Abstract: The replacement of animal testing for endpoints such as reproductive toxicity is a long-term goal. This study describes the possibilities of using simple (quantitative) structure-activity relationships ((Q)SARs) to predict whether a molecule may cross the placental membrane. The concept is straightforward, if a molecule is not able to cross the placental ...

Abstract: All compounds are considered to act by non-polar narcosis. This is well established for non-reactive compounds. Acute lethality is brought about by accumulation in cellular membranes causing their disruption and ultimately death of the organism. The ability of the compound to accumulate in a cellular membrane is thought to be related to its intrinsic ...

Abstract: In this study, a quantitative structure-property relationship (QSPR) model for the prediction of Henry's law constants of aliphatic hydrocarbons in air-water system has been developed, based on a data-set of 189 compounds. The well-known linear thermodynamic relation between the logarithm of Henry's law constant and solvation free energy has been used for ...

Abstract: This study presents an analysis of the ability of a two-parameter response surface, a multiple linear regression and a neural network model to produce global quantitative structure–activity relationships (QSARs) to predict the toxic potency of phenols to Tetrahymena pyriformis. The phenolic toxicity data set analysed is characterised by multiple mechanisms ...

Abstract: This study outlines the development of a series of quantitative mechanistic models enabling skin sensitization potency in the LLNA to be predicted for direct acting Michael acceptors. These models utilized several computational descriptors based on knowledge of the Michael addition reaction mechanism. The key descriptor was calculated using density functional ...

Abstract: A QSAR analysis has been carried out of the toxicity of 47 mono-substituted nitrobenzenes to the aquatic ciliate Tetrahymena pyriformis. The single most important parameter was the logarithm of the apparent partition coefficient (logD) at pH 7.35. 2- and 3-derivatives yielded an excellent correlation of toxicity with log D, Swain-Lupton field parameter and ...

Abstract: The process of validation of computational models (e.g., QSARs) may become the most important step in their development. Different requirements for the reliability and predictability of QSAR models have been described in the literature. Despite these formal recommendations there are few practical rules as to when to cease adding variables to a QSAR (i.e., what ...

Abstract: Reactive toxicity encompasses important endpoints such as skin and respiratory sensitization, hepatotoxicity and elevated acute aquatic toxicity. These adverse effects are initiated by, among others, electrophilic chemicals and those transformed into electrophiles; i.e. non-reactive chemicals activated into reactive electrophilic species by either a biotransformation ...

Abstract: Using abiotic thiol reactivity (EC50) and Tetrahymena pyriformis toxicity (IGC50) data for a group of halo-substituted ketones, esters and amides (i.e. SN2 electrophiles) and related compounds a series of structure-activity relationships are illustrated. Only the alpha-halo-carbonyl-containing compounds are observed to be thiol reactive with the order I > Br ...

Abstract: The toxicities of 34 benzonitriles to Tetrahymena pyriformis have been measured. Structure-activity relationships indicate that for these compounds different mechanisms of toxic action are taking place dependent on the nature of the substituent. Benzonitrile itself, some halogenated and the toluene derivatives model as non-polar narcotics; more polar substituents ...