A Conceptual Framework for the Interpretation of Biological Markers for Environmental Exposure Assessment

Human exposure to environmental contaminants occurs via air, water, soil, dust, food, and other environmental media. Given this multitude of sources, environmental exposure assessment is moving away from single route exposure assessment to more integrated measures of exposure. Biological markers are frequently advocated as appropriate exposure assessment tools since they provide a measure of internal dose integrated over all routes of exposure. However, contributing sources may be difficult to identify through use of biological markers, and thus, have had limited utility in the regulatory community. To explore the different perspectives on the use and application of biological markers for exposure assessors, epidemiologists, and regulatory personnel, we have developed a biological marker conceptual framework. This framework is developed as a paradigm for the interpretation of biological markers for environmental exposure assessment linking the exposure assessment and the health effects assessment perspectives regarding biological markers. Further, it incorporates issues of source-specific exposures, aggregate exposure assessment, route-specific contributions, and biological variation in response to exposure. This structure provides an approach to explore the current constraints in using biological markers to evaluate source-specific exposures. This framework is discussed in the context of currently available biological markers for lead, carbon monoxide, and toluene. Biological markers represent a complex tool to assess human exposures to environmental contaminants; the biological marker framework presents a structure for their interpretation recognizing that many of the determinants of exposure, bioavailablity, and toxicokinetics are still being evaluated. The conceptual framework presented here provides another tool for the researcher in assessing the utility of biological markers in exposure assessment and epidemiology.     

Peroxisomal proteomic approach for protein profiling in blue mussels (Mytilus edulis) exposed to crude oil

Peroxisomal proteomic protein profiles of exposure to marine pollution have been recently introduced in biomonitoring experiments. However, laboratory experiments to study the independent effect of common pollutants are needed to define a minimal protein expression signature (PES) of exposure to a specific pollutant. The aim of this study was to obtain PESs in blue mussels (Mytilus edulis) exposed to two different crude oil mixtures for future application in biomonitoring areas affected by oil spills. In the study, peroxisome-enriched fractions from digestive gland of M. edulis (L., 1758) were analysed by two-dimensional fluorescence difference electrophoresis (DIGE) and mass spectrometry (MS) after 3 weeks of exposure to crude oil mixtures: crude oil or crude oil spiked with alkylated phenols (AP) and extra polycyclic aromatic hydrocarbons (PAH) in a laboratory flow-through system. A minimal PES composed by 13 protein spots and unique PESs of exposure to the two different mixtures were identified. A total of 22 spots from the two-dimensional maps that had shown a significant increase or decrease in abundance in each of the exposed groups exposed were analysed. The hierarchical clustering analysis succeeded in discriminating the exposed groups from the control groups based on the unique PES. The PESs obtained were consistent with protein patterns obtained in previous field experiments. The results suggest that the protein profiles obtained by peroxisomal proteomics could be used to assess oil exposure in marine pollution assessments.     

Biomonitoring of chromium(VI) deposited in pulmonary tissues: Pilot studies of a magnetic resonance imaging technique in a post-mortem rodent model

The biomonitoring of individuals exposed to chromium(VI) by inhalation is often based on determinations of chromium in body fluids such as blood, plasma or urine, or on assessments of DNA damage in non-lung surrogate tissues such as peripheral blood lymphocytes. These techniques are of some use as biomarkers of internal exposure or biological effect, mainly in the case of soluble chromium(VI) compounds, but they provide at best only indirect information about chromium(VI) concentrations in the main target organ of interest - the lung. An urgent need exists for a non-invasive technique to permit the visualization and quantification of chromium(VI) in the lung of exposed humans. This study details the development of a lung imaging technique based on the detection of paramagnetic chromium using magnetic resonance imaging (MRI). The intracellular reductive conversion of chromium(VI) is a crucial bioactivation step in its carcinogenicity, and the MRI method described here relies on the conversion of non-paramagnetic (MRI 'silent') chromium(VI) to detectable paramagnetic species such as chromium(III). Initial studies with chromium(III) revealed that a range of 2.5-5 μg chromium(III) instilled in rat lung is considered to be the lower limit of detection of this method. It was possible to demonstrate the presence of 30 μg chromium(VI) in our post-mortem rat model. The ultimate objective of this work is to determine whether this technique has applicability to the biomonitoring of chromium(VI) inhalation exposures that result in internalized lung doses in human subjects.     

Environmental and occupational biomonitoring using the Comet assay

Biomonitoring of human populations exposed to potential mutagens or carcinogens can provide an early detection system for the initiation of cell disregulation in the development of cancer. In recent years, the Comet assay, also known as a “single cell gel” (SCG) electrophoresis assay, has become an important tool for assessing DNA damage in exposed populations. This is the method of choice for population-based studies of environmental and occupational exposure to air pollutants, metals, pesticides, radiation, and other xenobiotics as we show in this review. To appreciate the role of the Comet assay in the field of biomonitoring, we review data from 122 studies that employed the assay. These studies evaluated environmental versus occupational exposures and the levels of DNA damage in cells of individuals exposed in each case. Our review of the literature reveals the importance of the need to establish standard methodological conditions that affect unwinding and electrophoresis times and tail values (tail length, tail DNA, tail moment), with the goal of being able to compare data collected in different laboratories throughout the world. The Comet assay is susceptible to subtle artifacts of manipulation depending on the type and timing of sampling performed. Therefore, in the reporting of DNA damage detected by the Comet assay, the context of how the DNA damage was created also needs to be reported and considered in the interpretation of Comet assay results. The success of the Comet assay is reflected by its use over the past 20 years in the field of biomonitoring, and by the increasing number of studies that continue to report its use. As the shortcomings of the assay are identified and considered in the interpretation of DNA damage detection, the Comet assay will continue to provide improved reliability as a biomarker in human biomonitoring studies.     

Yale school of public health symposium on lifetime exposures and human health: the exposome; summary and future reflections

The exposome is defined as “the totality of environmental exposures encountered from birth to death” and was developed to address the need for comprehensive environmental exposure assessment to better understand disease etiology. Due to the complexity of the exposome, significant efforts have been made to develop technologies for longitudinal, internal and external exposure monitoring, and bioinformatics to integrate and analyze datasets generated. Our objectives were to bring together leaders in the field of exposomics, at a recent Symposium on “Lifetime Exposures and Human Health: The Exposome,” held at Yale School of Public Health. Our aim was to highlight the most recent technological advancements for measurement of the exposome, bioinformatics development, current limitations, and future needs in environmental health. In the discussions, an emphasis was placed on moving away from a one-chemical one-health outcome model toward a new paradigm of monitoring the totality of exposures that individuals may experience over their lifetime. This is critical to better understand the underlying biological impact on human health, particularly during windows of susceptibility. Recent advancements in metabolomics and bioinformatics are driving the field forward in biomonitoring and understanding the biological impact, and the technological and logistical challenges involved in the analyses were highlighted. In conclusion, further developments and support are needed for large-scale biomonitoring and management of big data, standardization for exposure and data analyses, bioinformatics tools for co-exposure or mixture analyses, and methods for data sharing.     

Biomonitoring of chromium(VI) deposited in pulmonary tissues: Pilot studies of a magnetic resonance imaging technique in a post-mortem rodent model

The biomonitoring of individuals exposed to chromium(VI) by inhalation is often based on determinations of chromium in body fluids such as blood, plasma or urine, or on assessments of DNA damage in non-lung surrogate tissues such as peripheral blood lymphocytes. These techniques are of some use as biomarkers of internal exposure or biological effect, mainly in the case of soluble chromium(VI) compounds, but they provide at best only indirect information about chromium(VI) concentrations in the main target organ of interest – the lung. An urgent need exists for a non-invasive technique to permit the visualization and quantification of chromium(VI) in the lung of exposed humans. This study details the development of a lung imaging technique based on the detection of paramagnetic chromium using magnetic resonance imaging (MRI). The intracellular reductive conversion of chromium(VI) is a crucial bioactivation step in its carcinogenicity, and the MRI method described here relies on the conversion of non-paramagnetic (MRI ‘silent’) chromium(VI) to detectable paramagnetic species such as chromium(III). Initial studies with chromium(III) revealed that a range of 2.5–5 μg chromium(III) instilled in rat lung is considered to be the lower limit of detection of this method. It was possible to demonstrate the presence of 30 μg chromium(VI) in our post-mortem rat model. The ultimate objective of this work is to determine whether this technique has applicability to the biomonitoring of chromium(VI) inhalation exposures that result in internalized lung doses in human subjects.     

Review of Information Resources to Support Human Exposure Assessment Models

Efforts to model human exposures to chemicals are growing more sophisticated and encompass increasingly complex exposure scenarios. The scope of such analyses has increased, growing from assessments of single exposure pathways to complex evaluations of aggregate or cumulative chemical exposures occurring within a variety of settings and scenarios. In addition, quantitative modeling techniques have evolved from simple deterministic analyses using single point estimates for each necessary input parameter to more detailed probabilistic analyses that can accommodate distributions of input parameters and assessment results. As part of an overall effort to guide development of a comprehensive framework for modeling human exposures to chemicals, available information resources needed to derive input parameters for human exposure assessment models were compiled and critically reviewed. Ongoing research in the area of exposure assessment parameters was also identified. The results of these efforts are summarized and other relevant information that will be needed to apply the available data in a comprehensive exposure model is discussed. Critical data gaps in the available information are also identified. Exposure assessment modeling and associated research would benefit from the collection of additional data as well as by enhancing the accessibility of existing and evolving information resources.     

Peroxisomal proteomic approach for protein profiling in blue mussels (Mytilus edulis) exposed to crude oil

Peroxisomal proteomic protein profiles of exposure to marine pollution have been recently introduced in biomonitoring experiments. However, laboratory experiments to study the independent effect of common pollutants are needed to define a minimal protein expression signature (PES) of exposure to a specific pollutant. The aim of this study was to obtain PESs in blue mussels (Mytilus edulis) exposed to two different crude oil mixtures for future application in biomonitoring areas affected by oil spills. In the study, peroxisome-enriched fractions from digestive gland of M. edulis (L., 1758) were analysed by two-dimensional fluorescence difference electrophoresis (DIGE) and mass spectrometry (MS) after 3 weeks of exposure to crude oil mixtures: crude oil or crude oil spiked with alkylated phenols (AP) and extra polycyclic aromatic hydrocarbons (PAH) in a laboratory flow-through system. A minimal PES composed by 13 protein spots and unique PESs of exposure to the two different mixtures were identified. A total of 22 spots from the two-dimensional maps that had shown a significant increase or decrease in abundance in each of the exposed groups exposed were analysed. The hierarchical clustering analysis succeeded in discriminating the exposed groups from the control groups based on the unique PES. The PESs obtained were consistent with protein patterns obtained in previous field experiments. The results suggest that the protein profiles obtained by peroxisomal proteomics could be used to assess oil exposure in marine pollution assessments.     

Multi-elemental determination of metals,metalloids and rare earth element concentrations in whole blood from the Canadian Health Measures Survey, 2009-2011

BackgroundAs part of Government of Canada’s Chemical Management Plan, substances containing aluminum (Al), bismuth (Bi), cerium (Ce), chromium (Cr), germanium (Ge), lanthanum (La), lithium (Li), neodymium (Nd), praseodymium (Pr), tellurium (Te), titanium (Ti) and yttrium (Y) were identified as priorities for risk assessment. Generating exposure estimates from all routes of exposure from multiple sources using a traditional approach for these elements can be challenging. The use of human biomonitoring (HBM) data would allow for direct and more precise assessment of the internal concentrations from all routes and all sources of exposure. There are no Canadian or North American population-level whole blood HBM data for the elements listed above. Therefore, this is the first biomonitoring project carried out to determine the concentrations of these elements from a nationally representative sample of Canadians.ObjectivesThe objective of this study was to generate whole blood concentrations for Al, Bi, Ce, Cr, Ge, La, Li. Nd, Pr, Te, Ti and Y in the Canadian population using biobank samples from the Canadian Health Measures Survey (CHMS) cycle 2 (2009–2011) for use in characterizing exposure in screening assessments and for establishing baseline concentrations to determine how exposures are changing over time.MethodsThe sample analysis was conducted by ICP-MS. A rigorous quality control and quality assurance process was implemented in order to generate data with high accuracy and precision while measuring low concentrations and minimizing possible inadvertent contamination.ResultsOf the elements analysed, the whole blood concentrations (μg/L) of Al, Ce, Cr, Ge, La, Nd, Pr, Te, Ti and Y in the Canadian population aged 3–79 years were below their respective method reporting limit (MRL). Two elements, Bi and Li were detected in 5 % and 66 % of the Canadian population. The median Li concentration was 0.47 μg/L.ConclusionThe results of this study provide information on concentrations of these elements in the Canadian population which can be utilized to characterize exposure in screening assessments and there by the potential for harm to human health. In addition, this study provides baseline HBM data which can be used as a comparative HBM dataset for other populations with similar exposure patterns.     

Serum levels of the extracellular domain of the epidermal growth factor receptor in individuals exposed to arsenic in drinking water in Bangladesh

Epidermal growth factor receptor-dependent mechanisms have been implicated in growth signal transduction pathways that contribute to cancer development, including dermal carcinogenesis. Detection of the extracellular domain of the epidermal growth factor receptor (EGFR ECD) in serum has been suggested as a potential biomarker for monitoring this effect in vivo. Arsenic is a known human carcinogen, producing skin and other malignancies in populations exposed through their drinking water. One such exposed population, which we have been studying for a number of years, is in Bangladesh. The purpose of this study was to examine the EGFR ECD as a potential biomarker of arsenic exposure and/or effect in this population. Levels of the EGFR ECD were determined by enzyme-linked immunosorbent assay in the serum samples from 574 individuals with a range of arsenic exposures from drinking water in the Araihazar area of Bangladesh. In multiple regression analysis, serum EGFR ECD was found to be positively associated with three different measures of arsenic exposure (well water arsenic, urinary arsenic and a cumulative arsenic index) at statistically significant levels (p≤0.034), and this association was strongest among the individuals with arsenic-induced skin lesions (p ≤ 0.002). When the study subjects were stratified in tertiles of serum EGFR ECD levels, the risk of skin lesions increased progressively for each increase in all three arsenic measures (also stratified in tertiles) and this increasing risk became more pronounced among subjects within the highest tertile of EGFR ECD levels. These results suggest that serum EGFR ECD levels may be a potential biomarker of effect of arsenic exposure and may indicate those exposed individuals at greatest risk for the development of arsenic-induced skin lesions.     

Serum levels of the extracellular domain of the epidermal growth factor receptor in individuals exposed to arsenic in drinking water in Bangladesh

Epidermal growth factor receptor-dependent mechanisms have been implicated in growth signal transduction pathways that contribute to cancer development, including dermal carcinogenesis. Detection of the extracellular domain of the epidermal growth factor receptor (EGFR ECD) in serum has been suggested as a potential biomarker for monitoring this effect in vivo. Arsenic is a known human carcinogen, producing skin and other malignancies in populations exposed through their drinking water. One such exposed population, which we have been studying for a number of years, is in Bangladesh. The purpose of this study was to examine the EGFR ECD as a potential biomarker of arsenic exposure and/or effect in this population. Levels of the EGFR ECD were determined by enzyme-linked immunosorbent assay in the serum samples from 574 individuals with a range of arsenic exposures from drinking water in the Araihazar area of Bangladesh. In multiple regression analysis, serum EGFR ECD was found to be positively associated with three different measures of arsenic exposure (well water arsenic, urinary arsenic and a cumulative arsenic index) at statistically significant levels (p≤0.034), and this association was strongest among the individuals with arsenic-induced skin lesions (p ≤ 0.002). When the study subjects were stratified in tertiles of serum EGFR ECD levels, the risk of skin lesions increased progressively for each increase in all three arsenic measures (also stratified in tertiles) and this increasing risk became more pronounced among subjects within the highest tertile of EGFR ECD levels. These results suggest that serum EGFR ECD levels may be a potential biomarker of effect of arsenic exposure and may indicate those exposed individuals at greatest risk for the development of arsenic-induced skin lesions.     

Human exposure to ultraviolet radiation at the Antipodes – a comparison between an Antarctic (67°S) and Arctic (75°N) location

. We used ultraviolet radiation dosimeters to investigate human exposure at two polar latitudes with a 24-h photoperiod: at Rothera Station (UK) (67°S) and at a field camp in the Haughton impact structure in the Canadian High Arctic (75°N). Mean personal UV radiation exposure in the Antarctic location was 4.3 times greater than that in the Arctic location, even in the absence of ozone depletion. More than zenith angle accounted for the higher UV exposure. Widespread snow and ice covers, and probably less atmospheric pollution, caused higher personal exposures. Although the mean exposures were higher in the Antarctic location, the mean exposure ratio in the Antarctic (0.20ǂ.09) was similar to the value measured in the Arctic (0.27ǂ.09) on clear days. We use the Antarctic ratio to provide quantitative estimates of UV-radiation exposure for workers at the Geographical South Pole for the winter solstice under a constant 24-h photoperiod. Exposure ratios can be used to translate measurements of UV radiation by horizontally fixed spectroradiometers into estimates of the mean exposures expected in populations at polar latitudes, although variations between individuals are large. The data have implications for determining the UV exposures of indigenous high-latitude populations.     

Estimation of population attributable fractions from fitted incidence ratios and exposure survey data, with an application to electromagnetic fields and childhood leukemia

Standard presentations of epidemiological results focus on incidence-ratio estimates derived from regression models fit to specialized study data. These data are often highly nonrepresentative of populations for which public-health impacts must be evaluated. Basic methods are provided for interval estimation of attributable fractions from model-based incidence-ratio estimates combined with independent survey estimates of the exposure distribution in the target population of interest. These methods are illustrated in estimation of the potential impact of magnetic-field exposures on childhood leukemia in the United States, based on pooled data from 11 case-control studies and a U.S. sample survey of magnetic-field exposures.     

Combining environmental exposure and genetic effect measurements in health outcome assessment.

The presence of overwhelming difficulties in assessing the extent or even the presence of a causal association between modern environmental exposures and disease has promoted the use of more complex models in the design of human biomonitoring studies. The concatenation of environmental exposure, genetic effect and individual susceptibility is a key issue in the assessment of risks for populations exposed to environmental pollutants. The use of a biological event laying in the causal pathway from exposure to outcome as surrogate end-point of disease, can potentially anticipate clinical diagnosis, offering a number of possibilities for application of preventive measures. Numerous biomarkers are currently employed to study human populations exposed to environmental carcinogens, among these, the frequency of chromosomal aberration (CA) in peripheral blood lymphocytes has the most abundant literature linking a genetic effect with the occurrence of cancer. Findings from recent epidemiological studies which have followed-up a large group of healthy subjects screened for CAs have lent further support to the use of chromosomal breakage as a relevant biomarker of cancer risk. The applicability of surrogate end-points of cancer on an individual basis thus far seems to be limited to few examples. On the other hand, from a public health outlook, increases in the frequency of surrogate end-points are suggestive of an increased risk of cancer, and for validated biomarkers such as CAs intervention policies and actions in exposed populations showing increased frequency of these end-points should be always recommended.     

Chromosomal aberrations in humans as genetic endpoints to assess the impact of pollution

The chromosomal aberration assay with peripheral blood lymphocytes has been used routinely during the last three decades to survey exposure of humans to various genotoxic agents. A large number of biomonitoring studies are based on this genetic endpoint. A great deal of data exists on occupational, life-style or medical exposure situations but less evidence of the validity of the assay is available with regards to environmental exposure. In the present paper we report our investigations on the impact of pollution in two different populations using chromosomal aberrations in human peripheral blood lymphocytes as a biomarker of chronic exposure to heavy metals and dioxins/furans for a long period and as a biomarker of acute exposure to accidentally released vinyl chloride in the air. In order to study genotoxic effects (chromosomal aberrations) of heavy metals and dioxins/furans, 52 exposed individuals from a polluted area were compared to 51 matched controls from a distant non-industrialized area. A statistically significant increase was observed in the frequency of chromosomal aberrations in peripheral blood lymphocytes from the exposed population (1.90% aberrant cells vs. 1.11% for the controls). In the case of the vinyl chloride accident, chromosomal aberrations were analyzed in peripheral blood lymphocytes from 29 potentially exposed and 29 non-exposed individuals (matched controls). The exposed group showed a statistically significant increase in the frequency of aberrant cells (1.47% vs. 1.07% for the controls).     

An evaluation of several methods for assessing the effects of occupational exposure to radiation

Several methods for the analysis of occupational radiation exposure data, including procedures based on Cox's proportional hazards model, are presented and evaluated. Issues of interest include the contribution of an external control, the effective handling of highly skewed exposure data, and the potential for detecting effects in populations occupationally exposed to radiation. Expressions for evaluating the power of various procedures are derived and applied to data from the Hanford population in order to determine power curves for detecting leukemia effects, with both additive and multiplicative linear models being used. It is found that the introduction of an external control can increase power, although not when an overall adjustment factor must be estimated from the data or when death rates for the study population are substantially lower than those for the control population. It is also found that very little power is lost if exposures are grouped. Finally, the power calculations indicate, as expected, that in analyses of occupationally exposed populations, such as the Hanford workers, there is very little chance of detecting radiation effects at the levels of our current estimates. However, power is reasonably good for detecting effects that are 10 to 15 times larger.     

Microwave effects on energy metabolism of rat brain

Rat brain was exposed to 591-MHz, continuous-wave (CW) microwaves at 13.8 or 5.0 mW/cm² to determine the effect on nicotinamide adenine dinucleotide, reduced (NADH), adenosine triphosphate (ATP) and creatine phosphate (CP) levels. On initiation of the in vivo microwave exposures, fluorimetrically determined NADH rapidly increased to a maximum of 4.0%–12.5% above pre-exposure control levels at one-half minute, then decreased slowly to 2% above control at three minutes, finally increasing slowly to 5% above control level at five minutes. ATP and CP assays were performed on sham- and microwave-exposed brain at each exposure time. At 13.8 mW/cm², brain CP level was decreased an average of 39.4%, 41.1%, 18.2%, 13.1%, and 36.4% of control at exposure points one-half, one, two three, and five minutes, respectively, and brain ATP concentration was decreased an average of 25.2%, 15.2%, 17.8%, 7.4%, and 11.2% of control at the corresponding exposure periods. ATP and CP levels of rat brain exposed to 591-MHz cw microwaves at 5 mW/cm² for one-half and one minute were decreased significantly below control levels at these exposure times, but were not significantly different from the 13.8 mW/cm² exposures. For all exposures, rectal temperature remained constant. Heat loss through the skull aperture caused brain temperature to decrease during the five-minute exposures. This decrease was the same in magnitude for experimental and control subjects. Changes in NADH, ATP, and CP levels during microwave exposure cannot be attributed to general tissue hyperthermia. The data support the hypothesis that microwave exposure inhibits mitochondrial electron transport chain function, which results in decreased ATP and CP levels in brain.     

Effects of 4-n-nonylphenol and 17beta-oestradiol on early development of the barnacle Elminius modestus

Pollutants that are present in the aquatic environment and cause abnormal endocrine function in wildlife populations have been termed endocrine disrupting chemicals (EDCs). The impacts of these chemicals on the reproduction and development of vertebrates has been shown to be significant in both field studies and laboratory experiments. Over the past decade the number of investigations into the impacts of EDCs that affect reproductive and sexual characteristics (reproductive EDCs) has increased and evidence of their potency is evident in numerous wildlife species and through data from in vitro tests. However, little information is available on whether chemicals which act as EDCs in vertebrate species affect aquatic invertebrates. The case of imposex in archeogastropods following exposure to tributyltin (TBT) is a notable exception. Moreover, a number of studies have shown that development, fecundity and reproductive output of some aquatic invertebrates are affected significantly by exposure to pollutants. In order to determine whether external signs of exposure to vertebrate EDCs can be observed and monitored in invertebrate species, we exposed larvae of the barnacle Elminius modestus to environmentally realistic concentrations of the xeno-oestrogen, 4-n-nonylphenol (NP), and the natural oestrogen, 17beta-oestradiol (E(2)). Early life stages (nauplii and cyprids) were also exposed in the laboratory to determine whether there were effects on the timing of larval development and settlement. Ovary development and size of juveniles was measured following chronic exposure. Exposure to NP in the concentration range 0.01-10 μg l(-1) resulted in disruption of the timing of larval development. Similar results were obtained with E(2). Pulse exposures showed that the timing of exposure is critical and exposures for a period of 12 months caused long-term effects. A linear, concentration-dependent response was not evident.     

Duration of exposure to environmental carcinogens affects DNA-adduct level in human lymphocytes

Background and objective: An important issue in human biomonitoring is determining how exposure duration affects the kinetics of molecular biomarkers. In this study we compare the influence of exposure variables on DNA adducts.

Methods: DNA adducts were analysed by 32P-postlabelling in lympho/monocytes of 677 Caucasian subjects.

Results: After correction for other variables, DNA adducts increased depending on the length of occupational and smoke exposures. Higher DNA adducts were detected in workers with more than 14 years of exposure than in workers with shorter exposures (RR?=?1.19, p?=?0.049) and in smokers with more than 10 years of exposure than in smokers with shorter exposure (RR?=?1.21, p <0.001).

Conclusions: Exposure length is the primary factor affecting DNA-adduct level in lympho/monocytes both in smokers and in occupationally exposed subjects.     

Joint PCB-Methylmercury Exposures and Neurobehavioral Outcomes

The level of intake at which methylmercury might result in neurobehavioral or neuro psychological deficits in children has been extensively debated in recent years. The human data base for methylmercury toxicity is very robust, particularly when compared with other environmental substances for which health guidance values have been developed by Federal organizations. However, despite the depth of the data base for methylmercury, some of the key studies have been clouded by the concurrent exposure of the study population to polychlorinated biphenys (PCBs) and other persistent organic pollutants (POPs). In this paper, the authors examine the key points comprising the methylmercury-PCB issue and contrast these with recent reports of concurrent methylmercury/PCB human exposures and laboratory studies. The authors conclude that research published to date concerning the Seychelles and Faroes Island populations suggests that both methylmercury and PCBs are jointly responsible for the effects reported in the Faroes. Further neurobehavioral testing in populations exposed to PCBs alone, as well as with methylmercury alone, is necessary to fully resolve the ongoing debate.