Abstract  Mature male Sprague-Dawley rats received a single IP injection of either 2,2',4,4',5,5'-hexachlorobiphenyl (HCB), 3,3',4,4'-tetrachlorobiphenyl (TCB) (300 microm/kg) in corn oil (10 ml/kg) or the corn oil vehicle alone, and were killed four days later after having been fasted overnight. The vehicle control group consisted of rats which were allowed free access to feed as well as pair-fed animals. Lipid analyses were conducted on liver, hepatic microsomes and serum. TCB- (but no HCB-) treatment resulted in a statistically significant increase in total liver lipids and triglycerides. Liver phospholipids remained unchanged. Both PCBs increased the cholesterol and phospholipids content of the liver microsomal fraction. Serum lipids measured were not statistically different from control values. While HCB had little effect on the fatty acid composition of liver lipids, TCB caused an increase in C 18:1 (n-9) and a decrease in C 20:4 (n-6). Both PCBs increased C 18:0 in the hepatic microsomal fraction, but TCB also decreased C 16:0. Neither PCB altered the fatty acid composition of serum total lipids. These data are consistent with the concept that specific alterations in lipid metabolism are dependent on the structure of the PCB.

Abstract  HAPAB Young Japanese quail and rats were fed a control diet or one containing 100 ppm of p,p'-DDT or Aroclor 1242. After two months the animals were killed and the livers excised and analyzed. Both Aroclor 1242 and p,p'-DDT increased liver weight and liver lipids in male and female rats. Feeding DDT or PCB reduced liver vitamin A concentration in both male and female rats. The reduction in concentration was greater than that attributable to the corresponding increase in liver size. Total liver vitamin A in treated male and female rats was approximately half that in controls. In male quail PCB and DDT increased liver weight and decreased liver vitamin A. No effects of the treatments could be seen in female quail due to the great variations in individual data, presumably because of mobilization of liver constituents in formation of egg yolk. When egg laying was suppressed by maintaining the female quail in the dark from the onset of maturity, PCB and p,p'-DDT increased liver weight. PCB decreased liver vitamin A concentration to one-half of the control level and the total liver vitamin A to two-thirds of the control level. Aroclor feeding to female quail in standard lighting depressed egg production but did not affect egg weight or eggshell thickness.

Abstract  Polychlorinated biphenyls (PCBs) are persistent environmental pollutants. Aroclor 1221 (A1221) and Aroclor 1254 (A1254) are commercial PCB mixtures with low and high number of chlorination, respectively. We have comparatively investigated effects of A1221 and A1254 on serum levels of thyroid hormones and thyroid gland histology in adult female Wistar rats. Animals were subcutaneously injected with A1221 (10 mg/kg) or A1254 (10 mg/kg) for six weeks. One group of animals served as control. At the end, all animals were decapitated and trunk blood collected. Serum levels of triiodothyronine (T3) and thyroxine (T4) were measured by the electrochemiluminescence immunoassay method. Thyroid glands were removed for histopathological examination under light microscopy. Serum total T4 levels were significantly increased in A1221- and A1254-treated rats (p < 0.05). Serum free T4 levels were significantly increased in the A1254-treated rats (p < 0.01), but not in the A1221-treated rats. In contrast, the treatment with A1221 caused a significant increase in serum free T3 concentrations (p < 0.05) but not with A1254. Notably, either A1221 or A1254 caused distinct histopathological changes, such as formation of many microfollicles in the thyroid gland, which mimic the changes seen in thyrotoxicosis. In conclusion, both PCB mixtures induce toxic effects in the thyroid gland regardless of their degree of chlorination. We suggest that these environmental contaminants may disrupt thyroid hormone homeostasis in exposed individuals and thus pose a threat to human health.

Abstract  1. In order to study the effects of polychlorinated biphenyls (PCBs) on American kestrels (Falco sparverius), groups of 6 female birds were fed toxic equivalent doses, estimated from rat studies, of either 2,3,3'4,4'-PCB (3 mg/kg/day) or 3,3',4,4',5-PCB (0.05 mg/kg/day) and a comparable dose of 2,2',4,4',5,5'-HxCB (4 mg/kg/day) for 4 weeks.
2. Livers were assayed for ethoxyresorufin OMICRON-deethylase (EROD), aminopyrine N-demethylase (APND) and aldrin epoxidase (AE) activity and also analyzed for concentrations of porphyrins by HPLC; abdominal fat was analyzed for residues of PCB congeners by GC/ECD.
3. Chronic dosing with 3,3',4,4',5-PCB (congener 126) caused significant induction of hepatic EROD and AE; dosing with 2,3,3'4,4'-PCB (congener 105) caused significant hepatic APND induction; dosing with 2,2',4,4',5,5'-HxCB (congener 153) caused significant induction of APND and AE.
4. None of the congeners had a significant effect on mean liver weight or mean hepatic porphyrin levels.
5. The data indicate that the relative response of kestrels to dosing with PCB congeners is different from both quail and rats.

Abstract  Rats were treated four days with an oral dose of 25 mg/kg/day of Delor 105 (polychlorinated biphenyls produced in Czechoslovakia). Significant increase in the relative liver weight, hepatal vitamin C, amount of proteins, p-nitroanisole 0-demethylase, aniline hydroxylase and cytochrome P-450 in isolated liver microsomes was observed. The levels of total blood cholesterol as well as HDL cholesterol were significantly elevated on the fourth day of the treatment. Close direct linear correlation between hepatal vitamin C and microsomal cytochrome P-450 was found.

Abstract  Polychlorinated biphenyls are persistent environmental pollutants that elicit a wide range of effects in humans and wildlife, mediated by the aryl hydrocarbon receptor. 3,3',4,4',5-pentachlorobiphenyl (PCB126) is the most potent congener with relative effect potencies ranging from 0.0026 to 0.857, and a toxic equivalency factor (TEF) of 0.1 set by an expert panel of the World Health Organization. In this study, the hepatic effects elicited by 300 microg/kg PCB126 were compared with 30 microg/kg 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in immature, ovariectomized female C57BL/6 mice. Comprehensive hepatic gene expression analyses with complementary histopathology, high-resolution gas chromatograph/high-resolution mass spectrometer tissue analysis, and clinical chemistry were examined. For temporal analysis, mice were orally gavaged with PCB126 or sesame oil vehicle and sacrificed after 2, 4, 8, 12, 18, 24, 72, 120, or 168 h. In the dose-response study, mice were gavaged with 0.3, 1, 3, 10, 30, 100, 300, 1000 microg/kg PCB126, 30 or 100 microg/kg TCDD and sacrificed after 72 h. 251 and 367 genes were differentially expressed by PCB126 at one or more time points or doses, respectively, significantly less than elicited by TCDD. In addition, there was less vacuolization and necrosis, and no immune cell infiltration, despite comparable or higher TEF-adjusted hepatic PCB126 levels. The functional annotation of differentially expressed genes was consistent with the observed histopathology. Collectively, the data indicate that 300 microg/kg PCB126 elicited a subset of weaker effects compared with 30 microg/kg TCDD in immature, ovariectomized C57BL/6 mice.

Abstract  The present study has compared the neurobehavioral effects of two structurally different PCB congeners or their combination in rats. Time-mated Long-Evans rats received daily injections of the coplanar PCB 77 (3,4 3',4'-TCB: 0.5 or 1.5 mg/kg), the di-ortho-chlorinated PCB 47 (2,4,2',4'-TCB: 1.5 mg/kg) or a congener mixture (0.5 mg/kg PCB 77 + 1.0 mg/kg PCB 47) from day 7 to 18 of gestation. The PCB exposure levels in brain and perirenal fat of dams and offspring were determined by GC/ECD on gestational day 19 (GD 19), postnatal day 21 (PND 21), and PND 45. PCB 77 was accumulated to a smaller degree than PCB 47. On GD 19, PCB 77 was found to a greater extent in the brains of the offspring than in the brains of the dams, whereas the level of PCB 47 was almost the same in dams and offspring. The testing of open-field behavior in male rats on PND 18 and PND 70 revealed an altered distribution of activity with enhanced activity in the inner zone in PCB 77-treated rats compared to all other groups, while the overall activity was not changed. Distance traveled and rearing behavior on PND 340 were elevated relative to controls in all PCB-treated groups, indicating age-related effects of maternal exposure. A step-down passive avoidance task revealed decreased latencies in the PCB 77 and combined exposure groups on PND 80. Only PCB 77-treated animals showed increased latencies on PND 100 on the haloperidol-induced catalepsy test. These results indicate long-term effects of maternal exposure to PCB 77 on emotional and motor functions. At the dose levels used in the present experiments, the two congeners given in combination did not cause additive or synergistic effects. Instead, concurrent exposure to PCB 47 seemed to counteract PCB 77-induced changes in the pattern of activity.

Abstract  This study investigated the effects of consumption of Great Lakes fish on progressive ratio performance, and on the pattern and concentrations of brain polychlorinated biphenyls (PCBs), dichlorodiphenyldichloroethene (DDE), and mirex in the rat. Adult, male Sprague-Dawley rats were fed a 30% diet of either Lake Ontario salmon (LAKE), Pacific Ocean salmon, or lab chow control for 20 or 65 days. Following the treatment regimen, half the rats from each group were sacrificed immediately for gas chromatographic analysis of organochlorine contaminants, and the other half were tested on a multiple fixed-ratio-progressive-ratio reinforcement schedule and then sacrificed for analysis. Consumption of Lake Ontario fish resulted in significantly higher levels of brain PCBs, DDE, and mirex relative to controls, but still well within human exposure ranges (<1 microg/g fat). Consumption of Lake Ontario fish for 20 or 65 days produced an average brain PCB concentration of 457 and 934 ng/g fat, respectively. Consumption of laboratory rat chow or Pacific Ocean salmon for 20 or 65 days produced an average brain PCB concentration of 240, 464, and 441 ng/g fat, respectively. Moreover, both LAKE-fed groups showed a much more heavily chlorinated pattern of brain PCBs than all control groups, as evidenced by both significant increases in the most heavily chlorinated PCB congeners and significant increases in the average chlorine biphenyl. All LAKE brains contained significant concentrations of DDE and mirex, whereas no control brains contained any detectable quantities. Analysis of progressive-ratio performance indicated that LAKE rats responded normally during fixed-ratio schedules but quit significantly sooner than control rats on a progressive-ratio 5 (PR5) schedule, indicating reduced persistence on progressively leaner reinforcement schedules. Analysis of brain PCBs indicated that total PCBs were most strongly related to PR5 performance. These data indicate that consumption by rats of contaminated Lake Ontario fish produces (1) increased concentrations of PCBs, DDE, and mirex in the brain, (2) a more heavily chlorinated distribution of PCBs in the brain, and (3) reduced persistence of progressive-ratio reinforcement schedules. While these behavioral changes are related to brain PCB level, more work is necessary before the effects can be directly attributed to PCBs.

Abstract  Toxic equivalency factor (TEF) has been proposed to estimate the risk of polychlorinated biphenyl (PCB) congeners. However, ortho chlorine substitution in the two phenyl rings gives each PCB its own pattern of toxicity which is different from the mechanism of action of 2,3,7,8-tetrachlorodibenzo-p-dioxin. The present study evaluated the effect of prenatal and postnatal exposure to a low dose of the mono-ortho pentachlorobiphenyl PCB 118 on thyroid hormone concentrations and EROD activity in rats. Moreover, the tissue distribution of PCB 118 following one oral dose was evaluated. Sprague-Dawley rats were treated by gavage on GD 6 with 375 microg of PCB 118/kg b.w. Decreases in thyroxine and TSH levels were observed in dams at the end of lactation. Perinatal exposure to a low dose of PCB 118 permanently disrupted the hypothalamo-pituitary-thyroid (HPT) axis leading to a significant increase in thyroxine levels in offspring, as a 'thyroid resistance syndrome'. It is noteworthy that no changes in hepatic EROD activity were detected in dams at the end of lactation, even in the presence of high amounts of PCB in liver. Based on hepatic EROD activity (as a biomarker for aryl hydrocarbon receptor (AhR) induction), the mechanism of thyroid homeostasis disruption seems to be AhR-independent. Additionally, the 'thyroid resistance syndrome' observed in our study indicates the need for further detailed investigations on the HPT axis. We conclude that not only TEF, but also AhR-independent responses should be taken into account for risk assessment of mono-ortho PCB congeners.

Abstract  The objective of the present study was to investigate whether neonatal exposure to single PCB congeners 3,3',4,4',5-pentachlorobiphenyl (IUPAC 126) (co-planar) and 2,3,3',4,4?-pentachlorobiphenyl (IUPAC 105) (mono-ortho co-planar like') when given as one single dose (0.14?14 mol/kg body weight per os) to 10 day old male NMRI mice could induce neurotoxic effects in the adult animal, as earlier seen for some ortho-substituted PCBs. Furthermore, to ascertain whether behavioural aberrations, both in spontaneous behaviour and in learning and memory function, were followed by changes in the cholinergic and/or the dopaminergic system, and whether behavioural changes could worsen with age. It was found that neonatal exposure to 3,3',4,4',5-pentachlorobiphenyl can induce persistent aberrations in spontaneous behaviour and that this derangement can grow worse with age. Furthermore, this exposure affected also learning and memory functions in the adult animal and in the animals showing this deficit, the cholinergic nicotinic receptors in the hippocampus were affected. Exposure to 2,3,3',4,4'-pentachlorobiphenyl, at the same dose or higher, did not cause any significant change in the investigated behavioural variables, spontaneous and swim-maze behaviour.

Abstract  Environmental pollutants that disrupt endocrine system might also affect the modeling and remodeling of bone. Environmental factors, irrespective of age and sex contribute for the development of secondary osteoporosis. Polychlorinated biphenyls have adverse effects on various organs including bone. The present study was designed to investigate the effects of PCB (Aroclor 1254) on femur bone and the ameliorative role of vitamin C or E. In this regard, four groups of adult male albino rats were used as control, PCB (2mg/kgb.wt.), PCB+vitamin C (100mg/kgb.wt.) and PCB+vitamin E (50mg/kgb.wt.). The bone formation markers (ALP, Collagen), bone resorption marker (TRAP), antioxidant enzymes (SOD, GPX and GST) and lipid peroxidation in the femur were studied. Aroclor 1254 treatment decreased the ALP activity and collagen, but increased the TRAP activity and lipid peroxidation. While it decreased the SOD and GPX activity, GST was unaltered. Interestingly, simultaneous administration of vitamin C or E prevented the adverse effects of Aroclor 1254 in the femur. In conclusion, the present investigation suggests that Aroclor 1254 induced oxidative stress affects femoral bone metabolism. However, vitamin C or vitamin E protected the femur from the oxidative stress.

Abstract  Developmental exposure to polychlorinated biphenyls (PCBs) has been associated with cognitive deficits in children. The current study assessed effects of gestational and lactational exposure to a commercial PCB mixture, Aroclor 1254 (A1254), on spatial learning and memory in rats, using the radial-arm maze (RAM). Pregnant Long-Evans females (10/dose group) were exposed to 0 or 6-mg/kg/day A1254 (po in corn oil) from gestation day (GD) 6 to weaning at postnatal day (PND) 21. After they reached adulthood, 1 male and 1 female from each litter were tested on a working/reference memory task using a 12-arm RAM. Eight of the 12 arms were baited, with the pattern of baited arms remaining the same on every trial for each rat. Compared to control males, the A1254-exposed males made significantly more working memory errors (2.15 +/- 0.13 and 3.20 +/- 0.18 errors +/- SEM for control and A1254 males, respectively) and reference memory errors (3.17 +/- 0.10 and 4.13+/-0.14 errors +/- SEM for control and A1254 males, respectively) on the RAM. In contrast, A1254-exposed females were not impaired relative to control females on the RAM. Drug challenges with dizocilpine (MK-801) and scopolamine did not differentially affect working or reference memory of control and exposed rats. These data suggest that perinatal exposure to A1254 may cause sex-specific deficits in spatial learning and memory, and that NMDA-mediated and muscarinic neurotransmission, as assessed with the drug challenges, were not markedly impaired in the A1254-exposed animals.

Abstract  Polychlorinated biphenyls (PCB), which are tumor promoters, have been found in human tissues for decades. Their contribution to cancer risk may only now start to appear, due to long human cancer latency and the nature of tumor promotion. Epidemiological associations have been seen between PCB exposure or tissue content and cancer at several sites. In rodents, tumor promotion by PCBs has been little studied in tissues other than liver. Previously, in an experiment modeling infant carcinogen exposure following PCBs received in milk, lung and liver tumors, initiated neonatally in mice by the environmental nitrosamine N-nitrosodimethylamine (NDMA), were promoted by later treatment with Aroclor 1254. The present study was undertaken to confirm and characterize the effects of Aroclor 1254 on tumor number, latency, size and malignancy. Male Swiss mice were given NDMA on postnatal day 4 and Aroclor 1254 (250 mg/kg) on day 8, and killed at intervals. Eight PCB congeners were quantified in the carcasses. Incidences of mice with NDMA-initiated lung tumors at 28 weeks of age were increased 2.5-fold by PCBs. Multiplicities of lung tumors were enhanced four-fold by PCBs at 28 and 52 weeks. By 72 weeks tumor numbers were similar in the NDMA-only and NDMA-PCB groups. Liver tumors first occurred in significant numbers at 52 weeks and only in mice receiving both NDMA and PCBs. As for the lung, at 72 weeks the incidence was high in both the NDMA-only and NDMA-PCB groups. Sizes of tumors and liver carcinoma incidence were not altered by PCB treatment. Carcass analysis revealed a significant positive association between lung tumor numbers at 28 weeks and relative percentage of 2,2',4,4',5-pentachlorobiphenyl, with no other correlations. The results confirm that PCBs promote lung as well as liver tumors, by triggering the early appearance of latent initiated tumors otherwise presenting in old age.

Abstract  Previous studies indicate that repeated exposure of weanling male Fischer 344 rats to Aroclor can cause immune system alterations but the pattern of effects suggested the release of corticosteroids may have played a role. Rats were exposed daily by gastric intubation to the polychlorinated biphenyl (PCB) Aroclor 1254 at 0.1, 1.0, 10, or 25 mg/kg for exposure durations of 5, 10 or 15 weeks. By the 15th week of dosing all groups displayed an elevation in the basal level of serum corticosterone but no change in adrenal weight. Further, rats exposed to Aroclor 1254 for 15 weeks and subjected to stress prior to serum collection displayed elevations in corticosterone levels equivalent to stressed control rats. The failure to observe altered adrenal structure indicative of hyperactivity in the presence of increased serum levels of corticosterone suggest these basal increases may be indirect rather than direct effects of Aroclor 1254.

Abstract  Sensitive assays for the induction of lung adenomas in A/J mice or skin papillomas in SENCAR mice failed to show activity for either 2,2',5,5'-tetrachlorobiphenyl or 2,2',5,5'-tetrachlorobiphenyl 3,4-oxide. Injections of the 3,4-oxide into preweanling A/J mice caused considerable mortality, whereas the parent hydrocarbon did not. Both 2,2',5,5'- and 2,2',4,4'-tetrachlorobiphenyl showed promoting activity for hepatic gamma-glutamyl transpeptidase-positive foci initiated in rat liver by treatment with diethylnitrosamine. The promoting activity of 2,2',4,4'-tetrachlorobiphenyl was approximately 10-fold greater than that of the 2,2',5,5'-isomer.

Abstract  Adult male rats were gavaged with a mixture of Aroclors 1254 and 1260 at a dose level of either 500 or 1000 mg/kg and were killed on post-gavage days 1, 3, 7 and 14. Total PCB concentrations and concentrations of serotonin and its major central metabolite, 5-hydroxyindoleacetic acid, were determined in the dorsal frontal cortex, lateral olfactory tract, hippocampus, medial-basal hypothalamus and brainstem. Differences in the initial concentrations and redistribution patterns of PCBs were observed in the brain regions examined. Serotonin concentrations were reduced in frontal cortex and hippocampus, unaffected in hypothalamus and brainstem and elevated in lateral olfactory tract. Serotonin metabolism, estimated by determination of the metabolite to neurotransmitter ratio, was elevated in all brain areas except for the lateral olfactory tract. These results demonstrate that following a single exposure to PCBs, there are significant changes in serotonin concentrations and metabolism in the adult rat. Furthermore, there are regional brain differences with regard to PCB concentrations and the direction and magnitude of neurochemical change induced by the PCBs.

Abstract  Polychlorinated biphenyls (PCBs) are a class of industrial compounds consisting of paired phenyl rings with various degrees of chlorination. They are now ubiquitous, persistent environmental contaminants that are routinely found in samples of human and animal tissues and are known to affect brain development. The effects of PCBs on brain development may be attributable, at least in part, to their ability to reduce circulating levels of thyroid hormone. However, the developmental effects of PCB exposure are not fully consistent with hypothyroidism. Because some individual PCB congeners interact strongly with various thyroid hormone binding proteins, several investigators have speculated that these congeners may be producing thyroid hormone-like effects on brain development. Therefore, we tested whether a mixture of PCBs, Aroclor 1254 (A1254), would produce an antithyroid or thyromimetic effect on the expression of known thyroid hormone-responsive genes in the developing brain. Pregnant female rats were fed various doses of A1254 (0, 1, 4, and 8 mg/kg) from gestational day 6 to weaning on postnatal day (P) 21. Pups derived from these dams were sampled on P5, P15, and P30. Total T4 was reduced by A1254 in a dose-dependent manner, but body weight of the pups or dams was not affected. The expression of RC3/Neurogranin and myelin basic protein was not affected by A1254 on P5 or P30. However, on P15, RC3/Neurogranin was elevated by A1254 in a dose-dependent manner, and myelin basic protein expression followed this general pattern. These data clearly demonstrate that the developmental effects of PCB exposure are not simply a function of PCB-induced hypothyroidism.

Abstract  Five-week-old male mice were given: 0.3, 1, 3, 10, 30, 100, or 300 ppm of 3,4,5,3?,4?,5?-hexachlorobiphenyl (HCB); 10, 30, 100 or 300 ppm of 2,4,5,2?,4?,5?-HCB, 2,3,6,2?,3?,6?-HCB, or 2,4,6,2?,4?,6?-HCB in feed daily for 28 days. HCB residue levels were determined in adipose tissue and liver. There were marked differences in dose response and severity of pathologic effects among the isomers. 3,4,5,3?,4?,5?-HCB was the most toxic isomer causing mortality, and body and organ weight effects at all dose levels, and was the only isomer which produced excess porphyrin accumulation. It was also the most concentrated isomer in fat and liver. 3,4,5,3?,4?,5?-HCB caused subcutaneous edema, enlargement of liver with accentuated hepatic lobular markings, fatty infiltration, hepatocellular swelling and necrosis, and atrophy of the thymus. 2,4,6,2?,4?,6?-HCB and 2,4,5,2?,4?,5?-HCB caused the same lesions but to a lesser degree. Slight cardiomyopathy was observed with 2,4,6,2?,4?,6?-HCB. The decreasing order of overall toxicity was 3,4,5-HCB >> 2,4,6-HCB > 2,4,5-HCB > 2,3,6-HCB.

Abstract  A group of three rhesus monkeys (M. mulatta) whose mothers had been fed 2.5 ppm PCBs (Aroclor 1248) in their diets through gestation and three months of nursing were tested for locomotor activity at 44 months of age. These animals had been hyperactive relative to controls at six and twelve months of age but were significantly hypoactive when compared to the same group of controls in the same apparatus in the 44-month test. Both groups showed within-session activity declines suggestive of reactivity which did not differ significantly between groups either within sessions or in their adaptation over the course of testing. This phenomenon represents a clear-cut delayed and possibly permanent effect of the early PCB exposure.

Abstract  Polychlorinated biphenyls (PCBs) are ubiquitous environmental contaminants that have been associated with cognitive deficits in children exposed in utero. Cognitive deficits due to PCB exposure have also been documented in animal models, but the underlying behavioral mechanisms responsible for those deficits remain to be elucidated. The current study examined the effects of gestational and lactational exposure to PCBs on spatial discrimination-reversal learning (spatial RL) in rats using standard two-lever operant testing chambers. Pregnant Long-Evans rats (10/dose) received either 0 or 6 mg/kg Aroclor 1254 (A1254) po in corn oil from gestational day 6 to postnatal day 21. One male and one female from each litter were tested on spatial RL beginning at 190-220 days of age. Animals were reinforced with a 45-mg food pellet for pressing the lever associated with the correct spatial location (either left or right). After reaching 85% correct performance for 2 consecutive days, the opposite spatial location was reinforced. Five of these position reversals were given. Male rats exposed to A1254 made significantly more total errors (121.6 +/- 12.5) on the first reversal than controls (90.7 +/- 5.8). In contrast, female rats exposed to A1254 exhibited deficits on the fourth and fifth reversals (23.6 +/- 4.2, 17.0 +/- 2.8 and 36.7 +/- 4.7, 26.8 +/- 2.5 for control and exposed animals, respectively). Response-pattern analyses in the A1254-exposed male and female rats revealed fundamental differences in the underlying behavioral mechanisms responsible for the deficits. A1254-exposed males exhibited an increased tendency to incorrectly respond to the previously correct stimulus (i.e., perseverate) following a reversal while A1254-exposed females exhibited impairments in their ability to make new associations with a reinforced spatial location (i.e., associative deficit). These data provide new insights into the underlying behavioral mechanisms that may be responsible for the spatial learning deficits observed in PCB-exposed rodents and monkeys.

Abstract  Aroclor 1254, a commercially produced mixture of polychlorinated biphenyls, is known to cause many adverse conditions, including neurotoxicity. It has been recently postulated that upregulation of N-methyl-d-aspartate receptors (NMDARs) and enhanced glutamate signalling which leads to excitotoxicity, is the mechanism of Aroclor-induced neurotoxicity. To obtain insights into the mechanisms underlying glutamatergic overstimulation, we investigated the function and expression of sodium-dependent glutamate transporters which are known to regulate extracellular glutamate concentrations in the brain. Exposure to Aroclor 1254 was found to significantly lower the uptake of radioactive glutamate into gliosomal fractions obtained from adult rat brains. It also markedly decreased the expression of both protein and mRNA of GLT-1, the main glial glutamate transporter. This indicates that downregulation of GLT-1 may potentially lead to disturbances in glutamate clearance. The expression of GLAST, another astroglial glutamate transporter, was unchanged under conditions of Aroclor toxicity. Conversely, we observed enhanced glutamate uptake into nerve-endings fractions paralleled by increased EAAC1 protein expression. This may reflect the induction of protective mechanisms.

Abstract  Exposure to polychlorinated biphenyls (PCBs) induce a broad spectrum of toxic effects in various organs including bone. The most susceptible age-groups to the toxic effects of PCBs are foetuses and infants. The aim of the present study was to quantitatively evaluate changes in bone geometry, mineral density and biomechanical properties following perinatal exposure to the PCB mixture, Aroclor 1254 (A1254), and to examine the persistence of observed bone alterations by following the offspring over time. Sprague-Dawley rat offspring were exposed to A1254 from gestational day 1 to post-natal day (PND) 23. Femur and tibia were collected on PNDs 35, 77 and 350 and were analyzed by peripheral quantitative computed tomography and biomechanical testing. At PND35, exposure to A1254 induced short, thin femur and tibia, with reduced mechanical strength of femoral neck. No treatment-related bone changes were detected in offspring at PND77 or PND350. In conclusion, the present investigation suggests that perinatal exposure to A1254 leads to shorter, thinner and weaker bones in juvenile rats at PND35, with these effects being absent at later time-points as exposure is discontinued. The results indicate that the observed bone effects are mainly driven by the dioxin-like congeners, although it cannot exclude the contribution of the non dioxin-like congeners to the exposure outcome.

Abstract  Hypothyroxinemia in rats has been well documented as a result of exposure to polychlorinated biphenyls (PCBs). Hypothetical mechanisms include induction of hepatic catabolic enzymes and cellular hormone transporters, and/or interference with plasma transport proteins. We hypothesized that if thyroxine displacement from transport proteins by PCBs occurs in vivo, it would result in increased free thyroxine (FT4). This study investigates the effects of a single oral dose of 2,2',4,4',5,5'-hexachlorobiphenyl (PCB 153 at 60 mg/kg) or 3,3',4,4',5,5'-hexachlorobiphenyl (PCB 169 at 1 mg/kg) on rats at 28 or 76 days of age. Total thyroxine (TT4) and FT4 were measured at 0.5, 1, 2, 4, 8, 24, or 48 hours post-dosing. Microsomal ethoxy- and pentoxy-resorufin-O-deethylase (EROD and PROD) activity and uridine diphosphoglucuronosyl transferase (UGT) activity were determined. No significant increase in TT4 or FT4 concentrations was seen at any time point. PCB 153 significantly decreased TT4 and FT4 in young and adult rats, with young rats showing a time-by-treatment interaction from 2 to 48 hours post-dosing in serum FT4. With PCB 169 exposure, young rats showed a decrease in FT4 only, whereas adult rats showed decreases in TT4 only. Hepatic EROD and PROD activities were both dramatically increased following PCB 169 and 153, respectively. Uridine diphosphoglucuronosyl transferase activity was increased only after PCB 169 exposure. These data demonstrate that neither PCB 153 nor PCB169 increased FT4, which supports the conclusion that these PCBs do not displace thyroxine from serum TTR, or if it does occur, there is no subsequent increase in serum FT4 in vivo.

Abstract  Rabbits were administered, orally, 300 mg of polychlorinated biphenyl Aroclor 1221, 1242 or 1254 once a week for 14 weeks. Elevated SGPT and SGOT levels occurred in the male and female 1254- and male 1242-treated rabbits as early as 2 weeks. The female 1242-treated rabbits had increased SGPT and SGOT activities at 4 and 8 weeks, respectively. These serum enzyme activities in the 1221-treated rabbits were similar to the controls during the 14-week period. Serum cholesterol concentrations were moderately elevated in the 1254-treated males throughout the experiment. The BUN, serum proteins, liver ALA-synthetase and hematologic values were similar in all groups. The livers in the 1254- and 1242-treated rabbits were significantly enlarged compared to the 1221-treated and control animals. The earliest change was megalohepatocytosis which was followed by subcapsular midzonal necrosis. In the 1254-treated rabbits, the midzonal necrosis was diffuse and frequently included most of the central part of the lobule. Fibrous connective tissue replaced the necrotic part of the lobules in the more severely affected livers. The rough endoplasmic reticulum in the livers of the 1254-treated rabbits appeared to have been destroyed. There was also atrophy of the uteri in the 1254-treated rabbits.

Abstract  The persistence of morphological changes in the liver produced by polychlorinated biphenyls (PCBs) was investigated. Male Sherman-rats were fed 500 parts per million (ppm) Aroclor-1254 (11097691) for 6 months. Five rats were killed 0, 1, 2, 3, 4, 6, 7, and 10 months after Aroclor feeding was discontinued. At autopsy, liver tissue was examined under electron and light microscopes. Adipose and liver tissue from exposed rats killed at 10 months and from unexposed controls were analyzed for PCBs by electron capture gas chromatography; adipose and hepatic composites were analyzed by gas chromatography/mass spectrometry. Livers of rats killed immediately comprised 6.32 percent of body weight, 3.6 percent at 4 months, and 3.34 percent at 8 months. Livers of control animals were 2.44 to 2.59 percent of body weight. Of 40 livers examined, hepatocytes were enlarged in 39, and all 40 showed either vacuolated or foamy cytoplasm because of increased lipid accumulation. Adenofibrosis was present in 36 livers, and a brown pigment was noted in the Kupffer cells and other macrophages in 25 livers. No signs of fibrosis regression were noted. Electron microscopy revealed numerous small lipid vacuoles in the cytoplasm of many hepatocytes, particularly in the latter part of the recovery phase. In adipose tissue, concentrations of PCBs ranged from 924 to 1688ppm. Liver concentrations ranged from 17.30 to 26.24ppm. The gas chromatogram was significantly different from that of standard Aroclor-1254. Three major Aroclor components were seen. These components contained isotopic clusters believed to be chlorines. The authors conclude that Aroclor consumption produces liver adenofibrosis. The reversibility of the lesion is not known. Metabolism of lower chlorinated biphenyls may account for the difference between Aroclors found in tissues and standard Aroclor-1254.