摘要:

Diallyl thioethers (DATEs), naturally occurring compounds present in garlic, were investigated for their putative ability to inhibit benzo[a]pyrene‐induced genotoxicity in ICR and C3H strains of mice. The mouse bone marrow micronudeus assay was used as an indicator of in vivo genotoxicity. A dose of 0.67 mmol total DATEs/kg body weight inhibited formation of micronucleated polychromatic erythrocytes (MPCEs) by 24%, and 0.33 mmol DATEs inhibited formation of MPCEs by 45%. Possibly the toxicity of DATEs accounted for less inhibition with the higher dose. Formation of MPCEs were inhibited only slightly by DATEs in C3H mice. These results indicate that the mouse bone marrow micronudeus assay can be used to identify organosulfur components of garlic that inhibit genotoxicity.

ISSN:0098-4108    

DOI:10.1080/15287399209531652

出版商:Taylor & Francis Group    

年代:1992

数据来源: Taylor

摘要:

Inhalation exposure to silicon dioxide is known to result in acute lung injury followed by pulmonary fibrosis. Recently it has been shown that the acute lung damage during influenza virus infection is also followed by a fibrogenic process. To investigate the interaction between silicon dioxide and influenza virus infection, mice were intratra‐cheally instilled with either alpha‐quartz or cristobalite and 3 d later infected by aerosol inhalation with influenza A/PR8/34 virus. At 30, 60, and 90 d after infection, groups of virus infected and noninfected mice were sacrificed and their lungs assessed for total and differential lavage cell counts, lung hydroxyproline content, and morpho‐metric analysis. The silica polymorphs did not alter the proliferation of virus in the lungs as quantitated by infectious virus titers of lung homogenates at 1, 5, 7, 10, and 13 d after infection. In noninfected animals, cristobalite was more reactive than alpha‐quartz. The virus infection, in all parameters measured at all time intervals, enhanced the overall fibrogenic response of the lungs to the mineral dusts, suggestive of an additive fibrogenic model. The data demonstrate that virus infection following silicon dioxide exposure results in an interaction that leads to an enhanced fibrogenic response.

ISSN:0098-4108    

DOI:10.1080/15287399209531653

出版商:Taylor & Francis Group    

年代:1992

数据来源: Taylor

摘要:

Treatment of rats with a single carcinogenic dose of CdCI2(i.e., 30 nmol/kg) caused severe hemorrhagic damage in the testis within the first 12 h after the metal. Subsequently, atrophy with calcification developed in the next 2–3 mo. Atrophied tissues regenerated during the 1 yr after exposure. Twelve hours after exposure to the Cd treatment, lipid peroxidation levels, Fe content, and cellular production of H2O2were remarkably elevated in testicular Leydig cells, the target cell population for Cd carcin‐ogenesis. At the same time, glutathione peroxidase activity rose, glutathione reduc‐tase and catalase activities were reduced, and superoxide dismutase activity was unchanged. Xanthine oxidase activity in Leydig cells was also elevated at 6 and 9 h after the Cd treatment. Reduced glutathione in testes was decreased and oxidized glutathione was increased 12 h after exposure to the metal. These facts suggest that the carcinogenic doses of Cd induced oxidative stress while compromising cellular defense mechanisms against such stress. Therefore, active oxygen species such as H2O2may have an important role in the initiation of carcinogenesis within the target cell population.

ISSN:0098-4108    

DOI:10.1080/15287399209531654

出版商:Taylor & Francis Group    

年代:1992

数据来源: Taylor

摘要:

Urethane‐hydrolyzing activity (urethanase) was found in the homogenates of liver, kidney, and lung of rats. The activity was significantly higher at acidic condition (pH 5.0) than that at neutral condition (pH 7.0) in every case. The highest activity among them was observed in a kidney homogenate preparation. The activities increased slightly with treatment by Triton X‐100. Intracellular distribution of urethanase in rat kidney was examined and found that the enzyme activity located mainly in the lyso‐somal fraction. The optimal pH was found to be 5.0. The enzyme activity was strongly inhibited by EDTA, whose 50% inhibitory concentration was 7.4 × 10−7M. Complete loss of the enzyme activity by the addition of EDTA was fully recovered by the addition of Zn2+, which suggested that urethanase belongs to the category of Zn enzyme.

ISSN:0098-4108    

DOI:10.1080/15287399209531655

出版商:Taylor & Francis Group    

年代:1992

数据来源: Taylor

摘要:

Metavanadate was evaluated for developmental toxicity in pregnant Swiss mice. Sodium metavanadate (NaVO3) was administered intraperitoneally on d 6–15 of gestation at doses of 0, 2, 4, or 8 mg/kg/d. On gestation d 18, all live fetuses were examined for external, visceral, and skeletal malformations and variations. Maternal toxicity was observed at 2, 4, and 8 mg/kg/d as evidenced by decreased weight gain during treatment. Increased resorptions and dead fetuses, increased percentage postimplantation loss, and reduced fetal body weight per litter were observed at 4 and 8 mg/kg/d. There were no significant increases in the type or incidence of external and skeletal anomalies, but a significant increase in the incidence of cleft palate was detected at 8 mg/kg/d. The lowest‐observed‐adverse‐effect level (LOAEL) for maternal toxicity was 2 mg NaVO3/kg/d, while 2 mg/kg/d was also the no‐observed‐adverse‐effect level (NOAEL) for significant developmental toxicity.

ISSN:0098-4108    

DOI:10.1080/15287399209531656

出版商:Taylor & Francis Group    

年代:1992

数据来源: Taylor

摘要:

The purpose of this study was to investigate the dermal absorption of chemicals in different physical forms when applied to female F344 rats. Chemicals were applied either as a solid, aqueous paste, suspension, or dissolved in the volatile vehicle etha‐nol. The chemicals investigated were [14C]‐2‐sec‐butyl‐4,6‐dinitrophenol (DNBP, 4.2 μmol), 2,4,5,2’ ,4’ ,5’ ‐[14C]‐hexachlorobiphenyl (HCB, 2.3 μmol), and 3,4,3’,4'‐[14C]‐tetrachlorobiphenyl (TCB, 0.5 μmol). The chemicals were applied on the clipped mid‐dorsal region of the rat over a 2.54‐cm2treatment area, which was then occluded. Urine and feces were collected and assayed for radioactivity. Twenty‐four hours post‐application, the treated skin was washed with a mixture (1:1) of soap and water, dried, and reoccluded. The animals were sacrificed at 120 h by exsanguination under ether anesthesia. Radioactivity in the blood, skin (treated and untreated), and carcass was assayed. Dermal absorption of DNBP‐derived radioactivity was approximately 50% of the recovered dose after application in the four physical forms, and the major route of excretion was via the urine. Twelve percent of the absorbed dose of DNBP was retained in the body. Dermal penetration of HCB‐derived radioactivity was 5–8% of the recovered dose after application in the four forms, and the major route of excretion was via the feces. Greater than 90% of the absorbed dose of HCB‐derived radioactivity was retained in the body. Dermal penetration of TCB‐derived radioactivity was 6–8% of the recovered dose in the four forms, and the major route of excretion was via the feces. Approximately 21% of the absorbed dose was retained in the body at 120 h. Absorption of each chemical applied either as solid, aqueous paste, or suspension was compared to the absorption of the same chemical in ethanol. Absorption of HCB applied as a solid was significantly higher (p < .05) as compared to HCB applied in ethanol. There were no other significant differences in the comparisons of absorption. The data indicate that the chemicals examined in this study can penetrate the skin as readily when applied either as a solid, aqueous paste, or suspension, as when applied in the volatile vehicle ethanol.

ISSN:0098-4108    

DOI:10.1080/15287399209531657

出版商:Taylor & Francis Group    

年代:1992

数据来源: Taylor

摘要:

Levels of polychlorinated dibenzo‐p‐dioxins (PCDD) and polychlorinated dibenzo‐furans (PCDF) were measured in human milk in a collaborative Scandinavian study with 10 samples from each of 7 locations in Norway and Sweden (total 70 samples) and 10 samples from Denmark. Four locations represented areas with different PCDD and PCDF sources and three background areas. Norwegian results are presented and related to the Danish and Swedish values.

ISSN:0098-4108    

DOI:10.1080/15287399209531658

出版商:Taylor & Francis Group    

年代:1992

数据来源: Taylor

摘要:

Future human exposure to inorganic mercury will probably lead to a few individuals occupationally exposed to high levels and much larger populations exposed to low or very low levels from dental fillings or from food items containing inorganic mercury; human exposure to methylmercury will be relatively low and depending on intake of marine food. Ideally, risk assessment is based on detailed knowledge of relations between external and internal dose, organ levels, and their relation to toxic symptoms. However, human data on these toxicokinetic parameters originate mainly from individuals or smaller populations accidentally exposed for shorter periods to relatively high mercury levels, but with unknown total body burden. Thus, assessment of risk associated with exposure to low levels of mercury will largely depend on data from animal experiments. Previous investigations of the toxicokinetics of mercuric compounds almost exclusively employed parenteral administration of relatively high doses of soluble mercuric salts. However, human exposure is primarily pulmonary or oral and at low doses. The present study validates an experimental model for investigating the toxicokinetics of orally administered mercuric chloride and methylmercuric chloride in mice. Major findings using this model are discussed in relation to previous knowledge.

ISSN:0098-4108    

DOI:10.1080/15287399209531659

出版商:Taylor & Francis Group    

年代:1992

数据来源: Taylor

摘要:

The purpose of this study was to determine the relationship between chemical suppression of natural killer (NK) cell activity in mice and chemical effects on susceptibility to murine cytomegalovirus (MCMV) infection. The goal was to provide a rational basis for applying MCMV as a host resistance model for immunotoxicity testing and to provide risk assessors some guidance in relating suppression of NK cell activity to enhanced risk of disease. Data from studies with eight chemicals administered in various doses and by various routes were evaluated, and a significant correlation was observed between chemical suppression of virus‐augmented NK cell activity and increased mortality due to MCMV infection. In contrast, effects of the same chemical treatments on spontaneous NK cell activity (i.e., basal activity in uninfected mice) did not correlate with effects of these chemicals on mortality due to MCMV. Although chemicals that suppressed spontaneous NK cell activity enhanced infection, the converse was not always true—that is, increased susceptibility to infection and suppression of virus‐augmented NK cell activity were observed on three occasions when spontaneous NK cell activity was unaffected. This latter phenomenon plus the fact that for two chemicals spontaneous NK was suppressed at concentrations twofold below that which affected mortality appear to account for the poor statistical correlation. Nevertheless, the data indicate that MCMV is a useful host resistance model to be applied in immunotoxicity testing when suppression of NK cell activity has been demonstrated. However, virus‐augmented activity may be a better indicator than spontaneous activity. The data also indicated that suppression of NK cell activity is predictive of increased susceptibility to infection and hence provides qualitative guidance (hazard identification) to risk assessors.

ISSN:0098-4108    

DOI:10.1080/15287399209531660

出版商:Taylor & Francis Group    

年代:1992

数据来源: Taylor

摘要:

Dichloro‐ and trichloroacetic acids (DCA and TCA) and chloroform are formed during chlorination disinfection of drinking water. The effects of DCA and TCA treatment on CHCI3toxicity were assessed in these studies. Male and female rats were gavaged with DCA or TCA (0.92 and 2.45 mmol/kg administered 3 times over 24 h). Three hours after the last dose CHCI3was injected ip (0.75 mg/kg). Male rats experienced some weight loss (15%) and slight increases of ALT and BUN, but there were no effects of either DCA or TCA on any of these responses. In females, CHCI3increased plasma ALT and this response was greater (up to threefold) in the DCA group, compared to saline controls. Similarly, BUN was increased by CHCI3and this was more severe (up to threefold) in both the DCA and TCA pretreated groups. These results show that CHCI3toxicity is increased by DCA and TCA, and this effect is gender‐specific, occurring only in females. DCA increases both liver and kidney toxicity, whereas TCA affects only kidney toxicity.

ISSN:0098-4108    

DOI:10.1080/15287399209531661

出版商:Taylor & Francis Group    

年代:1992

数据来源: Taylor