Subchronic and chronic toxicity of ingested 1,3-dichloropropene in dogs.
The potential toxicologic effects to dogs of 1,3-dichloropropene (1, 3-D), a soil fumigant used for the control of nematodes, were investigated. The 13-week subchronic toxicity study consisted of male and female beagle dogs (4/sex/dose group) given approximately 0, 5, 15, or 41 mg 1,3-D/kg body wt/day (approximately equivalent amounts of cis and trans isomers) via their diets. The 1-year chronic toxicity study consisted of male and female beagle dogs (4/sex/dose group) provided diets delivering approximately 0, 0.5, 2. 5, or 15 mg/kg body wt/day. The test material was stabilized in the feed by microencapsulation in a starch/sucrose matrix (80/20). In both the 13-week and the 1-year studies, the primary effect of 1,3-D in male and female dogs ingesting a dosage of >/=15 mg/kg/day was hypochromic, microcytic anemia. The anemia was regenerative, with increased erythropoietic activity characterized by polychromasia of erythrocytes and increased numbers of reticulocytes in peripheral blood. In the 13-week study, the anemia in dogs given 41 mg/kg/day progressively worsened over time, while the anemia in dogs given 15 mg/kg/day remained relatively constant between 42 and 90 days of dosing. Partial reversal of the anemia of high-dose animals occurred during a 5-week recovery period following the 13-week dosing regimen. In the 13-week study, terminal fasted body weights of males given 15 or 41 mg/kg/day were decreased 3 and 28%, respectively, and body weights of females given 5, 15, or 41 mg/kg/day were decreased 4.5, 12, and 24%, respectively, relative to controls. Males given 5 mg/kg/day for 13 weeks had no change in body weights relative to controls. In the 1-year study, the hypochromic microcytic anemia in dogs given 15 mg/kg/day remained relatively constant in severity between 3 and 12 months of treatment. Histopathologic alterations associated with anemia in the 1-year study consisted of increased hematopoiesis of the bone marrow and increased extramedullary hematopoiesis of the spleen. Body weights of males given 15 mg/kg/day were 5-12% lower than controls during the first 13 weeks of the study and 13-19% lower than controls during the remaining 9 months. Body weights of females given 15 mg/kg/day were 5-14% lower than controls over the majority of the dosing period. Males and females given 0.5 or 2.5 mg/kg/day for 1 year had no change in body weights relative to controls. A no-observed-effect level of 2.5 mg/kg/day was established for male and female dogs from the 1-year study.
Stebbins
K E
KE
Toxicology & Environmental Research and Consulting, The Dow Chemical Company, 1803 Building, Midland, Michigan 48674, USA.
Quast
J F
JF
Haut
K T
KT
Stott
W T
WT
D000284:Administration, Oral; D000498:Allyl Compounds / Q000633:toxicity*; D000747:Anemia, Hypochromic / Q000139:chemically induced; D000818:Animals; D002214:Capsules; D003402:Creatine Kinase / Q000097:blood; D004032:Diet; D004285:Dogs; D004334:Drug Administration Schedule; D004435:Eating / Q000187:drug effects; D004906:Erythrocyte Count / Q000187:drug effects; D005260:Female; D006400:Hematocrit; D006454:Hemoglobins / Q000378:metabolism; D006843:Hydrocarbons, Chlorinated; D007306:Insecticides / Q000633:toxicity*; D008297:Male; D017701:Reticulocyte Count / Q000187:drug effects; D016482:Urinalysis
D000498:Allyl Compounds; D002214:Capsules; D006454:Hemoglobins; D006843:Hydrocarbons, Chlorinated; D007306:Insecticides; C023891:1,3-dichloro-1-propene; D003402:Creatine Kinase