OBJECTIVES: The effects of occupational and leisure-time exposures on the risk of acute myeloid leukemia (AML) were investigated with emphasis on clonal chromosome aberrations (CCA) and morphological subtypes. METHODS: Consecutively diagnosed cases of AML (N=333) and 1 population referent per case were retrospectively included in the study. Information on worktasks, companies, and leisure-time activities was obtained with telephone interviews. Exposure probability and intensity were assessed by occupational hygienists. Associations were evaluated with logistic regression. RESULTS: Exposure to organic solvents was associated with an increased risk of AML [low exposure: OR 1.5 (95% confidence interval (95% CI) 1.0-2.3, moderate-high exposure: OR 2.3 (95% CI 1.0-5.0)]. For exposure to solvents, but not to benzene, the OR was 1.2 (95% CI 0.69-2.0) for "low" and 2.7 (95% CI 1.0-7.3) for "moderate-high" exposure. The observed effects increased with intensity and duration of exposure. The estimated effects were higher for patients >60 years of age at the time of diagnosis. The effect of exposure to organic solvents was not differential with regard to morphology [except possibly erythroleukemia: OR 4.2, 95% CI 1.0-17 or the presence of CCA in general]. No increased risk for AML with complex CCA or with total or partial losses of chromosomes 5 or 7 were observed, but a higher risk was found for AML with trisomy 8 (OR 11, 95% CI 2.7-42) as the sole aberration. CONCLUSIONS: Exposure to organic solvents was associated with an increased risk of AML. This association was not due to benzene exposure alone and may be modified by age. Furthermore, specific associations with trisomy 8, and possibly also erythroleukemia, were suggested.
OBJECTIVES: The sensitizing properties of organic acid anhydrides (OAA) were evaluated in a rat model. METHODS: The development of specific immunoglobulin (Ig)E and Ig G in serum was investigated after immunization with 14 OAA and 3 OAA conjugates. Brown Norway rats were injected intradermally with 0.1 ml of 0.2 M OAA in liquid paraffin or 1.4 mg of rat serum albumin conjugate in saline. Serum samples were collected after 4 weeks. Antibodies were analyzed with enzyme-linked immunosorbent assay. RESULTS: The serum titers of specific Ig E after immunization with the different free OAA varied from
OBJECTIVES: To investigate a broad range of occupational, hobby, and lifestyle exposures, suggested as risk factors for Philadelphia chromosome positive (Ph+) chronic myeloid leukaemia (CML). METHODS: A case-control study, comprising 255 Ph+CML patients from southern Sweden and matched controls, was conducted. Individual data on work tasks, hobbies, and lifestyle exposures were obtained by telephone interviews. Occupational hygienists assessed occupational and hobby exposures for each subject individually. Also, occupational titles were obtained from national registries, and group level exposure-that is, the exposure proportion for each occupational title-was assessed with a job exposure matrix. The effects of 11 exposures using individual data and two exposures using group data (organic solvents and animal dust) were estimated. RESULTS: For the individual data on organic solvents, an effect was found for moderate or high intensity of exposure (odds ratio (OR) 3.4, 95% confidence interval (95% CI) 1.1 to 11) and for long duration (15-20 years) of exposure (OR 2.1, 95% CI 1.1 to 4.0). By contrast, the group data showed no association (OR 0.69, 95% CI 0.27 to 1.8; moderate or high intensity versus no exposure). For extremely low frequency electromagnetic fields (EMFs), only individual data were available. An association with long occupational exposure to EMFs was found (OR 2.3, 95% CI 1.2 to 4.5). However, no effect of EMF intensity was indicated. No significant effects of benzene, gasoline or diesel, or tobacco smoking were found. OR estimates below unity were suggested for personal use of hair dye and for agricultural exposures. CONCLUSIONS: Associations between exposure to organic solvents and EMFs, and Ph+CML were indicated but were not entirely consistent.
To investigate whether methylhexahydrophthalic acid (MHHP acid) in urine and plasma can be used as a biomarker for exposure to methylhexahydrophthalic anhydride (MHHPA).
MHHPA in air was sampled by Amberlite XAD-2 and analysed by gas chromatography (GC) with flame ionisation detection. MHHP acid in urine and plasma was analysed by GC with mass spectrometric detection. Workers occupationally exposed to MHHPA were studied. Air levels of MHHPA were determined by personal sampling in the breathing zone. Urinary levels of MHHP acid, a metabolite of MHHPA, were determined in 27 workers. In eight workers all urine was collected at intervals during 24 h. Plasma levels of MHHP acid were determined in 20 workers.
The time-weighted average (TWA) air levels ranged from 5 to 60 micrograms MHHPA/m3 during 8-h workshifts. The urinary levels of MHHP acid increased during exposure and decayed after the end of exposure with an estimated half-life of about 6 h. A correlation was found between the TWA air levels of MHHPA and creatinine-adjusted MHHP acid levels in urine collected during the last 4 h of exposure. A correlation was also seen between the TWA air levels of MHHPA and the plasma concentrations of MHHP acid. An exposure to 20 micrograms MHHPA/m3 corresponded to about 140 nmol MHHP acid/mmol creatinine and about 40 nmol MHHP acid/l plasma.
The results indicate that MHHP acid in urine or plasma may be used for biological monitoring of the exposure to MHHPA.
Toluene diisocyanate (TDI) and methylene diphenyldiisocyanate (MDI) are used in large quantities in the polyurethane foam manufacturing industry. Both substances are mutagenic and at least TDI is carcinogenic to animals, but the occupational hazard with respect to cancer is not known. Cancer incidence and mortality patterns were therefore investigated in a cohort of 4154 workers from nine Swedish plants manufacturing polyurethane foam, employed for at least one year. Each workplace and job task in the nine plants was categorically assessed for each calendar year by an experienced occupational hygienist, for "no exposure", "low or intermittent exposure", or "apparent exposure" to TDI and MDI. The observed deficit for all cause mortality (standardised mortality ratio (SMR) 0.78, (95% confidence interval (95% CI) 0.66-0.93) became smaller (SMR 0.92) excluding the first 10 years since the start of exposure and was ascribed to a healthy worker effect. No increased risk for death from bronchial obstructive diseases was found. An almost statistically significant deficit occurred for all malignant neoplasms (standardised incidence ratio (SIR) 0.81, 95% CI 0.63-1.02); slight (not significant) increased risks were found for rectal cancer (SIR 1.66) and non-Hodgkin's lymphoma (SIR 1.53). The SIR for non-Hodgkin's lymphoma increased to 2.80 (95% CI 0.76-7.16) when the first 10 years since first exposure were excluded from the observation period. The corresponding figure for rectal cancer was 1.92 (95% CI 0.52-4.92). Further restricting the analysis to those who had experienced an apparent exposure to TDI or MDI increased the SIR for both rectal cancer (3.19, 95% CI 0.66-9.33), and non-Hodgkin's lymphoma (3.03, 95% CI 0.37-10.9). These estimates were based, however, on few incident cases. As the cohort is still young and little time has elapsed since the start of exposure, future follow ups will enable a more conclusive evaluation.
AIMS: To assess whether cancer incidence and mortality in chronic obstructive lung diseases were increased in the Swedish polyurethane foam industry cohort, updated with 11 more years of follow up. METHODS: The mortality and cancer incidence (1959-98) experienced by a cohort of 4175 male and female employees employed for at least one year in the period 1959-87 at one of nine Swedish polyurethane foaming plants were investigated. Comparisons were based on calendar year, sex, and five-year age group specific mortality and incidence rates for Sweden. Workplaces and job tasks were categorically assessed for exposure to toluene diisocyanate (TDI) and methylene diphenyldiisocyanate (MDI) by occupational hygienists. RESULTS: Fewer cancer cases than expected were observed, but the lung cancer incidence was enhanced in women. Women with "apparent exposure" to TDI or MDI did not, however, have a higher lung cancer incidence than those with "no or low exposure". Moreover, a nested case referent study did not find that polyurethane dust exposure had been more prevalent among the female lung cancer cases than among referents. No increased mortality in chronic obstructive lung diseases was observed in the cohort. CONCLUSIONS: Results support the findings from two other cohort studies of an increased lung cancer risk among female workers in the polyurethane foam manufacturing industry. Chance or confounding from smoking are not obvious explanations for the coherent findings. However, the study was not able to link isocyanate exposed employment with lung cancer risk.
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.
OBJECTIVE--To assess the association between occupational exposure to toluene diisocyanate or methylene diphenyldiisocyanate and risk of cancer. DESIGN--A cohort based case-referent study. STUDY BASE--7023 subjects employed during the period 1958 to 1987 in nine Swedish polyurethane foam manufacturing plants. MAIN OUTCOME MEASURES--Odds ratios adjusted with respect to the matching factors (age at risk, calendar year at risk, sex, and plant), calculated from the conditional logistic regression model. RESULTS--A non-significant association was found between high exposure to isocyanates and prostate cancer (OR 2.66, 90% confidence interval (90% CI) 0.39-18.1), which was not enhanced when an induction latency period of 10 years was applied. An association between isocyanate exposure and colon cancer was even weaker. No associations were seen for non-Hodgkin's lymphoma and rectal cancer. CONCLUSIONS--The tentative associations, derived from a previous cohort study, between isocyanate exposure and excess risk for non-Hodgkin's lymphoma and rectal cancer were not supported. Instead, non-significant associations with prostate cancer, and possibly colon cancer, were seen.
OBJECTIVE--To explore associations between exposure to cement dust and cause specific mortality and tumour morbidity, especially gastrointestinal tumours. DESIGN--A retrospective cohort study. SUBJECTS AND SETTING--2400 men, employed for at least 12 months in two Swedish cement factories. MAIN OUTCOME MEASURES--Cause specific morality from death certificates (1952-86). Cancer morbidity from tumour registry information (1958-86). Standardised mortality rates (SMRs; national reference rates) and standardised morbidity incidence rates (SIRs; regional reference rates) were calculated. RESULTS--An increased risk of colorectal cancer was found > or = 15 years since the start of employment (SIR 1.6, 95% confidence interval (95% CI) 1.1-2.3), mainly due to an increased risk for tumours in the right part of the colon (SIR 2.7, 95% CI 1.4-4.8), but not in the left part (SIR 1.0, 95% CI 0.3-2.5). There was a numerical increase of rectal cancer (SIR 1.5, 95% CI 0.8-2.5). Exposure (duration of blue collar employment)-response relations were found for right sided colon cancer. After > or = 25 years of cement work, the risk was fourfold (SIR 4.3, 95% CI 1.7-8.9). There was no excess of stomach cancer or respiratory cancer. Neither total mortality nor cause specific mortality were significantly increased. CONCLUSIONS--Diverging risk patterns for tumours with different localisations within the large bowel were found in the morbidity study. Long term exposure to cement dust was a risk factor for right sided colon cancer. The mortality study did not show this risk.
Total and cause specific mortality and cancer morbidity were studied among 1929 asbestos cement workers with an estimated median cumulative exposure of 2.3 fibre (f)-years/ml (median intensity 1.2 f/ml, predominantly chrysotile). A local reference cohort of 1233 industrial workers and non-case referents from the exposed cohort were used for comparisons. The risk for pleural mesothelioma was significantly increased (13 cases out of 592 deaths in workers with at least 20 years latency). No case of peritoneal mesothelioma was found. A significant dose response relation was found for cumulative exposure 40 years or more before the diagnosis, with a multiplicative relative risk (RR) of 1.9 for each f-year/ml. No relation was found with duration of exposure when latency was accounted for. There was a significant overrisk in non-malignant respiratory disease (RR = 2.6). The overall risks for respiratory cancer, excluding mesothelioma, and for gastrointestinal cancer were not significantly increased. Surprisingly, colorectal cancer displayed a clear relation with cumulative dose, with an estimated increase of 1.6% in the incidence density ratio for each f-year/ml (but not with duration of exposure).