Multiple air pollutant exposure and lung cancer in Tehran, Iran.

Lung cancer is the most rapidly increasing malignancy worldwide with an estimated 2.1 million cancer cases in the latest, 2018 World Health Organization (WHO) report. The objective of this study was to investigate the association of air pollution and lung cancer, in Tehran, Iran. Residential area information of the latest registered lung cancer cases that were diagnosed between 2014 and 2016 (N = 1,850) were inquired from the population-based cancer registry of Tehran. Long-term average exposure to PM10, SO2, NO, NO2, NOX, benzene, toluene, ethylbenzene, m-xylene, p-xylene, o-xylene (BTEX), and BTEX in 22 districts of Tehran were estimated using land use regression models. Latent profile analysis (LPA) was used to generate multi-pollutant exposure profiles. Negative binomial regression analysis was used to examine the association between air pollutants and lung cancer incidence. The districts with higher concentrations for all pollutants were mostly in downtown and around the railway station. Districts with a higher concentration for NOx (IRR = 1.05, for each 10 unit increase in air pollutant), benzene (IRR = 3.86), toluene (IRR = 1.50), ethylbenzene (IRR = 5.16), p-xylene (IRR = 9.41), o-xylene (IRR = 7.93), m-xylene (IRR = 2.63) and TBTEX (IRR = 1.21) were significantly associated with higher lung cancer incidence. Districts with a higher multiple air-pollution profile were also associated with more lung cancer incidence (IRR = 1.01). Our study shows a positive association between air pollution and lung cancer incidence. This association was stronger for, respectively, p-xylene, o-xylene, ethylbenzene, benzene, m-xylene and toluene.

Pérdida visual secundaria a intoxicación inhalatoria y cutánea por metanol y tolueno. A propósito de un caso / Secondary visual loss due to inhalation and cutaneous poisoning by methanol and toluene. Presentation of a clinical case

La intoxicación por ingesta de metanol es una entidad frecuentemente descrita en la literatura, no así la intoxicación vía transdérmica o inhalatoria. Suele cursar con daño multiorgánico variable, entre lo que destaca la afectación visual, neurológica y digestiva, así como las alteraciones metabólicas y electrolíticas que pueden llegar a causar la muerte. El contacto con tolueno por inhalación ocupacional o intencional puede producir también alteraciones neurológicas. En este artículo se expone el caso de una paciente mujer que acude al servicio de urgencias por pérdida visual bilateral secundaria a una intoxicación accidental (inhalatoria-transdérmica) con un disolvente que contenía metanol y tolueno, entre otros compuestos, y que durante el ingreso evoluciona favorablemente tras tratamiento con etanol en perfusión y corticoides

Methanol poisoning is often described in the literature, but not transdermal or inhalational poisoning. It usually involves variable multi-organ damage, among which visual, neurological, and gastrointestinal involvement, as well as the metabolic and electrolyte changes that can lead to death. Contact with toluene by occupational or intentional inhalation may also cause neurological abnormalities. This article describes the case of a female patient who was seen in the Emergency Department due to bilateral visual loss secondary to accidental poisoning (inhalation-transdermal) with a solvent containing methanol and toluene. She had a favourable outcome during admission after treatment with ethanol in perfusion and corticosteroids

[Generalized spinal cord atrophy and oligoclonal IgG band in the cerebrospinal fluid due to chronic toluene intoxication: a case report].

We herein report the case of a 54-year-old man who abused toluene for 25 years and gradually developed gait disturbance. Neurological findings showed mild cognitive impairment, hearing impairment, dysarthria, marked hyperreflexia of the limbs, spastic paraplegia, slight impairment of deep sensation, and urinary disturbance; however, there was no muscular atrophy. Serum antibodies against human T-lymphocytic virus 1 and aquaporin 4 were negative. Biochemical analysis did not show an increase in very-long-chain fatty acids. The cerebrospinal fluid was normal for the cell number and protein level but positive for oligoclonal IgG band, with a mildly increased IgG index. Brain MRI showed marked high intensity in the bilateral periventricular, deep cerebral and subcortical white matter as well as atrophy of the cerebrum, cerebellum and brainstem, and thinning of the corpus callosum. Spinal MRI showed marked atrophy of the lower cervical spinal cord, thoracic spinal cord, and conus medullaris. Spinal cord lesions are extremely rare in chronic toluene intoxications, and there are no reports of spinal cord atrophy. Lateral and ventral columns of the spinal cord are responsible for pyramidal tract signs, and insidious ongoing inflammation related to chronic toluene intoxication in the central nervous system is predicted to underlie the pathogenesis.

Secondary visual loss due to inhalation and cutaneous poisoning by methanol and toluene. Presentation of a clinical case. / Pérdida visual secundaria a intoxicación inhalatoria y cutánea por metanol y tolueno. A propósito de un caso.

Methanol poisoning is often described in the literature, but not transdermal or inhalational poisoning. It usually involves variable multi-organ damage, among which visual, neurological, and gastrointestinal involvement, as well as the metabolic and electrolyte changes that can lead to death. Contact with toluene by occupational or intentional inhalation may also cause neurological abnormalities. This article describes the case of a female patient who was seen in the Emergency Department due to bilateral visual loss secondary to accidental poisoning (inhalation-transdermal) with a solvent containing methanol and toluene. She had a favourable outcome during admission after treatment with ethanol in perfusion and corticosteroids.

Intoxicación por metanol por inhalación de disolvente / Methanol poisoning by solvent inhalation

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Medico-legal implications of toluene abuse and toxicity. Review of cases along with blood concentrations.

Toluene, a liquid aromatic hydrocarbon, is one of the most widely used industrial solvents, and is present in numerous paints, paint thinners, glues and other industrial and household products. It has become the most abused solvent in the world due to its rapid effects following inhalation. However, the numerous cases of fatal and non-fatal toluene-related intoxication reported in the literature have not yet been collected and discussed in the forensic setting. In this paper we aim to provide a review of the cases of toluene abuse and intoxication and the state of the art of the forensic toxicological analysis of toluene intoxications in the living and in the dead subject, from the early identification to the medico-legal interpretation of the toxicological result. We have identified a total of 45 papers regarding different aspects of toluene abuse, and divided them into three sections, namely sampling, storage and techniques of analysis, assessment in living subjects and post-mortem assessment. This article reports toluene concentrations in blood from 202 living subjects, 23 fatal toluene intoxications and 85 toluene related deaths. Toxicological results are discussed in relation to the clinical presentation (living subjects, including impaired drivers), and the manner of death according to the medical examiner reports (post-mortem examinations). Finally, we discuss the strengths and limitations of the review.

Niveles urinarios de ácido trans, trans mucónico y orto cresol en una población infanto-juvenil residente en Ciudad Autónoma de Buenos Aires y Conurbano Bonaerense / Urinary levels of trans, trans muconic and ortho cresol in an infant-juvenile population resident in the Autonomous City of Buenos Aires and the Conurbano of Buenos Aires

Introducción: la exposición crónica al benceno y tolueno produce alteraciones sobre la médula ósea y el sistema nervioso central, entre otros. En orina, el ácido trans, trans mucónico (t, t-MA) es uno de los biomarcadores de exposición al benceno y el o-cresol (oCre) al tolueno. Objetivo: analizar los resultados de los niveles de t, t-MA y oCre urinarios en una población infanto-juvenil residente en Ciudad Autónoma de Buenos Aires y Conurbano Bonaerense potencialmente expuesta a benceno y tolueno ambiental. Materiales y métodos: se realizó un estudio retrospectivo de los resultados de t, t-MA y oCre urinarios. Las muestras de orina ingresaron al laboratorio con solicitud de t, t-MA (n=1519) y oCre (n=1447) durante el período 2011-2017 (rango etario entre 0 a 19 años). El t, t-MA se cuantificó por UFLC con detector de arreglo de diodos y el oCre por CG con detector de ionización por llama. Resultados: la edad promedio de los pacientes fue de 4,8 años y la mediana 4,6 años.Las concentraciones de t, t-MA urinario fueron: menor de 50 μg/l (44,8%); entre 50-500 μg/l (52,1%) y mayores de 500 μg/l (3,1%). Expresadas por gramo de creatinina: entre 15-163 μg/g creatinina (60,4%) y mayores de 163 μg/g creatinina (39,6%). El límite de cuantificación de t, t-MA fue de 50 μg/l. Las concentraciones de oCre urinario fueron: menor de 0,20 mg/l (97,7%) y entre 0,20-0,50 mg/l (2,3%) y mayor de 0,50 mg/l (0%). Expresadas por gramo de creatinina: menor de 0,30 mg/g creatinina en el 0,8% y mayores de 0,30 mg/g creatinina en el 1,5%. El límite de cuantificación de oCre fue de 0,20 mg/l. Conclusiones: los resultados del trabajo podrían indicar una contaminación ambiental persistente, en especial en el Conurbano Bonaerense, donde debería continuarse el monitoreo de algunas zonas. Pero, por otro lado, es de vital importancia tener en cuenta los factores de confusión, tales como la dieta, la exposición al humo de tabaco ambiental (fumador pasivo) y la tasa de excreción renal que llevarían a una sobre-estimación de los resultados y a una incorrecta toma de decisiones.

Introduction: Chronic exposure to benzene and toluene produces alterations in the bone marrow and the central nervous system, among other effects. In urine, trans, trans muconic acid (t, t-MA) is one of the biomarkers of exposure to benzene and o-cresol (oCre), to toluene. Objective: To analyze the results of urinary t, t-MA and oCre levels in an infant-juvenile population resident in the Autonomous City of Buenos Aires and the Conurbano Bonaerense, potentially exposed to environmental benzene and toluene. Materials and methods: A retrospective study of urinary t, t-MA and oCre results was performed. The urine samples entered the laboratory with the request of t, t-MA (n = 1519) and oCre (n = 1447) during the period 2011- 2017. The age range of the population was between 0 and 19 years. The t, t-MA was quantified by UFLC with diode array detector and the oCre by GC with flame ionization detector. Results: The average age of the patients was 4.8 years and the median age was 4.6 years. The urinary concentrations of t, t-MA were: below 50 μg/l (44.8%); between 50-500 μg/l (52.1%) and above 500 μg/l (3.1%). Expressed per gram of creatinine: between 15-163 μg/g creatinine (60.4%) and greater 163 μg/g creatinine (39.6%). The limit of quantification of t, t-MA was 50 μg/l. The urinary oCre concentrations were: less than 0.20 mg/l (97.7%) and between 0.20-0.50 mg/l (2.3%). Expressed per gram of creatinine: less than 0.30 mg/g creatinine in 0.8% and greater than 0.30 mg/g creatinine in 1.5%. The limit of quantification of oCre was 0.20mg/l. Conclusions: The results of the study could indicate persistent environmental contamination, especially in the Conurbano Bonaerense, where monitoring of some areas should be continued. However, it is of vital importance to take into account the confounding factors, such as diet, exposure to environmental tobacco smoke (passive smoking) and the rate of renal excretion, which would lead to an over-estimation of the results and to incorrect decision-making.

Toluene Poisoning Presenting as Bilateral Basal Ganglia Haemorrhage.

Toluene is an aromatic hydrocarbon that is often used as a solvent in paints, paint thinners, glues, disinfectants and as an industrial solvent for the manufacturing of pharmaceuticals, paints and chemicals. Metabolic acidosis is a recognized complication of toluene poisoning. However, we here report an unusual case of toluene poisoning presenting with bilateral intracerebral haemorrhage.

Rhabdomyolysis with acute tubular necrosis following occupational inhalation of thinners.

Thinners are mixtures of organic solvents commonly containing toluene, xylene, acetone, hexane, benzene and methyl isobutyl ketone. This report describes a case of rhabdomyolysis with acute tubular necrosis and renal failure, most likely attributable to toluene, following occupational exposure to thinners while cleaning a steel water tank. These adverse health effects have previously been reported following acute poisoning or intentional inhalation by drug abusers, but rarely in the occupational setting. Poor working conditions, lack of health and safety training and delayed treatment contributed to the onset and severity of the patient's complications. This case emphasizes the need for strict control measures, including adequate ventilation, training on working in confined spaces, appropriate personal protective equipment and emergency rescue procedures in such settings. In addition, rhabdomyolysis, acute tubular necrosis and renal failure should be added to safety data material as possible complications of excessive inhalation of thinners.

Benzene poisoning, clinical and blood abnormalities in two Brazilian female gas station attendants: two case reports.

BACKGROUND: Brazilian gas station workers are chronically exposed to benzene, toluene, xylene (BTX) during their working time. Describe below two cases of latin female gas station workers with benzene poisoning symptoms and miscarriage history. CASE PRESENTATION: In both cases were identified complex chromosomal rearrangements (CCR) with fluorescence in situ hybridization, applied to whole chromosome paints by chromosomes 1, 2 and 4. The lower natural killer cell (NK) cells have also been observed in cases correspondents, especially the rare type of NK (NKbright) in their peripheral blood cells. CONCLUSIONS: It is known that acquired chromosomal aberrations are positively correlated with cancer and reproductive risk. In concordance, lower NK cytotoxicity increases the risk for cancer, as well. Thus, this is the first study providing hints on a possible causative relation of lower NK cytotoxicity and increase rates of chromosomal rearrangements including CCRs.

Detection of toluene in a body buried for years with a fatal cardiac contusion.

This report aimed to present the postmortem finding of toluene in a homicide victim buried under the ground for six years. The bones of the skull and limbs were exposed, and the remainder of the subcutaneous tissues, brain and heart had formed into adipocere. There were numerous fractures in the skull and the anterior side of the ribs. A cardiac contusion extending into the cavity of the right ventricle was also observed. No other obvious injuries were identified on the body. The concentration of toluene in the bone marrow within the head of the humerus was 58.4 µg/g. The cause of death was suspected as heart rupture, possibly from a forceful impact or compression of the anterior chest under toluene intoxication. This report presents a rare case where toluene intake by a human was disclosed by autopsy even after several years of death.

Acute toluene intoxication--clinical presentation, management and prognosis: a prospective observational study.

BACKGROUND: Toluene is one of the most widely abused inhaled drugs due to its acute neurologic effects including euphoria and subsequent depression. However, dangerous metabolic abnormalities are associated to acute toluene intoxication. It has been previously reported that rhabdomyolysis and acute hepatorenal injury could be hallmarks of the condition, and could constitute risk factors for poor outcomes. The objective was to describe the clinical presentation, to characterize the renal and liver abnormalities, the management and prognosis associated to acute toluene intoxication. METHODS: We prospectively assessed 20 patients that were admitted to a single center's emergency department from September 2012 to June 2014 with clinical and metabolic alterations due to acute toluene intoxication. RESULTS: The main clinical presentation consisted of weakness associated to severe hypokalemia and acidosis. Renal glomerular injury (proteinuria) is ubiquitous. Biliary tract injury (alkaline phosphatase and gamma-glutamyl transpeptidase elevations) disproportional to hepatocellular injury is common. Rhabdomyolysis occurred in 80% of patients, probably due to hypokalemia and hypophosphatemia. There were three deaths, all female, and all associated with altered mental status, severe acidosis, hypokalemia and acute oliguric renal failure. The cause of death was in all cases due to cardiac rhythm abnormalities. CONCLUSION: The hallmarks of acute toluene intoxication are hypokalemic paralysis and metabolic acidosis. Liver injury and rhabdomyolysis are common. On admission, altered mental status, renal failure, severe acidemia and female gender (not significant in our study, but present in all three deaths) could be associated with a poor outcome, and patients with these characteristics should be considered to be treated in an intensive care unit.

Cardiotoxic effect due to accidental ingestion of an organic solvent.

Toxic myocardial injury can be misdiagnosed as a myocardial infarction, resulting in the patient undergoing standard treatment for cardiac rehabilitation. However, such inadequate therapeutic strategies can lead to cardiovascular complications including dilated cardiomyopathy. This study presents a case of a 65-year-old man after accidental ingestion of organic solvents (toluene and xylene), whose condition demonstrated all the criteria for diagnosis of myocardial infarction. The qualitative determinations of the above mentioned volatile organic compounds (VOCs) in whole blood were carried out using a headspace sampling by means of gas chromatography. Cardiac catheterization revealed no specific coronary lesions, only a muscular bridge causing a 30-50% stenosis in the middle of the circumflex branch of the left coronary artery.

Reversible cerebral periventricular white matter changes with corpus callosum involvement in acute toluene-poisoning.

Substance poisoning, such as toluene intoxication, has seldom been reported in the relevant literature. The documented cerebral neuroimaging has mostly described reversible symmetrical white matter changes in both the cerebral and cerebellar hemispheres. This paper presents 2 patients with toluene poisoning, whose brain magnetic resonance imaging studies showed a similar picture that included extra involvement over the corpus callosum; however, such corpus callosum involvement has never been mentioned and is quite rare in the literature. We discussed the underlying neuropathological pathways in this article. Hopefully, these cases will provide first-line clinicians with some valuable information with regard to toluene intoxication and clinical neuroimaging presentations.

Changes in poly(ADP-ribosyl)ation patterns in workers exposed to BTX.

Occupational exposure to (benzene, toluene and xylene, BTX is common in the Chinese workplace. Chronic occupational exposure to benzene is associated with an increased risk of hematological malignancies such as acute myeloid leukemia (AML), but the underlying mechanisms are still unclear. This study investigates changes in poly(ADP-ribosyl)ation and DNA methylation in subjects occupationally exposed to a BTX. Blood DNA samples and exposure data were obtained from subjects with different levels of exposure, including 132 decorators, 129 painters, and 130 unexposed referents in a container-manufacturing factory in Shenzhen, China. Occupational exposure assessment included personal monitoring of airborne benzene, toluene and xylene. Hematological parameters were measured and the cytokinesis-block micronucleus (CBMN) assay was used to detect DNA damage in peripheral lymphocytes. Quantitative real-time PCR was used to detect the mRNA expression of poly(ADP-ribose) polymerase 1 (PARP1) and poly(ADP-ribose) glycohydrolase (PARG), DNA methyltransferases (DNMTs) including DNMT1, DNMT3a and DNMT3b, methyl-CpG-binding domain protein 2(MBD2). PARP1 assay was used to measure PARP activity. Airborne levels of benzene, toluene and xylene in the two exposed groups were significantly higher than those of controls (P<0.001). The two exposed groups (decorators, painters) showed decreased PARP1, DNMTs and MBD2 expression relative to controls (P<0.05), and PARP activity was also decreased (P<0.05). Decreased PARP1, DNMT1, DNMT3a, DNMT3b and MBD2 mRNA expression was correlated with increased airborne BTX (Pearson's r: -0.587, -0.314, -0.636, -0.567 and -0.592 respectively, P<0.001). No significant differences in hematological parameters and CBMN were found among the three groups. Together, these results suggest that decreased DNMTs, MBD2 and PARP1 might be involved in the global hypomethylation associated with BTX exposure, and the imbalance of PARP/PARG might participate in the down-regulation of DNMTs. This is the first human study to link altered poly(ADP-ribosyl)ation patterns, which reproduce the aberrant epigenetic patterns found in benzene-treated cells, to chronic occupational exposure to BTX.

American Society of Nephrology Quiz and Questionnaire 2013: electrolyte and acid-base.

The Nephrology Quiz and Questionnaire (NQ&Q) remains an extremely popular session for attendees of the annual meeting of the American Society of Nephrology. As in past years, the conference hall was overflowing with interested audience members. Topics covered by expert discussants included electrolyte and acid-base disorders, glomerular disease, ESRD/dialysis, and transplantation. Complex cases representing each of these categories along with single-best-answer questions were prepared by a panel of experts. Prior to the meeting, program directors of United States nephrology training programs answered questions through an Internet-based questionnaire. A new addition to the NQ&Q was participation in the questionnaire by nephrology fellows. To review the process, members of the audience test their knowledge and judgment on a series of case-oriented questions prepared and discussed by experts. Their answers are compared in real time using audience response devices with the answers of nephrology fellows and training program directors. The correct and incorrect answers are then briefly discussed after the audience responses, and the results of the questionnaire are displayed. This article recapitulates the session and reproduces its educational value for the readers of CJASN. Enjoy the clinical cases and expert discussions.

Benzene-contaminated toluene and acute myeloid leukemia: a case series and review of literature.

We report seven cases of acute myeloid leukemia (AML) with occupational exposure to a toluene-based hydrocarbon solvent. The cases were employed at a facility, which manufactured rubber belts and hoses, between 1950 and 2005 for periods ranging from 21 to 37 total years. Detailed histories were obtained for three workers who were diagnosed with AML within a 3-year period (2003-2005). Death certificates, medical records, and accounts by workers were reviewed. Benzene, a known cause of AML, is typically a contaminant of toluene. Benzene contamination in toluene and other widely used solvents and the potential for concurrent benzene exposure during usage of these solvents in occupational settings are discussed.

Age-dependent time courses of recovery for motor functions following acute toluene intoxication in rats.

Toluene is a psychoactive chemical found in many household products including adhesives and thinners. Inhalation of these vapors can cause euphoria and impairments in motor control and neurological functioning. Misuse and abuse of toluene is most common in children, which may in part be due to an age-dependent neurobehavioral sensitivity to toluene. Here we assessed the effects of acute binge-like toluene inhalations (15 or 30 min; ∼5,000 ppm) on tasks that examine locomotion, exploration, balance, gait, and neurological functioning for adolescent (1 month), young adult (2-3 months), adult (5-6 months), and older adult (10-12 months) rats. Both motor and neurological functions were impaired following acute toluene inhalation at all ages. However, only the duration to recover from deficits in motor functions differed among age groups, with adolescent and young adult rats requiring notably longer recovery times than older rats. Our results are suggestive of an age-dependent vulnerability to the intoxicating effects of toluene.