Organic solvents and cancer

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

Combining physiologically based pharmacokinetic modeling with Monte Carlo simulation to derive an acute inhalation guidance value for trichloroethylene

Using the Monte Carlo method and physiologically based pharmacokinetic modeling, an occupational inhalation exposure to trichloroethylene consisting of 7 h of exposure per day for 5 days was simulated in populations of men and women of 5000 individuals each. The endpoint of concern for occupational exposure was drowsiness. The toxicologic condition leading to drowsiness was assumed to be high levels of both trichloroethanol and trichloroethylene. Therefore, the output of the simulation or dose metric was the maximum value of the sum of the concentration of trichloroethylene in blood and the concentration of trichloroethanol within its volume of distribution occurring within 1 week of exposure. The distributions of the dose metric in the simulated populations were lognormal. To protect 99% of a worker population, a concentration of 30 ppm over a 7-h period of the work day should not be exceeded. Subjecting a susceptible individual (the 99th percentile of the dose metric) to 200 ppm (the ACGIH short-term exposure limit or STEL) for 15 min twice a day over a work week necessitates a 2.5-h rest in fresh air following the STEL exposure to allow the blood concentrations of trichloroethylene and trichloroethanol to drop to levels that would not cause drowsiness. Both the OSHA PEL and the ACGIH TLV are greater than the value of 30 ppm derived here. As well as suggesting a new occupational guidance value, this study provides an example of this method of guidance value derivation.     

A case-control study of fatty liver disease and organic solvent exposure

BACKGROUND: Clinical experience of cases of fatty liver disease (FLD) with exposure to organic solvents suggested a possible risk. METHODS: Thirty male cases of FLD, ages 20-59 years, with biopsy records at departments of pathology in southeast Sweden were compared to 120 male controls randomly drawn from the study area population. Questionnaire information was obtained about job titles and specific occupational exposures; exposure level categories were then assessed blindly for both cases and controls. Medical records for cases were scrutinized to elucidate possible confounding and/or interacting effects from alcohol, the use of drugs, and other diseases. RESULTS: Moderately intense and mixed solvent exposure for more than 1 year within the last 15 years prior to diagnosis resulted in an age-adjusted Mantel-Haenszel odds ratio of 4.3 (95% confidence interval (CI), 1.2-15); for intense exposure, the odds ratio was 7.7 (95% CI 1.7-48). Confounding from alcohol, use of drugs, other diseases, and overweight could be ruled out with reasonable confidence. CONCLUSIONS: This study indicates that occupational exposure to organic solvents may play a role in the development of FLD, as indicated earlier in case reports and in one small case-control study.     

Changes in birth weight, birth length and head circumference of Hungarian children in the county Baranya between 1968 and 1979-1981

Wildland (forest) firefighters are exposed to a wide range of carcinogenic polycyclic aromatic hydrocarbons (PAH) in forest fire smoke. PAH undergo metabolic activation and can subsequently bind to DNA. In this study, we investigated the association between occupational and dietary PAH exposures and the formation of WBC PAH-DNA adducts in a population of wildland firefighters. An enzyme-linked immunosorbent assay using an antiserum elicited against benzo(a)pyrene-modified DNA was used to measure PAH-DNA adducts in WBC obtained from 47 California firefighters at two time points, early and late in the 1988 forest fire season. PAH-DNA adduct levels were not associated with cumulative hours of recent firefighting activity. However, firefighters who consumed charbroiled food within the previous week had elevated PAH-DNA adduct levels, which were related to frequency of charbroiled food intake. These findings suggest that dietary sources of PAH contribute to PAH-DNA adduct levels in peripheral WBC and should be evaluated when using this assay to assess occupational and environmental PAH exposure.     

Occupational exposure to organic solvents and sleep-disordered breathing

STUDY OBJECTIVE: To investigate whether people with occupational exposure to organic solvents have a higher prevalence of obstructive sleep apnea syndrome (OSAS) than the general population and to examine the relationship between snoring and exposure to organic solvents. DESIGN AND PARTICIPANTS: Consecutive patients, aged 30-64 years, referred during a 3-year period to the sleep laboratory at Avesta Hospital, Sweden, because of suspected OSAS made up the patient groups. Following admission, patients underwent a simplified sleep apnea investigation and were divided into two groups, OSAS (n = 320) and snorers (n = 443). A random sample of 296 men and 289 women aged 30-64 years obtained from a register of all country residents maintained by the county tax authority served as referents (controls). Both patients and referents responded to two questionnaires, including questions about occupation, exposure to organic solvents, and other chemical and physical agents. RESULTS: Men with OSAS or snoring and women with snoring had more often been occupationally exposed to organic solvents than the referents, showing an almost twofold increase in risk for those exposed during whole workdays. For men, the risk of OSAS or snoring increased with increasing exposure. CONCLUSION: The result indicates that occupational exposure to organic solvents might cause sleep apnea. A new observation is that even snoring could be caused by exposure to organic solvents. It is important to elucidate whether exposure to organic solvents is a cause of OSAS, because such a finding may have important implications for prevention and treatment of sleep disturbances.     

A freshwater anaerobe coupling acetate oxidation to tetrachloroethylene dehalogenation

Strain TT4B has been isolated from anaerobic sediments known to be contaminated with a variety of organic solvents. It is a gram-negative, rod-shaped bacterium and grew anaerobically with acetate as the electron donor and tetrachloroethylene as the electron acceptor in a mineral medium. cis-Dichloroethylene was the halogenated product. This strain did not grow fermentatively and used only acetate or pyruvate as electron donors. Tetrachloroethylene and trichloroethylene were used as electron acceptors, as were ferric nitriloacetate and fumarate. Nitrogen and sulfur oxyanions were not able to substitute as the electron acceptor for this organism. Modest growth occurred in a two-phase system with 1 ml of hexadecane containing 50 to 200 mM tetrachloroethylene (aqueous concentrations, 25 to 100 microM) and 10 ml of anaerobic mineral solution with Na2S as the reducing agent. Growth was completely inhibited at tetrachloroethylene levels above 100 microM.     

Dose-dependent suppression of toluene metabolism by isopropyl alcohol and methyl ethyl ketone after experimental exposure of rats

In order to examine possible suppression of toluene metabolism due to coexposure to other solvents, female Wistar rats were exposed for 8 h to toluene alone (at 50 or 100 ppm), or in combination with either methyl ethyl ketone (at 50, 100, 200 or 400 ppm) or isopropyl alcohol (at 50, 100, 200, 400, 800 or 1600 ppm). Urine samples were collected for 24 h after initiation of each exposure, and subjected to analysis for two toluene metabolites, hippuric acid and o-cresol, both by HPLC. The excretion of hippuric acid, a major metabolite, was not modified when the concentrations of methyl ethyl ketone or isopropyl alcohol were low, i.e. 100 ppm or below, whereas it was reduced when methyl ethyl ketone or isopropyl alcohol concentrations were twice or more times higher than that of toluene. There were no changes in any cases in excretion of o-cresol, a minor metabolite. The observation after coexposure to methyl ethyl ketone or isopropyl alcohol at low concentration is in line with the negative interaction between toluene and methyl ethyl ketone as well as between toluene and isopropyl alcohol after occupational exposures at low concentrations. Metabolic interaction may take place when the exposure intensity is high, as observed in the present study and also after experimental exposure of volunteers to toluene and m-xylene, or occupational exposure to benzene and toluene.     

Wineglass pattern for vertical mammaplasty

OBJECTIVES: The objective of this study was to test the hypothesis that long-term occupational exposure to organic solvents may effect the levels and turnover of dopamine in man. METHODS: A study was performed on 17 patients with neuropsychiatric symptoms due to occupational solvent exposure, and 11 healthy non-exposed male volunteers (controls). Positron emission tomography (PET) was used to assess striatal dopaminergic function, using L-[11C]DOPA, [11C]nomifensine and [11C]raclopride as tracers. RESULTS: The rate of dopamine synthesis was significantly increased among subjects with occupational exposure to organic solvents compared with non-exposed controls. After controlling for the difference in age between exposed and controls, the effect of solvent exposure became less apparent and was reduced from +32% (P = 0.009) to +25% (P = 0.07). There were no differences with regard to the binding of [11C]nomifensine. Patients with and without the diagnosis of toxic encephalopathy did not differ with regard to their putaminal uptake of L-[11C]DOPA, [11C]nomifensine and [11C]raclopride. CONCLUSION: The data support the hypothesis that long-term exposure to organic solvents may increase the rate of dopamine synthesis in the brain without affecting the number of presynaptic terminals or postsynaptic dopamine receptors.     

Alcohol use and risk of posterior subcapsular opacities

We conducted a follow-up study of surgical cases of posterior subcapsular cataracts and their controls to evaluate the possible association of alcohol intake and posterior subcapsular opacities. Two hundred thirty-eight cases and controls were interviewed. Current alcohol intake and usual and maximum weekly consumption ever were assessed. In this population, 57% of the cases and 56% of the controls were nondrinkers, 22% of the cases and 36% of the controls had an average of seven or fewer drinks per week, and 17% of the cases and 8% of the controls had more than seven drinks per week. A matched pair analysis controlling for other known risk factors showed an increased risk associated with heavy alcohol use. Heavy drinkers were more likely to be cases than were nondrinkers (odds ratio, 4.6; P < .05), and light drinkers were not at an increased risk. This result suggests that heavy alcohol consumption may increase the risk of posterior subcapsular cataract.     

Evaluation of the developmental toxicity of trichloroethylene and detoxification metabolites using Xenopus

Potential mechanisms of trichloroethylene-induced developmental toxicity were evaluated using FETAX (Frog Embryo Teratogenesis Assay--Xenopus). Early Xenopus laevis embryos were exposed to trichloroethylene for 96 h in two separate definitive concentration-response assays with and without an exogenous metabolic activation system (MAS) and inhibited MAS. The MAS was treated with either carbon monoxide or cyclohexene oxide to modulate mixed-function oxidase (MFO) or epoxide hydrolase activity, respectively. Trichloroethylene metabolites: dichloroacetic acid, trichloroacetic acid, trichloroethanol, and oxalic acid were also evaluated in two separate definitive, static renewal tests. Addition of the MAS decreased the 96 h LC50 and EC50 (malformation) of trichloroethylene 1.8-fold and 3.8-fold, respectively. Addition of the carbon monoxide inhibited MAS decreased the developmental toxicity of activated trichloroethylene to levels approximating that of the parent compound. Cyclohexene oxide-inhibited MAS substantially increased the developmental toxicity of trichloroethylene. In addition, each of the metabolites tested were significantly less developmental toxic than the parent compound, trichloroethylene. Results indicate that a highly embryotoxic epoxide intermediate, trichloroethylene oxide, formed as the results of MFO mediated metabolism may play a significant role in the developmental toxicity of trichloroethylene in vitro.     

MST-16, a novel derivative of bis(2,6-dioxopiperazine), synergistically enhances the antitumor effects of anthracyclines

OBJECTIVE: The aim of this study was to evaluate whether toluene, like many other organic solvents and solvent mixtures, could impair color vision. SUBJECTS AND METHODS: We investigated color vision impairment in three groups of workers, two groups occupationally exposed to toluene and a nonexposed group. The first exposed group, group E1, comprised 41 workers (median value of toluene in air 35.00 ppm, range 11.3-49.3 ppm) and the second exposed group, group E2, comprised 32 subjects (median value of toluene in air 156.00 ppm, range 66.0-250.0 ppm). The nonexposed group, group NE, comprised 83 subjects. Color vision was evaluated by the Lanthony D-15 desaturated test according to Verriest's classification: type I, loss in the red-green range; type II, loss in the blue-yellow and red-green ranges, and type III, loss in the blue-yellow range. Subjects were classified as dyschromates if specific acquired loss was determined in at least one eye. In both exposed groups, exposure was evaluated by measurement of the concentration of toluene in the ambient air and in the blood. In group E2, level of hippuric acid and orthocresol in urine after the work shift were also determined. The Mann-Whitney U-test, t-test, chi 2-test, and Spearman's rank correlation and multiple regression analysis were used for statistical analysis. RESULTS: Type III dyschromatopsia was detected in all groups examined: 26.6% of the workers in group NE, 31.7% of those in group E1, and 50% of those in group E2. As many as 15.6% of the workers in group E2, 4.8% of those in group E1, and only 1.2% of those in group NE had type II dyschromatopsia. A statistically significant difference in the prevalence of total dyschromatopsia (type III + type II) was established among the three examined groups together (chi 2 = 14.13; df = 2; P < 0.01), between group E2 and group E1 (chi 2 = 4.96; P < 0.05), and between group E2 and group NE (chi 2 = 12.50; P < 0.005), whereas no significant difference was found between groups E1 and NE. Type III dyschromatopsia was significantly correlated with age in group NE (P < 0.01) and in group E1 (P < 0.005). In group E2, both type II (P < 0.05) and type III dyschromatopsia correlated with toluene in ambient air and with the duration of exposure to toluene (both P < 0.005). In group E2, total dyschromatopsia correlated significantly with toluene in ambient air and in blood (both P < 0.05) as well as with hippuric acid in urine after the work shift (P < 0.001). CONCLUSION: This study suggests that toluene can impair color vision.     

Meat, fat and risk of breast cancer: a case-control study from Uruguay

To examine whether meat intake modifies breast-cancer risk, a case-control study was conducted in Uruguay. Dietary patterns were assessed in detail (for cases, before diagnosis or symptoms occurred) using a food frequency questionnaire involving 64 food items, which allowed total energy intake to be calculated. Nutrient residuals were calculated through regression analysis. After adjustment for potential confounders (which included family history of breast cancer, menopausal status, body-mass index, total energy and total alcohol intake), an increased risk associated with consumption of total meat intake, red meat intake, total fat and saturated fat intake was observed. The strongest effect was observed for red meat intake (OR 4.2, 95% CL 2.3-7.7) for consumption in the upper quartile, after controlling for protein and fat intake. This suggests an independent effect for meat. Since experimental studies have shown a strong effect of heterocyclic amines in rat mammary carcinogenesis, further studies should be performed in human epidemiology, perhaps using biomarkers of heterocyclic amine exposure.     

Melanoma and occupation: results of a case-control study

OBJECTIVES: Associations between occupational exposures and the occurrence of cutaneous melanoma were examined as part of a large population based case-control study of 19 cancer sites. METHODS: Cases were men aged 35 to 70 years old, resident in Montreal, Canada, with a new histologically confirmed cutaneous melanoma (n = 103). There were two control groups, a randomly selected population control group (n = 533), and a cancer control group (n = 533) randomly selected from among subjects with other types of cancer in the large study. Odds ratios for the occurrence of melanoma were calculated for each exposure circumstance for which there were more than four exposed cases (85 substances, 13 occupations, and 20 industries) adjusting for age, ethnicity, and number of years of schooling. RESULTS: Significantly increased risk of melanoma was found for exposure to four substances (fabric dust, plastic dust, trichloroethylene, and a group containing paints used on surfaces other than metal and varnishes used on surfaces other than wood), three occupations (warehouse clerks, salesmen, and miners and quarrymen), and two industries (clothing and non-metallic mineral products). CONCLUSIONS: Most of the occupational circumstances examined were not associated with melanoma, nor is there any strong evidence from previous research that any of those are risk factors. For the few occupational circumstances which were associated in our data with melanoma, the statistical evidence was weak, and there is little or no supporting evidence in the scientific literature. On the whole, there is no persuasive evidence of occupational risk factors for melanoma, but the studies have been too small or have involved too much misclassification of exposure for this conclusion to be definitive.     

Resolution with vascular endoprosthesis after first angioplasty failure in the treatment of post-transplant stenosis of the renal artery

A thermal desorption-gas chromatography (GC) system was developed for use with commercial adhesive plasters used for monitoring exposure of hands to common solvents. The efficiency of solvent adsorption on the activated carbon pads located on the plasters was determined for acetone, trichloroethylene, D-limonene, methanol, ethyl methyl ketone, toluene, tetrachloroethylene and m-xylene. The degree of solvent recovery for the system was also investigated for each solvent, as was its sensitivity and reproducibility. All solvents exhibited > 90% adsorption on the pads at spiking levels of 100-200 ng for each solvent, except for m-xylene and d-limonene. Solvent recovery was dependent on the volatility of the solvent at spiking volumes of about 1 microliter per pad with solvents with boiling points above 110 degrees C showing recoveries of < 75%. Increasing primary desorption times and temperatures increased these values. The precision was good with RSD < 5% for all solvents over the range 0.5-5.0 microliters of applied solvent. It was possible to detect 15-60 ng of each solvent component within solvent mixtures on the pads with the exception of D-limonene. It is concluded that all solvents tested except D-limonene can be determined on the pads under the conditions for thermal desorption-GC analysis described. The pads were used under protective gloves with six workers using xylene isomers as solvent in the workplace, when apparent solvent breakthrough through their gloves was observed.     

A multidisciplinary approach to toxicological screening: II. Developmental toxicity

As part of the validation of an integrated bioassay for systemic toxicity, neurotoxicity, and developmental toxicity, we evaluated the effects of four pesticides, four chlorinated solvents, and two other industrial chemicals in Fischer 344 rats. The pesticides included carbaryl, triadimefon, chlordane, and heptachlor; the solvents included dichloromethane (DCM), carbon tetrachloride, trichloroethylene (TCE), and tetrachloroethylene (perchloroethylene, PER); and the industrial chemicals were di(2-ethylhexyl)phthalate (DEHP) and phenol. In the developmental toxicity studies, timed-pregnant rats were treated by gavage with vehicle or 1 of 2 dose levels of each compound on gestation d 6-19. The dams were allowed to deliver and their litters were examined on postnatal d 1, 3, and 6. Litter weights were determined on postnatal d 1 and 6. Implants were also counted to determine prenatal loss. Maternal toxicity was evidenced by dose-related alterations in weight gain for all 10 compounds. Clinical signs of maternal toxicity were present for all chemicals except chlordane and heptachlor. DEHP exposure resulted in the most pronounced developmental toxicity (high levels of pre- and postnatal mortality), whereas chlordane induced extensive postnatal loss. Of the solvents, only DCM did not cause a high incidence of full-litter resorption. Phenol, heptachlor, triadimefon, and carbaryl showed only slight potential for developmental toxicity. Malformations suggestive of teratogenicity included kinked tail (phenol), microphthalmia (TCE, PER, DEHP), and cleft palate with renal agenesis (DEHP). Although several findings (eye defects caused by TCE and PER, full-litter resorption and delayed parturition caused by PER, and delayed parturition/dystocia associated with triadimefon) have not been previously reported, the results are generally consistent with previous reports and highlight the importance and relative ease of incorporation of developmental evaluations into a multidisciplinary screening battery.     

Cardiac teratogenesis of halogenated hydrocarbon-contaminated drinking water

OBJECTIVES: The purpose of this study was to test the hypothesis that administration of trichloroethylene and dichloroethylene to pregnant rats during organogenesis would produce a significant fetal cardiac teratogenic effect. It was also hypothesized that administration of these compounds only before pregnancy would not be associated with fetal cardiac teratogenesis. BACKGROUND: Epidemiologic observations demonstrated an increased number of congenital cardiac defects in children whose mother resided in an area with drinking water contaminated by trichloroethylene and dichloroethylene. A prior provocative intrauterine exposure study in rats established a positive link between these contaminants and an increased number of fetal hearts with congenital cardiac defects. METHODS: Sprague-Dawley rats were given pure tap drinking water (control subjects) or water contaminated with high or low dose of trichloroethylene or dichloroethylene (experimental groups) during prepregnancy only, prepregnancy and pregnancy or during pregnancy alone. RESULTS: A total of 2,045 fetuses were examined. Trichloroethylene or dichloroethylene delivered exclusively in the period before pregnancy caused no increase in congenital cardiac malformations over the control level. Compared with the control group, rats exposed to these agents both before and during pregnancy, had a significantly greater number of fetuses with cogenital cardiac malformations. Trichloroethylene (high dose only) administered only during pregnancy produced a significant increase in cardiac defects. Other fetal variables, including noncardiac congenital abnormalities, showed no significant difference between control and treated groups. CONCLUSIONS: Trichloroethylene and dichloroethylene administered during organogenesis are cardiac, but not general, teratogens. The data indicate that these agents administered in drinking water to pregnant rats caused an increased number of congenital cardiac defects in rat fetuses.     

Elimination kinetics of volatile organics in humans using breath measurements

During the past decade significant strides have been made toward understanding the sources and factors which lead to volatile organic chemical (VOC) exposure in the general population. Less is known, however, about the impact of low-level environmental exposure on human health. Investigations are underway in a number of laboratories in an effort to determine the uptake, distribution, metabolism, and elimination kinetics for VOCs in humans. We examined the elimination kinetics for the third phase for ten VOCs--1,1,-trichloroethane, trichloroethylene, tetrachloroethylene, benzene, toluene, m,p-xylenes, o-xylene, ethylbenzene, p-dichlorobenzene, and limonene--in human subjects. Subjects were exposed to a variety of common consumer products and breath samples were collected post-exposure while the subjects spent up to 10 hr in a clean air environment. VOCs from breath samples were collected into canisters or onto Tenax GC cartridges and analyzed by gas chromatography-mass spectrometry. Exponential modeling of the decay data was performed to obtain kinetic parameters. The half-lives for trichloroethylene and 1,1,1-trichloroethane were approximately 5 to 8 hr for the four subjects. In general, the magnitude and range of variability was larger for toluene, limonene, and p-dichlorobenzene than for the other VOCs; the elimination rate spanning a few hours to a day or two. Thus, VOCs exhibit relatively short residence times in the body relative to other halo-carbons, such as polychlorinated biphenyls and dioxins.     

Metabolism of trichloroethylene in B6C3F1 mouse and human liver slices

Human and B6C3F1 mouse liver tissue was exposed to trichloroethylene (TCE) to determine metabolic rate constants. Using a novel volatile exposure system based on precision-cut tissue explants, TCE biometabolism was measured by appearance of a major oxidative product trichloroacetic acid (TCA). TCE metabolic rate was linear in this system to 150 minutes, allowing calculation of Michaelis-Menten kinetic parameters, Km and Vmax. Both human and mouse liver explants tolerated exposure to TCE up to 750 microM without evidence of cytotoxicity. Km values for mouse and human tissue were 215 and 30.6 microM TCE, respectively, and Vmax estimates were 6.14 and 0.47 ng TCA produced per mg protein*min-1, mouse and human, respectively. These results are consistent with other reports in describing the greater capacity of mice to metabolize TCE. Metabolic differences such as these must be considered when interpreting the implications of TCE-induced toxicity in rodent models for human health assessment.     

Renal cell cancer correlated with occupational exposure to trichloroethene

A previous cohort-study in a cardboard factory demonstrated that high and prolonged occupational exposure to trichloroethene (C2HCl3) is associated with an increased incidence of renal cell cancer. The present hospital-based case/control study investigates occupational exposure in 58 patients with renal cell cancer with special emphasis on C2HCl3 and the structurally and toxicologically closely related compound tetrachloroethene (C2Cl4). A group of 84 patients from the accident wards of three general hospitals in the same area served as controls. Of the 58 cases, 19 had histories of occupational C2HCl3 exposure for at least 2 years and none had been exposed to C2Cl4; of the 84 controls, 5 had been occupationally exposed to C2HCl3 and 2 to C2Cl4. After adjustment for other risk factors, such as age, obesity, high blood pressure, smoking and chronic intake of diuretics, the study demonstrates an association of renal cell cancer with long-term exposure to C2HCl3 (odds ratio 10.80; 95% CI: 3.36-34.75).     

Smoking tobacco, oral snuff, and alcohol in the etiology of squamous cell carcinoma of the head and neck: a population-based case-referent study in Sweden

BACKGROUND: This case-referent study was conducted to elucidate the role of selected exogenous agents in the etiology of head and neck cancer. The factors studied were tobacco smoking, alcohol intake, the use of moist oral snuff, dietary factors, occupational exposures, and oral hygiene. In this first report, the authors discuss the impact of tobacco smoking, the use of oral snuff, and alcohol consumption. METHODS: The study base was approximately 2 million person-years at risk and consisted of Swedish males age 40-79 years living in 2 geographic regions during the years 1988-1990. A total of 605 cases were identified in the base, and 756 controls were selected by stratified random sampling from population registries covering the base. RESULTS: Among those who were tobacco smokers at the time of the study, the relative risk of head and neck cancer was 6.5% (95% confidence interval, 4.4-9.5%). After cessation of smoking, the risk gradually declined, and no excess risk was found after 20 years. The relative risk associated with alcohol consumption of 50 grams or more per day versus less than 10 grams per day was 5.5% (95% confidence interval, 3.1-9.6%). An almost multiplicative effect was found for tobacco smoking and alcohol consumption. CONCLUSIONS: Tobacco smoking and alcohol intake had a strong interactive effect on the risk of squamous cell carcinoma of the head and neck. Moderate alcohol intake (10-19 grams per day) had little or no effect among nonsmokers. No increased risk was found for the use of Swedish oral snuff.