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PubMed1983

Chronic toxicity studies of vinyl acetate in Fischer rats.

A chronic toxicity test was carried out in groups of 20 male and female F344 rats with vinyl acetate dissolved in drinking water at two concentrations, 2500 and 1000 mg/liter. Treatment lasted for 2 years and did not lead to early death of the animals compared with untreated controls. The incidence of most types of neoplasm was similar in the treated and control groups. However, six females receiving the higher dose of vinyl acetate had adenoma or carcinoma of the thyroid and five had carcinoma of the uterus; the latter were not seen in the controls.

Animals↗
PubMed1990

The role of epoxidation in 4-vinylcyclohexene-induced ovarian toxicity.

4-Vinylcyclohexene (VCH) is present in gases discharged during synthetic rubber production. Chronic treatment of B6C3F1 mice and F-344 rats with VCH by gavage has been shown to induce ovarian tumors in mice but not in rats. Our objective was to understand the mechanism of the species difference in VCH-induced ovarian tumors. Since a critical step in the induction of ovarian tumors is destruction of the small oocyte, small oocyte counts obtained from serially sectioned ovaries were used as an index of toxicity. VCH or its epoxide metabolites [VCH-diepoxide, VCH-1,2-epoxide, and VCH-7,8-epoxide (in mice only)] were given to 28-day-old female mice and rats in corn oil, ip, at doses ranging from 0.07 to 7.4 mmol/kg body wt/day for 30 days. The dose which reduced the small oocyte count to 50% that of control was defined as the ED50. In mice, the ED50 for the reduction in small oocytes by VCH was 2.7 mmol/kg, whereas, no detectable oocyte loss occurred in rats at the highest dose of VCH (7.4 mmol/kg). The potency of the epoxides of VCH was greater than that of VCH in both species. The ED50 for oocyte loss by VCH-1,2-epoxide in mice and rats was 0.5 and 1.4 mmol/kg, respectively. In mice, VCH-7,8-epoxide had comparable potency to VCH-1,2-epoxide (ED50 = 0.7). VCH diepoxide was even more potent with ED50 values of 0.2 and 0.4 mmol/kg, in mice and rats, respectively. The dose response of the blood concentration of VCH-1,2-epoxide in mice after VCH showed that doses of VCH which caused minimal toxicity had the lowest blood level of this ovotoxic epoxide. Pretreatment of mice with the cytochrome P450 inhibitor chloramphenicol (200 mg/kg, ip) inhibited VCH epoxidation in vivo and in vitro and partially protected mice from VCH toxicity. Thus it appears that metabolism of VCH to epoxides and their subsequent destruction of oocytes are critical steps in VCH-induced ovarian tumors. Rats may be resistant to ovarian tumor induction by VCH because the amount of VCH converted to epoxides is insufficient to produce oocyte destruction.

Animals↗
PubMed1991

Epoxidation of 4-vinylcyclohexene by human hepatic microsomes.

Carcinogenicity studies have shown that chronic administration of 4-vinylcyclohexene (VCH) will induce ovarian tumors in B6C3F1 mice but not F-344 rats. This occurs because the blood level of the ovotoxic VCH metabolite, VCH-1,2-epoxide, is dramatically higher in VCH-treated female mice compared with rats. This species difference in VCH epoxidation is also reflected in the rate of VCH metabolism by hepatic microsomes (female mouse greater than female rat). The present study assessed the ability of microsomes obtained from human liver to metabolize VCH to epoxides since humans are exposed to VCH in certain occupational settings. The production of VCH-1,2-epoxide and VCH-7,8-epoxide from VCH (1 mM) by human hepatic microsomes was linear with respect to microsomal protein concentration (0.25-1.0 mg/ml) and incubation time (5-20 min). VCH-1,2-epoxide was the major metabolite, while the rate VCH-7,8-epoxide formation was about 6-fold lower and in some cases was below the limit of detection. There was no dramatic difference in the rate of VCH epoxidation by hepatic microsomes obtained from male and female humans. The rate of VCH-1,2-epoxide formation by female human hepatic microsomes was 0.71 +/- 0.35 nmol/mg microsomal protein/min (n = 4). This is 13- and 2-fold lower than the rate of VCH-1,2-epoxide formation by female mouse and rat hepatic microsomes, respectively. Therefore, if the rate of hepatic VCH epoxidation is the main factor which determines the ovotoxicity of VCH, then the results of these studies suggest that rats are the more appropriate animal model for extrapolation of animal data to humans.

Animals↗
PubMed1991

Improved nerve regeneration through piezoelectric vinylidenefluoride-trifluoroethylene copolymer guidance channels.

Piezoelectric materials generating electrical charges in response to mechanical strain may be used to stimulate axonal regeneration following nerve injury. Tubular nerve guidance channels were extruded from a vinylidenefluoride-trifluoroethylene copolymer using a melt-extrusion process. Unlike vinylidenefluoride homopolymer, the copolymer does not need mechanical stretching to achieve a dipole-containing crystal structure, enabling the fabrication of complex piezoelectric devices. Selected tubes were rendered piezoelectric in a high voltage corona poling apparatus. Crystal structure changes induced by poling were evaluated with differential scanning calorimetry. In contrast to unpoled samples, poled ones displayed a sharp endothermic peak and a greater heat of transition at the Curie temperature, indicative of an increase in crystal order and size. The piezoelectric output of poled tubes was characterized using a laser-monitored deflection system interfaced with a charge amplifier and oscilloscope. Poled tubes generated significant voltages in response to slight mechanical deformations. The magnitude of electrical output was independent of the poling polarity. Unpoled tubes showed no electrical output. Positive, negative and unpoled vinylidenefluoride-trifluoroethylene copolymer tubes were used to repair a 10 mm gap in transected sciatic nerves of adult rats. Nerves regenerated in positively poled channels had a significantly greater number of myelinated axons than those regenerated in unpoled channels 4 wk post-implantation. Negatively poled channels contained an intermediate number of myelinated axons. We concluded that piezoelectrically active vinylidenefluoride-trifluoroethylene copolymer tubes significantly enhance nerve regeneration as compared to chemically identical, unpoled tubes and that the polarity of the corona poling procedure used to fabricate piezoelectric materials may play a role in determining biological responses.

Animals↗
PubMed1996

Biomaterial-induced alterations of human neutrophils under fluid shear stress: scanning electron microscopical study in vitro.

Morphological changes of human polymorphonuclear neutrophils (PMN) adhering to hydrophilic (glass) and hydrophobic (FEP-Teflon, polyethylene, polypropylene) surfaces were studied in a parallel-plate flow chamber at the light and scanning electron microscopical levels. The PMN were exposed to a shear stress of 0.19 Pa (1.9 dynes cm-2) or were allowed to adhere without the stress component (static control) during 30 min for all four biomaterials. Observation by light microscopy was performed in situ in the flow chamber at 1, 5, 10, 15, 20, 25 and 30 min. The total number of adherent cells as a function of time and the activation status of the population on the basis of morphological criteria were determined. On the hydrophilic material adhesion of activated PMN was significantly higher (P < 0.05) than on the more hydrophobic surfaces. This effect was most pronounced for the adhesion of neutrophils to glass and polypropylene (PP). Polyethylene (PE) showed only minor adhesion rates. Scanning electron microscopy revealed details of cell shape changes and permitted a more precise classification of populations of neutrophils based on distinctive shapes. As PMN were exposed to shear stress on glass, the majority of cells exhibited surface veils, ridges and ruffles, suggesting a high level of cell migration. In this case, on polymeric surfaces the presence of filopodial networks (FEP-Teflon) and ameoboid cell shapes (PP and PE) was noted. The results suggest that a low shear stress, as well as various chemical and physical properties of biomaterial surfaces, are together responsible for differentiation of PMN populations on solid substrata.

Biocompatible Materials↗
PubMed1985

Effect of vinyl chloride on testis in rats.

A total of 300 male adult Wistar rats (180-220 g) were used. Animals were divided into four groups: control, vinyl chloride (VC) 10-, 100-, and 3000-ppm exposed groups. Seventy-five rats were used for each group. Inhalation exposure to VC was conducted 6 hr per day and 6 days per week. In the third, sixth, and twelfth month following exposure 8-30 rats of each group were killed. The others were under observation and sacrificed after 18 months. After exposure to VC, the organ and body weight ratio, such as the kidney, liver, spleen, and heart were increased, but those of the testis were decreased in the experimental groups in the sixth month. The differences between experimental groups and the control group were statistically significant (P less than 0.05 or P less than 0.01). The weights of testis were decreased and damage of testicular seminiferous tubules were found in rats by histopathological examination. Incidence of damage of testicular seminiferous tubules in the control, 10-, 100-, and 3000-ppm groups were 18.9, 29.7, 36.5, and 56.0%, respectively. There was an obvious dose-response relation between the concentration of VC and the incidence of testis damage, with a correlation coefficient of 0.993 (P less than 0.01). Statistically, the incidence of damage of testicular seminiferous tubules in rats in the 3000-ppm group and in 100-ppm group were significantly higher than that of the control group, respectively (P less than 0.001) and P less than 0.05).

Animals↗