Occupational exposure to organic solvents and risk of bladder cancer.

BACKGROUND: Bladder cancer has been linked to several occupations that involve the use of solvents, including those used in the dry-cleaning industry. OBJECTIVES: We evaluated exposure to solvents and risk of bladder cancer in 1182 incident cases and 1408 controls from a population-based study. METHODS: Exposure to solvents was quantitatively assessed using a job-exposure matrix (CANJEM). Exposure to benzene, toluene and xylene often co-occur. Therefore, we created two additional sets of metrics for combined benzene, toluene and xylene (BTX) exposure: (1) CANJEM-based BTX metrics and (2) hybrid BTX metrics, using an approach that integrates the CANJEM-based BTX metrics together with lifetime occupational histories and exposure-oriented modules that captured within-job, respondent-specific details about tasks and chemicals. Adjusted odds ratios (ORs) and 95% confidence intervals (95% CI) were estimated using logistic regression. RESULTS: Bladder cancer risks were increased among those ever exposed to benzene (OR = 1.63, 95% CI: 1.14-2.32), toluene (OR = 1.60, 95% CI: 1.06-2.43), and xylene (OR = 1.67, 95% CI: 1.13-2.48) individually. We further observed a statistically significant exposure-response relationship for cumulative BTX exposure, with a stronger association using the hybrid BTX metrics (ORQ1vsUnexposed = 1.26, 95% CI: 0.83-1.90; ORQ2vsUnexposed = 1.52, 95% CI: 1.00-2.31; ORQ3vsUnexposed = 1.88, 95% CI: 1.24-2.85; and ORQ4vsUnexposed = 2.23, 95% CI: 1.35-3.69) (p-trend=0.001) than using CANJEM-based metrics (p-trend=0.02). IMPACT: There is limited evidence about the role of exposure to specific organic solvents, alone or in combination on the risk of developing bladder cancer. In this study, workers with increasing exposure to benzene, toluene, and xylene as a group (BTX) had a statistically significant exposure-response relationship with bladder cancer. Future evaluation of the carcinogenicity of BTX and other organic solvents, particularly concurrent exposure, on bladder cancer development is needed.

The Associations Between Workplace Noise, Ototoxic Chemicals, and Tinnitus.

OBJECTIVE: To investigate the occupational risk factors associated with tinnitus in the Australian working population. DESIGN: The research was conducted using data collected from the Australian Workplace Exposure Survey-Hearing, a national cross-sectional study of 4970 workers conducted in 2016 to 2017. Workers were asked if they experienced tinnitus and if they answered affirmatively, they were asked about the frequency and length of the presentations. Based on their answers, each worker was categorized as having no tinnitus or any tinnitus, with an additional group of workers with any tinnitus subcategorized as having constant tinnitus. Exposure assessment was conducted using an automated expert assessment method. Exposures included daily noise (L Aeq,8h ), hand-arm vibration (A(8)), impulse noise, smoking status, styrene, trichloroethylene, toluene, n-hexane, p-xylene, ethylbenzene, lead, and carbon monoxide. Univariate and multivariate logistic regression models were used to examine the associations between workplace exposures and tinnitus. RESULTS: Workers with an estimated noise exposure above the workplace limit (L Aeq,8h > 85 dBA) had 1.73 (95% confidence interval [CI]: 1.42 to 2.11) increased odds of any tinnitus and 2.15 (95% CI: 1.60 to 2.89) odds of constant tinnitus. The odds of workers having any tinnitus increased with increasing noise exposure levels in a dose-response relationship that strengthened when considering only those with constant tinnitus. In the fully adjusted model, statistically significant associations were seen for lead exposure with both any and constant tinnitus, toluene exposure with constant tinnitus, and carbon monoxide exposure with any tinnitus. CONCLUSIONS: These results suggest that, in addition to workplace noise, occupational exposures to lead, toluene, and carbon monoxide are associated with tinnitus.

Molecular evidence of the amelioration of toluene induced encephalopathy by human breast milk mesenchymal stem cells.

Toluene was widely used volatile organic compound that accumulates in tissues with high lipid content. Stem cells have been proposed as an increasingly attractive approach for repair of damaged nervous system, we aimed to evaluate the ability of breast milk mesenchymal stem cells (MSc) to ameliorate toluene-induced encephalopathy. Sixty adult male albino rats were assigned to 3 groups, control, toluene, and toluene/breast milk-MSc. Neurological assessment was evaluated as well as serum levels of glial fibrillary acidic protein (GFAP), tumor necrosis factor-alpha (TNF-α), nerve growth factor (NGF), vascular endothelial growth factor (VEGF), tissue dopamine and oxidative markers. Gene expression of peroxisome Proliferator-Activated Receptor-Gamma (PPAR-É£), nuclear factor-kappaB (NF-kB), and interleukin-6 (IL-6) were evaluated. Moreover, histological and immunohistochemical investigation were done. Results revealed that toluene caused cerebral injury, as evidenced by a significant increase in serum GFAP, TNF-α, malondialdehyde (MDA) and nitric oxide (NO), a significant decrease in serum NGF, tissue dopamine and oxidative markers, besides, a non-significant change in VEGF. Toluene also caused changes in normal cerebral structure and cellular degeneration, including a significant decrease in the total number of neurons and thickness of frontal cortex. Meninges showing signs of inflammation with inflammatory cell infiltration and exudation, a significant decrease in MBP immunoreactivity, and increase in the percent of high motility group box protein-1 (HMGB1) positive cells. PPAR- É£, NF-kB, and IL-6 gene expression were all considerably elevated by toluene. These changes were greatly improved by breast milk MSc. Therefore, we conclude that breast milk MSc can attenuate toluene-induced encephalopathy.

Ambient BTEX exposure and mid-pregnancy inflammatory biomarkers in pregnant African American women.

Air pollution is associated with preterm birth (PTB), potentially via inflammation. We recently showed the mixture benzene, toluene, ethylbenzene, and xylene (BTEX) is associated with PTB. We examined if ambient BTEX exposure is associated with mid-pregnancy inflammation in a sample of 140 African-American women residing in Detroit, Michigan. The Geospatial Determinants of Health Outcomes Consortium study collected outdoor air pollution measurements in Detroit; these data were coupled with Michigan Air Sampling Network measurements to develop monthly BTEX concentration estimates at a spatial density of 300 m2. First trimester and mid-pregnancy BTEX exposure estimates were assigned to maternal address. Mid-pregnancy (mean 21.3 ± 3.7 weeks gestation) inflammatory biomarkers (high-sensitivity C-reactive protein, interleukin [IL]-6, IL-10, IL-1ß, and tumor necrosis factor-α) were measured with enzyme immunoassays. After covariate adjustment, for every 1-unit increase in first trimester BTEX, there was an expected mean increase in log-transformed IL-1ß of 0.05 ± 0.02 units (P = 0.014) and an expected mean increase in log-transformed tumor necrosis factor-α of 0.07 ± 0.02 units (P = 0.006). Similarly, for every 1-unit increase in mid-pregnancy BTEX, there was a mean increase in log IL-1ß of 0.06 ± 0.03 units (P = 0.027). There was no association of either first trimester or mid-pregnancy BTEX with high-sensitivity C-reactive protein, IL-10, or IL-6 (all P > 0.05). Ambient BTEX exposure is associated with inflammation in mid-pregnancy in African-American women. Future studies examining if inflammation mediates associations between BTEX exposure and PTB are needed.

Intoxicación por tolueno / Toluene poisoning

Resumen El ser humano está inmerso en un entorno donde inhala, ingiere o absorbe muchas sustancias químicas, de las cuales toman relevancia las exposiciones en los lugares de trabajo y las que causan la muerte en la práctica médico forense. El tolueno es un inhibidor neuronal asociado con daño progresivo del sistema nervioso central y periférico, su toxicidad puede ocurrir por inhalación involuntaria o deliberada y puede llevar incluso a la muerte. Se realizó una revisión bibliográfica en diferentes bases de datos, de los artículos publicados referentes al tema de los últimos ocho años, con el objetivo de revisar las características del químico, el metabolismo, las intoxicaciones agudas y las crónicas, así como sus implicaciones letales. Se concluye que para mejorar la pericia médico legal, al valorar casos de intoxicacion por tolueno se deben de contemplar los criterios de causalidad en los casos de enfermedad laboral y en sospecha de causa de muerte es fundamentantal el resultado toxicológico ante la ausencia de hallazgos específicos en la autopsia.

Abstract The human being is immersed in an environment where he inhales, ingests or absorbs many chemical substances, in forensic medical practice the exposures in the workplace and those that cause death take on relevance. Toluene is a neuronal inhibitor associated with progressive damage of the central and peripheral nervous system, its toxicity can occur by involuntary or deliberate inhalation and can even lead to death. A bibliographic review was carried out in different databases, of the published articles referring to the subject of the last eight years, with the objective of reviewing the characteristics of the chemical, the metabolism, both acute and chronic poisoning and its lethal implications. It is concluded that to improve the legal medical expertise when assessing cases of toluene poisoning, causality criteria must be considered in cases of occupational disease and in suspected cases of death the toxicology result is fundamental in the absence of specific findings in the autopsy.

Hypermethylation in Gene Promoters Are Induced by Chronic Exposure to Benzene, Toluene, Ethylbenzene and Xylenes.

BACKGROUND AND OBJECTIVE: Gas station attendants are occupationally exposed to benzene, toluene, ethylbenzene and xylene (BTEX) compounds and thus more susceptible to the biological effects of this mixture present in gasoline, especially due to the carcinogenicity of benzene. Furthermore, the harmful effects of BTEX exposure may be potentiated by genetic and epigenetic inactivation of critical genes. The objective was to evaluate such gene-BTEX interactions accessing the promoter methylation status of p14ARF, p16INK4A and GSTP1 in peripheral blood leukocyte samples. MATERIALS AND METHODS: The 59 exposed and 68 unexposed participants from Rio de Janeiro, Brazil, were included. The promoter methylation status was accessed by methylation-specific PCR (MSP) and GSTP1 Ile105Val polymorphism was investigated by PCR-restriction fragment length polymorphism (PCR-RFLP) technique. RESULTS: Both p14ARF and p16INK4A were significantly hypermethylated in exposed subjects compared to unexposed (p = 0.004 and p<0.001, respectively). Additionally, p16INK4A hypermethylation in the exposed group was correlated with chromosomal abnormalities (CAs) (p = 0.018), thus highlighting the influence of the gene-environment interactions on genome instability. Noteworthy, p16INK4A methylation was significantly associated with miscarriage among female attendants (p = 0.047), in which those who reported miscarriage exhibited hypermethylation in at least 2 of the 3 genes analyzed. The GSTP1 heterozygote genotype, which could affect the metabolism of benzene detoxification, was found in both groups but was more frequent in those occupationally exposed. No significant association was observed between GSTP1 genotypes and methylation status. CONCLUSION: Together, these findings indicate that gas station attendants with the aforementioned epigenetic and genetic profiles may be at greater risk of occupational BTEX exposure-induced genome instability, which could require concerted efforts to establish more preventive actions and constant biomonitoring in gas station attendants.

Maternal exposure to benzene and toluene and preterm birth. A longitudinal study

ABSTRACT BACKGROUND: Exposure to air pollutants has several effects on human health, including during pregnancy. OBJECTIVE: To identify whether exposure to benzene and toluene among pregnant women contributes to preterm delivery. DESIGN AND SETTING: Longitudinal study using data on newborns from mothers living in São José dos Campos (SP) in 2016, who had been exposed to benzene and toluene. METHODS: A logistic regression model with three hierarchical levels was constructed using maternal variables relating to newborns, and using benzene and toluene concentrations in quartiles. Occurrences of cesarean births, twins or malformations were excluded. Maternal exposure windows of 5, 10, 15, 30, 60 and 90 days prior to delivery were considered. RESULTS: Out of the 9,562 live births, 3,671 newborns were included and 343 newborns were born at less than 37 weeks of gestation (9.3%). The average birth weight was 3,167.2 g. Exposure to benzene and toluene was significantly associated (P = 0.04) with preterm delivery in the five-day window. There was no association in any of the other exposure windows. CONCLUSIONS: It was possible to identify that maternal exposure to benzene and toluene has an acute effect on preterm delivery.

[Analysis of the cardiovascular effects on workers expose to occupational benzene-toluene-xylene and noise in a painting workshop of an automobile company].

Objective: To learn about the cardiovascular health effects of workers expose to benzene-toluene-xylene and noise in painting workshop of automobile manufacturing enterprises, and to provide intervention measures and strategies for the health of workers. Methods: The effects of noise exposure, benzene-toluene-xylene exposure and combined exposure on workers' blood pressure and electrocardiogram were analyzed through epidemiological investigation, workplace monitoring and occupational health examination in several automobile enterprises which had carried out occupational hazard factors monitoring and occupational health examination in our hospital from April to October 2017. Results: There were differences in age, sex, working years, smoking, drinking and physical exercise among workers in different exposure groups (P<0.05) . The systolic blood pressure level of workers in benzene-toluene-xylene exposure group and combined exposure group was significantly different comparing with control group (P< 0.05) , After the factors of age and working years were adjusted. The abnormity rate of electrocardiogram in workers were not statistically significant in all groups (P>0.05) . Conclusion: The benzene-toluene-xylene exposure and noise combined with benzene-toluene-xylene exposure in painting workshop of automobile manufacturing enterprises has positive influence on the systolic blood pressure of workers. Regular physical examination and health intervention measures should be strengthened to improve health.

A general dose-response relationship for chronic chemical and other health stressors and mixtures based on an emergent illness severity model.

Current efforts to assess human health response to chemicals based on high-throughput in vitro assay data on intra-cellular changes have been hindered for some illnesses by lack of information on higher-level extracellular, inter-organ, and organism-level interactions. However, a dose-response function (DRF), informed by various levels of information including apical health response, can represent a template for convergent top-down, bottom-up analysis. In this paper, a general DRF for chronic chemical and other health stressors and mixtures is derived based on a general first-order model previously derived and demonstrated for illness progression. The derivation accounts for essential autocorrelation among initiating event magnitudes along a toxicological mode of action, typical of complex processes in general, and reveals the inverse relationship between the minimum illness-inducing dose, and the illness severity per unit dose (both variable across a population). The resulting emergent DRF is theoretically scale-inclusive and amenable to low-dose extrapolation. The two-parameter single-toxicant version can be monotonic or sigmoidal, and is demonstrated preferable to traditional models (multistage, lognormal, generalized linear) for the published cancer and non-cancer datasets analyzed: chloroform (induced liver necrosis in female mice); bromate (induced dysplastic focia in male inbred rats); and 2-acetylaminofluorene (induced liver neoplasms and bladder carcinomas in 20,328 female mice). Common- and dissimilar-mode mixture models are demonstrated versus orthogonal data on toluene/benzene mixtures (mortality in Japanese medaka, Oryzias latipes, following embryonic exposure). Findings support previous empirical demonstration, and also reveal how a chemical with a typical monotonically-increasing DRF can display a J-shaped DRF when a second, antagonistic common-mode chemical is present. Overall, the general DRF derived here based on an autocorrelated first-order model appears to provide both a strong theoretical/biological basis for, as well as an accurate statistical description of, a diverse, albeit small, sample of observed dose-response data. The further generalizability of this conclusion can be tested in future analyses comparing with traditional modeling approaches across a broader range of datasets.

Association of organic solvents and occupational noise on hearing loss and tinnitus among adults in the U.S., 1999-2004.

PURPOSE: Exposure to organic solvents and noise may be causal agents in the development of hearing loss and tinnitus. The objectives of the present study were to examine the association of organic solvents with hearing loss and tinnitus and to assess the interaction of organic solvent and occupational noise exposure on hearing loss and tinnitus. METHODS: A secondary data analysis of data from the National Health and Nutrition Examination Survey and Occupational Information Network (O*NET) among a study population ranging from 1085 to 2471 study participants from 1999 to 2004. Multiple multivariate logistic regression models were used to assess the associations of individual organic solvent exposures as measured by blood biomarkers (1,4-dichlorobenzene, benzene, ethylbenzene, styrene, toluene, o-xylene, and m-/p-xylene) with self-reported hearing loss, audiometrically assessed hearing loss, and self-reported tinnitus. Models were adjusted for age, gender, race/ethnicity, diabetes, non-occupational noise exposure, smoking, and income. Organic solvents found to be statistically significantly associated with the outcome after adjusting for covariates were tested for interaction with occupational noise exposure. RESULTS: Solvent exposure was not statistically significantly associated with self-reported tinnitus. Benzene (OR 1.43, 95% CI 1.15-1.78), ethylbenzene (OR 1.24, 95% CI 1.02-1.50), and toluene (OR 1.27, 95% CI 1.06-1.52) concentrations were statistically significantly associated with increased adjusted odds of high-frequency hearing loss. No statistically significant interaction was observed between these solvents and occupational noise on high-frequency hearing loss. CONCLUSIONS: We found no evidence of an association between organic solvents and tinnitus; however, there was evidence of an association between organic solvent exposure and prevalence of high-frequency hearing loss.

Maternal exposure to benzene and toluene and preterm birth. A longitudinal study.

BACKGROUND: Exposure to air pollutants has several effects on human health, including during pregnancy. OBJECTIVE: To identify whether exposure to benzene and toluene among pregnant women contributes to preterm delivery. DESIGN AND SETTING: Longitudinal study using data on newborns from mothers living in São José dos Campos (SP) in 2016, who had been exposed to benzene and toluene. METHODS: A logistic regression model with three hierarchical levels was constructed using maternal variables relating to newborns, and using benzene and toluene concentrations in quartiles. Occurrences of cesarean births, twins or malformations were excluded. Maternal exposure windows of 5, 10, 15, 30, 60 and 90 days prior to delivery were considered. RESULTS: Out of the 9,562 live births, 3,671 newborns were included and 343 newborns were born at less than 37 weeks of gestation (9.3%). The average birth weight was 3,167.2 g. Exposure to benzene and toluene was significantly associated (P = 0.04) with preterm delivery in the five-day window. There was no association in any of the other exposure windows. CONCLUSIONS: It was possible to identify that maternal exposure to benzene and toluene has an acute effect on preterm delivery.

Effects of ambient benzene and toluene on emergency COPD hospitalizations: A time series study in Hong Kong.

BACKGROUND: Although numerous studies have demonstrated that the criteria air pollutants increased the risk of exacerbation of chronic obstructive pulmonary disease (COPD), few have explored the effects of ambient benzene and toluene on COPD. OBJECTIVE: This study aimed to evaluate the short-term effects of ambient benzene and toluene on emergency COPD (eCOPD) hospitalizations. METHODS: We obtained daily mean and maximum concentrations of benzene and toluene during April 1, 2011 - December 31, 2014 from the Hong Kong Environmental Protection Department, and daily counts of eCOPD hospitalizations from the Hospital Authority. Generalized additive distributed lag models were used to estimate the percentage excess risk (ER%) of eCOPD hospitalizations per interquartile range (IQR) increase in ambient benzene and toluene. RESULTS: The ER% estimates of eCOPD hospitalizations post cumulative exposure of up to two days were 2.62% (95%CI: 0.17% to 5.13%) and 1.42% (0.16% to 2.69%), for per IQR increase of daily mean benzene (1.4µg/m3) and toluene (4.6µg/m3), respectively. People below the age of 65 had a significantly higher risk of eCOPD hospitalizations associated with daily maximum toluene than the elderly. CONCLUSIONS: Ambient benzene and toluene might be environmental stressors for acute exacerbations of COPD in the Hong Kong population.

Biological monitoring of low level exposure to benzene in an oil refinery: Effect of modulating factors.

The aim of the study was to investigate the effect of various factors that modulate the metabolism of benzene, including smoking habits, metabolic genotype of GST and co-exposure to toluene, on the levels of three biomarkers, i.e. urinary benzene (UB), S-phenylmercapturic acid (SPMA) and t,t-muconic acid (t,t-MA), in 146 refinery workers exposed to low levels of air benzene (AB) in the range <1.5-529.2 µg/m3 (mean value 32.6 µg/m3). The study confirmed the validity of SPMA as a good biomarker of benzene exposure even at low levels of exposure. It was also confirmed that cigarette smoking is the main confounding factor when assessing biological monitoring data of occupational exposure to AB. Our data indicate that the GSTT1, but not the GSTM1 genotype, significantly increases the urinary levels of SPMA, even at low levels of exposure. It is not known, though, whether subjects with a GSTT1 "null" genotype may be more susceptible to the effects of benzene. Finally, environmental toluene appears to inhibit the metabolism of benzene to SPMA even at low concentrations, also resulting in an underestimation by SPMA levels of the actual exposure of workers to benzene.

Occupational exposure to benzene, toluene, xylene and styrene and risk of prostate cancer in a population-based study.

OBJECTIVES: While several monocyclic aromatic hydrocarbons are classified as definite or possible carcinogens to humans, little data exist on their role in prostate cancer (PCa). We examined occupational exposure to benzene, toluene, xylene (BTX) and styrene and PCa risk in a population-based case-control study in Montreal, Canada. METHODS: Cases aged ≤75 years diagnosed with PCa in 2005-2009 (n=1920) and population controls frequency-matched on age (n=1989) provided detailed work histories. Experts evaluated the certainty, frequency and concentration of exposure to monocyclic aromatic hydrocarbons in each job lasting ≥2 years. Logistic regression estimated OR and 95% CIs for PCa risk, adjusting for potential confounders. RESULTS: Exposures to BTX were highly intercorrelated, except for durations of exposure at substantial levels. Ever exposure to any BTX was associated with overall PCa (OR 1.27, 95% CI 1.05 to 1.53), while the OR for styrene was 1.19. However, increases in risk were largely confined to low-grade tumours, with ORs of 1.33 (95%CI 1.08 to 1.64) and 1.41 (95% CI 0.85 to 2.31) for ever exposure to any BTX and styrene, respectively, and a duration response pattern for any BTX. Risks for low-grade tumours were elevated among men exposed ≥25 years at substantial levels of benzene (OR 2.32) and styrene (OR 2.44). Some cumulative exposure categories showed increased risks but without clear trends. CONCLUSION: Exposure to any BTX was associated with higher risks of overall PCa. Prolonged exposures at the substantial level to benzene and styrene increased risks of low-grade tumours. These novel findings were independent from PCa screening.

Effect of chronic toluene exposure on heart rhythm parameters.

BACKGROUND: Toluene is used extensively in various industrial processes, and an increasing number of workers are getting exposed to its vapor. Cardiac abnormalities that have been reported in association with toluene exposure (in toxic doses) are atrioventricular conduction abnormalities, sinus bradycardia, ventricular tachycardia, recurrent myocardial infarction, dilated cardiomyopathy, and coronary vasospasm. HYPOTHESIS: We aimed to investigate the effects of chronic toluene exposure on cardiac rhythm. METHODS: In this study, 40 workers in the polishing industry with more than 3 months of exposure to a mixture of organic solvents including toluene and 38 control subjects working in other fields who were matched by age, sex, smoking, habits, and living accommodation were investigated. Twelve-lead surface electrocardiogram and 24-hour Holter recordings were performed to determine QRS duration, PR duration (P and R wave interval on electrocardiograms), P wave dispersion, corrected QT dispersion, and heart rate variability parameters. RESULTS: The maximum heart rate was significantly lower in the toluene-exposed group compared to the control group (130.5 ± 15.1 vs 138.6 ± 16.0, P = 0.02). Corrected low frequency (cLF) and cLF/corrected high frequency (cHF) were also significantly lower in toluene-exposed group (43.6 ± 7.2 vs 50.7 ± 10.5, P = 0.01 and 1.4 ± 0.4 vs 2.2 ± 1.0, P < 0.01, respectively). Mean cHF, root-mean-square successive difference, and standard deviation of all five-minute NN interval means values were significantly higher in the toluene-exposed group (32.8 ± 8.1 vs 25.4 ± 8.2, P ≤ 0.01; 74.0 ± 46.1 vs 60.3 ± 59.4, P = 0.02; and 149.5 ± 77.0 vs 108.9 ± 43.2, P = 0.01, respectively). CONCLUSIONS: This study implies that chronic toluene exposure disturbs cardiac autonomy, particularly by suppressing sympathetic activity, and parasympathetic suppression also occurs with increased exposure duration. We also demonstrated that chronic toluene exposure was not associated with major cardiac arrhythmias and rhythm conduction system disorders.

Prenatal exposure to environmental pollutants and child development trajectories through 7 years.

BACKGROUND: Prenatal exposure to environmental pollutants such as mold, lead, pesticides, tobacco, and air pollutants has been suggested to impair cognitive development. Evidence is needed from longitudinal studies to understand their joint impact on child development across time. OBJECTIVE: To study associations between exposure to indoor environmental pollutants or outdoor air pollution during pregnancy and offspring cognitive development trajectories through 7 years. METHODS: We included 718 Mexican mother-child pairs. Prenatal exposure to indoor environmental pollutants (mold, ventilation, pesticides, tobacco smoke, and use of vidiartred clay pots) was self-reported by the mothers and integrated into an index, or objectively measured in the case of outdoor air pollutants (nitrogen oxides, benzene, toluene, and xylene). Child global cognitive development was measured at 12, 18, 60, or 84 months. Using Latent Class Growth Analysis, we identified three developmental trajectories (positive = 108, average = 362, low = 248). We used multinomial logistic models to test associations between environmental pollutant score (EPS) or outdoor air pollutants, and cognitive development trajectories. RESULTS: After adjustment for sociodemographic covariates, EPS was associated with the average (OR = 1.26 95%CI = 1.01, 1.55) and low (OR = 1.41 95%CI = 1.11, 1.79) trajectories compared to positive; where a unit increase in EPS means an additional prenatal exposure to a pollutant. There was no association between outdoor air pollutants and cognitive development trajectories. CONCLUSION: Children of women who reported higher exposure to indoor environmental pollutants during pregnancy were more likely to follow worse developmental trajectories through 7 years. These results support the development and testing of interventions to reduce exposure to environmental pollutants during pregnancy and early childhood as a potential strategy to improve long-term cognitive development.

Comparative solution equilibrium and structural studies of half-sandwich ruthenium(II)(η6-toluene) complexes of picolinate derivatives.

Five Ru(II)(η6-toluene) complexes formed with 2-picolinic acid and its various derivatives have been synthesized and characterized. X-ray structures of four complexes are also reported. Complex formation processes of [Ru(II)(η6-toluene)(H2O)3]2+ organometallic cation with the metal-free ligands were studied in aqueous solution in the presence of chloride ions by the combined use of 1H NMR spectroscopy, UV-visible spectrophotometry and pH-potentiometry. Solution stability, chloride ion affinity and lipophilicity of the complexes were characterized together with in vitro cytotoxic and antiproliferative activity in cancer cell lines being sensitive and resistant to classic chemotherapy and in normal cells as well. Formation of mono complexes such as [Ru(η6-toluene)(L)(Z)]+/0 (L: completely deprotonated ligand; Z = H2O/Cl-) with high stability and [Ru(η6-toluene)(L)(OH)] was found in solution. The pKa values (8.3-8.7) reflect the formation of low amount of mixed hydroxido species at pH 7.4 at 0.2 M KCl ionic strength. The complexes are fairly hydrophilic and show moderate chloride ion affinity and fast chloride-water exchange processes. The studied complexes exhibit no cytotoxic activity in human cancer cells (IC50 > 100 µM), only complexes formed with 2-picolinic acid (1) and its 3-methyl derivative (2) represented a moderate antiproliferative effect (IC50 = 84.8 (1), 79.2 µM (2)) on a multidrug resistant colon adenocarcinoma cell line revealing considerable multidrug resistant selectivity. Complexes 1 and 2 bind to human serum albumin covalently and relatively slowly with moderate strength at multiple binding sites without ligand cleavage.

Early-onset, Severe Chronic Obstructive Pulmonary Disease with Pulmonary Hypertension that was Likely Induced by Toluene Exposure.

Early-onset pulmonary emphysema is uncommon and its pathogenesis is poorly defined. A 30-year-old man was admitted to our intensive care unit with severe respiratory failure. Besides smoking heavily since the 14 years of age, he had habitually inhaled organic solvents, such as toluene, in his adolescence. High-resolution computed tomography showed evident pulmonary emphysema throughout the lung fields. Based on the findings of right heart catheterization, he was diagnosed with an acute exacerbation of chronic obstructive pulmonary disease complicated with pulmonary hypertension. Heavy smoking from a young age and exposure to toluene were the suspected causes of the patient's severe pulmonary emphysema.

Occupational exposure to solvents and bladder cancer: A population-based case control study in Nordic countries.

The objective of the study was to assess the relationship between exposure to selected solvents and the risk of bladder cancer. This study is based on the Nordic Occupational Cancer (NOCCA) database and comprises 113,343 cases of bladder cancer diagnosed in Finland, Iceland, Norway and Sweden between 1961 and 2005 and 566,715 population controls matched according to country, sex and birth year. Census-based occupational titles of the cases and controls were linked with the job exposure matrix created by the NOCCA project to estimate quantitative cumulative occupational exposures. A conditional logistic regression model was used to estimate hazard ratios (HRs) and their 95% confidence intervals (95% CI). Increased risks were observed for trichloroethylene (HR 1.23, 95% CI 1.12-1.40), toluene (HR 1.20, 95% CI 1.00-1.38), benzene (HR 1.16, 95% CI 1.04-1.31), aromatic hydrocarbon solvents (HR 1.10, 95% CI 0.94-1.30) and aliphatic and alicyclic hydrocarbon solvents (HR 1.08, 95% CI 1.00-1.23) at high exposure level versus no exposure. The highest excess for perchloroethylene was observed at medium exposure level (HR 1.12, 95% CI 1.02-1.23). The study provides evidence of an association of occupational exposure to trichloroethylene, perchloroethylene, aromatic hydrocarbon solvents, benzene and toluene and the risk of bladder cancer.