Leukemia in relation to occupational exposures to benzene and other agents: a case-control study nested in a cohort of gas and electric utility workers

BACKGROUND: Many occupational and environmental exposures have been implicated in the etiology of leukemia, but only a few, such as benzene, are well-established leukemogens. The risk of leukemia in a large cohort of gas and electricity utility workers with exposures to several suspected or confirmed carcinogens was investigated. METHODS: A case-control study nested within the cohort was conducted, with 72 leukemia cases identified among male workers, and 285 controls matched to the cases by year of birth. Only cases, and their matched controls, active in the company at the date of diagnosis were included. Exposure assessment was based on a job-exposure matrix (JEM) developed from expert judgment using a standardized procedure. RESULTS: The risk of leukemia was increased in workers with an estimated cumulative exposure to benzene > or = 16.8 ppm-years (OR = 3.6; 95% CI 1.1-11.7), and there was an indication of a dose-response relation (OR = 1.2; 95% CI 1.0-1.5 per 10 ppm-years increase in exposure). The link with benzene was more pronounced for acute leukemia than for chronic leukemia, but no association with a particular leukemia cell type was apparent. The risk of leukemia remained elevated for latency periods of 2, 5, or 10 years. CONCLUSIONS: From our evaluation, it could be estimated that the median TWA exposure to benzene among exposed workers was 0.16 ppm, i.e., within concentration ranges where an increased leukemia risk was usually not apparent in previous epidemiological studies. Although an increased leukemia risk may be real, it may also be related to other occupational factors not totally controlled for in the analysis, or to benzene exposures actually higher than expected.     

Exposure to benzene and risk of leukemia among shoe factory workers

OBJECTIVES: The study attempted to add years of follow-up to an earlier study describing excess leukemia among workers exposed to benzene-based glues in a shoe-factory and to conduct a quantitative exposure assessment of the exposure to benzene and the risk of leukemia. METHODS: The cohort comprised 1687 persons with complete work histories, at work on 1 January 1950, and followed through 31 December 1999. For each subject, time-specific cumulative exposure (ppm-years) was calculated as the sum of the products of job-specific concentrations of benzene (ppm) and the duration (years) for each job. Standardized mortality ratios (SMR) were estimated using national and regional rates specific for gender, age, and period. RESULTS: The cumulative exposure ranged from 0 to >500 ppm-years. The SMR values for all hematolymphopoietic malignancies and leukemia for the men and women combined were elevated in all but the lowest exposure category. Leukemia risk was significantly elevated in the highest exposure category and the most evident among the men. The SMR values for the men were 1.4 [95% confidence interval (95% CI) 0.2-5.0], 3.7 (95% CI 0.1-20.6), 3.0 (95% CI 0.4-10.9), and 7.0 (95% CI 1.9-18.0) for benzene, the cumulative exposure equaling <40, 40-99, 100-199, and >200 ppm-years, respectively. CONCLUSIONS: The results indicate that leukemia mortality is associated with exposure to benzene in this factory and that the risk increases with increasing cumulative exposure. The relevance of these findings for estimating risk at much lower levels is limited because of the small study size.     

Occupational history and exposure and the risk of adult leukemia in Shanghai

PURPOSE: Evaluation of the association of selected occupational exposures with leukemia risk. METHODS: Population-based case-control study of 486 leukemia subjects and 502 healthy controls residing in Shanghai from 1987 to 1989. Adjusted odds ratios (OR) were calculated for the association between occupational factors and leukemia risk. RESULTS: Significant increase in leukemia risk was observed in chemical manufacturing industry workers (OR=3.1, 95% CI=1.0-9.8). Increased risks for leukemia were observed from self-reported exposures to benzene (OR=1.7, 95% CI=1.1-2.6), radioactive materials (OR=3.7, 95% CI=1.3-10.2), synthetic fiber dust (OR=2.0, 95% CI=1.2-3.5), and toluene (OR=1.6, 95% CI=1.0-2.5). Dose-response relations of leukemia risk was observed with the duration of exposure to benzene (OR=3.3, 95% CI=1.6-6.9 for >or=15 years exposure; p for trend<0.01), radioactive materials (OR=5.2, 95% CI=1.1-24.7 for >or=15 years exposure; p for trend=0.02), paints (OR=2.3, 95% CI=1.2-4.7 for >or=15 years exposure; p for trend=0.09), and toluene (OR=2.9, 95% CI=1.3-6.7 for >or=15 years exposure; p for trend=0.02). CONCLUSIONS: Adult leukemia risk may be associated with working in the chemical industry, and exposure to benzene, synthetic fiber dust, radioactive materials, and toluene in the study population.     

Leukemia risk associated with low-level benzene exposure

BACKGROUND: Men who were part of an Australian petroleum industry cohort had previously been found to have an excess of lympho-hematopoietic cancer. Occupational benzene exposure is a possible cause of this excess. METHODS: We conducted a case-control study of lympho-hematopoietic cancer nested within the existing cohort study to examine the role of benzene exposure. Cases identified between 1981 and 1999 (N = 79) were age-matched to 5 control subjects from the cohort. We estimated each subject's benzene exposure using occupational histories, local site-specific information, and an algorithm using Australian petroleum industry monitoring data. RESULTS: Matched analyses showed that the risk of leukemia was increased at cumulative exposures above 2 ppm-years and with intensity of exposure of highest exposed job over 0.8 ppm. Risk increased with higher exposures; for the 13 case-sets with greater than 8 ppm-years cumulative exposure, the odds ratio was 11.3 (95% confidence interval = 2.85-45.1). The risk of leukemia was not associated with start date or duration of employment. The association with type of workplace was explained by cumulative exposure. There is limited evidence that short-term high exposures carry more risk than the same amount of exposure spread over a longer period. The risks for acute nonlymphocytic leukemia and chronic lymphocytic leukemia were raised for the highest exposed workers. No association was found between non-Hodgkin lymphoma or multiple myeloma and benzene exposure, nor between tobacco or alcohol consumption and any of the cancers. CONCLUSIONS: We found an excess risk of leukemia associated with cumulative benzene exposures and benzene exposure intensities that were considerably lower than reported in previous studies. No evidence was found of a threshold cumulative exposure below which there was no risk.     

Lymphohaematopoeitic cancer mortality among workers with benzene exposure

Lymphohaematopoeitic cancer mortality was examined among 4417 workers at a chemical plant by cumulative and peak benzene exposure. There was little evidence of increasing risk with increasing cumulative exposure for all leukaemias or acute non-lymphocytic leukaemias (ANL), or the other lymphohaematopoeitic cancers with the exception of multiple myeloma. For multiple myeloma, the SMRs were 1.1 (95% CI 0.3 to 2.5) in the non-exposed group, 1.4 (95% CI 0.2 to 5.1) in the <1 ppm-years, 1.5 (95% CI 0.2 to 5.4) in the 1–6 ppm-years, and 2.6 (95% CI 0.7 to 6.7) in the >6 ppm-years group. We found no trends by peak exposures for any of the cancers. However, when peak exposures over 100 ppm for 40 or more days were considered, the observed number of all leukaemias (SMR = 2.7, 95% CI 0.8 to 6.4), ANL (SMR = 4.1, 95% CI 0.5 to 14.9), and multiple myeloma (SMR = 4.0, 95% CI 0.8 to 11.7) were greater than expected. While the observed number of deaths is small in this study, the number of peak exposures greater than 100 ppm to benzene is a better predictor of risk than cumulative exposure. The dose rate of benzene and a threshold for exposure response may be important factors for evaluating lymphohaematopoietic risk.     

Cancer incidence in Swedish sterilant workers exposed to ethylene oxide.

OBJECTIVES--To assess the risk of cancer, especially leukaemia, in a cohort of sterilant workers exposed to ethylene oxide (EtO). METHODS--A cohort of 2170 workers employed for at least one year in two plants that produce disposable medical equipment sterilised with EtO has previously been established. The results of an update with four more years of observation are presented. The cancer incidence was assessed for the periods 1976 to 1990 and 1972 to 1990 and cause specific standardised incidence ratios (SIRs) were calculated. Individual cumulative exposure to EtO, expressed as ppm-years, was estimated and used in exposure-response analyses. RESULTS--Six lymphohaematopoietic tumours were observed (SIR 1.78, 95% confidence interval (95% CI) 0.65-3.88), of which two were leukaemias (SIR 2.44; 95% CI 0.30-8.81). When those with cumulative exposures to EtO below the median value (0.13 ppm-years) were excluded, and a minimum of 10 years induction latency period was applied, the incidence ratio for leukaemia increased further (SIR 7.14, 95% CI 0.87-25.8), but was still not significantly enhanced. CONCLUSIONS--The risk estimate for leukaemia increased, but non-significantly, with time since start of exposure, and with cumulative exposures to EtO above the median value. The subjects with leukaemia had, however, only slightly higher cumulative exposure estimates for EtO than the average cohort member. Nevertheless, the present results may add some minor evidence for an association between EtO and an increased risk of leukaemia.     

Occupational exposure to benzene and chromosomal structural aberrations in the sperm of Chinese men

Background: Benzene is an industrial chemical that causes blood disorders, including acute myeloid leukemia. We previously reported that occupational exposures near the U.S. Occupational Safety and Health Administration permissible exposure limit (8 hr) of 1 ppm was associated with sperm aneuploidy.Objective: We investigated whether occupational exposures near 1 ppm increase the incidence of sperm carrying structural chromosomal aberrations.Methods: We applied a sperm fluorescence in situ hybridization assay to measure frequencies of sperm carrying partial chromosomal duplications or deletions of 1cen or 1p36.3 or breaks within 1cen-1q12 among 30 benzene-exposed and 11 unexposed workers in Tianjin, China, as part of the China Benzene and Sperm Study (C-BASS). Exposed workers were categorized into low-, moderate-, and high-exposure groups based on urinary benzene (medians: 2.9, 11.0, and 110.6 µg/L, respectively). Median air benzene concentrations in the three exposure groups were 1.2, 3.7, and 8.4 ppm, respectively.Results: Adjusted incidence rate ratios (IRRs) and 95% confidence intervals (CIs) for all structural aberrations combined were 1.42 (95% CI: 1.10, 1.83), 1.44 (95% CI: 1.12, 1.85), and 1.75 (95% CI: 1.36, 2.24) and for deletion of 1p36.3 alone were 4.31 (95% CI: 1.18, 15.78), 6.02 (95% CI: 1.69, 21.39), and 7.88 (95% CI: 2.21, 28.05) for men with low, moderate, and high exposure, respectively, compared with unexposed men. Chromosome breaks were significantly increased in the high-exposure group [IRR 1.49 (95% CI: 1.10, 2.02)].Conclusions: Occupational exposures to benzene were associated with increased incidence of chromosomally defective sperm, raising concerns for worker infertility and spontaneous abortions as well as mental retardation and inherited defects in their children. Our sperm findings point to benzene as a possible risk factor for de novo 1p36 deletion syndrome. Because chromosomal aberrations in sperm can arise from defective stem cells/spermatogonia, our findings raise concerns that occupational exposure to benzene may have persistent reproductive effects in formerly exposed workers.     

Hairy cell leukaemia and occupational exposure to benzene.

OBJECTIVES: The role of occupational exposures in hairy cell leukaemia (HCL) was investigated through a multicentre, hospital based, case-control study. This paper analyses the role of exposure to benzene in HCL. METHODS: A population of 226 male cases of HCL and 425 matched controls were included in the study. Benzene exposure was evaluated by expert review of the detailed data on occupational exposures generated by case-control interviews. RESULTS: No association was found between HCL and employment in a job exposed to benzene (odds ratio (OR) 0.9 (95% confidence interval (95% CI) 0.6-1.3)). The sample included 125 subjects, 34 cases (15%), and 91 controls (21%) who had been exposed to benzene, as individually assessed by the experts, for at least one hour a month during one of their jobs. Benzene exposure was not associated with a risk of HCL (OR 0.8 (0.5-1.2)). No trend towards an increase in OR was detected for increasing exposures, the percentage of work time involving exposure to > 1 ppm, or the duration of exposure. No findings suggested a particular risk period, when the OR associated with the time since first or last exposure, or since the end of exposure, were examined. CONCLUSIONS: In conclusion, with the low exposures prevalent in the sample, the study did not show any association between benzene exposure and HCL.     

Benzene exposure and hematopoietic mortality: A long-term epidemiologic risk assessment

BACKGROUND: Previous studies of a cohort of rubber hydrochloride workers indicated an association between benzene exposure and excess mortality from leukemia and multiple myeloma. To determine whether risks remain elevated with increasing time since plant shutdown, we extended follow-up from 1981 through 1996. MATERIALS AND METHODS: We evaluated risk using standardized mortality ratios (SMR) and generalized Cox proportional hazards regression models. RESULTS: Five new leukemia cases were observed in benzene-exposed white males, but the summary SMR for this group declined from 3.37 (95% CI = 1.54-6.41) to 2.56 (95% CI = 1.43-4.22). In regression models, cumulative exposure was significantly associated with elevated relative risks for leukemia mortality. Four new multiple myeloma deaths occurred, three of which were in workers judged to be unexposed. CONCLUSIONS: These findings reaffirm the leukemogenic effects of benzene exposure and suggest that excess risk diminishes with time.     

Early-Life Exposure to Outdoor Air Pollution and Respiratory Health,Ear Infections,and Eczema in Infants from the INMA Study

Background: Prenatal and early-life periods may be critical windows for harmful effects of air pollution on infant health.Objectives: We studied the association of air pollution exposure during pregnancy and the first year of life with respiratory illnesses, ear infections, and eczema during the first 12–18 months of age in a Spanish birth cohort of 2,199 infants.Methods: We obtained parentally reported information on doctor-diagnosed lower respiratory tract infections (LRTI) and parental reports of wheezing, eczema, and ear infections. We estimated individual exposures to nitrogen dioxide (NO₂) and benzene with temporally adjusted land use regression models. We used log-binomial regression models and a combined random-effects meta-analysis to estimate the effects of air pollution exposure on health outcomes across the four study locations.Results: A 10-µg/m³ increase in average NO₂ during pregnancy was associated with LRTI [relative risk (RR) = 1.05; 95% CI: 0.98, 1.12] and ear infections (RR = 1.18; 95% CI: 0.98, 1.41). The RRs for an interquartile range (IQR) increase in NO₂ were 1.08 (95% CI: 0.97, 1.21) for LRTI and 1.31 (95% CI: 0.97, 1.76) for ear infections. Compared with NO₂, the association for an IQR increase in average benzene exposure was similar for LRTI (RR = 1.06; 95% CI: 0.94, 1.19) and slightly lower for ear infections (RR = 1.17; 95% CI: 0.93, 1.46). Associations were slightly stronger among infants whose mothers spent more time at home during pregnancy. Air pollution exposure during the first year was highly correlated with prenatal exposure, so we were unable to discern the relative importance of each exposure period.Conclusions: Our findings support the hypothesis that early-life exposure to ambient air pollution may increase the risk of upper and lower respiratory tract infections in infants.     

Occupational sunlight exposure and cancer incidence among Swedish construction workers

We studied sunlight exposure from outdoor work in relation to cancer, using data from 323,860 men participating in an occupational health service program of the Swedish construction industry. An experienced industrial hygienist assessed the exposure for 200 job tasks. We estimated relative risks (RRs) adjusted for age, smoking, and magnetic field exposure. There was an increased RR in the high-exposure group for myeloid leukemia [RR = 2.0, 95% confidence interval (95% CI) = 1.1-3.6] and lymphocytic leukemia (RR = 1.7, 95% CI = 0.9-3.2). For non-Hodgkin's lymphoma there was a 30% increase in risk in the high-exposure group (95% CI = 0.9-1.9). There was no increased risk of malignant melanoma, except for tumors of the head, face, and neck in the high-exposure group (RR = 2.0, 95% CI = 0.8-5.2), and we also found an increased risk for malignant melanoma of the eye in this group (RR = 3.4, 95% CI = 1.1-10.5). Outdoor workers had no increased risk of nonmelanoma skin cancer. Nevertheless, the RR for lip cancer (squamous cell carcinoma) among the high-exposure group was estimated at 1.8 (95% CI = 0.8-3.7). Among other sites, an increased risk of stomach cancer was suggested in this group (RR = 1.4, 95% CI = 1.0-1.9). The results for lymphoma, leukemia, and possibly also for stomach cancer might reflect a suppression of the immune system from ultraviolet light in outdoor workers.     

Radiation exposure and cancer mortality in uranium processing workers.

Data from the Comprehensive Epidemiology Data Resource (CEDR) allowed me to study patterns of cancer mortality in a cohort of 4,014 uranium-processing workers. Employing risk-set analysis for cohort data, I estimated the effects of external (gamma) and internal (alpha) radiation on cancer mortality. My results indicate that Fernald workers exposed to ionizing radiation experienced an increase in mortality from total cancer (per 100 mSv external dose rate ratio (RR) = 1.92; 95% confidence interval (CI) = 1.11-3.32), radiosensitive solid cancer (RR = 2.00; 95% CI = 1.02-3.94), and lung cancer (RR = 2.77; 95% CI = 1.29-5.95). Effects were strongest when exposure had occurred at older ages (>40 years). In addition, I observed an increase in lung-cancer mortality for workers exposed to > or =200 mSv of internal (alpha) radiation (RR = 1.92; 95% CI = 0.53-6.96). Furthermore, my results demonstrate the importance of a long follow-up time when studying solid cancers, the potential for bias due to worker selection associated with concomitant chemical exposures, problems of exposure measurement, confounding, and effect modification due to age at exposure. Owing to lack of data, a previous pooled analysis of uranium-processing workers could only partially address these issues.     

Estimated effects of solvents and mineral oils on cancer incidence and mortality in a cohort of aerospace workers

BACKGROUND: A retrospective cohort study of workers employed at a California aerospace company between 1950 and 1993 was conducted; it examined cancer mortality from exposures to the rocket fuel hydrazine. METHODS: In this study, we employed a job exposure matrix (JEM) to assess exposures to other known or suspected carcinogens-including trichloroethylene (TCE), polycyclic aromatic hydrocarbons (PAHs), mineral oils, and benzene-on cancer mortality (1960-2001) and incidence (1988-2000) in 6,107 male workers. We derived rate- (hazard-) ratios estimates from Cox proportional hazard models with time-dependent exposures. RESULTS: High levels of TCE exposure were positively associated with cancer incidence of the bladder (rate ratio (RR): 1.98, 95% confidence interval (CI) 0.93-4.22) and kidney (4.90; 1.23-19.6). High levels of exposure to mineral oils increased mortality and incidence of lung cancer (1.56; 1.02-2.39 and 1.99; 1.03-3.85), and incidence of melanoma (3.32; 1.20-9.24). Mineral oil exposures also contributed to incidence and mortality of esophageal and stomach cancers and of non-Hodgkin's lymphoma and leukemia when adjusting for other chemical exposures. Lagging exposure measures by 20 years changed effect estimates only minimally. No associations were observed for benzene or PAH exposures in this cohort. CONCLUSIONS: Our findings suggest that these aerospace workers who were highly exposed to mineral oils experienced an increased risk of developing and/or dying from cancers of the lung, melanoma, and possibly from cancers of the esophagus and stomach and non-Hodgkin's lymphoma and leukemia. These results and the increases we observed for TCE and kidney cancers are consistent with findings of previous studies.     

Exposure to magnetic fields among electrical workers in relation to leukemia risk in Los Angeles County

To Address the hypotheses that electrical workers are exposed to higher magnetic fields and are at higher risk of leukemia than nonelectrical workers, we performed a registry-based case-control study among men aged 20–64 years with known occupation who were diagnosed with cancer in Los Angeles County between 1972 and 1990. Controls were men with cancers other than those of the central nervous system or leukemia. Magnetic field measurements on workers in each electrical occupation and in a random sample of occupations presumed to be nonelectrical were used to estimate magnetic field exposures for each occupation. Among men in electrical occupations, 121 leukemias were diagnosed. With the exception of electrical engineers, magnetic field exposures were higher among workers in electrical occupations than in nonelectrical occupations. A weakly positive trend in leukemia risk across average occupational magnetic field exposure was observed (odds ratio [OR] per 10 milligauss increase in average magnetic field = 1.2, 95% confidence interval [CI] 1.0–1.5). A slightly stronger association was observed for chronic myloid leukemia, although only 28 cases occurred among electrical workers (OR 10 milligauss increase = 1.6, 95% CI = 1.2–2.0). The results were not materially altered by adjustment for exposure to several agents known or suspected to cause leukemia. Although not conclusive, these results are consistent with findings from studies based on job title alone that electrical workers may be at slightly increased risk of leukemia.     

Critical windows of exposure to household pesticides and risk of childhood leukemia

The potential etiologic role of household pesticide exposures was examined in the Northern California Childhood Leukemia Study. A total of 162 patients (0-14 years old) with newly diagnosed leukemia were rapidly ascertained during 1995-1999, and 162 matched control subjects were randomly selected from the birth registry. The use of professional pest control services at any time from 1 year before birth to 3 years after was associated with a significantly increased risk of childhood leukemia [odds ratio (OR) = 2.8; 95% confidence interval (CI), 1.4-5.7], and the exposure during year 2 was associated with the highest risk (OR = 3.6; 95% CI, 1.6-8.3). The ORs for exposure to insecticides during the 3 months before pregnancy, pregnancy, and years 1, 2, and 3 were 1.8 (95% CI, 1.1-3.1), 2.1 (95% CI, 1.3-3.5), 1.7 (95% CI, 1.0-2.9), 1.6 (95% CI, 1.0-2.7), and 1.2 (95% CI, 0.7-2.1), respectively. Insecticide exposures early in life appear to be more significant than later exposures, and the highest risk was observed for exposure during pregnancy. Additionally, more frequent exposure to insecticides was associated with a higher risk. In contrast to insecticides, the association between herbicides and leukemia was weak and nonsignificant. Pesticides were also grouped based on where they were applied. Exposure to indoor pesticides was associated with an increased risk, whereas no significant association was observed for exposure to outdoor pesticides. The findings suggest that exposure to household pesticides is associated with an elevated risk of childhood leukemia and further indicate the importance of the timing and location of exposure.     

A case-control study to investigate the risk of leukaemia associated with exposure to benzene in petroleum marketing and distribution workers in the United Kingdom.

OBJECTIVES: To investigate the risk of leukaemia in workers in the petroleum distribution industry who were exposed to low levels of benzene. METHODS: From the cohort of distribution workers, 91 cases were identified as having leukaemia on either a death certificate or on cancer registration. These cases were compared with controls (four per case) randomly selected from the cohort, who were from the same company as the respective case, matched for age, and alive and under follow up at the time of case occurrence. Work histories were collected for the cases and controls, together with information about the terminals at which they had worked, fuel compositions, and occupational hygiene measurements of benzene. These data were used to derive quantitative estimates of personal exposure to benzene. Odds ratios (OR) were calculated conditional on the matching, to identify those variables in the study which were associated with risk of leukaemia. Examination of the potential effects of confounding and other variables was carried out with conditional logistic regression. Analyses were carried out for all leukaemia and separately for acute lymphoblastic, chronic lymphocytic, acute myeloid and monocytic, and chronic myeloid leukaemias. RESULTS: There was no significant increase in the overall risk of all leukaemias with higher cumulative exposure to benzene or with intensity of exposure, but risk was consistently doubled in subjects employed in the industry for > 10 years. Acute lymphoblastic leukaemia tended to occur in workers employed after 1950, who started work after the age of 30, worked for a short duration, and experienced low cumulative exposure with few peaks. The ORs did not increase with increasing cumulative exposure. The risk of chronic lymphocytic leukaemia seemed to be related most closely to duration of employment and the highest risk occurred in white collar workers with long service. These workers had only background levels of benzene exposure. There was no evidence of an association of risk with any exposure variables, and no evidence of an increasing risk with increasing cumulative exposure, mean intensity, or maximum intensity of exposure. The patterns of risk for acute myeloid and monocytic leukaemia were different from those of the lymphoid subgroups, in which duration of employment was the variable most closely related to risk. Risk was increased to an OR of 2.8 (95% confidence interval (95% CI) 0.8 to 9.4) for a cumulative exposure between 4.5 and 45 ppm-years compared with < 0.45 ppm-years. For mean intensity between 0.2 and 0.4 ppm an OR of 2.8 (95% CI 0.9 to 8.5) was found compared with < 0.02 ppm. Risk did not increase with cumulative exposure, maximum intensity, or mean intensity of exposure when treated as continuous variables. Cases of acute myeloid and monocytic leukaemia were more often classified as having peaked exposures than controls, and when variables characterising peaks, particularly daily and weekly peaks, were included in the analysis these tended to dominate the other exposure variables. However, because of the small numbers it is not possible to distinguish the relative influence of peaked and unpeaked exposures on risk of acute myeloid and monocytic leukaemia. There was no evidence of an increased risk of chronic myeloid leukaemia with increases in cumulative exposure, maximum intensity, mean intensity, and duration of employment, either as continuous or categorical variables. Analyses exploring the sensitivity of the results to the source and quality of the work histories showed similar patterns in general. However, no increases in ORs for categories of cumulative exposure were found for acute myeloid and monocytic leukaemia in the data set which included work histories obtained from personnel records still in existence, although numbers were reduced. Analyses excluding the last five and 10 years of exposure showed a tendency for ORs to reduce for chronic lymphocytic leukaemia and chronic myeloid leukaemia, and to increase for acute myeloid and monocytic leukaemia. Limitations of the study include uncertainties and gaps in the information collected, and small numbers in subcategories of exposure which can lead to wide CIs around the risk estimates and poor fit of the mathematical models. CONCLUSIONS: There is no evidence in this study of an association between exposure to benzene and lymphoid leukaemia, either acute or chronic. There is some suggestion of a relation between exposure to benzene and myeloid leukaemia, in particular for acute myeloid and monocytic leukaemia. Peaked exposures seemed to be experienced for this disease. However, in view of the limitations of the study, doubt remains as to whether the risk of acute myeloid and monocytic leukaemia is increased by cumulative exposures of < 45 ppm-years. Further work is recommended to review the work histories and redefine their quality, to explore the discrepancies between results for categorical and continuous variables, and to develop ranges around the expose estimates to enable further sensitivity analyses to be carried out.     

In Utero Pesticide Exposure and Leukemia in Brazilian Children < 2 Years of Age

Background: An association between pesticide exposure and cancer has been suggested. Infant leukemia is a rare neoplasm and its association with maternal pesticide exposure has been poorly explored.Objectives: We investigated the association between pesticide exposure during pregnancy and leukemia in children < 2 years of age.Methods: A hospital-based case–control study was carried out in 13 Brazilian states during 1999–2007. Mothers of 252 cases and those of 423 controls were interviewed. Information on pesticide exposures 3 months before pregnancy, throughout pregnancy, and during breastfeeding was obtained. Unconditional logistic regression was used to estimate adjusted odds ratios (aORs) for associations between pesticide exposures and leukemia.Results: Associations with ever use of pesticides during pregnancy were observed for acute lymphoid leukemia (ALL) (aOR = 2.10; 95% CI: 1.14, 3.86) and acute myeloid leukemia (AML) (aOR = 5.01; 95% CI: 1.97, 12.7) in children 0–11 months of age, and with ALL (aOR = 1.88; 95% CI: 1.05, 5.23) at 12–23 months of age. According to reported maternal exposure to permethrin, higher risk estimates were verified for children 0–11 months of age (aOR = 2.47; 95% CI: 1.17, 5.25 for ALL; and aOR = 7.28; 95% CI: 2.60, 20.38 for AML). Maternal pesticide exposure related to agricultural activities showed an aOR of 5.25 (95% CI: 1.83, 15.08) for ALL, and an aOR of 7.56 (95% CI: 1.83, 31.23) for AML.Conclusions: These results support the hypothesis that pesticide exposure during pregnancy may be involved in the etiology of acute leukemia in children < 2 years of age.     

Occupational exposures and gastrointestinal cancers among Finnish women

A cohort including all female workers born 1906 through 1945 (n = 413,877) in Finland was identified through the Population Census of Finland of 1970. Incident cases of cancers of the gastrointestinal tract were explored during 1971 to 1995. Job titles in census records were converted to exposures of 31 occupational agents through a job-exposure matrix. For each agent, the product of level and probability of exposures was calculated and subdivided in three categories: zero, low and medium/high. Poisson regression models estimated relative risks (RR) for each agent, standardized for birth cohort, follow-up period, and socioeconomic status. Adjustment at job title level was done for alcohol use for cancers of the esophagus and liver and smoking for pancreatic cancer. The results showing either statistically significant RR at the medium/high level of exposure (RRH) or statistically significant trend (P < 0.05) over the exposure categories were considered as positive findings. Colon cancer risk (2009 cases) was positively associated with sedentary work (RRH 1.3, 95% CI = 1.1-1.6; P trend 0.001) and negatively associated with perceived workload (P trend = 0.007). For stomach cancer (1881 cases), we observed an association with exposure to electromagnetic fields (RRH 1.44, 95% CI = 1.01-2.05) and man-made vitreous fibers (MMVF) (p trend 0.03). Rectal cancer (1323 cases) showed an association with chromium (RRH 1.9, 95% CI = 1.2-3.1) and oil mist (RR 2.0; 95% CI = 1.0-3.9). For pancreas cancer (1302 cases) we found associations with exposure to chromium (RRH 1.8; 95% CI = 1.0-3.1; P trend 0.01), electromagnetic fields (RRH 1.8; 95% CI = 1.2-2.8; P trend 0.02), and sedentary work (RRH 1.3; 95% CI = 1.0-1.7; P trend 0.05). We found no significant associations between any FINJEM agents and cancers of the esophagus (389 cases), liver (389 cases), and gallbladder (651 cases). Having examined the associations between seven cancer sites and over 30 exposures there exists the real possibility that some of the associations detected are chance findings. Therefore, the associations observed should need to be confirmed in other studies.     

A cross-sectional survey of respiratory and general health outcomes among semiconductor industry workers

As part of the Semiconductor Health Study, we performed a cross-sectional survey to assess prevalence of specific nonreproductive health outcomes and their association with occupational exposures. A total of 3,175 persons from eight manufacturing sites across the U.S. completed a health and work questionnaire (78% participation rate). After adjusting for confounders, responses from fabrication room (fab) workers indicated a greater risk than those of nonfab workers for upper respiratory symptoms (relative risk [RR] = 1.08; 95% confidence interval [CI] = 1.03-1.13); a dose-response effect with hours per day spent in fabs was observed. Fab workers also had greater prevalence for persistent wheezing (RR = 1.82; 95% CI = 1.15-2.87), Dermatitis within the past year (RR = 1.19; 95% CI = 1.04-1.35), and alopecia (RR = 1.73; 95% CI = 1.16-2.54). Female sex, a somatization index score, and smoking were important nonoccupational covariates. Increased respiratory symptoms MAy result from occupational exposures in fabs; further research is needed to identify causal agents and develop prevention strategies.     

Cancer risk in oil refinery workers: a pooled mortality study in Italy

Background:Oil refinery workers are exposed to several well-established carcinogens and working in this type of industry has been classified by IARC as probable carcinogen to humans (Group 2A).Objectives:To examine the mortality experience of workers employed in four Italian oil refineries.Methods:The cohort included 5112 male workers ever employed between 1949 and 2011. The average follow-up period was 49 years. Standardized mortality ratios (SMR) and 95% Confidence Intervals (CI) were calculated using as reference age-gender-calendar specific regional rates. Analyses by duration of employment and latency were performed.Results:In the whole cohort, pleural cancer (6 deaths, SMR 1.59; 95% CI 0.71-3.53), brain cancer (14 deaths, SMR 1.47; 95% CI 0.87-2.49) and lymphatic leukemia (LL) (8 deaths, SMR 1.81; 95% CI 0.91-3.62) showed increased risks. All pleural cancers occurred after 10 years of latency and the highest risk was observed among workers with duration ≥20 years; the brain cancer excess was confined in the shortest duration and latency. The LL (and chronic lymphatic leukemia in particular) excess regarded workers with latency and duration longer than 20 years. Four deaths from acute myeloid leukemia (AML) were observed and all occurred after 20 years of latency (SMR 1.55, 95% CI 0.58-4.12); a two-fold-increased risk was observed in the longest duration. No increased risk for skin cancer has been observed in our study population.Conclusion:Our findings are consistent with recent evidence of an increased mortality from pleural and hematopoietic malignancies (AML and LL) among oil refinery workers. However, the lack of individual quantitative exposure data and the small number of observed events prevent the identification of the possible causal role of individual chemicals, including benzene, especially at the current very low exposure levels.Key words: Cohort study, cancer mortality, benzene, petrochemical industry, standardized mortality ratios