Exposure-related Effects Research Articles

"Holy Cow, Where do I Sign up?" Attitudes of Military Veterans Toward Epigenomic Biomarker Toxic Exposure Testing.

After the Sergeant First Class Heath Robinson Honoring Our Promise to Address Comprehensive Toxics Promise to Address Comprehensive Toxics (PACT) Act in 2022, there has been a great interest in studying toxic exposures encountered during military service. Development of epigenomic biomarkers for exposures could facilitate understanding of exposure-related health effects, but such testing could also provide unwanted information. We explored attitudes toward epigenomic biomarker research and the potential to test for past exposures using semistructured interviews with Veterans (n = 22) who experienced potentially harmful exposures. Twenty Veterans said they would hypothetically want to receive epigenomic information related to their toxic exposures and potential health impacts as part of a research study. Veterans identified 9 potential benefits, including promoting insights concerning intergenerational health, identification of early health interventions, and additional knowledge or explanation for their experiences. Sixteen participants noted potential risks, including psychological distress, receiving nonactionable, uncertain, or inaccurate results, and privacy and discrimination risks. Ten participants identified at least 1 condition in their children that they thought could be related to their exposure and most said they would be interested in receiving research results related to their children's and grandchildren's risk. Results suggest that Veterans might welcome benefits of epigenomic research related to military exposures, yet have some concerns about potential negative impacts.

Methylglyoxal induces cardiac dysfunction through mechanisms involving altered intracellular calcium handling in the rat heart

Methylglyoxal (MGO) is an endogenous, highly reactive dicarbonyl metabolite generated under hyperglycaemic conditions. MGO plays a role in developing pathophysiological conditions, including diabetic cardiomyopathy. However, the mechanisms involved and the molecular targets of MGO in the heart have not been elucidated. In this work, we studied the exposure-related effects of MGO on cardiac function in an isolated perfused rat heart ex vivo model. The effect of MGO on calcium homeostasis in cardiomyocytes was studied in vitro by the fluorescence indicator of intracellular calcium Fluo-4. We demonstrated that MGO induced cardiac dysfunction, both in contractility and diastolic function. In rat heart, the effects of MGO treatment were significantly limited by aminoguanidine, a scavenger of MGO, ruthenium red, a general cation channel blocker, and verapamil, an L-type voltage-dependent calcium channel blocker, demonstrating that this dysfunction involved alteration of calcium regulation. MGO induced a significant concentration-dependent increase of intracellular calcium in neonatal rat cardiomyocytes, which was limited by aminoguanidine and verapamil. These results suggest that the functionality of various calcium channels is altered by MGO, particularly the L-type calcium channel, thus explaining its cardiac toxicity. Therefore, MGO could participate in the development of diabetic cardiomyopathy through its impact on calcium homeostasis in cardiac cells.

IL-10-TG/TPO-T4 axis, the target of bis (2-ethylhexyl) tetrabromophthalate on thyroid function imbalance

Bis (2-ethylhexyl) tetrabromophthalate (TBPH) is a new type of brominated flame retardant. Some studies suggest that TBPH exposure may be associated with thyroid damage. However, there is a paucity of research on the authentic exposure-related effects and molecular mechanisms in animals or cells. In this study, we used male Sprague-Dawley (SD) rats and the Nthy ori3–1 cell line (the human thyroid follicular epithelial cell) to explore the potential effects of TBPH (5, 50, 500 mg/kg and 1, 10, 100 nM) on the thyroid. The genes and their proteins of cytokines and thyroid-specific proteins, thyroglobulin (TG), thyroid peroxidase (TPO), and sodium iodide cotransporter (NIS) were examined to investigate the possible mechanisms. At the end of the experiment, it was found that 50 and 500 mg/kg TBPH could increase the levels of total thyroxine (TT4) and free thyroxine (FT4) significantly. The messenger RNAs (mRNAs) of Tg, Tpo, Interleukin-6 (Il6), and Interleukin-10 (Il10) in the thyroid tissues from the rats treated with 500 mg/kg were enhanced clearly. Meanwhile, the mRNAs of TG, TPO, IL6, and IL10 were elevated in Nthy ori3–1 cells treated with 100 nM TBPH as well. The mRNAs of TG and TPO were elevated after the knockdown of IL6. To our surprise, after the knockdown of IL10 or the treatment of anti-IL-10-receptor (anti-IL-10-R) antibody, the mRNAs of TG and TPO were significantly reduced, and the effects of TBPH were diminished. In conclusion, our results suggested that the IL-10-IL-10R-TG/TPO-T4 axis is one important target of TBPH in the thyroid.

Assessing household fine particulate matter (PM2.5) through measurement and modeling in the Bangladesh cook stove pregnancy cohort study (CSPCS)

Biomass fuel burning is a significant contributor of household fine particulate matter (PM2.5) in the low to middle income countries (LMIC) and assessing PM2.5 levels is essential to investigate exposure-related health effects such as pregnancy outcomes and acute lower respiratory infection in infants. However, measuring household PM2.5 requires significant investments of labor, resources, and time, which limits the ability to conduct health effects studies. It is therefore imperative to leverage lower-cost measurement techniques to develop exposure models coupled with survey information about housing characteristics. Between April 2017 and March 2018, we continuously sampled PM2.5 in three seasonal waves for approximately 48-h (range 46 to 52-h) in 74 rural and semi-urban households among the participants of the Bangladesh Cook Stove Pregnancy Cohort Study (CSPCS). Measurements were taken simultaneously in the kitchen, bedroom, and open space within the household. Structured questionnaires captured household-level information related to the sources of air pollution. With data from two waves, we fit multivariate mixed effect models to estimate 24-h average, cooking time average, daytime and nighttime average PM2.5 in each of the household locations. Households using biomass cookstoves had significantly higher PM2.5 concentrations than those using electricity/liquefied petroleum gas (626 μg/m3 vs. 213 μg/m3). Exposure model performances showed 10-fold cross validated R2 ranging from 0.52 to 0.76 with excellent agreement in independent tests against measured PM2.5 from the third wave of monitoring and ambient PM2.5 from a separate satellite-based model (correlation coefficient, r = 0.82). Significant predictors of household PM2.5 included ambient PM2.5, season, and types of fuel used for cooking. This study demonstrates that we can predict household PM2.5 with moderate to high confidence using ambient PM2.5 and household characteristics. Our results present a framework for estimating household PM2.5 exposures in LMICs, which are often understudied and underrepresented due to resource limitations.

Bioaerosol-induced in vitro activation of toll-like receptors and inflammatory biomarker expression in waste workers

PurposeOccupational exposure to bioaerosols during waste handling remains a health concern for exposed workers. However, exposure-related health effects and underlying immunological mechanisms are still poorly described.MethodsThe present study assessed the inflammatory potential of work-air samples (n = 56) in vitro and investigated biomarker expression in exposed workers (n = 69) compared to unexposed controls (n = 25). These quantitative results were compared to self-reported health conditions.ResultsPersonal air samples provoked an activation of TLR2 and TLR4 HEK reporter cells in one-third of all samples, indicating that the work environment contained ligands capable of inducing an immune response in vitro. Monocyte levels, as well as plasma biomarker levels, such as IL-1Ra, IL-18 and TNFα were significantly higher in exposed workers, compared to the control group when confounding factors such as BMI, sex, age and smoking habits were accounted for. Furthermore, a significant exposure-related increase in midweek IL-8 levels was measured among exposed workers. Tendencies of increased prevalence of health effects of the respiratory tract were identified in exposed workers.ConclusionInhalable dust provoked TLR activation in vitro, indicating that an exposure-related immune response may be expected in susceptible workers. However, despite significant differences in inflammatory plasma biomarker levels between exposed and unexposed workers, prevalence of self-reported health effects did not differ between the groups. This may be due to the healthy worker effect, or other factors such as adequate use of personal protective respiratory devices or adaptation to the work environment with reduced activation of the immune system.

Toxicological evaluation of a polyherbal formulation on testicular function and gonadal histomorphology in exposed Wistar rats.

Dr Iguedo Goko Cleanser® is a herbal formulation (HF) widely marketed in southern Nigeria and purported to be very efficacious for the management of various diseases including giardiasis, toilet infections, hypertension, diabetes, ulcer, impotence, low libido, low sperm count amongst others. Medicinal plants reportedly produce an array of adverse reactions capable of inducing harmful conditions, including death. This study evaluated the subchronic toxicity concern of HF on testicular function and gonadal histoarchitecture in Wistar rats. Thirty Wistar rats of both sexes were randomly divided into six groups (5/group) and were orally administered HF for 60 days. The control groups received 5 mL/kg of distilled water; the treatment groups were administered 476.24 and 158.75 mg/kg body weight of HF each for both male and female rats. Using standard procedures, semen analysis was done for all male rats. Animals were anaesthetised and sacrificed on the 62nd day; the gonads were eviscerated, weighed and fixed in 10% buffered formalin for histopathological examinations. Significant (p < 0.05) increase in sperm count relative to control as well as spermatotoxic effects were observed in male rats. Histologically, the ovary presented some degrees of pathologies: cloggy appearing ovarian cortex with a display of a tumour-like cortical area, scantily displayed primordial follicles, haemorrhagic blood vessels, atretic secondary follicle, and eroding granulosa cells amongst others. Testicular histopathology showed abnormal seminiferous tubules' histoarchitecture, degenerated spermatids, distorted spermatogenic cells' orientation, and displaced spermatids into the luminal space. Herbal drugs are usually regarded to be completely safe due to their natural sources, however, this study discovered exposure-related toxic effects of Dr Iguedo Goko Cleanser® on testicular function and gonadal histomorphology. The findings recommend extreme caution with chronic use and avoidance whenever possible.

Measuring environmental exposures in people's activity space: The need to account for travel modes and exposure decay.

Accurately quantifying people's out-of-home environmental exposure is important for identifying disease risk factors. Several activity space-based exposure assessments exist, possibly leading to different exposure estimates, and have neither considered individual travel modes nor exposure-related distance decay effects. We aimed (1) to develop an activity space-based exposure assessment approach that included travel modes and exposure-related distance decay effects and (2) to compare the size of such spaces and the exposure estimates derived from them across typically used activity space operationalizations. We used 7-day-long global positioning system (GPS)-enabled smartphone-based tracking data of 269 Dutch adults. People's GPS trajectory points were classified into passive and active travel modes. Exposure-related distance decay effects were modeled through linear, exponential, and Gaussian decay functions. We performed cross-comparisons on these three functional decay models and an unweighted model in conjunction with four activity space models (i.e., home-based buffers, minimum convex polygons, two standard deviational ellipses, and time-weighted GPS-based buffers). We applied non-parametric Kruskal-Wallis tests, pair-wise Wilcoxon signed-rank tests, and Spearman correlations to assess mean differences in the extent of the activity spaces and correlations across exposures to particulate matter (PM2.5), noise, green space, and blue space. Participants spent, on average, 42% of their daily life out-of-home. We observed that including travel modes into activity space delineation resulted in significantly more compact activity spaces. Exposure estimates for PM2.5 and blue space were significantly (p < 0.05) different between exposure estimates that did or did not account for travel modes, unlike noise and green space, for which differences did not reach significance. While the inclusion of distance decay effects significantly affected noise and green space exposure assessments, the decay functions applied appear not to have had any impact on the results. We found that residential exposure estimates appear appropriate for use as proxy values for the overall amount of PM2.5 exposure in people's daily lives, while GPS-based assessments are suitable for noise, green space, and blue space. For some exposures, the tested activity space definitions, although significantly correlated, exhibited differing exposure estimate results based on inclusion or exclusion of travel modes or distance decay effect. Results only supported using home-based buffer values as proxies for individuals' daily short-term PM2.5 exposure.

S558 Association of Chronic Opioid Use With Dyssynergic Defecation: Dose and Exposure Effects

Introduction: While opioids can be effective management for analgesia, GI side effects can limit tolerability. Chronic opioid use (OU) is associated with opioid-induced constipation (OIC) through slowing of GI transit. Studies have noted possible associations between OU and dyssynergic defecation (DD). The aim of this study was to identify chronic OU amongst patients who underwent anorectal manometry (ARM) testing to determine dose or exposure related effects on anorectal function. Methods: We conducted a retrospective study of patients who had ARM from January 2015 to October 2021. OU was determined by pre-procedure questionnaire and medical record review. OU was considered at least one month of use at time of ARM and was standardized based on morphine milliequivalents (MMEs). Results: Demographics are summarized in Table. Of 773 patients undergoing ARM, 12.7% had chronic OU. OU was associated with having DD; Type 1 DD being most common (p< 0.001). Chronic OU patients were older than patients without OU (p< 0.001). ARM in chronic OU patients was performed more often for constipation, constipation and fecal incontinence, and constipation and diarrhea when compared to patients without OU (p=0.04). Chronic OU patients were more likely to have abnormal balloon expulsion time (BET) defined as > 60 seconds (p< 0.001). Within OU, patients were divided into low and high dose of opiates for likelihood of DD findings on ARM (Figure). The lowest group dosing that reached significance defined low OU as 0-10 MME and high OU as ≥10 MME (p=0.005). Of the 34 low dose patients, 67.6% had DD; of the 64 high dose patients, 95.3% had DD (p=0.004). High dose OU was associated with fewer normal ARM tests and more Type I-III DD (p=0.005). Of the chronic OU, high dose patients were more likely to have abnormal defecation index (DI) defined as < 1.4 compared to low dose patients (p=0.006). Conclusion: Our data suggests a correlation between OU and ARM indications as well as OU and DD. We also found that 10 MME was the opioid dose threshold above which there is a greater association with anorectal dysfunction. Chronic OU patients suffered from constipation, were older, and had greater abnormal BET than those without OU, suggesting exposure-dependent association with OU. DI was abnormal at high dose OU compared to low dose OU, suggesting dose-dependent association with OU. Our study suggests that OIC can be associated with DD in addition to the known delayed colonic transit.Figure 1.: Presence of Dyssynergic Defecation in Low Dose Opioid Use and High Dose Opioid Use Groups (Blue: Normal ARM, Orange: Dyssynergic Defecation on ARM) [p=0.004] Table 1. - Distributions and Variables for Non-Opioid Users and Opioid Users in Patients undergoing Anorectal Manometry Non-Opioid(n=675) All Opioid(n=98) p-Value Low Dose (0-10 MME) Opioid(n= 34) High Dose ( > 10 MME) Opioid(n=64) p-Value Gender Male 142 (20%) 24 (24%) 0.43 7 (20.6%) 17 (26.6%) 0.62 Female 533 (80%) 74 (66%) 27 (79.4%) 47 (73.4%) Age (mean) y 48.7 + 16.0 56.0 + 16.9 < 0.001 55.9 + 17.0 56.0 + 17.0 0.98 ARM Indication Constipation 511 (75.6%) 78 (79.6%) 0.04 24 (70.6%) 54 (84.4%) 0.14 Fecal Incontinence 120 (17.8%) 13 (13.3%) 8 (23.6%) 5 (7.8%) Constipation and Fecal incontinence 23 (3.5%) 5 (5.1%) 1 (2.9%) 4 (6.2%) Fecal Urgency 8 (1.2%) 0 - - Incomplete Defecation 2 (0.3%) 0 - - Diarrhea 10 (1.5%) 0 - - Constipation and Diarrhea 1 (0.1%) 2 (2%) 1 (2.9%) 1 (1.6%) ARM Result Normal 281 (41.6%) 14 (14.3%) < 0.001 11 (32.4%) 3 (4.7%) 0.005 Type I DD 174 (25.8%) 43 (34.9%) 10 (29.4%) 33 (51.6%) Type II DD 33 (4.9%) 9 (9.2%) 2 (5.9%) 7 (10.9%) Type III DD 116 (17.2%) 18 (18.4%) 6 (17.6%) 12 (18.8%) Type IV DD 71 (10.5%) 14 (14.3%) 5 (14.7%) 9 (14.1%) Defecation Index Abnormal (< 1.4) 502 (74.3%) 80 (81.6%) 0.13 21 (61.8%) 59 (92.2%) 0.006 Normal ( >1.4) 174 (25.7%) 18 (18.4%) 13 (38.2%) 5 (7.8%) Balloon Expulsion Time Abnormal ( >60sec) 238 (35.3%) 64 (65.3%) < 0.001 21 (61.8%) 43 (67.2%) 0.65 Normal (< 60 sec) 436 (64.7%) 34 (34.7%) 13 (38.2%) 21 (32.8%) Sensory Threshold Low 155 (22.9%) 26 (26.5%) 0.50 11 (32.4%) 15 (23.4%) 0.33 Normal 339 (50.1%) 43 (43.9%) 16 (47.1%) 27 (42.2%) High 182 (26.9%) 29 (29.6%) 7 (20.6%) 22 (34.4%) Mean sphincter pressure (resting) mmHg 64.60 + 23.6 63.50 + 25.3 0.66 58.6 + 25.3 66.1 + 25.2 0.16 Max sphincter pressure (squeeze) mmHg 157.5 + 68.0 147.0 + 62.9 0.15 138.6 + 64.9 151.5 + 61.8 0.33

Integration of probabilistic exposure assessment and risk characterization for perchlorate in infant formula and supplementary food.

Infants are the primary susceptible population to perchlorate exposure-related adverse health effects, while information on their dietary intake of perchlorate via infant food remains limited. This study determined perchlorate in six categories of baby food commodities commonly consumed by 0-36 months infants. A probabilistic approach with Monte Carlo simulation was used to estimate perchlorate's daily intake (EDI) considering uncertainty and variability. Results showed that the average perchlorate concentration in infant food ranged from 3.42 to 22.26μg/kg. The mean (SD) EDIs of perchlorate were 0.42(0.20), 0.62(0.20), and 0.46(0.14) μg/kg-bw/day for 0-6, 7-12, and 13-36-months infants, respectively. Infant formula was the major contributor (34%-74%) to EDIs of perchlorate in all age groups. Probabilistic risk characterization showed the cumulative probability of EDIs exceeding the RfD (0.70 μg/kg-bw/day) were 6.5%, 37.9%, and 4.5% for 0-6, 7-12, and 13-36-months infants, respectively. The cumulative risk of perchlorate exposure from different infant food intake should be noted.

Assessment of PM2.5-related health effects: A comparative study using multiple methods and multi-source data in China

In China, PM2.5 pollution has caused extensive death and economic loss. Thus, an accurate assessment of the spatial distribution of these losses is crucial for delineating priority areas for air pollution control in China. In this study, we assessed the PM2.5 exposure-related health effects according to the integrated exposure risk function and non-linear power law (NLP) function in 338 prefecture-level cities in China by utilizing online monitoring data and the PM2.5 Hindcast Database (PHD). Our results revealed no significant difference between the monitoring data and PHD (p value = 0.66 > 0.05). The number of deaths caused by PM2.5-related Stroke (cerebrovascular disease), ischemic heart disease, chronic obstructive pulmonary disease, and lung cancer at the national level estimated through the NLP function was 0.27 million (95% CI: 0.06–0.50), 0.23 million (95% CI: 0.08–0.38), 0.31 million (95% CI: 0.04–0.57), and 0.31 million (95% CI: 0.16–0.40), respectively. The total economic cost at the national level in 2016 was approximately US$80.25 billion (95% CI: 24.46–132.25). Based on a comparison of Z statistics, we propose that the evaluation results obtained using the NLP function and monitoring data are accurate. Additionally, according to scenario simulations, Beijing, Chongqing, Tianjin, and other cities should be priority areas for PM2.5 pollution control to achieve considerable health benefits. Our statistics can help improve the accuracy of PM2.5-related health effect assessments in China.

Prenatal exposure to air pollution is associated with altered brain structure, function, and metabolism in childhood.

Prenatal exposure to air pollution disrupts cognitive, emotional, and behavioral development. The brain disturbances associated with prenatal air pollution are largely unknown. In this prospective cohort study, we estimated prenatal exposures to fine particulate matter (PM2.5 ) and polycyclic aromatic hydrocarbons (PAH), and then assessed their associations with measures of brain anatomy, tissue microstructure, neurometabolites, and blood flow in 332 youth, 6-14 years old. We then assessed how those brain disturbances were associated with measures of intelligence, ADHD and anxiety symptoms, and socialization. Both exposures were associated with thinning of dorsal parietal cortices and thickening of postero-inferior and mesial wall cortices. They were associated with smaller white matter volumes, reduced organization in white matter of the internal capsule and frontal lobe, higher metabolite concentrations in frontal cortex, reduced cortical blood flow, and greater microstructural organization in subcortical gray matter nuclei. Associations were stronger for PM2.5 in boys and PAH in girls. Youth with low exposure accounted for most significant associations of ADHD, anxiety, socialization, and intelligence measures with cortical thickness and white matter volumes, whereas it appears that high exposures generally disrupted these neurotypical brain-behavior associations, likely because strong exposure-related effects increased the variances of these brain measures. The commonality of effects across exposures suggests PM2.5 and PAH disrupt brain development through one or more common molecular pathways, such as inflammation or oxidative stress. Progressively higher exposures were associated with greater disruptions in local volumes, tissue organization, metabolite concentrations, and blood flow throughout cortical and subcortical brain regions and the white matter pathways interconnecting them. Together these affected regions comprise cortico-striato-thalamo-cortical circuits, which support the regulation of thought, emotion, and behavior.

The PM2.5-bound polycyclic aromatic hydrocarbon behavior in indoor and outdoor environments, part II: Explainable prediction of benzo[a]pyrene levels

Among the polycyclic aromatic hydrocarbons (PAH), benzo[a]pyrene (B[a]P) has been considered more relevant than other species when estimating the potential exposure-related health effects and has been recognized as a marker of carcinogenic potency of air pollutant mixture. The current understanding of the factors which govern non-linear behavior of B[a]P and associated pollutants and environmental processes is insufficient and further research has to rely on the advanced analytical approach which averts the assumptions and avoids simplifications required by linear modeling methods. For the purpose of this study, we employed eXtreme Gradient Boosting (XGBoost), SHapley Additive exPlanations (SHAP) attribution method, and SHAP value fuzzy clustering to investigate the concentrations of inorganic gaseous pollutants, radon, PM2.5 and particle constituents including trace metals, ions, 16 US EPA priority PM2.5-bound PAHs and 31 meteorological variables, as key factors which shape indoor and outdoor PM2.5-bound B[a]P distribution in a university building located in the urban area of Belgrade (Serbia). According to the results, the indoor and outdoor B[a]P levels were shown to be highly correlated and mostly influenced by the concentrations of Chry, B[b]F, CO, B[a]A, I[cd]P, B[k]F, Flt, D[ah]A, Pyr, B[ghi]P, Cr, As, and PM2.5 in both indoor and outdoor environments. Besides, high B[a]P concentration events were recorded during the periods of low ambient temperature (<12 °C), unstable weather conditions with precipitation and increased soil humidity.

Implications of Sublethal Insecticide Exposure and the Development of Resistance on Mosquito Physiology, Behavior, and Pathogen Transmission.

Simple SummaryMosquitoes are one of the greatest threats to human lives; they transmit a wide range of pathogens, including viruses that cause lethal diseases. Mosquitoes are found in both aquatic (as larvae or pupae) and terrestrial (as adults) environments during their complex life cycle. For decades, insecticides have been systematically used on mosquitoes with the aim to reduce their population. Little is known about how the stress resulting from the exposure of mosquitoes to insecticides impacts the tri-partite relationship between the mosquitoes, their vertebrate hosts, and the pathogens they transmit. In this work, we review existing experimental evidence to obtain a broad picture on the potential effects of the (sub)lethal exposure of hematophagous mosquitoes to different insecticides. We have focused on studies that have advanced our understanding of their physiological and behavioral responses (including the mechanisms behind insecticide resistance) and the spread of pathogens by these vectors—understudied but critically important issues for epidemiology. Studying these exposure-related effects is of paramount importance for predicting how they respond to insecticide exposure and whether this exposure makes them more or less likely to transmit pathogens.For many decades, insecticides have been used to control mosquito populations in their larval and adult stages. Although changes in the population genetics, physiology, and behavior of mosquitoes exposed to lethal and sublethal doses of insecticides are expected, the relationships between these changes and their abilities to transmit pathogens remain unclear. Thus, we conducted a comprehensive review on the sublethal effects of insecticides and their contributions to insecticide resistance in mosquitoes, with the main focus on pyrethroids. We discuss the direct and acute effects of sublethal concentrations on individuals and populations, the changes in population genetics caused by the selection for resistance after insecticide exposure, and the major mechanisms underlying such resistance. Sublethal exposures negatively impact the individual’s performance by affecting their physiology and behavior and leaving them at a disadvantage when compared to unexposed organisms. How these sublethal effects could change mosquito population sizes and diversity so that pathogen transmission risks can be affected is less clear. Furthermore, despite the beneficial and acute aspects of lethality, exposure to higher insecticide concentrations clearly impacts the population genetics by selecting resistant individuals, which may bring further and complex interactions for mosquitoes, vertebrate hosts, and pathogens. Finally, we raise several hypotheses concerning how the here revised impacts of insecticides on mosquitoes could interplay with vector-mediated pathogens’ transmission.

Protein interaction, monocyte toxicity and immunogenic properties of cerium oxide crystals with 5% or 14% gadolinium, cobalt oxide and iron oxide nanoparticles – an interdisciplinary approach

Metal oxide nanoparticles are widely used in both consumer products and medical applications, but the knowledge regarding exposure-related health effects is limited. However, it is challenging to investigate nanoparticle interaction processes with biological systems. The overall aim of this project was to improve the possibility to predict exposure-related health effects of metal oxide nanoparticles through interdisciplinary collaboration by combining workflows from the pharmaceutical industry, nanomaterial sciences, and occupational medicine. Specific aims were to investigate nanoparticle-protein interactions and possible adverse immune reactions. Four different metal oxide nanoparticles; CeOx nanocrystals with 5% or 14% Gd, Co3O4, and Fe2O3, were characterized by dynamic light scattering and high-resolution transmission electron microscopy. Nanoparticle-binding proteins were identified and screened for HLA-binding peptides in silico. Monocyte interaction with nanoparticle–protein complexes was assessed in vitro. Herein, for the first time, immunogenic properties of nanoparticle-binding proteins have been characterized. The present study indicates that especially Co3O4-protein complexes can induce both ‘danger signals’, verified by the production of inflammatory cytokines and simultaneously bind autologous proteins, which can be presented as immunogenic epitopes by MHC class II. The clinical relevance of these findings should be further evaluated to investigate the role of metal oxide nanoparticles in the development of autoimmune disease. The general workflow identified experimental difficulties, such as nanoparticle aggregate formation and a lack of protein-free buffers suitable for particle characterization, protein analyses, as well as for cell studies. This confirms the importance of future interdisciplinary collaborations.

Prenatal exposure to air pollution is associated with childhood inhibitory control and adolescent academic achievement

BackgroundPrenatal air pollution exposure is associated with reductions in self-regulation and academic achievement. Self-regulation has been separately linked with academic achievement. Understudied, however, are the contributions of pollution exposure to inhibitory control, a facet of self-regulation, and whether pollution-related inhibitory control deficits are associated with impairment in academic achievement. MethodsParticipants were recruited from a prospective birth cohort. Measures of prenatal airborne polycyclic aromatic hydrocarbons (PAH) during the third trimester of pregnancy, inhibitory control (NEPSY Inhibition) at mean age = 10.4 years, and Woodcock-Johnson Tests of Achievement-III at mean age = 13.7 were available for N = 200 participants. Multiple linear regression examined sex-dependent and sex independent associations among prenatal PAH, childhood inhibitory control, and academic achievement during adolescence, and whether childhood inhibitory control mediated associations between prenatal PAH and academic achievement during adolescence, controlling for ethnicity, maternal country of birth, language of prenatal interview, maternal marital status, maternal years of education, material hardship, quality of home caregiving environment, and early life stress. ResultsAcross all participants, higher prenatal PAH was significantly associated with worse spelling skills (WJ-III Spelling, β = −0.16, 95%Confidence Interval [CI]: 0.30, −0.02, p = .02). Trend level associations between higher prenatal PAH and worse reading comprehension (WJ-III Passage Comprehension, β = −0.13, 95%CI: 0.28, 0.01, p = .07) and math skills (WJ-III Broad Math, β = −0.11, 95%CI: 0.25, 0.03, p = .11) were detected. Across all participants, higher PAH was significantly associated with worse inhibitory control (β = −0.15, 95%CI: 0.29,-0.01 p = .03). Better inhibitory control was significantly associated with better reading comprehension (WJ-III Passage Comprehension, β = 0.22, 95%CI: 0.09, 0.36, p < .002) and math skills (WJ-III Broad Math Index, β = 0.32, 95%CI: 0.19, 0.45, p < .001), and trend level associations with better spelling skills (WJ-III Spelling, β = 0.12, 95%CI: 0.02, 0.26, p = .10). Inhibitory control significantly mediated PAH-related achievement effects for Passage Comprehension (β = −0.61, 95%CI: 1.49, −0.01) and Broad Math Index (β = −1.09, 95%CI: 2.36, −0.03). ConclusionsHigher prenatal PAH exposure and lower childhood inhibitory control were associated with worse spelling, passage comprehension, and math in adolescence. Notably, childhood inhibitory control mediated PAH exposure-related effects on achievement in adolescents. Identifying these potential exposure-related phenotypes of learning problems may promote interventions that target inhibitory control deficits rather than content specific deficits.

Toxicity assessment of dimethyl carbonate following 28 days repeated inhalation exposure.

Dimethyl carbonate (DMC) has been used as a reagent in methylation reactions, can be used as paints, coatings, and adhesives, and is a chemical that is being used increasing, which poses a health hazard to workers who handle it. So, the toxic reactions of F344 rats with inhalation exposure to 600, 1600, and 5000 ppm concentrations for 6 hours, 5 days a week, 4 weeks was evaluated. During the exposure period, general signs were observed, body weight and food consumption were measured, and hematologic and blood biochemical tests, organ weight measurements, necropsy, and histopathological examination were performed after the end of exposure. During the exposure period, dimethyl carbonate was exposed to an average of 599.26±31.40, 1614.64±80.79 and 5106.83±297.13 ppm in the chambers of the T1, T2 and T3 test groups, respectively. During the test period, general signs, weight change, food consumption, organ weight measurement, necropsy, and histopathological examination did not show any effects related to exposure to the test substance. However, as a result of blood and blood biochemical tests, an increase in AST, ALP, APTT, and PT levels was observed. From these results, it is judged that liver is the target organ when repeated inhalation exposure of dimethyl carbonate, the test substance, for 4 weeks, and the exposure-related effects of the test substance were observed at PT and ALP levels up to 600 ppm exposure concentration, but NOEC (No Observed Effect Concentration) was determined to be less than 600 ppm because it was not judged as an adverse effect.

Prenatal developmental toxicity studies on fumes from oxidised asphalt (OA) in the rat

The prenatal developmental toxicity of the fumes of oxidised asphalt (OA) was tested by nose-only inhalation in the rat. The test material was generated by collecting fumes from the headspace of storage tanks filled with OA. The composition of these fumes was matched to fumes sampled at a workplace where the same OA was applied in a pour-and-roll operation, representing occupational exposure with high concentrations of fumes to not underestimate the possible hazard. In the main study, dams were exposed to 0, 53, 158 and 536 mg/m3 of fume (as total organic mass), for 6 h/day for 19 days p.c. The maternal NOAEC was 53 mg/m³ (lowest dose tested). In the high-dose group treatment-related effects on body weight gain were seen. In the mid- and high-dose groups treatment-related effects on food consumption, lung weights, and histopathological changes in lungs and the upper respiratory tract were observed. The NOAEC for prenatal developmental toxicity was 536 mg/m³ since no exposure-related effects were found in any of the exposure groups for any of the investigated reproductive endpoints. Furthermore, nose-only exposure to OA fumes in concentrations up to 536 mg/m³ from days 1–19 p.c. did not induce any significant fetal abnormalities.

Metal additive manufacturing and possible clinical markers for the monitoring of exposure-related health effects.

Additive manufacturing (AM) includes a series of techniques used to create products, in several different materials, such as metal, polymer or ceramics, with digital models. The main advantage of AM is that it allows the creation of complex structures, but AM promises several additional advantages including the possibility to manufacture on demand or replacing smaller worn parts by directly building on an existing piece. Therefore, the interest for and establishment of AM is rapidly expanding, which is positive, however it is important to be aware that new techniques may also result in new challenges regarding health and safety issues. Metals in blood and possible clinical effects due to metal exposure were investigated in AM operators at one of the first serial producing AM facilities in the world during two consecutive years with implementation of preventive measures in-between. As comparison, welders and office workers as control group were investigated. Health investigations comprised of surveys, lung function tests, antioxidant activity and vascular inflammation as well as renal- and hepatic function analysis. AM operators had significantly reduced nickel levels in blood (10.8 vs 6.2 nmol/L) as well as improved lung function (80 vs 92% of predicted) from year 1 to year 2. This is in line with previously published results displaying reduced exposure. Blood cobalt and nickel levels correlated with previously reported urinary levels, while blood chromium did not. Multivariate modelling showed that blood cobalt, antioxidant/inflammatory marker serum amyloid A1/serum paraoxonase/arylesterase 1 activity and the hepatic markers aspartate transaminase, alanine transaminase, and alkaline phosphatase were higher in AM operators compared to controls. The study show that the selected clinical analyses could function as a complement to metal analyses in biological fluids when investigating exposure-related health effects in AM operators. However, validation in larger cohorts is necessary before more definite conclusions could be drawn.

Long Term Exposure to Virgin and Recycled LDPE Microplastics Induced Minor Effects in the Freshwater and Terrestrial Crustaceans Daphnia magna and Porcellio scaber.

The effects of microplastics (MP) are extensively studied, yet hazard data from long-term exposure studies are scarce. Moreover, for sustainable circular use in the future, knowledge on the biological impact of recycled plastics is essential. The aim of this study was to provide long-term toxicity data of virgin vs recycled (mechanical recycling) low density polyethylene (LDPE) for two commonly used ecotoxicity models, the freshwater crustacean Daphnia magna and the terrestrial crustacean Porcellio scaber. LDPE MP was tested as fragments of 39.8 ± 8.82 µm (virgin) and 205 ± 144 µm (recycled) at chronic exposure levels of 1–100 mg LDPE/L (D. magna) and 0.2–15 g LDPE/kg soil (P. scaber). Mortality, reproduction, body length, total lipid content, feeding and immune response were evaluated. With the exception of very low inconsistent offspring mortality at 10 mg/L and 100 mg/L of recycled LDPE, no MP exposure-related adverse effects were recorded for D. magna. For P. scaber, increased feeding on non-contaminated leaves was observed for virgin LDPE at 5 g/kg and 15 g/kg. In addition, both LDPE induced a slight immune response at 5 g/kg and 15 g/kg with more parameters altered for virgin LDPE. Our results indicated different sublethal responses upon exposure to recycled compared to virgin LDPE MP.

Relationships among Inorganic Arsenic, Nutritional Status CpG Methylation and microRNAs: A Review of the Literature.

Inorganic arsenic is a naturally occurring toxicant that poses a significant and persistent challenge to public health. The World Health Organization has identified many geographical regions where inorganic arsenic levels exceed safe limits in drinking water. Numerous epidemiological studies have associated exposure to inorganic arsenic with increased risk of adverse health outcomes. Randomized clinical trials have shown that nutritional supplementation can mitigate or reduce exacerbation of exposure-related effects. Although a growing body of evidence suggests that epigenetic status influences toxicity, the relationships among environmental exposure to arsenic, nutrition, and the epigenome are not well detailed. This review provides a comprehensive summary of findings from human, rodent, and in vitro studies highlighting these interactive relationships.