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At least 19 recordsLinked to original sources

PubMed1976

Lupin alkaloids from teratogenic and nonteratogenic lupins. IV. Concentration of total alkaloids, individual major alkaloids, and the teratogen anagyrine as a function of plant part and stage of growth and their relationship to crooked calf disease.

The concentrations of total alkaloids and individual major alkaloids including the teratogen anagyrine were measured in various plant parts of teratogenic lupins as the plants matured. All alkaloids including angyrine were high in concentration in above-ground parts early in growth and decreased as plants matured, except for an increase in mature, intact seeds. Seeds were highest, followed by early growth leaves and stems. Roots were lowest with mature leaves and stems only slightly higher. Pregnant cows have the greatest risk of giving birth to calves with crooked calf disease when the concentration of the teratogen anagyrine is highest and the cows are in the susceptible 40-75 day gestation period when ingesting the plant.

Abnormalities, Drug-Induced↗

PubMed1976

Lupin alkaloids from teratogenic and nonteratogenic lupins. III. Identification of anagyrine as the probable teratogen by feeding trials.

Alkaloidal extracts from teratogenic lupins produced congenital deformities in calves typical of crooked calf disease when the extracts were administered to pregnant cows during the susceptible gestational period. These data and previous epidemiologic studies suggest that one of the four alkaloids in the preparation, anagyrine, is the responsible teratogen. Severity of the malformations was directly related to the level of anagyrine present in the preparations administered.

Abnormalities, Drug-Induced↗

PubMed1978

Cholinomimetic teratogens. VI. The interaction of cholinomimetic teratogens with the antimalarial drugs chloroquine and chlorguanide.

A typical syndrome of short and crooked neck together with muscular hytoplasia of the legs occurs with low incidence in chicken embryos following injection into the egg at 24 hours of incubation of the antimalarial drug chloroquine; but treatment at later stages does not have similar effects. When, however chloroquine was used in addition to carbachol or neostigmine at 96 hours of incubation the malformations caused by the two cholinomimetic compounds, i.e., carbachol and neostigmine, occurred with greatly increased frequency and tended also to be exaggerated in expression. Chlorguanide, another antimalarial drug, when used as additive, reduced the teratogenic effects of such compounds as decamethonium and neostigmine. It appears that the neuromuscular pathways to teratogenicity are for carbachol and neostigmine and for chloroquine clearly related, if at different levels of expressivity.

Abnormalities, Drug-Induced↗

PubMed1975

Teratogenicities of ophthalmic drugs. II. Teratogenicities and tissue accumulation of thimerosal.

Under the conditions of this study, systemically or topically applied thimerosal was found to have no teratogenic effect even when given in concentrations approaching the 50% lethal dose of these compounds. A comparison of topical and subcutaneous administration of thimerosal to rabbits shows that a substantial concentration of mercury was present in blood and tissues of the treated animals and their offspring. Thimerosal was found to cross the blood-brain and placenta barriers.

Administration, Topical↗

PubMed1978

Cyclopamine and related steroidal alkaloid teratogens: their occurrence, structural relationship, and biologic effects.

A spontaneous congenital deformity is produced in lambs whose dams consume Veratrum californicum on the 14th day of gestation. The deformity is generally expressed as cyclopia, cebocephaly, anophthalmia, or microphthalmia. This teratogenic effect is produced by certain steroidal alkaloid teratogens from the plant - most notably the compound cyclopamine. Cyclopamine is a C-nor-D-homo steroid with fused furanopiperidine rings E and F at right angles to the plane of the steroid because of spiro attachment at C-17 of the steroid. Among veratrum alkaloids, only those with an intact furan ring E were teratogenic in sheep, whereas those in which the peperidine ring is not rigidly positioned at right angles to the steroid were not. Many ruminants and laboratory animals are susceptible to the teratogen. It has wide species and tissue specificity and appears to have a direct effect on the embryo, not as a consequence of metabolic alteration of its structure nor as an indirect effect through a maternal influence. Other plant sources, notably potatoes, tomatoes, and eggplant contain related spirosolane steroidal alkaloids. Among naturally occurring spirosolanes, solasodine is teratogenic in hamsters, but neither tomatidine not diosgenin, the non-nitrogen containing analog of solasodine, is teratogenic. Results of these and other studies suggest that a basic nitrogen positioned alpha with respect to the steroidal plane and at appropriate distance beyond the D ring confers the teratogenicity on the molecule. Potato sprouts with high alkaloid content are teratogenic in hamsters, but tubers and peels are not.

Abnormalities, Drug-Induced↗

PubMed1992

The heat shock response: potential to screen teratogens.

The embryonic stress hypothesis of teratogenesis suggests that a proportion of all human congenital defects is due to a failure in essential gene transcription along with translational pre-emption by the heat shock response (HSR). We sought to determine the potential usefulness of the murine HSR to screen agents suspected of being human teratogens. The teratogenic potential of a selected group of known teratogenic (hyperthermia, insulin, retinoic acid and valproic acid) or non-teratogenic (cycloheximide, dinitrophenol and tetracycline) agents were administered to pregnant SWV mice at critical periods of neural tube closure. Following exposure to either teratogenic doses or at the highest dose possible that did not induce maternal toxicity for those compounds that were not teratogenic, the induction of heat shock protein (hsp) synthesis and changes in total protein synthesis were determined in lymphocytes isolated from murine spleens. The varied results obtained in these studies cast doubt on the value of the murine HSR to screen teratogens.

Abnormalities, Drug-Induced↗

PubMed1976

Methods for detecting teratogenic agents in man.

At a multidiscipline international meeting sponsored by L'Institut de la Vie held at Guadeloupe in January 1974, current methods for detecting teratogenic agents were outlined and discussed. Recommendations of the participants of the conference were: recognize the limitations of the present defenses against teratogenic agents; educate the public and medical profession about the known human teratogenic agents; select for animal teratogenicity screening among new and existing agents by emphasizing substances to which the entire population will be exposed, agents to which pregnant women are exposed, viruses which are found to persist in the human fetus, and agents which have become suspect from clinical experience; recognize that nearly all compounds have a fetotoxic dose but that this does not imply teratogenicity; encourage the development of new, quick in vitro testing methods for detecting teratogenic agents; monitor for sudden increases in the frequency of specific malformations in newborn infants and in aborted fetuses; assure that expert multidiscipline committees are available to evaluate the threat when suspected teratogens are reported; improve teratology information storage and retrieval systems by record linkage of clinical data, linkage between computer systems, and universal identifier system for chemical compounds and congenical malformations; foster the exchange of data, particularly those held by the pharmaceutical industry.

Amniocentesis↗

PubMedDate not supplied

The potential for teratogenicity of vitamin A and its congeners.

OBJECTIVE: To review the evidence for teratogenic potential associated with the use of vitamin A and synthetic retinoids in Australia. DATA SOURCES: Relevant indexed journal articles and standard drug information reference texts were identified by Medicine and library search. Information was also obtained from the Australian National Perinatal Statistics Unit. DATA EXTRACTION: We summarised human and animal data relating to the teratogenicity of vitamin A derivatives and synthetic retinoids, including case reports documenting systemic effects from topically administered drugs, pertinent information relating to the clinical pharmacokinetics and adverse effects of these compounds, and the approved and potential indications for the use of these agents. DATA SYNTHESIS: Extensive experimental evidence points to the teratogenicity of natural and synthetic retinoids in animals. Data confirming an effect in humans are not as good. Nevertheless case series, case reports and some epidemiological data regarding isotretinoin suggest that synthetic retinoids are similarly teratogenic in humans. Although there are extensive guidelines and legislation dealing with the use of these compounds in the United States and Australia, the potential for teratogenicity induced by vitamin A still exists. This is because retinoids and vitamin A continue to be prescribed for women of child-bearing potential and documented evidence from the United States reveals that not all prescribers comply with recommendations that minimise the risk of malformations. Non-prescription forms of vitamin A are available without a pregnancy hazard warning, and potentially teratogenic amounts are available from dietary sources. CONCLUSIONS: There exists a potential for teratogenicity in association with the use of both synthetic and natural retinoids in Australia. Monitoring systems currently in place in this country may not detect these malformations should they occur.

Abnormalities, Drug-Induced↗

PubMed1978

Teratogenic and cytogenetic effects of some plant-derived antitumor agents (vincristine, colchicine, maytansine, VP-16-213 and VM-26) in mice.

The teratogenic effects of three new plant-derived antitumor agents, maytansine, VP-16-213 and VM-26, were compared to the effects of vincristine and colchicine in pregnant Swiss albino mice that received a single ip injection of drug on day 6, 7 or 8 of gestation. Cytogenetic studies were also performed using maternal bone marrow and embryos obtained 48 hours after injection of maytansine, vincristine, VP-16-213, VM-26 and colchicine on day 6, 7 or 8 of gestation. A close correlation between teratogenic and cytogenetic effects was not noted among the compounds tested. Vincristine had greater embryotoxic and teratogenic activity than maytansine at equimolar doses (0.36 mu moles/kg), with the peak effects appearing after injection on day 7 of gestation. Colchicine, VP-16-213 and VM-26 were comparatively less potent than maytansine and vincristine, since doses of 2.5 mu moles/kg (colchicine and VP-16-213) and 1.5 mu moles/kg (VM-26) were required to elicit embryotoxic effects. At their teratogenic doses, all compounds induced various cranial abnormalities including exencephaly, hydrocephalus, anophthalmia and microtia, as well as major skeletal malformations. The teratogenic dose of vincristine is comparable to its effective antitumor dose in transplantable rodent tumor systems; in contrast, the teratogenic dose of maytansine in approximately 10-fold higher than its antitumor dose. Of the compounds studied, VP-16-213 and VM-26 exerted the most consistent cytogenetic effects in embryonic tissue. Alarge proportion of the structural chromosome aberrations induced in embryonic cells by VM-26 were stable and are most likely capable of surviving at least one cell division.

Abnormalities, Drug-Induced↗

PubMed1979

A teratogenicity study on hydroxyurea and diphenylhydantoin in cats.

Hydroxyurea, an antitumor drug and known teratogen in rat, miniature swine and dog, and diphenylhydantoin, a teratogen in mouse and rat, were assessed for teratogenic effects in cat. Pregnancies were induced, by synchronizing gonadotropin-stimulated estrus and ovulation with natural copulations. Hydroxyurea at 50 or 100 mg/kg, and sodium diphenylhydantoin at 1 or 2 mg/kg dosages, were administered orally in single daily doses from gestation days 10-22. Appropriate controls given empty capsules, were included for each drug. Cats were necropsied on gestation day 43. Fetuses were examined for external, visceral and skeletal malformations. Hydroxyurea at 50 mg/kg dose produced a low teratogenic activity and at 100 mg/kg a high incidence of non-pregnancy and resorptions with, consequently, fewer live fetuses. Diphenylhydantoin gave no clear evidence of teratogenicity at any test dose but was embryolethal at the maternally toxic dose of 2 mg/kg. So far, studies conducted suggest that the cat is a useful species for screening drugs and chemicals for their teratogenic potential.

Abnormalities, Drug-Induced↗

PubMed1992

The perception of teratogenic risk of cocaine.

While there has been a substantial increase in recreational use of cocaine by young adults, conclusive evidence for cocaine teratogenicity in humans is lacking, and even those believing the drug is teratogenic agree that the rates are quite small. While counseling pregnant women on their teratogenic risk, it was our impression that there is an unrealistically high perception of reproductive risk of cocaine. We wished to quantify the perception of teratogenic risk of cocaine by the public, physicians, and by pregnant women who were counseled following gestational exposure to the drug. Women taking cocaine during the first trimester of pregnancy (n = 54), controls with post secondary education (n = 30), and physicians (n = 30) were asked, using a visual analogue scale, to quantify the teratogenic risk of cocaine and the tendency to terminate/continue the pregnancy after first trimester exposure; in the case of the "public" and physicians this was a hypothetical question. Both physicians and the controls perceived cocaine to be teratogenic (13.4 +/- 11% risk of major malformations by physicians, and 56.5 +/- 22.8% by the "public"). The controls believed cocaine to be as hazardous as thalidomide (57.2 +/- 25.6% risk for thalidomide). Asked whether they would wish to terminate such pregnancy in their family, most physicians (56%) and the controls (70%) had a greater than 50% tendency to terminate.(ABSTRACT TRUNCATED AT 250 WORDS)

Abnormalities, Drug-Induced↗

PubMed1992

The enantiomers of the valproic acid analogue 2-n-propyl-4-pentynoic acid (4-yn-VPA): asymmetric synthesis and highly stereoselective teratogenicity in mice.

The teratogenic activities of R(+)- and S(-)-2-n-propyl-4-pentynoic acid (R and S-4-yn-VPA), the enantiomers of the highly teratogenic valproic acid (VPA) analogues (+/-)-4-yn-VPA, were investigated in mice. The enantiomers were prepared via asymmetric synthesis, each in three steps employing the chiral auxiliaries (4R,5S)-4-methyl-5-phenyl-2-oxazolidinone and S-4-benzyl-2-oxazolidinone. The determination of the absolute configurations and the optical purities is described. R(+)-4-yn-VPA contained 7%, and S(-)-4-yn-VPA 8%, of the respective antipodes. The aqueous solutions of the sodium salts of R- and S-4-yn-VPA were administered as single i.p. injections during early organogenesis in the mouse (day 8 of gestation) using the induction of exencephaly as the teratological end point. Dose/exencephaly curves indicated that S-4-yn-VPA is 7.5 times more teratogenic than its antipode, 1.9 times more teratogenic than (+/-)-4-yn-VPA and 3.9 times more teratogenic than the parent drug VPA. In contrast, the neurotoxicity (maternal toxicity) of the 4-yn-VPA enantiomers was found to be independent of the stereo-chemical configuration and lower than achieved after VPA administration. Due to its low neurotoxicity and highly stereoselective neural tube-inducing activity, S-4-yn-VPA should prove an important tool for the investigation of molecular mechanism of the teratogenic action in this class of compounds; R-4-yn-VPA could act as the negative control in these studies.

Abnormalities, Drug-Induced↗

PubMed1992

[Teratology and epidemiology in the study of environmental teratogens].

The processes of cellular migration, cellular differentiation and cellular multiplication are studied, since these are the basic developmental processes upon which teratogenic agents act resulting in congenital malformations. We also carefully analyze the interactions between teratogen-embryo in order to establish adequate parameters for analysis of environmental teratogens, as well as experimental teratogenesis and epidemiology. Information on the pathogenesis of congenital malformations obtained from experimental teratology in an adequate biological model, can be extrapolated to the human. The etiology of congenital malformations resulting from environmental teratogens can only be elucidated through epidemiology, since there is species specificity. Such a study must fulfill the following prerequisites: diagnosis of the congenital malformation, ruling out genetic factors in the family tree and determination of the exact time of exposure to the possible teratogen during the pregnancy.

Abnormalities, Drug-Induced↗

PubMed1992

Teratogenic assessment of four solvents using the Frog Embryo Teratogenesis Assay--Xenopus (FETAX).

The Frog Embryo Teratogenesis Assay--Xenopus (FETAX) was used to assess the teratogenic potential of four solvents. Embryos of the South African clawed frog, Xenopus laevis, were exposed for 96 h to ethanol, dimethyl sulfoxide (DMSO), formamide or glycerol formal. Exposure groups were maintained using a static renewal system in which the exposure media were changed at 24-h intervals. Survival was monitored at 24-h intervals. Length, as an indicator of growth effects, and developmental malformations were determined at the end of the assay (96 h). Using this information, the 96-h LC50, the 96-h EC50 (Malformation), and the no observable effect levels (NOELs) for mortality, malformation and length were determined for each solvent. The teratogenic index [TI = 96-h LC50/96-h EC50 (Malformation)] also was calculated for each of the solvents. DMSO appeared to be the least toxic or teratogenic solvent examined, with a pooled LC50 of 1.92%, a pooled EC50 (Malformation) of 1.57% and TI values of 1.20 and 1.24 in replicate trials. Formamide appeared to be the most toxic solvent, with a pooled LC50 of 1.04%. Data trends suggested that ethanol was the most teratogenic solvent tested, with a pooled EC50 (Malformation) of 1.04% and TI values of 1.42 and 1.50. The results obtained in the present work for ethanol and DMSO were compared to previously published FETAX results for these two solvents. The present results are in close agreement with these results from other laboratories, thus providing further evidence supporting the interlaboratory reproducibility of FETAX results.

Abnormalities, Drug-Induced↗

PubMed1976

[Teratogenic and mutagenic studies with caffeine in the animal experiment].

Principles of teratogenic and mutagenic actions are defined. The recent experimental studies with laboratory animals, and our investigations with caffeine-sodium benzoicum and with soluble coffee in pregnant rats and mice showed no teratogenicity. The results are compared with specific teratogenic effects of cytostatic agents. A teratogenicity of caffeine can be excluded, a mutagenicity in animal experiments can also not be proved.

Abnormalities, Drug-Induced↗

PubMed1977

Trypan blue: identification and teratogenic and oncogenic activities of its coloured constituents.

Three coloured substances frequently present as contaminants in commercial samples of trypan blue have been identified as those monoazo dyes in which 4-amino-3,3'-dimethyl-biphenyl, 4-amino-3,3'-dimethyl-4'-hydroxy-biphenyl or omicroc-tolidine are coupled to H-acid. These dyes have been synthesized and, together with purified samples of trypan blue, tested for teratogenic activity in mice and oncogenic activity in rats. Unpurified trypan blue was both teratogenic and oncogenic; purified trypan blue, was teratogenic but only weakly oncogenic; the monoazo dyes possessed neither activity. It is concluded that the main blue component of trypan blue is the teratogenic principle and that some as yet unidentified component of the purple fraction either is the main oncogenic principle or potentiates the action of the blue component.

Animals↗

PubMed1979

Teratogenic drugs inhibit tumour cell attachment to lectin-coated surfaces.

Interactions between embryonic cells are generally thought to have a central role in the control of development. When these morphogenic interactions are interrupted by either physical intervention or genetic defects, normal development is impaired. In accord with these experiments, specific interactions between embryonic cells have been demonstrated in several in vitro systems. Many investigators have described homotypic aggregation of chick embryo cells, and heterotypic specificity has been described. Because of the importance of morphogenic cell-cell interactions in development it follows that agents that interfere with these interactions, regardless of the interference mechanism, are potential teratogens. Here we have used a simple in vitro cell to surface recognition system in an attempt to screen for potential teratogens. We have found a very high correlation between inhibitory activity in the in vitro assay and reported teratogenic activity in human or animal studies. This suggests that many teratogenic agents may act by interfering, in an as yet unknown way, in normal cell to cell interactions.

Animals↗

PubMed1979

Teratogenic interaction of hyperthermia and vitamin A.

Exposure of pregnant hamsters to 60--75 min of hyperthermia on the 8th day of gestation causes malformations in some of the fetuses recovered near term. The feeding of large doses of vitamin A to pregnant hamsters on the 8th day of gestation causes many of the same types of malformations. When pregnant hamsters are treated with the minimal teratogenic hyperthermic stress plus the minimal teratogenic dose of vitamin A there is a clear augmentation of the teratogenic effect on the embryo. The implication that maternal hyperthermia may be an important synergistic factor for a variety of potentially teratogenic influences during pregnancy is discussed.

Abnormalities, Drug-Induced↗