The commercial production of infant food is undergoing rapid development, but control is limited. This study measured several toxic and essential elements in 77 food products intended for infants (<1 year). Concentrations of toxic metals in infant formulas were generally low, but cadmium and cobalt were higher than in breast milk, as were iron, manganese and selenium concentrations. Elevated arsenic in a rice-based dairy- and gluten-free porridge (3.2 μg/portion) and cadmium in some porridges (∼1 μg/portion) raise concern. Further, manganese in gruels and porridges with ∼1 mg/portion (not fortified), and even formulas (∼0.1 mg/portion; fortified) reached concerning exposure levels, especially if mixed with water containing manganese. Estimated intake of inorganic arsenic (median 1.7 μg/day, excluding fish) and cadmium (median 3.4 μg/day) from mixed foods at 9 months of age exceeded health-based guidance values. Continued control of contaminants and additives in infant food and evaluation of related health risks are warranted.

Exposure to metals and microorganisms can pose health risks. Historical books often contain pigments with metals, and fungi. The aim of this study is to obtain knowledge about exposure to eight metals and microorganisms in a library in Denmark. Personal exposure of staff handling historical books (high-exposure group) and indoor and outdoor air samples were collected in three well-ventilated sites of a library. Urine samples were collected the next morning from the high-exposure group, a low-exposure group (colleagues not handling historical books), and a reference group. Eight metals were measured in air and urine samples using inductively coupled plasma mass spectrometry (ICP-MS). Bacteria and fungal species were identified using MALDI-TOF MS. Personal exposure to metals was higher than in stationary indoor and outdoor air samples, particularly for arsenic (As), lead (Pb), mercury (Hg), and cadmium (Cd), and some were spread to the indoor air. Personal exposure to As, Cd, and Hg showed a significant correlation with Pb levels. The overall indoor/outdoor ratio of personal exposure exceeded 1 for all metals except antimony (Sb) indicating potential indoor source. Additionally, Cd and As concentrations in some urine samples exceeded Biological Limit and Guidance Values. Most fungal species detected belonged to Aspergillus and Penicillium, and eight species are xerophilic. In conclusion, library staff were exposed to higher concentrations of metals as compared to outdoor air, warranting further research across different tasks and days for staff handling historical books to understand these risks better.

The green transition relies on metals, requiring increased metal recovery from waste. However, exposure risks among metal recycling workers are poorly understood. We conducted a cross-sectional study to assess dust and metal exposure among 139 recycling workers from 13 Swedish metal recycling companies and 90 controls. We documented work practices through observations and questionnaires and assessed dust and metal exposures using a combination of individual air sampling (inhalable (ID) and respirable dust) and biomonitoring (blood and pre-/post-shift urine). ICP-MS was used to measure 39 metals in air, 47 in blood, and 42 in urine. Thirty-two % of the workers were involved in the recycling of e-waste. At most workplaces, dust control was insufficient, respiratory protective equipment was rarely or incorrectly used, and hygienic routines were inadequate. This was reflected in 6.2 times higher ID levels in recycling workers; 14 % exceeded the 5 mg/m3 exposure limit for ID, and some also exceeded limits for Pb, Cu, As, Cd, and Sb. Workers had elevated blood and/or urine levels of Pb, Hg, Al, Sb, Fe and Mn with known human toxicity, and of Y, Lu, In, Ga, W, and Te with limited or unknown toxicity. Furthermore, observed were also co-exposure patterns for those metals. Inhalation was the likely primary exposure route for Pb, Sb, Y, In, and Te. In conclusion, Swedish recycling workers were exposed to elevated levels of dust and metals, highlighting the need for ongoing monitoring of both known and emerging metals.

Chronic exposure to inorganic arsenic (As) in drinking water is a serious health concern but people differ in susceptibility. Naturally occurring As in Bolivian drinking water was recently reported, however, its long-term effects on the blood transcriptome remain unexplored. To bridge this gap, we conducted a transcriptome-wide analysis of whole blood cells from individuals in the Bolivian Andes. Blood and urine samples were collected for transcriptomic analysis, genotyping of AS3MT polymorphisms, and measurements of inorganic As metabolites in urine. Linear regression models were employed for extracting As-associated genes, and cell deconvolution to estimate cell fractions from the transcriptome. Functional annotations of the As-associated genes were performed using Ingenuity Pathway Analysis (IPA) and ClusterProfiler. Protein-protein interaction analysis was conducted to identify networks between As-associated genes. A total of 588 genes were identified from linear regression analysis and associated with downregulation of autophagy-related functions and a reduction in activated NK cells. Stratification by gender showed a significant enrichment of pathways related to carcinogenesis, oxidative stress, glucose metabolism, and epigenetic regulation in females, e.g., PI3K/AKT/MTOR signaling, HIF-1 signaling, insulin receptor signaling, and microRNA biogenesis pathway. Carriers of the AS3MT genotypes associated with a poorer As metabolism showed enrichment in DNA replication and cell proliferation, whereas carriers of the genotype associated with an efficient As metabolism showed suppression of autophagy and DNA damage pathways. Our data indicate the importance of the autophagy pathway in relation to As exposure, and its crosstalk with PI3K/AKT/mTOR and miRNA biogenesis, providing new insights into the biological pathway under As exposure. Overall, this study identified novel genome-wide changes in blood mRNA in response to long-term As exposure in Bolivia, an underrepresented population, laying groundwork for further study.

Inorganic arsenic is a known carcinogen. Telomere length (TL) and mitochondrial DNA copy number (mtDNAcn) in peripheral blood may serve as biomarkers for genotoxicity and cancer risk. Our aim is to assess if arsenic exposure influences TL and mtDNAcn in women living around Lake Poopó (Bolivia) from two ethnicities (Aymara-Quechua and Uru). Arsenic exposure was evaluated as the sum of arsenic metabolite concentrations in urine (U-As) measured by high-performance liquid chromatography online with hydride generation and inductively coupled plasma-mass spectrometry (HPLC-HG-ICP-MS), and as total arsenic in blood (B-As) measured by ICP-MS. Efficiency of arsenic metabolism was evaluated using the relative fractions of urinary metabolites, and arsenic methylating genetics (AS3MT rs3740393 and rs1046778) measured by TaqMan allelic discrimination or chip-based genotyping. TL and mtDNAcn were determined in blood by real-time PCR. Our results show that arsenic exposure (assessed as U-As and B-As) was associated with longer TL and higher mtDNAcn in this study population, and the associations were modified by arsenic metabolism capacity and AS3MT genotype.

Atmospheric fine particulate matter (PM2.5) is a critical indicator of air quality, with substantial implications for human health. Understanding the emission sources and chemical composition of PM2.5 is crucial for mitigating possible adverse health effects. This study spans five diverse cities on three continents from north and south hemisphere: Stockholm (Sweden), Kyoto (Japan), Limeira, Ribeirao Preto, and Caceres (Brazil). Our objective was to assess PM2.5 chemical composition and regional and long-range transport influences to identify the main sources of particulate air pollution at these cities during the winter/dry seasons. All studied cities but Kyoto exhibited PM2.5 levels above World Health Organization (WHO) guidelines, with the Brazilian cities experiencing the highest fine particle pollution levels, implying increased adverse health risks. We observed significant variations in concentrations of polycyclic aromatic compounds (PACs), monosaccharide anhydrides (MAs), and inorganic elements. Limeira exhibited the highest levels of total PACs (median level of 12.4 ng m-3), while Caceres displayed high variability of PACs, most likely due to episodic regional wildfire events. MA concentrations were significantly higher in Limeira and Ribeirao Preto and together with elevated levels of retene and potassium (K) they suggested a substantial influence of biomass burning. Backward air mass trajectory analysis suggested widespread Amazon and Savanna wildfires along with local fires as main contributors for these sites. All source identification approaches highlighted differences among the cities, with Stockholm and Kyoto showing influence of sources related to traffic emissions, waste burning, and long-range transport, and Brazilian cities traffic, industrial, biogenic, and more evident biomass burning. This cross-continental study provides valuable insights into PM2.5 composition and emission sources, emphasizing the impact of different emissions on air quality. Our findings underscore the importance of local strategies to mitigate air pollution and protect public health, especially in regions where PM2.5 levels consistently exceed recommended guidelines.

Intake of fish and seafood during pregnancy may have certain beneficial effects on fetal development, but measurement of intake using questionnaires is unreliable. Here, we assessed several candidate biomarkers of seafood intake, including long-chain omega 3 fatty acids (n-3 LCPUFA), selenium, iodine, methylmercury, and different arsenic compounds, in 549 pregnant women (gestational week 29) in the prospective birth cohort NICE (Nutritional impact on Immunological maturation during Childhood in relation to the Environment). Proportions of the fatty acids eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA) in erythrocytes were measured using gas chromatography with flame ionization detector. Selenium was measured in blood plasma and erythrocytes, mercury and arsenic in erythrocytes, and iodine and several arsenic compounds in urine, using inductively coupled plasma mass spectrometry, arsenic compounds after first being separated by ion exchange high-performance liquid chromatography (HPLC). Each biomarker was related to intake of total seafood and to intake of fatty and lean fish, and shellfish in third trimester, estimated from a semi-quantitative food frequency questionnaire filled out in gestational week 34. The pregnant women reported a median total seafood intake of 184 g/week (5th-95th percentiles: 34-465 g/week). This intake correlated most strongly with erythrocyte mercury concentrations (rho = 0.49, p < 0.001), consisting essentially of methylmercury, followed by total arsenic in erythrocytes (rho = 0.34, p < 0.001), and arsenobetaine in urine (rho = 0.33, p < 0.001), the main form of urinary arsenic. These biomarkers correlated well with intake of both fatty fish, lean fish, and shellfish. Erythrocyte DHA and plasma selenium correlated, although weakly, mainly with fatty fish (rho = 0.25 and 0.22, respectively, both p < 0.001). In conclusion, elevated concentrations of erythrocyte mercury and urinary arsenobetaine can be useful indicators of seafood intake, more so than the n-3 LCPUFAs. However, the relative importance of the biomarkers may differ depending on the type and amount of seafood consumed.

OBJECTIVE:To describe serum levels of calcium, copper, selenium, magnesium, iron and zinc and evaluate their relationship with maternal socio-demographic characteristics and dietary variables in women in the first trimester of pregnancy. METHOD:Cross-sectional study with 1279 participants from the INMA cohorts. RESULTS:The concentrations of the elements analyzed were within the normal range. Associations with higher levels of these metals were found for calcium with white meat intake (p=0.026), for copper with excess body weight (p <0.01), low social class (p=0.03) and being multipara (p <0.01), for magnesium with being over 35 years old (p=0.001), high social class (p=0.044), primiparous status (p=0.002) and low daily intake of bread (p=0.009) and legumes (p=0.020); for zinc with university education (p=0.039) and residence in Gipuzkoa (p <0.01), and for selenium with residence in Valencia (p <0.01), university education (p=0.001), vitamin B6 supplementation (p=0.006), fish intake (> 71g/day) (p=0.014) and having been born in Spain (p=0.001). Further, lower iron levels were associated with being overweight (p=0.021) or obese (p <0.001) and vitamin B12 supplementation (p=0.006). CONCLUSIONS:Our results suggest that trace elements in the analyzed cohorts are adequate for this stage of pregnancy. The variability in these elements is mainly linked to socio-demographic and anthropometric variables.

Background: Observational studies have indicated that elevated maternal fluoride exposure during pregnancy may impair child neurodevelopment but a potential impact on birth outcomes is understudied. Objectives: To evaluate the impact of gestational fluoride exposure on birth outcomes (birth size and gestational age at birth) and to assess the potential mediating role of maternal thyroid hormones. Methods: We studied 583 mother-child dyads in the NICE cohort in northern Sweden. Maternal fluoride exposure was assessed by measuring urinary concentrations at late pregnancy (median: 29th gestational week) using an ion selective electrode. Plasma levels of free and total thyroxine (fT4, tT4) and triiodothyronine (fT3, tT3), and thyroid stimulating hormone (TSH) were measured with electrochemiluminescence immunoassays. The infant's weight, length, head circumference, and gestational age at birth were extracted from hospital records. Results: Median urinary fluoride concentration was 0.71 mg/L (5th-95th percentile 0.31-1.9 mg/L; specific gravity adjusted). In multivariable-adjusted regression models, every 1 mg/L increase of maternal urinary fluoride was associated with a mean increase in birth weight by 84 g (95%CI: 30, 138), length by 0.41 cm (95% CI: 0.18, 0.65), head circumference by 0.3 cm (95%CI: 0.1, 0.4), and with increased odds of being born large for gestational age (OR = 1.39, 95%CI: 1.03, 1.89). Every 1 mg/L increase of maternal urinary fluoride was also associated with a mean increase of the plasma fT3:fT4 ratio (B = 0.007, 95%CI: 0.000, 0.014), but not with the hormones or TSH. In mediation analyses, the maternal fT3:fT4 ratio did not explain the urinary fluoride-birth size relationships. Discussion: Gestational urinary fluoride concentrations were associated with increased size at birth and even with increased odds of being born large for gestational age. The fluoride-related associations with increased size at birth were not explained by changes in maternal thyroid hormone levels.

Exposure to methylmercury (MeHg) through fish is a global public health problem. Exposure monitoring is essential for health risk assessment, especially in pregnant women and children due to the documented neurotoxicity. Herein, we evaluate a time series of MeHg exposure via fish in primiparous Swedish women, covering a time period of 23 years (1996-2019). The 655 included mothers were part of the POPUP study (Persistent Organic Pollutants in Uppsala Primiparas) conducted by the Swedish Food Agency (SFA). MeHg exposure was assessed via measurements of total mercury (Hg) in hair using either cold vapor atomic fluorescence spectrophotometry or inductively coupled plasma mass spectrometry, showing very good linear agreement (R-2 = 0.97). Maternal characteristics and fish consumption were obtained via questionnaires. The median concentration of total Hg in hair was 0.38 mg/kg (range 0.17 -1.5) in 1996 and 0.25 mg/kg (range 0.03-1.1) in 2019. On average the women consumed 11 8.2 meals of fish per month, and fish consumption was positively correlated with total Hg in hair (Spearman correlation: 0.39; p < 0.001). In multiple regression analyses, the geometric mean annual decrease of total Hg in hair was -2.5% (95% CI: -3.2, -1.8%). Total fish consumption increased up to 2011 (B: 0.32 times/month per year; 95% CI 0.17, 0.46) after which it started to decline (B: -0.66 times/month per year; 95% CI -0.92, -0.40). Moreover, both total Hg in hair and fish consumption was positively associated with maternal age and education, and inversely associated with pre-pregnancy BMI. In conclusion, the exposure to MeHg via fish appears to be slowly declining among Swedish pregnant women. (C) 2020 The Author(s). Published by Elsevier Ltd.

Indigenous people living in the Bolivian Andes are exposed through their drinking water to inorganic arsenic, a potent carcinogen. However, the health consequences of arsenic exposure in this region are unknown. The aim of this study was to evaluate associations between arsenic exposure and changes in cancer-related proteins in indigenous women (n = 176) from communities around the Andean Lake Poopó, Bolivia. Arsenic exposure was assessed in whole blood (B-As) and urine (as the sum of arsenic metabolites, U-As) by inductively coupled plasma-mass spectrometry (ICP-MS). Cancer-related proteins (N = 92) were measured in urine using the proximity extension assay. The median B-As concentration was 2.1 (range 0.60–9.1) ng/g, and U-As concentration was 67 (12–399) μg/L. Using linear regression models adjusted for age, urinary osmolality, and urinary leukocytes, we identified associations between B-As and four putative cancer-related proteins: FASLG, SEZ6L, LYPD3, and TFPI2. Increasing B-As concentrations were associated with lower protein expression of SEZ6L, LYPD3, and TFPI2, and with higher expression of FASLG in urine (no association was statistically significant after correcting for multiple comparisons). The associations were similar across groups with different arsenic metabolism efficiency, a susceptibility factor for arsenic toxicity. In conclusion, arsenic exposure in this region was associated with changes in the expression of some cancer-related proteins in urine. Future research is warranted to understand if these proteins could serve as valid biomarkers for arsenic-related toxicity.

Objective Metals have been suggested as a risk factor for amyotrophic lateral sclerosis (ALS), but only retrospective studies are available to date. We compared metal levels in prospectively collected blood samples from ALS patients and controls, to explore whether metals are associated with ALS mortality. Methods A nested ALS case–control study was conducted within the prospective EPIC (European Prospective Investigation into Cancer and Nutrition) cohort. Cases were identified through death certificates. We analyzed metal levels in erythrocyte samples obtained at recruitment, as a biomarker for metal exposure from any source. Arsenic, cadmium, copper, lead, manganese, mercury, selenium, and zinc concentrations were measured by inductively coupled plasma–mass spectrometry. To estimate ALS risk, we applied conditional logistic regression models. Results The study population comprised 107 cases (65% female) and 319 controls matched for age, sex, and study center. Median time between blood collection and ALS death was 8 years (range = 1–15). Comparing the highest with the lowest tertile, cadmium (odds ratio [OR] = 2.04, 95% confidence interval [CI] = 1.08–3.87) and lead (OR = 1.89, 95% CI = 0.97–3.67) concentrations suggest associations with increased ALS risk. Zinc was associated with a decreased risk (OR = 0.50, 95% CI = 0.27–0.94). Associations for cadmium and lead remained when limiting analyses to noncurrent smokers. Interpretation This is the first study to compare metal levels before disease onset, minimizing reverse causation. The observed associations suggest that cadmium, lead, and zinc may play a role in ALS etiology. Cadmium and lead possibly act as intermediates on the pathway from smoking to ALS. ANN NEUROL 20209999:n/a–n/a

Observational studies have indicated that low-to-moderate exposure to cadmium (Cd), lead (Pb), and mercury (Hg) adversely affects birth anthropometry, but results are inconclusive. The aim of this study was to elucidate potential impact on birth anthropometry of exposure to Cd, Pb, and Hg in pregnant women, and to identify the main dietary sources. In the NICE (Nutritional impact on Immunological maturation during Childhood in relation to the Environment) birth-cohort in northern Sweden, blood and urine were collected from pregnant women in early third trimester. Cd, Pb and Hg were measured in erythrocytes (n = 584), and Cd also in urine (n = 581), by inductively coupled plasma mass spectrometry. Dietary data were collected through a semi-quantitative food frequency questionnaire administered in mid-third trimester. Birth anthropometry data were extracted from hospital records. In multivariable-adjusted spline regression models, a doubling of maternal erythrocyte Cd (median: 0.29 mu g/kg) above the spline knot of 0.50 mu g/kg was associated with reduced birth weight (B: -191 g; 95% CI: -315, -68) and length (-0.67 cm; -1.2, -0.14). The association with birth weight remained when the analysis was restricted to never-smokers. Likewise, a doubling of erythrocyte Hg (median 1.5 mu g/kg, mainly MeHg) above 1.0 mu g/kg, was associated with decreased birth weight (-59 g; -115, -3.0), and length (-0.29 cm; -0.54, -0.047). Maternal Pb (median 11 mu g/kg) was unrelated to birth weight and length. Erythrocyte Cd was primarily associated with intake of plant derived foods, Pb with game meat, tea and coffee, and Hg with fish. The results indicated that low-level maternal Cd and Hg exposure were associated with poorer birth anthropometry. Further prospective studies in low-level exposed populations are warranted. (C) 2020 The Authors. Published by Elsevier Ltd.

Inorganic arsenic is one of the most toxic and carcinogenic substances in the environment, but many organisms, including humans, methylate inorganic arsenic to mono-, di-, and trimethylated arsenic metabolites, which the organism can excrete. In humans and other eukaryotic organisms, the arsenite methyltransferase (AS3MT) protein methylates arsenite. AS3MT sequences from eukaryotic organisms group phylogenetically with predicted eubacterial AS3MT sequences, which has led to the suggestion that AS3MT was acquired from eubacteria by multiple events of horizontal gene transfer. In this study, we evaluated whether 55 (out of which 47 were predicted based on protein sequence similarity) sequences encoding putative AS3MT orthologues in 47 species from different kingdoms can indeed methylate arsenic. Fifty-three of the proteins showed arsenic methylating capacity. For example, the predicted AS3MT of the human gut bacterium Faecalibacterium prausnitzii methylated arsenic efficiently. We performed a kinetic analysis of 14 AS3MT proteins representing two phylogenetically distinct clades (Group 1 and 2) that each contain both eubacterial and eukaryotic sequences. We found that animal and bacterial AS3MTs in Group 1 rarely produce trimethylated arsenic, whereas Hydra vulgaris and the bacterium Rhodopseudomonas palustris in Group 2 produce trimethylated arsenic metabolites. These findings suggest that animals during evolution have acquired different arsenic methylating phenotypes from different bacteria. Further, it shows that humans carry two bacterial systems for arsenic methylation: one bacterium-derived AS3MT from Group 1 incorporated in the human genome and one from Group 2 in F. prausnitzii present in the gut microbiome.

Background: Our studies of children in a rural Bangladeshi area, with varying concentrations of arsenic in well-water, indicated modest impact on child verbal cognitive function at 5 years of age. Objectives: Follow-up of arsenic exposure and children's cognitive abilities at school-age. Methods: In a nested sub-cohort of the MINIMat supplementation trial, we assessed cognitive abilities at 10 years of age (n = 1523), using Wechsler Intelligence Scale for Children (WISC-IV). Arsenic in maternal urine and erythrocytes in early pregnancy, in child urine at 5 and 10 years, and in hair at 10 years, was measured using Inductively Coupled Plasma Mass Spectrometry. Results: Median urinary arsenic at 10 years was 58 mu g/L (range 7.3-940 mu g/L). Multivariable-adjusted regression analysis showed that, compared to the first urinary arsenic quintile at 10 years (< 30 mu g/L), the third and fourth quintiles (30-45 and 46-73 mu g/L, respectively) had 6-7 points lower Full developmental raw scores (B: -7.23, 95% CI -11.3; - 3.18, and B: - 6.37, 95% CI -10.5; - 2.22, respectively), corresponding to similar to 0.2 SD. Verbal comprehension and Perceptual reasoning seemed to be affected. Models with children's hair arsenic concentrations showed similar results. Maternal urinary arsenic in early pregnancy, but not late pregnancy, showed inverse associations with Full developmental scores (quintiles 2-4: B: - 4.52, 95% CI - 8.61; - 0.43, B: - 5.91, 95% CI -10.0; -1.77, and B: - 5.98, 95%CI -10.2; -1.77, respectively, compared to first quintile), as well as with Verbal comprehension, Perceptual reasoning, and Processing speed, especially in girls (p < 0.05 for interaction of sex with Full developmental scores and Perceptual reasoning). In models with all exposure time points included, both concurrent exposure at 10 years and early prenatal exposure remained associated with cognitive abilities. Conclusions: Both early prenatal and childhood arsenic exposure, even at low levels (about 50 mu g/L in urine), was inversely associated with cognitive abilities at school-age, although the estimates were modest.

Elevated concentrations of inorganic arsenic, one of the most potent environmental toxicants and carcinogens, have been detected in well water around Lake Poopo, Bolivia This study aimed to assess human exposure to arsenic in villages around Lake Poopo and also to elucidate whether the metabolism and detoxification of arsenic in this population is as efficient as previously indicated in other Andean areas. We recruited 201 women from 10 villages around Lake Poopo. Arsenic exposure was determined as the sum concentration of arsenic metabolites (inorganic arsenic; monomethylarsonic acid, MMA; and dimethylarsinic acid, DMA) in urine (U-As), measured by HPLC-HG-ICP-MS. Efficiency of arsenic metabolism was assessed by the relative fractions of the urinary metabolites. The women had a wide variation in U-As (range 12-407 ug/L, median 65 mu g/L) and a markedly efficient metabolism of arsenic with low %MMA (median 7.7%, range: 2.2-18%) and high %DMA (80%, range: 54-91%) in urine. In multivariable-adjusted linear regression models, ethnicity (Aymara-Quechua vs. Uru), body weight, fish consumption and tobacco smoking were associated with urinary arsenic metabolite fractions. On average, the Uru women had 2.5 lower % (percentage unit) iAs, 22 lower %MMA and 4.7 higher %DMA compared with the Aymara-Quechua women. Our study identified several factors that may predict these women's arsenic methylation capacity, particularly ethnicity. Further studies should focus on mechanisms underlying these differences in arsenic metabolism efficiency, and its importance for the risk of arsenic-related health effects. (C) 2018 The Authors. Published by Elsevier B.V.

During the past decades, farmers in low to middle -income countries have increased their use of pesticides, and thereby the risk of being exposed to potentially genotoxic chemicals that can cause adverse health effects. Here, the aim was to investigate the con-elation between exposure to pesticides and genotoxic damage in a Bolivian agricultural population. Genoloxic effects were assessed in peripheral blood samples by comet and micronucleus (MN) assays, and exposure levels by measurements of 10 urinary pesticide metabolites. Genetic susceptibility was assessed by determination of null frequency of GSTM1 and GSTT1 genotypes. The results showed higher MN frequency in women and farmers active ?S years compared W their counterpart (P< 0.05). In addition, age, GST genotype, alcohol consumption, and type of water source influenced levels of genotoxic damage. Individuals with high exposure to Lebuconazole, 2,4-D, or cyfluthrin displayed increased levels of genotoxic damage (P< 0.05-0.001). Logistic regression was conducted to evaluate associations between pesticide exposure and risk of genotoxic damage. After adjustment for confounders, a significant increased risk of DNA strand breaks was found for high exposure to 2,4-D, odds ratio (OR) 1.99 (P < 0.05). In contrast, high exposure to pyrethroids was associated with a reduced risk of DNA strand breaks, OR 0.49 (P < 0.05). It was also found that high exposure to certain mixtures of pesticides (containing mainly 2,4-D or cyfluthrin) was significantly associated with increased level and risk of genotoxic damage (P < 0.05). In conclusion, our data show that high exposure levels to some pesticides is associated with an increased risk of genotoxic damage among Bolivian fariTters, suggesting that their use should be better controlled or limited. (C) 2019 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

INTRODUCTION:Copper (Cu) is an essential element involved in biological processes; however, excessive Cu could be harmful because of its reactive nature. Very few studies have evaluated its potential neurotoxic effects. We aimed to evaluate the association between maternal Cu levels and children's neuropsychological development. METHODS:Study subjects were mother-child pairs from the Spanish INMA (i.e. Childhood and Environment) Project. Cu was measured by inductively coupled plasma mass spectrometry in serum samples taken at the first trimester of pregnancy (2003-2005). Neuropsychological development was assessed using the Bayley Scales of Infant Development (BSID) at 12 months (n = 651) and the McCarthy Scales of Children's Abilities (MSCA) at 5 years of age (n = 490). Covariates were obtained by questionnaires during pregnancy and childhood. Multivariate linear and non-linear models were built in order to study the association between maternal Cu and child neuropsychological development. RESULTS:The mean ± standard deviation of maternal Cu concentrations was 1606 ± 272 μg/L. In the multivariate analysis, a negative linear association was found between maternal Cu concentrations and both the BSID mental scale (beta = -0.051; 95% confidence intervals [CI]: -0.102, -0.001) and the MSCA verbal scale (beta = -0.044; 95%CI:-0.094, 0.006). Boys obtained poorer scores than girls, with increasing Cu at 12 months (interaction p-value = 0.040 for the mental scale and 0.074 for the psychomotor scale). This effect modification disappeared at 5 years of age. The association between Cu and the MSCA scores (verbal, perceptive performance, global memory and motor, general cognitive, and executive function scales) was negative for those children with lowest maternal iron concentrations (<938μg/L). CONCLUSION:The Cu concentrations observed in our study were within the reference range established for healthy pregnant women in previous studies. The results of this study contribute to the body of scientific knowledge with important information on the possible neurotoxic capability of Cu during pregnancy.

Background: For trace element measurement in human breast milk, an accurate high-throughput sample preparation method would be desirable. In this study, a quick alkali sample dilution method was systematically compared to the traditional acid digestion pretreatment for measuring 10 trace elements in 237 human breast milk samples by inductively coupled plasma mass spectrometry (ICP-MS). Methods: The alkali method involved dilution of the breast milk samples with a solution consisting of 2% butanol, 0.05% EDTA, 0.05% Triton X-100 and 1% NH4OH. The mixtures were sonicated, centrifuged and analyzed by ICP-MS. Acid digestion was performed in HNO3 at 250 degrees C using a Milestone Ultra CLAVE II microwave digestion system. Results: Overall, the alkali dilution method gave higher analytical precision compared to acid digestion while LODs and recoveries were similar between the two methods. Spearman's correlations between measured element concentrations by the two sample preparation methods were strong (r(s) > 0.70) for all elements, except for Ca and Cd (r(s) < 0.50). Passing-Bablok regression analyses showed best agreement between the two methods for Li, Mg, Fe, Zn, Se and Cd (slopes 0.8-1.2). Evaluation of Bland-Altman difference plots showed best method agreement (lowest bias) for Na, Mg, Ca, Zn and Cd. Highest difference in element concentration between the methods was observed for iodine (96 ng/g by alkali dilution and 33 ng/g by acid digestion), probably due to formation of volatile species such as HI and I-2 in the acid matrix. Conclusions: The results indicate that the alkali dilution high-throughput sample preparation method is comparable to the more commonly used acid digestion method for ICP-MS measurements of some toxic and essential elements in human breast milk.

Purpose: We aimed to evaluate the distribution of individual epidermal growth factor receptor {EGFR) mutation subtypes found in routine cytological specimens. Patients and methods: A retrospective audit was performed on EGFR testing results of 1.874 consecutive cytological samples of newly diagnosed or treatment-naive Indonesian lung cancer patients (years 2015-2016). Testing was performed by ISO 15189 accredited central laboratory. Results: Overall test failure rate was 5.1%, with the highest failure (7.1%) observed in pleural effusion and lowest (1.6%) in needle aspiration samples. EGFR imitation frequency was 44.4%. Tyrosine kinase inhibitor (TKI)-sensitive common EGFR mutations (ins/dels exon 19, L858R) and uncommon mutations (G719X, T790M, L861Q) contributed 57.1% and 29%, respectively. Approximately 13.9% of mutation-positive patients carried a mixture of common and uncommon mutations. Women had higher EGFR mutation rate (52.9%) vs men (39.1%; p < 0.05). In contrast, uncommon mutations conferring either TKI responsive (G719X, L861Q) or TKI resistance (T790M, exon 20 insertions) were consistently more frequent in men than in women (67.3% vs 32.7% or 69.4% vs 30.6%; p < 0.05). Up to 10% EGFR mutation positive patients had baseline single mutation T790M, exon 20 insertion, or in coexistence with TKI-sensitive mutations. Up to 9% patients had complex or multiple EGFR mutations, whereby 48.7% patients harbored TKJ-resistant mutations. One patient presented third-generation TKI-resistant mutation L792F simultaneously withT T790M. Conclusion: Routine diagnostic cytological techniques yielded similar success rate to detect EGFR mutations. Uncommon EGFR mutations were frequent events in Indonesian lung cancer patients.