Chronic Low-level Exposure Research Articles

“Looking outside the forensic toxicology box – An approach to link results from the lab to public health”

Exposure to environmental contaminants from air pollution is being increasingly identified as a significant cause for a large portion of the global death burden and associated with severe adverse health outcomes, including pulmonary, cardiovascular or immunologic and neurologic diseases. Among these air pollutants, carbon monoxide (CO) finds its place as one of the main “suspects”. Especially in enclosed spaces CO poses a great health risk – whether its low level chronic exposures leading to permanent neurologic disorders or acute exposures that lead to death. In both cases, the job of a toxicologist is to accurately detect CO by using the appropriate analytical method. The job of an epidemiologist is to associate the CO levels to a health outcome. Errors in the exposure measurement can lead to real associations not being detected. Therefore, we reviewed measurement methods used for CO measurement and identified key sources of error, which could contribute to exposure misclassification. A novel approach to more accurately determine the total amount of CO in blood (TBCO) via gas-chromatography mass spectrometry (GC-MS) was developed and validated. The results obtained from this method were then used to “feed” CO exposure assessments. Exposure assessments in public health represent the tool that from exposure estimates lead to determination of risk estimates. Using the previously identified key sources of error together with the results obtained from the improved measurement method, we developed a simulation model to quantify the impact that changes in the error due to measurement improvement could have on the relative risk (RR) of CO exposure estimates in a study using exhaled breath CO (exCO) and personal CO monitors (pCO) to measure CO. Choice of biomarker, analytical method, number of samples/measurements, time of sampling, inter-individual variabilities and use of averages for population data were some of the identified potential sources of error and can contribute from 5% up to 80% to the total measurement error. The novel CO measurement method leads to improvements in CO concentrations ranging from 20%–80% (compared to currently used methods). When applying this to the simulation model, the RR was increased up to 18.3% for exCO and up to 30% for pCO. An improved measurement method for TBCO was validated and has shown promising results in improving accuracy of CO determinations in blood as well as showing better stability to a variety of storage conditions in clinical and forensic settings. Application of this method to exposure assessment data lead to significant reduction of measurement error, resulting in CO exposure estimates closer to the true CO burden on the population. Improvement of the CO measurement method not only directly affects the results obtained in clinical and forensic cases by allowing otherwise undetected cases to be known, but it can also indirectly influence the data that is used by public health authorities to create guidelines, to generate prevention, treatment and training plans, ultimately improving global health. The model used here for CO exposure can easily be expanded and applied to other types of exposures.

Chronic Effects of Dietary Pesticides on the Gut Microbiome and Neurodevelopment.

Many agricultural pesticides include substances that are known to be harmful to human health and while some have been banned from developed countries, they are still being used in developing countries such as Brazil. Recent studies have shown that low-level chronic dietary exposure to pesticides can affect the human gut microbiota. This possible hazardous effect of pesticides on human health has not been specifically recognized by government regulatory agencies. In Brazil, for instance, of the 10 best-selling active ingredients in pesticides in 2019, two are considered extremely toxic, Paraquat and Chlorpyrifos. Even though Paraquat has been banned in Brazil since 2020, the values of maximum residue limits (MRLs) of toxic pesticides allowed in the country are still higher than in other countries. Unfortunately, many developing countries still lack the resources and expertise needed to monitor adequately and systematically the presence of pesticide residues on food. In this work, we raise awareness to the danger the chronic exposure to high dietary levels of pesticides can pose to the public, especially considering their prolonged effects on the gut microbiome.

Long-Term Effects of Low-Level Blast Exposure and High-Caliber Weapons Use in Military Special Operators.

Chronic low-level blast exposure has been linked with neurological alterations and traumatic brain injury (TBI) biomarkers. Impaired smooth-pursuit eye movements (SPEM) are often associated with TBI. The purpose of this study was to determine whether long-term operators of low-level blast exposure or high-caliber weapons use displayed oculomotor behaviors that differed from controls. Twenty-six members of an elite military unit performed a computerized oculomotor testing task using an eye tracker and completed a concussion assessment questionnaire. The participants were split into a blast exposure group and control group. The blast exposure group had a history of exposure to low-level blasts or high-caliber weapon use. The results revealed significant differences in SPEM, saccades, and fixations between the blast exposure group and control group. The blast exposure group’s eye movements were slower, stopped at more frequent points when following a target, traveled further from the target in terms of both speed and direction, and showed higher rates of variation and inefficiency. Poor oculomotor behavior correlated with a higher symptom severity on the concussion assessment questionnaire. Military special operators exposed to long-term low-level blasts or high-caliber weapons usage displayed an impaired oculomotor behavior in comparison to controls. These findings further our understanding of the impact of long-term low-level blast exposure on the oculomotor behavior of military special operators and may inform practical implications for military training.

Low-level lead exposure during development differentially affects neurobehavioral responses in male and female mouse offspring: A longitudinal study

Early life low-level lead (Pb) exposure is still an alarming child health issue. To date, animal studies investigating the effects of low doses of Pb since early stages of life to adulthood are scarce. We investigated in a mouse model the behavioral effects of developmental exposure to low-level Pb yielding blood levels similar to those observed in child clinical literature. CD1 outbred mouse dams received Pb (25- or 100-ppm) via drinking water from two weeks pre-mating until the end of lactation. Offspring of both sexes underwent a longitudinal assessment of motor, socio-emotional, and cognitive endpoints from neonatal to adult stage. Pb levels were determined in several matrices (blood, brain and bone) up to six months after the end of exposure. We found that new born pups exposed to Pb have slightly altered motor patterns and reduced preference for the nest odor. Offspring of both sexes exposed to the lowest Pb dose showed diminished interest for social novelty stimuli as adults. Moreover, sex-dependent effects of Pb exposure were observed in the spatial learning and memory task, where males were selectively impaired. Finally, blood, brain and bone Pb levels were elevated in a dose dependent fashion up to six months after termination of exposure. We observed marked accumulation of Pb in bones, with higher Pb levels in 100-ppm exposed females than in males at 7 months of age. In conclusion, developmental Pb exposure caused mild alterations in early- and late-life behavioral domains, particularly involving olfactory and cognitive responses. These findings confirm the importance of animal models to understand how early chronic low-level lead exposure impacts on health in a life-course perspective.

Molecular Fates of Organometallic Mercury in Human Brain.

Mercury is ubiquitous in the environment, with rising levels due to pollution and climate change being a current global concern. Many mercury compounds are notorious for their toxicity, with the potential of organometallic mercury compounds for devastating effects on the structures and functions of the central nervous system being of particular concern. Chronic exposure of human populations to low levels of methylmercury compounds occurs through consumption of fish and other seafood, although the health consequences, if any, from this exposure remain controversial. We have used high energy resolution fluorescence detected X-ray absorption spectroscopy to determine the speciation of mercury and selenium in human brain tissue. We show that the molecular fate of mercury differs dramatically between individuals who suffered acute organometallic mercury exposure (poisoning) and individuals with chronic low-level exposure from a diet rich in marine fish. For long-term low-level methylmercury exposure from fish consumption, mercury speciation in brain tissue shows methylmercury coordinated to an aliphatic thiolate, resembling the coordination environment observed in marine fish. In marked contrast, for short-term high-level exposure, we observe the presence of biologically less available mercuric selenide deposits, confirmed by X-ray fluorescence imaging, as well as mercury(II)-bis-thiolate complexes, which may be signatures of severe poisoning in humans. These differences between low-level and high-level exposures challenge the relevance of studies involving acute exposure as a proxy for low-level chronic exposure.

From the discovery of combat gases to insecticides and bioterrorism – a brief history

The identification of organophosphate (OP) compounds dates back to the 1800s. OPare largely used pesticides in the agricultural field and households but prior use as a chemical weapon was considered during wars. Their toxicity on humans has been previously studied and addresses both acute intoxication and low-level chronic exposure. Symptoms of acute exposure describe a cholinergic syndrome with bradycardia, miosis, confusion, fasciculations, tearing, sialorrhea, diarrhea, bronchorrhea, and bronchospasm. The intermediate syndrome causes paralysis of the gait muscles, neck flexors, and respiratory failure. Moreover, unrestricted access to OP has increased the rate of suicide, accounting for around 30% of cases, increasing concern about OP availability. Western countries have drastically restricted access to OP by imposing regulations regarding handling these hazardous substances, but efforts have to be made to globally reduce this struggle

Fluoride Exposure and Age of Menarche: Potential Differences Among Adolescent Girls and Women in the United States

Fluoride exposure is associated with later pubertal development and decreased testosterone production in adolescent and adult males. However, its effects on female reproductive health and pubertal development are unclear. Therefore, we examined associations of fluoride exposure with reproductive health outcomes among adolescent girls and women in the United States. Participants were from The National Health and Nutrition Examination Surveys (2013 to 2016), aged 16–19 and identified as female. There were 524 and 460 participants with measures of plasma fluoride and household tap water fluoride respectively, who had at least one reproductive health outcome examined, and complete covariate data. We applied covariate adjusted survey-weighted linear or logistic regression to examine associations of fluoride exposure with age of menarche, menstrual cycle regularity, or serum sex steroid hormone levels. Median interquartile range (IQR) water and plasma fluoride concentrations were 0.48 (0.53) mg/L and 0.34 (0.30) µmol/L respectively. An IQR increase in water fluoride was associated with a 3.3 month earlier first menstrual period (B = − 0.28, 95%CI − 0.54, − 0.02, p = 0.05). Additionally, we observed a significant interaction between plasma fluoride and race/ethnicity in association with age of menarche (p = 0.01). Among Non-Hispanic Black adolescents, each IQR increase in plasma fluoride was associated with a 5-month earlier age of menarche (B = − 0.42, 95%CI − 0.61, − 0.23, p < 0.001). Potential impacts of chronic low-level fluoride exposure on reproductive health outcomes are an important area of study. Current study findings, as well as potential health disparities due to disproportionate fluoride exposure should be examined in prospective studies.

Linking Pollutants and Therapeutics to Heart Health: Key Characteristics of Cardiovascular Toxicants.

Linking Pollutants and Therapeutics to Heart Health: Key Characteristics of Cardiovascular Toxicants.

Corrigendum to: 228 Relationship of pesticide exposure with kidney function in NHANES: lessons from low level chronic exposure.

Corrigendum to: 228 Relationship of pesticide exposure with kidney function in NHANES: lessons from low level chronic exposure.

Validation of New ELISA Technique for Detection of Aflatoxin B1 Contamination in Food Products versus HPLC and VICAM.

Toxin-contaminated foods and beverages are a major source of illness, may cause death, and have a significant negative economic impact worldwide. Aflatoxin B1 (AFB1) is a potent toxin that may induce cancer after chronic low-level exposure. This study developed a quantitative recombinant AflR gene antiserum ELISA technique for aflatoxin B1 detection in contaminated food products. Aflatoxin B1 residuals from 36 food samples were analyzed with HPLC and VICAM. DNA was extracted from aflatoxin-contaminated samples and the AflR gene amplified using PCR. PCR products were purified and ligated into the pGEM-T vector. Recombinant plasmids were sequenced and transformed into competent E. coli (BL21). Molecular size and B-cell epitope prediction for the recombinant protein were assessed. The purified protein was used to induce the production of IgG antibodies in rabbits. Serum IgG was purified and labeled with alkaline phosphatase. Finally, indirect-ELISA was used to test the effectiveness of polyclonal antibodies for detection of aflatoxin B1 in food samples.

SAFETY ASSESSMENTS FOR SUPPORTING THE APPLICATION OF NUCLEAR TECHNOLOGY IN INDONESIA AND A COMPREHENSIVE STUDY ON HIGH NATURAL RADIOACTIVITY AREA

SAFETY ASSESSMENTS FOR SUPPORTING THE APPLICATION OF NUCLEAR TECHNOLOGY IN INDONESIA AND A COMPREHENSIVE STUDY ON HIGH NATURAL RADIOACTIVITY AREA. Historically BATAN was established to investigate the negative impacts of nuclear explosions previously conducted in the Pacific area. However, this governmental institute is presently tasked to carry out research and development as well as services in the field of radiation safety and metrology. Therefore, this study aim to determine the activities carried out by BATAN in assessing the safety of workers and the environment. For instance, a standard source of dosimetry laboratory (SSDL) is used in calibration services to successfully support radiotherapy, with the highest achievement in the Designated Institute (DI) for Ionizing Radiation. The health research covers the application of gamma rays to create malaria vaccine, diagnose metabolic diseases with nuclear medicine techniques, and microdosimetry through radiodiagnostic assessment. This study also determined the effective dose and epidemiological study of radioecology and radiation biology in Mamuju (HBRA), which provides a unique opportunity to examine the health effects of chronic low-level radiation exposure to humans. Furthermore, the authors collaborated with Hirosaki University to obtain valuable information on the essential need to assess the health and physical status as well as cytogenetic and deoxynucleotide acid (DNA) damages in the lymphocytes of local populations. Dosimetry study was conducted by direct measurement in the field area by analyzing external radiation exposure of indoor and outdoor gamma dose rate. The internal radiation assessment was conducted by taking urine and inhaled air (radon) from the residents. Studies through the cytogenetic response supported by γ-H2AX, G0, and G2 micronucleus assays and TP53 showed no impacts on the natural radiation with significant differences compared to the control. Marine radioecology studies and radionuclides monitoring throughout the Indonesian archipelago showed no negative impacts as well. Nuclear emergency practice needs to be routinely conducted in the Center for strengthening safety and security cultures.

Effects of non-ionizing electromagnetic fields on flora and fauna, Part 3. Exposure standards, public policy, laws, and future directions.

Due to the continuous rising ambient levels of nonionizing electromagnetic fields (EMFs) used in modern societies-primarily from wireless technologies-that have now become a ubiquitous biologically active environmental pollutant, a new vision on how to regulate such exposures for non-human species at the ecosystem level is needed. Government standards adopted for human exposures are examined for applicability to wildlife. Existing environmental laws, such as the National Environmental Policy Act and the Migratory Bird Treaty Act in the U.S. and others used in Canada and throughout Europe, should be strengthened and enforced. New laws should be written to accommodate the ever-increasing EMF exposures. Radiofrequency radiation exposure standards that have been adopted by worldwide agencies and governments warrant more stringent controls given the new and unusual signaling characteristics used in 5G technology. No such standards take wildlife into consideration. Many species of flora and fauna, because of distinctive physiologies, have been found sensitive to exogenous EMF in ways that surpass human reactivity. Such exposures may now be capable of affecting endogenous bioelectric states in some species. Numerous studies across all frequencies and taxa indicate that low-level EMF exposures have numerous adverse effects, including on orientation, migration, food finding, reproduction, mating, nest and den building, territorial maintenance, defense, vitality, longevity, and survivorship. Cyto- and geno-toxic effects have long been observed. It is time to recognize ambient EMF as a novel form of pollution and develop rules at regulatory agencies that designate air as 'habitat' so EMF can be regulated like other pollutants. Wildlife loss is often unseen and undocumented until tipping points are reached. A robust dialog regarding technology's high-impact role in the nascent field of electroecology needs to commence. Long-term chronic low-level EMF exposure standards should be set accordingly for wildlife, including, but not limited to, the redesign of wireless devices, as well as infrastructure, in order to reduce the rising ambient levels (explored in Part 1). Possible environmental approaches are discussed. This is Part 3 of a three-part series.

228Relationship of pesticide exposure with kidney function in NHANES: lessons from low level chronic exposure

Abstract Background Exposure to pesticides has been linked to many health outcomes. More recently, chronic kidney disease not related to diabetes or hypertension (CKDu) has been postulated to be related to rural occupational exposures in agricultural workers in several Low to Middle Income Country (LMIC) regions such as Mesoamerica and the Subcontinent. Our study wished to examine the relationship between pesticide exposure and kidney function. Methods We used the resources of pooled population from NHANES 2001-2004, 2007-2010 (n = 29,053). We examined pesticide exposure (logged, continuous) with kidney function as measured by glomerular filtration rate (derived from urinary creatinine) with and without presence of hypertension and diabetes. Logistic regression was adjusted for a range of cofactors such as age, sex, SES, tobacco, and heavy metals. Cadmium was used as a positive control. Results Pesticides 2,4-D, chlorpyrifos, malathion and 3-phenoxybenzoic acid (the major metabolite of deltamethrin) were associated with the increasing risk of kidney dysfunction (not with hypertension or diabetes) after adjusting for a range of known risk factors (OR 1.80 (1.47-2.21); 2.16 (1.57-2.98); 1.20 (0.94-1.54) and 1.40 (1.19-1.64), respectively). Cd was not associated with kidney dysfunction (OR 0.99 (0.81-1.21)), or acephate (OR 0.43 (0.13-1.48)). Conclusions Chronic or acute pesticide exposure may increase the risk of kidney dysfunction, which is not related to hypertension or diabetes in particular. It may have a different pathological pathway from heavy metal exposures and CKD. This has repercussions for interventions in LMIC agricultural practices. Key messages Pesticides are associated with kidney dysfunction not related to hypertension and diabetes.

Pesticide Exposure, Systems Biology, and Parkinson’s disease

BACKGROUND AND AIM: Since 1972, California law mandates the recording of all agricultural pesticide use to the pesticide use reports database, documenting nearly 50 years of applications of hundreds of pesticides. METHODS: We developed an untargeted “Pesticide-wide Association Study” approach for handling this vast exposure data in a community-based study of rural Central California residents to assess chronic and long-term health effects. RESULTS:Using this agnostic approach analyzing exposure information for 300 pesticides in a study of Parkinson’s disease (PD) n=1870, we have implicated 33 real-world pesticide profiles most strongly associated with PD (FDR0.01). The strength of this agnostic analysis is that it highlights out of all pesticides used in California the most strongly associated and suggests novel associations. For instance, our top associated pesticide was sodium chlorate (OR=1.26 per log-transformed lbs/acre applied, 95% CI=1.16-1.36, p=1.1e-8), a defoliant sprayed primarily on cotton. Correlation analysis revealed trends of co-applications and exposure clusters, including a cluster of 8 pesticides almost exclusively applied on cotton (97% reported usage). Based on overrepresentation analysis, the organophosphate, organoarsenic, and n-methyl-carbamate classes and the insecticide and solvent types were significantly overrepresented in the group of PD-associated pesticides. Linking the pesticides to tox21, we found these pesticides were linked to various mechanisms of interest in PD, including mitochondrial membrane permeability (enrichment p-value=1.8e-2), xenobiotic homeostasis (p=5.46e-5), and sex hormone homoeostasis (p=3.03e-3). We were further able to implicate PD specific pathways through integrative omics analysis, relating the matrix of PD-associated pesticides to matrices of multiple omic layers (methylome, metabolome, and genome), using systems biology to describe pesticide-associated biologic pathways perturbed more among patients versus controls, and thus contributing to PD even under chronic low-level exposure scenarios. CONCLUSIONS:We developed an exposure assessment approach based on novel tools in the era of big data and omics and implicate new pesticide exposures and biologic pathways in PD. KEYWORDS: Pesticides, systems biology, Parkinson's disease

Associations of Dietary Intake with Urinary Melamine Concentrations among Children aged 4-6 Years in the GAPPS Cohort

Describe how children are exposed to the environmental chemical melamine through their diets, and identify potential sources of contamination in children's diets. Melamine is an industrial chemical that may induce kidney injury at low dose exposures and kidney failure at high doses. Diet is a primary source of melamine exposure, yet little is known about exposure levels or dietary sources, particularly among children. Urinary melamine and metabolite concentrations were measured in 123 children aged 4-6 years in the Global Alliance to Prevent Prematurity and Stillbirth cohort. Children’s diets on the day preceding urine collection were assessed through 24-hour recalls. Associations of meat, fruit, and grain intakes with urinary melamine and metabolites were examined in primary analyses using generalized linear modeling. Remaining food groups were examined in secondary analyses. Melamine and ammelide concentrations were above the limit of detection (LOD) in 100% and 88% of samples, respectively. Ammeline concentrations were below the LOD in all samples. Mean urinary melamine and ammelide concentrations were 5.97 ng/mL (SD: 12.08) and 1.80 ng/mL (SD: 2.06), respectively. In minimally adjusted models, a doubling in fatty fish intake was associated with 74% (95% CI: 18%, 130%) greater melamine; this association was diminished in fully adjusted models. In full models, a doubling of yogurt intake was associated with 101% (95% CI: 33%, 167%) greater melamine; doubled dark green vegetable intake was associated with 59% (95% CI: 1%, 117%) lower ammelide. Exposure to melamine and ammelide was pervasive. Possible sources of melamine contamination including yogurt and fatty fish should be confirmed in larger samples. Additional study should clarify how chronic low-level melamine exposure affects children’s health.

Low-level cadmium doses do not jeopardize the insulin secretion pathway of β-cell models until the onset of cell death

BackgroundCadmium is an inescapable environmental pollutant that permeates the food chain and has been debatably associated with diabetes in humans. Purpose and proceduresTo probe the specific impact of low-level cadmium exposure on insulin production, largely sub-cytotoxic (50–500 nM) concentrations of cadmium chloride challenged the INS-1 and MIN6 rodent models of pancreatic β-cells for the longest possible time, up to 4 days, before sub-culturing. Main findingsThe concentration of detectable oxidants, the pattern of the actin cytoskeleton, the translocation of β-catenin, the activity of protein phosphatases, calcium traffic, and the phosphorylation status of several key signaling nodes, such as AMP kinase and mitogen activated kinases including nuclear translocation of Extracellular signal-Regulated Kinase, were all insensitive to the applied very low cadmium doses. Accordingly, low-level cadmium exposure did not alter the insulin secretion ability, the functional hallmark of β-cells, before the onset of cell death. ConclusionsThese data define an operational toxicological threshold for these cellular models of β-cells that should be useful to address insulin secretion and the diabetogenic effects of chronic low-level cadmium exposure in animal models and in humans.

Human Evolution and Dietary Ethanol.

The “drunken monkey” hypothesis posits that attraction to ethanol derives from an evolutionary linkage among the sugars of ripe fruit, associated alcoholic fermentation by yeast, and ensuing consumption by human ancestors. First proposed in 2000, this concept has received increasing attention from the fields of animal sensory biology, primate foraging behavior, and molecular evolution. We undertook a review of English language citations subsequent to publication of the original paper and assessed research trends and future directions relative to natural dietary ethanol exposure in primates and other animals. Two major empirical themes emerge: attraction to and consumption of fermenting fruits (and nectar) by numerous vertebrates and invertebrates (e.g., Drosophila flies), and genomic evidence for natural selection consistent with sustained exposure to dietary ethanol in diverse taxa (including hominids and the genus Homo) over tens of millions of years. We also describe our current field studies in Uganda of ethanol content within fruits consumed by free-ranging chimpanzees, which suggest chronic low-level exposure to this psychoactive molecule in our closest living relatives.

Effects of non-ionizing electromagnetic fields on flora and fauna, Part 2 impacts: how species interact with natural and man-made EMF.

Ambient levels of nonionizing electromagnetic fields (EMF) have risen sharply in the last five decades to become a ubiquitous, continuous, biologically active environmental pollutant, even in rural and remote areas. Many species of flora and fauna, because of unique physiologies and habitats, are sensitive to exogenous EMF in ways that surpass human reactivity. This can lead to complex endogenous reactions that are highly variable, largely unseen, and a possible contributing factor in species extinctions, sometimes localized. Non-human magnetoreception mechanisms are explored. Numerous studies across all frequencies and taxa indicate that current low-level anthropogenic EMF can have myriad adverse and synergistic effects, including on orientation and migration, food finding, reproduction, mating, nest and den building, territorial maintenance and defense, and on vitality, longevity and survivorship itself. Effects have been observed in mammals such as bats, cervids, cetaceans, and pinnipeds among others, and on birds, insects, amphibians, reptiles, microbes and many species of flora. Cyto- and geno-toxic effects have long been observed in laboratory research on animal models that can be extrapolated to wildlife. Unusual multi-system mechanisms can come into play with non-human species - including in aquatic environments - that rely on the Earth's natural geomagnetic fields for critical life-sustaining information. Part 2 of this 3-part series includes four online supplement tables of effects seen in animals from both ELF and RFR at vanishingly low intensities. Taken as a whole, this indicates enough information to raise concerns about ambient exposures to nonionizing radiation at ecosystem levels. Wildlife loss is often unseen and undocumented until tipping points are reached. It is time to recognize ambient EMF as a novel form of pollution and develop rules at regulatory agencies that designate air as 'habitat' so EMF can be regulated like other pollutants. Long-term chronic low-level EMF exposure standards, which do not now exist, should be set accordingly for wildlife, and environmental laws should be strictly enforced - a subject explored in Part 3.

Investigating the impact of long term exposure to chemical agents on the chromosomal radiosensitivity using human lymphoblastoid GM1899A cells

This study aimed to investigate the impact of chronic low-level exposure to chemical carcinogens with different modes of action on the cellular response to ionising radiation. Human lymphoblastoid GM1899A cells were cultured in the presence of 4-nitroquinoline N-oxide (4NQO), N-nitroso-N-methylurea (MNU) and hydrogen peroxide (H2O2) for up to 6 months at the highest non-(geno)toxic concentration identified in pilot experiments. Acute challenge doses of 1 Gy X-rays were given and chromosome damage (dicentrics, acentric fragments, micronuclei, chromatid gaps/breaks) was scored. Chronic exposure to 20 ng/ml 4NQO, 0.25 μg/ml MNU or 10 μM H2O2 hardly induced dicentrics and did not significantly alter the yield of X-ray-induced dicentrics. Significant levels of acentric fragments were induced by all chemicals, which did not change during long-term exposure. Fragment data in combined treatment samples compared to single treatments were consistent with an additive effect of chemical and radiation exposure. Low level exposure to 4NQO induced micronuclei, the yields of which did not change throughout the 6 month exposure period. As for fragments, micronuclei yields for combined treatments were consistent with an additive effect of chemical and radiation. These results suggest that cellular radiation responses are not affected by long-term low-level chemical exposure.

Cytokine profile in children exposed to chloroform and vanadium

Introduction. Pollution of drinking water and atmospheric air by anthropogenic haptens forms an imbalance of adaptive capacities of the immune system in children. The purpose of the work is to identify the features of the cytokine profile in children exposed to vanadium and chlorine-containing compounds (for example, chloroform). Materials and methods. We examined 283 children who live in conditions of chronic low-level peroral exposure to drinking water hyperchlorinated products. The control was a contingent of 224 children consuming drinking water of chloroform of adequate quality. We also examined 215 children living in conditions of chronic aerogenic low-level exposure to vanadium, the control being a contingent of 131 children living in the territory of conditional sanitary and hygienic well-being without any stationary sources of vanadium contamination of the atmospheric air. Chemical-analytical and immunoenzymometric methods were used in the study. Results. In children living under chronic oral exposure to drinking water hyperchlorination products, chloroform was identified in the blood, which normally should not be detected. In children living in an area with elevated levels of aerogenic vanadium load, the vanadium content in the blood was found to be statistically significant (p &lt; 0.001) 4.4 times higher than the upper limit of the reference interval. We have established that under conditions of blood contamination with chloroform Th2-shift of cytokine profile occurs - concentration cytokines IL4, IL6 increases statistically significantly, frequency of excess was 2.2 and 4.3 times in comparison with the values obtained in unexposed children ( p ≤ 0,001-0,031); under conditions of contamination of biological media with vanadium, a decrease in Th1 cytokine production was observed - the expression of the proinflammatory cytokine TNFα was statistically significantly depressed, the multiple of the decrease was 2.2 times as compared to the results obtained in children not exposed to vanadium ( p = 0.032). Conclusions. The presented results show the contamination of chloroform and vanadium to cause a multidirectional nature of changes in the cytokine profile of serum in exposed children with technogenic gaptenes, forming in the future various mechanisms of deterioration of immune response: activation of humoral (Th2-dependent), associated with chloroform contamination or cell suppression (Th1-dependent), associated with excess contamination of vanadium.