Few studies have examined whether exposure to chlorinated solvents is associated with increased risk of multiple myeloma (MM). Using occupational exposure information, we evaluated associations between the risk of MM and exposure to six chlorinated solvents: 1,1,1-trichloroethane (TCA), trichloroethylene (TCE), methylene chloride (DCM), perchloroethylene (PCE), carbon tetrachloride, and chloroform.
MM cases were identified through cancer registries and controls were identified in the general population. In-person interviews obtained lifetime occupational histories and additional information on jobs with likely solvent exposure. We reviewed each job and assigned exposure metrics of probability, frequency, intensity, and confidence using job-exposure matrices modified by job-specific questionnaire information. We used logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for associations between MM and having ever been exposed to each, and any, chlorinated solvent and also analyzed whether associations varied by duration and cumulative exposure. We also considered all occupations that were given the lowest confidence scores as unexposed and repeated all analyses.
Risk of MM was significantly elevated for subjects ever exposed to TCA (OR (95% CI): 1.8 (1.1–2.9)). Ever-exposure to TCE or DCM also entailed elevated, but not statistically significant, risks of MM; these became statistically significant when occupations that had low confidence scores were considered unexposed (TCE: 1.7 (1.0–2.7); DCM: 2.0 (1.2–3.2)). Increasing duration and cumulative exposure to TCE were associated with significantly increasing risk of MM when jobs given low confidence were considered unexposed. Increasing cumulative exposure to PCE was also associated with increasing MM risk. We observed non-significantly increased MM risks with exposure to chloroform; however, few subjects were exposed.
Evidence from this relatively large case-control study suggests that exposures to certain chlorinated solvents may be associated with increased incidence of MM; however, the study is limited by relatively low participation (52%) among controls.
multiple myeloma; chlorinated solvents; 1,1,1-trichloroethane (TCA); trichloroethylene (TCE); methylene chloride (DCM); perchloroethylene (PCE); carbon tetrachloride; chloroform
Biological indicators of exposure to solvents are often characterised by a high variability that may be due either to fluctuations in exposure or individual differences in the workers. To describe and understand this variability better a physiological model for differing workers under variable industrial environments has been developed. Standard statistical distributions are used to simulate variability in exposure concentration, physical workload, body build, liver function, and renal clearance. For groups of workers exposed daily, the model calculates air monitoring indicators and biological monitoring results (expired air, blood, and urine). The results obtained are discussed and compared with measured data, both physiological (body build, cardiac output, alveolar ventilation) and toxicokinetic for six solvents: 1,1,1-trichloroethane, trichloroethylene, tetrachloroethylene, benzene, toluene, styrene, and their main metabolites. Possible applications of this population physiological model are presented.
Previous epidemiologic findings suggest an association between exposure to trichloroethylene (TCE), a chlorinated solvent primarily used for vapor degreasing of metal parts, and non-Hodgkin lymphoma (NHL).
We investigated the association between occupational TCE exposure and NHL within a population-based case–control study using detailed exposure assessment methods.
Cases (n = 1,189; 76% participation rate) and controls (n = 982; 52% participation rate) provided information on their occupational histories and, for selected occupations, on possible workplace exposure to TCE using job-specific interview modules. An industrial hygienist assessed potential TCE exposure based on this information and a review of the TCE industrial hygiene literature. We computed odds ratios (ORs) and 95% confidence intervals (CIs) relating NHL and different metrics of estimated TCE exposure, categorized using tertiles among exposed controls, with unexposed subjects as the reference group.
We observed associations with NHL for the highest tertiles of estimated average weekly exposure (23 exposed cases; OR = 2.5; 95% CI, 1.1–6.1) and cumulative exposure (24 exposed cases; OR = 2.3; 95% CI, 1.0–5.0) to TCE. Tests for trend with these metrics surpassed or approached statistical significance (p-value for trend = 0.02 and 0.08, respectively); however, we did not observe dose–response relationships across the exposure levels. Overall, neither duration nor intensity of exposure was associated with NHL, although we observed an association with the lowest tertile of exposure duration (OR = 2.1; 95% CI, 1.0–4.7).
Our findings offer additional support for an association between high levels of exposure to TCE and increased risk of NHL. However, we cannot rule out the possibility of confounding from other chlorinated solvents used for vapor degreasing and note that our exposure assessment methods have not been validated.
cancer; non-Hodgkin lymphoma; occupational; solvents; trichloroethylene
Organic solvents have become ubiquitous in our environment and are essential for industry. Many women of reproductive age are incresingly exposed to solvents such as toluene in occupational settings (ie, long-term, lowconcentration exposures) or through inhalant abuse (eg, episodic, binge exposures to high concentrations). The risk for teratogenic outcome is much less with low to moderate occupational solvent exposure compared with the greater potential for adverse pregnancy outcomes, developmental delays, and neurobehavioral problems in children born to women exposed to high concentrations of abused organic solvents such as toluene, 1,1,1-trichloroethane, xylenes, and nitrous oxide. Yet the teratogenic effects of abuse patterns of exposure to toluene and other inhalants remain understudied. We briefly review how animal models can aid, substantially in clarifying the developmental risk of exposure to solvents for adverse biobehavioral outcomes following abuse patterns of use and in the absence of associated health problems and co-drug abuse (eg, alcohol). Our studies also begin to establish the importance of dose (concentration) and critical perinatal periods of exposure to specific outcomes. The present results with our clinically relevant animal model of repeated, brief, high-concentration binge prenatal toluene exposure demonstrate the dose-dependent effect of toluene on prenatal development, early postnatal maturation, spontaneous exploration, and amphetamine-induced locomotor activity. The results imply that abuse patterns of toluene exposure may be more deleterious than typical occupational exposure on fetal development and suggest that animal models are effective in studying the mechanisms and risk factors of organic solvent teratogenicity.
toluene; inhalant abuse; pregnancy; fetal; teratogen
Though toxicological experiments demonstrate the teratogenicity of organic solvents in animal models, epidemiologic studies have reported inconsistent results. Using data from the population-based National Birth Defects Prevention Study, we examined the relation between maternal occupational exposure to aromatic solvents, chlorinated solvents and Stoddard solvent during early pregnancy and neural tube defects (NTDs) and orofacial clefts (OFCs).
Cases of NTDs (anencephaly, spina bifida and encephalocele) and OFCs (cleft lip ± cleft palate and cleft palate alone) delivered between 1997 and 2002 were identified by birth defect surveillance registries in 8 states; non-malformed control infants were selected using birth certificates or hospital records. Maternal solvent exposure was estimated by industrial hygienist review of self-reported occupational histories in combination with a literature-derived exposure database. Odds ratios (OR) and 95% confidence intervals (CI) for the association between solvent class and each birth defect group and component phenotype were estimated using multivariable logistic regression, adjusting for maternal age, race/ethnicity, education, pre-pregnancy body mass index, folic acid supplement use and smoking.
The prevalence of exposure to any solvent among mothers of NTD cases (n=511), OFC cases (n=1163) and controls (n=2977) was 13.1%, 9.6% and 8.2%, respectively. Exposure to chlorinated solvents was associated with increased odds of NTDs (OR=1.96; CI=1.34, 2.87), especially spina bifida (OR=2.26; CI=1.44, 3.53). No solvent class was strongly associated with OFCs in these data.
Our findings suggest that maternal occupational exposure to chlorinated solvents during early pregnancy is positively associated with the prevalence of NTDs in offspring.
congenital abnormalities; occupational exposure; solvents
Trichloroethylene is commonly used as an industrial solvent and degreasing agent. The clinical features of acute and chronic intoxication with trichloroethylene are well-known and have been described in many reports, but hypersensitivity syndrome caused by trichloroethylene is rarely encountered. For managing patients with trichloroethylene hypersensitivity syndrome, avoiding trichloroethylene and initiating glucocorticoid have been generally accepted. Generally, glucocorticoid had been tapered as trichloroethylene hypersensitivity syndrome had ameliorated. However, we encountered a typical case of trichloroethylene hypersensitivity syndrome refractory to high dose glucocorticoid treatment. A 54-year-old Korean man developed jaundice, fever, red sore eyes, and generalized erythematous maculopapular rashes. A detailed history revealed occupational exposure to trichloroethylene. After starting intravenous methylprednisolone, his clinical condition improved remarkably, but we could not reduce prednisolone because his liver enzyme and total bilirubin began to rise within 2 days after reducing prednisolone under 60 mg/day. We recommended an extended admission for complete recovery, but the patient decided to leave the hospital against medical advice. The patient visited the emergency department due to pneumonia and developed asystole, which did not respond to resuscitation.
Trichloroethylene; hypersensitivity; hepatitis; occupational exposure; sepsis
There is evidence that exposure to chlorinated solvents may be associated with childhood medulloblastoma and primitive neuroectodermal tumor (M/PNET) risk. Animal models suggest genes related to detoxification and DNA repair are important in the carcinogenicity of these pollutants, however, there have been no human studies assessing the modifying effects of these genotypes on the association between chlorinated solvents and childhood M/PNET risk.
We conducted a case-only study to evaluate census tract-level exposure to chlorinated solvents and the risk of childhood M/PNET in the context of detoxification and DNA repair genotypes. Cases (n = 98) were obtained from Texas Children’s Hospital and MD Anderson Cancer Center. Key genotypes (n = 22) were selected from the Illumina Human 1M Quad SNP Chip. Exposure to chlorinated solvents (methylene chloride, perchloroethylene, trichloroethylene, and vinyl chloride) was estimated from the U.S. EPA’s 1999 Assessment System for Population Exposure Nationwide (ASPEN). Logistic regression was used to estimate the case-only odds ratios and 95% confidence intervals (CIs).
There were 11 significant gene-environment interactions associated with childhood M/PNET risk. However, after correcting for multiple comparisons, only the interaction between high trichloroethylene levels and OGG1 rs293795 significantly increased the risk of childhood M/PNET risk (OR = 9.24, 95% CI: 2.24, 38.24, Q = 0.04).
This study provides an initial assessment of the interaction between ambient levels of chlorinated solvents and potentially relevant genotypes on childhood M/PNET risk. Our results are exploratory and must be validated in animal models, as well as additional human studies.
Hazardous air pollutants; chlorinated solvents; DNA repair genes; detoxification genes; childhood medulloblastoma and primitive neuroectodermal tumor
Two patients showed evidence of chronic cardiac toxicity after repeated exposure to 1,1,1-trichloroethane. In both cases there was circumstantial evidence of a deterioration after routine anaesthetic use of the related compound halothane. An adolescent boy who sniffed trichloroethane presented with multiple ventricular arrhythmias during tonsillectomy. Follow up showed mild chronic left ventricular impairment. A 54 year old man had repeated industrial exposure to trichloroethane and deteriorated from mild stable cardiac failure to end stage cardiac failure after halothane anaesthesia for herniorrhaphy. Chronic cardiac toxicity is a previously unreported feature of this type of solvent exposure. Related compounds such as halothane may have a toxic interaction after exposure to trichloroethane.
Case–control studies suggest hydrocarbons increase end-stage renal disease (ESRD) risk. No cohort studies have been conducted.
An occupational database was matched to the U.S. Renal Data System, and the outcome of all-cause ESRD was examined using multivariable Cox regression. Sixteen individual hydrocarbons were studied, although exposures were not mutually exclusive.
For the 1973–2000 period, there was an approximate twofold increased risk of ESRD among workers exposed to trichloroethylene, 1,1,1-trichloroethane, and JP4 gasoline compared with unexposed subjects (all P < 0.05). Relative risk was greater than unity (P > 0.05) for several other hydrocarbons. Associations attenuated (all P > 0.05) when 2001–2002 data were included in the analyses.
Certain hydrocarbons may increase all-cause ESRD risk. Uncertainty regarding the mechanism for increased risk and the observed attenuation in risk in 2001–2002, as well as the overlap of exposures, complicates interpretation. Additional research is needed.
To analyze the relationship between exposure to chlorinated and aromatic organic solvents and malignant lymphoma in a multi-centre, population-based case-control study.
Male and female patients with malignant lymphoma (n = 710) between 18 and 80 years of age were prospectively recruited in six study regions in Germany (Ludwigshafen/Upper Palatinate, Heidelberg/Rhine-Neckar-County, Würzburg/Lower Frankonia, Hamburg, Bielefeld/Gütersloh, and Munich). For each newly recruited lymphoma case, a gender, region and age-matched (± 1 year of birth) population control was drawn from the population registers. In a structured personal interview, we elicited a complete occupational history, including every occupational period that lasted at least one year. On the basis of job task-specific supplementary questionnaires, a trained occupational physician assessed the exposure to chlorinated hydrocarbons (trichloroethylene, tetrachloroethylene, dichloromethane, carbon tetrachloride) and aromatic hydrocarbons (benzene, toluene, xylene, styrene). Odds ratios (OR) and 95% confidence intervals (CI) were calculated using conditional logistic regression analysis, adjusted for smoking (in pack years) and alcohol consumption. To increase the statistical power, patients with specific lymphoma subentities were additionally compared with the entire control group using unconditional logistic regression analysis.
We observed a statistically significant association between high exposure to chlorinated hydrocarbons and malignant lymphoma (Odds ratio = 2.1; 95% confidence interval 1.1–4.3). In the analysis of lymphoma subentities, a pronounced risk elevation was found for follicular lymphoma and marginal zone lymphoma. When specific substances were considered, the association between trichloroethylene and malignant lymphoma was of borderline statistical significance. Aromatic hydrocarbons were not significantly associated with the lymphoma diagnosis.
In accordance with the literature, this data point to a potential etiologic role of chlorinated hydrocarbons (particularly trichloroethylene) and malignant lymphoma. Chlorinated hydrocarbons might affect specific lymphoma subentities differentially. Our study does not support a strong association between aromatic hydrocarbons (benzene, toluene, xylene, or styrene) and the diagnosis of a malignant lymphoma.
The effects of fluorocarbons and chlorinated solvents on the cardiopulmonary system are reviewed. The new information, not hitherto reported, relates to the antagonistic action of inosine, a naturally occurring nucleoside formed in the body by deamination of adenosine. The effect of inosine on methylene chloride toxicity was investigated in open chest dogs anesthetized with pentobarbital sodium. Methylene chloride (5% in air or 50,000 ppm) elicited a decrease of ventricular contractility represented by the diminished left ventricular (dp/dt)max and myocardial contractile force measured directly with a Walton-Brodie strain gauge arch. Coronary blood flow decreased slightly after exposure to methylene chloride. Arterial blood pressure and heart rate did not change. The negative inotropic effect of methylene chloride was reversed or prevented to a substantial extent by intravenous infusion of inosine (5 mg/kg-min). The effect of the latter compound was also characterized by significant coronary vasodilation. It was shown by the experiments that the cardiostimulatory action of inosine was associated with improved hypoxic adaptability of the coronary blood vessels. In contrast, the effect of catecholamines (epinephrine and isoproterenol) was not accompanied by such a beneficial coronary vascular effect. On the basis of these results, the conclusion has been arrived at that inosine might be recommended as a useful antidote in methylene chloride poisoning in particular, and of poisoning by chlorinated solvents and fluorocarbons in general.
The neurotoxicity of methylene chloride (MC) is of special interest because of its acute effects on the central nervous system (CNS) and its metabolic conversion to carbon monoxide. A cohort study of retired airline mechanics was conducted to examine the hypothesis that long term exposure to MC results in lasting effects on the CNS. Retirees were studied to eliminate effects of current occupational exposures. The total retiree population (n = 1758) was surveyed to identify mechanics who met specific occupational, demographic, and medical criteria. A group of eligible retirees having long term exposure to MC and another group with low probability of exposure to solvents were given a comprehensive battery of physiological and psychological tests. The exposure groups were similar for all potential confounders that were measured. No statistically significant differences between groups were detected on outcome measures, although subtle differences in attention and memory were identified. Thus no firm evidence was found to support the hypothesis of lasting CNS effects in retired mechanics with long term exposure to MC.
Workers with long term exposure to mixtures of organic solvents below regulatory limits have been reported to experience mild, but clinically detectable, sensory or sensorimotor polyneuropathies. In conjuction with a cross sectional study of behavioural performance a clinical neurological evaluation was conducted among printers and spray painters to examine dose response relations. All 240 subjects completed an occupational history and symptom questionnaire and underwent a clinical neurological examination. On average, subjects had been employed on their current job for six years. Classification of solvent exposure for each subject was based on exposed versus non-exposed job titles and observations during an industrial hygiene walk-through or on the measured concentration of solvents in full shift personal air samples. The average full shift solvent concentration was 302 ppm for printing plant workers and 6-13 ppm for workers at other plants. Isopropanol and hexane were the major constituents. Neurological abnormalities consistent with mild polyneuropathy were found in 16% of subjects; none was clinically significant. Exposed/non-exposed comparisons showed slightly higher frequency of symptoms in the exposed subjects which was not related to solvent level. Subjects categorised as exposed during the walk- through survey also had poorer vibratory sensation measured at the foot and diminished ankle reflexes. In multiple linear regression models, however, controlling for age, sex, alcohol intake, and examiner, no significant (p less than 0.05) relation was found between solvent concentration and poor neurological function except for two point discrimination measured at the foot. This investigation has not provided evidence for dose related adverse neurological effects from exposure to moderately low levels of solvent mixtures for a relatively short duration, although this may be due to the shortness of exposure duration, the type of solvent exposure, or to selection factors.
Trichloroethylene (TCE) is a suspected renal carcinogen. TCE-associated renal genotoxicity occurs predominantly through glutathione S-transferase (GST) conjugation and bioactivation by renal cysteine beta-lyase (CCBL1). We conducted a case-control study in Central Europe (1,097 cases/1,476 controls), specifically designed to assess risk associated with occupational exposure to TCE through analysis of detailed job histories. All jobs were coded for organic/chlorinated solvent and TCE exposure (ever/never) as well as the frequency and intensity of exposure based on detailed occupational questionnaires, specialized questionnaires, and expert assessments. Increased risk was observed among subjects ever TCE-exposed (OR=1.63, 95% CI: 1.04–2.54). Exposure-response trends were observed among subjects above and below the median exposure [average intensity (OR=1.38, 95% CI:0.81–2.35; OR=2.34, 95% CI:1.05–5.21, p-trend=0.02)]. A significant association was found among TCE-exposed subjects with at least one intact GSTT1 allele (active genotype) (OR=1.88, 95% CI:1.06–3.33) but not among subjects with two deleted alleles (null genotype) (OR=0.93, 95% CI:0.35–2.44, p-interaction=0.18). Similar associations for all exposure metrics including average intensity were observed among GSTT1 active subjects (OR=1.56, 95% CI:0.79–3.10; OR=2.77, 95% CI:1.01–7.58, p-trend=0.02) but not among GSTT1 nulls (OR=0.81, 95% CI:0.24–2.72; OR=1.16, 95% CI:0.27–5.04, p-trend=1.00, p-interaction=0.34). Further evidence of heterogeneity was seen among TCE-exposed subjects with ≥1 minor allele of several CCBL1 tagging SNPs: [rs2293968, rs2280841, rs2259043, rs941960]. These findings provide the strongest evidence to date that TCE exposure is associated with increased renal cancer risk, particularly among individuals carrying polymorphisms in genes that are important in the reductive metabolism of this chemical, and provides biological plausibility of the association in humans.
The literature on environmental exposures and risk of non-Hodgkin Lymphoma(NHL) is inconsistent and no occupational exposures have been conclusively identified as causal factors. We used job exposure matrices to assess the association between occupational exposure to solvents in a population-based case-control study of NHL (N=1591 cases,N=2515 controls) in the San Francisco Bay Area between 1988 and 1995. Occupational histories were collected during in-person interviews and were coded according to the 1980 U.S. Department of Commerce Alphabetic Index of Industries and Occupations. Odds ratios (ORs) and 95% confidence intervals (CI) were adjusted for potential confounders. Our results have provided no support for an association between NHL and occupational exposure to solvents.
lymphoma, non-Hodgkin; case-control; occupational exposure; solvents
The serum activities of the liver enzymes alanine aminotransferase, aspartate aminotransferase, ornithine carbamyl transferase, and gamma-glutamyl transferase were examined in 47 paint industry workers and unexposed age matched referents. The workers were exposed to a mixture of industrial solvents, of which xylene was the main component in most cases. The median total exposure was about 50% of Swedish 1981 threshold limit values according to measurements of individual solvent exposure performed at the same time. No differences in enzyme activities were shown either when the whole exposed and referent groups were compared or when the five workers with outstanding solvent exposures of five times the TLV or more were compared with their referents. It is concluded that in most workers the liver seems to remain largely undamaged from inhalation exposure to a commonly used mixture of non-chlorinated solvents. In many workers this seems to hold true even for high exposures for limited periods.
Individual serum or plasma bile acid concentrations were measured by high performance liquid chromatography in two groups of workers with differing exposures: to hexachlorobutadiene (HCBD) and a mixture of other chlorinated solvents (SOLVENT) in study A; and trichloroethylene (TCE) in study B. Exposures to HCBD and TCE were associated with highly significant increases in a number of individual and summed bile acid measures, with a dose effect relation shown for HCBD. Exposure to SOLVENT was associated with significant decreases in three bile acid measures but this may have been due to misclassification of exposure. No association was found between any of the exposures and any of the standard tests of liver function. This preliminary study suggests that some chlorinated hydrocarbons are associated with raised bile acid concentrations in the blood of exposed workers. It may be that the changes in such concentrations reflect early and small disturbances of liver function. The significance and mechanism of the changes are yet to be determined.
At a given external dose of an inhaled chemical the internal dose or the amount absorbed into the body varies depending on pulmonary ventilation and other physiological factors. Such variability is of concern in the development of biological indices of occupational exposure to organic solvent vapours. This paper discusses how physiological factors may influence the pharmacokinetic behaviour of inhaled organic solvent vapours, especially in relation to monitoring of biological exposure. To illustrate the discussion a computer based physiological pharmacokinetic model was used describing quantitatively the influence of body size, body fat content, and sex on the pharmacokinetic behaviour of trichloroethylene. Absorption, distribution, metabolism and excretion of trichloroethylene were found to vary according to the different anatomical features of men and women. Body build (body weight and body fat content) also affected the pharmacokinetic behaviour of this solvent.
After an outbreak of severe lung disease among workers exposed to butter-flavoring chemicals at a microwave popcorn plant, we determined whether or not lung disease risk declined after implementation of exposure controls.
National Institute for Occupational Safety and Health staff performed eight serial cross-sectional medical and industrial hygiene surveys at the plant from November 2000 through August 2003. Medical surveys included standardized questionnaires and spirometry testing. Industrial hygiene surveys measured levels of production-related air contaminants, including butter-flavoring chemicals such as diacetyl. All diacetyl concentrations above detectable limits were corrected for the effects of absolute humidity and days to sample extraction.
Ventilation and isolation of the production process resulted in one to three orders of magnitude reductions in diacetyl air concentrations in different areas of the plant. Workers with past high exposures had stable chest symptoms over time; nasal, eye, and skin irritation symptoms declined. New workers had lower symptom prevalences and higher lung function than workers with past high exposures, and they did not worsen over time. In workers who had at least three spirometry tests, those with past high exposures were more likely to experience rapid declines in lung function than new workers.
Implemented controls lowered exposures to butter-flavoring chemicals and decreased lung disease risk for much of the plant workforce. Some workers with continuing potential for intermittent, short-term peak and measurable time-weighted exposures remain at risk and should use respiratory protection and have regularly scheduled spirometry to detect rapid lung function declines that may be work-related. Close follow-up of such workers is likely to yield additional information on risks due to peak and time-weighted exposure levels.
Eight volunteers were exposed for eight hours to about 200 ppm of 1,1,1-trichloroethane. On the next morning five series of five alveolar samples were collected for the simultaneous determination of PCO2 and 1,1,1-trichloroethane concentration. Three different methods of sampling were used: voluntary hyperventilation, 10-s breathholding, and "standard." A linear relationship between the alveolar concentrations of both gases was observed in all subjects. Expired air was also collected in two subjects and an analogous relationship was observed. Also the Bohr dead space was found to be of similar size for CO2 and for 1,1,1-trichloroethane. In the monitoring of solvent exposure by breath analysis it is suggested that the results should be corrected for hyperventilation or hypoventilation and for dilution of alveolar air with dead space air by a proportional adjustment of the solvent concentration at the mean normal adveolar PCO2 or by disregarding the samples with a PCO2 outside normal range. The PCO2 determination in 40 unselected workers has shown that in more than a third of them, to monitor exposure by breath analysis would have been of little meaning without such an adjustment or rejection criteria.
OBJECTIVES: To evaluate the relative merits of job specific questionnaires and various alternative assessment methods of occupational exposures often used in general population studies. METHODS: Subjects were participants in a hospital based case-control study of risk factors for male infertility. Estimates of exposure to organic solvents and chromium, based on job specific questionnaires, generic questionnaires, self reports of exposure, an external job exposure matrix (JEM), and a population specific JEM were compared with passive diffuse dosimeter results and measurements in urine. Urine samples from the end of the shift were analysed for metabolites of toluene, xylene, several glycol ethers, trichloroethylene, and chromium. Passive dosimeter date, metabolites of specific solvents, and urinary chromium concentrations were available for 89, 267, and 156 subjects, respectively. The alternative methods and measurements in urine were compared by means of the Cohen's kappa statistic and by computing the positive predictive value, sensitivity, and specificity of the alternative methods against measurements in urine. RESULTS: Passive dosimeter results indicated that exposure classifications with job specific questionnaire information could discriminate between high and low exposures. The kappa coefficients were < 0.4, so agreement between the various methods and measurements in urine was poor. Sensitivity of the methods ranged from 0.21 to 0.85, whereas specificity ranged from 0.34 to 0.94. Positive predictive values ranged from 0.19 to 0.58, with the highest values for job specific questionnaires. CONCLUSIONS: The results indicate that the implementation of job specific questionnaires in a general population study might be worth the extra expense it entails, bearing in mind the paramount importance of avoiding false positive exposure estimates when exposure prevalence is low.
Objectives: To evaluate the relation between occupational dust exposure and lung cancer in tin mines. This is an update of a previous study of miners with high exposure to dust at four tin mines in southern China.
Methods: A nested case-control study of 130 male lung cancer cases and 627 controls was initiated from a cohort study of 7855 subjects employed at least 1 year between 1972 and 1974 in four tin mines in China. Three of the tin mines were in Dachang and one was in Limu. Cumulative total exposure to dust and cumulative exposure to arsenic were calculated for each person based on industrial hygiene records. Measurements of arsenic, polycyclic aromatic hydrocarbons (PAHs), and radon in the work sites were also evaluated. Odds ratios (ORs), standard statistic analysis and logistic regression were used for analyses.
Results: Increased risk of lung cancer was related to cumulative exposure to dust, duration of exposure, cumulative exposure to arsenic, and tobacco smoking. The risk ratios for low, medium, and high cumulative exposure to dust were 2.1 (95% confidence interval (95% CI) 1.1 to 3.8), 1.7 (95% CI 0.9 to 3.1), and 2.8 (95% CI 1.6 to 5.0) respectively after adjustment for smoking. The risk for lung cancer among workers with short, medium, and long exposure to dust were 1.9 (95% CI 1.0 to 3.5), 2.3 (95% CI 1.3 to 4.1), and 2.3 (95% CI 1.2 to 4.2) respectively after adjusting for smoking. Several sets of risk factors for lung cancer were compared, and the best predictive model included tobacco smoking (OR=1.6, 95% CI 1.1 to 2.4) and cumulative exposure to arsenic (ORs for different groups from low to high exposure were 2.1 (95% CI 1.1 to 3.9); 2.1 (95% CI 1.1 to 3.9); 1.8 (95% CI 1.0 to 3.6); and 3.6 (95% CI 1.8 5 to 7.3)). No excess of lung cancer was found among silicotic subjects in the Limu tin mine although there was a high prevelance of silicosis. Exposures to radon were low in the four tin mines and no carcinogenic PAHs were detected.
Conclusions: These findings provide little support for the hypothesis that respirable crystalline silica induces lung cancer. Ore dust in work sites acts as a carrier, the exposure to arsenic and tobacco smoking play a more important part in carcinogenesis of lung cancer in tin miners. Silicosis seems not to be related to the increased risk of lung cancer.
Multi-tiered sampling approaches are common in environmental and occupational exposure assessment, where exposures for a given individual are often modeled based on simultaneous measurements taken at multiple indoor and outdoor sites. The monitoring data from such studies is hierarchical by design, imposing a complex covariance structure that must be accounted for in order to obtain unbiased estimates of exposure. Statistical methods such as structural equation modeling (SEM) represent a useful alternative to simple linear regression in these cases, providing simultaneous and unbiased predictions of each level of exposure based on a set of covariates specific to the exposure setting. We test the SEM approach using data from a large exposure assessment of diesel and combustion particles in the US trucking industry. The exposure assessment includes data from 36 different trucking terminals across the United States sampled between 2001 and 2005, measuring PM2.5 and its elemental carbon (EC), organic carbon (OC) components, by personal monitoring, and sampling at two indoor work locations and an outdoor “background” location. Using the SEM method, we predict: 1) personal exposures as a function of work related exposure and smoking status; 2) work related exposure as a function of terminal characteristics, indoor ventilation, job location, and background exposure conditions; and 3) background exposure conditions as a function of weather, nearby source pollution, and other regional differences across terminal sites. The primary advantage of SEMs in this setting is the ability to simultaneously predict exposures at each of the sampling locations, while accounting for the complex covariance structure among the measurements and descriptive variables. The statistically significant results and high R2 values observed from the trucking industry application supports the broader use of this approach in exposure assessment modeling.
An experimental portable local exhaust ventilation system was installed in three dental operatories where nitrous oxide was used routinely. Standard methods of exhaust ventilation design used in industry to control exposures to toxic airborne substances were applied to the dental operatory setting. The concentration of nitrous oxide in the dentists' breathing zones was measured before and after installation to determine the efficiency of the system in reducing occupational exposures. Results indicate that placement of the exhaust opening and exhaust air flow rate are important in determining the degree of control achieved. After the system had been installed in one operatory, peak exposures declined from over 600 parts per million (ppm) to less than 70 ppm: the time-weighted average exposure was below the NIOSH recommended level of 25 ppm. A permanently installed local exhaust ventilation system modeled after the portable one used in this pilot study may be feasible for most operatories and should not interfere with dental procedures. The results suggest that nitrous oxide exposures can be greatly reduced if dental operatories are equipped with local exhaust ventilation.
Aims: A case–control study was carried out between 1998 and 2000 to investigate the relation between systemic sclerosis and occupational exposure.
Methods: Eighty cases of systemic sclerosis admitted consecutively to the Department of Internal Medicine at the University Hospital of Tours from 1998 to 2000 were included. For each case, two age, gender, and smoking habits matched controls hospitalised during the same period in the same department were selected. A committee of experts was set up retrospectively to assess occupational exposure. Exposure to silica dust and organic solvents (such as trichlorethylene and other chlorinated solvents, and benzene and other aromatic solvents) was investigated using semiquantitative estimates of exposure. An exposure score was calculated for each subject based on probability, intensity, daily frequency, and duration of exposure for each period of employment. The final cumulative exposure score was obtained, taking into account all periods of employment.
Results: Significant associations with SS were observed for crystalline silica, trichlorethylene, chlorinated solvents, toluene, aromatic solvents, ketones, white spirit, epoxy resins, and welding fumes. Risk of SS was significantly associated with a high final cumulative exposure score of occupational exposure to crystalline silica, trichlorethylene, chlorinated solvents, welding fumes, and any types of solvents.
Conclusion: Results confirm the influence of occupational risk factors in the occurrence of SS in both men and women. The link is not only with silica but also with other compounds such as solvents.