted from reference 191
55
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PCBs were manufactured in one plant and u9ed in manufacturing
capacitors in four plants (one had discontinued use of PCBs 1 month
earlier). Biphenyl, not chlorobiphenyls, was present in the sixth plant
[191]. Air samples were collected in two fractions. A fraction associated
with particles >0.1/i was collected on filter paper, and a fraction
containing vapors and particles <0.lu in diameter was collected in two
serially-connected midget impingers containing n-hexane. Samples were
collected only from places where high concentrations of PCBs were expected
and not from the factory where PCB use had been discontinued.
The vapor concentration exceeded the particulate concentration in all
except the sample taken after spillage. Particulate matter was
characterized by GLC as containing the same chlorobiphenyl composition as
the PCB product used in the plant, whereas the vaporized material contained
one less chlorine atom/molecule than the PCB used in the plant.
PCBs were measured in the blood of the employees of six plants,
including 99 exposed workers and 32 controls [191], Concentrations of PCBs
in the blood sera of exposed workers averaged 370 ppb, whereas those of the
controls averaged 20 ppb. The workers exposed to PCBs in the plant that
had discontinued PCB use had 9erum PCB concentrations of 90 to 730 ppb
(average 460 ppb). Based on data from three of the plants, no relationship
was found between duration of exposure (from <1 to 20 years) and
concentration of PCBs in the blood [191],
Complaints of dermal ailments seemed to be unrelated to the blood PCB
concentrations and were considered to be due more to direct contact of the
skin with PCBs than to generalized intoxication. The principal dermal
findings included brown chromodermatosis of the dorsal joints of the hands
-------
and fingers and of Che nail bed, and acnelform exanthema. The latter also
Involved the jaw, back, and theighs In several cases. The investigators
[191] considered that there was a definite effect of PCBs on fat
metabolism, as shown by decreases In the concentrations of total, free, and
esterlfied cholesterols In the blood, and by trends In the same direction
for neutral fats, total glycerldes, phospholipids, and beta-llpoproteln In
the blood. There was evidence of mild disturbances of liver function
manifested by Increased SCOT, SGPT, and SAP activities and decreased
activity of serum chollnesterase. These enzyme activity changes were not
considered to be clinically significant.
Studies of 38 current and 80 former employees of a capacitor factory
in which Kanechlor 500 had been used from 1954 to about 1960 and Kanechlor
300 had been used from about 1960 to 1972, with PCB use having been
discontinued in April 1972, were reported by Hara et al in 1973 [192] and
again in 1974 [193]. (Presumably, this factory was the one stated by
Hasegawa et al [191] to have discontinued use of PCBs.) Current workers
included 17 who were engaged In the capacitor immersion process; the
remaining 21 workers were engaged in finishing and assembling operations.
The study concentrated on the 17 Immersion process workers. During
exposure to PCBs in March 1972, the concentrations of PCBs in the whole
blood of the immersion workers ranged from about 7 to 300 ppb, and were
closely related to years of exposure. One year later, blood PCB
concentrations had all decreased, but by varying amounts. For example, one
of two workers who initially had PCB concentrations in their blood of about
180 ppb had a concentration of <10 ppb 1 year later, while the other one
had a concentration >100 ppb. The average PCB blood concentration for the
57
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17 workers decreased to about 75% of the original value. Based on blood
samples collected about 6 and 12 months after use of PCBs was discontinued,
the blood PCB half-lives for the immersion workers were calculated. It was
found that the greater the duration of exposure, the greater the PCB half-
life (1 year of exposure, 3 months half-life; 10-15 years of exposure, 30
months half-life). This indicated to the investigators that blood served
as a PCB carrier, whereas fat served as a depot tissue [192],
While working with PCBs, many of the total group of employees had
dermal complaints (blackheads, 45%; acneiform eruptions, 37%; skin
irritations, 13%) [192], A year after discontinuance of exposure to PCBs,
these conditions had improved noticeably and only one or two blackheads
remained. No correlation was apparent when concentrations of PCBs and
triglycerides in the sera of a large number of workers were compared
graphically. The workers were also studied about 18, 24, and 36 months
after use of PCBs had been discontinued [193], During this period, blood
PCB concentrations decreased to about 10-20 ppb in all but two workers who
had been exposed to PCBs for 9 and 15 years. The skin disturbances were
reduced to vestigial markings on a few individuals. Comparisons with the
concentrations of triglycerides and PCBs in the sera of these workers
indicated that the proportion of workers with significant increases in
triglyceride concentrations increased as the concentrations of PCBs
increased. Of nine workers with blood PCB concentrations >50 ppb, five had
elevated triglyceride concentrations.
Examinations of 13 workers from an electrical capacitor manufacturing
plant for clinical manifestations of PCB toxicity were reported by Kitamura
et al [194] in 1973. Examinations were performed when the company
58
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discontinued the uae of PCBa in June 1972, and were performed twice
subsequently at 3-month intervala. The average length of worker exposure
to PCBs had been about 2.5 years. Iimnediately after discontinuance of PCB
use, the average PCB concentration in the blood of workers was 820 ppb,
ranging from 320 to 2,100 ppb [194]. The mean concentration fell to 310
ppb after 3 months, and to 200 ppb after 6 months. From these
observations, Kitamura et al [194] estimated the biological half-life of
the PCBs In the blood immediately following the cessation of exposure to be
about 90 days. No ^consistent correlation could be found between the
concentration of PCBs in the blood and the duration of exposure to PCBs.
Nail, hair, and gum color and color of the mucous membranes of the oral
cavity all were normal. Ten of the workers had varying degrees of skin
disorders on different parts of their bodies. The skin disorders included
seborrhea adlposa, acne vulgaris, and follicular papules on parts of the
body where direct contact with the PCBs normally did not occur. The
authors [194] concluded that PCBs probably had been an important factor In
the etiology of the skin disorders and that results of blood tests, hepatic
function tests, and urinalyses were normal. Serum triglycerides were not
determined.
A study by Inoue et al [195] of the health of workers in family-owned
silk-thread glossing factories In which PCBs were used was published in
1975. The study was initiated because PCB concentrations exceeding 100 ppb
had been found in the blood of a 73-year-old man who had undergone surgery.
His family ^operated a household thread-glossing factory. The family
members and the hired helper were studied. Serum concentrations of PCBs
resembling Kanechlor 500 ranged from 130 to 520 ppb. There was a close
-------
correlation between the PCB concentration in the blood and the degree of
involvement in the glossing work. The head of the household had skin
lesions and comedones on the face, back, and ears and had blood PCB
concentrations of 190-210 ppb. The rest of the people had practically no
skin abnormalities, and other findings (not described) were, in general,
considered of minor significance. A study of PCB contamination of the
premises and the air of the same factory was reported by Fujiwara et al
[33]. At the time the samples were taken, use of PCBs had been
discontinued. However, PCBs were found in air at 0.25 mg/cu m, in floor
boards at 80-130 ppm, in the dirt under the machinery at 10-900 ppm, and in
Che dust on steel frame beams at 110-180 ppm. The PCBs were similar to
those In Kanechlor 500.
Subsequent to the above study, Inoue et al [195] reported on the PCB
concentrations in samples of blood obtained from 54 other similarly
employed people. PCB concentrations of over 100 ppb, 50-99 ppb, 10-50 ppb,
and 0-9 ppb were found in 2, 5, 19, and 28 persons, respectively.
Correlative comparisons with the various functions performed in the
factories showed that those workers who had direct contact with the
glossing machines, those who maintained and repaired the machines, and
those who had over 20 years of work experience had the highest
concentrations of PCBs in their blood. Skin abnormalities and other
findings in these 54 persons were described as relatively mild. One of the
persons studied, a woman in her 10th month of pregnancy, had a serum PCB
concentration of 24 ppb. Following birth, the mother and daughter were
described as healthy with no evidence of abnormalities. The concentration
of PCBs in the mothers's milk was found to be 0.25 ppm, and after
60
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consultation, she stopped nursing her baby [195].
In 1974, Sato and Hasegawa [32] discussed their findings on PCB
residues in the workers and In the air of pressure-sensitive ("carbonless")
copying paper manufacturing plants 2 years after PCB use had been
discontinued. A PCB product comparable to Kanechlor 300 was still detected
in the workroom air of four of five factories at concentrations ranging
from 0.13 to 4.4 iig/cu m; in one factory PCBs comparable to a mixture of
Kanechlors 300, 400, and 500 were found at concentrations ranging from 0.15
to 1.2 /ig/cu m. Concentrations of PCBs in the blood sera of these workers,
as measured by GLC, ranged up to 73 ppb, compared to a maximum of about 20
ppb in controls. The authors [32] concluded that the blood PCB
concentrations in the workers war* still elevated.
PCB concentrations in the blood of three groups of employees with
different PCB exposure histories were presented in 1972 by Karppanen and
Kolho [198]. The first group of four men and five women had no known
occupational exposure to PCBs. The six women of the second group had been
exposed while handling PCBs in an analytical laboratory. The third group
of eight men and four women had worked, since 1968, in a plant where
Aroclor 1242 was impregnated into capacitors. The authors [198] stated
that the workroom air of the capacitor factory met internationally accepted
limits (presumably <1 mg/cu m), and that protection of the skin had been
given special attention. PCB measurements were made by GLC, using electron
capture detection. The unexposed group had blood PCB concentrations of
5.6-12 ppb, the analytical laboratory workers had concentrations of 36-63
ppb, and the capacitor plant workers had concentrations of 74-1,900 ppb.
Subcutaneous adipose tissue samples from two of the unexposed workers
61
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contained PCBs at 1.5 and 2.3 ppm; PCBa in their blood expressed as
concentrations in fat of the blood were 6.6 and 9.9 ppm, respectively. In
three capacitor plant workers, adipose tissue samples contained PCBs at
160, 285, and 635 ppm; PCBs in their blood, expressed as concentrations in
their blood fat, were 400, 305, and 700 ppm, respectively. All persons
examined were in good health. The capacitor plant workers had been under
special medical observation but the investigators were unable to detect any
biologic effect from the PCBs.
An epidemiologic investigation of 37 refuse workers who were
potentially exposed to PCBs emitted from incinerated waste was described by
Bumgarner et al [1991 in 1973. The control group consisted of 36 workers
from a lumber yard. Paired samples of scalp hair and blood were collected.
PCB residues in the hair and blood plasma were extracted and analyzed by
GLC with electron capture (EC) detection; rough quantitation was by
evaluation of five peaks associated with Aroclors 1254 and 1260. The lower
limit of detection was 1 ppb. Hematocrit, blood cholesterol, and blood
pressure also were determined. PCB residues in the blood plasmas of the
controls were detected in four workers and the maximum concentration was
4.2 ppb. Measurable concentrations of PCBs were found in the blood samples
of 32 of the 37 refuse workers; the average and maximum concentrations were
about 4 and 14 ppb, respectively. The concentrations of PCBs in plasma
were not related to duration of exposure, age, or race. PCBs were not
detected in hair samples (limit of detection, 1 ppb). Hematocrit, blood
cholesterol, and blood pressure values did not change at different PCB
concentrations.
62
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A survey of the health of 34 workers exposed to Aroclor 1242 during
manufacture of capacitors was discussed by Ouv et al [196] in 1976. The
Aroclor was an electrical-grade material that contained "no impurities."
»
Breathing zone samples were collected In lmplngers containing isopropanol.
It is not clear if all samples were collected from the breathing zones.
Nineteen workers were assigned to fill capacitors with Aroclor 1242 heated
to 70 C. These workers were exposed to FCBs at 1.08-1.44 mg/cu m. The
other 15 workers, located in a different room, were assigned to assemble
Aroclor-dipped capacitor components. These workers were exposed to PCBs at
0.32 mg/cu m. None of the 34 workers used protective clothing.
PCBs In the blood were separated by GLC and identified by their
retention times relative to aldrln. PCBs were not detected in the blood of
30 control subjects. For the two groups of PCB-exposed workers, averages
of measurable blood PCB concentrations are presented in Table III-8.
TABLE TII-8
AVERAGE OF DETECTABLE BLOOD PCB CONCENTRATIONS (ppb)
OF TWO GROUPS OF WORKERS
PCB
Retention Time
Relative to Aldrin
Exposure
No.
Group
Workers
0.69
1.31
1.47
1.96
Fillers
19
602(19)*
314(17)
391(13)
475(4>
Assemblers
15
140(14)
100(14)
899(5)
(0)
~Numbers In parentheses are the numbers of workers In whom more than a
trace of the PCB peak was detected.
Adapted from reference 196
63
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Distribution of PCBs in the blood of workers exposed while filling
the capacitors differed from that of workers who assembled the components.
The higher boiling components were present more frequently and to a greater
extent in the fillers.
Twelve of the workers (5 of 19, and 7 of 15) complained of mild
burning and irritation of the face, eyes, and skin, and 5 of these had
eczematous rashes on the hands and legs. One filler had chloracne.
Although individual abnormalities were found in SGPT, SAP, and bilirubin,
the average values for the exposed workers were within normal limits.
Bromsulphothalein retention tests were found to be elevated in four of the
seven fillers whose blood PCB concentrations were >500 ppb. The
investigators [196] reported no evidence of significant adverse responses
to PCB exposure in the workers with blood PCB concentrations below 200 ppb.
Subsequently, "more efficient" exhaust ventilation was installed and
the workers were advised to wear "suitable impervious gloves" [196]. Air
measurements, made after the ventilation change, indicated that the fillers
were being exposed to PCBs at 0.18-0.75 mg/cu ra and the assemblers at 0.08
mg/cu m. These were substantial reductions. However, blood PCB
concentrations that were found in 15 workers reexamined 2 months after the
ventilation change did not show any substantial reductions. The
investigators [196] speculated that this might have been because the
workers did not strictly follow the recommendation to wear protective
clothing.
Based on a search of chart records, Bahn (HA Sinclaire, written
communication, June 1976) reported a preliminary study of the incidence of
cancer in a group of 51 research and development employees and 41 refinery
64
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plant employees at a New Jersey petrochemical facility who were considered
likely to have been exposed to Aroclor 1254 for various periods between
1949 and 1957. The eight cancers observed in the study population through
December 31, 1975 were not significantly more than would be expected (5.7)
in a similar sample of the US population [200]. However of the eight
cancers, the three melanomas and the two cancers of the pancreas were
significantly different from calculated expectations. Some findings of
this preliminary investigation were described in a letter from Bahn et al
[201] to the editor of the New England Journal of Medicine.
In this preliminary study, PCB exposure histories were based on
recollections of two company employees. Exposures to other chemicals could
not be ascertained. The expected cancer rates were based on US population
data rather than on a rate for the locality of the petrochemical facility.
To correct these deficiencies in the preliminary study, a more intensive
investigation is being conducted (BN Kightlinger, written communication,
November 1976). A substantial change has occurred in the cohort since
release of the preliminary report by Bahn and her coworkers, and it seems
likely that the findings on this new cohort will differ significantly from
those of the preliminary study. The final report is not yet available.
In a study of current and former employees engaged in the manufacture
of PCBs, no cases of malignant melanoma or pancreatic cancer were found
from a review of the case histories of more than 300 employees (G Roush,
written communication, September 1976). Seven cases of lung cancer were
found from the death certificates of 50 former employees compared to an
expected number of 2.7. The data are preliminary and were not corrected
for age or smoking habits. The final report is not yet available.
65
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Animal Toxicity
Although there have been a few reports of dermal and inhalation
experiments with animals, most of the information on animal toxicity has
involved ingestion of PCBs in the diet or by intubation. Several animal
experiments have involved oral administration of PCBs for the lifetime of
the animal. These studies have demonstrated chronic changes in the
microscopic anatomy of the liver and other organs, effects on reproduction,
embryonic and fetal toxicity, effects on offspring from nursing, and
carcinogenic and teratogenic responses.
(a) Inhalation and Dermal Application Studies of PCB Mixtures
Absorption and distribution of inhaled PCBs were studied by Benthe et
al [97] in 1972. Groups of 4-6 male Wistar rats were exposed to aerosols
of a commercial PCB mixture containing 42% chlorine, Pydraul A 200,
commonly used in hydraulic fluids. Absorption and distribution of the PCBs
were studied through the measurement of PCB concentrations in liver, brain,
and adipose tissue. The aerosolB were produced in an aerosol generator at
180 C. The aerosols were cooled, the larger particles were separated out,
and the airborne PCBs were introduced into a chamber at a concentration of
30.4 ± 3.4 g/cu m. Groups of the rats were exposed for varying periods up
to 2 hours. It was found that 15 minutes of exposure was sufficient to
attain more than 50% of the PCB concentration of 69.7 Mg/g liver wet weight
that could be attained with 2 hours of exposure. Consequently, the
investigators used an exposure time of 30 minutes to study distribution of
PCBs to the tissues.
Immediately after 30 minutes of exposure, PCB concentrations were
maximal, at about 52 pg/g liver tissue, whereas they were at low
66
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concentrations in the other tiBSuea at 14 yg/g in adipose tissue, and 9
jjg/g in brain tissue. After 24 hours the PCB level in the brain attained a
maximum value of about 18 ;ig/g and within 36 hours the PCB concentration in
the adipose tissue attained a maximum of about 250 jig/g. By 48 hours the
concentrations of PCBa in the liver were reduced to about 3 Mg/g and in the
brain to about 5 ng/g, whereas the adipose tissue concentrations remained
above 200 jtg/g.
Experiments were reported by Rozanova [202] in 1943 In which rats
were exposed to a technical mixture of "tetrachlorodiphenyl" and
"pentachlorodiphenyl." The mixture, known as Solvol, was a transparent,
colorless, oily, very viscous liquid used for filling capacitors. The
"tetrachlorodiphenyl" component of the mixture had a distillation range of
220 to 245 C and the "pentachlorodiphenyl" component had a distillation
range of 242 to 260 C. The animals were exposed in a 22-liter chamber
through which air was drawn continually at a rate of 1-1.5 liters/minute,
after first passing through a glass gooseneck containing the liquid PCBs.
Air samples were taken from the chamber from time to time to determine the
PCB concentrations. The analytical method was not reported.
Four rats exposed for 3 hours at about 10 mg/liter became
uncoordinated and comatose and died within a day [202]. Autopsy findings
included liver necrosis and fatty degeneration, cloudy swelling of the
epithelial cells of the renal tubules, congestion in the heart and spleen,
and necrotic signs in the spleen. Three rats were exposed repeatedly to
vapors of Solvol at 0.5 mg/liter. One rat died after eight exposures, and
the other two were killed after 11 exposures. Five other rats were
repeatedly exposed at 0.25 mg/liter; one was killed after 16 exposures, and
-------
the others, which appeared to be in satisfactory condition, were killed
after 69 exposures. In these chronically exposed rats, gross and
microscopic findings were similar to, but less marked than, those found in
the acutely exposed animals. In addition, hyperplasia of the Kupffer cells
was found in the liver.
Treon et al [203] exposed groups of animals each comprised of 10
rats, 10 mice, 6 guinea pigs, 4 rabbits, and a cat to Aroclor 1242 or
Aroclor 1254 vapors 7 hours/day, 5 days/week for up to 31 week9. Aroclor
1242 exposures at concentrations of 8.6 jug/liter (0.83 ppm) for 3 weeks,
6.83 /jg/liter (0.66 ppm) for 17 weeks, or 1.9 ^g/liter (0.18 ppm) for 31
weeks. Exposures to Aroclor 1254 were at 1.5 Aig/liter (0.11 ppm) for 31
weeks or at 5.40 yg/liter (0.41 ppm) for 17 weeks. No consistent changes
in mortality, growth, pathology, organ size, liver function, or hematologic
parameters were found in animals exposed to Aroclor 1242, The animals
exposed to Aroclor 1254 vapors showed no changes in growth or mortality but
microscopic evidence of apparently reversible hepatic cellular injury was
found in all species except the cat at both exposure levels. Enlarged
livers were found in the animals exposed at 5.40 ^g/liter. An appreciable
incidence of pneumonia was found among the exposed and control animals, a
fact which could have confounded some of the results, but it is important
to note that liver changes, including fatty degeneration, were found in
exposed animals that were free of pneumonia.
Inhalation experiments with the commercial PCB product
"Decachlorodiphenyl" were reported by Berczy et al [98,99] in 1974, The
oral toxicity of this PCB product was investigated by Hunter et al [204],
who administered it in the diet to Sprague-Dawley rats at 1,000, 2,000,
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5,000, and 10,000 ppm for 4 weeks. All animals fed Decachlorodlphenyl
gained more weight than the controls and had greater liver to body weight
ratios. Other effects observed at 10,000 ppm Included increased spleen,
thyroid, and kidney weights relative to body weights, reduced hemoglobin
concentrations, and in males reduced rbc counts and hematocrits.
In one inhalation experiment [98], five male and five female rats
were exposed for 6 hours to particles of the PCB product at an average
concentration of 2.54 mg/liter. Seventy-eight percent of the particles
were in the range of 1-5 jon in diameter, 17% In the range of 5-15 jim, and
the remaining 5% were >15 ^m. During exposure there were repeated episodes
of blinking and sneezing. Signs of irritation disappeared after cessation
of exposure. During the subsequent 14-day observation period, food and
water consumption and growth of the rats were considered by the authors to
have been similar to those of the controls. No gross pathological changes
were seen when the rats were killed 14 days after removal from exposure
[98].
Subsequently [99], three groups of rats, each consisting of 8 males
and 8 females, were exposed 6 hours/day, 5 days/week for 4 weeks at average
concentrations of 4, 80, and 777 ^g/liter. A similar group of rats was
used as a control. In this experiment, where 85-90% of the particles were
in the 1-5 ^m range and 1-3% were >15 jan, no signs of irritation were seen
during the exposures at the lower concentrations and growth rates were
normal compared to controls. At the highest concentrations, frequent
blinking and sneezing were noted during the exposures, and the growth rate
of the males was slightly retarded (final body weights of 395 g vs 435 g
for controls). The liver weights, relative to body weight, were increased
69
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in males exposed at the highest concentration, and in females exposed at
the medium and high concentrations. Microscopic findings in the livers of
the rats exposed at the high concentration included occasional focal
aggregations of mononuclear cells with either parenchymal or periportal
distribution, and minimal degrees of periportal hepatocytic vacuolation,
and decreased centrilobular or periportal glycogen. These findings were
not considered by the authors [99] to be of toxicologic significance. A
statistically significant decrease in packed cell and mean cell volumes was
found in male rats exposed at the high concentration. In this group there
was also a low white cell count due to a decrease in the number of
lymphocytes, and increased thrombocyte activity. Blood glucose, SGOT, and
serum sodium concentrations were decreased.
Von Wedel et al [205] described in 1942 the results of an experiment
performed to determine the systemic effects of exposure of mice, guinea
pigs, and rabbits, by inhalation, ingestion, and dermal application to an
unspecified Aroclor. Concentrations and durations of exposure were not
specified for the inhalation and ingestion experiments. However, 0.5, 1.0,
or 1.5 ml of solutions containing 0.5 g Aroclor/ml were used for the dermal
applications. Within 5 days after the dermal applications, small papules
and blisters formed on the exposed skin areas and the external epidermal
layers became desquamated. In addition, subacute yellow atrophy of the
liver with some fatty infiltration was observed. Similar liver lesions
were produced in the inhalation experiment.
In 1944, Miller [206] administered Aroclor 1242 to rats, rabbits, and
guinea pigs by subcutaneous (sc) injection, by oral intubation, and by
dermal and corneal application. The PCB doses ranged from single doses of
70
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69 mg to small drops (approximately 17 mg) applied daily to the cornea of
rata for 25 days, to 1,380 mg injected daily into rabbits for 10 days.
Fatty degeneration and atrophy of the centrilobular cells of the liver were
the characteristic signs of toxicity. The greatest amounts of liver damage
were seen in guinea pigs, less was seen in rabbits, and the least amount in
rats, regardless of the dose, duration of exposure, or route of
administration. Necrotic lesions were also seen in the skin of animals
that received sc injections; signs of dermal irritation were seen after
applications to the skin. The conjunctival tissue presented no gross
changes when examined under magnification in the living animals. Since the
pathologic changes in Internal organs were similar regardless of method of
administration, this experiment indirectly demonstrated that PCBs could be
absorbed through the skin and the eye.
The effects of Solvol applied to the ears of rabbits were reported by
Parlbok [207] in 1954. Solvol was applied for 6 hours dally In doses of
0.7 to 3.76 g. A single application caused edema and inflammation of the
ear, and one rabbit died 7 days after the application. With multiple
doses, the animals died after 6-17 days. The dead animals, Including the
one that died after the single application, had fatty degeneration of the
livers.
Vos and Beems [208] reported in 1971 on the dermal toxicity of PCBs
in adult female New Zealand rabbits. Three commercial preparations of PCBs
were used: Clophen A60, Phenoclor DP6, and Aroclor 1260, Twenty-seven 1-ml
(118 mg) applications of each of these products (in lsopropanol), 5
times/week over 38 days, to the clipped and shaved backs of the rabbits
resulted in various manifestations of toxicity.
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In general, the toxic signs were most pronounced in the Clophen-
treated animals and least pronounced with Aroclor 1260. Dermal findings
included thickening of the skin due to hyperplasia and hyperkeratosis of
the epidermal epithelium, and dilation and plugging of hair follicles with
keratinous material. Microscopic study of liver sections showed a
considerable diversity of lesions, including centrilobular degeneration,
focal hydropic degeneration, focal necrosis, atrophy of centrilobular
parenchymal cells, cytoplasmic hyaline degeneration, pigmentation of
Kupffer cells, and, to a lesser extent, pigmentation of parenchymal cells.
Renal damage was found in all PCB-treated animals. The most common
findings were hydropic degeneration of the convoluted tubules, with nuclear
pyknosis, and bursting and lysis of the tubular epithelial cells [208],
Dilation of the renal tubules, filled with casts of necrotic epithelial
cells, was found in half the rabbits. These findings indicate that the
dermal application of PCB mixtures causes systemic lesions of the liver and
kidneys besides the direct effect on the skin. However, in other studies
[19,21,23], it was determined that Clophen A60, Phenoclor DP6, and Aroclors
1248 and 1254 were contaminated, to varying degrees 121], with highly toxic
tetra- and pentachlorodibenzofurans.
(b) General Effects of Oral Administration of PCB Mixtures
Single-dose oral LD50's of several PCBs reported in rats (JW Cook,
written communication, June 1970) generally indicated that as the degree of
chlorination increased, the acute toxicity decreased. The more highly
chlorinated products (Aroclors 1248-1268) were of approximately equal
toxicity (LDSO's of about 10 g/kg), whereas the LD50's of the less highly
chlorinated products (Aroclors 1221-1242) ranged from about 4 to 9 g/kg.
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The minimum lethal doses of these PCBs applied to the skin of rabbits were
generally in the range of 1-2 g except for 1221 which was in the range of
2-3 g and 1266 which was >2.5 g.
The immunosuppressive activity of Aroclor 1260 was described in 1972
by Vos and de RoiJ [209] who fed three groups of 12 6-week-old female
albino guinea pigs the FCB at 0, 10, or 50 pptn in their diets for 8 weeks.
Aroclor 1260 was analyzed and found to be free of contamination with
chlorinated dlbenzofurans, although it appeared to contain a minor
acnegenic impurity. In each group, six animals received sc Injections of
aluminum phosphate-adsorbed tetanus toxoid to stimulate the lymphoid system
(antitoxin production). The other six animals in each group served as
positive or negative controls. Cellulose acetate electrophoresis was used
to determine serum proteins, Including gamma-globulins. The gamma-
globulln-containlng cells in the popliteal lymph nodes were significantly
reduced in the stimulated animals fed PCBs. Serum gamma-globulin levels
were aignlflcantly decreased in the guinea pigs stimulated with tetanus
toxoid and fed 10 ppm of Aroclor 1260 in their diet. Increased serum
alpha-globulin levels were found in the stimulated guinea pigs fed either
10 or 50 ppm of the PCB, and significantly Increased concentrations of
albumin were found in the sera of both the stimulated and the unstimulated
guinea pigs fed the PCB at 10 ppm. Also, both the absolute and relative
weights of the cervical lymph nodes in the unstimulated group fed 10 ppm of
Aroclor 1260 were significantly reduced whereas those of the mesenteric
lymph nodes in the stimulated guinea pigs fed 10 and 50 ppm of PCB were
significantly increased. These findings indicate that some
immunosuppressive effect was produced by the feeding of PCBs. However, the
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decreases of the gamma-globulin levels were not found to be dose-related.
No evidence of any PCB-induced change vas observed in microscopically
examined stained sections of liver, kidneys, adrenals, and skin.
Vos and Van Driel-Grootenhuis [210] reported their studies of the
effects of PCB8 on the humoral and cell-mediated immunities of guinea pigs
in 1972. Three experiments were performed with different protocols. In
the first experiment, the authors investigated the humoral immune response
of guinea pigs fed 0, 10, 50, or 250 ppm of Clophen A60 in their diets and
stimulated with a single sc injection of tetanus toxoid 3 weeks after the
feeding regimen began. Suppression of humoral immunity was observed at the
50-ppm level. Microscopic examination of the liver9 revealed centrilobular
degeneration, cellular atrophy, cellular necrosis, and nuclear enlargement.
At the 250-ppm level, no antitoxin production was observed.
The diets of guinea pigs in a second experiment [210] contained 0,
10, or 50 ppm of Clophen A60 or 50 ppm of Aroclor 1260. Primary and
secondary antigenic stimulations with tetanus toxoid were given after 3 and
5 weeks. The experiment lasted 6 weeks. Suppression of the humoral immune
response was observed in groups fed 50 ppm of either PCB product.
Decreases in the weights of the thymuses and increases in liver weights
were observed at the 50-ppm Clophen A60 level and, to a lesser degree, at
the 50-ppm Aroclor 1260 level. The residual liver concentrations of PCBs
increased as the dose level and the duration of exposure increased.
In their third experiment, Vos and Van Driel-Grootenhuis [210] fed 30
guinea pigs diets containing Clophen A60 at 0, 50, or 250 ppm. After 3
weeks, the animals were challenged with 0.05 ml of Freund's complete
adjuvant followed in 47 days by an injection of 0,1 ml of avian tuberculin
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antigen. The animals were killed 2 days later. All animals of the 250-ppm
group died during the experiment, exhibiting retarded growth, atrophy and
depletion of the lymphoid system, and liver damage. Significantly
decreased thymus weights and increased liver weights also were observed,
and total white blood cell counts were reduced significantly.
Bruckner et al [211] administered Aroclor 1262 to rats by oral
intubation to determine its acute and subacute effects. Two groups of six
rats each were given single doses of either 2.5 or 6.0 g/kg of Aroclor
1242. The Initial effects observed at both dosages were the same for the
first 4 hours, le, diarrhea, decreased spontaneous activity and muscle
tone, decreased response to pain stimuli and mild chromodacryorrhea.
However, during the next 24 hours the group receiving 6.0 g/kg had profuse
diarrhea, adlpsla, oliguria, anorexia, erythema of the limbs, lack of
response to pain stimuli, and general weakness. Eventually, ataxia, coma,
and death followed. The condition of the rats receiving the lower dosage
gradually Improved after the first 24 hours and was normal at the end of 72
hours.
Another group of rats [211] that received single oral doses of 4 g
Aroclor 1242/kg showed weight loss, elevated packed red cell volumes,
Increased serum polymorphonuclear leukocytes, crenated red blood cells, and
Increased SGOT activities. All organs appeared normal except the livers
and kidneys. The livers exhibited foci of sudanophilic vacuolation. The
kidneys showed widely scattered foci of vacuolated tubular epithelial
cells.
In the subacute studies conducted by Bruckner et al [211], six rats
were given 100 mg of Aroclor 1242/kg orally every other day for 3 weeks;
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three control rats received 100 mg/kg of peanut oil on the same schedule.
Changes observed in the treated rats included increased liver weights,
decreased packed red blood cell volumes, increased SGOT activities and
marked increases in liver microsomal hydroxylating and N-demethylating
enzyme activities. Microscopic examinations of the livers and kidneys
revealed greater Increases in generalized lipid vacuoles than had been
found with the acute doses. When single ip doses of 100 mg Aroclor 1242/kg
were given to rats, increased N-demethylase and aniline hydroxylase
activities were observed after only 24 hours [211],
The effects of lower dietary levels of Aroclor 1242 on rats were
reported by Bruckner et al [212], who fed it to groups of six male Sprague-
Dawley rats at concentrations of 0, 5, or 25 ppm for 2, 4, or 6 months.
Small reductions in hematocrit and hemoglobin levels similar to those found
in other studies by Bruckner et al [211,213] were seen. Urinary excretion
of coproporphyrin was significantly increased and dose-dependent increases
in liver microsomal hydroxylase activity were measured at the time of each
sampling. Similar dose-dependent relationships were found in other
experiments [213,214], Proliferation of the hepatic endoplasmic reticulum
was seen after 2 months of ingesting a diet containing 25 ppm of Aroclor
1242; after 4-6 months of such ingestion, lipid vacuolization of the liver
was evident.
In 1974, Bruckner et al [213] reported reduced weight gain, hepatic
and renal damage, and an increase in urinary coproporphyrin excretion in
rats injected ip with a total of 1.6 g/kg of Aroclor 1242 during a 10-week
period. The hydroxylating and N-demethylating activities of the liver were
significantly elevated 24 hours after a single ip injection of 100 mg/kg of
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Aroclor 1242, with hydroxylating activity showing the greater increase.
Cytochromes P-450 and b5 and NADPH-cytochrome reductase activities of the
liver all were significantly Increased 3 days after dosing. A single dose
of 50 mg/kg gave similar but less marked effects, whereas 25 og/kg produced
significant Increases in only hydroxylatlng and N-demethylatlng activities.
Klmbrough et al [215] described in 1972 some effects of
chloroblphenyl mixtures on the livers of rats. Groups of 3- to 4-veek-old
male and female Sherman strain rats were given Aroclors 1254 and 1260 at 0,
20, 100, 500, and 1,000 ppm in their diets. Each group consisted of 10
males and 10 females. Food consumption was measured periodically. The
animals were fed the PCBs for 8 months.
One female fed 100 ppm of Aroclor 1260 died after 6 months and two
females fed 500 ppm died after 1 and 2 months. Eight females fed the 1,000
ppm diet died In 2-6 months. The rats fed 500 and 1,000 ppm gained less
weight than did the controls. At autopsy, livers of the male rats fed
Aroclor 1260 weighed significantly more than did livers of control male
rats. Livers of the females were larger than normal but the weight
differences were not statistically significant, although at 500 ppm the
fractions of body weight represented by the livers increased significantly
as a result of the reduced body weight gain. Microscopic findings in the
livers included hepatocytic hypertrophy, inclusions in the cytoplasm, brown
pigment in the Kupffer cells, lipid accumulations, and, at the higher
dietary levels, adenofibrosis. The nodular greyish-white areas that
represented extensive foci of adenofibrosis consisted of fibroblasts and
collagen that surrounded rosettes of epithelial cells [215].
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Aroclor 1254 produced similar results [215], One female and two male
rats died at 500 ppm, but none died at the lower dietary levels, and the
rats fed 500 ppm gained leas weight than did controls. Ultrastructural
changes in the livers of exposed animals consisted of proliferation of the
smooth endoplasmic reticulum (SER) and atypical raitrochondria. Similar
changes have been observed in other experiments with PCBs [131,212,216-
218], A major difference between the effects of the two products was the
much higher incidence of hepatic adenofibrosis at a lower dietary level of
Aroclor 1254 (100 ppm). In general, the effects of Aroclor 1254 on the
liver were more pronounced than those of Aroclor 1260.
In 1973, Kimbrough et al [219] reported the results of a study
conducted to determine whether morphologic changes produced in the liver
would regreas after ingestion of PCBs was stopped. Fifty male SPF Sherman
strain rats were given Aroclor 1254 at 500 ppm in their diets for 6 months,
and then were returned to normal diets. Groups of five rats were killed 0,
1, 2, 3, 4, 6, 8, and 10 months after ingestion of PCBs had been
discontinued. The livers and adipose tissues of the 10-month group were
analyzed for PCBs. Control animals were used in all evaluations and were
fed only laboratory chow.
The livers of exposed animals killed when exposure to Aroclor 1254
was discontinued were enlarged and most of the 40 livers studied
microscopically showed enlarged hepatocytes, increased lipid contents, and
adenofibrosis. A brown pigment was seen in the Kupffer cells and in other
macrophages of 15 livers. Small adenofibrotic lesions consisting of
glandular epithelial cells that formed ducts surrounded by slight amounts
of fibrotic tissue were seen; larger lesions had more extensive fibrosis
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and contained collagen. Similar findings had been reported earlier by
Klmbrough et al [215] and both in the areas of adenofibrosls and in
othewise normal hepatic tissue, Kirabrough [220] later reported finding
small clusters of glandular type cells, resembling those of pancreatic
tissue in general appearance and staining characteristics, in 15 of 36 rat
livers with adenofibrosls. The cells stained red with the stain used for
esterase, and developed a blue granular appearance vlth the stain used for
protein bound tryptophan. These staining reactions were suggestive of
those of salivary gland tissue to the author. The cells may * have been
derived from either ductal or vascular epithelium, but there is no evidence
to substantiate either suggestion [220],
Signs of regression of the adenoflbrotlc lesions were not noted
except for the disappearances of epithelial cells from the centers of the
lesions [219]. Liver weights did regress to normal after 10 months without
PCB exposure, but the lipid accumulation and the hypertrophy of the hepatic
cells remained unchanged. Analysis of adipose tissues from the final group
of rats killed showed that the FCB levels ranged from 924 to 1688 ppm
(mean, 1192 ppm). Liver PCB levels ranged from 17.3 ppm to 26.2 ppm (mean,
22.7 ppm). The PCB concentrations in the adipose tissue and liver9 of the
control animals were less than 1.0 ppm. The authors [219] were unable to
decide whether contamination of Aroclor 1254 with dibenzofuran was
responsible for the observed liver lesions [219],
Klmbrough and Linder [221] reported in 1974 the results of a PCB-
feeding experiment which they undertook to induce adenofibrotic lesions in
the livers of BALB/cJ inbred male mice, ie, lesions similar to those
previously observed in rats fed Aroclors 1254 and 1260. Two hundred mice,
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5-6 weeks old, were distributed randomly into 4 groups of 50 each. Two
groups were fed a ground diet containing 300 ppm of Aroclor 1254. At the
end of 6 months, one of these exposed groups was placed on a PCB-free diet
while the other exposed group continued on the test diet for another 5
months. The other two groups served as controls and were fed the plain
ground laboratory diet for the entire 11 months. The average PCB intake
was 49.8 mg/kg/day in the mice fed the PCB diet for the entire 11-month
period.
Livers of 45 of the 58 surviving control mice were found to be
normal. The other 13 had focal round-cell infiltrates and sometimes small
areas of necrosis and fibrosis. Skin abscesses, usually near the groin,
were identified in all 13 control mice with hepatic round-cell infiltrates.
These skin lesions were thought to be abscesses of the preputial glands.
In comparison, 10 hepatomas were identified in 9 of the 22 survivors in the
group fed the PCB diet for 11 months. These tumors consisted of well-
differentiated hepatocytes, relatively uniform in size but usually smaller
than the surrounding liver cells. They were well circumscribed and
surrounded by compressed hepatic parenchymal cells or strands of fibrous
tissue. In the larger tumors, there were areas in which the sinuses were
dilated and filled with a pink-staining amorphous material. No metastases
were seen on gross inspection of the organs, although no detailed
screening, such as serial sectioning of the lungs, was undertaken. Only
one small hepatoma, composed of well-differentiated hepatocytes, was
identified among the 24 survivors fed the PCB diet for only 6 months. The
authors [221] noted that the mouse strain used in this study rarely
develops hepatomas spontaneously.
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Adenofibrosis was identified in the livers of the mice subjected to
the 11-month PCB diet. These lesions, according to the authors [221], may
or may not be precursors of malignant lesions. They were seen in several
areas of each liver as fibrosis and as glandular formations of proliferated
epithelial cells replacing parenchymal cells. They formed ducts which
produced mucus and which were surrounded by connective tissue of varying
abundance.
Allen and Abrahamson [216] reported on morphologic and biochemical
changes In the livers of rats given Aroclors 1248, 1254, and 1260 at 1,000
ppm in their diets for 6 weeks. A control group was fed unsupplemented
chow. Each group contained 24 rats. Four rats were killed after
1,3,7,14,21, 28, and 42 days of exposure. White blood cells, hemoglobin
(Hb), hematocrit (Hct), differential white cell count, total serum
proteins, and blood urea nitrogen (BUN) were measured at each Interval.
Selected tissues were prepared for microscopic examination and the livers
were homogenized and analyzed for cytoplasmic protein, DNA, and RNA. Liver
microsomes were examined for aryl hydrocarbon hydroxylase, nitroreductase,
N-demethylase, and nitrophenylacetate hydroxylase activities, and for
cholesterol content.
All of the PCB-dosed rats failed to gain weight. The most severe
effects were noted with Aroclor 1248, followed by Aroclors 1254 and 1262.
All blood samples showed increases In Hb and Hct, with no changes in the
white blood cell counts. Neutrophils were Increased in the sera of all
treatment groups. There were no changes in BUN or in total serum protein
levels. Organ weights in all of the experimental rats constituted higher
percentages of total body weights than in controls; the livers showed four-
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fold increases in weight in all PCB-dosed groups. The increased liver
weights were discernible after only 1 day of exposure. Liver hypertrophy
was attributed to proliferation of SER, development of large concentric
arrays of membranes, and increases in lipid droplets within the cytoplasms
of the affected cells. Aroclor 1248 was the most, and 1262 the least,
toxic PCB product as judged by changes in liver histology. Liver
homogenates contained increased concentrations of protein and RNA, and
decreased concentrations of DNA. These changes were seen within 2 weeks
after initiation of feeding Aroclors 1248 and 1254; the protein and nucleic
acid concentrations then either leveled off or decreased after 4-6 weeks.
Aroclor 1262, however, did not induce these effects until 4 weeks after the
beginning of feeding; the initial changes were followed by reversals [216],
Liver microsomal fractions had increased protein and phospholipid
concentrations. These changes occurred earlier in the rats fed Aroclor
1248 and 1254 than in the Aroclor 1262-fed animals. Microsomal
nitroreductase activity, expressed on the basis of microsomal protein, was
variable in the animals fed Aroclors 1248 and 1254; however, all animals
fed Aroclor 1262 had progressive increases in nitroreductase activity. N-
demethylase activity increased early in the experimental period and
increased progressively in all treatment groups as the exposures continued.
Aryl hydrocarbon hydroxylase, glucose-6-phosphatase, and other esterase
activities increased initially, followed by continuous declines in activity
in the groups fed Aroclors 1248 and 1254. The rats fed Aroclor 1262 had
similar, but less marked, changes. When enzyme activities were expressed
as activity per total liver, all showed marked increases. After 6 weeks,
other degenerative changes in the liver occurred, such as dissolution of
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the concentric arrays of membranes, vesiculatlon of the endoplasmic
reticulum, and accumulation within the cytoplasm of lipid droplets that had
developed during the hypertrophic phase of the intoxication [216].
Allen et al [222] administered PCBs (Aroclor 1248) and
polychlorinated terphenyls (Aroclor 5460) to rhesus monkeys. Sixteen male
monkeys were distributed Into three groups. Group 1 consisted of six
animals and was fed a basal diet supplemented with 300 ppm of Aroclor 1248.
Group 2 consisted of six animals fed a basal diet containing 5,000 ppm of
Aroclor 5460. The remaining four monkeys constituted the control group and
were fed the standard colony diet. Each animal had access to 400 g of diet
dally. The physical status of the animals was evaluated dally and
"complete" blood studies were performed biweekly. Approximately 10 g of
liver tissue were removed from each animal during the 6th week (via
laparotomy) and during the 12th week (at necropsy) for biochemical and
microscopic evaluation.
Animals fed Aroclor 1248 lost an average of 26% of body weight; those
receiving Aroclor 5460 lost an average of 19% of body weight. Gross
changes seen In the animals fed Aroclor 1248 Included loss of hair from
head, neck, and back, puffy faces, edematous lips, and swollen eyelids with
purulent exudates around the eyes. These changes were seen within 1 month;
similar, but less marked changes were seen in the animals fed Aroclor 5460
[222].
Hematologic changes developed gradually. After 3 months, hemoglobins
had decreased by about 2 g/100 ml, and hematocrits had diminished from
about 40% to 33%. Total white blood cell counts did not change; however,
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there was a shift to the left in the differential count. Total serum
proteins decreased by about 1.5-2 g/100 ml, and there was a gradual shift
in the albumin/globulin ratio of the serum protein. No changes were seen
in SGOTor BUN. Both experimental groups had similar patterns of changes
[222].
At necropsy, both groups of animals showed extensive alopecia,
acneiform lesions of the skin, subcutaneous edema, liver hypertrophy with
fatty infiltration, and gastric mucosal hypertrophy and hyperplasia. Liver
hypertrophy was attributed mainly to proliferation of the hepatocytic SFR.
Gastric hypertrophy was characterized by thickened gastric mucosa, numerous
large cystic areas filled with mucin, and hyperplasia. Ulceration was
seen, as was invasion of the underlying mucosa by glandular-type epithelial
cells [222].
The authors [222] noted that, biochemically, the decreases observed
in the DNA concentrations of the livers of both experimental groups
reflected the hypertrophic cells observed microscopically, and the
increases in protein and RNA were said to be compatible with the
proliferated SER. Levels of microsomal protein per gram of protein were
not markedly altered, but decreases in the specific activities of esterase,
aniline hydroxylase, nitroreductase, and glucose-6-phosphatase became
apparent within 6 weeks, and persisted. N-demethylase activity was
increased at each examination.
The results of a toxicity study conducted on four young male rhesus
monkeys fed Aroclor 1242 at concentrations of 3, 10, 30, or 100 ppm were
reported by Bell [223], McNulty [94], and in a communication written in
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March 1977 by WP McNulty. All four monkeys on these diets died within 9
months. The monkeys had facial swelling, red and swollen eyelids,
conversion of all secretory-type cells of the stomach to mucous cells,
growth of mucous glands Into the muscular walls of the stomach, multiple
ulcers In the stomach, atrophy of the thymus gland, and either
disappearance of sebaceous glands or conversion of these glands to keratin
cysts, particularly in the eyelids.
Allen et al [104] and Allen and Norback [224] found gastric
hypertrophy and hyperplasia and focal ulceration of the stomach lining in
adult male rhesus monkeys fed single doses of 1.5 or 3.0 g of Aroclor 1248.
(c) Studies Involving Individual PCB Isomers
In 1972, Vos and Notanboom-Ram [225] discussed the comparative
toxicities of dermally applied 120-mg doses of 2,2',4,4*,5,5'-
hexachlorobiphenyl and Aroclor 1260. The PCBs, dissolved In lsopropanol,
were applied 20 times to the clipped and shaved backs of three groups of
four rabbits each, 5 times/week for 4 weeks. The control group received
only lsopropanol. The Aroclor 1260 sample was found to be "free" of
chlorinated dlbenzofurans (limit of detection, 1 ppm), and because of the
nature of the chemical reactions utilized in the synthesis of
2,2' ,4 ,4' ,5,5 '-hexachlorobiphenyl. Dermal applications of these PCBs
resulted in early macroscopic skin lesions and morbid liver changes similar
to those found by Vos and Beems [208]. These liver lesions included
centrllobular degeneration and liver cell atrophy, focal cytoplasmic
hyaline degeneration of the hepatocytes, enlarged nuclei, loss of glycogen
and proliferation of SER. The authors [225] concluded that, although the
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major acnegenic action of crude PCB mixtures results from the presence of
chlorinated dibenzofurans, PCBa have acnegenic actions of their own.
Hansell and Ecobichon [217] described the effects of a series of
chemically pure chlorobiphenyls on rat liver morphology. Biphenyl and a
series of isomerically 'pure mono-, di-, tetra-, hexa-, and
octachlorobiphenyls of known composition were administered intraperitoneal
(ip) injections in daily doses of 50 mg/kg to groups of seven young male
Woodlyn strain Wistar rats for 3 consecutive days. The rats were killed 4
days after the final injections had been made and sleeping times after
phenobarbital administration had been determined, The major microscopic
alterations observed were proliferation of the hepatocytic SER, changes in
the rough endoplasmic reticulum, and increased numbers of lipid droplets
and microbodies. However, in the rats administered isomerically pure hexa-
and octachlorobiphenyls, there were additional changes in hepatic
morphology, including large numbers of hepatocytes with cytoplasmic
vacuoles and small foci of necrosis involving five or six cells. Biphenyl
and 2,21-dichlorobiphenyl appeared not to induce extensive proliferation of
the SER, but with the other compounds the SER proliferation appeared to be
related to the degree of chlorination, especially to the presence of a
chlorine in the 4 and/or 4' positions.
The investigators [217] also injected groups of seven rats ip with
daily doses of 100 mg/kg of either 4-mono-, 4,4'-di-, or 2,5,2',5'-
tetrachlorobiphenyl for 7 days; all rats from each group were killed 24
hours after the last injections. This regimen caused more pronounced
alterations in hepatocytic ultrastructure than those observed after the 3-
day experiments. Marked proliferation of SER and increased numbers of
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mlcrobodles and lipid droplets were noted, as were a large number of
necrotic foci, centrilobular necrosis, and proliferation of biliary
ductules. The most severe lesions were seen in the group receiving 4,4'-
dichlorobiphenyl. There was not the increase in hepatic weight and cell
size noted by other authors [219,226], Hansell and Ecobichon [217]
observed that this apparent anomaly may have been due to the duration of
PCB administration, only 3-7 days, and to the relatively low dosages.
Allen et al [226], in a series of experiments, studied the toxicity
of 2,2',5,5'-tetrachlorobiphenyl in rats and rhesus monkeys. In the first
experiment, 5-week-old rats were separated into five groups consisting of
five males and five females each. After being fasted overnight, each of
these groups was administered by gavage a single dose of one of the
following amounts of the compound dissolved In corn oil: 0, 0,5, 1.0, 1.5,
or 2.0 g/kg. Each dose had a total volume of 1 ml. After the dose had
been given, blood was taken for complete blood counts. Eighteen of the AO
PCB-dosed rats died within 3 days. The dead animals included all those
given 2.0 g/kg, 7 rats from the group given 1.5 g/kg, and 1 rat from the
1.0 g/kg group. The rats were observed for 21 days after which complete
blood counts were performed and the surviving animals were killed and
necropsied. The major pathologic changes observed in the animals that died
were marked regressions of lymphocytes in the spleen and lymph nodes and of
cortical thymocytes. With the exception of hemorrhage and atrophy of the
thymus, which were related to the decrease in the cortical thymocytes, and
enlargement of the liver and kidneys, all tissue samples were normal when
compared with those from the nonexposed group.
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The second experiment was conducted to determine the effects of
hepatic microsomal enzyme activity on the responses of male Sprague-Dawley
rats to 2,2',5,5'-tetrachlorobiphenyl [226], The rats were separated into
6 groups of 10 animals each. Group 1 was a positive control given four ip
injections of 75 mg/kg of the microsomal enzyme inhibitor, SKF 525A, at 8-
hour intervals. Group 2 was given four daily sc injections of 75 mg/kg of
phenobarbital. Group 3 was the general control. Groups 4, 5, and 6
received 1.25 g/kg of the chlorobiphenyl in 1 ml of com oil by gastric
intubation; group 5 was dosed with the chlorobiphenyl 24 hours after 4 days
with daily sc doses of 75 mg/kg of phenobarbital. Group 6 received 75
mg/kg of SKF 525A ip 2 hours prior to administration of 2,2* ,5,5'-
tetrachlorobiphenyl, and every 8 hours thereafter for 24 hours. Within 4
days, all the rats in group 5 and 50% in group 4 had died whereas none had
died in group 5, which was pretreated with phenobarbital. The findings
that pretreatment with phenobarbital allowed complete survival of rats
after an LD50 dose of the PCB, whereas pretreatment with SKF 525A caused
100% mortality, indicated to the investigators that metabolic
transformation by endoplasmic reticulum enzymes resulted in deterification
[226].
The third experiment was performed to compare the differences between
the responses of rats to 2,2 ' ,5,5'-tetrachlorobiphenyl and Aroclor 1248
[226]. Twelve male rats were placed in three groups of four animals each;
group 1 was fed 100 ppm of Aroclor 1248 in its diet, group 2 was given 100
ppm of the 2,2',5,5' isomer in its diet, and group 3 (control) was fed the
staple ground meal diet. After 4 weeks of these feeding regimens, the rats
were fasted for 24 hours, killed, and necropsied; blood was also collected
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at this time. There were no detectable differences In general appearance,
food consumption, activity, growth rate, or blood chemistries between the
two experimental groups and the control group. The only significant
difference at autopsy was an increase In liver weight as a percentage of
body weight of the animals fed Aroclor 1248: 4.46 ± 0.112, compared with
3.38 ± 0.132 for those fed 2,2',5,5'-tetrachloroblphenyl and 3.0 ± 0.122
for the controls. Proliferation of the endoplasmic reticulum within the
hepatic cells was observed In the Aroclor 1248-fed animals. The N-
demethylase activity and the cytochrome P-450 content of the microsomal
fraction of homogenized liver from the Aroclor 1248-fed rats were Increased
whereas the activity of aniline hydroxylase and glucose-6-phosphatase In
this fraction had decreased. There were Increases In the concentrations of
protein and RNA and a decrease In the DNA content of the liver homogenates
from the Aroclor-fed animals. The livers of rats fed the isomer had
similar but less marked changes In concentrations of protein, RNA, and DMA.
The mean concentration of microsomal protein In liver was Identical with
that of the controls but was more variable. A significant Increase In the
mean activity of N-demethylase was found.
The fourth experiment [226] was performed to determine the effects of
2,2',5,5'-tetrachloroblphenyl on non-human primates. Seven adult male
rhesus monkeys were given 18 mg/kg of the PCB Isomer dissolved In 2.5 ml of
corn oil and three controls were given 2.5 ml of corn oil, all by gavage
after a 24-hour fast. Complete blood counts had been done on each animal
prior to intubation. Immediately after treatment, the animals were placed
in metabolism cages and their urine and feces analyzed for 2,2',5,5'-
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tetrachlorobiphenyl by GLC. On the 14th day of the experiment the animals
were fasted for 24 hours, killed, and necropsied. Tissues were taken for
light and electron microscopy and GLC. No overt clinical effects were seen
in the treated monkeys. Over 12% of the PCB was recovered unmodified in
the feces but only minute amounts were present in the urine. Only the
adipose tissue and adrenals had high PCB assays, and microscopically,
except for a moderate proliferation of hepatocytic SER, all tissues were
normal. DNA was slightly decreased in liver homogenates of exposed animals
and hepatic microsomal cytochrome P-450 was increased.
Torok [227], in 1976, reported a study of pregnancy in NMRI mice
treated with 2,2'-dichlorobiphenyl. The mice were separated into three
groups, with group 1 (37 mice) serving as the control; group 2 (18 mice)
received the PCB in oral doses of 375 mg/kg/day on days 1-3 of gestation,
and group 3 (37 mice) received 750 mg/kg/day on the same schedule.
Administration of the PCB at either level resulted in longer intervals from
breeding to parturition: 18.2 days for controls, 19.4 days for mice
treated with the PCB at 375 mg/kg/day, and 21.8 days in mice treated at 750
mg/kg/day. There also were reductions in the numbers of dams with litters
and in the mean litter size. Reductions were greatest in group 3. The
authors [227] concluded that the effects were due to delayed implantation,
(d) Reproductive and Teratogenic Effects of PCB Mixtures
Curley et al [101] studied the transplacental movement of PCBs in
rats. Three groups of 90-day-old female rats were paired with male rats of
the same age. All were fed standard laboratory chow by the authors, who
designated the day of insemination as day 0. Aroclor 1254 was given in
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doses of 0, 10, and 50 mg/kg in peanut oil (presumably by oral intubation)
once a day on days 7 through 15 of pregnancy to groups 1, 2, and 3,
respectively.
On the 20th day after insemination, fetuses were taken by Caesarean
section from three rats of each PCB-exposed group and from tvo control
rats. The fetuses from each experimental group were divided into two lota
and analyzed as duplicate samples for PCBs. Ten rats from each of the
three experimental groups were allowed to deliver spontaneously. When the
offspring were 5 days old, six mothers from each exposed group and two from
the control group were separated from their litters for several hours and
then returned for 1 hour of nursing. The contents (milk) of the pups'
stomachs were analyzed for PCBs. Litters from three rats in each
experimental group were allowed to survive until weaning at 21 days of age.
These baby rats then were killed and their tissues analyzed for PCBs by GLC
with EC detection [101].
The rats subjected to Caesarean section had normal fetal complements,
in both size and number, and in the rats allowed ro deliver spontaneously
there were no significant differences in average litter size and weight
among the three groups. However, the three groups, with 0, 10, or 50-mg/kg
doses of Aroclor 1254, had 0, 1, and 4 stillbirths on the average,
respectively [101],
Analvses of the tissues of the Caesarean-delivered pups showed
measurable levels of PCB-derived components in the exposed groups only.
The mean PCB concentrations were <0.12, 0.63 ± 0.06, and 1.38 i 0,06 ug/gt
respectively, for groups 1, 2, and 3. Although the PCB dose for group 3
was five times that of group 2 (50 vs 10 mg/kg Aroclor 1254), the average
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amount of PCB-derived components measured in the fetuses from these two
groups differed by only two-fold. The authors suggested that the PCB
distribution between the mothers and their fetuses may not have been
uniform and that a partial (unspecified) barrier may have existed [101],
Livers were increased in size and had enlarged hepatocytes in 15 of
21, and 15 of 20 weanling rats from groups 2 and 3, respectively. Some
rats from group 3 showed vacuolization of the hepatocytic cytoplasm (10 of
20), and 5 of 20 exhibited bile duct proliferation. Morphologic changes in
%
the liver were more pronounced at the higher dose [101],
PCB-derived components were detected in litter-pooled milk at mean
concentrations of <0.75, 20.60 ± 1.59, and 66.34 ± 8.36 yg/g in groups 1,
2, and 3, respectively. The authors [101] concluded that the morphologic
changes identified in the livers of exposed weanling rats were probably
caused by PCBs transmitted to the pups in the milk from the dams [101],
Reproductive effects of feeding Aroclors 1254 and 1260 to Sherman
strain rats for two generations were reported by Linder et al [228] in
1974. In preliminary experiments, the two mixtures were fed to groups of
10 females at 100 and 500 ppm in the diet. Two similar groups served as
controls. The diets, fed for 67 days before the first mating, were
continued through gestation and lactation. After weaning of the first
litters, the parents continued to be fed the diets. After being fed PCBs
for a total of 186 days, they were again mated and the diets fed through
the second gestation and lactation. Feeding Aroclor 1254 at 500 ppm
resulted in only 4 first litters being born (2 alive), with no survivors to
weaning. Consequently, feeding Aroclor 1254 at 500 ppm was discontinued.
With Aroclor 1254 at 100 ppm, there was little indication from either the
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first or second mating of reduced fertility, or increased death in utero or
during the nursing period. Aroclor 1260 fed at 100 ppm for 67 days had no
apparent effect on reproduction, litter size, or survival of the first
litters; however after being fed for 186 days, only 5 second litters were
born from 9 mated females, compared to 9 out of 10 in the controls. At 500
ppm, Aroclor 1260 resulted in more pups dead at birth in first litters,
reduced second litter size, and fewer litters being weaned (3 of 8 first
litters; 2 of 6 second litters).
Subsequently, Linder et al [228] fed groups of 20 female Sherman rats
Aroclor 1254 at 1, 5, 20, and 100 ppm and Aroclor 1260 at 5, 20, and 100
ppm. Appropriate control groups with similar numbers of rats were used.
The experimental plan was similar to that described above except that the
F1 generation pups continued to be fed the F2 generation diet until they
reproduced the F2 generation. The first matlngs of the F1 generation were
after they were exposed to PCBs in utero, in milk, and in the diet for 125—
129 days. The F1 generation rats fed Aroclor 1254 at 20 and 100 ppm were
mated a second time after a total of 274 days of PCB exposure.
Rats exposed to Aroclor 1254 at dietary levels of 20 ppm or more had
fewer pups in their litters than the controls [228]. There were also fewer
F2 generation pups than controls. Second litters born from rats fed 100
ppm of Aroclor 1254 had Increased mortality and markedly decreased mating
performance. Dietary levels of 5 ppm Aroclor 1254 and 100 ppm Aroclor 1260
had no effect on reproduction in rats exposed through two generations.
Liver weights were Increased in 21-day-old F1 male weanlings at 1 ppm of
Aroclor 1254 and in either sex of F1 and F2 weanlings at 5 ppm or higher of
both Aroclors 1254 and 1260.
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Villeneuve et al [229], in 1971, wrote about fetotoxic effects of
Aroclors 1221 and 1254 in rabbits. Twenty-four mature female rabbits were
divided into six groups each comprised of two control and four experimental
does. Experimental animals were given the Aroclors orally at 1.0 and 10
mg/kg/day beginning after mating and continuing through gestation.z They
were killed 28 days after mating. Neither Aroclor had a fetotoxic effect
at either dose level. Liver weights expressed as percentages of body
weight were significantly heavier in the does fed 10 mg/kg Aroclor 1254
than in controls (4.29 vs 2.79%). Liver weights of the other experimental
does and of all fetuses were not significantly different from controls.
In another experiment reported by Villeneuve et al [230], 16 mature
female rabbits were separated into four groups and, after mating, were
dosed orally with 0, 12.5, 25, or 50 mg/kg of Aroclor 1254 daily for the
first 28 days of gestation. The 50-mg/kg group had three pregnancies.z One
pregnant female died on the 11th day and contained nine fetuses. A second
one died on the 17th day and contained six resorption sites. The third
female aborted three dead fetuses on the 28th day. Two rabbits in the 25-
mg/kg group had normal fetuses. A third rabbit aborted her litter on the
2Sth day and died. The four animals in this group showed an average weight
loss of 26 g and liver weights found at autopsy 29 days after mating
averaged 5.11% of their body weights. Autopsies were performed on the
fetuses of the two rabbits which had conceived in the 12.5-mg/kg group; the
first rabbit had two normal fetuses, with six resorption sites, while the
second aborted two fetuses on the 27th day and was found on autopsy to
contain one partially resorbed and two dead fetuses. The two dead fetuses
obtained on autopsy showed subcutaneous cephalic hemorrhages and had
-------
asymmetric skulls. Average weight gain of Che females during pregnancy was
265 g, and their liver weights averaged 6.03% of their body weights.
Controls gained 65A g during pregnancy, and their livers averaged 2.66% of
their body weights.
In their third experiment, Villeneuve et al [230] gave each animal in
three groups of six female rabbits 25 mg/kg Aroclor 125A In corn oil
(orally). Controls received corn oil alone. A control group and one
exposure group were dosed from day 1 through day 28, and another control
and an exposure group were dosed from day 7 through day 28. Administration
of Aroclor 125A at 25 mg/kg/day from day 1 through day 28 resulted in
abortions in two of four rabbits. Their average weight gain was 2A5 g and
liver weights averaged 6,03% of their body weights (controls, 531 g weight
gain; liver weights, 2.65% of body weight). In the second group
administered PCBs, one of four rabbits aborted. Average weight gain was
156 g and the liver weights averaged A.82% of the body weights.
PCB concentrations In various tissues of six rabbits and their
fetuses, chosen at random from the above groups, were determined by Grant
et al [231]. Concentrations of PCBs were higher in the livers of the
fetuses than in their mothers: 5.A vs 2.1 ppm at a dose of 1 mg/kg; 78.1 vs
69.5 ppm at 12.5 mg/kg; and 375.3 vs 12A.2 at 25 mg/kg. In other tissues,
PCB concentrations yere generally less in the fetuses than in the dams.
Allen et al [232] in 197A presented evidence of possible fetotoxicity
in a 9hort term PCB feeding experiment with 12 adult female rhesus monkeys.
The monkeys ranged In age from 7 to 10 years and had an average weight of
5.6 kg. Each previously had delivered at least one infant and the
menstrual cycle of each had been recorded for at least 2 years. Six of the
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monkeys were fed an unspecified diet containing 25 ppm of Aroclor 1248 for
2 months. The other six monkeys were controls. After 2 months, the PCB-
exposed animals were placed on PCB-free diets of commercial monkey chow.
The monkey which had consumed the largest amount of PCBs died on the
128th day of the experiment [232]. At the beginning of the 5th month, ie,
3 months after the test animals had been removed from the PCB-containing
diet, the remaining five test monkeys and the six controls were mated
again. Three PCB-exposed monkeys were thought to have conceived since each
showed the characteristic post-conceptual bleeding, lack of the subsequent
menstrual period, and an enlarged uterus. Two either aborted or reabsorbed
their fetuses during the 2nd month of pregnancy and the third monkey
delivered a well-developed but smaller-than-normal (375 g t 1 g vs 544 g ±
101 g) infant. High concentrations of PCBs were found in the adipose
tissues and adrenals of this infant with means of 27.7 and 24.4 fig/g,
respectively, as compared to a range from 0.0L to 0.98 jig/g in the other
infant tissues analyzed. The PCB levels in the placenta averaged 0.9 #ig/g,
and 50 Mg/g in the mother's adipose tissue. Two additional attempts were
made to breed the nonpregnant females during the next 5 months. Only the
controls became pregnant and all delivered normal infants. Six of the
monkeys were fed an unspecified diet containing 25 ppm of Aroclor 1248 for
2 months. The other six monkeys were used as controls. After 2 months,
the PCB-exposed animals were placed on PCB-free diets of commercial monkey
chow.
In 1976, Barsotti et al [233] and Allen and Barsotti [234] reported
their findings on reproductive dysfunction in female and male adult rhesus
monkeys fed Aroclor 1248 in their diets. One test group of female monkeys
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received 2.5 pptn and the other group received 5.0 ppm of Aroclor 1248 in a
commercial diet. The control group, containing 12 females and 6 males, was
fed the commercial diet alone. Females received 200 g, and the males
received 300 g of their respective diets daily. Food left in the feeding
cups at the end of the day was removed and weighed to determine the daily
intake. After the end of the first 6 months, the average PCB intakes were
180 and 364 mg for females fed the 2.5- and 5.0-ppm diets, respectively
[233].
Some of the exposed females began to exhibit the characteristic skin
and blood chemistry signs of PCB intoxication within 2 months. At 6
months, all exhibited these signs in varying degrees. Menstrual cycles
were irregular and menstrual bleeding was excessive and prolonged [233].
The conception rates for the control females and for those fed the
2.5-ppm Aroclor diet were 12 of 12 and 8 of 8, respectively, whereas 6 of 8
females fed the 5.0-ppm Aroclor diet conceived [233], All 12 of the
control group pregnancies resulted in normal births, compared to 5 and 1,
respectively, for the exposed females fed the 2.5- and 5.0-ppm diets.
Three of the eight fetuses of monkeys fed the 2.5-ppm Aroclor diet were
resorbed shortly after conception. Profuse uterine hemorrhaging was
observed rather than the implantation bleeding which usually occurred 17
days after conception, according to the authors [233], The two females
from the group fed the 5.0-ppm diet who did not conceive initially were
bred five times without success. Of the six females of this group that did
become pregnant, three aborted at 46, 67, and 107 days of gestation; one
fetus was resorbed, one was stillborn, and one delivered normally. The six
live infants born to PCB-fed mothers had body weights that were less than
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normal for the colony by one to two standard deviations. These infants
began showing signs of PCB toxicity (acne, swollen eye lids, increased skin
pigmentation) after nursing their mothers for less than 2 months [234]. In
samples obtained from three of their mothers after the infants developed
the poisoning signs, the milk contained PCBs at 0.154-0.397 ppm, and the
milk fat from a fourth mother contained 16.44 ppm. Three of the Infants
died 44-112 days after birth.
The effects of Aroclor 1254 on reproductive performance and fetal
integrity were evaluated in beagle dogs and Hormel miniature swine by FL
Earl et al (written communication, 1976). Aroclor 1254 was administered
orally in capsules as a solution in corn oil to 46 purebred beagle bitches
once daily after the 1st day of gestation. Ten bitches were given 0.25
mg/kg/day, 16 were given 1 mg/kg/day, and 20 were given 5 mg/kg/day.
Sixteen untreated bitches served as controls.
The data presented show that Aroclor 1254 at 5 mg/kg/day
significantly interfered with reproductive performance and was teratogenic
in the beagle. When Aroclor 1254 was administered at 0.25 and 1.0
mg/kg/day, no effects on reproduction were observed but the incidence of
patent fontanelles in the offspring of the 1.0-mg/kg/day group was
increased sharply. Dosage at 5.0 mg/kg/day resulted in 45.5% resorptions
(4-fold increase over the control rate) and an average of only two live
pups per litter. Patent fontanelles were present in 50% of the offspring.
Earl and his coworkers fed Aroclor 1254 to Hormel miniature swine in
doses of 1.0 (4 sows), 10.0 (6 sows), and 30.0 (7 sows) mg/kg/day for 21
days before breeding and throughout gestation. Five sows served as
controls. The 1-mg/kg/day dose produced a statistically significant
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percentage of fetal resorptions (23%). Increasing the dose to 10 mg/kg/day
lowered the fertility rate to 50% (80% in controls) and increasing the dose
to 30 mg/kg/day lowered the fertility rate to 43%. Cleft palate and
syndactyly in three feet were observed in one fetus from the group fed 10
mg/kg/day. At this dose level, there was also a significant decrease in
survivability with only 71% of the offspring alive after 5 days. At the
30-mg/kg/day dose, 14 of the IS implantations were resorbed and teratogenic
abnormalities were present in 100% of the observed fetuses. Cleft palates,
syndactyly, and patent fontanelles were the teratogenic effects observed.
The fact that pigs are normally born with closed fontanelles Increases the
slgnflcance of the teratogenic findings.
(e) Studies on Mutagenicity and Cytotoxicity
To evaluate the effects of PCRs on the testes of rats, Dlkshlth et al
[235] administered, by oral intubation, 50 mg/kg/day of Aroclor 1254
dissolved in corn oil to a group of 18 adult male Sprague-Dawley rats for 7
consecutive days. A control group of 18 rats received corn oil without
PCBs. Three rats from each group were killed 1, 7, 15, and 30 days after
the last FCB administration. The testes and epldldymises were separated
and weighed, as were the livers. Microscopic, histochemical (acid
phosphatase), and cytogenetic examinations were performed. Rats used for
cytogenetic examination were injected ip with colchicine 2 hours before
being killed and the chromosomes in testicular tissues were examined.
No effects on weight or gross appearance of either the testes or
epididymis were noted, nor was there evidence of atrophy or hypertrophy of
the testes. The only structural changes noted in the testes of the exposed
group was a proliferation of interstitial tissue cells. These cells showed
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an increase in acid phosphatase activity, which, according to the authors
[235], denoted a change from particulate enzyme localization in testicular
interstitial cells of the controls to a disseminated, diffuse localization
in the testes of the exposed group.
Cytogenetic analyses showed similar chromosomal configurations in
both the control and the exposed groups. In the PCB-treated rats, some
apparently sporadic abnormal chromosomes were seen in a few of the
metaphase figures; chromosomal abnormalities also included breaks, exchange
%
figures, chromatin bridges at anaphase, and chromosome fragments. The
significance of these findings was unclear to the authors [235].
Green et al [236] looked for mutagenic effects in the bone marrow and
spermatogonia! cells of male Osborne-Mendel rats fed various doses of PCBs.
Rats were given Aroclor 1242 either in single oral doses of 1,250, 2,500,
or 5,000 mg/kg or in multiple oral doses of 500 mg/kg/day for 4 days.
Aroclor 1254 was administered orally in daily doses of 75, 150, or 300
mg/kg for 5 days. The Aroclors were mixed with corn oil, except the 5,000-
mg/kg dose of Aroclor 1242, which was given undiluted. Controls were fed
uncontaminated corn oil. The animals were given Colecimid (a colechicine
derivative) at 4 mg/kg 24 hours after PCB dosing was completed and they
were killed 3 hours later.
Aroclor 1242 produced no statistically demonstrable evidence of
chromosomal damage in bone marrow cells at doses of 1,250 or 2,500 mg/kg,
or at the 500-mg/kg dose level [236]. At 5,000 mg/kg, there appeared to be
an increase in the number of chromosomal abnormalities. However, since
most of the changes occurred in one animal, the findings were not
considered to be significant. Aroclor 1254 did not produce statistically
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significant numbers of chromosomal abnormalities in bone marrow cells at
any dose level tested. A statistically significant number of chromosomal
abnormalities was not identified in spermatogonlal cells from rats fed
Aroclor 1242. Spermatogonial cells from rats given Aroclor 1254 were not
examined since the results with the more acutely toxic Aroclor 1242 were
negative. All observed chromosomal lesions were single chromatids. The
authors [236] did not exclude the possibility of point mutations since the
procedures used in this experiment would not have detected such damage.
Green et al [237] also Investigated the possible induction of
dominant lethality in rats given Aroclor 1242 or Aroclor 1254 by oral
intubation. Except for the positive controls, results showed
nonreproducible positive effects that were not related to dose or stage
sensitivity. The authors concluded that the two Aroclors did not appear to
be mutagenic.
Wyndham et al [116] performed the "Ames" bacterial test for
mutagenicity on a variety of PCBs, using Salmonella typhimurium mutant
strain TA1538. A comparison was made of the mutagenic potentials of
Aroclor 1254, 2,2',5,5'-tetrachlorobiphenyl, Aroclor 1268, Aroclor 1221,
and 4-chlorobiphenyl. The results showed clearly that as the degree of
chlorination decreased, the mutagenic potential Increased. A concentration
of 100 jig of 4-chlorobiphenyl in the test medium gave over 2,000 revertant
colonies/plate. The more highly chlorinated biphenyls showed very little
activity as mutagens.
Hoopingarner et al [238] studied the toxicities of various Aroclors
at 50 ppm in the culture medium of Chinese hamster cells, and found
increasing toxicity (measured by cell population survival) with decreasing
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chlorination. Aroclor 1016 appeared to be disproportionately cytotoxic, on
the basis of its chlorine content, suggesting to the authors that this
product contained certain toxic components in higher proportions than
either Aroclor 1232 or Aroclor 1242, which it resembled
chromatographically. Aroclor 1254 at 100 ppm showed no apparent effect on
Che chromosomal integrity of human lymphocytes in vitro.
Popper et al [239] studied the effect of hepatic microsomal
biotransformation systems from control mice and from mice treated with PCBs
on the mutagenic potentials of the primary carcinogen N-methyl-N'-nitro-N-
nitrosoguanidine (MNNG), and the secondary carcinogen dimethylnitrosamine
(DMN). Hepatic microsomes were isolated from male Swiss-Web9ter mice that
had been given 500 mg/kg of Aroclor 1254 4 days earlier, and from untreated
control mice. The mutagenicities of MNNG and DMN were assayed by a
bacterial auxotroph reversion test using Bacillus subtllis.
Microsomes prepared from the livers of the PCB-treated mice had 2-3
times as much cytochrome P-450 activity as the controls [239]. DMN added
directly to the cultures was not mutagenic at concentrations as high as 300
mM. However DMN was converted to a mutagen when exposed to such microsomes
in the presence of an NADPH-generating system. When MNNG was incubated
with isolated microsomes, its mutagenic activity was reduced. The authors
concluded that isolated hepatic microsomes can modifv the biologic
activities of mutagens and that the hepatic microsomal biotransformation
system could play a key role in chemical mutagenesis.
(f) Studies on Tumorigenesis
Kimbrough et al [218] distributed 400, 21- to 26-day-old weanling,
Sherman strain, "COBS" female rats randomly into two equal-size groups.
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Half of the rats were fed a plain commercial laboratory chow. The other
200 were fed laboratory chow containing 100 ppm of Aroclor 1260. The dosed
group of rata was fed the PCB diet until 6 weeks before they vere killed at
the age of 23 months. Autopsies were performed on these rats as veil as
those that died before the exposures ended.
Microscopic examination was completed on 184 dosed animals and 173
controls. From a few to multiple elevated tan nodules were found on the
liver surfaces of 170 PCB-fed rats. The nodules varied from 0.1 to several
cm in diameter. Only one such abnormality was found in the controls. Of
the tumors, 26 of those In exposed animals and the 1 from the control
animal were hepatocarcinomic; the other 144 experimental animals had
hepatocellular nodules that were described as characteristic of neoplastic
nodules or synomously, hyperplastic nodules. The authors (218] said
"neoplastic nodules are part of the spectrum of response to
hepatocarcinogens and must be included in the evaluation of tumorigenesis."
Tumors identified and analyzed from other organs had no unusual features;
no apparent differences in incidence were observed between the experimental
and control groups [218],
Evidence of PCB-induced hepatocarcinomas was reported by a group of
Japanese investigators in 1972 [240] and in 1973 [241], Nine groups of 12
male dd mice were fed a commercial stock diet supplemented with 100, 250,
or 500 ppm of Kanechlors 300, 400, or 500. A control group of eight mice
was fed the stock diet. All mice were given water ad libitum. After 32
weeks, the animals were starved for 18 hours, killed, and examined
macroscopically for tumors. Seven of the 12 mice fed Kanechlor 500 at 500
ppm developed hyperplastic liver nodules and five had well-developed
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hepatocellular carcinomas. None of the mice fed Kanechlor 500 at lower
concentrations or Kanechlor 400 or 300 at any concentration developed
hepatocarcinomas,
In 1973, Kimura and Baba [242] described neoplastic changes in the
livers of rats exposed to Kanechlor 400. Thirty 10-week-old rat9 were
separated into an experimental group of 10 males and 10 females and a
control group of 5 males and 5 females. The experimental group was fed a
diet supplemented with olive oil containing various concentrations of
Kanechlor 400. The control group received an olive oil-supplemented diet.
The diet of the experimental group of rats contained 38.5 ppm of Kanechlor
400 for the first 4 weeks, followed by 77 ppm for 8 weeks, 154 ppm for 3
weeks, 308 ppm for 3 weeks, and 616 ppm for 8 weeks. Body weights were
checked weekly and showed rapid decreases during the 616-ppm feeding
period; for this reason the Kanechlor 400 content of the diet was reduced
to 462 ppm for the next 32 weeks. The total feeding period for the
experimental and control animals was about 58 weeks (400 days).
All rats that ingested total doses of more than 700 mg of Kanechlor
400 developed hypertrophy of the liver [242], Pale brown nodules were
present on the parietal and cut surfaces of the livers of female rats that
had ingested more than 1,200 mg of PCBs. However, none of the male rats
had such hepatic nodules, despite having ingested equal or greater amounts
of Kanechlor 400, On microscopic examination, the livers of female rats
were observed to have fatty degeneration and multiple adenomatous nodules
that appeared to be benign neoplastic lesions. Males did not develop such
neoplastic lesions; however, their livers did exhibit fatty degeneration.
Lung abscesses, pneumonia, splenic atrophy, and intracranial abscesses were
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found frequently in the experimental group. The authors [242] thought that
resistance to infection was lowered in the rats fed Kanechlor 400,
A formal rulemaking hearing was convened August 20, 1976 by the US
Environmental Protection Agency on its proposed toxic pollutant water
effluent standards for PCBs (Federal Register 42:6532-55, February 2,
1977). Part of the testimony concerned comparative studies in which groups
of 100 male and female Charles River rats were fed 1, 10, and 100 ppm of
Aroclors 1242, 1254, or 1260 for 24 months. The survival of the rats was
poor and the experiment was said to hav« been inconsistently reported. A
reevaluation of the pathology slides revealed the occurrence of liver
tumors (hepatomas and cholangiohepatomas) in the rats fed any one of the
three Aroclor products. The incidence of liver tumors in the rats dosed at
100 ppm was 3/20 for Aroclor 1242, 6/27 for Aroclor 1254, and 7/27 for
Aroclor 1260, compared with 0/20 for the controls. In addition to the
tumors there was a high frequency of nodular hyperplasia. The incidence of
nodular hyperplasia at 100 ppm was 8/20 for Aroclor 1242, 13/27 for Aroclor
1254, and 7/27 for Aroclor 1260, compared with 1/23 for the controls.
Nodular hyperplasia in the rats dosed at 10 ppm occurred in 2/10 for
Aroclor 1242, 3/26 for Aroclor 1254, and 9/23 for Aroclor 1260, and 1/23
for the controls. The incidence of tumors of the pituitary gland also was
elevated in each treated group.
Correlation of Exposure and Effect
(a) Absorption, Metabolism, Excretion, and Body Burdens
It has been demonstrated in experimental animals that PCBs can be
absorbed into the blood from inhaled air [97] and from the digestive tract
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[50,51,95,96]. Qualitatively, the effects in experimental animals from
absorption by either route were similar [98,99,202-206]. When PCBs were
applied to the skin, certain effects, such as those on the liver, were
similar to those obtained when PCBs were ingested or inhaled [205-208].
Thus, it appears that PCBs were also absorbed by this route.
In experimental animals, most PCB isomers were metabolized in varying
degrees to more polar compounds such as hydroxylated derivatives
[41,48,49,51-56,58-81,85,8?]. The more highly chlorinated isomers were
metabolized slowly and accumulate in the tissues [41,50,51,55,61-64,66,82-
84,96,103,107-110]. The hydroxylated derivatives were excreted in the
bile, urine, and milk [41,48,50-56,58-61,63-66,69,71-80,85]. Unmetabolized
compounds were excreted in feces, milk, and hair [41-44,50,51,53-56,100-
102], and traces were found in urine [42,51-55,57-62,103-105].
In man, the metabolism of PCBs has not been studied. However,
finding that PCB isomers that are difficult to metabolize become
concentrated in residual PCBs of tissues from the general population, from
persons who have ingested PCBs, and from those with occupational exposure
suggests that man metabolizes, eliminates, and stores the compounds in ways
similar to those of animals [7,36,136,168,171-175]. Determinations of PCBs
or their metabolites in urine or feces of humans have not been reported.
PCBs have been found in human hair [102,142], Excretion in human milk of
PCBs with compositions similar to those in blood, has been reported in
association with general environmental exposures and following ingestion
and occupational exposures [143,144,168,192], These findings of PCBs in
human hair and milk also suggest metabolism and excretion similar to those
of animals.
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Because PCBs are widespread in the environment, detectable
concentrations have been found in tissues and body fluids of a substantial
portion of the US population [36 ,102,134,135,137,140,144]. Detectable
concentrations have been found in up to 62% of blood serum samples, with
concentrations ranging up to 30 ppb [137]. In emaciated patients, blood
PCB concentrations as high as 100 ppb have been found [140]. PCB
concentrations in about three-fourths of adipose tissue samples from the
general population were <1 ppm, and the remainder were mostly in the range
of 1-2 ppm [36,136]. Usually the PCB isomers found in blood and adipose
tissue have been penta-, hexa-, and heptachloroblphenyls [7,135,136], and a
high correlation was found between the concentrations in these two tissues
[141]. PCB isomers in cord blood were qualitatively identical to those in
maternal blood [138]. PCB isomers excreted in human milk were similar or
identical to those in blood [168], and the concentrations in milk were
positively correlated with adipose tissue concentrations [143], In human
milk samples from the general US population, PCB concentrations up to 13
ppm (fat basis) have been reported (EP Savage, written communication,
February 1977).
These concentrations of PCBs in blood, adipose tissue, and milk of
the general US population arise from dietary intakes estimated to be of the
order of 10-20 ^g/day [46] and from inhalation of air that may contain up
to 100 ng/cu m [26,38].
(b) Irritation Effects and Chloracne
The first reports of adverse effects of PCBs on workers included
chloracne [120,123,130], digestive disturbances [123], irritation of mucous
membranes [120,123,130], and impotence [123]. The exposures associated
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with these effects were not well-defined either qualitatively or
quantitatively. When PCBs were first being manufactured, (in mostly open
systems) the exposures were to benzene and unidentified intermediates in
addition to PCBs [120], Jones and Alden [120] and Schwartz [123] did not
report exposure concentrations in their studies. However, Drinker et al
[125] indicated that average concentrations of PCBs ranged from about 0.5
to 1.5 mg/cu m in 30 factories, which may have included the factories
studied by Schwartz [123]. On the basis of these reports [120,123,125], it
would appear that chloracne and some other systemic effects occurred with
early PCB preparations when their average concentrations in workroom air
were below 1.5 mg/cu m. Elkins [130] found that airborne PCB
concentrations approaching 10 mg/cu m in capacitor-impregnating operations
in Massachusetts were "unbearably" irritating to the workers, but there
were no apparent toxic effects with concentrations that averaged up to 5.8
mg/cu m. Elkins [130] did not describe the processes or the PCBs used.
Puccinelli [186] found that when capacitors were filled with Aroclor
1254 heated to 70-80 C, PCB concentrations of about 5-7 mg/cu m resulted.
The workers studied by Puccinelli [186] developed chloracne after 4-8
months of exposure. In studying similar processes, Hofmann and Meneghini
[187] found that chloracne developed after 2,5-4 months of exposure. These
investigators [187] also described the development of areas of brown skin
on the foreheads of workers. They did not describe the PCBs used or the
exposure concentrations. Reports of the development of chloracne in
Americans, who worked in operations which used heated PCBs, appeared in
1964 and 1969 [188,189], In one of the processes [188], an Aroclor with a
chlorine content of 65% and containing both PCBs and polychlorinated
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terphenyls was used; the FCB used In the other process [189] was not
described, but extensive skin exposure from wearing PCB-solled clothing and
from Immersion of unprotected hands Into the PCB mixture was described.
A case of chloracne that developed In an Australian worker after
exposure to Aroclor 1242 at concentrations of 1-2 mg/cu m was reported by
Ouw et al [196], The PCB preparation was heated during a capacitor-filling
process. Complaints of process workers Included Irritation of the face,
eyes, and skin. Eczematous rashes were also found on their hands and legs.
In the reports of chloracne development in occupations Involving PCBs
(where environmental concentrations of PCBs were measured) [125,130,186-
189,196], the sampling and analytical methods did not distinguish between
vapor and particulate forms of the PCBs. However, a common factor in many
of these reports [186-189,196] was the use of heat in the process which
would tend to generate PCB vapors.
In their study of capacitor and PCB manufacturing plants in Japan,
Hasegawa et al [191] found that concentrations of PCR vapors (or particles
<0.1 m in diameter) exceeded the concentrations of PCBs in particles >0.1
tim in diameter. The compositions of PCBs in the particulate were similar
to those in the PCB preparations in use, but the le9s highly chlorinated
compounds were concentrated in the vapors. In this 9tudy, where PCB vapors
ranged from 0.026 to 0.965 mg/cu m and PCBs in the larger airborne
particulates ranged from 0.19 to 0.650 mg/cu m (maximum total PCBs of 1.6
mg/cu o), dermal ailments included a brown chromodermatosis of the hands
and chloracne. The workers had been exposed to PCBs from <1 to 20 years.
Meigs et al [190] described a process in which chloracne developed
where the exposures had to have been to PCB vapors. The PCB which was used
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as a heat-exchange medium was not described, but PCB concentrations were
reported to be about 0.1 mg/cu m in the workroom air where the workers were
exposed. Under these conditions, chloracne developed after a minimum of 5
months of exposure.
Chloracne has also been studied in connection with determinations of
PCB concentrations in blood. Hara et al [192,193] found whole blood PCB
concentrations of 7 to 300 ppb in Japanese workers engaged in capacitor
filling. About 40% of these workers had chloracne and 13% had irritation
of the skin. Kitamura et al [ 194] found PCBs at 320-820 ppb in blood
samples from Japanese workers engaged in capacitor manufacture. Skin
ailments, including chloracne, were found in 10 of 13 workers studied.
Inoue et al [195] found chloracne in a man exposed to PCBs in a silk-
glossing factory who had a concentration of about 200 ppb of PCBs in his
blood, but they [195] found what were described as relatively mild skin
abnormalities in 28 other workers engaged in similar processes who had
blood PCB concentrations mostly under 100 ppb (2 had concentrations >100
ppb). Ouw et al [196] concluded from their study of capacitor workers that
no adverse effects were found in workers with blood PCB concentrations <200
PPb •
Studies of PCB-exposed workers where chloracne has not been found
include those of Levy et al [197], Karppanen and Kolho [198], and Bumgarner
et al [199]. In the study by Karppanen and Kolho [198], workers who had
been exposed to PCBs for A years in a capacitor-impregnating operation had
PCB concentrations of 74-1,000 ppb in samples of their blood. The
environmental exposure concentrations of PCBs were reported to meet
"internationally accepted standards." Other factors of the work situation,
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such as the skin protection used, were not reported. In the study by Levy
et al [197], workers who had been exposed to PCBs for 2.5-18 years had
concentrations of PCBs in samples of their blood ranging from 36 to 286
ppb, PCB exposure concentrations at the time of the study were 0.013-0.264
mg/cu m. Although some of the workers complained of throat or eye
Irritation, and some skin rashes were found, no cases of chloracne were
seen. Fron the description of the work situation, it is unlikely that skin
exposure to liquid or solid PCBs was an important factor in the total
exposure of these workers. In their study of refuse workers, Bumgarner et
al [199] found blood PCB concentrations to be 4-14 ppb. One possible
source of exposure of these workers was airborne incinerator effluents, and
it is unlikely that additional exposure from skin contact occurred.
Although skin exposure was unlikely in these two reports [197,199]
where chloracne was not found, skin exposure is not necessary for chloracne
to develop. Chloracne has been observed in Japanese people estimated to
have ingested total PCB doses of 0,3-4 g [146,164-167], and chloracne-like
lesions have been produced in experimental rhesus monkeys fed PCBs at 3 ppm
in their diets [222].
Thus, although eliminating exposure of the skin through engineering
control's and using appropriate protective clothing and work practices will
reduce the total absorption of PCBs, these practices will not necessarily
eliminate chloracne. The data indicate that chloracne may occur with
exposures to PCB vapor concentrations as low as 0.1 mg/cu m for several
months, and with PCB concentrations in the blood of about 200 ppb.
Ill
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(c) Effects Referable to the Liver
Some clinical and autopsy findings in Yusho, the disease that
occurred after ingestion of PCB-contaminated rice oil by humans, were
indicative of liver injury [155-158,179-181]. These findings included
changes in liver cell anatomy considered consistent with microsomal enzyme
stimulation and increased SAP activity. Effects that persisted for several
years Included decreased concentrations of iron and bilirubin in the serum
[155,179] and increased serum concentrations of triglycerides. The latter
were found to increase with residual concentrations of PCBs in the serum
[180].
The maximum amounts of PCBs consumed by individuals manifesting these
effects were estimated to have been of the order of 3-4 g total intake over
several months [165]. For two Yusho patients a daily PCB consumption of 67
fig/kg for 3 months was estimated [167]. The maximum intake would have been
of the order of 50 ppm in the diet or 0.5-1 mg/kg/day. For comparative
purposes, absorption of PCBs from inhalation during maximum occupational
exposures that have been reported (10 mg/cu m) probably did not exceed 0.15
mg/kg/day.
The extent to which PCB consumption was responsible for the effects
on the liver is not known since the contaminated oil also contained PCDFs
[20,160] in quantities that could have resulted in a maximum PCDF
consumption of 20-50 mg. Autopsy findings 1-3 years after the poisonings
indicated unusually high concentrations of PCDFs (0.3-2.5 jag/g) relative to
PCBs (3.5-5.6 Mg/g) in liver fat [L60],
Although most animal feeding experiments have been conducted with
dietary levels of PCBs that are much higher than those ingested by Yusho
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patients, others have been conducted with dietary PCB levels that seem to
confirm the Yusho findings. Experiments have been reported with various
commercial PCB mixtures (Aroclors 1242, 1254, 1260, and Clophen A60) added
to the diet at 1-10 ppm [101,209-212,215,228,233], These experiments
demonstrated Increased liver weights at all concentrations, dose dependent
stimulation of microsomal enzyme activities, detectable proliferation of
the SER at concentrations of 10-100 ppm, and other microscopic changes
Including enlarged hepatocytes, hepatocytlc vacuolization, and, with
prolonged exposures, development of adenoflbrosls.
At high PCB concentrations (>1.5 mg/cu m), Inhalation experiments
with animals have demonstrated Increased liver weights [98,99,202,203].
Microscopic changes similar to those seen from PCB Ingestion were found In
livers of rats after Inhalation of Aroclor 1254 at 1.5 mg/cu m or more
[203], and from other commercial preparations (Decachlorodlphenyl and
Solvol) at much higher concentrations (>4 mg/cu m) [99,202],
These data from the Yusho poisonings and from animal experiments
Indicate that hepatic effects seen In human are similar to those seen In
animals. They also Indicate that some commercial preparations may be less
severe liver poisons than others, but the data are not definitive In this
regard. The ingestion experiments demonstrated increased liver weights
from feeding PCBs at 1 ppm, and increasing evidence of liver injury as
dietary PCB levels were increased. A dietary level of 1 ppm may be
considered roughly equivalent to a daily intake of the order of 0.01-0.02
mg/kg, which would be somewhat similar to the Intake from inhaling PCBs at
1 mg/cu m.
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Several reports of occupational exposures to PCBs have Involved the
liver in various ways [123,125,127,186,190,191,197,198,200].
In the earliest reports of PCB toxicity [123,135,127], the PCBs were
mixed with chlorinated naphthalenes. The mixtures caused many cases of
chloracne and, in some cases, jaundice. Liver cirrhosis with superimposed
yellow atrophy was found in at least one fatality [125]. Similar findings
have not been reported where exposures were to only PCBs in the absence of
chlorinated naphthalenes.
Mention of nausea and digestive disturbances in some reports
[123,197] may have indicated liver injury. In the study by Schwartz [123],
neither liver function test findings nor exposure concentrations were
reported. In the Levy et al report [197], liver function tests (SAP, SGOT,
SGPT, total bilirubin) performed at the time of the study did not indicate
current liver injury. The workers had been exposed to unidentified-PCBs at
0.013-0.264 mg/cu m, and blood PCB concentrations were 36-286 ppb. Even
though there were no findings of current liver injury, these investigators'
[197] examination of past medical records showed occasional findings
indicative of slight liver injury (elevated serum enzymes, triglycerides,
and uric acid), A report of a worker who was removed from further exposure
after experiencing nausea on exposure to an askarel containing Aroclor 1254
was not accompanied by liver function test results or exposure
concentration data (In the Matter of General Electric Company, File No.
2833, New York State Department of Environmental Conservation, 1975).
More conclusive studies of liver function were reported by Meigs et
al [190], Hasegawa et al [191], Hara et al [192,193], and Ouw et al [196].
Of the workers exposed to vapors of an undefined PCB at 0.1 mg/cu m in the
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study by Meigs et al [190], liver function tests were performed on seven.
Findings in six of the workers were normal and, in the other one, cephalin
flocculation and thymol turbidity tests were on the borderline of
abnormality. Hasegawa et al [191] found some changes In liver function
tests (increased SGOT, SGPT, and SAP, and decreased serum cholinesterase
and lipids) of 99 workers exposed to Kanechlors but the investigators
considered that only the decreased serum lipids were significant. PCB
exposure concentrations at the time of the study were 0.065-1.6 mg/cu m.
The workers had exposure histories of <1 to 20 years. PCB concentrations
in blood samples of the workers averaged 370 ppb.
Hara et al [192] did not find evidence of a correlation of serum
triglyceride concentrations with blood PCB concentrations during the first
year after the work with PCBs was discontinued. However, when the same
workers were studied 2 years after stopping work with PCBs, the proportion
of workers with elevated serum triglycerides increased as residual blood
PCB levels increased [193], The effect was particularly prominent in
workers with residual blood PCB concentrations >50 ppb. In a study of 34
workers exposed to Aroclor 1242 in capacitor manufacture, Ouw et al [196]
found individual abnormalities In SGPT, SAP, and serum bilirubin, but
average values for the group were normal. Bromsulphaleln retention tests
were elevated in four workers. Ouw et al [196] considered that there were
no adverse responses In workers with blood PCB concentrations below 200
ppb. The PCB exposure concentrations were 0.32-1.44 mg/cu m.
No evidence of Impaired liver function was found In other studies
[186,194,195,198] where PCB exposures were reported as: Aroclor 1254 at 5-7
mg/cu m for 2-4 years [186]: Kanechlors at >0.25 mg/cu m [1951: and
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unidentified PCBs at <1 mg/cu m for 4 years [198],
Evidence relating to impaired liver function from occupational
exposures to PCBs is generally consistent with findings in Yusho patients
and in animal studies that indicated some effects could be expected from
PCB intakes equivalent to PCB inhalation at about 1 mg/cu m. The
occupational exposure studies show occasional evidence of liver injury in
workers exposed at concentrations of 0.013-0.264 mg/cu m [197], 0.1 mg/cu m
[190], 0.045-1,6 mg/cu m [191], and 0.32-1.44 mg/cu m [196], Whether the
observed effects occurred with exposures at the lower end of all these
ranges is not known.
The occupational exposure studies also showed delayed recovery of
normal serum triglycerides after exposures to PCBs stopped [193], The
elevated serum triglycerides were related to the higher residual blood PCB
concentrations, and these in turn were related to the years of exposure.
Residual PCBs have repeatedly been shown to be the more highly chlorinated
isomers and those metabolized with greater difficulty
[7,36,51,83,103,110,135,136].
Summaries of effects of PCBs on humans and animals are presented in
Tables III-9 and 111-10, respectively.
Carcinogenclty, Mutagenicity, Teratogenicity, and Effects on Reproduction
(a) Carcinogenicity
There is extensive evidence for formation of arene oxide
intermediates during the metabolism of PCBs by several species including
rhesus monkeys [51,68,69,74,75,81,115,116,118]. Arene oxide formation was
also proposed as a plausible intermediate in the metabolism of the slowly
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metabolized 2,2',4,A1,5,5'-hexachlorobiphenyl [70,79], Binding PCB
metabolites to nuclear components of liver cells has been demonstrated on
administration of PCBs to monkeys [51], and to rats [81], and by in vitro
experiments [51,82,86,116,117]. This Information is sufficient to arouse
suspicions that PCBs could have carcinogenic potential in humans.
Hepatomas were produced in 170 of 184 examined female rats fed
Aroclor 1260 at 100 ppm from 3-4 to 23 months of age [218], and in 9 of 22
BALB/cj male mice fed Aroclor 1254 at 300 ppm for 11 months [221]. The
tumors found In the rats included 26 hepatocarclnomas and 144 neoplastic
nodules. Only one liver tumor, a hepatocarclnoma, was found in 173 control
rats.
In another report (Federal Register 42:6532-55. February 2, 1977),
dose-related incidences of liver tumors were reported In rats fed Aroclors
1242, 1254, or 1260 at 1, 10, and 100 ppm in the diet for 24 months. No
liver tumors were reported in rats fed the diets containing PCBs at 1 ppm.
Only one tumor, a hyperplastic nodule (neoplastic nodule), was found in 23
controls. Neoplastic nodules were found In the livers of rats fed the diet
containing 10 ppm of PCBs (2/10, 3/26, and 9/23 for Aroclor 1242, 1254, and
1260, respectively). Higher tumor incidences were found when diets
containing PCBs at 100 ppm were fed (11/20, 19/27, and 14/27 for Aroclors
1242, 1254, and 1260, respectively) and the tumor9 included hepatomas and
cholangiohepatomas (3, 6, and 7 for Aroclors 1242, 1254 and 1260,
respectively). In this experiment the incidence of pituitary tumors was
high in PCB-fed rat9.
In a study sponsored by the National Cancer Institute, Aroclor 1254
was fed to groups of 24 rats at 25, 50, and 100 ppm in the diet. No liver
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tumors were found in the controls, in the experimental females at any dose
level, or in experimental males fed PCBs at 25 ppm. However,
hepatocellular carcinomas were found in a male rat fed Aroclor 1254 at 50
ppm and in two males fed the PCB at 100 ppm. The data also indicated that
the incidence of leukemias in males was dose-related (3/24 in controls;
8/24 in rats fed 100 ppm).
Kanechlors have also been found to produce liver tumors when fed to
mice and rats [240,241,242]. Of 12 mice fed Kanechlor 500 at 500 ppm for
32 weeks, 7 developed neoplastic liver nodules and 5 had well-developed
hepatocellular carcinomas [240,241], In this experiment which had only 12
mice/group and continued for only 32 weeks, liver tumors were not found
with Kanechlors 300 and 400 or with lower dose levels of Kanechlor 500.
However in another experiment [242], Kanechlor 400 fed to 10 male and 10
female rats for 58 weeks did produce liver tumors in the females. In this
experiment the amounts fed (38-616 ppm) varied from time to time, but were
in the 308-616 ppm range for the last 43 weeks.
These findings from animal studies indicated to NIOSH that PCBs have
potential carcinogenic activity in humans. They indicate, but do not
conclusively demonstrate, with the dietary levels used, that the less
highly chlorinated mixtures (Aroclor 1242 and Kanechlors 300 and 400) have
less carcinogenic potential than the more highly chlorinated mixtures
(Aroclors 1254 and 1260 and Kanechlor 500). However, all PCB mixtures
adequately tested in rats and mice have shown carcinogenic activity. The
intakes of PCBs at the lowest dietary level that has produced tumors in
rats (10 ppm) would be somewhat comparable to intakes from occupational
exposures at 5-10 ng/cu m. However PCBs are slowly eliminated from the
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body and the higher chlorinated compounds may accumulate in the body for
years. Thus animal experiments that are limited to 2 years by the life
span of the animals may not be Informative relative to workers exposed for
up to 45 years.
In humans, there are no adequate studies to confirm or deny
carcinogenicity although preliminary data suggest that among Yusho
patients, deaths due to cancers exceed expectations [160,161] and
preliminary studies of two occupatlonally exposed groups in the US Indicate
that the occurrence of certain cancers may be excessive (HA Sinclaire,
written communication, June 1976; G Roush, written communication, September
1976). However, the two reports are not consistent as to the types of
cancers found to occur more frequently than expected.
(b) Mutagenicity
Several PCBs and PCB mixtures, including the 4- and the 2,2' ,5,5' —
Isomers and Aroclors 1221, 1254, and 1260, were subjected to the "Ames"
test for mutagenicity [116], Although 4-chlorobiphenyl had mutagenic
activity in this test, the more highly chlorinated PCBs showed very little
activity. Aroclor 1254 did not cause significant chromosomal changes in
the testes of rats after it was administered for 7 days at 50 mg/kg/day
[235]. In another experiment [236], neither Aroclor 1254 administered at
300 mg/kg/day for 5 days nor Aroclor 1242 administered at 500 mg/kg/day for
4 days produced chromosomal aberrations in spermatagonial or bone marrow
cells of rats. These mixtures also did not produce any evidence of
dominant lethal mutations in rats [237], Although PCBs have little
mutagenic potential, they may alter the mutagenicity and carcinogenicity of
other compounds by stimulating microsomal enzyme activities [239],
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(c) Teratogenicity
PCBs have been found in embryonic and fetal tissues of humans
[139,168] and experimental animals [101] after introduction of PCBs into
the maternal body, demonstrating that the potential for direct teratogenic
effects exists. Several experiments have been conducted with rats
[101,228], rabbits [229], monkeys [232], and dogs and pigs (FL Earl et al,
written communication, 1976) that are relevent to a discussion of PCB
teratogenicity. In some of these experiments, the PCBs were administered
by gavage and doses were reported in mg/kg; in other experiments, the PCBs
were reported as ppm fed in the diet. For purposes of relative comparison,
50 ppm in the diet can be equated to 1 mg/kg/day. This is the order of
magnitude of the maximum rate of PCB intake by Yusho patients. Animal
experiments have used PCBs in dietary-equivalent amounts of 1-2,500 ppm.
In most experiments with PCBs administered in amounts equivalent to dietary
levels of 100 ppm or more, fetotoxicity (resorptions, absortions) has been
such that teratogenic effects may have been masked [101,228,229]. In the
two-generation feeding study of rats by Linder et al [228], no terata were
reported. This study covered Aroclor 1254 in the concentration range of 1-
100 ppm and Aroclor 1260 in the range of 5-100 ppm. Although terata were
not reported, Aroclor 1254 concentrations of 20-100 ppm resulted in reduced
litter sizes. In rhesus monkeys [232], feeding Aroclor 1248 at 2.5 and 5
ppm caused abortions in some cases and lower than normal birth weights, but
no terata were reported. In dogs, terata were not found in pups born from
dams fed the equivalent of 12 ppm in the diet, but were present when 48- or
200-ppm equivalents were fed. Sows fed the equivalent of 50 ppm in the
same experiment had high rates of resorptions and, at 10-30 times this
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level, terata were definitely present in the piglets (FL Earl et al,
written communication, 1976).
Although there were retarded intrauterine growth and signs of PCB
toxicity in Yusho babies at birth, no terata were reported
[149,159,176,182,183]. A normal baby was born to a woman exposed to PCBs
in her work. The PCB exposure concentrations were not reported but the PCB
concentration in her blood was 25 ppb at the time the baby was born.
These studies indicate that PCBs have teratogenic potential for
humans* However, the terata observed in animals occurred at levels at or
above doses equivalent to the maximum doses of the Yusho patients and at
intake rates 3-4 times greater than Intakes _ expected from inhalation at
maximum reported occupational exposures.
(d) Other Effects on Reproduction
Feeding rats Aroclor 1254 at 5 ppm or Aroclor 1260 at 100 ppm had no
effects on reproduction over two generations [228]. At higher dietary
levels, reproductive effects Included poor mating performances, fewer
lltter9, reduced litter size, and high postnatal death rates in the
litters. In rabbits, Aroclors 1221 and 1254 were not fetotoxic when
administered only during gestation in amounts equivalent to dietary levels
of about 50-500 ppm [229]. However, when administered during gestation at
higher levels (600-2,500 ppm dietary equivalent), Aroclor 1254 caused
resorptions, abortions, maternal death, and, in two fetuses, asymmetric
skulls [230]. Delaying administration of PCBs until after the first week
of pregnancy did not eliminate the effects.
Feeding rhesus monkeys Aroclor 1248 at 25 ppm for 2 months resulted
in a high degree of infertility that persisted for at least 8 months after
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the last ingestion of PCBs [232], In another experiment, rhesus monkeys
fed Aroclor 1248 at 2.5 and 5 ppm for 6 months had irregular menstrual
cycles with excessive and prolonged bleeding [233], Even though these
monkeys conceived well on mating, resorptions and abortions were frequent,
and infertility was common in subsequent matings [233]. Nursing infants
developed chloracne-like signs within 2 months and infants frequently died
during the nursing period. The milk contained PCBs at 0.154-0.397 ppm
[234].
There are no reports of infertility or abortions attributed to human
PCB consumption or exposure. There are reports of undesirable effects in
children born to mothers exposed to PCBs in the diet and of undesirable
effects developing from nursing such mothers.
Babies born from mothers with Yusho were often dark colored and
developed signs of Yusho after nursing [176,182,183], In at least one
case, Yusho developed in a baby who was only exposed to PCBs by nursing
[182], Concentrations of PCBs in milk were not determined at the time of
the Yusho poisoning. A milk sample obtained after birth of a normal baby
from a woman exposed to PCBs at work contained PCBs at 0.25 ppm, and
nursing was discontinued [195]. The woman's exposure history and time of
last exposure were not given, but PCBs were present in her blood at 24 ppb.
Based on the findings in monkeys [234] the decision to not nurse the baby
seems entirely justified.
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TABLE III-9
EFFECTS OF PCBa ON HUMANS
FCB Intake
Expoaure Index
Source
Duration Environmental, Blood
Amount/kind (ppb)
Effects
Ref.
Ingestion
Occupational
Up to 8 mon 0.3-4g
Kanechlor 400
Not known 10 mg/cu m
4-8 mon
5-7 mg/cu ra
Aroclor 1254
2.5-4 mon Not reported
<1-20 yr
0.2-1.6
mg/cu m
Kanechlors
2.5 yr ave. Not reported
Kanechlors
Not reported >0.25 mg/cu m
Not reported
2.5-18 yr
0.013-0.27
mg/cu m
Not reported
>50 Yusho
Unbearable
irritation
Chloracne,
no liver
injury
Chloracne,
hyperpig-
mentation
370, ave. Chloracne,
hyperpig-
mentation,
liver injury
820, ave. Chloracne,
no liver
130-520
36-286
14 mon ave. 0.1 mg/cu m
Not reported
" Not reported
refuae workers
<1-14
injury
Chloracne,
liver injury
Irritation,
liver injury
Chloracne,
liver injury
No effects
145-
185
130
186
187
191
194
195
197
190
199
123
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TABLE III-9 (CONTINUED)
EFFECTS OF PCBs ON HUMANS
PCB Intake
Exposure
Index
Source
Duration
Environmental
Amount/kind
, Blood
(ppb)
Effects
Ref.
Occupational
2-23 yr
0.32-1.44
mg/cu m
Aroclor 1242
>200
Chloracne,
liver injury
196
If
1-23 yr
0.32-1.44
mg/cu m
Aroclor 1242
<200
No effects
196
ll
Up to 15 yr
Not reported
Kanechlor9
7-300
Chloracne,
elevated
triglycerides
192,
193
If
Not reported
Not reported
Kanechlor9
24
10-100
Normal baby
Mild chlor-
acne
195
II
4 year8
(>1 mg/cu m)
Aroclor 1242
74-1,900
No effects
198
General
environment
Continuous
Air, 1-100
Food, 10-20
jug/d
>1-30
No effects
137-
141
124
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TABLE III-10
EFFECTS OF PCB INHALATION ON ANIMALS
Exposure Conditions
Material og/cu m Duration Species Effects Ref.
Pydraul A 200
30,000
2 hr
Rats
PCB in liver, 70 ppm
97
Solvol
10,000
3 hr
100% mortality,
Liver necrosis
202
II
250-500
8-69 3-hr
exposures
>1
Liver necrosis, hyper-
plasia of Kupffer cells
202
Decachloro-
dlphenyl
2,500
6 hr
fl
Irritation, no
gross effects
98
11
800
6 hr/d,
5 d/wk,
4 wk
Irritation, increased
liver weights, micro-
scopic liver changes
blood cell changes
99
• 4
4 and 80
fl
H
No irritation,
increased liver
weights In females
99
Aroclor 1242
8.6
7 hr/d,
5 d/wk,
3 wk
Mouse,
rat, cat
guinea
Pig.
rabbit
None
•
203
M
6.8
7 hr/d,
5 d/wk,
17 wk
H
It
203
It
1.9
7 hr/d,
5 d/wk,
31 wk
11
H
203
Aroclor 1254
5.4
7 hr/d,
5 d/wk,
17 wk
It
Microscopic
liver
changes
203
tl
1.5
7 hr/d,
5 d/wk,
31 wk
ri
Microscopic
liver changes;
reversible
203
125
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IV. ENVIRONMENTAL DATA AND BIOLOGIC EVALUATION
Environmental Concentrations
Two reports of workroom air concentrations of PCBs appeared in 1954
[186,190], Puccinelli [186] studied the concentrations in air of a
capacitor factory in Italy, using the methods of Elkins [130], and found
concentrations in 500-liter air samples of 5.2-6.4 mg/cu m. Miegs et al
[190] did not report on the analytical methods they used to determine
concentrations of PCBs in thq breathing zones of workers exposed when a
heat exchange unit in a Connecticut factory leaked. From the description
of the factory, it is likely that the exposures were largely to vapors; the
concentration found was 0.1 mg/cu m.
In 1959, Elkins [130] reported that over a number of years, PCBs in
some Massachusetts plants ranged up to 10.5 mg/cu m of air (Table IV-1),
TABLE IV-1
PCB CONCENTRATIONS MEASURED IN MASSACHUSETTS FACTORIES
Process
PCB Concentrations
Maximum
(mg/cu m)
Average
Capacitor impregnating
10.5
5.8
ri
5.5
4.5
M
0.3
0.2
Capacitor soldering
0.9
0.8
Oil mixing
1.1
0.6
Regulator filling
0.2
0.1
Adapted from reference 130
126
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Of 21 air samples collected in capacitor impregnating operations,
Elkins considered that hazardous concentrations (>1 ppm for Aroclor 1242;
>0.5 ppm for Aroclor 1254) existed in 15. While the sampling and
analytical methods used were not documented, Elkins [130] recommended
sampling with either a fritted bubbler or two lmplngers In series, both
containing amyl acetate, and analyzing by the sulfur lamp method.
Occupational environmental studies were conducted in five Japanese
plants by Hasegava et al [191]. Kanechlors 200 (predominantly
dichlorobiphenyls), 300 (mostly trichlorobiphenyls), and 400 (mostly
tetrachloroblphenyls) were used or manufactured In the plants. Air samples
were drawn through filter paper to collect particulate matter and normal
hexane to collect vapors and analyzed by GLC. The data are summarized In
Table III-7. In the paired samples, the vapor concentrations exceeded the
particulate concentrations. One of the plants was a blphenyl recovery
plant where PCBs were not used. In this plant, PCB concentrations were
<0.02 mg/cu m. In the PCB manufacturing plant, PCB vapor concentrations
were 0.026-0.163 mg/cu m, and particulate PCB concentrations were 0.019-
0.037 mg/cu m. Higher PCB concentrations were found in the capacitor
plants: 0.095-0.965 mg/cu m of vapors, and 0.20-0.65 mg/cu m of
particulates. In one particulate sample collected In a capacitor plant
after a spill, the PCB concentration was 6.2 mg/cu m.
Staiff et al [243] in a 1974 report were concerned about emissions
from burned-out PCB-containing ballasts in fluorescent fixtures in their
laboratory. The Investigators collected samples in two midget impingers,
containing ethylene glycol and connected in series. The samples were
analyzed by GLC. PCB concentrations in the air ranged from 0.012 to 0.166
127
-------
mg/cu m when the ballasts burned out and were 0,002 mg/cu m 3 days later.
In a 1976 report of a survey of Australian workers exposed to Aroclor
1242, Ouw et al [196] listed breathing zone concentrations ranging from
0.32 to 2.22 mg/cu m before corrective measures were taken, and from 0.08
to 0.75 mg/cu m after installing improved ventilation. Breathing zone
samples were collected at 30 liters/minute using Greenburg-Smith impingers
containing 75 ml of isopropanol. The concentrations found are shown in
Table IV-2.
TABLE IV-2
PCB CONCENTRATIONS IN THE AIR INSIDE A CAPACITOR PLANT BEFORE
AND AFTER IMPROVEMENT OF EXHAUST VENTILATION SYSTEM
Areas in the Impregnation Room
PCB
Before
Concentrations
mg/cu m
After
Area in the unloading tank in front
of exhaust register from operator's
breathing zone
1.44
0.75
Area in the unloading tank not in
front of exhaust register
2.22
0.7
General atmosphere near tank
1.08
0.18
Soldering area
0.32
0.08
Adapted from reference 196
Exposures of electrical and materials technicians during 1976 to PCBs
contained in materials they tested were evaluated by Levy et al [197]. Air
samples were collected on magnesium silicate "Florisil" at 50 ml/minute for
128
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4-8 hours and analyzed by GLC utilizing electron capture detection.
Breathing zone samples were collected on a single day from nine employees
for 8 hours. The concentrations in the nine breathing zone samples, which
would represent TWA exposure concentrations for the day, ranged from 0.014
to 0.073 mg/cu m. Concentrations of PCBs in nine point source samples
collected over 4-8 hours on each of 3 days ranged from 0.013 to 0.264 mg/cu
m, and in 19 room air samples collected over 4 hours on each of 3 days,
from 0.08 to 0.16 mg/cu m.
A plant manufacturing PCBs in the US was surveyed for worker exposure
in July 1976 [244], Three Aroclors (1016, 1242, and 1254) were made in the
PCB production area. To begin the process, biphenyl and chlorine were
piped into a chlorinator with a catalyst and allowed to react. Two
separate groups of chlorinators were used for Aroclors 1242 and 1254. The
product resulting from the reaction passed through a purifying operation,
or to a distillation column as In the case of converting Aroclor 1242 to
Aroclor 1016, and then on to the storage tanks. Mixing tanks were used to
give the desired properties to the final product.
Although the operation was outdoors and theoretically a closed
system, potential for employee exposure existed when samples were drawn or
leaks occurred. Local exhaust ventilation was used In two operations: (1)
while filling 55-gallon drums, hoses were placed near the openings, and (2)
when employees tested samples drawn from the chlorinators, their work
station was equipped with an exhaust fan and hood.
Eleven personal and seven area air samples were taken in the PCB
production area for 6-8 hours at a flow rate of 200 cc/minute [244], PCBs
were collected on Florisil, desorbed with hexane, and analyzed by GLC with
129
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EC detection. Aroclor 1016 was the PCB produced on the sampling dates, and
it was used as the standard for quantitating airborne PCBs. Personal air
sample concentrations of PCBs reported as Aroclor 1016 ranged from 20 to 86
Aig/cu m, while PCBs in area samples ranged from 16 to 55 Kg/cu m. The data
are presented in Table IV-3.
TABLE IV-3
PCB CONCENTRATIONS FOUND IN A PLANT MANUFACTURING PCBs
ON 2 CONSECUTIVE DAYS Oig/cu m)*
Personal Air Samples
Job Title
7/21/76
7/22/76
Premium operator
47
20
Second operator
46
43
Column operator
64
51
Still operator
40
86
Standard operator
-
61
Distribution operator
54
36
Area Air Samples
Location
7/21/76
2/22/76
Drumming
43
51
Temperature testing
25
52
Chlorinators
55
36
Incinerator burner
16
-
*Total sampling time varied from 409 to 4 55 minutes and sample volumes
varied from 67.6 to 201.6 liters.
Adapted from reference 244
130
-------
Sato and Hasegawa [32] studied concentrations of FCBs In factories
that had discontinued their use in production of pressure-sensitive copying
paper 2 years earlier. PCB concentrations In the factories had not been
determined when PCBs were being used, but were considered [3] to have been
similar to those found by Hasagawa et al [196] in capacitor manufacturing
plants. The concentrations found by Sato and Haswgawa [32] at the time of
sampling ranged from 0.13 to 4.4 ug/cu tn. The PCB concentrations In the
outdoor air around the factories were 0.043-0.09 /ig/cu m [3].
Another study * of contamination In factories after PCB use had been
discontinued was reported by Fujlwara et al [33]. These Investigators
found 0.25 mg/cu m In air of a factory that had previously used PCBs in
silk glossing. In addition to air contamination, PCBs were found In the
dust around machinery and In the floor boards.
PCB concentrations found In the air of some other factories and their
surrounding environments in Japan were summarized In 1976 by Tatsukawa
[245]. Concentrations found before 1957 in a factory producing
transformers and capacitors ranged from 0.39 to 4.5 mg/cu m. The factory
was said to have been old-fashioned with bad ventilation [245],
Concentrations found in warehouses for carbonless copying paper in 1972
ranged from 2 to 70 #ig/cu m. In the same year, concentrations of 0.04-0.05
/ig/cu m were found in a university laboratory where PCBs were used, and
concentrations of 0.006-0.12 jig/cu m were found in areas of mills that
recycled paper. Background concentrations found In urban areas of Tokyo,
Osaka, and Mat9uyama City were <0.002-0.04 jug/cu m.
Background concentrations of PCBs in ambient air over the US have
been reported in ng/cu m quantities [26,38]. Average concentrations of
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about 100 ng/cu m were found in Florida and Colorado in 1975 [38],
Control of Exposure
The present primary use of PCBs is as dielectric or insulating fluids
for electrical capacitors and transformers. Potential hazards of PCBs in
these industries result from inhalation and dermal exposures. It is here
that engineering controls, such as local exhaust systems, are necessary.
Local exhaust systems should be designed and operated in conformance
with American National Standard Z9.2-1971 Fundamentals Governing the Design
and Operation of Local Exhaust Systems [246], Guidelines for handling
capacitor and transformer askarels include the following recommendations
from the American National Standards Institute (ANSI) [4]: (1) Enclosed
systems of sealed piping, properly gasketed joints, valves, containers, and
processing chambers should be used for any portion of the operation where
askarel temperatures may exceed 55 C; (2) Enclosure should preferably
extend to all other portions of the system insofar as practicable; (3)
Operations utilizing PCBs should be isolated from other manufacturing areas
to avoid cross contamination; (4) Provision should be made for adequate
ventilation and regulation of manufacturing operations to avoid open
exposure to askarels; (5) When askarels are used at elevated temperatures
(especially 55 C or higher), engineering controls must be applied, either
by the use of closed systems or by effective local exhaust ventilation with
general workroom exhaust.
Durfee et al [247] cited the following potential sources of air
emissions of PCBs in transformer and capacitor manufacturing operations:
(1) vapor exhaust from stream jet ejectors; (2) evaporation from accidental
132
-------
spills; (3) evaporation from hot surfaces as part of flood-filling,
inspection, or holding operations; (A) vacuum pump exhausts; (5)
evaporation from plant waste water.
There are currently no commercially available fluids which can be
considered as totally acceptable substitutes for PCBs in the broad range of
AC capacitors, nor are there substitute dielectric systems which would
satisfy reliability and safety requirements In most applications [28].
Transformers containing PCBs represent only about 5% of the US transformer
market, and are used only where safety and reliability are of prime
Importance. For new Installations, building and installation design
provisions could be made to accommodate the use of filled, open dry-type,
or sealed dry-type transformers. Major construction changes would be
required to compensate for the fire resistance of askarel-filled units if
existing askarel-filled transformers are to be replaced with oil-filled
units of equivalent electrical ratings [4].
Environmental Sampling and Analytical Methods
(a) Air Sampling
Before discussing the various methods available for sampling airborne
PCBs, it is pertinent to discuss the criteria for an ideal sampling device.
NIOSH evaluated an Industrial worker's exposure and found that sampling In
the breathing zone gives a truer picture of actual exposure than does area
sampling. The first criterion for an ideal air sampling device then is
that it be amenable to personal sampling. In addition, it should be light,
compact, and small enough so that workers can pursue their daily activities
without being aware of its presence. The second criterion is that the
133
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sampling device have a sufficient capacity for PCBs to enable the
collection of an air sample representative of a typical workday. Thirdly,
recovery of PCBs from the sampling device should be quantitative or, at the
least, reproducible. Finally, the sample must be stable in or on the
sampling device between the time of sampling and the time of analysis.
This latter criterion is hardly of concern here due to the general
stability of PCBs.
An air sampling procedure using fritted bubblers or impingers filled
with toluene was published by ANSI in 1974 [4]. Neither the sampler
capacity nor the sampling efficiency had been experimentally evaluated.
Where high sampling flow rates or high capacities were required, additional
bubblers or impingers in series were recommended.
Bidleman and Olney [248] used porous polyurethane foam for collecting
samples of atmospheric PCBs. They found that the polyurethane foam showed
excellent collection efficiency (99% or better) for tri-, tetra-, and
pentachlorobiphenyls. The authors [248] did not address the matter of
sample recovery from the sorbent.
In an environment where carbonless copy paper was being used,
Nishiyama et al [249] collected PCBs by drawing the air through a cooled
column filled with Shimalite, a gas chromatographic solid support similar
to Chromosorb W. The collection efficiency of the device was 95% and the
PCB9 were eluted from the column with hexane. Other investigators used 5%
glycerol-coated Florisil for collecting organochlorine pesticides and PCBs
from air [250], Collection efficiencies were 90-100% for PCBs.
Harvey and Steinhauer [251] collected ambient air samples of PCBs
using 0.25% OV-17 silicone oil coated on ceramic saddles (distillation
134
-------
column packing). The collection efficiency of thia device was 70%. More
recently, Glam et aL [252] found that aorbent tubes packed with deactivated
Florisil could be used for collecting PCBs and phthalates from air [252] .
These compounds were found to be effectively retained by Florisil. The
authors did not discuss efficiency of recovery.
In 1976, Laveskog and Lindskog [253] described a stack sampling
device for chlorinated hydrocarbons which they used for PCB collection.
This device utilized glass wool for the collection of particulates followed
by a sorbent, 25-40% Aplezon M on Chromosorb W, to collect vapors. The
collection efficiency of the column was 99%, and desorption efficiency with
absolute ethanol was 87%. The authors investigated charcoal as a sorbent,
but found It unsuitable for their purposes since the PCBs could only be
recovered by extraction in a soxhlet apparatus with chloroform which in
turn could not be used with electron capture detection.
Occupational Safety and Health Administration (OSHA) workers have-
used charcoal tubes for personal air sampling for PCBs (RG Kupel, written
communication, 1976). While the sampling device would be expected to have
good capacity for PCBs, recovery from charcoal is not quantitative. Little
other information is known about this method.
A NIOSH Standards Completion Program Report [254] indicated that PCBs
with 54% chlorine content were effectively trapped on a fibrous glass
filter. However, the presence of PCB vapor either apparently was not
addressed or was assumed to be negligible. This may not be a valid
assumption, particularly since another report from the same program [255]
showed that PCBs with 42% chlorine content have appreciable vapor pressure.
135
-------
NIOSH has also investigated the method of Giam et al [252], using
Florisil as a sampling medium, in industrial environments. Flori9il (30/48
mesh) was placed in a tube similar to that used in the charcoal tube method
for solvents, 100 mg in the front section and 50 rag in the back. The
retention capacity of this sampling device for PCBs was evaluated under
laboratory and field conditions, using various vapor generation techniques.
In laboratory experiments, PCBs at 10 yg/liter and 75£ relative humidity
were sampled through a 100-mg Florisil bed at 0.2 liter/minute with no
evidence of breakthrough after U hours (48 liters). Of 21 samples
collected on Florisil in a capacitor plant, only 6 had PCBs on the backup
section and all 6 backup sections contained 1% or less of the total PCBs in
the tube. The volumes of air sampled ranged up to 61 liters, and PCB
concentrations in air as high as 1.5 /xg/liter were measured. Other
laboratory experiments showed that PCBs could be desorbed quantitatively
from Florisil with hexane. Results from Florisil tube and impinger samples
taken side by side in the capacitor plant and analyzed with a single
commercial PCB product as a standard were statistically similar.
Impingers are not suitable for personal sampling and are inconvenient
to use because they must be recharged with the sampling solvent frequently
and mu9t be used in series. The handling of absorber solutions is
difficult because of the potential for spillage and leakage of the solvent
and samples during transport to and from the sampling site. Solid sorbent
sampling devices are well suited for personal sampling since they are
relatively small, and personnel wearing the devices quickly become unaware
of their presence, enabling more representative sampling. Shipment of
these devices is relatively simple.
136
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Of the solid sorbent sampling devices discussed, Florlsll-fllled
Cubes are deemed the most advantageous because Florlsll has a high capacity
for PCBs and can be quantitatively desorbed; field evaluations have shown
that Florlsll-fllled tubes are easier to handle and more convenient than
iaplngers. Therefore, the Florlsll-fllled tube method Is recommended for
collection of PCBs from air, as detailed In Appendix I.
(b) Analytical
The chemistry of PCBs was extensively reviewed by Hutzlnger et al
[1], and PCB analytical chemistry has been reviewed by several authors
[256-264] but only references pertinent to selection of an analytical
method for determination of PCBs in industrial air samples will be
discussed here. Of the analytical techniques available, the one most
widely used for determining PCBs Is GLC with EC detection. This technique
Is rapid, precise, and very sensitive. The far greater sensitivity of EC
detection compared with that of the flame ionization detector (FID) is
demonstrated by comparison of their relative responses to various PCB
Isomers, shown in Table IV-4 [1],
137
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TABLE IV-4
RELATIVE MOLAR RESPONSES OF ELECTRON-CAPTURE AND FLAME-IONIZATION
DETECTORS TO SOME PCBs
PCB
Relative Molar
Response
Electron Capture
Flame Ionization
2-chloro
1.00
1.00
3-chloro
0.20
0,92
4-chloro
1.10
0.87
2,2 '-dichloro
5.16
0.99
2,4-dichloro
17.7
0.86
2 ,6-dichloro
32.0
0.91
3,3'-dichloro
6.10
0.94
3,4-dichloro
15.2
0.86
4,4'-dichloro
5.97
0.81
2,4,4'-trichloro
135
0.78
2,2'4,4'-tetrachloro
106
0.87
2,2'6,6'-tetrachloro
20.6
0,90
3,3'4,4'-tetrachloro
396
0.87
3,3'5,5'-tetrachloro
320
0.85
2,3,4,5-tetrachloro
367
0.87
2,3,5,6-tetrachloro
259
0.71
2,2'4,4 *6,6'-hexachloro
34 7
3,3*4,4'5,5'-hexachloro
726
2,2'3,4*5,5*6,6'-octachloro
1,180
2,2'3,3*5,5*6,6'-octachloro
1,150
decachloro
1,410
Adapted from reference 1
During the GLC-EC detection analysis of PCBs, multicomponent mixtures
of various PCBs are almost always encountered. The samples analyzed may or
may not resemble a commercial PCB mixture. If so, the appropriate
commercial PCB mixture can be used as a standard for quantitation; if not,
a commercial mixture should not be used. Quantitation cannot be accurate
since it is based on incomplete resolution of PCR isomers. Even If
complete resolution were possible, all PCB isomers are not available for
standards and the specific EC detection response of each isomer would need
138
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to be known.
Many different methods have been used to "quantitate" or estimate
PCBs. Heights or areas of one [263], tvo [264], three [265], or more
[266,267], or of all chromatographic peaks [268-270] of a given sample have
been used for comparison with standard commercial PCB mixtures• The chief
disadvantage of such methods Is that when the chromatogram of the sample
does not closely resemble that of the standard the estimates are neither
precise nor accurate. An Improvement upon these methods Is the use of
mixed PCB standards, as described by Beezhold and Stout [271], This
procedure Involves mixing various proportions of different PCB commercial
mixtures, such as Aroclor 1242 and Aroclor 1254, and obtaining sets of
chromatograms. The chromatogram most closely resembling the sample is
selected and the corresponding mixture Is used as the standard.
Sawyer [269], in a collaborative study, evaluated the quantitation of
PCBs in chicken fat. He found that the use of the total peak area or the
sum total of all peak heights gave better results than did the use of
selected peaks. The use of mixed standards gave good results when the
composition which best duplicated the response pattern of the sample was
used. This was adopted as an official method by the Association of
Official Analytical Chemists [272],
Using a different approach to standardization, Rote and Murphy [273]
produced a standard response curve using Aroclors 1232, 1242, 1248, 1254,
1260, and 1262. Thi9 plot was of the total area responses on the GLC
trace divided by the weights of the Aroclors injected versus the average
number of chlorine atoms in the molecule. The peaks in each chromatogram
were identified as to chlorine content per chlorobiphenyl molecule, and
139
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each sample could then be quantitated using the response curve. The
accuracy of this method is not greater than that of the methods previously
mentioned, since it has been shown that the response of EC detection varies
greatly with the degree of chlorine substitution and also with the relative
position of the chlorine substitution [1],
Risebrough et al [274] and Collins et al [268] used dichlorodiphenyl-
dichloroethylene (p,p'-DDE) as a standard and assumed that the response of
each chlorobiphenyl isomer was equal to that of p,p'-DDE. This method can
only be grossly approximate, since the response of EC detection to
individual PCB isomers varies greatly [1],
Risebrough et al [274] also reported the use of microcoulometric
detection to determine total chlorine content, using a commercial PCB
mixture as a standard. Sawyer [269] compared the EC detection with the
microcoulmetric and electrolytic conductivity detectors and found that the
latter two detectors are subject to more operational problems than is the
EC detection.
An analytical method utilizing a computer for the quantitation of
PCBs was described by Zobel [275] . This method would not be of value for
routine sample analysis in industrial hygiene laboratories because of the
expense or unavailability of a computer.
The method of Webb and McCall [276] involves standardization of an
Aroclor mixture whose peak-by-peak composition has been determined as
weight percentages of the total. Since the response-to-weight factor is
known for each peak, the actual weight equivalent of each peak in the
sample can be calculated despite vast differences of overall GLC patterns.
To utilize this method as a standard procedure, it is necessary that some
140
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agency serve as a central repository for distribution of the reference
materials. Presently, standards for Aroclors 1242, 1254, and 1260 as
dilute solutions In lso-octane are available from Webb and McCall [276].
However, a fully characterized standard for the widely used Aroclor 1016 Is
not available. Potential future sources for these types of standards nay
be either the Association of Official Analytical Chemists or the US Food
and Drug Administration. These organizations currently are Interested in
this method [277] and are planning to test it collaboratively.
The US Environmental Protection Agency has adopted the method of Webb
and McCall [276] as a recommended procedure for quantitation of PCBs In
industrial effluents [278]. Other Investigators have also concluded that
this method Is the best available method of quantitation [279].
Berg et al f280} investigated the quantitation of PCBs in terms of
derivatives. PCBs could be quantitatively converted by catalytic
dechlorination to blcyclohexyl. However the authors [280] found that the
relatively low level of sensitivity, because blcyclohexyl had to be
determined by GLC with FID, was a marked disadvantage. They [280] found
that treatment of PCBs with anitmony pentachloride under elevated
temperatures and anhydrous conditions gave good yields (85%) of
decachlorobiphenyl which could be determined by GLC with EC detection.
Armour [281] evaluated the perchlorination procedure of Berg et al
[280] to determine its utility as a routine method for the confirmatory
quantitation of PCBs. It wa9 found necessary to modify that procedure
because of observed inconsistencies in the efficiency of conversion of
Aroclors 1254 (90-100%) and 1242 (30-70^) to decachlorobiphenyl. Armour
[281] attributed this to volatilization of the lower molecular weight PCB
141
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components during solvent evaporation before their reaction with antimony
pentachloride. The remedy selected was to end evaporation while a small
amount (0.1 ml) of solvent still remained, but this rendered the choice of
solvents a more critical matter because of possible interferences during
the perchlorination step. Chloroform was the solvent chosen because it
minimized volatility and reacted favorably at the selected conditions. The
increased pressure produced as a result of this substitution of chloroform
required discontinuing use of flame-sealed Carius tubes as recommended by
Berg et al [280] for containing the elevated temperature-pressure
perchlorination reaction. The recommended substitute was a vacuum
hydrolysis tube having the same volume specifications (10 mm O.D. X 150
mm), a tight Teflon sealing valve, and a side venting arm [281],
Other modifications devised by Armour [281] included the addition of
methanol to the reaction mixture's extract to produce an azeotrope with the
residual chloroform which could then be evaporated to a small volume before
dilution, preparatory to determination of decachlorobiphenyl. To determine
the feasibility of a shortened reaction time, Armour et al tested iron as a
catalyst, but decided that although a reaction time of 6 hours with iron
catalyst resulted in quantitative (99% average conversion for six Aroclors)
and reproducible (83-110%) conversions, the catalytic modification offered
little advantage over the overnight procedure.
Perchlorination has been used for the quantitation of PCBs by others
[282,283]. While the sole perchlorination product was usually
decachlorobiphenyl, there have been reports of undesired byproducts
resulting from contamination of the antimony pentachloride with bromide
ions [284,285], Results of NIOSH investigations indicate that this
H2
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contamination problem can be eliminated by vacuum distillation of the
antimony pentachlorlde. Factors for converting decachlorobiphenyl to
Aroclors are presented in Table IV-5.
TABLE IV-5
FACTORS TO CONVERT DECACHLOROBIPHENYL TO AN EQUIVALENT AMOUNT OF AROCLOR
Aroclor
Average
Molecular
Weight
Q*
1221
188.5
0.38
1232
223
0.45
1242
257.5
0.52
1016
257.5
0.52
1248
292
0.59
1254
326.4
0.65
1260
361
0.72
1262
395.3
0.79
Calculated by dividing the average molecular weight by 499, the molecular
weight of decachlorobiphenyl
Adapted from reference 281
From a review of the literature, NIOSH concludes that the simplest
method of PCB quantitation involves standardization of samples with single
commercial mixtures of PCBs. Should the composition of a sample not
closely resemble that of a single commercial PCB mixture, the most accurate
and precise method of quantitation available would be that of
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perchlorination, which seems to offer the best approach for determining
total PCB content in samples when the initial concentrations of individual
PCB8 are of little or no concern.
N10SH recommends desorption of PCBs from Florisil with hexane,
analysis by GLC, and quantitation of the sample by comparison with a
standard PCB mixture of similar composition (Appendix II). If a PCB
mixture with a composition similar to that of the sample is not available
as a standard, NIOSH recommends converting the sample PCBb to
decachlorobiphenyl for quantitation.
The methodology presented in Appendices I and II has been tested with
Aroclor 1016 in the laboratory and in practice. Operating parameters found
by NIOSH are presented in the Appendices.
Biologic Evaluation
While there is presently no adequate method for biologically
monitoring industrial workers for exposure to PCBs, additional research may
make feasible the routine measurement of residues of these .compounds in
blood or other body fluids.
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V. WORK PRACTICES
The employment of good work practices 1b required If hazardous
occupational exposures to PCBs are to be prevented. The carcinogenic,
teratogenic, dermatologic, and fetotoxlc effects of PCBs largely determine
the nature of necessary work practices.
(a) All locations where occupational exposure to PCBs occurs
should be established as regulated areas and posted with signs warning
persons of the procedures necessary upon entering or leaving.
Vhen an otherwise closed PCB system Is opened, eg, during the loading
and unloading of storage tanks, the following work practices are desirable:
(1) Only authorized personnel should be permitted In the area;
(2) Adequate ventilation should be provided and the exhaust air
should not be discharged Into any environment until It has been adequately
decontaminated;
(3) To prevent skin contact with PCBs, workers should be required
to wear and use PCB-reslstant protective clothing and equipment, including
respirators.
(4) Upon leaving regulated areas, workers should be required to
remove such protective clothing and equipment and place it in impervious
containers pending either decontamination or disposal;
(5) After removing such protective clothing and equipment, workers
should be required to wash their hands, forearms, and faces, and to shower
after the last exposure of the day.
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Whenever a worker must come into direct contact with PCB3, eg, during
cleanup of spills or maintenance of vessels, PCB-resistant protective
clothing and an appropriate respirator must be worn.
(b) Leakage and Spill Procedures
PCB spills are to be cleaned up promptly, either by the use of
sorbent materials, such as sawdust, or by trapping and removal through
pumping or other suitable means. In case of spillage of PCBs on clothing,
the contaminated clothing should be removed as soon as practical, the skin
should be thoroughly washed, and the clothing should be laundered or
disposed of properly. Facilities and procedures for such cleanup must be
provided at manufacturing facilities producing capacitors and transformers,
because spills of PCBs are quite likely to occur during the filling and
handling of such devices. Users of PCB-filled transformers should inspect
them periodically for leakage. If leakage is found, the cause should be
corrected and the spillage should be soaked up with sawdust or other
absorbent material. The leak area should be cleaned finally with rags
soaked with an appropriate safe solvent. Leaky transformer gaskets can be
sealed temporarily by painting over the leaky area with epoxy cement.
Refer to Transformer Askarel Inspection and Maintenance Guide [25], and
Guidelines for Handling and Disposal of Capacitor and Transformer Grade
Askarels Containing Polychlorinated Biphenyls [4] for further maintenance
procedures.
(c) Emergencies
In emergencies, immediate measures must be taken to eliminate
hazardous conditions. Non-essential workers must be evacuated until the
emergency no longer exists. Any worker having visible contamination of the
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skin with PCBs must shower Immediately unless other action Is warranted.
(d) Respiratory Protection
To ensure against Inadvertent exposure to PCBs, workers' respirators
must be properly selected, fitted, and maintained. A guide to Industrial
respiratory protection [286] has been developed which contains sufficient
Information to enable the establishment and maintenance of a respirator
program that meets the requirements outlined In 29 CFR 1910,134. The guide
[286] Includes Information on respirator selection, use, maintenance, and
Inspection, as well as a complete description of various types of
respirators and their advantages and limitations, respirator fitting
procedures, wearer training Instructions, and physiologic and psychologic
constraints on respirator use.
Several NIOSH studies [287-289] have shown that respiratory
protection may be Inadequate In many occupational situations, eg, abrasive
blasting, coal mining, and paint spraying. For this reason, respirators
are generally regarded by NIOSH as a type of control to be used only where
engineering controls cannot be used, made adequate, or provided.
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VI. DEVELOPMENT OF STANDARD
Basis for Previous Standards
In 1942, the Subcommittee on Threshold Limits of the National
Conference of Governmental Industrial Hygienists compiled a list of maximum
permissible concentrations of atmospheric contaminants recommended by
various state industrial hygiene units [290], The eight states that made
recommendations for PCBs (chlorodiphenyls) were unanimous in recommending 1
mg/cu m. No basis for the recommendations was given.
Cook [291], in his 1945 listing of Maximum Allowable Concentrations
of Industrial Atmospheric Contaminants, cited PCB standards for California
and Utah of 1 mg/cu m and Oregon of 0.3 mg/cu m. He [291] also cited
unofficial guidelines for Massachusetts of 5 mg/cu m and for New York of 1
mg/cu m and he recommended 1 mg/cu m, based on the report of Drinker [132],
The American Conference of Governmental Industrial Hygienists (ACGIH)
began listing PCBs (chloro di phenyl) with "toxic dusts, fumes and mists"
in its recommendations of maximum allowable concentrations of air
contaminants for 1946 [292], It compiled its 1946 list from its 1942 list
[290] and from Cook's [291] list, and continued to recommend 1 mg/cu m for
PCBs.
The ACGIH continued to recommend 1 mg/cu m for PCBs (chlorodiphenyl)
until 1956 when it specified 1 mg/cu m as the limit for PCBs with 42%
chlorine and proposed a limit of 0.5 mg/cu m for PCBs with 54% chlorine
[293]. Each recommendation was clearly defined as a threshold limit value
(TLV) for an 8-hour TWA concentration to which it was "felt" workers could
be repeatedly exposed without adverse effect on their health.
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In 1961, the ACGIH added the notation "skin" to the TLV of those
substances, including PCBs, which in liquid form can penetrate the skin to
cause systemic effects [294,295].
In 1962, the ACGIH published documentation of its TLV recommendations
[296], Based on information in the reports of Schwartz [123], Drinker et
al [125], Meigs et al [190], and Treon et al [203], the ACGIH [296]
concluded that for PCBs chlorinated to 42%, 1 mg/cu m would seem to offer
reasonably good protection against severe systemic toxicity but may not
guarantee complete freedom from chloracne. They also cited the information
[207] that PCBs could be absorbed through the skin, causing fatty
degeneration of the liver. In documenting Its recommendation for PCBs
containing 54% chlorine, the ACGIH [296] cited Drinker et al [125], Drinker
[132], and Treon et al [203], and on the basis of these reports It [296]
considered that 0.5 mg/cu m appeared to be reasonable for repeated
occupational exposures.
The American Industrial Hygiene Association's Hygienic Guide
"Chlorodiphenyls (containing 42% and 54% chlorine)" [297], published In
1965, adopted the ACGIH recommendations for time-weighted average exposures
and suggested a short-exposure tolerance for PCBs of 10 mg/cu m to prevent
unbearable irritation, based on the report of Elkins [130], The Hygienic
Guide [297] provided information that minimum lethal doses applied to the
skin of rabbits for 24 hours were 1 g/kg for PCBs containing 42% and 1.5
g/kg for PCBs containing 54% chlorine. It also recommended avoiding
prolonged or repeated skin contact, and it recommended laundering of
contaminated clothing before reuse, protecting the eyes from liquid
splashes, treatment of the eyes if PCBs were splashed into them, and
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periodic examinations to detect early evidence of skin irritation or liver
damage.
In 1970, the International Labour Office published permissible levels
of toxic substances for several nations [298]. The PCB standards for six
nations are given in Table VI-1.
TABLE VI-1
PERMISSIBLE LEVELS OF PCBs FOR SIX NATIONS
Country
Standard
Type of
(mg/cu m)
Standard
Czechoslovakia
42% Chlorine
1.0
MAC
54% Chlorine
0.5
If
Finland
42% Chlorine
1.0
MAC 8-hour
54% Chlorine
0.5
If
Poland
0.1
MAC
Romania
42% Chlorine
1.0
ft
54% Chlorine
0.5
fl
USSR
1.0
H
Yugoslavia
42% Chlorine
0.5
1 f
54% Chlorine
0.5
f f
Adapted from reference 298
In 1975, Winell [299] compiled a list of international occupational
hygienic standards for chemicals, including "chlorodiphenyl." She listed
values for Sweden of 0.5 mg/cu m and for the German Democratic Republic of
1.0 mg/cu m. In both countries the standards were the same for PCBs
containing 42% and 54% chlorine. The standards listed for the Federal
Republic of Germany were 1.0 mg/cu m for PCBs containing 42% chlorine and
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0.5 mg/cu m for those with 54% chlorine, respectively.
The TLV documentations for PCBs published by the ACGIH in 1976 [300]
did not differ significantly from the original documentations [296].
However, the ACGIH [300] recalled, citing von Wedel et al [205], that
several deaths due to liver atrophy occurred among workers exposed to fumes
of chlorobiphenyls and chloronaphthalenes, but pointed out that relatively
few, if any reports had appeared of sytemic poisoning of workers exposed
only to fumes of PCBs.
The ACGIH has retained a TWA of 1 mg/cu m as the TLV fo? PCBs with
42% chlorine content and a TWA of 0.5 mg/cu m as the TLV for those with 54%
chlorine content (through 1976) [301]. However, a tentative short-term
exposure limit (TLV-STEL) was added to the recommendations in 1976. STEL
is defined by ACGIH [299] as the maximum concentration to which workers can
be exposed for up to 15 minutes continuously without suffering from
irritation, chronic or irreversible tissue change, or narcosis of
sufficient degree to increase accident proneness, impair self-re9cue, or
materially reduce work efficiency. According to the ACGIH [301], the STEL
is to be considered a maximum allowable concentration, or absolute ceiling
not to be exceeded at any time during the 15-minute excursion period; such
excursions are not to occur more than 4 times a day and there must be at
least 60 minutes between them. The STEL recommended for PCBs was 1 mg/cu m
regardless of the degree of chlorinatlon. This recommendation was made on
the basis chat the TLV documentation for PCRs [300] suggested that the
values should be ceilings never to be exceeded, rather than TWA values for
8 hours of exposure [301],
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The 1968 ACGIH recommendations [302], adopted as the federal
standards for PCBs (29 CFR 1910.1000, Table G-l) are TWA 8-hour exposure
concentrations of 1.0 mg/cu m for mixtures containing 42% chlorine and 0.5
mg/cu m for mixtures containing 54% chlorine.
Basis for the Recommended Standard
(a) Permissible Environmental Limit
The major effects that have been found in workers exposed to PCBs are
chloracne [186-191,195,196], liver injury [190-193,196], and irritation of
skin and mucous membranes [192,196,197], Exposures at peak PCB
concentrations of 5-10 mg/cu m have been reported as "unbearably"
irritating [ 130].
Chloracne has been reported after occupational exposure to Aroclors
1242 [196] and 1254 [186], and to various Kanechlors [191,192,194,195], as
well as after ingestion of Kanechlor 400 [146,153], Chloracne has
frequently been associated with processes where the PCBs were heated [186—
189,196]. The methodology in most of the exposure studies did not
differentiate between vapor and particulate forms of the PCBs
[186,190,196]. In one study of Kanechlors in capacitor manufacturing
plants where chloracne was common, vapor (or small particulate)
concentrations (0,095-0.95 mg/cu m) exceeded particulate concentrations
(0.02-0.65 mg/cu m) [191]. In another capacitor plant where heated Aroclor
1254 was used, exposure concentrations were 5-7 mg/cu m, but the vapor
components were not seperately determined [186]. In this plant, chloracne
developed among workers after 4-8 months of exposure. A study of workers,
in a plant where the work situation indicated the exposures were to PCB
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vapors, showed chat chloracne developed after a minimum of 5 months and an
average of 14 months of exposure [190]. In this study, exposure
concentrations of an undefined PCB were reported as 0.1 mg/cu m. In other
studies where PCB concentrations were not measured, chloracne developed
after 3-8 months of exposure [187,189].
These data show that chloracne can develop after prolonged exposures
to PCBs in concentrations as low as 0.1 mg/cu m, and that as the PCB
exposure concentrations Increase, the duration of exposure required for the
development of chloracne decreases. The data also indicate that PCBs in
the vapor phase may contribute substantially to development of chloracne.
However, they do not prove that only PCB vapors cause chloracne.
Particulate PCBs have been shown to be absorbed from inhaled air by
experimental animals [97], and Ingested PCBs have caused chloracne
[146,153]. Occupational exposure to a variety of PCB mixtures (Aroclors
1242, and 1254, various Kanechlors, and others) has caused chloracne, and
no commercial PCB mixture has been shown to have more or less
chloracnegenlc properties than others.
There are some studies of PCB workers in which chloracne was not
found [197-199]. In one of these studies, the Aroclor 1242 concentrations
were imprecisely reported [198] and in the others the PCB mixtures were
undefined [199], The report by Levy et al [197] gave possible PCB exposure
concentrations of 0.013-0.264 mg/cu m and breathing zone concentrations of
0.014-0.073 mg/cu m. Thus the data indicate that chloracne may be
prevented by keeping PCB exposures below 0.1 mg/cu m (100 ug/cu m).
In some of the studies where chloracne developed, signs of liver
injury were not found [186,194,195], but in the majority of studies where
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chloracne was found, there were also indications of liver injury [190-
193,196], Evidence of impaired liver function was found by other
investigators [197] in a study where workers had not developed chloracne.
Meigs et al [190] found evidence of slight liver injury in workers exposed
to PCBs at 0.1 mg/cu m, and Levy et al [197] found historical evidence of
liver injury in the medical records of workers in the plant where they
found exposures were <0.25 mg/cu m. Among the findings in these medical
records were elevated serum triglycerides [197], Abnormal serum
triglycerides have been found in exposed workers by others [191-193], and
in the Japanese people who accidentally consumed PCBs [155,157,158,175,179-
181], The effect on serum triglycerides in workers was related to duration
of exposure [193] and, in the workers and in the Yusho patients, to
residual PCBs in the blood [175,180,193]. In the Japanese workers who were
removed from exposure, the effect remained for at least 2 years [193].
Other indications of liver injury in exposed workers included
occasional findings of elevated serum enzyme activities, and abnormalities
in various other liver function tests [190,191,196,197], A level of
exposure at which liver injury will not occur is not indicated by the
occupational exposure studies, since evidence of liver injury has been
found in the occupational studies with the lowest PCB concentrations. It
is not possible to determine whether liver injury occurred with exposures
at the lower levels of all the occupational exposure ranges reported, but
to protect workers from any liver injury it seems that exposures should be
maintained below 0.01 mg/cu m (10 ^g/cu-m).
Animal experiments do not demonstrate a safe exposure level either.
Although Treon et al [203] found no evidence of liver injury in
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experimental animals (rabbits, guinea pigs, cats, rats, and mice) exposed
to Aroclor 1242 at concentrations of 1.9-8.6 tng/cu m for up to 31 weeks,
Ouw et al [196] found evidence of liver Injury In workers exposed to
Aroclor 1242 at 0.32-1.44 mg/cu m. In their experiments with Aroclor 1254,
Treon et al [203] found microscopic evidence of liver injury in animals
exposed at 1.5 mg/cu for 31 weeks. Under et al [228] found Increased
liver weights in rats fed Aroclor 1254 at 1 pprn for two generations. The
intake of PCBs at this dietary level can be compared to the intake from
Inhalation exposure at about 0.1-0.2 mg/cu m; thus, the animal experiments
appear to confirm indications of liver Injury In workers exposed to PCBs in
this range. The combined studies of Levy et al [197], Meigs et al [190],
Hasegawa et al [191], and Ouw et al [196], and the animal studies
[203,228], provide further support to the conclusion that PCB exposures
must be maintained at lower levels to prevent liver Injury than to prevent
chloracne.
Since indications of liver injury can be found in reports of both
occupational studies [190,191,196] and animal experiments [203,228] with
the lowest PCB exposure, there is no proof of an exposure level that is
adequately low to prevent liver injury.
The prevention of liver injury is of particular concern because there
is substantial evidence that arene oxides are formed during the metabolism
of PCBs by animals [51,68,69,74,75,81,115,116,118], and the data offer no
reason to suspect that humans metabolize PCBs differently from animals.
PCB metabolites have been demonstrated to bind to nuclear components of
hepatic cells of rhesus monkeys [51] and rats [81] and this is sufficient
evidence to arouse suspicions that PCBs could be potential carcinogens in
155
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the workplace. Commercial PCB preparations that have been adequately
tested in rats [218,242] (Federal Register 42:6532-55, February 2, 1977)
and mice [221,240,241] have been demonstrated to cause liver tumors. No
liver tumors were found in rats fed Aroclors 1242, 1254, and 1260 at 1 ppm
in the diet, but each of these mixtures produced tumors at 10 ppm (Federal
Register 42:6532-55, February 2, 1977). In this same experiment a high
incidence of pituitary tumors was found in PCB-fed rats. In Yusho patients
[160,161], and in American workers (written communications, HA Sinclaire,
June 1976; G Rousch, September 1976), preliminary studies only indicate
that the occurrence of certain cancers may be excessive. However, the
findings in rats and mice demonstrate reproducible production of liver
tumors after ingestion of various PCB mixtures, and NIOSH concludes that
PCBs in workplace air are potential carcinogens.
Additional concerns for the health of workers and their families are
adverse reproductive effects [228,230,232,233], including terata in animals-
fed various PCBs (FL Earl et al, written communication, 1976), and adverse
effects in human and animal infants nursed by PCB-exposed mothers
[101,182,233]. PCBs resembling those in maternal blood both qualitatively
and quantitatively have been found in human cord blood and in tissues of
newborn humans and animals [101,138,139,168], Fetal resorptions were
common, and dose related incidences of terata were found in pups and
piglets when bitches and sows were fed Aroclor 1254 at 1 mg/kg/day or more.
Terata were not found in babies of Yusho patients (maximum consumption of
PCBs of about 0.15 mg/kg/day); however, many undesirable effects including
low birth weights and chloracne-like lesions at birth and after nursing
were found [176,182,183].
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Based on the findings of adverse reproductive effects, on its
conclusion that PCBs are potential carcinogens in humans and on its
conclusion that occupational and animal studies have not demonstrated a
level of exposure that will not subject the worker to possible liver
injury, NIOSH recommends that the TWA concentrations of PCBs in the
breathing zone of workers be maintained at or below the minimally
detectable TWA concentration for up to a 10-hour workday, AO-hour workweek.
NIOSH considers the minimally detectable concentration of PCBs for the
monitoring of occupational exposures to be 1 jug/cu m, based on its review
of the literature and the methodology presented in Appendices I and II.
Maintenance of exposures -to PCBs at or below this concentration
should reduce risks of reproductive and carcinogenic effects, and protect
the employees from metabolic dysfunction, hepatic injury, and dermal
effects due to PCB exposures during their working lifetimes.
It is recognized that employees handling PCBs may have skin contact
with these substances, potentially resulting in dermatologic and systemic
effects. Consequently, appropriate work practices, training programs, and
other measures should be required, regardless of the concentrations of
airborne PCBs. Therefore, occupational exposure to PCBs has been defined
as working with PCBs or with equipment containing PCBs that can become
airborne or that can spill or splash on the skin or into the eyes, or the
handling of any solid products that may result in exposure to PCBs by skin
contact or by inhalation.
(b) Sampling and Analysis
Based on an evaluation of the literature and on its own studies,
NIOSH recommends sampling and analysis for PCBs as detailed in Appendices I
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and II. Florisil has been selected as the solid sorbent for PCBs because
it will collect vapors as well as particulates and PCBs can be
quantitatively recovered from it. The recommended Florisil sampling tubes
have been shown to have an adequate sorption capacity (at least 100 jig) for
monitoring occupational exposures at the recommended limit for up to a 10-
hour workday. NIOSH has used the sampling method for monitoring TWA
occupational exposures at 10-250 ng/cu m [197,244] by sampling at about 200
ml/minute for the entire workday. Total sample volumes of up to 100 liter9
%
were collected. At 1 yg/cu m, 100 liters of air would contain 100 ng of
PCBs. The lower ]imit of PCB detection by GLC with EC detection was found
to be 32 pg/4-yl injection. Since the contents of the Florisil tubes are
dissolved in 5 ml of solvent, this represents a total of 40 ng of adsorbed
PCBs. Although NIOSH recommends sampling at 200 ml/minute, it may be
feasible to use pumps that sample at faster rates if there are analytical
difficulties with samples of about 100 liters due to low concentrations of
PCBs.
(c) Medical Surveillance
Occupational exposure to PCBs has been shown to cause signs of liver
injury and impaired liver function. Ouw et al [196], Hasegawa et al [191],
and Levy et al [197] all found occasional incidents of elevated serum
enzymes: exposure conditions under which these will not occur are not
known. Therefore, NIOSH recommends determination of SGOT and SGPT
initially and at annual intervals. The responsible physician may also wish
to determine serum triglyceride concentrations since these have been found
to be abnormal in some workers chronically exposed to PCBs [191-193,197].
Especially, elevated serum triglyceride concentrations have been found to
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be related to duration of exposure and to the concentration of residual
PCBs in the blood [193].
Although the data indicate that the recommended standard will prevent
chloracne, it is not knovn that it will prevent other skin ailments. NIOSH
recommends that in comprehensive physical examinations, special emphasis be
given to the condition of the skin.
PCBs fed to bitches and sows have been found to be teratogenic (FL
Earl et al, written communication, 1976). Although terata have not been
observed in human babies whose mothers had been exposed to PCBs
[176,182,183], PCBs have been found in human embryos and fetuses
[138,139,168], and undesirable effects (abnormal skin color and low birth
weights) have been observed in neonates [176,182,183] born after their
mothers had ingested PCBs. A woman who was occupatlonally exposed to PCBs
had a blood PCB concentration of 25 ppb when her normal baby was born
[195]. NIOSH considers that its recommended standard will protect unborn
babies but recommends that women exposed to PCBs at work be advised pf the
potential hazards of PCB exposure to unborn children.
PCBs have been found in milk of women who have been exposed to PCBs
[168,195] and babies have been adversely affected after being nursed by
PCB-exposed mothers [182]. A safe level of PCBs in the milk of mothers
occupatlonally exposed to PCBs i9 not known. Human milk samples in the
general US population usually contain detectable amounts of PCBs, and about
one-third of the whole milk samples have been found to contain >50 ppb and
up to about 350 ppb (EP Savage, written communication, February 1977), It
is not known if all the mothers from whom these samples were taken nursed
their babies without effect. Infant monkeys who were nursed by mothers
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in their milk at 150-350 ppb became sick and developed chloracne [234],
After consultation, the woman who was occupationally exposed to PCBs and
who had PCBs in her milk at about 250 ppb, stopped nursing her baby out of
concern for its health [195], Based on these considerations, NIOSH
recommends that women working with PCBs be counseled concerning the
advisability of nursing their babies.
(d) Personal Protective Equipment and Clothing
PCBs applied to the skin or cornea of experimental animals have been
shown to cause local lesions and liver and kidney injuries [205-208,225],
One worker who developed chloracne after 3 months of exposure to PCBs was
described as having frequently immersed his hands in the PCB mixture and
his clothes were described as often being impregnated with PCBs [189],
Employees working with an askarel containing 60% Aroclor 1254 frequently
developed skin rashes which were considered by the company physician to be
allergic or contact dermatitis from the askarel (In the Matter of General
Electric Company, File No. 2833, New York State Department of Environmental
Conservation, 1975). Other complaints of these workers that were ascribed
to the askarel included irritation of the eyes, nose and throat. Levy et
al [197] and Ouw et al [196] found that employees exposed to PCBs at 0.013-
0.264 mg/cu m and 0.32-1,44 mg/cu m, respectively, complained of similar
irritations and, on examination, there were findings of skin rashes and
nasal irritation. Ouw et al [196] considered that one reason the blood PCB
concentrations in workers they studied did not decline (after improvements
in the ventilation system had reduced the environmental concentrations of
PCBs) was because the workers did not comply with the recommendations for
protecting their skin from PCB contact.
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Based on these reports [189,196,197,205-208,225], NIOSH recommends
that employees working in situations where skin contact may occur be
provided with clothing that Is impervious to PCBs and that will cover all
body surfaces where contact may occur. To prevent splashing PCBs into the
eyes, NIOSH recommends that employees wear appropriate goggles or safety
glasses In accordance with 29 CFR 1910.133 and ANSI Z87.1-1968, Since
NIOSH has found PCBs to be potential carcinogens and recommends that
exposures be maintained at or below 1 jig/cu m, it considers that only a
self-contained breathing apparatus with a full facepiece operated in the
positive-pressure mode will provide adequate protection when workers are in
areas where higher concentrations exist. Based on NIOSH studies [287-289],
other respiratory protective devices are not considered adequate to provide
the needed protection.
(e) Other Considerations
Engineering controls are recommended to maintain PCBs in closed
systems to reduce exposures to the extent feasible. Such a recommendation
is consistent with the Toxic Substances Control Act (Public Law 94-469) and
with the need to protect employees from exposure to PCBs. However, there
are situations, such as in accidental leakage from closed systems and In
repair of equipment, when PCBs may not be confined. The recommended
standard prescribes general work practices for PCBs as well as emergency
work practices. Employees should be informed of the hazards of working
with PCBs, and trained in the recommended general work practices and the
procedures to follow in emergencies. The advantages to their health of
complying with the work practices and medical monitoring requirements of
the recommended standard should be explained to the employees. As Ouw et
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al [196] pointed out, Improving air quality does not go far in alleviating
the workers' body burdens of PCBs without their cooperation in implementing
the recommendations for protecting their skin from PCB contact.
NIOSH also recommends certain sanitation practices to minimize intake
of PCBs by employees. Among these practices is the requirement that
employees be provided with clean work clothing daily and that they change
clothing before leaving work. The importance of this measure to the
employee and the employee's family is exemplified in finding up to 180 ppm
of PCBs in the dust of PCB-workers' homes [36], PCBs may remain in
contaminated premises for years [33]. Partly for the same reason, and
because PCBs in contact with the skin can be irritating [196,197] and also
because they have caused systemic effects in experimental animals [205—
208,225], NIOSH recommends that workers shower before leaving work.
Toxic effects from ingestion of PCB9 have been well documented in
humans [145-185] and experimental animals [10L,209-224,226-237,240-248].
Workers may have an intake of PCRa from their normal diet of 10-20 jig/day
[46], and the maximum additional intake expected from NIOSH's recommended
allowable work exposures might be of the order of 10 tig. NIOSH recommends
that workers wash their hands before eating and that food, drinks, and
smoking materials not be permitted in PCB work areas. The importance of
this recommendation may be evaluated by considering that one drop of PCBs
spilled on food, in drinks, or otherwise conveyed into the mouth may
contain about 50 fig of PCBs, compared to a total intake of 20-30 jig from
other sources, including allowable occupational exposures.
Because the consequences of working with PCBs may be substantial,
NIOSH recommends that entry into PCB work areas be restricted to authorized
162
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employees whose entry is logged dally, and whose exposures are monitored at
least annually to ensure that airborne exposures are at or below the
recommended TWA limit.
163
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VII. RESEARCH NEEDS
There is a clear need for information in the following areas:
(a) The effects of chronic exposure of animals and humans to PCBs
at low concentrations require investigation. Epidemiologic studies of
occupational groups and information on concentrations of PCBs in workroom
air and any related clinical findings would be useful.
(b) Chronic exposures of animals to PCBs at concentrations in the
range of the recommended environmental limit.
(c) Studies of the reproductive histories of women who have been
exposed to PCBs in their occupational environments, including studies of
status and development of infants born to these women.
(d) The absorption efficiencies of various PCB mixtures by the
dermal and respiratory routes.
(e) The method of transport of PCBs in the blood and the partition
between blood on the one hand, and fat stores and milk, on the other.
(f) A problem that confounds our understanding of the toxicity of
PCBs is that of the toxic activity of contaminants associated with PCBs,
The contaminants found in commercially important PCB products should be
identified, prepared in pure form and studied toxicologically both as
individual substances and as mixtures with other, related compounds.
(g) Studies regarding methods of removing PCBs from the skin
(cleansing).
(h) Studies on the use of various barrier creams as a means of
minimizing dermal exposure to PCBs.
164
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(1) There Is uncertainty regarding baseline values for PCBs In the
blood of humans; research should be conducted to determine baseline values
for the general population and for non-exposed Industrial populations.
165
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1974
252. Giam CS, Chan HS, Neff GS: Rapid and inexpensive method for
detection of polychlorinated biphenyls and phthalates in air. Anal
Chem 47:2319-20, 1975
253. Laveskog A, Lindskog A: Chlorinated hydrocarbons in the atmosphere.
Chem Ing Tech 48:65, 1976 (Synopsis)
254. NIOSH Standards Completion Program: Chlorodiphenyl (54% Chlorine),
Method No. S121, Cincinnati, US Dept Health, Education, and Welfare,
Public Health Service, Center for Disease Control, National Institute
for Occupational Safety and Health, 1976, 15 pp
255. NIOSH Standards Completion Program: Chlorodiphenyl (42% Chlorine),
Method No. S120, Failure Report. Cincinnati, US Dept Health,
Education, and Welfare, Public Health Service, Center for Disease
Control, National Institute for Occupational Safety and Health, 1976,
7 pp
256. Fishbein L: Chromatographic and biological aspects of
polychlorinated biphenyls. J Chromatogr 68:345-426, 1972
257. Fishbein L: Chromatography of Environmental Hazards, Vol II. New
York, Elsevier Scientific Publishing Co, pp 529-77, 1973
258. Interdepartmental Task Force on PCBs: Polychlorinated Biphenyls and
the Environment, Report No. ITF-PCB-72-1, Springfield, Va, US Dept
of Commerce, National Technical Information Service, COM-72-10419,
1972, pp 23-40
259. Oswald E0, Albro PW, McKinney JD: Utilization of gas-liquid
chromatography coupled with chemical ionizatron and electron impact
mass spectrometry for the investigation of potentially hazardous
environmental agents and their metabolites. J Chromatogr 98:363-448,
1974
260. Cook JW: Some chemical aspects of polychlorinated biphenyls (PCBs).
Environ Health Perspect, Experimental issue No. 1, April 1972, pp 3-
13
261. Sarofim»AF: PCBs—Environmental Impact—Analytical Methods. Environ
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262. Sherma J: Gas-chromatography analysis of polychlorinated blphenyls
and other nonpesticide organic pollutants. Adv Chromatogr 12:141-76,
1975
263. Koeman JH, Ten Noever De Brauw MC, De Vos RH: Chlorinated biphenyls
in fish, mussels and birds from the river Rhine and the Netherlands
coastal area. Mature 221:1126-28, 1969
264. Skrentny RF, Hemken RW, Dorough HW: Silo sealents as a source of
polychlorobiphenyl (PCB) contamination of animal feed. Bull Environ
Contam Toxicol 6:409-16, 1971
265. Zitko V: Polychlorinated biphenyls and organochlorine pesticides in
some freshwater and marine fishes. Bull Environ Contam Toxicol
6:464-70, 1971
266. Keil JE, Priester LE, Sandifer SH: Polychlorinated biphenyl (Aroclor
1242)—Effect of uptake on growth, nucleic acids, and chlorophyll of
a marine diatom. Bull Environ Contam Toxicol 6:156-59, 1971
267. Hansen DJ, Parrlsh PR, Lowe JI, Wilson AJ Jr, Wilson PD: Chronic
toxicity, uptake, and retention of Aroclor 1254 in two estuarlne
fishes. Bull Environ Contam Toxicol 6:113-19, 1971
268. Collins GB, Holmes DC, Jackson FJ: The estimation of
polychlorobiphenyls. J Chromatogr 71:443-49, 1972
269. Sawyer LD: Collaborative study of the recovery and gas
chromatographic quantitation of blphenyl-DDT combinations In fish. J
Assoc Off Anal Chem 56:1015-23, 1973
270. Finsterwalder CE: Collaborative study of the determination of
polychlorinated biphenyls in paperboard. J Assoc Off Anal Chem
57:518-21, 1974
271. Beezhold FL, Stout VF: The use and effect of mixed standards on the
quantitation of polychlorinated biphenyls. Bull Environ Contam
Toxicol 10:10-15, 1973
272. Pesticide Residues, in Horwitz W, Senzel A, Reynolds H, Park DL
(eds): Official Methods of Analysis of the Association of Analytical
Chemists, ed 12. Association of Official Analytical Chemists, 1975,
pp 518-28
273. Rote JW, Murphy PG: A method for the quantitation of polychlorinated
biphenyl (PCB) Isomers. Bull Environ Contam Toxicol 6:377-84, 1971
274. Risebrough RW, Reiche P, Olcott HS: Current progress In the
determination of polychlorinated biphenyls. Bull Environ Contam
Toxicol 4:192-201, 1969
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275. Zobel MGR: Quantitative determination of polychlorinated
biphenyls—A computer approach. J Assoc Off Anal Chem 57:791-95,
1974
276. Webb RG, McCall AC: Quantitative PCB standards for electron capture
gas chromatography. J Chromatogr Sci 11:366-73, 1973
277. Burke JA: Report on chlorinated pesticides. J Assoc Off Anal Chem
59:338-40, 1976
278. Method for Polychlorinated Biphenyls (PCBs) in Industrial Effluents.
Cincinnati, Environmental Protection Agency, Environmental Monitoring
Support Laboratory, 1976, 40 pp
279. Chau ASY, Sampson RCJ: Electron capture chromatographic methodology
for the quantitation of polychlorinated biphenyls—Survey and
compromise. Environ Lett 8:89-101, 1975
280. Berg OW, Diosady PL, Rees GAV: Column chromatographic separation of
polychlorinated biphenyls from chlorinated hydrocarbon pesticides,
and their subsequent gas chromatographic quantitation In terms of
derivatives. Bull Environ Contain Toxicol 7:338-47, 1972
281. Armour JA: Quantitative perchlorination of polychlorinated biphenyls
as a method for confirmatory residue measurement and identification.
J Assoc Off Anal Chem 56:987-93, 1973
282. Hutzinger 0, Safe S, Zltko V: Analysis of chlorinated aromatic
hydrocarbons by exhaustive chlorination—Qualitative and structural
aspects of the perchloro-derivatives of biphenyl, naphthalene,
terphenyl, dibenzofuran, dibenzodioxin and DDE, Int J Environ Anal
Chem 2:95-106, 1972
283. Mizutani T, Matsumoto M: Determination of polychlorinated biphenyls
by an exhaustive chlorination method. Shokuhin Eiseigaku Zasshi
13:398-404, 1972 (Abst.)
284. Huckins JN, Swanson JE, Stalling DL: Perchlorination of
polychlorinated biphenyls. J Assoc Off Anal Chem 57: 416-17, 1974
285. Trotter WJ, Young SJV: Limitation on the use of antimony
pentachloride for perchlorination of polychlorinated biphenyls, J
Assoc Off Anal Chem 58:466-68, 1975
286. Pritchard JA: A Guide to Industrial Respiratory Protection, No. NIOSH
76-189, Cincinnati, US Dept Health, Education, and Welfare, Public
Health Service, Center for Disease Control, National Institute for
Occupational Safety and Health, 1976, 150 pp
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287. Blair A: Abrasive Blasting Respiratory Protective Practices, No.
NIOSH 74-104. Cincinnati, US Dept Health, Education, and Welfare,
Public Health Service, Center for Disease Control, National Institute
for Occupational Safety and Health, 1974, 116 pp
288. Harris HE: Coal Mine Dust Respiratory Protective Devices, Final
Report Prepared by the Eastern Associated Coal Corporation for NIOSH
Contract No. CPE 70-127. Cincinnati, US Dept Health, Education, and
Welfare, Public Health Service, Center for Disease Control, National
Institute for Occupational Safety and Health, 1974, 221 pp
289. Toney CR, Barnhart WL: Performance Evaluation of Respiratory
Protective Equipment Used in Paint Spraying Operations, NIOSH No.
76-177. Cincinnati, US Dept Health, Education, and Welfare, Public
Health Service, Center for Disease Control, National Institute for
Occupational Safety and Health, 1976, 110 pp
290. National Conference of Governmental Industrial Hyglenlsts: Report of
the Subcommittee on Threshold Limits, in Transactions of the 5th
Annual Meeting, NCGIH, Washington, April 9, 10, 1942, pp 163,164
291. Cook WA: Maximum allowable concentrations of industrial atmospheric
contaminants. Ind Med 14:936-46, 1945
292. American Conference of Governmental Industrial Hyglenlsts: Report of
the Sub Committee on Threshold Limits, in Proceedings of the 8th
Annual Meeting, ACGIH, Chicago, April 7-13, 1946, pp 54-56
293. American Conference of Governmental Industrial Hyglenlsts: Report of
the Committee on Threshold Limits, in Transactions of the 18th Annual
Meeting, ACGIH, Philadelphia, April 21-24, 1956, pp 70,72,73,76,78
294. American Conference of Governmental Industrial Hyglenlsts: Report of
Committee on Threshold Limits, in Transactions of the 23rd Annual
Meeting, ACGIH, Detroit, April 9-12, 1961, pp 120-22
295. American Conference of Governmental Industrial Hyglenlsts: Threshold
Limit Values for 1961, Adopted at the 23rd Annual Meeting, ACGIH,
Detroit, April 9-12, 1961. Cincinnati, ACGIH, 1961, p 8
296. American Conference of Governmental Industrial Hyglenlsts, Committee
on Threshold Limit Values: Documentation of Threshold Limit Values,
ed 1. Cincinnati, ACGIH, 1962, pp 26,27
297. Chlorodiphenyls (containing 42% and 54% chlorine), in Hygienic Guide
Series. Am Ind Hyg Assoc J 26:92-94, 1965
298. Permissible levels of Toxic Substances in the Working Environment—
6th Session of the Joint ILO/WHO Committee on Occupational Health,
Geneva, June 4-10, 1968, Occupational Safety and Health Series No.
20. Geneva, International Labour Office, 1970, pp 182-87,
197,204,223,231,331,346
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299. Winell M: An international comparison of hygienic standards for
chemicals in the work environment. Ambio 4:34-36, 1975
300. American Conference of Governmental Industrial Hygienists:
Documentation of the Threshold Limits of Substances in Workroom Air,
ed 3. Cincinnati, ACGIH, 3rd printing 1976, pp 51,52
301. American Conference of Governmental Industrial Hygienists: Report of
the ACGIH Committee on Threshold Limits for the Air of Workplaces, in
Transactions of the 38th Annual Meeting, ACGIH, Atlanta, May 17-21,
1976, pp 27,28,30-36,158-60,164,184
302. American Conference of Governmental Industrial Hygienists: Threshold
Limit Values for 1968—Recommended and Intended Values, Adopted at
the 30th Annual Meeting, ACGIH, St. Louis, May 13, 1968, pp 1,3,5,7
190
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IX. APPENDIX I
SAMPLING PROCEDURE FOR
COLLECTION OF POLYCHLORINATED BIPHENYLS
General Requirements
(a) Air samples representative of the breathing zones of workers
oust be collected to determine the exposure from each Job or from the
specific operation In each work area.
(b) Suggested records:
(1) Date and time of sample collection;
(2) Pump model and serial number;
(3) Sample tube type and number;
(4) Sampling duration;
(5) Total sample volume;
(6) Location of sampling;
(7) Temperature, pressure, and relative humidity at time of
lampllng:
(8) Other pertinent Information.
Calibration
Since the accuracy of environmental sampling can be no greater than
the accuracy of the air volume -measurement, the accurate calibration of the
sampling pump is essential to the correct estimation of the volume of the
sample that is collected. The required frequency of calibration is
dependent on the use, care, and handling to which the pump Is subjected.
Pumps should be calibrated initially and recalibrated if misused or
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repaired. If pumps receive hard usage, more frequent calibration may be
necessary. Regardless of use, maintenance and calibration should be
performed on a regular schedule and records of these should be kept.
The accuracy of calibration depends on the type of instrument used as
a reference. The choice of calibration Instrument will depend largely upon
where the calibration Is to be performed. Ordinarily, pumps should be
calibrated in the laboratory. For laboratory testing, primary standards,
such as a spirometer or a soapbubble meter, are recommended, although other
standard calibration instruments, such as a vet-test meter or dry gas
meter, can be used. The calibration setups will be similar for all
instruments.
Instructions for calibration with the soapbubble meter follow. If
another calibration device is selected, equivalent procedures should be
used. Since thezflowrate of a pump depends on the pressure drop across the
sampling device, in this case a "Florisil" tube, the pump must be
calibrated .while operating with a representative tube in line. The
calibration system should be assembled in series following this order:
soapbubble metex, water manometer, Florisil tube, and pump.
(a) Check the voltage of the pump battery with a voltmeter to
ensure adequate voltage for calibration, and change or charge the battery
if necessary.
(b) Turn on the pump and moisten the inside of the soapbubble
meter by immersing the buret in the soap solution and drawing bubbles up
the inside until they travel the entire buret length without bursting.
(c) Adjust the pump rotameter to provide the desired flowrate.
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(d) Check the water manometer to ensure that the pressure drop
across the sampling train does not exceed 2,5 Inches of water at 0.2
liter/minute.
(e) Start a soapbubble up the buret and measure with a stopwatch
the time required for it to move between calibration marks.
(f) Repeat procedure (e) at least twice, average the results, and
calculate the flowrate from the volume between the preselected marks
divided by the time required for the soapbubble to traverse the distance.
(g) Record the volume measured, elapsed time, pressure drop, air
temperature, atmospheric pressure, serial number of pump, date, time, and
name of person performing the calibration.
(h) The rotameter reading should be corrected for temperature and
pressure, if necessary.
Sampling
(a) Samples should be collected as near as practicable to the
faces of workers without interfering with freedom of movement.
(b) Samples should be collected to permit determination of TWA
exposures for every job involving exposure to PCBs and In sufficient
numbers to express the variability of the exposures In the work situation.
(c) Apparatus for Breathing Zone Sampling
(1) Pump, battery-operated, with clip for attachment to the
worker's clothing. Airflow through the pump should be controlled within 5%
of the desired rate during the entire sampling period.
(2) Sorbent Tubes
Glass tubes at least 7 cm long with 6 mm I.D. and containing
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two sections of 30/48 mesh deactivated Florisil. (Florisil, 30/60 mesh, is
sieved to the proper mesh size.) The front section, preceded by a glass
wool plug, contains 100 mg adsorbent, and the backup section contains 50
mg. A urethane foam plug is placed between these sections and also behind
the backup section. The ends of the tube are flame-sealed to prevent
contamination before use.
Deactivate the Florisil before packing the tubes by drying a weighed
amount at 105 C for 45 minutes. After cooling to room temperature, add the
Florisil to a round bottom flask which can be attached to a rotary
evaporator. Add water at 3 ml/100 g of Florisil (ie, 3% W/W water) and
turn the mixture in the rotary evaporator for 1 hour or until it is
uniformly mixed (free-flowing).
(d) Collection and Shipping of Samples
(1) Immediately before sampling, break each end of the
sorbent tube to provide an opening at least one-half the internal diameter
of the tube (2 mm).
(2) The smaller, or backup, section of Florisil should be
positioned nearest the sampling pump.
(3) The sorbent tube must be vertical during sampling.
Tubes should not be placed in a horizontal position since this may lead to
"channeling" of the sorbent bed.
(4) Do not pass air being sampled through any hose or
tubing before it enters the tube.
(5) Collect the air sample at a flow rate of 200 cc/minute
or less to obtain the total sample volume required. The recommended
maximum sampling volume for this method is 50 liters.
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(6) Cap the sorbent tubes with Inert plastic caps
Immediately after sampling. Under no circumstances are rubber caps to be
used. Label tubes and note precise location assignments.
(7) Handle one additional tube in the same manner as the
sample tubes except that no air is to be drawn through It. Label this tube
as a blank.
(8) If the tubes are to be shipped, pack them tightly to
minimize breakage In transit.
(9) Do not subject the»tubes to extremes of temperatures or
to low pressures.
(10) . Provide bulk samples of the PCB preparation whose .
presence in the environment is suspected to the analytical laboratory. Do
not transport these bulk materials in the same container as the samples or
blank tubes. If possible, also provide a bulk air sample to use for
qualitative Identification.
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X. APPENDIX II
ANALYTICAL METHOD FOR POLYCHLORINATED BIPHENYLS
Principle of the Method
A known volume of air is drawn through a tube containing Florisil to
adsorb the PCBs present in the air sample. The collected PCBs are desorbed
with hexane, and the resulting solutions are analyzed using ga9-llquld
chromatography with electron capture detection. The concentration of PCBs
relative to a standard PCB preparation is read from a standard curve. If
the air sample is found to differ significantly in composition from
available PCB standards, then use the alternate procedure of
perchlorination described in paragraph (b)7 of Procedure.
Range and Sensitivity of the Standard Analysis
NIOSH has found with Aroclor 1016, that the minimum detectable amount
of PCB is 32 pg/4 pi. With a total desorption volume were 5 ml, this would
represent a total sample of AO ng of Aroclor 1016. Thus the method is
capable of detecting a concentration of 40 ng in a 1 cu m air sample, or a
concentration of about 1 yg/cu m in an air sample of 50 liters. The upper
range of the analytical method is apparently limitless depending only upon
the degree of dilution needed to maintain the concentration of the sample
within the linear range of the electron capture detector (32 pg to 3
ng/injection). In practice, concentrations in workplace air have been
found to be as high as 1.5 mg/cu m.
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Interferences
(a) Strict measures to avoid contamination are required when using
the electron capture detector. Foremost, the syringe oust be thoroughly
cleaned after each injection. Hexane to be used In the analytical
procedure should be periodically analyzed by GLC for purity. It should
show no chromatographic peaks later than 45 seconds, if less than 5 jil have
been injected.
(b) Any compound which has nearly the same retention tine on the
GLC column as one of the PCBs is an lnterferent. This type of Interference
can often be overcome by changing the GLC operating conditions or by
selecting another column. Retention time data on a single column, or even
on a number of columns, cannot be considered as proof of chemical identity.
It Is important, therefore, that a sample of the bulk mixture of PCBs be
analyzed at the aame time as the contents of the sample tubes so that
chemical identification of possible Interferences can be made.
(c) The Interferences which have been reported in the literature
In the GLC analysis of PCBs are not expected to be important for this
method.- Chlorinated pesticides, such as DDT, DDE, etc, have been reported
as interferences due to coextractlon with PCBs during workup of samples
such as water, tissue, soil, or biologic fluids. In the case of personal
air sampling in an industrial environment, these Interferences would not be
present In amounts chat would significantly Interfere unless they were
manufactured in the aame area. Thus, unless these chlorinated pesticides
are specifically known as potential interferents, extra cleanup or
separation steps for these materials are not necessary.
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(d) Sulfur-containing compounds in petroleum products have been
reported as interferences.
(e) If present in the PCB mixture, biphenyl will be an
interference when samples are analyzed by perchlorination; however, PCBs
for the purpose of this recommended standard include biphenyl.
(f) Brominated impurities in antimony pentachloride have also been
found to lead to Interferences in perchlorination procedures. Results from
NIOSH laboratories indicate, however, that these brominated impurities may
be removed by^vacuum distillation of the antimony pentachloride.
Precision and Accuracy
The performance characteristics of the method as found by NIOSH are
presented below.
(a) The volume of air sampled can be measured to ±1% if a pump
with a calibrated volume indicator is used. Volumes calculated from
initial flow rate settings may be less accurate (±5%) because of changes in
flow rate during sampling.
(b) At airborne PCB concentrations of up to 10 mg/cu m, the front
section of the Florisil tube has a 100% collection efficiency for 50-liter
air samples.
(c) Recovery of known amounts of PCBs adsorbed on Florisil is
quantitative (100%).
(d) Sealed tubes or desorbed sample solutions can be stored for 2
months without PCB loss.
(e) The precision of the analysis is dependent upon the precision
and sensitivity of the technique used to quantitate the GLC peaks of the
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samples and standards. The precision of the standard analytical procedure
has a relative standard deviation of 4.4%.
(f) The average conversion of PCBs to decachlorobiphenyl is about
100% with a relative standard deviation of about 2%.
(g) Recovery of decachlorobiphenyl subjected to the
decachlorlnatlon procedure is >99* with a relative standard deviation of
1.81.
(h) The accuracy of these procedures Is not known; accuracy
depends on the ability to separate and identify each compound in the PCB
mixture and to compare each with a known standard. Many of the Isomers in
commercial PCB mixtures have not been separated or identified, and
standards for many of the isomers are not available.
Advantages of the Sampling and Analytical Methods
(a) The sampling device Is small, portable, and involves no
liquids.
(b) The capacity of the solid sorbent sampling device for PCBs is
large and recovery of PCBs from the sorbent is quantitative.
(c) The contents of the sample collection tubes are analyzed by
means of a rapid Instrumental method.
(d) Interferences are minimal, and mo9t of those which do occur
can be eliminated by altering chromatographic conditions.
(e) The perchlorination procedure provides qualitative
confirmation and quantitative measure of PCBs, since it is based on
measurement of the single GLC-EC detection response of decachlorobiphenyl.
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Disadvantages of the Sampling and Analytical Methods
(a) The precision of the sampling method is limited by the
reproducibility of the pressure drop across the tubes. Pressure drop
changes will result in variability in the flow rate and cause the sampling
volume to be imprecisely known because the pump is usually calibrated for
only one tube.
(b) A substantial difference between the composition of PCBs in
the air sample and that of the commercial PCB mixture being used as a
standard will result in a large error in accuracy when the standard
analytical procedure is used, since estimation of the PCB content of the
sample is based on comparison with such a PCB mixture.
Apparatus
(a) Gas liquid chromatograph equipped with an electron capture
detector capable of maintaining a detector temperature of 350 C.
(b) Glass column (6 feet x 2 mm I.D.) packed with 1.5% OV-17/1,95%
QF-1 on 80/100 mesh Supelcoport.
(c)
Vials (20-ml), with aluminum-lined caps.
(d)
Microliter syringe (10-^1).
(e)
Volumetric flasks (10-ml for standards) with glass
stoppers.
(f)
Method for determining peak areas.
(8)
Culture tubes, 13 x 100 mm, with unlined screw top
caps.
(h)
Oven, capable of maintaining 160 C ± 5 C.
(i)
Sand bath.
Vortex mixer.
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Reagents
(a)
Hexane, pesticide-grade quality.
(b)
Nitrogen carrier gas, prepurified.
(c)
PCB mixture under study.
(d)
Antimony pentachloride, distilled under vacuum.
(e)
Decachlorobiphenyl.
(f)
Sodium sulfate, anhydrous.
(g)
Hydrochloric acid, 20% aqueous.
Calibration and Standards
(a) Standardization Procedure
Use the particular PCB mixture as the standard that was being used in
the work area in which air samples were taken. Prepare standards in hexane
at concentrations ranging from 8 to 500 ng/ml. Calibration curves should
be established daily since the electron capture detector response may vary
from day to day. Plot the standard curve in terms of concentration (ng/ml)
versus area. Since the injection volumes of the standard and the sample
are identical, the concentration of the sample can be read directly from
the standard curve.
(b) Alternate Standardization Procedure (Perchlorination)
The product of the perchlorination of the PCB mixture with antimony
pentachloride is decachlorobiphenyl. Standards of decachlorobiphenyl are
prepared in hexane at concentrations ranging from 70 to 440 ng/yl.
Calibration curves are established daily since the electron capture
detector response may vary from day to day. The standard curve is plotted
in terms of concentration (ng/ml) versus peak area. Since the injection
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volume of the standard and the sample are identical, the concentration of
the sample can be read directly from this curve.
Procedure
(a) Cleaning of Equipment
All glassware used for the laboratory analysis should be washed with
a detergent, throughly rinsed with tap water, distilled water, pesticide-
grade acetone, and finally pesticide-grade hexane and then dried.
(b) Analysis of Samples
(1) Preparation of Samples
Score each tube with a file and place the glass wool and front
section in a clean, dry vial. Place the separating urethane foam plug, the
i
back section of the sorbent, and the retaining urethane foam plug in a
second clean, dry vial. The front and back sections are analyzed
separately.
(2) Desorption of Samples
Prior to analysis, pipet 5.0 ml of hexane into each vial.
Florisil particles should not be allowed to cling to the glass above the
solvent. A minimum desorption time of 10 minutes is required before
analysis.
(3) Gas-liquid chromatographic conditions for PCB
determination by this procedure are:
(A) Nitrogen carrier gas flow rate, 60 ml/minute.
(B) Injector temperature, 300 C.
(C) Interface and detector temperatures, both 325 C.
(D) Column temperature, 180 C.
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(4) Sample Injection
The solvent-flush technique Is recommended for Injection of
materials Into the GLC apparatus. With this method, the following
procedure would be used to Inject 4 yl of sample. Three microliters of
hexane would be drawn into the syringe, followed by 1 itl of air, followed
by 4 jil of sample solution. After the needle Is removed from the sample
solution, 1 additional jil of air Is drawn Into the syringe to minimize
evaporation at the tip of the needle. The plunger now rests at the 9-yl
mark. Inject at least 7 jil of the syringe contents Into the gas
chromatogram. Not less than 1 til of flush-solvent should be used. Larger
volumes of flush may give a solvent peak which Interferes with sample
component peaks. The syringe must be cleaned with hexane after each
Injection.
(5) Preliminary Analysis
Using the solvent-flush method of subsection b(4), Inject 1 jil
of sample and 1 Ail of flush-solvent at the conditions specified under
subsection b(3). If the sample Is too concentrated, further dilutions will
be necessary to bring the concentration of the sample solution Into the
linear range of the electron capture detector. Once the concentration of
the sample is appropriately adjusted, Its chromatogram should be compared
to that of a standard to determine If the air sample Is qualitatively
different in composition from the standard. If there is little difference
between the two chromatograms, then proceed with the standard analysis
using the PCB mixture for standardization, subsection b(6). On the other
hand, sheuld there be a significant difference between the two
chromatograms (such that comparison with the PCB mixture could result in
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gross error), then use the alternate procedure for standardization,
subsection b(7).
(6) Standard Analysis
Select at least five prominent peaks in the sample chromatogram and compare
their heights or areas with those of the standard. Calculate the
concentration of PCBs by comparing the heights or areas of the selected
peaks in the sample chromatogram of those in the standard chromatograms of
known amounts of material.
(7) Alternate Standardization Procedure
A 200-^1 aliquot of the sample is placed in a 13-tnm x 100-mm culture
tube and the hexane is slowly evaporated with dry nitrogen until 10 jil or
less remain. Do not allow hexane to climb the tube during evaporation and
do not allow the sample to evaporate to dryness. Immediately add 0.2-0.5
ml of distilled antimony pentachloride with a disposable pipet as rapidly
as possible (antimony pentachloride decomposes rapidly in air) and cap the
tube. The sample should remain light yellow after this addition, but if
the Bample turns dark brown or black, it must be discarded and another
aliquot of that sample must be used. All samples are placed together in a
sand bath. There should be no liner in the cap of the tube, since most
liners are attacked by antimony pentachloride. A sample of
decachlorobiphenyl is treated in a manner similar to the samples. The sand
bath containing all of the treated samples is placed in a preheated oven at
160 C for at least 3 hours. Samples may also be treated overnight. After
perchlorination, the sand bath is removed from the oven and the samples are
removed from the sand and allowed to cool to room temperatur®. To each
sample is added dropwise 0.5 ml of 20% hydrochloric acid. This mixture is
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then extracted four times with 1-2 ml of hexane each time. Each extract is
passed through a funnel containing approximately 0.5 g of anhydrous sodium
sulfate (retained by a glass wool plug) into a 10-ml volumetric flask. The
volume of the sample is brought to 10 ml by rinsing the pipet, sodium
sulfate, and funnel tip with hexane. The funnel should not rest on thezlip
of the flask during filtration. The glass wool plug and sodium sulfate in
the funnel are replaced after each sample. An aliquot of the sample
solution is injected under the GLC conditions described above. The
solvents flush technique is recommended using 2 til of solvent back flush
and 6 /xl of standard or sample solution. The syringe must be cleaned with
hexane after each injection. The height or area of the decachlorobiphenyl
peak is compared to that of the decachlorobiphenyl standard and the weight
of decachlorobiphenyl present is calculated.
(8) Gas-liquid chromatographic conditions for
decachlorobiphenyl determination:
(A) Nitrogen carrier gas flow rate, 90 ml/minute.
(B) Injector temperature, 300 C.
(C) Interface and detector temperature, 325 C.
(0) Column temperature, 220 C.
(c) Determination of Desorption Efficiency
NIOSH has found average desorption efficiency is >99.3%, thus,
results of sample analyses need not be corrected for desorption efficiency.
Calculations
(a) Standard Analytical Procedure
The following are the steps in the calculation of concentrations of
205
-------
PCBs in air when determined with a PCB mixture as the standard.
(1) Add the heights or areas of several selected prominent
peaks (at least five) in the chromatogram, compare with the total heights
or areas of those same peaks in the standard, and read the concentration of
the sample solution (ng/ml) from the standard curve.
(2) Multiply the concentration, in ng/ml, of the sample
solution by the total volume, in ml, of the sample solution and calculate
the weight of PCBs in the sample. Make corrections for the blanks if
necessary.
(3) Add the weights found on the front and the back
sections of the tube to find the total weight of PCBs in the air sample.
(4) Divide the total weight of the PCBs in the air sample
by the volume, in liters, of air sampled and report the PCB concentration
in ng/liter or its equivalent in n$/cu m.
(b) Alternate Standardization Procedure
The following are the steps in the calculation of concentrations of
PCBs in air using the perchlorination method.
(1) The height or area of the decachlorobiphenyl peak in
the chromatogram of the sample aliquot is compared to the height or area of
the decachlorobiphenyl peak in the chromatograms of the standard. The
concentration of decachlorobiphenyl in the sample aliquot is read from the
standard curve.
(2) The concentration of decachlorobiphenyl in this aliquot
(ng/ml) is multiplied by the total volume (ml) of the sample solution to
give the total weight of PCBs in the sample as decachlorobiphenyl.
206
-------
(3) The weights of PCBa, as decachlorobiphenyl, found on
the front and back sections of the tube are summed, corrections for blanks
are made, and the total weight of PCB, as decachlorobiphenyl, in the air
sample is calculated.
(4) The total weight of PCB is divided by the volume of air
sampled and the air concentration is reported in ng/liter or its equivalent
in Mg/cu m.
207
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XI. APPENDIX III
MATERIAL SAFETY DATA SHEET
General instructions for preparing a Material Safety Data Sheet
(MSDS) are presented in this chapter. The examples used in the text are
for illustrative purposes and are not intended to apply to any specific
compound or product. Applicable information about a specific product or
material shall be supplied in the appropriate block of the MSDS,
The product designation is inserted in the block in the upper left
corner of the first page to facilitate filing and retrieval. Print in
upper case letters as large as possible. It should be printed to read
upright with the sheet turned sideways. The product designation is that
name or code designation which appears on the label, or by which the
product is sold or known by employees. The relative numerical hazard
ratings and key statements are those determined by the guidelines in
Chapter V, Part B, of the NIOSH publication, An Identification System for
Occupationally Hazardous Materials. The company identification may be
printed in the upper right corner if desired.
(a) Section I. Product Identification
The manufacturer's name, address, and regular and emergency telephone
numbers (including area code) are inserted in the appropriate blocks of
Section I. The company listed should be a source of detailed backup
information on the hazards of the material(s) covered by the MSDS. The
listing of suppliers or wholesale distributors is discouraged. The trade
name should be the product designation or common name associated with the
material. The synonyms are those commonly used for the product, especially
208
-------
formal chemical nomenclature. Every known chemical designation or
competitor's trade name need not be listed.
(b) Section II. Hazardous Ingredients
The "materials" listed In Section II shall be those substances which
are part of the hazardous product covered by the MSDS and individually meet
any of the criteria defining a hazardous material. Thus, one component of
a multlcomponent product might be listed because of Its toxicity, another
component because of Its flammablllty, while a third component could be
Included both for Its toxicity and its reactivity. Note that a MSDS for a
single component product must have the name of the material repeated in
this section to avoid giving the Impression that there are no hazardous
ingredients.
Chemical substances should be listed according to their complete name
derived from a recognized system of nomenclature. Where possible, avoid
using common names and general class names such as "aromatic amine,"
"safety solvent," or "aliphatic hydrocarbon" when the specific name is
known.
The "%" may be the approximate percentage by weight or volume
(indicate basis) which each hazardous ingredient of the mixture bears to
the whole mixture. This may be indicated as a range or maximum amount, ie,
"10-40% vol" or "10% max wt" to avoid disclosure of trade secrets.
Toxic hazard data shall be stated in terms of concentration, mode of
exposure or test, and animal used, eg, "100 ppm LC50-rat," "25 og/kg LD50-
skin-rabbit," "75 ppm LC man," or "permissible exposure from 29 CFR
1910.1000," or, if not available, from other sources of publications such
as the American Conference of Governmental Industrial Hygienists or the
209
-------
American National Standards Institute Inc. Flashpoint, shock sensitivity
or similar descriptive data may be used to indicate flammability,
reactivity, or similar hazardous properties of the material.
(c) Section III. Physical Data
The data in Section III should be for the total mixture and should
include the boiling point and melting point in degrees Fahrenheit (Celsius
in parentheses); vapor pressure, in conventional millimeters of mercury (mm
Hg); vapor density of gas or vapor (air ¦ 1); solubility in water, in
parts/hundred parts of water by weight; specific gravity (water " 1);
percent volatiles (indicate if by weight or volume) at 70 degrees
Fahrenheit (21.1 degrees Celsius); evaporation rate for liquids or
sublimable solids, relative to butyl acetate; and appearance and odor.
These data are useful for the control of toxic substances. Boiling point,
vapor density, percent volatiles, vapor pressure, and evaporation are
useful for designing proper ventilation equipment. This information is
also useful for design and deployment of adequate fire and spill
containment equipment. The appearance and odor may facilitate
identification of substances stored in improperly marked containers, or
when spilled.
(d) Section IV. Fire and Explosion Data
Section IV should contain complete fire and explosion data for the
product, including flashpoint and autoignition temperature in degrees
Fahrenheit (Celsius in parentheses); flammable limits, in percent by volume
in air; suitable extinguishing media or materials; special firefighting
procedures; and unusual fire and explosion hazard information. If the
product presents no fire hazard, insert "NO FIRE HAZARD" on the line
210
-------
labeled "Extinguishing Media."
(e) Section V. Health Hazard Information
The "Health Hazard Data" should be a combined estimate of the hazard
of the total product. This can be expressed as a TWA concentration, as a
permissible exposure, or by some other Indication of an acceptable limit.
Other data are acceptable, such as lowest LD50, If multiple components are
Involved.
Under "Routes of Exposure," comnents In each category should reflect
the potential hazard from absorption by the route In question. Comments
should Indicate the severity of the effect and the basis for the statement,
If possible. The basis might be animal studies, analogy with similar
products, or human experiences. Comments such as "yes" or "possible" are
not helpful. Typical comments might be:
Skin Contact—single short contact, no adverse effects likely;
prolonged or repeated contact, irritation, and cracking.
Readily absorbed through the skin with severe systemic effects.
Eye Contact—some pain and mild transient irritation; no corneal
scarring.
"Emergency and First Aid Procedures" should be written in lay
language and should primarily represent first-aid treatment that could be
provided by paramedical personnel or individuals trained in first aid.
Information in the "Notes to Physician" section should include any
special medical information which would be of assistance to an attending
physician including required or recommended preplacement and periodic
medical examinations, diagnostic procedures, and medical management of
overexposed workers.
211
-------
(f) Section VI. Reactivity Data
The comments in Section VI relate to safe storage and handling of
hazardous, unstable substances. It is particularly important to highlight
instability or Incompatibility to common substances or circumstances such
as water, direct sunlight, steel or copper piping, acids, alkalies, etc.
"Hazardous Decomposition Products" shall include those products released
under fire conditions. It must also include dangerous products produced by
aging, such as peroxides in the case of some ethers. Where applicable,
shelf life should also be indicated.
(g) Section VII. Spill or Leak Procedures
Detailed procedures for cleanup and disposal should be listed with
emphasis on precautions to be taken to protect workers assigned to cleanup
detail. Specific neutralizing chemicals or procedures should be described
in detail. Disposal methods should be explicit including proper labeling
of containers holding residues and ultimate disposal methods such as
"sanitary landfill," or "incineration." Warnings such as "comply with
local, state, and federal antipollution ordinances" are proper but not
sufficient. Specific procedures should be identified.
(h) Section VIII. Special Protection Information
Section VIII requires specific information. Statements such as
"Yes," "No,"' or "If Necessary" are not informative. Ventilation
requirements should be specific as to type and preferred methods. Specify
respirators as to type and NIOSH or US Bureau of Mines approval class, ie,
"Supplied air," "Organic vapor canister," "Suitable for dusts not more
toxic than lead," etc. Protective equipment must be specified as to type
and materials of construction.
212
-------
(1) Section IX. Special Precautions
"Precautionary Statements" shall consist of the label statements
selected for use on the container or placard. Additional Information on
any aspect of safety or health not covered In other sections should be
Inserted In Section IX. The lower block can contain references to
published guides or ln-house procedures for handling and storage.
Department of Transportation markings and classifications and other
freight, handling, or storage requirements and environmental controls can
be noted.
(J) Signature and Filing
Finally, the name and address of the responsible person who completed
the MSDS and the date of completion are entered. This will facilitate
correction of errors and Identify a source of additional Information.
The MSDS shall be filed In a location readily accessible to workers
potentially exposed to the hazardous material. The MSDS can be used as a
training aid and basis for discussion during safety meetings and training
of new employees. It should assist management by directing attention to
the need for specific control engineering, work practices, and protective
measures to ensure safe handling and use of the material. It will aid the
safety and health staff In planning a safe and healthful work environment
and In suggesting appropriate emergency procedures and sources of help In
the event .of harmful exposure of employees.
213
-------
MATERIAL SAFETY DATA SHEET
1 PRODUCT IDENTIFICATION
MANUFACTURER'S NAME
REGULAR TELEPHONE NO
EMERGENCY TELEPHONE NO
ADDRESS
TRADE NAME
SYNONYMS
II HAZARDOUS INGREDIENTS
MATERIAL OR COMPONENT
HAZARD DATA
III PHYSICAL DATA
BOILING POINT.. ?60 MM HC
MELTING POINT
SPECIFIC GRAVITY
-------
IV FIRE AND EXPLOSION DATA
'LASH POINT
ITEST METHOD!
AUTOIGNITION
TEMPERATURE
Flammable limits in air. % ev vol.
cower
UPPfR
EXTINGUISHING
MEOfA
SPICIAt f IRE
FIGHTING
PROCEOURES
UNUSUAL FIRE
ANO EXPLOSION
HA2ARO
V HEALTH HAZARD INFORMATION
HE J
IZARO DATA
ROUTES OF EXPOSURE
INHALATION
SKIN CONTACT
SKIN ABSORPTION
kYfcontact
INGESTION
EFFECTS OF OVEREXPOSURE
ACUTE OVEREXPOSURE
CHRONIC OVEREXPOSURE
EMERGENCY ANO FIRST AfO PROCEOURES
EVES
SKIN
INHALATION
INGESTION
NOTES TO PHYSICIAN
215
-------
VI REACTIVITY DATA
CONDITIONS CONTRIBUTING TO INST ABILITY
INCOMPATIBILITY
HAZARDOUS DECOMPOSITION PROOUCTS
CONDITIONS CONTRIBUTING TO HAZARDOUS POLYMERIZATION
VII SPILL OR LEAK PROCEDURES
STEPS TO BE TAKEN IF MATERIAL IS RELEASED OR SPILLED
NEUTRALIZING CHEMICALS
WASTE OISPOSAL METHOD
VIII SPECIAL PROTECTION INFORMATION
VENTILATION REQUIREMENTS
SPECIFIC PERSONAL PROTECTIVE EQUIPMENT
RESPIRATORY ISPEClFY IN OETAILI
EYE
gloves
OTHER CLOTHING AND EQUIPMENT
I
216
-------
IX SPECIAL PRECAUTIONS
PRC CAUTIONARY
statements
OTHCR MANODNC ANO
STORACC RCQUlRCMiNTS
PRIPAREO BV
AOORESS
DATE
217
-------
TABLE XII-1
CHEMICAL AND PHYSICAL PROPERTIES OF SOME AROCLORS
Aroclor
Chlorine,
% w/w
Distillation
Range, C
(corrected)
Density
g/ml
25 C
Flash-
point*
F
Fire-
Point*
F
Appearance
1221
20.5-21.5
275-320
1.18
286-302
349
Clear, mobile oil
1232
31.4-32.5
290-325
1.26
305-310
460
It
1242
42
325-366
1.38
384-356
none**
It
1248
48
340-375
1.44
379-384
if
II
1254
54
365-390
1.54
none**
II
Light-yellow vlsous liquid
1260
60
385-420
1.62
11
11
Light-yellow soft, sticky resin
1262
62
390-425
1.64
It
H
Light-yellow sticky, viscous resin
1268
68
435-450
1.82
II
tl
White to off-white powder
*Cleveland Open Cup
**None to boiling point
Adapted from reference 1
-------
TABLE XII-2
QUALITATIVE AND PERCENT CHLOROBIPHENYL AND BIPHENYL COMPOSITIONS OF COMMERCIAL PCB PREPARATIONS
(Qualitatively major peaks = M, minor peak* = m. ambiguous identities = T; quantitatively, percentages rounded)
CL-Substituted Positions Commercial Preparation Designations (trade names omitted)
mi
1221
1221
1221
1232
1016
1242
1242
1242
I2U
1241 I2S4 12S4 12S4 *50
12U 12M
0
13
16
m
16
m
OS
m
m
m
m
2
28
32
m
35
in
1
m
08
m
m
m
in
3
3
m
3
4
19
19
m
20
m
2
tn
m
2.3
04
2.4
4
3
2
1
<07
m
<01
m
m
2.5
02
Ir
m
m
2.6
03
04
ti
a
2.2"
9
5
m
5
n
7
m
<10
M
m
ra
m
2.3'
3
m
2
m
1
m
m
M
m
m
m
2.4'
14
10
m
11
m
II
m
in
2.3.3'
01
ti
M?
2.3.4'
li
2.4.5
2.4 6 '
2.2'.4
03
m
m
4
m
II
M
m
8
m
m
2.3 .4'
m
m
4
m
<15
M
m
<13
m
IB
2.4.4'
0?
m
m
4
ra
1
M'
m
3
2 2'5
06
06
m
12
m
2
H
n
01
m
ai
2.3'.5
02
9
m
M
m
<13
2.4'.5
02
m
m
10
m
m
m
m
n
2.2V6
m
1
m.
m
m
m
in
2.3 fi
03
M'
2 4.6
2
M
m
m
3.4 5
2'.3.4
01
ti
m
16
M
in
21
03 m
n
3 3.4
m
34 4
2
M
-------
TABLE XII-2 (Continued)
QUALITATIVE AND PERCENT CHLOROBI PHENYL AND BIPHENYL COMPOSITIONS OF COMMERICAL PCB PREPARATIONS
(Qualitatively major peaks = M. minor peAks = m. Ambiguous identities = ?; quantitatively, percentages rounded)
CL-Substituted Positions Commercial Preparation Designations (trade names omitted)
ro
ro
O
? .3.5
ii
3'3' 5
3.4' 5
lr
2 3.4.5
2 3> 6
2.3 '5.6
2.2 .3 4
3
2.3 3' 4
04
M
'2.3.4.4-
m
2.2' 3.5
M>
2.3 3' 5
2.3 4 .5
02
2.2' 3.6
<2
2.3.3.6
6
M>
2.3.4.6
tr
M?
2.3.4.5
2.4.4.5
2.2.4.6
2 3' 4.6
<2
M?
2.4.4'.6
ti
2-3.4.5
M'
3 3' 4.5
3 4.4.5
2 2\3.3"
1
2.2.3.4-
tr
2.2-3 5-
1 m
2.2' 3.6'
1
2.3 3.4-
4
m
2.3.3.5'
2.2.4.4'
m
1 m
2 2'.4.5'
3 m
12
M'
2 2 .4.6'
0 1
2.3.4.4'
lr m
m
2.3.4.5'
2.3' 5.5'
M»
2.2' 5 5'
0 14
2 m
lr
M'
1 07
7 m
m m
m
M 2 <0.4
-------
N»
1221 1221 1221 1221 1232 1011 1242 1242 1242 1241 1241 I2M 12M 12S4 *50 12C0 12M 12<0 MO
2.2.5.6 2
2.2'.6.6' 3
3.3.4.4 1
3.3'.4.5-
3.3.5 5'
r.r.s- 6
r 3.4.5' 0 5 m 9 II m 24 M4 <0.4 m
2.3'.4'.6 m
2 3.4.5.6
2.2'.3.4 5 ,
2.3.3.4.5
2.3.4.4'.5
2.2' 3.4.6
2.3.3.4.6
2.3.4.4.6
2.2'.3 5 6
2.3.3' 5 6
2.3.4' 5.6
2.2'.3.3'.4 . 1
2.2' 3.4.4'
<16
2.2'.3 4.5' ^ * 23-7 II- m m 1
K 2.2' 3.4.6'
2 3.3'.4.4' m M 4 <4
2.3 3'.4.5'
2.2'.3.3'.5
2.2'.3.4'.5 5
2.2".3 5.5' M 2 ¦ 1
2.2'.3.5.6'
2 3.3'.4' 5
2.3.3' 5.5'
2.2'.3.3'.6 m m hi II 3 0.3
2.2'.3 4'.6 "> "
2 2' 3 5.6 m M> ml4M42M3
2.2'.3.6.6' "> m m m
2.3.3.4.6 m m m M 8 m 3
2.3.3'.5' 6 m
2.2'.3',4 5 m m M 1 m
2.2" 4.4'.5 ' tn m m m 2 m II 2 m It
2.2' 4.5 5" 01m mlrnmM7 M 6
2.2'.4.5.6'
2.3'l4.4'.5 W m 1 m 14 II 5 <16 m 2
2.3'.4.5.5'
2.2' 3' 4.6 If
2.2' 1,4-6 8 M?
-------
TABLE Xll-2 (Continued)
QUALITATIVE AND PERCENT CHI.OROBIPHENYL ANI) BIPHENYL COMPOSITIONS OF COMMERCIAL PCB PREPARATIONS
(Qualitatively major peaks = M, minor peakn = m, ambiguous identities = ?; quantitatively, percentages rounded)
CL-Suhstiluted Positions Cummercinl Preparation Designations (trade names omitted)
12? I 1221 1221 1221 1212 1«16 1242 1242 1242 124t 12*8 1254 1254 12S4 ASS 12W 12U 12M MS
2.2'.4.5'.6
2,2',4,6,6'
2,3'.4.4'.6
2.3'.4,5.6
2.3.3'.4',5'
2.3.4.4'.5'
2.3.4.5,5'
2.3.4.5,6
3.3'.4,4',5
3.3.4,5.5'
2.2.3,4,5,6
2.3,3',4,5,6
2.3,4.4'.5.6
2.2'.3.3'.4,5
2.2'. 3.4,4'. 5
2.2'.5.4.5.5'
2.2'.3.4.5.6'
2.3.3.4,4.5 m 0 8 <9 m 2
2.3.3.4.5.5'
2.2'.3.3.4.6
2.2'.3.4.4',6
2,2'.3.4,5',6
2.2'.3.4.6.6'
2.3.3'.4.4.6 m m
2.3,3'.4.5',6
2.2'.3.3'.5.6
2.2',3.4'.5.6
2.2'.3.5.5'.6 n 1 3
2 2'.3.5.6 6'
2 3.3'.4'.5.6
2.3.3'.5.5'.6
2.2'. 3.3'. 4,4' J rn 1 M 2
2.2'.3.3.4,5' <1 2
2.2' 3.4,4',5' m 12 M 5 M m 11
2,3.3' M'.5' m
2.2',3.3'.4 6' m M 2 M 3'
2.2'.3,4.4',6'
------- |