Prevalidation of the Embryonic Stem Cell Test (EST)—A New In Vitro Embryotoxicity Test

Scholz, Gabriele; Genschow, Elke; Pohl, Ingeborg; Bremer, Suzanne; Paparella, Martin; Raabe, H.-M.; Southee, J. A.; Spielmann, Horst

doi:10.1016/s0887-2333(99)00046-6

Cited by 118 publications

(101 citation statements)

References 10 publications

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“…An algorithm eventually integrates these three values to obtain an evaluation of predicted embryotoxicity. As required by the EST standardized protocol, 20,21 due to the higher sensitivity of mES to toxic agents, as compared to NIH3T3 differentiated cells, different concentrations of the tested compound are to be used for the two cell lines in order to obtain …”

Section: Articlementioning

confidence: 99%

“…In parallel, we have evaluated whether an in vitro test, the embryonic stem cell test 20,21 might provide reliable predictive information on SWCNTs' embryotoxicity. The EST is an in vitro test validated by the European Centre for the Validation of Alternative Methods (ECVAM) that allows reliably classifying chemical compounds as strong, weak, or nonembryotoxic, without using animal experimentation.…”

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confidence: 99%

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Low Doses of Pristine and Oxidized Single-Wall Carbon Nanotubes Affect Mammalian Embryonic Development

Massimiani²,

et al. 2011

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Several in vitro and in vivo studies suggest local and systemic effects following\ud exposure to carbon nanotubes. No data are available, however, on their possible\ud embryotoxicity in mammals. In this study, we tested the effect of pristine and\ud oxidized single-wall carbon nanotubes (SWCNTs) on the development of the mouse\ud embryo. To this end, SWCNTs (from 10 ng to 30 μg/mouse) were administered to\ud female mice soon after implantation (postcoital day 5.5); 10 days later, animals \ud were sacrificed, and uteri, placentas, and fetuses examined. A high percentage of\ud early miscarriages and fetal malformations was observed in females exposed to\ud oxidized SWCNTs, while lower percentages were found in animals exposed to the\ud pristine material. The lowest effective dose was 100 ng/mouse. Extensive vascular\ud lesions and increased production of reactive oxygen species (ROS) were detected\ud in placentas of malformed but not of normally developed fetuses. Increased ROS\ud levels were likewise detected in malformed fetuses. No increased ROS production\ud or evident morphological alterations were observed in maternal tissues. No fetal \ud and placental abnormalities were ever observed in control animals. In parallel,\ud SWCNT embryotoxicity was evaluated using the embryonic stem cell test (EST), a\ud validated in vitro assay developed for predicting embryotoxicity of soluble\ud chemical compounds, but never applied in full to nanoparticles. The EST predicted\ud the in vivo data, identifying oxidized SWCNTs as the more toxic compound

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Section: Articlementioning

confidence: 99%

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confidence: 99%

Low Doses of Pristine and Oxidized Single-Wall Carbon Nanotubes Affect Mammalian Embryonic Development

Massimiani²,

et al. 2011

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“…2: Contingency table comparing in vive and in vitro classifications tended to be most affeeted when nonembryotoxie substanees were tested (Scholz et al, 1999a;Gensehow et al, 2002). A balaneed eombination of the end points of the eytotoxieity test with undifferentiated and differentiated cells and the differentiation assay is known to give the most accurate results (Scholz et al, 1999b). In eomparison to the ECVAM experiments, our results (aeeuraey of 81%) are a slight improvement on the predietion model used in the ECVAM study, whieh resulted in an aeeuraey of 78% (also classified as being "good") (Gensehow et al, 2004).…”

Section: Resultsmentioning

confidence: 64%

“…The EST, along with the whole embryo culture assay and the limb bud micromass assay, have been validated in an extensive study sponsored by ECVAM, the European Centre for the Validation of Alternative Methods (Scholz et al, 1999b;Genschow et al, 2000Genschow et al, , 2002Genschow et al, and 2004. The EST assays resulted in an initial set of 6 chemieals being 93% correctly elassified, and 78% of the 14 chemie als were correctly elassified in the formal validation study.…”

Section: Introductionmentioning

confidence: 99%

The embryonic stem cell test for the early selection of pharmaceutical compounds

Whitlow

Bürgin²,

Clemann³

2007

ALTEX

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“…Test models in vitro include those of whole embryo culture, ES cell micro mass cultivation, testicular cells, ovarian cells, and the EST [11]. With the advantage that only permanent cell lines are used, and consequently, no pregnant animals need be sacrificed to obtain embryonic cells, tissues or organs, EST validated by ECVAM was one of the most widely models to predict developmental toxicity [12]. ECVAM validation research has shown that prediction accuracy of EST for non-and weak embryotoxic compounds is 78%, and is 100% for strong embryotoxicants [13].…”

Section: Discussionmentioning

confidence: 99%

Assessment of the Developmental Toxicity of Epidermal Growth Factor using Embryonic Stem Cell Test

Chen¹,

Cao²,

Su³

et al. 2014

Trop. J. Pharm Res

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Purpose: To determine whether epidermal growth factor (EGF) is involved in reproductive developmental toxicity, using the embryonic stem cell test (EST), as well as ascertain how EGF influences embryonic development. Methods: To predict developmental toxicity on the basis of reducing cell viability and inhibition of differentiation of embryonic stem cells, EST was used to assess changes in different blastodermic genes and expression of proteins including ectodermal-specific genes Pax6, NF-H and glial fibrillary acidic protein (GFAP), mesodermal-specific genes BMP4, GATA4, and MyoD, viz, transthyretin (TTR)

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Prevalidation of the Embryonic Stem Cell Test (EST)—A New In Vitro Embryotoxicity Test

Cited by 118 publications

References 10 publications

Low Doses of Pristine and Oxidized Single-Wall Carbon Nanotubes Affect Mammalian Embryonic Development

Low Doses of Pristine and Oxidized Single-Wall Carbon Nanotubes Affect Mammalian Embryonic Development

The embryonic stem cell test for the early selection of pharmaceutical compounds

Assessment of the Developmental Toxicity of Epidermal Growth Factor using Embryonic Stem Cell Test

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