摘要:

AbstractThe present studies evaluated the teratogenic potential and reproductive toxicity of Policosanol, a new hypocholesterolemic drug. Policosanol was administered by oral gavage to Sprague‐Dawley rats and New Zealand White rabbits during the period of organogenesis at dosages up to 500 and 1,000 mg/kg/day, respectively. There was no evidence of teratogenicity or any other embryonal toxicity. In a fertility and reproductive study female rats were treated with Policosanol by oral gavage at dosages up to 500 mg/kg/day, 2 weeks prior to mating and throughout mating and pregnancy to day 21 of lactation. Males were given treatment 60 days before and during mating. Reproductive parameters of mothers were normal. There was no evidence that treatment affected the survival, postnatal growth, or behavior of the offspring. No maternal treatment‐related adverse side effects occurred in these studies. It is concluded that Policosanol was not teratogenic in either rats or rabbits, nor did it induce reproductive toxicity in rats. © 1994 Wiley‐Lis

ISSN:0270-3211    

DOI:10.1002/tcm.1770140302

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

年代:1994

数据来源: WILEY

摘要:

AbstractThe dose‐response of the teratogenic potency of the thalidomide (Thd) derivative EM12 was evaluated in the common marmoset (Callithrix jacchus). The smallest daily dose found to be effective was 30 μg EM12/kg body wt. This is the lowest dose of a Thd derivative ever reported to induce severe skeletal abnormalities. Ten micrograms EM12/kg body wt may be considered the no‐observed‐adverse‐effect‐level (NOAEL) under the experimental conditions chosen.The teratogenic potencies of the two EM12 enantiomers were tested at 100 μg/kg body wt, the dose which just induces an almost 100% effect in the case of the racemate. The S(−)‐EM12 was found to induce typical severe limb abnormalities such as amelia, phocomelia, and radius aplasia, and none of the exposed fetuses were devoid of skeletal defects. In contrast, only few and minor skeletal defects were observed after application of the R(+) enantiomer. Although a pronounced teratogenic potency of the R(+)‐EM12 can now largely be excluded, these low‐dose studies are not sufficient to completely rule out any teratogenic potential of this enantiomer, since racemisation to small amounts of the S(−) form may occur in vivo.Further studies with Thd derivatives which are unable to racemise are necessary to prove the assumed complete ineffectiveness of the R(+) enantiomers.

ISSN:0270-3211    

DOI:10.1002/tcm.1770140303

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

年代:1994

数据来源: WILEY

摘要:

AbstractChick embryos were exposed intra‐amniotically to the thymidine analog bromodeoxyuridine (BrdU) in order to study its embryotoxic and genotoxic effects. Teratogenic effects were observed at doses of BrdU which failed to produce mitotic inhibition, clastogenic effects or any significant increase in sister chromatid exchanges. Clastogenic effects and depressed cell proliferation were observed only at high embryolethal doses. Thus, BrdU‐induced teratogenicity was independent of genotoxic effects manifested at chromosomal level. On the contrary, a significant increase of DNA single strand breaks was detected even 24 hours after the administration of teratogenic dose. BrdU incorporation in the DNA does not appear to prevent embryonic cells from mitotic proliferation. Whether the single strand breaks in DNA would ultimately lead to BrdU‐induced teratogenesis in chick embryos remained undetermined. © 1994 Wiley‐L

ISSN:0270-3211    

DOI:10.1002/tcm.1770140304

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

年代:1994

数据来源: WILEY

摘要:

AbstractThis study was performed to determine whether malformations induced inXenopus laevisembryos by exposures to divalent nickel, cobalt, or cadmium chlorides in FETAX assays persist after the tadpoles undergo metamorphosis to juvenile frogs. Embryos were exposed for four days to EC50concentrations of Ni2+, Co2+, or Cd2+under the standard conditions of FETAX assays; thereafter, the exposures were discontinued and the tadpoles were kept in aquaria through metamorphosis. Controls were treated similarly, without exposure to metals. At 13 weeks of age, surviving frogs were killed and examined for malformations. Control and metal‐exposed groups ofXenopusdid not differ significantly in their median ages at metamorphosis, mean body weights, or survival at 13 weeks. Overall incidences of malformations found in Ni2+−, Co2+−, or Cd2+−exposed frogs at 13 weeks of age were 55, 40, and 51%, respectively (P<0.01 vs. 3% in controls). The malformations of metal‐exposed frogs included retinal depigmentation, diastematomyelia, scoliosis, kyphosis, phocomelia, sacro‐pelvic and hind‐limb deformities, and dysplasias of the heart, kidney, ovary, and gut. © 1994 W

ISSN:0270-3211    

DOI:10.1002/tcm.1770140305

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

年代:1994

数据来源: WILEY

摘要:

AbstractWe report here the results obtained using the dithiocarbamate fungicides thiram and ziram to investigate the induction of chromosomal aberrations (CAs) in Chinese hamster ovary (CHO) cells both in the absence and presence of S9 metabolism, and in a Chinese hamster epithelial liver (CHEL) cells which retain metabolic competence to activate different classes of promutagens/procarcinogens. Both thiram and ziram proved to be strong chromosome breaking agents in the CHEL cells and CHO cells in the presence of S9 metabolism. These findings suggest that thiram and ziram require metabolic conversion to become genetically active, and corroborate the evidence that CHEL cells are suitable to activate and detect a broad spectrum of chemical procarcinogens including these two pesticides. © 1994 Wiley‐Liss, I

ISSN:0270-3211    

DOI:10.1002/tcm.1770140306

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

年代:1994

数据来源: WILEY

ISSN:0270-3211    

DOI:10.1002/tcm.1770140301

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

年代:1994

数据来源: WILEY