Developmental toxicity of sarin in rats and rabbits. 1996

J B LaBorde, and H K Bates, and J C Dacre, and J F Young
Division of Reproductive and Development Toxicology, National Center for Toxicological Research, Jefferson, AR 72079, USA.

Sarin (Agent GB, isopropyl methylphosphonofluoridate) is an organophosphate cholinesterase inhibitor. Sarin (Type I or Type II) was administered by gavage to CD rats on d 6-15 of gestation at dose levels of 0, 100, 240, or 380 micrograms/kg/d and to New Zealand White (NZW) rabbits on d 6-19 of gestation at dose levels of 0, 5, 10, or 15 micrograms/kg/d. Females were weighed on gestational days (GD) 0, 6-16 for rats and 6-20 for rabbits, and immediately prior to termination (GD 20 for rats and GD 29 for rabbits). All animals were monitored daily for clinical signs of toxicity throughout dosing and until sacrifice. At necropsy, gravid uteri were weighed and examined for the number and status of implants (live, resorbed, or dead). Individual fetal body weight, malformations, and variations (external, visceral, and skeletal) were recorded. Rat and rabbit dams in the high-dose groups exhibited significant signs of maternal toxicity and increased maternal mortality. Examination of gravid uteri revealed no statistical differences among treatment groups in the incidence of resorptions or of dead or malformed fetuses, or in average body weight of live fetuses per litter. These results show no evidence or developmental toxicity in the CD rat or NZW rabbit following exposure to either Type I or Type II sarin during embryonic differentiation and major organogenesis, even at a dose that produced maternal toxicity.

UI MeSH Term Description Entries
D008297 Male Males
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
D011817 Rabbits A burrowing plant-eating mammal with hind limbs that are longer than its fore limbs. It belongs to the family Leporidae of the order Lagomorpha, and in contrast to hares, possesses 22 instead of 24 pairs of chromosomes. Belgian Hare,New Zealand Rabbit,New Zealand Rabbits,New Zealand White Rabbit,Rabbit,Rabbit, Domestic,Chinchilla Rabbits,NZW Rabbits,New Zealand White Rabbits,Oryctolagus cuniculus,Chinchilla Rabbit,Domestic Rabbit,Domestic Rabbits,Hare, Belgian,NZW Rabbit,Rabbit, Chinchilla,Rabbit, NZW,Rabbit, New Zealand,Rabbits, Chinchilla,Rabbits, Domestic,Rabbits, NZW,Rabbits, New Zealand,Zealand Rabbit, New,Zealand Rabbits, New,cuniculus, Oryctolagus
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
D002800 Cholinesterase Inhibitors Drugs that inhibit cholinesterases. The neurotransmitter ACETYLCHOLINE is rapidly hydrolyzed, and thereby inactivated, by cholinesterases. When cholinesterases are inhibited, the action of endogenously released acetylcholine at cholinergic synapses is potentiated. Cholinesterase inhibitors are widely used clinically for their potentiation of cholinergic inputs to the gastrointestinal tract and urinary bladder, the eye, and skeletal muscles; they are also used for their effects on the heart and the central nervous system. Acetylcholinesterase Inhibitor,Acetylcholinesterase Inhibitors,Anti-Cholinesterase,Anticholinesterase,Anticholinesterase Agent,Anticholinesterase Agents,Anticholinesterase Drug,Cholinesterase Inhibitor,Anti-Cholinesterases,Anticholinesterase Drugs,Anticholinesterases,Cholinesterase Inhibitors, Irreversible,Cholinesterase Inhibitors, Reversible,Agent, Anticholinesterase,Agents, Anticholinesterase,Anti Cholinesterase,Anti Cholinesterases,Drug, Anticholinesterase,Drugs, Anticholinesterase,Inhibitor, Acetylcholinesterase,Inhibitor, Cholinesterase,Inhibitors, Acetylcholinesterase,Inhibitors, Cholinesterase,Inhibitors, Irreversible Cholinesterase,Inhibitors, Reversible Cholinesterase,Irreversible Cholinesterase Inhibitors,Reversible Cholinesterase Inhibitors
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
D005314 Embryonic and Fetal Development Morphological and physiological development of EMBRYOS or FETUSES. Embryo and Fetal Development,Prenatal Programming,Programming, Prenatal
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
D000284 Administration, Oral The giving of drugs, chemicals, or other substances by mouth. Drug Administration, Oral,Administration, Oral Drug,Oral Administration,Oral Drug Administration,Administrations, Oral,Administrations, Oral Drug,Drug Administrations, Oral,Oral Administrations,Oral Drug Administrations

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