RESUMEN
1. Abrin and ricin are highly toxic plant proteins which are very similar in structure and function and inhibit protein synthesis in eukaryotes. 2. Rats have been immunised against either toxin using formaldehyde-toxoids by three subcutaneous injections at intervals of 3 weeks. For abrin, serum titres in 14 out of 15 rats were raised to between 1:12800 and 1:51200 after two injections, 6 weeks from the start of the experiment. Titres of between 1:256 and 1:1024 were also measured in lung washes after challenge with active abrin toxin. 3. The three major antibody classes, IgG, IgM and IgA were present in the immune sera but IgG and IgA only were detected in lung washes. The proportion of IgA to IgG was higher in the lung fluid than in sera. Rats immunised by abrin toxoid were protected against 5 LCt50's of abrin by inhalation but others exposed to ricin were not. 4. For ricin, serum titres ranged from 1:800 to 1:25600 after two injections and after a third injection the titre range was the same but population samples were weighted towards the higher titres. All rats immunised with ricin toxoid survived the challenge of 5 LCt50's of ricin toxin by inhalation over the observation period of 28 days post-challenge. 5. Representative immunised rats (abrin toxoid) were taken at various times post-exposure, humanely killed and tissues were examined for pathological changes. It was concluded that an apparently severe lung lesion occurred at a later time than in non-immunised, toxin challenged rats. This damage was not lethal over the experimental observation periods. 6. Immunisation by the sub-cutaneous route therefore protects against lethality from challenge by inhalation of ricin or abrin toxins but does not prevent significant lung damage.
Asunto(s)
Abrina/toxicidad , Inmunización , Enfermedades Pulmonares/prevención & control , Ricina/toxicidad , Toxoides/uso terapéutico , Abrina/administración & dosificación , Administración por Inhalación , Animales , Peso Corporal/efectos de los fármacos , Líquido del Lavado Bronquioalveolar/química , Formaldehído/farmacología , Inmunoglobulina A/sangre , Inmunoglobulina G/sangre , Inmunoglobulina M/sangre , Inyecciones Subcutáneas , Pulmón/efectos de los fármacos , Pulmón/patología , Enfermedades Pulmonares/inducido químicamente , Masculino , Adhesión en Parafina , Ratas , Ricina/administración & dosificaciónRESUMEN
The subacute percutaneous toxicity of dipropylene glycol monomethyl ether (DPM) in male rats dosed 5 days/week for 4 weeks under both occluded and unoccluded conditions has been assessed and compared to the percutaneous toxicity of ethylene glycol monomethyl ether (EGM). DPM caused no significant changes in the clinical chemistry, haematology, or pathology, whereas EGM caused changes in the haematology and clinical chemistry, and both testicular and bone marrow damage at doses of 1000 mg/kg per day.
Asunto(s)
Glicoles de Etileno/toxicidad , Glicoles de Propileno/toxicidad , Administración Tópica , Animales , Relación Dosis-Respuesta a Droga , Glicoles de Etileno/administración & dosificación , Masculino , Glicoles de Propileno/administración & dosificación , Ratas , Ratas Endogámicas , Valores de Referencia , SolventesRESUMEN
The ability of trichothecenes, in particular T2 toxin (T2), to cause irritant effects on the skin has been investigated in laboratory rodents and rabbits. Quantitatively, T2 was found to be highly potent in this respect, causing irritant reactions on rat skin at contamination densities of less than 1 microgram.cm-2. The first appearance of skin effects was delayed for approximately 6 h after application, irrespective of the dose applied. Similarly, variation in solvent or injection into or beneath the skin failed to accelerate the onset of the irritant reaction. An aqueous soap solution was largely effective in removing low doses of T2 from the skin, but was ineffective in removing larger doses. However, washing the contaminated skin with polyethylene glycol 300 was very effective at removing even large doses of T2 from the skin. The macrocyclic trichothecene verrucarin A was of comparable irritancy to T2 on rat skin. Diacetoxyscirpenol and nivalenol were less potent.
Asunto(s)
Descontaminación , Irritantes , Sesquiterpenos/toxicidad , Piel/efectos de los fármacos , Toxina T-2/toxicidad , Animales , Relación Dosis-Respuesta a Droga , Femenino , Polietilenglicoles/farmacología , Conejos , Ratas , Ratas Endogámicas , Absorción Cutánea/efectos de los fármacos , Jabones , SolventesRESUMEN
The acute intravenous, intragastric, subcutaneous, intraperitoneal and intratracheal toxicity of T2 toxin has been studied in rats, mice, guinea-pigs, and pigeons. The acute LD50 values obtained varied between 1.0 and 14 mg X kg-1, there being little difference between the various routes in any given species. T2 caused vomiting in pigeons at doses of one fifth or less the LD50. In rats doses of 3.0 and 5.0 mg X kg-1 T2 produced lymphopenia, reticulocytosis, and in the highest dose groups normoblastaemia. Additionally, changes in plasma alkaline phosphatase and aspartate aminotransferase activities were seen. Histological changes were observed in lymphoid organs and were most severe in the thymus, lymph nodes, and Peyer's patches. The spleen was less severely affected. Gastrointestinal changes consisting of dead and dying lymphoid cells throughout the lamina propria were seen together with, in some cases, mucosal ulceration. The time course of the development and of the reversal of the changes was followed.
Asunto(s)
Sesquiterpenos/toxicidad , Toxina T-2/toxicidad , Administración Oral , Animales , Coagulación Sanguínea/efectos de los fármacos , Columbidae , Femenino , Cobayas , Infusiones Parenterales , Dosificación Letal Mediana , Masculino , Ratones , Ratas , Especificidad de la Especie , Toxina T-2/administración & dosificación , TráqueaRESUMEN
The acute toxicity of p-aminopropiophenone (PAPP) to three species of laboratory animals has been investigated using solutions in dimethylsulphoxide (DMSO) for intravenous and oral (intragastric) administration. In addition, methaemoglobinaemia and Heinz-body haemolytic anaemia are described.
Asunto(s)
Propiofenonas/toxicidad , Administración Oral , Animales , Relación Dosis-Respuesta a Droga , Femenino , Cobayas , Cuerpos de Heinz/efectos de los fármacos , Inyecciones Intravenosas , Dosificación Letal Mediana , Masculino , Metahemoglobinemia/inducido químicamente , Ratones , Propiofenonas/administración & dosificación , Ratas , Factores de TiempoRESUMEN
The single dose oral toxicity of 4- dimethylaminophenol (DMAP) was examined in mice, rats and guinea-pigs and the intravenous toxicity in mice. The oral LD50 in female mice was 946 mg kg-1, in male rats, 780 mg kg-1, in female rats 689 mg kg-1 and in female guinea-pigs 1032 mg kg-1. The intravenous LD50 in female mice was 70 mg kg-1. Dosing with DMAP at the maximum tolerated dose produced Heinz body haemolytic anaemia in rats and Heinz bodies unaccompanied by anaemia in mice. Rats showed biochemical and histological evidence of renal tubular changes.