Abstract  Hydroxylated polychlorinated biphenyl (OH-PCB) is a major metabolite of PCB, which is an endocrine disruptor. In this study, we investigated the neurobehavioral effects of prenatal exposure to a very low dose of OH-PCB (4-hydroxy-2', 3, 3', 4', 5'-pentachlorobiphenyl, 4-OH-pentaCB) in mice. 4-OH-pentaCB, dissolved in corn oil, was orally given at 0.1 ug/30 ul/animal/day to pregnant mice from gestation days 11 to 17. In the open field test, the number of ambulation and rearing drastically increased among 4-OH-pentaCB exposed mice compared with the control. However, 4-OH-pentaCB exposure had no effect on passive avoidance. These results suggest that an extremely low dose of 4-OH-pentaCB may selectively disrupt neurobehavioral functions involved in ambulation and rearing in mice.

Abstract  Fetopathic effects of polychlorinated biphenyls (PCBs) were studied in rats. The purpose of the study was to investigate the possibility that PCBs could be transferred transplacentally from the mother to the fetus. Pregnant Wistar-rats were administered 0, 25, 75, 225, or 675 milligrams per kilogram (mg/kg) Kanechlor-400 (12737870) (KC), a commercial PCB preparation, by stomach tube on day 1 of gestation. The effects on the course of pregnancy and delivery were evaluated. Mortality was recorded, and selected dams were necropsied. After birth, selected offspring were examined for malformations. Growth was monitored up to about 60 days of age. Pregnant rats were administered tritium (H-3) labeled KC shortly before delivery. Eighteen or 48 hours later, the dams were killed, and maternal and fetal tissues were assayed for H-3 activity. All dams given 225 and 675mg/kg KC died on day 10. An increasing trend toward stillbirth and postnatal death was seen. Dose/dependent histopathological changes were found in maternal livers and kidneys. These included swollen hepatocytes and partial degeneration in the liver, and tubular dilatation and congestion in the kidneys. Follicular atrophy in the spleen and pulmonary edema were seen in the 225 or 675mg/kg group. No fetal abnormalities were found. H-3 activity was found in the placenta, amnion, and fetal body. The authors suggest that KC can be transferred transplacentally, even though no histopathological changes were found in the fetuses.

Abstract  A mixture of tetrachlorinated-biphenyls and pentachlorinated-biphenyls (1336363) (sovol) was studied for its effect on and absorption through the skin of rabbits. Application of 1.3 to 3 grams of sovol to the external surface of the ear for six hours produced edema, which subsided, and inflammation after five days. The ear became rigid and hard with scabs and subsequent falling out of new epithelium and hair. One rabbit died after application and on autopsy fatty degeneration of the liver was found. Studies showed that the route of entry was through the skin and not by inhalation.

Abstract  Polychlorinated biphenyls (PCB) are persistent environmental chemicals that are known thyroid hormone disrupters. Frequently the disruption of one endocrine axis and the timing of the disruption have an impact on other interdependent hormonal responses. Although the mechanisms for the interdependency of thyroid hormones and leptin have not been fully characterized, both are linked to development and regulation of metabolism. Furthermore, PCB accumulation in depot fat could potentially alter leptin production. In the present study 15-and 30-day-old Sprague-Dawley rats were exposed gestationally and lactationally to 1.25 ppm of Aroclor 1254 degrees, a mixture of 52 PCB congeners, via maternal diet, to determine the effect on leptin and thyroid hormones. Additionally, young adult female rats were fed 1.25 PCB for 21 days and the same hormones were assessed. Serum leptin concentrations were determined by a sensitive murine leptin ELISA (DSL, Inc., Webster, TX). Serum thyroid hormone levels were determined by RIA kits (MP Biomedicals, Carson, CA). Leptin concentrations were significantly depressed in 15-day-old animals exposed to PCB when compared to same-aged control animals, while thyroid hormones were similar in control and experimental animals. Thirty-day-old PCB treated rats displayed significantly elevated leptin levels and depressed triiodothyronine concentrations. Young adult rats exposed to PCB for 21 days displayed significantly depressed leptin concentrations, however PCB had no effect on thyroid hormones in this group. In summary, exposure to dietary PCB, at relatively low concentrations, is leading to measurable alterations in serum leptin levels. We speculate that the accumulation of fat-soluble PCB in adipocytes may be sufficient to cause these alterations. Further investigation into the mechanism causing leptin alteration and long-term effects of such alterations is warranted.

Abstract  HEEP COPYRIGHT: BIOL ABS. LIVER AMINOPYRINE N DEMETHYLASE KINETICS

Abstract  The effects of the PCBs mixture, Aroclor 1254, as modifiers of monooxygenases were studied in rabbits and mice. From data presented, it is not possible to generalize the biological effects of PCBs observed with rats, namely, that they are potent, nonspecific inducers of monooxygenase activities. This environmental pollutant enhanced microsomal drug-metabolizing enzymes in livers of rabbits and C57Bl/6J and DBA/2J mice. In rabbit lung, it inhibited, and in rabbit kidney, it enhanced the metabolism of ethylmorphine. Further, at dosages used, PCBs were poor inducers of aryl (benzo(a)pyrene) hydroxylase activity in livers of C57BL/6J and DBA/2J mice; they enhanced aryl hydrocarbon hydroxylase activity in rabbit kidney but caused a significant depression of its activity in rabbit lung. These studies demonstrate that the biologic impact of the widely distributed environmental pollutant, PCBs, may differ in different species and emphasize the need to carry out toxicological studies in more than one species of animals. The differential effects observed on various organs may also be important determinants of organ-targeted chemical toxicity.

Abstract  Biochemical parameters in blood and urine of pregnant mink fed commercial PCB, CB fractions and mixtures of the latter were examined. Mink were fed PCB fractions starting about 35 days before mating and continuing for 50 days thereafter. In 1990, mink were exposed to PCB for 53-69 days and were sacrificed 10, 17 and 26 days after mating. Blood samples were obtained at the time of sacrifice. No significant alterations were registered for the urinary parameters. Animals fed commercial PCB, but not fractions of CBs, all had elevated alanine aminotransferase (S-ALAT) (p < 0.05). Mink fed commercial PCB, individual or combined CB fractions had lowered (p < 0.05) alkaline phosphatase (S-ALP). Lowered (p < 0.05) serum bile acids (S-BA) were recorded in animals fed commercial PCB or 2-4-ortho + 1 -ortho + 0-ortho and 2-4-ortho + 0-ortho. The presence of bi- and tricyclic contaminants counteracted some of the observed biochemical changes, in particular decreases in S-fructosamine and in S-cholesterol. This protective effect and the lack of reponse in animals fed the contaminants could be attributed to induction of catalytic enzymes. Patterns of S-ALAT, S-ALP, S-BA, S-cholesterol and S-fructosamine for animals fed 2-4-ortho resembled the pattern for the control groups, whereas the combination of 2-4-ortho + 0-ortho CBs resulted in a pattern which was similar to that in animals fed commercial PCB. Significant differences from control animals were more frequent in animals given 0-ortho than 1 -ortho CBs. The patterns of biochemical changes for groups of animals fed 0-ortho CBs alone or in combination with other CBs best reproduced the pattern of the animals fed commercial PCB. The biochemical changes observed indicate the feeding of PCB or fractions of CBs causes a disturbance in hepatocytes

Abstract  Adult deer mice testes were subjected to routine histopathology following exposure to Aroclor 1254 supplemented diet (5 ppm), for 30 days. Body and testicular weight revealed no statistical significance between the control and treated animals. From a histological standpoint the testes of the controls were similar to normal murids and other animals. In contrast, the testes from treated animals displayed seminiferous tubules with significant degenerative alterations. These alterations included fewer layers of seminiferous epithelium exaggerated intercellular spaces and appearance of pyknotic nuclei. Most tubules displayed subluminal nuclei that morphologically could be identified as part of spermatozoa heads and these usually lacked tails, indicating that the treatment interfered with spermiogenesis. Therefore, we concluded that Aroclor 1254 as an environmental contaminant is highly destructive to seminiferous tubules, and that these histological alterations undoubtedly are responsible for the depressed fertility in Peromyscus following chronic exposure to PCBs, that has been reported in the literature.

Abstract  The development of second-generation nestling American kestrels (Falco sparverius) was altered by in ovo exposure of only one parent to polychlorinated biphenyls (PCBs). Polychlorinated biphenyls appear to alter nestling development through both maternally and paternally mediated effects. In 1998, F0 parent kestrels consumed approximately 5 to 7 microg total PCBs/g bird/d (Aroclors 1248:1254: 1260) for approximately 100 d prior to eggs hatching; these eggs, containing total PCB concentrations of 34.1 microg/g, produced 13 F1 offspring, which were then paired in 1999 with unexposed kestrels to examine developmental effects of maternal or paternal in ovo PCB exposure. Using a toxicokinetics model, eggs from the maternally exposed group had predicted PCB levels of 0.03 to 0.34 microg/g, with enriched higher chlorinated congeners. Polychlorinated biphenyl concentrations in eggs of all generations have recently been found in eggs and nestlings of free-ranging eagles. Consistent with the first generation, maternally exposed F2 females generally were larger, had altered growth rates, and delayed maximal growth and fledging compared with control females. Maternally exposed F2 males were heavier but had shorter bones, grew more quickly and earlier, and fledged 2 d later than control males. In the maternally exposed group, concentrations of plasma triiodothyronine were elevated in F2 females but suppressed in F2 males. Paternally exposed F2 hatchlings of both sexes were comparable in size to controls with the exception of having longer tarsi bones, but subsequently showed slower, delayed growth (both sexes) and fledging (females) and lower thyroxine concentrations (males). The alterations in thyroid hormones in the F2 generation are discussed in light of the enrichment of higher chlorinated PCB congeners and hydroxylated PCB congeners. The developmental changes in the kestrel nestlings are likely a function of several possible mechanisms involving maternal PCB deposition, parental behavior, and neurobehavioral and endocrine-thyroid function in nestlings.

Abstract  Adult male rhesus monkeys (Macaca mulatta) were given oral treatment of either Aroclor 1242 or vehicle (corn oil and glycerol) at a dose of 200 microg/kg body wt/day for 6 months to investigate the effects of the pollutant on plasma testosterone and the morphology of testes and accessory glands. Aroclor 1242 treatment significantly decreased testicular size and testosterone levels in plasma and adversely affected spermatogenic activity by disrupting epithelial organization. All components of the germinal epithelium were greatly reduced. The spermatogonia were either hypertrophied or had shrunken vesiculated cytoplasm with distorted mitochondria and nuclear pyknosis. Changes were milder in the Sertoli cells, where nuclear infoldings were reduced. Characteristic features of treated Leydig cells were the presence of electron-dense and electron-opaque zones, appearing as plaques, cell membrane abnormalities, and high variability in nuclear shape and heterochromatin distribution. All the Aroclor 1242-treated accessory glands contained more connective tissue than their vehicle-treated counterparts. The epithelium contained many layers of irregularly shaped necrotic cells possessing stereocilia in the epididymides, either hypochromic and hypertrophied or hyperchromic and hypotrophied cells in the prostate and shrunken cuboidal cells with elongated nuclei in the seminal vesicles. In conclusion, Aroclor 1242 treatment causes severe structural alterations on gonads and accessory organs in adult male rhesus monkeys, and these effects could be mediated through both estrogen and Ah receptors.

Abstract  Previous studies have shown that oral exposure of rats to polychlorinated biphenyls (PCBs) results in reduced 5-hydroxytryptamine (5-HT) concentrations in certain brain regions. In the present study, we investigated whether the PCB mixture Aroclor 1254 (0.33 mg/g body weight as a single oral dose) can inhibit the activity of tryptophan hydroxylase (TPH), the rate-limiting enzyme in 5-HT synthesis, and reduce 5-HT concentrations in selected brain areas. In two separate experiments, Aroclor 1254 exposure consistently reduced TPH activity in the brainstem (7.2 and 8.7%), frontal cortex (17.4 and 14.8%), and hypothalamus (10.7 and 9.4%) without altering the rats' food intake or growth. Moreover, Aroclor 1254 accumulation in the frontal cortex demonstrated a negative correlation with TPH activity (correlation coefficient -0.82). In addition, 5-HT concentrations decreased in the brainstem and frontal cortex after Aroclor 1254 exposure by 9.1 and 19.7%, respectively. These results suggest that the Aroclor 1254-induced decreases in 5-HT concentrations in certain areas of the rat brain are due to inhibition of TPH activity, similar to our recent observations in Atlantic croaker, and that TPH is one of the targets of PCB neurotoxicity in both fish and mammals.

Abstract  Polychlorinated biphenyl (PCB)-based transformer fluids belong to a class of environmentally persistent mixtures with known toxic effects. Here, we studied the acute effects of Askarel (which contains Aroclor 1260) and two substitute transformer fluids (the silicone oil-based DC561 and the mineral oil-based ENOL C) on rat testicular steroidogenesis. Single intraperitoneal (ip; 10 mg/kg body weight) or bilateral intratesticular (itt; 25 microg/testis) injections of Askarel markedly decreased serum androgen levels 24 hr after administration. In acute testicular cultures from these animals, chorionic gonadotropin-stimulated progesterone and androgen productions were severely attenuated. When itt was injected or added in vitro, Askarel inhibited 3ss-hydroxysteroid dehydrogenase (3ssHSD), stimulated 17[alpha]-hydroxylase/lyase (P450c17), and did not affect 17ss-hydroxysteroid dehydrogenase in testicular postmitochondrial fractions. The ip-injected Askarel did not affect 3ssHSD, but inhibited P450c17, suggesting that a more intensive metabolism of peripherally injected Askarel reduces the circulating levels of active ingredients below the threshold needed for inhibition of 3ssHSD and generates a derivative that inhibits P450c17. In contrast to Askarel, itt-injection (25 microg/testis) of DC561 and ENOL C did not affect in vivo and in vitro steroidogenesis. These findings show the acute effects of Askarel, but not silicone and mineral oils, on testicular steroidogenesis.

Abstract  Polychlorinated hydrocarbons, including polychlorinated biphenyls (PCBs), polychlorinated dibenzo-p-dioxins (PCDDs), and polychlorinated dibenzofurans (PCDFs), are ubiquitous environmental contaminants that bioconcentrate in the food chain. Numerous studies have demonstrated mink (Mustela vison) to be one of the most sensitive species to this group of compounds. In recent studies, a lesion characterized by osteoinvasion of epithelial cells into the mandible and maxilla of young mink fed diets containing 3,3',4,4',5-pentachlorobiphenyl (PCB 126) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) was observed. The objective of the present study was to determine if proliferation of maxillary and mandibular squamous epithelia could be induced in ranch mink exposed to environmentally-derived polychlorinated hydrocarbons (PCBs, PCDDs, and PCDFs) in utero, during lactation, and throughout the growth period. Adult female mink were fed diets containing 0, 10, 20, or 30% carp (Cyprinus carpio) collected from the Saginaw River, Bay City, Michigan, USA, that provided 0.03, 0.83, 1.1, and 1.7 mg total PCBs (tPCBs)/kg feed and 2.5, 28, 47, and 73 ng TCDD toxic equivalents (TEQs)/kg feed, respectively, three weeks prior to breeding through weaning of the resulting offspring. Mink kits were maintained on their respective diets for up to 27 weeks of age. At 6 and 27 weeks of age, six to eight mink in each treatment group were necropsied and their jaws examined for evidence of maxillary and mandibular squamous epithelial proliferation. Results indicated that inclusion of up to 30% carp in the diet (1.7 mg tPCBs/kg feed, 73 ng TEQs/kg feed) had no effect on mink reproduction and kit survivability. However, maxillary and mandibular squamous epithelial proliferation was evident in four of the seven 27-week-old juveniles in the 20% carp group (1.1 mg tPCBs/kg feed, 47 ng TEQs/kg feed) and six of the eight juveniles in the 30% carp group (1.7 mg tPCBs/kg feed group, 73 ng TEQs/kg feed). Hepatic concentrations of tPCBs and TEQs increased in both the 6-week-old kits and the 27-week-old juveniles as the percentage of dietary carp increased. The livers of 6-week-old kits were also assessed for the presence of polybrominated diphenyl ethers, which increased as the percentage of Saginaw River carp in the diet increased.

Abstract  Polychlorinated biphenyls (PCBs) and methylmercury (MeHg) are persistent organic pollutants accumulating in the food chain. Pre- and neonatal exposure to these neurotoxicants may affect brain development and lead to long-lasting alterations in cerebral function, which can result in motor alterations in youth and/or adulthood. Some neurotoxicants induce gender specific effects. The aims of the present work were to: (1) assess the effects of developmental exposure to MeHg, PCB 153 or PCB 126 on spontaneous locomotor and vertical activity and motor coordination when the rats are 2-month old; (2) assess whether perinatal exposure to combinations of MeHg with PCB153 or PCB126 alter the effects of the individual neurotoxicants; (3) follow the progression of motor alterations when the rats are 3-, 5- and 7-month old; (4) assess if the effects are similar or different in males and females. Pregnant rats were treated with MeHg (0.5mg/kgday); PCB126 (100ng/kgday) or PCB153 (1mg/kgday) or with combinations of MeHg with each PCB, administered in food from gestational day 7 until weaning at post-natal day 21. PCB 126 impaired motor coordination at 2 months in males but not in females. PCB 153 impaired coordination both in males and females. Combinations of MeHg with PCB153 or PCB126 did not affect motor coordination, indicating that MeHg counteracts the effects of the PBCs. The combination of MeHg and PCB153 induces hypolocomotion at 2 months but hyperactivity at 7 months while the individual compounds did not induce any effect. PCB126 induced gender selective effects, reducing locomotor activity at 2 months in females but not in males. The combination of MeHg and PCB126 behaves as PCB126 alone. All compounds and combinations tested induce gender-selective alterations in vertical activity. The effects on locomotor and vertical activity change with age in the same rats. At 2 months all compounds and combinations reduce vertical activity in females but not in males. At 7 months all treatments induced hyperactivity both in males and females, except MeHg+PCB126. In conclusion, the results show that: (a) many motor alterations induced by most compounds are different in males and females; (b) mixtures of MeHg with PCBs 153 or 126 induce different effects that the individual compounds; (c) different types of motor activity (spontaneous locomotion, vertical activity and motor coordination) are affected differently by the same neurotoxicant or mixture; and (d) the effects on locomotor and specially on vertical activity change with the age of the rat. Most compounds reduce activity at youth (2 months) and induce hyperactivity at adulthood (5-7 months). The change from hypo- to hyperactivity occurs earlier in males.

Abstract  Mink (Mustela vison) were fed diets containing ocean fish (control diet, 0.0 ppm polychlorinated biphenyls, PCBs) or Saginaw Bay carp to provide 0.25, 0.5, or 1.0 ppm PCBs to examine the effect of PCBs on homeostasis of binding sites for ovarian steroid hormones. Ranch-raised mink fed Great Lakes fish contaminated with PCBs, or treated with PCBs directly, have demonstrated reproductive impairment including anovulation, fetal resorption, delayed ovulation, increased gestation, and decreased litter size. Previous studies have demonstrated that estrogen and progesterone levels are unaltered in mink treated with PCBs, suggesting that the effect of PCBs on reproduction is not mediated through alterations in hormone homeostasis. In vitro studies have demonstrated that the most likely means by which PCBs exert antiestrogenic ability is through a down-regulation of the estrogen receptor in normally estrogen-responsive tissues such as liver and uterus. Hepatic and uterine estrogen binding site concentrations were measured in female mink consuming diets containing PCBs for up to 18 mo at up to 1 ppm. Hepatic estrogen binding site concentrations generally decreased with increasing dietary PCB concentrations. Uterine estrogen binding site concentration did not decrease in these animals. Uterine progesterone receptor concentration also did not change with increasing PCB consumption. In total, the response of hepatic and uterine estrogen and uterine progesterone binding sites in mink fed diets containing Saginaw Bay carp suggests that concentrations of PCBs available to uterine tissue may not have been sufficient to decrease uterine estrogen receptor, despite their effect on hepatic estrogen receptor.

Abstract  Exposure to polychlorinated biphenyl (PCB) has been shown to produce cognitive deficits in both humans and laboratory animals. However, no study to date has identified long-term brain changes which could account for these problems. This study employed Timm's silver sulfide staining to visualize the hippocampal mossy fibers in Sprague-Dawley rats continuously exposed to either 125 ppm Aroclor 1254 or untreated control food beginning in utero. Reduced growth of hippocampal intra-and infra-pyramidal (II-P) mossy fibers were found in PCB treated rats compared to controls. Other measured hippocampal subdivisions remained relatively unaffected by PCB treatment, as did cortical thickness. The changes observed in hippocampal morphology in response to PCB exposure are the first to provide a potential explanation for at least part of the long-term PCB-induced cognitive deficits.

Abstract  The effects of technical polychlorinated biphenyl (PCB) preparations on urinary excretion of cortisol and estrone-sulfate in pregnant minks were investigated. Female minks (Mustela-vison) were administered diets containing: 2 milligrams (mg) Clophen-A50 (8068448); clophen fractions consisting of PCBs containing one to four chlorine atoms substituted in the ortho position (noncoplanar PCBs) or nonortho substituted PCBs (planar PCBs); a synthetic mixture of planar PCBs; or a mixture of polychlorinated naphthalenes and dibenzofuran contaminants (contaminant fraction) for 84 to 96 days (experiment-I). Other minks were fed diets containing 1.64mg aroclor-1254 (11097691) and the analogous fractions used in experiment-I for 79 to 94 days (experiment-II). Animals in both experiments were mated 4 to 6 weeks after the start of dosing. Dosing was continued up to 5 days postpartum. In experiment-I, all groups excreted similar amounts of cortisol for 10 to 15 days after mating. In clophen fed minks, significantly elevated amounts of cortisol were excreted about 30 days before delivery. Cortisol excretion in minks fed the contaminant fraction was also increased 25 and 30 days before delivery. Estrone-sulfate excretion was significantly increased only in clophen fed animals 10 days before to 5 days after delivery. In experiment-II, aroclor-1254 fed minks excreted significantly larger amounts of cortisol than the other groups 33 to 29 days before delivery. Excretion of cortisol by mink fed fractions containing planar and noncoplanar PCBs was significantly increased 32 and 21 to 25 days before delivery. All groups showed increased excretion of estrone-sulfate between 42 and 17 days before delivery. The increases were progressive and similar in all groups. The authors conclude that PCB feeding during certain stages of pregnancy increases urinary excretion of cortisol and estrone-sulfate in minks. When comparing with previous fetal resorption data, the study data indicate that the ovary or corpus luteum may be the source of urinary estrone-sulfate.

Abstract  Polychlorinated biphenyls (PCBs) are ubiquitous and persistent environmental contaminants that disturb normal endocrine functions, including gonadal functions in humans and mammals. PCBs (Aroclor 1254) - induced toxic manifestations are associated with the production of free radicals. Lycopene belongs to the group of natural carotenoids, which are found in many fruits, vegetables and other green plants. Lycopene, the most potent antioxidant protects against oxidative damage. The present study was conducted to elucidate the protective role of lycopene against Aroclor 1254-induced changes in Leydig cellular steroidogenic acute regulatory (StAR) protein, cytochrome P450 side chain cleavage (P450 scc) enzyme expression and 3beta-hydroxy steroid dehydrogenase (3beta-HSD) activity. The rats were divided into four groups. Each group consists of six animals. Group I rats were administered with corn oil intraperitoneally (i.p.) for 30 days. Group II rats were treated with Aroclor 1254 (i.p.) 2mgkg(-1)body weight (bwt)day(-1) for 30 days. Group III rats were treated with Aroclor 1254 (i.p.) 2mgkg(-1)bwtday(-1) along with simultaneous supplementation of lycopene 4mgkg(-1)bwtday(-1) (gavage) for 30 days. Group IV rats administered with lycopene alone at the dose of 4mgkg(-1)bwt day(-1) (gavage) for 30 days. After 24h of the last treatment, animals were decapitated, blood was collected and serum testosterone level was estimated by radioimmunoassay (RIA). Testes were removed and Leydig cells were isolated in aseptic condition. StAR protein, cytochrome P450 scc enzyme expression were studied by Western blot analysis and 3beta-HSD activity was estimated spectrophotometrically. Aroclor 1254 treatment significantly reduced the serum testosterone level. Simultaneous supplementation of lycopene maintained the serum testosterone to near normal. Aroclor 1254 exposure decreased Leydig cellular StAR protein, cytochrome P450 scc enzyme expression and activity of 3beta-HSD. However, simultaneous supplementation of lycopene improved Leydig cellular StAR protein, cytochrome P450 scc expression and activity of 3beta-HSD. These results suggested that lycopene have ameliorative role against Aroclor 1254 induced Leydig cell dysfunction.

Abstract  3,3′,4,4′-Tetrachlorobiphenyl (TCBP) was administered orally to adult female Sprague–Dawley rats in the oral dosage regimen, 5 mg∙kg−1∙day−1 for 21 days, followed by a 22-day postdosing period. Control animals received either the corn-oil vehicle (1 mL∙kg−1∙day−1) or no treatment. 3,3′,4,4′-TCBP distributed preferentially into the adipose tissue and liver, and apparent steady-state xenobiotic concentrations were attained in the adipose tissue (8 μg/g) and liver (300 ng/g) prior to the cessation of dosing. The 3,3′,4,4′-TCBP concentrations in the serum, brain, kidneys, and thymus gland were lower and more variable than those in the adipose tissue and liver. During the postdosing period, 3,3′,4,4′-TCBP was eliminated from the adipose tissue and liver by apparent first-order kinetics with elimination half-life values of 2.5 days and 0.8 day, respectively. The major route of excretion of unmetabolized 3,3′,4,4′-TCBP was via the feces, and the amount excreted over 24 h did not exceed 8% of the dose administered on any given day. Throughout the experiment, there were no differences in the body weight or food and water intake for the 3,3′,4,4′-TCBP-treated animals compared with the corn-oil-treated and nontreated rats. There was a significant increase in liver weight and a significant decrease in thymus gland weight for the 3,3′,4,4′-TCBP-treated rats compared with the corn-oil-treated rats at the cessation of dosing and at 11 days thereafter, but there were no observable histological changes in these organs as assessed by light microscopy. By the end of the postdosing period, there were no significant differences in the liver and thymus gland weights among the 3,3′,4,4′-TCBP-treated, corn-oil-treated, and non-treated rats. Hepatic microsomal cytochrome P-450 content was significantly greater for the 3,3′,4,4′-TCBP-treated rats compared with the corn-oil-treated animals at the end of the dosing period and during the subsequent postdosing period.

Abstract  Polychlorinated biphenyls (PCBs) are persistent environmental pollutants. Two PCB mixtures, Aroclors 1221 and 1254 have been suggested to have estrogenic and anti-estrogenic properties, respectively. We have examined whether these PCB mixtures modulate bone turnover and vertebral histology in intact and ovariectomized (ovx) rat models. Thirty-two adult female rats were divided into four groups subcutaneously receiving 4% DMSO (control), A1221 (10 mg/kg), A1254 (10 mg/kg) oestradiol (E2, 30 microg/kg). These compounds were injected to the animals for a period of 6 weeks at two daily intervals. In the second model, rats (n=32) were ovx and allowed to recover for a period of 3 weeks. Control group received vehicle (4% DMSO) alone. Remaining rats were divided into three groups and injected (s.c.) with A1221, A1254 and E2 for 5 weeks. Urine samples were collected prior to end of the experiments. Then, all animals were decapitated. Serum parathyroid hormone (PTH), calcitonin and osteocalcin levels were determined by immunoradiometric method. Serum concentrations of alkaline phosphatase (ALP), calcium and inorganic phosphate were determined by enzymatic-colorimetric method. Urinary deoxypyridinoline (DPD) was measured by ELISA. Lumbar vertebrae (L2) of all animals were dissected out and processed for light microscopy. Levels of urinary DPD were significantly lowered in E2 -treated intact rats (p<0.001). Ovx significantly increased urinary DPD excretion (p<0.01) compared to intact control values. Administration of A1221 and A1254 had no significant effects in intact rats, however, they significantly reduced (p<0.05) and increased (p<0.001) urinary DPD levels in ovx rats, respectively. Neither of the PCB mixtures significantly changed serum osteocalcin and ALP levels in intact or ovx rats (except A1221 increased ALP in intact model, p<0.01). Both PCB mixtures had differential effects on serum PTH, calcitonin, calcium and inorganic phosphate concentrations. Treatment with A1221 reversed the adverse effects of ovariectomy on L2 histology. However, A1254 produced necrotic areas in vertebral bone, and this effect was expanded in ovx animals. Our findings suggest that both Aroclor compounds interfere with bone turnover mechanisms, particularly in ovx rats.

Abstract  PCB153, one of the 3 dominant congeners in the food chain, causes the disruption of the endocrine system in humans and animals. In order to elucidate the effects of PCB153 on the biosynthesis, biotransformation, regulation, metabolism, and transport of thyroid hormones (THs), Sprague-Dawley (SD) rats were dosed with PCB153 intraperitoneally (i.p.) at 0, 4, 16 and 32 mg/kg/day for 5 consecutive days and sacrificed 24 h after the last dose. Results showed that after treatment with PCB153, serum total thyroxine (TT4), total triiodothyronine (TT3), and thyrotropin releasing hormone (TRH) decreased, whereas serum thyroid stimulating hormone (TSH) concentration did not alter. The serum sodium iodide symporter (NIS), thyroid peroxidase (TPO), and thyroglobulin (Tg) levels decreased. The mRNA expressions of type 2 and 3 deiodinases (D2 and D3) reduced, but the type 1 deiodinase (D1) showed no significant change. The TSH receptor (TSHr) and TRH receptor (TRHr) levels declined. PCB153 induced hepatic enzymes, and the UDPGTs, CYP2B1, and CYP3A1 mRNA levels were significantly elevated. Taken together, the observed results from the present study indicated that PCB153 disrupted thyroid hormone homeostasis through influencing synthesis-associated proteins (NIS, TPO and Tg), deiodinases, receptors (TSHr and TRHr), and hepatic enzymes, and the decrease of D3 expression might be the compensatory response of body.

Abstract  The present study assessed if eating a diet of fish, spiked with persistent organic pollutants (POPs), affects gene and protein expression in the maturing mouse brain. Juvenile female Balb/c mice (22 days of age) were exposed for 28 days to fish-based diets spiked with the dioxin 2,3,7,8-tetrachlorodibenzodioxin (TCDD) or the non dioxin-like (NDL) chemicals hexabromocyclodocecane (HBCD), 2,2'4,4'-tetrabromodiphenylether (BDE-47) or 2,2'4,4',5,5'-hexachlorobiphenyl (CB-153) at doses approximating their respective lowest observed adverse effect levels (LOAEL). It was found that all POPs elicited changes in neural gene and protein expression profiles. Bioinformatic analysis of gene expression data highlighted the importance of the aryl hydrocarbon receptor (AHR) in dioxin toxicity and revealed that zinc regulation in the brain is targeted by TCDD through the AHR. Calcium homeostasis was affected by both TCDD and the NDL chemicals. In contrast to the transcriptomic analysis, the proteomics data did not allow for a clear distinction between DL and NDL responses in the juvenile brain but indicated that proteins associated with excitotoxicity were affected in all exposure groups. Integrated interpretation of data led to the conclusion that the dietary contaminants investigated in the present study breach the blood brain barrier (BBB) and accumulate in the juvenile brain where they may induce excitotoxic insults by dysregulation of the otherwise tightly controlled homeostasis of calcium and zinc. Overall, the findings of the present study highlight the need for further assessment of the risks associated with early life exposure to foodborne POPs.

Abstract  HEEP COPYRIGHT: BIOL ABS. Sixty female white-footed mice (Peromyscus leucopus) were fed either ad lib or 70% ad lib diets for 5 wk. During the last 3 wk of feeding a polychlorinated biphenyl (Aroclor 1254) was incorporated into the diets at levels of 0, 25 or 100 ppm (based on ad lib intake). Polychlorinated biphenyl ingestion increased liver weights, reduced pentobarbital-induced sleep times, and generally reduced plasma corticoid levels but had no effect on reproductive organ weights or the incidence of estrus (as judged by vaginal smears). Feed restriction caused marked atrophy of the ovaries and uterus and reduced the incidence of estrus.