摘要:

Purified quercetin, as well as diets containing quercetin at 0.1% and 0.2%, are mutagens to Salmonella typhimurium TA100. This mutagenicity is enhanced with the S9 metabolic activation system. The urine of Fischer rats fed the 0.2% quercetin diet also is mutagenic with the 59 activation system, but the feces of these animals exhibited enhanced mutagenicity only without activation. This may indicate different quercetin metabolites in urine and feces. Rats fed these diets for 64 wk showed no consistent tissue lesions, carcinogenicity, or reproductive changes. Male rats fed 0.2% quercetin showed lowered blood serum glutamic oxaloacetic transaminase and urea nitrogen levels, but these values do not reflect pathological changes.

ISSN:0098-4108    

DOI:10.1080/15287398409530565

出版商:Taylor & Francis Group    

年代:1984

数据来源: Taylor

摘要:

Male C3H[He] mice (40 per group) were treated with 25‐μl applications of undiluted ethyl acrylate, 1% acrylic acid, or 1% butyl acrylate on the dorsal skin 3 times weekly for their lifetime. A negative control group received acetone (diluent) only, and a positive control group received 0.1% 3‐methylcholanthrene (MC). No epidermal tumors were observed in the animals that received any of the three test substances. In the positive control group, 39 animals had skin tumors, including 33 with confirmed squamous‐cell carcinomas. Nonneoplastic skin changes such as dermatitis, dermal fibrosis, epidermal necrosis, and hyperkeratosis were observed in several mice that received ethyl acrylate. No statistically significant effects on survival were seen. Therefore, there was no evidence for local carcinogenic activity of acrylic acid, ethyl acrylate, or butyl acrylate under the conditions of these studies.

ISSN:0098-4108    

DOI:10.1080/15287398409530566

出版商:Taylor & Francis Group    

年代:1984

数据来源: Taylor

摘要:

Differences in the profiles of developmental toxicity for four structurally diverse chemical compounds have been defined following prenatal exposure in the rat. Diethylstil‐bestrol (DES), 3,4,3’,4'‐tetrachlorobiphenyl (4CB), zeranol, and cadmium were administered by gavage to Sprague‐Dawley rats daily from d 6 through d 18 of gestation. Dams were sacrificed at four prenatal endpoints and the numbers of live and dead fetuses and resorbed embryos were counted. Additional dams were allowed to bring their litters to term, and their offspring were monitored until they reached adulthood. DES induced prenatal death primarily in early embryonic life, and also during parturition. 4CB increased mortality from late in gestation up to 24 h after birth, and altered the sex ratio of survivors by selectively acting against males in utero. Exposure to zeranol resulted in embryolethality only. Cadmium was not lethal to the conceptus at any dose below the dose that caused maternal mortality. Only 4CB had an obvious teratogenic effect, causing intestinal hemorrhage. All compounds produced transient perinatal decreases in the weight of the offspring.

ISSN:0098-4108    

DOI:10.1080/15287398409530567

出版商:Taylor & Francis Group    

年代:1984

数据来源: Taylor

摘要:

Primary cultures of myocardial cells were used to evaluate the cardiotoxic potential of various tricyclic antidepressants (TCAs). Lactate dehydrogenase (LDH) leakage, cellular viability, and beating rates were measured to compare the cardiotoxicity of amitrip‐tyline, desipramine, imipramine, and nortriptyline. Tricyclic antidepressants were added to the cultures to give final concentrations of 1 × 10‐5, 7 × 10−4, and 1 × 10−3M. Treatments lasted 1 and 4 h. All TCAs tested caused significant release of LDH and decreased cellular viability when added at 1 × 10−3M for 1 and 4 h. Amitriptyline was the only compound that caused significant LDH release 4 h after exposure to lower doses. Decreased viability was observed 4 h after exposure to all TCAs at a concentration of 1 × 10−4and 1 × 10−3M. Arrhythmias were observed 1 h after exposure to 1 × 10−5and 7 × 10−4M amitriptyline. All doses of amitriptyline inhibited beating 4 h after exposure. Imipramine, desipramine, and nortriptyline at a concentration of 1 × 10−5M decreased the beating rates of cultured myocytes 1 and 4 h after exposure. Arrhythmias and/or total inhibition of beating were observed when the cultures were exposed to higher concentrations of these compounds. Based on these data, the rank order of cardiotoxicity was amitriptyline > imipramine = desipramine > nortriptyline.

ISSN:0098-4108    

DOI:10.1080/15287398409530568

出版商:Taylor & Francis Group    

年代:1984

数据来源: Taylor

摘要:

Adult White Leghorn hens were divided into 75 groups of 10 birds each. Five groups received the prototype mixed‐function oxidase (MFO) enzyme inducer phenobarbital (PB) at a dosage of 50 mg/kg body weight for 3 consecutive days by intraperitoneal (i.p.) injection, 5 groups received the MFO enzyme inducer β‐naphthoflavone (βNF) at 20 mg/kg body weight for 2 consecutive days by i.p. injection, while the remaining 5 groups did not receive an inducer. At 24 h after the last injection, the birds received a single oral dose of tri‐o‐tolyl phosphate (TOTP) (an organophosphate that produces delayed neurotoxicity after metabolic activation by the MFO system) in doses of 62.5, 125, 250, or 500 mg/kg body weight. Corn oil served as the vehicle control. At 48 h after the administration of TOTP, half the birds in each of the 15 groups were killed for determination of whole‐brain neurotoxic esterase (NTE) activity. The remaining birds were observed for the subsequent 19 d for onset of clinical signs characteristic of delayed neurotoxicity. Birds receiving βNF prior to TOTP were protected by the inducer when compared to birds receiving PB + TOTP or TOTP alone. This was indicated by less severe clinical signs as well as less inhibition of whole‐brain NTE activity. The protective effect offered by βNF may be due to induction of enzymes responsible for the inactiva‐tion of the neurotoxic metabolite.

ISSN:0098-4108    

DOI:10.1080/15287398409530569

出版商:Taylor & Francis Group    

年代:1984

数据来源: Taylor

摘要:

Growing sheep were grazed for 152 d on grass‐legume forage growing on soll that had been amended with municipal sewage sludge from Syracuse, N. Y., at 224 metric tons per hectare. Cadmium was higher, but not significantly (p > 0.05), in tissues of sheep fed the sludge‐grown forage as compared to controls. No significant differences between the sludge or control treatments were found in weight of the complete or cauda epi‐didymis or in percent progressive motility of cauda epididymal sperm. The sludge‐treatment group had significantly larger testes (p < 0.025) when expressed as a percentage of body weight, and higher blood uric acid values (p < 0.05). There were no observable changes in tissue ultrastructure of liver, kidney, muscle, or testes as examined by electron microscopy in either of the treatment groups. There were no significant differences for rate of animal weight gain, carcass weight, dressing percentage, or quality or yield grade of the carcases between the treatment groups.

ISSN:0098-4108    

DOI:10.1080/15287398409530570

出版商:Taylor & Francis Group    

年代:1984

数据来源: Taylor

摘要:

The biological activity of the volatile part of the particulate phase of cigarette‐smoke condensate, the semivolatile fraction, has been examined, since the constituents of this material are accessible to selective filtration. Such a process offers a possibility to reduce the biological activity of total cigarette smoke without appreciably affecting the taste. Cigarette‐smoke condensate, obtained from domestic American blend type cigarettes, was therefore separated into a nonvolatile and a semivolatile fraction, and the latter was fractionated by liquid‐liquid extractions into four subfractions; acids, phenols, bases, and neutrals. The biological activity of these fractions was investigated using six in vitro short‐term tests, of which two, the Ames test and the induction of sister chromatid exchanges, provided information on their genotoxicity, and the other four provided information on their cytotoxicity by measuring inhibition of cell growth, Inhibition of oxidative metabolism, membrane damage, and ciliotoxicity.

ISSN:0098-4108    

DOI:10.1080/15287398409530571

出版商:Taylor & Francis Group    

年代:1984

数据来源: Taylor

摘要:

Pulmonary macrophages (PM) are involved in the clearance of inhaled particulate matter from the lung. PM also are capable of metabolizing xenobiotics such as benzo[a]pyrene (BaP). The objective of this investigation was to measure the ability of PM isolated from dogs to metabolize BaP coated onto diesel exhaust particles and to compare this metabolism with that of BaP in solution. PM were isolated from male beagle dogs and incubated with 1 μM [14C/BaP (solution or diesel particle coated) for select times up to 48 h. After incubation of PM with [14C]BaP, both the cells and the media were individually analyzed for [14C]BaP metabolites by high‐performance liquid chromatography. Total quantities of [14C]BaP metabolites in both the media (125 pmol/106cells) and cells (45 pmol/106cells) increased with incubation time for up to 48 h. BaP‐9, 10‐diol and BaP‐7,8‐diol were the major metabolites in organic extracts from the culture media, whereas BaP‐7,8‐diol and BaP‐4,5‐diol were the major metabolites in extracts of cells. Small quantities of BaP phenols and BaP quinones were detected in both the cells and media. Total quantities of BaP metabolites (20–30 pmol/106cells) were not significantly different when PM were incubated for 24 h with either /14C]BaP in solution or [C]BaP coated on diesel particles. The data suggest that particles retained in lungs are capable of being acted upon by PM metabolizing enzymes and that the ensuing metabolism may play an important role in the metabolic fate of organic material inhaled on particulate matter.

ISSN:0098-4108    

DOI:10.1080/15287398409530572

出版商:Taylor & Francis Group    

年代:1984

数据来源: Taylor

摘要:

An isolated perfused New Zealand rabbit lung preparation was used to investigate the effects of a cocarcinogen, ferric oxide (Fe2O3), on the metabolism of benzo[a]pyrene (BaP), a ubiquitous potent carcinogen that has been associated with the increased incidence of human bronchiogenic carcinoma in occupational and urban settings. [14C]‐BaP was administered intratracheally to an isolated perfused lung (IPL) preparation with and without Fe2O3after intraperitoneal pretreatment of the whole animal with BaP or intratracheal pretreatment of the whole animal with Fe2O3and/or BaP. BaP and its metabolites were isolated from serial blood samples up to 180 min after administration of [14C]BaP to the IPL. BaP and its metabolites were also isolated from lung tissue, washout fluid, macrophage, and trachea bronchi at the end of the perfusion at 180 min. Patterns of BaP metabolites were determined by chromatographic techniques and liquid scintillation counting.

ISSN:0098-4108    

DOI:10.1080/15287398409530573

出版商:Taylor & Francis Group    

年代:1984

数据来源: Taylor

摘要:

Rat liver microsomal metabolism of 8‐fluorobenzo[a]pyrene (8‐fluoro‐BaP) generated 3‐hydroxy‐8‐fluora‐BaP, 8‐fluoro‐BaP trans‐4,5‐dihydrodiol, and 8‐fluoro‐BaP, 3,6‐quinone as major products. A minor metabolite of 8‐fluoro‐BaP was tentatively assigned as 8‐fluoro‐BaP 9,10‐dihydrodiol. Metabolism of 9‐fluorobenzo[a] pyrene (9‐fluoro‐BaP) gave 3‐hydroxy‐9‐fluoro‐BaP, 9‐fluoro‐BaP trans‐4,5‐dihydrodiol, 9‐fluoro‐BaP trans‐7,8‐dihydrodiol, and 9‐fluoro‐BaP 3,6‐quinone. All three dihydrodiol metabolites were optically active. Comparison of the circular dichroism spectra of BaP 4R,5R‐dihydrodiol, 6‐bromo‐BaP 7R,8R‐dihydrodiol, and 6‐fluoro‐BaP 7R,8R‐dihydrodiol with those of the respective dihydrodiol metabolites allowed assignments of an R,R absolute configuration to the major enantiomers of the three dihydrodiol metabolites.

ISSN:0098-4108    

DOI:10.1080/15287398409530574

出版商:Taylor & Francis Group    

年代:1984

数据来源: Taylor