ISSN:0040-3709    

DOI:10.1002/tera.1420460317

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

年代:1992

数据来源: WILEY

ISSN:0040-3709    

DOI:10.1002/tera.1420460302

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

年代:1992

数据来源: WILEY

ISSN:0040-3709    

DOI:10.1002/tera.1420460303

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

年代:1992

数据来源: WILEY

摘要:

AbstractWe reprot here a premature female infant with agnathia, lowset but normally formed ears, a downward eye slant, choanal atresia and a cleft palate. She had severe respiratory distress and died despite maximum intervantion at 5 days of age. Autopsy revealed situs inversus totalis; crossed fused renal ectopia; agnathia; normal thyroid, larynx, trachea, and bronchi; incomplete lobation of the lungs; immature pulmonary development with early hyaline membranes; and a normal central nervous system. This lack of significant central nervous system abnormalities distinguishes this infant from the majority of previously reported infants with agnathia and situs inversus. © 1992 Wiley‐Liss, I

ISSN:0040-3709    

DOI:10.1002/tera.1420460304

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

年代:1992

数据来源: WILEY

摘要:

AbstractDichloroacetic acid (DCA) is a principal by‐product of the chlorine disinfection of water containing humic and fulvic acids, and is also a drug of interest in the therapeutic management of metabolic disorders. The developmental effects of DCA were evaluated in the pregnant Long‐Evans rat. In two separate studies, animals were dosed by oral intubation on gestation days 6–15 (plug = 0) with 0, 900, 1,400 1,900 or 2,400 mg/kg/day and 0, 14, 140, or 400 mg/kg/day. The vehicle control was distilled water. Maternal observations included clinical signs, weight change, and gross evaluation of organ weights and uterine contents at necropsy (day 20). Corpora lutea were counted and uteri stained for implantation sites. Live fetuses were examined for external, skeletal, and soft tissue malformations. Seven dams died during treatment (1,400 mg 1/19, 1,900 mg 2/19, 2,400 mg 4/21), and maternal weight gain was reduced at all except the lowest treatment levels. Liver, spleen, and kidney weights increased in a dose‐related manner. The mean percentage of resorbed implants per litter was significantly elevated at ≥900 mg/kg/day. Live fetuses showed dose‐dependent reductions in weight and length at doses above 140 mg/kg. Statistically significant frequencies of soft tissue malformations ranged from 2.6% (140 mg/kg) to 73% (2,400 mg/kg). These were principally in the cardiovascular system and predominantly comprised defects between the ascending aorta and the right ventricle. Skeletal malformations were not observed in significant numbers in any dose group. We conclude that the no observed adverse effect level (NOAEL) for the developmental toxicity of DCA in the rat was 14 mg/kg/day, a dose level that produced obvious treatment‐related maternal effects. © 1992 W

ISSN:0040-3709    

DOI:10.1002/tera.1420460305

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

年代:1992

数据来源: WILEY

摘要:

AbstractDichloroacetic acid (DCA) is a by‐product of the chlorine disinfection of water and may occur in treated water at levels exceeding 100 μg/L. Previous studies revealed teratogenic effects, particularly heart malformations, at high doses (900–2,400 mg/kg given on days 6–15 of pregnancy). In a series of three studies, groups of 7–10 Long‐Evans rats were dosed with 1,900 mg/kg of DCA on days 6–8, 9–11, or 12–15; with 2,400 mg/kg on days 10, 11, 12, or 13; and with 3,500 mg/kg on days 9, 10, 11, 12, or 13, in an attempt to determine the most sensitive period and further characterize the heart defect. In a fourth study, six dams were treated with 1,900 mg/kg of DCA days 6–15 of pregnancy, and 56 fetuses were harvested for light microscopy of the heart. Eight control fetuses from four litters were also examined. No heart malformations were seen in the groups treated with 1,900 mg/kg DCA days 6–8 but were present in the group treated on days 9–11 and 12–15, with the higher incidence occurring on days 12–15. Single doses of 2,400 mg/kg DCA given on days 10, 11, 12, or 13 resulted in a much lower incidence of cardiac malformations, which occurred only on days 10 and 12. The high dose of DCA (3,500 mg/kg) did not increase the incidence of heart defects but showed that dosing on day 9 as well as on days 10 and 12 would produce the defect. The defects seen were characterized as high interventricular septal defects (H‐IVSD). Light microscopy showed that the defect was caudal to the semilunar valves, with the anterior right wall of the aorta communicating with the right ventricle. Another aspect of the defect is at the level of the semilunar valves, with the right cusp or sinus of Valsalva in communication with the right ventricle. The defects are discussed more fully and methods for further study sugge

ISSN:0040-3709    

DOI:10.1002/tera.1420460306

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

年代:1992

数据来源: WILEY

摘要:

AbstractThe immunomodulator tilorone hydrochloride was administered (gastric intubation) once to time‐pregnant Upj:TUC(SD)spf (Sprague‐Dawley) rats in four experiments. In experiment 1, tilorone (250 or 500 mg/kg) was administered on day 10 of gestation. The dams were killed 4 or 72 hr after dosing. Interferon‐like activity and drug levels were determined in maternal blood, spleen, and thymus, as well as in the embryos. In experiment 2, the test groups received progesterone (2 mg/kg), or tilorone (200 or 400 mg/kg), or progesterone and tilorone. The dams from each group were killed 24 or 48 hr after receiving tilorone. Experiment 3 was similar to experiment 2, except that the dams were killed on gestation day 20. In experiment 4, tilorone (400 mg/kg) was administered on gestation day 17, 18, or 19, and the dams were killed 24 hr after dosing or on gestation day 20. In all four experiments, tilorone‐related maternal toxicity (regardless of whether progesterone also was administered) was observed, as characterized by marked decreases in weight gain, the occurrence of clinical signs, and in experiment 1 by decreased thymus weights, 72 hr postdosing. Dose‐related increases in the mean number of dead embryos and in serum interferon titers occurred 72 hr postdosing. In experiment 2, there was an increase in the number of dams in the 400‐mg/kg (tilorone only) group with dead embryos only, 24 hr postdosing; similar results occurred in both the 200‐ and 400‐mg/kg groups, 48 hr postdosing. However, in the groups that also received progesterone, a partial prevention of such embryolethality was evident. In experiment 3, embryotoxicity again was observed in both tilorone‐treated groups, whereas several of the dams that were also given progesterone through day 19 of gestation experienced at least a partial prevention of the embryolethal effects of tilorone. In experiment 4, no fetotoxicity was observed despite the severe maternal toxicity evident. © 19

ISSN:0040-3709    

DOI:10.1002/tera.1420460307

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

年代:1992

数据来源: WILEY

摘要:

AbstractAcute exposures to sodium arsenite (50 μM) were embryotoxic in day 10 rat embryos exposed in vitro. Sodium arsenite–induced embryotoxicity was characterized by decreased growth (crown‐rump length, somite number, and embryo protein content) and abnormal development (hypoplastic prosencephalon, abnormal somites, and abnormal flexion of the tail). At embryotoxic exposures, sodium arsenite also induced the synthesis of three heat shock proteins (hsps), one of which is recognized by a monoclonal antibody specific for the heat‐inducible hsp 72. In addition, sodium arsenite induced the accumulation of heat‐inducible hsp 70 mRNA. Although the abnormal morphologies induced by sodium arsenite and hyperthermia appear to be different, the stress response as measured by the synthesis of hsps, the accumulation of hsp 72 protein, and the accumulation of hsp 70 mRNA is similar in embryos exposed to these two embryotoxic agents. Thus, sodium arsenite and hyperthermia both induce a stress response; however, the relationship between the induction of a stress response and the subsequent abnormal development that ensues is unclear. © 1992 Wiley

ISSN:0040-3709    

DOI:10.1002/tera.1420460308

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

年代:1992

数据来源: WILEY

摘要:

AbstractIn data of the U.S. Collaborative Preinatal Study (CPS), the Drug Epidemiology Unit (DEU) reported a relative risk of about 2.3 between maternal female sex hormone exposure during months 1 to 4 of pregnancy and cardiovascular malformation in infants (Heinonen et al., '77a N. Engl. J. Med.,296:67–70). Wiseman and Dodds‐Smith ('84) reexamined the original CPS data and found the DEU had made errors in classification of exposure and disease of some cases. Also they challenged the classification of cases as “exposed” in those born to mothers who received the compounds outside the day 19 to 50 window of cardiovascular embryogenesis. Wiseman and Dodds‐Smith stated that their reanalysis “clearly showed that there was [in the data used by the DEU] no statistically significant association between exposure in the critical organogenic period of pregnancy and cardiac malformation in offspring.” They did not undertake any statistical analysis, but their reanalysis resulted in a widespread nonacceptance of the association reported by the DEU. The study reported here reclassified the cases of the original DEU study in accord with the implications of the Wiseman and Dodds‐Smith reanalysis of exposure and disease. After this reclassification, an effect magnitude measure of association, the relative risk rose from 2.33 to 2.48 and remained nominally significant statistically at the .05 level. Thus, if anything, the quantitative consequences of the Wiseman and Dodds‐Smith review of the data, when applied in an unbiased manner, result in an increase in the measure of effect. The increase is consistent with the theoretical epidemiological expectation that correction of random errors in a database and of other non‐differential misclassification, willtendto raise the estimate of an underlying association in the population studied. While these results reestablish the reported association, they do not, of course, prove that the positive association represents causal induction of defects in conceptuses by female sex hormones. ©

ISSN:0040-3709    

DOI:10.1002/tera.1420460309

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

年代:1992

数据来源: WILEY

摘要:

AbstractA recent case report by Shepard et al. (Teratology43:113–117, 1991) suggested that single ventricle may result from maternal cocaine ingestion by inducing coronary occlusion in the developing fetal heart. We used data from the Atlanta Birth Defects Case‐Control Study and the Metropolitan Atlanta Congenital Defects Program (MACDP) to investigate the role of maternal cocaine ingestion in the induction of single ventricles. We identified through the MACDP 58 case infants with a single ventricle, 27 who were study subjects in the Atlanta Birth Defects Case‐Control Study, and 31 who were not. We conducted a case‐control study with the 27 Atlanta Birth Defects Case Control Study infants, frequency‐matched to control infants by race, hospital of birth, and calendar quarter of birth. None of the 27 case infants were exposed to cocaine during early pregnancy, but 7 (0.43%) of the control infants were exposed during early pregnancy. Using MACDP data, we conducted an analysis of trends for prevalence of single ventricle in the metropolitan area. No upward trend in single ventricle was detected for 1968 through 1990. Our data suggest that even if maternal cocaine ingestion during pregnancy is a cause of single ventricle, most cases appear to be unrelated to this exposure. © 1992 Wiley

ISSN:0040-3709    

DOI:10.1002/tera.1420460310

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

年代:1992

数据来源: WILEY