Skip to main content
PMC home page
Environmental Health Perspectives logoLink to Environmental Health Perspectives
. 1993 Dec;101(Suppl 6):177–200. doi: 10.1289/ehp.93101s6177

Benzene toxicity and risk assessment, 1972-1992: implications for future regulation.

D J Paustenbach 1, R D Bass 1, P Price 1
PMCID: PMC1520014  PMID: 8020442

Abstract

Acute and chronic exposure to benzene vapors poses a number of health hazards to humans. To evaluate the probability that a specific degree of exposure will produce an adverse effect, risk assessment methods must be used. This paper reviews much of the published information and evaluates the various risk assessments for benzene that have been conducted over the past 20 years. There is sufficient evidence that chronic exposure to relatively high concentrations of benzene can produce an increased incidence of acute myelogenous leukemia (AML). Some studies have indicated that benzene may cause other leukemias, but due to the inconsistency of results, the evidence is not conclusive. To predict the leukemogenic risk for humans exposed to much lower doses of benzene than those observed in most epidemiology studies, a model must be used. Although several models could yield plausible results, to date most risk assessments have used the linear-quadratic or conditional logistic models. These appear to be the most appropriate ones for providing the cancer risk for airborne concentrations of 1 ppb to 10 ppm, the range most often observed in the community and workplace. Of the seven major epidemiology studies that have been conducted, there is a consensus that the Pliofilm cohort (rubber workers) is the best one for estimating the cancer potency because it is the only one with good exposure and incidence of disease data. The current EPA, OSHA, and ACGIH cancer potency estimates for benzene are based largely on this cohort. A retrospective exposure assessment and an analysis of the incidence of disease in these workers were completed in 1991. All of these issues are discussed and the implications evaluated in this paper. The range of benzene exposures to which Americans are commonly exposed and the current regulatory criteria are also presented.

Full text

PDF
181

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. APPUHN E., GOLDECK H. Früh- und Spätschäden der Blutbildung durch Benzol und seine Homologen. Arch Gewerbepathol Gewerbehyg. 1957;15(4):399–428. [PubMed] [Google Scholar]
  2. Aksoy M. Different types of malignancies due to occupational exposure to benzene: a review of recent observations in Turkey. Environ Res. 1980 Oct;23(1):181–190. doi: 10.1016/0013-9351(80)90104-8. [DOI] [PubMed] [Google Scholar]
  3. Aksoy M., Dinçol K., Akgün T., Erdem S., Dinçol G. Haematological effects of chronic benzene poisoning in 217 workers. Br J Ind Med. 1971 Jul;28(3):296–302. doi: 10.1136/oem.28.3.296. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Aksoy M., Dinçol K., Erdem S., Dinçol G. Acute leukemia due to chronic exposure to benzene. Am J Med. 1972 Feb;52(2):160–166. doi: 10.1016/0002-9343(72)90065-4. [DOI] [PubMed] [Google Scholar]
  5. Aksoy M., Erdem S. Followup study on the mortality and the development of leukemia in 44 pancytopenic patients with chronic exposure to benzene. Blood. 1978 Aug;52(2):285–292. [PubMed] [Google Scholar]
  6. Andersen M. E., Clewell H. J., 3rd, Gargas M. L., Smith F. A., Reitz R. H. Physiologically based pharmacokinetics and the risk assessment process for methylene chloride. Toxicol Appl Pharmacol. 1987 Feb;87(2):185–205. doi: 10.1016/0041-008x(87)90281-x. [DOI] [PubMed] [Google Scholar]
  7. Andrews L. S., Lee E. W., Witmer C. M., Kocsis J. J., Snyder R. Effects of toluene on the metabolism, disposition and hemopoietic toxicity of [3H]benzene. Biochem Pharmacol. 1977 Feb 15;26(4):293–300. doi: 10.1016/0006-2952(77)90180-0. [DOI] [PubMed] [Google Scholar]
  8. Arp E. W., Jr, Wolf P. H., Checkoway H. Lymphocytic leukemia and exposures to benzene and other solvents in the rubber industry. J Occup Med. 1983 Aug;25(8):598–602. [PubMed] [Google Scholar]
  9. Au W. W., Ramanujam V. M., Ward J. B., Jr, Legator M. S. Chromosome aberrations in lymphocytes of mice after sub-acute low-level inhalation exposure to benzene. Mutat Res. 1991 Jun;260(2):219–224. doi: 10.1016/0165-1218(91)90011-a. [DOI] [PubMed] [Google Scholar]
  10. Austin H., Delzell E., Cole P. Benzene and leukemia. A review of the literature and a risk assessment. Am J Epidemiol. 1988 Mar;127(3):419–439. doi: 10.1093/oxfordjournals.aje.a114820. [DOI] [PubMed] [Google Scholar]
  11. Blank I. H., McAuliffe D. J. Penetration of benzene through human skin. J Invest Dermatol. 1985 Dec;85(6):522–526. doi: 10.1111/1523-1747.ep12277325. [DOI] [PubMed] [Google Scholar]
  12. Bois F. Y., Smith M. T., Spear R. C. Mechanisms of benzene carcinogenesis: application of a physiological model of benzene pharmacokinetics and metabolism. Toxicol Lett. 1991 May;56(3):283–298. doi: 10.1016/0378-4274(91)90157-2. [DOI] [PubMed] [Google Scholar]
  13. Bois F. Y., Woodruff T. J., Spear R. C. Comparison of three physiologically based pharmacokinetic models of benzene disposition. Toxicol Appl Pharmacol. 1991 Aug;110(1):79–88. doi: 10.1016/0041-008x(91)90291-l. [DOI] [PubMed] [Google Scholar]
  14. Bond G. G., McLaren E. A., Baldwin C. L., Cook R. R. An update of mortality among chemical workers exposed to benzene. Br J Ind Med. 1986 Oct;43(10):685–691. doi: 10.1136/oem.43.10.685. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Brett S. M., Rodricks J. V., Chinchilli V. M. Review and update of leukemia risk potentially associated with occupational exposure to benzene. Environ Health Perspect. 1989 Jul;82:267–281. doi: 10.1289/ehp.8982267. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Brodfuehrer J. I., Chapman D. E., Wilke T. J., Powis G. Comparative studies of the in vitro metabolism and covalent binding of 14C-benzene by liver slices and microsomal fraction of mouse, rat, and human. Drug Metab Dispos. 1990 Jan-Feb;18(1):20–27. [PubMed] [Google Scholar]
  17. Brugnone F., Perbellini L., Faccini G. B., Pasini F., Maranelli G., Romeo L., Gobbi M., Zedde A. Breath and blood levels of benzene, toluene, cumene and styrene in non-occupational exposure. Int Arch Occup Environ Health. 1989;61(5):303–311. doi: 10.1007/BF00409385. [DOI] [PubMed] [Google Scholar]
  18. Burmaster D. E., Maxwell N. I. Time- and loading-dependence in the McKone model for dermal uptake of organic chemicals from a soil matrix. Risk Anal. 1991 Sep;11(3):491–497. doi: 10.1111/j.1539-6924.1991.tb00634.x. [DOI] [PubMed] [Google Scholar]
  19. CURLETTO R., CICONALI M. [On benzol-induced blood disease]. Med Lav. 1962 Aug-Sep;53:505–546. [PubMed] [Google Scholar]
  20. Cassidy M. K., Houston J. B. In vivo assessment of extrahepatic conjugative metabolism in first pass effects using the model compound phenol. J Pharm Pharmacol. 1980 Jan;32(1):57–59. doi: 10.1111/j.2042-7158.1980.tb12846.x. [DOI] [PubMed] [Google Scholar]
  21. Cassidy M. K., Houston J. B. In vivo capacity of hepatic and extrahepatic enzymes to conjugate phenol. Drug Metab Dispos. 1984 Sep-Oct;12(5):619–624. [PubMed] [Google Scholar]
  22. Cox L. A., Jr Biological basis of chemical carcinogenesis: insights from benzene. Risk Anal. 1991 Sep;11(3):453–464. doi: 10.1111/j.1539-6924.1991.tb00631.x. [DOI] [PubMed] [Google Scholar]
  23. Crawford D. R., Greenberger J. S. Active oxygen transforms murine myeloid progenitor cells in vitro. Int J Cancer. 1991 Nov 11;49(5):744–749. doi: 10.1002/ijc.2910490519. [DOI] [PubMed] [Google Scholar]
  24. Cronkite E. P., Bullis J., Inoue T., Drew R. T. Benzene inhalation produces leukemia in mice. Toxicol Appl Pharmacol. 1984 Sep 15;75(2):358–361. doi: 10.1016/0041-008x(84)90219-9. [DOI] [PubMed] [Google Scholar]
  25. DEGOWIN R. L. BENZENE EXPOSURE AND APLASTIC ANEMIA FOLLOWED BY LEUKEMIA 15 YEARS LATER. JAMA. 1963 Sep 7;185:748–751. doi: 10.1001/jama.1963.03060100028011. [DOI] [PubMed] [Google Scholar]
  26. DEGOWIN R. L. BENZENE EXPOSURE AND APLASTIC ANEMIA FOLLOWED BY LEUKEMIA 15 YEARS LATER. JAMA. 1963 Sep 7;185:748–751. doi: 10.1001/jama.1963.03060100028011. [DOI] [PubMed] [Google Scholar]
  27. DI GUGLIELMO G., IANNACCONE A. Inhibition of mitosis and regressive changes of erythroblasts in acute erythropathy caused by occupational benzene poisoning. Acta Haematol. 1958 Mar;19(3):144–147. doi: 10.1159/000205425. [DOI] [PubMed] [Google Scholar]
  28. Da Silva C., Fan X. T., Castagna M. Benzene-mediated protein kinase C activation. Environ Health Perspect. 1989 Jul;82:91–95. doi: 10.1289/ehp.898291. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Dean B. J. Genetic toxicology of benzene, toluene, xylenes and phenols. Mutat Res. 1978;47(2):75–97. doi: 10.1016/0165-1110(78)90014-3. [DOI] [PubMed] [Google Scholar]
  30. Eastmond D. A., Smith M. T., Irons R. D. An interaction of benzene metabolites reproduces the myelotoxicity observed with benzene exposure. Toxicol Appl Pharmacol. 1987 Oct;91(1):85–95. doi: 10.1016/0041-008x(87)90196-7. [DOI] [PubMed] [Google Scholar]
  31. Erexson G. L., Wilmer J. L., Steinhagen W. H., Kligerman A. D. Induction of cytogenetic damage in rodents after short-term inhalation of benzene. Environ Mutagen. 1986;8(1):29–40. doi: 10.1002/em.2860080104. [DOI] [PubMed] [Google Scholar]
  32. Fori A., Pacifico E., Limonta A. Chromosome studies in workers exposed to benzene or toluene or both. Arch Environ Health. 1971 Mar;22(3):373–378. [PubMed] [Google Scholar]
  33. Forni A., Moreo L. Cytogenetic studies in a case of benzene leukaemia. Eur J Cancer. 1967 Nov;3(4):251–255. doi: 10.1016/0014-2964(67)90005-9. [DOI] [PubMed] [Google Scholar]
  34. Gad-El Karim M. M., Sadagopa Ramanujam V. M., Legator M. S. Correlation between the induction of micronuclei in bone marrow by benzene exposure and the excretion of metabolites in urine of CD-1 mice. Toxicol Appl Pharmacol. 1986 Sep 30;85(3):464–477. doi: 10.1016/0041-008x(86)90354-6. [DOI] [PubMed] [Google Scholar]
  35. Gad-El-Karim M. M., Harper B. L., Legator M. S. Modifications in the myeloclastogenic effect of benzene in mice with toluene, phenobarbital, 3-methylcholanthrene, Aroclor 1254 and SKF-525A. Mutat Res. 1984 Mar;135(3):225–243. doi: 10.1016/0165-1218(84)90126-5. [DOI] [PubMed] [Google Scholar]
  36. Gaido K. W., Wierda D. Modulation of stromal cell function in DBA/2J and B6C3F1 mice exposed to benzene or phenol. Toxicol Appl Pharmacol. 1985 Dec;81(3 Pt 1):469–475. doi: 10.1016/0041-008x(85)90418-1. [DOI] [PubMed] [Google Scholar]
  37. Gaido K. W., Wierda D. Suppression of bone marrow stromal cell function by benzene and hydroquinone is ameliorated by indomethacin. Toxicol Appl Pharmacol. 1987 Jul;89(3):378–390. doi: 10.1016/0041-008x(87)90157-8. [DOI] [PubMed] [Google Scholar]
  38. Gallinelli R. Leucosi acuta paramieloblastica da benzolismo cronico in una studentessa di scuola d'arte per il mosaico. Med Lav. 1966 Apr;57(4):257–261. [PubMed] [Google Scholar]
  39. Girard R., Revol L. La fréquence d'une exposition benzénique au cours des hémpathies graves. Nouv Rev Fr Hematol. 1970 Jul-Aug;10(4):477–483. [PubMed] [Google Scholar]
  40. Glatt H., Padykula R., Berchtold G. A., Ludewig G., Platt K. L., Klein J., Oesch F. Multiple activation pathways of benzene leading to products with varying genotoxic characteristics. Environ Health Perspect. 1989 Jul;82:81–89. doi: 10.1289/ehp.898281. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Goguel A., Cavigneaux A., Bernard J. Les leucémies benzéniques. Bull Inst Natl Sante Rech Med. 1967 May-Jun;22(3):421–441. [PubMed] [Google Scholar]
  42. Goldstein B. D. Benzene toxicity. Occup Med. 1988 Jul-Sep;3(3):541–554. [PubMed] [Google Scholar]
  43. Goldstein B. D. Benzene toxicity: a critical evaluation: hematotoxicity in humans. J Toxicol Environ Health Suppl. 1977;2:69–105. [PubMed] [Google Scholar]
  44. Goldstein B. D., Snyder C. A., Laskin S., Bromberg I., Albert R. E., Nelson N. Myelogenous leukemia in rodents inhaling benzene. Toxicol Lett. 1982 Oct;13(3-4):169–173. doi: 10.1016/0378-4274(82)90206-5. [DOI] [PubMed] [Google Scholar]
  45. Gonasun L. M., Witmer C., Kocsis J. J., Snyder R. Benzene metabolism in mouse liver microsomes. Toxicol Appl Pharmacol. 1973 Nov;26(3):398–406. doi: 10.1016/0041-008x(73)90276-7. [DOI] [PubMed] [Google Scholar]
  46. Guberan E., Kocher P. Pronostic lointain de l'intoxication benzolique chronique: contrôle d'une population 10 ans aprés l'exposition. Schweiz Med Wochenschr. 1971 Dec 11;101(49):1789–1790. [PubMed] [Google Scholar]
  47. Hanzlik R. P., Hogberg K., Judson C. M. Microsomal hydroxylation of specifically deuterated monosubstituted benzenes. Evidence for direct aromatic hydroxylation. Biochemistry. 1984 Jun 19;23(13):3048–3055. doi: 10.1021/bi00308a031. [DOI] [PubMed] [Google Scholar]
  48. Harper C., Drew R. T., Fouts J. R. Species differences in benzene hydroxylation to phenol by pulmonary and hepatic microsomes. Drug Metab Dispos. 1975 Sep-Oct;3(5):381–388. [PubMed] [Google Scholar]
  49. Hedli C. C., Snyder R., Witmer C. M. Bone marrow DNA adducts and bone marrow cellularity following treatment with benzene metabolites in vivo. Adv Exp Med Biol. 1991;283:745–748. doi: 10.1007/978-1-4684-5877-0_98. [DOI] [PubMed] [Google Scholar]
  50. Henderson R. F., Sabourin P. J., Bechtold W. E., Griffith W. C., Medinsky M. A., Birnbaum L. S., Lucier G. W. The effect of dose, dose rate, route of administration, and species on tissue and blood levels of benzene metabolites. Environ Health Perspect. 1989 Jul;82:9–17. doi: 10.1289/ehp.89829. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Hernberg S., Savilahti M., Ahlman K., Asp S. Prognostic aspects of benzene poisoning. Br J Ind Med. 1966 Jul;23(3):204–209. doi: 10.1136/oem.23.3.204. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Ikeda M., Otsuji H., Imamura T. In vivo suppression of benzene and styrene oxidation by co-administered toluene in rats and effects of phenobarbital. Xenobiotica. 1972 Mar;2(2):101–106. doi: 10.3109/00498257209111041. [DOI] [PubMed] [Google Scholar]
  53. Infante P. F., Rinsky R. A., Wagoner J. K., Young R. J. Leukaemia in benzene workers. Lancet. 1977 Jul 9;2(8028):76–78. doi: 10.1016/s0140-6736(77)90074-5. [DOI] [PubMed] [Google Scholar]
  54. Infante P. F., White M. C. Benzene: epidemiologic observations of leukemia by cell type and adverse health effects associated with low-level exposure. Environ Health Perspect. 1983 Oct;52:75–82. doi: 10.1289/ehp.835275. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. Inoue O., Seiji K., Watanabe T., Kasahara M., Nakatsuka H., Yin S. N., Li G. L., Cai S. X., Jin C., Ikeda M. Mutual metabolic suppression between benzene and toluene in man. Int Arch Occup Environ Health. 1988;60(1):15–20. doi: 10.1007/BF00409373. [DOI] [PubMed] [Google Scholar]
  56. Irons R. D., Dent J. G., Baker T. S., Rickert D. E. Benzene is metabolized and covalently bound in bone marrow in situ. Chem Biol Interact. 1980 May;30(2):241–245. doi: 10.1016/0009-2797(80)90130-1. [DOI] [PubMed] [Google Scholar]
  57. Irons R. D. Quinones as toxic metabolites of benzene. J Toxicol Environ Health. 1985;16(5):673–678. doi: 10.1080/15287398509530777. [DOI] [PubMed] [Google Scholar]
  58. Ishimaru T., Okada H., Tomiyasu T., Tsuchimoto T., Hoshino T., Ichimaru M. Occupational factors in the epidemiology of leukemia in Hiroshima and Nagasaki. Am J Epidemiol. 1971 Mar;93(3):157–165. doi: 10.1093/oxfordjournals.aje.a121242. [DOI] [PubMed] [Google Scholar]
  59. Jensen B. L., Caldwell M. W., French L. G., Briggs D. G. Toxicity, ultrastructural effects, and metabolic studies with 1-(o-chlorophenyl)-1-(p-chlorophenyl)-2,2-dichloroethane(o,p'-DDD) and its methyl analog in the guinea pig and rat. Toxicol Appl Pharmacol. 1987 Jan;87(1):1–9. doi: 10.1016/0041-008x(87)90078-0. [DOI] [PubMed] [Google Scholar]
  60. Johansson I., Ingelman-Sundberg M. Hydroxyl radical-mediated, cytochrome P-450-dependent metabolic activation of benzene in microsomes and reconstituted enzyme systems from rabbit liver. J Biol Chem. 1983 Jun 25;258(12):7311–7316. [PubMed] [Google Scholar]
  61. Kalf G. F. Recent advances in the metabolism and toxicity of benzene. Crit Rev Toxicol. 1987;18(2):141–159. doi: 10.3109/10408448709089859. [DOI] [PubMed] [Google Scholar]
  62. Kearney C. A., Dunham D. B. Gasoline vapor exposures at a high volume service station. Am Ind Hyg Assoc J. 1986 Sep;47(9):535–539. doi: 10.1080/15298668691390188. [DOI] [PubMed] [Google Scholar]
  63. King A. G., Landreth K. S., Wierda D. Hydroquinone inhibits bone marrow pre-B cell maturation in vitro. Mol Pharmacol. 1987 Dec;32(6):807–812. [PubMed] [Google Scholar]
  64. Kipen H. M., Cody R. P., Crump K. S., Allen B. C., Goldstein B. D. Hematologic effects of benzene: a thirty-five year longitudinal study of rubber workers. Toxicol Ind Health. 1988 Dec;4(4):411–430. doi: 10.1177/074823378800400401. [DOI] [PubMed] [Google Scholar]
  65. Kipen H. M., Cody R. P., Goldstein B. D. Use of longitudinal analysis of peripheral blood counts to validate historical reconstructions of benzene exposure. Environ Health Perspect. 1989 Jul;82:199–206. doi: 10.1289/ehp.8982199. [DOI] [PMC free article] [PubMed] [Google Scholar]
  66. Kohli P., Brunner H. E., Siegenthaler W. Erythroleukämie nach chronischer Benzolintoxikation. Untersuchung der Ferro- und Erythrocytenkinetik mit radioaktivem Eisen und Chrom. Schweiz Med Wochenschr. 1967 Mar 25;97(12):368–373. [PubMed] [Google Scholar]
  67. LUDWIG H., WERTHEMANN A. [Benzene myelopathies]. Schweiz Med Wochenschr. 1962 Mar 31;92:378–384. [PubMed] [Google Scholar]
  68. Lamm S. H., Walters A. S., Wilson R., Byrd D. M., Grunwald H. Consistencies and inconsistencies underlying the quantitative assessment of leukemia risk from benzene exposure. Environ Health Perspect. 1989 Jul;82:289–297. doi: 10.1289/ehp.8982289. [DOI] [PMC free article] [PubMed] [Google Scholar]
  69. Lee E. W., Kocsis J. J., Snyder R. Acute effect of benzene on 59Fe incorporation into circulating erythrocytes. Toxicol Appl Pharmacol. 1974 Feb;27(2):431–436. doi: 10.1016/0041-008x(74)90214-2. [DOI] [PubMed] [Google Scholar]
  70. Leong B. K. Experimental benzene intoxication. J Toxicol Environ Health Suppl. 1977;2:45–61. [PubMed] [Google Scholar]
  71. Longacre S. L., Kocsis J. J., Snyder R. Influence of strain differences in mice on the metabolism and toxicity of benzene. Toxicol Appl Pharmacol. 1981 Sep 30;60(3):398–409. doi: 10.1016/0041-008x(81)90324-0. [DOI] [PubMed] [Google Scholar]
  72. Luke C. A., Tice R. R., Drew R. T. The effect of exposure regimen and duration on benzene-induced bone marrow damage in mice. II. Strain comparisons involving B6C3F1, C57B1/6 and DBA/2 male mice. Mutat Res. 1988 Aug;203(4):273–295. doi: 10.1016/0165-1161(88)90018-0. [DOI] [PubMed] [Google Scholar]
  73. Luke C. A., Tice R. R., Drew R. T. The effect of exposure regimen and duration on benzene-induced bone-marrow damage in mice. I. Sex comparison in DBA/2 mice. Mutat Res. 1988 Aug;203(4):251–271. doi: 10.1016/0165-1161(88)90017-9. [DOI] [PubMed] [Google Scholar]
  74. Maibach H. I., Anjo D. M. Percutaneous penetration of benzene and benzene contained in solvents used in the rubber industry. Arch Environ Health. 1981 Sep-Oct;36(5):256–260. doi: 10.1080/00039896.1981.10667633. [DOI] [PubMed] [Google Scholar]
  75. Mallein M. L., Bryon P. A., Fiere D., Girard R. Cryptoleucose aiguë ou anémie réfractaire benzénique (Deux nouveaux cas. Arch Mal Prof. 1971 Sep;32(9):577–579. [PubMed] [Google Scholar]
  76. Maltoni C., Conti B., Cotti G. Benzene: a multipotential carcinogen. Results of long-term bioassays performed at the Bologna Institute of Oncology. Am J Ind Med. 1983;4(5):589–630. doi: 10.1002/ajim.4700040503. [DOI] [PubMed] [Google Scholar]
  77. Maltoni C., Cotti G., Valgimigli L., Mandrioli A. Zymbal gland carcinomas in rats following exposure to benzene by inhalation. Am J Ind Med. 1982;3(1):11–16. doi: 10.1002/ajim.4700030104. [DOI] [PubMed] [Google Scholar]
  78. Maltoni C., Scarnato C. First experimental demonstration of the carcinogenic effects of benzene; long-term bioassays on Sprague-Dawley rats by oral administration. Med Lav. 1979 Sep-Oct;70(5):352–357. [PubMed] [Google Scholar]
  79. Maniashin Iu A., Savchenkov M. F., Sidnev G. V. Toksichnost' benzola dlia zhivotnykh razlichnogo vozrasta. Farmakol Toksikol. 1968 Mar-Apr;31(2):250–253. [PubMed] [Google Scholar]
  80. Marcus W. L. Chemical of current interest--benzene. Toxicol Ind Health. 1987 Mar;3(1):205–266. doi: 10.1177/074823378700300108. [DOI] [PubMed] [Google Scholar]
  81. McKone T. E. Dermal uptake of organic chemicals from a soil matrix. Risk Anal. 1990 Sep;10(3):407–419. doi: 10.1111/j.1539-6924.1990.tb00524.x. [DOI] [PubMed] [Google Scholar]
  82. McMichael A. J., Spirtas R., Kupper L. L., Gamble J. F. Solvent exposure and leukemia among rubber workers: an epidemiologic study. J Occup Med. 1975 Apr;17(4):234–239. [PubMed] [Google Scholar]
  83. Medinsky M. A., Sabourin P. J., Lucier G., Birnbaum L. S., Henderson R. F. A toxikinetic model for simulation of benzene metabolism. Exp Pathol. 1989;37(1-4):150–154. doi: 10.1016/s0232-1513(89)80036-2. [DOI] [PubMed] [Google Scholar]
  84. Money C. D., Gray C. N. Exhaled breath analysis as a measure of workplace exposure to benzene ppm. Ann Occup Hyg. 1989;33(2):257–262. doi: 10.1093/annhyg/33.2.257. [DOI] [PubMed] [Google Scholar]
  85. Monson R. R., Nakano K. K. Mortality among rubber workers. I. White male union employees in Akron, Ohio. Am J Epidemiol. 1976 Mar;103(3):284–296. doi: 10.1093/oxfordjournals.aje.a112226. [DOI] [PubMed] [Google Scholar]
  86. Murray F. J., John J. A., Rampy L. W., Kuna R. A., Schwetz B. A. Embryotoxicity of inhaled benzene in mice and rabbits. Am Ind Hyg Assoc J. 1979 Nov;40(11):993–998. doi: 10.1080/15298667991430604. [DOI] [PubMed] [Google Scholar]
  87. Nomiyama K., Nomiyama H. Respiratory elimination of organic solvents in man. Benzene, toluene, n-hexane, trichloroethylene, acetone, ethyl acetate and ethyl alcohol. Int Arch Arbeitsmed. 1974;32(1):85–91. doi: 10.1007/BF00539098. [DOI] [PubMed] [Google Scholar]
  88. Ott M. G., Townsend J. C., Fishbeck W. A., Langner R. A. Mortality among individuals occupationally exposed to benzene. Arch Environ Health. 1978 Jan-Feb;33(1):3–10. doi: 10.1080/00039896.1978.10667299. [DOI] [PubMed] [Google Scholar]
  89. PARKE D. V., WILLIAMS R. T. Studies in detoxication. XLIX. The metabolism of benzene containing (14C1) benzene. Biochem J. 1953 May;54(2):231–238. doi: 10.1042/bj0540231. [DOI] [PMC free article] [PubMed] [Google Scholar]
  90. Paustenbach D. J., Clewell H. J., 3rd, Gargas M. L., Andersen M. E. A physiologically based pharmacokinetic model for inhaled carbon tetrachloride. Toxicol Appl Pharmacol. 1988 Nov;96(2):191–211. doi: 10.1016/0041-008x(88)90080-4. [DOI] [PubMed] [Google Scholar]
  91. Paustenbach D. J., Price P. S., Ollison W., Blank C., Jernigan J. D., Bass R. D., Peterson H. D. Reevaluation of benzene exposure for the Pliofilm (rubberworker) cohort (1936-1976). J Toxicol Environ Health. 1992 Jul;36(3):177–231. doi: 10.1080/15287399209531633. [DOI] [PubMed] [Google Scholar]
  92. Picciano D. Cytogenetic study of workers exposed to benzene. Environ Res. 1979 Jun;19(1):33–38. doi: 10.1016/0013-9351(79)90031-8. [DOI] [PubMed] [Google Scholar]
  93. Purcell K. J., Cason G. H., Gargas M. L., Andersen M. E., Travis C. C. In vivo metabolic interactions of benzene and toluene. Toxicol Lett. 1990 Jul;52(2):141–152. doi: 10.1016/0378-4274(90)90148-f. [DOI] [PubMed] [Google Scholar]
  94. Ramsey J. C., Andersen M. E. A physiologically based description of the inhalation pharmacokinetics of styrene in rats and humans. Toxicol Appl Pharmacol. 1984 Mar 30;73(1):159–175. doi: 10.1016/0041-008x(84)90064-4. [DOI] [PubMed] [Google Scholar]
  95. Reddy M. V., Blackburn G. R., Schreiner C. A., Mehlman M. A., Mackerer C. R. 32P analysis of DNA adducts in tissues of benzene-treated rats. Environ Health Perspect. 1989 Jul;82:253–257. doi: 10.1289/ehp.8982253. [DOI] [PMC free article] [PubMed] [Google Scholar]
  96. Rickert D. E., Baker T. S., Bus J. S., Barrow C. S., Irons R. D. Benzene disposition in the rat after exposure by inhalation. Toxicol Appl Pharmacol. 1979 Jul;49(3):417–423. doi: 10.1016/0041-008x(79)90441-1. [DOI] [PubMed] [Google Scholar]
  97. Rinsky R. A. Benzene and leukemia: an epidemiologic risk assessment. Environ Health Perspect. 1989 Jul;82:189–191. doi: 10.1289/ehp.8982189. [DOI] [PMC free article] [PubMed] [Google Scholar]
  98. Rinsky R. A., Smith A. B., Hornung R., Filloon T. G., Young R. J., Okun A. H., Landrigan P. J. Benzene and leukemia. An epidemiologic risk assessment. N Engl J Med. 1987 Apr 23;316(17):1044–1050. doi: 10.1056/NEJM198704233161702. [DOI] [PubMed] [Google Scholar]
  99. Rinsky R. A., Young R. J., Smith A. B. Leukemia in benzene workers. Am J Ind Med. 1981;2(3):217–245. doi: 10.1002/ajim.4700020305. [DOI] [PubMed] [Google Scholar]
  100. Robustelli della Cuna G., Favino A., Biscaldi G. P., Pollini G. Trasformazione in leucemia cuta di un caso di mielopatia involutiva benzolica. Haematologica. 1972;57(1):65–89. [PubMed] [Google Scholar]
  101. Rozman C., Woessner S., Saez-Serrania J. Acute erythromyelosis after benzene poisoning. Acta Haematol. 1968;40(4):234–237. doi: 10.1159/000208909. [DOI] [PubMed] [Google Scholar]
  102. Rushton L. A 39-year follow-up of the U.K. oil refinery and distribution center studies: results for kidney cancer and leukemia. Environ Health Perspect. 1993 Dec;101 (Suppl 6):77–84. doi: 10.1289/ehp.93101s677. [DOI] [PMC free article] [PubMed] [Google Scholar]
  103. SAITA G., VIGLIANI E. C. [On the leukemogenic action of benzol]. Med Lav. 1962 Oct;53:581–586. [PubMed] [Google Scholar]
  104. SAITA G., VIGLIANI E. C. [On the leukemogenic action of benzol]. Med Lav. 1962 Oct;53:581–586. [PubMed] [Google Scholar]
  105. SAVILAHTI M. Mehr als 100 Vergiftungsfälle durch Benzol in einer Schuhfabrik; Beobachtungen über hämatologische Symptome und Krankheitsverlauf während eines Jahres. Arch Gewerbepathol Gewerbehyg. 1956;15(2):147–157. [PubMed] [Google Scholar]
  106. Sabourin P. J., Bechtold W. E., Birnbaum L. S., Lucier G., Henderson R. F. Differences in the metabolism and disposition of inhaled [3H]benzene by F344/N rats and B6C3F1 mice. Toxicol Appl Pharmacol. 1988 Jun 15;94(1):128–140. doi: 10.1016/0041-008x(88)90343-2. [DOI] [PubMed] [Google Scholar]
  107. Sammett D., Lee E. W., Kocsis J. J., Snyder R. Partial hepatectomy reduces both metabolism and toxicity of benzene. J Toxicol Environ Health. 1979 Sep;5(5):785–792. doi: 10.1080/15287397909529789. [DOI] [PubMed] [Google Scholar]
  108. Sato A., Nakajima T. Dose-dependent metabolic interaction between benzene and toluene in vivo and in vitro. Toxicol Appl Pharmacol. 1979 Apr;48(2):249–256. doi: 10.1016/0041-008x(79)90030-9. [DOI] [PubMed] [Google Scholar]
  109. Schnatter A. R., Katz A. M., Nicolich M. J., Thériault G. A retrospective mortality study among Canadian petroleum marketing and distribution workers. Environ Health Perspect. 1993 Dec;101 (Suppl 6):85–99. doi: 10.1289/ehp.93101s685. [DOI] [PMC free article] [PubMed] [Google Scholar]
  110. Seiji K., Jin C., Watanabe T., Nakatsuka H., Ikeda M. Sister chromatid exchanges in peripheral lymphocytes of workers exposed to benzene, trichloroethylene, or tetrachloroethylene, with reference to smoking habits. Int Arch Occup Environ Health. 1990;62(2):171–176. doi: 10.1007/BF00383594. [DOI] [PubMed] [Google Scholar]
  111. Sellyei M., Keleman E. Chromosome study in a case of granulocytic leukaemia with 'Pelgerisation' 7 years after benzene pancytopenia. Eur J Cancer. 1971 Feb;7(1):83–85. doi: 10.1016/0014-2964(71)90099-5. [DOI] [PubMed] [Google Scholar]
  112. Smith M. T., Yager J. W., Steinmetz K. L., Eastmond D. A. Peroxidase-dependent metabolism of benzene's phenolic metabolites and its potential role in benzene toxicity and carcinogenicity. Environ Health Perspect. 1989 Jul;82:23–29. doi: 10.1289/ehp.898223. [DOI] [PMC free article] [PubMed] [Google Scholar]
  113. Snyder C. A., Goldstein B. D., Sellakumar A. R., Albert R. E. Evidence for hematotoxicity and tumorigenesis in rats exposed to 100 ppm benzene. Am J Ind Med. 1984;5(6):429–434. doi: 10.1002/ajim.4700050603. [DOI] [PubMed] [Google Scholar]
  114. Snyder C. A., Goldstein B. D., Sellakumar A. R., Bromberg I., Laskin S., Albert R. E. The inhalation toxicology of benzene: incidence of hematopoietic neoplasms and hematotoxicity in ARK/J and C57BL/6J mice. Toxicol Appl Pharmacol. 1980 Jun 30;54(2):323–331. doi: 10.1016/0041-008x(80)90202-1. [DOI] [PubMed] [Google Scholar]
  115. Snyder R., Dimitriadis E., Guy R., Hu P., Cooper K., Bauer H., Witz G., Goldstein B. D. Studies on the mechanism of benzene toxicity. Environ Health Perspect. 1989 Jul;82:31–35. doi: 10.1289/ehp.898231. [DOI] [PMC free article] [PubMed] [Google Scholar]
  116. Snyder R., Lee E. W., Kocsis J. J., Witmer C. M. Bone marrow depressant and leukemogenic actions of benzene. Life Sci. 1977 Dec 15;21(12):1709–1721. doi: 10.1016/0024-3205(77)90149-7. [DOI] [PubMed] [Google Scholar]
  117. Spear R. C., Bois F. Y., Woodruff T., Auslander D., Parker J., Selvin S. Modeling benzene pharmacokinetics across three sets of animal data: parametric sensitivity and risk implications. Risk Anal. 1991 Dec;11(4):641–654. doi: 10.1111/j.1539-6924.1991.tb00653.x. [DOI] [PubMed] [Google Scholar]
  118. Subrahmanyam V. V., McGirr L. G., O'Brien P. J. Peroxidase/hydrogen peroxide--or bone marrow homogenate/hydrogen peroxide--mediated activation of phenol and binding to protein. Xenobiotica. 1990 Dec;20(12):1369–1378. doi: 10.3109/00498259009046635. [DOI] [PubMed] [Google Scholar]
  119. TEISINGER J., BERGEROVA-FISEROVA V., KUDRNA J. Metabolismus benzenu u cloveka. Prac Lek. 1952 Jun;4(3):175–188. [PubMed] [Google Scholar]
  120. TOUGH I. M., BROWN W. M. CHROMOSOME ABERRATIONS AND EXPOSURE TO AMBIENT BENZENE. Lancet. 1965 Mar 27;1(7387):684–684. doi: 10.1016/s0140-6736(65)91835-0. [DOI] [PubMed] [Google Scholar]
  121. Tabershaw I. R., Lamm S. H. Benzene and leukaemia. Lancet. 1977 Oct 22;2(8043):867–869. [PubMed] [Google Scholar]
  122. Tice R. R., Costa D. L., Drew R. T. Cytogenetic effects of inhaled benzene in murine bone marrow: induction of sister chromatid exchanges, chromosomal aberrations, and cellular proliferation inhibition in DBA/2 mice. Proc Natl Acad Sci U S A. 1980 Apr;77(4):2148–2152. doi: 10.1073/pnas.77.4.2148. [DOI] [PMC free article] [PubMed] [Google Scholar]
  123. Timbrell J. A., Mitchell J. R. Toxicity-related changes in benzene metabolism in vivo. Xenobiotica. 1977 Jul;7(7):415–423. doi: 10.3109/00498257709035801. [DOI] [PubMed] [Google Scholar]
  124. Torres A., Giralt M., Raichs A. Coexistencia de antecedentes benzólicos crónicos y plasmocitoma múltiple. Presentación de dos casos. Sangre (Barc) 1970;15(2):275–279. [PubMed] [Google Scholar]
  125. Travis C. C., Bowers J. C. Protein binding of benzene under ambient exposure conditions. Toxicol Ind Health. 1989 Dec;5(6):1017–1024. doi: 10.1177/074823378900500609. [DOI] [PubMed] [Google Scholar]
  126. Travis C. C., Quillen J. L., Arms A. D. Pharmacokinetics of benzene. Toxicol Appl Pharmacol. 1990 Mar 1;102(3):400–420. doi: 10.1016/0041-008x(90)90037-u. [DOI] [PubMed] [Google Scholar]
  127. Travis C., Bowers J. Altered pharmacokinetics of soil-adsorbed benzene administered orally in the rat. Bull Environ Contam Toxicol. 1990 Aug;45(2):197–207. doi: 10.1007/BF01700184. [DOI] [PubMed] [Google Scholar]
  128. Tunek A., Högstedt B., Olofsson T. Mechanism of benzene toxicity. Effects of benzene and benzene metabolites on bone marrow cellularity, number of granulopoietic stem cells and frequency of micronuclei in mice. Chem Biol Interact. 1982 Mar 15;39(2):129–138. doi: 10.1016/0009-2797(82)90116-8. [DOI] [PubMed] [Google Scholar]
  129. Tunek A., Platt K. L., Przybylski M., Oesch F. Multi-step metabolic activation of benzene. Effect of superoxide dismutase on covalent binding to microsomal macromolecules, and identification of glutathione conjugates using high pressure liquid chromatography and field desorption mass spectrometry. Chem Biol Interact. 1980 Dec;33(1):1–17. doi: 10.1016/0009-2797(80)90040-x. [DOI] [PubMed] [Google Scholar]
  130. VIGLIANI E. C., SAITA G. BENZENE AND LEUKEMIA. N Engl J Med. 1964 Oct 22;271:872–876. doi: 10.1056/NEJM196410222711703. [DOI] [PubMed] [Google Scholar]
  131. Vianna N. J., Polan A. Lymphomas and occupational benzene exposure. Lancet. 1979 Jun 30;1(8131):1394–1395. doi: 10.1016/s0140-6736(79)92022-1. [DOI] [PubMed] [Google Scholar]
  132. Vigliani E. C., Forni A. Benzene and leukemia. Environ Res. 1976 Feb;11(1):122–127. doi: 10.1016/0013-9351(76)90115-8. [DOI] [PubMed] [Google Scholar]
  133. Vigliani E. C., Forni A. Benzene and leukemia. Environ Res. 1976 Feb;11(1):122–127. doi: 10.1016/0013-9351(76)90115-8. [DOI] [PubMed] [Google Scholar]
  134. Vigliani E. C. Leukemia associated with benzene exposure. Ann N Y Acad Sci. 1976;271:143–151. doi: 10.1111/j.1749-6632.1976.tb23103.x. [DOI] [PubMed] [Google Scholar]
  135. Voytek P. E., Thorslund T. W. Benzene risk assessment: status of quantifying the leukemogenic risk associated with the low-dose inhalation of benzene. Risk Anal. 1991 Sep;11(3):355–357. doi: 10.1111/j.1539-6924.1991.tb00613.x. [DOI] [PubMed] [Google Scholar]
  136. WOLF M. A., ROWE V. K., MCCOLLISTER D. D., HOLLINGSWORTH R. L., OYEN F. Toxicological studies of certain alkylated benzenes and benzene; experiments on laboratory animals. AMA Arch Ind Health. 1956 Oct;14(4):387–398. [PubMed] [Google Scholar]
  137. Wallace L. A. Major sources of benzene exposure. Environ Health Perspect. 1989 Jul;82:165–169. doi: 10.1289/ehp.8982165. [DOI] [PMC free article] [PubMed] [Google Scholar]
  138. Wallace L. A., Pellizzari E. D. Personal air exposures and breath concentrations of benzene and other volatile hydrocarbons for smokers and nonsmokers. Toxicol Lett. 1987 Jan;35(1):113–116. doi: 10.1016/0378-4274(87)90094-4. [DOI] [PubMed] [Google Scholar]
  139. Wester R. C., Maibach H. I., Gruenke L. D., Craig J. C. Benzene levels in ambient air and breath of smokers and nonsmokers in urban and pristine environments. J Toxicol Environ Health. 1986;18(4):567–573. doi: 10.1080/15287398609530894. [DOI] [PubMed] [Google Scholar]
  140. White M. C., Infante P. F., Walker B., Jr Occupational exposure to benzene: a review of carcinogenic and related health effects following the U.S. Supreme Court decision. Am J Ind Med. 1980;1(2):233–243. doi: 10.1002/ajim.4700010214. [DOI] [PubMed] [Google Scholar]
  141. Witz G., Rao G. S., Goldstein B. D. Short-term toxicity of trans,trans-muconaldehyde. Toxicol Appl Pharmacol. 1985 Sep 30;80(3):511–516. doi: 10.1016/0041-008x(85)90396-5. [DOI] [PubMed] [Google Scholar]
  142. Wolman S. R. Cytologic and cytogenetic effects of benzene. J Toxicol Environ Health Suppl. 1977;2:63–68. [PubMed] [Google Scholar]
  143. Wong O. An industry wide mortality study of chemical workers occupationally exposed to benzene. II. Dose response analyses. Br J Ind Med. 1987 Jun;44(6):382–395. doi: 10.1136/oem.44.6.382. [DOI] [PMC free article] [PubMed] [Google Scholar]
  144. Wong O., Harris F., Smith T. J. Health effects of gasoline exposure. II. Mortality patterns of distribution workers in the United States. Environ Health Perspect. 1993 Dec;101 (Suppl 6):63–76. doi: 10.1289/ehp.93101s663. [DOI] [PMC free article] [PubMed] [Google Scholar]
  145. Yardley-Jones A., Anderson D., Jenkinson P. C., Lovell D. P., Blowers S. D., Davies M. J. Genotoxic effects in peripheral blood and urine of workers exposed to low level benzene. Br J Ind Med. 1988 Oct;45(10):694–700. doi: 10.1136/oem.45.10.694. [DOI] [PMC free article] [PubMed] [Google Scholar]
  146. Yardley-Jones A., Anderson D., Lovell D. P., Jenkinson P. C. Analysis of chromosomal aberrations in workers exposed to low level benzene. Br J Ind Med. 1990 Jan;47(1):48–51. doi: 10.1136/oem.47.1.48. [DOI] [PMC free article] [PubMed] [Google Scholar]
  147. Yardley-Jones A., Anderson D., Parke D. V. The toxicity of benzene and its metabolism and molecular pathology in human risk assessment. Br J Ind Med. 1991 Jul;48(7):437–444. doi: 10.1136/oem.48.7.437. [DOI] [PMC free article] [PubMed] [Google Scholar]
  148. Yin S. N., Li G. L., Tain F. D., Fu Z. I., Jin C., Chen Y. J., Luo S. J., Ye P. Z., Zhang J. Z., Wang G. C. Leukaemia in benzene workers: a retrospective cohort study. Br J Ind Med. 1987 Feb;44(2):124–128. doi: 10.1136/oem.44.2.124. [DOI] [PMC free article] [PubMed] [Google Scholar]
  149. Young R. J., Rinsky R. A., Infante P. F., Wagoner J. K. Benzene in consumer products. Science. 1978 Jan 20;199(4326):248–248. doi: 10.1126/science.199.4326.248-a. [DOI] [PubMed] [Google Scholar]
  150. Zenz C. Benzene--attempts to establish a lower exposure standard in the United States. A review. Scand J Work Environ Health. 1978 Jun;4(2):103–113. doi: 10.5271/sjweh.2717. [DOI] [PubMed] [Google Scholar]

Articles from Environmental Health Perspectives are provided here courtesy of National Institute of Environmental Health Sciences

RESOURCES