Hematotoxicity and carcinogenicity of inhaled benzene.
CBA/Ca male mice have been exposed to benzene in air at 10, 25, 100, 300, 400, and 3000 ppm for variable intervals 6 hr/day, 5 days/week for up to 16 weeks. Two weeks of inhaling 10 ppm produced no hematologic effects; 25 ppm induced a significant lymphopenia. Inhalation of 100, 300, and 400 ppm produced dose-dependent decreases in blood lymphocytes, bone marrow cellularity, marrow content of spleen colony-forming units (CFU-S) and an increased fraction of CFU-S in DNA synthesis. Exposure of mice to 300 ppm for 2, 4, 8, and 16 weeks produced severe lymphopenia and decrease in marrow CFU-S. Recovery was rapid and complete after 2 and 4 weeks of exposure. After 8 and 16 weeks of exposure, recovery of lymphocytes was complete within 8 weeks. It took 16 weeks for the CFU-S to recover to that of the age-matched controls after 8 weeks of exposure and 25 weeks to recover to age-matched after 16 weeks of exposure. Inhalation of 3000 ppm for 8 days was less damaging than inhalation of 300 ppm for 80 days (same integral amount of benzene inhaled). The inhalation of 3000 ppm has not increased the incidence of leukemia or shortened its latency for development. Inhalation of 300 ppm 6 hr/day for 16 weeks significantly increases the incidence of myelogenous neoplasms in male CBA/Ca mice. Inhalation of 100 ppm for same interval does not influence incidence of myelogenous neoplasms but does increase incidence of solid neoplasms particularly in female CBA/Ca mice. Benzene is a potent carcinogen in CBA/Ca mice.
Cronkite
E P
EP
Medical Department, Brookhaven National Laboratory, Upton, NY 11973.
Drew
R T
RT
Inoue
T
T
Hirabayashi
Y
Y
Bullis
J E
JE
D000280:Administration, Inhalation; D000818:Animals; D001554:Benzene / Q000633:toxicity*; D002273:Carcinogens; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004912:Erythrocytes / Q000187:drug effects; D005260:Female; D006402:Hematologic Diseases / Q000139:chemically induced*; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D009503:Neutropenia / Q000139:chemically induced
D002273:Carcinogens; D001554:Benzene