Macrocytic-megaloblastic anemia in male B6C3F1 mice following chronic exposure to 1,3-butadiene.
In the present study exposure to 1,3-butadiene (BD) resulted in a macrocytic-megaloblastic anemia in male B6C3F1 mice following chronic inhalation of 1250 ppm for 6 to 24 weeks. Treatment-related changes evident after 6 weeks of exposure included a decrease in circulating erythrocytes, total hemoglobin, and hematocrit and an increase in mean corpuscular volume. A leukopenia, due primarily to a decrease in segmented neutrophils, and a five- to sixfold increase in circulating micronuclei were observed after 6 and 24 weeks of exposure. These changes were not accompanied by a significant alteration in mean corpuscular hemoglobin concentration, an increase in circulating reticulocytes, or circulating nucleated erythrocytes. A consistent treatment-related alteration in bone marrow cellularity was not found. However, flow cytofluorometric analysis of bone marrow DNA cell cycle kinetics revealed a 44% increase in proliferative index relative to controls, due primarily to an increase in the proportion of cells in S phase. These findings are consistent with a treatment-related macrocytic-megaloblastic anemia and indicate the bone marrow to be an important target organ for BD toxicity.
D000748:Anemia, Macrocytic / Q000139:chemically induced*; D000749:Anemia, Megaloblastic / Q000139:chemically induced*; D000818:Animals; D001853:Bone Marrow / Q000187:drug effects / Q000473:pathology*; D002070:Butadienes / Q000633:toxicity*; D004247:DNA / Q000032:analysis; D004906:Erythrocyte Count / Q000187:drug effects; D006400:Hematocrit; D006454:Hemoglobins / Q000032:analysis; D007958:Leukocyte Count / Q000187:drug effects; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009153:Mutagens / Q000633:toxicity*; D010976:Platelet Count / Q000187:drug effects
D002070:Butadienes; D006454:Hemoglobins; D009153:Mutagens; D004247:DNA; C031763:1,3-butadiene