A high throughput screening system for predicting chemically-induced reproductive organ deformities
| Jazyk: | angličtina |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Reproductive toxicity
Mechanistic validation Unclassified drug RAPID - Risk Analysis for Products in Development Halosulfuron methyl Reproductive organ deformities Life Di(n hexyl)phthalate 4 pyrimethamine Diglyme Phthalic acid benzyl butyl ester Cyproconazole Molinate Reporter gene Androgen receptor Carbamazepine Triclopyr Benomyl Genital malformation Healthy Living Mancozeb Pentachlorophenol Estrogen activity 2 ethylhexanoic acid Fenachlorazol ethyl Dibutyltindichloride Glycolic acid Bis(trichloromethyl)sulfone High throughput screening Acetylsalicylic acid Food and Nutrition Animal model Animal experiment Life and Social Sciences Nutrition Toxic substance 2 methoxyethanol Carbendazim ELSS - Earth Nonhuman 4 dextro isopropylamine salt Cyanazine Toxicity testing Rat Estrogen–androgen reporter gene assay Prediction Cellosolve acetate Controlled study Prothioconazole |
| Popis: | There is a great need for alternative testing methods for reproductive toxicants that are practical, fast, cost-effective and easy to interpret. Previously we followed a pragmatic approach using readily available tests, which was successful in predicting reproductive toxicity of chemicals [13]. This initial battery still contained apical tests and is fairly complex and low in its throughput. The current study aimed to simplify this screening battery using a mechanistic approach and a panel of high throughput CALUX reporter gene assays. A mechanistic approach was taken to validate this high throughput test battery. To this end it was challenged with two preselected sets of chemicals addressing two major apical effect classes relevant in reproductive toxicity. We found selectivity in this battery in that 82% of the compounds inducing reproductive organ deformities were predicted correctly, while for compounds inducing neural tube defects this was the case in 47% only. This is consistent with the mechanisms of toxicity covered in the battery. The most informative assays in the battery were ERalpha CALUX to measure estrogenicity and the AR-anti CALUX assay to measure androgen receptor antagonism. © 2014 Elsevier Inc. |
| Databáze: | OpenAIRE |
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