Acute toxicity assessment of azadirachtin-based pesticides using murine hybridoma and oyster cells

In vitro acute toxicities of azadirachtin-containing pesticides (Neemix and Bioneem), formulated with neem tree extracts, and pure azadirachtin (AZA), the believed active ingredient, were studied using hybridoma and oyster cells and were compared to results obtained using the standard in vivo Daphnia pulex toxicity assay. Neem-based pesticides showed relatively high toxicity to both hybridoma and oyster cells at concentrations of 1 microg AZA/mL and higher. The IC50 values for hybridoma cells were 2.15 microg AZA/mL for Neemix and 1.67 pg AZA/mL for Bioneem. Oyster cells had IC50 values of 2.18 microg AZA/mL for Neemix and 9.46 pg AZA/mL for Bioneem. Purified AZA, however, did not appear to be as toxic as the formulations. D. pulex was also more sensitive to neem-based pesticide exposure than that of pure AZA. The applications and limits of these two in vitro models for testing the acute toxicity of AZA-based pesticides are discussed in comparison with the in vivo D. pulex test.     

First report on development of quantitative interspecies structure-carcinogenicity relationship models and exploring discriminatory features for rodent carcinogenicity of diverse organic chemicals using OECD guidelines

Different regulatory agencies in food and drug administration and environmental protection worldwide are employing quantitative structure-activity relationship (QSAR) models to fill the data gaps related with properties of chemicals affecting the environment and human health. Carcinogenicity is a toxicity endpoint of major concern in recent times. Interspecies toxicity correlations may provide a tool for estimating sensitivity towards toxic chemical exposure with known levels of uncertainty for a diversity of wildlife species. In this background, we have developed quantitative interspecies structure-carcinogenicity correlation models for rat and mouse [rodent species according to the Organization for Economic Cooperation and Development (OECD) guidelines] based on the carcinogenic potential of 166 organic chemicals with wide diversity of molecular structures, spanning a large number of chemical classes and biological mechanisms. All the developed models have been assessed according to the OECD principles for the validation of QSAR models. Consensus predictions for carcinogenicity of the individual compounds are presented here for any one species when the data for the other species are available. Informative illustrations of the contributing structural fragments of chemicals which are responsible for specific carcinogenicity endpoints are identified by the developed models. The models have also been used to predict mouse carcinogenicities of 247 organic chemicals (for which rat carcinogenicities are present) and rat carcinogenicities of 150 chemicals (for which mouse carcinogenicities are present). Discriminatory features for rat and mouse carcinogenicity values have also been explored.