In a study of the hepatotoxicity of heptacholor (1, 4, 5, 6, 7, 8, 8-heptachloro 3a, 4, 7, 7 a-tetrahydro-4, 7-methanoindene), a major compound of chlordane, the effect of heptachlor on the respiratory activity (oxidative phosphorylation and electron transport) of rat liver mitochondria was investigated. Heptachlor at a final concentration of 50 μM with succinate as substrate decreased the respiratory control index (RCI) due to a marked inhibition of state 3 respiration and a slight inhibition of state 4 respiration. One hundred uM heptachlor with succinate as substrate suppressed the states 3 and 4 respiration almost completely. On the other hand, heptacholor at a final concentration ranging from 50 to 100 μM with β-hydroxybutylate (β-HB) slightly decreased the RCI and decreased the RCI hardly at all with ascorbate plus N, N, N', N', -tetramethylphenylene diamine (TMPD) as substrate. Hepta-chlor at a concentration of 50 μM in the presence of succinate also decreased the ADP/O ratio of mitochondria. The mode of inhibition of succinate oxidation by heptacholor apparently is a noncompetitive inhibiton, as shown by Lineweaver-Burk plot.
Effects of single intraperitoneal administration of trichloroethylene, 1, 1, 1-tri-chloroethane, and carbon tetrachloride (positive control) on the plasma contents of lipopro-teins were investigated in rats. Plasma was fractionated to VLDL, LDL, and HDL by sequential ultracentrifugation. On the administration of carbon tetrachloride at 30 to 1000 mg/kg, VLDL and HDLwere reduced dose-dependently, but the reduction in LDL was not dose-dependent. With trichloroethylene at 30 to 300 mg/kg, the lipid contents of VLDL and LDL fractions were decreased. At 1000 mg/kg, VLDL and LDL was increased by the trichloroethylene. The HDL was decreased with increasing doses of trichloroethylene at 30 to 1000 mg/kg. With 1, 1, 1-trichloroethane at 100 to 300 mg/kg, VLDL and LDL were increased. The HDL levels rose at 100 mg/kg but fell at 1000 mg/kg. Thus trichloroethylene impairs VLDL formation at low doses. 1, 1, 1-Trichloroethane stimulates the VLDL synthesis at low doses and inhibits it at high doses. The decreases in HDL at high doses of trichloroethylene and 1, 1, 1-trichloroethane resulted from the inhibition of HDL synthesis. Liver-to-body weight ratios were raised with increasing doses of carbon tetrachloride, trichloroethylene, and 1, 1, 1-trichloroethane. Plasma GOT and GPT activities rose at much higher doses of solvents than dose levels which produce the changes in lipoproteins and the increases in liver weights. The liver enlargement appeared to be a sensitive marker of hepatotoxicity related to the changes in lipoproteins, the profile of which was different in three solvents.
A method for determining phosphine was developed using adsorption sampling followed by colorimetric measurement. Two types of adsorbent used in this study were prepared from silica gel by impregnation with potassium permanganate (1% w/w) or (mercury(II) chloride and sodium chloride) (0.2 + 0.2% w/w). Each adsorbent (150 mg) packed in a glass tube had the capacity to adsorb 0.3 ppm of phosphine in 3l of test gas passing through at a rate of 300 ml/min without breakthrough. The adsorbed phosphine was desorbed into solutions as phosphate and the recovered phosphate was determined by ICP-AES or by one of two kinds of colorimetric methods for phosphate based on the molybde-num blue method, i.e., the colorimetric method following JIS K 0102 and that following the NIOSH Manual of analytical method, No. S 332. When 0.01 ppm of phosphine in 3 l of test gas was adsorbed on the potassium permanganate adsorbent and determined by the JIS method, 93.8% of the phosphine was recovered as phosphate with a CV of 12.9% (n=3). This method was applicable to field surveys of phosphine in workplaces. The other method with the mercury(II) chloride adsorbent followed by the NIOSH method resulted in lower recovery of phosphate in low phosphine concentration range. ICP-AES was less sensitive than the colorimetries. The effect of coexistent arsenite or silicate on the colorimetry of phosphate was assessed.
An experimental inhalation system was developed for fumes generated from powders of high melting point metals such as chromium, nickel, manganese and iron. The system consisted of a plasma flame metal sprayer as a fume generator, a granular bed type fume collector, a fluidized bed aerosol generator, an exposure and a control chamber of a horizontal-flow type and inhalant monitoring and controlling units. Performance of the chambers was ensured by a distribution test using flyash as a test aerosol. Using this system, rats were exposed to chromium fumes for one week or to nickel fumes for two months. The exposure concentrations of the chromium and nickel fumes were 1.85 ± 0.55 mg/m3 and 0.51±10.15 mg/m3 (mean±SD), near the target levels of 2 mg/m3 and 0.5 mg/m3, respectively. The mass median aerodynamic diameter and the geometric standard deviation of the chromium fumes were 2.1μm and 2.00, respectively. Those of the nickel fumes were 3.7μm and 1.74, respectively. Species analysis of these fume particles revealed that 26.4% of the total chromium was hexavalent and the residue was trivalent and that 1-3% of the total nickel was nickel(III) and the residue was nickel(II). Inhaled-metal concentrations in the lungs showed steady increases with the exposure periods and were within the normal range of variation. On the basis of these results, it is concluded that this system is useful for long-term inhalation experiments using high melting point metal fumes.