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diabetes research, diabetes studies, diabetes education, diabetes facts, diabetes information, diabetes info, diabetes articles, glucose, blood glucose levels, glucose levels, blood glucose, glucose metabolism, glucose intolerance, glucose tolerance
diabetes research, diabetes studies, diabetes education, diabetes facts, diabetes information, diabetes info, diabetes articles, glucose, blood glucose levels, glucose levels, blood glucose, glucose metabolism, glucose intolerance, glucose tolerance

The Diabetes Studies --- 1 to 33
linking Diabetes with PCBs and Dioxins

diabetes research, diabetes studies, diabetes education, diabetes facts, diabetes information, diabetes info, diabetes articles, glucose, blood glucose levels, glucose levels, blood glucose, glucose metabolism, glucose intolerance, glucose tolerance

This is not a complete list of all diabetes research on glucose metabolism and exposure to PCBs and Dioxin.  For more studies, visit the TOXNET database operated by the National Library of Medicine (the source of these abstracts).   Further diabetes information is presented in other pages of this website (see Diabetes Table of Contents)

diabetes research, diabetes studies, diabetes education, diabetes facts, diabetes information, diabetes info, diabetes articles, glucose, blood glucose levels, glucose levels, blood glucose, glucose metabolism, glucose intolerance, glucose tolerance
Study #1                                   key findings are presented at the top of each study

  • the possibility exists that PCBs and diabetes are causality related
  • PCB pharmacokinetics could be altered among patients with diabetes
  • serum levels of PCBs in subjects with diabetes or their offspring may put them at increased risk of PCB-induced changes in thyroid metabolism or neurodevelopment
Polychlorinated biphenyls (PCBs) are persistent pollutants that are ubiquitous in the food chain; detectable amounts are in the blood of nearly everyone. Their effect on humans at background levels of exposure is an area of active investigation. Increased blood levels of dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin), a PCB-like compound, have recently been reported among subjects with diabetes, suggesting that PCB levels could be similarly elevated. To test this hypothesis, we examined a group of pregnant women whose serum PCB levels had been measured and whose diabetes status had been previously recorded. Using stored serum from a large birth cohort study, we conducted a cross-sectional study of 2,245 pregnant women, of whom 44 had diabetes (primarily type 1) and 2,201 were control subjects. The adjusted mean serum level of PCBs among the subjects with diabetes was 30% higher than in the control subjects (P= 0.0002), and the relationship of PCB level to adjusted odds of diabetes was linear. The possibility exists that PCBs and diabetes are causality related; alternatively, the pharmacokinetics of PCBs could be altered among patients with diabetes. At any event, if the association is replicated in other studies, increased serum levels of PCBs in subjects with diabetes or their offspring may put them at increased risk of PCB-induced changes in thyroid metabolism or neurodevelopment. (Longnecker et al, 2001) Full article: http://care.diabetesjournals.org/cgi/content/full/24/6/1099

Study #2

  • diabetic rats were more vulnerable to PCB induced metabolic changes
  • PCBs increased the rate of ascorbic acid excretion in diabetic rats 15-30 times
  • PCBs increased the rate of cytochrome P-450 and b(5) elevation
  • PCBs increased cholesterol in diabetic rats
The effects of dietary polychlorinated-biphenyls (1336363) (PCB) in streptozotocin (STZ) induced diabetic rats on lipid metabolism, ascorbic-acid metabolism and hepatic microsomal cytochrome-P-450 activity were investigated. Male Wistar-rats were injected intraperitoneally with 60mg/kg body weight of streptozotocin to induce diabetes. Two groups of rats, non diabetic (Group-C) and diabetic (Group-D) were fed for 9 days with a 20 percent casein based control diet, or with a diet containing 200mg/kg PCB (Groups-P and PD). After 7 days of feeding, urine was collected for ascorbic-acid excretion assay, and blood glucose, total cholesterol, and serum triglycerides were analyzed, as were the level of cytochrome-P-450 and cytochrome-b(5). Results indicated that body weight was decreased in STZ induced diabetic rats whether they were fed PCB or not. Urinary ascorbic-acid excretion in PCB fed rats in Group-D was 15 times higher than control rats in Group-C. PCB feeding created an increase of 30 times higher urinary ascorbic-acid excretion in Group-P rats than in Group-C. Urinary ascorbic-acid excretion in Group-PD was 60 fold greater than Group-C. Ascorbic-acid in liver and kidney was shown to be lower in Group-D than in Group-C as well as lower in Group-PD than in Group-P. Liver microsomal cytochrome-P-450 and cytochrome-b(5) were elevated in both diabetic and non diabetic rats on the PCB diet. Serum cholesterol was also increased in PCB fed Groups-P and PD. The authors conclude that PCB treatment increased the metabolic changes in lipids and ascorbic-acid in STZ induced rats. (Kawai-Kobayashi et al, 1988)

Study #3

  • diabetic rats were more vulnerable to PCB induced metabolic changes
  • acetoacetate and beta-hydroxybutyrate in blood were markedly reduced
  • decreased activity of pyruvate carboxylase, PEPck and glucose-6-phosphatase (G6Pase) in diabetic liver
  • study used PCB commercial mixture Aroclor 1254
Normal and alloxan-diabetic rats were fed ground Purina Laboratory Chow with or without 500 ppm of PCB Aroclor 1254 (AR) ad lib for 2 weeks. In both normal and diabetic rats, AR administration decreased food consumption, weight gain and blood glucose concentration, and increased liver weight, liver:body weight ratio, total liver lipid, liver protein and malic enzyme (ME) activity. In the normal rat, AR increased the concentrations of acetoacetate and beta-hydroxybutyrate in blood, but in the diabetic rat the concentrations were markedly reduced. AR administration decreased the activity of phosphoenolpyruvate carboxykinase (PEPck) in normal liver and the activities of pyruvate carboxylase (PC), PEPck and glucose-6-phosphatase (G6Pase) in diabetic liver. (Mehlman et al, 1975)

Study #4

  • PCBs cause massive liver accumulation of uroporphyrin, which is also seen in diabetes
  • PCBs induce cytochrome P450, particularly the 1A2 isozyme, which may be a factor in uroporphyrin accumulation
  • ascorbic acid (Vitamin C) may counteract the effect
The purpose of this project is to determine the mechanism by which 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and related planar polychlorinated aromatic hydrocarbons such as polychlorinated biphenyls (PCBs) cause massive liver accumulation of uroporphyrin (URO). This phenomenon is also seen in human Porphyria Cutanea Tarda (PCT). PCT is usually associated with alcohol consumption, use of the contraceptive pill, hemodialysis or diabetes. An additional goal of this project is to determine the relationships of the uroporphyrias caused by TCDD and other conditions. However most of the work has centered on that caused by TCDD and related compounds. Liver cells in tissue culture are used as models for the human and intact animal conditions. A focus was to find suitable culture models and to determine the mechanism of the process of URO accumulation. We have shown a key role in the uroporphyria of TCDD and PCB-induced cytochrome P450 particularly the 1A2 isozyme. We have shown that the role of the P450 is to catalyze the oxidation of uroporphyrinogen (UROgen). Recently, we demonstrated that ascorbic acid prevents URO accumulation by the chick hepatocytes and isolated microsomes. The site of action of the ascorbate was the first step of the UROgen oxidation and ascorbate was competitive with UROgen. The mechanism of the oxidation is not completely understood. Our results suggest that UROgen is a substrate of the P450 and that ascorbate somehow competes for the oxidizing moiety of the P450. More recently, we have used a rat strain (ODS) that requires ascorbate in its diet to test whether normal levels of ascorbate suppress uroporphyria and deficiency increases uroporphyria. Rats were treated with 3-methylcholanthrene (MC) and 5-aminolevulinate (ALA) and were maintained on 3 different dietary levels of ascorbate. We found that low levels of dietary ascorbate (50 and 200 ppm) resulted in a large accumulation of hepatic uroporphyrin in animals treated with MC plus ALA. At 800 ppm, hepatic uroporphyrin was quite low, similar to that in normal rats that synthesize their own ascorbate. The levels of dietary ascorbate did not affect the induction of P450 1A2 that is an essential participant in the uroporphyrin accumulation. These data suggest that ascorbate has an important role in regulating uroporphyrin in vivo, and validates results obtained in tissue culture and in vitro systems for studying the mechanism of the effect of ascorbate. Recent investigations determined whether iron loading of the ODS rat decreased liver ascorbate. The effect of iron loading was quite small. We also found that 11/13 of a group of PCT patients had plasma levels of ascorbate that were clearly in the deficient range. This was probably due to a poor diet. Smoking, an inducer of P4501A2, was quite common. CLINICAL RELEVANCE: The relationship of the TCDD/PCB caused uroporphyria to the more common human PCT is not yet known. Our results suggest that the potential role of P4501A2 in this disease needs to be investigated. Furthermore, our work suggests that ascorbic acid prevents this condition. In fact our data suggests that PCT is not more common because UROgen oxidation is prevented in humans by normal levels of ascorbate. This represents a new and specific role of ascorbate in human disease. (Sinclair, 1998)

Study #5

  • chemicals which alter endocrine function (such as PCBs) may alter glucose metabolism
  • Diabetes mellitus might arise as a result of occupational exposure or heighten the susceptibility to occupational diseases
Many environmental and occupational agents have been shown to cause detrimental effects on endocrine function and growing scientific evidence supports the hypothesis that such alterations may produce serious consequences for health. Although those chemicals mimicking (or contrasting) estrogenic or androgenic actions have raised great concern, the relevance of disruption of other hormonal pathways is not negligible. This paper reviews endocrine effects of chemicals and physical agents in man, in laboratory animals and in in vitro experiments. Effects on the hypothalamus, pituitary, pineal gland, thyroid, parathyroid and calcium metabolism, adrenal glands and glucose metabolism are discussed. Metals (lead, manganese, cadmium, organotin compounds), solvents (benzene, dioxane, styrene, tetrachloroethylene, toluene), organochlorine compounds (PCB, TCDD) and physical agents were shown to cause blood-level alterations and affect the circadian rhythm. Diabetes mellitus might arise as a result of occupational exposure or heighten the susceptibility to occupational diseases. Melatonin has been proposed as the link between environmental/occupational factors and the immunologic and neoplastic diseases, which in addition to disturbances of the circadian timing system, feature pineal hormone reduction. Thyroid gland diseases (goiter, autoimmune thyroiditis, carcinoma) are associated with exposure to many chemical or physical agents. Disruptions of calcium control secondary to metal exposures, as well as the effect of radiation on parathyroid, are addressed. Adrenal cortex and medulla function alterations by several chemical agents are considered. (Baccarelli, 1999)

Study #6

  • PCBs produce a release of insulin from RINm5F hormone producing cells
  • non-coplanar PCBs caused the effect, but coplanar PCBs did not
  • study used PCB commercial mixture Aroclor 1254, and PCBs 47, 153 and 77
Polychlorinated biphenyls (PCBs) possess a variety of biological effects, including alterations in growth, development and metabolism, that may be dependent on insulin. However, no reports on the action of PCBs on cells which produce and secrete insulin are available. The current study examined the ability of a commercial mixture of PCBs (Aroclor 1254) and three specific PCB congeners, to alter the release of insulin using the hormone producing cell line RINm5F. Exposure of cells to Aroclor 1254 (A-1254) produced a concentration-dependent increase in media insulin reaching a peak, when expressed as percent of control, at 30 min. In spite of continued exposure, media insulin relative to control declined and no treatment-related difference was observed at 48 hrs. Cellular levels of the hormone declined as much as 50% by that time. The insulin releasing action of A-1254 was mimicked by each of the non-coplanar congeners 2,2',4,4'-tetrachlorobiphenyl (TCB) and 2,2',4,4',5,5'-hexachlorobiphenyl (HCB) but the coplanar congener 3,3',4,4'-TCB showed no significant activity. These results indicate that PCBs are capable of producing a release of insulin from RINm5F cells, an effect that is unlikely to be associated with coplanar congeners that initiate their action by binding to the Ah-receptor. (Fischer et al, 1996)

Study #7

  • PCBs induce a release of insulin
  • insulin release is linked to PCB induced increase in intracellular free calcium
  • calcium and CaM kinase II may play a role in PCB-induced insulin release
  • insulin release by PCBs is independent of the activation of MAPKs
  • study used PCB commercial mixture Aroclor 1254 and PCBs 47 and 153
Polychlorinated biphenyls (PCBs) are environmental contaminants that induce release of insulin in rat insulinoma cells, RINm5F (Fischer et al., Life Sci. (1996) 59, 2041-2049). In the present study the mechanisms of this effect were investigated using noncytotoxic concentrations (10 microg/ml) of a PCB mixture, Aroclor-1254, and the pure PCB congeners 2,2',4,4'-tetrachlorobiphenyl and 2,2',4,4',5, 5'-hexachlorobiphenyl. Treatment of RINm5F cells with each of these agents resulted in a rapid increase in intracellular free calcium. The presence of extracellular calcium was required for PCB-induced insulin release because removal of calcium from the medium attenuated the effect. In addition, pretreatment of RINm5F cells with the calcium channel blocker verapamil also blocked PCB-induced insulin release. To determine whether PCB-related insulin release could be associated with the enzyme, calcium/calmodulin-dependent kinase II (CaM kinase II), RINm5F cells were pretreated with the CaM kinase II inhibitor KN-93. PCB-induced insulin release was completely blocked by KN-93. Under similar treatment conditions, PCBs also induced the activity of mitogen-activated protein kinases (MAPK) 1 and 2. However, inhibition of MAPK activation by a specific inhibitor, PD-98059 (10.0 microM) did not prevent insulin release induced by PCBs. The results of the present investigation suggest a role for calcium and CaM kinase II in PCB-induced insulin release. Furthermore, the results suggest that insulin release by PCBs is independent of the activation of MAPKs. (Fischer et al, 1999)

Study #8

  • insulin sensitivity was depressed increasingly with period of administration of PCBs
  • disturbed glucose and lipid metabolism
  • increases in total cholesterol, HDL-C, triglyceride, lipid peroxide and T3 in blood plasma
  • study used PCB commercial mixture Kanechor (KC) 400
Insulin sensitivity was assessed by euglycemic insulin clamp method in the rats given Kanechlor (KC)-400 for 1 to 12 weeks. As a result, insulin sensitivity was depressed increasingly with period of administration of KC-400. Increases in total cholesterol, HDL-C, triglyceride, lipid peroxide and T3 in blood plasma were also observed in the experimental rats. Voluntary daily activity of rats given KC-400, especially in a later half of night-time, had been depressed since approximately 9 weeks after start of the experiment. It was concluded that depression of insulin sensitivity might be related to not only disturbance of glucose and lipid metabolism, but reduced daily activity in conjunction with disturbed thyroid function. (Nishizumi et al, 1995)

Study #9

  • non-coplanar PCBs may affect insulin release
  • use of Ah-receptor binding and its effects to assess PCB toxicity may no longer be defensible because of effects of non-coplanar congeners
Research into the mechanism of toxicity of PCBs has focused on the Ah receptor. However, it is becoming increasingly clear that certain ortho-chlorine-substituted, non-coplanar PCB congeners having low affinity for the Ah receptor exhibit important biological activities. Actions of non-coplanar PCB congeners in a variety of biological systems have been discovered and the mechanisms for these effects are being elucidated. The objectives of this symposium are to examine the state of knowledge concerning the mechanisms of toxic action of non-coplanar PCBs and to identify similarities and differences using a variety of biological systems. Effects to be considered will include: neurotoxicity, estrogenicity, insulin release, neutrophil function, calcium regulation, and relevant signal transduction systems. Finally, the symposium addresses the need to consider non-coplanar congeners within the context of risk assessment. The use of Ah-receptor binding and its associated biological effects to assess the total toxicity of PCBs may no longer be defensible because of the actions produced by non-coplanar congeners. This symposium provides documentation for that conclusion and focuses attention on emerging mechanisms of PCB action that have received relatively little attention to date. The topics presented should be of interest to toxicologists interested in mechanisms of action, in PCB risk assessment, and in regulatory toxicology. (Fischer et al, 1998)

Study #10

  • PCBs induce or inhibit important enzymes affecting glucose and lipid metabolism
Administration of xenobiotics to rats results in hypercholesterolemia and in the induction of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase and malic enzyme. To investigate the mechanism of the induction of the enzymes by xenobiotics, the effects of xenobiotics on gene expressions for HMG-CoA reductase, malic enzyme, and cytochrome P-450 in rat liver and in cultured hepatocyte were investigated. The treatment of rats with polychlorinated biphenyls (PCB) as a xenobiotic induced mRNAs for HMG-CoA reductase and malic enzyme as well as CYP2B1/2 (cytochrome P-450b/e). Other xenobiotics, 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (DDT), and chloretone, also increased HMG-CoA reductase mRNA. In an investigation of diurnal rhythm of mRNA for HMG-CoA reductase, the induction by PCB was observed in a dark period. Induced expressions of HMG-CoA reductase gene and malic enzyme gene by PCB were observed in primary cultured rat hepatocytes and showed that the action of PCB on the geneexpression relating to lipid metabolism was directed on hepatocytes. The induction was observed only in hepatocytes cultured on Engelbreth-Holm-Swarm sarcoma basement membrane gel (EHS-gel), not on type I collagen, which is usually used for monolayer culture of hepatocytes. The induction of CYP2B1/2 gene expression also was observed only in the cells cultured on EHS-gel. The induction of HMG-CoA reductase and malic enzyme by PCB required dexamethasone. However, the addition of dexamethasone per se to medium containing insulin did not show an inductive effect on levels of mRNA for HMG-CoA reductase and malic enzyme. From the data of diurnal variation and hepatocyte culture experiment, HMG-CoA reductase and malic enzyme are considered to be induced by PCB through the so-called "permissive effect" of glucocorticoid. (Oda et al, 1999)

Study #11

  • dioxin reduces glucose transport, which is an important factor in the down regulation of lipoprotein lipase (LPL) activity (certain PCBs are dioxin-like)
  • depression of LPL activity in fat tissue is associated with dioxin-induced wasting syndrome and may have a role in the associated serum hyperlipidemia produced by dioxin
  • PCBs and dioxin both reduce LPL activity through binding to the Ah receptor
Lipoprotein lipase (LPL) is important in the process of triglyceride storage in adipose tissue. Depression of LPL activity in adipose tissue is associated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced wasting syndrome and may have a role in the associated serum hyperlipidemia produced by TCDD. The 3T3-L1 cell line was used as an in vitro model, independent of hormonal, nutritional, or other interfering factors associated with in vivo studies, in order to systematically examine the mechanism of action of TCDD. TCDD produced a statistically significant (P < 0.05) time- and dose-dependent decrease in LPL activity. Results of experiments with Ah-receptor blockers and structure activity studies with different polychlorinated biphenyl (PCB) and dioxin congeners were consistent with reduction of LPL activity being mediated by the Ah receptor. Culturing of 3T3-L1 cells without glucose or with cytochalasin B, a blocker of facilitative glucose transporters (GLUT), was effective in reducing LPL activity (P < 0.05). TCDD did not further reduce LPL activity in cytochalasin B pretreated 3T3-L1 cells or in 3T3-L1 cells cultured in glucose-free media. Dexamethasone pretreatment, which is known to increase GLUT expression in 3T3-L1 cells, prevented the reduction of LPL activity by TCDD. Protein tyrosine kinase activities, assayed using gamma-32P-ATP and RR-SRC, a src specific peptide substrate, were significantly increased (P < 0.05) over control levels by both TCDD and glucose deprivation. Furthermore, results of experiments treating 3T3-L1 cells with either insulin, EGF, 8-Br-cAMP, TPA, or genistein, alone or in combination with TCDD, were generally consistent with the hypothesis that lowered intracellular glucose and altered cellular kinase activities may be involved in reduction of LPL activities by TCDD. Further work is needed to confirm and better understand the role protein phosphorylation plays in TCDD-mediated alteration of glucose disposition and LPL activity. In summary, TCDD reduced LPL activity in 3T3-L1 cells as seen in vivo. Manipulation of glucose transport through a number of experimental approaches produced changes in 3T3-L1 LPL activity consistent with results of previous investigators showing glucose to be a positive regulator of LPL activity and consistent with our hypothesis that TCDD-mediated reduction of glucose transport is an important factor in the down regulation of LPL activity by TCDD. (Olson, 1998)

Study #12

  • PCBs increased in the blood serum with the loss of body fat during the first 12-18 months, then decreased
Biosphere 2 is a closed ecological space of 7-million cubic feet near Tucson, AZ, containing 7 biomes: rain forest, Savannah, ocean, marsh, desert, agricultural station, and habitat for humans and domestic animals. Sealed inside, 4 men and 4 women maintained themselves and the various systems for 2 years. All organic material, all water, and nearly all air was recycled, and virtually all food was grown inside. On the low calorie but nutrient-dense diet available, the men sustained 18% and the women 10% weight loss, mostly within the first 6 to 9 months. The nature of the diet duplicated rodent diets that had been shown to enhance health, lower disease incidence, and retard aging. Using blood specimens frozen at different points during and after the 2 years, determinations were made of a number of biochemical parameters judged to be pertinent based on past studies of rodents and monkeys on similar diets. These included blood lipids, glucose, insulin, glycosylated hemoglobin, renin, and others. The results clearly suggest that humans react to such a nutritional regime similarly to other vertebrates. In addition to these studies, and because this was a tightly closed, isolated environment, the levels of insecticides or pollutants or their derivatives were determined in the sera of 2 crew members. It was found that levels of the lipophilic toxicant DDE and the "total PCB" load increased with the loss of body fat during the first 12-18 months inside Biosphere 2, then decreased. (Walford et al, 1999)

Study #13

  • dioxin alters enzyme activity related to glucose metabolism (certain PCBs are dioxin-like)
The effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (1746016) (TCDD) on glucagon induction of phosphoenolpyruvate-carboxykinase (PEPCK) activity in primary rat hepatocytes (PRH) was reported. Incubation of PRH from male Sprague-Dawley-rats with 100 nanomoles TCDD for up to 90 hours did not significantly lower PEPCK activity compared to control values. Induction of PEPCK activity was not seen when PRH from rats given 125 micrograms/kilogram TCDD orally 4 days before PRH isolation were treated with dexamethasone prior to insulin withdrawal and treatment with glucagon. This hormonal regimen resulted in two fold inductions of PEPCK activity in PRH from rats treated with vehicle only and in PRH incubated with TCDD for 24 hours (hr) in-vitro. Ethoxyresorufin-O-deethylase (EROD) activity of PRH from TCDD treated rats was induced at time of culture and declined at a steady rate to 60% within 48hr of culture. Induction of EROD activity in PRH incubated with TCDD did not reach a maximum value within 48hr. Incubation of PRH with TCDD for 48hr resulted with significantly lower hormonal induction of PEPCK whether glucagon or cyclic-adenosine-monophosphate was used. Maximum EROD activity induction was observed after 48 to 72hr in-vitro incubation with TCDD. The author concludes that the observed reduction of PEPCK induction is a direct result of TCDD action on the liver cell, not involving nonhepatic mediating factors. (Stahl, 1995)

Study #14

  • the pancreas is a target of PCB toxicity
Hepatic morphological changes induced by polychlorinated biphenyls (PCBs) were studied in rats. Sherman-rats were administered Aroclor-1260 (11096825) or Aroclor-1254 (11097691) by oral gavage over a concentration range to determine the acute median lethal dose (LD50). Dead animals were necropsied. Sherman-rats were fed Aroclor-1260 or Aroclor-1254 at concentrations of 0, 20, 100, 500, or 1,000 parts per million (ppm) for 8 months. The animals were observed for mortality. The livers of dead and surviving animals were examined by light and electron microscopy. Exact LD50 rates for acute oral dosing could not be calculated. Estimated LD50 was around 4,000 to 10,000 milligrams per kilogram for both PCBs. Necropsies showed hemorrhaging into the lung, stomach, and pancreas. Ulcerative foci surrounded by a severe inflammatory reaction were observed in the duodenum and occasionally in the glandular part of the stomach. Feeding Aroclor-1260 for 8 months caused no deaths in male rats and a dose related increase in mortality in females. Five of 10 males and 8 of 10 females fed 1,000ppm Aroclor-1254 died. Two of 10 males and 1 of 10 females fed the 500ppm dose died. The lower doses did not cause mortality. Hypertrophy of liver cells, inclusions of the cytoplasm, lipid accumulation, adenofibrosis, increase in smooth endoplasmic reticulum, and atypical mitochondria were the most prominent morphological changes observed in the livers of treated rats. Lipid vacuoles were occasionally surrounded by concentric membranes. The morphologic changes were generally in animals treated with Aroclor-1254. The authors conclude that the toxicity of PCBs decreases as the extent of chlorination increases. The significance of the adenofibrosis will be investigated further to establish if it is an irreversible lesion and whether it is transplantable. (Kimbrough et al, 1972)

Study #15

  • increased activity of the beta-cells of the pancreas (the beta-cells make insulin)
  • marked dilatation of rough endoplasmic reticulum (RER) and vesiculation of RER in the beta-cells
  • hyperplastic Golgi complexes in the beta-cells
  • reduced number of secretory granules in the beta-cells
  • increased number of mitochondria and mitochondrial changes in the beta-cells
  • increased activity of the adrenal zona fasciculata
  • study used PCB commercial mixture Aroclor 1254
A morphological study of the beta-cell of the pancreas in rats chronically exposed to polychlorinated biphenyls is presented. In rats who received 200ppm Aroclor 1254 in their drinking water for 13 months, marked dilatation of rough endoplasmic reticulum (RER), vesiculation of RER, hyperplastic Golgi complexes, a reduced number of secretory granules, an increased number of mitochondria and mitochondrial changes were observed. Numerous acinar-beta and beta-acinar cells were also present. These structural features suggested an increased activity of the beta-cells in these animals. Since in previous studies an increase in the activity of the adrenal zona fasciculata of rats exposed to polychlorinated biphenyls was found, the present findings were considered a result of solicitation of beta-cells for carbohydrates' homeostasis. (Wassermann et al, 1975)

Study #16

  • PCBs impair enzyme regulation
  • PCBs exert impacts by influencing membrane fluidity
  • study used PCB commercial mixture Aroclor 1254
Regulation of cytochromes P-450 21-hydroxylase (P-450C21) and P-450 17 alpha-hydroxylase/C17,20-lyase (P-450(17) alpha,lyase) activities and impairment of this regulation by Aroclor 1254 was studied in guinea-pig adrenal microsomes. In a membrane depleted system, a decrease in the normally predominant, P-450C21 activity and an increase in P-450(17) alpha,lyase activities was observed. The same deviations were observed in intact microsomes with increase in the reaction temperature (0-40 degrees C). Breaks in Arrhenius plots for activities of P-450C21 and P-450(17) alpha,lyase correlate with transition temperatures reported for the microsomal membrane. These results point to: (1) preference of a gel state membrane for catalytic expression of P-450C21 suggesting a clustered organization of this P-450 species with reductase; (2) preference of a fluid membrane for lyase activity suggesting a random collision mechanism for reduction of P-450(17) alpha,lyase. Aroclor 1254 introduced to reaction mixtures containing intact microsomes elicited basically the same changes as caused by depletion of the microsomal membrane or by increase in the incubation temperature. Lack of effect of Aroclor 1254 on P-450C21 and P-450(17) alpha,lyase activities in the membrane depleted system demonstrates that its interference with monooxygenase activities is mediated by the microsomal membrane. The similarities between altered cytochrome P-450 mediated activities in the presence of Aroclor 1254 and the deviations observed in the membrane depleted system or upon increase in the incubation temperature may suggest that this chemical exerts its impacts by influencing membrane fluidity. (GOLDMAN et al, 1992)

Study #17

  • PCBs are selectively incorporated into the hepatopancreas in molluscs and into rat livers
The marine mollusc Aplysia californica was fed seaweed Rhodymenia palmata contaminated with polychlorinated biphenyls (PCBs) at a high (experimental) and low (control) level for a period of 18 days in flow-through systems which limited the animals to dietary uptake. The assimilation of PCBs, determined by subtraction of fecal output from food intake, was greater at the high dosage (94 | 29%) than at the low dosage (84 | 22%). Assimilation selectivity of the different cogeners favored those with lower chlorine content, and discriminated against those chlorinated in the para position one one of the rings. After assimilation, selectivity for incorporation into the hepatopancreas favored those congeners with higher chlorine contents over those with but 1 to 3 chlorines on the molecule. Similarities between incorporation into the liver of rats and into the hepatopancreas of Aplysia were found, suggesting that common mechanisms for bioaccumulation, and by extension, physiologic effects, may be present in such diverse species of the animal kingdom. (JAHAN-PARWAR et al, 1990)

Study #18

  • PCBs alter enzyme activity in rats
  • PCB-induced effects were significantly less pronounced in old than in young animals
  • while activity was induced in insuline- and triiodothyronine-containing medium, this increase was significantly greater with PCBs present.
The lipogenic enzymes fatty acid synthase (FAS; EC 2.3.1.85), citrate cleavage enzyme (CCE; EC 4.1.3.8), malic enzyme (ME; EC 1.1.1.40), glucose-6-phosphate dehydrogenase (G6PDH; EC 1.1.1.49) and 6-phosphogluconate dehydrogenase (PGDH; EC 1.1.1.44) were investigated in liver and in brown adipose tissue (BAT) of Wistar rats under various dietary conditions and in the presence of 15 to 250 ppm (approximately 0.045-0.75 mumol/kg chow) polychlorinated biphenyls (PCBs). In response to refeeding starved animals, enzyme activities in both tissues increased to above normal levels and thereafter exhibited pronounced oscillations of their activities. The extent of increase depended on the carbohydrate and fat content of the diet. The lipogenic enzymes could be grouped in two categories according to their sensitivity to dietary carbohydrate: FAS and CCE responded faster to smaller changes in dietary composition, while ME, G6PDH and PGDH required larger changes and more time to respond. Diet-induced alterations of enzyme activities were of the same order of magnitude in liver and BAT. They were age-dependent, being more pronounced in young animals. Independent of the type of dietary manipulations, activities changed in a coordinate fashion, i.e., the changes of the activities of all 5 enzymes occurred at similar ratios to each other with an identical time course. Feeding PCB-containing diets resulted in a considerable increase of the activities of the lipogenic enzymes in liver, which was significantly greater with ME, G6PDH and PGDH. The effect was dose-dependent but transient. In liver the response to PCB feeding was identical in male and female animals, whereas in BAT lipogenic activities increased in females, but decreased in males. Refeeding starved animals with a PCB-containing diet led to an additional stimulation of the normal refeeding-induced increase of the enzyme activities in liver and BAT. This PCB-induced increase was 2-fold for FAS and CCE, but up to 15-fold for the other enzymes. All PCB-induced effects were significantly less pronounced in old than in young animals. In primary hepatocytes activities increased in hormone-free medium in the presence of PCBs. While activity was induced in insuline- and triiodothyronine-containing medium, this increase was significantly greater with PCBs present. (Boll et al, 1994)

Study #19

  • PCBs alter enzyme activity in the hepatopancreas of crayfish
  • study used PCB commercial mixture Aroclor 1254
The inducibility of the freshwater crayfish (Astacus astacus) biotransformation enzymes with model inducers (Aroclor 1254, beta-Naphthoflavone, Phenobarbital) were investigated three days after intra cephalothoracic injection in the fasting crayfish at 5 degrees C. Of the monooxygenase activities, 7-ethoxycoumar in O-deethylase increased in the hepatopancreas significantly (p less than 0.05) after beta-naphthoflavone administration. Benzo(a)pyrene hydroxylase did not change. Aroclor 1254 and phenobarbital injection elevated hepatopancreatic glutathione S-transferase activity (p less than 0.05). (Lindstrom-Seppa et al, 1986)

Study #20

  • PCBs induce growth of pancreatic tissue inside the liver
Pancreatic-type tissue induced in the livers of rats treated with polychlorinated biphenyls was characterized by transmission electron microscopy and high-resolution immunocytochemistry. The cells of pancreatic-type tissue were arranged as acini and in small groups. By electron microscopy the pancreatic-type tissue showed features very similar to normal pancreatic acinar tissue, such as well developed rough endoplasmic reticulum (RER), large numbers of mature zymogen granules, and a basally located nucleus. Protein A-gold immunocytochemical technique showed localization of amylase and trypsinogen over the zymogen granules and RER. These findings confirm that this tissue in the liver is morphologically and functionally identical to pancreatic acinar tissue. (Rao et al, 1986)

Study #21

  • PCBs increase enzyme activity in the pancreas
Fatty acid ethyl esters (FAEE) are formed following the administration of ethanol and have previously been associated with toxicological effects in animals and humans. It has been suggested that the enzyme responsible, FAEE synthase, has both structural and catalytic properties very similar to a glutathione S-transferase (GST). Since GSTs are inducible, their induction could be associated with enhanced FAEE formation and toxicity. In the present study, rats were administered beta-naphthoflavone, phenobarbital, ethanol, or Aroclor 1254, and hepatic FAEE synthase and GST activities were measured. beta-Naphthoflavone and ethanol did not induce either activity. Phenobarbital increased GST activity in the liver but not in lung or pancreas. Only Aroclor 1254, which increased GST activity in liver and pancreas, increased FAEE synthase activity and then only in the liver. Thus, in comparison with GST activity, FAEE synthase activity is very limited in its ability to be induced. (Carlson et al, 1995)

Study #22

  • PCBs may be linked to an increase in fibrous areas in the pancreas of Fox River and Green Bay fish
The sediment in Lower Fox River and Lower Green Bay caused a little degree of pollution. The results of the paper suggested that the concentration of PCBs was higher while the concentration of FCDFs and PCDDs were lower in sediments. Moreover, there were PCBs and pesticides in fish sampled from each collected site. Examinations with histopathological method indicated that the infection rate with parasites in fish is high; Meanwhile, necrotic tissue and granuloma were found in liver, fibrous area in pancreas appeared, but tumor was not found in the fish. (Zhang et al, 1997)

Study #23

  • PCBs are Type II inducers of enzymes in the hepatopancreas of crabs
Type II inducers (7,8-benzoflavone, benzo(a)-pyrene and 3-methylcholanthrene) as well as Aroclor 1254, significantly increase benzo(a)pyrene monooxygenase activity in crab hepatopancreas while type I inducer (phenobarbital) does not enhance benzo(a)pyrene monooxygenase activity. 3-methylcholanthrene and benzo(a)pyrene treatment of crabs significantly increase cytochrome P-450 content. Benzo(a)pyrene monooxygenase induction in hepatopancreas of 3-methylcholanthrene treated crabs was inhibited by simultaneous treatment with cycloheximide but not by actinomycin D. Actinomycin D insensitivity can be explained involving a regulatory pattern of induction on the posttranscriptional and/or translational, rather than transcriptional level. (Batel et al, 1988)

Study #24

  • PCBs caused severe vacuolation in the pancreatic exocrine tissue surrounding the portal veins in pinfish
Bioassays were conducted to determine the acute toxicities of the (environmentally significant) polychlorinated biphenyl (PCB) Aroclor 1016 in flowing sea water to American oysters (Crassostrea virginica), brown shrimp (Penaeus aztecus), grass shrimp (Palemonetes pugio), and pinfish (Lagodon rhomboides), and to determine its chronic toxicity to, and uptake and retention by pinfish. Acute 96-h EC50 median effective concentration) or LC50 (lethal concentration 50% kill) were: oysters, 10.2 mu/l; brown shrimp, 10.5 mug/l; grass shrimp, 12.5 mug/l. The PCB was not toxic to pinfish at 100 mug/l for 96 h, but significantly mortality occurred when pinfish were exposed to 32 mug/l of Aroclor 1016 for 42 days. Pinfish exposed to 1 mug/l for 56 days accumulated the chemical with maximum concentrations attained in whole-fish by 21 to 28 days. Maximum whole-body residue (wet weight) was 17,000 x the nominal concentration in test water. Tissue alterations, such as severe vacuolation in the pancreatic exocrine tissue surrounding the portal veins, occurred in pinfish exposed to 32 mug/l of Aroclor 1016 for 42 days. (Hansen et al, 1974)

Study #25

  • PCBs caused pancreatic duct hyperplasia, in a dose/response relationship
The toxic effects of the soot that contaminated a State Office Building in Binghamton, New York, due to a fire involving a transformer which contained polychlorinated biphenyls (PCBs) were evaluated in guinea-pigs and rabbits. Male and female Hartley-guinea-pigs were treated with a single oral dose of 1 to 500mg/kg soot and were necropsied 42 days later. No toxic effects were seen after doses of 1 or 10mg/kg. Severe toxicity was seen in animals receiving 500mg/kg, including death in two of the six females. Oral median lethal doses (LD50s) of soot and its benzene extract in female guinea-pigs were 410mg/kg soot and 327mg/kg soot equivalent. In female guinea-pigs, the oral LD50s of 2,3,7,8-tetrachlorodibenzo-p-dioxin (1746016), one of the main constituents of the soot, was 19 micrograms/kilogram (microg/kg) in aqueous methyl-cellulose and 2.5microg/kg in corn oil. Overall body weight was significantly decreased in both sexes treated with 500mg/kg. Thymus weight was decreased in both sexes after doses of 100 and 500mg/kg. Reductions of absolute and relative kidney weights were observed in male guinea-pigs treated with 100 or 500mg/kg. Microscopic examination revealed dose related pancreatic duct hyperplasia and salivary gland metaplasia in males. Serum triglyceride levels were elevated in males at doses of 100 or 500mg/kg and in females at 500mg/kg. Male and female New-Zealand-white-rabbits treated with dermal application of soot for 24 hours showed no overt toxicity, but hepatic centrilobular hypertrophy was observed in both sexes. A local serous inflammation was seen after dermal application of soot extract. The authors conclude that dermal toxicity is altered by the soot matrix, and that acute oral toxicity is markedly diminished by an aqueous vehicle in comparison to a corn oil vehicle. (Silkworth et al, 1982)

Study #26

  • both dechlorinated and regular PCBs stimulate insulin secretion
  • partly degrading PCBs doesn’t change the insulin effect
The reductive dechlorination of polychlorinated biphenyls (PCBs) by anaerobic bacteria has recently been established as an important environmental fate of these compounds. This process removes chlorines directly from the biphenyl ring with replacement by hydrogen, resulting in a product mixture in which the average number of chlorines per biphenyl is reduced. In this study, dechlorination of commercial PCB mixtures (Aroclors 1242 and 1254) by microorganisms eluted from PCB-contaminated sediments of the River Raisin (Michigan) and Silver Lake (Massachusetts) caused a depletion in the proportion of highly chlorinated PCB congeners and an accumulation of lesser-chlorinated congeners. Dechlorination occurred primarily at the meta and, to a much lesser extent, para positions of biphenyl. The concentrations of the coplanar congeners including 3,3',4,4',5-pentachlorobiphenyl, the most potent dioxinlike congener, were significantly lowered by reductive dechlorination. Microbial reductive dechlorination of commercial PCB mixtures caused a substantial reduction in biologic activities in several instances. It significantly lowered or eliminated the inhibitory effects of Aroclors on fertilization of mouse gametes in vitro. Similarly, the dechlorinated product mixtures had substantially lower ethoxyresorufin-O-deethylase induction potencies and showed less ability to induce activating protein 1 transcription factor activity as compared to the unaltered Aroclors. In other assays the same dechlorinated product mixtures demonstrated biologic activities similar to the nondechlorinated Aroclors, including the ability of PCB mixtures to stimulate insulin secretion and cause neutrophil activation. The data presented here establish that the biologic activities of commercial PCB mixtures are altered by microbial reductive dechlorination and that an assessment of their toxic potential requires an array of tests that include the different mechanisms associated with PCBs. (Mousa et al, 1998)

Study #27

  • with saturating levels of insulin, enzyme activities were induced, but addition of PCBs result in an additive effect.
  • PCBs influence gluconeogenic and lipogenic enzymes, in a dose-dependent manner
  • some genetic strains are more sensitive to PCBs
The effects of dietary polychlorinated biphenyls (PCBs) (30-2000 ppm) on activities of gluconeogenic (phosphoenolpyruvate carboxykinase-PEPCK, and fructose 1,6-bisphosphatase-FdPase) and lipogenic enzymes (fatty acid synthase-FAS, ATP citrate lyase-ACL, malic enzyme-ME, glucose 6-phosphate dehydrogenase-G6PDH, and 6-phosphogluconate dehydrogenase-PGDH) were studied in livers of the female Sprague-Dawley and Wistar rat. PCB amounts accumulating in the liver reflected the extent of dietary exposure. The Wistar strain was more sensitive to PCBs than the Sprague-Dawley strain. Of the Clophentype PCBs those containing 60 and 64% chlorine displayed the most pronounced effects. Activities of gluconeogenic enzymes (PEPCK and FdPase) were dose-dependently decreased by PCBs, PEPCK being considerably more sensitive. This decrease was also found under conditions where the activity of PEPCK was induced (administration of adrenalin, glucagon or cAMP, feeding high protein diets, starvation). Activities of lipogenic enzymes were induced by PCBs. The increase was much greater with ME, G6PDH and PGDH (up to 10-fold) than with FAS and ACL (approximately 2-fold). PCB effects were dose-dependent, but transient. In cultured hepatocytes basal activities of lipogenic enzymes were induced by PCBs in the absence of hormones. With saturating levels of insulin or triiodothyronine, enzyme activities were also induced, but addition of PCBs resulted in an additive effect. These results suggest that in the female rat PCBs can mimic the actions of certain hormones by affecting either hormone levels, hormone receptor systems or regulatory systems. (Boll et al, 1998)

Study #28

  • subchronic exposure to PCBs seems to have no effect on the plasma leptin levels or the glucose-6-phophatase activities
Female minks (Mustela vison) fed diets based on freshwater, marine or mixed fish were exposed to 1 mg of polychlorinated biphenyls (PCBs) a day for 21 weeks. The plasma leptin and thyroxine concentrations and the glucose-6-phosphatase and glycogen phophorylase activities in the liver were measured at the end of the experiment. The plasma thyroxine concentrations were significantly higher in the group exposed to PCBs. The mean plasma leptin concentration and glucose-6-phosphatase activity was the highest in the group that had the lowest body-mass index (BMI). The glycogen phophorylase activity was the highest in the freshwater fish-control group. The results suggest that the amount of fat in the body of the female minks is not the only determinant of the plasma leptin levels, but the leptin levels seem to rise with a lowered BMI unlike in rodents or humans. The positive correlation between the leptin levels and the glucose-6-phosphatase activity suggests increased gluconeogenesis with high leptin levels. Subchronic exposure to PCBs seems to have no effect on the plasma leptin levels or the glucose-6-phophatase activities, but it elevates significantly the plasma thyroxine levels with a mechanism that remains unknown. (Nieminen et al, 2000)

Study #29

  • significant decrease of the chaperone proteins (glucose regulated proteins) in the endoplasmic reticulum
The present study was addressed on the effect of 3,3',4,4',5-pentachlorobiphenyl (PenCB) to the expression of glucose regulated protein (GRP) 78 and GRP94 in liver endoplasmic reticulum of rat by treatment with the schedule after acute or subacute exposure. In the acute exposure, male Wistar rats received PenCB in corn oil at once a dose of 25 mg/kg i.p., then at 5 days after treatment the microsomes were prepared. Free- and pair-fed control groups were given the vehicle. The microsomal proteins were separated on SDS-PAGE, transferred to membrane and blotted using anti-sera to the GRPs. The reduction of GRP78 and GRP94 was associated significantly with the acute exposure. In subacute exposure, the rats received PenCB in corn oil at once a dose of 0.1 or 1.0 mg/kg i.p. At 4 weeks after treatment, liver microsomes were obtained. The expression level of GRP78 and GRP94 are also decreased at 1.0 mg PenCB/kg treatment as similar as the acute exposure. But the reduction was not notable at 0.1 mg PenCB/kg treatment. GRP78 and GRP94 are a member of GRPs and the expression is regulated by glucose in cells as stress proteins. GRP78 and GRP94 have also the function for chaperone protein. Chaperone proteins have important physiological functions against synthesized and/or denatured proteins, which include assembling, folding of proteins. Our results suggested that a part of the toxicity of PenCB is associated to significant decrease of the chaperone proteins in the endoplasmic reticulum. (Tasaki et al, 1999)

Study #30

  • PCBs activate the hypothalamus-pituitary-interrenal (HPI) axis
  • lower hyperglycemic response to confinement
Activation of the hypothalamus-pituitary-interrenal (HPI) axis is characteristic of stress responses, which may result from a variety of environmental challenges. To investigate whether the stress response, and in particular the HPI axis, in tilapia (Oreochromis mossambicus) is compromised by short-term exposure to PCB 126, fish of both sexes were fed diets containing PCB 126 (50 microg/kg fish . day) for 5 days. In the first approach, which was performed twice, fish were acutely stressed for periods varying between 1 and 30 min at the end of the exposure period; in the second approach fish were sampled at the end of the exposure period either at rest or after 2 h of stress (confinement). After 5 days, the body weights in all experiments were significantly lower in PCB-fed fish than in control fish. There were no changes in basal plasma glucose levels, plasma ion concentrations, or branchial, renal, and intestinal Na,K-ATPase activity following PCB exposure. In the first experimental approach, in which fish experienced acute sampling stress, plasma cortisol levels reached lower levels in PCB-fed fish than in controls. This suggests an impaired ability to acutely activate interrenal steroidogenesis in PCB-treated tilapia. Adrenocorticotropic hormone (ACTH)- and cAMP-stimulated in vitro cortisol release from superfused head kidneys was lower in tissues from tilapia exposed to PCB 126 than in tissues from control animals. This effect persisted after 24 h in vitro, which, together with the high PCB 126 concentrations measured in the head kidneys of PCB-fed fish, may indicate direct toxic effects on the interrenal cells. The second experimental approach demonstrated that basal plasma cortisol and ACTH levels were not influenced by PCB treatment, but that the basal ACTH content of the rostral pars distalis (RPD) of the pituitary gland of PCB-fed fish was lower than that of control fish. After 2 h confinement, plasma cortisol levels and ACTH content of the RPD rose to similar values in both groups, whereas plasma ACTH levels were higher in confined PCB-fed fish than in confined controls. PCB-fed fish showed a lower hyperglycemic response to confinement than control fish. Confinement resulted in similarly elevated renal and intestinal Na,K-ATPase activities in both PCB-fed and control fish; branchial enzyme activities were not affected. Since PCB did not affect Na,K-ATPase activities and plasma ion concentrations, it is concluded that the effects of PCB 126 on the HPI axis in tilapia are not secondary to ionoregulatory dysfunction. (Quabius et al, 1997)

Study #31

  • fat levels in the diet influence the enzyme impacts of PCB exposure
The authors have studied the character of changes in the content of cytochrome P450 and b5, in the oxidation rate of amidopyrine, dimethyl-aniline and aniline, in the NADPH- and ascorbate-dependent lipid peroxidation systems, as well as in glucose-6-phosphatase and acetylesterase activities in the liver microsomes of the rats on semisynthetic diets, including 50% (according to calorific value) of butter or sunflower oil, or receiving fat-free diet (0.5% of sunflower oil) in different terms (4 and 70 days) after a single intragastric administration of a mixture of polychlorinated diphenyls, chlorinated biphenyl (500 mg/kg). It is shown that the degree and character of the microsomal enzymes studied, as well as the changes in the liver structure under the action of chlorinated biphenyl depend, to a certain extent, on the quality and quantity of fat in the diet. (Lashneva et al, 1989)

Study #32

  • low PCB exposures (.1 ppm) decreased serum glucose
  • study used PCB 126
The systemic toxicity of 3,3',4,4',5-pentachlorobiphenyl (PCB 126) following subchronic dietary exposure was investigated in Sprague-Dawley rats. PCB 126 was administered to rats of both sexes at concentrations of 0.1, 1.0, 10, or 100 ppb in their diet for 13 weeks. Another group of rats received a loading dose of 5 micrograms PCB/kg body wt at the start of the feeding period followed by exposure to 10 ppb PCB diet for the same period of time as the other groups. Growth suppression and decreased food consumption were observed in the highest dose groups of both sexes. Increased organ/body weight ratios for the liver occurred in the 10 and 100 ppb groups of both sexes. Rats of both sexes exposed to the highest dose of the PCB also exhibited increased relative kidney, spleen, and brain weights. Hematological and most serum biochemical changes were confined to the 100 ppb groups. These included elevated alkaline phosphatase, bilirubin, cholesterol, and aspartate aminotransferase, and decreased serum glucose, hemoglobin, erythrocytes, hematocrit, and platelets. A dose-dependent increase in liver ethoxyresorufin-O-deethylase activity was observed in rats of both sexes starting at 0.1 ppb. A dose-dependent increase in liver uroporphyrin levels was observed in both sexes and significant changes occurred in the female rats at 1.0 ppb and higher dose groups. Decreased liver vitamin A was observed in the 10 ppb group and higher in both sexes. Kidney vitamin A was elevated in the 100 ppb group. No statistically significant changes were noted in concentrations of brain biogenic amines. PCB126 residues were 10-fold higher in liver than in fat. Treatment-related histopathological changes were observed in the thymus, thyroid, bone marrow, and liver of rats exposed to the 10 ppb diet, but increased frequency of mild changes was observed in most of these tissues at the 1.0 ppb level. Based on the above data, the no adverse effect level was judged to be 0.1 ppb in the diet or 0.01 micrograms/kg body wt/day. (Chu et al, 1994)

Study #33

  • decreased plasma glucose levels
Adult male mallards were exposed to 0, 4, 20, 100, 250, and 500 mg/kg Aroclor 1254 by gavage twice per week for 5 weeks. Immunotoxic effects, as measured by antibody titers to sheep erythrocytes, natural killer cell activity and lymphocyte mitogenesis to phytohemagglutinin, were not detected as a consequence of polychlorinated biphenyl (PCB) exposure. Hepatic cytochrome P450 activities were measured as microsomal dealkylations of ethoxyresorufin (EROD) and pentoxyresorufin (PROD). Significant elevations in EROD and PROD were noted at 20 mg/kg and peaked in birds treated with 100 mg/kg. Total P450 was induced beginning at 100 mg/kg and peaked at 250 mg/kg. Relative liver weights were dose-dependently increased following treatment with 100 mg/kg or more. Thyroid weights were significantly increased in PCB-treated birds treated with 100 mg/kg or greater, but no significant histological abnormalities were observed, except at the highest dose. Plasma total triiodothyronine (T3) was decreased in a dose-dependent manner, with a significant lowest-observed-adverse-effect level (LOAEL) of 20 mg/kg. T3 was decreased following 7 days treatment with 100 mg/kg. The no-observed-adverse-effect level (NOAEL) was 4 mg/kg for decreased T3. Plasma glucose levels were decreased on days 28 and 35 in mallards treated with 500 mg/kg, while other clinical plasma biochemistry parameters were unaltered by PCB treatment. Plasma corticosterone levels were unchanged by PCB treatment. These results indicate that thyroid hormone levels and P450 activity in mallards are sensitive to subchronic PCB exposure in the absence of gross toxic effects and immunotoxicity. (Fowles et al, 1997)

Continue with the 66 Studies involving Diabetes, PCBs and Dioxin --- Part 2

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diabetes research, diabetes studies, diabetes education, diabetes facts, diabetes information, diabetes info, diabetes articles, glucose, blood glucose levels, glucose levels, blood glucose, glucose metabolism, glucose intolerance, glucose tolerance

diabetes research, diabetes studies, diabetes education, diabetes facts, diabetes information, diabetes info, diabetes articles, glucose, blood glucose levels, glucose levels, blood glucose, glucose metabolism, glucose intolerance, glucose tolerance


diabetes research, diabetes studies, diabetes education, diabetes facts, diabetes articles, glucose, blood glucose levels, glucose levels, blood glucose, glucose metabolism, glucose intolerance, glucose tolerance