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Bisphenol A (BPA) is a weak xenestrogen (ADI = 50 microg kg(-1), US EPA) which is mass-produced, with potential for human exposure. To study absorption, distribution, excretion, and metabolism of BPA, BPA labeled with carbon-14 was administered p.o. to male and female Fischer (F344) rats at relatively low doses (20, 100, and 500 microg kg(-1)), and i.v. injected at 100 and 500 microg kg(-1). 14C-BPA (500 microg kg(-1)) was also administered orally to pregnant and lactating rats to examine the transfer of radioactivity to fetuses, neonatal rats, and milk. Radioluminographic determination using phosphor imaging plates was employed to achieve highly sensitive determination of radioactivity. Absorption ratios of radioactivity after three oral doses were high (35-82%); parent 14C-BPA in the circulating blood was quite low, however, suggesting considerable first-pass effect. After an oral dose of 100 microg kg(-1) 14C-BPA, the radioactivity was distributed and eliminated rapidly, but remained in the intestinal contents, liver, and kidney for 72 h. The major metabolite in the plasma and urine was BPA glucuronide, whereas most of the BPA was excreted with the feces as free BPA. A second peak in the time-course of plasma radioactivity suggested enterohepatic recirculation of BPA glucuronide. There was limited distribution of 14C-BPA to the fetus and neonate after oral administration to the dam. Significant radioactivity was not detected in fetuses on gestation days 12 and 15. On day 18, however, radioactivity was detected in the fetal intestine and urinary bladder 24 h after oral dosing of 14C-BPA to the pregnant rats. Part of radioactivity was transferred to neonatal rats from the milk of the treated lactating dam and remained in the intestine of the neonates after 24-h nursing by an untreated dam.

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C o m b i n e d a c t i o n o f v e n o m a n d r i c i n. R e l a t i o n o f a g g l u t i n a t i o n and

The principal points brought out in the present article are the following. 1. Wild rats captured in this country carry in their kidneys a spirochete which possesses the morphological and pathogenic properties characteristic of Spirochata icterohamorrhagia discovered by Inada in the Japanese form of infectious jaundice. 2. Cultures of the American, Belgian, and Japanese strains of the spirochete were obtained by a special technique described, the first two strains having been cultivated artificially for the first time. 3. Animals actively immunized against the Japanese strain resist inoculation, not only of the same strain, but also of the Belgian and American strains. The Belgian strain produces immunity equally effective against all three strains. Experiments to. ascertain whether the immunity afforded by the American strain also protects against the Japanese and Belgian strains are in progress. 4. These findings warrant the conclusion that the spirochetes designated here as the Japanese, Belgian, and American strains are probably identical. 5. On account of its distinctive features, a new genus, Leptospira, has been suggested as the designation of this organism.

The absorption, distribution, metabolism, and excretion of 3-(N-formylhydroxylamino) propylphosphonic acid monosodium salt (fosmidomycin), a new antibiotic, were investigated in rats and dogs after i.v. and oral dosing. After i.v. administration of 10 mg/kg of body weight, [14C]-fosmidomycin was excreted mainly in the urine (about 90% of dose within 72 h); and only a little was excreted in the expired air (14CO2) and bile of rats (less than 1% of dose), which suggested the absence of enterohepatic circulation. After oral administration of 10 mg/kg of body weight to rats, 34% and 61% of dose were excreted in the urine and faeces, respectively, suggesting about 30% gastro-intestinal absorption. No metabolites were found by autoradiography of the urine after thin layer chromatography. Radioactivity levels in the serum essentially agreed with the unchanged fosmidomycin levels determined by reverse isotope dilution method. [14C]-fosmidomycin was rapidly distributed in the tissues of rats, and was maintained in high concentration in the liver, kidneys, and bone. The serum level data after i.v. administration closely fitted a 3-compartment open model with first order kinetics after nonlinear least squares regression by NONLIN. The half-lives of the serum level curves for the early, midway, and terminal phases were: 0.13, 0.51, and 17.3 h, respectively in rats; and 0.44, 0.75, and 2.0 h, respectively in dogs.