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Environmental Health Perspectives May 1985Commercial mixtures of polychlorinated biphenyls (PCBs) and polybrominated biphenyls (PBBs) can cause hepatocellular carcinoma in rats and mice. Present evidence... (Review)
Review
Commercial mixtures of polychlorinated biphenyls (PCBs) and polybrominated biphenyls (PBBs) can cause hepatocellular carcinoma in rats and mice. Present evidence indicates that these chemicals act as promoters and not initiators of hepatocarcinogenesis. Our results show that Firemaster BP-6 (FM) and its nontoxic major congener, 2,2', 4,4', 5,5'-hexabromobiphenyl (HBB), act as promoters in the two-stage model for hepatocarcinogenesis devised by Pitot and associates. A toxic congener, 3,3', 4,4', 5,5'-HBB, also was assessed for tumor-promoting activity. This congener, though not in FM, is similar to TCDD, in that both cause 3-methylcholanthrene (MC)-type induction of hepatic microsomal enzymes and produce similar toxic responses. FM contains several congeners which are mixed-type inducers in that they induce MC-type and phenobarbital (PB)-type enzymes. The toxicity of FM is most likely associated with its congeners which are mixed-type inducers and not to relatively nontoxic congeners such as 2,2', 4,4', 5,5'-HBB which are strictly PB-type inducers. Congener 3,3', 4,4', 5,5'-HBB acted as a tumor promoter only at a dose that was hepatotoxic. A synergistic effect on tumor promoting ability was produced by combining a nontoxic and nonpromoting dose of 3,3', 4,4', 5,5'-HBB with a promoting dose of 2,2', 4,4', 5,5'-HBB. Our results suggest that synergism between toxic and nontoxic congeners in FM may explain why mixtures such as FM have greater promoting ability than individual congeners. Our results also indicate that with PBB, toxicity and carcinogenicity are not necessarily related.
Topics: Animals; Cocarcinogenesis; Drug Synergism; Liver Neoplasms, Experimental; Mice; Polybrominated Biphenyls; Polychlorinated Biphenyls; Rats
PubMed: 2992924
DOI: 10.1289/ehp.856035 -
Environmental Health Perspectives Apr 1981Chronic ingestion of modest doses of dietary iodine, radiation, and polyhalogenated biphenyls (PCB's and PBB's) are environmental factors with known or suspected adverse... (Review)
Review
Chronic ingestion of modest doses of dietary iodine, radiation, and polyhalogenated biphenyls (PCB's and PBB's) are environmental factors with known or suspected adverse effects on the human thyroid. Iodine consumption in the United States is approaching 1 mg daily for a large segment of the population. Data are reviewed which support the need for concern regarding the long-term adverse effects of dietary iodine on thyroid function, particularly in certain susceptible individuals. Environmental sources of radiation pose a significant risk of thyroid cancer and hypothyroidism under certain circumstances which may be intentional, inadvertent, or accidental. Exposure to polyhalogenated biphenyls during manufacture or as industrial pollutants are hazardous to man and to wildlife in moderate or large quantities and perhaps also in small amounts. The need to investigate the potential harm posed by these factors in the quantities commonly encountered is emphasized.
Topics: Adolescent; Adult; Child; Diet; Environment; Goiter; Graves Disease; Humans; Hypothyroidism; Iodine; Polybrominated Biphenyls; Polychlorinated Biphenyls; Thyroid Diseases; Thyroid Gland; Thyroid Neoplasms; Thyroiditis, Autoimmune
PubMed: 6263611
DOI: 10.1289/ehp.813871 -
National Toxicology Program Technical... Jun 1983Firemaster FF-1, a flame retardant composed of polybrominated biphenyls (PBB), was responsible for widespread environmental contamination and animal losses in Michigan...
Firemaster FF-1, a flame retardant composed of polybrominated biphenyls (PBB), was responsible for widespread environmental contamination and animal losses in Michigan starting in 1973. This study was undertaken to characterize the long-term toxic and carcinogenic potential of this PBB mixture in rats and mice of each sex. Fisher 344/N rats and B6C3F1 mice were given 125 oral doses of PBB over a 6-month period--0, 0.1, 0.3, 1.0, 3.0, or 10.0 mg/kg body weight/day (5 days/week). A dose-related decrease in body weight gain was observed in both male and female rats and male mice, although there was no significant difference in food consumption. At the end of the 6-month exposure, there was a dose-dependent decrease in thymus weights in rats. The liver appeared to be the primary target organ. Dose-related hepatotoxic effects were characterized by a marked increase in liver weight, with accentuation of hepatic lobular markings. Microscopically, there was moderate to marked hepatocellular swelling, disorganization and single cell necrosis of hepatocytes, fatty infiltration, and bile duct proliferation. At the 6-month observation, atypical hepatocellular foci were observed at a low incidence in dosed rats and mice. Hepatic porphyrin levels were markedly increased in both rats and mice, excessively in females. Levels of porphyrin tended to decrease gradually, primarily in mice, following cessation of exposure. The significant decreases in serum thyroxine (T4) and triiodothyronine (T3) in rats suggest that PBB may interfere with thyroid hormone secretion. Total serum protein was decreased in dose-related fashion in female rats primarily due to dose-related decreases in albumin. There was a significant increase in the serum levels of gamma glutamyl transpeptidase (GGTP) in female rats given 10.0 mg/kg of PBB. There was a dose-related decrease in serum glucose in female rats, a dose-related decrease in the serum triglyceride level in dosed male rats, except at the lowest dose (0.1 mg/kg), and a dose-related increase in the serum levels of cholesterol in both male and female rats. Serum levels of GGTP were increased only in female mice given 10.0 mg/kg of PBB. There was a 5- to 6-fold increase in the activity of serum glutamic pyruvic transaminase (SGPT) in male and female mice in the 10.0 mg/kg groups. Serum enzyme activity of alkaline phosphate (AP) was also increased in mice given the highest dose of PBB. There was a significant dose-related increase in the serum levels of cholesterol in female mice, and the highest dose group was significantly greater than the control female mice. Serum glucose was significantly decreased in female mice administered 10.0 mg/kg of PBB. To determine the carcinogenic potential of PBB, rats and mice dosed for 6 months were observed without exposure to PBB for an additional 23 or 24 months, respectively (lifetime observation). The dosing (0.3 mg/kg or higher dose levels) shortened the survival time in male rats, whereas no such effect was observed in dosed females. There was also evidence of shortened survival time in the 10.0 mg/kg PBB-dosed mice. A significantly higher incidence of atypical hepatocellular foci, neoplastic nodules, hepatocellular carcinomas, and cholangiocarcinomas was observed in dosed rats. The incidence of hepatocellular carcinoma was increased in both male and female mice (highest dose level) compared with control male and female mice. The incidence of hepatic neoplasms appeared to be dose dependent in rats and mice. Liver tumors were observed primarily in those groups of animals to which PBB was given in doses sufficient to induce readily observable hepatic toxicity. Under the conditions of these studies, polybrominated biphenyl mixture (Firemaster FF-1) was carcinogenic for Fisher 344/N rats and B6C3F1 mice of each sex, inducing neoplastic nodules, hepatocellular carcinomas, and cholangiocarcinomas in rats and hepatocellular carcinomas in mice. Other toxicities included porphyrogenic effects and hepatotoxicity. Levels of Evidence of Carcinogenicity: Male Rats: Positive Female Rats: Positive Male Mice: Positive Female Mice: Positive Synonym: Firemaster FF-1
PubMed: 12750749
DOI: No ID Found -
Molecules (Basel, Switzerland) Mar 2023Tetrabromobisphenol A (TBBPA) is a known endocrine disruptor employed in a range of consumer products and has been predominantly found in different environments through... (Review)
Review
Tetrabromobisphenol A (TBBPA) is a known endocrine disruptor employed in a range of consumer products and has been predominantly found in different environments through industrial processes and in human samples. In this review, we aimed to summarize published scientific evidence on human biomonitoring, toxic effects and mode of action of TBBPA in humans. Interestingly, an overview of various pretreatment methods, emerging detection methods, and treatment methods was elucidated. Studies on exposure routes in humans, a combination of detection methods, adsorbent-based treatments and degradation of TBBPA are in the preliminary phase and have several limitations. Therefore, in-depth studies on these subjects should be considered to enhance the accurate body load of non-invasive matrix, external exposure levels, optimal design of combined detection techniques, and degrading technology of TBBPA. Overall, this review will improve the scientific comprehension of TBBPA in humans as well as the environment, and the breakthrough for treating waste products containing TBBPA.
Topics: Humans; Biological Monitoring; Flame Retardants; Polybrominated Biphenyls
PubMed: 36985477
DOI: 10.3390/molecules28062505 -
Environmental Health Perspectives Sep 1985Halogenated aromatic xenobiotics such as the chlorinated and brominated biphenyls, naphthalenes, dibenzodioxins, and dibenzofurans are widespread environmental... (Review)
Review
Halogenated aromatic xenobiotics such as the chlorinated and brominated biphenyls, naphthalenes, dibenzodioxins, and dibenzofurans are widespread environmental contaminants. The number, position, and nature of the halogen atoms as well as the structure of the aromatic rings influence the disposition of these chemicals in living systems. Absorption is governed primarily by the physical properties of lipophilicity and solubility. Distribution through the blood occurs by nonspecific binding to plasma proteins and cellular components. Liver and adipose tissue are the major depots. Metabolism is a prerequisite for excretion. The highly substituted isomers tend to be resistant to metabolism. The route of excretion shifts from urine to feces with increasing size and number of halogen atoms. Although pharmacokinetic modeling has allowed some predictions to be made from one compound to another or across species, more information on metabolism is required in order to improve the ability to predict the disposition in humans of this class of toxic environmental pollutants.
Topics: Absorption; Adipose Tissue; Animals; Benzofurans; Cricetinae; Dibenzofurans, Polychlorinated; Dogs; Environmental Pollutants; Guinea Pigs; Hydrocarbons, Halogenated; Kinetics; Liver; Mice; Naphthalenes; Polybrominated Biphenyls; Polychlorinated Biphenyls; Polychlorinated Dibenzodioxins; Rats; Solubility; Structure-Activity Relationship; Tissue Distribution
PubMed: 2998745
DOI: 10.1289/ehp.856111 -
Postepy Higieny I Medycyny... May 2013Development of the chemical industry leads to the development of new chemical compounds, which naturally do not exist in the environment. These chemicals are used to... (Review)
Review
Development of the chemical industry leads to the development of new chemical compounds, which naturally do not exist in the environment. These chemicals are used to reduce flammability, increase plasticity, or improve solubility of other substances. Many of these compounds, which are components of plastic, the new generation of cosmetics, medical devices, food packaging and other everyday products, are easily released into the environment. Many studies have shown that a major lipophilicity characterizes substances such as phthalates, BPA, TBBPA and PCBs. This feature allows them to easily penetrate into living cells, accumulate in the tissues and the organs, and affect human and animal health. Due to the chemical structures, these compounds are able to mimic some endogenous hormones such as estradiol and to disrupt the hormone homeostasis. They can also easily pass the placental barrier and the blood-brain barrier. As numerous studies have shown, these chemicals disturb the proper functions of the nervous system from the earliest moments of life. It has been proven that these compounds affect neurogenesis as well as the synaptic transmission process. As a consequence, they interfere with the formation of the sex of the brain, as well as with the learning processes, memory and behavior. Additionally, the cytotoxic and pro-apoptotic effect may cause neurodegenerative diseases. This article presents the current state of knowledge about the effects of phthalates, BPA, TBBPA, and PCBs on the nervous system.
Topics: Animals; Benzhydryl Compounds; Blood-Brain Barrier; Chemical Industry; Environmental Pollutants; Humans; Nervous System; Phenols; Phthalic Acids; Plastics; Polybrominated Biphenyls; Polychlorinated Biphenyls
PubMed: 23752602
DOI: 10.5604/17322693.1051001 -
Regulatory Toxicology and Pharmacology... Mar 2019Tetrabromobisphenol A (TBBPA) is a flame retardant used in a variety of products, including epoxy and polycarbonate resins. Relevant exposure to TBBPA has been assessed...
Tetrabromobisphenol A (TBBPA) is a flame retardant used in a variety of products, including epoxy and polycarbonate resins. Relevant exposure to TBBPA has been assessed by measuring TBBPA in the blood of humans. Here, we derive Biomonitoring Equivalents (BEs) for TBBPA to interpret these, and future biomonitoring results for TBBPA in humans. The available toxicity risk values (TRVs) for TBBPA were all based on toxicology studies in rats. Several studies have been conducted in which TBBPA in blood of rats were measured following controlled oral doses of TBBPA. These data provide a robust relationship from which to derive BEs. BEs of 5.6 and 13.0 μg total TBBPA/L plasma were calculated for available cancer and non-cancer TRVs, respectively. Several studies have measured TBBPA in serum, with median concentrations less than 0.1 μg/L, indicating considerable margins of safety (MOS) for TBBPA based on the currently available biomonitoring studies.
Topics: Animals; Environmental Monitoring; Flame Retardants; Humans; Polybrominated Biphenyls; Rats
PubMed: 30593853
DOI: 10.1016/j.yrtph.2018.12.014 -
Environmental Pollution (Barking, Essex... Oct 2022Tetrabromobisphenol A (TBBPA) is the most used flame retardant worldwide and has become a threat to aquatic ecosystems. Previous research into the degradation of this...
Tetrabromobisphenol A (TBBPA) is the most used flame retardant worldwide and has become a threat to aquatic ecosystems. Previous research into the degradation of this micropollutant in anaerobic bioreactors has suggested several identities of putative TBBPA degraders. However, the organisms actively degrading TBBPA under in situ conditions have so far not been identified. Protein-stable isotope probing (protein-SIP) has become a cutting-edge technique in microbial ecology for enabling the link between identity and function under in situ conditions. Therefore, it was hypothesized that combining protein-based stable isotope probing with metagenomics could be used to identify and provide genomic insight into the TBBPA-degrading organisms. The identified C-labelled peptides were found to belong to organisms affiliated to Phytobacter, Clostridium, Sporolactobacillus, and Klebsilla genera. The functional classification of identified labelled peptides revealed that TBBPA is not only transformed by cometabolic reactions, but also assimilated into the biomass. By application of the proteogenomics with labelled micropollutants (protein-SIP) and metagenome-assembled genomes, it was possible to extend the current perspective of the diversity of TBBPA degraders in wastewater and predict putative TBBPA degradation pathways. The study provides a link to the active TBBPA degraders and which organisms to favor for optimized biodegradation.
Topics: Anaerobiosis; Biodegradation, Environmental; Bioreactors; Ecosystem; Isotopes; Polybrominated Biphenyls; Proteogenomics
PubMed: 35872283
DOI: 10.1016/j.envpol.2022.119786 -
Environment International Apr 2020Widespread polybrominated biphenyls (PBBs) contamination occurred in Michigan from 1973 to 1974, when PBBs were accidentally substituted for a nutritional supplement in...
Serum concentrations of polybrominated biphenyls (PBBs), polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) in the Michigan PBB Registry 40 years after the PBB contamination incident.
Widespread polybrominated biphenyls (PBBs) contamination occurred in Michigan from 1973 to 1974, when PBBs were accidentally substituted for a nutritional supplement in livestock feed. People who lived in the state were exposed to PBBs via several routes including ingestion, inhalation and skin absorption. PBBs sequestered in lipid-rich matrices such as adipose tissue, are slowly eliminated after entering the human body, and can also be transferred from a mother to her offspring through the placenta and breastfeeding. Due to the long biological half-lives of PBBs, as well as concerns from the exposed community, biomonitoring measurements were conducted from 2012 to 2015. Because of their similar structures, serum PBBs, polychlorinated biphenyls (PCBs), and polybrominated diphenyl ethers (PBDEs) were all measured 40 years after the PBB contamination incident (N = 862). The serum PBB-153 levels among the original highly-exposed groups (i.e., chemical workers, the family of chemical workers, and individuals who lived on or received food from the contaminated farms) remains significantly higher than other Michigan residents. Several predictors such as sampling age, sex, and smoking status were significantly associated with the serum levels of some persistent organic pollutants (POPs). Higher average values and also wider ranges of serum POP levels were found in this study compared to the National Health and Nutrition Examination Survey (NHANES), with the most substantial difference in serum PBB-153. This was true for all groups of Michigan residents including those who were not part of the above-described highly-exposed groups. Moreover, the people born after the contamination incident began also have higher serum PBB-153 levels when compared with more recent NHANES data (2010-2014), which suggests potential intergenerational exposure and/or continued environmental exposure following the contamination period.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Child; Child, Preschool; Environmental Exposure; Environmental Pollutants; Female; Halogenated Diphenyl Ethers; Humans; Intergenerational Relations; Male; Michigan; Middle Aged; Nutrition Surveys; Polybrominated Biphenyls; Polychlorinated Biphenyls; Pregnancy; Registries; Young Adult
PubMed: 32062441
DOI: 10.1016/j.envint.2020.105526 -
Toxicology Mar 2022Tetrabromobisphenol A (TBBPA) is a flame retardant that can contaminate the environment and human being, acting as an endocrine disruptor. Several studies propose a...
Tetrabromobisphenol A (TBBPA) is a flame retardant that can contaminate the environment and human being, acting as an endocrine disruptor. Several studies propose a correlation between TBBPA exposure and adverse health outcomes, however, at vascular level TBBPA effects are still poorly understood. Thus, considering that the vascular tonus is regulated by vasoactive substances (serotonin and histamine) which are involved in some pathological processes, this work aimed to analyse the direct effects and the 24 h exposure of TBBPA on the human umbilical artery (HUA) and to investigate its signalling pathway. Using organ bath technique, endothelium-denuded HUA rings were contracted with serotonin (5-HT, 1 μM), histamine (His, 10 μM) and potassium chloride (KCl, 60 mM), and the exposure (0-24 h) of different concentrations of TBBPA (1, 10 and 50 μM) were evaluated. Besides, the vascular mode of action of TBBPA was studied through the analysis of cyclic guanosine monophosphate and calcium channels activity, pathways involved in relaxation and contraction of HUA, respectively. Our results demonstrated that the direct effects of TBBPA induce a vasorelaxation of HUA. The maximum relaxant effect was observed at 100 μM of TBBPA with 63.74%, 64.24% and 30.05%, for 5-HT-, His- or KCl-contracted arteries respectively. The 24 h TBBPA exposure altered the vasorelaxant response pattern of sodium nitroprusside and nifedipine. This effect is due to the involvement of TBBPA with the NO/sGC/cGMP/PKG pathway and the interference in calcium influx. Furthermore, using the real-time quantitative polymerase chain reaction, TBBPA clearly modulates L-type calcium and large-conductance Ca 1.1 α- and β -subunit channels, and soluble guanylyl cyclase and protein Kinase G. So, at vascular level TBBPA induces changes in HUA after TBBPA exposure.
Topics: Calcium; Cyclic GMP; Histamine; Humans; Nitric Oxide; Nitric Oxide Donors; Polybrominated Biphenyls; Potassium Channels; Serotonin; Vasodilation
PubMed: 35321852
DOI: 10.1016/j.tox.2022.153158