Sub-chronic effects of styrene and styrene oxide on lipid peroxidation, glutathione contents and glutathione reductase activities in the liver and brain were examined after intraperitoneal administration to rats 3 times a week for 7 weeks. Styrene (300, 400 and 500 mg/kg) and styrene oxide (200 and 300 mg/kg) increased lipid peroxidation in the liver after 7 weeks of treatment. Hepatic lipid peroxidation in rats treated with a higher dose of styrene oxide (400mg/kg) was significantly enhanced even after 2 weeks of treatment. On the other hand, no change in lipid peroxidation was observed in the brain under the above conditions. Neither glutathione contents nor glutathione reductase activities in the liver and brain were altered at 40 h after the last of these sub-chronic treatments. To elucidate the cause of lipid peroxidation, the time courses of glutathione content after treatment with either styrene or styrene oxide (300 mg/kg) were studied in more detail. Significant decreases in both the GSH and GSSG contents were detected shortly after these treatments and the levels recovered to the control values at 40 h in these organs, although the changes were less significant in the brain of rats treated with styrene. These results suggest that enhancement of lipid peroxidation in the liver after treatment with styrene or styrene oxide was a consequence of repeated depletions of glutathione to certain critical levels and delayed recovery of lipid peroxides.

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The repeated intravenous injections (RIVInj) of 5 mg/kg/day leptophos [O-(4-bromo-2, 5-dichlorophenyl) O-methyl phenylphos-phonothioate] for 3 consecutive days caused delayed ataxia in 4 out of 9 hens (44.4%). And one out of 9 hens (11.1%) given RIVInj of 3 mg/kg leptophos for 5 days was affected with ataxia. Twenty hens, however, which received a single intravenous injection (SIVInj) of 15 mg/kg leptophos did not exhibit any delayed neuropathic signs at all. Thus, delayed neurotoxicity was increased by the subdividing RIVInj of the critical dose which was shown in the SIVInj of leptophos. The leptophos concentration in plasma and liver decreased very rapidly after finish of either SIVInj or RIVInj. Although no significant differences were observed in the biological half life of leptophos in plasma by different dosages, the mean level of leptophos decreased significantly with frequency of injections. On the contrary, the evident accumulation of leptophos was observed in only sciatic nerve with RIVInj. Leg muscle maintained relatively high level of leptophos after the last injection. These results suggest that leptophos seems to transfer from blood to affinitive tissues such as sciatic nerve or leg muscles and to accumulate there easily in initial stage after repeated iv injections, and that this causes the enhancement of neuropathy with repeated administrations of divided critical dose of leptophos in both iv and oral administration.

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To investigate a magnitude of analytic errors brought by certain interfering substances to the chemical method using Jaffe-reaction for determination of creatinine, two sorts of values determined by the chemical method and by the HPLC method were compared between each other, in blood samples obtained from control and cephaloridine (CER)-administered rats. The rats that received an intravenous injection of CER in dose of 1, 000 mg/kg body weight, showed two peaks at the 1-hour and on the 3-day. Since the color development of CER determined in the chemical method showed that 1 g of CER corresponded to 0.0208 g of creatinine, the results of plasma CER determination proved that the first peak was ascribable to the color development of CER. As to the second peak, no significant difference was observed between the values of the two methods. This finding denoted that, when the creatinine levels were elevated, the two sorts of values due to the two methods approached to one another, and suggested that the ratio of "endogenous Jaffe-reaction-positive pseudo-creatinine chromogens" to "total Jaffe-reaction-positive chromogens" would be decreased according as the "true" creatinine was increased. In the control rats, the ratio to "total Jaffe-reaction-positive chromogens" was 60% in terms of "true" creatinine, and 40% in terms of "endogenous Jaffe-reaction-positive pseudo-creatinine chromogens".

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The effect of α-naphthylisothiocyanate (ANIT) on blood clearance of ^&lt99m&gtTc-phytate (^&lt99m&gtTc-P) in rats was examined, and blood clearance test of ^&lt99m&gtTc-P was compared with the cases of serum transaminase test, serum bilirubin test or histological test of the liver. The disappearance rate of ^&lt99m&gtTc-P from blood decreased with the increase in dose of ANIT and with the passage of time after the ANIT administration. Changes of the blood clearance of ^&lt99m&gtTc-P after ANIT treatment in rats may be influenced by the disorder in the hepatocytes rather than in the bile ductule cells. The blood clearance test of ^&lt99m&gtTc-P in rats showed a sensitive reaction for the acute hepatic dysfunction induced by ANIT equally to the serum transaminase test, the serum bilirubin test or the histological test of the liver.

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Groups of 21 male and 21 female Sprague-Dawley (SD) rats were fed diets containing pyriproxyfen at concentrations of 0, 80, 400, 2, 000 and 10, 000ppm for 6 months. No death was found in any group. Alopecia in the neck and/or back, and soft feces were noticed in both sexes fed 10, 000ppm. A marked decrease in body weight gain was observed in both sexes fed 10, 000ppm throughout the treatment period, accompanying a decrease in food-consumption and an increase in water-intake during the initial stage of treatment. In terms of urinalysis, proteinuria, increases in K excretion, and, in number, yellowness or browish-yellowness in appearance, were observed in both sexes fed 10, 000ppm. In females fed 10, 000ppm, increases in bilirubin, Na excretion and specific gravity, and a decrease in keton bodies, were observed. In hematology, decreases in erythrocyte count, bemoglobin concentration and hematocrit value, were observed in both sexes fed 10, 000ppm and in males fed 2, 000ppm. Also, an increase in MCH (in males), decreases in MCHC and platlet count (in females) were observed in 10, 000ppm group. Blood biochemistry revealed increases in total protein, albumin, α 2-globulin fraction, blood urea nitrogen, calcium (in both sexes fed 10, 000ppm), A/G ratio (in males fed 2, 000 and 10, 000ppm), total cholesterol, phospholipid (in males fed 2, 000 and 10, 000ppm, and in females fed 10, 000ppm), sodium (in females fed 2, 000 and 10, 000ppm), γ-glutamyl transpeptidase activity (in males fed 10, 000ppm) and α₁-globulin fraction (in females fed 10, 000ppm), and decreases in glucose, GOT (in both sexes fed 10, 000ppm), β-globulin fraction (in males fed 2, 000 and 10, 000ppm, and in females fed 10, 000ppm), GPT (in females fed 2, 000 and 10, 000ppm), triglyceride, potassium (in males fed 10, 000ppm), and cholinesterase activity (in female fed 10, 000ppm). In organ weight, increases in liver (in males fed 2, 000 ppm and 10, 000ppm, and in females fed 10, 000ppm), kidney (in both sexes fed 10, 000ppm) and thyroid (in females fed 10, 000ppm) and a decrease in pituitary (in females fed 2, 000 and 10, 000ppm) were observed. Gross patholoty revealed a higher incidence of blackish-brown coloration of the liver, and a lower incidence of accentuated lobular pattern of the liver (in males fed 10, 000ppm). An enlargement of the liver was seen in a few of both sexes fed 10, 000ppm. Histopathological examination showed that the sole effect attributable to treatment of this compound was on slight hypertrophy in the liver of both sexes fed 10, 000ppm, with a higher incidence. Based on the above results, pyriproxyfen administered to SD rats for 6 months revealed slight toxic effects such as an increased liver weight associated with hypertrophy of hepatocyte and an increased kidney weight at the highest dose level at which body weight gain was clearly suppressed. It is coricluded that the non-effective level is 400ppm for both sexes (24.0mg/kg for males, 27.5mg/kg for females).

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