The carcinogenicity of discontinuous inhaled benzene exposures in CD-1 and C57Bl/6 mice
Tóm tắt
Groups of male C57Bl and CD-1 mice were exposed to benzene via inhalation using two different exposure protocols. One protocol consisted of repetitive week-long exposures to 300 ppm benzene (6 h/d×5 d/wk) interrupted by 2 weeks of non-exposure. The exposure pattern (1 week of exposure followed by 2 weeks of non-exposure) was continued until the death of the last exposed animal. The second protocol consisted of exposures to 1200 ppm benzene (6 h/d×5 d/wk) for 10 weeks. Exposures were then terminated and the animals allowed to live out their lives. For each protocol, appropriate age-matched control mice received comparable exposures to filtered, conditioned air. The discontinuous exposure patterns mimic the patterns of exposure often encountered in the workplace and, in addition, prolong the survival of exposed animals so as to maximize potential tumorigenic responses. Both exposure protocols were markedly hematotoxic to both mouse strains as measured by peripheral blood counts. Both strains of mice responded to the intermittent 300 ppm benzene exposures with elevated incidences of malignant tumors. Particularly noteworthy was a 35% incidence of zymbal gland tumors in the C57Bl mice. In contrast, only the CD−1 mice responded to the 1200 ppm benzene exposures delivered over 10 weeks with elevated tumor incidences. A 46% incidence of lung adenoma was particularly striking in these mice. Neither of the benzene exposure protocols induced elevated incidences of leukemia/lymphoma in either strain. These studies demonstrate that discontinuous exposures to benzene are tumorigenic and that a lifetime exposure to benzene, even if delivered at a lower concentration and in an intermittent exposure pattern, is more tumorigenic than a short-term exposure to benzene.
Tài liệu tham khảo
Chemical and Engineering News, June 11, 1984
Cronkite E, Bullis J, Inoue T, Drew R (1984) Benzene inhalation produces leukemia in mice. Toxicol Appl Pharmacol 75: 358–361
Drew RT, Laskin S (1973) Environmental inhalation chambers. In: Gay WI (ed) Methods of animal experimentation, Vol 4. Academic Press, New York, pp 1–41
Goldstein BD (1977) Hematotoxicity in humans. In: Laskin S, Goldstein BD (eds) Benzene toxicity, a critical evaluation. J Toxicol Environ Health Suppl 2: 69–105
International Agency for Research on Cancer (1982) Vol 29. Annex: 391–398
Maltoni C, Scarnato C (1979) First demonstration of the carcingenic effects of benzene. Med Lav 5: 352–357
Maltoni C, Conti B, Cotti G (1983) Benzene: a multipotential carcinogen. Results of long-term bioassays performed at the Bologna Institute of Oncology. Am J Ind Med 4: 589–630
National Research Council (1980) Drinking water and health, Vol 3. Academy Press, Washington, DC, pp 80–86, 261–262
Percy DH, Jonas AM (1971) Incidence of spontaneous tumors in CD-1 HaM/ICR mice. J Natl Cancer Inst 46: 1045–1065
Peto R, Pike MX (1973) Conservation of the approximation E (O-E)2/E in the logrank test for survival data or tumor incidence data. Biometrics 29: 579–584
Snyder CA (1987) Benzene. In: Snyder R (ed) Ethel Browning's Toxicity and metabolism of industrial solvents, 2nd Edn, Vol I. Elsevier, Amsterdam, pp 3–37
Snyder CA, Goldstein BD, Sellakumar A, Wohlman S, Bromberg I, Erlichman M, Laskin S (1978) Hematotoxicity of inhaled benzene to Sprague-Dawley rats and AKR mice at 300 ppm. J Toxicol Environ Health 4: 605–618
Snyder CA, Goldstein BD, Sellakumar A, Bromberg I, Laskin S, Albert RE (1980) The inhalation toxicology of benzene: incidence of hematopoietic neoplasms and hematotoxicity in AKR/J and C57Bl/6J mice. Toxicol Appl Pharmacol 54: 323–331
Snyder CA, Goldstein BD, Sellakumar A, Bromberg I, Laskin S, Albert RE (1982) Toxicity of chronic benzene inhalation: CD-1 mice exposed to 300 ppm. Bull Environ Contam Toxicol 29: 385–391
Snyder CA, Goldstein BD, Sellakumar A, Albert RE (1984) Evidence for hematotoxicity and tumorigenesis in rats exposed to 100 ppm benzene. Am J Ind Med 5: 429–435
Stoner G, Conran P, Greisiger E, Stober J, Morgan M, Periera M (1986) Comparison of two routes of chemical administration on the lung adenoma response in strain A/J mice. Toxicol Appl Pharmacol 82: 19–31
Toxicology and carcinogenesis studies of benzene in F344/N rats and B6C3F1 mice. National Toxicology Program, NTP TR 289, NIH Publication No. 86-2545, US Dept of Health and Human Services, 1986