Reproductive toxicity of dimethyl methyl phosphonate (DMMP) in the male Fischer 344 rat. 1984

J K Dunnick, and B N Gupta, and M W Harris, and J C Lamb

Dimethyl methyl phosphonate (DMMP) has been considered for use by the U.S. Armed Forces as a nerve gas simulant in a variety of experimental situations to simulate the physical properties of nerve gases, but not the neurotoxic properties. Dimethyl methyl phosphonate is also used as a flame retardant for urethane foams and polyester resins. This study was conducted to determine the reproductive toxicity of DMMP after subchronic dosing. DMMP was administered to male Fischer 344 rats by gavage 5 days/week for 90 days at dosages of 0, 250, 500, 1000, and 2000 mg/kg, and all animals survived this dosing schedule. At Day 84, the rats were mated to untreated female Fischer 344 rats. There was a dose-related decrease in sperm count, sperm motility, and the male fertility index. The male fertility index was 70, 75, 60, 40, and 0% in the 0, 250, 500, 1000, and 2000 mg/kg dose groups. DMMP acted as a dominant lethal mutagen as demonstrated by an increase in the number of resorptions with increasing doses of the drug. The percentage of resorptions in the control group was 6.1% and increased to 14.9, 37.8, and 79.1% in the 250, 500, and 1000 mg/kg groups, respectively. The testes of the male rats were examined histologically to determine the relationship between reproductive function and pathologic abnormalities. DMMP altered reproductive function at all dose levels, while histologic abnormalities of the testis were seen only in the high-dose group. Changes in the testes of the high-dose animals were characterized by lack of spermatogenesis or by degeneration, vacuolization, and necrosis of cells in the spermatogenic tubules. Histopathologic abnormalities of the kidney were seen in some animals from each of the dosed groups and microscopic changes of the prostate were seen in some of the high-dose animals.

UI MeSH Term Description Entries
D008297 Male Males
D009943 Organophosphorus Compounds Organic compounds that contain phosphorus as an integral part of the molecule. Included under this heading is broad array of synthetic compounds that are used as PESTICIDES and DRUGS. Organophosphorus Compound,Organopyrophosphorus Compound,Organopyrophosphorus Compounds,Compound, Organophosphorus,Compound, Organopyrophosphorus,Compounds, Organophosphorus,Compounds, Organopyrophosphorus
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
D011467 Prostate A gland in males that surrounds the neck of the URINARY BLADDER and the URETHRA. It secretes a substance that liquefies coagulated semen. It is situated in the pelvic cavity behind the lower part of the PUBIC SYMPHYSIS, above the deep layer of the triangular ligament, and rests upon the RECTUM. Prostates
D011916 Rats, Inbred F344 An inbred strain of rat that is used for general BIOMEDICAL RESEARCH purposes. Fischer Rats,Rats, Inbred CDF,Rats, Inbred Fischer 344,Rats, F344,Rats, Inbred Fisher 344,CDF Rat, Inbred,CDF Rats, Inbred,F344 Rat,F344 Rat, Inbred,F344 Rats,F344 Rats, Inbred,Inbred CDF Rat,Inbred CDF Rats,Inbred F344 Rat,Inbred F344 Rats,Rat, F344,Rat, Inbred CDF,Rat, Inbred F344,Rats, Fischer
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
D001835 Body Weight The mass or quantity of heaviness of an individual. It is expressed by units of pounds or kilograms. Body Weights,Weight, Body,Weights, Body
D005260 Female Females
D005298 Fertility The capacity to conceive or to induce conception. It may refer to either the male or female. Fecundity,Below Replacement Fertility,Differential Fertility,Fecundability,Fertility Determinants,Fertility Incentives,Fertility Preferences,Fertility, Below Replacement,Marital Fertility,Natural Fertility,Subfecundity,World Fertility Survey,Determinant, Fertility,Determinants, Fertility,Fertility Determinant,Fertility Incentive,Fertility Preference,Fertility Survey, World,Fertility Surveys, World,Fertility, Differential,Fertility, Marital,Fertility, Natural,Preference, Fertility,Preferences, Fertility,Survey, World Fertility,Surveys, World Fertility,World Fertility Surveys
D005327 Fetal Resorption The disintegration and assimilation of the dead FETUS in the UTERUS at any stage after the completion of organogenesis which, in humans, is after the 9th week of GESTATION. It does not include embryo resorption (see EMBRYO LOSS). Fetal Resorptions,Resorption, Fetal,Resorptions, Fetal

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