Monkey Studies - PCB effects on Thyroid Function

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Monkey Studies --- PCB effects on Thyroid Function

Summary of Study Results

(Each of the bullets below represent findings in the studies. Some studies had multiple findings.)

reduced thyroxine (T4) levels (2 studies)

reduced free thyroxine (FT4) levels (2 studies)

reduced triiodothyronine (T3) levels (2 studies)

effects appeared as soon as 2 weeks after adults were dosed (2 studies)

increased thyroid follicular cell hyperplasia

uptake of T3-resin significantly elevated

significantly affects thyroid gland morphology and hormone metabolism

enlarged thyroid gland

numerous other effects

Aroclor 1254 did not significantly affect any of the variables associated with thyroid function.

increased number of lysosomes in thyroid follicular epithelial cells

Monkey Thyroid Studies

The Monkey Studies

Study #1

reduced thyroxine (T4) levels
reduced free thyroxine (FT4) levels
reduced triiodothyronine (T3) levels
effects appeared as soon as 2 weeks after adults are dosed
study used PCB 77

Marmoset monkeys were treated with oral doses of 0.1, 1 or 3 mg 3,4,3',4'-tetrachlorobiphenyl (TCB) per kg body weight 2 times a week for 18-23 weeks. Histological examination of the thyroid gland revealed a dose-dependent follicular cell hyperplasia. The morphological changes were associated with various disturbances of thyroid function. The average serum thyroxine (T4) levels during the treatment period were reduced by more than 99% in monkeys receiving 3 mg TCB/kg, by 81% in marmosets on a dose of 1 mg TCB/kg, and by 35% with 0.1 mg TCB/kg. The reduction in serum T4 levels was established from the earliest time point (2 weeks) throughout the whole dosing period (18-23 weeks). The reduction in serum T4 levels was reflected in decreased free thyroxine (FT4) index in the 1 and 3 mg TCB/kg dose groups. Serum triiodothyronine (T3) levels were lowered in the 3 mg/kg dose group already after 2 weeks. Evidence for decreased binding to carrier proteins is suggested by increased T3 resin uptake in the highe (incomplete abstract) (Van den Berg et al, 1988)

Study #2

increased thyroid follicular cell hyperplasia
reduced thyroxine (T4) levels
reduced free thyroxine (FT4) levels
reduced T3 levels
uptake of T3-resin significantly elevated
significantly affects thyroid gland morphology and hormone metabolism
effects appeared as soon as 2 weeks after adults are dosed
study used PCB 77

The effect of 3,4,3',4'-tetrachlorobiphenyl (TCB) on thyroid function and histomorphology was studied in monkeys. Adult female marmoset-monkeys were given 0, 0.1, 1, or 3mg/kg TCB orally biweekly for up to 23 weeks. Blood samples were obtained at selected times and assayed for thyroxine (T4), triiodothyronine (T3), T3-resin, and thyrotropin (TSH). The free thyroxine (FT4) index was determined. Monkeys given 3mg/kg TCB were killed after 18 weeks and the rest after 23 weeks. The thyroids were removed and examined for histopathological changes. TCB induced a dose related increase in follicular cell hyperplasia. TCB reduced serum T4 concentrations in a dose dependent manner. Monkeys receiving 3mg/kg TCB had T4 concentrations reduced to 0.1 percent of the control value, those receiving 1mg/kg had T4 concentrations reduced to 19 percent of the control value, and those given 0.1mg/kg had T4 concentrations corresponding to 65 percent of the control value. These decreases occurred as soon as 2 weeks after dosing. The FT4 index was decreased to 3 and 20 percent of the control value in monkeys given 3 and 1mg/kg TCB, respectively, by 2 weeks. Serum T3 concentrations were reduced to 41 percent of the control value in the 3mg/kg group. T3-resin uptake was significantly elevated 2 weeks after the start of dosing. The authors conclude that TCB significantly affects thyroid gland morphology and hormone metabolism in marmoset-monkeys. (Van de Berg et al, 1988)

Study #3

enlarged thyroid gland
numerous other effects
study used PCB 77

Chronic toxicity of 3,4,3',4'-tetrachlorobiphenyl (TCB) in cotton-top-marmoset-monkeys (Callithrix-jacchus) was studied. Young adult female monkeys were given orally 0, 0.1, 1, or 3mg/kg TCB in corn-oil twice a week for up to 23 weeks. Monkeys that received 3mg/kg of TCB lost 34 percent of body weight after about 18 weeks and were in poor health. The 1mg/kg group initially lost 21 percent of body weight, and weight loss stabilized after 10 weeks. Dose related clinical signs included skin lesions, alopecia, abnormal nail growth, and nodular enlargement in the mammillary area. No signs of toxicity were observed in animals fed 0.1mg/kg of TCB. Thyroid, salivary glands, and mesenteric lymph nodes were enlarged in all high dose animals at 18 weeks. The thymus was severely atrophic. No significant differences were seen for liver, kidney, heart, and lung in any of the treated animals. The high dose group had higher liver and heart weights. The most prominent histologic changes were seen in the eyelid, skin, and the mucosa of duodenum and stomach in the 1 and 3mg/kg groups. Numerous other histopathologic changes were observed in a variety of tissues. The lesions were most severe in the high treatment group. Hematocrit levels decreased in all groups and were lowest in the high dose monkeys. Red blood cell counts in the high dose group were significantly lower after 12 and 18 weeks of exposure. A significant increase in leukocyte count was seen in all groups 2 weeks after TCB exposure began. The cholesterol level increased by about 50 percent and triglyceride concentration was consistently higher in the high dose group. The authors conclude that the marmoset-monkey may be a valuable model for studies of polychlorinated biphenyl toxicity in humans. (Van den Berg et al, 1988)

Study #4

Aroclor did not significantly affect any of the variables associated with thyroid function.
study used PCB commercial mixture Aroclor 1254

Hematological, biochemical, and hormonal changes resulting from ingestion of PCB aroclor-1254 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 #5

increased number of lysosomes in thyroid follicular epithelial cells
study used PCB commercial mixture Aroclor 1254

Aroclor 1254, at a dose level of 280 micrograms/kg body weight equivalent to 200 micrograms/kg/day, was given 5 days per week to rhesus monkeys over a 27 to 28 month period. Terminal clinical signs of varying severity included fingernail detachment, exuberant nail beds, weight loss, stomatitis and normocytic anemia. At necropsy the bone marrow was hypocellular with increased M:E ratio and cytoplasmic vacuoles in erythroid precursor cells. Histopathologic lesions included dilatation of the tarsal gland ducts, atrophy or absence of splenic and lymph node germinal centers, bone marrow depletion, gingival erosion and ulceration, moderate mucinous hypertrophic gastropathy with cystic dilatation of occasional gastric glands, hepatocellular enlargement and necrosis, hypertrophy of biliary duct epithelium, hyperplasia of biliary ducts, hypertrophy of the gall bladder epithelium, and an equivocal increase in the number of lysosomes in thyroid follicular epithelial cells. PCB tissue concentrations were lowest (incomplete abstract) (Tryphonas et al, 1986)

References