Subject(s)
Methacrylates/toxicity , Nitriles/toxicity , Pregnancy, Animal/drug effects , Abortion, Veterinary/chemically induced , Animals , Body Weight/drug effects , Edema/chemically induced , Embryonic and Fetal Development/drug effects , Fallopian Tubes/drug effects , Female , Lethal Dose 50 , Litter Size/drug effects , Male , Pregnancy , Rats , Rats, Inbred StrainsABSTRACT
The toxicity, uptake, tissue distribution, elimination, and covalent binding of 2-[14C]methyl-[2.3-14C]acrylonitrile (MeAN) in male Sprague-Dawley rats were investigated. Following an oral administration of 100 mg/Kg body weight (0.5 LD50, 8 microCi/Kg bw) the rats exhibited several signs of toxicity including ataxia, convulsions, mild diarrhea, salivation, lacrimation, and bladder urine retention. The treated animals excreted 43% of the 14C in the urine, 14% in the feces, and 2.5% in the expired air as 14CO2 in 10 days. Hydrogen cyanide was not detectable. Red blood cells retained significant amounts of radioactivity for more than 10 days after treatment. MeAN was extensively absorbed through the gastrointestinal tract and distributed in all the tissues of the rats. The major concentrations of the radioactivity were found with up to 25% of the administered dose in bone, liver, spleen, kidney, blood, and the gastrointestinal tract. This study indicates that MeAN is rapidly absorbed and distributed and the major route of excretion is urinary.
Subject(s)
Methacrylates/toxicity , Nitriles/toxicity , Air/analysis , Animals , Behavior, Animal/drug effects , Erythrocytes/metabolism , Feces/chemistry , Lethal Dose 50 , Male , Methacrylates/pharmacokinetics , Nitriles/blood , Nitriles/pharmacokinetics , Rats , Rats, Inbred Strains , Subcellular Fractions/metabolism , Tissue DistributionABSTRACT
The interaction of 2[14C]methyl-2,3[14C]acrylonitrile (MeAN) with the components of blood and its disposition in male Sprague-Dawley rats has been investigated. Following an oral administration of 100 mg/kg (0.5 LD50, 8 microCi/kg), the rats excreted 43% of the [14C] in the urine, 15% in the feces and 2.5% in the expired air as 14CO2 in 5 days. Hydrogen cyanide (H14CN) was not detectable. The red blood cells retained significant amounts of radioactivity for more than five days after administration, whereas the [14C]-activity in plasma declined sharply. More than 50% of the radioactivity in erythrocytes was detected as covalently bound to cytoplasmic (hemoglobin) and membrane proteins. A small amount of radioactivity was also found in the heme fraction. About 13% of the total dose administered was recovered as thiocyanate in the plasma and the urine. These results suggest that the toxicity of MeAN may be attributable to the whole molecule and not entirely to the in vivo liberation of cyanide.
