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Single Dose Range-Finding Studies of Melphalan (NSC-8806) in Dogs and Mice.

PB88133921

Publication Date	1987
Personal Author	Placke, M. E.; Habash, D. L.; Page, J. G.
Page Count	101
Abstract	Single intravenous doses of Melphalan were administered to both dogs (3.0, 1.5 or 0.75 mg/kg) and mice (22-2.5 mg/kg). Two dogs (3.0 mg/kg and 1.5 mg/kg groups) were necropsied in a moribund condition on Study Day 9. Mortality occurred in mice in the range of (22-15 mg/kg). Probit analysis of the mice data estimated the LD50 values to be 20.8 mg/kg for males and 24.4 mg/kg for females. There was a steep dose response curve which suggested little difference between nontoxic and lethal doses. There was evidence of delayed clinical toxicity in both species. Delayed onset in dogs (3 mg/kg) appeared 8-9 days post-dosing. Delayed onset in mice occurred 6-22 days after treatment (22-10 mg/kg, males) (22-15 mg/kg, females). Mice showed decreases in group mean body weight with reversal of depressed body weight gain in surviving animals. Both species showed dose-related decreases in WBC's (day 8, dogs ; day 5, mice) with WBC values returning to normal ranges by the end of a 28-day observation period. All treated mice showed both decreased platelet values and segmented neutrophils (day 5). PK data suggested a triphasic plasma decay curve and a Vd of 0.3L/kg in dogs. Microscopically, there was widespread, moderate to marked lymphocytic depletion in all hematopoietic tissue in bone marrow and spleen in the two dogs that were necropsied. No anatomical pathology studies were conducted on the other dogs or any of the mice.
Keywords	Toxicology Drugs Antineoplastic agents Toxicity Bioassay Laboratory animals Mice Dogs Dose rate Melphalon NSC 8806
Source Agency	National Cancer Institute
NTIS Subject Category	57Y - Toxicology 57Q - Pharmacology & Pharmacological Chemistry
Corporate Authors	Battelle Toxicology Program Office, McLean, VA.; National Cancer Inst., Bethesda, MD. Toxicology Branch.; Battelle Columbus Div., OH.
Supplemental Notes	Also pub. as Battelle Columbus Div., OH. rept. no. G7707-52-54-87. Prepared in cooperation with Battelle Columbus Div., OH. Sponsored by National Cancer Inst., Bethesda, MD. Toxicology Branch.
Document Type	Technical Report
Title Note	Study rept. (Final),
NTIS Issue Number	198807
Contract Number	N01-CM-1-7365

Single Dose Range-Finding Studies of Melphalan (NSC-8806) in Dogs and Mice.

Single Dose Range-Finding Studies of Melphalan (NSC-8806) in Dogs and Mice.
PB88133921

Publication Date	1987
Personal Author	Placke, M. E.; Habash, D. L.; Page, J. G.
Page Count	101
Abstract	Single intravenous doses of Melphalan were administered to both dogs (3.0, 1.5 or 0.75 mg/kg) and mice (22-2.5 mg/kg). Two dogs (3.0 mg/kg and 1.5 mg/kg groups) were necropsied in a moribund condition on Study Day 9. Mortality occurred in mice in the range of (22-15 mg/kg). Probit analysis of the mice data estimated the LD50 values to be 20.8 mg/kg for males and 24.4 mg/kg for females. There was a steep dose response curve which suggested little difference between nontoxic and lethal doses. There was evidence of delayed clinical toxicity in both species. Delayed onset in dogs (3 mg/kg) appeared 8-9 days post-dosing. Delayed onset in mice occurred 6-22 days after treatment (22-10 mg/kg, males) (22-15 mg/kg, females). Mice showed decreases in group mean body weight with reversal of depressed body weight gain in surviving animals. Both species showed dose-related decreases in WBC's (day 8, dogs ; day 5, mice) with WBC values returning to normal ranges by the end of a 28-day observation period. All treated mice showed both decreased platelet values and segmented neutrophils (day 5). PK data suggested a triphasic plasma decay curve and a Vd of 0.3L/kg in dogs. Microscopically, there was widespread, moderate to marked lymphocytic depletion in all hematopoietic tissue in bone marrow and spleen in the two dogs that were necropsied. No anatomical pathology studies were conducted on the other dogs or any of the mice.
Keywords	Toxicology Drugs Antineoplastic agents Toxicity Bioassay Laboratory animals Mice Dogs Dose rate Melphalon NSC 8806
Source Agency	National Cancer Institute
NTIS Subject Category	57Y - Toxicology 57Q - Pharmacology & Pharmacological Chemistry
Corporate Authors	Battelle Toxicology Program Office, McLean, VA.; National Cancer Inst., Bethesda, MD. Toxicology Branch.; Battelle Columbus Div., OH.
Supplemental Notes	Also pub. as Battelle Columbus Div., OH. rept. no. G7707-52-54-87. Prepared in cooperation with Battelle Columbus Div., OH. Sponsored by National Cancer Inst., Bethesda, MD. Toxicology Branch.
Document Type	Technical Report
Title Note	Study rept. (Final),
NTIS Issue Number	198807
Contract Number	N01-CM-1-7365