摘要:

AbstractThe morphology of otoliths in CD‐1 mouse and Syrian hamster fetuses exposed to the fungicide dinocap were evaluated at the end of gestation. Pregnant mice were dosed by gavage with 0, 10, 15, 30, or 60 mg/kg/day dinocap in corn oil on days 7–16 of gestation. Pregnant hamsters were dosed by the same route with 0, 50, 100, or 200 mg/kg/day on days 7–14 of gestation. At the end of gestation (day 18 in mice, day 15 in hamsters) dams were killed and all fetuses were removed and fixed overnight in 70% ethanol. Fetal heads were then removed, left in 70% ethanol for at least 3 days, and then dehydrated in a graded ethanol series and cleared with methyl salicylate. Otoliths were examined by darkfield microscopy, and each otolith was scored for morphological completeness on a scale of 0 to 3. Otolith development was complete by day 18 of gestation in control mouse fetuses. Otolith development was complete in many, but not all, of the hamster fetuses by day 15 of gestation. In the mouse, dinocap exposure inhibited fetal otolith formation in a dose‐related manner, with a significant effect on total otolith score occurring at 10 mg/kg/day and above. Dinocap affected otolith formation in the hamster only at 100 mg/kg/day (200 mg/kg/day was embryolethal), concommitant with severe maternotoxicity and fetotoxicity. The results of this study indicate that the CD‐1 mouse is more sensitive than the Syrian golden hamster to the effects of dinocap on otolith development, and that otolith morphology can be easily examined in the mouse and hamster fetuses at term, although not by techniques currently used for fetal examination in standard teratology bioassays (e.g., Segment II

ISSN:0040-3709    

DOI:10.1002/tera.1420390602

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

年代:1989

数据来源: WILEY

摘要:

AbstractJapanese quail eggs were injected with 1‐(2‐chlorophenyl)‐1‐(4‐chlorophenyl)‐2,2,2‐trichloroethane p,p′‐DDT (1–10 mg), 1,1‐bis(4‐chlorophenyl)‐2,2,2‐trichloroethane p,p′‐DDT (1–10 mg), or, in one study, 0.5 mg chlordecone dissolved in 50 μl of corn oil on day 1 of incubation. Hatchability was not decreased by p,p′‐DDT or p,p′‐DDT, as compared to corn‐oil‐injected controls, but was reduced in progeny of parents injected in ovo with either isomer. Tremor was observed for up to 4 days posthatching only in birds injected with 1.75–10 mg p,p′‐DDT or chlordecone. Survivability to 5 weeks posthatch was reduced (± 50%) in birds injected in ovo with 6.25–7.5 mg, p,p′‐DDT or 1.75‐5 mg p,p′‐DDT as compared to corn oil (96%). Reproductive behaviors were attenuated in birds injected during development with p,p′‐DDT, both DDT isomers decreased the total number of ovipositions, and p,p′‐DDT increased the total number of eggshell malformations. Neither body weights nor reproductive organ weights at 12 weeks were affected by injection of either isomer. Exposure to DDT did not affect acquisition of a matched‐to‐sample food‐reinforced response or subsequent responding on a random interval schedule of reinforcement. In another experiment, total circulating erythrocyte numbers were reduced in females after injection in ovo with p,p′‐DDT but not after injection with p,p′‐DDT. A primary humoral immune response was not affected by in ovo exposure to either isomer of DDT. In ovo exposure to p,p′‐DDT but not to p,p′‐DDT had long‐term and estrogen‐like effects on behavior and hematology in Japanese quail. Posthatch prima

ISSN:0040-3709    

DOI:10.1002/tera.1420390603

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

年代:1989

数据来源: WILEY

摘要:

AbstractAH23848 is a potent thromboxane A2‐receptor blocker inhibiting platelet aggregation in vitro and in vivo. Oral administration to pregnant rats during days 7–16 of pregnancy, at doeses of 0, 10, 45, or 200 mg/kg twice daily, resulted in dose‐related maternal, embryonic, and fetal toxicity. The most notable observation was herniation of the diaphragm occurring in 1.5 and 100.0% of fetuses at the 45 and 200 mg/kg doses, respectively, when examined at term. A further study at 150 mg/kg twice daily during days 7–16, 7–11, or 12–16 of pregnancy revealed incidences of diaphragmatic hernia up to 42%. Herniation varied from small areas of eventration of membranous diaphragm to fetuses with apparent total absence of the diaphragm. The positions of the hernias in the diaphragm, following dosing over varying periods of organogenesis, reflected the chronology of diaphragm formation in the rat. The teratology of AH23848 was unrelated to its thromboxane A2‐receptor blocker properties but was related to a chemical breakdown product, 4‐biphenylmethanol. Some substituted biphenyl compounds appear to be specific teratogens in the rat, with their effects targeted at the developing diaphragm. A possible mechanism of herniation is the interference with muscularisation of the membranous diaphragm, resulting in weakness

ISSN:0040-3709    

DOI:10.1002/tera.1420390604

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

年代:1989

数据来源: WILEY

摘要:

AbstractFemale CD‐1 mice were exposed to Tordon 202c (a picloram and 2,4‐D combination herbicide) in the drinking water at concentrations of 0.21, 0.42, and 0.84% for 60 days prior to mating with untreated males. One‐half of the pregnant females subsequently continued treatment throughout gestation while the remaining females were maintained on distilled water. Fetal weight, crown–rump length, placental weight, and maternal gestational weight gain were reduced in a dose‐dependent manner following combined preconceptional and gestational exposure. The incidence of malformed fetuses (cleft palate, renal agenesis, hydronephrosis, unilateral testicular agenesis, and umbilical hernia) and fetuses with variants (especially incomplete ossification of the skeleton) were increased in a dose‐dependent manner following combined exposure. Increased maternal mortality and decreased preconception weight gain were observed in the highest‐dosage group. Relative maternal liver weight was increased in a dose‐dependent manner. The results suggest that combined preconceptional and gestational exposure to Tordon 202c is required for teratogenesis and fetal growth depression. Preconceptional exposure alone is not effective in increasing the risk for

ISSN:0040-3709    

DOI:10.1002/tera.1420390605

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

年代:1989

数据来源: WILEY

摘要:

AbstractIt has been reported that acetylcholine induces cardiac anomalies in the chick embryo. Thus, we studied hemodynamic effects of this drug in the chick embryo and also compared them with those in the rat embryo since we found that the effect of caffeine was different between the chick and rat embryos. Acetylcholine was given at doses of 5, 0.5, and 0.05 μg into the vitelline vein in chick embryos at Hamburger–Hamilton stage 21 and at a dose of 0.5 μg into the placenta in rat embryos at gestational day 12. In the chick embryo, heart rate was reduced to 91, 88, and 87% of control at the end of injection of 0.05, 0.5, and 5 μg, respectively, then returned to the baseline level. Vitelline arterial blood pressure was 110% of control with 0.05 μg, 134% with 0.5 μg, and 142% with 5 μg at 1 min after injection. The dorsal aortic blood flow decreased with time after injection, but it was increased only by a 5 μg dose at the end of injection. The vascular resistance increased in a dose‐dependent manner. In the rat embryo, the change of heart rate was qualitatively similar to that of the chick embryo. The blood pressure did not change significantly. The blood flow velocity at the outflow tract decreased at the end of injection, which indicated the decrease in cardiac output, along with slowing of heart rate, then returned to the control level thereafter. We conclude that acetylcholine has a vasoconstrictive effect at this stage of the chick embryo and its teratogenicity may not be explained by an hemodynamic effect based on a one‐to‐one relation of cause and effect and that there is species difference in hemodynamic effects but significance of this result is t

ISSN:0040-3709    

DOI:10.1002/tera.1420390606

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

年代:1989

数据来源: WILEY

摘要:

AbstractExposure of female mice to ethylene oxide by inhalation 1 or 6 h after mating produced not only multitemporal death of conceptuses but also high rates of abnormalities among surviving fetuses. In contrast, only marginal effects were observed when females were exposed 9 or 25 h after mating. The abnormalities found among 17 day gestation live fetuses were predominated by hydrops and eye defects, which, together, constitute 54% of all anomalies. Most of the remaining anomalies were distributed among 5 other types: small size, cleft palate, and cardiac, abdominal wall, or extremity and/or tail defects. In a follow‐up study, the fetuses of females treated 6 h postmating were examined at 11–15 days gestation and the progression of fetal death and of malformations was studied. Results indicate that the expression of most fetal anomalies does not become apparent until late in gestation. Several of these induced anomalies are similar to common human sporadic birth defects. This new class of experimentally induced fetal anomalies provides a new avenue for investigating zygotic biology and a system for studying the progression of aberrant developm

ISSN:0040-3709    

DOI:10.1002/tera.1420390607

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

年代:1989

数据来源: WILEY

摘要:

AbstractAdriamycin (2.5–10.0μg) was administered to 41/2 and 5 day embryonic chicks (Hamburger‐Hamilton developmental stages 24–26) to investigate the effect of the drug on cardiovascular morphogenesis. The drug produced dose‐related increases in both mortality rate and malformation frequency with a maximum incidence of 82% cardiovascular anomalies following a dose of 10.0 μg/egg (P<.001 relative to saline controls). Frequencies of embryos with ventricular septal defect (P<.005), dextroposition of the aorta (P<.005), or aortic arch anomalies (P<.05) were significantly higher than among controls. In a second study, embryos were pretreated with ouabain (12.2 μg), verapamil (0.5 μg), coenzyme Q10(100 μg, 200μg), or vitamin E (1.0 mg, 5.0 mg)—agents previously shown to protect against adriamycin‐induced cardiotoxicity. Pretreatment of embryos with ouabain significantly reduced the incidence of cardiovascular malformations induced by adriamycin from 55 to 21% (P<.05). A major protective effect was observed relative to the induction of ventricular septal defect, the frequency of which was reduced from 45 to 14% (P<.05). However, administrations of verapamil, coenzyme Q10, or vitamin E did not have an appreciable effect on adriamycin‐induced frequencies of cardiovascular malformations. Negative inotropism is suggested as a mechanism for adriamycin‐induced cardiac anomalies but w

ISSN:0040-3709    

DOI:10.1002/tera.1420390608

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

年代:1989

数据来源: WILEY

摘要:

AbstractThe effects of sera from different types of human diabetes (type I with and without ketoacidosis; type II treated with insulin or Daonil or untreated) on the in vitro development of early preimplantation mouse embryos were studied. In controls, 20% of blastocysts failed to develop successfully when grown for 72 h in RPMI medium supplemented with 10% fetal bovine serum and 50% nondiabetic human serum. In experiments using 50% diabetic serum, the highest embryotoxic effect was found in type‐I diabetes with and without ketoacidosis: The percents of undeveloped embryos were 66 and 58, respectively. In type‐II diabetes, embryotoxic effects were found among all studied types: The percent of undeveloped blastocysts varied from 36% in insulin‐treated type‐II diabetes to 44% in untreated type‐II diabetes. A high correlation was found between the number of undeveloped embryos and the blood concentrations of metabolic diabetic factors: glucose (r = .53–.64 in type‐I diabetes), B‐HOB (r = .7–.77 in type‐II diabetes untreated or treated with Daonil), acetoacetate (r = .66 in insulin‐treated type‐II diabetes), and HbA1c(r = .89 in insulin‐treated type‐II diabetes or .99 in Daonil‐treated type‐II diabetes). A concentration of 80% serum was embryotoxic when obtained from nondiabetic or from diabetic human. The possible role of diabetic metabolic factors in causing increased risk of spontaneous abortions and infertility am

ISSN:0040-3709    

DOI:10.1002/tera.1420390609

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

年代:1989

数据来源: WILEY

摘要:

AbstractMany new chemicals come into use each year, and the need for rapid and cost‐effective methods for testing developmental toxicity is apparent. Establishing reliable in vitro techniques is important to a tier approach to testing for developmental toxicity. The fetal mouse salivary gland was selected as a possible test system because several interacting developmental processes occur in gland growth, and development is quantifiable by counting lobes. For each chemical tested, 20 glands from 13‐day embryos were treated in a control media and in three concentrations of the test chemicals. The number of lobes present after 48 hours is dependent on the number of lobes at explanation. Glands with different numbers of lobes at explantation were compared by dividing the number of lobes present after 48 hours by the number present at explantation to determine a growth ratio. Mean growth ratios were used to construct dose‐response curves, and from these curves the concentration that reduced growth by 50% (TP50) was determined. Comparisons with in vivo data were made by calculating three ratios; the TP50was divided into the lowest teratogenic dose, the lowest maternal toxic dose, and the dose that was lethal to 50%. Four in vivo teratogens, 6‐aminonicotinamide, cytochalasin B, hydroxyurea, and 3‐acetylpyridine, all had ratios much higher than 1, indicating a very sensitive response by the glands. One in vivo teratogen, dexamethasone, had much lower ratios, indicating less sensitivity. Acetaminophen, a nonteratogen in vivo, actually stimulated growth of the glands at 10−5M and had very low ratios indicating a minimal response by

ISSN:0040-3709    

DOI:10.1002/tera.1420390610

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

年代:1989

数据来源: WILEY

摘要:

AbstractThelidgap‐Steinmutation is one of a series of alleles that cause the birth defect open eyes in mice. Previously it was known that cortisone administered during pregnancy prevents the defect in somelidgap‐Steinfetuses. In this study, the hypothesis thatlidgap‐Steinis a hypomorph of effect intermediate between that of its alleleslidgap‐Miller(least abnormal) andlidgap‐Gates(most abnormal) was tested in a dose‐response, time‐response, and scanning electron microscopic study. Cortisone produced a response at doses of 20–80 mg/kg, with maximum cure of 30% in right eyes, 24% in left eyes, and 13% bilaterally. There was significantly more response in right than in left eyes. The response was slight at doses of less than 20 mg/kg and dropped to zero at the highest dose of 120 mg/kg. Treatment on days 13 or 14 gave the maximum response, with little or no response to treatment on days 10, 11, 12, 15, or 16. Severity of defect, measured as the size of gap in open eyes on day 18, was not reduced as the frequency of open eyes was reduced; most unclosed eyes remained wide open. The much lower level of maximum bilateral response to cortisone inlidgap‐Stein(13%) than inlidgap‐Miller(94%) is entirely compatible with the h

ISSN:0040-3709    

DOI:10.1002/tera.1420390611

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

年代:1989

数据来源: WILEY