Current Environmental Exposure Research Articles

The Protective Effect of the Supplementation with an Extract from Aronia melanocarpa L. Berries against Cadmium-Induced Changes of Chosen Biomarkers of Neurotoxicity in the Brain-A Study in a Rat Model of Current Lifetime Human Exposure to This Toxic Heavy Metal.

Since even low-level environmental exposure to cadmium (Cd) can lead to numerous unfavourable health outcomes, including damage to the nervous system, it is important to recognize the risk of health damage by this xenobiotic, the mechanisms of its toxic influence, and to find an effective protective strategy. This study aimed to evaluate, in a female Wistar rat model of current human environmental exposure to Cd (1 and 5 mg/kg of diet for 3-24 months), if the low-to-moderate treatment with this element can harm the brain and whether the supplementation with a 0.1% Aronia melanocarpa L. (Michx.) Elliott berries (chokeberries) extract (AE) can protect against this effect. The exposure to Cd modified the values of various biomarkers of neurotoxicity, including enzymes (acetylcholinesterase (AChE), sodium-potassium adenosine triphosphatase (Na+/K+-ATPase), phospholipase A2 (PLA2), and nitric oxide synthase 1 (NOS1)) and non-enzymatic proteins (calmodulin (CAM), nuclear factor erythroid 2-related factor 2 (Nrf2), and Kelch-like ECH-associated protein 1 (KEAP1)) crucial for the functioning of the nervous system, as well as the concentrations of calcium (Ca) and magnesium (Mg) and some metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in the brain tissue. The co-administration of AE, partially or entirely, protected from most of the Cd-induced changes alleviating its neurotoxic influence. In conclusion, even low-level chronic exposure to Cd may adversely affect the nervous system, whereas the supplementation with A. melanocarpa berries products during the treatment seems a protective strategy.

Effects of metformin on wild fathead minnows (Pimephales promelas) using in-lake mesocosms in a boreal lake ecosystem

Due to its widespread use for the treatment of Type-2 diabetes, metformin is routinely detected in surface waters globally. Laboratory studies have shown that environmentally relevant concentrations of metformin can adversely affect the health of adult fish, with effects observed more frequently in males. However, the potential risk to wild fish populations has yet to be fully elucidated and remains a topic of debate. To explore whether environmentally relevant metformin exposure poses a risk to wild fish populations, the present study exposed wild fathead minnows (Pimephales promelas) to 5 or 50 μg/L metformin via 2 m diameter in-lake mesocosms deployed in a natural boreal lake in Northern Ontario at the International Institute for Sustainable Development - Experimental Lakes Area (IISD-ELA). Environmental monitoring was performed at regular intervals for 8-weeks, with fish length, weight (body, liver and gonad), condition factor, gonadosomatic index, liver-somatic index, body composition (water and biomolecules) and hematocrit levels evaluated at test termination. Metabolic endpoints were also evaluated using liver, brain and muscle tissue, and gonads were evaluated histologically. Results indicate that current environmental exposure scenarios may be sufficient to adversely impact the health of wild fish populations. Adult male fish exposed to metformin had significantly reduced whole body weight and condition factor and several male fish from the high-dose metformin had oocytes in their testes. Metformin-exposed fish had altered moisture and lipid (decrease) content in their tissues. Further, brain (increase) and liver (decrease) glycogen were altered in fish exposed to high-dose metformin. To our knowledge, this study constitutes the first effort to understand metformin's effects on a wild small-bodied fish population under environmentally relevant field exposure conditions.

Metabolites are overlooked in environmental risk assessments and monitoring of pharmaceuticals: The case study of pantoprazole

The proton-pump inhibitor pantoprazole (PPZ) is one of the most consumed pharmaceuticals worldwide. Despite its high usage, reported PPZ concentrations in environmental water samples are comparatively low, which can be explained by the extensive metabolism of PPZ in the human body. Since most previous studies did not consider human PPZ metabolites it can be assumed that the current environmental exposure associated with the application of PPZ is substantially underestimated. In our study, 4′-O-demethyl-PPZ sulfide (M1) was identified as the predominant PPZ metabolite by analyzing urine of a PPZ consumer as well as the influent and effluent of a wastewater treatment plant (WWTP) using liquid chromatography coupled to high resolution mass spectrometry (LC-HRMS). M1 was found to be ubiquitously present in WWTP effluents (max. concentration: 3 000 ng/L) and surface waters in Germany. On average, the surface water concentrations of M1 were approximately 30 times higher than those of the parent compound PPZ. Laboratory scale experiments demonstrated that activated carbon can considerably adsorb M1 und thus improve its removal during wastewater and drinking water treatment. Laboratory ozonation experiments showed a fast oxidation of M1, accompanied by the formation of several ozonation products. Certain ozonation products (identities confirmed via synthesized reference standards) were also detected in water samples collected after ozonation in a full-scale WWTP. Overall lower signal intensities were observed in the effluents of a sand filter and biologically active granular activated carbon filter, suggesting that the compounds were significantly removed during these post-ozonation treatment stages.

Is Chronic Kidney Disease Due to Cadmium Exposure Inevitable and Can It Be Reversed?

Cadmium (Cd) is a metal with no nutritional value or physiological role. However, it is found in the body of most people because it is a contaminant of nearly all food types and is readily absorbed. The body burden of Cd is determined principally by its intestinal absorption rate as there is no mechanism for its elimination. Most acquired Cd accumulates within the kidney tubular cells, where its levels increase through to the age of 50 years but decline thereafter due to its release into the urine as the injured tubular cells die. This is associated with progressive kidney disease, which is signified by a sustained decline in the estimated glomerular filtration rate (eGFR) and albuminuria. Generally, reductions in eGFR after Cd exposure are irreversible, and are likely to decline further towards kidney failure if exposure persists. There is no evidence that the elimination of current environmental exposure can reverse these effects and no theoretical reason to believe that such a reversal is possible. This review aims to provide an update on urinary and blood Cd levels that were found to be associated with GFR loss and albuminuria in the general populations. A special emphasis is placed on the mechanisms underlying albumin excretion in Cd-exposed persons, and for an accurate measure of the doses-response relationships between Cd exposure and eGFR, its excretion rate must be normalised to creatinine clearance. The difficult challenge of establishing realistic Cd exposure guidelines such that human health is protected, is discussed.

Fate and effects of a new generation fluorosurfactant (cC6O4) in freshwater mesocosms

Per- and polyfluorinated alkyl substances (PFAS) have raised international concerns due to their widespread use, environmental persistence and potential bioaccumulative and ecotoxicological effects. Therefore, the chemical industry has been dedicated to develop new generation fluorosurfactants which are aimed to replace the most concerning PFAS. Here we investigated the fate and effects of cyclic C6O4 (cC6O4), a compound used as alternative to long-chain perfluorocarboxylic acids, in freshwater mesocosms located in the Mediterranean region (Spain) over a period of 90 days. cC6O4 was applied as ammonium salt once at the following nominal concentrations: 0 µg/L (control), 1 µg/L, 20 µg/L, 400 µg/L, and 8,000 µg/L. The study shows that cC6O4 is relatively persistent in water (dissipation: 34–37 % after 90 days), has very low sorption capacity to sediments (sediment-water partition coefficient: 0.18–0.32 L/kg) and very limited bioconcentration (BCF: 0.09–0.94), bioaccumulation (BAF: 0.09–4.06) and biomagnification (BMF: 0.05–0.28) potential. cC6O4 did not result in significant adverse effects on aquatic populations and communities of phytoplankton and zooplankton at the tested concentrations. As for the macroinvertebrate community, the ephemeropteran Cloeon sp. showed a population decline at the highest test concentration on day 60 onwards, and a significant effect on the macroinvertebrate community was identified on the last sampling day at the same exposure level. Therefore, the calculated NOEC for cC6O4 in freshwater mesocosms exposed over a period of 90 days was 400 µg/L, which corresponded to a time weighted average concentration of 611 µg/L, given the water evaporation in the test systems. This concentration is about an order of magnitude higher than the highest exposure concentration monitored in freshwater ecosystems. Therefore, it can be concluded that cC6O4 poses insignificant ecological risks for freshwater plankton and macroinvertebrate communities given the current environmental exposure levels.

The Protective Impact of Aronia melanocarpa L. Berries Extract against Prooxidative Cadmium Action in the Brain-A Study in an In Vivo Model of Current Environmental Human Exposure to This Harmful Element.

Cadmium (Cd) is a prooxidant that adversely affects human health, including the nervous system. As exposure of the general population to this heavy metal is inevitable, it is crucial to look for agents that can prevent the effects of its toxic action. An experimental model on female rats of current lifetime human exposure to cadmium (3-24-months' treatment with 1 or 5 mg Cd/kg diet) was used to test whether low-level and moderate intoxication can exert a prooxidative impact in the brain and whether supplementation with a 0.1% extract from the berries of Aronia melanocarpa L. (Michx.) Elliott (AE; chokeberry extract) can protect against this action. Numerous parameters of the non-enzymatic and enzymatic antioxidative barrier, as well as total antioxidative and oxidative status (TAS and TOS, respectively), were determined and the index of oxidative stress (OSI) was calculated. Moreover, chosen prooxidants (myeloperoxidase, xanthine oxidase, and hydrogen peroxide) and biomarkers of oxidative modifications of lipids, proteins, and deoxyribonucleic acid were assayed. Cadmium dysregulated the balance between oxidants and antioxidants in the brain and led to oxidative stress and oxidative injury of the cellular macromolecules, whereas the co-administration of AE alleviated these effects. To summarize, long-term, even low-level, cadmium exposure can pose a risk of failure of the nervous system by the induction of oxidative stress in the brain, whereas supplementation with products based on aronia berries seems to be an effective protective strategy.

Dietary Exposure to Environmentally Relevant Levels of Chemical Contaminants Reduces Growth and Survival in Juvenile Chinook Salmon.

Chemical pollution can degrade aquatic ecosystems. Chinook salmon in contaminated habitats are vulnerable to health impacts from toxic exposures. Few studies have been conducted on adverse health outcomes associated with current levels and mixtures of contaminants. Fewer still address effects specific to the juvenile life-stage of salmonids. The present study evaluated contaminant-related effects from dietary exposure to environmentally relevant concentrations and mixture profiles in juvenile Chinook salmon from industrialized waterways in the U.S. Pacific Northwest using two end points: growth assessment and disease susceptibility. The dose and chemical proportions were reconstituted based on environmental sampling and analysis using the stomach contents of juvenile Chinook salmon recently collected from contaminated, industrialized waterways. Groups of fish were fed a mixture with fixed proportions of 10 polychlorinated biphenyls (PCBs), 3 dichlorodiphenyltrichloroethanes (DDTs), and 13 polycyclic aromatic hydrocarbons (PAHs) at five concentrations for 35 days. These contaminant compounds were selected because of elevated concentrations and the widespread presence in sediments throughout industrialized waterways. Fork length and otolith microstructural growth indicators were significantly reduced in fish fed environmentally relevant concentrations of these contaminants. In addition, contaminant-exposed Chinook salmon were more susceptible to disease during controlled challenges with the pathogen Aeromonas salmonicida. Our results indicate that dietary exposure to contaminants impairs growth and immune function in juvenile Chinook salmon, thereby highlighting that current environmental exposure to chemicals of potential management concern threatens the viability of exposed salmon.

Quantitative Metabolism and Urinary Elimination Kinetics of Seven Neonicotinoids and Neonicotinoid-Like Compounds in Humans.

Reverse dosimetry, i.e., calculating the dose of hazardous substances that has been taken up by humans based on measured analyte concentrations in spot urine samples, is critical for risk assessment and requires metabolic and kinetic data. We quantitatively studied the metabolism of seven major neonicotinoid and neonicotinoid-like compounds (NNIs) after single oral doses in male volunteers and determined key kinetic parameters and urinary elimination for NNIs together with their metabolites. Complete and consecutive urine samples were collected over 48 h. All samples were analyzed by tandem mass spectrometry, following liquid or gas chromatographic separation. Single- and group-specific NNI metabolites were quantified, i.e., hydroxylated and N-dealkylated NNIs and NNI-associated carboxylic acids and their glycine derivatives. Large, substance-dependent variations of key toxicokinetic parameters were observed. Mean times of concentration maxima (tmax) in urine varied between 2.0 (imidacloprid) and 25.8 h (N-desmethyl-clothianidin), whereas mean urinary elimination half-times (t1/2) were between 2.5 (acetamiprid) and 49.5 h (sulfoxaflor). Mean 48 h excretion fractions (Fue's) were between 0.03% (2-chloro-1,3-thiazole-5-carboxylic acid glycine) and 84% (clothianidin). In contrast, the interindividual differences of Fue's between the volunteers for each of the NNIs and their metabolites remained low (below a factor of 2 between the maximum and minimum derived Fue with the exception of 6-chloronicotinic acid in the acetamiprid dose study). The obtained quantitative data enabled choosing appropriate biomarkers for exposure assessment and, at the same time, for risk assessment by reverse dosimetry at current environmental exposures, i.e., comparing the calculated doses that have been taken up to currently available acceptable daily intakes of NNIs.

Alpha-synuclein at the interface between depression and neurodegeneration: Evidence from epidemiological and genetic data

Parkinson’s disease (PD) and Alzheimer’s disease (AlzD) are the two most common neurodegenerative disorders. Although these two disorders differ in terms of their underlying pathophysiology, clinical features, and course, there is a certain degree of overlap between them. This overlap may be partly related to alpha-synuclein (α-synuclein)-mediated neuropathological changes. Recent evidence has found that depression is associated with increased subsequent risk of both these neurological disorders and α-synuclein may also play a pathogenic role in depression. In the current study, epidemiological, population genetic, and environmental exposure data were examined in relation to the estimated prevalence of depressive disorders, PD, and AlzD using a cross-sectional, country-level analysis. The results showed a significant relationship between depressive disorders and neurodegenerative disorders, a possible shared genetic vulnerability related to the functional polymorphisms of SNCA gene, and potential gene-environment interactions involving fine particulate matter pollution. The significance of these results is discussed in light of existing translational, clinical, and epidemiological research on the links between these disorders.

Polychlorinated Diphenyl Ethers in the Environment: A Review and Future Perspectives.

Polychlorinated diphenyl ethers (PCDEs) are a class of synthetic halogenated aromatic compounds, which have gradually attracted widespread attention due to potential environmental risks to humans and ecosystems. This paper presents a literature review of research on PCDEs using PubMed, Web of Science and Google Scholar as search engines/databases with no constraints on publishing year or number. A total of 98 publications on the sources, environmental levels, environmental behavior and fate, synthesis and analysis and toxicology of PCDEs were retrieved. Existing studies have shown that PCDEs widely exist in the environment with the ability of long-range transport, bioaccumulation and biomagnification, which are almost comparable to polychlorinated biphenyls. They can elicit adverse effects including hepatic oxidative stress, immunosuppression, endocrine disorders, growth retardation, malformations, reduced fertility and increased mortality in organisms, among which some seem to be related to the activation of the aryl hydrocarbon receptor. PCDEs can be metabolized into other organic pollutants, such as hydroxylated and methoxylated PCDEs and even polychlorinated dibenzo-p-dioxins and furans through biotransformation, photolysis and pyrolysis reactions in the environment. Compared with reviews on PCDEs published previously, some new information and findings are summarized in this review, such as new sources, current environmental exposure levels, main metabolism pathways in aquatic organisms, acute toxicity data for more species and relationships between structural parameters and toxicity and bioaccumulation potentials of PCDE congeners. Finally, current research deficiencies and future research perspectives are proposed to facilitate the assessment of health and ecological risks of PCDEs.

Rapid quantification of seven major neonicotinoids and neonicotinoid-like compounds and their key metabolites in human urine

Neonicotinoids and neonicotinoid-like compounds (NNIs) are frequently used insecticides worldwide and exposure scenarios can vary widely between countries and continents. We have developed a specific and robust analytical method based on liquid chromatography-electrospray tandem mass spectrometry coupled to online-SPE (online-SPE-LC-ESI-MS-MS) to analyze the seven most important NNIs from a global perspective together with nine of their key metabolites in human urine. The method also includes the neonicotinoid-like flupyradifurone (FLUP), an important future substitute for classical neonicotinoids, and two of its major human metabolites, 5-hydroxy– and N-desfluoroethyl-FLUP. Validation of the method was carried out using pooled urine samples from low-dose human metabolism studies and spiked urine samples with a wide range of creatinine concentrations. Depending on the analyte, the limits of quantitation were between 0.06 and 2.1 µg L−1, the inter-day and intra-day imprecisions ≤6%, and the mean relative recoveries between 89% and 112%. The method enabled us to successfully quantify NNIs and their metabolites at current environmental exposures in 34 individuals of the German general population and 43 pregnant women from Brazil with no known occupational exposures to NNIs.

DNA methylation in clonal duckweed (Lemna minor L.) lineages reflects current and historical environmental exposures.

Environmentally induced DNA methylation variants may mediate gene expression responses to environmental changes. If such induced variants are transgenerationally stable, there is potential for expression responses to persist over multiple generations. Our current knowledge in plants, however, is almost exclusively based on studies conducted in sexually reproducing species where the majority of DNA methylation changes are subject to resetting in germlines, limiting the potential for transgenerational epigenetics stress memory. Asexual reproduction circumvents germlines, and may therefore be more conducive to long-term inheritance of epigenetic marks. Taking advantage of the rapid clonal reproduction of the common duckweed Lemna minor, we hypothesize that long-term, transgenerational stress memory from exposure to high temperature can be detected in DNA methylation profiles. Using a reduced representation bisulphite sequencing approach (epiGBS), we show that temperature stress induces DNA hypermethylation at many CG and CHG cytosine contexts but not CHH. Additionally, differential methylation in CHG context that was observed was still detected in a subset of cytosines, even after 3-12 generations of culturing in a common environment. This demonstrates a memory effect of stress reflected in the methylome and that persists over multiple clonal generations. Structural annotation revealed that this memory effect in CHG methylation was enriched in transposable elements. The observed epigenetic stress memory is probably caused by stable transgenerational persistence of temperature-induced DNA methylation variants across clonal generations. To the extent that such epigenetic memory has functional consequences for gene expression and phenotypes, this result suggests potential for long-term modulation of stress responses in asexual plants.

Polystyrene microplastics induce autophagy and apoptosis in birds lungs via PTEN/PI3K/AKT/mTOR.

Microplastics (MPs) seriously pollute and potentially threaten human health. Birds are sentinels of environmental pollutants, which respond quickly to contamination events and reveal current environmental exposure. Therefore, birds are good bioindicators for monitoring environmental pollutants. However, the mechanism of lung injury in birds and the role of the PTEN/PI3K/AKT axis are unknown. In this study, broilers treated with different polystyrene microplastics (PS-MPs) (0, 1, 10, and 100 mg/L) were exposed to drinking water for 6 weeks to analyze the effect of PS-MPs on lung injury of broilers. The results showed that with the increase of PS-MPs concentration, malonaldehyde (MDA) content increased, and catalase (CAT) and glutathione (GSH) activity decreased, further leading to oxidative stress. PS-MPs caused the PI3K/Akt/mTOR pathway to be inhibited by phosphorylation, and autophagy accelerated formation (LC3) and degradation (p62), causing autophagy. In PS-MPs exposed lung tissues, the expression of Bax/Bcl-2 and Caspase family increased, and MAPK signaling pathways (p38, ERK, and JNK) showed an increase in phosphorylation level, thus leading to cell apoptosis. Our research showed that PS-MPs could activate the antioxidant system. The antioxidant system unbalance-regulated Caspase family, and PTEN/PI3K/AKT pathways initiated apoptosis and autophagy, which in turn led to lung tissue damage in chickens. These results are of great significance to the toxicological study of PS-MPs and the protection of the ecosystem.

Per- and polyfluoroalkyl substances (PFAS) and male reproductive function in young adulthood; a cross-sectional study

BackgroundPer- and polyfluoroalkyl substances (PFAS) are a large family of persistent industrial chemicals with endocrine disrupting properties. ObjectivesTo examine biomarkers of reproductive function in young adult males according to current environmental exposure to single and combined PFAS. MethodsThe study population consisted of young men (n = 1041, age 18–21) from the Fetal Programming of Semen Quality (FEPOS) cohort. These men were recruited from pregnancies included in the Danish National Birth Cohort (DNBC) between 1996 and 2002. From 2017 to 2019, participants answered an online questionnaire, completed a clinical examination and provided a blood and a semen sample. Exposure to 15 PFAS was measured in plasma. Six compounds were quantified above the limit of detection in at least 80% of the participants. We applied negative binomial regression and weighted quantile sum (WQS) regression models to assess associations between single and combined exposure to PFAS and measures of semen quality, testicular volume and reproductive hormones among the young men. ResultsWe found no consistent associations between plasma concentrations of PFAS, semen quality and testicular volume. Higher levels of single and combined PFAS were associated with slightly higher levels of follicle-stimulating hormone (FSH) (WQS 4% difference, 95% confidence interval: 0, 9). Perfluorooctanoic acid (PFOA) was the main contributor to this finding with positive signals also from perfluorodecanoic acid (PFDA) and perfluorohexane sulfonic acid (PFHxS). DiscussionWe examined exposure to a range of common PFAS in relation to biomarkers of male reproductive function and found an association with higher levels of FSH among young men from the general population in Denmark. Further studies on especially combined exposure to PFAS are needed to expand our understanding of potential endocrine disruption from both legacy and emerging compounds in relation to male reproductive function.

Care of the Immigrant Child.

Care of the Immigrant Child.

Environmental exposure during travel: A research review and suggestions forward.

Daily travel through the urban fabric exposes urban dwellers to a range of environmental conditions that may have an impact on their health and wellbeing. Knowledge about exposures during travel, their associations with travel behavior, and their social and health outcomes are still limited. In our review, we aim to explain how the current environmental exposure research addresses the interactions between human and environmental systems during travel through their spatial, temporal and contextual dimensions. Based on the 104 selected studies, we identify significant recent advances in addressing the spatiotemporal dynamics of exposure during travel. However, the conceptual and methodological framework for understanding the role of multiple environmental exposures in travel environments is still in an early phase, and the health and wellbeing impacts at individual or population level are not well known. Further research with greater geographical balance is needed to fill the gaps in the empirical evidence, and linking environmental exposures during travel with the causal health and wellbeing outcomes. These advancements can enable evidence-based urban and transport planning to take the next step in advancing urban livability.

Effects of past environmental tobacco smoke exposure on the menstrual cycle and menstrual phase-related symptoms: A cross-sectional study.

This study examined the effects of current and past environmental tobacco smoke exposure on the menstrual cycle and menstrual phase-related symptoms in nonsmoking Japanese women of child-bearing age. Of 5000 women who agreed to participate, 3935 were analyzed (932 smokers, 2326 nonsmokers, and 677 past smokers). Nonsmokers were divided into three groups based on smoking status and environmental tobacco smoke exposure: nonsmokers without exposure (n = 352), nonsmokers with past exposure (n = 1196) and nonsmokers with current exposure (n = 778). Participants completed a questionnaire on background characteristics, environmental tobacco smoke exposure (location and relationship to smokers), abnormal menstrual cycle, days of menstrual cycle and menstrual cycle-related symptoms experienced in the past 3 months (assessed by the Menstrual Distress Questionnaire). Mean age was 29.7 ± 7.0 (20-44) years. Compared with nonsmokers without environmental tobacco smoke exposure, current smokers had the highest risk of an abnormal menstrual cycle (adjusted odds ratio [OR], 1.74 [1.194-2.545]), followed by nonsmokers with past exposure (adjusted OR, 1.70 [1.171-2.464]), past smokers (adjusted OR, 1.60 [1.081-2.366]) and nonsmokers with current environmental tobacco smoke exposure (adjusted OR, 1.49 [0.901-1.212]). Irrespective of environmental tobacco smoke exposure, current smokers reported significantly more severe premenstrual and menstrual symptoms than nonsmokers, and nonsmokers with past environmental tobacco smoke exposure had significantly more severe premenstrual and menstrual symptoms than nonsmokers without environmental tobacco smoke exposure. Past environmental tobacco smoke exposure, especially during childhood or adolescence, might harm women's reproductive health when they reach reproductive age.

Deregulation of whole-transcriptome gene expression in zebrafish (Danio rerio) after chronic exposure to low doses of imatinib mesylate in a complete life cycle study

Imatinib mesylate (IM) is an anticancer drug that belongs to tyrosine kinase inhibitors. We report the results of the first investigation of the chronic exposure of zebrafish (Danio rerio) to IM. The exposure to IM (0.01, 1 and 100 μg/L) was initiated in adult fish and continued through hatching and the offspring generation for seven months. In addition to standard toxicological endpoints, induction of genotoxic effects and whole-genome transcriptome of liver samples of offspring generation of zebrafish were analysed. Exposure to IM did not affect the survival and growth of zebrafish, did not cause any histopathological changes, but it induced a marginal increase in the chromosomal damage in blood cells. The whole-genome transcriptome analyses demonstrated dose-dependent increase in the number of differentially expressed genes with a significantly higher number of deregulated genes in female fish compared to male. Differentially expressed genes included genes involved in response to DNA damage, cell cycle control and regulation of circadian rhythm. Based on the low genotoxic activity and the pattern of the changes in DNA damage responsive genes we consider that at current environmental exposure levels, IM represents low risk for genotoxic effects in aquatic organisms. Exposure to IM also induced deregulation of the expression of genes associated with steroidogenesis and hormone metabolism and function, which indicates hormone-disrupting activity of IM that has not been studied so far. The study provide new information on the potential consequences of chronic exposure to the residues of tyrosine kinase inhibitors, which remain to be further explored.

Abstract IA11: Timing of environmental contributions to cancer in a multigenerational cohort

Abstract Transdisciplinary studies of environmental risk factors for cancer can discover paths to prevention. Using breast cancer as a case study, we review findings on the relation of a ubiquitous legacy environmental chemical, DDT, to breast cancer in three generations in the Child Health and Development Studies cohort. Although banned in the U.S. and in many places worldwide in the 1970s, the DDT story illustrates the potential role of legacy environmental chemicals in current cancer etiology. We demonstrate the importance of accounting for windows of susceptibility and induction time to cancer and provide evidence for multigenerational and transgenerational effects relevant to breast cancer risk in current generations. Findings provide proof of concept that the current environment may have lasting effects 60 years in the future. Findings support prudent management of current environmental exposures with known biologic toxicity. Waiting 60 years to understand human effects is too late to protect the public health and prevent cancer. The Child Health and Development Studies (CHDS) is a 60-year, prospective follow-up of 20,000 pregnancies that occurred in the 1960s and the resultant generations. The CHDS provides unique and valuable data to characterize how pregnancy and in utero exposures and responses contribute to disease risk in multiple generations. Maternal perinatal blood samples simultaneously provide the opportunity to measure the pregnancy exposome for Generation 1 mothers, the in utero exposome for Generation 2, and the germline exposome for Generation 3. In the CHDS we are also able to study the grandpaternal exposome in relation to granddaughters’ breast cancer risk factors, a design that estimates transgenerational effects via the paternal line. CHDS generations are tracked for place of residence, cancer risk factors, and cancer incidence to provide high quality of evidence avoiding errors of recall and accurate exposure assessment. We review breast cancer findings for Generation 1 (cohort mothers), Generation 2 (cohort daughters), and Generation 3 (cohort granddaughters). We describe perinatal DDT associations with breast cancer in mothers and daughters, with breast density in daughters, and with breast cancer risk factors in granddaughters. We show the results of next steps to uncover mechanisms, including DNA methylation patterns in breast cancer-related genes in the daughters’ generation associated with in utero DDT exposure, and the correlation of the maternal metabolome with DDT in mothers. We also compare the human, observational metabolomics data in maternal perinatal serum with parallel data from controlled experimental studies in mice designed to replicate the DDT dose and perinatal exposure in our human cohort. Along with DDT, we show findings on the relation of in utero exposure to PFASs, a class of chemicals of current concern that were also present in the 1960s. Along with grandmaternal associations, we also show early findings on some grandpaternal variables that are independently correlated with granddaughter breast cancer risk factors. We highlight findings based on high-resolution metabolomics data and exposome analyses in conjunction with epidemiologic data. These metabolomics data serve as important molecular footprints that result from gene and environmental interactions. We employ novel computational and statistical approaches to facilitate the interpretation of these high-dimensional data and integrative analysis, draw insights on the biologic effects of DDT and PFASs compounds, and explore the implication of findings on risk for breast cancer. Citation Format: Barbara A. Cohn. Timing of environmental contributions to cancer in a multigenerational cohort [abstract]. In: Proceedings of the AACR Special Conference on Environmental Carcinogenesis: Potential Pathway to Cancer Prevention; 2019 Jun 22-24; Charlotte, NC. Philadelphia (PA): AACR; Can Prev Res 2020;13(7 Suppl): Abstract nr IA11.

Conditionings of population exposure to electromagnetic fields associated with the rational use of 5G radiocommunication networks in Poland

In 2017, preparations were made in Poland to provide all citizens with access to the Internet at a speed of at least 30 Mb/s, and at a speed of at least 100 Mb/s for 50% of households. This goal is to be realized, among others, by means of the fifth generation (5G) radio-communication networks. This work presents the assumptions of the 5G network structure and estimates of the level of population exposure toelectromagnetic fields related to their rational use. It was also analyzed whether, from the technical point of view, 5G networks could be implemented while respecting the currently acceptable level of electromagnetic field intensity in Poland (7 V/m), taking into account the current environmental exposure caused by antennas of cellular base stations. This is a contribution to the ongoing discussion on the need to change the requirements in Poland in order to limit the level of population exposure to electromagnetic fields. Based on the available documentation of the proposed technical standards, the theoretical analysis of environmental exposure to the electromagnetic field emitted by 5G systems shows that, with rational power management, obtaining the expected (compatible with 5G standards) quality of connections via base stations installed outside of buildings and using intelligent antenna systems with controlled beams, it will be possible to maintain the electric field strength and power density below the current limit values in places accessible to the public (<7 V/m, <0.1 W/m2). Med Pr. 2020;71(2):245-53.