Japanese quail were administered 100 mg/kg chlorophenyl-labeled [UC] fenvalerate, a-cyano-3phenoxybenzyl 2-(4-chlorophenyl)isovalerate, for study of its distribution, elimination, and metabolism. Ninety percent of the administered dose was eliminated in the excreta within the first 24 h. In addition to fenvalerate, the following metabolites were present: benzeneacetic acid, 4-chloro-a-(l-methylethyl)-, cyano(3-phenoxy-4-hydroxyphenyl)methyl ester [4'-OH-fenvalerate]; benzeneacetic acid, 4-chloro-a-(1-methylethyl)-, (aminocarbonyl)(3-phenoxyphenyl)methyl ester [CONH2-fenvalerate]; 4-chloro-a-(lmethylethyl)benzeneacetic acid [Cl-V acid]; 4-chloro-a-(2-hydroxy-1-methylethyl)benzeneacetic acid [4-OH-C1-V acid].In time course studies radiocarbon peaked at 3 h (9 pg/g) in the liver and gradually declined, while in the blood it peaked within 2 h and fell quickly to an equilibrium value of 1.5 pg/mL blood. In liver microsomal and isolated heptatocyte preparations of Japanese quail and rat, the following metabolites were identified: Cl-V acid, 4-OH-C1-V acid, 4'-OH-fenvalerate, CONH2-fenvalerate. Oxidation was found to be the predominant route of degradation either pre-or posthydrolysis of the parent compound. Rapid excretion, lesser absorption, and faster metabolism probably explain the lower toxicity of fenvalerate to birds compared to rats.

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The effect of acrylonitrile (VCN) on erythrocyte lipid metabolism was investigated in vitro in metabolically active red cells from male Sprague-Dawley rats containing three types of hemoglobins: oxyhemoglobin, methemoglobin, and carbon monoxyhemoglobin. VCN at the concentration of 10 mM rapidly depleted erythrocyte glutathione (GSH) (75% of control) and induced lipid peroxidation (274% of control). Degradation of oxy- and methemoglobin was directly proportional to the extent of lipid peroxidation (r = 0.89). Addition of glucose to the incubation medium decreased hemoglobin degradation while it slightly increased VCN-induced lipid peroxidation. The highest amount of lipid peroxidation occurred in erythrocytes containing carbon monoxyhemoglobin and glucose. In the isolated red cell membranes incubated with 10 mM VCN, the lipid peroxidation was 400% of controls. VCN (25 mM) noncompetitively inhibited erythrocyte membrane Na+/K(+)-ATPase activity and the degree of inhibition was inversely proportional to the reaction temperature (r = -0.88). These findings indicate that the VCN induced hemoglobin degradation and lipid peroxidation are two extremes of a spectrum of oxidative damage in red cells leading to a change in physical state of membrane structure causing inhibition of adenosine triphosphate (ATPase) activity.

N,N'-Dimethylaminopropionitrile (DMAPN), a major component of the NIAX catalyst ESN, is known to cause urinary bladder dysfunction in exposed workers. In order to investigate the mechanism of DMAPN toxicity, we carried out time-course (0-72 h) and dose-response (175-700 mg/kg) studies on the effects of DMAPN in rats and mice. Treated animals exhibited several signs of toxicity including loss of body weight, reduced water consumption, and bladder urine retention, as well as bladder injury. DMAPN-induced bladder injury was characterized by distended bladders with marked diffuse submucosal and subserosal edema, petechial hemorrhage, and multifocal perivascular inflammatory infiltrates. The qualitative and quantitative analysis of urine indicated hypoosmolality, aciduria, hematuria, proteinuria, and oliguria. Elevated levels of creatinine and urea levels in plasma were indicative of renal dysfunction. Within hours following DMAPN administration, the animals exhibited a significant increase in urinary retention that resolved between 60 and 72 h. Rats excreted about 44% of the administered DMAPN dose unchanged in the urine, while mice excreted only about 6% of the dose. Commercially available DMAPN metabolites, administered by gavage, produced toxic effects less adverse than DMAPN. The biochemical effects of DMAPN included depletion of glutathione and increased lipid peroxidation in target organs, including urinary bladder and kidney. These studies indicate that there are species differences in DMAPN toxicity. The differences may be due to differences in the formation of reactive metabolic intermediates of DMAPN.