摘要:

AbstractThe teratogenicity of phenytoin may result from its enzymatic bioactivation to a reactive intermediate, which interacts irreversibly with fetal tissues. Since glutathione (GSH) is involved in the detoxification of many reactive intermediates, N‐acetylcysteine (NAC), a glutathione precursor, was evaluated for its effects on murine fetal development and phenytoin teratogenicity. NAC, 100 to 275 mg/kg, was given intraperitoneally (ip) or per os (po), or as 266 to 410 mg/kg in the drinking water, at various times before or after phenytoin, 65 to 75 mg/kg ip, on gestational days 12 and 13. Dams were killed on gestational day 19, fetal resorptions were noted, and fetuses were examined for anomalies. Significant reductions in phenytoin‐induced fetal weight loss and cleft palates were observed when NAC was given by gavage 6 hours after phenytoin or in the drinking water with the lower dose of phenytoin. NAC administered in the drinking water also reduced the incidence of resorptions produced by the higher dose of phenytoin and enhanced postpartum survival in fetuses exposed to 65 or 75 mg/kg phenytoin (P<.05). Conversely, the incidence of resorptions increased when NAC was given by gavage at other times before or after phenytoin, by single or repetitive ip injections, or in high concentrations in the drinking water (P<.05). When given with the higher dose of phenytoin, NAC administered via the drinking water significantly increased the incidence of phenytoin‐induced cleft palates and fetal weight loss (P<.05). Similar results were obtained with a single ip injection of NAC and a lower dose of phenytoin. Thus, when given orally, NAC can partially reduce phenytoin teratogenicity and embryopathy. However, altering the route of NAC administration, or increasing the dose of phenytoin and/or NAC, enhanced phenytoin embryotoxicity, and NAC alone at higher doses had embryopathic ef

ISSN:0270-3211    

DOI:10.1002/tcm.1770080202

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1988

数据来源: WILEY

摘要:

AbstractThe objective of this study was to examine the effect of smokeless tobacco (ST) on the development of the CD‐1 mouse fetus. ST was administered continuously via Alzet osmotic minipumps during the critical gestational days 7–14 and 6–13. Two ST dosages were administered, 3.2 mg/ml (Dosage I) and 6.4 mg/ml (Dosage II), which yielded plasma nicotine levels within the range comparable to those of an average ST user or smoker (36.0 ng/ml).Plasma nicotine levels were maintained in the range of 29.4 ± 4.8 ng/ml to 44.3 ± 16.0 ng/ml for the Dosage I group of dams, and in the range of 34.6 ± 10.9 ng/ml of 75.5 ± 19.9 ng/ml for the Dosage II group of dams. The main effect on the fetus was weight reduction, with Dosage I producing a tendency toward weight reduction (p = .08). Dosage II produced a significant 8.6% weight reduction from normal (p<.0001) and an increase in fetal deaths (p<.03). Dosage I produced an increase in the incidence of hemorrhages and supernumerary ribs, and a significant delay (p<.05) in ossification of the supraoccipital bone, the sacrococcygeal vertebrae, and the bones of the forefoot and hindfoot. There were no significant differences between placental weights. Weights of dams were significantly reduced only at the higher ST exposure levels.We conclude that at plasma nicotine levels comparable to those of an average ST user, ST produces weight reduction, delayed ossification, and increase in hemorrhages and fetolethality in the CD‐1

ISSN:0270-3211    

DOI:10.1002/tcm.1770080203

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1988

数据来源: WILEY

摘要:

AbstractDuring organogenesis, mouse embryos were treated transplacentally with MMC and DMBA. The clastogenic and SCE‐inducing effects of MMC and the clastogenic effects of DMBA were analyzed in metaphases from whole embryo suspensions. Positive effects were observed on all the days of pregnancy on which the embryos were analyzed, i.e., on days 10, 11, 12, and 13. Whereas the MMC‐induced SCE‐frequencies did not change significantly during the tested period, the clastogenic effects of MMC and DMBA varied drastically. Extremely high aberration rates were observed in embryos on day 11; on the other days the aberration rates were much lower. Factors that might have given rise to these stage‐related effects are di

ISSN:0270-3211    

DOI:10.1002/tcm.1770080204

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1988

数据来源: WILEY

摘要:

AbstractNitrous oxide (N2O), an anesthetic gas, has been implicated as a human teratogen. The mechanism for its developmental toxicant effects is not known but may involve depression of embryonic macromolecular synthesis caused by alterations in precursor concentrations. Such changes might be caused by decreased folate levels. Pregnant rats were exposed to 50% N2O for 24 hours on day 10 of gestation; this is not an anesthetic dose. Embryos were removed immediately after exposure and grown in a rodent whole embryo culture system for 4 hours in medium containing radiolabeled precursors for RNA or protein. Exposure to N2O decreased embryonic DNA and RNA contents but did not alter number of somite pairs or protein content. Such treatment also decreased incorporation of radiolabeled uridine into acid‐precipitable RNA. There was no difference between control and treated embryos in the incorporation of radiolabeled leucine into protein. There were also no differences between control and exposed embryos in the level of acid‐soluble purines. The lower DNA and RNA contents in N2O‐treated embryos are apparently not the result of decreased levels of adenine or gu

ISSN:0270-3211    

DOI:10.1002/tcm.1770080205

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1988

数据来源: WILEY

摘要:

AbstractMajor efforts have been made in the development of a system that takes the reviewer step‐by‐step by the use of the developmental toxicity and exposure assessment data to a recommended risk assessment and risk management position. Thereupon a set of regulatory decisions can be arrived at that are backed up by sound scientific analysis. Examples of pesticides that have been found to be teratogenic in animal testing are provided to demonstrate the process of use of exposure data in making risk assessment and management decisi

ISSN:0270-3211    

DOI:10.1002/tcm.1770080206

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1988

数据来源: WILEY

ISSN:0270-3211    

DOI:10.1002/tcm.1770080201

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1988

数据来源: WILEY