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Human Heart Disease --- Studies 31-60
linking PCBs with Triglyceride changes 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 pages and discussion
on these results, go to the Heart
Table of Contents.
Study #31
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PCB poisoned individuals had elevated triglyceride levels
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ocular (eye) toxicity included blurring of vision, burning
sensations, eye soreness, eyestrain, discharges and eyelid swelling
The effects of exposure to polychlorinated-biphenyls (1336363)
(PCBs) were reviewed and discussed, with emphasis on the ocular effects.
Topics included physical and chemical properties, uses, PCB poisoning outbreaks,
toxicity, dermatologic symptoms, ocular toxicity, treatment, and controversies
involving human exposure to PCBs. Symptoms and signs of ocular toxicity
included blurring of vision, burning sensations, eye soreness, eyestrain,
discharges and eyelid swelling. Data from blood analyses of PCB poisoned
individuals did not demonstrate any abnormalities except for elevated
triglyceride levels. No effective treatment for the excess exposure
to PCBs was available, although some symptomatic relief may be obtained.
The effects of occupational exposure or exposure due to PCB related fires
were discussed. (Baldassare et al, 1989)
Study #32
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different laboratories reported significantly different serum
lipid PCB levels from the same sample
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improved analytical methods are needed
At two laboratories, an analytical method to determine polychlorinated
biphenyls (PCBs) in serum was evaluated for its ability to recover in vitro-spiked
PCBs from bovine and human serum. Statistically significant differences
(p < 0.05) were found in the results obtained for the two matrices at
both laboratories. Previously an interlaboratory bias between the laboratories
of +3.3% had been established by using bovine serum; however, with human
serum the average interlaboratory bias was -9.5% resulting in a change
in absolute bias of approximately 13%. The analytes determined in the
base materials before they were in vitro-spiked with PCBs were dichlorodiphenyldichloroethylene
(p,p'-DDE), PCBs, and serum lipids (i.e., total cholesterol, triglycerides,
free cholesterol and phospholipids). The concentration of analytes and
lipids was higher in base human serum than in base bovine serum. (Burse
et al, 1992)
Study #33
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elevated blood-serum triglycerides were frequent symptoms
in 1,081 people poisoned with PCBs
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study involved unknown mixtures of PCBs
The status of the toxicologic, carcinogenic, teratogenic,
and mutagenic aspects of the PCBs of greatest relevance to man is reviewed.
Summaries of oral and dermal toxicity of Aroclors to rats and rabbits indicate
that they are of low acute toxicity. Lethal affects appear to be cumulative.
Summaries of PCB-induced pathologic changes show liver alterations and
skin lesions to be the most striking change in mammals, whereas fluid in
the pericardial sac, kidney damage, and reduced spleen are found in birds.
The toxic nature of contaminating polychlorodibenzofurans is pointed out.
Effects of low level feeding show reduced rate of weight gain, increased
kidney and liver weights, and elevated serum alkaline phosphatase. Morphological
and ultrastructural changes in livers of treated rats are described. Acute
and chnroic feeding studies resulted in fewer and smaller offspring, decreased
weanling survival, and lowered mating indices in rats; and body weight
loss, eggshell thinning, and poor egg hatchability in chickens. Bladder
cancers, heptaomas, lung abscesses, pneumonia, spleen atrophy, intracranial
abscesses, hyperplasia and dysplasia of gastric mucosa, fetotoxicity, abortions,
maternal deaths, and stillbirths have been observed in mammalian species.
A high incidence of chromosomal aberrations has been reported in ring doves,
but none was observed in human lymphocyte cultures, rat bone marrow or
spermatogonia. Suppressed immunological responses have been observed in
ducks, guinea pigs, rabbits, and chickens. An outbreak of PCB poisoning
in Japan in 1968 resulted in 1081 patients being affected by chloracne,
blindness, gastrointestional symptoms, skin discoloration in infants of
poisoned mothers, decreased birth weights, increased urinary 17-ketosteriods,
respiratory distress, a hematological picture suggesting inflammation,
and elevated blood-serum triglycerides. (Fishbein, 1974)
Study #34
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PCBs are statistically associated with cardiovascular disease
risk factors
The principal human enteric aerobic and anaerobic bacteria,
Escherichia coli and Bacteroides fragilis, were cultured in the presence
of . 01 and . 1 ppm DDT and PCB. The bacteria were assayed for dry weight
and total lipids. DDT at the 0. 1 ppm level increased the growth of E.
coli, but had no effect at . 1 ppm. Neither DDT nor PCB significantly altered
the total lipid content. DDT at the 1. 0 ppm level depressed B. fragilis
growth, but did not affect lipid levels. PCB at the . 1 ppm level significantly
increased growth of B. fragilis but significantly depressed lipid synthesis
at both concentrations. The effect appeared dose dependent. All cultures
metabolized DDT to its derivative DDE. Several replicates showed traces
of DDE as well. DDT and PCB are statistically associated with cardiovascular
disease risk factors, but the mechanism does not appear to be that
of increased lipid anabolism by enteric bacteria. (Greer et al, 1974)
Study #35
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PCBs are considered a protoxicant in the circulatory system,
possibly through effects on cytochrome P450 and enzymes
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study used PCB commercial mixture Aroclor 1254
In view of the potential role of the cytochrome P450 (CYP)
and microsomal epoxide hydrolase (mEH) biotransformation enzymes in the
metabolism of protoxicants in the circulatory system, we examined
CYP and mEH expression in several primary cultures of human umbilical vein
endothelial cells (HUVEC), each established from a different individual.
Total RNA was isolated from untreated cells and cells 72 hr after exposure
to dimethyl sulfoxide (DMSO), Arochlor 1254 (PCB), and beta-naphthoflavone
(BNF) Specific mRNA transcripts were examined by Northern blotting and
reverse transcriptase-coupled polymerase chain reaction (RT) analyses.
CYP2E1, CYP3A, and CYP1A2 mRNAs were not detectable in any of the cultures
by Northern blot analysis with radiolabeled oligomer probes; however, CYP1A1
mRNA was detected using this procedure in HUVEC cultures exposed to betaNF
for 72 hr. Using RT/PCR, constitutive levels of CYP1A1, CYP1A2, CYP2E1,
and CYP3A gene expression in HUVEC cultures were (incomplete abstract)
(Farin et al, 1994)
Study #36
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disruption of cell-growth, differentiation or apoptosis (cell
death) during embryonic or fetal development could lead to cardiovascular
dysfunction (heart disease)
Communication mechanisms [extra-, intra-, and gap junctional
inter-cellular communication (GJIC)] control, from the fertilized egg,
through embryogenesis to maturity and aging, whether a cell proliferates,
differentiates, dies by apoptosis, or if differentiated, adaptively responds
to endogenous and exogenous signals. From the egg to the 100 trillion cells
in the human body, health is maintained when these communication processes
between stem, progenitor and terminally differentiated cells are integrated.
Each cell choice involves 'epigenetic' mechanisms to alter the expression
of genes at the transcriptional, translational or post-translational levels.
Disruption of the communication mechanisms can be either adaptive or maladaptive.
Modulation of extra-cellular communication, either by genetic imbalances
of growth factors, hormones or neurotransmitters or by environmental, exogenous
chemicals can trigger signal transducing intra-cellular mechanisms. These
intra-cellular signals can modulate gene expression at the transcriptional,
translational or post-translational levels while also modulating GJIC.
Untimely or chronic disruption of GJIC during embryonic or fetal development
could lead to embryonic lethality or teratogenesis. By modulation of
GJIC, homeostatic control of cell growth, differentiation or apoptosis
could lead to specific diseases, such as neurological, cardiovascular,
reproductive or endocrinological dysfunction. Chemical modulation or oncogene
down-regulation of GJIC in initiated tissues has been shown to lead to
tumor promotion. Genetic syndromes carrying a mutated gap junction gene,
together with some transgenic and knock-out gap junction gene mice, provide
evidence for the importance of this organelle found only in metazoans.
Implications for 'thresholds' to toxicants and for risk assessment are
evident. (Trosko et al, 1998)
Study #37
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serum PCB concentrations were elevated, but within the normal
range
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PCBs were weakly correlated with systolic blood pressure
and liver enzyme activities, at background levels
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study involved unknown mixture of PCBs
Area and personal air samples were analyzed for ethylene-oxide
(75218), glycols, and adipic-acid (124049) at the Witco Chemical Corporation
(SIC-2816), Perth Amboy, New Jersey from November to December, 1983 and
May, 1984. The evaluation was requested by the union to investigate possible
health effects due to polychlorinated biphenyls (PCBs), glycols,
and ethylene-oxide. The evaluation was assigned to the New Jersey State
Department of Health. Medical examinations which included spirometry testing
and serum PCB determinations were given to 52 workers. Medical and work
histories were obtained. Ethylene-oxide exposures averaged 0.7 to 7.1 parts
per million (ppm). The OSHA standard for ethylene-oxide is 1.0ppm. Glycol
concentrations averaged less than 0.7ppm. Adipic-acid concentrations ranged
from 0.47 to 0.79 milligram per cubic meter. There are no federal standards
for glycols and adipic-acid. Mucosal irritation and bronchitis were reported
by 56 and 27 percent of the workers, respectively. One second forced expiratory
volumes were significantly reduced. Serum PCB concentrations were elevated,
but within the normal range. They were weakly correlated with systolic
blood pressure and liver enzyme activities. The authors conclude that
health hazards due to ethylene-oxide and airborne fatty acid exposures
exist. Recommendations include improving ventilation and work practices
and implementing an OSHA approved respirator program. (Cummings et al,
1985)
Study #38
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PCBs concentrate in brown fat
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longest retention time in the bronchial epithelium and renal
tubules
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study used PCB 101
Single doses of 2,4,5,2',5-pentachlorobiphenyl uniformly
labeled with 14-C have been administered intravenously and orally to mice.
Whole-body autoradiograms and scintillation counting of tissue samples
have shown that most radioactivity leaves the circulation for the tissues
within one hour. Peak concentrations varied, being highest in brown
fat, which after 24 hours comprised the major reservoir of the unchanged
compound in the body. Radioactivity disappeared rather rapidly drom most
other tissues, although the longest retention occurred in bronchial
epithelium and some parts of the renal tubules. The excretion
of radioactivity was mainly through the bile, into feces, with a half-time
of six days. There was little unchanged compound in the feces, the major
metabolite was a hydroxylated derivative, both free and conjugated. (Berlin
et al, 1975)
Study #39
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PCBs may play a role in atherosclerosis by causing endothelial
cell dysfunction and a decrease in the barrier function of the vascular
endothelium
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study used PCBs 77, 114 and 153
Environmental chemicals, such as polychlorinated biphenyls
(PCBs), may be atherogenic by disrupting normal functions of the vascular
endothelium. To investigate this hypothesis, porcine pulmonary artery-derived
endothelial cells were exposed to 3,3',4,4'-tetrachlorobiphenyl (PCB
77), 2,3,4,4',5-pentachlorobiphenyl (PCB 114), or 2,2',4,4',5,5'-hexachlorobiphenyl
(PCB 153) for up to 24 hours. These PCBs were selected for their varying
binding avidities with the aryl hydrocarbon (Ah) receptor and differences
in their induction of cytochrome P450. PCB 77 and PCB 114 significantly
disrupted, in a dose-dependent manner, endothelial barrier function by
allowing an increase in albumin transfer across endothelial monolayers.
These PCBs also contributed markedly to cellular oxidative stress, as measured
by 2,7-dichlorofluorescin (DCF) fluorescence and lipid hydroperoxides,
and caused a significant increase in intracellular calcium ([Ca2+]i) levels.
Enhanced oxidative stress and [Ca2+]i in PCB 77- and PCB 114-treated cells
were accompanied by increased activity and content of cytochrome P450 1A
and by a decrease in the vitamin E content in the culture medium. In contrast
to the effects of PCB 77 and PCB 114, cell exposure to PCB 153 had no effect
on cellular oxidation, [Ca2+]i, or endothelial barrier function. These
results suggest that certain PCBs may play a role in the development
of atherosclerosis by causing endothelial cell dysfunction and a decrease
in the barrier function of the vascular endothelium. It is possible
that interaction of PCBs with the Ah receptor and activation of the cytochrome
P450 1A subfamily are involved in this pathology. (Toborek et al, 1995)
Study #40
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linoleic acid can amplify PCB-induced endothelial cell dysfunction
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severe toxicity of PCBs in the presence of linoleic acid
may be due in part to the generation of epoxide and diol metabolites
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study used PCB 77
Selected dietary lipids may increase the atherogenic effects
of environmental chemicals, such as polychlorinated biphenyls (PCBs), by
cross-amplifying mechanisms leading to dysfunction of the vascular endothelium.
We have shown previously that the omega-6 parent fatty acid, linoleic acid,
or 3,3',4,4'-tetrachlorobiphenyl (PCB 77), an aryl hydrocarbon (Ah)
receptor agonist, independently can cause disruption of endothelial barrier
function. Furthermore, cellular enrichment with linoleic acid can amplify
PCB-induced endothelial cell dysfunction. We hypothesize that the amplified
toxicity of linoleic acid and PCBs to endothelial cells could be mediated
in part by cytotoxic epoxide metabolites of linoleic acid called leukotoxins
(LTX) or their diol derivatives (LTXD). Exposure to LTXD resulted in a
dose-dependent increase in albumin transfer across endothelial cell monolayers,
whereas this disruption of endothelial barrier function was observed only
at a high concentration of LTX. Pretreatment with the cytosolic epoxide
hydrolase inhibitor 1-cyclohexyl-3-dodecyl urea partially protected against
the observed LTX-induced endothelial dysfunction. Endothelial cell activation
mediated by LTX and/or LTXD also enhanced nuclear translocation of the
transcription factor NF-kappa B and gene expression of the inflammatory
cytokine IL-6. Inhibiting cytosolic epoxide hydrolase decreased the LTX-mediated
induction of both NF-kappa B and the IL-6 gene, whereas the antioxidant
vitamin E did not block LTX-induced endothelial cell activation. Most importantly,
inhibition of cytosolic epoxide hydrolase blocked both linoleic acid-induced
cytotoxicity, as well as the additive toxicity of linoleic acid plus PCB
77 to endothelial cells. Interestingly, cellular uptake and accumulation
of linoleic acid was markedly enhanced in the presence of PCB 77. These
data suggest that cytotoxic epoxide metabolites of linoleic acid play a
critical role in linoleic acid-induced endothelial cell dysfunction. Furthermore,
the
severe toxicity of PCBs in the presence of linoleic acid may be due in
part to the generation of epoxide and diol metabolites. These findings
have implications in understanding interactive mechanisms of how dietary
fats can modulate dysfunction of the vascular endothelium mediated by certain
environmental contaminants. (Slim et al, 2001)
Study #41
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PCBs cause vascular endothelial cell dysfunction by modulating
intracellular glutathione, which subsequently leads to activation of stress-specific
kinases
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inhibition of glutathione synthesis by buthionine-sulphoximine
can increase the PCB -induced stress response and lead to cell death
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study used PCB 77
Exposure to environmental contaminants, such as polychlorinated
biphenyls (PCBs), may severely compromise normal function of vascular
endothelial cells (EC). We have previously shown that PCB 77 (3,3',4,4'-tetrachlorobiphenyl),
an arylhydrocarbon receptor (AhR) agonist, can induce oxidative stress
in cultured EC. We now show that PCB 77 can activate EC and induce a cellular
stress response that is reflected by the activation of c-Jun N-terminal/stress-activated
protein kinases (JNK/SAPK). Our data also suggest that this PCB 77-mediated
stress response can be modulated by the intracellular glutathione content.
EC treated with buthionine-sulphoximine (BSO), an inhibitor of glutathione
synthesis, further enhanced PCB-induced JNK/SAPK activity. This stress
response was sustained only in the presence of BSO plus PCB 77. Media supplementation
with the glutathione precursor N-acetyl-cysteine (NAC) reduced PCB 77-induced
JNK/SAPK. Intracellular glutathione also may be implicated in PCB-induced
EC apoptosis. Individual treatment with PCB, BSO, or linoleic acid induced
activation of caspase 3. Compared to PCB 77 alone, annexin V activity was
further amplified during combined treatment with BSO and PCB 77. DNA fragmentation
was mostly observed when cells were treated with both BSO and PCB 77. The
caspase 3-specific inhibitor DEVD-CHO protected cells against PCB 77/BSO-mediated
apoptosis and inhibited the caspase activity without affecting JNK/SAPK
activation or cellular glutathione levels. These results suggest that AhR
ligands, such as PCB 77, cause vascular EC dysfunction by modulating
intracellular glutathione, which subsequently leads to activation of stress-specific
kinases. Furthermore, inhibition of glutathione synthesis by BSO
can further potentiate the PCB 77-induced stress response and ultimately
lead to apoptotic cell death. (Slim et al, 2000)
Study #42
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serum concentrations of triglycerides and total cholesterol
were significantly associated with the blood PCB level
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study involved unknown mixture of PCBs
A cross-sectional study on the association between the results
of blood test and the blood concentration of PCB was conducted on the chronic
Yusho patients. The subjects were 265 Yusho patients (134 men and 131 women)
who received the annual nationwide health examination for Yusho in 1993.
The results of the blood test and questionnaire survey at the annual health
examination were used for the analyses using ANCOVA. Serum levels of triglycerides,
total cholesterol, GOT, GPT, gamma-GTP, total bilirubin, and conjugated
bilirubin were associated with the blood concentration of PCB adjusting
for sex, age, drinking habit, smoking habit and body mass index (BMI).
Because the distribution of the serum levels was strongly skewed to the
right except that of serum concentration of total cholesterol, they were
log transformed to approximate to the Normal distribution. The association
between age and the blood concentration of PCB was significant (P <
0.001), although the associations of sex, drinking habit, smoking habit
and BMI to the blood concentration of PCB were not significant. With the
adjustment for sex, age, drinking habit, smoking habit and BMI, the serum
concentrations of triglycerides and total cholesterol were significantly
associated with the blood PCB level expressed by loge (blood concentration
of PCB in ppb-1) (P = 0.02 and P < 0.001, respectively). The associations
of serum levels of GOT, GPT, gamma-GTP, total bilirubin and conjugated
bilirubin to the PCB level were not significant. The results of this study
suggests the need of careful observation on the serum lipids of Yusho patients,
especially those with high concentration of blood PCB, because the serum
concentrations of total cholesterol and triglycerides are prominent risk
factors of heart diseases. (Tokunaga et al, 1999)
Study #43
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PCBs increased 0.13 ppb (p = 0.001) per 10 mg/dl serum cholesterol.
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positive association between fish consumption and PCB concentrations
among women in the Northeast and Midwest
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the most important predictors of PCBs were age, serum cholesterol,
and residence in the Midwest or Northeast
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study involved unknown mixture of PCBs
We evaluated predictors of plasma concentrations of dichlorodiphenyldichloroethylene
(DDE), a metabolite of dichlorodiphenyltrichloroethane (DDT), and polychlorinated
biphenyls (PCBs) in a group of 240 women, controls from a breast cancer
case-control study nested in the Nurses' Health Study. We considered personal
attributes such as age, serum cholesterol, region of residence, adiposity,
lactation, and dietary intake. DDE levels increased 0.17 ppb/year of age
(p = 0.0003), and PCBs increased 0.08 ppb (p = 0.0001). DDE and PCBs
increased 0.20 (p = 0.02) and 0.13 ppb (p = 0.001), respectively, per 10
mg/dl serum cholesterol. Women living in the western United States
had higher levels of DDE (mean = 11.0 ppb; p = 0.003), and women in the
Northeast and Midwest had higher levels of PCBs (mean = 5.6 ppb; p = 0.0002)
as compared to women from other parts of the country (mean DDE = 6.3; mean
PCBs = 4. 5 ppb). Levels of DDE could not be predicted from consumption
of meat, fish, poultry, dairy products, vegetables, fruits, and grains.
There was a positive association between fish consumption and PCB concentrations
among women in the Northeast and Midwest. Using data from the cases
in the nested case-control study to assess the predictive ability of the
models, we confirmed that the most reliable predictors of DDE were age
and serum cholesterol, and the most important predictors of PCBs were
age, serum cholesterol, and residence in the Midwest or Northeast.
The null results for the majority of the food variables suggest that specific
dietary factors, other than fish, are not currently a substantial contributor
to human exposure to DDE and PCBs. (Laden et al, 1999)
Study #44
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For PCBs, the most likely biomarkers of effect included some
form of alteration in lipid metabolism (serum triglyceride/cholesterol
levels)
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study involved unknown mixture of PCBs
One of the major goals of the Great Lakes Action Plan is
to actively accumulate and assess toxicological information on persistent
toxic substances found in the Great Lakes basin. As part of Health Canada's
commitment to this plan, a review of biomarkers for the environmental contaminants
polychlorinated biphenyls (PCBs) and polychlorinated dibenzodioxins/dibenzofurans
(PCDDs/PCDFs) was conducted. In general, while food consumption was identified
as the major source of human exposure to both contaminant groups, certain
commodities, such as fish, milk and dairy products, and meat, were found
to predominate. Due to the ubiquitous nature of these environmental contaminants
and their propensity to bioaccumulate, all humans will have detectable
body burdens, which in certain cases can be positively associated with
the consumption of particular foods (i.e., PCBs and freshwater fish from
the Great Lakes). When dealing with environmental exposure only, relating
specific effect biomarkers to contaminant exposure or tissue levels was
difficult, due in part to the complex nature of the exposure and the nonspecific
nature of the effect. For PCBs, the most likely biomarkers of
effect included some form of alteration in lipid metabolism (serum triglyceride/cholesterol
levels) and elevation of hepatic-related enzymes, aspartate aminotransferase
(AST) and gamma-glutamyltransferase (GGT). Cross-species extrapolation
also indicates the potential for neurotoxicologic effects to occur in humans.
For PCDDs/PCDFs, dermatologic lesions (chloracne) and indications of hepatic
enzyme induction have been documented, but primarily due to occupational
or high acute accidental exposures. Recent evidence suggests that neonates
may represent a potential at-risk population due to relatively high exposure
to PCDDs/PCDFs, as with PCBs, during breast feeding as compared to standard
adult dietary intake. Future areas of potential benefit for biomarker development
include immunologic and endocrine effects, primarily based on biologic
plausibility from experimental animal research. (Feeley, 1995)
Study #45
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therapy achieved significant reductions in total cholesterol
levels
To investigate the therapeutic effects of rice bran fiber
(30 g/day) and cholestyramine (12 g/day) for Yusho, clinical signs and
symptoms, and laboratory examinations were studied before, during and after
14 day-treatment in four patients with Yusho. The increases of bowel movements
and abdominal distention were observed in two of these patients, although
no effect was seen in physical findings. In peripheral blood cells, red
blood cell counts decreased significantly, from 430 +/- 47 x 10(4)/mm3
(mean +/- SD) to 378 +/- 48 x 10(4)/mm3 (p < 0.01) after therapy. Hemoglobin
as well as hematocrit levels were also reduced significantly afer the therapy.
However, no significant effect of the treatment was observed in white blood
cell counts or platelet counts. In biochemical parameters, a significant
depression was observed in total cholesterol levels after the therapy
(from 262 +/- 31 mg/dl to 179 +/- 33 mg/dl; p < 0.005). A significant
elevations was observed in serum levels of alanine aminotransferase and
sodium, while significant depressions were found in serum levels of cholinesterase,
total protein, albumin, gamma-globulin, and potassium. (Tsuji et al, 1993)
Study #46
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high blood pressure has a dose-response relationship with
serum PCB levels
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serum triglyceride and cholesterol levels were higher in
the group with elevated serum PCBs
In late 1983, we conducted a cross-sectional epidemiologic
study to evaluate persons at risk of exposure to three chemical waste sites
by comparing clinical disease end points and clinical chemistry parameters
with serum polychlorinated biphenyls (PCB) levels. A total of 106 individuals
participated in the study. The only statistically significant finding in
regard to self-reported, physician-diagnosed health problems was a dose-response
relationship between serum PCB levels and the occurrence of high blood
pressure; however, this association failed to achieve statistical significance
(p = 0.08) when we controlled for possible confounding effects of both
age and smoking. Serum triglyceride and cholesterol levels were also
higher in the group with elevated serum PCBs; additionally, there were
isolated statistically significant correlations of serum aspartate aminotransferase
(SGOT) with serum lipid fraction-adjusted PCB level (r = -0.21) and serum
albumin (r = -0.24) and total bilirubin (r = 0.30) with serum PCB level.
Although the ranges of serum levels reported herein from exposures to PCBs
in the general environment are lower than those that have been associated
with acute symptoms or illness in other studies, whether these levels
are associated with long-term health risks is not known. Associations
of such chronic, low-dose exposures with observable health effects as suggested
by this
study must be evaluated further before any final conclusions
can be drawn. (Stehr-Green et al, 1986)
Study #47
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certain PCBs cause a significant change in bilayer fluidity
in phospholipid bilayers in the presence and absence of cholesterol
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other PCBs do not have this effect
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study used PCBs 77 and 155
The objective of this study was to test the hypothesis that
porphyrin-inducing drugs act at least in part by disrupting membrane lipids.
The porphyrin-inducing steroids, 3 alpha-hydroxy-5 alpha-pregnane-11,20-dione
(alfaxalone) and 3 alpha-hydroxy-5 alpha-pregnan-20-one induce considerably
greater fluidity changes in spin-labelled phospholipid-cholesterol bilayers
than do the corresponding 3 beta-hydroxy steroids which are also less potent
as porphyrin inducers. The steroids did not cause any significant change
in spin-labelled vesicles lacking cholesterol. The porphyrin-inducing compound
3,5-diethoxycarbonyl-1,4-dihydro-2,4,6-trimethylpyridine and a series of
analogues caused fluidity changes in phospholipid bilayers in the presence
and absence of cholesterol. The porphyrin-inducing nonplanar 2,2',4,4'-6,6'-hexachlorobiphenyl
caused a significant change in bilayer fluidity in phospholipid bilayers
in the presence and absence of cholesterol. Since the planar 3,3',4,4'-tetrachlorobiphenyl,
allylisopropylacetamide (AIA), and griseofulvin are potent porphyrin-inducing
compounds, but do not fluidize a lipid bilayer, it was clear that the original
hypothesis required modification. No evidence could be obtained to support
the idea that a subset of porphyrin-inducing drugs exists which are membrane
fluidizers and whose common mechanism of action as porphyrin-inducers might
be revealed by a common pattern of porphyrin accumulation in chick embryo
liver cells. It is suggested that those porphyrin-inducing compounds with
membrane-fluidizing properties might fluidize the nuclear membrane, thus
facilitating the transfer of an induction specific RNA for delta-aminolevulinic
acid synthetase from the nucleus to the cytoplasm. (Marks et al, 1982)
Study #48
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PCB levels were positively associated with gamma-glutamyl
transpeptidase level, serum cholesterol level, and measured blood pressure
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study involved unknown mixture of PCBs
The geometric mean serum level of polychlorinated biphenyls
(PCBs) of 458 persons in a communitywide study was 17.2 microgram/L, with
80% to 90% having levels within the range found in other community groups.
As a dependent variable, PCB levels were found to be positively related
to age, even when controlled for all other variables associated with PCB
level: sex, local fish consumption, obesity, serum cholesterol level, and
alcohol consumption. No major point source of PCB contamination was found,
and fish taken in the drainage of a major population center had mean PCB
levels below the current enforceable Food and Drug Administration tolerance
of 5 mg/kg. As an independent variable, serum PCB levels were positively
associated with gamma-glutamyl transpeptidase level, serum cholesterol
level, and measured blood pressure. The PCB-blood pressure association,
which was independent of age, sex, body mass index, and social class, must
be confirmed in other exposed populations. (Kreiss et al, 1981)
Study #49
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PCBs are associated with various serum lipids
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six groups of investigators have found associations between
PCB or chlorinated pesticide levels and blood pressure
Mean serum levels of polychlorinated biphenyls (PCBs) in
U.S. population groups without occupational exposure to PCBs are usually
between 4 and 8 ng/mL, with 95% of individuals having serum PCB measurements
of less than 20. Subpopulations consuming fish taken from contaminated
waters, such as Lake Michigan and near Triana, AL, have mean serum PCB
levels several times those found in other general population groups and
ranges that extend into concentrations found in industrial populations
involved in capacitor manufacture. Two studies of general populations and
several studies of industrial workers have demonstrated associations
of PCBs with various serum lipids and liver enzyme levels. Six groups
of investigators have found associations between PCB or chlorinated pesticide
levels and blood pressure. Research efforts are needed in clarifying
determinants of serum-adipose partition ratios; the utility of urinary
porphyrins as a measure of subclinical hepatic effects; human metabolites
and excretion of chlorinated hydrocarbons; and the relation, if any, between
blood pressure and organochlorine compounds when controlled for confounding
variables. Established cohorts, such as those in Triana, Lake Michigan
sportsfishers, the Michigan PBB cohort, residents of farms with PCB-lined
silos, and occupational groups, could all be studied further with attention
to these research questions. (Kreiss, 1985)
Study #50
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clear positive association between blood PCB and serum triglyceride
in patients 20 years after PCB exposure
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study involved unknown mixture of PCBs
Associations of blood PCB concentration with serum levels
of triglyceride, gamma-GTP, total-, and conjugated-bilirubin were investigated
in "Yusho" patients twenty years after outbreak, using the information
obtained from the medical examinations in 1988 and 1989. Study subjects
were 259 patients in 1988, and 268 patients in 1989, including 190 patients
who consecutively received both examinations. Blood PCB concentrations
(mean +/- SE) were 4.78 +/- 0.22 ppb in 1988, and 4.47 +/- 0.17 ppb in
1989. The results of blood-chemical analysis were compared among four categorized
concentrations of blood PCB, using the analysis of variance. Significant
difference was observed for triglyceride (1988: p < 0.025, 1989: p <
0.005), but not for gamma-GTP, total-, and conjugated-bilirubin. In 1988,
the mean triglyceride levels were 108, 137, 145, and 166 mg/dl at <
2.7, > or = 2.7, > or = 4.1, and > or = 6.1 ppb of blood of PCB, respectively.
Corresponding figures in 1989 were 106, 129, 154, and 156 mg/dl at <
2.7, > or = 2.7, > or = 4.0, and > or = 5.7 ppb of blood PCB, respectively.
Thus, clear positive association between blood PCB and serum triglyceride
was observed in the patients twenty years after exposure. (Hirota et al,
1993)
Study #51
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elevated triglycerides in humans
Polychlorinated biphenyls became worldwide environmental
contaminants during five decades of industrial use. They cause cancer in
some animals and are suspected of causing birth defects and elevated
triglycerides in humans. The risk to humans from low-level exposure
is unclear. No clinical symptoms have yet been identified in people who
eat contaminated fish, a major source of low-level exposure. (Thurston,
1988)
Study #52
-
no relationship found between PCBs and cholesterol, hematocrit
or blood pressure
-
study involved unknown mixture of PCBs
Since refuse workers may be exposed to polychlorinated-biphenyl
(PCB) (1336363) residues from the burning of automobiles, tires, transformers,
and wire insulation, a study was done among 37 refuse burners and 36 controls
in Charleston County, S.C. All Ss were male volunteers with about equal
numbers of black and white men in the two groups. The subjects' ages ranged
from 20 to over 60 years old. The study investigated whether refuse burners
experience PCB build up in their plasma as a result of exposure to burning
waste materials; whether demographic variables such as age, race, and duration
of exposure affect plasma PCB levels; whether clinical parameters of hematocrit,
cholesterol,
and blood pressure can be related to plasma PCB concentration; and whether
human scalp hair can serve as an indicator of PCB exposure. Paired plasma,
hair, and urine samples were obtained and analyzed. Hematocrit,
cholesterol
levels, and blood pressure readings were obtained. All analyses for
PCB were by gas/liquid chromatography, utilizing an electron capture detector.
By statistical analysis, all hair and urine samples were negative for PCB.
Detectable plasma PCB levels were found in 81 percent of the refuse burners
and in only 11 percent of the controls. It was concluded that refuse burners
showed significantly higher PCB levels in their plasma and are potentially
a population at risk. Demographic factors such as race, weight, and
years employed showed no relation to plasma PCB levels, a possible exception
being an age interaction with plasma PCB levels. The clinical parameters
investigated showed no relation to plasma PCB levels. Hair was shown
to have no utility as a PCB exposure index. (Bumgarner et al, 1973)
Study #53
-
no significant correlation found between PCB levels and cholesterol
or high-density lipoprotein
-
PCBs had a significant effect on the SGOT liver enzyme (serum-glutamic-oxaloacetic-transminase)
-
study involved unknown mixture of PCBs
Study of 120 male workers in a railway locomotive and carriage
maintenance works, in which there had been exposure to transformer fluids
containing PCBs for nearly 40 years, to determine the prevalence of increased
PCB absorption and the presence of potentially related clinical and metabolic
abnormalities. Workers were categorised as "exposed", "nominally exposed"
and "non-exposed". Evidence of dermatotoxicity and elevated PCB levels
was found most frequently in the "exposed group", correlating well with
age and duration of employment; significant correlations were found between
plasma PCB and STG and SGOT levels; no significant correlations were
found between PCB levels and levels of cholesterol, high-density lipoprotein
cholesterol or levels studied on liver function tests other than SGOT (serum-glutamic-oxaloacetic-transaminase).
Further analysis relating frequency of reported direct contact with PCB
levels suggested a dermal route of exposure. (Chase et al, 1982)
Study #54
-
fat levels of PCBs correlate with urinary 17-hydroxycorticosteroid
excretion
-
serum PCB concentrations correlate with serum gamma-glutamyl-transpeptidase.
-
no differences in fasting serum triglycerides, total cholesterol,
low density lipoproteins, high density lipoproteins, or very low density
lipoproteins.
-
study involved unknown mixture of PCBs
Concentrations of polychlorinated biphenyls (PCB) were analyzed
in body tissues of exposed workers. Studies were made with 55 present and
past transformer repairmen exposed to PCB and 56 unexposed comparison workers.
Blood samples were examined for proteins, lipids, cholesterol, albumin,
bilirubin, and enzymes indicative of liver function. Serum concentrations
of triglycerides and lipoproteins were determined in subjects fasting overnight.
Urine samples were analyzed for steroids, porphyrins, half life of antipyrine
(60800), and excretion of administered 17-hydroxycorticosteroid over 24
hours. Serum and adipose tissues were obtained for PCB analysis by gas
chromatography with electron capture detection and by mass spectroscopy.
Adipose tissue lipid and serum PCB concentrations were 2.1 parts per million
(ppm) and 12.2 parts per billion (ppb), respectively, in currently exposed
workers. The corresponding values were 0.083 ppm and 5.9ppb in previously
exposed workers, and 0.6ppm and 4.6ppb in unexposed workers. Differences
in serum albumin and lactate-dehydrogenase were seen in exposed and comparison
subjects. After adjustment for confounding variables, no correlations were
observed between indices of liver function and either adipose or serum
PCB concentrations. There were no differences in fasting serum triglycerides,
total cholesterol, low density lipoproteins, high density lipoproteins,
or very low density lipoproteins. There was a correlation between
adipose PCB concentrations and urinary 17-hydroxycorticosteroid excretion
and with serum PCB concentrations and serum gamma-glutamyl-transpeptidase.
These associations were possibly due to microsomal enzyme induction. No
correlation was seen between adipose PCB concentrations and any serum lipid
component,
possibly because of partition phenomena. In the exposed workers, eight
quantifiable PCB congeners were found. The author believes these findings
will be useful in generating dose effect data. (Emmett et al, 1985)
Study #55
-
no correlation found between blood PCB and triglycerides,
total cholesterol, or beta lipoprotein.
-
studies involved unknown mixtures of PCBs
Polychlorinated biphenyls (PCB) in the blood of industrial
workers were investigated. A total of 105 workers involved in producing
silk or wool thread, 7 workers involved in marine paints, and 14 farmers
living near a capacitor factory were examined and compared to 23 Yusho
patients, patients characterized by bony degeneration thought to be caused
by cadmium (7440439) poisoning. Nineteen of 63 silk workers had a PCB concentration
greater than 50 parts per billion.
PCB was found in the oil used in the silk reeling machines;
one child with a high PCB concentration had been contaminated by its mother's
milk. Declines in PCB concentrations in blood were only found in children
of the occupationally exposed workers, perhaps as an outcome of growth.
The blood profile of the PCB in the different groups reflected the types
of PCB to which they had been exposed. Medical exams showed occasional
acneform, but no significant correlation was found between blood PCB
and the amounts of triglycerides, total cholesterol, or beta lipoprotein.
The paint workers had a higher PCB concentration than normal comparisons,
but there was a significant decrease in PCB concentration over the 6 years
of the study. The farmers were suspected to have been contaminated by using
the agricultural water near the capacitor factory. The authors conclude
that workers occupationally exposed to PCB do not have the same symptoms
as Yusho patients. (Takamatsu et al, 1984)
Study #56
-
no significant associations between lipid PCB levels and
clinical indicators of hepatotoxicity, hypertension, or pulmonary
impairment
-
study involved PCB commercial mixtures Aroclor 1254, 1242,
and 1016
A group of capacitor workers who had direct occupational
exposure to Aroclor-1254 (11097691), Aroclor-1242 (53469219), and Aroclor-1016
(12674112) during the period of time from 1946 through 1977 was placed
under medical surveillance in 1976 and has been continuously followed since
that time. In portions of the facilities where PCBs were being handled,
the mean air levels were 679 and 310 micrograms/cubic meter in late 1975
and early 1977, respectively. After the ban on polychlorinated biphenyls
(PCBs), the levels dropped to 60 micrograms/cubic meter in early 1978,
30 in mid 1980 and 16 in 1983. Only 5 to 10% of the facility population
had direct or peripheral exposure to bulk PCBs and the attendant air levels.
However, ambient air PCB levels are believed to have been above background
levels throughout the facility. This group presented some indications of
nonAhR
mediated microsomal enzyme induction during the period of direct exposure,
but no chloracne or increased cancer mortality. Multiple regression studies
revealed no significant associations between lipid PCB levels and clinical
indicators of hepatotoxicity, hypertension, or pulmonary impairment.
(Brown et al, 1991)
Study #57
-
serum triglyceride concentrations showed no consistent relation
to PCB concentrations
-
small study size and low PCB concentrations
-
study involved unknown mixture of PCBs
A cohort of 16 municipal workers engaged in cleaning oil
from old transformers was examined for possible health effects from exposure
to polychlorinated biphenyls (PCBs). In addition to the evaluation of routine
clinical parameters (history, physical examination, liver function tests,
serum triglycerides, serum PCB values), a new screening technique for the
presence of oncogene proteins in serum using monoclonal antibodies was
used to ascertain the potential carcinogenic risk from exposure in these
workers. Except for one individual, serum PCB concentrations were found
to be relatively low in this cohort, probably due to the observance
of appropriate protective precautions. The results of liver function test
were within normal limits and serum triglyceride concentrations showed
no consistent relation to PCB concentrations. Six individuals, all
of whom were smokers, showed abnormal banding patterns for fes oncogene
related proteins. The individual with the highest serum PCB concentration
also exhibited significantly raised levels of the H-ras oncogene related
P21 protein in his serum. These oncogene protein findings may be indicative
of an increased risk for the development of malignant disease in these
individuals. (Brandt-Rauf et al, 1988)
Study #58
-
blood pressure was not associated with blood PCB levels and
PCB patterns
-
study involved unknown mixture of PCBs
Correlations of blood polychlorinated biphenyl (PCB) levels
or PCB patterns and blood pressures were studied in 59 patients with yusho
(PCB poisoning) above 40 years old. In spite of the passage of 13 years
from the onset, 52.5% of these patients still have PCB levels higher than
the range found in the general population. The frequency of hypertension
in the patients was 16.9%, a value similar to that expected on the basis
of the rate for a population of the same age and sex compositions. As an
independent variable, the blood pressure of patients was not associated
with blood PCB levels and PCB patterns. No PCB blood pressure association
was confirmed in 20 patients with PCB levels persistently higher than 5
ppb for 9 years. On the other hand, age, obesity and habitual alcohol intake,
known influencing factors for hypertension, tended to be positively associated
with elevated blood pressure in these yusho patients. (Akagi et al, 1985)
Study #59
-
study was flawed by assuming cardiovascular deaths were unassociated
with PCB exposure
-
study involved unknown mixture of PCBs
To address earlier reports of excess cancer mortality associated
with employment at a large transformer manufacturing plant, each plant
operation was rated for seven exposures: Pyranol (a mixture of polychlorinated
biphenyls and trichlorobenzene), trichloroethylene, benzene, mixed
solvents, asbestos, synthetic resins, and machining fluids. Site-specific
cancer deaths among active or retired employees were cases; controls
were selected from deaths (primarily cardiovascular deaths) presumed to
be unassociated with any of the study exposures. Using job records,
we then computed person-years of exposure for each subject. All subjects
were white males. The only unequivocal association was that of resin systems
with lung cancer (odds ratio = 2.2 at 16.6 years of exposure, P = 0.001,
in a multiple logistic regression including asbestos, age, year of death,
and year of hire). Certain other odds ratios appeared larger, but no other
association was so robust and remained as disti (incomplete abstract) (Greenland
et al, 1994)
Study #60
-
the cardiovascular system is a potential target organ for
PCB poisoning
-
the collective occupational experience with PCB fluids provides
no evidence for adverse PCB effects other than dermal effects.
Polychlorinated biphenyls (PCBs) continue to be of great
environmental and occupational health interest. This review summarises
the major clinical findings reported in individuals incurring the greatest
PCB exposure - those persons working in the manufacturing or repair of
electrical capacitors or transformers. The potential target organs addressed
in the studies reviewed include the liver, lungs, skin, cardiovascular
system, nervous system, certain endocrine systems, the blood/immune
system, and the gastrointestinal and urinary tracts. After careful analysis,
the weight of evidence suggests that the only adverse health effects attributable
to high, occupational PCB exposures are dermal. This review confirms and
extends the observations of others, i.e., that the collective occupational
experience with PCB fluids provides no evidence for adverse PCB effects
on any other organ systems. (JAMES et al, 1993)
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