The Undervalued Effects of Polychlorinated Biphenyl Exposure on Breast Cancer.

The incidence of breast cancer across the world has been on the rise in recent decades. Because identified risk factors can only explain a relatively small portion of the cases, environmental exposure to organic pollutants is suspected to play a role in breast cancer etiology. Polychlorinated biphenyls (PCBs) are among the most abundant pollutants, and the impact of their exposure on breast cancer risk has been extensively studied in recent decades. However, the results of most epidemiologic studies do not support an association between PCB exposure and breast cancer risk. We hypothesized that the effects of PCBs on breast cancer might have been undervalued for reasons such as insufficient recognition of the confounding effects of several factors and lack of attention on the innate heterogeneity of PCB mixtures or breast cancer. After reviewing the evidence in the existing literature, we concluded that early life exposure, known risk factors of breast cancer, and impact of exposure to other pollutants are the main sources of confounding effects and have potentially masked the associations between PCBs and breast cancer. Because PCBs are mixtures of congeners with varied properties, and because breast cancers of different subtypes are etiologically distinct diseases, the absence of stratified subgroup analysis on individual PCBs and patients with specific biological subtypes and insufficient attention paid to the results of these subgroup analyses may result in an underestimation of the correlations between PCBs and breast cancer. In future studies, these factors must be taken into consideration when exploring the effect of PCB exposure on breast cancer risk.

A Bayesian multi-dimensional couple-based latent risk model with an application to infertility.

Motivated by the Longitudinal Investigation of Fertility and the Environment (LIFE) Study that investigated the association between exposure to a large number of environmental pollutants and human reproductive outcomes, we propose a joint latent risk class modeling framework with an interaction between female and male partners of a couple. This formulation introduces a dependence structure between the chemical patterns within a couple and between the chemical patterns and the risk of infertility. The specification of an interaction enables the interplay between the female and male's chemical patterns on the risk of infertility in a parsimonious way. We took a Bayesian perspective to inference and used Markov chain Monte Carlo algorithms to obtain posterior estimates of model parameters. We conducted simulations to examine the performance of the estimation approach. Using the LIFE Study dataset, we found that in addition to the effect of PCB exposures on females, the male partners' PCB exposures play an important role in determining risk of infertility. Further, this risk is subadditive in the sense that there is likely a ceiling effect which limits the probability of infertility when both partners of the couple are at high risk.

Spatial and seasonal variations, sources, air-soil exchange, and carcinogenic risk assessment for PAHs and PCBs in air and soil of Kutahya, Turkey, the province of thermal power plants.

Atmospheric and concurrent soil samples were collected during winter and summer of 2014 at 41 sites in Kutahya, Turkey to investigate spatial and seasonal variations, sources, air-soil exchange, and associated carcinogenic risks of polycyclic aromatic hydrocarbons (PAHs) and polychlorinated biphenyls (PCBs). The highest atmospheric and soil concentrations were observed near power plants and residential areas, and the wintertime concentrations were generally higher than ones measured in summer. Spatial distribution of measured ambient concentrations and results of the factor analysis showed that the major contributing PAH sources in Kutahya region were the coal combustion for power generation and residential heating (48.9%), and diesel and gasoline exhaust emissions (47.3%) while the major PCB sources were the coal (thermal power plants and residential heating) and wood combustion (residential heating) (45.4%), and evaporative emissions from previously used technical PCB mixtures (34.7%). Results of fugacity fraction calculations indicated that the soil and atmosphere were not in equilibrium for most of the PAHs (88.0% in winter, 87.4% in summer) and PCBs (76.8% in winter, 83.8% in summer). For PAHs, deposition to the soil was the dominant mechanism in winter while in summer volatilization was equally important. For PCBs, volatilization dominated in summer while deposition was higher in winter. Cancer risks associated with inhalation and accidental soil ingestion of soil were also estimated. Generally, the estimated carcinogenic risks were below the acceptable risk level of 10-6. The percentage of the population exceeding the acceptable risk level ranged from <1% to 16%, except, 32% of the inhalation risk levels due to PAH exposure in winter at urban/industrial sites were >10-6.

Occurrence, distribution, and dechlorination of polychlorinated biphenyls and health risk assessment in Selangor River basin.

Polychlorinated biphenyls (PCBs) were monitored in surface water collected in the Selangor River basin, Malaysia, to identify the occurrence, distribution, and dechlorination process as well as to assess the potential adverse effects to the Malaysian population. Ten PCB homologs (i.e., mono-CBs to deca-CBs) were quantitated by using gas chromatography-mass spectrometry (GC/MS). The total concentration of PCBs in the 10 sampling sites ranged from limit of detection to 7.67 ng L-1. The higher chlorinated biphenyls (tetra-CBs to deca-CBs) were almost not detected in most of the sampling sites, whereas lower chlorinated biphenyls (mono-CBs, di-CBs, and tri-CBs) dominated more than 90 % of the 10 homologs in all the sampling sites. Therefore, the PCB load was estimated to be negligible during the sampling period because PCBs have an extremely long half-life. The PCBs, particularly higher chlorinated biphenyls, could be thoroughly dechlorinated to mono-CBs to tri-CBs by microbial decomposition in sediment or could still be accumulated in the sediment. The lower chlorinated biphenyls, however, could be resuspended or desorbed from the sediment because they have faster desorption rates and higher solubility, compared to the higher chlorinated biphenyls. The health risk for the Malaysia population by PCB intake that was estimated from the local fish consumption (7.2 ng kg-1 bw day-1) and tap water consumption (1.5 × 10-3-3.1 × 10-3 ng kg-1 bw day-1) based on the detected PCB levels in the surface water was considered to be minimal. The hazard quotient based on the tolerable daily intake (20 ng kg-1 bw day-1) was estimated at 0.36.

Distribution, sources and risk assessment of polychlorinated biphenyls in soils from the Midway Atoll, North Pacific Ocean.

Concentrations of 28 polychlorinated biphenyls (PCBs) were assessed in soils from the Midway Atoll in the central North Pacific Ocean. The analytical procedure involved the application of accelerated solvent extraction (ASE) and gas chromatography coupled with ion trap mass spectrometric detection (GC/ITMS) for identification and quantification. Among the 28 PCB congeners studied, 26 of them, except CB195 and CB209, were detected in the analyzed samples at different frequencies. The total concentrations of 28 indicator PCBs (ΣPCBs) ranged from 2.6 to 148.8 ng g⁻¹ with an average value of 50.7 ng g⁻¹ and median of 39.5 ng g⁻¹. Sources and congeners' pattern of PCB were investigated in the soil of Midway Atoll. The principal component analysis indicated that the compositions of PCBs in most of the soil samples were similar. The total concentrations of PCBs were used to assess the cancer risk probabilities in humans via ingestion, dermal contact and inhalation of soil particles. Very low cancer risk was found in all soil samples caused by ΣPCBs.

Specimen pooling for efficient use of biospecimens in studies of time to a common event.

For case-control studies that rely on expensive assays for biomarkers, specimen pooling offers a cost-effective and efficient way to estimate individual-level odds ratios. Pooling helps to conserve irreplaceable biospecimens for the future, mitigates limit-of-detection problems, and enables inclusion of individuals who have limited available volumes of biospecimen. Pooling can also allow the study of a panel of biomarkers under a fixed assay budget. Here, we extend this method for application to discrete-time survival studies. Assuming a proportional odds logistic model for risk of a common outcome, we propose a design strategy that forms pooling sets within those experiencing the outcome at the same event time. We show that the proposed design enables a cost-effective analysis to assess the association of a biomarker with the outcome. Because the standard likelihood is slightly misspecified for the proposed pooling strategy under a nonnull biomarker effect, the proposed approach produces slightly biased estimates of exposure odds ratios. We explore the extent of this bias via simulations and illustrate the method by revisiting a data set relating polychlorinated biphenyls and 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene to time to pregnancy.

Circulating levels of persistent organic pollutants are related to retrospective assessment of life-time weight change.

BACKGROUND: Persistent organic pollutants (POPs) have been suggested to be linked to obesity. We have previously shown that less-chlorinated PCBs were positively related to fat mass, while highly-chlorinated PCBs were inversely related to obesity. OBJECTIVE: The aim of the present evaluation is to investigate the relationship between retrospective assessed life-time change in body weight (20-70 years) with circulating POP levels measured at age 70 years. METHODS: 1016 subjects aged 70 years were investigated in the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUSs) study. 16 PCBs and 3 OC pesticides were analyzed using HRGC/HRMS. Current body weight was measured and participants self-reported their weight at age 20. RESULTS: The average estimated weight change over 50 years was 14.4 kg. Both the sum of OC pesticide concentrations (4.3 kg more weight gain in quintile 5 vs. quintile 1, p<0.0001) and the sum of the less-chlorinated PCBs were positively related to the estimated weight change (3.7 kg more weight gain in quintile 2 vs. quintile 1, non-linear relationship p=0.0015). In contrast, the sum of concentrations of highly-chlorinated PCBs were inversely related to estimated weight change (8.4 kg less weight gain in quintile 5 vs. quintile 1, p<0.0001). CONCLUSION: High levels of OC pesticides and the less-chlorinated PCBs at age 70 were associated with a pronounced estimated weight change over the previous 50 years. However, the opposite was seen for highly-chlorinated PCBs. Differences in mode of action, toxicokinetics, non-linear relationships and reverse causation might explain these discrepancies.

Menstrual cycle characteristics in European and Inuit women exposed to persistent organochlorine pollutants.

BACKGROUND: Previous inconsistent results suggest that menstrual cycles may be disturbed by exposure to polychlorinated biphenyls (PCBs) and 1,1-dichloro-2,2-bis (p-chlorophenyl)-ethylene (DDE). METHODS: Information on menstrual cycle characteristics were obtained by questionnaires, and PCB and DDE were measured in serum samples from a total of 1494 women from Greenland, Swedish fishermen's wives, and inhabitants of Warsaw in Poland and Kharkiv in Ukraine. RESULTS: No consistent effects of PCB and DDE exposure on menstrual cycle characteristics were observed across populations. Within populations, we observed increased risks of short cycles (< or =24 days) among Swedish fishermen's wives exposed to high levels of PCB [odds ratio (OR) 2.5, confidence interval (CI) 1.2-5.1], and increased risk of long cycles (> or =32 days) among Polish women exposed to high levels of DDE (OR 3.1, CI 1.1-8.6). However, in Greenland it seemed that high levels of PCB or DDE were protective against long menstrual cycles (OR 0.7 CI 0.5-0.96 and OR 0.7 CI 0.5-0.99, respectively). CONCLUSIONS: It is unlikely that exposure to PCB and DDE is a main cause of menstrual disturbances. Genetic differences or dietary factors may be involved in the non-homogenous associations of organochlorine exposure and menstrual cycle between countries.

Assessment of inhalation exposures and potential health risks to the general population that resulted from the collapse of the World Trade Center towers.

In the days following the collapse of the World Trade Center (WTC) towers on September 11, 2001 (9/11), the U.S. Environmental Protection Agency (EPA) initiated numerous air monitoring activities to better understand the ongoing impact of emissions from that disaster. Using these data, EPA conducted an inhalation exposure and human health risk assessment to the general population. This assessment does not address exposures and potential impacts that could have occurred to rescue workers, firefighters, and other site workers, nor does it address exposures that could have occurred in the indoor environment. Contaminants evaluated include particulate matter (PM), metals, polychlorinated biphenyls, dioxins, asbestos, volatile organic compounds, particle-bound polycyclic aromatic hydrocarbons, silica, and synthetic vitreous fibers (SVFs). This evaluation yielded three principal findings. (1) Persons exposed to extremely high levels of ambient PM and its components, SVFs, and other contaminants during the collapse of the WTC towers, and for several hours afterward, were likely to be at risk for acute and potentially chronic respiratory effects. (2) Available data suggest that contaminant concentrations within and near ground zero (GZ) remained significantly elevated above background levels for a few days after 9/11. Because only limited data on these critical few days were available, exposures and potential health impacts could not be evaluated with certainty for this time period. (3) Except for inhalation exposures that may have occurred on 9/11 and a few days afterward, the ambient air concentration data suggest that persons in the general population were unlikely to suffer short-term or long-term adverse health effects caused by inhalation exposures. While this analysis by EPA evaluated the potential for health impacts based on measured air concentrations, epidemiological studies conducted by organizations other than EPA have attempted to identify actual impacts. Such studies have identified respiratory effects in worker and general populations, and developmental effects in newborns whose mothers were near GZ on 9/11 or shortly thereafter. While researchers are not able to identify specific times and even exactly which contaminants are the cause of these effects, they have nonetheless concluded that exposure to WTC contaminants (and/or maternal stress, in the case of developmental effects) resulted in these effects, and have identified the time period including 9/11 itself and the days and few weeks afterward as a period of most concern based on high concentrations of key pollutants in the air and dust.

[Biological monitoring and risk assessment]. / Monitoraggio biologico e valutazione del rischio.

Risk assessment in occupational medicine is the part of risk analysis where physicians also contribute. A risk is the probability of an adverse health effect and derives from the hazard posed by a given chemical and from exposure characteristics. Due to the complexity of this process, models are used in occupational medicine, where risk factors are identified and exposure estimated, combined with an understanding of the severity of possible effects. Theoretically, the advantages of biological monitoring are obvious. However, the paucity of available data on biological monitoring limits its uses. Moreover, the utilization of data on biological monitoring requires evaluation of their significance. Examples are discussed to highlight advantages and limitations of biological monitoring data in both hazard and risk assessments. They include exposure to polycyclic aromatic hydrocarbons, benzene, other carcinogens, paraquat and polychlorinated biphenyls.

Quality assessment of bed sediments of the Po River (Italy).

Comprehensive and contemporary evaluations of physical, chemical and toxicological endpoints have been performed on bed sediments of the Po River, the major Italian watercourse. Two extensive sampling campaigns were conducted in summer and winter low-flow conditions. Composite sediment samples were collected from ten reaches of the main river: the first was located in the upper region (ambient control), and the others downstream of the confluences of nine principal tributaries. The two sampling programs were paralleled by contemporary investigations on the macroinvertebrate community. The particle-size composition along the Po River showed a relatively uniform distribution of fine sand, a progressive downstream decrease of coarse sands and a corresponding increase of fine materials. The levels of polychlorinated biphenyls (PCB), polycyclic aromatic hydrocarbons (PAH), extractable organo halides (EOX), Cd, Cr, Cu, Hg, Ni, Pb and Zn were determined in sediment fine particles (< 63 microm), and showed marked changes across the ten river reaches. Their longitudinal trends, as those of organic carbon and total nitrogen, were very similar and largely independent of the survey season. Sediment quality benchmarks were used to evaluate sediment chemistry, and, although the overall level of contamination was from moderate to low, the reaches located downstream of the tributaries Dora Riparia, Dora Baltea, Lambro and Oglio were considered to be at risk. Sediments were tested for toxicity on Oncorhynchus mykiss, Ceriodaphnia dubia, Raphidocelis subcapitata and Vibrio fischeri. The toxicity tests were conducted both with sediment extracts and whole samples. Sediment extracts showed toxic potentials that were consistent with the spatial distribution of contaminants. Whole-sediment toxicity showed moderate/low effects which also included false positives and negatives. Alterations of the macroinvertebrate community were found for many kilometers downstream of Dora Riparia, and with a seasonal dependence, also in other reaches of the Italian river. Principal component analysis (PCA) was used to describe the longitudinal and temporal changes of the Po River, and allowed the selection of the most useful and discriminating indicators.

Probabilistic risk assessment of reproductive effects of polychlorinated biphenyls on bottlenose dolphins (Tursiops truncatus) from the Southeast United States Coast.

High levels of polychlorinated biphenyls (PCBs) have been reported in the tissues of some species of marine mammals. The high concentrations are of concern because a growing body of experimental evidence links PCBs to deleterious effects on reproduction, endocrine homeostasis, and immune system function. Much of the recent research has focused on determining the exposure of marine mammal populations to PCBs, but very little effort has been devoted to the actual risk assessments that are needed to determine the expected impacts of the documented exposures. We describe a novel risk assessment approach that integrates measured tissue concentrations of PCBs with a surrogate dose-response relationship and leads to predictions of health risks for marine mammals as well as to the uncertainties associated with these predictions. Specifically, we use PCB tissue residue data from three populations of bottlenose dolphins (Tursiops truncatus), study the feasibility of published dose-response data from a surrogate species. and combine this information to estimate the risk of detrimental reproductive effects in female dolphins. Our risk analyses for dolphin populations near Beaufort (NC, USA), Sarasota (FL, USA), and Matagorda Bay (TX, USA) indicate a high likelihood that reproductive success, primarily in primiparous females, is being severely impaired by chronic exposure to PCBs. Excess risk of reproductive failure, measured in terms of stillbirth or neonatal mortality, for primiparous females was estimated as 60% (Beaufort), 79% (Sarasota), and 78% (Matagorda Bay). Females of higher parity, which have previously off-loaded a majority of their PCB burden, exhibit a much lower risk.

Assessment of contamination and biomarker responses in two species of herons on the St. Lawrence river.

This study was undertaken to validate potential biomarkers of exposure and effects due to chemical contaminants in breeding colonies of the Great Blue Heron and the Black-crowned Night-Heron on the St. Lawrence River. Eggs and fledglings from both species were collected from many colonies along the River. The fledglings from colonies in freshwater and brackish water were more contaminated by mercury and PCBs than those from estuarine and gulf colonies. With respect to fledglings of the two heron species, some morphometric and blood biochemical measurements, including plasma thyroid hormones and retinol, were significantly different among colonies. Significant differences were also observed in liver retinoids, EROD and porphyrins among colonies. The results of this study suggest that plasma retinoids and thyroid hormones are good biomarkers of exposure and effects, and are sufficiently sensitive to reflect local and regional variations in contamination. Along with the measure of contaminants in egg and plasma, they constitute non-invasive biomarkers which represent an important criteria for long term monitoring of wildlife species. It is concluded that the Great Blue Heron is an appropriate sentinel species in the surveillance network for the St. Lawrence River.

Assessment of injury to fish and wildlife resources in the Grand Calumet River and Indiana Harbor Area of Concern, USA.

This article is the second in a series of three that describes the results of a Natural Resource Damage Assessment (NRDA) conducted in the Grand Calumet River and Indiana Harbor Area of Concern (IHAOC). The assessment area is located in northwest Indiana and was divided into nine reaches to facilitate the assessment. This component of the NRDA was undertaken to determine if fish and wildlife resources have been injured due to exposure to contaminants that are associated with discharges of oil or releases of other hazardous substances. To support this assessment, information was compiled on the chemical composition of sediment and tissues; on the toxicity of whole sediments, pore water, and elutriates to fish; on the status of fish communities; and on fish health. The data on each of these indicators were compared to regionally relevant benchmarks to assess the presence and extent of injury to fish and wildlife resources. The results of this assessment indicate that injury to fish and wildlife resources has occurred throughout the assessment area, with up to five distinct lines of evidence demonstrating injury within the various reaches. Based on the frequency of exceedance of the benchmarks for assessing sediment and tissue chemistry data, total polychlorinated biphenyls is the primary bioaccumulative contaminant of concern in the assessment area. It is important to note, however, that this assessment was restricted by the availability of published bioaccumulation-based sediment quality guidelines, tissue residue guidelines, and other benchmarks of sediment quality conditions. The availability of chemistry data for tissues also restricted this assessment in certain reaches of the assessment area. Furthermore, insufficient information was located to facilitate identification of the substances that are causing or substantially contributing to effects on fish (i.e., sediment toxicity, impaired fish health, or impaired fish community structure). Therefore, substances not included on the list of COCs cannot necessarily be considered to be of low priority with respect to sediment injury (e.g., metals, polycyclic aromatic hydrocarbons, alkanes, alkenes, organochlorine pesticides, phthalates, dioxins, and furans, etc.).

Congener-distribution patterns and risk assessment of polychlorinated biphenyls, dibenzo-p-dioxins and dibenzofurans in Korean human milk.

Polychlorinated dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs) and biphenyls (PCBs) were analyzed by high-resolution gas chromatography/high-resolution mass spectrometry in human milk samples from an urban and an industrial area in Korea. All PCB congeners were analyzed to characterize the congener distribution as well as to evaluate the toxic equivalent quotient (TEQ) values and the total concentration. In homologue distributions of PCBs, two distinct patterns were found. The mean concentrations of PCDD/Fs and PCBs were 15.13 and 5.64 TEQ pg/g fat (based on WHO TEF, 1997), respectively. The contamination in Korean human milk is comparable to that found in other countries. From these results a daily intake of 60 TEQ pg/kg/day for an infant was estimated. The assumptions were that the infant breast feeds for 1 year, has an average body weight of 10 kg during this period, and ingests 800 g/day of human milk containing a mean concentration of 20.84 TEQ (PCDD/Fs) pg/g fat (based on primipara mothers).

Changes to the TEF schemes can have significant impacts on regulation and management of PCDD/F and PCB.

The changes recommended by the World Health Organisation (WHO) to the toxic equivalency factors (TEFs) for polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDD/F) and the recommendation to extend both the TEF scheme and the tolerable daily intake (TDI) to include "dioxin-like" PCB congeners have significant implications for regulators who have relied heavily on the International TEF (I-TEF) scheme in setting and monitoring limits and exposure to these compounds. This paper examines example data sets of sources, environmental concentrations, food and exposure to indicate likely changes in calculated toxic equivalent (TEQ) due to the recommended changes to TEFs. Many published data sets available do not provide congener specific data for PCDD/F which limits the ability to recalculate TEQs. There are even fewer congener specific data published to enable calculation of TEQs for the dioxin-like PCBs. In general TEQs calculated using the WHO scheme for emissions to air were found to show small increases (in the order of 1-10%) in comparison to the I-TEQ (for PCDD/F), some sludge samples showed substantial decreases (up to 70%). Levels in food and calculations of exposure showed that the change to TEFs for PCDD/F increased calculated exposure by 10-20% while the change to PCB TEFs decreased calculated TEQ attributable to PCB by 0-10%. The effects of including PCB in the overall TEQ and the changes to TEFs for PCDD/F substantially increase calculated TEQ exposure. Congener specific data should be presented to allow calculation of desired TEQ and the impact of the changes on emission limits, regulations on sludge use and environmental quality standards should all be carefully considered. The absence of data on emissions of dioxin-like PCB means that it is not possible to estimate with any certainty the impact on overall TEQ emissions of including the nominated PCB. Given the potential for confusion with the proliferation of TEFs and the extension to include both PCDD/F and PCB in the calculation of TEQs it is important that great care is taken to clearly express which compounds are included and which TEF scheme has been applied in each case.

Risk based management of contaminated sediments: consideration of spatial and temporal patterns in exposure modeling.

This paper addresses interactions among foraging behavior, habitat preferences, site characteristics, and spatial distribution of contaminants in developing PCB exposure estimates for winter flounder at a hypothetical open water dredged material disposal site in the coastal waters of New York and New Jersey (NY-NJ). The implications of these interactions for human health risk estimates for local recreational anglers who fish for and eat flounder are described. The models implemented in this study include a spatial submodel to account for spatial and temporal characteristics of fish exposures and a probabilistic adaptation of the Gobas bioaccumulation model that accounts for temporal variation in concentrations of hydrophobic contaminants in sediment and water. We estimated the geographic distribution of a winter flounder subpopulation offshore of NY-NJ based on species biology and its vulnerability to local recreational fishing, the foraging area of individual fish, and their migration patterns. We incorporated these parameters and an estimate of differential attraction to a management site into a spatially explicit model to assess the range of exposures within the population. The output of this modeling effort, flounder PCB tissue concentrations, provided exposure point concentrations for an estimate of human health risk through ingestion of locally caught flounder. The risks obtained for the spatially nonexplicit case are as much as 1 order of magnitude higher than those obtained with explicit consideration of spatial and temporal characteristics of winter flounder foraging and seasonal migration. This practice of "defaulting" to extremely conservative estimates for exposure parameters in the face of uncertainty ill serves the decision-making process for management of contaminated sediments in general and specifically for disposal of dredged materials. Consideration of realistic spatial and temporal scales in food chain models can help support sediment management decisions by providing a quantitative expression of the confidence in risk estimates.