HBM4EU chromates study - Usefulness of measurement of blood chromium levels in the assessment of occupational Cr(VI) exposure.

Occupational exposures to hexavalent Chromium (Cr(VI)) can occur in welding, hot working stainless steel processing, chrome plating, spray painting and coating activities. Recently, within the human biomonitoring for Europe initiative (HBM4EU), a study was performed to assess the suitability of different biomarkers to assess the exposure to Cr(VI) in various job tasks. Blood-based biomarkers may prove useful when more specific information on systemic and intracellular bioavailability is necessary. To this aim, concentrations of Cr in red blood cells (RBC-Cr) and in plasma (P-Cr) were analyzed in 345 Cr(VI) exposed workers and 175 controls to understand how these biomarkers may be affected by variable levels of exposure and job procedures. Compared to controls, significantly higher RBC-Cr levels were observed in bath plating and paint application workers, but not in welders, while all the 3 groups had significantly greater P-Cr concentrations. RBC-Cr and P-Cr in chrome platers showed a high correlation with Cr(VI) in inhalable dust, outside respiratory protective equipment (RPE), while such correlation could not be determined in welders. In platers, the use of RPE had a significant impact on the relationship between blood biomarkers and Cr(VI) in inhalable and respirable dust. Low correlations between P-Cr and RBC-Cr may reflect a difference in kinetics. This study showed that Cr-blood-based biomarkers can provide information on how workplace exposure translates into systemic availability of Cr(III) (extracellular, P-Cr) and Cr(VI) (intracellular, RBC-Cr). Further studies are needed to fully appreciate their use in an occupational health and safety context.

HBM4EU chromates study - Overall results and recommendations for the biomonitoring of occupational exposure to hexavalent chromium.

Exposure to hexavalent chromium [Cr(VI)] may occur in several occupational activities, e.g., welding, Cr(VI) electroplating and other surface treatment processes. The aim of this study was to provide EU relevant data on occupational Cr(VI) exposure to support the regulatory risk assessment and decision-making. In addition, the capability and validity of different biomarkers for the assessment of Cr(VI) exposure were evaluated. The study involved nine European countries and involved 399 workers in different industry sectors with exposures to Cr(VI) such as welding, bath plating, applying or removing paint and other tasks. We also studied 203 controls to establish a background in workers with no direct exposure to Cr(VI). We applied a cross-sectional study design and used chromium in urine as the primary biomonitoring method for Cr(VI) exposure. Additionally, we studied the use of red blood cells (RBC) and exhaled breath condensate (EBC) for biomonitoring of exposure to Cr(VI). Personal measurements were used to study exposure to inhalable and respirable Cr(VI) by personal air sampling. Dermal exposure was studied by taking hand wipe samples. The highest internal exposures were observed in the use of Cr(VI) in electrolytic bath plating. In stainless steel welding the internal Cr exposure was clearly lower when compared to plating activities. We observed a high correlation between chromium urinary levels and air Cr(VI) or dermal total Cr exposure. Urinary chromium showed its value as a first approach for the assessment of total, internal exposure. Correlations between urinary chromium and Cr(VI) in EBC and Cr in RBC were low, probably due to differences in kinetics and indicating that these biomonitoring approaches may not be interchangeable but rather complementary. This study showed that occupational biomonitoring studies can be conducted successfully by multi-national collaboration and provide relevant information to support policy actions aiming to reduce occupational exposure to chemicals.

The role of antioxidants and 25-hydroxyvitamin D during pregnancy in the development of allergic diseases in early school-age children - Polish Mother and Child Cohort Study.

Purpose: Based on the available data, alterations of the antioxidant defense as well as the vitamin status in mothers may affect the prenatal process of lung and immune system development as a pathophysiological background of increased prevalence of allergic diseases. The primary aim of the current study was to assess the associations among cord blood concentrations of zinc (Zn); copper (Cu); selenium (Se); ß-carotene; and vitamin A, E, and D, and the occurrence of atopic dermatitis, food allergy, allergic rhinitis, and asthma in early school-age children. Methods: We evaluated 211 children, 7-9 years old, from the Polish Mother and Child Cohort Study. the women were interviewed during pregnancy to collect demographic and socioeconomic data, and the medical and reproductive history. At delivery, umbilical cord blood plasma was sampled. Seven to nine years after the birth, the child's exposure and health status (including skin-prick test and spirometry for allergy assessment and urine sample for cotinine level) were examined. In the analyses, a multivariable model was applied. Results: Statistically significant relationships were found among Zn; Cu; Se; and vitamin A, E, and D concentrations in cord blood; and the prevalence of food allergy, allergic rhinitis, atopic dermatitis, and asthma in children ages 7-9 years after adjustment for several confounders. Conclusion: We showed an imbalance in the antioxidant defense system in cord blood, which may lead to the occurrence of allergic diseases later in life. The maternal diet may have substantial potential to modify immune tolerance and, consequently, the development of allergic disease in the offspring.Clinical trial NCT01861548, www.clinicaltrials.gov.

Setting up a collaborative European human biological monitoring study on occupational exposure to hexavalent chromium.

The EU human biomonitoring initiative, HBM4EU, aims to co-ordinate and advance human biomonitoring (HBM) across Europe. Within its remit, the project is gathering new, policy relevant, EU-wide data on occupational exposure to relevant priority chemicals and developing new approaches for occupational biomonitoring. In this manuscript, the hexavalent chromium [Cr(VI)] study design is presented as the first example of this HBM4EU approach. This study involves eight European countries and plans to recruit 400 workers performing Cr(VI) surface treatment e.g. electroplating or stainless steel welding activities. The aim is to collect new data on current occupational exposure to Cr(VI) in Europe and to test new methods for Cr biomonitoring, specifically the analysis of Cr(VI) in exhaled breath condensate (EBC) and Cr in red blood cells (RBC) in addition to traditional urinary total Cr analyses. Furthermore, exposure data will be complemented with early biological effects data, including genetic and epigenetic effects. Personal air samples and wipe samples are collected in parallel to help informing the biomonitoring results. We present standard operational procedures (SOPs) to support the harmonized methodologies for the collection of occupational hygiene and HBM samples in different countries.

Micronutrients during pregnancy and child psychomotor development: Opposite effects of Zinc and Selenium.

Studies on the impact of micronutrient levels during different pregnancy periods on child psychomotor functions are limited. The aim of this study was to evaluate the association between maternal plasma concentrations of selected micronutrients, such as: copper (Cu), zinc (Zn), selenium (Se), and child neuropsychological development. The study population consisted of 539 mother-child pairs from Polish Mother and Child Cohort (REPRO_PL). The micronutrient levels were measured in each trimester of pregnancy, at delivery and in the cord blood. Psychomotor development was assessed in children at the age of 1 and 2 years using the Bayley Scales of Infant and Toddler Development. The mean plasma Zn, Cu and Se concentrations in the 1st trimester of pregnancy were 0.91±0.27mg/l, 1.98±0.57mg/l and 48.35±10.54µg/l, respectively. There were no statistically significant associations between Cu levels and any of the analyzed domains of child development. A positive association was observed between Se level in the 1st trimester of pregnancy and child language and motor skills (ß=0.18, p=0.03 and ß=0.25, p=0.005, respectively) at one year of age. Motor score among one-year-old children decreased along with increasing Zn levels in the 1st trimester of pregnancy and in the cord blood (ß=-12.07, p=0.003 and ß=-6.51, p=0.03, respectively). A similar pattern was observed for the association between Zn level in the 1st trimester of pregnancy and language abilities at one year of age (ß=-7.37, p=0.05). Prenatal Zn and Se status was associated with lower and higher child psychomotor abilities, respectively, within the first year of life. Further epidemiological and preclinical studies are necessary to confirm the associations between micronutrient levels and child development as well as to elucidate the underlying mechanisms of their effects.

Urinary cadmium levels in active and retired coal miners.

A meta-analysis, based upon 24 publications, showed a significantly elevated risk for urinary bladder cancer amongst miners. In European underground hard coal mining areas, an increased risk for urinary bladder cancer development was noted among hard coal miners, in particular in three investigations in the greater Dortmund area. However, the cause remains unclear. As cadmium (Cd), which was reported to be a bladder carcinogen in humans and is a constituent of coal, the aim of this study was to determine urinary Cd levels in active and retired hard coal miners and assess whether hard coal miners demonstrated elevated metal levels. In total, 103 retired and 25 active hard coal miners as well as 18 controls without any history of hard coal mining were investigated for urinary Cd levels. Urinary Cd concentrations, in addition to other elements, were analyzed in spot urines by ICP-MS-based multi-element analysis in a Department for Forensic and Clinical Toxicology. Limit of detection (LOD) for Cd was 0.5 µg/L. Reference value for occupationally non-exposed working age population was 0.8 µg/L. In total, 49% of all underground coal miners were exposed to coal dust, 12% to grinded rock, and 39% to both. Urinary Cd levels in retired as well as active coal miners and controls were clearly below the Biological Exposure Index. Urinary Cd concentration is a suitable biomarker to evaluate the metallic load of the body, as the half-life is > than 10 years. The detected urinary Cd levels in retired and active coal miners indicated underground hard coal miners were not apparently exposed to Cd to a occupationally-relevant concentration.

The time-dependent health and biochemical effects in rats exposed to stainless steel welding dust and its soluble form.

Welding processes that generate fumes containing toxic metals, such as hexavalent chromium (Cr(VI)), manganese (Mn), and nickel (Ni), have been implicated in lung injury, inflammation, and lung tumor promotion in animal models. The principal objective of this study was to determine the dynamics of toxic effects of inhalation exposure to morphologically rated welding dust from stainless steel welding and its soluble form in TSE System with a dynamic airflow. We assessed the pulmonary toxicity of welding dust in Wistar rats exposed to 60.0 mg/m3 of respirable-size welding dust (mean diameter 1.17 µm) for 2 weeks (6 h/day, 5 days/week); the aerosols were generated in the nose-only exposure chambers (NOEC). An additional aim included the study of the effect of betaine supplementation on oxidative deterioration in rat lung during 2 weeks of exposure to welding dust or water-soluble dust form. The animals were divided into eight groups (n = 8 per group): control, dust, betaine, betaine + dust, soluble-form dust, soluble-form dust + betaine, saline and saline + betaine groups. Rats were euthanized 1 or 2 weeks after the last exposure for assessment of pulmonary toxicity. Differential cell counts, total protein concentrations and cellular enzyme (lactate dehydrogenase-LDH) activities were determined in bronchoalveolar lavage (BAL) fluid, and corticosterone and thiobarbituric acid reactive substances (TBARS) concentrations were assessed in serum. The increase in polymorphonuclear (PMN) leukocytes in BAL fluid (a cytological index of inflammatory responses of the lung) is believed to reflect pulmonary toxicity of heavy metals. Biomarkers of toxicity assessed in bronchoalveolar fluids indicate that the level of the toxic effect depends mainly on the solubility of studied metal compounds; biomarkers that showed treatment effects included: total cell, neutrophil and lymphocyte counts, total protein concentrations, and cellular enzyme (lactate dehydrogenase) activity. Betaine supplementation at 250 mg/kg/day in all study rats groups attenuated stress indices, and corticosterone and TBARS serum levels, and simultaneously stimulated increase of polymorphonuclear cells in BALF of rats. The study confirmed deleterious effect of transitory metals and particles during experimental inhalation exposure to welding dusts, evidenced in the lungs and brain by increased levels of total protein, higher cellular influx, rise of LDH in BALF, elevated TBARS and increased corticosterone in serum of rats. Our result confirm also the hypothesis about the effect of the welding dusts on the oxidative stress responsible for disturbed systemic homeostasis and impairment of calcium regulation.

Selenium status during pregnancy and child psychomotor development-Polish Mother and Child Cohort study.

BACKGROUND: The studies on the impact of selenium (Se) levels in different pregnancy periods on child psychomotor functions are limited. The aim of this study was to evaluate the impact of prenatal Se on child neurodevelopment. METHODS: The study population consisted of 410 mother-child pairs from Polish Mother and Child Cohort. Se levels were measured in each trimester of pregnancy, at delivery, and in cord blood by graphite furnace atomic absorption spectrometry. Psychomotor development was assessed in children at the age of 1 and 2 y using the Bayley Scales of Infant and Toddler Development. RESULTS: Plasma Se levels decreased through pregnancy (from 48.3 ± 10.6 µg/l in the first trimester to 38.4 ± 11.8 µg/l at delivery; P < 0.05). A statistically significant positive association between Se levels in the first trimester of pregnancy and motor development (ß = 0.2, P = 0.002) at 1 y of age, and language development (ß = 0.2, P = 0.03) at 2 y of age was observed. The positive effect of Se levels on cognitive score at 2 y of age was of borderline significance (ß = 0.2, P = 0.05). CONCLUSION: Prenatal selenium status was associated with child psychomotor abilities within the first years of life. Further epidemiological and preclinical studies are needed to confirm the association and elucidate the underlying mechanisms of these effects.

Matrix metalloproteinases and genetic mouse models in cancer research: a mini-review.

Carcinogenesis is a multistep and also a multifactorial process that involves agents like genetic and environmental factors. Matrix metalloproteinases (MMPs) are major proteolytic enzymes which are involved in cancer cell migration, invasion, and metastasis. Genetic variations in genes encoding the MMPs were shown in human studies to influence cancer risk and phenotypic features of a tumor. The complex role of MMPs seems to be important in the mechanism of carcinogenesis, but it is not well recognized. Rodent studies concentrated particularly on the better understanding of the biological functions of the MMPs and their impact on the pathological process, also through the modification of Mmp genes. This review presents current knowledge and the existing evidence on the importance of selected MMPs in genetic mouse models of cancer and human genetic association studies. Further, this work can be useful for scientists studying the role of the genetic impact of MMPs in carcinogenesis.

Lipid peroxidation and glutathione peroxidase activity relationship in breast cancer depends on functional polymorphism of GPX1.

BACKGROUND: Since targeting oxidative stress markers has been recently recognized as a novel therapeutic target in cancer, it is interesting to investigate whether genetic susceptibility may modify oxidative stress response in cancer. The aim of this study was to elucidate whether genetic polymorphism in the antioxidant enzymes is associated with lipid peroxidation in breast cancer. METHODS: We conducted a study among Polish women, including 136 breast cancer cases and 183 healthy controls. The analysis included genetic polymorphisms in five redox related genes: GPX1 (rs1050450), GPX4 (rs713041), SOD2 (rs4880), SEPP1 (rs3877899) and SEP15 (rs5859), lipid peroxidation, the activities of antioxidant enzymes determined in blood compartments as well as plasma concentration of selenium - an antioxidant trace element involved in cancer. Genotyping was performed using the Real Time PCR. Lipid peroxidation was expressed as plasma concentration of thiobarbituric acid reactive substances (TBARS) and measured with the spectrofluorometric method. Glutathione peroxidase activity was spectrophotometrically determined in erythrocytes (GPx1) and plasma (GPx3) by the use of Paglia and Valentine method. Spectrophotometric methods were employed to measure activity of cytosolic superoxide dismutase (SOD1) in erythrocytes (Beauchamp and Fridovich method) and ceruloplasmin (Cp) in plasma (Sunderman and Nomoto method). Plasma selenium concentration was determined using graphite furnace atomic absorption spectrophotometry. RESULTS: Breast cancer risk was significantly associated with GPX1 rs1050450 (Pro198Leu) polymorphism, showing a protective effect of variant (Leu) allele. As compared to the control subjects, lipid peroxidation and GPx1 activity were significantly higher in the breast cancer cases, whereas ceruloplasmin activity was decreased. After genotype stratification, both GPx1 activity and TBARS concentration were the highest in GPX1 Pro/Pro homozygotes affected by breast cancer. At the same time, there was a significant correlation between the level of lipid peroxidation and GPx1 activity among the cancer subjects possessing GPX1 Pro/Pro genotype (r = 0.3043; p = 0.0089), whereas such a correlation was completely absent in the cases carrying at least one GPX1 Leu allele as well as in the controls (regardless of GPX1 genotype). CONCLUSIONS: GPX1 polymorphism may be an important factor modifying oxidative stress response in breast cancer subjects. Further studies are needed to elucidate its potential clinical significance.

Biological monitoring and the influence of genetic polymorphism of As3MT and GSTs on distribution of urinary arsenic species in occupational exposure workers.

PURPOSE: To examine the differences in urinary arsenic metabolism patterns in men affected by occupational exposure, we performed a study on 149 participants­workers of a copper mill and 52 healthy controls without occupational exposure. To elucidate the role of genetic factors in arsenic (As) metabolism, we studied the associations of six polymorphisms: As3MT Met287Thr (T>C) in exon 9; As3MT A>G in 5'UTR; As3MT C>G in intron 6; As3MT T>G in intron 1; GSTP1 Ile105Val and GSTO2 T>C. METHODS: Air samples were collected using individual samplers during work shift. Urine samples were analyzed for total arsenic and arsenic chemical forms (As(III); As(V), MMA, DMA, AsB) using HPLC-ICP-MS. A specific polymerase chain reaction was done for the amplification of exons and flanking regions of As3MT and GSTs. RESULTS: The geometric mean arsenic concentrations in the air were 27.6 ± 4.9 µg/m(3). A significant correlation (p < 0.05) was observed between arsenic in air and sum of iAs +MMA and iAs. As3MT (rs3740400) GG homozygotes showed significantly (p < 0.05) higher %iAs (21.8 ± 2.0) in urine than GC+CC heterozygotes (16.0 ± 2.1). A strong association between the gene variants and As species in urine was observed for GSTO2 (rs156697) polymorphism. CONCLUSIONS: The findings of the study point out that the concentration of iAs or the sum of iAs + MMA in urine can be a reliable biological indicator of occupational exposure to arsenic. This study demonstrates that As3MT and/or GSTs genotype may influence As metabolism. Nevertheless, further studies investigating genetic polymorphism in occupational conditions are required.

Today's oxidative stress markers.

Oxidative stress represents a situation where there is an imbalance between the reactive oxygen species (ROS) and the availability and the activity of antioxidants. This balance is disturbed by increased generation of free radicals or decreased antioxidant activity. It is very important to develop methods and find appropriate biomarkers that may be used to assess oxidative stress in vivo. It is significant because appropriate measurement of such stress is necessary in identifying its role in lifestyle-related diseases. Previously used markers of oxidative stress, such as thiobarbituric acid reactive substances (TBARS) or malondialdehyde (MDA), are progressively being supplemented by new ones, such as isoprostanes (IsoPs) and their metabolites or allantoin. This paper is focusing on the presentation of new ones, promising markers of oxidative stress (IsoPs, their metabolites and allantoin), taking into account the advantage of those markers over markers used previously.

Rad51C: a novel suppressor gene modulates the risk of head and neck cancer.

We conducted a case-control study to investigate the possible association between the head and neck cancer (HNC) and genetic variability of Rad51C tumor suppressor gene. Eight polymorphic sites spanning over non-coding regions of Rad51C promoter, exon 1 and intron 1 were genotyped in 81 HNC cases and 156 healthy controls using the real-time PCR technique. One investigated site turned out to be not polymorphic, while among the remaining seven sites a significant HNC risk-increasing effect was found for rs16943176 (c.-118G>A), rs12946397 (c.-26C>T) and rs17222691 (c.145+947C>T) on both allelic (OR=1.8; p<0.05) and genotypic (OR=2.0; p<0.05) level. Furthermore, our data seem to provide marginal evidence, that this effect might possibly be confined to women only (OR=2.8; p=0.05 for allelic and OR=3.7; p=0.05 for genotypic comparisons). These SNPs were found to co-segregate together forming two distinct, HNC risk-modulating haplotypes. The genetic variability of Rad51C might thus be of relevance with respect to HNC risk.

The role of zinc, copper, plasma glutathione peroxidase enzyme, and vitamins in the development of allergic diseases in early childhood: The Polish mother and child cohort study.

It has been hypothesized that the increase in allergic disorders may, in part, be a consequence of changing diet. The primary aim of this study was to assess the associations between occurrence of atopic dermatitis; food allergy; the incidence of wheeze inhaled glucocorticosteroid use in children during the 1st year of life; and cord blood concentrations of copper, zinc, vitamins (A and E), and glutathione peroxidase activity. We evaluated 240 1-year-old children from the Polish Mother and Child Cohort Study. Women were interviewed during pregnancy to collect demographic and socioeconomic data and medical and reproductive history. Exposure to tobacco constituents was assessed based on questionnaire data. At delivery, umbilical cord blood plasma was sampled. One year after the birth, the child's exposure and health status were examined. In the analyses a multivariable model was used. Higher zinc and copper concentrations in cord blood were associated with increased likelihood of wheezing in 1-year-old children. This effect was seen only among children exposed to tobacco smoke at home. We also showed significantly lower activity of glutathione peroxidase enzyme 3 in umbilical cord blood plasma of children with atopic dermatitis during the 1st year of life. There were no significant associations between vitamin A and E concentrations in plasma and children's health. We showed imbalance in the antioxidant defense system in cord blood, which may lead to development of atopic dermatitis or wheezing in infancy. The association between maternal nutrient status during pregnancy and child's health is complex and interacts with other environmental factors such as tobacco exposure. This study was a part of the clinical trial NCT01861548 registered at ClinicalTrials.gov.

Functional polymorphisms in the matrix metalloproteinase genes and their association with bladder cancer risk and recurrence: a mini-review.

Molecular pathogenesis of muscle invasive bladder cancer and non-muscle invasive bladder cancer is incompletely elucidated. It is believed that matrix metalloproteinases, which are involved in the processes of uncontrolled extracellular matrix substrates degradation and participate in modulating the activity of a variety of non-matrix proteins, can contribute to carcinogenesis. Polymorphisms in the MMP genes associated with unique genomic changes in bladder cancer patients are still being investigated to discover direct links with pathophysiological mechanisms. Because of the functional polymorphisms in the MMP genes, which have a proven or likely effect on their protein expression, they could possibly affect the tumor process. The current mini-review synthesizes findings regarding the association of genetic polymorphisms in the MMP genes with bladder cancer risk and recurrence in patients. We discuss the current views on the feasibility of genetic polymorphisms in the MMP1, 2, 3, 7, 8, 9 and 12 genes as a risk, and prognostic markers for patients with bladder cancer. The majority of the research described in the present mini-review proves that the genetic polymorphism in the MMP1 (rs1799750) is the most widely studied, and suggests that the rare genotype, 2G2G, of that gene might show increased susceptibility for bladder cancer, especially among smokers. However, existing statistically significant associations between the genetic polymorphisms in the MMP genes and bladder cancer risk have not been clearly shown, and further studies are necessary in order to positively confirm them or dispel potential false hopes.

Health effects and arsenic species in urine of copper smelter workers.

The aim of this study was to compare indices of exposure in workers employed at different work posts in a copper smelter plant using neurophysiological tests and to evaluate the relationship between urinary arsenic species with the aid of sensitive respiratory and renal biomarkers. We have attempted to elucidate the impact of different arsenic speciation forms on the observed health effects. We focused on the workers (n = 45) exposed to atmospheres containing specific diverse mixtures of metals (such as those occurring in Departments of Furnaces, Lead and Electrolysis) compared to controls (n = 16). Subjective symptoms from the central (CNS) and the peripheral (PNS) nervous system were recorded and visual evoked potential (VEP), electroneurography (ENeG) and electroencephalography (EEG) curves were analysed. Levels of airborne lead (PbA), zinc (ZnA) and copper (CuA) and Pb levels in blood (PbB) and the relationships between airborne As concentrations (AsA) and the urinary levels of the inorganic (iAs); As(+3), As(+5) and the organic; methylarsonate (MMA(V)), dimethylarsinate (DMA(V)) and arsenobetaine (AsB) arsenic species were determined by Inductively Coupled Plasma Mass Spectrometry (ICP-MS). Effects of exposure were expressed in terms of biomarker levels: Clara cell protein (CC16) in serum as early pulmonary biomarker and ß2-microglobulin (ß2M) in urine and serum, retinol binding protein (RBP) as renal markers, measured by sensitive latex-immunoassay (LIA). Abnormal results of neurophysiological tests, VEP, EEG and ENeG showed dominant subclinical effects in CNS and PNS of workers from Departments of Lead and Furnace. In group of smelters from Departments of Furnace exposed to arsenic above current TLV, excreted arsenic species As(+3) and As(+5) seemed to reduce the level of Clara cell protein (CC16), thereby reducing anti-inflammatory potential of the lungs and increasing the levels of renal biomarker (ß2M) and copper in urine (CuU). The study confirmed deleterious arsenic effects to the kidney by increased levels of low-molecular weight protein in urine and the extent of the renal copper accumulation/excretion. The results of our work also support the usefulness of application of the sensitive neurophysiologic tests, such as VEP, EEG and ENeG, for the detection of early subclinical effects of the exposure of the nervous system in copper smelters.

Distribution of molybdenum in soft tissues and blood of rats after intratracheal instillation of molybdenum(IV) sulfide nano- and microparticles.

There is still little literature data on the toxicity and safety of the commonly used molybdenum (Mo) disulfide which is present in the working as well as living environments. Thus, an experiment was carried out involving rats, with single and repeated intratracheal exposure (in the latter case, 7 administrations at 2-week intervals with the analysis performed after 90 days) to lower (1.5 mg Mo kg-1 b.w.) and higher (5 mg Mo kg-1 b.w.) doses of molybdenum(IV) sulfide nanoparticles (MoS2-NPs) and microparticles (MoS2-MPs). The analysis of Mo concentrations in the tail and heart blood as well as in soft tissues (lung, liver, spleen, brain), after mineralization and bioimaging, was meant to facilitate an assessment of its accumulation and potential effects on the body following short- and long-term exposure. The multi-compartment model with an exponential curve of Mo concentration over time with different half-lives for the distribution and elimination phases of MoS2-MPs and MoS2-NPs was observed. After 24 h of exposure, a slight increase in Mo concentration in blood was observed. Next, Mo concentration indicated a decrease in blood concentration from 24 h to day 14 (the Mo concentration before the second administration), below the pre-exposure concentration. The next phase was linear, less abrupt and practically flat, but with an increasing trend towards the end of the experiment. Significantly higher Mo concentrations in MoS2-NPs and MoS2-MPs was found in the lungs of repeatedly exposed rats compared to those exposed to a single dose. The analysis of Mo content in the liver and the spleen tissue showed a slightly higher concentration for MoS2-NPs compared to MoS2-MPs. The results for the brain were below the calculated detection limit. Results were consistent with results obtained by bioimaging technique.

Urinary concentrations of phthalate/DINCH metabolites and body mass index among European children and adolescents in the HBM4EU Aligned Studies: A cross-sectional multi-country study.

BACKGROUND: Phthalates are ubiquitous in the environment. Despite short half-lives, chronic exposure can lead to endocrine disruption. The safety of phthalate substitute DINCH is unclear. OBJECTIVE: To evaluate associations between urinary concentrations of phthalate/DINCH metabolites and body mass index (BMI) z-score among children and adolescents. METHOD: We used Human Biomonitoring for Europe Aligned Studies data from 2876 children (12 studies, 6-12 years, 2014-2021) and 2499 adolescents (10 studies, 12-18 years, 2014-2021) with up to 14 phthalate/DINCH urinary metabolites. We used multilevel linear regression to assess associations between phthalate/DINCH concentrations and BMI z-scores, testing effect modification by sex. In a subset, Bayesian kernel machine regression (BKMR) and quantile-based g-computation assessed important predictors and mixture effects. RESULTS: In children, we found few associations in single pollutant models and no interactions by sex (p-interaction > 0.1). BKMR detected no relevant exposures (posterior inclusion probabilities, PIPs < 0.25), nor joint mixture effect. In adolescent single pollutant analysis, mono-ethyl phthalate (MEP) concentrations were associated with higher BMI z-score in males (ß = 0.08, 95 % CI: 0.001,0.15, per interquartile range increase in ln-transformed concentrations, p-interaction = 0.06). Conversely, mono-isobutyl phthalate (MiBP) was associated with a lower BMI z-score in both sexes (ß = -0.13, 95 % CI: -0.19, -0.07, p-interaction = 0.74), as was sum of di(2-ethylhexyl) phthalate (∑DEHP) metabolites in females only (ß = -0.08, 95 % CI: -0.14, -0.02, p-interaction = 0.01). In BKMR, higher BMI z-scores were predicted by MEP (PIP=0.90) and MBzP (PIP=0.84) in males. Lower BMI z-scores were predicted by MiBP (PIP=0.999), OH-MIDP (PIP=0.88) and OH-MINCH (PIP=0.72) in both sexes, less robustly by DEHP (PIP=0.61) in females. In quantile g-computation, the overall mixture effect was null for males, and trended negative for females (ß = -0.11, 95 % CI: -0.25, 0.03, per joint exposure quantile). CONCLUSION: In this large Europe-wide study, we found age/sex-specific differences between phthalate metabolites and BMI z-score, stronger in adolescents. Longitudinal studies with repeated phthalate measurements are needed.

Genetic polymorphisms in matrix metalloproteinases (MMPs) and tissue inhibitors of MPs (TIMPs), and bladder cancer susceptibility.

OBJECTIVES: To elucidate genetic polymorphisms of the matrix metalloproteinases (MMPs) MMP1 (rs1799750), MMP2 (rs243865), MMP9 (rs3918242), MMP12 (rs2276109) and tissue inhibitors of MMPs (TIMPs) TIMP1 (rs2070584) and TIMP3 (rs9619311) genes that may be involved in susceptibility to bladder cancer (BC). PATIENTS AND METHODS: We enrolled 241 patients with BC and 199 controls. Genomic DNA samples were extracted from peripheral blood and polymorphisms were analysed by high-resolution melting analysis and by real-time polymerase chain reaction using TaqMan fluorescent probes. RESULTS: Of the six evaluated polymorphisms of MMPs and TIMPs, only one was found to be associated with BC risk. There was a significant difference for MMP1 (rs1799750) 2G/1G+1G/1G genotype (odds ratio [OR] 0.62, 95% confidence interval [CI] 0.39-0.98; P = 0.042). Additionally, there was a joint effect of this genotype on BC risk among 'ever smokers' (OR 0.51, 95% CI 0.28-0.89; P = 0.019), but not in 'never smokers'. The combined genotype MMP2 -1306C/T (rs243865) allele T with MMP9 -1562C/T (rs3918242) allele T was found to increase BC risk (OR 2.00, 95% CI 1.10-3.62; P = 0.022). CONCLUSIONS: Our results suggest that genetic variations in five polymorphisms of MMPs and TIMPs are not associated with a high risk of BC. Only MMP1 polymorphism may be related to the risk of BC, notably in 'ever smokers'. Our study suggests that the effects of polymorphisms of MMPs and TIMPs on BC risk deserve further investigation.

Relationship between intensity of night shift work and antioxidant status in blood of nurses.

PURPOSE: Light-at-night exposure can disrupt the human circadian rhythm via clock gene expressions. The circadian rhythm influences antioxidant enzymes' activity and cellular mRNA levels of these enzymes. The employees working based on a shift system adjust to the changes occurring both on the cell level and on the level of the whole organism. Therefore, a question should be answered whether shift work disturbs oxidant-antioxidant balance and/or generates oxidative stress. METHODS: A cross-sectional study was conducted among nurses selected from the Local Registry of the Chamber of Nurses and Midwives in Lodz: 359 nurses worked daily only and 349 working rotating night shifts. These two groups differed significantly in respect of age (p < 0.0001), menopausal status (p < 0.0001), and current smoking habit (p = 0.02). The average total work duration was significantly shorter (12.4 years) in nurses working currently rotating night shifts who worked significantly longer on night shifts than day-workers (26.6 years). RESULTS: We found statistically significant higher red blood cell glutathione peroxidase in nurses working on night shifts (21.0 ± 4.6 vs. 20.0 ± 5.0 U/g Hb, p < 0.009) after adjusting for age, oral contraceptive hormone use, smoking, and drinking alcohol during last 24 h. Statistically significant lower vitamin A and E levels were found in the premenopausal women working in rotating system (0.690 ± 0.238 vs. 0.786 ± 0.262 µg/ml, p < 0.0001 for vitamin A and 10.93 ± 4.15 vs. 12.78 ± 4.75 µg/ml, p < 0.0001 for vitamin E). The marker of lipid peroxidation (TBARS concentration) was significantly lower in the premenopausal nurses than postmenopausal ones working day shifts only (2.06 ± 0.76 vs. 2.21 ± 0.80 nmol/ml, p < 0.038). We observed that erythrocyte GSH-Px activity rose statistically significant in nurses working more night shifts per month (p < 0.01). CONCLUSIONS: The results quoted above seem to support the existence of an association between light-at-night exposure and blood glutathione peroxidase activity in female shift workers. Nevertheless, in order to explain the mechanisms of this association, we need more studies.