bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of developmental toxicity of coniine to rats and rabbits
Authors: Forsyth Carol S. , Frank Anthony A. 
Published: June 2005

AbstractConium maculatum (poison hemlock, CM) is teratogenic in several domestic species, presumably due to its piperidine alkaloids, including coniine, which has been verified to be teratogenic in cattle. Coniine/CM teratogenicity culminates in production of arthrogryposis. The purpose of this study was to evaluate coniine‐induced teratogenicity in two laboratory animal species, Sprague‐Dawley rats and New Zealand white rabbits. Pregnant rats were given coniine (25 mg/kg body weight) by oral gavage at 8‐hour intervals on gestation days 16–18. Pregnant rabbits were given coniine (40 mg/kg body weight) by oral gavage at 8‐hour intervals on gestation days 20–24. Rats were killed on day 19 and rabbits on day 29. Fetuses were immediately removed, weighed, and examined for external abnormalities. Alternate fetuses were either stained for skeletal examinations with alizarin red‐S or fixed in Bouin's solution for visceral examination. Symptoms of maternal intoxication due to coniine administration were observed in both the rat and the rabbit, and higher doses were uniformly lethal. Rabbits treated with coniine appeared to lose more weight and eat less than controls, but there was no statistically significant difference between groups. Fetal weights were significantly lower in coniine‐exposed rat and rabbit fetuses indicating fetotoxicity. The only statistically significant treatment‐related visceral or skeletal malformation was a reduction of cranial ossification of rabbit fetuses, probably related to maternal toxicity. Coniine‐exposed rabbit litters tended to be affected by arthrogryposis (no bony deformities noted on skeletal exam) more than controls (2/6 vs. 0/9). The lesion was characterized as hyperflexion of the antebrachial‐carpal joint with supination. Although this was not statistically significant, the incidence rate was significantly (p < 0.01) increased when compared to historical controls. This study indicates coniine is not teratogenic to rats and weakly teratogenic to rabbits. The reason for the lack of sensitivity to teratogenicity in these laboratory animal species as compared to domestic species is currently unknown. © 1993 Wiley‐Liss, Inc.
Methyl methacrylate: Inhalation developmental toxicity study in rats
Authors: Solomon H. M. , McLaughlin J. E. , Swenson R. E. , Hagan J. V. , Wanner F. J. , O'hara G. P. , Krivanek N. D. 
Published: June 2005

AbstractMethyl methacrylate (99.9% pure) was administered by vapor inhalation exposure to five groups (27 rats/group) of presumed pregnant rats (Crl:CD) at concentrations of 0 (control), 99, 304, 1,178, and 2,028 ppm for 6 hr/day on days 6–15 of gestation (G). Maternal body weight, feed consumption, and clinical signs were recorded throughout gestation. Dams were euthanized on day 20 G. Each uterus was weighed and corpora lutea, implantation sites and resorptions were counted. The number of fetuses per litter were counted and their location within the uterus recorded. All fetuses were weighed, sexed and examined for external and skeletal alterations. One half of the fetuses from each litter were examined for visceral alterations. No treatment‐related deaths were noted at any concentration tested. Treatment‐related effects on maternal body weight and feed consumption were noted at all exposure levels. The decreases in maternal body weight at 99 and 304 ppm were minimal and transient since they returned to control values by the next weighing period. When exposure was discontinued, body weight gain and feed consumption in all exposure groups returned to control values. There were no treatment‐related changes in the number of litters produced or in the mean number per litter of corpora lutea, implantations, resorptions, live or dead fetuses, or sex ratio. Fetal body weights were similar between the control and treated groups. There were no treatmentrelated increases in the type or incidence of external, visceral, or skeletal malformations, developmental variations, or variations indicative of retarded development. Exposure to methyl methacrylate concentrations up to 2,028 ppm resulted in no embryo or fetal toxicity or malformations even at exposure levels that resulted in maternal toxicity. © 1993 Wiley‐Liss, Inc.
Sodium valproate‐induced cardiovascular abnormalities in the Jcl:ICR mouse fetus: Peak sensitivity of gestational day and dose‐dependent effect
Authors: Sonoda Tohru , Ohdo Shozo , Ohba Ken‐Ichi , Okishima Takahiro , Hayakawa Kunio 
Published: June 2005

AbstractSodium valproate was administered to Jcl:ICR mice in order to determine its effect on cardiovascular development. A single dose of 600 mg/kg of sodium valproate was injected intraperitoneally on gestational days 6, 7, 8, or 9. In same animals, a single dose of 300, 400, 500, or 700 mg/kg was injected on gestational day 7. On day 18 of gestation, dams were laparotomized to observe number of live, dead and resorbed fetuses. In addition, live fetuses were examined for cardiovascular abnormalities. Although cardiovascular abnormalities were noted in 3% of live fetuses and in 26% of litters in the group treated on day 6 (600 mg/kg), there was no significant difference from the control group, suggests that there may have been a biologically significant increase, although not a statistically significant increase. Cardiovascular abnormalities were found in 30%, 11%, and 8% of live fetuses in the groups treated with 600 mg/kg on days 7, 8, and 9, respectively. These represented a statistically significant increase in effects as opposed to the control groups. Among the varying dosages administered on day 7 of gestation, cardiovascular abnormalities occurred in 2%, 6%, 16%, and 36% of live fetuses in groups treated with 300, 400, 500, and 700 mg/kg, respectively, showing a significant dose‐dependent increase. These cardiovascular abnormalities observed were divided into the following groups: ventricular septal defect, endocardial cushion defect, transposition of the great arteries, doubleoutlet right ventricle, tricuspid atresia, and hypoplastic left heart syndrome. Maternaldeath did not occur at any treatment level. © 1993 Wiley‐Liss, Inc.
Prevention by Tiron (sodium 4,5‐dihydroxybenzene‐1,3‐disulfonate) of vanadate‐induced developmental toxicity in mice
Authors: Domingo Jose L. , Bosque M. Angeles , Luna Margarita , Corbella Jacinto 
Published: June 2005

AbstractVanadate is embryotoxic and fetotoxic in golden hamsters, mice and rats. Tiron (sodium 4,5‐dihydroxybenzene‐1,3‐disulfonate), a chelating agent widely used in analytical chemistry, is an effective antidote in the treatment of oral or parenteral vanadate poisoning. The present study evaluated the effect of administration of Tiron on sodium metavanadate (NaVO3)‐induced developmental toxicity in mice. NaVO3 (25 mg/kg, i.p.) was injected on day 12 of gestation, whereas Tiron was injected subcutaneously at 0, 24, 48, and 72 hr after NaVO3 administration. Tiron effectiveness was assessed at dosage levels of 0, 250, 500, and 1,000 mg/kg. Cesarean sections were performed on gestation day 18. All live fetuses were examined for external, internal, and skeletal malformations and variations. Amelioration by Tiron of NaVO3 developmental toxicity was evidenced by a significant decrease in the number of resorbed fetuses, an increase in the mean fetal weight, and a reduction in the incidence of the skeletal variations caused by NaVO3. According to these results, Tiron offers encouragement with regard to its therapeutic potential for pregnant women exposed to vanadate. However, further investigations, including the effect of increasing the time interval between acute vanadate exposure and initiation of Tiron therapy, are required. © 1993 Wiley‐Liss, Inc.
Retinoic acid induces changes in the rhombencephalic neural crest cells migration and extracellular matrix composition in chick embryos
Authors: Balbás J. A. Moro , Gato A. , Revuelta M. I. Alonso , Pastor J. F. , Represa J. J. , Barbosa E. 
Published: June 2005

AbstractChick embryos at 9–10 stages (Hamburger and Hamilton: J Morphol 88:49–82, 1951) have been treated with all‐trans retinoid acid (RA) (0.5 μg, 1.5 μg, and 2.5 μg) to determine the pattern and mechanism of RA‐induced effects on early cephalic development. We found that while 0.5 μg RA did not produce any significant dysmorphogenesis, 2.5 μg RA elicited wide malformation of both cephalic and trunk regions. However, 1.5 μg RA produced selective and specific changes at the cephalic level, which consisted of morphological alterations, changes in neural crest cells (NCC) migration and extracellular matrix (ECM) composition. Morphological alterations included hypoplasia of the first three branchial arches, swelling of either anterior cardinal veins or dorsal aortae, and atrophy of branchial arch arteries. Concurrently NCC did not migrate away, remaining clustered on the dorsal surface of the rhombencephalon, and in some cases they shifted into the neural tube cavity. Accordingly, the second branchial arch showed a reduction of the mesenchymal cellular population. The extracellular matrix in RA‐injected embryos showed changes in glycosaminoglycans (GAGs) concentration as compared with controls, that is, an increase in the non‐sulphated GAGs, stained with alcian blue 8GX at 2.5 pH, and a decrease in the sulphated GAGs stained with alcian blue 8GX at 1 pH. These quantitative changes reflected alterations in the pattern of distribution and composition of the GAGs within the cephalic ECM, which specifically consisted in an increase of the hyaluronic acid and a decrease of the chondroitin sulphate. Our findings indicate that RA is involved in abnormal cephalic development, suggesting that RA may effect neural crest cell migration via changes in the GAGs of the ECM. © 1993 Wiley‐Liss, Inc.
Cadmium‐induced inhibition of proliferation and differentiation of embryonal carcinoma cells and mechanistic aspects of protection by zinc
Authors: Piersma A. H. , Roelen B. , Roest P. , Haakmat‐Hoesenie A. S. , Van Achterberg T. A. E. , Mummery C. L. 
Published: June 2005

AbstractMurine embryonal carcinoma cells have been used in in vitro models to study the effects of cadmium chloride on proliferation and differentiation of early embryonic cells. This approach allows the various cell types within the early embryo as well as several developmental mechanisms to be dissected and studied in isolation using larger numbers of cells than would be readily available from the embryo itself. The present study shows that both embryonal carcinoma cell proliferation and differentiation into parietal endoderm are inhibited by cadmium chloride. The effects are counteracted by the additional presence of zinc chloride. The uptake of cadmium into the cells is inhibited in the presence of zinc chloride, suggesting that competition between these metals for passage into the cells contributes to the mechanism underlying the protective effect of zinc. In addition, metallothionein gene expression is enhanced more rapidly after simultaneous incubation with zinc chloride, indicating that the attenuating effect of zinc on cadmium toxicity is also partly attributable to detoxification by metallothioneins. © 1993 Wiley‐Liss, Inc.
Real time micro‐fiberoptic monitoring of endogenous fluorescence in the rat conceptus during hypoxia
Authors: Thorsrud Bjorn A. , Harris Craig 
Published: June 2005

AbstractA micro‐fiberoptic methodology has been developed for noninvasive, real time measurement of endogenous pyridine nucleotide fluorescence from the surface of the visceral yolk sac (VYS) in intact, viable rat conceptuses. Gestational day (GD) 10–12 conceptuses are maintained in a customized perifusion system, which allows for control of oxygenation, as well as the continuous measurement of pH and oxygen concentration in the effluent perifusate. Miniaturized light guides were constructed by drawing 250 μm ESKA acrylic optical fibers through a stainless steel sheath with a high strength epoxy polymer. A single fiber supplied the excitation signal from a mercury arc lamp at a wavelength of 366 nm. The emission signal was returned via three additional fibers, electronically amplified, processed, and recorded, using a dual channel lamp‐compensated fluorometer, optimized for detection of reduced pyridine nucleotides at 455 nm. Endogenous fluorescence in the conceptus was monitored by placing the polished tip of the sensor directly on the surface of the VYS. Oxygen‐equilibrated conceptuses, exposed to 100% nitrogen, produced a reproducible biphasic surface fluorescence peak, which returned to baseline levels upon reoxygenation of the perifusate. This biphasic response consisted of an initial rapid rise in fluorescence (phase I), followed by an attenuated rate in fluorescence signal increase (phase II). The hypoxia produced age‐dependent rates of fluorescence change during phase I, while phase II remained relatively unchanged throughout GD 10–12. These results demonstrate the ability to monitor endogenous fluorescence, non‐invasively and in real time, during the period of organogenesis in the intact rat conceptus and will provide valuable information in studies of embryonic metabolism and response to chemical embryotoxicants. © 1993 Wiley‐Liss, Inc.
Effect of in utero exposure to diagnostic ultrasound on the postnatal survival and growth of mouse
Authors: Hande M. Prakash , Devi P. Uma 
Published: June 2005

AbstractPregnant Swiss albino mice were exposed to 3.5 MHz diagnostic ultrasound for 10 min (upper limit for ISPTP = 1 W/cm2 and for ISATA = 240 m W/cm2, acoustic power = ∼65 m W) on day 3.5 (preimplantation period), 6.5 (early organogenesis period), 11.5 (late organogenesis period), or 14.5 (early fetal period) of gestation. The offspring were observed for changes in litter size at birth, and sex ratio at 4 weeks of age, and postnatal mortality and growth retardation up to 6 weeks of age. No significant difference from control in litter size or sex ratio was observed in the offspring exposed to ultrasound on any of the gestation days studied. Exposure at the early organogenesis period produced a marginally significant increase in the postnatal mortality. A significant number of ultrasound exposed animals showed lesser body weights than the control group. However this growth retardation was transient and the normal growth pattern was restored by 6 weeks of age. It is concluded that the early stages in mouse gestation may be sensitive to the lethal effects of ultrasound than the later stages of pregnancy. Even though a small increase in the postnatal mortality was observed in the ultrasound exposed animals, the normal growth was not affected in the surviving animals except for a transient growth retardation. Low birth weight may be a characteristic effect of exposure only at the preimplantation period. © 1993 Wiley‐Liss, In.
In vitro embryotoxicity of N‐methyl‐N‐(7‐propoxynaphthalene‐2‐ethyl)hydroxylamine (QAB): Evidence for N‐dehydroxylated metabolite as a proximate dysmorphogen
Authors: Terlouw Gerrard D. C. , Namkung Moses J. , Juchau Mont R. , Bechter Rudolf 
Published: June 2005

AbstractThe rat conceptus biotransforms N‐methyl‐N‐(7‐propoxynaph‐thalene‐2‐ethyl) hydroxylamine (QAB) in vitro to 7‐propoxynaphthalen‐2‐ylacetic acid (QAA) and six more (M1 to M6) metabolites. Thus far, M4 has been identified as N‐demethyl‐QAB and M6 as N‐desoxy‐QAB. We investigated which of these two metabolites might be involved in QAB‐embryotoxicity in vitro. Conceptuses were cultured from day 9.5 to 11.5 post‐coitum, and were exposed to N‐demethyl‐QAB or N‐desoxy‐QAB either in the culture medium or by microinjection directly into the amniotic cavity. When added to the culture medium, N‐demethyl‐QAB (No Observed Adverse Effect Level, NOAEL, for growth 122 μM and for differentiation 41 μM) was less active than QAB itself (NOAEL for growth and differentiation 12 μM). N‐desoxy‐QAB caused severe growth retardation and an impairment of differentiation at a concentration of 11 μM (NOAEL 3.6 μM). As regards causing anomalies, the NOAEL of N‐demethyl‐QAB (41 μM) was 10‐fold higher than that of QAB (NOAEL 3.9 μM) and that of N‐desoxy‐QAB (NOAEL 3.6 μM). At an intraamniotic concentration of 0.7 mM, N‐demethyl‐QAB caused no effects on growth and differentiation and no increase of anomalies was observed, whereas QAB and N‐desoxy‐QAB each elicited an increase in dysmorphogenic embryos at equimolar concentrations without affecting growth and differentiation. It is, therefore, concluded that N‐desoxy‐QAB, but not N‐demethyl‐QAB, could be a proximate dsymorphogen responsible for the embryotoxicity/teratogenicity of QAB in vitro.© 1993 Wiley‐Liss, Inc.
Descriptive epidemiology of small intestinal atresia, Atlanta, Georgia
Authors: Cragan Janet D. , Martin M. Louise , Moore Cynthia A. , Khoury Muin J. 
Published: June 2005

AbstractTo describe the epidemiology of small intestinal atresia (SIA) in Atlanta, Georgia, from 1968 through 1989, we used the Metropolitan Atlanta Congenital Defects Program, an active, population‐based surveillance system for birth defects diagnosed during the first year of life. We identified 176 infants with SIA, a prevalence of 2.8 per 10,000 livebirths. Among black infants, the prevalence was 3.7 per 10,000 livebirths, significantly higher than the prevalence of 2.4 per 10,000 among white infants [relative risk (RR) = 1.6, 95% confidence interval (CI) = 1.1,2.1]. Nine infants were each one member of a unique pair of twins. The prevalence among twin infants was 7.3 per 10,000, significantly higher than the prevalence of 2.8 per 10,000 among singletons (RR = 2.7, 95% CI = 1.4,5.2). Forty‐nine percent of the infants had duodenal atresia, 36% had jejunal atresia, and 14% had ileal atresia. Two infants (1%) had atresia at an unspecified site in the small intestine. We grouped the infants by anatomic location of SIA into four categories: isolated SIA (53%), SIA with multiple unrelated defects (21%), sequences (16%), and syndromes (10%). We then compared the isolated and multiple unrelated defects groups by gender, race, maternal age, birth weight and one‐year mortality for each location of SIA. Among black infants the prevalence of isolated jejunal atresia was 1.4 per 10,000, significantly higher than the prevalence of 0.2 per 10,000 among white infants (RR = 6.3, 95% CI = 2.9, 13.5). The increased prevalence of these defects among twins was a particularly interesting finding. © 1993 Wiley‐Liss, Inc.This article is a US Government work and, as such, is in the public domain in the United States of America.
Patterns of growth deficiency in rats exposed in utero to undernutrition, ethanol, or the neuroteratogen methylazoxymethanol (MAM)
Authors: Gavin Claire E. , Kates Barbara , Gerken Laurie A. , Rodier Patricia M. 
Published: June 2005

AbstractChildren and experimental animals exposed to ethanol (EtOH) in utero commonly have low birthweights, and many remain small at maturity. Low body weight or small stature in adulthood may reflect an inability to recover from in utero growth retardation, or it may reflect a separate, postnatal growth deficiency. In this study, daily body weights (postnatal days 1 to 60) were compared among the offspring of the following groups of Long Evans rats: dams fed liquid diet containing 35% EtOH‐derived calories; their pairfed and chow‐fed controls; and dams exposed to methylazoxymethanol (MAM) in two previous studies, in which offspring exhibited reduced numbers of growth hormone releasing factor (GRF) neurons. All treatments produced a number of offspring with weight deficits beginning after birth and persisting into maturity. Three distinct patterns of growth deficiency were observed: (1) weight loss relative to controls in the first weeks of life, seen in offspring exposed to EtOH, pair feeding, or MAM on gestation day 13 (G13); (2) a delay in the onset of the prepubertal growth spurt, seen in all EtOH‐exposed offspring and in G13 MAM‐exposed dwarfs; and (3) failure to sustain the prepubertal growth spurt, seen only after exposure to MAM on G14. The results of this study support the view that prenatal EtOH exposure is capable of affecting postnatal growth specifically; moreover, the pattern of growth deficiency seen in EtOH‐exposed offspring was distinct from that of the undernourished offspring of pair‐fed dams. © 1994 Wiley‐Liss, Inc.
Epidemiologic characteristics of phenotypically distinct neural tube defects among 0.7 Million California births, 1983–1987
Authors: Shaw Gary M. , Jensvold Nancy G. , Wasserman Cathy R. , Lammer Edward J. 
Published: June 2005

AbstractIsolated neural tube defects (NTDs) appear to have different risk factors compared to nonisolated NTDs. To extend those observations, we explored routinely collected child and parental characteristics as possible risk factors among isolated versus nonisolated NTD cases, among high versus low spina bifida cases, and among open versus skin‐covered spina bifida cases. Fetuses and liveborn infants with anencephaly or spina bifida among the 1983‐‐87 cohort of births and fetal deaths (n = 712,863) were ascertained by the California Birth Defects Monitoring Program. One hundred and ninety‐three anencephalic cases and 272 spina bifida cases were compared to a random sample of 5,000 liveborn infants. Among anencephalic cases, 55% were livebirths and 85% were isolated. The proportion of males was similar to females across all subgroups. Increased risks were found for Hispanic whites, with risk estimates highest for nonisolated cases (odds ratio = 4.0, 95% confidence interval [1.5,10.5]). Among spina bifida cases, 92% were livebirths, 81 % isolated, 82% open, and 86% were low. More males were found among the group with isolated high open defects, and fewer males were found among the group of all closed defects. The proportion of males was similar to females in all other subgroups. Cases were more likely to be Hispanic with risks largest for high open defects (odds ratio = 2.9, [1.2,6.6]), particularly for nonisolated cases. This study provides some evidence that further classifications of NTDs may reveal subgroupings of cases with different etiologies. © 1994 Wiley‐Liss, Inc.