摘要:

It has been suggested that the good correlations found between carcinogenic potency in mice and in rats could be an artifact. The artifact suggested arises because there are four correlations to consider—interspecies correlations of toxicity, interspecies correlations of carcinogenic potency, and two intraspecies correlations between toxicity and carcinogenic potency—and the existence of any three implies the fourth. It was argued that the intraspecies correlations between toxicity and potency were due to criteria for data selection. Here we discuss the correlations in detail and show that they are principally due to the experimental observation that there are few cases where most or all animals in a bioassay get cancer. We conclude that the correlations between carcinogenic potency are valid.

ISSN:0098-4108    

DOI:10.1080/15287398709530957

出版商:Taylor & Francis Group    

年代:1987

数据来源: Taylor

摘要:

To understand the mechanisms of toxicity of 2,4‐dichlorophenoxyacetic acid (2,4‐D) and 2,4,5‐trichlorophenoxyacetic acid (2,4,5‐T), we have studied their effects on the cytoskeletal organization, particularly microtubules (MT) and microfilaments (MF), DNA synthesis, and the synthesis and composition of cytoskeletal proteins in mouse 3T3 cells. Exposure of cells to 2,4‐D or 2,4,5‐T resulted in a dose‐dependent inhibition of DNA synthesis; 50% inhibition occurred at 2.21 mM and 0.90 mM for 2,4‐D and 2,4,5‐T, respectively. Furthermore, a strong synergistic inhibition of DNA synthesis was produced by mixtures (each having a total concentration of 1.25 mM) of 2,4‐D with 2,4,5‐T. Similarly, 2,4,5‐T is more potent than 2,4‐D in causing cytoskeletal perturbation as revealed by fluorescence microscopy. Treatment of cells with 2,4‐D (2.5 mM) or 2,4,5‐T (1.25 mM) for 20 h resulted in severe MT aggregation and the appearance of large bundles, which were organized in a rope‐like structure in the former and a dramatic octopus‐like pattern in the latter. Further, MT bundling is particularly severe in the cell center. Under these conditions, marked changes in MF organization also occurred as evidenced by clustering and crisscrossing of MF in the perinuclear region. A 1:1 mixture (final = 1.25 mM) of 2,4‐D and 2,4,5‐T, a formulation equivalent to Agent Orange composition, also induced a dramatic perturbation to the organization of MT and MF, resulting in the formation of ring‐like structures. MT bundling is still apparent, especially around the outer edge of the “rings.” MF are localized predominantly along the cell periphery, where they appear to be aggregated tightly forming patches. Surprisingly, the synthesis and composition of cytoskeletal proteins, which are resistant to detergent extraction but released by CaCl2, are essentially unaffected by 2,4‐D or 2,4,5‐T. These results suggest that the dramatic perturbation of the cytoskeletal morphology caused by these herbicides probably only results from a structural reorganization and redistribution of MT and MF.

ISSN:0098-4108    

DOI:10.1080/15287398709530958

出版商:Taylor & Francis Group    

年代:1987

数据来源: Taylor

摘要:

The effects of acute exposure to polychlorinated biphenyls (PCBs) on porphyrin synthesis and cytochrome P‐450‐dependent monooxygenases in the small intestine and liver were studied in male Japanese quail. The birds were dosed orally with the PCB mixture, Aroclor 1242, or the individual PCB isomers, 2,4,2’,4'‐tetrachlorobiphenyl (2‐TCB) and 3,4,3’,4'‐tetrachlorobiphenyl (3‐TCB), and were killed 48 h later. All the PCB compounds caused a significant increase in porphyrin content and δ‐aminolevulinic acid synthetase (ALA‐S) activity in the small intestine and liver. Increases in porphyrins were greater in the small intestine than in liver. However, a smaller increase in ALA‐S activity occurred in the small intestine than in liver, suggesting that ALA‐S induction is not a major mechanism for the increased porphyrin content of small intestine. All the test compounds significantly increased the cytochrome P‐450 content of liver. In the small intestine, cytochrome P‐450 content was increased by Aroclor 1242 and 2‐TCB but not by 3‐TCB. The activity of 7‐ethoxyresorufin O‐deethylase, however, was increased by all test compounds in both liver and small intestine. In contrast, there was a striking difference between small intestine and liver in the induction of 7‐ethoxycoumarin O‐deethylase (ECOD) activity by Aroclor 1242. In the liver, ECOD activity was unchanged or decreased, but in the small intestine, ECOD activity increased linearly with dose. No tissue difference in ECOD activity was observed after treatment with 2‐TCB or 3‐TCB. These findings suggest that acute exposure to a given PCB results in marked differences between small intestine and liver in porphyrin metabolism and in the induction of cytochrome P‐450 isozymes and associated monooxygenases.

ISSN:0098-4108    

DOI:10.1080/15287398709530959

出版商:Taylor & Francis Group    

年代:1987

数据来源: Taylor

摘要:

Ethyl ether extracts derived from coffee were tested for in vitro estrogenic and in vivo uterotropic activities. Coffee extracts, unlike tea and cocoa, were found to actively compete with 17ß‐estradiol for uterine cytosol binding sites. The biologically active fractions possessed an unique ultraviolet absorbance spectrum that excluded them from containing flavonoid, coumestan, or resorcyclic acid lactone constituents. Coffee extracts administered to immature female mice for 3 d in feeding studies displayed significant (p < 0.05) uterotropic responses, which were similar to results obtained in mice treated with a standard 17ß‐estradiol dose. Additional studies in mice disclosed that coffee extracts did not reduce the uterotropic effect normally induced by 17ß‐estradiol when administered simultaneously with estradiol. The complete estrogenic effects of coffee constituents, coupled with their failure to inhibit a biological response evoked by estradiol, strongly suggest that coffee contains constituent(s) that are weakly estrogenic.

ISSN:0098-4108    

DOI:10.1080/15287398709530960

出版商:Taylor & Francis Group    

年代:1987

数据来源: Taylor

摘要:

The immunotoxicologic effects of d‐limonene were determined. This naturally occurring substance is widely used in food flavorings and is a common additive in cosmetics. In the present study, BALB/c mice were treated with d‐limonene for 9 wk. Effects on T‐ and B‐cell responses were determined after 4 and 8 wk of treatment. Concanavalin‐A responses at 8 wk, but not 4 wk, were suppressed in treated mice. A similar trend was observed for phytohemagglutinin and lipopolysaccharide responses. Evidence was presented that d‐limonene had polyclonal activator action. Mice primed with keyhole limpet hemocyanin (KLH) prior to initiation of d‐limonene treatment had suppressed primary and secondary anti‐KLH responses. Mice treated with d‐limonene prior to KLH priming produced significant increased antibody responses. Additional evidence for polyclonal stimulation was obtained by histopatho‐logic examination of secondary lymphoreticular tissue. Significant secondary follicle development and prominent lymphoid nodules and aggregates were found in the pancreas and intestinal mucosa, particularly apparent in mice receiving the highest d‐limonene dosage.

ISSN:0098-4108    

DOI:10.1080/15287398709530961

出版商:Taylor & Francis Group    

年代:1987

数据来源: Taylor

摘要:

The effects that divalent metals have on nickel‐induced suppression of natural killer (NK) cell activity were studied in mice. Male CBA/J mice were given a single intramuscular injection of metal salt on a body weight basis. The metal doses used were the following: nickel chloride, 4.5–36 μg/g; manganese chloride, 20–80 μg/g; magnesium acetate, 50–200 μg/g; zinc acetate, 2–8 μg/g; or calcium acetate, 12.5–50 μg/g. Twenty‐four hours after metal injection, splenic NK cell activity was assessed using a51Cr‐release assay. Ni significantly (p< 0.01) suppressed NK activity, while Mn significantly (p< 0.01) enhanced NK activity. No alteration in NK activity was observed in mice injected with Mg, Ca, or Zn. Since these divalent metals have been shown to have antagonistic effects on Ni‐induced carcinogenicity and toxicity, they were used in combination with Ni to determine if such antagonisms exist for NK cell activity. The injection of Ni and Mn in combination at a single site resulted in the enhancement of NK activity, although this enhancement was at a level below that observed following the injection of Mn alone. Injection of Mg, Zn, or Ca in combination with Ni did not affect NK activity compared to saline controls. In contrast, the injection of Ni in one thigh followed immediately by Mn, Mg, Ca, or Zn into the other thigh resulted in significant suppression of NK activity for all metals compared with saline controls. An interesting finding was that the injection of Ni followed immediately by Mn into the opposite thigh resulted in even greater reductions in NK activity than Ni alone. Suppression of NK activity by Ni and Mn injected at separate sites was not seen when Mn injection preceded Ni injection by 1 h. These data indicate that both the divalent metal and the timing of its injection relative to Ni injection are critical for altering Ni‐induced suppression of NK cell activity.

ISSN:0098-4108    

DOI:10.1080/15287398709530962

出版商:Taylor & Francis Group    

年代:1987

数据来源: Taylor

摘要:

Stack‐collected fly‐ash particles from a commercial pulverized‐coal power plant were extracted with 60/40 w/w benzene‐methanol to remove as much of the organic fraction as possible. The extract was sequentially fractionated on a series of high‐performance liquid chromatography columns, and the Salmonella bacterial mutagenicity assay using both normal and nitroreductase‐deficient strains was used to localize the most mutagenic fractions. Selected fractions were analyzed by a variety of techniques, including gas chromatography with dual‐flame ionization and thermionic nitrogen‐phosphorus detectors, gas chromatography‐mass spectrometry, directprobe low‐resolution or low‐voltage mass spectrometry, and high‐resolution mass spectrometry.

ISSN:0098-4108    

DOI:10.1080/15287398709530963

出版商:Taylor & Francis Group    

年代:1987

数据来源: Taylor

摘要:

The lethal toxicity of inorganic (HgCl2) and organic (CH3HgCl) mercury chloride was compared forCoturnix(Japanese quail,Coturnixjaponica) of different ages from hatch through adulthood by single‐dose acute oral and intramuscular injections and by a 5‐d dietary trial. Sublethal mercury toxicity was studied by evaluation of plasma and brain cholinesterase activity. CH3HgCl was more toxic than HgCl2in all tests at each age tested. LD50s consistently increased over the first 4 wk for both acute methods and both mercurials and then stabilized. The striking difference between single‐dose acute and 5‐d dietary tests was that CH3HgCl averaged about twice as toxic as HgCl2by both acute methods, compared to 100 times as toxic by the dietary method. For example, at 2 wk of age, the oral LD50s for CH3HgCl and HgCl2were 18 and 42 mg/kg and the dietary LC50s were 47 and 5086 ppm. When birds were fed HgCl2and developed clinical signs of intoxication, they could recover once treatment was withdrawn; however, on CH3HgCl, clinical signs often commenced after treatment was withdrawn, and then actually intensified for several days and culminated in death.

ISSN:0098-4108    

DOI:10.1080/15287398709530964

出版商:Taylor & Francis Group    

年代:1987

数据来源: Taylor

摘要:

The subchronic inhalation toxicity of methanol was evaluated in rats and monkeys. Animals were exposed to 0, 500, 2000, and 5000 ppm methanol vapor for 6 h/d, 5 d/w, for 4 wk. The only treatment‐ and dose‐related effect noted was that of mucoid nasal discharge in rats, which was considered reflective of upper respiratory tract irritation. No consistent treatment‐related effects were found for organ or body weights or for histopathologic or ophthalmoscopic examinations. Overall, these findings support the use of the present American Council of Governmental Industrial Hygienists threshold limit value (TLV) of 200 ppm and short‐term exposure limit (STEL) of 250 ppm for exposure to methanol vapor.

ISSN:0098-4108    

DOI:10.1080/15287398709530965

出版商:Taylor & Francis Group    

年代:1987

数据来源: Taylor

摘要:

This study examined the effects of ozone (O3) inhalation on mucociliary clearance from the tracheobronchial tree. Rabbits were exposed for 2 h at 0.1, 0.25, and 0.6 ppm or for 2 h/d for 74 consecutive days at 0.25 and 0.6 ppm. Clearance was assessed by measuring the retention of radioactivity tagged, inert tracer particles inhaled immediately after the single 2‐h exposure, or 24 h after 2, 7, or 14 of the daily exposures. Single exposures resulted in a concentration‐related trend toward retarded particle clearance, with a statistically significant difference occurring after exposure to 0.6 ppm. Intermittent exposures produced no significant change in clearance rate, although there was a suggestion of retarded clearance at early time points at both 0.25 and 0.6 ppm.

ISSN:0098-4108    

DOI:10.1080/15287398709530966

出版商:Taylor & Francis Group    

年代:1987

数据来源: Taylor