RESUMEN
The embryotoxicity and teratogenicity of methylhydrazine, 1,1-dimethylhydrazine, and 1,2-dimethylhydrazine were investigated with pregnant Fischer-344 rats. The compounds were administered ip on d 6-15 of pregnancy. A dose-dependent reduction in maternal weight gains occurred for all three compounds. A dose-related teratogenic effect did not occur for any of the three compounds. Embryotoxicity, manifested as reduced 20-d fetal weights, occurred only in the 1,1-dimethylhydrazine and 1,2-dimethylhydrazine high-dose treatment groups. The results indicate that none of the three methylated hydrazine derivatives are selectively embryotoxic or teratogenic in the rat.
Asunto(s)
Dimetilhidrazinas/toxicidad , Metilhidrazinas/toxicidad , Monometilhidrazina/toxicidad , Teratógenos/toxicidad , 1,2-Dimetilhidrazina , Animales , Peso Corporal/efectos de los fármacos , Femenino , Reabsorción del Feto/inducido químicamente , Inyecciones Intraperitoneales , Embarazo , Ratas , Ratas Endogámicas F344RESUMEN
The effect of JP-10, the major component of cruise missile fuel, on the development of embryonic rats was evaluated. Pregnant females were exposed via inhalation to 600 ppm or orally dosed with 250, 500 or 1000 mg JP-10/kg on gestation days 6-15. In a separate experiment both fetal and maternal blood levels of JP-10 were monitored during an inhalation exposure. Moderate signs of toxicity including tremors and convulsions were observed in the pregnant females receiving the higher doses. JP-10 was not selectively embryotoxic in the rat when administered by gavage or inhalation. Blood levels of JP-10 in the fetuses were about one half the maternal blood levels at steady state.
Asunto(s)
Feto/efectos de los fármacos , Indanos/toxicidad , Indenos/toxicidad , Anomalías Inducidas por Medicamentos , Animales , Peso Corporal/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Femenino , Embarazo , Ratas , Ratas Endogámicas F344Asunto(s)
Ácidos Decanoicos/farmacología , Dioxinas/farmacología , Fluorocarburos , Leucemia L5178/fisiopatología , Leucemia Experimental/fisiopatología , Mutágenos , Mutación , Dibenzodioxinas Policloradas/farmacología , Animales , Supervivencia Celular/efectos de los fármacos , Ácidos Decanoicos/toxicidad , Ratones , Pruebas de Mutagenicidad , Dibenzodioxinas Policloradas/toxicidadRESUMEN
The mutagenicity of 4 known intercalating agents acridine orange (AO), quinacrine mustard (QM), proflavin (PF) and ethidium bromide (EB) has been investigated in L5178Y mouse lymphoma cells. Methyl methanesulfonate (MMS) was used as a positive control in these studies. AO, QM and PF induced mutation in the excess thymidine- and thioguanine-selective systems. These 3 compounds were negative in the ouabain- and cytosine-arabinoside-selective systems while EB was positive only in the cytosine arabinoside system. It would appear that the EB-induced mutagenesis is different from that of AO, QM and PF though all are intercalating agents. Since the molecular origin of cytosine arabinoside mutants is unknown, further interpretation of the EB results is not possible.
Asunto(s)
Naranja de Acridina/farmacología , Acridinas/farmacología , Etidio/farmacología , Sustancias Intercalantes/farmacología , Leucemia L5178/genética , Leucemia Experimental/genética , Mutágenos , Proflavina/farmacología , Mostaza de Quinacrina/farmacología , Quinacrina/análogos & derivados , Animales , Supervivencia Celular/efectos de los fármacos , Leucemia L5178/fisiopatología , Metilmetanosulfonato/farmacología , Ratones , MutaciónAsunto(s)
Diazepam/uso terapéutico , Metilhidrazinas/envenenamiento , Monometilhidrazina/envenenamiento , Muscimol/uso terapéutico , Oxazoles/uso terapéutico , Piridoxina/uso terapéutico , Animales , Relación Dosis-Respuesta a Droga , Quimioterapia Combinada , Masculino , Ratones , Ratones Endogámicos ICR , Muscimol/metabolismo , Convulsiones/prevención & controlRESUMEN
The mutagenicity of hydrazine, monomethylhydrazine (MMH), 1,1-dimethylhydrazine (UDMH) and 1,2-dimethylhydrazine (SDMH) in L5178Y mouse-lymphoma cells has been investigated. Hydrazine, UDMH and SDMH induced thymidine mutation, in the absence of extraneous metabolic activation. Dose-response curves were produced for these compounds. MMH did not induce thymidine mutation. All 4 compounds were negative in the ouabain, thioguanine and cytosine arabinoside selective systems. Induction of mutation by hydrazine and UDMH is correlated with toxicity. This is not the case for SDMH-induced mutation. Hydrazine, UDMH and SDMH produce different ratios of large and small thymidine-resistant clones. The compounds appear to have different modes of action in the cell.
Asunto(s)
Hidrazinas/farmacología , Mutágenos , Animales , Hidrazinas/toxicidad , Leucemia L5178/genética , Ratones , Pruebas de Mutagenicidad , Timidina/genéticaRESUMEN
The second generation of ballistic missiles and boosters, characterized by increased range and quick reaction capability, required the development of new high-energy storage propellants. This exploration led to the introduction of hydrazine (Hz), monomethylhydrazine (MMH), and 1,1-dimethylhydrazine (UDMH) into the USAF inventory. These compounds are all storable, noncryogenic, high-energy fuels which may be used alone or in combination as mixed amine fuels. Early toxicology experiments were to produce data on acute and subacute effects of the propellants in order to set standards for test and operational procedures to protect propellant handlers. The early work indicated that, despite similar chemical characteristics, there were marked differences between the compounds in terms of toxicological mechanisms. Since the propellant systems have been used for some 15 years, recent emphasis on toxicology has been centered on the more chronic effects and on an increasing body of evidence from animal experiments that the compounds may possess oncogenic potential as well as chronic systemic effects. This paper addresses itself to data leading up to current occupational standards.
Asunto(s)
Hidrazinas/toxicidad , Enfermedades Profesionales/inducido químicamente , Alopecia/inducido químicamente , Animales , Conducta Animal/efectos de los fármacos , Peso Corporal/efectos de los fármacos , Carcinógenos , Dimetilhidrazinas/toxicidad , Relación Dosis-Respuesta a Droga , Exposición a Riesgos Ambientales , Femenino , Hemólisis/efectos de los fármacos , Humanos , Hígado/efectos de los fármacos , Masculino , Concentración Máxima Admisible , Metabolismo/efectos de los fármacos , Monometilhidrazina/toxicidad , Mutación/efectos de los fármacos , Neoplasias/inducido químicamente , Enfermedades Respiratorias/inducido químicamente , Convulsiones/inducido químicamente , Contaminación Química del AguaAsunto(s)
Propelentes de Aerosoles/toxicidad , Aerosoles/toxicidad , Hidrocarburos Halogenados/toxicidad , Propelentes de Aerosoles/metabolismo , Animales , Arritmias Cardíacas/inducido químicamente , Biotransformación , Perros , Haplorrinos , Hemodinámica/efectos de los fármacos , Humanos , Hidrocarburos Halogenados/metabolismo , Miocardio/metabolismo , Manifestaciones Neurológicas , Consumo de Oxígeno/efectos de los fármacos , Conejos , RatasAsunto(s)
Clorofluorocarburos de Metano/farmacología , Incendios/prevención & control , Hemodinámica/efectos de los fármacos , Hidrocarburos Halogenados/farmacología , Miocardio/metabolismo , Animales , Glucemia/metabolismo , Presión Sanguínea/efectos de los fármacos , Circulación Coronaria/efectos de los fármacos , Perros , Ácidos Grasos no Esterificados/sangre , Femenino , Frecuencia Cardíaca/efectos de los fármacos , Lactatos/sangre , Masculino , Oxígeno/sangre , Consumo de Oxígeno/efectos de los fármacos , Piruvatos/sangre , Factores de TiempoRESUMEN
A versatile nylon jacket was designed for mixed-breed dogs to permit easy access to cardiac instrumentation and to protect the leads when not in use.
Asunto(s)
Animales de Laboratorio , Perros , Animales , Cateterismo Cardíaco/instrumentación , Cateterismo Cardíaco/veterinaria , Perros/fisiología , Corazón/fisiología , Nylons , TransductoresRESUMEN
Rats and dogs were protected from the effects of lethal doses of ingested ethylene glycol (EG) with pyrazole (P), an inhibitor of liver alcohol dehydrogenase. Rats given 1.35 ml/100 g of EG followed by 2.2 mmol/kg of P i.p. at 6 and 30 hours postingestion survived. Untreated control animals died. Dogs were given either 10.0 or 12.5 ml/kg of EG and treatment was begun 6 hours later. The control treatment consised of NaHC03 administered i.v. according to the calculated base deficit, B-complex vitamins with ascorbic acid, hydrocortisone, and 5 per cent glucose in water. The addition postexposure to this treatment of 0.9 mmol/kg of P and 0.5 mmol/kg of P at 6 and 30 hours, respectively, constituted the experimental therapy. In summary: with 10 ml/kg of EG, no P, 2 of 5 dogs survived; 12.5 ml/kg of EG, no P, 0/1; 10 ml/kg of EG plus P, 9/11; 12.5 ml/kg of EG plus P, 12/22. Dogs that succumbed had large numbers of oxalate crystals in their kidneys at necropsy. The surviving dogs had few oxalate crystals in their kidneys at the time of unilateral nephrectomy (2 weeks postexposure) or necropsy (30 days postexposure). Several clinical factors were identified as useful prognostic indicators in the treatment of EG poisoning. The results suggested that pyrazole, despite its marked toxicity, may be of clinically significant value in the treatment of ethylene glycol poisoning when therapy is initiated withing 6 hours of exposure.