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PCBs (Polychlorinated Biphenyls)
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Two of the Centers for Children's Environmental Health and Disease Prevention Research are studying the effects of polychlorinated biphenyls, or PCBs, on human health. The University of Illinois Children’s Center is examining the effects of PCBs and methylmercury on neurodevelopment, studying the mechanisms of PCB toxicity and developing education and intervention strategies to reduce exposure to these chemicals. The Mount Sinai Children’s Center has been characterizing children’s exposures to chemicals including PCBs, pesticides, DDT, chlordane and lead in three birth cohorts, evaluating susceptibility factors related to these exposures and examining neurological development in these children.
PCBs have been demonstrated to cause a variety of adverse health effects, and have been shown to cause cancer and health effects in animals, including effects on the immune system, nervous system and endocrine system. Studies in humans provide evidence for potential carcinogenic and non-carcinogenic effects of PCBs which may be interrelated, as alterations in one system can have significant implications for other systems of the body.
PCBs can act as endocrine-disrupting chemicals, or endocrine disruptors (EDCs or EDs), environmental chemicals which can interfere with the endocrine system by affecting hormone receptors. PCBs are also known to act as estrogen receptors (ERs), androgen receptors and thyroid hormone receptors and can interfere with enzymes in steroid hormone biosynthesis and metabolism. (Salama et al. 2003).
PCBs began to be used commercially in the 1930s, in products including capacitors and transformers, and as additives in pesticides, paints, plastics and carbonless copy paper. Their usefulness is based primarily on their chemical stability, low flammability, and physical properties, including as electrical insulators. These chemicals were produced as complex mixtures with varying combinations of the 209 isomers, or congeners. Two of the major North American producers were Monsanto, which marketed them under the name Aroclor, and General Electric, which used the name Pyranol. More than 1.5 billion pounds of PCBs were produced in the U.S. before most uses were prohibited in the late 1970s, but due to their chemical stability they continue to persist in the environment. Because they are fat-soluble, they tend to concentrate in the fatty tissues of fish and other species including humans, and biomagnify within the food chain.
Children's Centers Research on PCBs
University of Illinois – FRIENDS Children’s Environmental Health Center
The FRIENDS (Fox River Environment and Diet Study) Children's Environmental Health Center at the University of Illinois, Urbana-Champaign, is researching the interactive effects of PCBs and Methylmercury (MeHg) on cognitive, sensory and motor development in children. The Center was created due to concerns about consumption of fish contaminated with these chemicals in the Fox River and other rivers and lakes in northeastern Wisconsin. Projects include assessment of a birth cohort exposed to PCBs and MeHg through maternal consumption of local fish and two complementary laboratory-based projects to determine the mechanisms through which these contaminants may induce neurological deficits in children. An additional focus is to develop effective educational strategies to reduce exposure to these fish-borne contaminants.
Projects
This project is a prospective birth cohort study of Hmong and Lao women of reproductive age who live in Green Bay and Appleton, Wisconsin, who often eat fish caught from the Fox River, which is contaminated with PCBs and methylmercury (MeHg). This project is designed to study the impact of prenatal exposure to these chemicals on cognitive, motor, and auditory function in children, as they may be at risk for neurodevelopmental deficits. Illinois Children’s Center researchers found that rats exposed to a mixture of PCBs formulated to duplicate those in the Fox River during early development suffered from permanent hearing loss. As a result, audiologists with the Green Bay research team are assessing cochlear function in newborn infants in the birth cohort.
In this project, rats are fed a mixture of PCBs and methylmercury formulated to mimic actual human exposure to these chemicals from contaminated fish caught from the Fox River in Green Bay, Wisconsin, and offspring go through a battery of cognitive, motor, and auditory tests. Brian Powers, a graduate student in the Schantz lab, observed auditory deficits in rats exposed to the Fox River PCB mixture during early development. The rats experienced permanent deficits in auditory function and the findings suggested that this was the result of damage to the cochlea. These data were used to develop a testing strategy used to assess hearing in newborn infants in the community-based study. In other research, rats exposed to the Fox River PCB mix during early development had problems with inhibitory control. When placed in an operant box with a lever to press, the rats had trouble holding back a response when one was not necessary or appropriate. Similar problems have been reported in PCB-exposed children and in children diagnosed with ADHD.
This laboratory-based project directed by Dr. Richard Seegal is looking at the mechanisms by which PCBs and methylmercury may alter central nervous system function. Using a number of experimental models, including laboratory rodents and tissues from these animals, Dr. Seegal and his team are investigating the effects of PCBs and MeHg, both individually and in combination, on neurotransmitter systems in the brain responsible for learning and behavior. So far, data suggests the effects of simultaneous exposure to these two neurotoxicants may be greater than the sum of the effects of exposure to the toxicants individually. These studies may have a significant impact on risk assessment decisions and the establishment of advisories for the consumption of fish contaminated with the chemicals. Dr. Seegal has also observed that a critical period exists early in development where animals are more susceptible to PCBs and MeHg. The turning point appears to be around the time of weaning, and this finding may have potential correlates with humans.
This laboratory, which is located in the School of Medicine and Biomedical Sciences at the State University of New York at Buffalo is capable of providing a highly sophisticated analysis of PCBs and MeHg, as well as PBDEs, pesticides and other environmental contaminants. It is one of the few labs in the country that can parse the more than 209 potential PCB congeners that exist in the environment.
Educational Video:
A number of educational materials have been created by the Illinois Children's Center, including a simplified fishing advisory in English, Hmong and Lao, specific to the bodies of water fished by this population. An educational video was also created to teach basic concepts about contaminants in fish, instruct viewers how to use the fishing advisory and demonstrate how to clean and prepare the fish so as to limit PCB exposure.
Green Bay Area Fishing Advisories:
- English
Version (PDF) (632kb, 8pp, About
PDF)
- Hmong Version (PDF) (595KB, 7pp, About PDF)
Mount Sinai Medical Center – Center for Children’s Environmental Health and Disease Prevention Research
Projects
The project "Growing Up Healthy in East Harlem," began by enrolling more than 130 families into a controlled research study of pesticide and PCB exposure reduction using Integrated Pest Management (IPM). The project continues within the same cohort studying the built environment and associated endocrine-disrupting (ED) exposures and their effects on growth and development on 6-8 year-old children. Researchers are characterizing exposures and potential sources of pesticides, PCBs and other EDs, such as personal care products, including phthalates and alkyl phenols.
- Exposure to Indoor Pesticides and PCBs and their Effects on Growth and Neurodevelopment in Urban Children (1998-2003)
This epidemiologic research project seeks to determine whether pesticides and PCBs have adverse effects on the neurological development of children in the inner city and whether these effects are still evident in adult life. This project is a prospective study of neurodevelopment and health outcomes in relation to antenatal exposures to PCBs, chlorpyrifos and other environmental toxicants as well as diet in an ethnically diverse birth cohort of New York City infants delivered at Mount Sinai Hospital. In this study, about 400 girls ages 4-6 will be monitored for at least 5 years to measure markers of puberty including breast development. Researchers are examining risk factors for early development including ED exposures, genetic characteristics, physical activity and body size.
This epidemiologic research project is a retrospective cohort study of the relationship between prenatal exposure to polychlorinated biphenyl (PCBs) and neurodevelopmental outcomes in young African-American men and women, now in their 20's and 30's, who have been followed through childhood and adolescence. Their cognitive ability and other domains of neuropsychological status were re-evaluated in this project. Pre-natal maternal serum samples were stored and used to assess prenatal PCB exposure. This research examined whether timing of pubertal development is affected by exposure to endocrine disruptors (EDs) such as PCBs. Results show that PCBs, but not DDE, were strongly associated with income, a socioeconomic status indicator, in this cohort. Also, maternal levels of ortho-substituted PCBs were associated with reduced weight through 17 years of age among girls but not among boys. Tri-ortho-substituted PCBs were marginally associated with increased height in boys. Although limited by sample size, these results suggest that prenatal exposure to PCBs may affect growth, especially in girls, and that ortho-substitution is an important determinant of its effect on growth.
This project is an experimental neurodevelopmental study intended to elucidate the mechanism by which PCBs and other environmental agents adversely affect neuroendocrine and early reproductive development. Using a female rat model, this project examines the role of developing GnRH neurons and their neuronal and glial inputs in the neuroendocrine dysfunctions that occur in organisms exposed to environmental toxicants.
In two recently established (1998-2001) East Harlem birth cohorts, researchers found evidence for common (but not universal) exposure to organophosphate and pyrethroid pesticides. Exposures to PCBs and related chlorinated hydrocarbons were quite low, but PCB levels were still associated with fish intake. Researchers at Mt. Sinai are conducting neurobehavioral and anthropometric assessments, including percent body fat, at the child’s 4th, 6th, and 7th year. The aim is to assess how in utero and/or childhood exposure to pesticides and endocrine disruptors, specifically organophosphates, pyrethroids, PCBs, phthalates, and bisphenol A, might be associated with childhood growth and neurodevelopment in children in New York City. Possible modulating effects of genetic polymorphisms and enzymatic activity are also being evaluated.
- Rats exposed to the Fox River PCB mix during early development show permanent hearing loss (Illinois Children’s Center, Powers et al. 2006). abstract | full text
- Rats exposed to the Fox River PCB mix during early development have problems
with inhibitory control. Similar problems have been reported in PCB-exposed
children and in children diagnosed with ADHD (Illinois, Sable
et al., in press
). - The effects of simultaneous exposure to PCBs and methylmercury may be greater than the sum of the effects of exposure to each toxicant individually (Illinois, Widholm et al. 2004).
- Animal studies suggest that exposure to PCBs during critical periods of neuronal development may increase the concentration of dopamine in the brain, and thereby alter behavior (Illinois, Seegal et al. 2005)
- Maternal PCB levels in the Mt. Sinai cohort, while very low, were associated with fish intake (Wolff et al. 2005).
- In utero exposure to PCBs produced decrements in intelligence that were still evident at age 17 years in a population of African-American men (Mt. Sinai, Longnecker et al. 2003)
- In the laboratory, in utero exposures of rat pups to certain PCBs, chlorpyrifos and methoxychlor caused profound elevation of Gonadotropin-Releasing Hormone (GnRH) mRNA levels. This finding suggests exposures to these chemicals during fetal life may disrupt the reproductive neuroendocrine axis (Mt. Sinai)
- Maternal levels of ortho-substituted PCBs have been shown to be associated with reduced weight through 17 years of age among girls but not among boys., and results suggest that prenatal exposure to PCBs may affect growth, especially in girls, and that ortho-substitution is an important determinant of its effect on growth (Mt. Sinai, Lamb et al. 2006).
- Researchers at the Mt. Sinai Children’s Center have found suggestive relationships between prenatal environmental biomarkers and birth outcomes. Higher levels of DDE, the principal metabolite of DDT, were associated with smaller birthweight and head circumference. Head circumference was inversely associated with maternal levels of PON1 activity, an enzyme which detoxifies organophosphate pesticides, while birth length was shorter for mothers with the PON192RR (slow detoxifier) genotype compared with the PON192QQ (fast) genotype (Mt. Sinai, in press).
Kostyniak PJ, Hansen LG, Widholm JJ, Fitzpatrick RD, Olson JR, Helferich JL, et al. 2005. Formulation and Characterization of an Experimental PCB Mixture Designed to Mimic Human Exposure from Contaminated Fish. Toxicol Sci 88(2):400-411.
Lamb
MR, Taylor S, Liu X, Wolff MS, Borrell L, Matte TD, Susser ES,
Factor-Litvak
P 2006. Prenatal exposure to polychlorinated biphenyls and postnatal
growth: a structural analysis. Environ Health Perspect May 2006;114(5):779-85.
Landrigan P 2001. Pesticides and Polychlorinated biphenyls (PCBs): An Analysis of the Evidence that they Impair Children’s Neurobehavioral Development. Mol. Genet. Metab. 73(1):11-7.
Longnecker MP, Wolff MS, Gladen BC, Brock JW, Granjean P, Jacobson JL, Korrick SA, Rogan WJ, Weisglas-Kuperus N, Hertz-Picciotto I, Ayotte P, Stewart P, Winneke G, Charles MJ, Jacobson SW, Dewailly E, Boersma ER, Altshul LM, Heinzow B, Pagano JJ, Jensen AA 2003. Comparison of polychlorinated biphenyls (PCBs) levels across studies of human neurodevelopment. Environ Health Persp 111:65-70.
Powers BE, Widholm JJ, Lasky RE, Schantz SL. 2006. Auditory Deficits in Rats Exposed to an Environmental PCB Mixture during Development. Toxicol Sci 89(2):415-422.
Roegge, CS and Schantz, SL (in press). Motor Function following developmental exposure to PCBs and/or MeHg Neurotoxicology and Teratology.
Roegge CS, Wang VC, Powers BE, Klintsova AY, Villareal S, Greenough WT, et al. 2004. Motor impairment in rats exposed to PCBs and methylmercury during early development. Toxicol Sci 77(2):315-324.
Sable HJK, Schantz SL (in press). Executive function following developmental exposure to polychlorinated biphenyls (PCBs): What animal models can tell us. In: Models of Cognitive Impairment (Buccafusco J, Levin E, eds):CRC Press.
Salama J, Chakraborty TR, Ng L, Gore AC 2003. Effects of polychlorinated biphenyls on estrogen receptor-beta expression in the anteroventral periventricular nucleus. Environ Health Perspect. 2003 Aug;111(10):1278-82.
Seegal RF, Brosch KO, Okoniewski RJ. 2005. Coplanar PCB congeners increase uterine weight and frontal cortical dopamine in the developing rat: implications for developmental neurotoxicity. Toxicol Sci 86(1):125-131.
Wolff MS, Deych E, Ojo F, Berkowitz GS 2005. Predictors of organochlorines in New York City pregnant women, 1998-2001. Environ Res. 2005 Feb;97(2):170-7.
Wolff MS, Teitelbaum SL, Windham G, Pinney SM, Britton JA, Chelimo C, Godbold J, Biro F, Kushi LH, Pfeiffer CM, Calafat AM (in press). Pilot study of Urinary Biomarkers of Phytoestrogens, Phthalates, and Phenols in Girls. Environ Health Perspect. Available online at http://dx.doi.org/10.1289/ehp.9488
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EPA provides a number of ways to learn about PCBs, their health effects, laws and regulations that govern PCBs, and approved companies that handle PCB-containing waste. For more information, please visit http://www.epa.gov/pcb.
Additional children's center research information is available on the Complex Chemical Mixtures and Heavy Metals topic page.
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