____________________________________________________________

ATSDR Case Studies in Environmental Medicine

Polychlorinated Biphenyl(PCB) Toxicity

Issue 12                      June 1990

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     ENVIRONMENTAL ALERT...                                  

     -    PCBs have caused elevated liver enzyme levels and
          chloracne in humans, and may have reproductive
          effects.

     -    PCBs cause cancer in animals and may be
          carcinogenic in humans.

     -    PCBs are environmentally persistent and
          concentrate upward in the food chain.

*****************************************************************

This monograph is one in a series of self-instructional
publications designed to increase the primary care
provider's knowledge of hazardous substances in the environment
and to aid in the evaluation of potentially
exposed patients. See page 17 for further information about
continuing medical education credits and continuing
education units.



Guest Contributor:  Roger Wabeke, CIH; Richard Weinstein, MD, MPH
Guest Editor:       Gideon Letz, MD
Peer Reviewers:     Charles Becker, MD; Jonathan Borak, MD;
                    Joseph Cannella, MD;Bernard Goldstein, MD;
                    Alan Hall, MD; Richard J. Jackson, MD, MPH;
                    Jonathan Rodnick, MD; Robert Wheater, MS;
                    Brian Wummer, MD


              U.S. DEPARTMENT OF HEALTH & HUMAN SERVICES
                         Public Health Service
           Agency for Toxic Substances and Disease Registry




How to use this issue...

This issue begins with a composite case study that describes a
realistic encounter with a patient. This description is followed
by a pretest. The case study is further developed through
Challenge questions at the end of each section. To fully benefit
from this monograph, readers are urged to answer each question
when it is presented.(Answers to the Pretest and Challenge
questions are found on pages 15 and 16.) The monograph ends with
a post test which can be submitted to ATSDR for continuing
medical education (CME) credit or continuing education units
(CEU). See page 17 for further instructions on how to receive
these credits.

The objectives of this monograph on PCBs are to help you: 

-    Explain why PCBs are an acute and chronic health hazard

-    Describe the known factors contributing to PCB toxicity

-    Identify potential environmental or occupational sources of
     exposure to PCBs

-    Identify evaluation and treatment protocols for persons
     exposed to PCBs

    List sources of information on PCBs

                         Contents

Case Study ...................
Pretest ......................
Exposure Pathways ............
Who's at Risk.................
Biologic Fate.................
Physiologic Effects...........
Clinical Evaluation ..........
Treatment and Management .....
Standards and Regulations ....
Suggested Reading List........
Answers to Questions .........
Sources of Information .......
Posttest and Credits .........


This issue is prepared with the assistance of those who share a
common concern for physician education, public health, and the
environment, including the following organizations: American
Academy of Family Physicians (AAFP), American Academy of
Pediatrics (AAP), American College of Emergency Physicians
(ACEP), American College of Occupational and Environmental
Medicine (ACOEM), American Medical Association (AMA), Association
of State and Territorial Health Officials (ASTHO), and the
Society of Teachers of Family Medicine (STFM). Final
responsibility for the contents and views expressed in this
monograph resides with ATSDR.


Agency for Toxic Substances and Disease Registry
Project Officers: Max Lum, EdD, and Donna Orti, MS                
Prepared by DeLima Associates, San Rafael, California,under
Contract No. 205-88-0636.


Case Study

A 48-year-old handyman with progressive cystic acne and abnormal
liver function. You have been treating a 48-year-old man
conservatively for his facial acne vulgaris. He first sought
treatment about 3 months ago, remarking that such blemishes are
typical for a teenager but he never had them during adolescence.
Therapy was initiated with benzoyl peroxide washes and topical
antibiotics, in addition to instructions for skin hygiene. When
no real improvement was noted, oral antibiotics were prescribed.
Due to continued lack of efficacy, this regimen was later
supplemented by Retin-A (tretinoin) cream. 
The patient has returned for a follow-up visit and complains that
the acne is worse. On examination, you agree, and tell the
patient you would like to refer him to a dermatologist for
Accutane(TM) (isotretinoin)therapy. A serum biochemical and
hematology profile are ordered to document baseline values before
therapy begins. 

To your surprise, the biochemical panel reveals the following
abnormalities: total bilirubin 2.8 mg/dL (normal 0-1.5), direct
bilirubin 0.4 mg/dL (normal 0-0.4), SGPT (ALT) 74 IU/L (normal
0-50), SGOT (AST) 88 IU/L (normal 0-50), GGPT (GGT) 190 IU/L
(normal 15-85), LDH 230 IU/L (normal 50-225). Other testing,
including complete blood count, alkaline phosphatase, BUN,
creatinine, and urinalysis are within normal limits.

On questioning, the patient denies history of hepatitis, contact
with hepatitis patients, other liver difficulties or blood
transfusion. He informs you he has Gilbert's syndrome and has had
elevated bilirubin levels in the past. There is no family history
of cardiovascular disease or cancer. The patient does not smoke;
he drinks 2 to 3 bottles of beer each evening, and sometimes more
on weekends. He is currently taking no medications other than
those mentioned. Review of systems is otherwise unremarkable. 
Social history reveals the patient is married with three teenaged
children; his wife and children are in good health. They live in
a high-rise apartment building where the patient has been
handyman and part-time building manager for the last year. He
spends much time in the basement area, which includes a
workshop,- recreation room with pool table, and laundry and
heating facilities. An avid fisherman, he spends most weekends
fishing in Lake Michigan with his two sons. Physical examination
reveals mild, nontender hepatomegaly without jaundice. His acne,
which is most prominent on the upper face lateral to the
eyebrows, began about 8 months ago. 

* Use of trade names is for identification only and does not
imply endorsement by the Public Health Service or the U.S.
Department of Health and Human Services. 


____________________________________________________

PRETEST

(a)  What should be included in the patient's problem list?


(b)  What is a differential diagnosis for the patient's altered
     liver enzymes?

(c)  What tests would be useful in helping you arrive at a
     diagnosis?

Answers to the Pretest can be found on page 15.
________________________________________________________

Challenge

(1)  Additional information for the case study: in response to
     your persistent detailed questioning regarding his hobbies
     and possible contact with hepatotoxins, the patient reveals
     that while in the basement workshop he frequently wipes up a
     "dark, oily discharge" near a large electrical transformer
     in the work area. The discharge has also resulted in a gummy
     residue on tools and other surfaces. He mentions he
     sometimes feels dizzy and nauseated after working in the
     basement all day. Is there an association between the
     clinical findings and this additional information?
_______________________________________________________________

Exposure Pathways


-    PCBs persist in the environment, concentrating upward in the
     food chain.

-    The primary nonoccupational source of PCB exposure is food,
     especially fish from contaminated water.


Polychlorinated biphenyls (PCBs) are a family of 209 chemicals
with varying numbers of chlorine atoms attached in varying
positions to two connected benzene rings (Figure 1). Commercial
PCB products are always mixtures of PCBs and are usually
contaminated with small amounts of polychlorinated dibenzofurans
(furans) or polychlorinated dibenzodioxins (dioxins).
Contamination by furans is a concern because their toxicity is
generally much greater than that of PCBs. 

Because of their insulating and nonflammable properties, PCBs
have been used as heat exchange and dielectric fluids in
transformers and capacitors, hydraulic and lubricating fluids,
diffusion pump oils, plasticizers, extenders for pesticides, and
as ingredients of caulking compounds, paints, adhesives, and
flame retardants. PCBs have also been used in inks and carbonless
paper. Trade names for PCBs include Aroclor, Askarel, Eucarel,
Pyranol, Dykanol, Clorphen, Asbestos Diaclor, Nepolin, and
EEC-18.*

PCB mixtures are colorless to dark brown oils, viscous liquids,
or sticky resinous semi-solids. They evaporate slowly at room
temperature; however, their volatility increases dramatically
with small increases in temperature. Overheated equipment that
contains PCBs can vaporize significant quantities of these
compounds, causing an inhalation hazard, especially in areas
where ventilation is poor.

Today PCBs are found mainly in transformers and capacitors
manufactured before the U.S. Environmental Protection Agency
(EPA) banned the production of PCBs in 1977. Many of these old
transformers and capacitors are still contained in industrial
equipment (such as welding equipment), medical equipment(such as
X-ray machines), and household appliances (such as
refrigerators). Ballasts of fluorescent light fixtures may
contain PCBs. During normal lighting operation, the PCBs are
entirely enclosed; however, when the capacitor wears out, it may
burn or break and leak PCBs.

PCBs can be released into the general environment from poorly
maintained toxic waste sites; by illegal or improper dumping of
PCB wastes, such as transformer fluids; through leaks or fugitive
emissions from electrical transformers containing PCBs; and by
disposal of PCB-containing consumer products in municipal
landfills. PCBs have been found in at least 271 of 1177 hazardous
waste sites on the EPA National Priorities List. Of the 1.25
billion pounds of PCBs produced in this country since 1929, about
450 million pounds have found their way into the environment. The
chemical stability of these synthetic compounds accounts for
their persistence in the environment. Another important reason
for their persistence is their resistance to biodegradation. Low
levels of PCBs can be found throughout the world. PCBs in water
or on soil surfaces evaporate and return to earth by rainfall or
settling of dust particles. Because PCBs strongly adsorb to soil
particles, significant leaching from soil and translocation to
plants do not occur. Although PCBs are widespread in the aquatic
environment, their low water solubility helps to prevent high
concentrations in drinking water supplies.

_______________________________________________________________
* Use of trade names is for identification only and does not
imply endorsement by the Public Health Service or the U.S.
Department of Health and Human Services .
_______________________________________________________________


Food can be a major source of PCB exposure, usually from fish and
animal fat. PCBs are lipophilic; they preferentially separate
from water and adsorb to sediment. Bottom feeders and other
aquatic organisms then ingest and accumulate PCBs, resulting in
bioconcentration upward in the food chain. Composite analysis of
commercial whole fish collected from Lake Ontario in 1980 found
PCB levels of 0.11 to 4.90 parts per million (ppm).

The toxicity of PCBs was dramatically illustrated in 1968 when
over 1600 people in Japan were poisoned by cooking oil
contaminated with PCBs from a heat transfer unit. The
contaminating oil likely contained furans and dioxins, compounds
generally more toxic than PCBs themselves. The ensuing illnesses
became known as "Yusho" (rice oil disease).
_________________________________________________
CHALLENGE

1) additional information for the case study: In response to your
persistent, detailed questioning regarding his hobbies and
possible contact with hepatotoxins, the patient reveals that
while in the basement workshop he frequently wipes up "dark oily
discharge" near a large electrical transformer in the work area. 
The discharge has also resulted in a gummy residue on tools and
other surfaces. He mentions he sometimes feels dizzy and
nauseated after working in the basement all day.

Is there an association between the clinical findings and this
additional information?
____________________________________________________


Who's at Risk

-    Certain workers can be exposed to PCBs during repair of
     equipment and accidents or spills.

-    Fetuses and neonates may be more sensitive to PCBs than
     adults; nursing infants are at increased risk of exposure
     from PCB-exposed mothers.

-    Persons with compromised hepatic function may metabolize
     PCBs less efficiently than healthy persons.


Although PCBs are no longer manufactured in the United States,
the greatest potential for exposure to PCBs still occurs in the
workplace. For example, workers may inhale or have dermal contact
with PCBs during repair or maintenance of process equipment or
electrical transformers and during accidents or spills involving
PCBs. Exposure can also occur in disposal of PCB-containing
materials at hazardous waste sites. Occupations entailing risk of
PCB exposure include, but are not limited to, the following:

     electric cable repair
     electroplating
     emergency response
     firefighting
     hazardous waste hauling/site operating
     heat exchange equipment repair
     maintenance cleaning
     metal finishing
     paving and roofing
     pipe fitting/plumbing
     timber products manufacturing
     transformer/capacitor repair
     waste oil processing
     
Nonoccupational exposures have also occurred. The public has
encountered PCBs through illegal roadside dumping of hazardous
waste oils and through inhalation of smoke and soot from
transformer or capacitor fires. Pyrolysis of PCBs can produce
dioxins and furans, placing smoke-inhalation victims at increased
risk of exposure to these toxic compounds.

Fetuses and neonates are potentially more sensitive to PCBs than
adults because of transplacental distribution and physiologic
differences. They lack the hepatic microsomal enzyme systems that
facilitate metabolism and excretion of PCBs. Furthermore, PCBs
accumulate in breast milk. Nursing infants are at additional risk
because human milk contains a steroid that inhibits PCB
glucuronidation and excretion. Other populations potentially more
sensitive to PCBs are persons with compromised hepatic
functioning, including those with incompletely developed
glucuronide conjugation mechanisms due to congenital disorders
such as Gilbert's syndrome, and persons with hepatic infections.
Persons taking medications potentially toxic to the liver may
also be at increased risk. 
__________________________________________

CHALLENGE

2) Are other sources of PCB exposure likely for the patient
described in this study?
__________________________________________


Biologic Fate

-    PCBs are stored in lipid tissues.

-    The liver is the primary site of PCB metabolism.

-    The slow metabolism of PCBs leads to bioaccumulation.

PCBs are readily absorbed into the body but slowly metabolized
and excreted. After absorption, PCBs partition between the
aqueous and lipid compartments of the body in a biphasic pattern.
During the first day after PCBs were administered to laboratory
animals, they were distributed mainly to the liver and muscle
tissue. In a second phase, PCBs were redistributed to the adipose
tissue, skin and other fat-containing organs. More highly
chlorinated PCBs redistribute to adipose tissue to a greater
extent than do PCBs with a lower percentage of chlorine; the
presence of more highly chlorinated PCBs appears to delay
excretion of the lesser chlorinated compounds for reasons not
clearly understood.

The liver is the primary site of PCB metabolism by hydroxylation
and conjugation with glucuronic acid and sulfates. The rate of
metabolism depends on the number and position of chlorine atoms,
with lesser chlorinated isomers being more readily metabolized .

Excretion of PCBs is slow, so bioaccumulation occurs even at low
exposure levels. As long as exposure continues, a true steady
state is never achieved. PCBs metabolized with more difficulty
are excreted almost exclusively by the binary route; metabolites
of PCBs with a smaller percentage of chlorination are eliminated
through bile and urine. Urinary metabolites are in the form of
conjugates, including glucuronides and sulfates. 

There are essentially no pharmacokinetic data for humans. PCB
half-lives in the rat range from 1 day to 460 days depending on
the degree of chlorination. Background levels in human sera are
typically less than 20 parts per billion (ppb), and residues
measured in human milk have ranged from 40 to 100 ppb. Reported
levels in adipose tissue range from 1 to 2 ppm. 

_______________________________________

CHALLENGE

3) Explain why patients with Gilbert's syndrome may be at
increased risk of adverse effects due to PCB exposure.
________________________________________

Physiologic Effects

-    PCBs have low potential to cause acute effects.

-    EPA considers PCBs to be probable human carcinogens.

In humans, PCB toxicity affects the skin and liver, and may have
developmental effects. Metabolic, reproductive, endocrine, and
immunosuppressive effects have been noted in animals, but have
not been adequately studied in humans. Although data from animal
studies indicate that PCBs are definitely animal carcinogens,
data from PCB-exposed human populations are inconsistent and
inconclusive. 

Dermatologic Effects

-    PCB-induced chloracne can reflect systemic toxicity.


Chloracne is the only overt effect of PCB exposure in humans, but
absence of chloracne does not rule out exposure. There is no
reliable dose-response model for chloracne in exposed
populations; the dose-response relationship may be dependent upon
individual predisposition. Chloracne typically develops weeks or
months after exposure. The lesions are often refractory to
treatment and can last for years. One case persisted for more
than 30 years.

The acneform lesions arise from altered differentiation of acinar
sebaceous base cells into keratinocytes. The chin, periorbital,
and malar areas are affected most often, although lesions may
also appear on the chest, arms, thighs, genitalia, and buttocks-
areas not commonly affected by acne vulgaris. The most
distinctive lesions are cystic and measure from 1 to 10
millimeters (mm). Other prominent lesions are comedo. The cysts
and comedones can become inflamed and secondarily infected. The
papules and cysts may be surrounded by edema and erythema.
Chloracne may result not only from dermal contact but also from
ingestion and generally indicates systemic toxicity. 

Besides chloracne, Yusho patients had hyperpigmentation of the
skin, Conjunctive, gingiva, and nails. These pigmentation
disturbances have also been noted in some PCB-exposed workers.


Hepatic Effects

-    High-level PCB exposure may produce elevated levels of liver
     enzymes.

-    Evidence suggests that PCBs cause hepatotoxicity in humans.

Epidemiologic studies and clinical surveys indicate that severe
occupational exposure to PCBs can increase serum liver enzymes.
The enzyme levels often show inconsistent patterns, however, and
increases generally have not been associated with hepatic
dysfunction, although approximately 10% of the Yusho patients
experienced jaundice. Asymptomatic hepatomegaly has been reported
in workers, many of whom had concomitant elevated serum PCB
levels. Some researchers believe that aspartate aminotransferase
(SGOT or AST) and gamma glutamyl transpeptidase (GGTP or GGT) are
the most sensitive indicators of PCB exposure in humans, and that
changes in these liver enzymes may occur at exposure levels below
those at which chloracne appears. Liver damage, histologically
documented, is the most consistent finding among laboratory
animals tested with PCBs. 

Increases in urinary porphyrin levels have been noted in a study
of workers with low-level PCB exposure. Changes in porphyrin
metabolism may be triggered by the induction of liver microsomal
enzymes. PCBs are more potent enzyme inducers than phenobarbital,
a drug that occasionally causes clinical problems due to its
enzyme-inducing effects, and PCBs' enzyme-inducing effects can
persist long after cessation of exposure. The health implications
for enzyme induction include the occurrence of disease secondary
to increased metabolism of endogenous or exogenous substances,
and interference in medical therapy due to increased metabolism
of administered drugs.  

Reproductive and Developmental Effects

-    PCBs have a potential to cause developmental and fetotoxic
     effects in humans.

The Yusho incident documents PCBs' potential to cause
developmental and fetotoxic effects in humans. Two of the Yusho
mothers had stillbirths; 10 of 13 infants had abnormal skin
pigmentation, 9 of 13 had ocular discharge, and 12 of 13 were
smaller than average. Two infants developed Yusho from breast
feeding. In contrast, the authors of a study of nursing infants
whose mothers were occupationally exposed to PCBs found no
adverse health effects. Contaminants in the PCB oil cannot be
ruled out as factors in Yusho disease. Follow-up of the Yusho
infants revealed no persistent morphologic or behavioral
abnormalities.


In laboratory animals, changes in estrous cycles, failure of ovum
implantation, increased frequency of spontaneous abortions, and
low birth weight of offspring have been reported after PCB
exposure. No teratogenic effects have been reported in studies of
humans or animals. 

Carcinogenicity

-    PCBs are considered potential human carcinogens on the basis
     of results from animal studies.

The epidemiologic evidence is insufficient to evaluate the
potential of PCBs as human carcinogens. Although Yusho victims
showed a slightly higher rate of deaths from neoplasms 15 years
after the incident, the data were not adjusted for age or smoking
and drinking patterns. Cancer data from other human populations
are inconsistent and inconclusive.

Data from animal studies have shown that PCBs cause
hepatocarcinomas, pituitary tumors, leukemia, Lymphomas, and
gastrointestinal tract tumors. On the basis of these data, EPA
considers PCBs to be probable human carcinogens.

__________________________________________________

CHALLENGE

4) Is there a need to be concerned about PCB exposure when the
clinical effects of the patient in the case study seems so
limited?
___________________________________________________


Clinical Evaluation


History and Physical Examination

A detailed history will facilitate the diagnosis of chronic PCB
poisoning. Pertinent information includes occupational histories
of all household members, medications, and diet, including
ethanol intake. During the physical examination, physicians
should pay particular attention to the skin and hepatic system.
Encountering a patient with PCB toxicity should trigger
consideration of whether this is a sentinel event, indicating the
possibility of other similarly exposed persons such as coworkers
or family members.

Signs and Symptoms

Acute Exposure

-    Chloracne is the only known overt sign of PCB toxicity;  
     however, absence of  chloracne does not rule out exposure.

PCBs have very low potential for producing acute toxic effects.
The only overt sign of PCB exposure is chloracne, which is
described on page 7. Acneform lesions do not appear in all
severely exposed patients (only 82% of Yusho patients had
chloracne); therefore, its absence does not rule out exposure.
New cases of chloracne should be reported to the local or state
health department.

Elevated liver enzymes are the most sensitive effect of PCB
exposure in animals and have been detected in several human
epidemiologic studies. Hepatomegaly has also been noted in
some PCB-exposed workers.

Chronic Exposure

-    Because of an EPA ban on PCB production in 1977, chronic
     exposure in the workplace is uncommon today.

Many people chronically exposed to PCBs have had no overt
signs or symptoms of toxicity. In others, reported signs and
symptoms of exposure with hepatic involvement have included
weight loss, anorexia, nausea, vomiting, jaundice, and abdominal
pain.  The degree of liver injury was related to the degree of
chlorination of PCBs, dose and duration of exposure, and possible
concurrent exposure to other hepatotoxins, infectious agents, or
certain medications. Headache, dizziness, and edema have also
been reported. Chronic PCB exposure in the workplace is unlikely
to occur today.

Laboratory Tests

Direct Biologic Indicators

-    Serum or adipose tissue PCB levels may indicate exposure,
     but they are difficult to interpret clinically.


Some researchers believe that PCB blood levels after long-term
exposure correlate well with adipose tissue levels. However,
PCB analysis of either blood or adipose tissue is expensive and
time-consuming and is not recommended unless exposure has
been massive. Breast milk analysis for PCBs should not be
considered unless the exposure is severe. PCBs detected in
breast milk are not necessarily an indication that breast-feeding
should be stopped.

Indirect Biologic Indicators

-    Elevated liver-enzyme levels are of limited value in
     diagnosing PCB exposure.

Liver function tests may be the most sensitive sign of PCB
toxicity in the absence of chloracne; however, these measures
are of questionable value because they are nonspecific. Also,
normal liver enzyme values do not rule out significant exposure;
body burden still may be elevated. PCB conjugates can often be
detected in urine after exposure. Their analysis is expensive,
unreliable, and not recommended.


________________________________________

CHALLENGE

5) What confirmatory laboratory tests can be ordered to establish
the diagnosis of PCB exposure?

6) Additional information for the case study: The patient
requests a serum PCB analysis. The laboratory reports a level of
125 ppb, with no normal range indicated. How will you interpret
this report?
__________________________________________


Treatment and Management

Acute Exposure

-    There is no antidote for PCB exposure; treatment is
     symptomatic.

In the event of PCB splashes in the eyes, irrigate with tepid
water immediately for at least 15 minutes, and follow with
ophthalmic evaluation. Remove contaminated clothing and discard
properly. Gently wash affected skin with soap and warm water for
at least 15 minutes.

In the rare event that PCB-containing substances are ingested,
induce vomiting immediately if the patient is conscious. Gastric
lavage may be subsequently administered at a medical facility
until the gastric washings are clear. Activated charcoal has not
been proven beneficial, but is not contraindicated. Exposed
persons should have periodic follow-up examinations with
particular attention to hepatic function and dermal lesions.

Chronic Exposure

-    Removal from the source is the goal of treatment for PCB
     exposure.

There is no specific treatment for PCB toxicity. Diagnostic
workup should be limited to liver function tests and dermatology
examination, with skin biopsy of lesions. Initial treatment of
chloracne is based on cessation of exposure, good skin hygiene,
and use of dermatology measures commonly employed for acne
vulgaris. If these measures are not efficacious, the patient
should be referred to a dermatologist. 

The carcinogenic potential of PCBs should be carefully reviewed
with the patient, primarily to allay anxiety. Since there are no
known methods of reducing reserves of PCBs in lipid tissues,
attempts to purge the body of PCBs should not be undertaken.
Saunas and nutritional therapies have no proven efficacy. Crash
diets risk mobilizing PCBs stored in fat. 
Since PCBs are hepatotoxins, history of exposure to other
potentially hepatotoxic agents should be obtained and patients
should be encouraged to avoid exposure to other hepatotoxins such
as antibiotics or medications with known hepatotoxicity, alcohol,
and chlorinated solvents. 

Standards and Regulations 

Workplace

Air

-    OSHA's PEL is 1000 Fg/m3 for PCBs containing no more than
     42% chlorine, and 500 Fg/m3 for compounds containing up to 
     54% chlorine.

The Occupational Safety and Health Administration's (OSHA)
permissible exposure limit (PEL) is a time-weighted average (TWA)
airborne concentration of 1000 Rg/m3 for PCBs containing 42%
chlorine (average molecular formula of C12H7CI3). PCBs with 54%
chlorine and an average molecular formula of C12H5Cls have a PEL
of 500 Rg/m3. Both standards encompass all physical forms:
aerosols, vapor, mist, sprays, and PCB-laden dust particles. OSHA
considers that PCBs are absorbed through intact skin; therefore,
dermal and inhalation exposure routes should be evaluated by an
industrial hygienist. 

The National Institute for Occupational Safety and Health (NIOSH)
recommends a 1 0-hour TWA of 1 ,ug/m3 based on the minimum
reliable detectable concentration and potential carcinogenicity
of PCBs. NIOSH also recommends that all workplace exposures be
reduced to the lowest feasible level. 

Environment

Water

-    EPA does not have a standard for PCBs in drinking water. 

EPA considers PCBs a probable human carcinogen and prohibits
industrial discharges under the Clean Water Act Effluent
Guidelines. Currently, there is no legal maximum contaminant
level for PCBs in drinking water. However, EPA advises that the 
level Of PCBs in drinking water be limited to 0.5 ug/L on the
basis of carcinogenicity at 10-4 and 10-6 risk levels.


Food

The Food and Drug Administration (FDA) mandates tolerances of 0.2
to 3.0 ppm PCBs for all foods, with a tolerance level in fish of
2 ppm. FDA also limits PCBs in plastic food-packaging materials
to 10 ppm. 
                                       -
Challenge

What regulatory steps should be taken for the situation described
in the case study?


Suggested Reading List


Clinical

Kimbrough RD. Human health effects of polychlorinated biphenyls
(PCBs) and polybrominated biphenyls (PBBs). Annu Rev Pharmacy
Toxicol 1987;27:87.

Letz G. The toxicology of PCBs-an overview for clinicians. West J
Med 1983;138:534-40.

McKenna JP, Moskovitz M, Cox JL. Abnormal liver function tests in
asymptomatic patients. Am Fam  Physician 1989;39(3):117-26.

Epidemiology

Acquavella JF, Hanis NM, Nicolich MJ, Phillips SC. Assessment of
clinical, metabolic, dietary, and  occupational correlations with
serum polychlorinated biphenyl levels among employees at an
electrical capacitor manufacturing plant. J Occup Med
1986;28(11):1177-80.

Fischbein A, Wolff MS, Bernstein J. Selikoff IJ. Dermatological
findings in capacitor manufacturing workers  exposed to
dielectric fluids containing polychlorinated biphenyls (PCBs).
Arch Environ Health  1982;37(2):69-74.

Weaver G. PCB contamination in and around New Bedford, Mass.
Environmental Science Technology  1983;18:22A-7A.

Toxicology

Fischbein L. Toxicology of chlorinated biphenyls. Annu Rev
Pharmacol 1974.14: 139-56. 

MARC (International Agency for Research on Cancer). IARC
monographs on the evaluation of the carcinogenic risk of
chemicals to humans. Lyon, France: World Health
Organization,1982.

Related Government Documents

Agency for Toxic Substances and Disease Registry. Toxicological
profile for selected PCBs. Atlanta: US Department of Health and
Human Services, Public Health Service, 1989. NTIS report no.
PB/89/225403/AS .

Environmental Protection Agency. Drinking water criteria document
for polychlorinated biphenyls (PCBs). Washington, DC: US
Environmental Protection Agency,1988. EPA report no.
ECAO-CIN-414.

Answers to Questions

Pretest

The pretest can be found on page 1.

(a) The patient's problem list includes acne vulgaris, which is
atypical because of the location of the lesions and their late
onset without history of outbreaks during adolescence. The mildly
altered liver functions are nonspecific in their interpretation
and clinically unexpected. Gilbert's syndrome is a hereditary,   
relatively common, benign, unconjugated hyperbilirubinemia. It
may contribute to the laboratory findings of elevated bilirubin
(especially after a fast) but would not explain the clinical
picture or elevated liver enzymes.

(b) The combination of asymptomatic hepatomegaly and mild
nonspecific elevations of hepatic enzymes  in this case is
suggestive of a chronic inflammatory liver process or hepatitis.
The causes of hepatitis can be classified as drug-induced, toxic,
infectious, genetic, and connective tissue disease-associated.   
The major cause of liver disease in the United States is alcohol
ingestion. Less common are environmental exposures, resulting 
in either acute or chronic toxic hepatitis. Infectious
hepatitides
include those due to the viruses such as A (infectious), B
(serum), C (transfusion-associated) and other possible agents of 
non-A, non-B hepatitis. Some connective tissue diseases such as 
lupus erythemaosus are associated with a specific type of
hepatitis.
Hepatitis may also occur with Epstein-Barr virus and 
cytomegalovirus infections.

Infiltrative diseases such as sarcoidosis or amyloidosis, and
rare genetic diseases such as Wilson's disease, primary 
hemochromatosis, and alpha1-antitrypsin deficiency must 
be excluded.

(c) Viral serology and a heterophil antibody test should be
considered. If there are suggestive signs or symptoms, a serum 
iron and total iron binding capacity, serum copper and
ceruloplasmin, 
and antinuclear antibodies may be helpful. Assays for suspected
hepatotoxins may also be of value. Further evaluation may include 
ultrasound and percutaneous liver biopsy.


Sources of Information

More information on the adverse effects of PCBs and the treatment
and management of PCB-exposed persons can be obtained from 
ATSDR, your state and local health departments, and university
medical
centers. "Case Studies in Environmental Medicine: 
Polychlorinated Biphenyl (PCB) Toxicity " is one of a
series. For clinical inquiries, contact ATSDR, Division of Health 
Education, Office of the Director, at (404) 639-6204.

Posttest and Credits

Continuing education credit is available to health professionals
who use this monograph and complete the posttest. The criterion 
for awarding continuing medical education (CME) credits and 
continuing education units (CEU) is a posttest score of 70% or
better.

The Centers for Disease Control and Prevention (CDC) is
accredited by the Accreditation Council for Continuing
Medical Education (ACCME) to sponsor continuing medical education
for physicians, and by the International Association for
Continuing 
Education and Training (IACET) to sponsor continuing education 
units for other health professionals.

The Agency for Toxic Substances and Disease Registry, in joint
sponsorship with CDC, is offering 1 hour of CME credit in
Category 1 
of the Physician's Recognition Award of the American Medical 
Association and 0.1 hour of CEU for other health professionals
upon 
completion of this monograph.

In addition, the series Case Studies in Environmental Medicine
has 
been reviewed and is acceptable for credit by the following
organizations:

The American Academy of Family Physicians (AAFP). This program
has been reviewed and is acceptable for 1 prescribed hour by the
 American Academy of Family Physicians. (Term of Approval:
beginning 
January 1992.) For specific information, please consult the AAFP
Office 
of Continuing Medical Education.

The American College of Emergency Physicians (ACEP). Approved by
the American College of Emergency Physicians for one hour per
issue 
of ACEP Category I credit.

The American Osteopathic Association (AOA). AOA has approved this
issue for 1 credit hour of Category 2-B credit.

The American Association of Occupational Health Nurses (AAOHN).
AAOHN has approved this program for 1.2 contact hours. Applicant
will 
receive the assigned code number in the award letter.

The American Board of Industrial Hygiene (ABIH). ABIH has
approved this program for 0.5 certification maintenance (CM)
point per 3 Case
 Studies. The CM approval number is 2817.

.

           POSTTEST: POLYCHLORINATED BIPHENYLS (PCBs)

Circle all correct answers and transfer your answers to page 19.

1. Significant PCB exposure may occur from
   a. eating fish from PCB-contaminated waters
   b. exposure to leaking transformers
   c. eating a vegetarian diet
   d. inhaling soot or smoke from transformer or capacitor fires
   e. drinking alcoholic beverages

2. Although little is currently understood about the biologic
     fate of PCBs in humans, what is known includes which 
     of the following facts?
   a. PCB excretion is slow
   b. PCBs may bioaccumulate in adipose tissue
   c. highly chlorinated PCBs may delay excretion of less highly
     chlorinated PCBs
   d. the primary site of PCB metabolism is the liver
   e. background levels of PCBs in serum are generally higher
     than those in adipose tissue or breast milk

3. Which of the following statements is (are) false?
   a. chloracne can reflect systemic toxicity
   b. liver enzymes are always elevated by PCBs
   c. Exposed populations have shown adverse developmental
     effects from PCBs
   d. PCBs are known human carcinogens 
   e. a sensitive indication of PCB exposure in humans is cardiac
     dysfunction

4. PCBs have been considered carcinogenic because
   a. they are associated with increased rates of hepatic cancer
     in humans
   b. they are immunosuppressive in humans
   c. they are associated with thymic atrophy in humans
   d. they are associated with increased rates of many cancers in
     animals
   e. (a) and (d)

5. PCBs are associated with which of the following abnormalities
  a . anemia
  b.  hypothyroidism
  c.  leukopenia
  d . elevated CPK isoenzymes
  e.  elevated liver enzymes

6. Signs of PCB toxicity by inhalation exposure may include
   a. persistent chloracne and weight loss
   b. ascites
   c. abdominal discomfort
   d. abnormal liver function
   e. pancreatitis

7. In the treatment and management of PCB-exposed persons, you
     should
   a. recommend that the patient avoid contact with other known
     hepatotoxins
   b. administer mineral oil in response to acute ingestion
   c. follow up with particular attention to hepatic function and
     dermal lesions
   d. initially treat chloracne the same as you would acne
     vulgaris
   e. place the patient on a crash diet to purge the body of PCBs

8. PCB-induced chloracne is characterized by
   a. raised urticarial welts
   b. septic patches with raised pustular furuncles
   c. cystic papules and comedones
   d. small grouped vesicles with regional lymph nodes enlarged
   e. a distribution that may include the periorbital area,
     chest, and buttocks