Bibliografie tematiche / Testing of teratogens

Letteratura scientifica selezionata sul tema "Testing of teratogens"

Autore: Grafiati

Pubblicato: 22 giugno 2024

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Articoli di riviste sul tema "Testing of teratogens":

Amacher, David E., Jeanne Stadler, Shelli J. Schomaker e Christian Verseil. "The Comparative Testing of Eight Coded Chemicals in the Rat Limb Bud Micromass and Rat Embryo Culture Systems". Alternatives to Laboratory Animals 24, n. 6 (dicembre 1996): 945–52. http://dx.doi.org/10.1177/026119299602400609.

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When cultured at high density, mesenchymal cells from rat limb buds proliferate and differentiate into chondrocytes. Inhibition of this in vitro chondrogenic process has been used for the preliminary evaluation of teratogenic potential. Alternatively, intact post-implantation rat embryos, maintained in short-term culture, provide a system for the in vitro study of abnormal development not limited to the skeletal system. Both systems isolate the test agent from maternal metabolism and pharmacokinetic restraints. In this study, drug-associated selective inhibition of alcian blue uptake by cartilage proteoglycans, in micromass cultures of limb bud cells prepared from 13-day-old rat embryos, was used to assess teratogenic potential in vitro following exposure for 48 hours to eight coded compounds (acetylsalicylic acid, isoniazid. penicillin G, saccharine, vincristine sulphate, 6-aminonicotinamide, retinoic acid, and amaranth). Following drug exposure, cultures were incubated for another 96 hours, and the cells were then fixed and stained with 0.5% alcian blue. Bound dye was then extracted and quantitated. In parallel cultures, cell viability was measured by neutral red uptake, and protein content was assayed by using the bicinchoninic acid method. Except for retinoic acid and vincristine sulphate, the maximum test concentration was 1000μg/ml. Inhibition of alcian blue uptake (> 50%) was noted at 0.001μg/ml vincristine sulphate, 0.5/μg/ml retinoic acid and 5μg/ml 6-aminonicotinamide, demonstrating that strong teratogens inhibit differentiation in micromass cultures at lower concentrations than those which affect limb cell viability. When the same eight compounds were tested in a 24-hour embryo culture model, dysmorphogenesis was evident at 0.005μg/ml vincristine sulphate, 0.1μg/ml retinoic acid and 0.3μg/ml 6-aminonicotinamide. For the other five chemicals, little or no toxicity was noted up to the maximum test concentration in either model. We conclude that the two test systems, both based on the developing rat embryo, are consistent with each other, and that either of them would be useful for the preliminary screening of potential teratogens.

Piersma, Aldert H., Rudolf Bechter, Nathalie Krafft, Beat P. Schmid, Jeanne Stadler, Aart Verhoef, Christian Verseil e Jacob Zijlstra. "An Interlaboratory Evaluation of Five Pairs of Teratogens and Non-teratogens in Post-implantation Rat Embryo Culture". Alternatives to Laboratory Animals 24, n. 2 (marzo 1996): 201–9. http://dx.doi.org/10.1177/026119299602400211.

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The usefulness of the post-implantation rat embryo culture method in screening xenobiotic compounds for developmental toxicity was validated in four laboratories with five pairs of compounds. This approach was chosen to provide information on the interlaboratory reproducibility of the results and to compare the effects of chemical analogues in embryo culture. By testing analogous compounds which are known to have different embryotoxic potencies in vivo, the discriminating power of the embryo culture method for the compound classes under study could be optimally assessed. The classes selected for testing were triazole antifungals, phthalic ester metabolites, substituted pyridines, sulphonamides and methylated xanthines. In summary, it was possible to distinguish between the compounds in three of the pairs, it was not possible to discriminate between the compounds of one pair, and it was possible to discriminate between the compounds of the other pair at two out of the four laboratories. The embryo culture results generally show a good correspondence with the embryotoxic properties of the compounds tested in vivo, although the embryo culture method appeared to be able to discriminate between only some of the pairs of chemical analogues. Some discrepancies may have arisen among the laboratories, because of methodological differences. These results suggest that the post-implantation rat embryo culture method may be a useful tool for screening xenobiotics within classes of compounds known to interfere with embryogenesis during the period of development represented in culture.

Uretsky, Michael E., e Ralf G. Rahwan. "Problems of Conditioning Xenopus Laevis Tadpoles with Standard Avoidance-Response Learning Paradigms". Psychological Reports 79, n. 3 (dicembre 1996): 763–73. http://dx.doi.org/10.2466/pr0.1996.79.3.763.

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The amphibian Xenopus laevis embryo (tadpole) provides a satisfactory alternative to mammalian screening for structural teratogens. Testing was undertaken to extend the usefulness of this species for behavioral teratogenicity testing. One simple and eight operant conditioning paradigms were examined: none elicited learning in Xenopus embryos. Adaptation to the conditioning stimulus (light) and freezing in response to the unconditioned stimulus (shock) were responses incompatible with conditioned learning.

Bell, Susan Givens. "Drug Screening in Neonates". Neonatal Network 35, n. 5 (2016): 321–26. http://dx.doi.org/10.1891/0730-0832.35.5.321.

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AbstractGestational substance exposure continues to be a significant problem. Neonates may be exposed to various substances including illicit drugs, prescription drugs, and other legal substances that are best not used during pregnancy because of their potential deleterious effects as possible teratogens or their potential to create dependence and thus withdrawal in the neonate. Screening the newborn for gestational substance exposure is important for both acute care and early intervention to promote the best possible long-term outcomes. This column provides insight into what is known about the extent of substance use by pregnant women, an overview of neonatal biologic matrices for drug testing, and a discussion of the legal implications of neonatal substance screening.

Brent, Robert L. "Utilization of Animal Studies to Determine the Effects and Human Risks of Environmental Toxicants (Drugs, Chemicals, and Physical Agents)". Pediatrics 113, Supplement_3 (1 aprile 2004): 984–95. http://dx.doi.org/10.1542/peds.113.s3.984.

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Toxicology studies using animals and in vitro cellular or tissue preparations have been used to study the toxic effects and mechanism of action of drugs and chemicals and to determine the effective and safe dose of drugs in humans and the risk of toxicity from chemical exposures. Studies in pregnant animals are used to determine the risk of birth defects and other reproductive effects. There is no question that whole animal teratology studies are helpful in raising concerns about the reproductive effects of drugs and chemicals, but negative animal studies do not guarantee that these agents are free from reproductive effects. There are examples in which drug testing was negative in animals (rat and mouse) but was teratogenic in the human (thalidomide), and there are examples in which a drug was teratogenic in an animal model but not in the human (diflunisal). Testing in animals could be improved if animal dosing using the mg/kg basis were abandoned and drugs and chemicals were administered to achieve pharmacokinetically equivalent serum levels in the animal and the human. Because most human teratogens have been discovered by alert physicians or epidemiology studies, not animal studies, animal studies play a minor role in discovering teratogens. In vitro studies play an even less important role, although they are helpful in describing the cellular or tissue effects of the drugs or chemicals. One cannot determine the magnitude of human risks from these in vitro studies. Performing toxicology studies on adult animals is performed by pharmaceutical companies, chemical companies, the Food and Drug Administration, many laboratories at the National Institutes of Health, and scientific investigators in laboratories throughout the world. Although a vast amount of animal toxicology studies are performed on pregnant animals and numerous toxicology studies are performed on adult animals, there is a paucity of animal studies using newborn, infant, and juvenile animals. This deficiency is compounded by the fact that there are very few toxicology studies performed in children. That is why pregnant women and children are referred to as “therapeutic orphans.” When animal studies are performed with newborn and developing animals, the results demonstrate that generalizations are less applicable and less predictable than the toxicology studies in pregnant animals. Although many studies reveal that the infant and the developing animal have difficulty in metabolizing drugs and are more vulnerable to the toxic effects of environmental chemicals, there are exceptions that indicate that infant and developing animals may be less vulnerable and more resilient to some drugs and chemicals. In other words, the generalization indicating that developing animals are always more sensitive to environmental toxicants is not valid. For animal toxicology studies to be useful, animal studies have to use modern concepts of pharmacokinetics and toxicokinetics, as well as method-of-action studies to determine whether animal data can be used for determining human risk. One example is the inability to determine carcinogenic risks in humans for some drugs and chemicals that produce tumors in rodents, because the oncogenesis is the result of peroxisome proliferation, a reaction that is of diminished importance in humans. Scientists can use animal studies to study the toxicokinetic and toxicodynamic aspects of environmental toxicants, but they have to be performed with the most modern techniques and interpreted with the highest level of scholarship and objectivity. Threshold exposures, maximum permissible exposures, and toxic effects can be estimated but have to be interpreted with caution when applying them to the human. Well-performed epidemiology studies are still the best method for determining the human risk and the effects of environmental toxicants.

Lauschke, Karin, Andreas Frederik Treschow, Mikkel Aabech Rasmussen, Nichlas Davidsen, Bjørn Holst, Jenny Emnéus, Camilla Taxvig e Anne Marie Vinggaard. "Creating a human-induced pluripotent stem cell-based NKX2.5 reporter gene assay for developmental toxicity testing". Archives of Toxicology 95, n. 5 (4 marzo 2021): 1659–70. http://dx.doi.org/10.1007/s00204-021-03018-y.

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AbstractTo test large numbers of chemicals for developmental toxicity, rapid in vitro tests with standardized readouts for automated data acquisition are needed. However, the most widely used assay, the embryonic stem cell test, relies on the counting of beating embryoid bodies by visual inspection, which is laborious and time consuming. We previously developed the PluriBeat assay based on differentiation of human induced pluripotent stem cells (hiPSC) that we demonstrated to be predictive for known teratogens at relevant concentrations using the readout of beating cardiomyocytes. Here, we report the development of a novel assay, which we term the PluriLum assay, where we have introduced a luciferase reporter gene into the locus of NKX2.5 of our hiPSC line. This enabled us to measure luminescence intensities instead of counting beating cardiomyocytes, which is less labor intensive. We established two NKX2.5 reporter cell lines and validated their pluripotency and genetic stability. Moreover, we confirmed that the genetically engineered NKX2.5 reporter cell line differentiated into cardiomyocytes with the same efficiency as the original wild-type line. We then exposed the cells to valproic acid (25–300 μM) and thalidomide (0.1–36 µM) and compared the PluriBeat readout of the cardiomyocytes with the luminescence intensity of the PluriLum assay. The results showed that thalidomide decreased luminescence intensity significantly with a higher potency and efficacy compared to the beating readout. With this, we have developed a novel hiPSC-based assay with a standardized readout that may have the potential for higher throughput screening for developmental toxicity.

Sennsfelder, Laëtitia, Susie Guilly, Sébastien Leruste, Ludovic Hoareau, Willy Léocadie, Pauline Beuvain, Meïssa Nekaa et al. "Description of Copy Number Variations in a Series of Children and Adolescents with FASD in Reunion Island". Children 10, n. 4 (7 aprile 2023): 694. http://dx.doi.org/10.3390/children10040694.

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Background: Fetal Alcohol Spectrum Disorders (FASD) are the most common cause of neurocognitive impairment and social inadaptation, affecting 1 birth in 100. Despite the existence of precise diagnostic criteria, the diagnosis remains difficult, often confounded with other genetic syndromes or neurodevelopmental disorders. Since 2016, Reunion Island has been a pilot region for the identification, diagnosis, and care of FASD in France. Objective: To evaluate the prevalence and the types of Copy Number Variations (CNV) in FASD patients. Methods: A retrospective chart review of 101 patients diagnosed with FASD in the Reference Center for developmental anomalies and in the FASD Diagnostic Center of the University Hospital was performed. Records of all patients were reviewed to obtain their medical history, family history, clinical phenotype, and investigations, including genetic testing (CGH- or SNP-array). Results: A rate of 20.8% (n = 21) of CNVs was found including 57% (12/21) of pathogenic variants and 29% (6/21) of variants of uncertain signification (VUS). Conclusion: A particularly high number of CNVs was found in children and adolescents with FASD. It reinforces the plea for a multidisciplinary approach for developmental disorders to explore both environmental factors, such as avoidable teratogens and intrinsic vulnerabilities, especially genetic determinants.

Ting, Keh-Chuh, Modan Gill e Orlando Garbin. "GC/MS Screening Method for Phthalate Esters in Children's Toys". Journal of AOAC INTERNATIONAL 92, n. 3 (1 maggio 2009): 951–58. http://dx.doi.org/10.1093/jaoac/92.3.951.

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Abstract Phthalate esters are commonly added into polyvinyl chloride (PVC) as softeners to make the plastic material flexible. Phthalates are suspected cancer-causing agents and possible teratogens; they have been linked to liver and kidney damage, as well as the underdevelopment of reproductive organs in humans and animals. Public safety concerns about human exposure to phthalates are on the rise because they do not chemically bond to PVC and leach from the material over time. Following the lead of the European Union and Japan in restricting the use of certain phthalates, a legal limit of 0.1 in children's toys was established by the California State Legislature (AB-1108). In addition to its mission to protect public health and the environment from toxic harm, the California Department of Toxic Substances Control (DTSC) has been delegated the role of lead agency for consumer product safety. To support DTSC's Green Chemistry activities, the Environmental Chemistry Laboratory Mobile Laboratory Team has developed an on-site screening method to monitor phthalates in children's toys. This method is simple, fast, and effective, with ample sensitivity to quantify the 6 restricted phthalates in children's toys at 100 ppm (limit of quantitation = 100 g/g) which is 10 times lower than the legal allowable level of 0.1. Additionally, the method has a high throughput capability and enables testing of approximately 610 samples per day, depending on the complexity of the sample matrix and concentration. This method is designed to survey the 6 phthalates in children's toys and other consumer products for compliance with the threshold of 0.1 (1000 ppm).

Sethi, Nikunj, Rohit Mahar, Sanjeev K. Shukla, Akhilesh Kumar e Neeraj Sinha. "A novel approach for testing the teratogenic potential of chemicals on the platform of metabolomics: studies employing HR-MAS nuclear magnetic resonance spectroscopy". RSC Advances 5, n. 33 (2015): 26027–39. http://dx.doi.org/10.1039/c5ra00671f.

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The objective is to develop a quick, reliable method for testing the teratogenic potential of a new chemical entity (NCE) on the platform of metabonomics, as an alternative to conventional procedures.

Sethi, Nikunj, Rohit Mahar, Sanjeev K. Shukla, Akhilesh Kumar e Neeraj Sinha. "Correction: A novel approach for testing the teratogenic potential of chemicals on the platform of metabolomics: studies employing HR-MAS nuclear magnetic resonance spectroscopy". RSC Advances 5, n. 66 (2015): 53341. http://dx.doi.org/10.1039/c5ra90058a.

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Correction for ‘A novel approach for testing the teratogenic potential of chemicals on the platform of metabolomics: studies employing HR-MAS nuclear magnetic resonance spectroscopy’ by Nikunj Sethi et al., RSC Adv., 2015, 5, 26027–26039.

Più fonti

Tesi sul tema "Testing of teratogens":

Carro, Tiffany. "Development and evaluation of a viable chicken egg assay to determine the metabolic fate of xenobiotic and other teratogenic compounds". Access to citation, abstract and download form provided by ProQuest Information and Learning Company; downloadable PDF file, 137 p, 2007. http://proquest.umi.com/pqdweb?did=1372020111&sid=5&Fmt=2&clientId=8331&RQT=309&VName=PQD.

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Perez, Castiglioni Monica Patricia. "Le statut juridique des cellules souches : de la greffe d’organes à la thérapie cellulaire". Electronic Thesis or Diss., Paris 8, 2021. http://www.theses.fr/2021PA080048.

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Les cellules souches en tant que produits cellulaires à finalité thérapeutique (PCT) ou en tant que médicaments de thérapie innovante (MTI) dans le cadre de la médecine régénératrice ont révolutionné la médecine du XXIe siècle. Face aux découvertes récentes de nouvelles cellules souches créées par les chercheurs (parthénotes, cellules souches clonées, cellules iPS), d’autres possibilités de thérapie régénérative surgissent au fil du temps.Le droit, qui a toujours accompagné l’évolution scientifique et technique de la thérapie cellulaire depuis le XVIIe siècle, doit être plus que jamais présent pour protéger l’être humain qui se prête aux nouveaux traitements ou à l’expérimentation. L’évolution historique de cette révolution thérapeutique nous permet de montrer l’importance de la réflexion juridique et éthique pour le progrès scientifique. Des questionnements anciens, comme le statut de l’être prénatal et l’autorisation de cryopréservation des tissus ou des cellules autologues, ressurgissent face à la présence de cellules souches humaines embryonnaires surnuméraires et aux succès de la thérapie régénérative. Des traitements tératogènes et des épisodes de maltraitance des femmes en cours de grossesse ont détruit ou endommagé des milliers d’enfants à naître. Une reconnaissance de la vie prénatale est proposée dans certaines circonstances pour protéger l’embryon et le fœtus avant leur naissance
Stem cells as cellular products for therapeutic purposes (PCT) or as advanced therapy drugs (ITNs) within the framework of regenerative medicine have revolutionized the medicine of the 21st century. Faced with recent discoveries of new stem cells created by researchers (parthenotes, cloned stem cells, iPS cells), other possibilities for regenerative therapy are emerging over time.The law, which has always accompanied the scientific and technical development of cell therapy since the 17th century, must be more present than ever to protect human beings who lend themselves to new treatments or to experimentation. The historical development of this therapeutic revolution allows us to show the importance of legal and ethical reflection for scientific progress.Old questions, such as the status of the prenatal being and the authorization for cryopreservation of autologous tissues or cells, are re-emerging in the face of the presence of supernumerary human embryonic stem cells and the success of regenerative therapy. Teratogenic treatments and episodes of child abuse during pregnancy have destroyed or damaged thousands of unborn children. Recognition of prenatal life is offered in certain circumstances to protect the embryo and fetus before birth

Pavlíková, Zuzana. "Testování embryotoxicity vybraných lidských teratogenů na zárodcích kuřete". Master's thesis, 2012. http://www.nusl.cz/ntk/nusl-312523.

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Teratogenes are external environmental factors that can cause a developmental or a congenital defect in exposed individuals. The methods used for detecting the embryotoxic effect of substances are the classic when laboratory mammals are used and the alternative which use in vitro and in ovo systems. The main difference between these two is that the alternative methods lack metabolism of maternal organism. The metabolism of maternal organism brings a high variability of results to systems of the classic methods. We used two alternative methods in this thesis, both using chicken embryo. The first of them was in ovo method called CHEST (Jelínek, 1977). CHEST method can be used for administration of tested substances from ED2 to ED6. The disadvantage of this method is due to the dilution of the tested substance after subgerminal application at ED2. Therefore we developed in vitro method called SANDWICH. No dilution occurs while using the SANDWICH method. The aim of this study was to develop in vitro method SANDWICH while using proven teratogene (all-trans retinoic acid) and its solvent (dimethyl sulfoxide), to estimate beginning of the embryotoxicity dose range for both substances using CHEST and SANDWICH, and finally to compare obtained results. We confirmed the embryotoxic effect of all-trans...

Libri sul tema "Testing of teratogens":

Southeast, Asian Workshop on Short-term Assays for Detecting Environmental Mutagens Carcinogens and Teratogens (2nd 1989 Bangkok and Chiang Mai Thailand). Environmental mutagens, carcinogens, and teratogens: Principles and short-term assays : proceedings of the Second Southeast Asian Workshop on Short-term Assays for Detecting Environmental Mutagens, Carcinogens, and Teratogens, held in Bangkok and Chiang Mai, Thailand, February 6-17, 1989. Chiang Mai, Thailand: Star Press, 1991.

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National Research Council (U.S.). Subcommittee on Reproductive and Developmental Toxicology. Evaluating chemical and other agent exposures for reproductive and developmental toxicity. Washington, D.C: National Academy Press, 2001.

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Joint American-Swiss Seminar on Alternative Embryotoxicity and Teratogenicity Tests (1984 Zurich, Switzerland). In vitro embryotoxicity and teratogenicity tests: Joint American-Swiss Seminar on Alternative Embryotoxicity and Teratogenicity Tests, Zürich, November 12, 1984. A cura di Homburger Freddy e Goldberg Alan M. Basel, Switzerland: New York, 1985.

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Brusick, David. Principles of genetic toxicology. 2^a ed. New York: Plenum Press, 1987.

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Persaud, T. V. N. Teratological Testing. Springer, 2012.

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Teratogenicity Testing Methods in Molecular Biology Hardcover. Humana Press, 2012.

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Environmental mutagens, carcinogens, and teratogens: Principles and short-term assays : Proceedings of the Second Southeast Asian Workshop on Short-term ... Chiang Mai, Thailand, February 6-17, 1989. Star Press, 1991.

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Mohl, Virginia Kathleen. Genetic differences in the murine heat shock response: Implications in testing for teratogen susceptibility. 1988.

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Mathiesen, Amber, e Kali Roy. Foundations of Perinatal Genetic Counseling. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780190681098.001.0001.

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Foundations of Perinatal Genetic Counseling provides an overview of the core concepts needed to practice perinatal genetic counseling, including the basics of pregnancy, the genetic counseling appointment, family and pregnancy history, prenatal screening, prenatal diagnosis, common indications, carrier screening, management of high-risk pregnancy, assisted reproductive technology, preimplantation genetic screening and diagnosis, and common situations arising in perinatal genetic counseling. It discusses general obstetrical information as it pertains to perinatal genetic counseling, including topics such as calculating gestational age, understanding gravidity and parity, and reproductive options. This book reviews the key components of a perinatal genetic counseling session and how to take a perinatal family, medical, and pregnancy history, as well as a prenatal risk evaluation based on age, family and pregnancy history, testing results, and ultrasound findings. It includes a detailed description of both prenatal screening and diagnostic testing options, including maternal serum screening, cell-free DNA testing, amniocentesis, and chorionic villus sampling. It also provides an explanation of carrier testing, including methods of testing, types of conditions, and indications for testing. This text provides information on the indications for referral to a perinatal genetic counselor such as age-related risks, personal and family history, ultrasound anomalies, teratogen exposure, recurrent pregnancy loss, and preconception counseling. It also reviews the management and types of referrals made in a high-risk pregnancy. Assisted reproductive technology is reviewed as well as descriptions of preimplantation genetic diagnosis and screening. It also describes common psychosocial and ethical situations encountered in perinatal genetic counseling.

(US), National Research Council, Board on Environmental Studies and Toxicology, Committee on Toxicology e Subcommittee on Reproductive and Developmental Toxicity. Evaluating Chemical and Other Agent Exposures For Reproductive and Developmental Toxicity. National Academies Press, 2001.

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Capitoli di libri sul tema "Testing of teratogens":

Abel, Ernest L. "Testing Animal Behavioral Teratogens". In Behavioral Teratogenesis and Behavioral Mutagenesis, 195–226. Boston, MA: Springer US, 1989. http://dx.doi.org/10.1007/978-1-4613-0735-8_7.

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Alves-Pimenta, Sofia, Bruno Colaço, Paula A. Oliveira e Carlos Venâncio. "Biological Concerns on the Selection of Animal Models for Teratogenic Testing". In Methods in Molecular Biology, 61–93. New York, NY: Springer New York, 2018. http://dx.doi.org/10.1007/978-1-4939-7883-0_3.

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Alves-Pimenta, Sofia, Bruno Colaço, Paula A. Oliveira e Carlos Venâncio. "Development Features on the Selection of Animal Models for Teratogenic Testing". In Methods in Molecular Biology, 67–104. New York, NY: Springer US, 2024. http://dx.doi.org/10.1007/978-1-0716-3625-1_3.

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Steele, Christopher E., e Graham P. Copping. "Teratogen testing". In Postiplantation Mammalian Embryos, 221–34. Oxford University PressOxford, 1990. http://dx.doi.org/10.1093/oso/9780199630882.003.0012.

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Abstract Chapters 1 to 10 of this book deal primarily with normal postimplantation development. In this chapter (see also Chapters 12 and 15) we consider the problem of abnormal embryogenesis. In humans, 65-70% of malformations are without known cause, approximately 20% result from genetic transmission, 3-5% from chromosomal aberrations, 4-6% from various extrinsic factors, and 3--4% from exposure to drugs and other chemicals (1). The substances responsible for the defects in this last category are known as teratogens and, although they are implicated in only a small proportion of the total malformations in humans, they are the most amenable to control. It is the identification and investigation of these substances that form the subject of this chapter.

Clark, Robin D., e Cynthia J. Curry. "Intrauterine Growth Restriction". In Genetic Consultations in the Newborn, a cura di Robin D. Clark e Cynthia J. Curry, 11–16. Oxford University Press, 2019. http://dx.doi.org/10.1093/med/9780199990993.003.0002.

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This chapter reviews isolated and syndromic intrauterine growth restriction (IUGR) or small for gestational age infants. The differential diagnosis of intrauterine growth restriction includes placental, maternal, and fetal causes. Maternal causes of IUGR include exposure to teratogens, various maternal illnesses, and multiple gestation. Infant causes include congenital infection, chromosomal aneuploidy, and multiple syndromes including primordial dwarfism. Other causes include genomic imprinting errors (Russell Silver syndrome and IMAGe syndrome) and endocrine and metabolic causes, the lipodystrophies, and skeletal dysplasias including SHOX deficiency. The evaluation of IUGR usually includes a SNP microarray and often targeted or gene panel testing. A clinical case presentation features an infant with Majewski (microcephalic) osteodysplastic primordial dwarfism (MOPD II) .

Clark, Robin D., e Cynthia J. Curry. "Craniosynostoses". In Genetic Consultations in the Newborn, a cura di Robin D. Clark e Cynthia J. Curry, 91–100. Oxford University Press, 2019. http://dx.doi.org/10.1093/med/9780199990993.003.0013.

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This chapter reviews background information about the incidence, risk factors, genetics, recurrence risk, and epidemiology of single suture and multiple suture craniosynostosis including isolated and syndromic varieties. The discussion on the differential diagnosis of craniosynostosis summarizes its common causes, including teratogenic agents (fluconazole, maternal thyroid disorders, methotrexate, valproic acid), chromosome anomalies, and Mendelian disorders that involve extracranial malformations. The relationship between premature closure of cranial sutures of postnatal onset and positional plagiocephaly, prematurity, and microcephaly are examined. This chapter provides recommendations for testing, evaluation and management. A clinical case presentation features an infant with Saethre–Chotzen syndrome, whose mildly affected relatives had not been diagnosed.

"Induction of Low-Molecular-Weight Heat-Shock Proteins in Drosophila and Human Embryonic Lineage Cells After Teratogen Exposure". In Advances In Animal Alternatives For Safety And Efficacy Testing, 131–44. CRC Press, 1997. http://dx.doi.org/10.1201/9781439805817-20.

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Abbott, Barbara D. "Experimental Models for the Study of Oral Clefts". In Cleft Lip And Palate, 193–202. Oxford University PressNew York, NY, 2002. http://dx.doi.org/10.1093/oso/9780195139068.003.0015.

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Abstract Toxicology and teratology studies routinely utilize animal models to determine the potential for chemical and physical agents to produce reproductive and developmental toxicity, including birth defects such as cleft palate (CP). The standardized teratology screen typically tests compounds in two species, one of which is a nonrodent. The laboratory rat and rabbit are often the species of choice for such screens. However, research examining the mechanisms through which agents induce their teratogenic effects has been conducted in a variety of mammalian species, including mice, rats, and hamsters, as well as in nonmammalian species, including birds, fish, and frogs. A variety of in vitro models are also available to researchers interested in the study of palatogenesis. The literature presenting palatal research is extensive, and many outstanding studies could be cited in which a wide range of models were developed and applied; however, it is beyond the scope of this chapter to present more than a brief overview of some of these models and an example of their application in the study of environmental contaminants. An overview of in vivo and in vitro models is presented and the specialized requirements for research addressing the etiology of clefting are discussed. The final section of the chapter provides examples of these models, testing the environmental contaminant 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD).

"Cancer Institute (NCI), the National Institute for Environmental Health Sciences (NIEHS), the National Center for Toxicological Research (NCTR) and the National Institute for Occupational Safety and Health (NIOSH). Within the NTP Carcinogenesis Testing Program, a cancer bioassay is a two-sex, two-species, lifetime study of experimental animals, usually rats and mice; beginning at weaning, ending 104 weeks after initiation, and using multiple dose levels of the chemical being tested. This bioassay used to determine if a chemical causes cancer, and if it produces damaging effects on certain organ systems: liver, lung, kidney, endocrine systems, etc. The study of a single compound expensive, costing about five hundred thousand dollars, and takes up to five years to complete. The National Toxicology Program publishes a technical report upon completion of a bioassay and review of the results by an indepen-dent Board of Scientific Counselors. Reproductive and Developmental Toxicology Program The National Toxicology Program has a program to assess the effects of chemicals on reproductive function and development. Structural teratology testing (the testing of chemicals to determine if they produce malformations) was begun in FY79. Eight to ten chemicals are tested for teratogenic effects annually. Fetuses are examined at two different levels: gross, readily apparent malformations are noted; and 2) histopathological examinations are conducted to pinpoint less readily apparent, microscopic malformations. Selected priority chemicals are also screened to determine potential reproductive hazard through germ-cell mutations. C. Genetic Toxicology Program The Genetic Toxicology Program tests chemicals for mutagenici-ty, validates existing test systems and develops new short-term test methods. The mutagenicity testing program divided into three phases. Phase I involves Salmonella mutagenicity assays and mammalian cell cultures. Phase II includes Drosophila systems. Phase III utilizes in vivo mammalian assays. All chemicals selected for general toxicology and lifetime bioassays are tested first using the Salmonella mutagenesis". In Dangerous Properties of Industrial and Consumer Chemicals, 16. CRC Press, 1994. http://dx.doi.org/10.1201/9781482293500-9.

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