-
Toxicology and Industrial Health Mar 1987Benzene is one of the world's major commodity chemicals. It is derived from petroleum and coal and is used both as a solvent and as a starting material in chemical...
Benzene is one of the world's major commodity chemicals. It is derived from petroleum and coal and is used both as a solvent and as a starting material in chemical syntheses. The numerous industrial uses of benzene over the last century need not be recounted here, but the most recent addition to the list of uses of benzene is as a component in a mixture of aromatic compounds added to gasoline for the purpose of replacing lead compounds as anti-knock ingredients. The best known and longest recognized toxic effect of benzene is the depression of bone marrow function seen in occupationally exposed individuals. These people have been found to display anemia, leucopenia, and/or thrombocytopenia. When pancytopenia, i.e., the simultaneous depression of all three cell types, occurs and is accompanied by bone marrow necrosis, the syndrome is called aplastic anemia. In addition to observing this decrease in humans and relating it to benzene exposure, it has been possible to establish animal models which mimic the human disease. The result has been considerable scientific investigation into the mechanism of benzene toxicity. Although the association between benzene exposure and aplastic anemia has been recognized and accepted throughout most of this century, it is only recently that leukemia, particularly of the acute myelogenous type, has been related to benzene. The acceptance of benzene as an etiological agent in aplastic anemia in large measure derives from our ability to reproduce the disease in most animals treated with sufficiently high doses of benzene over the necessary time period. Unfortunately, despite extensive efforts in several laboratories, it has not been possible to establish a reproducible, reliable model for the study of benzene-induced leukemia. The recent demonstration that several animals exposed to benzene either by inhalation or in the drinking water during studies by Drs. B. Goldstein and C. Maltoni suggests that such a model may be forthcoming. Nevertheless, at this time it is not clear whether bone marrow damage of the type that leads to aplastic anemia is required for the development of leukemia. Most studies of benzene toxicity have involved dosing animals with benzene either by inhalation or by injection, using high doses to ensure a toxic response. Very few studies have concentrated on the oral route of administration and none have concentrated on administering benzene by mouth at the low doses occasionally detected in drinking water.(ABSTRACT TRUNCATED AT 400 WORDS)
Topics: Air Pollutants, Occupational; Animals; Benzene; Bone Marrow; Carcinogens; Food Contamination; Humans; United States
PubMed: 3590206
DOI: 10.1177/074823378700300108 -
Journal of Toxicology and Environmental... Nov 2000
Review
Topics: Animals; Benzene; Bone Marrow Diseases; Carcinogens; Humans; Leukemia; Occupational Diseases; Occupational Exposure; Risk Assessment
PubMed: 11086936
DOI: No ID Found -
Environmental Health Perspectives Jul 1989Considering the very large industrial usage of benzene, studies in risk assessment aimed at the evaluation of carcinogenic risk at low levels of exposure are important.... (Review)
Review
Considering the very large industrial usage of benzene, studies in risk assessment aimed at the evaluation of carcinogenic risk at low levels of exposure are important. Animal data can offer indications about what could happen in humans and provide more diverse information than epidemiological data with respect to dose-response consideration. We have considered experiments investigating metabolism, short-term genotoxicity tests, DNA adduct formation, and carcinogenicity long-term tests. According to the different experiments, a saturation of benzene metabolism and benzene effects in terms of genotoxicity seems evident above 30 to 100 ppm. Below 30 to 60 ppm the initiating effect of benzene seems to be linear for a large interval of dosages, at least judging from DNA adduct formation. Potential lack of a promoting effect of benzene (below 10 ppm) could generate a sublinear response at nontoxic levels of exposure. This possibility was suggested by epidemiological data in humans and is not confirmed or excluded by our observations with animals.
Topics: Animals; Benzene; Carcinogens; Dose-Response Relationship, Drug; Male; Mice; Mutagens; Rats; Risk
PubMed: 2676496
DOI: 10.1289/ehp.8982171 -
Advances in Experimental Medicine and... 1996
Review
Topics: Animals; Benzene; Biotransformation; Carcinogens; Humans; Risk Assessment
PubMed: 8794220
DOI: 10.1007/978-1-4757-9480-9_34 -
Journal of Toxicology and Environmental... Nov 2000
Review
Topics: Animals; Benzene; Environmental Exposure; Humans; Occupational Exposure; Risk Assessment
PubMed: 11086957
DOI: 10.1080/00984100050166532 -
The Annals of Occupational Hygiene Nov 1972
Topics: Benzene; Environmental Exposure; Humans; Models, Biological; Occupational Medicine; Phenols
PubMed: 4648250
DOI: 10.1093/annhyg/15.2-4.409 -
Acta Biologica Hungarica Jun 2015Using NMR spectroscopy benzene derivatives were detected in mycelia of Fusarium graminearum, a pathogen of wheat and maize. In previous studies F. graminearum was found...
Using NMR spectroscopy benzene derivatives were detected in mycelia of Fusarium graminearum, a pathogen of wheat and maize. In previous studies F. graminearum was found to cause cancer to humans and benzene derivatives were detected in breath of cancer sufferers. Surprisingly, no study found benzene derivatives to be the cancerous agents in F. graminearum. In this study we detected benzene derivatives in F. graminearum and propose to study their role as cancer agents.
Topics: Benzene; Fusarium; Humans; Magnetic Resonance Spectroscopy; Mycelium
PubMed: 26081280
DOI: 10.1556/018.66.2015.2.11 -
Annals of Science Apr 2015Kekulé first suggested a hexagonal structure for benzene in 1865. For over a half-century after, chemists struggled to reconcile proposed structures for benzene and...
Kekulé first suggested a hexagonal structure for benzene in 1865. For over a half-century after, chemists struggled to reconcile proposed structures for benzene and other aromatic compounds with their resistance to chemical transformation and tendency to maintain the type during reaction. The combined structural and reactivity features of these compounds were eventually covered by the term 'aromaticity'. Kekulé, Bamberger and Thiele had each proposed a criterion for aromaticity; all were either empirically contradicted or incapable of evaluation. In the 1930s, two rival quantum mechanical methods succeeded in establishing a physical basis for aromaticity. Using valence bond theory, Pauling attributed benzene's stability to its being a resonance hybrid of several Lewis structures. Calculating resonance energies was challenging but manipulating Lewis structures was not; that procedure provided qualitative insights into aromatic structure and reactivity. Resonance theory appealed especially to organic chemists and eclipsed Hückel's contemporaneous molecular orbital approach, which remained relatively inaccessible. In the 1950s, however, simple rules derived from Hückel's mathematics, combined with proton NMR data, provided seemingly universal criteria for aromaticity. In the event, post-1950 discoveries of non-organic, three-dimensional compounds such as ferrocene and the fullerenes that exhibit aromatic properties led chemists to doubt the utility and universality of 'aromaticity' as a concept. A recent consensus maintains that aromaticity is a multi-variable phenomenon that cannot be reduced to a strict definition, a property it shares with other core chemical concepts such as 'acidity' and 'reactivity'.
Topics: Benzene; Chemistry, Organic; History, 19th Century; History, 20th Century; History, 21st Century; Quantum Theory; Terminology as Topic
PubMed: 26104167
DOI: 10.1080/00033790.2015.1007526 -
Regulatory Toxicology and Pharmacology... Apr 1989Cancer risk from exposure to benzene for a working lifetime was estimated from data obtained in studies with rodents. Cancers of the Zymbal gland and the blood-forming... (Review)
Review
Cancer risk from exposure to benzene for a working lifetime was estimated from data obtained in studies with rodents. Cancers of the Zymbal gland and the blood-forming system were selected as endpoints for the assessment because of their consistent occurrence. The combined metabolites were judged from toxicological data to be the best representative of the reactive agent. Because of similarity in the percentages of lifetime exposed in the rodent studies and in the occupational setting, the amount metabolized/day as a result of exposures 5 days a week for a lifetime was judged to be an appropriate dose paradigm for this assessment. Derived Michaelis-Menton constants were used to convert the doses of combined metabolites from the pharmacokinetic studies to the doses used in the bioassays. Scaling across species was based on allometric relationships. Experimental data were used to scale doses across species with body weight ratios raised to the exponents of 0.74 for the inhalation route and 1.0 for the oral route. The occupational lifetime cancer risk estimated from rodent data was 6 to 14 cases/1000 workers, which is consistent with the 9.5 to 174 leukemia cases/1000 estimated by others from epidemiological data. Implications of these estimates and uncertainties associated with making them are discussed.
Topics: Animals; Benzene; Carcinogens; Humans; Occupational Diseases; Risk
PubMed: 2655040
DOI: 10.1016/0273-2300(89)90035-4 -
Advances in Experimental Medicine and... 1991
Review
Topics: Animals; Benzene; Biomarkers; Drug Resistance; In Vitro Techniques; Mice; Mice, Inbred Strains; Sorbic Acid; Species Specificity
PubMed: 2069029
DOI: 10.1007/978-1-4684-5877-0_77