[Strongly increased risk of acute myeloid leukemia among gasoline service station workers].
Explore the source record for details and available documents.
Adult↗
Biomedical subjects
T Bellander
Publications and source records attributed to T Bellander.
Cancer morbidity in nitrate fertilizer workers.
A cohort of 2,131 male nitrate fertilizer workers was evaluated for cancer morbidity from 1963 to 1986. No significant increase in total cancer, stomach cancer (5 actual vs 6.7 expected cases), or lung cancer (13 vs 13 expected) was found. On the other hand, 26 actual cases of prostate cancer were observed vs 16 expected cases (standardized morbidity ratio, SMR = 161; 95%, confidence interval, CI = 107-239). This risk increase however, was, not enhanced by applying at least a 10-year latency period. In a cohort of 1,148 male fertilizer workers who had never been exposed to nitrate, there was an increased incidence of lung cancer (SMR = 151,95% CI = 103-220) but not of stomach cancer or prostate cancer. There was no association between airborne nitrate exposure dose and total cancer, stomach cancer, lung cancer or prostate cancer, respectively.
Adult↗
Biological effects in a chemical factory with mutagenic exposure. I. Cytogenetic and haematological parameters.
Analysis in two independent laboratories demonstrated no significant differences in chromosome aberrations or micronuclei in lymphocytes from peripheral blood between workers in a chemical factory (exposed to a mixture of chemicals, such as piperazine, low levels of ethylene oxide and formaldehyde, aromatic nitrogen compounds, and other aromatic compounds) compared to unexposed control subjects. The chemical workers had significantly higher counts of lymphocytes (3.57 vs. 2.82 X 10(9)/l; P less than 0.001), eosinophils (0.27 vs. 0.20 X 10(9)/l; P = 0.005), and basophils (0.06 vs. 0.05 X 10(9)/l; P = 0.01) than the controls. Twenty workers exposed to piperazine had higher total numbers of B-lymphocytes than control subjects.
Adult↗
Biological effects in a chemical factory with mutagenic exposure. II. Analysis of unscheduled DNA synthesis and adenosine diphosphate ribosyl transferase, epoxide hydrolase, and glutathione transferase in resting mononuclear leukocytes.
A chemical plant, where an increased number of non-Hodgkin's lymphomas and myelomas had been observed, was monitored for genotoxic effects occurring in peripheral mononuclear leukocyte samples from 76 exposed workers. Biochemical markers sensitive to DNA repair and drug metabolism were used as the indicators of genotoxic risk. Unscheduled DNA synthesis (UDS) and covalent binding induced by N-acetoxy-N-acetyl-2-aminofluorene (NA-AAF) and constitutive and gamma ray induced adenosine diphosphate ribosyl transferase (ADPRT) activities were highly and significantly elevated over the corresponding values for a control group of 48 postal workers. Microsomal and soluble epoxide hydrolases and glutathione transferase activities directed towards trans-stilbene oxide and 1-chloro-2,4-dinitrobenzene were not significantly altered in the exposed group. The exposure in this factory was complex, involving over 100 chemicals including several well known carcinogens. However, no apparent significant associations to exposure could be established.
Acetoxyacetylaminofluorene↗
Biological effects in a chemical factory with mutagenic exposure. III. Urinary mutagenicity and thioether excretion.
Eighty-five workers in a chemical plant, in which there was an increased frequency of B-lymphocyte tumours (myelomas and lymphomas) and lung cancer, did not excrete higher amounts of thioethers in urine than 48 control subjects. The chemically exposed workers had, however, a higher excretion of thioethers in urine during shift compared to an exposure-free period. The bacterial fluctuation test showed a statistically significantly increased mutagenic activity for E. coli Wp2 uvrA, but not for Salmonella TA98, in the urine of the exposed workers compared with the controls. However, no difference in excretion was found in the chemical workers between work and an exposure free-period. Further, no association of thioether or mutagen excretion with any specific chemical exposure (e.g. ethylene oxide and formaldehyde) in the plant could firmly be established.
Adult↗
Excretion of N-mononitrosopiperazine in urine in workers manufacturing piperazine.
Piperazine has been shown to nitrosate in vivo to N-mononitrosopiperazine (MNPZ) by oral intake. Urine from workers exposed to piperazine in a chemical plant was analysed for nitrosamines by gas chromatography-thermal energy analysis. In five out of 11 exposed cases, MNPZ excretion in urine was 0.3 to 4.7 micrograms/24 h (during and after a work shift). In four cases, MNPZ was detected in some urine samples, and in two cases MNPZ was not detected (less than 0.1 ng/ml). The individual excretion was strongly dependent on piperazine exposure, which ranged from 0.06 to 1.7 mg/m3 (time-weighted average; Spearman's rank correlation 0.78, P = 0.01). The MNPZ excretion showed no significant correlation with nitrite or nitrate in saliva (both: r = 0.50, P = 0.10).
Adult↗
Excretion of N-mononitrosopiperazine after low level exposure to piperazine in air: effects of dietary nitrate and ascorbate.
The secondary amine piperazine may be nitrosated in vivo, following oral intake or occupational exposure by inhalation. The suspected carcinogen N-mononitrosopiperazine could be formed in the human stomach, and in part excreted in the urine. In this study, 0.4 microgram N-mononitrosopiperazine, determined by gas chromatography-Thermal Energy Analysis, was observed in the urine in one of four volunteers, at an experimental exposure by inhalation of 0.3 mg piperazine/m3. The intake of spinach and beetroot caused an increased nitrosation of piperazine, and up to 1.7 microgram N-mononitrosopiperazine was excreted in the urine in the four individuals. This excretion indicates that about 5% of the absorbed piperazine dose was converted to N-mononitrosopiperazine. With the same nitrate-rich diet, but with the addition of citrus fruits and fresh vegetables, the highest excretion was 0.6 microgram N-mononitrosopiperazine. The excretion was significantly correlated with the ratio between the maximum level of nitrite in saliva and the ascorbate level in plasma. There was also a significant interindividual variation. N,N'-Dinitrosopiperazine was not found in any sample of urine.
Administration, Inhalation↗
Small airways function in workers exposed to piperazine.
An N2 wash-out technique was used to estimate the small airways function in 22 male workers, exposed to the asthma-inducing amine piperazine, and in 22 referent subjects, with similar smoking habits and age. The volume of trapped gas (VTG) was determined before and after a bronchial provocation with an aerosol of 0.25 ml 0.01% metacholine solution. No difference in VTG was observed between the piperazine-exposed workers and the referent subjects, either before or after the metacholine provocation. This indicates that a time-weighted average (TWA) exposure of about 0.1 mg piperazine/m3 does not cause small airways disease in non-asthmatic workers. Further, age and smoking habits were significantly associated with VTG.
Adult↗
N-mononitrosopiperazine in urine after occupational exposure to piperazine.
We have shown previously that intake of the drug piperazine can result in the endogenous formation of N-mononitrosopiperazine (NPZ; Bellander et al., 1985). The present investigation deals with the possibility of endogenous formation of NPZ due to occupational exposure to piperazine in a chemical plant.
Chemical Industry↗
Determination of piperazine in working atmosphere and in human urine using derivatization and capillary gas chromatography with nitrogen- and mass-selective detection.
A reliable routine method is presented for the determination of piperazine down to the sub-ppm level in aqueous solutions and in urine. The method includes a two-phase derivatization procedure with ethyl- or isobutyl chloroformate as the reagent, followed by a capillary gas chromatographic determination using nitrogen- or mass selective detection. The addition of ammonia ensured a quantitative recovery. Detection limits for piperazine in urine were ca. 20 ng/ml using nitrogen-selective and ca. 1 ng/ml with mass-selective detection. The calibration plots were linear in the investigated range, 100-10,000 ng/ml with nitrogen-selective and 30-3000 ng/ml with mass-selective detection. The precision was ca. 6% at a concentration of 300 ng/ml. Acid anhydrides were investigated as alternative reagents in the two-phase derivatization procedure, and heptafluorobutyric acid anhydride in aqueous solutions gave approximately 100% recovery. However, in urine the recoveries of the investigated acid anhydride derivatives were unsatisfactory.
Air Pollutants, Occupational↗
Mortality and cancer morbidity among workers in a chemical factory.
A retrospective cohort study was performed on a group of 664 male workers employed for at least one month during the period 1942-1979 in a chemical factory. Both established and suspected carcinogens had been handled in the plant, primarily piperazine, but also urethane, ethylene oxide, formaldehyde, and organic solvents. A significantly increased mortality, compared with the regional death rate, was observed in the cohort. The increase was mainly due to violent deaths and cardiovascular diseases. No rise in death rates was observed for asthma, bronchitis or emphysema, in spite of other evidence of a high risk of occupational asthma, due to exposure to piperazine. A statistically significant increase in cancer morbidity was observed for malignant lymphoma/myelomatosis when an induction latency time of at least 10 years was used. Furthermore, an increase in bronchial cancer was noted, but it was statistically significant only when an induction-latency time of at least 15 years was used. A case-referent study within the cohort did not reveal any significant association between any specific chemical exposure and cancer morbidity.
Adult↗
Formation of N-mononitrosopiperazine in the stomach and its excretion in the urine after oral intake of piperazine.
Piperazine, a secondary amine widely used as an anthelmintic drug, nitrosates rapidly in vitro to form two N-nitrosamines. Anhydrous piperazine and a drug formulation were found to have a content of 0.2 to 20 micrograms of the suspected carcinogen N-mononitrosopiperazine per gram piperazine, but no detectable amounts of the carcinogen N,N'-dinitrosopiperazine. The aim of this study was to investigate the possible nitrosation of the drug piperazine in man. Thirty minutes after oral administration of 480 mg piperazine to four fasting, healthy, male volunteers, gastric juice contained 140 to 230 micrograms/liter N-mononitrosopiperazine as determined by gas chromatography-thermal energy analysis. The total amount produced by endogenous formation in the stomach is estimated to have been 30 to 66 micrograms. N-Mononitrosopiperazine was not detected in blood, but was excreted in the urine, mainly in the first 6 hr (0.07 to 2.1 micrograms) with half of this appearing within 3 hr. Internal acidification of the urine did not affect the excretion or content. N,N'-Dinitrosopiperazine was not found in any sample of gastric juice, blood, or urine. The excretion of piperazine was in accordance with earlier findings. Coadministration of 2 g ascorbic acid resulted in a significant but incomplete and varying inhibition of both the nitrosation in the stomach and the excretion in urine.
Administration, Oral↗
Piperazine-induced airway symptoms: exposure-response relationships and selection in an occupational setting.
The heterocyclic secondary amine piperazine is known to cause asthma. In a cohort of 602 workers, employed during the period 1942-1979, at a chemical industry where piperazine is handled, a study conducted by means of a mailed questionnaire showed a strong exposure-response relationship as to frequency of work-related airway symptoms indicating asthma. In the most exposed group about a third of the workers had experienced such symptoms. Age, length of employment, smoking habits, and previous work-related asthmatic symptoms, but not atopy, modified the response. Further, there was an association between piperazine exposure and chronic bronchitis. In the most exposed group every fourth subject had chronic bronchitis. The frequency was modified by smoking habits; atopy was a confounder. Although many subjects, especially high-exposed ones, left work because of airway symptoms, there was no difference in occurrence of airway symptoms between former and present employees, ie, no "healthy worker selection" ("survivor population effect").
Asthma↗
Piperazine-induced occupational asthma.
Asthmatic reactions were studied among some 130 factory workers who handled amines and other chemicals. Among present employees, we found 15 cases of asthma associated with occupational exposure to chemicals; among former employees there were at least 18. The inducing agent was judged to be piperazine in 29 persons and ethylenediamine (EDA) in three. The asthma was of the late or dual type; immediate reactions alone were to seen. No one had attacks of asthma before employment, and atopic subjects were not preferentially affected. Routine spirometry revealed airway obstruction in fewer than half of the recent cases. Tests of nonspecific bronchial reactivity with methacholine in six subjects with recent asthma showed hyperactivity in five, while tow subjects with earlier asthma did not have hyperactivity. Bronchial provocation tests with piperazine in one subject were positive both in the factory and in the laboratory. The level of piperazine was 1.2 mg/m3 time-weighted average (TWA) in a work place associated with induction of the asthmatic state, and 0.3 mg/m3 in a place connected with attacks in "sensitized" subjects.
Adult↗
Acute myeloid leukemia among petrol station attendants.
The risk of acute myeloid leukemia (AML) within different occupations was studied, using occupational information obtained from the Swedish 1970 census. Follow-up in the Swedish Cancer Register was carried out from 1971 to 1984. Among male petrol station attendants, 10 cases were observed versus 2.8 expected (observed/expected = 3.6, 95% confidence interval 1.7-6.6). For several decades, Swedish petrol has contained 3-5% of benzene. Thus, a hypothesis was that benzene had contributed to the excess risk. The work histories of the 10 cases were reconstructed through interviews with surviving relatives and were compatible with the hypothesis. However, because the air benzene exposures at petrol stations always have been lower than benzene exposures associated previously with an increased risk of AML, the leukemogenic effect of benzene may have been potentiated by other petrol or vehicle exhaust components.
Adult↗