In the USA Monsanto manufactured and marketed commercial mixtures under the trade name “Aroclor”. These were produced by ferric-chloride-catalyzed chlorination of biphenyl. They were sold at several weight percentages of chlorine, each with its own characteristic distribution of PCB congeners. Similar mixtures, prepared by analogous processes, with correspondingly similar distributions of congeners, were manufactured outside the USA, and were marketed under a variety of other trade names.

The naming convention for the Aroclor products follows the model “Aroclor 1242”, where the 12 indicates the 12-carbon biphenyl nucleus, and the last two digits the weight percentage of chlorine. Typical Aroclor designations...

PCBs were produced by chlorination of biphenyl and marketed with respect to the percentage of their chlorine content (by weight). The commercial production started about 60 years ago. The commercial products were available under several tradenames; e.g., Clophen (produced by Bayer AG, Germany), Aroclor (by Monsanto, USA), Kanechlor (by Kanegafuchi, Japan), Santotherm (by Mitsubishi, Japan), Phenoclor and Pyralene (by Prodolec, France). The total amount produced worldwide is estimated at 1.5 million tons (Ivanov and Sandell 1992, Rantanen 1992).

Depending on the degree of chlorination of the PCB mixture, their physico-chemical properties, like inflammability or electric conductivity, brought about a wide...

Polychlorinated biphenyls (PCBs) share with DDT the distinction of being among the first historically recognized persistent organic pollutants (POPs). Many of the same chemical and physical properties that had made them such desirable industrials also made them one of the most widespread contaminants in the environment (MBR, 1995).

Until recently it was believed that there were no natural sources of PCBs. However, PCBs not associated with anthropogenic activities were identified in ash from the 1980 volcanic eruption of Mt. St. Helens, and subunits of PCBs have also been identified as components of two glycopeptides identified fromAmylocolatopsissp. (Expert panel,...

As documented elsewhere in this book, PCBs are potential human carcinogens and are potentially toxic to both humans and wildlife. Aquatic sediments are the major worldwide sink for PCBs (NRC, 1979); PCBs persist in the sediments, accumulate in biota, and biomagnify in the food chain. Cleanup of these sediments is a national priority, but the sheer volume of sediments involved means that in many cases cleanup is only likely to happen if cost-effective and environmentally compatible methods forin situtreatment are developed.

Over the past 15 years it has become increasingly clear that microbially mediated PCB dechlorination in aquatic...

It has long been recognized that one of the reasons PCB are so persistent in the environment is that as a class of compounds, they are resistant to biotransformation (metabolism) in animals as well as by micro-organisms. There are, however, big differences between individual congeners in the ease of biotransformation. An understanding of the uptake, distribution, biotransformation and elimination of individual polychlorinated biphenyl congeners is important for a number of reasons. The rates of these processes, for a particular congener, are important factors controlling the body burden of an individual. The toxic effects of certain PCB congeners are associated with...

Various attempts have been made to determine if PCB exposure path-ways are important qualitative as well as quantitative determinants of possible adverse health effects. The most convincing data are related to perinatal exposures following maternal consumption of sports fish (Jacobson, 2001) and contaminated rice oil (Guo, 2001). Even though different PCB congeners are known to have different actions (e.g.,Safe, 1994; 2001; Pessah, 2001; Hansen, 1998), the profiles of PCBs from various sources are not well-defined. An A system based on mobility and persistence showed promise in predicting source-specific chlorobiphenyl combinations. The author proposes about 24 major steady state peaks...

Polychlorinated biphenyls (PCBs) are industrial chemicals that were used as dielectrics and flame retardants, or in cooling fluids and lubricants. Unfortunately, PCBs have escaped into the environment where they persist and accumulate in animal and human tissues. These characteristics, their propensity to persist and to bioaccumulate, raise concerns about the long-term health effects of these chemicals. They induce various toxic effects like immunosuppression and endocrine disruption in animals and chloracne in humans. PCB mixtures induce liver cancer in rodents (Silberhornet al.1990). In addition, about a dozen epidemiological studies have reported creased mortality due to liver, gall bladder, biliary...

At least 78 of the 209 possible PCB isomers and congeners can exist as rotational isomers that are enantiomeric to each other. The requirement for chirality is that neither phenyl ring possesses a plane of symmetry that passes through the central C-C bond perpendicular to the plane of the ring. Rotation around the central C-C bond takes place via coplanar transition states, where the number oforthosubstituents and their size (e.g. Br›Cl) increase the steric hindrance and consequently the energy barrier to racemization. PCB derivatives with only twoorthochlorine atoms racemize quickly at room temperature because of...

The combination of DB-XLB columns with benchtop El-mass-spectral detection achieved resolution and measurement of almost all significant Aroclor congeners. This poster will illustrate the extent of resolution of all 209 congeners in a combined mixture of the standards using this GC-MS system. The quantitative performance of the system when calibrated against a 6-level inclusive standard curve based on combining 5 of the 9AccuStandard Inc.mixes (comprising most of the “Aroclor” congeners) to measure significantly different congener distributions in two different types of Aroclor 1254 will be displayed.² Results of a quantitative comparison of the linear response ranges of 2...

Czech countries belong to the countries with a relatively high body burden of PCBs due to their use in the past (WHO, 1996, Černá and Bencko, 1999). Therefore, the Czech Republic implemented a monitoring system in 1994 to provide a better overview of environmental exposure levels to the important pollutants, including PCBs (Kliment et al. 1997).

For the normal population, food represents the main route of environmental exposure to PCBs/PCDDs/PCDFs. According to the System of Monitoring the Environmental Impact on Population Health of the Czech Republic, the intake of PCBs (expressed as sum of 7 indicator PCB congeners) for the...

Chromatograms of environmental materials extracts, obtained by CGC with separation on a single column, are very complex. The complexity of analyte composition arises from the presence of other congeners besides determined PCB and the possibility of coexistence of other halo-organic compounds. Because of the complexity of the obtained extracts, the following seven PCB congeners were chosen for analysis: 28, 52, 101, 118, 138, 153 and 180 (Erickson 1997, Lang 1992, Kannanet al.1993, Grimvall and Ostman 1994 and Sonchik 1983). MS and ECD detectors were used for PCB detection in contaminated water and in extracts from water after PCB...

This contribution is part of a report concerning the level of contamination by selected POPs including PCBs in the countries of Central and Eastern Europe (Holoubek et al., 1999).

The region of Central and Eastern Europe discussed in this paper appears as the shaded area as follows:

In the former Czechoslovakia, PCBs were manufactured from 1959 to 1984 in a chemical plant in eastern Slovakia under the commercial name Delor. Of the total 21,482 tons produced (plus about 1,600 tons of PCB wastes), 46% was exported, and the remainder was destined for the home market of former Czechoslovakia. Within both...

The growing use of sewage sludge for agriculture, among other things, requires not only control of heavy metals concentrations but also control of hazardous substances like PCBs (Oleszkiewicz 1998). Problems of transport dynamics and the degree of leaching of PCBs from sewage sludge under influence of water are still little understood (Ericson 1997, Lang 1992, BerthouexandGan 1991, Gnepink et al. 1991, Frosts al. 1993). In this study of PCB leaching dynamics from sludge, the changes of PCB contents in sludge before and after leaching were determined, and the dynamic of PCB leaching from sewage sludge was defined. Lysimetric columns were...

Burkholderia (Pseudomonas)sp. strain LB400 (Bopp, 1986) possesses a catabolic pathway that allows the organism to grow on biphenyl as a sole source of carbon and energy (Fig. 1). This pathway is also responsible for cooxidation of several chlorinated and polychlorinated biphenyls (Ahmed and Focht, 1973; Furukawaet al,1979). Biphenyl dioxygenase catalyzes the first reaction of the pathway and transforms biphenyl intocis-2,3-dihydroxy-2,3-dihydro-l-phenylcyclohexa-4,6-diene (cis-biphenyl dihydrodiol) (Gibsonet al.,1973; Haddock and Gibson, 1995). The enzyme consists of three protein components that catalyze addition of both atoms of molecular oxygen to the substrate (Haddocket al.,1993) (Figure 2). Reductase...

Polychlorinated biphenyl (PCB) mixtures were produced for fifty years in the United States under the trade name Aroclor. PCBs were used industrially as dielectric fluids and flame retardants. Several hundred million pounds of PCBs were released into the environment during and following their production (Abramowicz 1990). PCBs persist in soil and sediments, and their lipophilic nature facilitates bioaccumulation in fatty tissues of animals (Hooperet al.1990). Concern about health hazards, specifically the immunotoxicity of PCBs, has arisen as a result of the bioaccumulation of these compounds.

While individual exposures to small doses of PCBs may seem insignificant, these doses...

Occupational exposures to PCBs, compared with environmental exposures, have, in general, involved higher exposures to mixtures of congeners, which have varied over time. Previous studies have focused on electrical utilities, as well as capacitor and transformer manufacturing, workers. Exposures at these sites were mixed exposures, not only to various PCB congeners, but also to solvents used in degreasing, lead used in soldering, benzene contaminants, and at least in one plant, to chlorinated naphthalenes. Few studies to date have been able to separate clearly the effects of these different exposures. Investigations of health effects have relied on two general types of...

In 1971, when Monsanto voluntarily restricted its PCB sales to manufacturers of “closed systems” (i.e. electrical equipment), it had 3000 customers for its “Aroclor” line of industrial fluids, resins, and waxes. Sales to the 17 North American electrical equipment manufacturers, which had consumed about half of the total output, continued until 1977. Thus, opportunities for occupational exposure to PCB products were widespread, and particularly extensive in the manufacturing and servicing of transformers and capacitors.

Concerns as to the possible health effects associated with such exposures arose in the mid-1970s, just as manufacturing use was being phased out, and led to...

The majority of material reviewed in this chapter addresses effects of background-level exposure to PCBs in humans. By background-level PCB exposure, we mean exposure experienced by the general public, resulting primarily from normal diet (Agency for Toxic Substances and Disease Registry, 1998), and not from unusual circumstances of occupation, accident, or local contamination. We also reviewed selected studies of populations with high consumption of fish or marine mammals, because they are not considered elsewhere in this volume. We will use the term “low-level” PCB exposure to encompass both background-level PCB exposure and PCB exposure in populations with high intake of...

Breast cancer is the most common cancer among women in the United States, with 182,800 new invasive cases and 40,800 deaths among women estimated for 2000 (ACS, 2000). Incidence rates vary among geographic regions within the U.S., with higher rates for women in the northeast U.S. (Devesa, 1995) and California (Laden et al., 1997). Considerable variation in incidence has been observed among countries, ranging from as much as five-to ten-fold. Migrant studies have also shown that breast cancer incidence rates change as women move from low-risk countries to those with higher rates (Kelsey & Horn-Ross, 1993). Changes in documented risk...

During the 1970’s, Wayland Swain and others at the U.S. Environmental Protection Agency (EPA)’s Large Lakes Research Station in Grosse He, Michigan, became concerned about the relatively heavy concentrations of PCBs in Great Lakes fish, particularly in Lake Michigan and southern Lake Huron. The Large Lakes Research Station is an EPA facility dedicated to monitoring environmental risks to the Great Lakes basin. In the mid-1970’s, the EPA sponsored a study of Lake Michigan sports fishermen directed by Harold Humphrey of the Environmental Epidemiology Division, Michigan Department of Public Health. Humphrey’s staff interviewed fishermen on the docks in 11 communities along...

Polychlorinated biphenyls (PCBs), polychlorinated dibenzofurans (PCDFs), and polychlorinated dibenzodioxins (PCDDs) are among the most important persistent organic pollutants found throughout the world and in various biological tissues, including human populations. PCDFs and PCDDs are of no commercial value, but are produced and released into the environment as byproducts during many industrial processes such as chlorine bleaching, incineration, and manufacture or disposal of chlorine-containing products. PCBs were manufactured for many purposes including dielectric fluid in transformers, and lubricants for heavy machinery. PCBs became recognized as potentially harmful environmental contaminants in the 1970s (Jensen, 1987), and their use and manufacture were prohibited...

Recognition of polychlorinated biphenyls (PCBs) and related compounds as potential human neurodevelopmental toxicants was largely a consequence of two mass poisonings, the first in Japan in 1968 (a.k.a. Yusho) and a second similar episode in Taiwan in 1979 (a.k.a. YuCheng). In both poisoning episodes PCB-contaminated rice oil was ingested and many of those who consumed the oil and their subsequent children became ill (Rogan, et al., 1982; 1988; Yamashita et al., 1985; Yoshimura et al., 1978; Yu et al., 1991). The developmental effects of substantial pre-and postnatal exposures resulting from these poisoning episodes are well documented in Taiwan (Guo et...

The Belgian dioxin crisis was neither the first dioxin crises, nor one of the largest, nor even was it caused mainly by dioxin. In the Yusho and Yuchen episodes, rice oil was contaminated by PCBs during oil processing and the contamination detected through effects on public health; adverse effects were essentially attributed to the furans and contaminants of the PCB mixtures. In the French PCB crisis (1976) high levels of PCBs (Phenoclor DP6) were detected in cheeses during food controls for export. The source was identified as contamination from “technical oil” used in farm engines and especially in reapers and...

This paper reviews data from incidents that have been of some significance in the development of the understanding of PCB, dioxin and dibenzofuran levels and exposures in the United States and worldwide. The data are taken from the senior author’s previous and current research, highlighting the varying mixtures of these xenobiotics by presenting environmental, food, and human data from different countries. Given that these chemicals are for the most part synthetic and did not exist prior to the twentieth century, it is to be expected that mixtures of these chemicals will change over time, as will the sources and levels...

Polychlorinated biphenyls (PCBs) are industrial compounds previously used for several commercial applications requiring highly stable products that were miscible with other organic compounds. PCBs also exhibit excellent dielectric properties and were extensively used as dielectric fluids in transformers and capacitors (Hutzinger,et al.,1974; Brinkman and De Kruif, 1980; Ballschmiter,et al,1989). A range of commercial PCB products with different properties could be prepared by varying their chlorine content. The lower chlorinated PCBs such as Aroclor 1221 (21 % Cl by weight) are colorless mobile liquids, whereas some of their higher chlorinated preparations such as Aroclor 1254 (54% Cl...

Polychlorinated biphenyls (PCBs) are a group of synthetic halogenated aromatic hydrocarbons (HAHs) that have been widely dispersed in the environment. The unique chemical properties and low cost of producing PCBs have contributed to their extensive industrial use (De Voogt and Brinkman, 1989). The high lipophilicity and chemical stability of PCBs have resulted in widespread environmental contamination and accumulation in biota. PCBs are found in extracts of virtually all environmental samples and human tissues (Safe, 1993; Hansen, 1998). Currendy it is unclear if the presence of PCBs in biological tissues is causally or coincidentally related with human health problems (Hansen, 1998)....

Among the many effects of PCB exposure in vertebrates, the best characterized are alterations in the levels and activities of the cytochrome P450 (CYP) enzymes. The CYP enzymes, also known as the microsomal mixed function oxidase system, represent the predominant biotransformation pathway in the body. CYP enzymes play a key role in the bioaccumulation and potential toxicity of PCBs and other halogenated hydrocarbons found in the food chain because they catalyze the initial step in xenobiotic metabolism. Therefore, CYP enzymes are important determinants of susceptibility to environmental contaminant exposure. Knowledge about CYP enzymes has increased dramatically in volume and sophistication...

Polychlorinated biphenyls (PCBs) are widely spread environmental contaminants present in aquatic and terrestrial ecosystems. The commercially available PCBs are ubiquitous chemical mixtures composed of isomers of varying chlorine content and exhibiting varying toxic potency (reviewed by Safe, 1994).

PCBs are resistant to decomposition in the natural environment. Consequently they persist in the environment and migrate widely through natural atmospheric and water transport mechanisms (Gregor et al., 1989). Although PCBs are only slightly soluble in water, they dissolve readily in oils and the fatty tissues offish, birds, animals and humans (reviewed by Safe et al., 1994; and Canters & de Snoo,...

Atherosclerosis is the underlying cause of the vast majority of cardiovascular diseases that have a devastating impact on public health. It is a disease with a complex cellular manifestation in which a prominent early feature is the accumulation of specific leukocytes in the subendothelial space of the artery. Dysfunction of endothelial cells is a critical underlying cause of the initiation of atherosclerosis, in addition to regulating the mode of lesion progression. One of the important functions of the endothelium, that is compromised in atherosclerosis, is its ability to act as a permeability barrier to the entry of blood borne elements...

The potential neurotoxicity of polychlorinated biphenyls (PCBs) was first recognized following a mass poisoning that occurred in western Japan in 1968. In that incident over 1000 people became ill after ingesting rice oil contaminated with PCBs. The contamination occurred when PCBs leaked from equipment used to heat the oil during processing. The disease, referred to as Yusho or “rice oil disease,” was characterized by dermal lesions including chloracne and hyperpigmentation of the skin, but many Yusho patients also reported neurologic symptoms including memory loss as well as numbness, hypoesthesia and neuralgia of the limbs (Urabe et al., 1979). Pregnant women...

Although the manufacture and use of polychlorinated biphenyls (PCBs) was banned in the United States in 1977 due to their toxicity and widespread dispersion (Suenagaet al.,1975; Safeet al.,1987; Erickson, 1997), PCBs continue to be considered a risk to both wildlife and humans (Kubiaket al.,1989; Seegal, 1996; Stewartet al.,1999; Tuomisto and Hagmar, 1999; Giesy and Kannan, 1998). Indeed, the number of research articles published since the early 1970s confirms this concern: since 1974 there have been, on average, approximately 150 articles published per year dealing with the effects of exposure to PCBs (Fig...

Polychlorinated biphenyls (PCBs) are a family of 209 structurally related congeners, of which 113 are detectable in the environment (Crispet al.,1998). PCBs are a serious environmental concern due to their ubiquity and persistence in both aquatic and terrestrial habitats. The chlorination pattern of the PCB congener determines the planarity of these compounds, and also their relative toxicity. Much attention has focused on the toxic effects of coplanar PCBs due to their ability to interact with the aryl hydrocarbon receptor (AhR). However, many PCBs do not bind AhR, and there is growing interest in the effects of these compounds...

Polychlorinated biphenyls (PCBs) are well known to reduce the concentrations of thyroid hormones in the circulation of experimental animals (Bastomskyet al.,1976; Brouweret al.,1998). Moreover, circulating levels of PCBs have been reported to co-vary with various measures of thyroid status in humans (Koopman-Esseboomet al.,1997; Osiuset al.,1999). These observations form the basis for the hypothesis that PCBs disrupt thyroid hormone action by reducing circulating levels of thyroid hormone. This hypothesis is particularly important to explore because thyroid hormone is known to be essential in brain development and because PCB contamination is enormously widespread. Therefore,...

The ability of organisms to develop resistance to toxic chemicals has been recognized for decades. Genetically heritable resistance to pesticides, heavy metals and drugs by non-vertebrate groups, namely insects, plants and bacteria, is well-documented (Taylor and Feyereisen, 1996; Walker et al., 1996; Nebert and Carvan, 1997). In contrast, the ability of vertebrates to develop heritable tolerance to toxic chemicals has received very little attention. The few studies that exist for wildlife vertebrates focus primarily on fish and demonstrate a growing number of populations with signs of acquired resistance to toxic chemicals (Hahn, 1998). Studies in mammals are limited, and while...

Polychlorinated hydrocarbons such as 2,3,7,8-tetrachlorodibenzo-ρ-dioxin (TCDD) and polychlorinated biphenyls (PCBs) exhibit sexrelated differences in liver tumor susceptibility, with females affected more frequently. Dioxin and dioxin-like agents produce their toxic and carcinogenic effects via binding to the intracellular aryl hydrocarbon (Ah) receptor, which translocates to the nucleus to act as a protein transcription factor (Safe 1994). One of the gene families that is responsive to DNA binding by the Ah receptor is the CYP1 family of the cytochrome P-450 monooxygenase enzymes (Burkeet al.1994). CYP1A enzymes are known to catalyze the metabolism of 17-β-estradiol to 2-hydroxy and 4-hydroxy catechol forms...

Estrogen modulation by PCBs and other environmental factors such as PAHs continues to be a major public health issue. Apparent estrogen modulationin vivo,while very relevant, can have an extremely complex mechanism that includes direct action of the agent with the estrogen pathway or altered metabolism of the 17ß-estradiol (E²) natural estrogen, competitive estrogen receptor (ER) binding, or metabolism of the environmental contaminant itself to form an ER ligand. We have combined a group of assays in an attempt to detect and characterize the mechanism of potential estrogen disruptors in the relatively pristinein vitroenvironment.

The MCF-7 Focus...

Vitellogenin is a serum protein occurring naturally in adult female non-mammalian vertebrates (Ho, 1987). Vitellogenin is the precursor molecule for egg yolk, which is essential as the source of metabolic energy for the developing embryo. The liver synthesizes vitellogenin and secretes it into the bloodstream. Developing oocytes take up vitellogenin from the blood and then cleave it into the egg-yolk proteins, lipovitellins and phosvitins (Bergink and Wallace, 1974). The synthesis, secretion and uptake of vitellogenin are regulated by the endocrine system (Wallace and Bergink, 1974; Tata and Smith, 1979; Ho, 1987).

Vitellogenin synthesis in vertebrates is largely under control of...

The purpose of the present investigation was to examine the doseresponse relationship of a reconstituted PCB-mixture composed according to the congener pattern found in human breast milk. Female Long Evans rats were fed diets containing 0, 5, 20 or 40 mg/kg of the reconstituted PCBs. Exposure started prior to conception and was terminated at birth. Because of PCB transfer via the milk, exposure of the offspring ended at weaning. Internal PCB concentrations in the brain were higher at weaning than at birth in the offspring, while they decreased in dams during this period. Serum concentrations of estradiol and testosterone were...

Polychlorinated biphenyls (PCBs) are a class of lipophilic, persistent man-made chemicals that despite their restricted use in 1978 still exist as complex mixtures in the environment and in human matrices, including blood, adipose tissue, breast milk and fetal tissue (McFarland and Clarke, 1989). PCBs are considered potential endocrine disruptors due to their ability to act as estrogens, anti-estrogens and goitrogens (Hansen, 1998). There have been numerous, but inconsistent, reports of adverse effects on male reproduction following prenatal or postnatal exposure to PCBs in laboratory rodents. These effects include alterations in testis, accessory gland and ventral prostate weight, reduced serum testosterone...

Polychlorinated biphenyls (PCBs) are environmentally persistent compounds with known carcinogenic and hepato-, immuno-, and neurotoxicant activity. Chronicin vivotreatment with PCBs also leads to fetal toxicity, developmental malformation, decrease in reproductive ability, and multiple testicular abnormalities (Sager, 1984; Brezner et al., 1984; Safe, 1994; Hansen, 1999). Several studies also addressedin vivoandin vitroeffects of PCBs on steroidogenesis in gonadal and adrenal tissues (Freeman and Idler, 1975; Goldman and Yawetz, 1992; Miranda et al., 1992; Kovacevic et al., 1995). However, the mechanism of PCB actions in reproductive tissues has been incompletely characterized. In general, the coplanar and...

Polychlorinated biphenyls (PCBs), may be atherogenic and lead to cardiovascular disease by disrupting normal Functions of the vascular endothelium. To investigate this hypothesis, endothelial cells were exposed to 3,3’, 4,4’-tetrachlorobiphenyl (PCBs 77), 2,3,4,4’, 5-pentachlorobiphenyl (PCB 114) or 2,2’, 4,4’, 5,5’-hexachlorobiphenyl (PCB 153) for up to 24 hours. These PCBs were selected for their varying binding avidity with the aryl hydrocarbon (Ah) receptor and differences in their induction of cytochrome P450. PCB 77 and 114 significantly disrupted endothelial barrier function, increased activity and content of cytochrome P450 1A, and contributed markedly to cellular oxidative stress and activation of the oxidative stress-sensitive...

There is evidence that certain environmental contaminants, such as coplanar polychlorinated biphenyl (PCB) congeners and related compounds, e.g., 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), are associated with vascular endothelial cell dysfunction (Stegeman et al., 1995; Toborek et al., 1995; Hennig et al.,1999). PCBs and their metabolites may remain in the blood circulation for extended time periods. Endothelial cells are in direct contact with plasma components and other circulating substances and are thus vulnerable to PCB insult, that can lead to severe endothelial cell dysfunction. Apoptotic endothelial cell death and other types of endothelial dysfunction may be critical events in vascular diseases such as atherosclerosis...

Polychlorinated biphenyls (PCBs) have been banned from production in many countries since the 1970s, but they persist in our environment. In fact, PCBs present in the food chain are routinely measured in animal and human food sources, as well as their tissues. PCBs, especially higher chlorinated PCBs, may selectively induce cytochrome P450s (Parkinson et al. 1983). Induced cytochrome P- 450 isozymes may themselves be a source of reactive oxygen species (ROS) (Schlezinger et al. 2000; Schlezinger et al. 1999) or may catalyze the oxidation of other PCBs, especially lower chlorinated PCBs, to mono- and di-hydroxy metabolites. The latter may then...

Phenobarbital is a well-known hepatic tumor promoter (Pitot et al., 1987). Upon administration, phenobarbital induces cytochrome P-450 2B1/2, similar to ortho-substituted PCBs, and transiently increases cell proliferation and decreases apoptosis (Bursch et al., 1984; Jirtle and Meyer, 1991). Although the promoting activity of phenobarbital is most likely related to the effects on altered cell proliferation or apoptosis, the mechanisms of these effects have not been elucidated. The initial alteration is hypothesized to be an oxidative stress environment (Aniya et al., 1993). Phenobarbital has been shown to increase the activity of the stress-related transcription factor NFKB, thereby supporting our hypothesis (Li...

Polychlorinated biphenyls (PCBs), either as a commercial mixture (Aroclor 1254) or as individual congeners, have been shown to release insulin from the clonal insulin producing cell line RINm5F (Fischer et al., 1996). This biological effect was observed using the individual congeners 2,2',4,4'-tetrachlorobiphenyl (TeCB) and 2,2\4,4’,5,5’-hexachlorobiphenyl (HCB), but not with 3,3’,4,4’- TeCB. These results suggested that this biological activity was associated with relatively non-coplanar congeners possessing di-ortho substitutions and not with coplanar, dioxin-like congeners. The PCB-induced release of insulin into media was rapid in onset and reached a maximum by approximately 30 minutes. In the continued presence of PCBs, a decline...

The genetic basis for tumor initiation by such agents as oncogenic viruses, ultraviolet radiation, or strongly mutagenic chemicals has been long recognized (Williams, 1997). Conversely, the epigenetic bases for tumor promotion by non-mutagenic or weakly mutagenic animal carcinogens, such as the PCBs, dioxins, and other persistent organic pollutants, are but poorly understood. What is known is that tumor-promoting activity is a property shared by a wide variety of chemical substances. More than half of all chemicals subjected to chronic, maximum tolerated dose bioassay, regardless of whether natural or synthetic, have produced animal tumors, and hence made legally designatable as carcinogens...

Polychlorinated biphenyls (PCBs) are ubiquitous in our environment and are routinely measured in animal and human tissue. PCBs have a multitude of effects in exposed organisms (reviewed in Dobson and van Esch, 1993 and this volume). One major concern is whether PCBs are also carcinogenic. Human epidemiological studies are inconclusive: several authors could not detect an increase in cancer in exposed populations, whereas others, especially those who published their findings during the last 10 years, do see significant increases of cancers at multiple organ sides (reviewed in Cogliano et al., 1998). The NIH ranks PCBs in their ninth report on...

As described previously (Silberhorn et al., 1990), the evidence that PCBs are carcinogens in laboratory animals is very strong. To determine the mechanisms by which PCBs are carcinogenic, many investigators have examined the stages of carcinogenesis that PCBs may affect. The promotion of carcinogenesis has been extensively studied. The evidence that PCBs have promoting activity and possible mechanisms of this activity are presented in this chapter.

The promoting activity of PCBs was suggested in early rodent carcinogenicityen it was found by Ito et al. (1973) that coadministration in the diet of PCBs (Kanechlor 500) with the known hepatocarcinogenic benzene hexachlorides...

Progression is the conversion of initiated and promoted cells into cancer cells. This stage of neoplasia is characterized by an increased growth rate, metastasis, aneuploidy and evolving karyotypic instability. The stage of progression has been examined in experimental models of skin and liver cancer. Early experiments of multistage epidermal carcinogenesis demonstrated that neoplasms occur at a high frequency when complete carcinogens are applied chronically (Shubik et al., 1950). In the skin model, it was demonstrated that chronic application of an initiator to mouse skin shortened the latency to neoplasia (Roe et al., 1972; Hennings, et al., 1985). The stage of...

Polychlorinated biphenyls (PCBs) display a large array of toxic effects including hepatotoxicity, neurotoxicity, immunotoxicity as well as dermal, reproductive and endocrine toxicity (Safe, 1994). Evidence of carcinogenicity in rodents has also been reported, suggesting the promoting activity of PCBs (Ito et al., 1973; Kimbrough et al., 1975; Morgan et al., 1981; Shaeffer et al., 1984; Norback and Weltman, 1985; Rao and Banerji., 1988; Mayes et al., 1998). However, despite some indication of mutagenic potential of PCBs (Peakall et al., 1972; Wyndham et al., 1976; Wong et al., 1979; Sargent et al, 1989; Butterworth et al., 1995) and a report of...

Polychlorinated biphenyls (PCBs) are industrial chemicals that were widely used in transformers, capacitors and other applications. Unfortunately PCBs were found to persist in the environment and hence were banned from production in the US in the 1970’s. The persistence of these chemicals raises concerns about health consequences. Moreover, PCBs are still released to the environment from landfills, incineration of municipal refuse and sewage sludge, and improper (or illegal) disposal of PCB-containing materials. Humans are exposed to PCBs mainly through food. Parts per billion levels of PCBs are found in sera of Americans while much higher (parts per million) levels may...

Polychlorinated biphenyls (PCBs) belong to the family of synthetic chlorinated organic compounds with properties of being thermally, physically, and chemically stable, making them well suited for a variety of industrial applications. Introduction of halogen atoms into the aromatic rings make these compounds less volatile, more lipophilic and more resistant to oxidation. Because of these properties, PCBs tend to bioconcentrate, bioaccumulate, and biomagnify. Today PCBs are categorized as universally distributed environmental pollutants and a matter of concern.

PCBs have been released into the environment mainly through industrial waste, mishaps involving transformers, and improper and careless waste disposal practices. Humans exposed to...

Commercial mixtures of polychlorinated biphenyls (PCBs) are complete carcinogens in rodents, and several of these mixtures and individual PCB congeners are efficacious in the promotion of hepatocarcinogensis. Issues of PCBs’ involvement in initiation of cancer are less clear. PCBs are metabolized to dihydroxy and quinone metabolites by liver microsomes. The oxidation of dihydroxy PCB metabolites is accompanied by the generation of reactive oxygen species (ROS) that leads to the formation of DNA strand breaks in cell-free systems. To study whether the genotoxic properties of PCB metabolites may also be detected in cells in culture, we employed the comet assay, a...

Polychlorinated biphenyls (PCBs) have been commercially available since 1929 (Tanabe, 1988). PCBs were used in transformers and capacitors as dielectrics, in hydraulic systems, in the formulation of lubricating and cutting oils, in pesticides, and as additives in paints, copying paper, adhesives, sealants and plastics (World Health Organization, 1976; Pomerantz, 1978). Although the production of PCBs has been banned or limited since 1970, they still persist in the environment. Due to their lipophilicity, PCBs bioconcentrate and bioaccumulate (reviewed by Lang, 1992; and Safe, 1994). Chronic exposure to PCBs in animals and humans causes a variety of effects, including decreased body weight...

Commercial polychlorinated biphenyls (PCBs) are complete carcinogens in rodents; however, their initiating (DNA damaging) activity has not been conclusively demonstrated. In the present study, we reacted synthetic 2-phenyl-1,4-benzoquinones of 2-chloro- (2-CBQ), 3-chloro- (3-CBQ), 4-chloro- (4-CBQ), 3,4-dichloro- (3,4-CBQ) and 3,4,5-trichloro (3,4,5-CBQ) biphenylsin vitrowith calf thymus DNA at pH 5.0, 7.4 and 9.5 for 4 h at 37 °C. Analysis of 4-CBQ-derived DNA adducts by nuclease PI-version of ³²P-postlabeling showed a similar adduct pattern at all the pHs tested; the reactivity with DNA was in the following descending order: pH 5.0 > pH 9.5 >> pH 7.4. A similar observation...

Zinc is an essential trace element for humans and animals. It plays its role as a constituent or co-factor in over 200 enzymes involved in carbohydrate, protein, lipid and nucleic acids metabolism. Its deficiency in humans has been reported to result in a variety of physiological abnormalities like stunted growth, hypogonadism, immune impairment and others (McClain et al., 1985).

Epidemiological studies have indicated that zinc deficiency is possibly associated with increased risk of upper GI tract cancers in humans (Schrauzer et al., 1977; Van Rensburg, 1981). In experimental systems, the information is rather contradictory. While transplantable tumors grow poorly in...

The toxicity of polychlorinated biphenyls (PCB) has been reported in many species, including humans (Kimborough, 1987; McConnell, 1985). In rats and mice, PCBs, and Aroclor 1254 in particular, stimulate the growth of normal liver tissue and promote liver tumours at both the preneoplastic and neoplastic stage (Preston et al., 1981, Silberhorn et al., 1990). In human populations exposed either accidentally or occupationally to PCBs, evidence for PCB carcinogenicity is inconclusive, with reports of either excess cancer at sites such as the liver, rectum, gall bladder and biliary tract, or no significant increases in the overall cancer rate (Safe, 1989; Silberhorn et al., 1990)...

Polychlorinated biphenyls (PCBs) are environmental pollutants that have been withdrawn from commerce but still persist in nature. Since they were banned, the environmental levels of these compounds have decreased in many areas in industrialized countries (Sanders et al., 1994). Even though their levels are decreasing in many areas, there are still concerns about their toxic effects as human exposure to these compounds is close to or in excess of the tolerable limit. PCBs, both as commercial products and as contaminants in nature, exist as complex mixtures of individual congeners. Each congener is identified by the number and position of chlorine...

Polychlorinated biphenyls (PCBs) are environmental contaminants that, due to their persistence and lipophilicity, accumulate in the food chain and become concentrated in fatty tissues. Toxic effects of commercial PCB products include liver hypertrophy, neoplastic nodules, and hepatocellular carcinoma. Previous studies have led to the general view that carcinogenicity of PCBs and related compounds is due to their activity as promoters (Silberhorn et al., 1990; Glauert et al., 2001). The mechanisms of the promoting activity of PCBs, however, have not been determined. Other hepatic tumor promoters act by increasing cell proliferation, inhibiting apoptosis, or both. These changes are brought about by...

Before a decision can be made about what analysis to use to quantitate total PCBs and dioxin like congeners you have to know what each of the analyses can perform and what limitations there are when a method is used. The following is a general explanation of the analyses available to the risk assessment community.

Historically Aroclor analysis has been the method of choice for environmental laboratories in the US probably due to its prolific use in identifying releases of PCB from transformers, capacitors, and industrial hydraulic systems. Aroclors are mixtures of chlorinated biphenyls manufactured by Monsanto and are numbered...

Many risk assessments attempt to determine whether an environmental exposure poses a health risk by comparing environmental levels to previously derived reference values¹ (called “reference doses” and “slope factors” at the U.S. EPA). While many researchers are familiar with the adverse effects caused by PCBs, fewer are familiar with the considerations that go into developing the reference values used in risk assessments. This paper discusses the PCB reference values and some special considerations in their development and application.

The National Research Council(NRC1983)described a fourstep process that has been followed in most risk assessments. The first step,hazard assessment,...

Polychlorinated biphenyls, or PCBs, are a group of synthetic organic chemicals that consist of 209 individual chlorinated biphenyls (also called congeners). Although the manufacture and sale of PCBs were generally stopped in the U.S. more than 20 years ago, PCBs remain in old electrical equipment and persist in environmental media (e.g., air, surface water, groundwater, soils, sediment, fish and other food products). Under the Comprehensive Environmental Response, Compensation, and Liability Act (also known as the Superfund), the U.S. Environmental Protection Agency (USEPA)¹ evaluates current and future human exposures to PCBs in these environmental media. USEPA uses a process for evaluating...