摘要:

A large number of residents on the southwest coast of Taiwan suffer from an endemic peripheral vascular disease called blackfoot disease. Although the etiology has been investigated since 1958, the cause of blackfoot disease remains unknown. Certain substances contained in artesian well water have been implicated as causal factors, including arsenic as the predominant element. Data in this study demonstrated that in the well water collected from blackfoot disease regions of Taiwan there was a marked increase in total arsenic concentrations, with the predominant species being inorganic arsenical compounds. The concentrations of organic methyl arsenicals were present in minimal amounts. The excretion of total arsenic, inorganic arsenic, monomethylarsonic acid, and trimethylarsenic acid in the urine of patients afflicted with blackfoot disease was significantly higher than for control subjects. Further, in patients with blackfoot disease the concentrations of total arsenic and inorganic arsenic were markedly elevated in the hair and fingernails. Data suggest that blackfoot disease is associated with individuals ingesting well water contaminated with arsenic primarily in the inorganic form and that hair, fingernails, or urine specimens serve as equally effective biomarkers of exposure. The fact that arsenic intoxication as manifested by blackfoot disease is still prevalent despite the stoppage of well-water consumption for two decades illustrates the persistent nature of arsenic action.

ISSN:1528-7394    

DOI:10.1080/009841098159376

出版商:Informa UK Ltd    

年代:1998

数据来源: Taylor

摘要:

The organic arsenicals monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA) are the primary metabolites of inorganic arsenic, a known human carcinogen. The objective of this study was to examine if dose would affect the excretion and terminal tissue disposition of MMA and DMA in the mouse. 14C-MMA (4.84 and 484 mumol/ kg) and-DMA ( 8.04 and 804 mumol/kg) were administered to female micevia the tail vein. The mice were placed in metabolism cages for collection of urine (1, 2, 4, 8, 12, and 24 h) and feces ( 24 h) . The animals were then sacrificed at 24 h and tissues were removed and analyzed for radioactivity. The urine was also analyzed for parent compound and metabolites. Urinary excretion of MMA- and DMA-derived radioactivity predominated over fecal excretion. Dose did not affect the overall urinary excretion of both compounds. However, fecal excretion was significantly lower in the low-dose MMA-treated animals as opposed to in the high-dose group, whereas in the high-dose DMA-treated group excretion was lower than in the low-dose DMA group. The retention of radioactivity was low ( <2% of dose) and the distribution pattern similar for both compounds, with carcass > liver >kidney > lung. The concentration of radioactivity (% dose/ g tissue) was greater in kidney than in liver, lung, and blood for both compounds. The distribution and concentration of MMA-derived radioactivity was significantly greater in the liver and lung of the high-dose group. The MMA-treated animals excreted predominantly MMA in urine and lower amounts of DMA (<10% of the dose). The percentage excreted as DMA was significantly higher in the low-dose MM A group. In the urine of DMA-treated anim als, an unstable metabolite and the parent compound were detected. Overall, it appears the dose of organic arsenical administered has a minimal effect on its excretion and terminal tissue disposition in the mouse. The rapid elimination and low retention of MMA and DMA explain in part their low acute toxicity.

ISSN:1528-7394    

DOI:10.1080/009841098159385

出版商:Informa UK Ltd    

年代:1998

数据来源: Taylor

摘要:

The investigations reported here were conducted to gain a better understanding of the comparative toxicity of selenium. Sodium selenate and selenomethionine were administered to young adult ICR female mice. Peripheral leukocyte counts and ratios of agranulocyte (Ag) to granulocyte (G) leukocytes were determined from blood that was collected at regularly scheduled intervals. Data indicated that both forms of selenium induced a transient yet marked decrease in the number of circulating leukocytes (leukopenia) following serial injections ( 2 mg Se/ kg/injection) . The leukopenia was more extensive and of a greater duration for selenomethionine-treated mice. For selenate-injected anim als the Ag/ G ratio increased sharply while the ratio shift for selenomethionine-injected mice was significantly less. Data are interpreted in regard to the different possible modes of action of selenate and selenomethionine on peripheral leukocytes causing leukopenia and the variable Ag/G ratio values.

ISSN:1528-7394    

DOI:10.1080/009841098159394

出版商:Informa UK Ltd    

年代:1998

数据来源: Taylor

摘要:

A distillate of light alkylate naphtha ( CAS number 64741-66-8; LAN distillate) was administered via inhalation, 6 h/ d, 7 d/wk to 4 groups of Sprague-Dawley rats (10/sex/ dose) at target concentrations of 0 (filtered air control), 5, 12.5, or 25g/m 3 with the highest dose exceeding 60% of the lower explosive limit of LAND. Exposure began 2 wk prior to mating and continued throughout gestation until postnatal d 4 for females or for 8 consecutive weeks for males. No apparent clinical signs indicative of systemic toxicity were observed in the F and F animals of either sex. Inhalation exposure to 0 1 LAND up to and including the 25 g/ m 3 dose level had no effect on parental food consumption, body weights, absolute and relative organ weights, and reproductive indices. All groups had comparable delivery data and a fertility index 80% . Pups in all groups showed comparable birth weights, weight gain, a viability index ( postnatal d 4) for all groups of 97% , and no histopathological changes. In the dams, there were no significant differences in the mean numbers of corpora lutea, implantation sites, and resorptions recorded at necropsy. In the males, the only remarkable findings at necropsy were a small right epididymis and testis seen in one mid-dose male and an abscess on the right epididymis of a high-dose male. In both cases, the dams that had been bred to these males produced normal litters. There were no test material-related microscopic changes observed in the testes and epididymis of the F male rats or ovaries of the F0 0 female rats exposed to LAND. Under the conditions of this experiment, the noobserved-adverse-effect level (NOAEL) for LAND via inhalation in rats is established at greater than 24.7 g/ m 3 (analytical concentration) .

ISSN:1528-7394    

DOI:10.1080/009841098159402

出版商:Informa UK Ltd    

年代:1998

数据来源: Taylor

摘要:

The fungal toxin fumonisin B (FB ) is a contaminant of corn-based foods and feeds pro1 1 duced by members of the genus Fusarium. Fumonisin B toxicity was examined using gav1 age administration of purified toxin to female Sprague-Dawley rats. For 11 consecutive days each rat received a single dose of FB at the following concentrations: control 1 (saline), 1, 5, 15, 35, or 75 mg FB /kg body weight/d. Significantly depressed body 1 weight and food consumption occurred at 35 and 75 mg FB /kg/d. By the end of the dos1 ing period there were no significant changes in food consumption. Kidneys and bone marrow were most sensitive to FB exposure. Changes in renal morphology were observed 1 from 5 to 75 mg FB /kg/d, accompanied by transient changes in urine osmolality and 1 urine enzyme levels. Increased cellular vacuolation was the primary change associated with bone-marrow toxicity, starting at doses of 5 mg FB /kg/d. Hepatotoxicity was indi1 cated by reduced liver weight, elevated serum alanine amonitransferase (ALT), and mild histopathological changes occurring at doses of 15 mg FB /kg/d and higher. Increased 1 cytoplasmic vacuolation of adrenal cortex cells occurred in rats treated with 15 mg FB /kg/d and higher, indicating that the adrenals are also potential targets of FB . Elevated 1 1 serum cholesterol, which is a consistent response to FB was observed at 5 mg FB /kg/d 1, 1 and higher. Based on responses in this study, gavage is an appropriate substitute for longer feeding studies. Compared to previous work with male rats, gender-related differences in FB responses lacked consistency but indicated that males may be marginally 1 more sensitive than female Sprague-Dawley rats.

ISSN:1528-7394    

DOI:10.1080/009841098159411

出版商:Informa UK Ltd    

年代:1998

数据来源: Taylor

摘要:

Metabolism of 2-nitrofluoranthene (2-NFA), one of the most abundant and genotoxic environmental pollutants in air, and of a mixture of 2-nitrofluoranthene and 3-nitrofluoranthene (3-NFA) was studied using (1) the fungus Cunninghamella elegans ATCC 36112 and (2) rat liver microsomes. The fungal metabolites were separated by reversedphase high-performance liquid chromatography ( HPLC) and identified by 1H nuclear magnetic resonance ( NMR) spectrometry, ultraviolet (UV)-visible spectroscopy, and online atmospheric-pressure chemical ionization/ mass spectrometry ( APCI/MS) . The fungus metabolized 82% of 2-nitro-\[3H]-fluoranthene to 2-nitrofluoranthene 8-sulfate and 2-nitrofluoranthene 9-sulfate. Metabolism of a mixture of 2- and 3-nitrofluoranthene by C. elegans similarly produced 2-nitrofluoranthene 8- and 9-sulfate and 3-nitrofluoranthene 8- and 9-sulfate as major metabolites. In addition, a glucoside conjugate of 3- hydroxy-2-nitrofluoranthene was tentatively identified by APCI/MS analysis. When rat liver microsomes were incubated with a mixture of 2- and 3-nitrofluoranthene for 1 h, in addition to the trans -7,8- and 9,10-dihydrodiols reported previously for 2-nitrofluoranthene, several novel metabolites were produced including 2-nitrofluoranthene trans -4,5- dihydrodiol and 2-nitrofluoranthene trans -8,9-dihydrodiol, the trans -4,5-dihydrodiol of 3-nitrofluoranthene, and phenolic products of both 2- and 3-nitrofluoranthene. The fungal metabolism of the 2- and 3-nitrofluoranthene mixture was similar to the metabolism of individual nitrofluoranthenes; however, the mammalian metabolism of the nitrofluoranthene mixture showed differences in regioselectivity at positions C4, C5, C8, and C9.

ISSN:1528-7394    

DOI:10.1080/009841098159420

出版商:Informa UK Ltd    

年代:1998

数据来源: Taylor