Article

Occupational exposure to chlorinated aliphatic hydrocarbons and risk of astrocytic brain cancer

Authors:
To read the full-text of this research, you can request a copy directly from the authors.

Abstract

Chlorinated aliphatic hydrocarbons (CAHs) were evaluated as potential risk factors for astrocytic brain tumors. Job-exposure matrices for six individual CAHs and for the general class of organic solvents were applied to data from a case-control study of brain cancer among white men. The matrices indicated whether the CAHs were likely to have been used in each industry and occupation by decade (1920-1980), and provided estimates of probability and intensity of exposure for “exposed” industries and occupations. Cumulative exposure indices were calculated for each subject. Associations of astrocytic brain cancer were observed with likely exposure to carbon tetrachloride, methylene chloride, tetrachloroethylene, and trichloroethylene, but were strongest for methylene chloride. Exposure to chloroform or methyl chloroform showed little indication of an association with brain cancer. Risk of astrocytic brain tumors increased with probability and average intensity of exposure, and with duration of employment in jobs considered exposed to methylene chloride, but not with a cumulative exposure score. These trends could not be explained by exposures to the other solvents.

No full-text available

Request Full-text Paper PDF

To read the full-text of this research,
you can request a copy directly from the authors.

... There was little evidence of associations in the studies of breast cancer [36], pancreatic cancer [37], kidney cancer [38] or rectal cancer [39]. Two case-control studies of dichloromethane exposure and brain cancer have been conducted [40,41]. The stronger of these studies in terms of detail of exposure data was the Heineman et al. study based on cases identified using death certificates from southern Louisiana, northern New Jersey, and the Philadelphia area, with confirmation of diagnosis using hospital records [41]. ...
... Two case-control studies of dichloromethane exposure and brain cancer have been conducted [40,41]. The stronger of these studies in terms of detail of exposure data was the Heineman et al. study based on cases identified using death certificates from southern Louisiana, northern New Jersey, and the Philadelphia area, with confirmation of diagnosis using hospital records [41]. Controls (frequency matched to cases by age, year of death, and study area) were randomly selected from the death certificates of white males who died of causes other than brain tumors, cerebrovascular disease, epilepsy, suicide, and homicide. ...
... The job exposure matrix approach is based on work in the 1990s by the National Cancer Institute [42,43]. There is a considerable range among these studies, however, in the detail and quality of the exposure information upon which the classification scheme could be applied, from death certificate occupation data [36,37,40], to interview-based information on most recent and usual jobs [38], to a lifetime job history [39,41]. Dell et al. noted the limitation of the lack of direct exposure measures in this type of assessment, and the difficulty in categorizing jobs with occasional exposure to a specific solvent [44]. ...
Article
Full-text available
Dichloromethane (methylene chloride) is a widely used chlorinated solvent. We review the available epidemiology studies (five cohort studies, 13 case-control studies, including seven of hematopoietic cancers), focusing on specific cancer sites. There was little indication of an increased risk of lung cancer in the cohort studies (standardized mortality ratios ranging from 0.46 to 1.21). These cohorts are relatively small, and variable effects (e.g., point estimates ranging from 0.5 to 2.0) were seen for the rarer forms of cancers such as brain cancer and specific hematopoietic cancers. Three large population-based case-control studies of incident non-Hodgkin lymphoma in Europe and the United States observed odds ratios between 1.5 and 2.2 with dichloromethane exposure (ever exposed or highest category of exposure), with higher risk seen in specific subsets of disease. More limited indications of associations with brain cancer, breast cancer, and liver and biliary cancer were also seen in this collection of studies. Existing cohort studies, given their size and uneven exposure information, are unlikely to resolve questions of cancer risks and dichloromethane exposure. More promising approaches are population-based case-control studies of incident disease, and the combination of data from such studies, with robust exposure assessments that include detailed occupational information and exposure assignment based on industry-wide surveys or direct exposure measurements.
... Much less information is available about the specific factors involved in the increased risk observed for some occupations. By using job-exposure matrices (JEM), there is some inconclusive evidence of a higher risk among those exposed to solvents [Rodvall et al., 1996], chlorinated aliphatic hydrocarbons [Heineman et al., 1994;Anttila et al., 1995], and lead [Cocco et al., 1998b]. Those exposed to pesticides have shown a higher risk when compared to the general population [Blair et al., 1983;Figa-Talamanca et al., 1993]. ...
... Exposure to some solvents and PAH has been related to brain cancer incidence [Anttila et al., 1995] and mortality [Heineman et al., 1994], and specifically with glioma [Rodvall et al., 1996]. No association with these substances was found in our data. ...
Article
Full-text available
BACKGROUND: Occupational exposures may be related to the development of brain cancer. The objective was to estimate occupational-specific risk of gliomas and meningiomas among Swedish men and women gainfully employed in 1970 over the period 1971-1989, and the influence of occupational exposure to chemical substances. METHODS: A dataset linking cancer diagnoses from the Swedish national cancer register to occupational and demographical data obtained in the 1970 census was used to fit log-linear Poisson models, in order to obtain relative risks adjusted by age, period, geographical area and town size. Exposure to 13 chemicals was assessed using a Swedish job-exposure matrix. RESULTS: The main findings of this study among men were the increased risk of glioma with occupational exposure to arsenic, mercury, and petroleum products and of meningioma with lead. Women in occupational sectors with a higher socio-economic status showed an increased incidence of both, gliomas and meningiomas. CONCLUSIONS: Occupational exposure to some chemicals appeared to be related with an increased risk of glioma and meningioma in men. Exposures involved in glioma and meningioma development seemed to be different
... Exposure to magnetic fields has also been associated with an increased risk of glioblastoma multiforme in men (Villeneuve et al, 2002). Two studies have found an association between maternal consumption of nitrosamine, which is found in cured meats, and the incidence of childhood astrocytomas (Preston- Martin, 1982) and exposure to these compounds has been proposed as a potential risk factor astrocytoma (Heineman et al 1994). Exposure to high levels of organic solvents such as methylene chloride, has also been shown associated with an increase in incidence of glioblastoma (Heineman et al, 1994). ...
... Two studies have found an association between maternal consumption of nitrosamine, which is found in cured meats, and the incidence of childhood astrocytomas (Preston- Martin, 1982) and exposure to these compounds has been proposed as a potential risk factor astrocytoma (Heineman et al 1994). Exposure to high levels of organic solvents such as methylene chloride, has also been shown associated with an increase in incidence of glioblastoma (Heineman et al, 1994). While these findings may implicate an environmental component to this form of cancer, they do not explain the disproportionate number of men compared to women who develop glioblastoma tumors. ...
... Three consecutive case-control studies of glioma and other cause deaths used occupational information from death certificates, 13 next-of-kin interviews 14 and job-exposure matrices 15 16 to estimate solvent exposure with the strongest association for methylene chloride and risk of glioma with increasing probability of exposure and with increasing duration of exposure in high-exposed jobs. 15 Using a different set of job-exposure matrices associating women's occupations on death certificates with estimated intensity and probability of exposure to chlorinated solvents, Cocco et al 17 found an increased risk for solvents and, in particular, for methylene chloride by increasing probability of exposure, but not by intensity of exposure. ...
... Only one previous study 12 included interviews with cases and controls. In the others, occupational information was obtained entirely from cases, 11 from proxies [13][14][15] or was based on a single occupation on a death certificate. 17 Of the two population-based participantinterviewed case-control brain cancer studies reporting on solvent exposure to date, Rodvall et al 12 reported a positive association based on self-reported and assessed exposure to solvents (benzene, toluene, trichloroethylene and xylene) by 15 cases and 20 controls. ...
Article
Full-text available
Objectives: Occupational exposure to chlorinated aliphatic solvents has been associated with an increased cancer risk, including brain cancer. However, many of these solvents remain in active, large-volume use. We evaluated glioma risk from non-farm occupational exposure (ever/never and estimated cumulative exposure) to any of the six chlorinated solvents--carbon tetrachloride, chloroform, methylene chloride, trichloroethylene, tetrachloroethylene or 1,1,1--trichloroethane-among 798 cases and 1175 population-based controls, aged 18-80 years and non-metropolitan residents of Iowa, Michigan, Minnesota and Wisconsin. Methods Solvent use was estimated based on occupation, industry and era, using a bibliographic database of published exposure levels and exposure determinants. Unconditional logistic regression was used to calculate ORs adjusted for frequency matching variables age group and sex, and age and education. Additional analyses were limited to 904 participants who donated blood specimens (excluding controls reporting a previous diagnosis of cancer) genotyped for glutathione-S-transferases GSTP1, GSTM3 and GSTT1. Individuals with functional GST genes might convert chlorinated solvents crossing the blood-brain barrier into cytotoxic metabolites. Results: Both estimated cumulative exposure (ppm-years) and ever exposure to chlorinated solvents were associated with decreased glioma risk and were statistically significant overall and for women. In analyses comparing participants with a high probability of exposure with the unexposed, no associations were statistically significant. Solvent-exposed participants with functional GST genes were not at increased risk of glioma. Conclusions: We observed no associations of glioma risk and chlorinated solvent exposure. Large pooled studies are needed to explore the interaction of genetic pathways and environmental and occupational exposures in glioma aetiology.
... Chlorinated aliphatic hydrocarbons pass through the blood-brain barrier because of their high solubility in fats (Sato and Nakajima, 1979). Exposure to methylene chloride, carbon tetrachloride, tetrachloroethylene, and trichloroethylene assessed through a job exposure matrix showed a higher risk of astrocytic brain cancers (Heineman et al., 1994). ...
... The strongest association was noted for methylene chloride, for which relative risks increased with duration of employment and average intensity of exposure (Heineman at al., 1994). ...
Article
Full-text available
A retrospective mortality and cancer incidence study of former nuclear weapons assemblers from the Iowa Army Ammunitions Plant was conducted. This study examined whether or not workers at the plant exhibited higher rates of mortality or cancer as a result of their work-related activities. Potential exposures included radiation, beryllium, asbestos, and solvents. Cancer incidence was determined by calculating standardized incidence ratios (SIR) and using the Iowa population as reference. SIRs were calculated on 3,889 workers from1969-2005. Overall and cause-specific mortality was determined by calculating standardized mortality ratios (SMR) and using the U.S. and Iowa populations as reference. SMRs were calculated on 5,743 workers from 1947-2005. The SIR results showed that overall cancer incidence was lower than the Iowa population. Using the Iowa population as reference, the SMR analyses for men demonstrated excesses for all cancers (SMR 1.09, 95% CI 1.02-1.17), lung cancer (SMR 1.38, 95% CI 1.24-1.54), diseases of the respiratory system (SMR 1.15, 95% CI 1.03-1.46), mesothelioma (SMR 6.20, 95 % 1.28-18.1), asbestosis (SMR 9.28, 95% CI 1.12-33.5) and COPD (SMR 1.27, 95% CI 1.10-1.46). Significantly lower SMRs were observed stomach cancer and ischemic heart disease. For women excesses were observed for all cancers (SMR 1.41, 95% CI 1.17-1.69), lung cancer (SMR 2.47, 95% CI 1.72-3.44), ischemic heart disease (SMR 1.32, 95% CI 1.09-1.58), respiratory diseases (SMR 1.59, 95% CI 1.14-2.16), and COPD (SMR 2.47, 95% CI 1.60-3.65). Using the U.S. population, men experienced lower overall mortality while women had significantly higher overall mortality. In conclusion, the SIR portion of the study showed overall lower cancer incidence for both men and women. This may be due to the Healthy Worker Effect and the limited dates of study. There are no cancer registry data before 1969 thus missing cancers with short induction periods. Workers may have also moved out of the Iowa and had a cancer diagnosis in another state. Compared to Iowa population, there was an excess of respiratory disease deaths and deaths from lung cancer in both men and women. Considering the significant respiratory exposures workers may have experienced, further study with a nested case-control design is suggested.
... C1-C5 low-carbon aliphatic hydrocarbons are the basic raw materials for petrochemical industry, especially ethylene and propylene, and C4 and C5 conjugated olefins. These are the most widely used in petrochemical industry (Domańska and Marciniak 2008;Heineman et al. 2010;Stroud et al. 2010). Unsaturated fatty acids are essential fatty acids that maintain the relative fluidity of the cell membrane to preserve the normal physiological functions of the cells. ...
Article
Cotinus nana W. W. Smith is a valued landscape shrub and a good afforestation species that is also widely used in the pharmaceutical industry. In this study, the use of Cotinus nana’s bark (CNB) as biofuel and a biochemical under the catalysis of nano-Co3O4/NiO was explored by various thermogravimetric methods and Fourier transform infrared (FTIR) analysis. The bark powder was extracted using a methanol/benzene solution, and then analyzed by FTIR and gas chromatography-mass spectrometry (GC-MS). The results showed that the pyrolysis products of CNB are rich in phenols, alcohols, and biofuels. The Co3O4 and NiO act as nanometal catalysts in the release of pyrolysis gases, accelerating the precipitation of gaseous products. Among them, NiO has the most obvious catalytic effect in the pyrolysis process of the material components. At the same time, in the temperature range of 40 to 850 °C, as the pyrolysis rate of the sample increases, the pyrolysis process becomes more intense. In contrast, the contents of the extracts N,N-diethyl-formamide, butyric acid, and oleic acid are not only widely used in industry, but also play a pivotal role in medicine. Therefore, the bark of Cotinus nana is an excellent plant material for biofuels and biochemicals.
... incidence in humans but these studies are also often confounded by multiple exposures of the subjects involved (Blair et. al., 1990(Blair et. al., , 1998. In one case-control study, elevated risks for brain cancer associated with long exposures to carbontetrachloride were observed, but again the subjects were exposed to a number of other chemicals (Heineman et. al., 1994). The carcinogenicity of carbontetrachloride has been studied in experimental animals (Nagano et. al., 1998;NCI, 1976) and it has been classified as a group 2B carcinogen , indicating that there is sufficient evidence of CCl4 carcinogenicity in animals, and it is considered as 'possibly carcinogenic to humans' (IARC, 1999a). As with chlo ...
... Associations of human glial brain cancers were observed with exposure to chlorinated solvents carbon tetrachloride, trichloroethylene, tetrachloroethylene and methylene chloride which were strongest for the methylene chloride (also called dichloromethane) Heineman et al., 1994). This nonflammable, colorless volatile liquid is utilized as a solvent in paint removers but is also employed as a solvent in the production of pharmaceuticals, as a degreasing agent, as an ethane foam blowing agent, in aerosol formulations and in electronics manufacturing. ...
Article
Full-text available
Many investigations exist regarding the effect of the DNA repair enzyme MGMT (O6-methylguanine- DNA-methyltransferase)-encoding gene methylation on the antineoplasticity of temozolomide in glioblastoma patients. However, there exist surprisingly lesser studies regarding the associations between MGMT enzyme biochemistry with glial carcinogenesis. MGMT involves in risk of malignancies associated with ionizing radiation, smoking, exposure to polycyclic aromatic hydrocarbons, chlorinated solvents, vinylchloride and hairdyes. All these factors are also proposed to link with gliomagenesis, yet MGMT interactions with these carcinogens in gliomagenesis are not studied yet. In future, MGMT sequencing may be employed in vulnerable populations working in industries associated with exposure to these carcinogens to develop preventive strategies. Given that MGMT is involved in DNA repair, a polymorphism may simultaneously modify the risk of gliomas while enhancing temozolomide cytotoxicity in both marrow and tumor cells.
... Exhaustive studies on electromagnetic fields, pesticides, solvents, and other chemicals have largely been inconclusive [3]. However, one study did suggest an association with exposure to carbon tetrachloride [10] and methylene chloride [11]. CMV may oncogenically promote GBM [5][6][7]. ...
Article
Full-text available
High-grade gliomas are the most common primary brain tumors in adults. However, with an incidence of 4/100,000 per year, glioblastoma multiforme is uncommon enough to make simultaneous presentation of identical tumors in husband and wife exceedingly rare. We report the fourth couple in the literature presenting with malignant astrocytomas concurrently. Despite being divorced and living apart for two decades, they presented on the same day, overhearing and recognizing each other’s voice in the emergency room. We include here the molecular characteristics of the tumors in both husband and wife, favoring the independent development of concurrent primary glioblastomas. Despite the number of conjugal presentations reported, genotoxicity and gliomagenesis may remain a completely independent event in spouses, dependent on endogenous factors damaging DNA. The slowly increasing incidence of gliomas, with nearly 100% correct nosologic recognition of this tumor entity, may lead to further recognition of independent but concurrent brain tumors in spouses.
... However, there are many occupations in the building and construction and agriculture where low-level solvent exposure may be encountered. With regard to specific solvent exposures, results have been inconsistent, but methylene chloride has been associated with astrocytic brain cancer (Heineman et al, 1994). Many past occupational studies that investigated the generic exposure of 'solvents' were limited due to poor exposure assessment methodology, small numbers, and the presence of multiple chemical exposures (Benke et al, 2001). ...
Article
Background: The aetiology of glioma remains largely unknown. Occupational solvent exposure has been suggested as a putative cause of glioma, but past studies have been inconsistent. We examined the association between a range of solvents and glioma risk within the INTEROCC project, a study of brain tumours and occupational exposures based on data from seven national case-control studies conducted in the framework of the INTERPHONE study. We also investigated associations according to tumour grade. Methods: Data from the seven countries were standardised and then combined into one aggregate data set. Pooled odds ratios (ORs) were estimated for adjusted models that included sex, age, country-region of residence and level of educational attainment. Exposures to any solvent or 11 specific solvents or subgroups were assessed using a modified version of the FINJEM job exposure matrix (JEM) specifically developed for the study, called INTEROCC-JEM. Results: Analysis included 2000 glioma cases and 5565 controls. For glioma and ever/never exposure to any solvent, the OR was 0.91 (95% confidence interval: 0.74-1.11). All ORs were <1.0 for specific solvents/subgroups. There were no increases in risk according to high or low grade of tumour. Conclusions: The results of this study show no consistent associations for any solvent exposures overall or by grade of tumour.British Journal of Cancer advance online publication 14 September 2017; doi:10.1038/bjc.2017.285 www.bjcancer.com.
... Exposure among inspectors, truck drivers, and warehouse workers was considered to occur sporadically, by contact and/or by inhalation. Different exposure levels, as defined in qualitative or semiquantitative terms, have been shown to differentiate in an exponential and not a linear fashion (Gomez et al. 1994). Therefore, we made the assumption that subjects with sporadic and indirect exposure to DDT had a daily intake corresponding to 110 2 times that of subjects directly exposed as DDT applicators. ...
Article
To explore endocrine effects in relation to para,paradichloro-diphenyl-dichloro ethylene (p,p-DDE) body burden and past occupational exposure to its precursor dichloro-diphenyl-trichloro ethane (DDT), we assayed serum sex hormones, including serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), 17-estradiol (E2), testosterone and sex hormone binding globulin (SHBG), and p,p-DDE levels in 107 male participants in a 1946–1950 anti-malarial campaign in Sardinia, Italy. Cumulative DDT exposure during the anti-malarial operations was retrospectively estimated from detailed reports of the anti-malarial agency. Ortho,paraDDE, and its precursor ortho,para-DDT were always below the detection limit. p,p-DDT was detected in 14/107 subjects, and p,p-DDE in 106/107 subjects. The median lipid-adjusted p,p-DDE serum concentration over the total study population was 396 parts per billion (interquartile range 157–1045), and it did not vary according to the job at the time of anti-malarial operations, nor was it affected by cumulative DDT exposure. LH, FSH, and SHBG, but not testosterone or E2, showed a significant positive correlation with age. Neither current serum p,p-DDE nor past cumulative DDT exposure affected sex hormone concentrations. Our results suggest that (1) the low current p,p-DDE serum concentration does not affect serum hormone levels, and (2) past cumulative DDT exposure is not correlated with the current p,p-DDE serum level, nor does it show persistent effects on serum hormone levels.
... The risk posed to human health by DCM is uncertain because no long-term adverse effects have been seen following occupational exposure. A number of cohort studies have not provided any epidemiological evidence to link DCM exposure with a higher incidence of human cancer [17][18][19]. ...
Article
Recently, cholangiocarcinoma has epidemically developed among young adult workers of a printing company in Japan. Exposure to organic solvents including 1,2-dichloropropane and/or dichloromethane is supposed to be associated with the carcinoma development. The metabolism of dichloromethane proceeds through a Theta-class glutathione S-transferase (GST) T1-1-catalyzed pathway, where its reactive intermediates have been implicated in genotoxicity and carcinogenicity. This study examined features of the carcinogenic process of the cholangiocarcinoma developed in the printing company. Surgically resected specimens of the cholangiocarcinoma cases were analyzed, where all cases were associated with precursor lesions such as biliary intraepithelial neoplasia (BilIN) and/or intraductal papillary neoplasm of the bile duct (IPNB). Immunohistochemical analysis confirmed constitutional expression of GST T1-1 in normal hepatobiliary tract. Immunostaining of γ-H2AX, a marker of DNA double strand break, showed that its expression was significantly increased in foci of BilIN, IPNB and invasive carcinoma as well as in non-neoplastic biliary epithelial cells of the printing company cases when compared to that of control groups. In the printing company cases, immunohistochemical expression of p53 was observed in non-neoplastic biliary epithelial cells and BilIN-1. Mutations of KRAS and GNAS were detected in foci of BilIN in one out of 3 cases of the printing company. These results revealed different carcinogenic process of the printing company cases, suggesting that the exposed organic solvents might act as a carcinogen for biliary epithelial cells by causing DNA damage, thereby contributing to the carcinoma development.
... Dacarbazine Ohgaki and Kleihues 2005 Diethyl sulfate Ohgaki and Kleihues 2005 Diisopropyl sulfate Ohgaki and Kleihues 2005 Dimethyl sulfate Ohgaki and Kleihues 2005 Epichlorohydrin Ohgaki and Kleihues 2005 Ethylnitrosourea Ohgaki and Kleihues 2005 Formaldehyde Ohgaki 2009 Glycidol Ohgaki and Kleihues 2005 Hair dyes Connelly and Malkin 2007 n-Hexane Beall et al. 2001 Lead van Wijngaarden and Dosemeci 2006; Clapp et al. 2008 Mercury Ohgaki 2009; Clapp et al. 2008 Methyl methanesulfonate Ohgaki and Kleihues 2005; Heineman et al. 1994 ...
Article
Full-text available
Age-adjusted brain cancer rates vary more than fourfold among US counties, but risk factors underlying this variation have not been identified. The only known risk factor for brain cancer is ionizing radiation at therapeutic dose levels. Lifestyle factors are not known to affect brain cancer risk; hypothetical risks from environmental or occupational exposures to numerous chemicals have been suggested, but no consistent results have emerged in populations exposed to chemicals via oral intake or inhalation. We investigated whether county-by-county brain cancer incidence rates and mortality rates were correlated with patterns of local ambient air pollution. We utilized central-site ambient measurement data for criteria air pollutants, and inhalation exposure concentrations of hazardous air pollutants (HAPs) as predicted by the US EPA National Air Toxics Assessment. We selected 30 HAPs that had been variously hypothesized in the context of a link to brain cancer risk. We also included a regression on density of domestic cattle populations given that viruses have been implicated in brain cancer and cattle are a well-known reservoir for a variety of viruses. The analyses yielded correlations that were mostly null or negative, with similar results obtained for brain cancer incidence and mortality rates. The cattle density correlations were slightly positive and statistically significant. Given the limitations of this exploratory analysis, further research is needed to investigate the role of environmental chemical exposures in brain cancer risk. Our findings suggest that county-by-county differences in air pollution exposure concentrations are not likely to be explanatory factors for variations in brain cancer rates.
... Another means of improving the performance of a matrix is to introduce not only the occupation but also the industrial sector or the facility or the work environment. Accuracy improves, with a reduction in the classification errors and a consequent improvement in statistical power (Bouyer and Hemon, 1994), as mentioned by several studies (Kauppinen and Partanen, 1988;Heineman et al., 1994;Kelsh et al., 2000). Considering the difficulties of using jobs, as defined in the personnel files, which are not precise enough to be associated with occupational risks, we decided to develop a Facility-Exposure Matrix, "CEA-EXPO", rather than, a Job-Exposure Matrix. ...
Article
Full-text available
A "Facility-Exposure Matrix" (FEM) is proposed to assess exposure to chemical carcinogens and radionuclides in a cohort of nuclear workers. Exposures are to be attributed in the following way: a worker reports to an administrative unit and/or is monitored for exposure to ionising radiation in a specific workplace. These units are connected with a list of facilities for which exposure is assessed through a group of experts. The entire process of the FEM applied in one of the nuclear centres included in the study shows that the FEM is feasible: exposure durations as well as groups of correlated exposures are presented but have to be considered as possible rather than positive exposures. Considering the number of facilities to assess (330), ways to simplify the method are proposed: (i) the list of exposures will be restricted to 18 chemical products retained from an extensive bibliography study; (ii) for each of the following classes of facilities: nuclear reactors, fuel fabrication, high-activity laboratories and radiation chemistry, accelerators and irradiators, waste treatment, biology, reprocessing, fusion, occupational exposure will be deduced from the information already gathered by the initial method. Besides taking into account confusion factors in the low doses epidemiological study of nuclear workers, the matrix should help in the assessment of internal contamination and chemical exposures in the nuclear industry.
... Unlike our study, Heineman and colleagues found some evidence for an increased risk of astrocytic brain tumours related to occupational exposure to DCM, and weak or no evidence for the other five solvents evaluated, although they did observe some elevated ORs for carbon tetrachloride and TCA. 26 Similarly, Cocco and colleagues found some evidence for an increased risk in women of central nervous system tumours, in general, related to DCM, but no clear pattern by probability or intensity of exposure; they did not examine risks in men. 27 Cocco and colleagues did not assess exposure to specific chlorinated solvents other than DCM, although they did evaluate chlorinated aliphatic hydrocarbons as a group, nor did they specifically evaluate risks of glioma or benign meningioma. ...
Article
Full-text available
Chlorinated solvents are classified as probable or possible carcinogens. It is unknown whether exposure to these agents increases the risk of malignant or benign brain tumours. Our objective was to evaluate associations of brain tumour risk with occupational exposure to six chlorinated solvents (ie, dichloromethane, chloroform, carbon tetrachloride, 1,1,1-trichloroethane, trichloroethylene and perchloroethylene). 489 glioma cases, 197 meningioma cases and 799 controls were enrolled in a hospital-based case-control study conducted at three USA hospitals in Arizona, Massachusetts and Pennsylvania. Information about occupational history was obtained through a detailed inperson interview that included job-specific modules of questions such that the interview was tailored to each individual's particular work history. An industrial hygienist assessed potential solvent exposure based on this information and an exhaustive review of the relevant industrial hygiene literature. Unconditional logistic regression models were used to calculate OR and 95% CI for each solvent for ever/never, duration, cumulative, average weekly and highest exposure. Overall, we found no consistent evidence of an increased risk of glioma or meningioma related to occupational exposure to the six chlorinated solvents evaluated. There was some suggestion of an association between carbon tetrachloride and glioma in analyses restricted to exposed subjects, with average weekly exposure above the median associated with increased risk compared with below the median exposure (OR = 7.1, 95% CI 1.1 to 45.2). We found no consistent evidence for increased brain tumour risk related to chlorinated solvents.
... A usual job with medium or high exposure to carbon tetrachloride was independently associated with development of GBM; examples of such occupations included dry cleaners, firemen, chemists, machinists, and radio/TV repairmen. The association of carbon tetrachloride and other chlorinated aliphatic hydrocarbons has been reported previously [18]. An epidemiologic investigation showed elevated brain cancer mortality was associated with cumulative exposure to chlorinated hydrocarbons [19]. ...
Article
Full-text available
Glioblastoma multiforme (GBM) is the most common adult primary malignant brain tumor. Ninety percent of adult GBM patients die within 24 months after diagnosis. The etiology of GBM is unknown. The Honolulu Heart Program (HHP) and Honolulu-Asia Aging Study (HAAS) are prospective, cohort studies of cardiovascular and neurodegenerative disease based on 8,006 Japanese-American men followed since 1965. The Japan Hawaii Cancer Study provides data on incident cancer cases in the HHP/HAAS cohort. We used data from these studies to obtain epidemiologic information about GBM. GBM cases were identified by searching the 1965-1998 databases using International Classification of Diseases (ICD-9) codes. Nine histologically confirmed GBM cases, 58-80 years old, were identified. The incidence rate was 6.2/100,000 person-years. Records of each case were reviewed. Selected variables from the first three examinations (1965-1968; 1968-1970; 1971-1974) were used to identify potential candidate GBM risk factors. A multivariate Cox proportional hazards model showed sugar intake and occupational exposure to carbon tetrachloride were independently and significantly associated with development of GBM.
... HAPs are a heterogeneous grouping of toxicants including chlorinated solvents (e.g., vinyl chloride), aromatic solvents (e.g., benzene), and heavy metals (e.g., cadmium). Among these pollutants, there is limited and equivocal evidence that chlorinated solvents are associated with adult [10,11] and childhood brain tumors [3,12,13]. Chlorinated solvents are a family of chemical compounds that are commonly used in many industrial settings. ...
Article
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 US 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.
Chapter
Malignant tumors of the central nervous system in adults comprise a heterogeneous group of malignancies, the largest subgroups comprising astrocytomas, ependymomas, and oligodendrogliomas. Glioblastomas are the most common tumor type, and they have dismal prognosis. Due to differences in cell type of origin, as well as pathogenesis, it is plausible that their etiology also differs between tumor types.
Chapter
The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has re‐evaluated tetrachloroethylene [127‐18‐4] to derive a maximum concentration at the workplace (MAK value), considering all toxicity endpoints. Available study reports and publications are described in detail. Results from human studies do not point to a genotoxic potential of tetrachloroethylene. In vitro and in vivo studies in mammalian cells do not show a distinct genotoxic potential. From epidemiologic and animal studies there is concern that tetrachloroethylene could be carcinogenic for humans; therefore, tetrachloroethylene has been classified in Carcinogen Category 3B. However, since carcinogenic effects are judged to be not predominantly caused by genotoxic mechanisms, a MAK value can be derived. Neurotoxicity is considered the most sensitive endpoint for tetrachloroethylene. In volunteers, repeated daily 4‐hour inhalation exposure caused small but significant effects on visual evoked potentials. The NOAEC was 10 ml/m3, but as only weak effects were observed at the LOAEC of 50 ml/m3, 20 ml/m3 is regarded as the NAEC. As a doubling of uptake is expected under workplace conditions, a MAK value of 10 ml/m3 has been set. As the critical effect is systemic, tetrachloroethylene is assigned to Peak Limitation Category II. The default excursion factor of 2 is set as the half‐life in the central nervous system is unknown. There is limited evidence suggesting that women working in a dry‐cleaner have an increased risk of spontaneous abortion. But the limited validity of the studies is not sufficient to prove a causal relationship. In developmental toxicity studies, NOAECs for developmental toxicity of 65 and 217 ml/m3 in rats, 500 ml/m3 in rabbits, and a LOAEC of 217 ml/m3 in mice were obtained. The NOAEC for behavioural toxicity in the offspring of treated rats was 100 ml/m3. The differences between these NOAECs as well as the LOAEC and the MAK value are considered so large that damage to the embryo or foetus is unlikely when the MAK value is observed. Therefore, tetrachloroethylene is classified in Pregnancy Risk Group C. Sensitization is not expected due to results of animal studies and experience in humans. Skin contact is expected to contribute significantly to the systemic toxicity of tetrachloroethylene. Therefore, designation with an “H” is confirmed.
Article
Background This study was carried out in response to worker concerns over their exposure to lead solder and chlorinated solvents at automotive electronics manufacturing plants in Huntsville, Alabama. Methods A study of 4396 United Autoworkers members ever‐employed at the plants between 1972 and 1993 was conducted with mortality follow‐up through 2016. Poisson regression was used to estimate mortality rate ratios (RR) according to employment characteristics, including calendar period of employment. Results Pre‐1977 hires exhibited elevated adjusted rates of all‐cause (RR, 1.29; 95% confidence interval [CI], 1.09‐1.52), cardiovascular (RR, 1.38; 95% CI, 1.03‐1.86), and digestive system (RR, 2.31; 95% CI, 1.04‐5.10) disease mortality relative to the most recent hire group (1984‐1993). Never‐ versus ever‐employment in a skilled trade job was associated with elevated adjusted rates of all‐cause, all‐cancer, and cardiovascular disease mortality. Nervous system disorder mortality was greatest among 1977‐1983 hires. Conclusions Elevated mortality among pre‐1977 hires is consistent with worker concerns over greater exposure to hazards at the original plant building.
Article
Background Workers raised concerns over suspected excesses of mortality at automotive electronics manufacturing facilities in Huntsville, Alabama. Methods A study of 4396 UAW members ever‐employed at Huntsville facilities between 1972 and 1993 was conducted with mortality follow‐up through 2016. Standardized Mortality Ratios (SMRs) were estimated using U.S. and Alabama reference rates. Results Relative to U.S. rates, there was a modest excess of all‐cause mortality among White female workers (SMR 1.08, 95%CI: 0.99‐1.18) and among all workers hired <1977 at the original plant building (SMR 1.10, 95%CI: 0.99‐1.22). There was excess nervous system disorder (SMR 1.24, 95%CI: 0.91‐1.65) and brain and nervous system cancer (SMR 1.31, 95%CI: 0.67‐2.28) mortality. Estimates for several causes of interest were imprecise. Conclusions All‐cause mortality estimates were greater than anticipated based on results from other UAW cohorts. The excess of nervous system disease mortality is consistent with other studies of electronics workers exposed to lead‐solder and chlorinated solvents.
Article
Background: The health risks associated with dichloromethane (DCM) for the general population living near industrial activities have not yet been quantified, primarily due to lack of epidemiological datasets. In the absence of such human data, we undertook a cancer cluster investigation in Cyprus around a historically using DCM plant producing shoe soles that were globally exported. We designed the methodology to investigate the possible existence of a cancer cluster in the area around the factory (point zero) and within a radius of 500 meters. Methods: A retrospective comparative population study was designed using a group of cancer patients living or working in the chosen geographical area around the factory. Results: Mean stack emissions of DCM of 88 mg/Nm3 and flow rates of 850 g/h exceeded the permissible DCM limits established for industrial zones. Brain and central nervous system (CNS) cancer incidence rates showed significant (P < 0.001) increase in the study area around the plant when compared with those observed in other areas of Cyprus. Calculated standardized incidence ratios for brain/CNS after adjusting for the age at diagnosis ranged from 11.3-25.7 [mean 6.5 (3.02 : 12.3)] for the study area. Conclusions: We showed the association between chronic, unintentional DCM exposures and brain/CNS cancer cases for the general population located in a residential area being in close proximity with a plant historically emitting DCM.
Chapter
Malignant tumors of the central nervous system (CNS) occur mainly in the brain, as the anatomic site is in the other parts of the CNS only in <10 %. Less than 10 % of gliomas are spinal, and their most common histological type is ependymoma, but low-grade astrocytomas are not infrequent. Brain and other CNS cancers make up approximately 2 % of all primary cancers and, with a global total of 238,000 cases, rank as the 16th most common type of cancer. The occupational etiology of brain cancers has not been well established. Increased brain cancer risks have been reported in agricultural occupations and among physicians. However, the specific agents that could explain the excesses have not been identified. High doses of ionizing radiation increase the risk, but the role of the doses within the current workplace regulations is unclear, with the effect size predicted by linear extrapolation from higher doses being very low. Despite considerable efforts, no consistent evidence linking occupational exposure to electromagnetic fields or pesticides with brain cancer risk has been obtained.
Chapter
This chapter contains details on 12 unsaturated halogenated hydrocarbons. The considered chemicals are 1,3-dichloropropene, cis- and trans-1,2-dichloroethylene, dichloroacetylene, allyl chloride, hexachlorobutadiene, β-chloropropene, vinylidene chloride, vinyl chloride, vinyl bromide, vinyl fluoride, trichloroethylene, and tetrachloroethylene. These compounds are used as fumigants, pesticides, solvents, and chemical intermediates. This chapter follows the outline determined for compounds and includes physical and chemical properties, production and use, exposure assessment, toxic effects (experimental animal and epidemiology studies), standards, regulations, and guidelines, and studies on environmental impact.
Article
Considerable amounts of chlorinated solvents compounds were identified and measured in raw water and soil samples collected during several month studies, along the Somes River near Dej city region of Romania. The most common organochlorine solvents detected were trichloroethylene (C2HCl3), tetrachloroethylene (C2Cl4), carbon tetrachloride (CCl4) and chloroform (CHCl3) with the range between 3.05 - 68.92 μg L-1, 5.62 - 55.48 μg L-1, 2.11 - 29.45 μg L-1 and 0.37 - 80.29 μg L-1. They were detected using a mass spectrometer coupled at a gas chromatograph with electron capture detector and quantified using chlorinated solvent standards. Organochlorine compounds have different chemical properties that lead into a broad range to uses. Many of them have significant biological activities and some of them can be very toxic for plant, animals and humans. Because of that they present seriously environmental concern. This study presents the source of the pollution and also the levels of these pollutants in river water and the soil.
Article
Considerable amounts of chlorinated solvents compounds were identified and measured in raw water and soil samples collected during several month studies, along the Somes river near Dej city region of Romania. The most common organochlorine solvents detected were trichloroethene (C2HCl 3), tetrachloroethene (C2Cl4), carbon tetrachloride (CCl4) and chloroform (CHCl3) with the range between 3.05-68.92,5.62-55.48,2.11-29.45 and 0.37-80.29 μg I-1'. They were detected using a mass spectrometer coupled at a gas Chromatograph with electron capture detector and quantified using chlorinated solvent standards. Organochlorine compounds have different chemical properties that lead to a broad range of applications. Many of them have significant biological activities and some of them can be very toxic for plant, animals and humans. Because of that they present serious environmental concern. This study presents the source of the pollution and also the levels of these pollutants in river water and the soil.
Article
To examine associations between occupational exposure to selected organic solvents and meningioma. A multicentre case-control study conducted in seven countries, including 1906 cases and 5565 controls. Occupational exposure to selected classes of organic solvents (aliphatic and alicyclic hydrocarbons, aromatic hydrocarbons, chlorinated hydrocarbons and 'other' organic solvents) or seven specific solvents (benzene, toluene, trichloroethylene, perchloroethylene, 1,1,1-trichloroethylene, methylene chloride and gasoline) was assessed using lifetime occupational histories and a modified version of the FINJEM job-exposure matrix (INTEROCC-JEM). Study participants were classified as 'exposed' when they had worked in an occupation for at least 1 year, with a 5-year lag, in which the estimated prevalence of exposure was 25% or greater in the INTEROCC-JEM. Associations between meningioma and each of the solvent exposures were estimated using conditional logistic regression, adjusting for potential confounders. A total of 6.5% of study participants were ever exposed to 'any' solvent, with a somewhat greater proportion of controls (7%) ever exposed compared with cases (5%), but only one case was ever exposed to any chlorinated hydrocarbon (1,1,1-trichloroethane). No association was observed between any of the organic solvents and meningioma, in either men or women, and no dose-response relationships were observed in internal analyses using either exposure duration or cumulative exposure. We found no evidence that occupational exposure to these organic solvents is associated with meningioma.
Article
We searched MEDLINE and EMBASE for epidemiologic studies on occupational exposure to methylene chloride and risk of cancer. Estimates of study-specific odds ratios (ORs) were calculated using inverse-variance-weighted fixed-effects models and random-effects models. Statistical tests for heterogeneity were applied. We summarized data from five cohort studies and 13 case-control studies. The pooled OR for multiple myeloma was (OR 2.04; 95 % CI 1.31-3.17) in relation to occupational exposure to methylene chloride but not for non-Hodgkin's lymphoma, leukemia, breast, bronchus, trachea and lung, brain and other CNS, biliary passages and liver, prostate, pancreas, and rectum. Furthermore, we focused on specific outcomes for non-Hodgkin's lymphoma and multiple myeloma because of exposure misclassification. The pooling OR for non-Hodgkin's lymphoma and multiple myeloma was 1.42 (95 % CI 1.10-1.83) with moderate degree of heterogeneity among the studies (I (2) = 26.9 %, p = 0.205). We found an excess risk of multiple myeloma. The non-Hodgkin's lymphoma and leukemia that have shown weak effects should be investigated further.
Article
Purpose of the study During these last decades, the incidence of brain cancer has increased in the world population. Their etiologic factors are not clearly identified. The purpose of the study is to determine the clinical and professional profile of the patients suffering from Primary Malignant Brain Tumours (PMBT). Method This study is an exhaustive descriptive investigation carried out in 2004, which has interested patients with PMBT whose records have been collected from the Neurosurgery Service). The collection of the data is based on the medical files and on a standardized questionnaire which was related to professional and extra-professional data of the patients. Results Data from a total of 102 patients suffering from PMBT was collected. Glioblastoma was the most frequent histological type (61.6%). The interview has interested only 82 patients, 72 of them had an occupational activity. Workmen category was predominant (62%). The agricultural sector was the most represented with 47% of the workers who were exposed to manures and varied pesticides from average duration of 37.4±4.7 years followed by the industrial sector for 11% of the workers. Odd jobs were noted for 75% of the patients and 45% of those who had handled varied pesticides. Patients who reside in the vicinity of high voltage transmission electric lines (< 50 m) represented 21% of our studied population. Conclusion In this study, an elevated frequency of brain cancer among farmers who were exposed to manures and varied pesticides was found. Other analytical epidemiologic studies are necessary to determine the role of the pesticides and manures in the genesis of brain cancer.
Article
(This article is a US Government work and, as such, is in the public domain in the United States of America.)
Article
Objective: To reconstruct agent-specific occupational exposures for a cohort of jet engine manufacturing workers for use in an epidemiological mortality study. Methods: Potential chemical and physical exposures at eight jet engine manufacturing and overhaul/repair plants were evaluated for the period 1952 to 2001. Eleven agents were selected for detailed examination, and a job-exposure matrix was constructed. Results: Quantitative exposure estimates were generated for metalworking fluids, nickel, cobalt, chromium, solvents, and incomplete combustion aerosol from metalworking fluids. Qualitative exposure estimates were assigned for ionizing radiation, electromagnetic fields, polychlorinated biphenyls, and lead-cadmium. All exposures showed decreasing trends over the study period. Conclusions: The quantitative exposure levels generated in this study were lower than early contemporaneous professional practice recommendations and were similar to or lower than published data from other industries.
Article
Opinion statement: Standard treatment of anaplastic astrocytoma (AA) in good performance patients consists of maximal safe surgical resection followed by focal, fractionated, external beam radiotherapy (RT) alone or in combination with concurrent and adjuvant temozolomide (TMZ). Since prospective data regarding the use of chemoradiotherapy for AA is lacking, the practice is based on the extrapolation of results from a randomized study in glioblastoma (GB). Whether the data from the GB study can and should be extrapolated is controversial, although a large multicenter, randomized, phase III study is underway to define optimal initial AA treatment. Patients should be tapered off corticosteroids completely or to the lowest dose necessary to treat neurologic dysfunction. Anti-epileptic drugs (AED) are not indicated unless there is a history of seizure; levetiracetam is the preferred AED in malignant glioma (MG). Unless there is evidence of intracranial hemorrhage, venous thromboembolism (VTE) should be treated with low-molecular-weight heparin (LMWH) therapy. At recurrence, patients with good performance status are usually treated with cytotoxic chemotherapy following, or in lieu of, repeat surgery. TMZ is the preferred chemotherapeutic agent in patients without prior exposure; lomustine is recommended for tumors resistant to TMZ. In patients with neurologic dysfunction secondary to tumor edema and mass effect who are not amenable to surgery, the use of bevacizumab is associated with improved neurologic function and better quality of life. Given the limited treatment options at tumor recurrence, consideration for enrollment on a clinical trial is encouraged.
Chapter
This article contains details on eleven unsaturated halogenated hydrocarbons. These compounds are used as fumigants, pesticides, and chemical intermediates. This chapter follows the outline determined for compounds and includes physical and chemical properties, odor and warning properties, exposure assessment in air and workplace, Toxic effects includes data on the human experience, epidemiology studies, community methods for monitoring, and the standards, regulations and guidelines are discussed.
Article
Full-text available
Introduction This study contains an analysis of the risks of exposure to Dichloromethane (DCM). It also expounds the selection of several priority applications of DCM enabling restrictions on marketing and use to be considered as one of the means of reducing risks. An analysis of the socio-economic consequences of such restrictions of marketing and use are presented. Risk assessment Noteworthy is that this six-month risk assessment project can in no way be compared with the in-depth, multi-year assessments currently in progress under the Existing Substances Programme of the EU. What we did was mainly re-evaluate a number of existing extensive risk assessments on DCM (e.g. IPCS, Environmental Health Criteria 164, 1996; RIVM, Integrated Criteria Document Dichloromethane by Slooff and Ros, 1988; and ECETOC, technical reports nos. 26, 32, 34). Based on these documents, we arrived at criteria for the evaluation of short-term and long-term exposure of humans to DCM reflected in Table 0.1. The table includes data derived -as far as possible -in line with the EU Technical Guidance Document for Evaluation of Substances, and also lists the ranges of current occupational health standards applicable in EU countries.
Article
The mortality experience of two overlapping cohorts of employees engaged in the manufacture of photographic film support was evaluated to assess the potential chronic health effects of methylene chloride exposure. In the first analysis, we examined causes of death among 1311 men initially employed between 1946 (when the solvent was first used) and 1970; in the second, we updated mortality in a 1964 to 1970 employed cohort of 1013 men. Follow-up was through 1994. The mean exposure among members of the 1946 to 1970 cohort was 39 ppm (8-hour time-weighted average) for 17 years, and the median length of follow-up from first exposure was 34 years. Members of the 1964 to 1970 cohort received an average exposure of 26 ppm for 24 years; median time from first exposure was 35 years. Compared with general population vital statistics, mortality in both cohorts was below expectation for all causes of death, ischemic heart disease, and cancer, including such sites as the lung and liver, which were target organs identified in animal toxicology studies. No statistically significant increases were observed for any cause of death. The combined results of this study and three others in the photographic film and textile fibers industries (approximately 7300 subjects) show that long-term exposure to methylene chloride does not increase the risk of death from any cause including specific diagnoses that have been associated with this widely used solvent.
Article
Chlorination of drinking water results in the generation of low levels of numerous chlorinated hydrocarbons due to the reaction of chlorine with naturally occurring organic compounds in the water. Concern has been raised about the safety of these chlorinated contaminants as several of them, most notably chloroform (trichloromethane), have been shown to be carcinogenic in long-term rodent bioassays and weak correlations between trihalomethane levels in drinking water and an increased risk of bladder and colorectal cancer in humans have been found. Chloroform and carbon tetrachloride induce liver cancer in rats and mice only at doses where significant hepatotoxicity is observed and have been classed as non-genotoxic carcinogens. We have investigated the ability of chloroform, carbon tetrachloride and 1,1,1-trichloroethane to induce deletions via intrachromosomal recombination in the yeast Saccharomyces cerevisiae. Chloroform and carbon tetrachloride induced this genotoxic recombination event at similar doses, 1,1,1-Trichloroethane gave only a weak response in the DEL recombination assay and only at the highest dose. We further show that chloroform and carbon tetrachloride, but not trichloroethane, induced oxidative free radical species in our yeast strain. The free radical scavenger N-acetylcysteine reduced chloroform-induced toxicity and recombination, and both chloroform and carbon tetrachloride were able to oxidize the free radical-sensitive reporter compound dichlorofluorescein diacetate in vivo. The implications of these findings to the carcinogenic activities of the three compounds are discussed.
Article
Environmental quality standards (EQSs) have been established as desirable levels to be maintained for protection of human health and the conservation of the living environment by Basic Environment Law. EQSs in ambient air had been set for 10 substances (sulfur dioxide (SO(2)), carbon monoxide (CO), suspended particulate matter (SPM), nitrogen dioxide (NO(2)) and photochemical oxidants (Ox), benzene, tetrachloroethylene, trichloroethylene, dioxins and dichloromethane) and guideline values for 7 (acrylonitorile, vinyl chloride monomer, mercury, nickel compounds, 1,3-butadiene, chloroform and 1,2-dichloromethane) in Japan by 2009. EQSs for the classical (or traditional) air pollutants, SO(2), CO, SPM, NO(2) and Ox, were set according to the minimal requirement to protect human health, based on evidence from epidemiological studies conducted before the 1970s. In 1996, the Central Environment Council designated substances which may be hazardous air pollutants and substances requiring priority action, and adopted the concept of risk assessment to set EQSs and guideline values. A life-long risk level (virtually safe dose) of 10(-5) was used to set EQS for benzene, and guideline values for vinyl chloride monomer, nickel compounds, and 1,3-butadiene. EQSs for trichloroethylene, tetrachloroethylene and dichloromethane, and guideline values for acrylonitorile and mercury were set using uncertain factors and lowest observed adverse effect (LOAEL)/no observed adverse effect level (NOAEL). The results of animal experiments were utilized to set guideline values for chloroform and 1,2-dichloroethane. The benchmark approach and human equivalent concentration (HEC) were adopted for 1,2-dichloroethane. The history of setting EQSs and guideline values for hazardous air pollutants is one of adopting new concepts into risk assessment.
Article
To update the mortality experience of employees of a factory that produced cellulose triacetate film base at Brantham in the United Kingdom and generate information on the effects of exposure to methylene chloride, in particular, mortality from cardiovascular disease and cancers of the lung, liver and biliary tract, pancreas and brain. All 1,785 male employees with a record of employment at the film factory in 1946-1988 were followed through 2006, including 1,473 subjects exposed to methylene chloride on average for 9 years at a concentration of 19 ppm (8 h time-weighted average). A total of 559 deaths occurred during the follow-up period. In the subcohort of workers exposed to methylene chloride, substantially reduced mortalities compared with national and local rates were found for all causes, all cancers, and all the principal cancer sites of interest except for brain cancer. There was a small excess of brain cancer deaths (8 observed and 4.4 expected), but no evidence of an association with exposure to methylene chloride. Lung cancer mortality was significantly reduced in exposed workers, even compared to the low mortality rate in the local population (SMR 55). In contrast, mortality from ischaemic heart disease in exposed workers was slightly increased compared with local rates (SMR 102), but was lower in active employees (SMR 94; local rates), where a direct effect of exposure to methylene chloride should be concentrated. The study provided no indication that employment at the plant, or exposure to methylene chloride, had adversely affected the mortalities of workers.
Article
Full-text available
The goal of the studies described in this thesis was to foster the increased use of emerging scientific information and innovative methods in chemical risk assessments, in order to assure the protection of public health while limiting the economic and social consequences of over-regulation. The thesis demonstrates approaches for incorporating biokinetic and mechanistic data and mathematical modeling in risk assessment, focusing on mode of action evaluation, physiologically based biokinetic (PBBK) modeling, and benchmark dose-response (BMD) modeling. The ability of PBBK modeling to describe the interaction between chemical-specific properties, physiology, and age-dependent biochemical processes and to predict the resulting variation in risks across individuals in a population at different ages is also shown. Finally, the thesis provides cancer risk assessments for vinyl chloride, trichloroethylene, and perchloroethylene using the methodologies described in the thesis. Overall, the research described in this thesis demonstrates that the use of mode-of-action evaluation, PBBK modeling, and quantitative dose-response modeling can greatly increase the opportunity for the use of biokinetic and mechanistic data in risk assessment, resulting in approaches that are more appropriately tailored to the specific chemical and therefore provide a more accurate assessment of the potential hazards associated with human exposures.
Article
Full-text available
Trichloroethylene (TCE) has been an industrial chemical of some importance for the past 50 years. First synthesized by Fischer in 1864, TCE has enjoyed considerable industrial usage as a degreaser and limited medical use as an inhalation anesthetic and analgesic. This TCE overview provides a narrative survey of the reference literature. Highlights include history, nomenclature, physical and chemical properties, manufacture, analysis, uses, metabolism, toxicology, carcinogenic potential, exposure routes, recommended standards, and conclusions. Chemically, TCE is a colorless, highly volatile liquid of molecular formula C2HCl3. Autoxidation of the unstable compound yields acidic products. Stabilizers are added to retard decomposition. TCE's multitude of industrial uses center around its highly effective fat-solvent properties. Metabolically, TCE is transformed in the liver to trichloroacetic acid, trichloroethanol, and trichloroethanol glucuronide; these breakdown products are excreted through the kidneys. Most toxic responses occur as a result of industrial exposures. TCE affects principally the central nervous system (CNS). Short exposures result in subjective symptoms such as headache, nausea, and incoordination. Longer exposures may result in CNS depression, hepatorenal failure, and increased cardiac output. Cases of sudden death following TCE exposure are generally attributed to ventricular fibrillation. Current interest in TCE has focused on recent experimental data that implicate TCE as a cause of hepatocellular carcinoma in mice. No epidemiological data are available that demonstrate a similar action in humans. The overall population may be exposed to TCE through household cleaning fluids, decaffeinated coffee, and some spice extracts. The NIOSH recommended standard for TCE is 100 ppm as a time-weighted average for an 8-hr day, with a maximum allowable peak concentration of 150 ppm for 10 min.
Article
Full-text available
Water/air, blood/air, oil/air, oil/water, and oil/blood partition (or solubility) coefficients of 17 aromatic hydrocarbons and ketones were measured by a newly developed vial-equilibration method, which needs no direct measurements of the concentration either in the liquid or in the air phase, but only the gas chromatographic peak heights of the air in the sample (in which a test material is contained) and reference vessels (containing no test material). It was found that the blood/air partition coefficients for aromatic hydrocarbons are correlated closely with the product of water/air and oil/air partitiion coefficients, whereas those for ketones are almost in the same range as the water/air, irrespective of the oil/air partition coefficients.
Article
Full-text available
A retrospective cohort study of 14,457 workers at an aircraft maintenance facility was undertaken to evaluate mortality associated with exposures in their workplace. The purpose was to determine whether working with solvents, particularly trichloroethylene, posed any excess risk of mortality. The study group consisted of all civilian employees who worked for at least one year at Hill Air Force Base, Utah, between 1 January 1952 and 31 December 1956. Work histories were obtained from records at the National Personnel Records Centre, St. Louis, Missouri, and the cohort was followed up for ascertainment of vital state until 31 December 1982. Observed deaths among white people were compared with the expected number of deaths, based on the Utah white population, and adjusted for age, sex, and calendar period. Significant deficits occurred for mortality from all causes (SMR 92, 95% confidence interval (95% CI) 90-95), all malignant neoplasms (SMR 90, 95% CI 83-97), ischaemic heart disease (SMR 93, 95% CI 88-98), non-malignant respiratory disease (SMR 87, 95% CI 76-98), and accidents (SMR 61, 95% CI 52-70). Mortality was raised for multiple myeloma (MM) in white women (SMR 236, 95% CI 87-514), non-Hodgkin's lymphoma (NHL) in white women (SMR 212, 95% CI 102-390), and cancer of the biliary passages and liver in white men dying after 1980 (SMR 358, 95% CI 116-836). Detailed analysis of the 6929 employees occupationally exposed to trichloroethylene, the most widely used solvent at the base during the 1950s and 1960s, did not show any significant or persuasive association between several measures of exposure to trichloroethylene and any excess of cancer. Women employed in departments in which fabric cleaning and parachute repair operations were performed had more deaths than expected from MM and NHL. The inconsistent mortality patterns by sex, multiple and overlapping exposures, and small numbers made it difficult to ascribe these excesses to any particular substance. Hypothesis generating results are presented by a variety of exposures for causes of death not showing excesses in the overall cohort.
Article
Full-text available
Mortality among 5365 members of a dry cleaning union in St. Louis, Missouri, was less than expected for all causes combined (SMR = 0.9) but slightly raised for cancer (SMR = 1.2). Among the cancers, statistically significant excesses occurred for oesophagus (SMR = 2.1) and cervix (SMR = 1.7) and non-significant excesses for larynx (SMR = 1.6), lung (SMR = 1.3), bladder (SMR = 1.7), thyroid (SMR = 3.3), lymphosarcoma and reticulosarcoma (SMR = 1.7), and Hodgkin's disease (SMR = 2.1). Mortality from emphysema was also significantly raised (SMR = 2.0). Eleven of the 13 deaths from oesophageal cancer occurred among black men. The risk of this cancer showed a significant association with estimated cumulative exposure to dry cleaning solvents (rising to 2.8-fold in the highest category) but not with level or duration of exposure. Mortality from kidney cancer was not excessive as reported in other studies. Excesses for emphysema and cancers of the larynx, lung, oesophagus, bladder, and cervix may be related to socioeconomic status, tobacco, or alcohol use. Although the number of deaths was small, the greatest risk for cancers of the lymphatic and haematopoietic system (fourfold) occurred among workers likely to have held jobs where exposures were the heaviest. Small numbers and limited information on exposure to specific substances complicates interpretation of this association but is unlikely to be due to confounding by tobacco use. It was not possible to identify workers exposed to specific dry cleaning solvents but mortality among those entering the union after 1960, when use of perchloroethylene was predominant, was similar to those entering before 1960.
Article
Full-text available
Mortality was studied among 1271 employees of a cellulose fiber production plant in Rock Hill, South Carolina, in the United States. Each subject was employed for at least three months between 1 January 1954 and 1 January 1977 in jobs that entailed exposure to the highest concentrations of methylene chloride. In the cohort 122 deaths were identified through 1 September 1986, and mortality rates for the cohort were compared with mortality rates for York County, South Carolina. Deficit mortality was observed for cancers of the respiratory system, breast, and pancreas and from ischemic heart disease. Excess mortality was observed for cancers of the buccal cavity and pharynx and the liver and biliary tract, and for melanoma as well. The largest relative excess was for liver and biliary tract cancers. There were only four deaths in this category; however, three of the four deaths were cancer of the biliary tract (3 observed, 0.15 expected, standardized mortality ratio 20).
Article
Full-text available
Detailed job histories and information about other suspected risk factors were obtained during interviews with 272 men aged 25-69 with a primary brain tumor first diagnosed during 1980-1984 and with 272 individually matched neighbor controls. Separate analyses were conducted for the 202 glioma pairs and the 70 meningioma pairs. Meningioma, but not glioma, was related to having a serious head injury 20 or more years before diagnosis [odds ratio (OR) = 2.3; 95% confidence interval (CI) = 1.1-5.4], and a clear dose-response effect was observed relating meningioma risk to number of serious head injuries (P for trend = 0.01; OR for greater than or equal to 3 injuries = 6.2; CI = 1.2-31.7). Frequency of full-mouth dental X-ray examinations after age 25 related to both glioma (P for trend = 0.04) and meningioma risk (P for trend = 0.06). Glioma, but not meningioma risk, related to duration of prior employment in jobs likely to involve high exposure to electric and magnetic fields (P for trend = 0.05). This risk was greatest for astrocytoma (OR for employment in such jobs for greater than 5 years = 4.3; CI = 1.2-15.6). More glioma cases had worked in the rubber industry (discordant pairs 6/1) and more worked in hot processes using plastics (9/1). More meningioma cases had jobs that involved exposure to metal dusts and fumes (discordant pairs 13/5), and six of these cases and two controls worked as machinists. Finally, there was a protective effect among glioma pairs relating to frequency of use of vitamin C and other vitamin supplements (P for trend = 0.004); the OR for use at least twice a day was 0.4 (CI = 0.2-0.8).
Article
Full-text available
An exploratory study of brain tumors in adults was carried out using 215 cases diagnosed in Southern Ontario between 1979 and 1982, with an individually matched, hospital control series. Significantly elevated risks were observed for reported use of spring water, drinking of wine, and consumption of pickled fish, together with a significant protective effect for the regular consumption of any of several types of fruit. While these factors are consistent with a role for N-nitroso compounds in the etiology of these tumors, for several other factors related to this hypothesis, no association was observed. Occupation in the rubber industry was associated with a significant relative risk of 9.0, though no other occupational associations were seen. Two previously unreported associations were with smoking nonfilter cigarettes with a significant trend and with the use of hair dyes or sprays. The data do not support an association between physical head trauma requiring medical attention and risk of brain tumors and indicate that exposure to ionizing radiation and vinyl chloride monomer does not contribute any appreciable fraction of attributable risk in the population studied. The findings warrant further detailed investigation in future epidemiologic studies.
Book
This book seeks to present, through a combination of morphological data and physiological and neurological studies, a comprehensive survey of our knowledge of the human brain. The major emphasis is upon structural organisation, based upon the evolution of this most complex of organs. However, functional aspects, including experimental research and clinical findings, have also been incorporated, broadening the interest for students of neurobiology and clinical medicine.
Article
Little is known about the etiology of tumors of the brain and central nervous system (CNS); however, epidemiologic studies have indicated recently that excess brain and CNS tumor risk may be associated with employment in certain occupations or industries. Some studies have shown that certain white-collar professional groups (eg, artists, laboratory professionals, veterinarians, embalmers) appear to have an elevated risk of brain tumors, and they raise the issue of a diagnostic sensitivity bias. Some blue-collar occupational groups, including rubber workers, oil refinery workers, chemical plant workers, polyvinyl chloride workers, machinists, and others, have been reported to have an elevated risk of brain tumors. Most of these workers are potentially exposed to multiple chemicals; nevertheless they have some exposures in common, for example, exposure to organic solvents, lubricating oil, acrylonitrile and vinyl chloride, formaldehyde, polycyclic aromatic hydrocarbons, and phenolic compounds.
Article
Consider two matched independent series of binomial variates whose odds ratios are assumed constant, i.e. ψ = (p1iq2i)/(p2iq1i)(i =1, ..., b). Under the assumption that all marginals in each of the 2 × 2 tables are fixed, exact and approximate methods of point and interval estimation of ψ are reviewed and derived. The methods are illustrated and compared in a numerical example.
Article
A published method for analyzing multiple 2×2 contingency tables arising in retrospective studies of disease is extended in application and form. Extensions of application include comparisons of age-adjusted death rates, life-table analyses, comparisons of two sets of quantal dosage-response data, and miscellaneous laboratory applications as appropriate. Extensions in form involve considering multiple contingency tables with arbitrarily many rows and/or columns, where rows and columns are orderable, and may even be on a continuous scale. The assignment of some score for each row or column is essential to use of the method. With scores assigned, a deviation of the sum of cross products from expectation, and its variance conditioned on all marginal totals, are computed for each table and a chi square is determined corresponding to the grand total of the deviations. For various specific instances and for various scoring procedures, the procedure extends or is equivalent to the asymptotic form of many known non-parametric techniques.
Article
Consider a random sample, x1, …, xn, from a Poisson distribution. The Rao-Blackwell theorem and the completeness property of this distribution are exploited to show that E(kj\σxi = X) = x¯ (i = 1, 2, …) and to find higher conditional moments of the sample cumulants. Some possible applications to the testing of the fit of the Poisson distribution are suggested.
Book
This book discusses the ongoing battle against the effects of pesticides, herbicides, fungicides, and other toxic agents. It points out gaps in present-day research, illustrate other diseases that can mimic chemical toxicity, and emphasize thorough consideration of all aspects in a given incident prior to administering an antidote. The book offers a compiled data on target organ toxicity involving the liver, kidneys, and lungs - detailing the rapid, recent progress in this area. The coverage also highlights reproductive toxicology, food additives, asphixiant gases, and pulmonary toxicology. The partial contents are: Absorption, distribution, Biotransformation, Conjugation, and Excretion of Xenobiotics, Hepatotoxicity, Pulmonary Toxiology, Reproductive and Perinatal toxicology, Toxicology of Insecticides, Rodenticides, Herbicides, and Fungicides, Mechanisms of Metal-Induced Cell Injury, Food Additives: A Benefit/Risk Dilemma, Animal Toxins, and Toxic Effects of Chemicals on the Immune System.
Article
A historical prospective study of cancer in lamp manufacturing workers in one plant was conducted. All men and women who worked for a total of at least 6 months and were employed at some time between 1960 and 1975 were included. Work histories were abstracted and subjects were divided according to whether they had worked in the coiling and wire drawing area (CWD). Cancer morbidity from 1964 to 1982 was ascertained via the provincial registry, and was compared with the site-specific incidence in Ontario, adjusting for age, sex and calendar period. Of particular interest were primary breast and gynecological cancers in women. The cancers of a priori concern were significantly increased in women in CWD, but not elsewhere in the plant. The excess was greatest in those with more than 5 yr exposure (in CWD) and more than 15 yr since first working in CWD, with eight cases of breast and gynecological cancers observed in this category compared with 2.67 expected. Only three cancers occurred in men in CWD. Environmental measurements had not been made in the past and little information was available on substances used in the 1940s and 1950s, the period when the women with the highest excess began employment. It is known that methylene chloride and trichlorethylene have been used, but not enough is known about the dates and patterns of use to draw any conclusions about their relationship with the increase in disease.
Article
In the past 30 years, the incidence of pancreatic cancer has increased substantially. The disease now causes more deaths than all other malignant neoplasms, except those of the colorectal region, lung, and breast. A study in over 115 hospitals in five metropolitan areas showed that males with pancreatic cancer were more often employed in the dry cleaning business or in occupations involving close exposure to gasoline, increasing the risk for pancreatic cancer up to five times. Females at risk for pancreatic cancer were more likely to smoke cigarettes, to have uterine myomas, and to have undergone oophorectomy or spontaneous abortions. Generally, these patients were of higher social class and drank more wine and decaffeinated coffee than demographically similar controls. Assessment of the effects of several factors showed that relative risks increased 34-fold among females and nearly sixfold among males. While no single factor accounts for the preponderance of pancreatic cancer, a combination of factors—each associated with a relatively small risk enhancement—may very well do so. (JAMA 1981;245:147-152)
Article
Tetrachloroethane was used by the Army during World War II in the impregnation of clothing for protection against mustard gas. Thirty-nine chemical processing companies were formed: ten used tetrachloroethane as a solvent for the clothing impregnite and the remainder used a water solvent process. An age-specific analysis of mortality in relation to race, rank, and military occupational specialty (MOS) was performed in which observed numbers of deaths from principal cause groups were compared with those expected according to U.S. standard mortality rates. Overall cancer mortality for 1,099 white males with tetrachloroethane exposure was 1.26 times that of 1,319 men not involved in the impregnation process. The risks for leukemia, lymphoma, and cancers of the genital organs were moderately elevated, but the numbers were small and no significant excesses were observed. (C)1981 The American College of Occupational and Environmental Medicine
Article
Partition coefficients of water/air, blood/air, oil/air, and oil/water for twenty chlorianted hydrocarbons, which were determined by means of a vial-equilibration method, were examined in relation to their chemical structures and threshold limit values (TLVs) recommended by the American Conference of Governmental Industrial Hygienists. The TLV was correlated closely with the blood/air partition coefficient and with the product of the water/air and the oil/air partition coefficient except for carbon tetrachloride and o-dichlorobenzene. A relation between partition coefficients and toxicity of these hydrocarbons is also described.
The purpose of this investigation was to determine whether similar carboxyhemoglobin (COHb) values obtained from inhaling carbon monoxide or methylene chloride have the same behavioral effects. The effects were assessed by the performance of 12 humans on a visual-manual, dual-task, and an auditory vigilance task. The results indicated that both substances in concentrations sufficient to produce 5-percent COHb significantly impaired human performance under difficult or demanding task conditions. The conclusion was that carbon monoxide, the main metabolite of methylene chloride, was responsible for the observed performance decrements.
Article
Associations between site- and sex-specific county cancer mortality rates and levels of trihalomethanes (THM's) in drinking water were examined after adjustment of rates for the influence of multiple socioeconomic, industrial, and demographic factors. U.S. counties with sampled supplies were grouped by percent of the county population receiving water from the supply, as well as by region of the country. For two sites (bladder and lung), county rates were also adjusted for the activity level in specific high-risk industries. Positive correlations with THM levels were observed for several cancers, including bladder and brain cancers in both sexes, and non-Hodgkin's lymphoma and kidney cancer in males. Stomach cancer in females showed a negative association. Bladder cancer mortality rates showed the strongest and most consistent association with a THM exposure index, after control for differences in social class, ethnic group, urban versus rural residence, region of the United States, and industrialization of the county. These ecologic associations suggested that further evaluation in analytic investigations is warranted.
Article
The incidence of brain cancer has increased dramatically over the last decades in most developed countries. Whether these trends can be attributed to improved diagnosis is not clear. To determine the effect of new imaging technology on increased rates of brain cancer, we assessed the level of detection for neurological disorders when computed tomography (CT) and magnetic resonance imaging (MRI) results were not available. A neurologist performed a blind review of hospital charts from 356 randomly selected patients, hospitalized between 1985 and 1989 for neurological disorders, including brain cancer. All prediagnosis information except CT and MRI results was used as a basis for diagnostic re-evaluation. Also, a random sample of 151 brain cancer patients diagnosed between 1960 and 1965 was selected for a description of diagnostic methods used during that period. A comparison between the original diagnoses and the re-evaluations for patients in the 1985-1989 sample indicated that there was, among the diseases selected, a 24% misclassification when CT scans and MRI were not available. In particular, 20% of brain tumors were undetected (95% confidence interval = 15%-25%), and 10% of non-tumor disorders were inaccurately labeled as brain tumors in the absence of these tests. The repeatability of the re-evaluations was 86%. Among elderly North Americans, at least twofold increases in brain cancer incidence were observed over the last two decades. Since our findings show that CT scans and MRI are responsible for the detection of about 20% of brain tumors, we conclude that other factors also are responsible for the observed trends.
Article
The authors argue that one can never be certain whether an exposure variable which is measured with error is subject to differential misclassification in either a case-control study or a cohort study. They present hypothetic examples that demonstrate that even when misclassification is nondifferential in a 2 x 3 table, the observed odds ratios in the 2 x 2 table created by collapsing over two exposure levels can be either in the opposite direction from or more extreme than the odds ratio that would be obtained if exposures were classified correctly. The anomalies are explained by the observation that the 2 x 2 tables exhibit differential misclassification. In general, collapsing over categories which have different risks of disease and different probabilities of exposure misclassification can induce differential misclassification and even nonconservative estimates of relative risk. Collapsing of exposure levels can occur in the analysis or at the exposure assessment stage. Since indistinguishable categories can be collapsed implicitly, blind assessment of exposure, i.e., assignment without knowledge of disease status, does not guarantee that misclassification is nondifferential.
Article
Mortality findings in a 1964 to 1970 cohort of 1013 hourly-wage men exposed to methylene chloride were substantially unchanged after 4 additional years of observation through 1988. Mean exposure was 26 ppm (8-hour time-weighted average) for 23 years; median follow-up from first exposure was 33 years. A comparison with death rates in both general population and industrial referents showed nonsignificant deficits in observed-expected ratios for such hypothesized causes as lung and liver cancer and ischemic heart disease. Overall mortality from 1964 to 1988 (n = 238) was significantly decreased v both referent groups. The study had 90% power to detect relative risks of 1.7 and 1.3 for lung cancer and ischemic heart disease, respectively; power was inadequate for hepatic cancer. No pancreatic cancer deaths occurred since the 1984 follow-up; eight have been observed v 4.2 expected (P = .13). An analysis of dose response for selected causes of death demonstrated no statistically significant trend according to either career methylene chloride exposure or latency. Similar results were observed when the data were analyzed using Poisson regression modeling.
Article
Standardized proportional mortality ratios and mortality odds ratios were calculated for 583 deaths between 1950 and 1986 among employees who had worked for at least 10 years at a facility manufacturing missile and aircraft guidance systems. There was a statistically significant excess of brain cancer proportional mortality (PMR = 16/3.8 = 4.2, p = .0001). Among hourly employees, 12 brain cancer deaths occurred for 2.7 expected (PMR = 4.4, p = .00005). The PMR for brain cancer increased from 1.8 (p = .45) among hourly workers with less than 20 years to 8.7 (p = .000003) in those with more than 20 years employment. Work in "clean rooms," where gyroscopes were assembled, was associated with the brain cancer excess but did not fully account for it. Among 105 deceased hourly women, all three brain cancer deaths occurred among gyro assemblers working in clean rooms, and the risk increased with duration in clean rooms. Although the proportion of brain cancer deaths among hourly men with clean-room experience was similar to that for women, only three of the seven male brain cancer deaths occurred in this group. The suspect agents include gyro fluids and chlorofluorocarbon solvents.
Article
Work history records and fitness reports were obtained for 1,767 marine inspectors of the U.S. Coast Guard between 1942 and 1970 and for a comparison group of 1,914 officers who had never been marine inspectors. Potential exposure to chemicals was assessed by one of the authors (RP), who is knowledgeable about marine inspection duties. Marine inspectors and noninspectors had a deficit in overall mortality compared to that expected from the general U.S. population (standardized mortality ratios [SMRs = 79 and 63, respectively]). Deficits occurred for most major causes of death, including infectious and parasitic diseases, digestive and urinary systems, and accidents. Marine inspectors had excesses of cirrhosis of the liver (SMR = 136) and motor vehicle accidents (SMR = 107), and cancers of the lymphatic and hematopoietic system (SMR = 157), whereas noninspectors had deficits for these causes of death. Comparison of mortality rates directly adjusted to the age distribution of the inspectors and noninspectors combined also demonstrated that mortality for these causes of death was greater among inspectors than noninspectors (directly adjusted ratio ratios of 190, 145, and 198) for cirrhosis of the liver, motor vehicle accidents, and lymphatic and hematopoietic system cancer, respectively. The SMRs rose with increasing probability of exposure to chemicals for motor vehicle accidents, cirrhosis of the liver, liver cancer, and leukemia, which suggests that contact with chemicals during inspection of merchant vessels may be involved in the development of these diseases among marine inspectors.
Article
Occupational risks of bladder cancer among nonwhite men were assessed based on interviews with 126 cases and 383 controls conducted during the National Bladder Cancer Study, a population-based, case-control study conducted in 10 areas of the United States. Our findings indicated that nonwhite men who were ever employed as auto workers have an elevated risk of bladder cancer [relative risk (RR) = 2.3; 95% confidence intervals (CI) = 0.8-6.4] with a significant positive trend in RR with increasing duration of employment (P = .017) and with the RR rising to 4.7 for those employed at least 10 years. Dry cleaners, ironers, and pressers also experienced increased bladder cancer risk (RR = 2.8, CI = 1.1-7.4). Nonsignificant excesses of similar magnitude to those seen among white men were found for nonwhite men employed in several other occupations. Overall, our findings suggest that the risk of occupational bladder cancer among white and nonwhite men is similar. When inconsistencies between whites and nonwhites did occur, they appeared either due to chance or possibly racial differences in exposure among men within the same industry and occupation. In all, we estimate that the population attribute risk for occupation among nonwhite U.S. men is 27% (CI = 9% to 56%), which is slightly higher than the estimate of 21% to 25% previously reported for white U.S. men, although this difference was not statistically significant.
Article
A case-referent study was conducted on the risk of brain tumors among workers exposed to organic chemicals in petroleum refining and chemical manufacturing. Brain tumor cases in northern New Jersey, Philadelphia, and the Gulf Coast of Louisiana were identified from death certificates of a recent three-year period. The cases (N = 300) were white men aged greater than or equal to 30 years with a confirmed diagnosis of glioblastoma multiforme, astrocytoma, or a mixed glioma with astrocytic cells. The referents (N = 386) were white men who died from causes other than brain tumor, epilepsy, cerebrovascular disease, suicide, or homicide and were frequency-matched with the cases on age at death, year of death, and study area. Next-of-kin were interviewed for complete occupational histories. No statistically significantly elevated odds ratios (OR) were associated with employment in the chemical industry. The risk of astrocytic tumors was elevated among the subjects with production or maintenance jobs in petroleum refining (OR 1.7, 95% confidence interval 0.7-4.2); however, it decreased with duration employed. There were nonsignificant excess risks of astrocytic tumors among the men exposed to cutting fluids (OR 1.6) or organic solvents (OR 1.3), and also among the subjects exposed to lubricating oils (OR 1.4), organic solvents (OR 1.5), or cutting fluids (OR 1.8) for greater than or equal to 20 years.
Article
The most malignant form of all brain tumors is the supratentorial astrocytoma. Little is known about its etiology, but exogenous factors have been blamed. In this case-control study, 78 astrocytoma patients have been compared with 197 clinical and 92 population controls. An extensive questionnaire was used to gather information about occupational and residential environment exposure. Inquiries concerning groups of or individual chemicals elicited low rates of affirmative response, with negligible differences between cases and controls. However, the questions “working at an airfield” and “living near a petrochemical plant” indicated elevated risks in comparison with both control groups; so too did “living near a municipal sewage treatment plant.” These results focus attention on exposure to organic compounds and should be considered together with similar findings in current research. No other occupation, branch of industry, or vicinity questions showed differences between cases and controls, with the exception of “living in the neighborhood of a paper mill or a saw mill,” which gave moderately increased relative risks. A separate report gives the results from the nonoccupational part of the study.
Article
A case-referent study was undertaken to look for occupational risk factors among patients with glioma treated in a neurological hospital in Paris between 1975 and 1984. In the study group were 125 men with gliomas (aged less than or equal to 65) and 238 patients (also less than or equal to 65) admitted for non-neoplastic, non-malformative vascular diseases in the same department during the same period constituting the reference group. All diagnoses were confirmed by tomodensitometry. Information on occupational history was obtained from a postal questionnaire and from medical records. Comparison of cases and referents showed a significant excess risk among teachers (OR = 4.1) and a raised risk among wood workers (OR = 1.6). Four of nine cases of glioma who had been employed as wood workers reported that a colleague had suffered from glioma (those reports were confirmed by hospital records). None were reported among 11 referent wood workers. Using a complementary questionnaire on wood work, exposure assessment to wood preservatives and solvents showed that frequent exposure to organochlorine wood preservatives and to organic solvents occurred more often among cases than referent wood workers (p less than 0.10).
Article
Brain tumor risk associated with electrical and electronics jobs and with occupational exposure to microwave and radiofrequency (MW/RF) electromagnetic radiation was evaluated with the use of data from a death certificate-based case-control study of brain tumors and occupational risk factors in northern New Jersey, Philadelphia, PA, and southern Louisiana. Next-of-kin of 435 white men who died of a primary brain tumor and of 386 controls who died from other causes were interviewed to obtain information on lifetime occupational history and other factors that might be related to excess brain tumor risk. The relative risk (RR) for all brain tumors was elevated among men exposed to MW/RF radiation [RR = 1.6; 95% confidence interval (Cl) = 1.0, 2.4] and was significantly elevated among men exposed for 20 or more years. All of the excess risk for MW/RF radiation-exposed subjects was derived from jobs that involved the design, manufacture, repair, or installation of electrical or electronic equipment (RR = 2.3; 95% Cl = 1.3, 4.2), while risk of brain tumors among MW/RF radiation-exposed subjects who never worked in electrical or electronics jobs was not elevated (RR = 1.0; 95% Cl = 0.5, 1.9). Furthermore, risk was elevated for electronics workers who were considered to have no exposure to MW/RF radiation. Among electrical and electronics workers, risk was highest for engineers, teachers, technicians, repairers, and assemblers combined (RR = 3.9; 95% Cl = 1.6, 9.9) and was limited to excess risk from astrocytic tumors (RR = 4.6; 95% Cl = 1.9, 12.2). Risk of astrocytic tumors among these electronics manufacture and repair workers increased with duration of exposure to tenfold among those employed for 20 or more years. Among electricians and power and telephone linemen combined (electrical tradesmen), the RR for astrocytic tumors was slightly elevated, but not statistically significant (RR = 1.8), and showed no consistent evidence of a duration-response relationship. Electrical tradesmen are exposed to extremely low frequency electromagnetic radiation, while men in some jobs associated with electronics manufacture and repair are exposed to electromagnetic radiation in the very high frequency and ultra-high frequency ranges and also may be exposed to soldering fumes, solvents, and a variety of other chemicals.
Article
To assess the potential chronic health effects of methylene chloride, the mortality experience of a maturing 1964 to 1970 cohort of 1,013 hourly men was evaluated through 1984. On average, employees were exposed at a rate of 26 ppm (eight-hour time-weighted average) for 22 years; median latency was 30 years. Compared with the general population, no statistically significant excesses were observed for such hypothesized causes as lung cancer (14 observed v 21.0 expected), liver cancer (0 v 0.8), and ischemic heart disease (69 v 98.1); dose-response relationships based on career methylene chloride exposure and latency were not demonstrated. Among nonhypothesized causes, a significant deficit was reported for total deaths (176 v 253.2). None of the industrial referent comparisons achieved statistical significance. Sufficient power was available to detect relative risks of 1.6 for lung malignancy and 1.3 for ischemic heart disease. In contrast, there was inadequate power to identify meaningful risk levels for hepatic cancer. With 14 combined lung and liver cancer deaths observed v 36.3 predicted (P less than .0001), the mortality estimate projected from a mathematical model derived from an animal bioassay substantially overestimated cancer mortality for these sites. This inconsistency emphasizes the need to incorporate epidemiologic evidence in assessing the human health risks associated with long-term exposure to this widely used solvent.
Article
To evaluate the carcinogenic potential from occupational exposure to perchloroethylene (PCE), a retrospective cohort mortality study of workers employed in the dry cleaning industry was conducted among 1,690 workers from four labor unions. The majority of the cohort had potential exposure to petroleum solvents as well as to PCE while working in the dry cleaning industry. Mortality from primary cancer of the liver was of particular interest, due to the findings of excess liver cancer in mice exposed to PCE. Other sites of cancer were also of interest. A total of 493 deaths were observed, whereas 575.5 were expected based on US mortality rates. Mortality from all cancers combined was greater than expected (142 observed v 122.9 expected). No deaths due to liver cancer were observed. Urinary tract cancer was the only specific site where there was a statistically significant excess in observed deaths (12 observed v 4.7 expected). There was some consistency in these findings across the four individual unions and across race/sex groups. A subcohort of workers who were employed only in dry cleaning shops that used PCE as their primary solvent was identified from the union records. There was only one death from urinary tract cancer, whereas 1.3 deaths were expected in this subcohort.
Article
Numerous studies have suggested that employment in the oil refining and chemical manufacturing industries may be associated with excess brain tumor risk. A case-referent study was undertaken to evaluate brain tumor risk by occupation and industry in three geographic areas (northern New Jersey, Philadelphia, and the Gulf Coast of Louisiana) with a heavy concentration of these industries. Seven hundred and eighteen white men dying from brain tumor at age 30 years or older were ascertained from death certificates for 1978-1981. The referents were men who died of other causes, excluding epilepsy and stroke. Usual occupation and industry were obtained from the death certificates, and the maximum likelihood estimates of the relative risk were calculated for specific industries and occupations. Small nonsignificant excess risks of brain tumors were seen among persons whose usual employment was in the petroleum refining, electrical equipment manufacturing, health services, and educational services industries. Compared with other white-collar professionals, health diagnosticians, teachers, and artists/designers had a significantly elevated brain tumor risk. Among blue-collar workers, the only group with a significantly elevated brain tumor risk was precision metal workers, who are exposed to metal dusts and fumes and substances used as coolants, lubricants, and degreasers.
Article
Studies of the etiology of rapidly fatal diseases often use data from surrogate sources. To assess the validity of the wife as a source of exposure information, 80 wives were interviewed in 1983-1984 for the same histories provided earlier by their husbands, who were cases in a case-control study of lung cancer in New Mexico, 1980-1982. Both interviews obtained detailed information concerning lifetime occupational history, smoking habits, and consumption of certain foods high in vitamin A. With regard to lifetime occupational histories, the wives reported significantly fewer jobs. Concordance of the coded histories was approximately 50% for occupation and industry, but was higher for the last job and usual job held. Wives correctly reported the cigarette smoking status of their husbands. For the number of cigarettes smoked per day, wives tended to report 20 cigarettes smoked even when their husbands smoked substantially more or less. The mean frequencies of consumption of certain food items based on the two sources were comparable. However, the percentage of exact agreement and the kappa statistics were generally low.
Article
Case-cotrol studies of fatal diseases often rely on occupational histories provided by next of kin, but little is known about the accuracy of information obtained in this way. As an adjunct to a survey of occupation and cancer in men under the age of 55, the authors have compared employment histories elicited independently from a sample of middle aged men and their wives. The findings illustrate the limitations of histories obtained by proxy, particularly through self administrered questionnaires. When studies are based on occupational data recalled from memory, allowance must be made for the source of the histories, and negative results must be interpreted with caution.
Article
Epidemiological evidence of an occupational risk of brain cancer has been reported in four industries where chemical exposures are likely, most recently in a series of prospective studies in the petrochemical industry. However, only in the case of vinyl chloride exposure has an occupational central nervous system carcinogen been identified. This report reviews the convergence of epidemiological and laboratory evidence that established the occupational carcinogenicity of vinyl chloride, and discusses in detail the current evidence for an occupational risk of brain tumors in the petrochemical industry.
Article
A case-referent study was done on the possible association between primary liver cancer (ICD 155.0) and occupational exposures. In all, 374 cases were reported to the Finnish Cancer Registry in 1979 and 1980. After the exclusion of wrong diagnoses, nonrespondents and cases for whom the primary site was uncertain, 126 cases (64 men and 62 women) remained. Each case was matched for sex, age (+/- 5 years), vital status and geographical district with two cases of coronary infarction selected from hospital records without any knowledge of occupational history. Nonrespondence (38%) reduced the number to 175 referents (82 men and 92 women). A questionnaire on former employment and tasks was mailed to living subjects (6 + 6) and to the next of kin of deceased patients. An industrial hygienist then evaluated the exposure history blindly and, whenever necessary, contacted the workplace or the next of kin for more details. Only exposures commencing 10 years or more before diagnosis were considered. Altogether six female cases but no referent had been exposed to solvents. One had been exposed to chlorinated solvents in dry cleaning and two others had used both carbon tetrachloride and aromatic and aliphatic solvents. Three cases had been exposed to mixtures of aliphatic and aromatic solvents, but not chlorinated hydrocarbons. By contrast, the men did not differ with regard to exposure to solvents. Two cases and five referents were classified as having been exposed to solvent mixtures. The present results are hypothesis generating only, and the excess solvent exposure found for women must be confirmed in other studies before any conclusions can be drawn.
Article
The mortality experience of 440 laundry and dry cleaning workers for the period 1975-81 was analyzed, using Oklahoma death certificate data. Results did not show an overall increase in total cancer, but an elevated risk was found for homicide, lung cancer, and kidney cancer. A decrease in risk was noted for ischemic heart disease and for breast cancer.
Article
Stemhagen, A. (New Jersey State Dept of Health, Trenton, NJ 08625), J. Slade, R. Altman and J. Bill. Occupational risk factors and liver cancer: a retrospective case-control study of primary liver cancer in New Jersey. Am J Epidemiol 1983; 117: 443–54. A retrospective case-control study was conducted to identify occupational risk factors associated with primary liver cancer in New Jersey, with particular focus on agricultural occupations and pesticide exposures. Hospital record room, tumor registry, and death certificate searches for the diagnosis of primary liver cancer resulted in identification of 959 cases of which 335 were subsequently confirmed. Interviews were completed for 265 persons with liver cancer diagnosed between January 1, 1975 and March 1, 1980 and for 530 matched controls; 96% of all interviews were conducted with family members of deceased or incompetent study subjects. Analyses of employment in agricultural occupations identified male farm laborers as having an odds ratio of 1.89 (95% confidence interval (Cl) 1.19–3.00). An estimated relative risk of 3.20 (Cl 1.11–9.21) was found for males engaged in wlnemaking. Among nonag-rlcultural occupations, elevated risks were found for males working as bartenders and those employed in eating and drinking places, laundries and dry cleaning services, and gasoline service stations. An elevated risk of liver cancer was also associated with females employed as cleaning service workers. Hepatitis and cirrhosis could not be evaluated as risk factors in this study. Dose-response trends by level of alcohol consumption were found for both males and females.
Article
In the reported experiments, two compounds, vinyl chloride and acrylonitrile, appeared to cause brain tumors, neuroblastomas and gliomas (oligodendrogliomas), respectively, when given by inhalation. Such an effect is not seen with vinyl chloride at 500 ppm and below and with acrylonitrile at 10 ppm and below. The overall incidence of brain tumors (different types and totals) in Sprague-Dawley rats following exposure, respectively, by inhalation and ingestion to different industrial compounds, without taking into account concentrations and duration and schedule of treatment, is presented. It appears that when the level of dose and the type of tumor are not considered, the incidence of brain tumors may be 'lowered' to borderline levels. Such an 'artifact' finding, in our opinion, is extremely important, and it stresses the point that, in epidemiological investigations in humans, reference must always be made to defined types of tumors and to groups of individuals with the same level of exposure (homogeneous groups). Our research in the field of carcinogenesis is now being extended to other industrial compounds. Furthermore, in consideration of the higher responsiveness of embryos and newborn animals, we are now testing a series of compounds (including some of the ones considered in this report), by treating the breeders from the 12th day of pregnancy, and continuing the exposure of offsprings up to adult age.
Article
In May 1971, the Epidemiology Branch of the National Cancer Institute published the volume 'Patterns in Cancer Mortality in the United States: 1950-1967.' The authors have now extended the information previously presented by providing more detailed data for each site, lengthening the interval covered by 10 years, and by preparing three-dimensional graphs for the 22 sites with sufficient data for this purpose. The graphs may be helpful to readers who prefer them to massive tables for quick review of a series of cancers with respect to age, sex, color, and single calendar year. The three-dimensional figures (or tables) reveal differences in trend that may suggest hypotheses about etiology or pathogenesis. Tables and graphs show the numbers of cancer deaths by site annually in each age group. The result is at times dramatically different from the corresponding mortality rates. For example, because of the baby boom in the 1950's, the number of adolescent males with testicular cancer rose sharply in the 1970's, although no change occurred in the mortality rates. Tables and graphs are also provided for proportionate mortality, i.e., the numbers of deaths due to a given cancer among all causes by year, age, sex, and race. The relative frequency of cancer as a cause of death in a particular population group is thus indicated. For example, leukemia (all forms) accounted for 12% of deaths among girls 5-9 years of age in 1963, which has different implications than the corresponding mortality rate, i.e., 4.2/100,000 in the same year. By contrast, one may note that the leukemia mortality rate in 1963 among women 70-74 years old was 24.0/100,000, which accounted for less than 1% of all deaths.
Article
Acute hepatotoxicity has been described in patients exposed to either trichloroethylene or 1,1,1-trichloroethane, but there have been previous reports of chronic liver disease induced by these agents. We describe a patient who developed cirrhosis and portal hypertension after repeated bouts of acute hepatotoxicity caused by trichloroethylene and a final episode of 1,1,1-trichloroethane-induced liver injury.
Article
Patients with gliomas of the central nervous system hospitalized during the period January 1979--March 1980 at the Neurological Institute C. Besta of Milan were compared with controls admitted to the Institute in the same period for nonneoplastic neurologic diseases or benign tumors. The comparison was based on occupational history, smoking habits, and alcohol consumption. Two analyses were carried out: the first by case-control pairs matched for age, sex, and residence; the second by age, sex, and residence stratification. Patients with glioma were more likely than controls to have worked in agricultural activities and showed a relative risk of 5.0 (p = 0.043) in the matched analysis and 1.9 (p = 0.113) in the analysis by stratification. This high risk was confined to those who performed agricultural work after 1960, suggesting a possible etiologic role of exposure to organic pesticides, fertilizers, and herbicides, which have only recently been commonly used in Italy. No significant difference was observed between cases and controls in regard to other analyzed occupations and habits.
Article
Ninety-two cases of brain tumor in children less than 10 years old were compared with 92 matched controls for parental occupational history. Cases were more likely than controls to show material occupations involving chemical exposure, paternal occupations involving solvents, and employment of father in the aircraft industry. These three factors were not affected by adjustment for the potential confounding variables examined in this study.
Article
The numbers of deaths by cause among 1,292 white male metal polishers and platers identified from obituary listings in the Journal of the Metal Polishers, Buffers, Platers, and Allied Workers International Union were compared to an expected distribution based on the white male population of Illinois and the U.S. The proportions of deaths due to cancers of the esophagus and the liver were high, particularly among those over 65 and those listed as metal polishers or platers on the death certificate. The PCMRs for these two tumors were also moderately elevated. Despite methodologic limitations, these findings, along with the known use in this industry of chromium and nickel, strong acid and alkaline solutions, and the solvents trichloroethylene and tetrachloroethylene, suggest that metal polishers and platers may be subject to exposures capable of inducing cancer.
Article
Available epidemiologic information related to halogenated hydrocarbons and cancer is reviewed. Many chlorinated hydrocarbons, both pesticides and solvents, have been shown to possess mutagenic or carcinogenic properties in bacterial test systems and animal experiments. Rather few substances have been associated with human cancer, but relatively few studies have been conducted.
Article
The mortality patterns of 671 female laundry and dry cleaning workers for the period 1963--1977 were analyzed, using Wisconsin death certificate data. Results fail to show an overall increase in malignant neoplasms, but elevated risk was found for cancers of the kidney and genitals (unspecified), along with a smaller excess of bladder and skin cancer and lymphosarcoma.