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The Monkey Studies
| The 5 studies listed below involved PCB exposed monkeys
and showed significant changes in cholesterol, triglycerides, lipoproteins,
enzymes and other blood factors linked with cardiovascular disease.
For more information, see Heart
Table of Contents. |
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Study #1
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significant positive correlation between PCBs and plasma
triglycerides
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significant negative correlations between PCBs and plasma
total cholesterol, HDL-chol, VLDL plus LDL-chol, and total carnitine (which
is involved in fatty acid metabolism)
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causal relationship between plasma lipid changes and PCB
intake
Sixty-seven female Rhesus-monkeys were randomly assigned
to treatment groups receiving 5, 20, 40, or 80 micrograms/kilogram (microg/kg)
of Aroclor-1254 (27323188) orally, daily for 152 weeks in an effort to
study the effects of long term polychlorinated biphenyl (PCB) exposure
on plasma lipid and carnitine concentrations. The concentration of PCBs
in the blood was highly positively correlated (r = 0.92, P < 0.001)
with the dose level administered, ranging from 12 parts per million (ppm)
in the 5microg/kg group to 212ppm in the 80microg/kg group. The overall
effect of increasing the dose of PCB was to increase plasma triglycerides,
and reduce total cholesterol, high density lipoprotein cholesterol (HDL-chol),
very low density lipoproteins (VLDL) plus low density lipoprotein cholesterol
(LDL-chol), and total carnitine (which is involved in fatty acid metabolism).
The suppression of HDL-chol and carnitine reached significance only at
the 80 microg/kg dose level, while the suppression of total cholesterol
became significant at the 40 microg/kg dose level. A significant positive
correlation was found between PCB concentrations and plasma triglycerides,
and significant negative correlations were noted between PCB concentrations
and plasma total cholesterol, HDL-chol, VLDL plus LDL-chol, and total carnitine.
No significant correlation was found between HDL-chol and triglycerides
nor between carnitine and triglycerides. All of the lipid/lipoprotein changes
were significantly (P | 0.05) correlated with blood PCB concentration.
These data, obtained after 152 weeks of continuous daily exposure of a
primate model to PCB support a causal relationship between plasma lipid
changes and PCB intake. Previously, causality has been refuted on the
premise that the commonly obs (incomplete abstract) (Bell et al, 1994)
Study #2
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PCBs significantly decreased serum cholesterol and total
bilirubin concentrations
Hematological, biochemical, and hormonal changes resulting
from ingestion of aroclor-1254 (11097691) (aroclor) during the prebreeding
phase were studied in female rhesus-monkeys (Macaca-mulatta). The study
was part of a 6.5 year investigation of the effects of prenatal and lactational
polychlorinated biphenyl (PCB) exposure in rhesus-monkeys. Eighty menstruating
female monkeys, average age 11.1 years, ingested capsules containing 0,
5, 20, 40, or 80 micrograms per kilogram aroclor daily until steady state
PCB concentrations in their adipose tissue were obtained. Blood samples
were collected at monthly or bimonthly intervals to determine standard
hematologic and serum biochemical parameters, serum hydrocortisone concentrations,
and immunoglobulin-A (IgA), immunoglobulin-G (IgG), and immunoglobulin-M
(IgM) antibody concentrations in response to sheep red blood cell immunization.
Differential serum protein analyses and thyroid evaluations were performed
at these times. Serum estrogen and progesterone concentrations were determined
during one menstrual cycle. Skin biopsies were obtained from the scapular
area 1 month before and 10 and 20 months after the start of dosing to examine
the effects of aroclor on sebaceous gland area. Aroclor significantly
decreased erythrocyte and reticulocyte counts, hematocrits, mean platelet
volumes, serum cholesterol and total bilirubin concentrations, and
IgG, IgA, and IgM antibody responses to sheep red blood cells. The T-cytotoxic
and T-suppressor ratios were significantly increased. Among the serum protein
fractions, aroclor induced significant increases in the alpha1 and alpha2
globulin concentrations. No significant effects on serum estrogen or progesterone
concentrations during menstrual cycling were detected. Aroclor did not
significantly affect any of the variables associated with thyroid function.
Aroclor significantly decreased the number of sebaceous gland lobules per
histological length after 20 months of dosing. The authors conclude that
aroclor produces changes in a number of hematologic, serum chemistry, and
immune function variables in rhesus-monkeys at doses lower than previously
reported for nonhuman primates. (Arnold et al, 1993)
Study #3
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serum triglyceride, cholesterol, and total lipids decreased
progressively
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the total lipids decrease was statistically significant
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the albumin/globulin ratio shifted and serum glutamic-pyruvic-transaminase
activity increased
The effects of low concentrations of polychlorinated biphenyls
(PCB) on reproduction were studied in monkeys. Menstrual cycles, sperm
counts, and morphological spermatozoa features of adult Rhesus-monkeys
were evaluated for 6 months. Monkeys received 2.5 or 5.0 parts per million
(ppm) Aroclor-1248 (12672296) in the diet. After 7 months, females were
mated with control males and males were mated with control females during
a 5 day period. Animals were observed daily and were weighed monthly. Serum
chemistry was determined monthly. At intervals, an inguinal subcutaneous
fat biopsy was taken from selected animals and evaluated for PCB. Experimental
groups lost an average of 15.1 percent of their initial weight in 6 months
with constant diet intake. Animals ingested about 90 and 180 milligrams
(mg) PCB on the 2.5 and 5.0ppm diets, respectively. Within 2 months of
the experiment, animals began showing typical signs of PCB intoxication.
Serum
triglyceride, cholesterol, and total lipids decreased progressively. The
total lipids decrease was statistically significant. The albumin/globulin
ratio shifted and serum glutamic-pyruvic-transaminase activity increased.
Fat biopsies in females showed PCB isomer accumulation in adipose tissue.
After 4 months, menstrual cycles were altered with duration of menses increasing
or being absent. The conception rate in 5ppm PCB animals was decreased
when compared to controls; six out of eight animals that conceived had
three abortions, one resorption, one stillborn, and one normal birth. All
females that received 2.5ppm PCB conceived but three had resorptions. Male
animals had no gross breeding capabilities altered. The authors conclude
that adult female monkeys have serious reproductive effects after PCB exposure.
(Barsotti et al, 1976)
Study #4
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PCBs caused hypoalbuminemia and increased alkaline phosphatase,
serum glutamic oxaloacetic transaminase, serum glutamic pyruvic transaminase,
lactic dehydrogenase, cholesterol, triglycerides, total bilirubin and direct
bilirubin values
Aroclor 1254 and Aroclor 1248, at doses of 11.7 and 4.7 mg/kg
body weight (equivalent to 5 and 2 mg/kg/day), were given 3 days per week
to groups of cynomolgus monkeys, and caused weight loss, fingernail loss,
facial edema, epiphora, and death. Blood and adipose tissue PCB concentrations
rose with the length of treatment. Tissue concentrations in blood, adipose
tissue, liver and kidneys were highest in monkeys treated with Aroclor
1254, reflecting dose differences. There was considerable variation, both
within and between groups, in hematologic responses to PCB treatment. Aroclor
1254-treated monkeys had depressed and weakly responsive erythropoiesis.
Aroclor 1248-treated Monkeys had active but ineffective or depressed erythropoiesis
with severe macrocytic or moderate normocytic anemia. Biochemical determination
of blood serum constituents revealed treatment and time-related trends
towards hypoalbuminemia and increased alkaline phosphatase, serum glutamic
oxaloacetic transaminase, serum glutamic pyruvic transaminase, lactic dehydrogenase,
cholesterol, triglycerides, total bilirubin and direct bilirubin values.
Pathologic lesions common in both Aroclor groups were dilatation of meibomian
glands duct; mucinous hyperplasia of the gastric mucosa; atrophy and loss
of germinal centers in the splenic and other lymphoid follicles; enlargement,
fatty degeneration, and necrosis of hepatocytes; bile duct and gall bladder
epithelial cell hypertrophy and hyperplasia; and thyroid aberrations in
follicular cell size and number of intracytoplasmic lysosomes. Lesions
seen exclusively in an Aroclor 1254-treated monkey were widespread mucinous
metaplasia and hyperplasia of the fundic mucosa. The results suggest that
in general, cynomolgus monkeys may be more refractory or less susceptible
to PCB toxicity than rhesus monkeys and, that Aroclor 1248 may be more
toxic than Aroclor 1254. (Tryphonas et al, 1984)
Study #5
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increased triglycerides were associated with dioxin and PCBs
Humans and animals are exposed daily to a complex mixture
of polyhalogenated aromatic hydrocarbons (PHAHs). Previous work has shown
that exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is associated
with a dose-dependent increase in the incidence and severity of endometriosis
in the rhesus monkey. Dioxin-like chemicals can also exert effects in combination
with TCDD via the aryl hydrocarbon receptor. This study demonstrates that
the serum levels of TCDD and specific dioxin-like PHAH congeners were increased
in TCDD-treated animals with endometriosis 13 years after the TCDD exposure.
Nine TCDD-exposed and 6 unexposed female rhesus monkeys were evaluated
for serum content of relevant compounds and for endometriosis by surgical
laparoscopy. Additional studies were done on 4 animals that died 7 to 11
years after exposure to TCDD and 4 lead-treated animals with no history
of PHAH treatment. For TCDD-exposed and unexposed animals, TCDD exposure
correlated with an increased serum TCDD concentration. Furthermore, TCDD
exposure and an elevated serum TCDD concentration were associated with
increased serum levels of triglycerides, 1,2,3,6,7,8-hexachlorodibenzofuran,
3,3',4,4'-tetrachlorobiphenyl (TCB) and 3,3'4,4',5-pentachlorobiphenyl
(PnCB). Importantly, the animals with elevated serum levels of 3,3',4,4'-TCB,
3,3',4,4',5-PnCB and an increased total serum TEQ had a high prevalence
of endometriosis, and the severity of disease correlated with the serum
concentration of 3,3,',4,4'-TCB. Increased serum concentrations of coplanar
PCBs were also present in lead-treated animals. Implications of these findings
for human health and the prevalence of endometriosis in humans will be
discussed. (Rier et al, 2001).
References
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