Dominant lethal study of sulfur mustard in male and female rats. 1993

L B Sasser, and J A Cushing, and J C Dacre
Biology and Chemistry Department, Pacific Northwest Laboratory, Richland, WA 99352-0999.

Sulfur mustard (HD) (bis(2-chloroethyl)sulfide) is a strong alkylating agent with known mutagenic and suspected carcinogenic properties, but occupational health standards have not been established. The purpose of this study was to determine the dominant lethal effect in male and female rats dosed orally with HD, for which currently available data are ambiguous. Sprague-Dawley rats of each sex, 6-7 weeks old, were orally administered 0, 0.08, 0.20 or 0.50 mg kg-1 HD 5 days a week for 10 weeks, after which dominant lethal studies were conducted during the post-exposure period. The studies were conducted in two phases: a female dominant lethal phase in which treated or untreated males were mated with treated females and their fetuses were evaluated 14 days after copulation; and a male dominant lethal phase in which treated males cohabited with untreated females for 5 days and fetuses were evaluated 14 days after the mid-point of the week of cohabitation, for each of 10 weeks. In addition, motility, population size and morphology were measured in sperm obtained from the cauda epididymis. Parental growth rates were reduced in both sexes treated with the high level of HD. Female dominant lethal effects were not observed, although significant male dominant lethal effects were observed in HD-exposed male rats mated to untreated females at 2 and 3 weeks' post-exposure. These effects, which included increases of early fetal resorptions and preimplantation losses and decrease in total live embryo implants, were most consistently observed at a dose of 0.50 mg kg-1. A significant P(P < 0.05) increase in the percentage of abnormal sperm was detected in males exposed to 0.50 mg kg-1 HD. The timing of dominant lethal effects is consistent with an effect during the post-meiotic stages of spermatogenesis, possibly involving the generally sensitive spermatids.

UI MeSH Term Description Entries
D008297 Male Males
D009151 Mustard Gas Severe irritant and vesicant of skin, eyes, and lungs. It may cause blindness and lethal lung edema and was formerly used as a war gas. The substance has been proposed as a cytostatic and for treatment of psoriasis. It has been listed as a known carcinogen in the Fourth Annual Report on Carcinogens (NTP-85-002, 1985) (Merck, 11th ed). Dichlorodiethyl Sulfide,Sulfur Mustard,Bis(beta-chloroethyl) Sulfide,Di-2-chloroethyl Sulfide,Mustardgas,Psoriazin,Yellow Cross Liquid,Yperite,Di 2 chloroethyl Sulfide,Gas, Mustard,Mustard, Sulfur,Sulfide, Di-2-chloroethyl,Sulfide, Dichlorodiethyl
D011247 Pregnancy The status during which female mammals carry their developing young (EMBRYOS or FETUSES) in utero before birth, beginning from FERTILIZATION to BIRTH. Gestation,Pregnancies
D012098 Reproduction The total process by which organisms produce offspring. (Stedman, 25th ed) Human Reproductive Index,Human Reproductive Indexes,Reproductive Period,Human Reproductive Indices,Index, Human Reproductive,Indexes, Human Reproductive,Indices, Human Reproductive,Period, Reproductive,Periods, Reproductive,Reproductive Index, Human,Reproductive Indices, Human,Reproductive Periods
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D005260 Female Females
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013094 Spermatozoa Mature male germ cells derived from SPERMATIDS. As spermatids move toward the lumen of the SEMINIFEROUS TUBULES, they undergo extensive structural changes including the loss of cytoplasm, condensation of CHROMATIN into the SPERM HEAD, formation of the ACROSOME cap, the SPERM MIDPIECE and the SPERM TAIL that provides motility. Sperm,Spermatozoon,X-Bearing Sperm,X-Chromosome-Bearing Sperm,Y-Bearing Sperm,Y-Chromosome-Bearing Sperm,Sperm, X-Bearing,Sperm, X-Chromosome-Bearing,Sperm, Y-Bearing,Sperm, Y-Chromosome-Bearing,Sperms, X-Bearing,Sperms, X-Chromosome-Bearing,Sperms, Y-Bearing,Sperms, Y-Chromosome-Bearing,X Bearing Sperm,X Chromosome Bearing Sperm,X-Bearing Sperms,X-Chromosome-Bearing Sperms,Y Bearing Sperm,Y Chromosome Bearing Sperm,Y-Bearing Sperms,Y-Chromosome-Bearing Sperms
D017207 Rats, Sprague-Dawley A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company. Holtzman Rat,Rats, Holtzman,Sprague-Dawley Rat,Rats, Sprague Dawley,Holtzman Rats,Rat, Holtzman,Rat, Sprague-Dawley,Sprague Dawley Rat,Sprague Dawley Rats,Sprague-Dawley Rats
D051381 Rats The common name for the genus Rattus. Rattus,Rats, Laboratory,Rats, Norway,Rattus norvegicus,Laboratory Rat,Laboratory Rats,Norway Rat,Norway Rats,Rat,Rat, Laboratory,Rat, Norway,norvegicus, Rattus

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