Toxicant Body Burden Research Articles

Assessment of the Health Status of Children Exposed to Industrial Toxicants in the Towns with Developed Non-Ferrous Metallurgy of the Sverdlovsk Region

Introduction: In the Sverdlovsk Region, the risks posed by cadmium, arsenic and lead exposures account for higher disease rates in the most sensitive groups of population. Recent studies have shown that these toxicants have an effect on mineral metabolism, damage to liver cells, kidneys, immunity indicators, and the nervous system. Objective: To assess the levels of cadmium, lead and arsenic in biological fluids of preschool children aged 3–6 years, living in towns with developed non-ferrous metallurgy, and possible changes in the health status at the detected level of toxicity. Materials and methods: The study was conducted in six towns of the Sverdlovsk Region with developed non-ferrous metallurgy. Environmental pollution in the study areas was assessed based on data of socio-hygienic monitoring. Biological monitoring was carried out to establish the levels of toxicants in blood and urine of children. A descriptive analysis of chronic morbidity in preschool children was performed, and the results of a special health examination of children (including that by a pediatrician and a neurologist) were presented. Mathematical modeling using decision trees was carried out. Results: Health monitoring data indicate an excess of the average regional prevalence rates in the studied preschoolers in nine disease categories. According to the results of an in-depth examination of the preschool children, diseases of the skin and subcutaneous tissue, diseases of the respiratory system, blood diseases and individual disorders involving the immune mechanism, and digestive diseases prevailed. Among concomitant diseases, the most prevalent were diseases of the digestive, nervous, and respiratory systems. Assessment of the neurological status showed that the largest percentage of children had residual cerebral insufficiency, attention deficit hyperactivity disorder, and cerebrastenic syndrome. Biomonitoring results indicated a higher level of lead, arsenic and cadmium in the biological fluids of those children. Mathematical modeling demonstrated statistically significant correlations between lead, cadmium, and arsenic concentrations in environmental objects, biomonitoring results, and clinical and laboratory examination data of children (the blood levels of alanine aminotransferase, zinc, total protein, phagocytic index, and the carrier of the marker of apoptosis CD95+). Conclusions: The results of biological monitoring were consistent with data on chronic morbidity in preschool children. Modeling data provided the body burden of toxicants, above which deviations of clinical and laboratory parameters from the reference values may occur. The findings can be used in implementation of targeted measures for disease prevention.

Environmental Endocrine Disruptors and Endometriosis.

As a consequence of industrialization, thousands of man-made chemicals have been developed with few undergoing rigorous safety assessment prior to commercial use. Ubiquitous exposure to these compounds, many of which act as endocrine-disrupting chemicals (EDCs), has been suggested to be one factor in the increasing incidence of numerous diseases, including endometriosis. Endometriosis, the presence of endometrial glands and stroma outside the uterus, is a common disorder of reproductive-age women. Although a number of population-based studies have suggested that exposure to environmental EDCs may affect a woman's risk of developing this disease, results of epidemiology assessments are often equivocal. The development of endometriosis is, however, a process occurring over time; thus, a single assessment of toxicant body burden cannot definitively be linked to causation of disease. For this reason, numerous investigators have utilized a variety of rodent models to examine the impact of specific EDCs on the development of experimental endometriosis. These studies identified multiple chemicals capable of influencing physiologic processes necessary for the establishment and/or survival of ectopic tissues in rodents, suggesting that these compounds may also be of concern for women. Importantly, these models serve as useful tools to explore strategies that may prevent adverse outcomes following EDC exposure.

In vivo contaminant partitioning to silicone implants: Implications for use in biomonitoring and body burden

Silicone polymers are used for a wide array of applications from passive samplers in environmental studies, to implants used in human augmentation and reconstruction. If silicone sequesters toxicants throughout implantation, it may represent a history of exposure and potentially reduce the body burden of toxicants influencing the risk of adverse health outcomes such as breast cancer. Objectives of this research included identifying a wide variety of toxicants in human silicone implants, and measuring the in vivo absorption of contaminants into silicone and surrounding tissue in an animal model. In the first study, eight human breast implants were analyzed for over 1400 organic contaminants including consumer products, chemicals in commerce, and pesticides. A total of 14 compounds including pesticides such as trans-nonachlor (1.2–5.9ng/g) and p,p′-DDE (1.2–34ng/g) were identified in human implants, 13 of which have not been previously reported in silicone prostheses. In the second project, female ICR mice were implanted with silicone and dosed with p,p′-DDE and PCB118 by intraperitoneal injection. After nine days, silicone and adipose samples were collected, and all implants in dosed mice had p,p′-DDE and PCB118 present. Distribution ratios from silicone and surrounding tissue in mice compare well with similar studies, and were used to predict adipose concentrations in human tissue. Similarities between predicted and measured chemical concentrations in mice and humans suggest that silicone may be a reliable surrogate measure of persistent toxicants. More research is needed to identify the potential of silicone implants to refine the predictive quality of chemicals found in silicone implants.

Clinical Detoxification: Elimination of Persistent Toxicants from the Human Body

Clinical Detoxification: Elimination of Persistent Toxicants from the Human Body

Levels of persistent organic pollutant and their predictors among young adults

Exposure to persistent organic pollutants (POPs), such as polychlorinated biphenyls (PCBs), dichlorodiphenyldichloroethane ( p,p′ -DDE), and hexachlorobenzene (HCB) continues to be of concern due to their ubiquitous distribution and high persistence. Current toxicant body burden is still a primary concern within the Akwesasne Mohawk Nation since other studies conducted within the community have shown relationships between these POPs and endocrine disruption. In this article we describe the levels of these toxicants in young adults of the Akwesasne Mohawk Nation between the ages of 17 and 21 years of age (mean age 18.1 years), and investigate potential influences of their current body burden. Seventeen congeners in fourteen chromatographic peaks were detected in 50% or more of the individuals sampled (geometric mean [GM] of the sum of these congeners = 0.43 ppb). Congeners 118, 138[+163 + 164] and 153 had the highest rate of detection (⩾98%) within the Akwesasne young adults. Of the other organochlorines, HCB (GM = 0.04 ppb) and p,p′-DDE (GM = 0.38 ppb) were found in 100% and 99% of the sample respectively. Significantly higher levels of PCBs were found among individuals who were breastfed as infants, were first born, or had consumed local fish within the past year. When compared to levels of p, p′-DDE, HCB, and 13 specific congeners reported by the CDC for youth between the ages of 12 and 19 years, the geometric means of several congeners (CBs 99, 105, 110, and 118) among the Akwesasne were higher than the reported CDC 90th percentile. In contrast, levels of CB 28 in Akwesasne young adults were ∼50% or less than those of the CDC cohort. p,p′-DDE and HCB levels were generally higher in the CDC cohort (GM of 0.516 and 0.065 ppb, respectively for Mohawks vs. 2.51 and 0.123, respectively, for CDC). Concentrations of non-persistent PCBs among this sample of Akwesasne young adults were higher than those reported by the CDC suggesting continued exposure, but lower than those associated with severe contamination. Additional research into the concentration trends of individual PCB congeners within Akwesasne youth and young adults is warranted to further improve our insight into the determinants and influences of organochlorine concentrations within members of the Akwesasne community.

Identification of hepatotoxicity related genes induced by toxaphene in HepG2 cells

Toxaphene is a bioaccumulative, persistent, and toxic pollutant. Toxaphene is one of the 12 priority of Persistent Organic Pollutants (POPs) intended for global action by the United Nations Environment Program (UNEP) Governing Council. POPs are manmade synthetic chemicals highly resistant to biodegradation, with a high affinity for bioaccumulation (due to their hydrophobic and/or lipophilic nature) and biomagnification in the environment and living organisms, including humans. Once deposited in humans (mainly in adipose tissue), they form stable compounds that result in a lasting toxic body burden. Most human populations are exposed to mixtures of POPs originated either from local or remote sources. Toxaphene is ubiquitous in air, water, soil, and biological matrices, as well as in major environmental compartments. Toxaphene has effects on various organs such as thyroid, bone, skin, kidneys, and blood cells and especially, revealed strong toxicity to liver. In this study, we identified genes related to hepatotoxiciy induced by toxaphene in human hepatocellular carcinoma (HepG2) cells using microarray and gene ontology (GO) analysis. Through microarray analysis, we identified 1,647 up- and 2,251 down-regulated genes changed by more than 1.5-fold and P-values 0.001 by toxaphene. And after GO analysis, we determined several key pathways which known as related to hepatotoxicity such as MAPK signaling pathway, complement and coagulation cascades, tight junction. Thus, our present study suggests that genes expressed by toxaphene may provide a clue for hepatotoxic mechanism of toxaphene.

Multistressor interactions in the zebrafish ( Danio rerio): Concurrent phenanthrene exposure and Mycobacterium marinum infection

The simultaneous exposure of organisms to toxicants and disease causing agents poses a serious risk to important stocks. Worldwide, aquatic animal disease outbreaks have been increasing in both frequency and severity, and many have been associated with anthropogenic environmental change. Little is known about the complex interactions of the immune system and biotransformational pathways of vertebrates; however, urbanization and coastal development create a scenario in which a wide range of species are exposed to chemical pollutants in conjunction with a wide spectrum of ubiquitous, opportunistic pathogens. These interactions can severely compromise organismal health. Potential effects include decreased fitness, increased predation, decreased fecundity, reduced metabolic activity, suppressed immune function and mortality. Recent attention has been paid to immunomodulation in toxicant exposed fishes. In our current study we investigated the effects of the common polycyclic aromatic hydrocarbon phenanthrene in conjunction with Mycobacterium marinum infection in the zebrafish, Danio rerio. The goal of our study was to elucidate the interactions between stressors in the host organism. Fish were exposed to either a high or low dose of phenanthrene, infected with M. marinum or received a combination exposure of toxicant and bacteria. Results of our study were evaluated using survivorship analysis, toxicant body burden, and histology. Our data show an interaction between M. marinum infection and exposure to a high dose of phenanthrene in the zebrafish. Survivorship was significantly reduced for animals only exposed to the high dose of phenanthrene as compared to all other experimental groups. The increased survivorship for fish exposed to both Mycobacterium and a high dose of phenanthrene suggests an antagonistic interaction between stressors. Body burden data, which show significant differences in the ratio of phenanthrene:metabolites between experimental groups, suggests a disruption of the biotransformational pathway. We postulate that the inflammatory response, initiated by bacterial infection, is impeding the ability of the zebrafish to completely metabolize phenanthrene. In addition, the correlation between reduced metabolite production and increased survival indicates that phenanthrene metabolites are more toxic than the parent compound. Our study underscores the importance of investigating multiple stressor interactions as a way to better understand complex environmental interactions.

Elimination of persistent toxicants from the human body

There is compelling evidence that various chemical agents are important determinants of myriad health afflictions--several xenobiotics have the potential to disrupt reproductive, developmental, and neurological processes and some agents in common use have carcinogenic, epigenetic, endocrine-disrupting, and immune-altering action. Some toxicants appear to have biological effect at miniscule levels and certain chemical compounds are persistent and bioaccumulative within the human body. Despite escalating public health measures to preclude further exposures, many people throughout the world have already accrued a significant body burden of toxicants, placing them at potential health risk. As a result, increasing discussion is underway about possible interventions to facilitate elimination of persistent toxicants from the human organism in order to obviate health affliction and to potentially ameliorate chronic degenerative illness. An overview of the clinical aspects of detoxification is presented with discussion of established and emerging interventions for the elimination of persistent xenobiotics. Potential therapies to circumvent enterohepatic recirculation and a case report highlighting a clinical outcome associated with detoxification are also presented for consideration.

Toxicant Exposure and Mental Health—Individual, Social, and Public Health Considerations

Thoughts and moods are the result of biological processes; disordered thoughts and moods may be the result of disordered biological processes. As brain dysfunction can manifest with emotional symptoms or behavioral signs, the etiology of some mental health afflictions and some abnormal conduct is pathophysiological rather than pathopsychological. Various studies confirm that some chemical toxicants which modify brain physiology have the potential to affect mood, cognitive function, and to provoke socially undesirable outcomes. With pervasive concern about myriad chemical agents in the environment and resultant toxicant bioaccumulation, human exposure assessment has become a clinically relevant area of medical investigation. Adverse exposure and toxicant body burden should routinely be explored as an etiological determinant in assorted health afflictions including disordered thinking, moods, and behavior. The impact of toxicant bioaccumulation in a patient with neuropsychiatric symptoms is presented for consideration as an example of the potential benefit of recognizing and implementing exposure assessment.

Environmental Contaminants in Breast Milk

Toxic environmental contaminants can be transferred from mother to infant via breastfeeding. Persistent organic pollutants (POPs) are a family of lipophilic stable chemicals that bioaccumulate in adipose tissue and create a lasting toxic body burden. Breastfeeding provides a significant source of exposure to POPs early in human life, the effects of which are unknown, and is the subject of a growing body of research. Despite the possibility of harm from environmental contaminants in breast milk, breastfeeding is still recommended as the best infant feeding method. This article reviews what is known about POPs in breast milk and their effect on infant development to inform clinicians about the issue, provide recommendations for practice, and promote environmental and public health policies that reduce human exposure to harmful pollutants.

Evolution of chemical contaminant and toxicology studies, part 2 - case studies of Selenium and Arsenic

As the second of a two part series discussing the evolution of the field of environmental toxicology, this paper presents two case studies: selenium and arsenic. Developments over several decades in the understanding of the behaviour of arsenic and selenium in different chemical forms in various compartments of the environment are discussed. Selenium was initially thought to be toxic, but later investigations showed it to be an essential micronutrient with a variety of biochemical functions, and, importantly, that there is a very narrow gap between the essential and the toxic body burden. Arsenic, on the other hand, has not yet had an essential role established, but enjoys an interesting and notorious history of usage. Arsenic contamination of the drinking water supplies for many millions of people has been a major catalyst for much research into understanding arsenic chemistry in aquifer systems and also arsenic metabolism and toxicity. The relationships between chemical form, bioavailability, toxicity and metabolism of these two semi-metals are being established, especially with use of sophisticated and sensitive analytical instrumentation and biochemical techniques.

A physiological model to predict xenobiotic concentration in fish

A physiological model was developed to estimate fish body toxicant load based on information regarding the chemical exposure regime, fish body weight, lipid content and oxygen uptake. The general model was tested in which an oxygen database (OXYREF) was used to predict fish toxicant body burden. Based on the quantitative analysis, it was shown that the model was reliable and accurate in estimating fish body burden of a number of non-metabolized aquatic toxicants. This modified model possesses some functional reality which enables more realistic predictions, making it useful in the practice of aquatic environmental risk assessment.

Interactions between genetic predisposition and environmental toxicants for development of lung cancer.

Significant interindividual variations in health outcome may be caused by the inheritance of variant polymorphic genes, such as CYP2D6 and CYP2E1 for activation, and GSTM1 and GSTT1 for detoxification of chemicals. However, mechanistic studies linking the inheritance of predisposing genes with genotoxic effects towards cancer have yet to be systematically conducted. We have studied 54 lung cancer patients and 50 matched normal controls, who have been cigarette smokers, to elucidate the role of polymorphic genes in cancer. Our data indicates that the inheritance of unfavorable CYP2D6, CYP2E1, and GSTT1 genes in strongly correlated with the smoking-related lung cancer. For heavy cigarette smokers (> 30 pack-years), the smoking habit is the strongest predictor of lung cancer risk irrespective of the inheritance of unfavorable metabolizing genes. For moderate to light smokers (< 30 pack-years), the genetic predisposition plays an important role for the risk (odds ratio = 3.46; 95% Cl = 0.46-40.2). Using a subgroup of the study population, we observed that cigarette smokers having the defective GST genes have significantly more chromosome aberrations as determined by the fluorescence-in-situ-hybridization (FISH) technique than smokers with the normal GST genes (P < 0.001). In conclusion, our study provides data to indicate that individuals who have inherited unfavorable metabolizing genes have increased body burden of toxicants to cause increased genetic damage and to have increased risk for cancer. Studies like ours can be used to understand the basis for interindividual variations in cancer outcome, to identify high risk individuals and to assess health risk.

Interactions between genetic predisposition and environmental toxicants for development of lung cancer

Significant interindividual variations in health outcome may be caused by the inheritance of variant polymorphic genes, such as CYP2D6 and CYP2E1 for activation, and GSTM1 and GSTT1 for detoxification of chemicals. However, mechanistic studies linking the inheritance of predisposing genes with genotoxic effects towards cancer have yet to be systematically conducted. We have studied 54 lung cancer patients and 50 matched normal controls, who have been cigarette smokers, to elucidate the role of polymorphic genes in cancer. Our data indicates that the inheritance of unfavorable CYP2D6, CYP2E1, and GSTT1 genes is strongly correlated with the smoking-related lung cancer. For heavy cigarette smokers (<30 pack-years), the smoking habit is the strongest predictor of lung cancer risk irrespective of the inheritance of unfavorable metabolizing genes. For moderate to light smokers (<30 pack-years), the genetic predisposition plays an important role for the risk (odds ratio = 3.46; 95% CL = 0.46–40.2). Using a subgroup of the study population, we observed that cigarette smokers having the defective GST genes have significantly more chromosome aberrations as determined by the fluorescence-in-situ-hybridization (FISH) technique than smokers with the normal GST genes (P < 0.001). In conclusion, our study provides data to indicate that individuals who have inherited unfavorable metabolizing genes have increased body burden of toxicants to cause increased genetic damage and to have increased risk for cancer. Studies like ours can be used to understand the basis for interindividual variations in cancer outcome, to identify high risk individuals and to assess health risk. Environ. Mol. Mutagen. 30:196–204, 1997. © 1997 Wiley-Liss, Inc.

Differential sensitivity of marine infaunal amphipods to tributyltin

Three species of infaunal gammaridean amphipods, Rhepoxynius abronius (Phoxocephalidae), Eohaustorius washingtonianus, and E. estuarius (Haustoriidae) were tested in a water-only system to assess their sensitivity to tributyltin (TBT) without the influence of factors that could affect bioavailability. When mortality (LC50) was the endpoint, the results indicated that R. abronius was ≈20 times more tolerant to tributyltin than either haustoriid species; however, when mortality plus reburial behavior (EC50) was assessed, the difference was only about 10 times. The bioconcentration factor (BCF) was also consistently lower in R. abronius (11.1 to 16.5 times) than in the haustoriids; however, when the LD50 was calculated, the concentration in the tissues associated with 50% mortality for each species was not significantly different. The large disparity in species' response is attributed to reduced uptake and a potentially greater ability to metabolize this compound by R. abronius. An analysis of TBT uptake confirmed that R. abronius was able to accumulate less TBT and hence maintain a low body burden for a given water concentration. The results of a separate uptake study were used to formulate a hypothesis for observed differences in reburial behavior. Because the rate of TBT uptake was lower in R. abronius, we propose that the slower rise in toxicant body burden allowed for a gradual response in this species which included a sublethal effect (non reburial), compared to a rapid rise in the body burden for E. estuarius which caused the response to quickly proceed from no effect to death.

Physiological effects of metal toxicity on the tropical freshwater shrimp Microbrachium carcinus (Linneo, 1758)

Pilot tests were performed to determine the level at which Zn ++ and Cu ++ ceased to be acutely toxic in Macrobrachium carcinus. The data indicated that the static 96h-LC 50 values for Zn ++ and Cu ++ were 0·2 and 0·1 mg litre −1 respectively. A differential reduction in respiration and ammonia excretion rates was noted with increasing concentrations of these metals in the water. These levels may in a toxic body burden and a progressive deterioration of gill efficiency. A decrease in respiration and ammonia excretion rates resulted in a decrease in O:N ratios, upon exposure to Zn ++ and Cu ++ concentrations. The ratios obtained indicate that these metals, also increased dependence on carbohydrate or lipid reserves.