摘要:

The effect of dietary tansy ragwort (Senecio jacobaea,), a plant containing pyrrolizidine alkaloid (PA), on mineral metabolism in rats was studied. In experiment 1, rats were fed a dietary level of 5% tansy ragwort. At intervals of 1, 2, 4, 6, and 8 wks animals were killed and tissue mineral levels determined. As compared to comparable controls, rats fed tansy ragwort showed by 6 wk elevated liver and spleen copper levels, and a trend to increased iron levels. Experiment 2 was a 3 × 4 factorial experiment with added dietary copper levels of 0, 50, and 250 ppm, and tansy ragwort levels of 1, 1, 2.5, and 5%. Liver copper levels increased markedly with increasing levels of tansy ragwort and supplemental copper; at 0, 50, and 250 ppm added copper, liver copper levels were 4, 18, and 21 times greater in rats fed 5% tansy ragwort as compared to those with no tansy ragwort. Increases in spleen copper were noted with 5% tansy ragwort and supplemental copper. Higher liver copper levels were observed when a casein‐based diet rather than a soybean‐meal diet was used, suggesting an effect of phytate in soybean meal in reducing copper absorption. In the last experiment,59Fe was administered to rats fed diets with or without tansy ragwort. After 5 wk on tansy ragwort, rats showed very low levels of59Fe in erythrocytes, tibia, and liver, and elevated levels in the spleen, suggesting either an impairment of hematopoesis or accelerated erythrocyte destruction as a result of PA consumption. These results indicate that PAs cause increased liver copper content and cause disturbances in iron metabolism.

ISSN:0098-4108    

DOI:10.1080/15287398209530293

出版商:Taylor & Francis Group    

年代:1982

数据来源: Taylor

摘要:

Sprague‐Dawley rats of both sexes were given, in place of their drinking water, full‐strength or 50 or 25% dilutions of either brewed or instant decaffeinated coffees for about 6 mo from weaning. These levels are equivalent to the human consumption of about 50, 25, or 12 cups of coffee per day. Controls were given either distilled water, or full‐strength or a 25% solution of regular brewed coffee. The rats were bred twice after 91 d to assess reproduction and teratogenicity. The parent animals given decaffeinated coffees and 100% regular coffee drank less than the rats given water, while the rats given 25% regular coffee drank more. No effects on body weight gain or feed efficiency were seen, except that the group given 100% regular coffee gained significantly less weight than the water controls. None of the coffee treatments had a significant effect on reproductive characteristics such as conception rate, number born, or number weaned. During the second pregnancy, no significant effects from the coffee treatments were seen on early embryotoxicity measured in dams sacrificed on d 13 of pregnancy or fetal toxicity in dams sacrificed on d 21. No significant fetal abnormalities due to any of the coffee treatments were observed in either soft‐tissue or skeletal examinations, although there was a significant increase in unossified sternebrae in the fetuses from dams given the full‐strength regular coffee.

ISSN:0098-4108    

DOI:10.1080/15287398209530294

出版商:Taylor & Francis Group    

年代:1982

数据来源: Taylor

摘要:

Certain limitations on the flexibility of small‐animal inhalation exposure systems are overcome by the machine control and monitoring of the concentration of the gas or vapor of interest. Computer assistance of chamber operation allows the user to simulate time‐varying concentration profiles accurately and repeatedly. We exposed rats to seven different profiles in which the maximum concentration of carbon tetrachloride (CCl4) was 1500 ppm and the product of concentration times time (C X TV was 4500 ppm.h. The purpose was to determine the effects of systematically varying the shape of the concentration profile on the expression of hepatotoxicity of a chemical about which much was already known. All of the exposures were conducted within a span of 6 h. Examination of the severity of vacuolation and pattern of necrosis could be used to distinguish some of the exposure profiles from others. For example, vacuolation was less severe when ‘two equal pulses were presented with an interval of 60 min, rather than 180–240 min. The indexes of necrosis varied in a more complex way, and the differences among the profiles that accounted for the differences in the patterns of the histopathological changes were not immediately apparent. We concluded that the characteristic of a time‐related variation in concentration is one of the determinants of the inhalation hepatotoxicity of CCl4and that the simple, time‐weighted, average concentration may not always fairly represent the best model for the study of problems in inhalation toxicology.

ISSN:0098-4108    

DOI:10.1080/15287398209530295

出版商:Taylor & Francis Group    

年代:1982

数据来源: Taylor

摘要:

Groups of 50 male and female Fischer 344 rats and male and female B6C3Flmice were fed diets containing 6000 or 12,000 (rats) or 3000 or 6000 (mice) mg di(2‐ethylhexyl) phthalate (DEHP)/kg feed for 103 consecutive wk. Concurrent controls (50 of each sex and species) were fed diet without the addition of DEHP. Treatment with DEHP did not affect survival rates for rats or mice, nor did it alter the amount of food consumed. Mean body weight gains of treated male rats (6000 and 12,000 mg/kg), female rats (12,000 mg/kg), and female mice (3000 and 6000 mg/kg) were less than those of the corresponding controls. Seminiferous tubular degeneration and hypertrophy of cells in the anterior pituitary were observed in male rats at 12,000 mg/kg, and chronic inflammation of the kidney and seminiferous tubular degeneration were observed in male mice at 6000 mg/kg. Neither clinical signs of toxicity nor nonneoplastic lesions were detected in the other treated groups at incidences greater than in the corresponding controls.

ISSN:0098-4108    

DOI:10.1080/15287398209530296

出版商:Taylor & Francis Group    

年代:1982

数据来源: Taylor

摘要:

Pregnant mice were given one of three treatment regimens during mid (11 to 13 d) or late (16 to 18 d) gestation: benzo[a]pyrene (BaP) (150 μg/g body weight), 150 R X‐irradiation, or X‐irradiation + BaP. A group of virgin mice were injected with BaP after birth (at 1 wk or 16 wk) with doses similar to or higher than those to which progeny of pregnant mice were exposed in utero. The offspring exposed during fetal life showed a marked suppression in anti‐SRBC plaque‐forming cells (PFC) 1 wk after birth (pups), followed by an apparent recovery at 4 wk. Return to the immuno‐suppressed state seen in pups was most noticeable in adults encountering BaP alone during gestation. In this group, increased tumor incidence was associated with a sustained reduction in PFC response. In contrast, after fetal exposure to X‐rays or injection with BaP postnatally, immune competence was not appreciably different from normal in late life and tumor incidence was only slightly higher than controls with X‐rays or a high dose (150 μg/g body weight) of BaP. When X‐rays were given in conjunction with BaP, it appeared that immune suppression was abated and tumor incidence reduced. The effect of BaP on PFC and tumor incidence varied according to the time in gestation when the carcinogen was given. After mid‐gestation insult, immune suppression was most pronounced in 19S PFC, while after late gestation, suppression was more severe in 7S antibody formation. The liver was the primary target for tumor growths in males. In females, a high incidence of ovarian tumors was seen, but only after mid‐gestation exposure. The frequency of lung tumors increased following late gestation insult in both sexes. These data show that (1) susceptibility to injury of different components of the developing humoral immune system and the disposition of the sexes for tumor induction are functions of the gestationai time of exposure to BaP, and (2) animals exposed prenatally to the carcinogen are more sensitive to immune suppression and increased tumor incidence than those exposed postnatally. The results support the contention that immune deficiency (suppression) influences the increase in neoplastic expression.

ISSN:0098-4108    

DOI:10.1080/15287398209530297

出版商:Taylor & Francis Group    

年代:1982

数据来源: Taylor

摘要:

The tissue distribution and excretion of [14C]’ benzyl chloride was investigated in adult male and female Fischer 344/N rats after administration of a single oral dose of [14C] benzyl chloride in corn oil at 25 mg/kg, data was correlated with histopathologic and toxicity findings elicited from a 27–37‐wk repeated‐dose oral toxicity study of benzyl chloride. Radioactivity was detected in all tissues selected for examination. Elimination of the isotope occurred predominantly in the urine. Female rats excreted the isotope at a faster rate than the males and also maintained slightly lower tissue concentrations (with the exception of the blood and kidneys). Isotope recovery was achieved at 90% in the urine and feces of female rats at 24 h, compared with an 80% recovery rate in males. Concentrations of radioactivity were high in the gastrointestinal tract, reflecting the route of administration; however, the squamous stomach and the small intestine consistently retained higher concentrations of isotope than the glandular stomach. Results of acute toxicity and organ histopathology studies in animals dosed with benzyl chloride for 27–37 wk are compatible with the organ distribution and excretion of [14C] benzyl chloride. Histopathologic findings included severe acute and chronic gastritis, hyperkeratosis and hyperplasia of the squamous stomach, and progressive lesions of the heart ranging from proliferation of interstitial cells to acute necrosis of myocardial fibers. Both of these studies suggest that the squamous stomach is a target organ for benzyl chloride or one of its metabolites.

ISSN:0098-4108    

DOI:10.1080/15287398209530298

出版商:Taylor & Francis Group    

年代:1982

数据来源: Taylor

摘要:

The disposition kinetics of ethylene oxide, ethylene glycol, and 2‐chloroethanol were studied following their intravenous administration to beagle dogs. Plasma concentration of ethylene oxide was found to decline exponentially with a mean rate constant of 0.024 ± 0.008 min‐1(mean ± SD) and total body clearance of 20.0 ± 5.2 ml/kg.min. Ethylene oxide was found to be metabolized mainly to ethylene glycol, which had a mean plasma half‐life of 221.0 ± 77.7 min and a total body clearance of 2.13 ± 0.58 ml/kg.min. Between 7 and 24% of intravenously administered ethylene oxide was eliminated in the urine as ethylene glycol within 24 h. The elimination half‐life and clearance values for 2‐chlorethanol were 40.8 ± 5.7 min and 10.3 ±1.7 ml/kg.min, respectively. The pharmacokinetic data gathered in the present investigation suggest that ethylene glycol rather than 2‐chloroethanol is the major metabolite of ethylene oxide in the dog.

ISSN:0098-4108    

DOI:10.1080/15287398209530299

出版商:Taylor & Francis Group    

年代:1982

数据来源: Taylor

ISSN:0098-4108    

DOI:10.1080/15287398209530272

出版商:Taylor & Francis Group    

年代:1982

数据来源: Taylor