摘要:

The interrelationships among carcinogenicity, mutagenicity, acute toxicity (LD50), and a number of molecular descriptors were studied by computerized data analysis methods on the data base generated by the International Program for the Evaluation of Short‐Term Tests for Carcinogens (IPESTTC). With the use of statistical regression methods, three main associations were evidenced: (1) the well‐known correlation between carcinogenicity and mutagenicity; (2) a correlation between mutagenicity and toxicity (LD50 ip in mice); and (3) a correlation between toxicity and a recently introduced estimator of the free energy of binding of the molecules to biological receptors.

ISSN:0098-4108    

DOI:10.1080/15287398909531275

出版商:Taylor & Francis Group    

年代:1989

数据来源: Taylor

摘要:

The tumor incidence rate is modeled for various tumors in a database of control animals [Fischer 344 rats and (C57BL/6 × C3H)F1mice] originally developed by the national Toxicology Program and recently augmented to include additional sacrifice data by Portier et al. (1986). These rates are assumed to follow a clonal two‐stage model of carcinogenesis where cells in the various tissues are allowed to be in one of three states arbitrarily defined as a “normal” state, an “initiated” state, and a “tumor present” state. The parameters of this clonal two‐stage model have a direct interpretation with regard to the mechanism of action and in some cases may suggest a common mechanism for various tumors in the different sex/species groups. Also, the risk of dying (from all causes) in tumor‐bearing animals is compared to the risk of dying in non‐tumor‐bearing animals via estimates of relative risk. In general, it was found that the risk of dying was elevated for most tumors. The purpose of this analysis is to provide estimates of baseline tumor rates and relative risks, which are useful in the design and analysis of future carcinogenicity experiments.

ISSN:0098-4108    

DOI:10.1080/15287398909531276

出版商:Taylor & Francis Group    

年代:1989

数据来源: Taylor

摘要:

The results are given from monitoring a commercial closed‐formula cereal‐based rodent diet (Purina 5010), two open‐formula cereal‐based diets (NIH‐31 and NIH‐07), and one purified diet (AIN‐76) for selected nutrients and contaminants. The observed concentrations of nutrients (protein, fat, vitamin A, and thiamine) approximated the manufacturer specifications for closed‐formula cereal diet, while the average concentrations of nutrients found in the open‐formula cereal diets were well above the nominal concentrations. Nominal concentrations for these open‐formula diets tended to be close to the minimum values that were observed. Except for protein levels, greater variation in nutrient concentrations was found in the purified diet than in the cereal diets. Contaminants were generally much lower in the purified diet than in the cereal diets, but the variation of contaminants was about equal in the two types of diets. Open‐ and closed‐formula cereal diets appear to be very similar to each other in the degree of variation of nutrients and contaminants. Cadmium, lead, and selenium are the constituents of greatest concern in assuring the quality of the rodent diets that were evaluated.

ISSN:0098-4108    

DOI:10.1080/15287398909531277

出版商:Taylor & Francis Group    

年代:1989

数据来源: Taylor

摘要:

The role of glutathione (GSH) and ornithine decarboxylase‐antizyme (ODC‐AZ) in the regulation of the chloroform‐mediated stimulation of rat hepatic ornithine decarboxy‐lase (ODC) was investigated. We have previously implicated roles for each while examining the chloroform effect on crude cytosolic enzyme preparations. In this study we examined the effect of pretreatment with diethyl maleate (DEM), a GSH‐depleting agent, on the chloroform stimulation of the two forms of the rat hepatic ODC enzyme and the sensitivity of these two forms to inhibition by the ODC‐AZ. While the pretreatment with DEM provided a greater amount of the two forms of the ODC enzyme, it also resulted in a differential stimulation of each form when compared to chloroform alone. Additionally, Peak II was 20–25% more sensitive to the same amount of ODC‐AZ then Peak I ODC activity.

ISSN:0098-4108    

DOI:10.1080/15287398909531278

出版商:Taylor & Francis Group    

年代:1989

数据来源: Taylor

摘要:

To determine the metabolic disposition of [14C]‐2‐mercaptobenzothiazole (MBT) and [14C]‐2‐mercaptobenzothiazole disulfide (MBTS), male and female rats were dosed topically. Topical doses were 36.1 μg/animal for [14C]MBT and 33.6 μg/animal for [14C]MBTS. Although more MBT passed through the skin than MBTS and although, relative to rats, guinea pigs absorbed a greater percentage of the dose (33.4% compared to 16.1–17.5% of the MBT and 12.2% compared to 5.94–7.87% for MBTS), the disposition of radioactivity derived from the two compounds was similar. Washing of the skin removed more of the radioactivity from guinea pigs than from rats.

ISSN:0098-4108    

DOI:10.1080/15287398909531279

出版商:Taylor & Francis Group    

年代:1989

数据来源: Taylor

摘要:

The xylidide 2,6‐dimethylaniline (2,6‐DMA) has produced carcinomas and papillary adenomas in the nasal cavity of rats at high dietary doses (3000 ppm) in a 2‐yr bioassay. The objective of the present study was to measure the covalent binding of 2,6‐DMA to DNA of rat ethmoid turbinate tissues and, for comparison, to DNA of rat liver. The potent hepatocarcinogen 2‐acetylaminofluorene (AAF) was studied as a positive control for adduct formation and covalent binding index (CBI) calculation. Both 2,6‐DMA and AAF were administered as14C‐(ring)‐labeled agents to naive rats and to rats pre‐treated for 9 d with unlabeled 2,6‐DMA or AAF.

ISSN:0098-4108    

DOI:10.1080/15287398909531280

出版商:Taylor & Francis Group    

年代:1989

数据来源: Taylor

摘要:

Previous reports have demonstrated that cadmium‐ (Cd‐) induced testicular necrosis is an age‐dependent process. However, little information exists on age‐related intestitial cell (IC) damage in the rat after acute exposure to Cd. In this study in vitro and in vivo measures of testicular damage were utilized to compare the sensitivity of these measures and to further investigate age‐related Cd‐induced testicular damage. Testes, epididymides, and seminal vesicle weights, serum testosterone (sT), hCG‐stimulated sT, and basal and stimulated IC testosterone (T) production were compared in rats 21 d following an injection of 2 mg Cd/kg at 9, 37, 67, and 97 d of age. The only Cd‐related change noted for immature rats was an 84% reduction in sT. In rats injected when 37 d old, hCG‐stimulated sT and epididymides and seminal vesicle weights, although depressed, were not significantly altered. However, all other measurements were significantly depressed. All measures of testicular damage were significantly depressed in rats injected at 67 and 97 d of age.

ISSN:0098-4108    

DOI:10.1080/15287398909531281

出版商:Taylor & Francis Group    

年代:1989

数据来源: Taylor

摘要:

The effect of procarbazine, an antineoplastic drug, on the reproductive system of male Syrian hamsters was studied. Exposure to procarbazine (5 daily doses ranging from 20 to 500 mg/kg body weight) resulted in 5‐ to 7.5‐fold increase in sperm abnormalities, diminished sperm counts, and smaller testes within 4 wk. Transmission electron micrographs showed severe damage to the acrosomal plasma membrane and nucleus of the sperm head in treated hamsters. These findings corroborate the detrimental effect of procarbazine on the germinal tissue and strengthen the basis for using the sperm morphology assay for the detection of mutagens and possibly other germ‐cell toxicants in an in vivo mammalian system.

ISSN:0098-4108    

DOI:10.1080/15287398909531282

出版商:Taylor & Francis Group    

年代:1989

数据来源: Taylor

摘要:

The toxicities of 1‐nitropyrene (NP) and benzo[a]pyrene (BaP), inhaled alone and in combination with particles and an irritant gas, were examined to evaluate synergisms among the organic compounds, particles, and gas. Croups of F344 rats were exposed 2 h/d, 5 d/wk for 4 wk to atmospheres of pure NP aerosol (7.5 mg/m3), and to these same compounds adsorbed to Ga2O3particles (27 mg/m3) both with and without coexposure to 5 ppm SO2. Rats were also exposed to Ga2O3and SO2alone. Measurements were made of lung burdens of Ga2O3particles and retention of radiolabeled tracer particles after the cessation of exposure to evaluate effects on particle clearance. Bronchoalveolar lavage fluid was analyzed to assess inflammation and cytotoxicity. Histopathology was examined to assess the nature and extent of lung injury. Particle clearance was significantly impaired (p< .05) in all groups whose exposure atmosphere included Ga2O3, but was not significantly changed in the other exposure groups.

ISSN:0098-4108    

DOI:10.1080/15287398909531283

出版商:Taylor & Francis Group    

年代:1989

数据来源: Taylor

摘要:

We determined the overall external counting efficiency of radiolabeled particles deposited in the sheep lung. This efficiency permits the noninvasive calculation of the number of particles and microcuries (μCi) from gamma‐scintillation lung images of the live sheep. Additionally, we have calculated the attenuation of gamma radiation (120 keV) by the posterior chest wall and the gamma‐scintillation camera collection efficiency of radiation emitted from the lung.

ISSN:0098-4108    

DOI:10.1080/15287398909531284

出版商:Taylor & Francis Group    

年代:1989

数据来源: Taylor