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Phase II Report of Task I: Intravenous Lethality and Toxicity Studies in CD2F1 Mice and Sprague-Dawley Rats and Toxicity Study in Beagle Dogs of Spirohydantoin Mustard (NSC-172112).

PB83149518

Publication Date	1982
Personal Author	Liao, J. T. F.; Collins, W. T.; Hiles, R. A.; Karcher, R. V.; Frick, S.
Page Count	357
Abstract	Spirohydantoin mustard (NSC-172112) was administered intravenously to mice, rats, and dogs for the evaluation of lethality and toxicity. In the single dose range-finding study in mice, death in two males and decreased motor activity in one male were the only toxic signs observed. Due to low mortality and the concentration limit of the test article, the single dose lethality was not performed in mice. In the five daily dose range-finding and lethality study in mice, there was no apparent sex difference in the calculated lethality doses. The combined sex LD10, LD50, and LD90 were 8.3, 11.0, and 14.5 mg/kg/day (24.9, 33.0, and 43.5 mg/m2/day). Both sexes had fairly steep dose-response curves. Decreases in body weight and motor activity, piloerection, and increase in respiration rate were the most frequently observed toxic effects. All the clinical signs were reversible but the recovery of body weight was slow. In the five daily dose toxicity study in mice, decreases in body weight and motor activity and rough hair coat were observed. Damages in the hematopoietic tissues were reflected as leukoepnia, lymphopenia, neutropenia, reticulocytopenia, and decreases in HCT, HGB, and RBC. Reversibility of all hematologic changes was apparent, except for a slight leukopenia on day 29.
Keywords	Toxicology Antineoplastic agents Drugs Toxicity Dosage Dose rate Parenteral infusions Mice Dogs Rats Laboratory animals Liver Gastrointestinal system Reproductive system Lethal dosage Spirohydantoin mustard NSC 172112
Source Agency	National Cancer Institute
NTIS Subject Category	57Y - Toxicology 57Q - Pharmacology & Pharmacological Chemistry
Corporate Authors	Springborn Inst. for Bioresearch, Inc., Spencerville, OH.; National Cancer Inst., Bethesda, MD.; Battelle Toxicology Program Office, Vienna, VA.
Supplemental Notes	Sponsored in part by Battelle Toxicology Program Office, Vienna, VA. Portions of this document are not fully legible.
Document Type	Technical Report
Title Note	Final rept. 15 Jan 82-14 Jun 82.
NTIS Issue Number	198308
Contract Number	N01-CM-17365

Phase II Report of Task I: Intravenous Lethality and Toxicity Studies in CD2F1 Mice and Sprague-Dawley Rats and Toxicity Study in Beagle Dogs of Spirohydantoin Mustard (NSC-172112).

Phase II Report of Task I: Intravenous Lethality and Toxicity Studies in CD2F1 Mice and Sprague-Dawley Rats and Toxicity Study in Beagle Dogs of Spirohydantoin Mustard (NSC-172112).
PB83149518

Publication Date	1982
Personal Author	Liao, J. T. F.; Collins, W. T.; Hiles, R. A.; Karcher, R. V.; Frick, S.
Page Count	357
Abstract	Spirohydantoin mustard (NSC-172112) was administered intravenously to mice, rats, and dogs for the evaluation of lethality and toxicity. In the single dose range-finding study in mice, death in two males and decreased motor activity in one male were the only toxic signs observed. Due to low mortality and the concentration limit of the test article, the single dose lethality was not performed in mice. In the five daily dose range-finding and lethality study in mice, there was no apparent sex difference in the calculated lethality doses. The combined sex LD10, LD50, and LD90 were 8.3, 11.0, and 14.5 mg/kg/day (24.9, 33.0, and 43.5 mg/m2/day). Both sexes had fairly steep dose-response curves. Decreases in body weight and motor activity, piloerection, and increase in respiration rate were the most frequently observed toxic effects. All the clinical signs were reversible but the recovery of body weight was slow. In the five daily dose toxicity study in mice, decreases in body weight and motor activity and rough hair coat were observed. Damages in the hematopoietic tissues were reflected as leukoepnia, lymphopenia, neutropenia, reticulocytopenia, and decreases in HCT, HGB, and RBC. Reversibility of all hematologic changes was apparent, except for a slight leukopenia on day 29.
Keywords	Toxicology Antineoplastic agents Drugs Toxicity Dosage Dose rate Parenteral infusions Mice Dogs Rats Laboratory animals Liver Gastrointestinal system Reproductive system Lethal dosage Spirohydantoin mustard NSC 172112
Source Agency	National Cancer Institute
NTIS Subject Category	57Y - Toxicology 57Q - Pharmacology & Pharmacological Chemistry
Corporate Authors	Springborn Inst. for Bioresearch, Inc., Spencerville, OH.; National Cancer Inst., Bethesda, MD.; Battelle Toxicology Program Office, Vienna, VA.
Supplemental Notes	Sponsored in part by Battelle Toxicology Program Office, Vienna, VA. Portions of this document are not fully legible.
Document Type	Technical Report
Title Note	Final rept. 15 Jan 82-14 Jun 82.
NTIS Issue Number	198308
Contract Number	N01-CM-17365