Effects Of Polybrominated Biphenyls Research Articles

Previously identified and unidentified polybrominated biphenyl congeners in serum from people living in an electronic waste dismantling area in China

The effects of polybrominated biphenyls (PBBs) on human health have previously attracted much attention, but recent studies of PBBs have been focused on BB-153 and a few other congeners. PBB concentrations in serum samples from residents of an area containing an electronic waste dismantling site were determined in this study. The total PBB concentrations (i.e., the sums of the concentrations of the 35 PBB congeners) were 229–1360 ng/g lipid. The BB-153 concentrations were markedly higher in the samples from people living in the electronic waste dismantling area than in samples from people living in a nearby control area. BB-153 was found in all of the samples from the study exposure area but the concentrations were relatively low (0.07–4.70 ng/g lipid). High BB-1 concentrations were found for the first time in serum from people living in both the electronic waste dismantling and control areas. The BB-1 concentrations were 211–1280 ng/g lipid. The retention times of the 35 PBB standards and PCBs (polychlorinated biphenyls) with similar structures were used to predict the retention times of unidentified PBB congeners to allow the PBB distributions in the serum samples to be identified. A total of 26 previously unidentified PBB congeners were identified in the human serum samples. BB-5, BB-35, BB-79, and BB-109 were found in >50% of the samples. The PBB patterns in the serum samples were different from the patterns previously found in serum after a PBB contamination incident in 1973, so the health risks currently posed by PBBs are worth studying.

The effects of polybrominated biphenyls and perchlorinated terphenyls on in vitro fertilization in the mouse.

Polybrominated biphenyls (PBBs) and perchlorinated terphenyls (PCTs) are industrial chemicals that are long-lasting environmental contaminants. Although in vivo effects of PBBs on reproduction are documented, no information is available on the effects of these chemicals on sperm-egg interactions or fertilization. The present study was undertaken to determine the toxic potential of PBBs and PCTs on in vitro fertilization (IVF) in the mouse. 2-Bromobiphenyl, 4-bromobiphenyl, o-terphenyl, m-terphenyl, and p-terphenyl were added to the IVF medium at various concentrations. Oocytes collected from superovulated B6D2F1 mice were maintained in a medium containing the chemicals. Capacitated sperm were then added and the dishes cultured in a humidified atmosphere at 37 degrees C in 5% CO2 + 95% air. Oocytes were assessed for fertilization 20-24 h after insemination. polybrominated biphenyls and PCTs reduced the IVF rate at the higher dosages. Furthermore, an increased incidence of abnormal two-cell embryos and degenerative oocytes was observed at the 1 and 10 micrograms/ml concentrations of PBBs and PCTs. These results indicate that PBBs and PCTs adversely effect IVF and increase the incidence of abnormal embryos and oocyte degeneration in the mouse.

Effects of polybrominated biphenyls upon rat urinary protein patterns as detected by two-dimensional electrophoresis

Five-month-old female Sherman rats were dosed by gavage with 0 or 500 mg of Firemaster BP-6 (polybrominated biphenyls, PBBs) per kg body weight as a 5% solution in corn oil and then maintained on normal diet and waterad libitum. Urine pools from test and control groups of five fasting rats were collected once a month, up to 179 days after the test rats were dosed. PBB-dosed animals showed significantly higher (p=0.0003) creatinine-corrected proteinuria. Two-dimensional electrophoresis (2DE) and silver staining were used to determine differences in urinary protein patterns between test and control rats. Dosed animals excreted new proteins with higher molecular weight and more basic isoelectric points than controls. The appearance of numerous, new proteins excreted by the PBB-dosed rats demonstrates the utility of 2DE for the sensitive detection of possible health effects from toxicant exposure.

Effects of polybrominated biphenyls on metabolism of testosterone by rat hepatic microsomes

Polybrominated biphenyls (PBBs) have produced alterations in the male reproductive system of several species. These alterations may be a consequence of modified metabolism of androgens. The purpose of this investigation was to determine the effects of PBBs on hepatic microsomal metabolism of testosterone in vitro. Hepatic microsomes were prepared from male and female rats exposed to 0 or 100 ppm PBBs from Day 8 of gestation until they were killed at 1, 2, or 4 months of age. Testosterone and its metabolites were identified and quantified utilizing high-performance liquid chromatography or gas-liquid chromatography. Steroid identification was confirmed with gas chromatography/mass spectrometry. Hydroxylation of testosterone to 7α- and 6β-hydroxytestosterone in microsomes from both sexes at all ages was increased by pretreatment with PBBs. Microsomal conversion of testosterone to 16 α-hydroxytestosterone and androstenedione was enhanced by PBBs in females at all ages and in 1 month-old males but not from males of 2 and 4 months of age. Reduction of testosterone to dihydrotestosterone and dihydroandrosterone was inhibited in microsomes from both sexes at all ages by pretreatment with PBBs. These results support the contention that the effects of PBBs on the male reproductive system may be due, at least in part, to altered metabolism of testosterone.

Effect of Polybrominated Biphenyls (PBB) on the Pituitary-Thyroid Axis of the Rat

AbstractThe effects of polybrominated biphenyls (PBB) on the pituitary-thyroid axis were investigated in male rats. PBB was administered by gavage for 20 days at 1, 3, or 6 mg/kg/day; controls were gavaged with vehicle alone. PBB treatment had no effect on body weight. There was a definite time- and dose-dependent reduction in plasma thyroxine (T4) levels after 10 and 20 days of PBB administration. Reduced plasma T4 levels were correlated with increased plasma TSH levels at 20 days. In rats treated with 6 mg/kg PBB, an increase in 5-hr thyroidal 131I uptake was seen, with a decrease in 131I incorporation into monoiodotyrosine and an increase in intrathyroidal iodine. In contrast to propylthiouracil, acute administration of PBB had little effect on intrathyroidal radioiodine accumulation and incorporation into iodoamino acids. Liver and thyroid weights remained elevated at 2 and 5 months after the last 1 and 3 mg/kg PBB administration, respectively, and plasma T4 levels were significantly lower than contro...

Altered metabolism of progesterone by hepatic microsomes from rats following dietary exposure to polybrominated biphenyls

Polybrominated biphenyls (PBBs) have produced a variety of effects including alterations in the endocrine system and in activity of microsomal mixed function oxidases (MFOs). Since steroid sex hormones are substrates for MFOs, certain effects of PBBs on the endocrine system may be a consequence of enhanced steroid sex hormone catabolism. Therefore, the purpose of this investigation was to determine the effects of PBBs on hepatic microsomal metabolism of progesterone in vitro. Hepatic microsomes were prepared from rats exposed to 0 or 100 ppm PBBs from Day 8 of gestation until they were killed at 4 (male and female), 12 (male), or 21 (female) weeks of age. Progesterone and its metabolites were identified and quantified utilizing high-pressure liquid chromatography and/or thin-layer chromatography with liquid scintillation spectrometry. Steroid identification was confirmed with gas chromatography/mass spectrometry. Metabolism of progesterone to 16α- or 6β-hydroxyprogesterone was increased by pretreatment with PBBs. Effects of PBBs on progesterone metabolism were dependent on sex. Alterations in metabolism of progesterone by PBBs were compared to effects of phenobarbital or 3-methylcholanthrene. Stimulation of hepatic 16α- and 6β-progesterone hydroxylase following PBBs resembled that produced by phenobarbital. These results support the contention that effects of PBBs on the endocrine system may be due, at least in part, to accelerated metabolism of steroid sex hormones.

Animal toxicology

Animal toxicology

Effects of polybrominated biphenyls on kidney function and activity of renal microsomal enzymes.

Polybrominated biphenyls (PBBs) cause hepatic microsomal enzyme stimulation and histopathological alterations in several organs, including kidney. Concern about effects of PBBs on the health of newborns has increased after the discovery of PBBs in milk of nursing mothers. Therefore, it was of interest to investigate the effects of PBBs on kidney function and the activity of renal microsomal enzymes in adult and immature animals. Seven and eleven day old pups were treated with a single IP injection of either peanut oil or 150 mg/kg PBBs (FireMaster BP-6) in peanut oil. Adult virgin rats were fed diet containing 0 or 100 ppm PBBs for 30 or 90 days. Treatment with PBBs only retarded weight gain after 90 days exposure. Kidney-to-body weight ratio was not altered by PBBs. Arylhydrocarbon hydroxylase activity was increased while epoxide hydratase activity was decreased (adults) or not affected (immature rats) in kidney following treatment with PBBs. Administration of PBBs had no effect on blood urea nitrogen, the clearance of inulin, p-aminohippurate (PAH), or fractional sodium excretion. Similarly, the in vitro accumulation of PAH and N-methylnicotinamide (NMN) by thin renal cortical slices and ammoniagenesis and gluconeogenesis in renal cortical slices were not affected by PBBs. In conclusion, treatment with PBBs resulted in modification of the activity of renal microsomal enzyme activities but had no detectable effect on renal function.

Effects of polybrominated biphenyls (PBB) on immune response in rodents.

Studies were performed to investigate the effects of FireMaster FF-1, a chemical fire retardant consisting of a mixture of polybrominated biphenyls (PBB), on immune functions in mice and rats. Animals received 22 daily treatments of 0.03, 0.3, 3.0, or 30 mg PBB/kg body weight in a period covering 30 days. PBB exposure severely depressed cell mediated immunity in both mice and rats at the higher dosage levels as indicated by depressed responsiveness of splenic lymphocytes to mitogenic stimulation by polyclonal T-cell activators. Additionally, humoral immunity was depressed in mice at the 30.0 ppm dosage level. Assays for humoral immune functions included antibody production, serum immunoglobulin levels, and mitogenic stimulation of splenic lymphocytes to a polyclonal B-cell activator. These studies indicate that PBB exposure can lead to suppression of both humoral and particularly cell-mediated immune responses.

Effects of PBBs on cattle. I. Clinical evaluations and clinical chemistry.

Toxicosis was induced in pregnant heifers by feeding 25,000 mg/head/day of FireMaster BP-6, a commercial blend of polybrominated biphenyls (PBB). The PBB feeding decreased dry matter intake approximately 50% by 4 days exposure. Emaciated animals became anorexic a few days prior to death at 33 to 66 days. Weight losses of heifers average 80 kg. Other clinical signs observed were dehydration, diarrhea, excessive salivation and lacrimation, fetal death, abortion, and general depression as evidenced by depressed heart and respiratory rates. Clinical signs were apparent after 10 days exposure and progressively intensified along with loss of condition until death. Clinicopathologic changes included significantly increased serum glutamic-oxaloacetic transaminase and decreased serum calcium by 30 days exposure. Lactate dehydrogenase, urea nitrogen, and bilirubin were elevated, and serum albumin decreased by 36 to 40 days. Principal urine changes were decreased specific gravity and moderate proteinuria. Pregnant heifers fed 0.25 or 250 mg/head/day for 60 days and nonpregnant heifers fed 250 mg/head/day for 180 days displayed neither clinical signs nor clinicopathologic changes indicating adverse effects from PBB exposure. Post-exposure, all heifers exposed to PBB for 60 days calved normally with zero calf mortality and were successfully rebred. Milk production was not different from control animals. Birth weights of calves from dams exposed to 250 mg PBB/head/day were significantly greater than calves of dams exposed to 0 mg or 0.25 mg/head/day. PBB exposure of dams produced no detrimental effects on calves as indicated by clinical signs, clinicopathologic changes, or performance.

Effects of PBBs on Cattle. I. Clinical Evaluations and Clinical Chemistry

Toxicosis was induced in pregnant heifers by feeding 25,000 mg/head/day of FireMaster BP-6, a commercial blend of polybrominated biphenyls (PBB). The PBB feeding decreased dry matter intake approximately 50% by 4 days exposure. Emaciated animals became anorexic a few days prior to death at 33 to 66 days. Weight losses of heifers average 80 kg. Other clinical signs observed were dehydration, diarrhea, excessive salivation and lacrimation, fetal death, abortion, and general depression as evidenced by depressed heart and respiratory rates. Clinical signs were apparent after 10 days exposure and progressively intensified along with loss of condition until death. Clinicopathologic changes included significantly increased serum glutamic-oxaloacetic transaminase and decreased serum calcium by 30 days exposure. Lactate dehydrogenase, urea nitrogen, and bilirubin were elevated, and serum albumin decreased by 36 to 40 days. Principal urine changes were decreased specific gravity and moderate proteinuria. Pregnant heifers fed 0.25 or 250 mg/head/day for 60 days and nonpregnant heifers fed 250 mg/head/day for 180 days displayed neither clinical signs nor clinicopathologic changes indicating adverse effects from PBB exposure. Post-exposure, all heifers exposed to PBB for 60 days calved normally with zero calf mortality and were successfully rebred. Milk production was not different from control animals. Birth weights of calves from dams exposed to 250 mg PBB/head/day were significantly greater than calves of dams exposed to 0 mg or 0.25 mg/head/day. PBB exposure of dams produced no detrimental effects on calves as indicated by clinical signs, clinicopathologic changes, or performance.

Effect of polybrominated biphenyls on renal tubular transport of organic ions

Polybrominated biphenyls (PBBs) entered the food supply in 1973 and have since been shown to be toxic to animals. PBBs stimulate renal mixed function oxidase in developing rats. Since the renal organic ion transport systems are important in the elimination of several xenobiotics from plasma, further investigations of the renal effects of PBBs were conducted. Adult female rats were given a single intraperitoneal injection of 130–165 mg PBBs/kg body weight. After J day there was a significant increase in total liver lipids. The liver weight/body weight ratio was higher after 8 days in the PBB‐treated animals. These changes were still apparent 48 days after injection, when the study was terminated. Kidney weight was not altered by treatment, nor was accumulation by renal cortical slices of the organic base N‐methylnicotinamide (NMN). Uptake of the organic acid p‐aminohippuric acid (PAH) appeared to be elevated throughout the study, but this was only significant at 32 days after injection. Direct exposure of ...

Stimulation of hepatic microsomal metabolism in mice by a mixture of polybrominated biphenyls

The pattern of stimulation of hepatic microsomal mixed function oxidases has been studied in female NMRI mice following a single ip injection of 150 mg/kg polybrominated biphenyls (PBBs) and compared to the patterns produced by phenobarbital (PB), 3 X 100 mg/kg; 3-methylcholanthrene (MC), 3 X 20 mg/kg; and these two agents administered together at these doses. Cytochrome P450, ethylmorphine N-demethylase, and epoxide hydratase reached maximums of 200, 200, and 350% of control values, respectively, at 48 hr after treatment with PBBs. Ethoxycoumarin O-deethylase and arylhydrocarbon hydroxylase were maximally increased to 400 and 180% of control values, respectively, 96 hr after PBBs. The reduced cytochrome P450 ethylisocyanide difference spectra and the inhibition of ethoxycoumarin O-deethylase and arylhydrocarbon hydroxylase activity by metyrapone and alpha-naphthoflavone indicated that the characteristics of the cytochrome P450 and the cytochrome P450-dependent enzymes changed with time after administration of PBBs. These results indicate that the enzyme-stimulating properties of PBBs alter, changing from PB-like to MC-like, with time after administration. These findings provide an explanation for the effects of PBBs on the toxicity of bromobenzene, indicating that PBBs represent a new and previously unrecognized calss of toxicity-modifying agents sharing properties of both PB and MC.