ATSDR Case Studies in
Environmental Medicine
Polychlorinated Biphenyl (PCB) Toxicity
Agency for Toxic Substances and Disease Registry
Issue 12, June 1990
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 careprovider's knowledge of hazardous substances
in the environmentand to aid in the evaluation of potentiallyexposed patients.
See page 17 for further information aboutcontinuing medical education credits
and continuingeducation 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,, MD; 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 arealistic
encounter with a patient. This description is followedby a pretest. The
case study is further developed throughChallenge questions at the end of
each section. To fully benefitfrom this monograph, readers are urged to
answer each questionwhen it is presented.(Answers to the Pretest and Challengequestions
are found on pages 15 and 16.) The monograph ends witha post test which
can be submitted to ATSDR for continuingmedical education (CME) credit or
continuing education units(CEU). See page 17 for further instructions on
how to receivethese 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
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 Pretest Questions
Sources of Information
Posttest and Credits
Posttest: Polychlorinated Biphenyls (PCBs)
This issue is prepared with the assistance of those who share acommon
concern for physician education, public health, and theenvironment, including
the following organizations: AmericanAcademy of Family Physicians (AAFP),
American Academy ofPediatrics (AAP), American College of Emergency Physicians(ACEP),
American College of Occupational and Environmental Medicine (ACOEM), American
Medical Association (AMA), Associationof State and Territorial Health Officials
(ASTHO), and theSociety 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, Ed.D., and Donna Orti, MS, Prepared by DeLima Associates, San Rafael,
California, underContract No. 205-88-0636.
Case Study
A 48-year-old handyman with progressive cystic acne and abnormalliver
function. You have been treating a 48-year-old manconservatively for his
facial acne vulgaris. He first soughttreatment about 3 months ago, remarking
that such blemishes aretypical for a teenager but he never had them during
adolescence.Therapy was initiated with benzoyl peroxide washes and topicalantibiotics,
in addition to instructions for skin hygiene. Whenno real improvement was
noted, oral antibiotics were prescribed.Due to continued lack of efficacy,
this regimen was latersupplemented by Retin-A (tretinoin) cream.
The patient has returned for a follow-up visit and complains thatthe
acne is worse. On examination, you agree, and tell thepatient you would
like to refer him to a dermatologist forAccutane(TM) (isotretinoin)therapy.
A serum biochemical andhematology profile are ordered to document baseline
values beforetherapy begins.
To your surprise, the biochemical panel reveals the followingabnormalities:
total bilirubin 2.8 mg/dL (normal 0-1.5), directbilirubin 0.4 mg/dL (normal
0-0.4), SGPT (ALT) 74 IU/L (normal0-50), 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, contactwith
hepatitis patients, other liver difficulties or bloodtransfusion. He informs
you he has Gilbert's syndrome and has hadelevated bilirubin levels in the
past. There is no family historyof cardiovascular disease or cancer. The
patient does not smoke;he drinks 2 to 3 bottles of beer each evening, and
sometimes moreon weekends. He is currently taking no medications other thanthose
mentioned. Review of systems is otherwise unremarkable.Social history reveals
the patient is married with three teenagedchildren; his wife and children
are in good health. They live ina high-rise apartment building where the
patient has beenhandyman and part-time building manager for the last year.
Hespends much time in the basement area, which includes aworkshop,- recreation
room with pool table, and laundry andheating facilities. An avid fisherman,
he spends most weekendsfishing in Lake Michigan with his two sons. Physical
examinationreveals mild, nontender hepatomegaly without jaundice. His acne,which
is most prominent on the upper face lateral to theeyebrows, began about
8 months ago.
- Use of trade names is for identification only and does notimply 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?
Challenge Question
(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 chemicalswith varying
numbers of chlorine atoms attached in varyingpositions to two connected
benzene rings (Figure 1). CommercialPCB products are always mixtures of
PCBs and are usuallycontaminated with small amounts of polychlorinated dibenzofurans(furans)
or polychlorinated dibenzodioxins (dioxins).Contamination by furans is a
concern because their toxicity isgenerally much greater than that of PCBs.
Because of their insulating and nonflammable properties, PCBshave been
used as heat exchange and dielectric fluids intransformers and capacitors,
hydraulic and lubricating fluids,diffusion pump oils, plasticizers, extenders
for pesticides, andas ingredients of caulking compounds, paints, adhesives,
andflame retardants. PCBs have also been used in inks and carbonlesspaper.
Trade names for PCBs include Aroclor, Askarel, Eucarel,Pyranol, Dykanol,
Clorphen, Asbestos Diaclor, Nepolin, andEEC-18.
PCB mixtures are colorless to dark brown oils, viscous liquids,or sticky
resinous semi-solids. They evaporate slowly at roomtemperature; however,
their volatility increases dramaticallywith small increases in temperature.
Overheated equipment thatcontains PCBs can vaporize significant quantities
of thesecompounds, causing an inhalation hazard, especially in areaswhere
ventilation is poor.
Today PCBs are found mainly in transformers and capacitorsmanufactured
before the U.S. Environmental Protection Agency(EPA) banned the production
of PCBs in 1977. Many of these oldtransformers and capacitors are still
contained in industrialequipment (such as welding equipment), medical equipment(such
asX-ray machines), and household appliances (such asrefrigerators). Ballasts
of fluorescent light fixtures maycontain PCBs. During normal lighting operation,
the PCBs areentirely enclosed; however, when the capacitor wears out, it
mayburn or break and leak PCBs.
PCBs can be released into the general environment from poorlymaintained
toxic waste sites; by illegal or improper dumping ofPCB wastes, such as
transformer fluids; through leaks or fugitiveemissions from electrical transformers
containing PCBs; and bydisposal of PCB-containing consumer products in municipallandfills.
PCBs have been found in at least 271 of 1177 hazardouswaste sites on the
EPA National Priorities List. Of the 1.25billion pounds of PCBs produced
in this country since 1929, about450 million pounds have found their way
into the environment. Thechemical stability of these synthetic compounds
accounts fortheir persistence in the environment. Another important reasonfor
their persistence is their resistance to biodegradation. Lowlevels of PCBs
can be found throughout the world. PCBs in wateror on soil surfaces evaporate
and return to earth by rainfall orsettling of dust particles. Because PCBs
strongly adsorb to soilparticles, significant leaching from soil and translocation
toplants do not occur. Although PCBs are widespread in the aquaticenvironment,
their low water solubility helps to prevent highconcentrations in drinking
water supplies.
- Use of trade names is for identification only and does notimply 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 andanimal
fat. PCBs are lipophilic; they preferentially separatefrom water and adsorb
to sediment. Bottom feeders and otheraquatic organisms then ingest and accumulate
PCBs, resulting inbioconcentration upward in the food chain. Composite analysis
ofcommercial whole fish collected from Lake Ontario in 1980 foundPCB levels
of 0.11 to 4.90 parts per million (ppm).
The toxicity of PCBs was dramatically illustrated in 1968 whenover 1600
people in Japan were poisoned by cooking oilcontaminated with PCBs from
a heat transfer unit. Thecontaminating oil likely contained furans and dioxins,
compoundsgenerally more toxic than PCBs themselves. The ensuing illnessesbecame
known as "Yusho" (rice oil disease).
Challenge
Additional information for the case study: In response to yourpersistent,
detailed questioning regarding his hobbies andpossible contact with hepatotoxins,
the patient reveals thatwhile in the basement workshop he frequently wipes
up "dark oilydischarge" near a large electrical transformer in
the work area.The discharge has also resulted ina gummy residue on tools
andother surfaces. He mentions he sometimes feels dizzy andnauseated after
working in the basement all day.
Is there an association between the clinical findings and thisadditional
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 theworkplace. For example,
workers may inhale or have dermal contactwith PCBs during repair or maintenance
of process equipment orelectrical transformers and during accidents or spills
involvingPCBs. Exposure can also occur in disposal of PCB-containingmaterials
at hazardous waste sites. Occupations entailing risk ofPCB 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 hasencountered
PCBs through illegal roadside dumping of hazardouswaste oils and through
inhalation of smoke and soot fromtransformer or capacitor fires. Pyrolysis
of PCBs can producedioxins and furans, placing smoke-inhalation victims
at increasedrisk of exposure to these toxic compounds.
Fetuses and neonates are potentially more sensitive to PCBs thanadults
because of transplacental distribution and physiologicdifferences. They
lack the hepatic microsomal enzyme systems thatfacilitate metabolism and
excretion of PCBs. Furthermore, PCBsaccumulate in breast milk. Nursing infants
are at additional riskbecause human milk contains a steroid that inhibits
PCBglucuronidation and excretion. Other populations potentially moresensitive
to PCBs are persons with compromised hepaticfunctioning, including those
with incompletely developedglucuronide conjugation mechanisms due to congenital
disorderssuch as Gilbert's syndrome, and persons with hepatic infections.Persons
taking medications potentially toxic to the liver mayalso be at increased
risk.
Challenge Question
2) Are other sources of PCB exposure likely for the patientdescribed
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 metabolizedand excreted.
After absorption, PCBs partition between theaqueous and lipid compartments
of the body in a biphasic pattern.During the first day after PCBs were administered
to laboratoryanimals, they were distributed mainly to the liver and muscletissue.
In a second phase, PCBs were redistributed to the adiposetissue, skin and
other fat-containing organs. More highlychlorinated PCBs redistribute to
adipose tissue to a greaterextent than do PCBs with a lower percentage of
chlorine; thepresence of more highly chlorinated PCBs appears to delayexcretion
of the lesser chlorinated compounds for reasons notclearly understood.
The liver is the primary site of PCB metabolism by hydroxylationand conjugation
with glucuronic acid and sulfates. The rate ofmetabolism 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 lowexposure
levels. As long as exposure continues, a true steadystate is never achieved.
PCBs metabolized with more difficultyare excreted almost exclusively by
the binary route; metabolitesof PCBs with a smaller percentage of chlorination
are eliminatedthrough bile and urine. Urinary metabolites are in the form
ofconjugates, including glucuronides and sulfates.
There are essentially no pharmacokinetic data for humans. PCBhalf-lives
in the rat range from 1 day to 460 days depending onthe degree of chlorination.
Background levels in human sera aretypically less than 20 parts per billion
(ppb), and residuesmeasured in human milk have ranged from 40 to 100 ppb.
Reportedlevels in adipose tissue range from 1 to 2 ppm.
Challenge Question
3) Explain why patients with Gilbert's syndrome may be atincreased 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 havedevelopmental
effects. Metabolic, reproductive, endocrine, andimmunosuppressive effects
have been noted in animals, but havenot been adequately studied in humans.
Although data from animalstudies indicate that PCBs are definitely animal
carcinogens,data from PCB-exposed human populations are inconsistent andinconclusive.
Dermatologic Effects
- PCB-induced chloracne can reflect systemic toxicity.
Chloracne is the only overt effect of PCB exposure in humans, butabsence
of chloracne does not rule out exposure. There is noreliable dose-response
model for chloracne in exposedpopulations; the dose-response relationship
may be dependent uponindividual predisposition. Chloracne typically develops
weeks ormonths after exposure. The lesions are often refractory totreatment
and can last for years. One case persisted for morethan 30 years.
The acneform lesions arise from altered differentiation of acinarsebaceous
base cells into keratinocytes. The chin, periorbital,and malar areas are
affected most often, although lesions mayalso appear on the chest, arms,
thighs, genitalia, and buttocksareas not commonly affected by acne vulgaris.
The mostdistinctive lesions are cystic and measure from 1 to 10millimeters
(mm). Other prominent lesions are comedo. The cystsand comedones can become
inflamed and secondarily infected. Thepapules and cysts may be surrounded
by edema and erythema.Chloracne may result not only from dermal contact
but also fromingestion and generally indicates systemic toxicity.
Besides chloracne, Yusho patients had hyperpigmentation of theskin, Conjunctive,
gingiva, and nails. These pigmentationdisturbances 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 severeoccupational
exposure to PCBs can increase serum liver enzymes.The enzyme levels often
show inconsistent patterns,however, andincreases generally have not been
associated with hepaticdysfunction, although approximately 10% of the Yusho
patientsexperienced jaundice. Asymptomatic hepatomegaly has been reportedin
workers, many of whom had concomitant elevated serum PCBlevels. Some researchers
believe that aspartate aminotransferase(SGOT or AST) and gamma glutamyl
transpeptidase (GGTP or GGT) arethe most sensitive indicators of PCB exposure
in humans, and thatchanges in these liver enzymes may occur at exposure
levels belowthose at which chloracne appears. Liver damage, histologicallydocumented,
is the most consistent finding among laboratoryanimals tested with PCBs.
Increases in urinary porphyrin levels have been noted in a studyof workers
with low-level PCB exposure. Changes in porphyrinmetabolism may be triggered
by the induction of liver microsomalenzymes. PCBs are more potent enzyme
inducers than phenobarbital,a drug that occasionally causes clinical problems
due to itsenzyme-inducing effects, and PCBs' enzyme-inducing effects canpersist
long after cessation of exposure. The health implicationsfor enzyme induction
include the occurrence of disease secondaryto increased metabolism of endogenous
or exogenous substances,and interference in medicai therapy due to increased
metabolismof 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 causedevelopmental and
fetotoxic effects in humans. Two of the Yushomothers had stillbirths; 10
of 13 infants had abnormal skinpigmentation, 9 of 13 had ocular discharge,
and 12 of 13 weresmaller than average. Two infants developed Yusho from
breastfeeding. In contrast, the authors of a study of nursing infantswhose
mothers were occupationally exposed to PCBs found noadverse health effects.
Contaminants in the PCB oil cannot beruled out as factors in Yusho disease.
Follow-up of the Yushoinfants revealed no persistent morphologic or behavioralabnormalities.
In laboratory animals, changes in estrous cycles, failure of ovumimplantation,
increased frequency of spontaneous abortions, andlow birth weight of offspring
have been reported after PCBexposure. No teratogenic effects have been reported
in studies ofhumans or animals.
Carcinogenicity
- PCBs are considered potential human carcinogens on the basis of results
from animal studies.
The epidemiologic evidence is insufficient to evaluate thepotential of
PCBs as human carcinogens. Although Yusho victimsshowed a slightly higher
rate of deaths from neoplasms 15 yearsafter the incident, the data were
not adjusted for age or smokingand drinking patterns. Cancer data from other
human populationsare inconsistent and inconclusive.
Data from animal studies have shown that PCBs causehepatocarcinomas,
pituitary tumors, leukemia, Lymphomas, andgastrointestinal tract tumors.
On the basis of these data, EPAconsiders PCBs to be probable human carcinogens.
Challenge
4) Is there a need to be concerned about PCB exposure when theclinical
effects of the patient in the case study seems solimited?
Clinical Evaluation
History and Physical Examination
A detailed history will facilitate the diagnosis of chronic PCBpoisoning.
Pertinent information includes occupational historiesof all household members,
medications, and diet, includingethanol intake. During the physical examination,
physiciansshould pay particular attention to the skin and hepatic system.Encountering
a patient with PCB toxicity should triggerconsideration of whether this
is a sentinel event, indicating thepossibility of other similarly exposed
persons such as coworkersor 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 isdescribed on page 7. Acneform
lesions do not appear in allseverely exposed patients (only 82% of Yusho
patients hadchloracne); therefore, its absence does not rule out exposure.New
cases of chloracne should be reported to the local or statehealth department.
Elevated liver enzymes are the most sensitive effect of PCBexposure in
animals and have been detected in several humanepidemiologic studies. Hepatomegaly
has also been noted insome 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 overtsigns or symptoms
of toxicity. In others, reported signs andsymptoms of exposure with hepatic
involvement have includedweight loss, anorexia, nausea, vomiting, jaundice,
and abdominalpain. The degree of liver injury was related to the degree
ofchlorination of PCBs, dose and duration of exposure, and possibleconcurrent
exposure to other hepatotoxins, infectious agents, orcertain medications.
Headache, dizziness, and edema have alsobeen reported. Chronic PCB exposure
in the workplace is unlikelyto 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-termexposure
correlate well with adipose tissue levels. However,PCB analysis of either
blood or adipose tissue is expensive andtime-consuming and is not recommended
unless exposure hasbeen massive. Breast milk analysis for PCBs should not
beconsidered unless the exposure is severe. PCBs detected inbreast milk
are not necessarily an indication that breast-feedingshould 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 PCBtoxicity in
the absence of chloracne; however, these measuresare 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 bedetected in urine after exposure. Their analysis is expensive,unreliable,
and not recommended.
Challenge Question
5) What confirmatory laboratory tests can be ordered to establishthe
diagnosis of PCB exposure?
6) Additional information for the case study: The patientrequests a serum
PCB analysis. The laboratory reports a level of125 ppb, with no normal range
indicated. How will you interpretthis 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 tepidwater immediately
for at least 15 minutes, and follow withophthalmic evaluation. Remove contaminated
clothing and discardproperly. Gently wash affected skin with soap and warm
water forat least 15 minutes.
In the rare event that PCB-containing substances are ingested,induce
vomiting immediately if the patient is conscious. Gastriclavage may be subsequently
administered at a medical facilityuntil the gastric washings are clear.
Activated charcoal has notbeen proven beneficial, but is not contraindicated.
Exposedpersons should have periodic follow-up examinations withparticular
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. Diagnosticworkup should
be limited to liver function tests and dermatologyexamination, with skin
biopsy of lesions. Initial treatment ofchloracne is based on cessation of
exposure, good skin hygiene,and use of dermatology measures commonly employed
for acnevulgaris. If these measures are not efficacious, the patientshould
be referred to a dermatologist.
The carcinogenic potential of PCBs should be carefully reviewedwith the
patient, primarily to allay anxiety. Since there are noknown 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. Crashdiets risk mobilizing PCBs stored in fat.Since PCBs are hepatotoxins,
history of exposure to otherpotentially hepatotoxic agents should be obtained
and patientsshould be encouraged to avoid exposure to other hepatotoxins
suchas 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 PELof 500 Rg/m3. Both standards encompass all physical forms:aerosols,
vapor, mist, sprays, and PCB-laden dust particles. OSHAconsiders that PCBs
are absorbed through intact skin; therefore,dermal and inhalation exposure
routes should be evaluated by anindustrial hygienist.
The National Institute for Occupational Safety and Health (NIOSH)recommends
a 1 0-hour TWA of 1 ,ug/m3 based on the minimumreliable detectable concentration
and potential carcinogenicityof PCBs. NIOSH also recommends that all workplace
exposures bereduced 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 prohibitsindustrial
discharges under the Clean Water Act EffluentGuidelines. Currently, there
is no legal maximum contaminantlevel for PCBs in drinking water. However,
EPA advises that thelevel Of PCBs in drinking water be limited to 0.5 ug/L
on thebasis of carcinogenicity at 10-4 and 10-6 risk levels.
Food
The Food and Drug Administration (FDA) mandates tolerances of 0.2to 3.0
ppm PCBs for all foods, with a tolerance level in fish of2 ppm. FDA also
limits PCBs in plastic food-packaging materialsto 10 ppm.
Challenge Question
What regulatory steps should be taken for the situation describedin the
case study?
Suggested Reading List
Clinical
Kimbrough RD. Human health effects of polychlorinated biphenyls(PCBs)
and polybrominated biphenyls (PBBs). Annu Rev PharmacyToxicol 1987;27:87.
Letz G. The toxicology of PCBs-an overview for clinicians.
West JMed 1983;138:534-40.
McKenna JP, Moskovitz M, Cox JL. Abnormal liver function
tests inasymptomatic patients. Am Fam Physician 1989;39(3):117-26.
Epidemiology
Acquavella JF, Hanis NM, Nicolich MJ, Phillips SC. Assessment
ofclinical, metabolic, dietary, and occupational correlations withserum
polychlorinated biphenyl levels among employees at anelectrical capacitor
manufacturing plant. J Occup Med1986;28(11):1177-80.
Fischbein A, Wolff MS, Bernstein J. Selikoff IJ. Dermatologicalfindings
in capacitor manufacturing workers exposed todielectric 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
RevPharmacol 1974.14: 139-56.
MARC (International Agency for Research on Cancer). IARCmonographs
on the evaluation of the carcinogenic risk ofchemicals to humans. Lyon,
France: World HealthOrganization,1982.
Related Government Documents
Agency for Toxic Substances and Disease Registry. Toxicologicalprofile
for selected PCBs. Atlanta: US Department of Health andHuman Services, Public
Health Service, 1989. NTIS report no.PB/89/225403/AS .
Environmental Protection Agency. Drinking water criteria
documentfor polychlorinated biphenyls (PCBs). Washington, DC: USEnvironmental
Protection Agency,1988. EPA report no.ECAO-CIN-414.
Answers to Pretest Questions
(a) The patient's problem list includes acne vulgaris,
which isatypical because of the location of the lesions and their lateonset
without history of outbreaks during adolescence. The mildlyaltered liver
functions are nonspecific in their interpretationand clinically unexpected.
Gilbert's syndrome is a hereditary,relatively common, benign, unconjugated
hyperbilirubinemia. Itmay contribute to the laboratory findings of elevated
bilirubin(especially after a fast) but would not explain the clinicalpicture
or elevated liver enzymes.
(b) The combination of asymptomatic hepatomegaly and mildnonspecific
elevations of hepatic enzymes in this case issuggestive 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 alcoholingestion. Less
common are environmental exposures, resultingin either acute or chronic
toxic hepatitis. Infectious hepatitidesinclude those due to the viruses
such as A (infectious), B(serum), C (transfusion-associated) and other possible
agents ofnon-A, non-B hepatitis. Some connective tissue diseases such aslupus
erythemaosus are associated with a specific type of hepatitis.Hepatitis
may also occur with Epstein-Barr virusandcytomegalovirus infections.
Infiltrative diseases such as sarcoidosis or amyloidosis,
andrare genetic diseases such as Wilson's disease, primaryhemochromatosis,
and alpha1-antitrypsin deficiency mustbe excluded.
(c) Viral serology and a heterophil antibody test should
beconsidered. If there are suggestive signs or symptoms, a serumiron and
total iron binding capacity, serum cxopper and ceruloplasmin,and antinuclear
antibodies may be helpful. Assays for suspectedhepatotoxins may also be
of value. Further evaluation may includeultrasound and percutaneous liver
biopsy.
Sources of Information
More information on the adverse effects of PCBs and the
treatmentand management of PCB-exposedpersons can be obtained fromATSDR,
your state and local health departments, and university medicalcenters.
"Case Studies in Environmental Medicine:Polychlorinated Biphenyl (PCB)
Toxicity " is one of aseries. For clinical inquiries, contact ATSDR,
Division of HealthEducation, Office of the Director, at (404) 639-6204.
Posttest and Credits
Continuing education credit is available to health professionalswho
use this monograph and complete the posttest. The criterionfor awarding
continuing medical education (CME) credits andcontinuing education units
(CEU) is a posttest score of 70% or better.
The Centers for Disease Control and Prevention (CDC) isaccredited
by the Accreditation Council for ContinuingMedical Education (ACCME) to
sponsor continuing medical educationfor physicians, and by the International
Association for ContinuingEducation and Training (IACET) to sponsor continuing
educationunits for other health professionals.
The Agency for Toxic Substances and Disease Registry, in
jointsponsorship with CDC, is offering 1 hour of CME credit in Category
1of the Physician's Recognition Award of the American MedicalAssociation
and 0.1 hour of CEU for other health professionals uponcompletion of this
monograph.
In addition, the series Case Studies in Environmental Medicine
hasbeen reviewed and is acceptable for credit by the following organizations:
The American Academy of Family Physicians (AAFP). This
programhas been reviewed and is acceptable for 1 prescribed hour by the
American Academy of Family Physicians. (Term of Approval: beginningJanuary
1992.) For specific information, please consult the AAFP Officeof Continuing
Medical Education.
The American College of Emergency Physicians (ACEP). Approved
bythe American College of Emergency Physicians for one hour per issueof
ACEP Category I credit.
The American Osteopathic Association (AOA). AOA has approved
thisissue 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
willreceive the assigned code number in the award letter.
The American Board of Industrial Hygiene (ABIH). ABIH hasapproved
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.
- Significant PCB exposure may occur from
- eating fish from PCB-contaminated waters
- exposure to leaking transformers
- eating a vegetarian diet
- inhaling soot or smoke from transformer or capacitor fires
- drinking alcoholic beverages
- Although little is currently understood about the biologic fate of
PCBs in humans, what is known includes which of the following facts?
- PCB excretion is slow
- PCBs may bioaccumulate in adipose tissue
- highly chlorinated PCBs may delay excretion of less highly chlorinated
PCBs
- the primary site of PCB metabolism is the liver
- background levels of PCBs in serum are generally higher than those
in adipose tissue or breast milk
- . Which of the following statements is (are) false?
- chloracne can reflect systemic toxicity
- liver enzymes are always elevated by PCBs
- Exposed populations have shown adverse developmental effects from PCBs
- PCBs are known human carcinogens
- a sensitive indication of PCB exposure in humans is cardiac dysfunction
- PCBs have been considered carcinogenic because
- they are associated with increased rates of hepatic cancer in humans
- they are immunosuppressive in humans
- they are associated with thymic atrophy in humans
- they are associated with increased rates of many cancers in animals
- (a) and (d)
- PCBs are associated with which of the following abnormalities
- anemia
- hypothyroidism
- leukopenia
- elevated CPK isoenzymes
- elevated liver enzymes
- Signs of PCB toxicity by inhalation exposure may include
- persistent chloracne and weight loss
- ascites
- abdominal discomfort
- abnormal liver function
- pancreatitis
- In the treatment and management of PCB-exposed persons, you should
- recommend that the patient avoid contact with other known hepatotoxins
- administer mineral oil in response to acute ingestion
- follow up with particular attention to hepatic function and dermal
lesions
- initially treat chloracne the same as you would acne vulgaris
- place the patient on a crash diet to purge the body of PCBs
- PCB-induced chloracne is characterized by
- raised urticarial welts
- septic patches with raised pustular furuncles
- cystic papules and comedones
- small grouped vesicles with regional Iymph nodes enlarged
- a distribution that may include the periorbital area, chest, and buttocks
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