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Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Benzene, a common industrial chemical and a component of gasoline, is radiomimetic and exposure may lead progressively to aplastic anaemia, leukaemia, and multiple myeloma. Although benzene has been shown to cause many types of genetic damage, it has consistently been classified as a non-mutagen in the Ames test, possibly because of the inadequacy of the S9 microsomal activation system. The metabolism of benzene is complex, yielding glucuronide and sulphate conjugates of phenol, quinol, and catechol, L-phenylmercapturic acid, and muconaldehyde and trans, trans-muconic acid by ring scission. Quinol is oxidised to p-benzoquinone, which binds to vital cellular components or undergoes redox cycling to generate oxygen radicals; muconaldehyde, like p-benzoquinone, is toxic through depletion of intracellular glutathione. Exposure to benzene may also induce the microsomal mixed function oxidase, cytochrome P450 IIE1, which is probably responsible for the oxygenation of benzene, but also has a propensity to generate oxygen radicals. The radiomimetic nature of benzene and its ability to induce different sites of neoplasia indicate that formation of oxygen radicals is a major cause of benzene toxicity, which involves multiple mechanisms including synergism between arylating and glutathione-depleting reactive metabolites and oxygen radicals. The occupational exposure limit in the United Kingdom (MEL) and the United States (PEL) was 10 ppm based on the association of benzene exposure with aplastic anaemia, but recently was lowered to 5 ppm and 1 ppm respectively, reflecting a concern for the risk of neoplasia. The American Conference of Governmental Industrial Hygienists (ACGIH) has even more recently recommended that, as benzene is considered an A1 carcinogen, the threshold limit value (TLV) should be decreased to 0.1 ppm. Only one study in man, based on nine cases of benzene associated fatal neoplasia, has been considered suitable for risk assessment. Recent re-evaluation of these data indicated that past assessments may have overestimated the risk, and different authors have considered that lifetime exposure to benzene at 1 ppm would result in an excess of leukaemia deaths of 9.5 to 1.0 per 1000. Although in this study, deaths at low levels of benzene exposure were associated with multiple myeloma and a long latency period, instead of leukaemia, which might justify further lowering of the exposure limit, the risk assessment model has been found to be non-significant for response at low levels of exposure. The paucity of data for man, the complexity of the metabolic activation of benzene, the interactive and synergistic mechanisms of benzene toxicity and carcinogenicity, the different disease endpoints (aplastic anaemia, leukaemia, and multiple myeloma), and different individual susceptibilities, all indicate that in such a complex scenario, regulators should proceed with caution before making further changes to the exposure limit for this chemical.
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PMID:The toxicity of benzene and its metabolism and molecular pathology in human risk assessment. 185 46

The hematotoxicity of benzene exposure has been well known for a century. Benzene causes leukocytopenia, thrombocytopenia, pancytopenia, etc. The clinical and hematologic picture of aplastic anemia resulting from benzene exposure is not different from classical aplastic anemia; in some cases, mild bilirubinemia, changes in osmotic fragility, increase in lactic dehydrogenase and fecal urobilinogen, and occasionally some neurological abnormalities are found. Electromicroscopic findings in some cases of aplastic anemia with benzene exposure were similar to those observed by light microscopy. Benzene hepatitis-aplastic anemia syndrome was observed in a technician with benzene exposure. Ten months after occurrence of hepatitis B, a severe aplastic anemia developed. The first epidemiologic study proving the leukemogenicity of benzene was performed between 1967 and 1973 to 1974 among shoe workers in Istanbul. The incidence of leukemia was 13.59 per 100,000, which is a significant increase over that of leukemia in the general population. Following the prohibition and discontinuation of the use of benzene in Istanbul, there was a striking decrease in the number of leukemic shoe workers in Istanbul. In 23.7% of our series, consisting of 59 leukemic patients with benzene exposure, there was a preceding pancytopenic period. Furthermore, a familial connection was found in 10.2% of them. The 89.8% of our series showed the findings of acute leukemia. The possible factors that may determine the types of leukemia in benzene toxicity are discussed. The possible role of benzene exposure is presented in the development of malignant lymphoma, multiple myeloma, and lung cancer.
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PMID:Hematotoxicity and carcinogenicity of benzene. 267 98

Benzene. The evidence for carcinogenicity of benzene in humans was evaluated by the IARC in 1982 as follows: "It is established that human exposure to commercial benzene or benzene-containing mixtures can cause damage to the haematopoietic system, including pancytopenia. The relationship between benzene exposure and the development of acute myelogenous leukaemia has been established in epidemiological studies. "Reports linking exposure to benzene with other malignancies were considered to be inadequate for evaluation. "There is sufficient evidence that benzene is carcinogenic to man." This evaluation now warrants some elaboration and updating. While the epidemiological evidence concerning benzene carcinogenicity is strongest for acute myelocytic leukaemia, there is some limited evidence of increased risks of chronic myeloid and chronic lymphocytic leukaemia. In addition, recent studies have suggested an increased risk of multiple myeloma, while others indicate a dose-related increase for total lymphatic and haematopoietic neoplasms. Corroborative evidence for such a generalized effect comes from experimental studies showing that exposure to benzene depresses all lympho-haematopoietic cell lines. While only limited evidence of benzene carcinogenicity in experimental animals exists, the recent findings of the National Toxicology Program (NTP, 1984) in the U.S.A. and Maltoni et al. (1985) strongly indicate that benzene is an experimental carcinogen. Toluene and xylene. While no direct human evidence is available, there is recent evidence of carcinogenicity of toluene and xylene at high concentrations in experimental animals. It should also be noted that any future epidemiological observations of cancer risks associated with toluene or xylene would have to take account of the suspected effects of benzene impurities.
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PMID:Carcinogenicity of benzene, toluene and xylene: epidemiological and experimental evidence. 305 47

A nested case-control study found that the excess of leukemia, identified among the male members of the Health Watch cohort, was associated with benzene exposure. Exposure had been retrospectively estimated for each individual occupational history using an algorithm in a relational database. Benzene exposure measurements, supplied by Australian petroleum companies, were used to estimate exposure for specific tasks. The tasks carried out within each job, the products handled, and the technology used, were identified from structured interviews with contemporary colleagues. More than half of the subjects started work after 1965 and had an average exposure period of 20 years. Exposure was low; nearly 85% of the cumulative exposure estimates were at or below 10 ppm-years. Matched analyses showed that leukemia risk increased with increasing cumulative benzene exposures and with increasing exposure intensity of the highest-exposed job. Non-Hodgkin lymphoma and multiple myeloma were not associated with benzene exposure. A reanalysis reported here, showed that for the 7 leukemia case-sets with greater than 16 ppm-years cumulative exposure, the odds ratio was 51.9 (5.6-477) when compared to the 2 lowest exposed categories combined to form a new reference category. The addition of occasional high exposures, e.g. as a result of spillages, increased exposure for 25% of subjects but for most, the increase was less than 5% of total exposure. The addition of these exposures reduced the odds ratios. Cumulative exposures did not range as high as those in comparable studies; however, the recent nature of the cohort and local handling practices can explain these differences.
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PMID:Health Watch exposure estimates: do they underestimate benzene exposure? 1593 97

Human exposure to benzene in work environment is a global occupational health problem. After inhalation or absorption, benzene targets organs viz. liver, kidney, lung, heart and brain etc. It is metabolized mainly in the liver by cytochrome P450 multifunctional oxygenase system. Benzene causes haematotoxicity through its phenolic metabolites that act in concert to produce DNA strand breaks, chromosomal damage, sister chromatid exchange, inhibition of topoisomerase II and damage to mitotic spindle. The carcinogenic and myelotoxic effects of benzene are associated with free radical formation either as benzene metabolites or lipid peroxidation products. Benzene oxide and phenol have been considered as proheptons. Liver microsomes play an important role in biotransformation of benzene whereas in kidney, it produces degenerative intracellular changes. Cohort studies made in different countries suggest that benzene induces multiple myeloma in petrochemical workers. Though extensive studies have been performed on its toxicity, endocrinal disruption caused by benzene remains poorly known. Transgenic cytochrome P450 IIE1 mice may help in understanding further toxic manifestations of benzene.
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PMID:Biochemical toxicity of benzene. 1616 67

A case-control study nested in the Health Watch cohort of petroleum industry workers, investigated whether the excess of lymphohematopoetic cancers, identified among male members of the Health Watch cohort, was associated with benzene exposure. Cases of non-Hodgkin's lymphoma (n = 31), multiple myeloma (n = 15), and leukemia (n = 33) were identified between 1981 and 1999. Cases were age-matched to five controls. Exposure was retrospectively estimated for each occupational history using an algorithm in a relational database. Benzene exposure measurements, supplied by Australian petroleum companies, were used to estimate exposure for specific tasks. The tasks carried out within the job, the products handled, and the technology used, were identified from interviews with contemporary colleagues. More than half of the subjects started work after 1965 and had an average exposure period of 20 years. Exposure was low, 85% of the cumulative exposure estimates were <10 ppm years. Matched analyses showed that non-Hodgkin's lymphoma and multiple myeloma were not associated with benzene exposure. Leukemia risk, however, was significantly increased for the subjects with greater than 16 ppm years cumulative exposure, odds ratio (OR) 51.9 (5.6-477) or with greater than 0.8 ppm intensity of highest exposed job. Cumulative exposures were similar to those found in comparable studies. The inclusion of occasional high exposures, for example, as a result of spillages, reduced the ORs, when the exposure was treated as either a continuous or a categorical variable. Our data demonstrate a strong association between leukemia and modest benzene exposure. The choice of cut-point and reference group has a marked effect on the ORs, but does not change the overall conclusions.
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PMID:The health watch case-control study of leukemia and benzene: the story so far. 1711 94

Benzene exposure has been shown to be related to acute myelogenous leukemia, while the association with multiple myeloma and non-Hodgkin lymphoma has been a much-debated issue. We performed a historical cohort study to investigate whether workers employed in Norway's upstream petroleum industry exposed to crude oil and other products containing benzene have an increased risk of developing various subtypes of hematologic neoplasms. Using the Norwegian Registry of Employers and Employees we included all 27,919 offshore workers registered from 1981 to 2003 and 366,114 referents from the general working population matched by gender, age, and community of residence. The cohort was linked to the Cancer Registry of Norway. Workers in the job category "upstream operator offshore", having the most extensive contact with crude oil, had an excess risk of hematologic neoplasms (blood and bone marrow) (rate ratio (RR) 1.90, 95% confidence interval (95% CI): 1.19-3.02). This was ascribed to an increased risk of acute myelogenous leukemia (RR 2.89, 95% CI: 1.25-6.67) and multiple myeloma (RR 2.49, 95% CI: 1.21-5.13). There were no statistical differences between the groups in respect to non-Hodgkin lymphoma. The results suggest that benzene exposure, which most probably caused the increased risk of acute myelogenous leukemia, also resulted in an increased risk of multiple myeloma.
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PMID:Increased risk of acute myelogenous leukemia and multiple myeloma in a historical cohort of upstream petroleum workers exposed to crude oil. 1790 34