Benzen. Dokumentacja proponowanych wartości dopuszczalnych poziomów narażenia zawodowego

• Autorzy: Lebrecht G. , Czerczak S. , Szymczak W.

Warianty tytułu

EN

Benzene

• Języki publikacji: PL

Abstrakty

PL

Benzen jest jednym z najbardziej rozpowszechnionych związków organicznych. Jest otrzymywany z ropy naftowej podczas katalitycznego reformingu, w procesach alkalizacji i odwodornienia pochodnych benzenu, a także podczas cyklizacji i aromatyzacji węglowodorów parafinowych. Benzen znajduje zastosowanie w przemyśle chemicznym jako produkt wyjściowy w syntezie organicznej. Stanowi wysokoenergetyczny składnik benzyny silnikowej. Liczbę osób potencjalnie narażonych zawodowo na benzen w Polsce ocenia się na 8000. W 1997 r. stwierdzono, że około 1450 osób pracowało w narażeniu na benzen o stężeniach powyżej obowiązującej wartości NDS. Publikowane w światowym piśmiennictwie dane odnośnie do poziomów narażenia na różnych stanowiskach pracy podają informacje o stężeniach benzenu w zakresie 0,16 mg/mJ -266 mg/m3, przy czym około 60% pracowników jest narażonych na benzen o stężeniu około 0,32 mg/m3, a tylko 1% - na benzen o stężeniu większym. Ze względu na zawartość benzenu w benzynie i spalinach silników samochodowych oraz w dymie tytoniowym narażenie pozazawodowe na benzen staje się istotnym problemem. Innym źródłem pozazawodowego narażenia na benzen jest obecność benzenu w produktach spożywczych i w wodzie pitnej. Benzen wchłania się głównie w postaci par drogą oddechową a ciekły benzen jest wchłaniany przez skórę. U ludzi ostre zatrucia benzenem o dużych stężeniach (od 10 000 do 65 200 mg/m3 przez 5 -1O min) prowadzą do śmierci, poprzedzonej objawami narkotycznymi, arytmią i zaburzeniem oddychania. U zwierząt doświadczalnych w zatruciach ostrych benzen wykazuje niewielką toksyczność, na co wskazują wartości dawek LD50 i LC50: dla szczurów wynoszą one 3000 _ 5870 mg/kg m.c., wartość LC50 dla szczurów wynosi 44600 mg/m3/4 h, a dla myszy - 32000 mg/m3. Śmierć zwierząt następowała w wyniku zaburzeń w układzie sercowo-naczyniowym, oddechowym i nerwowym. Po długotrwałym działaniu par benzenu o małych stężeniach zaznacza się wpływ związku na krew i narządy krwiotwórcze. O hematotoksyczności benzenu zarówno u ludzi, jak i u zwierząt świadczy spadek liczby jednego lub wielu elementów komórkowych krwi obwodowej, prowadzącego do niedokrwistości aplastycznej, leukopenii lub trombocytopenii. W zaawansowanych przypadkach dochodzi do znacznego zmniejszenia liczby wszystkich elementów morfotycznych - pancytopenii, często poprzedzającej wystąpienie białaczki. U osób narażonych na benzen występowanie białaczek zostało potwierdzone na podstawie wyników badań epidemiologicznych. Obserwuje się ostrą białaczkę szpikową, przewlekłą białaczkę szpikową i limfatyczną oraz szpiczaka mnogiego. U zwierząt doświadczalnych obok białaczek obserwowano występowanie raka gruczołu Zymbala, jamy nosowej i gębowej, gruczołu napletkowego oraz jajników. Benzen nie jest czynnikiem mutagennym w testach in vitro. Natomiast związek ten i/lub jego metabolity w warunkach in vivo mogą indukować aberracje chromosomowe, powodować wzrost częstości mikrojąder lub wymiany chromatyd siostrzanych. Benzen podany do jamy otrzewnej może powodować uszkodzenia morfologiczne plemników. Genotoksyczność benzenu wykazano u ludzi zawodowo narażonych na ten związek. Benzen nie jest teratoge- nem dla zwierząt; embriotoksyczność i fetotoksyczność benzenu stwierdzono jedynie wówczas, gdy stosowane stężenia były również toksyczne dla matek. Wyniki licznych badań epidemiologicznych pozwalają uznać benzen za czynnik kancerogenny dla układu krwiotwórczego i chłonnego człowieka. W 1ARC zakwalifikowano ten związek do grupy 1., czyli uznano benzen za czynnik rakotwórczy dla ludzi. Benzen jest uznany za związek rakotwórczy dla ludzi w USA i w większości państw europejskich. W ustawodawstwie polskim związek ten również umieszczono w wykazie substancji o udowodnionym działaniu rakotwórczym dla ludzi (kategoria 1.), a także w wykazie prac wzbronionych pracownikom młodocianym i kobietom w ciąży. W Polsce dotychczas najwyższe dopuszczalne stężenie benzenu (NDS) w powietrzu środowiska pracy wynosi 10 mg/m3, a wartość NDSCh - 40 mg/mJ. Na podstawie wyników badań epidemiologicznych, a także przyjmując za efekt krytyczny białaczkotwórcze działanie benzenu, proponuje się ustalenie wartości NDS benzenu na poziomie 1,6 mg/m3 (podobnie jak zrobiono to w ACGIH). Ze względu na charakter efektu krytycznego nie ustala się wartości NDSCh benzenu. Za wartość DSB benzenu przyjęto poziom kwasu S-fenylomerkapturowego w moczu, czyli 25 pg/g kreatyniny i kwasu trans-, transmukonowego - 500 pg/g kreatyniny.

EN

Benzene is a clear, flammable, liquid with a characteristic odor. Leukaemia is the main effect at longterm occupational exposure to benzene. The unit risk of leukaemia, i.e. the lifetime risk attributable to the inhalation exposure to 1.6 mg/m3 benzene was assessed by many authors from the results of epidemiological studies on subjects occupationally exposed to benzene. Based on these epidemiological data the Expert Group for Chemical Agents establishment an 8-hour MAC (TWA) value of 1,6 mg/m3. There are no bases for establishing benzene MAC (STEL). The Expert Group also recommended BAIs for benzene: 5-Phenylomercapturic acid in urine 25 jag/g creatinine and trans, trans muconic acid in urine 500 ug/g creatinine.

Słowa kluczowe

PL

benzen; narażenie zawodowe; NDS; działanie toksyczne

EN

benzene; occupational exposure; NDS; toxic effects

• Wydawca: Centralny Instytut Ochrony Pracy - Państwowy Instytut Badawczy
• Czasopismo: Podstawy i Metody Oceny Środowiska Pracy
• Rocznik: 2003
• Tom: Nr 1 (35)
• Strony: 5--60
• Opis fizyczny: Bibliogr. 174 poz., rys., tab.

Twórcy

autor

Lebrecht G.

• Instytut Medycyny Pracy im. prof. dr. med. Jerzego Nofera 90-950 Łódź ul. św. Teresy 8

autor

Czerczak S.

• Instytut Medycyny Pracy im. prof. dr. med. Jerzego Nofera 90-950 Łódź ul. św. Teresy 8

autor

Szymczak W.

• Instytut Medycyny Pracy im. prof. dr. med. Jerzego Nofera 90-950 Łódź ul. św. Teresy 8

Bibliografia

• 1. ACGIH (2000) Threshold limit values for chemical substances and physical agents and biological esposure indices. American Conference of Governmental Industrial Hugienists.
• 2. Aksoy M., Endem S., Dincol G. (1974) Leukemia in shoe workers exposed chronically to benzene. Blood 44,837-84.
• 3. Aksoy M. i in. (1971) Hematological effects of chronic benzene poisoning in 217 workers. Br. J. Ind. Med. 28,296-302.
• 4. Aksoy M. i in. (1972) Details of blood changes in 32 patients with pancytopenia associated with long-term exposure to benzene. Br. J. Ind. Med. 29, 56-64.
• 5. Aksoy M, Endem S. (1978) Follow-up study in mortality and the development of leukemia in 44 pancytopenic patients with chronic exposure to benzene. Blood 52, 285-290.
• 6. Anderson D., Richardson CR. (1981) Issues relevant to the assessment of chemically induced chromosome damage in vivo and their relationship to chemical mutagenesis. Mutat. Res. 90, 261-272.
• 7. Aoyama K. (1996) Effects of benzene inhalation on lymphocyte subpopulations and immunoresponse in mice. Toxicol. Appl. Pharmacol. 85, 92-10 1.
• 8. Arp E. W, Wolf P.H, Checkoway H (1983) Lymphocytic leukemia and exposure to benzene and other solvents in the rubber industry. J. Occup. Med. 25, 598-602.
• 9. Ashby J., Tennant R.W (1988) Chemical structure Salmonella mutagenicity and extent of carcinogenicity as indicatros of genotoxic carcinogens among 222 chemicals tested in rodents by the u.s. NCJINTP. Mutat. Res. 204,17.
• 10. Avis S.P., Hutton CJ. (1993) Acute benzene poisoning: a report of three fatalities. J. Forensic Sci. 38(3), 599-602.
• 11. Baarson K.A, Synder CA., Albert R.E. (1984) Repeated exposure of C57BI mice to inhaled benzene at 10 ppm markedly depresed erythropoietic colony formation. Toxicol. Lett. 20, 337-342.
• 12. Baarson K.A i in. (1982) The hematotoxic effects of inhaled benzene on peripheral blood, bone marrow and spleen cells are increased by ingested ethanol. Toxicol. Appl. Pharmacol. 64, 393.
• 13. Barale R. i in. (1985) Benzene induces micronuclei in circulating erytrhrocytes of chronically treated mice. Mutat. Res. 144, 193-196.
• 14. Baslo A, Aksoy M (1982) Neurological abnormalities in chronic benzene poisoning: a study of six patients with aplastic anemia and two with preleukemia. Environ. Res. 27,457-465.
• 15. Berlin M, Gage J. C, Gullberg B. (1980) Breth concentration as an index to the health risk from benzene. Scand J. Work Environ. Health. 6,104-111.
• 16. Boogaard P.J., van Sittert N.l. (1995) Biological monitoring of exposure to benzene: A comparison between S-phenylmercapturic acid, trans, trans muconic acid and phenol. Occup. Environ. Med. 52, 611- 620.
• 17. Braier L, Francone M (1950) Phenomenes hemolytiques du benzene et ses homoloques. Arch. MaI. Prof. 11,367-369.
• 18. Brief R.S., Lynch 1., Bernath T. (1980) Benzene in the workplace. Am. Ind. Hyg. Assoc. J. 41, 611-623.
• 19. Carpenter CP., Shaffer CB., Weil CS. (1944) Studies on the inhalation of 1,3-butadiene: with a comparison of its narcotic effects with benzol, toluol, and styrene and a note on the elimination of styrene by the human. J. Ind. Hyg. Toxicol. 26, 69-78.
• 20. Choy WN., McGregor J.T., Shelby MD. (1985) Induction of micronuc1ei by benzene in B6C3Fl mice: Retrospective analysis of peripheral blood smears from NTP carcinogenic bioassay. Mutat. Res. 143, 55-59.
• 21. Cody R.P. l m. (1993) Hematologic effects of benzene. Job - specific trends during the first year employment among a cohort of benzene - exposed rubber workers. J. Occup. Med. 35(8),776.
• 22. Cronin H.J. (1924) Benzol poisoning in rubber industry. Boston Med. Surv. J. 191, 1164.
• 23. Cronkie E.P., lnoue T., Carsten A.L. (1982) Effects of benzene inhalation on murine pluripotent stem cells. J. Toxicol. Environ. Health 9, 411-421.
• 24. Cronkie E.P., Drew R.T., lnoue T. (1985) Benzene hematotoxicity and leukemogenesis. Am. J. Ind. Med. 7,447-456.
• 25. Cronkie E.P., Inoue T. (1989) Hematotoxicity and carcinogenicity of inhaled benzene. Environ. Health Persp. 82,97-108.
• 26. Decoufle P., Blattner W.A, Blair A (1983) Mortality among chemical workers exposed to benzene and other agents. Environ. Res. 30, 16-25.
• 27. Dean BJ. (1978) Genetic toxicology of benzene, toluene, xylenes, and phenols. Mutat. Res. 47, 75-97.
• 28. De Flora S. i in. (1984) Genotoxic activity and potency of 135 compounds in the Ames reversion test and in a bacterial DNA-repair test. Mutat. Res. 133, 161-198.
• 29. Deichmann W.B., Mac Donald, Bemol E. (1963) The hemopoietic tissue toxicity of benzene vapours. Toxicol. Appl. Pharmacol. 5,201-224.
• 30. Dempster AN., Evans HL, Synder C.A (1984) The temporaI relationship between bechavioral and hematological effects of inhalted benzene. Toxicol. Appl. Pharmacol. 76, 195-203.
• 31. Denton J.E., Potter G.D., Santolucito JA (1981) Effects of lead on benzene metabolizm. J. Toxico. Environ. Health. 7, 893.
• 32. Dow (1992) Initial submission: Effects of benzene vapour in the pig and rat pertaining to hematology and immunology with cover letter dated 05/14192 EPA/OTS.
• 33. Dowty BJ., Laster J.L, Storer J. (1976) The transplacental migration and accumulation in blood of volatile organie constituents. Ped. Res. 10,696-701.
• 34. Dutkiewicz, T. (1971) Wchłanianie par benzenu w drogach oddechowych u ludzi. Bromat. Chem. Toksykol. 4, 443. Environmental Health Criteria - Benzene WHO, Geneva, 1993.
• 35. Erexson GL, Wilmer J.L, Steinhagen w.H. (1986) Induction of cytogenetic damage in rodents after short-term inhalation of benzene. Environ. Mutagen. 8,29-40.
• 36. Fabianova E. i in. (1999) Occupational cancer in Central European countries. Env. Health Persp. 107(3), 279-282.
• 37. Farris G.M, Everitt J.I., Irons R.D. (1993) Carcinogenicity of inhaled benzene in CBA mice. Fund. Appl. Toxicol. 20(4), 503-507.
• 38. Feldt E.G. (1985) Evaluation of the mutagenic hazard s of benzene and some of its derivatives. Gig. Sanit. 7,21-23.
• 39. Fishbeck W.A, Townsend J.C, Swank MC. (1980) Effects of chronic occupational exposure to measured cancentration of benzene. Toxicology. 15,219-232.
• 40. Flury F. (1928) Toxicities in modem industry. Ha Pharmacological - toxicoloical aspects of intoxicants in modem industry. Arch. Exp. Path. Pharm. 138,65.
• 41. Frantic E., Homychova M, Horvath M (1994) Relative acute neurotoxicity of solvents: Isoeffective air concentrations of 48 compounds evaluated in rats and mice. Environ. Res. 66, 173-185.
• 42. Frant; T.J. (1984) Percutaneous absorption on the relevance of in vitro data. J. Invest. Dermatol. 64, 190-195.
• 43. Gad El Karim MN., Harper BL, Legator MS. (1984) Modifications in the myelocIlastogenic effect of benzene in mice with toluene, phenobarbital, 3-methyIcholanthrere, Aroclor 1254 and SKF-525A. Mutat. Res. 135, 225-243.
• 44. Gerarde H. w.: Toxicology and biochemisty of aromatic hydrocarbons. Amsterdam, Elsevier Science Publishers.
• 45. Gemer-Smidth P., Friedrich M. (1978) The mutagenic effect of benzene, toluene and xylene studied by the SCE technique. Mutat. Res. 58, 313-316.
• 46. Glatt H. i in. (1989) Multiple activation pathways of benzene leading to products with varying genotoxic characteristics. Environ. Health Perspect. 82, 81-89.
• 47. Główny Urząd Statystyczny - Ochrona Środowiska. Warszawa, 1997.
• 48. Girard R. i in. (1970) Leukocyte alkaline phoshatose and benzene exposure. Med. Lav. 61, 502-508.
• 49. Goguel A, Covigneau. A, Bernard J (1967) Les leucemies benzenique de la region parisienne entre 1950 et 1955. (Etude de 50 observations). Nouv. Rev. Fr. Hematol. 7,465.
• 50. Goldstein B.D. (1977) Hematotoxicity in humans. Benzene toxicity. A critical evaluation. J. Toxicol. Environ. Health. 2,69.
• 51. Green J.D., Snyder CA, LoBue l: (1981) Acute and chronic dose/response effects of inhaled benzene on multipotenital hemotopoietic stem (CFV-s) an dgranulocyte/makrophage progenietor (GM-CVF-s) cells in CD-1 mice. Toxicol. Appl. Pharmacol. 58,492-502.
• 52. Greenburg L. (1926) Benzol poisoning as an industrial hazard. Public Health Reports. 41, 1357-1375.
• 53. Hamilton A (1922) The growing menace of benzene (benzol) poisoning in American industry. J. Am. Med. Assoc. 78, 627-630.
• 54. Hanke J., Dutkiewicz T., Piotrowski J. (1961) The absorption of benzene through the skin in men. Med. Pr. 12,413-426.
• 55. Haris N.M. i in. (1982) Epidemiology study of refinery and chrmical plant workers. J. Occup. Med. 24, 203-212.
• 56. Henderson R.F., Sabourin P.J., Bechtold W.E. (1989) The effect of dose, dos e rate, route of administration and species on tissue and blood levels of benzen e metabolites. Envrion. Health Perspect. 82,9
• 57. Hernberg S. i in. (1966) Prognostic aspects of benzene poisoning. Br. J. Ind. Med. 23, 204-209.
• 58. Hite M. i in. (1980) The effect of benzene in the micronuc1eus test. Mutat. Res. 77,149.
• 59. HSDB (1999) Hazarodus Substances Data Bank.
• 60. Hsieh G.C, Shouma R.P., Parker R.D.R. (1988) Subc1inical effects of groundwater contaminants: I Altemation of humoral and cellular immunity by benzene in CD-1 mice. Arch. Envrion. Contam. Toxicol. 17,151.
• 61. Hshieh G.C, Parker R.D.R., Shanna R.P. (1988) Subc1inical effects of groundwater contaminants: II ALtemation of regional brain monoarnine neurotransmitters by benzene in CD-1 mice. Arch. Envrion.b Contam. Toxicol. 17,799.
• 62. Hsieh G.C; Shanna R.P., Parker R.D. (1991) Hypotalamic - pituitary - adrenocortical axis activity and immune function after oral exposure to benzene and toluene. Immunopharmacology, 21(1), 23.
• 63. Huff J. E. i in. (1989) Multiple-site carcinogenicity of benzene in Fischer 344 rats and B6C3F1 mice. Environ. Health Perspect. 82,125-163.
• 64. Hunter CJL(1-96g) Solvents with-reference to studies on the pharmacodynamics of benzene. Proc. R. Soc. Med. 61, 913-915.
• 65. Hunter C.S., Blair D. (1972) Pharmacokinetic studies in man. Ann. Occup. Hyg. 15, 193.
• 66. Hurley Y. F., Chevric J. W., McLaren W. (1991) Exposure to benzene and mortality from leukemia: results from coke oven and other coal product workers (letter). Br. J. Ind. Med. 48(7), 502-503.
• 67. IARC(1982) IARC Monogrpahs on the evaluation of the carcinogenic risk of chemicals to humans. Vol.29. Some industrial chemical and dyestuffs. Lyon, France.
• 68. IARC(1987) Monographs on evoluation of carcinogenic risks to human. Suplement 7. Lyon.
• 69. Infante P.F., Rinsky R.A., Wagoner J.K. (1977) Leukemia in benzene workers. Lancet, 2, 76-78.
• 70. Infante P.F. (1978) Leukemia among worekrs exposed to benzene. Tex. Rep. Biol. Med. 37, 153-16l.
• 71. IPCS(1993) Environmental Health Criterio. No 150 WHO.
• 72. Jenkis L.J, Jones R.A., Siegel J. (1970) Long-term inhalation screening sutdies, of benzene, toluene, o-xylene and cumene on experimental animal. Toxicol. Appl. Pharmacol. 16,818-823.
• 73. Kimmel CA., Wilson J.G. (1973) Skeletal deviations in rats. Molfomations or variations? Teratology, 8, 309-316.
• 74. Kipen H.M., Cody R.P., Goldstein B.D. (1989) Use of longitudinal analysis of peripheral blood counts to valid historical recontruciton of benzene exposure. Environ. Helath Persp. 82, 199-206.
• 75. Kissling M., Spech B. (1971) Chromosome aberrations in experimental benzene intoxication. Helv. Med. Acta,36, 59-66.
• 76. Kraut A., Lilis R., Marcus M. (1988) Neurotoxic effects of solvent exposure on sewage treatment workers. Arch. Environ. Health. 43, 263-268 .
• 77. Kuna R.A., Kapp R. W (1981) Embryotoxic/teratogenic potential of benzene vapor in rats. Toxicol. Appl. Pharamcol. 57, l.
• 78. Lagorio S. i in. (1994) Mortality of filIing station attendants. Scand. J. Work Emviron. Helath, 20, 331- 338. '
• 79. Lange A., Smolik R., Zatonski W (1973) Leukocyte agglutinins in workers exposed to benzene, toluene and xylene. Int. Arch. Arbeitsmed. 31,45.
• 80. Lange A., Smolik R., Zatonski W (1973) Serum immunoglobulin levels in workers exposed to benzene, toluene and xylene. Int. Arch. Arbeitsmed. 31, 37-44.
• 81. Lehrert G., Ladendorf R.D., Szadkowski D. (1978) The relevance of organic solvents for the organization of screening test in occupational medicine. Results of toxicological analyses of more than 6000 samples. Int. Arch. Occup. Environ. Helath. 41, 95.
• 82. Li L, Sun W, Gong Z. (1992) Effect of low benzene exposure on neurobehavioral function, AChE in blood and bone marrow picture in mice. Biomed. Environ. Sci. 5(4), 349-354.
• 83. Li GL i in. (1986) Benzene-specific increase in leukocyte alkaline phosphate activity in rats exposed to vapors of various organic solvents. J. Toxicol. Envrion. Helath. 19,581-589.
• 84. Longcare S. i in. (1981) Toxicological and biochemical effects of repeated administration of benzene in mice. J. Toxicol. Environ. Health. 7, 223-237. -
• 85. Magos G.A., Lorenzana-Jimenez M., Vidrio H. (1990) Toluene and benzene inhalation influences on verticular arrhytmias in the rat. Neurotoxicol. Teratol. 12(2), 119-124.
• 86. Maltoni C, Cont B., Cotti G. (1985) Experimental studies on benzene carcinogenicity at the Boloqna Institute of Oncology: Current results and on going research. Am. J. Ind. Med. 7,415-446 .
• 87. Maltoni C., Ciliberti A., Cotti G. (1989) Benzene on experimetnal multipotential carcinogen: Results of the long-term bioassays performed at the Boloquna Institute of Oncology. Environ., Health Perspect. 82, 109-124.
• 88. Maltoni C; Conti B., Cott G. (1983) Benzene: a multipotential carcinogen: results of long-term bioassays peformed at the Boloqna Institute of Oncology. Am. J. Ind. Med. 4(5), 589-630.
• 89. MAK-Werten (1985/86) Toxicologischarbeitsmedizinische Begrundung von Mak-Werten-Benzol, 1-53.
• 90. Marimoto K. (1976) J. Ind. Health. 18,23.
• 91. McMahon TF., Birmbaum L.S. (1991) Age-related changes in disposition and metabolism of benzene in male C57BUGN mice. Drug. Metab. 19(6), 1052-1057.
• 92. McMichel AJ., Spirtas R., Kupper L.L. (1964-1972) An epidemiologic study of a mortality within a cohort of rubber workers, J. Occup. Med. 1974,16,458.
• 93. McMichel AJ. i in. (1975) Solvent exposure and leukemia among rubber workers - an epidemiological study. J. Occup. Med. 17,234.
• 94. McMichel AJ. i in. (1976) Mortality among rubber workers relationship to specific jobs. J. Occup. Med. 18,178.
• 95. Medinsky MA., Sabourin PJ., Luciev G. (1989) A physiological model for simulation of benzene metabolism by rats and mice. Toxicol. Appl. Pharmacol. 193-206.
• 96. Midzenski M.A i in. (1992) Acute high dose exposure to benzene in shipyard workers. Am. J. Ind. Med. 22,553.
• 97. Murray FJ., John J.A., Rampy L.W (1979) Embriotoxicity of inhaled benzene in mice and rabbits. Am. Ind. Hyg. Assoc. J. 40, 993-998.
• 98. Nakum L.H, Hoff HE. (1934) The mechanism of sudden death in experimental acute benzol poisoning. J. Pharmacol Exp. Ther. 50, 336-345.
• 99. Nau C.A., Neal J., Thorton M (1966) C9-C12fraction obtained from petroleum distildates. Arch. Environ. Health. 12, 382-393.
• 100. . Nomiyama K., Nomiyama H (1974) Respiratory elimination of organic solvents in man: Benzene, toluene, n-hexane, trichloroethylene, acetone, ethyl acetone and ethyl alcohol. Int. Arch. Arbeitsmed. 32, 85-91.
• 101. Nomiyama K., Nomiyama H (1974) Respiratory retention, uptake and excretion of organic solvents in man: benzene, toluene, n-hexane, trichloroetylene, acetone, ethyl acetate, and ethyl alcohol. Int. Areh. Arbeitsmed. 32, 75-83.
• 102. NTP, National Toxieology Programm (1986) Technical Report Series No 289 Toxicology and carcinogenesis studies of benzen e in F344/N rats and B6C3Fl mice (garage studies) Researeh Triangle Park, NC: US Department of Health and Human Services, Public Health Service, National Institute of Health N.H. Publication No 86-2545.
• 103. Oberly TJ., Bewsey BJ., Probst G.S. (1984) An evaluation of the L5178YTK +/- mouse lymphoma forward mutation assay using 42 chemicals. Mutat. Res. 125,291.
• 104. OSRA (1985) Occupational exposure to benzene proposed rule and notice of hearing. U.S. Department of Labor, Occupational Safety and Health Administration.
• 105. Ott M.G., Townserd J.C, Fisbeck WA (1978) Mortality among workers occupationaly exposed to benzene. Arch. Environ. Helath. 33, 3-10.
• 106. Painter R.B., Howard R. (1982) The HeLa-DNA synthesis inhibition test as a rapid screen for mutagenic carcinogens. Mutat. Res. 92,427-437.
• 107. Parke D. v., Wilians R. T (1953) Studies in detoxification 54. The metabolism of benzene (a) The formation of phenylglucuronide and phenylsulphuric aeid from [14C]benzene (b) the metaboli sm of [14C] phenol. Biochem. J. 1953,54,337-340.
• 108. Paustenbach DJ., Price P.S, Ollison W (1992) Reevaluation of benzene exposure for the Pliofilm (rubberworker) cohort (1936-1976). J. Toxicol. Environ. Health. 36(3), 177.
• 109. Pekari K. (1994) Biological monitoring of benzene, toluene and styrene. Kuopio University Printing Offiee.
• 110. Pelleck-Walker P., Beumer LL: (1986) DNA damage in L5178YS eells following exposure to benzene metabolites.Ind. Pharmaeol. 30,42-47.
• 111. PiccianoD. (1979) Cytogenic study of workers exposed to benzene. Environ. Res. 19,33.
• 112. Pollini G. i in. Chromosome changes in lymphocytes five years after benzene haemopathy. Med. Lav. 969,60,743.
• 113. Rickert D.E., Bater TS., Bus 1.S. (1979) Benzene disposition in the rat after exposure by inhalation. Toxieol. Appl. Pharmaeol. 49, 417-423.
• 114. Rinsky R.A. i in. (1989) Benzene and leukemia: a review of the literature and risk assessment. Am. J. Epidemiol. 129, 1084.
• 115. Rinsky R.A., Smith A.B., Hornung R. (1987) Benzene and leukemia: an epidemiological risk assessment. N. Eng. J. Med. 316,1044.
• 116. Rinsky R.A., Young R.J., Smith A.B. (1981) Leukemia in benzene workers. Am. J. Ind. Med. 2,217. Am.
• 117. Romieu I. i in. (1999) Environmental exposure to volatile organic compounds among workers in Mexico City as assessed by personal monitors and blood concentrations. Envrion. Health Perspect. 107(7), 51l.
• 118. RTECS, Registry of Toxie Effects of Chemical Substances Cincinnati (2000), National Institutes for Oceupational Safety and Health.
• 119. Rozenthal G.J., Snyder CA. (1985) Modulation of the immune response to Listeria monocytogenes by benzene inhalation. Toxieol. Appl. Pharmaeol. 80, 502.
• 120. Rozen MG., Synder C.A., Albert R.E. (1984) Depresion in B- and T-lymphocyte mitogen-induced blastogenesis in mice exposed to low concentrations of benzene. Toxicol. Lett. 20,343-349 .
• 121. Rozen MG., Synder CA. (1985) Protracted exposure of C57BU6 miee to 300 ppm benzene depresses Band T-Iymphocyte number and mitogen responses. Evidence for thymic and bone marrow proliferation in response to the exposures. Toxicology. 37, 13-26.
• 122. Rozporządzenie Rady Ministrów z dnia 10.09.1996 r. w sprawie wykazu prac wzbronionych kobietom. DzU nr. 11.
• 123. Rozporządzenie Rady Ministrów z dnia 2l.09.1991 r. w sprawie wykazu prac wzbronionych młodocianym. DzU nr l.
• 124. Rushton L., Adderson M. (1981) Case control study to investigate to association between exposure to benzene and deaths from leukemia in oil refinery workers. Br. J. Cancer. 43, 77-84.
• 125. Ruiz.N.A., Augusto L.G.s., Vassallo l. (1994) Bone marrow morphology in patients with neutropenia due to chronie exposure to organic solvents (benzene): early lesions. Path. Res. Pract. 190, 151-154.
• 126. Rushton L., Alderson M (1981) An epidemiological survey of eight oil refineries in Britain. Br. J. Ind. Med. 38, 225-234. .
• 127. Sabourrin P.J., Chen B. T, Lucier GL (1987) Effect of dose on the absorption and excretion of [14C] benzene administered orally or by inhalation in rats and mice. Toxicol. App;. Pharmacol. 87, 325-336.
• 128. Sasiadek M, Jagielski L, Smolik R. (1989) Lokation of breakpoints in the karyotype of workers professionally exposed to benzene. Mutat. Res. 124,235-240.
• 129. Sato A., Vakajima T (1979) Dose-depondent metaboli c integration between benzene and toluene in vivo and in vitro. Toxieol. Appl. Phamracol. 48, 249-256.
• 130. Savilatni M (1956) Over 100 cases of benzene poisoning in a shoe factory. Arch. Gwerbepathol. Gewerbehyg. 15, 147.
• 131. Schottenfeld D. i in. (1981) A prospective of morbidity and mortality in petroleum industry employes in the United States. A Preliminary Report, New York, 247-265.
• 132. Schrenk H.H., Yant W.P. Pearce S.J. (1941) Absorption, distribution and elimination of benzene by body tissues and fluids of dogs exposed to benzene vapour. J. Ind. Ryg. ToxicoI. 23, 20-34. .
• 133. Sherwood R.J. (1972) Benzene: the interpretation of monitoring results. Ann. Occup. Ryg. 15,409-421.
• 134. Sherwood J.R., Sinclair G.C (1999) New PBPK model applied to old occupational exposure to benzene. AIHA Journal 60, 259-265.
• 135. Siou G., Conan L., ElHaitem M (1981) Evaluation of the clastogenic action of benzene by oral administration with 2 cytogenetic techniques in mouse and Chinese hamster. Mutat. Res. 90, 273-278.
• 136. Smidth V.P. i in. (1980) Zur Hepatotoxizitat von Benzol, 1,1,2,2-Tetrachloroethan und Tetrachlorkohlenstoff. Z. Gesamte Ryg. 26, 167-172.
• 137. Smith TN. (1996) The mechanism of benzene - induced leukemia: A hypthesis and speculations on the causes of leukemie. Environ. Health Perspect. 104(6), 1209.
• 138. Snyder CA., Goldstein B.D., Sellakumar A.R. (1984) Evidence for hematotoxicity and tumorigenesis in rats exposed to 100 ppm benzene. Am. J. Ind. Med. 5,429-434.
• 139. Snyder CA., Sellakumar A.R., James D.J. (1988) The carcinogenicity of discontinous inhaled benzene exposure in CD-l and C57Bl/6 mice. Arch. ToxicoI. 62, 331-335. .
• 140. Srobova J., Teisinger J., Skramovsky S. (1950) Absorption and elimination of inaled benzene in man. Arch. Ind., Ryg. Occup. Med. 2, 1-8.
• 141. Styles J.A., Richardson CR. (1984) Cytogenetic effects of benzene: dosimetric studies on rats exposed to benzen e vapor. Mutat. Res. l35, 203-209.
• 142. Swenberg J.A., Petzold GL, Harbach P.R. (1976) In vitro DNA damage/alkaline elution assay for predriting carcinogenic potentiaI. Biochem. Biophys. Res. Commun. 72, 732-738.
• 143. Teisinger J., Fiserova-Bergerova v., Kudra J. (1952) The metabolism of benzene in man. Pracovni. Lekarstvi. 4,175-188.
• 144. Thorpe J.J. (1974) Epidemiological survey of leukemia in persons potentially exposed to benzene. in. Occup. Med. 17,375.
• 145. Tice R.R., Costa DL, Drew R.T (1980) Cytogenetic effects of inhaled benzene in murine bon e marrow: Inhalation of sister chromatid exchanges, chromosomai aberrations and ceIlular proIiferation inhibition in DBA/2 mice. Proc. Nat!. Acad. Sci. 77,2148.
• 146. Toft K. i in. (1982) Toxic effects on mouse bone marrow caused by inhalation of benzene. Arch. ToxicoI. 51,295-302. 1
• 147. Tondel M, Persson B., Carstensen J. (1995) Myelofibrosis and benzene exposure. Occup. Med. 45(1), 51-52.
• 148. Topham J.C (1980) Do induced sperm-head abnomralities in mice specifically identify mammalian mutagens rather than carcinogens? Mutat. Res. 74, 379-387.
• 149. Tough I.M, Curt Brown W.M (1965) Chromosome aberrations and exposure to ambient benzene. Lancet
• 150. Tough I.M i in. (1970) Chromosome studies on workers exposed to atmospheric benzene. The possible influence of age. Eur. J. Cance 6, 49.
• 151. Toxicologicalprofile for benzene (1997) U.S. Departmen of Health and Human Service.
• 152. Tsai SP; Wen CP., Weiss N.S. (1983) Retrospective mortality and medical surveillance studied of worker sin benzene areas of rafineries. J. Occup. Med. 25, 685-692.
• 153. Ungvary G., Tatrai E. (1985) On the embriotoxic effects of benzen e and its alkyl derivatives in mice, rats andrabbits. Arch. Toxicol. Suppl. 8,425-430.
• 154. van Siuert N.1., Boogard P.J., Benlink G.D. (1993) Application of the urinary S-phenylmercapturic acid testas a biomarker for low levels of exposure in industry. Br. J. Ind. Med. 50(5),460.
• 155. VianaN.J., Polan A. (1979) Lmphosomas and occupational benzene exposure. Lancet 30, 1394.
• 156. Vigliani E.C, Saita G. (1964) Benzene and leukemia. New Engl. J. Med. 271, 872.
• 157. Vigliani E.C (1976) Leukemia associated with benzene exposure. Ann. NY Acad Sci. 271,143-151.
• 158. Ward CB., Kuna R.A., Snyder N.K. (1985) Subchronic inhalation toxicity of benzen e in rats and mice. Am. J. Ind., Med. 7,457-473.
• 159. Watanabe G.J., Yoshida S. (1970) The teratogenic effect of benzene in preqnant mice. Acta Med Biol. 17(4),285.
• 160. Wells M.S., Nerland D.E. (1991) Hematotoxicity and concentration-dependent conjugation of phenol in mice following inhalation exposure to benzene. Toxicol. Letter 56(1-2), 159-166.
• 161. WesterR.C, Maibach H.J., Gruenke L.D. (1986) Benzene levels in ambient air and breath of smokers and nonsmokers in urban and pristine environments. J. Toxicol. Health. 18,567-573.
• 162. Winek CL., Collom W.D. (1971) Benzene and toluene fatalities. J. Occup. Med. 13, 259-261.
• 163. Winek CL., Collom W.D., Wedt CH. (1967) Fata J benzene exposure by glue sniffing. Lancet 25,683.
• 164. Withey R.J., Hall 1.W. (1975) The joint toxic action of perchloroethylene with benzene or toluene in rats. Toxicology. 4, 5-15.
• 165. Witz G. i in. (1990a) Comparative metabolism of benzene trans, transmuconic acid in DBA/2N and Biochem Pharmacol. 190,40,1275-1280.
• 166. Witz G. i in. (1990b) Genetic toxicity of the benzene metabolite trans,trans-muconic acid in mammalian and bacterial cells. Mutat. Res. 240, 295.
• 167. Wong o. (1987b) An industry wide mortality study of chemical workers occupationally exposed to benzene II. Dose response analyses. Br. J. Ind. Med. 44, 382.
• 168. Yardley-Jones ,A., Anderson D., Jenkinson P.C (1988) Genotooxic effects in peripheral blood and urine of workers exposed to low level benzene. Br. J. Ind. Med. 45, 694-700.
• 169. Yin S. i in. (1987a) Occupational exposure to benzen e in China. Br. J. Ind. Med. 44,192 195.
• 170. Yin S. i in. (1987b) Symptoms and signs of workers exposed to benzene, toluene or the combination. Ind. Health. 25, 113-130.
• 171. Wolf M. A. i in. (1956) Toxicological studies of certain alkylated benzenes and benzene. AMA Arch. Ind. Health. 14,387.
• 172. Wong O. (1987a) An industry wide mortality study of chemical workers occupationally exposed to benzene 1. General results. Br. J. Ind. Med. 44, 365-381.
• 173. Yu R., Weisel CP. (1998) Measurement of benzene in human breath associated with an environmental exposure. J. Exp. Ana!. Environ. Epidemiol 6(3), 261-277.
• 174. Zhurkov V.S., Fel'dt E.G., Kosyakov V.V. (1983) Dependence of the frequency of chromosomal aberrations in mouse bone marrow cells on concentration (dose) and mode of administration of benzene. Bull. Exp. Biol. Med. 96, l741-l743.
• --------------------------------------------------------------------------------------------------------