Decision tree SAR models for developmental toxicity based on an FDA/TERIS database

Humans are exposed to thousands of environmental chemicals for which no developmental toxicity information is available. Structure-activity relationships (SARs) are models that could be used to efficiently predict the biological activity of potential developmental toxicants. However, at this time, no adequate SAR models of developmental toxicity are available for risk assessment. In the present study, a new developmental database was compiled by combining toxicity information from the Teratogen Information System (TERIS) and the Food and Drug Administration (FDA) guidelines. We implemented a decision tree modeling procedure, using Classification and Regression Tree software and a model ensemble approach termed bagging. We then assessed the empirical distributions of the prediction accuracy measures of the single and ensemble-based models, achieved by repeating our modeling experiment many times by repeated random partitioning of the working database. The decision tree developmental SAR models exhibited modest prediction accuracy. Bagging tended to enhance the accuracy of prediction. Also, the model ensemble approach reduced the variability of prediction measures compared to the single model approach. Further research with data derived from animal species- and endpoint-specific components of an extended and refined FDA/TERIS database has the potential to derive SAR models that would be useful in the developmental risk assessment of the thousands of untested chemicals.     

A novel tryptamine-appended rhodamine-based chemosensor for selective detection of Hg2+ present in aqueous medium and its biological applications

A novel rhodamine–tryptamine conjugate–based fluorescent and chromogenic chemosensor (RTS) for detection of Hg²⁺ present in water was reported. After gradual addition of Hg²⁺ in aqueous methanol solution of RTS, a strong orange fluorescence and deep-pink coloration were observed. The probe showed high selectivity towards Hg²⁺ compared to other competitive metal ions. The 1:1 binding stoichiometry between RTS and Hg²⁺ was established by Job’s plot analysis and mass spectroscopy. Initial studies showed that the synthesized probe RTS possessed fair non-toxicity and effectively passed through cell walls of model cell systems, viz., human neuroblastoma (SHSY5Y) cells and cervical cells (HeLa) to detect intercellular Hg²⁺ ions, signifying its utility in biological system. The limit of detection (LOD) was found to be 2.1 nM or 0.42 ppb by fluorescence titration. Additionally, the potential relevance of synthesized chemosensor for detecting Hg²⁺ ions in environmental water samples has been demonstrated.

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Decision tree SAR models for developmental toxicity based on an FDA/TERIS database

Humans are exposed to thousands of environmental chemicals for which no developmental toxicity information is available. Structure-activity relationships (SARs) are models that could be used to efficiently predict the biological activity of potential developmental toxicants. However, at this time, no adequate SAR models of developmental toxicity are available for risk assessment. In the present study, a new developmental database was compiled by combining toxicity information from the Teratogen Information System (TERIS) and the Food and Drug Administration (FDA) guidelines. We implemented a decision tree modeling procedure, using Classification and Regression Tree software and a model ensemble approach termed bagging. We then assessed the empirical distributions of the prediction accuracy measures of the single and ensemble-based models, achieved by repeating our modeling experiment many times by repeated random partitioning of the working database. The decision tree developmental SAR models exhibited modest prediction accuracy. Bagging tended to enhance the accuracy of prediction. Also, the model ensemble approach reduced the variability of prediction measures compared to the single model approach. Further research with data derived from animal species- and endpoint-specific components of an extended and refined FDA/TERIS database has the potential to derive SAR models that would be useful in the developmental risk assessment of the thousands of untested chemicals.     

Chemistry of 1,2,4-trioxanes relevant to their mechanism of action. Part 1: Reaction with Fe(II) salts

Reactions of 6-(1′-phenylvinyl)-1,2,4-trioxanes 2-5, with FeCl₂·4H₂O, FeBr₂, and a combination of hemin (bovine) and reduced glutathione (GSH) under various conditions have been studied.     

Higher isoprenoids—VII: A new approach to the degradation of cyclolaudenol side-chain

An efficient new procedure for the degradation of cyclolaudenyl acetate to 3β - acetoxy - 4,4,14α -trimethyl - 9, 19 - cyclo - 5α - pregnan - 20 - one and/or 3β - acetoxy - 4,4,14α - trimethyl - 9,19 - cyclo - 5α -androstan - 17 - one is described. The key-step is simultaneous base-catalysed dehydrohalogenation and isomerisation of the resulting olefin, of a suitably derived halide.