Chemical exposure levels in printing workers with cholangiocarcinoma.

OBJECTIVE: This study aimed to identify chemicals used by printing workers with cholangiocarcinoma, as well as the levels of exposure to the chemicals. METHODS: Information necessary to identify chemicals used by printing workers with cholangiocarcinoma and to estimate chemical exposure concentrations was obtained from the Ministry of Health, Labour and Welfare, Japan. Working environment concentrations of the chemicals in the printing rooms were estimated using a well-mixed model, and exposure concentrations during the ink removal operation were estimated using a near-field and far-field model. Shift time- weighted averages (TWA) of exposure concentrations were also calculated. RESULTS: Two workers from each of three small printing plants examined suffered from cholangiocarcinoma, and all six of these workers had been exposed to 1,2-dichloropropane (1,2-DCP) for 10-16 years. The estimated working environment concentrations of 1,2-DCP in the printing rooms were 17-180 ppm and estimated exposure concentrations during the ink removal operation were 150-620 ppm. Shift TWA values were estimated to be 62-240 ppm. Four of the six workers had also been exposed to dichloromethane (DCM) at estimated working environment concentrations of 0-98 ppm and estimated exposure concentrations during the ink removal operation of 0-560 ppm. Shift TWA values were estimated to be 0-180 ppm. Other chlorinated organic solvents (1,1,1-trichloroethane, 1,1-dichloro-1-fluoroethane) and petroleum solvents (gasoline, naphtha, mineral spirit, mineral oil, kerosene) were also used in the ink removal operation. CONCLUSIONS: All six printing workers with cholangiocarcinoma were exposed to very high levels of 1,2-DCP for a long term.

[A couple suffering acute respiratory illness due to waterproofing spray exposure].

The patients were a 28-year-old man and a his 27-year-old wife. The husband smoked a cigarette immediately after using a waterproofing spray, and developed fever, cough, and dyspnea 15 min later. The wife had nausea 2 hours later. Nine hours later, the husband visited a local clinic, and was referred to our hospital because of hypoxemia. In addition, chest CT showed ill-defined areas of increased density, predominantly in the bilateral upper lung fields, with interlobular septal thickening, and he was hospitalized. Although the wife was asymptomatic at the time of examination, she had chest CT findings similar to those of her husband, and was also hospitalized. After admission, the husband received steroid pulse therapy and oxygen inhalation for his symptoms and hypoxemia, with return of arterial blood gas analysis results to normal on the third day. The wife had no symptoms or hypoxemia during her hospital stay. Their chest CT findings improved on the seventh day after admission, and they were discharged. Thus, it appears that the couple suffered from acute respiratory illness due to waterproofing spray exposure, and probably heat degradation products from cigarette smoking caused the husband to have severe symptoms.

Cognitive impairment and olfactory panic from occupational exposure to VOCs.

BACKGROUND: A Canadian government clerical worker in her early thirties developed frontal lobe dysfunction from inhalation of volatile organic compounds off-gassed during an office renovation. METHODS: Pulmonary function, bronchial provocation, allergy testing, and a brain (SPECT) scan were performed. RESULTS: SPECT scanning showed frontotemporal hypoperfusion and neuropsychologic testing revealed deficits in verbal learning and poor organizational memory. CONCLUSIONS: A significant component of this worker's impairment was the development of "olfactory panic," a debilitating aversion to odor accompanied by symptoms of panic. The Ontario Workplace Safety and Insurance Appeals Tribunal granted entitlement for her cognitive difficulties and olfactory panic as a result of her toxic exposure.

In silico toxicology: simulating interaction thresholds for human exposure to mixtures of trichloroethylene, tetrachloroethylene, and 1,1,1-trichloroethane.

In this study, we integrated our understanding of biochemistry, physiology, and metabolism of three commonly used organic solvents with computer simulation to present a new approach that we call "in silico" toxicology. Thus, we developed an interactive physiologically based pharmacokinetic (PBPK) model to predict the individual kinetics of trichloroethylene (TCE), perchloroethylene (PERC), and methylchloroform (MC) in humans exposed to differently constituted chemical mixtures of the three solvents. Model structure and parameterization originate from the literature. We calibrated the single-compound PBPK models using published data and described metabolic interactions within the chemical mixture using kinetic constants estimated in rats. The mixture model was used to explore the general pharmacokinetic profile of two common biomarkers of exposure, peak TCE blood levels and total amount of TCE metabolites generated, in rats and humans. Assuming that a 10% change in the biomarkers corresponds to a significant health effect, we calculated interaction thresholds for binary and ternary mixtures of TCE, PERC, and MC. Increases in the TCE blood levels led to higher availability of the parent compound for glutathione conjugation, a metabolic pathway associated with kidney toxicity/carcinogenicity. The simulated change in production rates of toxic conjugative metabolites exceeded 17% for a corresponding 10% increase in TCE blood concentration, indicating a nonlinear risk increase due to combined exposures to TCE. Evaluation of metabolic interactions and their thresholds illustrates a unique application of PBPK modeling in risk assessment of occupational exposures to chemical mixtures.

Organic solvents and cancer.

Epidemiologic evidence on the relationship between organic solvents and cancer is reviewed. In the 1980s, more than a million persons were potentially exposed to some specific solvents in the United States; in Canada, 40 percent of male cancer patients in Montreal had experienced exposure to solvents; in the Finnish population, one percent was regularly exposed. There is evidence for increased risks of cancer following exposure to: trichloroethylene (for the liver and biliary tract and for non-Hodgkin's lymphomas); tetrachloroethylene (for the esophagus and cervix--although confounding by smoking, alcohol, and sexual habits cannot be excluded--and non-Hodgkin's lymphoma); and carbon tetrachloride (lymphohematopoietic malignancies). An excess risk of liver and biliary tract cancers was suggested in the cohort with the high exposure to methylene chloride, but not found in the other cohorts where an excess risk of pancreatic cancer was suggested. 1,1,1-trichloroethane has been used widely, but only a few studies have been done suggesting a risk of multiple myeloma. A causal association between exposure to benzene and an increased risk of leukemia is well-established, as well as a suggested risk of lung and nasopharynx cancer in a Chinese cohort. Increased risks of various gastrointestinal cancers have been suggested following exposure to toluene. Two informative studies indicated an increased risk of lung cancer, not supported by other studies. Increased risks of lymphohematopoietic malignancies have been reported in some studies of persons exposed to toluene or xylene, but not in the two most informative studies on toluene. Occupation as a painter has consistently been associated with a 40 percent increased risk of lung cancer. (With the mixed exposures, however, it is not possible to identify the specific causative agent[s].) A large number of studies of workers exposed to styrene have evidenced no consistent excess risk of all lymphohematopoietic malignancies, although the most sensitive study suggested an excess risk of leukemia among workers with a high exposure.

Alteraciones neuropsicológicas en trabajadores expuestos a neurotóxicos / Neuropsychological disorders in workers exposed to neurotoxics

La neurotoxicidad es un grave problema de salud pública debido al incremento de sustancias neurotóxicas y a la gran cantidad de trabajadores expuestos. Gran cantidad de sustancias de uso común en la industria. Tales como solventes, metales y plaguicidas, provocan alteraciones neurotóxicas a concentraciones por debajo de los límites permisibles, produciendo cambios importantes en la función psicológica y el comportamiento, que se expresan en trastornos funcionales que interfieren en las tareas cotídianas e incrementan la accidentabilidad. En este artículo se revisa la literatura científica sobre los efectos neurotóxicos de solventes, plomo, mercurio y plaguicidas, y se comentan aspectos metodológicos de interés para el diseño de investigaciones epidemiológicas. Como conclusión, es notoria la existencia de evidencias que demuestran el efecto neurotóxico de gran cantidad de sustancias usadas en la industria. Así mismo, consideramos importante continuar realizando investigaciones sobre el tema, y sobre todo, La necesidad de tomar medidas preventivas para proteger la salud del trabajador

Adverse pregnancy outcomes in relation to water contamination, Santa Clara County, California, 1980-1981.

An epidemiologic study was conducted to investigate a suspected cluster of adverse outcomes of pregnancies conceived in 1980-1981 among women who resided in a census tract in Santa Clara County, California that was thought to be exposed to drinking water from a well contaminated by an organic solvent, trichloroethane. A comparison census tract that received water from a different source was selected on the basis of demographic comparability. The cluster was confirmed; the odds ratio for spontaneous abortion was 2.3 (95% confidence interval (Cl) 1.3-4.2) after adjustment by multiple logistic regression for maternal risk factors, including maternal age, alcohol consumption, smoking, and prior fetal loss. The relative risk for congenital malformations was 3.1 (95% Cl 1.1-10.4). Because of the lack of precise information on the timing and extent of contamination, the pattern of spontaneous abortion rates throughout the study period cannot be used to either support or refute a causal inference.

Scleroderma after occupational exposure to trichlorethylene and trichlorethane.

Three cases of scleroderma, developed after occupational exposure to trichlorethylene and trichlorethane are described. The question is raised whether exposure to these chlorohydrocarbon solvents may be an etiological factor.

Activities of chlorinated ethane and ethylene compounds in the Salmonella/rat microsome mutagenesis and rat hepatocyte/DNA repair assays under vapor phase exposure conditions.

Three chlorinated ethane and ethylene solvent products were examined for their genotoxicity in the Salmonella/microsome mutagenesis and hepatocyte primary culture DNA repair assays using vapor phase exposures. The positive control in this study, monochloroethylene (vinyl chloride), induced reversion mutation of Salmonella tester strains TA100 and TA1535 with enhancement by an exogenous activation system and elicited unscheduled DNA synthesis in rat hepatocytes in culture. Exposures to 1,1,1-trichloroethane (methyl chloroform) or 1,1,2-trichloroethylene samples which contained stabilizers resulted in increased recovery of revertant colonies of Salmonella at concentrations causing greater than 96% cell killing. However, these stabilized materials did not induce DNA repair and low-stabilized trichloroethylene did not induce reversion mutation or DNA repair. Exposure of Salmonella tester strains and hepatocytes to highly toxic vapor concentrations of technical grade 1,1,2,2-tetrochloroethylene, low-stabilized and stabilized, increased reversion mutation and elicited DNA repair. Tetrachloroethylene of high purity was not genotoxic. With all of these test products, the presence of an Aroclor-induced rat liver subcellular enzyme preparation in the mutagenesis assay did not have any effect on the results. These observations suggest that stabilizers or unknown impurities normally present at low concentrations in these products are responsible for the positive responses observed at the high exposure concentrations achievable under in vitro test conditions.