A benchmark dose analysis of prenatal exposure to polychlorinated biphenyls

Benchmark dose (BMD) analysis is used to determine levels of exposure to environmental contaminants associated with increased public health risk. In this study we used a benchmark approach to evaluate the risks associated with prenatal exposure to polychlorinated biphenyls (PCBs). We evaluated for intellectual impairment a cohort of children whose prenatal PCB exposure had been assessed from biologic specimens. We calculated BMDs and lower-bound confidence limits (BMDLs) for four end points using four sets of risk criteria. BMDLs were estimated using three different statistical methodologies. The BMDs and BMDLs were remarkably consistent across the four end points for each set of risk criteria, but differed substantially for the different risk criteria. The proportion of the sample considered at risk ranged from 9.8% for the least protective criteria to 74.1% for the most protective. Two methodologies, likelihood ratio and bootstrapping, generated generally similar BMDLs. BMD analysis provides a straightforward, reliable method for evaluating levels of exposure associated with increased public health risk. In the analyses performed in this study, the number of individuals considered at risk depended more on the risk criterion selected than on the outcome assessed.     

Neutrophil function after exposure to polychlorinated biphenyls in vitro.

Polychlorinated biphenyls (PCBs) are known to be immunotoxic, yet the effects on neutrophil (PMN) function are not well characterized. We incubated PMNs isolated from rat peritoneum with a mixture of PCB congeners, Aroclor 1242, in the absence or presence of either phorbol myristate acetate (PMA) to stimulate generation of superoxide anion (O2-) or N-formyl-methionyl-leucyl-phenylalanine (fMLP) to induce degranulation (measured as release of beta-glucuronidase). Aroclor 1242 alone stimulated O2- production at a concentration of 10 micrograms/ml. Significant cytotoxicity was not observed under these conditions. This concentration of Aroclor 1242 also increased O2- generation in PMNs activated with 20 ng PMA/ml. In the presence of a concentration of PMA (2 ng/ml) that by itself did not stimulate production of O2-, 1 microgram Aroclor 1242/ml caused significant generation of O2-, indicating synergy between Aroclor 1242 and PMA. Aroclor 1242 caused release of beta-glucuronidase from quiescent PMNs; however, in PMNs stimulated with fMLP to undergo degranulation, Aroclor 1242 inhibited release of beta-glucuronidase. The effects of two PCB congeners, one that binds to the Ah receptor (3,3', 4,4'-tetrachlorobiphenyl) and one that has little affinity for this receptor (2,2', 4,4'-tetrachlorobiphenyl) were examined. 3,3', 4,4'-Tetrachlorobiphenyl had no effect on PMN function in vitro, whereas 2,2', 4,4'-tetrachlorobiphenyl had effects similar to those observed with Aroclor 1242. These results indicate that PCBs affect PMN function in vitro in a complex manner, stimulating or inhibiting function under different conditions. These effects are apparently not mediated through the Ah receptor.     

Accidental exposure of children to polychlorinated biphenyls

Children exposed to polychlorinated biphenyls (PCBs) while playing with parts of a capacitor had elevated serum concentrations of lower chlorinated PCBs, similar to Arochlor^® 1242. These levels declined over 11 months of followup to about half their initial values, from a mean of 12.9 to 6.3 ppb (parts per billion, ng/mL) among four children. In comparison, other persons in the same household and a reference group of persons seen in the same geographic area had serum levels of Aroclor 1242-like PCBs below the limit of detection (<5 ppb). All three groups—the children, household members, and geographic referentsalso had higher chlorinated PCBs in their serum similar to Aroclor^® 1260 (HPCBs). HPCB concentrations were similar in these groups (approximately 2 ppb) and did not decline significantly.     

Electrophysiologic and behavioral effects of perinatal and acute exposure of rats to lead and polychlorinated biphenyls

Lead and polychlorinated biphenyls (PCBs) both cause a reduction of intelligence quotient and behavioral abnormalities in exposed children that have features in common with attention deficit hyperactivity disorder. We have used rats as a model to study the effects of both perinatal and acute exposure to lead or PCBs in an effort to compare and understand the mechanisms of these nervous system decrements. Long-term potentiation (LTP) is an electrophysiologic measurement that correlates well with cognitive ability. We have determined the effects of chronic perinatal exposure to lead or PCB 153 as well as acute application of these substances to isolated brain slices, with recordings in two areas of the hippocampus, CA1 and CA3. Both substances, whether chronically or acutely applied, significantly reduced LTP in CA1 in animals at age 30 and 60 days. In CA3, they reduced LTP in 30-day animals but potentiated it in 60-day animals. Although neither lead nor PCB 153 alters baseline synaptic transmission at low stimulus strengths, at higher levels they induce changes in the same direction as those of LTP. These results show surprisingly similar actions of these quite different chemicals, and the similarity of effects on chronic and acute application indicates that effects are both pharmacologic and developmental. Behavioral studies of rats exposed to PCBs from contaminated fish show hyperactivity, impulsiveness, and increased frustration relative to unexposed controls. These results demonstrate that lead and PCBs have similar effects on synaptic plasticity and behavior and suggest that the compounds may act through a common mechanism.     

Prenatal exposure to polychlorinated biphenyls and postnatal growth: a structural analysis

Normal endocrine function in utero and early in childhood influences later height and weight attainment. Polychlorinated biphenyls (PCBs) are persistent environmental contaminants with suspected endocrine-disrupting properties. PCBs may mimic or inhibit hormone and endocrine processes based in part on their structural configuration, with non-ortho-substituted PCBs having a coplanar orientation and ortho-substituted PCBs becoming increasingly noncoplanar. Coplanar and noncoplanar PCBs have known differences in biologic effect. Animal studies link prenatal PCB exposure to adverse birth and early-life growth outcomes, but epidemiologic studies are conflicting. We examined whether prenatal exposure to PCBs, categorized by their degree of ortho-substitution, affected childhood height and weight attainment in 150 children (109 boys and 41 girls) with African-American mothers born at the Columbia-Presbyterian Hospital from 1959 through 1962. Stratifying by sex, we used regression models for repeated measures to investigate associations between maternal levels of PCBs and height and weight through 17 years of age. 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, our 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.     

Amateur radio operators and exposure to polychlorinated biphenyls

In September, 1982, the Special Studies Branch, Chronic Diseases Division, Center for Environmental Health, Centers for Disease Control, was alerted to the possibility that oils in certain oil-filled devices used by amateur radio operators throughout the country were contaminated with polychlorinated biphenyls (PCBs). To evaluate the possible exposures and concomitant health risks, we conducted an exposure assessment study in two phases: an evaluation of the prevalence of environmental contaminations and an assessment of human exposure. Of 77 oil samples collected, only 2 were contaminated above a 50-ppm level; analyses of blood specimens collected from these two owner-operators showed serum PCB-levels which were well within a "normal" or expected background range. Although, on the basis of these limited data, PCBs from contaminated oils do not appear to be a hazard to amateur radio operators, we recommend that PCB-contaminated oils should not be used because of the continuing potential for exposure from either inhalation or direct contamination.     

Occupational exposure to polychlorinated biphenyls in electrical workers. I. Environmental and blood polychlorinated biphenyls concentrations.

Industrial exposure to polychlorinated biphenyls (PCBs) and internal dose were investigated in 80 worker exposed for many years to PCB mixtures with a 42% chlorine content (Pyralene 3010 and Apirolio). PCBs were determined by liquid gas chromatography on samples taken from workroom air, workroom surfaces and tools, the palms of the hand, and the blood of the workers. In the workroom air samples, PCB concentrations ranged from 48 to 275 micrograms/m3. All tested surfaces and tools were heavily contaminated, with a range from 0.2 to 159 micrograms PCBs per cm2 of surface. Considerable amounts of PCBs were detected on the palms of the hands of the workers (2-28 microgram/cm2 of skin surface). In blood, total PCB concentrations from 88 to 1319 micrograms/kg were observed: comparing the blood concentrations of low and high chlorine content biphenyls, a significant difference was found for the low-chlorinated biphenyl concentrations between workers currently exposed and workers exposed only in the past. In groups of workers who were homogeneous as regards work area and job, the PCB concentrations in the blood were closely correlated with the length of actual occupational exposure to these compounds. These findings led to the conclusion that absorption of PCBs in these workers had occurred mainly through the skin, therefore industrial preventive surveillance must take this route of exposure into account. Since blood PCB concentrations appear to be correlated with the length of exposure, PCB determination on whole blood may be used to monitor industrial and environmental exposure to PCBs.     

Mortality after exposure to polychlorinated biphenyls and polychlorinated dibenzofurans: a 40-year follow-up study of Yusho patients

A 40-year follow-up study was conducted to examine mortalityamong 1,664 patients in Japan suffering from "Yusho," a diseasecaused by ingestion of rice oil contaminated with polychlorinatedbiphenyls and polychlorinated dibenzofurans. To evaluate theeffects of exposure on mortality, the authors calculated standardizedmortality ratios. National mortality rates for major causesof death were used as reference points. A total of 1,596 Yushopatients (95.9%) were followed until death or the end of thestudy (December 31, 2007). The standardized mortality ratiosfor most major causes of death were not significantly elevated,with the exceptions of all types of cancer (standardized mortalityratio (SMR) = 1.37, 95% confidence interval (CI): 1.11, 1.66),liver cancer (SMR = 1.82, 95% CI: 1.06, 2.91), and lung cancer(SMR = 1.75, 95% CI: 1.14, 2.57) in males. In addition, thestandardized mortality ratios for all cancers, liver cancer,and lung cancer among males tended to decrease over time. Resultsfrom this study suggest that the carcinogenicity of polychlorinatedbiphenyls and polychlorinated dibenzofurans must be taken intoaccount when evaluating mortality risk. cohort studies; food contamination; mortality; neoplasms; polychlorinated biphenyls     

Worker exposure to polychlorinated biphenyls in elastic polysulphide sealant renovation

Worker exposure to polychlorinated biphenyls (PCBs) in renovation of prefabricated houses was assessed by biological monitoring of 24 PCB congeners including the 10 most abundant PCBs in elastic polysulphide sealants. Serum samples from 22 exposed and 21 non-exposed men were analysed using gas chromatography-mass spectrometry with negative chemical ionization. Total PCB concentration of 24 PCB congeners in workers' serum varied between 0.6 and 17.8 microg/l (mean 3.9 microg/l, median 1.9 microg/l). The Finnish upper reference limit for occupationally non-exposed persons (3 microg/l) was exceeded in the serum samples of 10 workers. Concentrations for non-exposed persons were 0.3-3.0 microg/l (mean 1.7 microg/l, median 1.5 microg/l). The concentration for the sum of the 10 most abundant PCB congeners in elastic polysulphide sealants in serum samples taken in autumn after the renovation season was 2-10 times higher than in samples from the same workers (n=5) taken in the previous spring. The concentrations of PCB congeners PCB 28, 52, 77, 101, 138, 153 and 180 in hygienic samples taken from the breathing zone of the workers were low, ranging from not detected to 3.1 microg/m3. The concentrations of PCB 28 and 52 in sera were positively correlated with the concentrations in air samples taken from the breathing zone of six workers (r=0.70 and 0.80).     

Environmental exposure to polychlorinated biphenyls and breast cancer risk

Breast cancer is a major public health problem in the United States and in most industrialized countries. Although epidemiologic studies have identified a number of established risk factors for this disease, these factors explain only a small proportion of breast cancer incidence. Environmental exposure has been implicated in breast cancer etiology because of the vast geographic variation in breast cancer incidence rates across countries and regions within countries. Further, the steady increase in breast cancer rates over the past decades points to a potential role of environmental exposure in its development. One suspected environmental factor is the polychlorinated biphenyls (PCBs), which were manufactured commercially for a variety of industrial applications from the 1930s until the 1970s. PCBs have been associated with estrogenic, tumor promoting, and immunosuppressive activities, all of which are relevant in the development of breast cancer. The purpose of this review is to summarize the growing body of epidemiological evidence on the association between environmental PCB exposure and breast cancer risk. Three major types of study design have been used to investigate such a relation: clinic-based case-control studies, retrospective case-control studies, and nested case-control studies. Although findings from clinic-based case-control studies tend to point to an adverse effect of high PCB body burden on risk, the results from the more methodologically sound retrospective and nested studies do not provide strong support for a role of PCBs in breast cancer development. The association between PCB exposure and risk among racially and genetically susceptible subgroups may warrant further investigation. Methodological challenges in the design and analysis of epidemiologic studies on PCBs and breast cancer risk are discussed.     

Metabolic and health consequences of occupational exposure to polychlorinated biphenyls

In surveys of three groups of workers occupationally exposed to polychlorinated biphenyls (PCBs) serum PCB concentrations were quantitated as lower chlorinated biphenyls (L-PCBs) and higher chlorinated biphenyls (H-PCBs). Serum L-PCB and H-PCB concentrations were many times greater among workers employed in power capacitor manufacturing than exposed areas. Statistically significant positive correlations of symptoms suggestive of mucous membrane and skin irritation, of systemic malaise, and altered peripheral sensation were noted with increasing concentrations of serum PCB. No clinical abnormalities attributable to exposure to PCB were observed. Serum PCB concentrations were positively and significantly correlated with glutamic-oxalacetic transaminase (SGOT), serum gamma-glutamyl transpeptidase (GGTP), and plasma triglyceride, and inversely correlated with plasma high density lipoprotein-cholesterol. These correlations were present across all study sites. These findings are indicative of PCBs' physiological effect on the liver, whose long-range health significance is unknown. Nevertheless, the consistent positive association of serum PCB with plasma triglyceride and negative association with plasma HDL-cholesterol may have long-term cardiovascular consequences.     

Neonatal and childhood teeth in relation to perinatal exposure to polychlorinated biphenyls and dibenzofurans: observations of the Yucheng children in Taiwan

In order to determine the effect of perinatal polychlorinated biphenyls and dibenzofurans (PCBs/PCDFs) exposure on neonatal and childhood teeth in Yucheng children, we carried out complete dental examinations on 73 Yucheng children born to mothers who ingested high levels of PCBs/PCDFs and 75 matched controls, aged 7-11 years, in 1992. Ten of 73 (10%) exposed children were reported to have borne teeth during the neonatal period, while none of the controls did. The exposed group also had a significantly higher percentage of teeth with congenitally missing tooth germ compared to the controls (29 vs 2.7%) or rotation (19 vs 2.7%). The percentages of developmental defects increased significantly with increasing maternal serum PCB levels, childhood PCB and PCDF levels, and the duration of breast feeding. The maternal PCB level clearly played a more important role in an increased risk of neonatal teeth and developmental defects. The defects were apparent from the lowest tertile, with a total PCB level of <10 ppb in maternal serum measured nearest to childbirth. The number of permanent teeth tended to be less in exposed children than in the control group from the age of 11 years onwards. Our present study has demonstrated for the first time a dose-response relationship between perinatal PCBs/PCDFs exposure and dental defects.