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Human Heart Disease --- Studies 1-30
linking PCBs with Cholesterol, Lipid Levels and other
Cardiovascular Effects
This may not be a complete list of all heart research
involving PCB exposures. For more studies, visit the TOXNET
database operated by the National Library of Medicine (the source of these
abstracts.) Keep in mind that these studies are not all equal in size or
quality. Some were published in peer-reviewed journals, while others were
simply presented at conferences. A few are duplicates by the same author
(one conference-based, another published) but we presented both because
the descriptions were slightly different. For more discussion on
these results, go to the Heart
Table of Contents.
Study #1
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PCBs cause endothelial cell dysfunction, which is a trigger
for cardiovascular disease
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Vitamin E and other antioxidants may limit endothelial cell
injury by PCBs
Our findings suggest that exposure to specific environmental
contaminants can trigger diseases of the vasculature, e.g., cardiovascular
disease. In addition, high-fat diets may potentiate and diets high
in antioxidant nutrients may protect against PCB-mediated endothelial cell
dysfunction. Our data give an insight into the potential use of vitamin
E and related antioxidants to limit PCB-mediated cell injury. These studies
are significant for providing new insights into potential nutrition interventions
in diseases that can be induced by the toxicity of PCBs and other halogenated
compounds. (Hennig et al, 2000)
Study #2
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chemically induced endothelial dysfunction needs consideration
as a risk factor in cardiovascular disease
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PCBs may act with other chemicals to cause circulatory damage
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study used PCB 126
Autoradiography was used to investigate the cellular sites
of irreversible binding of 3H-labelled 7,12-dimethylbenz[a]anthracene (DMBA)
and benzo[a]pyrene (B[a]P) in mice. Autoradiograms obtained from solvent-extracted
tape-sections revealed an even distribution of DMBA- and B[a]P-derived
radioactivity in control mice lacking sites of selective binding in the
tissues. In mice pretreated with a cytochrome P4501A (CYP1A) inducer, beta-naphthoflavone
(BNF) or 3,3',4,4', 5-pentachlorobiphenyl (PCB 126), a noticeable
accumulation of bound radioactivity was observed in the pulmonary alveolar
region. Increased labelling was also observed in heart tissue of induced
mice. As demonstrated by microautoradiography of tissues from CYP1A-induced
mice treated with 3H-DMBA or 3H-B[a]P in vivo, irreversible binding in
lung tissue was present in endothelial cells of arteries and veins, in
the alveolar septal walls, and in type 2 pneumocytes. In heart tissue,
binding was confined to endothelial cells of arteries, capillaries and
veins. In liver, binding was found in the hepatocytes as well as in endothelial
cells of the portal veins, whereas no binding was seen in endothelial cells
of the sinusoids, central veins, or arteries. These findings were confirmed
in vitro using 3H-DMBA-exposed precision-cut slices, indicating that reactive
intermediates of DMBA and B(a)P were formed in situ. The addition of the
CYP1A inhibitor ellipticine abolished binding in the target endothelial
cells. Increased endothelial binding in the lungs and liver of CYP1A-induced
mice was concomitant with increased 7-ethoxyresorufin O-deethylase (EROD)
and DMBA hydroxylase activity. In heart, endothelial binding was positively
correlated with EROD, but not with DMBA hydroxylase. The results suggest
that endothelial cells may be targets for CYP-dependent activation of
such toxicants as polycyclic aromatic hydrocarbons. Consequently, the
possibility that chemically induced endothelial dysfunction is a risk factor
in the aetiology of cardiovascular disease demands consideration. (Granberg
et al, 2000)
Study #3
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most excess deaths were due to cardiovascular disease
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study involved unknown mix of PCBs
Herbicide spray crews employed by a Canadian power company
between 1950 and 1967 had a higher than expected death rate, with a standardized
mortality ratio of 157% (CI 130%-194%). In 1991, the cohort consisted of
225 former sprayers of whom 127 were still alive and 98 had died. Eligibility
for inclusion in the cohort was based on employer records; and a history
of spraying for 30 days or more in at least one spray season. Deaths expected
were based on age-specific population mortality rates for New Brunswick.
The all-age SMR for the total cohort was 159%. After 1958, however, waste
transformer oil [PCB oil] was added to the phenoxy-herbicide spray
mixture, the oil representing 10% of the final mixture. Spray crews wore
no protective clothing. Subdividing the cohort into spray years 1950-1958
and 1959-1967 yielded SMRs of 146% (CI 115%-184%); and 215% (CI 139%-318%),
respectively. The transformer oil was used during the period 1959-1967.
Most
excess deaths were due to cardiovascular disease. (Hary et al, 1997)
Study #4
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significantly increased mortality from cardiovascular diseases
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mortality occurred 20 years after PCB exposure
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study involved unknown mix of PCBs
Mortality and cancer incidence were investigated among 242
male capacitor manufacturing workers, exposed to polychlorinated biphenyls
(PCBs) for at least six months between 1965 and 1978. Mortality and cancer
incidence were followed from 1965 to 1991. There was a significantly
increased mortality from cardiovascular diseases among those employed
for at least five years in high-exposed jobs, with a latency of 20 years.
There were two cases of cancer of the liver and bile ducts, which previously
has been associated with PCB exposure, both in epidemiological and animal
experimental studies. No data on smoking habits were available. The study
supports some previous findings of an increased risk of cancer of the liver
and bile ducts after exposure to PCBs. The reason for the excess of cardiovascular
deaths in the high-exposure group is not known and deserves evaluation
in future studies. (Gustavsson et al, 1997)
Study #5
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triglycerides, cholesterol, total bilirubin, beta-glu, and
5'nuc correlated positively and significantly with log concentrations of
serum total PCBs
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highly chlorinated PCBs (Aroclor 1260) had significant, positive
correlations with several serum analytes
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less chlorinated PCBs (Aroclor 1242) correlated significantly
and negatively only with HDL-cholesterol
Sera from individuals exposed to polychlorinated-biphenyls
(1336363) (PCBs) was studied to examine the relation between observed PCB
and DDE (72559) concentrations and serum lipids. Fasting sera were obtained
from about 100 people who lived or worked in the vicinity of an electrical
equipment manufacturing facility. Individuals who had contact with PCB
contaminated soil or the equipment itself that contained dielectric fluid
containing PCBs, or who ate PCB contaminated fish were considered to be
at risk. Twelve serum analytes [triglycerides, cholesterol, total and conjugated
bilirubin, high-density-lipoprotein cholesterol (HDL-C), alkaline phosphatase
(AP), gammaglutamyl transferase (GGT), aspartate aminotransferase (AST),
alanine aminotransferase (ALT), beta-glucuronidase (beta-glu), alanine
aminopeptidase (AAP), and 5'-nucleotidase (5'nuc)] were measured to investigate
their correlation with exposure to polychlorinated biphenyls (PCBs) and
1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (DDT). The relationship between
serum lipids, lipophilic toxicants, and the analytes was also evaluated.
The beta-glu, 5'nuc, triglycerides, cholesterol, and total bilirubin
correlated positively and significantly with log concentrations of serum
total PCBs and 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDE),
a metabolite of DDT. The more highly chlorinated PCBs (Aroclor 1260)
had significant, positive correlations with several serum analytes,
but the less chlorinated PCBs (Aroclor 1242) correlated significantly
and negatively only with HDL-cholesterol. Triglyceride- and cholesterol-rich
lipoproteins were added to serum to determine the effects of lipids on
these assays. Several were spuriously elevated. AP and beta-glu were not
affected by lipoprotein addition with the methods used in this study. AAP
was increased significantly only at triglyceride concentrations exceeding
400 mg/dl. Lipoproteins may be elevated because of deranged lipid metabolism
in response to PCBs, or PCBs may be elevated because elevated lipoproteins
are present, as in familial triglyceridemia, a relatively common dyslipoproteinemia.
Serum PCB concentrations ranged from 0 to 36 micrograms/liter (microg/l)
for Aroclor-1242 (53469219), from 2 to 43microg/l for the more highly chlorinated
Aroclor-1260 (11096825), and from 4 to 75microg/l for total PCBs. After
controlling for age, triglycerides, and cholesterol, none of the liver
enzymes showed a significant association with total PCB concentrations.
The beta-glucuronidase concentrations, however, increased by 1 unit per
liter for every microgram per liter of DDE. Log cholesterol was also an
independent predictor of log DDE concentrations. Log triglyceride and
log cholesterol concentrations were both independent predictors of log
PCB concentrations in multiple linear regression analysis. These findings
indicate that there was a higher correlation of Aroclor-1260 with serum
analytes than was the case for Aroclor-1242. Congener specific analysis
would be helpful in the evaluation of effects of PCBs in studies that seek
to correlate PCBs with toxic effects. Because this relationship is not
well understood with respect to cause and effect, we propose the further
use in epidemiological investigations of assay methods that are little
affected by blood lipids yet are correlated with PCB concentrations. Congener-specific
quantification of PCBs would help elucidate the effects of PCBs on assays
used to monitor health effects. (Steinberg et al, 1986)
Study #6
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lipoprotein abnormalities are standard clinical signs or
symptoms of PCB poisoning
Characteristics of chloracne, associated clinical signs and
symptoms, characteristics of chloracnegens, their sources and environmental
distribution, are reviewed. Chloracne is defined as an acneiform eruption
due to poisoning by halogenated aromatic compounds having a specific molecular
shape. Substances unequivocally proved to cause chloracne in humans include
chloronaphthalenes, polychlorinated-biphenyls, polybrominated-biphenyls,
polychlorinated-dibenzofurans, polychlorinated-dibenzodioxins, tetrachloroazobenzene
(14047097), and tetrachloroazoxybenzene (21232473). Cutaneous manifestations
of chloracne including distribution of the lesions, their morphology, pigmentation,
hypertrichosis, sweating, erythema, and phrynoderma are described. Ophthalmic
changes are also sometimes noted in severe poisoning. Chloracne cases resulting
from the explosion at Seveso, Italy are discussed. Evidence suggesting
that variation of the route of absorption of a chloracnegen alters the
distinctive features of poisoning is considered. Properties of chloracnegens
are discussed. The biological basis of chloracne, in particular its predilection
for certain areas of skin, is unknown. Animal models are discussed. Histological
changes are described. Clinical signs and symptoms in noncutaneous systems
include weight loss, hepatic effects, lipoprotein abnormalities,
central and peripheral neurological effects, pulmonary changes, and moderate
elevation of urinary porphyrins. Gastrointestinal effects, musculoskeletal
changes, immunological alterations, teratogenicity and fetotoxicity are
described, but such effects are rare and their association with chloracne
is unclear. Studies of the carcinogenicity of chloracnegens are examined;
results are incomplete. Industrial sources of chloracnegens and incidents
of human environmental exposure are described. The authors conclude that
whenever chloracne is encountered, a full personal and environmental investigation
must be made. (Crow et al, 1983)
Study #7
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PCBs were present at increased levels in heart patients
This study aims to elucidate if any association exists between
the development of arteriosclerotic disease and contamination of the internal
human environment with certain organochlorine compounds (OCCs). For this
purpose the levels of DDT isomers and their metabolites, and of lindane,
dieldrin, heptachlor epoxide, and polychlorinated biphenyls (PCBs)
were determined in blood serum of 11 patients suffering from slight to
moderate (group A), and 24 patients with moderate to severe (group B),
arteriosclerotic lesions. The control group consisted of 27 patients with
no obvious manifestations of arteriosclerosis. The main findings of the
study in comparison with the control group were: Mean OCC residue levels
in blood were slightly higher in group A and markedly so in group B; The
variability and the extent of departure from normality of distributions
of organochlorine insecticides (OCIs) decreased, whereas those of PCBs
increased, in arteriosclerotic patients (more markedly in group B);
The degree of correlation between blood serum levels of various OCCs was
elevated in group A and low in group B. It remains to be ascertained whether
changes in the body burden of OCCs are primary, resulting from increased
exposure to and absorption of these compounds which thus contribute to
the development of arteriosclerosis, or are of secondary origin, due to
inhibition of xenobiotic metabolism caused by interference of the arteriosclerotic
process with the functions of drug metabolizing enzymes of liver microsomes.
(Pines et al, 1986)
Study #8
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cholesterol, albumin, triglycerides, and low density lipoproteins
correlate with PCB levels
The influence of serum lipid and albumin concentrations in
altering the partition relationship between the serum and adipose tissue
concentrations of individual polychlorinated-biphenyl (1336363) (PCB) peaks
was investigated using regression analysis. Fused silica capillary gas
chromatography with electron capture detection was used to determine these
peaks in three groups of men: 35 with current occupational exposure to
PCBs, 17 with past exposure, and 56 with no history of occupational exposure.
A
significant correlation was noted for serum cholesterol, albumin, triglycerides,
low density lipoproteins, and very low density lipoproteins with log
serum PCB levels for more than one PCB peak. Significant correlations were
noted between age, body fat content, and average servings of fish per day
with log serum PCB levels for more than one PCB peak. The authors suggest
that due to partitioning phenomena, in studies where the association between
serum PCBs and other variables is examined, a need exists to adjust for
serum cholesterol. The authors conclude that there may be questions concerning
conclusions drawn about the effects of PCBs under conditions where such
adjustments have not been made or where simultaneous adipose tissue PCB
measurements have not been made. In determining the significance of the
level of PCB in the serum, it is vital that the level of serum cholesterol
and, to a lesser extent, of albumin be considered. (Guo et al, 1987)
Study #9
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PCBs inversely correlated with plasma high density lipoprotein
cholesterol
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serum PCB concentrations significantly correlated with glutamic-oxalacetic-transaminase,
serum gamma-glutamyl-transpeptidase, and plasma triglyceride activity
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may have long-term cardiovascular consequences
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study measured both lower and higher chlorinated forms of
PCBs
A health survey of three groups of workers occupationally
exposed to polychlorinated biphenyls (PCBs) was performed. Workers were
employed in an electric equipment manufacturing facility and public and
private utility companies. Ambient PCB concentrations and personal samples
were assayed. Workers completed a questionnaire concerning work hygiene,
alcohol and tobacco consumption, and family and personal medical histories.
They were given physical examinations and standard complete blood and urine
analyses, including cell counts, enzyme activity, and cholesterol determination.
PCB components were quantitated as lower chlorinated biphenyls (L-PCB)
and higher chlorinated biphenyls (H-PCB) using gas chromatography. Serum
L-PCB and H-PCB concentrations were many times greater among workers employed
in power capacitor manufacturing than among the general population, even
comparing employees never assigned to work in PCB-exposed areas. Work environment
PCB concentrations ranged from 0 to 264 micrograms per cubic meter (microg/m3),
with the highest amount at the electrical equipment manufacturing facility.
Skin smear samples showed PCB concentrations as high as 668microg/m3 (electrical
equipment manufacturer) and 487microg/m3 (private utility). Mean serum
low PCB concentrations among equipment manufacturing workers ranged from
8 to 50 times, and mean serum high PCB concentrations from 2 to 4 times
the community background value. Mean serum low PCB values were much greater
among workers at the equipment manufacturer than at the utilities, whereas
high PCB values were comparable among these groups. Coughing, irritated
eyes, loss of appetite, tingling in the hands (altered peripheral sensation)
[neuropathy], rash or dermatitis, and systemic malaise were significantly
associated with both serum high and low PCB values. Serum PCB concentrations
significantly correlated with glutamic-oxalacetic-transaminase, serum gamma-glutamyl-transpeptidase,
and plasma triglyceride activity, and inversely correlated with plasma
high density lipoprotein cholesterol. These correlations were present
across all study sites. No overt clinical dysfunction was seen. The authors
conclude that plasma chemical changes are evidence of a physiological effect
of PCB exposure on the liver, whose long-range health significance was
unknown. The authors suggest that PCB exposure be minimized. Results with
skin smear samples show that ambient air samples do not accurately register
total PCB exposure. The consistent positive association of serum PCB with
plasma triglyceride and negative association with plasma HDL-cholesterol
may have long-term cardiovascular consequences. (Smith et al, 1982)
Study #10
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epidemiological studies showed serum PCB concentrations positively
associated with serum triglyceride and cholesterol concentrations
Human health effects of polychlorinated-biphenyls (1336363)
(PCBs) and polybrominated-biphenyls (59536651) (PBBs) were reviewed. Studies
have indicated that PCBs are ubiquitous and very persistent in the environment,
resulting in widespread human exposure. Most human PCB exposure in the
United States resulted from eating fish from contaminated waters. PBBs
do not occur in the environment to any significant extent because they
have less commercial use than PCBs. PBBs and PCBs accumulate preferentially
in adipose tissue. In laboratory animal studies, PCBs generally affected
reproduction, exerted immunotoxic effects, and induced liver tumors in
rodents. Epidemiological studies showed that serum PCB concentrations
were positively associated with serum triglyceride and cholesterol concentrations.
Occupational exposure resulted in chloracne, pruritus, and eye, nose, and
throat irritation. PCBs affect the liver by inducing the mixed function
oxidase system. No conclusive evidence of human liver cancer resulting
from occupational exposure to PCBs has been obtained. Poisoning incidents
resulting from PCB contamination of rice-oil were described. The rice oil
contained both PCBs and polychlorinated dibenzofurans (PCDFs) and caused
chloracne, skin pigmentation, impaired liver function, and compromised
immune system function. Widespread, low level exposure occurred to individuals
living in the lower Michigan peninsula after a commercial PBB mixture was
inadvertently mixed with cattle feed. Symptoms in exposed persons did not
correlate well with PBB body burden. In laboratory animals, PBBs caused
effects similar to those of PCBs. Teratogenicity, thymus atrophy, and hepatocellular
carcinomas have been observed. The author concludes that acute poisoning
outbreaks have occurred only after exposure to a combination of PCBs and
PCDFs. Exposures to PCBs or PBBs alone have caused only minor acute effects.
No significant chronic health effects have been causally associated with
PCB or PBB exposure. (Kimbrough, 1987)
Study #11
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increased cholesterol levels
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increased serum triglycerides
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increased liver enzyme gamma-glutamyltranspeptidase (GGTP)
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increased liver enzyme serum glutamic-oxaloacetic transaminase
(SGOT)
A review of human morbidity and mortality studies on the
effects of polychlorinated biphenyls (PCBs), as well as experimental animal
studies, was presented. Since PCB exposure was rarely limited to a single
congener, the review dealt with the effects of complex mixtures of PCBs,
possibly containing polychlorinated dibenzodioxins (PCDDs) and polychlorinated
dibenzofurans (PCDFs). Abnormal dermatological symptoms, such as chloracne,
were considered clinical signs of occupational exposure to PCBs. Other
commonly reported symptoms, including burning sensations in the eyes or
skin and rashes, were concurrent with exposure while chloracne persisted
for years. Findings of elevation of the liver enzymes gamma-glutamyltranspeptidase
(GGTP) and serum glutamic-oxaloacetic transaminase (SGOT), and serum triglycerides
and cholesterol levels were cited. The elevation of diastolic blood
pressure with increased serum PCB levels in the general population was
discussed. Studies of infants born to PCB exposed mothers showed lower
birth weights, psychomotor development and poorer short term memory. Chronic
animal studies using PCBs uncontaminated with PCDFs were described, demonstrating
the production of precancerous lesions. The incidence of the lesions was
directly related to the degree of PCB chlorination. Studies in rats and
mice found hepatocellular carcinomas produced by exposure to Aroclor-1260
(11096825), Aroclor-1254 (11097691) and Kanechlor-500 (37317412). Significant
increases in lymphomas and leukemias with PCB exposure were also reported.
Based on the presented evidence, PCBs were considered animal carcinogens,
acting as promoting agents. The ability of PCBs to alter the metabolism
of other carcinogens was discussed. Several studies of human mortality
following PCB exposure were discussed in which cancer mortality rates for
exposed workers were significantly elevated for cancers of the liver, biliary
tract and gallbladder, and for skin melanoma. (Nicholson et al, 1994)
Study #12
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serum cholesterol levels are significant predictors for PCB
levels in the serum
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study involved unknown mixture of PCBs
The health effects of low level exposure to polychlorinated-biphenyls
(PCB) were evaluated in a survey of 205 workers (52.7 percent males and
47.3 percent females) employed at a capacitor manufacturing plant, using
serum PCB levels as an indicator. The levels of PCB in the serum ranged
from 0 to 424 parts per billion (ppb), with a geometric average of 18.2ppb;
more than 70 percent of the workers had levels below 30ppb and only 39
percent were considered to have been actually exposed to PCB occupationally.
According to the outcome of linear multiple regression analysis, the most
significant predictors for the levels of PCB in the serum were cumulative
occupational exposure, lifetime fish consumption, length of employment,
and serum cholesterol levels; of these, length of employment and
occupational exposure contributed stronger and equally to the regression
analysis model for log serum PCB; serum triglycerides, serum glutamic-oxaloacetic-transaminase,
serum glutamic-pyruvic-transaminase, and lactate-dehydrogenase were not
significant predictors of log serum PCB. The authors conclude that there
was no evidence of acute exposure to PCB in the workers employed at the
electrical capacitor manufacturing facility surveyed, and that the strong
contribution of length of employment and occupational exposure were indicative
of the contribution of dermal contact and inhalation to the levels of PCB
in the serum of the workers. (Acquavella et al, 1986)
Study #13
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triglyceride exceeded normal range in one study group and
not in the other
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cholesterol and hepatic functions were normal
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studies involved unknown PCB mixtures
Workers occupationally exposed to polychlorinated biphenyls
(PCB) and Yusho patients were compared. Blood samples were collected from
selected silk workers (SIC-2282), marine paint workers (SIC-2851), and
patients suffering from the neurological disease, Yusho. PCB and related
compounds were measured by gas chromatography. Medical examinations were
performed on all groups. The workers occupationally exposed to PCB and
the Yusho patients showed higher blood PCB concentrations than comparisons,
sometimes as high as 50 parts per billion. The source of PCB to the silk
workers was the old oil in the silk reeling machines. The PCB of the silk
workers was similar to the KC-500 mix, whereas the marine paint workers
were exposed to the KC-600 mix. The PCB concentration of the workers in
marine paint declined with time, unlike that of the other exposed subjects.
Among the silk spinning group, triglyceride values exceeded the normal
range, although cholesterol concentration and hepatic function were normal.
Yusho patients had triglyceride concentration, cholesterol concentration,
and hepatic function within the normal range. The Yusho patients and
the workers with marine paints had a higher incidence of skin disorders.
The concentration of polychlorinated quaterphenyl (PCQ) was high among
the Yusho patients. The authors conclude that PCB is less hazardous to
workers' health than PCQ, which is especially high in Yusho patients. (Takamatsu
et al, 1985)
Study #14
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serum cholesterol levels in humans are directly proportional
to PCB levels
Studies involving polychlorinated biphenyls (PCBs) are reviewed.
PCBs are a class of halogenated aromatic compounds, including halogenated
biphenyls, naphthalenes, dibenzodioxides, and dibenzofurans. PCBs persist
in the environment and are retained in tissue because they are lipid soluble.
They affect reproduction, suppress the immune system, cause tumors in laboratory
rodents, cause hepatic porphyria, and cause chick edema in chickens. Cell
mediated immunity is impaired by PCB, although the degree of impairment
is determined by the type of isomers present. PCBs are not teratogenic,
but they are fetotoxic, producing cleft palates, subcutaneous edema, and
hemorrhage. PCBs are passed to mammalian offspring in the milk. 2,3,7,8-Tetrachloro-dibenzo-p-dioxin
(1746016) (TCDD) is known to cause hepatocellular carcinomas and squamous
carcinomas of the oropharynx and lungs. Subcutaneous sarcomas and tumors
of the thyroid are also noted. The primary source of PCB exposure to the
general United States population is fish from contaminated water. Serum
cholesterol levels in humans are directly proportional to PCB levels.
The concentration of PCB in human milk is particularly high. There is no
clear evidence of harm to humans from PCB, but research is inconclusive.
The author concludes that PCB may be a cancer promoter, but additional
studies on exposed human cohorts, such as fishermen, must be done before
any conclusions about the effects of PCB on humans can be reached. (Kimbrough,
1985)
Study #15
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induction of liver enzymes and elevation of serum triglycerides
and cholesterol concentrations have been consistently observed.
Occupational exposure to polychlorinated-biphenyls (1336363)
(PCBs) and the carcinogenic potential of PCBs were reviewed. Studies in
laboratory animals were reviewed. These have shown that chronic exposure
to PCBs containing 40 to 60 percent chlorine induces precancerous lesions
in the liver such as neoplastic nodules or altered foci in mice and rats.
The incidence of the lesions was strongly correlated with the degree of
chlorination. Long term exposure to aroclor-1260 (11096825) and Kanechlor-500
(61788338) produced a high incidence of hepatocellular carcinomas in rats
and mice, respectively. PCBs also produced lymphomas and leukemias. PCBs
have shown promotional ability in rats and mice. Human morbidity studies
have shown that human exposure to PCBs commonly results in skin abnormalities
such as acneform eruptions and folliculitis. Induction of liver enzymes
and elevation of serum triglycerides and cholesterol concentrations have
been consistently observed. Human mortality studies have provided strong
evidence that PCBs produce cancer of the liver, biliary tract, and gallbladder
and suggestive evidence that PCBs increase the risk of cancer of the lymphatic
and hematopoietic systems. A discussion of PCB use and sources of occupational
exposure in Ontario was included as an appendix. (Industrial Disease Standards
Panel, 1987)
Study #16
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plasma triglyceride level showed a significantly positive
correlation with blood PCB level
In December, 1983, the New York State Health Department interviewed
52 persons who were exposed to known levels of polychlorinated-biphenyl
(1336363) (PCB) oil from an office building electrical malfunction in Syracuse,
New York. Sixty-eight nonexposed persons were matched to the exposed group
by sex, age, employer, and job description. Information was collected concerning
demographic characteristics and chemical exposure histories, as well as
medical history and tobacco product and alcoholic beverage use. Blood samples
were taken for the determination of PCB, complete blood count (CBC), aluminum,
globulins, calcium, phosphorus, cholesterol, triglycerides, urea, nitrogen,
uric acid, creatinine, direct and total bilirubin, alkaline-phosphatase,
lactic-dehydrogenase, serum glutamic-oxaloacetic-transaminase, serum glucose,
serum glutamic-pyruvic-transaminase, sodium, potassium, chloride and serum
iron levels. A brief followup interview was held 6 weeks later and all
but the PCB level and CBC were repeated. The slight elevation in mean
blood PCB level in the exposed group was not statistically significant.
A significant difference in mean PCB level was noted between persons who
had more than two drinks per day versus those who drank two drinks or fewer.
Utility company employees had the highest mean blood PCB level of all occupations
studied, with firemen second. Among the exposed group, no significant mean
serum PCB level differences were noted between persons who were located
in parts of the building with higher environmental PCB levels. After controlling
for the effects of age and alcohol consumption, plasma triglyceride
level was the only blood chemistry variable to show a significantly positive
correlation with blood PCB level. Age was significantly related to
blood PCB level in both the exposed and unexposed groups, being higher
in older persons. The authors conclude that no serious clinical symptoms
were seen in the exposed group. (Stark et al, 1986)
Study #17
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PCBs are correlated with beef, lamb, and fish consumption
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chlorinated hydrocarbon concentrations are correlated with
levels of plasma cholesterol
Associations between reported consumption in animal products
and chlorinated hydrocarbon concentrations were examined in 297 elderly
people who lived in Germany. Consumption of beef and lamb was correlated
positively with hexachlorobenzene (HCB), beta-hexachlorocyclohexane (beta-HCH),
total polychlorinated biphenyls (PCBs), and total dichloro- diphenyl-trichloroethane
(DDT) (r = .13-.19, p < .05). Consumption of saltwater fish was correlated
positively with alpha-HCH, dieldrin, and PCBs (r = .12 p < .05).
Other univariate predictors were body mass index, plasma cholesterol,
pork consumption, poultry consumption, and age. Multivariate linear models
of predictors of each chlorinated species were constructed, and some form
of meat was used as the main predictor; the sum of all meats (exclusive
of fish) was the best predictor of dieldrin and In(alpha-HCH) concentrations.
Beef and lamb consumption was a positive predictor of HCB, heptachlor epoxide,
total DDT, and beta- (incomplete abstract) (DEVOTO et al, 1998)
Study #18
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lipoproteins take part in the uptake and egress of PCBs from
skin fibroblasts
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study used PCB 153
The uptake of 2,4,5,2',4',5'-hexachlorobiphenyl (35065271)
(HCB) and its interaction with serum lipoproteins was investigated in skin
fibroblast cells. Human normal skin fibroblasts and familial hypercholesterolemic
cells were treated with HCB alone, HCB before incubation with low density
lipoproteins (LDL), high density lipoproteins (HDL), or very low density
lipoproteins (VLDL), or with lipoproteins alone. Cells were examined by
fluorescence microscopy. DNA was measured fluorometrically. Cytoplasmic
inclusions were apparent at 3 hours after treatment with HCB. After 24
hours large numbers of inclusions were present. The HCB induced inclusions
were lipoidal. When cells were treated with HCB and incubated with HDL
and LDL there was a decline in inclusions and lipidosis. No decrease in
inclusions was observed with VLDL. When HCB was added at the same time
as lipoproteins and remained in the solutions for 24 hours, there was a
marked increase in lipidosis. No cholesterol nor cholesteryl ester was
evident in the cytoplasmic inclusions. The authors conclude that lipoproteins
take part in the uptake and egress of HCB from skin fibroblasts. (Kling
et al, 1984)
Study #19
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serum PCB levels were positively and significantly correlated
with triglycerides, cholesterol, total bilirubin, conjugated bilirubin,
beta-glucuronidase, 5'-nucleotidase, serum apolipoprotein-Al, serum apolipoprotein-B,
urinary creatinine, and urinary alanine-aminopeptidase
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study involved unknown mixture of PCBs
In response to a request from the Indiana State Board of
Health, a follow up study was conducted of workers occupationally exposed
to polychlorinated-biphenyls (1336363) (PCBs) at the Westinghouse Electric
Corporation's Transmission and Distribution Components Division (SIC-3629),
Bloomington, Indiana. A cross sectional study had been conducted in 1977.
Workers in the high and low serum PCB groups from that study were invited
to participate; 60 of 66 workers originally studied participated in this
study. Those in the high level group were on the average 5.6 years older
than the low PCB group. Use of PCBs was discontinued in 1977. By 1985 the
levels of serum PCB concentrations in the low group had decreased by an
average of 85% of the 1977 value. Levels in the high PCB group had decreased
by an average of 90%. No clinical abnormalities attributable to PCB exposure
were noted. Serum PCB levels were positively and significantly correlated
with triglycerides, cholesterol, total bilirubin, conjugated bilirubin,
beta-glucuronidase, 5'-nucleotidase, serum apolipoprotein-Al, serum apolipoprotein-B,
urinary creatinine, and urinary alanine-aminopeptidase. According to
the authors, the biochemical findings are indicative of the physiological
effects of PCBs on lipid metabolism, liver function and kidney function.
The clinical significance of these findings 8 years after occupational
exposures had ceased is unknown. (Steele et al, 1990)
Study #20
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PCBs are taken into human plasma albumin
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PCB distribution between different lipoproteins was very
similar to distribution of cholesterol
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PCB binding to lipoproteins and albumin has important biological
implications
The distribution of carbon-14 labeled toxaphene (8001352)
was studied among lipoprotein fractions in-vitro and in-vivo using rat
and human plasma. The association of carbon-14 labeled DDT (50293) and
carbon-14 labeled PCB (1336363) with different plasma lipoproteins
was investigated under identical experimental conditions. Adult female
Sprague-Dawley rats were injected intraperitoneally with carbon-14 labeled
toxaphene or carbon-14 labeled PCB. Blood samples were taken after 10 minutes
and 2 hours. For in-vitro samples, plasma pooled from three men or ten
rats was added to vials contained labeled toxaphene, DDT, or PCB, and incubated
for 16 to 18 hours. Sequential ultracentrifugation was used to isolate
plasma lipoproteins. The distribution of DDT and PCB between different
fractions of human plasma was similar, with the highest uptake seen
in the albumin rich bottom fraction (BF), in which more than 50% of
the total radioactivity was recovered. A higher proportion of radioactivity
appeared in the BF in in-vivo compared to the in-vitro studies. This shift
toward the BF increased with time from 10 minutes to 2 hours after injection.
The effect may therefore be due to a continuous in-vivo production of metabolites
of the respective substance. In rat plasma the distribution of the three
lipophilic xenobiotics between different lipoproteins was very similar
to the distribution of cholesterol between these fractions. The findings
indicate the important biological implications of the binding of lipophilic
xenobiotics to plasma lipoproteins and albumin. (Mohammed et al, 1990)
Study #21
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PCB exhibits a homogeneous distribution among lipoproteins
and the heaviest fraction.
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70 to 75 percent of HCB partitioned into plasma and 25 to
30 percent to the erythrocytes
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study used PCB 153
The uptake, distribution, and transfer of 2,2',4,4',5,5'-hexachlorobiphenyl
(35065271) (HCB) were examined in-vitro with human and rat whole blood,
plasma, and lipoprotein fractions. Blood was taken from Sprague-Dawley-rats
and humans. Incorporation of carbon-14 labeled HCB in plasma, erythrocytes,
and high and low density lipoproteins was determined after sedimentation
of erythrocytes and ultracentrifugal fractionation of plasma at varying
temperatures. Each isolated fraction was incubated alone with HCB. The
transfer of HCB among lipoproteins was studied by incubating one labeled
lipoprotein with other unlabeled fractions. Concentrations of protein and
triacylglycerol were altered to determine the effect on movement of HCB
among lipoprotein fractions. Proteins in the bottom fraction were added
to the incubations to examine competition for HCB uptake. In both rat and
human whole blood 70 to 75 percent of HCB partitioned into plasma and
25 to 30 percent to the erythrocytes. The uptake in plasma was rapid
and rose with temperature. Distribution of HCB among lipoproteins
was 20 to 30 percent in very low density proteins and 15 to 25 percent
in high density proteins. Over 25 percent of HCB was found in the remaining
bottom fraction. Each fraction incubated alone with HCB was capable of
uptake. The transfer of HCB among lipoproteins was dependent on the concentration
of both protein and triacylglycerol in the incubations. Albumin and a steroid
binding globulin in the bottom fraction competed with the lipoproteins
for HCB uptake. The authors conclude that HCB exhibits a homogeneous
distribution among lipoproteins and the heaviest fraction. (Vomachka
et al, 1983)
Study #22
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PCB's are fat soluble and mainly transported by triglycerides
(TG) with lipoproteins
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study measured levels of PCBs 138, 153 and 180
PCB's are toxic pollutants accumulating in adipose tissue.
They are transferred to the developing organism during gestation. PCB cord
blood levels are associated with neuromotor deficits in human neonates.
Blood PCB contamination levels are studied in 14 "healthy" mother-infant
pairs for the congeners 138, 153, 180 in both mother (37th wk gestation,
and 10 d postnatally) and neonate (cord blood). Since PCB's are fat
soluble and mainly transported by triglycerides (TG) with lipoproteins,
PCB's are presented in relation to TG content. PCB congeners were measured
by capillary gas chromatography with electron capture and mass spectrometric
detection. TG were determined by an enzymatic method (SMAC). Cord blood
TG levels were +/- 17% of those in the mother antenatally (0.49 versus
2.79 mmol/L). Mean maternal antenatal PCB congener (138, 153 and 180)
levels in mg/mol TG were: 0.26 (SD 0.12), 0.40 (SD 0.19) and 0.25 (SD 0.12),
respectively, almost similar to those in cord blood (0.27 (SD 0.13), 0.39
(SD 0.22) and 0.22 (SD 0.13), respectively). After delivery mean maternal
PCB congeners in mg/mol TG increased (0.48 (SD 0.24), 0.71 (SD 0.38) and
0.19 (SD 0.24), respectively), as compared to prenatal levels. Maternal
plasma PCB's at end of gestation are +/- 6 x as high as those in the corresponding
neonate. However, when PCB's are expressed per TG content, levels are similar.
This suggests an equilibrium between two major PCB-containing fat compartments
in blood on both sides of placenta. The increase of PCB's in terms of TG
after delivery may reflect their mobilisation from fat and/or liver to
the maternal circulation. PCB levels in organs (e.g. brains) of deceased
fetuses and newborns will provide additional information on the extent
of the problem. (Huisman et al, 1992)
Study #23
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100 percent of the dioxin was associated with plasma and
none with red blood cells (some PCBs are dioxin-like)
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in plasma, 84 to 89 percent of dioxin could be recovered
from lipoprotein fractions
Studies on the distribution of 2,3,7,8-tetrachlorodibenzo-p-dioxin
(1746016) (TCDD) in human blood serum components were summarized. Analyses
of centrifuged whole blood samples spiked with tritium (H-3) labeled TCDD
found that 100 percent of the TCDD was associated with the plasma and
none with the red blood cells. In plasma, 84 to 89 percent of the
H-3 activity could be recovered from the lipoprotein fractions. Recoveries
of radiolabel from the various lipoprotein fractions were very low density
lipoproteins 10 to 30 percent, low density lipoproteins 60 percent, and
high density lipoproteins 10 to 30 percent. Most of the H-3 activity in
the lipoprotein free plasma fraction was associated with proteins such
as albumin and had molecular weights on the order of 60,000 daltons. Analysis
of 24 human serum and adipose tissue samples indicated that on a per lipid
basis the adipose tissue/serum TCDD partition coefficient was 1.09. When
expressed on a whole weight basis the partition coefficient was 158. In
a study of the effects of fasting on serum polychlorinated biphenyls, hexachlorobenzene
(118741), and p,p'-DDE (72559) concentrations, which were used as surrogates
for TCDD, in 20 volunteers who underwent two overnight fasts, it was found
that fasting did not significantly affect the concentrations when the data
were corrected for total serum lipid concentrations. The authors conclude
that measuring TCDD concentrations is a valid technique for assessing human
TCDD exposures. (Needham et al, 1989)
Study #24
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methylsulfonyl metabolites of PCBs were distributed equally
among the LDL and HDL fractions.
The concentrations of chlorinated biphenyls (CBs), 1, 1-bis(4-chlorophenyl)-2,2-dichloroethene
(DDE), hexachlorobenzene (HCB), and the methylsulfonyl metabolites of CBs
(MeSO(2)-CBs) and DDE (MeSO(2)-DDE) were determined in human plasma samples
and in the fractions obtained by ultracentrifugation of plasma into very-low-density
(VLDL), low-density (LDL), high-density (HDL) lipoprotein and lipoprotein
depleted (LPDP) fractions (containing primarily albumin). The concentrations
of triacylglycerols, cholesterol, phospholipids, and apolipoprotein B (apoB)
were determined. The organochlorine compounds were associated with all
fractions, but predominantly with the LPDP fraction. On an average 44%
of CBs, 61% of MeSO(2)-CBs, 73% of DDE, 77% of MeSO(2)-DDE, and 45% of
HCB were distributed in the LPDP fraction. A tendency to greater association
of 3-methylsulfonyl substituted than of corresponding 4-methylsulfonyl
substituted chlorobiphenyls to the LPDP fraction was noticed. Among the
lipoprotein fractions, LDL was the main carrier of HCB, DDE and CBs. MeSO(2)-DDE
was predominantly found in HDL and MeSO(2)-CBs were distributed equally
among the LDL and HDL fractions. Calculating the concentrations of
organochlorine compounds in relation to the content of apoB, the levels
were about 10 times higher in VLDL than in LDL. (NOREN et al, 1999)
Study #25
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organochlorines have a high affinity for lipoproteins
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study used PCB commercial mixture Aroclor 1260
A study was made of the binding pattern of several organochlorine
residues (OCR), with particular interest in hexachlorobenzene (118741)
(HCB) and dichlorodiphenyl-dichloroethene (72548) (p,p'-DDE). Experiments
were done in-vivo and in-vitro in adult female Sprague-Dawley-rats and
in-vitro in human blood. An attempt was made to determine the stability
of the binding to carriers and its effects on the distribution kinetics.
Rats were given single oral doses of HCB, p,p'-DDE, Aroclor-1260
(11096825), pentachlorophenol (87865) (PCP), or hexachlorocyclohexane (608731)
(HCH). For in-vitro experiments, blood or plasma was incubated in glass
tubes which had had organochlorine compounds dried on the surface. The
findings indicated a high affinity of organochlorine residues for lipoproteins.
These findings did not differ between in-vivo and in-vitro experiments.
The rapid release of residues by elution through a reverse phase column
indicated that binding to blood carriers was very weak. The authors conclude
that specific transfer to tissues through lipoprotein receptors, if they
exist, is of little significance in OCR distribution. (Gomez-Catalan et
al, 1991)
Study #26
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PCB 153 is used as a model of lipophilic (fat-loving) compounds
which are unmetabolizable
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PCB excretion from the body is influenced by increases or
declines in fat storage
2,4,5,2',4'5'-Hexachlorobiphenyl (6-CB)-a polychlorinated
biphenyl (PCB) congener resistant to metabolism in most species-has become
a major residue in the biosphere including human adipose tissue. Its
use as a model of unmetabolizable lipophilic compounds and as a tool in
toxicokinetics in the last two decades is reviewed. This extremely
water-insoluble compound is transported in plasma by albumin and lipoproteins.
Binding to these plasma proteins appears to be important for uptake and
release processes in different tissues. The redistribution kinetics of
6-CB as well as its pronounced adipose tissue storage and a very slow excretion
with the faeces has been established in long-term animal studies. Excretion
is strongly influenced by an increasing or diminishing adipose storage
compartment size. Other minor pathways of elimination, e.g., via hair,
become also important in the absence of metabolism and renal excretion,
6-CB has revealed the possibility of an almost quant (incomplete abstract)
(Muhlebach et al, 1991)
Study #27
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serum triglyceride concentrations were significantly correlated
with blood PCB levels
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study involved unknown mixtures of PCBs
A follow-up study of capacitor manufacturing workers exposed
to polychlorinated biphenyls (PCBs) and their children was conducted since
1973. PCB levels in whole blood of workers as well as in breast milk of
the exposed lactating mothers were approximately 10 to 100 times those
of nonexposed Japanese. Blood PCB levels had a statistically significant
correlation with the duration of PCB handling and breast milk PCB levels.
The rate of decline of blood PCB levels, as well as the changes of the
gas chromatograph of blood PCB over 7 years was found to vary with the
kind of PCB handled. The levels of blood PCB tended to be higher in the
children fed PCB-contaminated breast milk for a long period. The great
majority of workers handling PCBs had dermatologic complaints. Discontinuance
of contact with PCB led to gradual improvement of these lesions. Abnormal
results in the blood chemistry of the workers were rare, while serum
triglyceride concentration was significantly correlated with blood PCB
levels in 1974. In the questionnaire study, the number of complaints
in children born from mothers who had handled PCBs, especially those fed
breast milk for a long period, was conspicuously higher than that in control
groups. Several children were found to have the same medical findings as
in Yusho; however, they have not been diagnosed as PCB-poisoned, because
these findings were neither so serious nor related to the blood PCB levels.
(Hara, 1985)
Study #28
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elevated triglyceride and serum enzyme levels due to PCB
exposure
A review of the data and a summary of findings regarding
the potential human health hazards of polychlorinated biphenyls (PCBs),
polychlorinated dibenzofurans (PCDFs), polychlorinated dibenzo-p-dioxins
(PCDDs), and related compounds resulting from electrical equipment fires
or failures were presented. Physical and chemical properties of PCBs, use
of PCBs in electrical equipment, potential for exposure to PCBs and related
compounds following fire or failure of electrical equipment, and exposure
limits were presented as background data. Toxic responses noted in PCB,
PCDF, or PCDD treated animals are analogous, however, individual compound
potencies vary with regard to the degree and position of chlorination.
A soot sample collected after a transformer fire in New York in 1981 yielded
5000 micrograms/gram (microg/g) PCBs, 48microg/g 2,3,7,8-tetrachlorodibenzofuran
(51207319), and 1.2microg/g 2,3,7,8-tetrachlorodibenzo-p-dioxin (1746016).
The median lethal dose (LD50) of the soot in aqueous methyl-cellulose,
when administered in a single oral dose in guinea-pigs, was 410mg/kg; the
LD50 of a benzene extract of the soot was 327mg/kg. Reported health effects
in humans upon exposure to PCBs include chloracne, hyperpigmentation,
gastrointestinal disturbances, elevated serum enzyme and triglyceride
levels, and numbness of the extremities. As prudent public health policy,
NIOSH recommends that occupational exposure to PCBs, PCDFs, and PCDDs resulting
from electrical equipment fires or failures be controlled to the lowest
feasible limit. Keeping occupational exposures as low as possible involves
recognition of potential hazard, assessment of exposure, personal protective
clothing, respiratory protection, decontamination and worker protection
programs, post decontamination testing, and medical surveillance. (NIOSH,
1986)
Study #29
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increases in plasma triglyceride concentrations were the
chief adverse effect of PCB absorption
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study involved unknown mixtures of PCBs
The effects of exposure to polychlorinated-biphenyls (1336363)
(PCBs) in sewage sludge on metabolism were studied in 148 persons.
Most subjects were exposed to PCBs through gardening, through occupational
exposure or as families of exposed workers. Unexposed persons were used
for comparison. Personal histories were obtained. Serum levels of PCBs
were determined by gas chromatography. The highest concentrations of PCBs
were found in electrical capacitor manufacturing employees. The amount
of PCBs in 19 members of workers' families were higher than in the unexposed
group. Serum PCB concentrations were high in older subjects, in males,
and in those not wearing gardening gloves. No consistent abnormality
patterns were found in medical histories or physical examinations. No clinical
abnormalities were associated with serum PCB concentrations. Toxicologic
evaluations showed that increases in plasma triglyceride concentrations
were the chief adverse effect on PCB absorption. The authors note that
the effects of PCBs on human health are not well defined. (Baker et al,
1980)
Study #30
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synthesis of triglyceride and phospholipids increased dramatically
due to PCBs
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PCB toxicity may be related to its capacity to alter phosphoglyceride
metabolism
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PCBs interact with acetate to cause enhanced effects
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study used PCB 153
The effect of 2,4,5,2',4',5'-hexachlorobiphenyl (35065271)
(HCB) on phospholipid and glyceride synthesis was investigated in human
skin fibroblasts. Normal skin fibroblasts and familial hypercholesterolemic
cells were cultured and incubated with 5.5, 27, or 55 micromolar concentrations
of radiolabeled HCB for 3 or 24 hours. Radiolabeled acetate and glycerol-3-phosphate
were used as substrates in different experiments. Cells were analyzed for
phospholipids and triglyceride. When acetate was the substrate synthesis
of triglyceride and phospholipids increased dramatically with HCB;
a lesser effect was noted on diglyceride synthesis. Incorporation of glycerol-3-phosphate
into phospholipids and diglycerides was decreased but no significant change
in triglyceride formation was noted. Hypercholesterolemic skin fibroblasts
showed increased incorporation of acetate into phospholipids and triglycerides
at low concentrations of HCB and decreased incorporation at higher concentrations.
There was a significant increase in triglyceride content when skin fibroblasts
were treated with HCB. There was no significant change in phospholipid
content of skin fibroblasts after treatment with HCB at lower concentrations.
The differences in actions with acetate and glycerol-3-phosphate were attributed
to the fact that acetate is a precursor of some compounds that are converted
to phospholipids and glycerides. The authors conclude that toxicity
of HCB may be related to its capacity to alter phosphoglyceride metabolism.
(Beranek et al, 1984)
Continue with Studies
31 to 60 regarding PCBs and Heart Disease
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