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As the world’s population grows, so does the need for more and more animal feed. In 2006, the EU banned the use of antibiotics and other chemicals in order to reduce chemical residues in food consumed by humans. It is well known that oxidative stress and inflammatory processes must be combated to achieve higher productivity. The adverse effects of the use of pharmaceuticals and other synthetic compounds on animal health and product quality and safety have increased interest in phytocompounds. With the use of plant polyphenols in animal nutrition, they are gaining more attention as a supplement to animal feed. Livestock feeding based on a sustainable, environmentally friendly approach (clean, safe, and green agriculture) would also be a win–win for farmers and society. There is an increasing interest in producing healthier products of animal origin with a higher ratio of polyunsaturated fatty acids (PUFAs) to saturated fatty acids by modulating animal nutrition. Secondary plant metabolites (polyphenols) are essential chemical compounds for plant physiology as they are involved in various functions such as growth, pigmentation, and resistance to pathogenic organisms. Polyphenols are exogenous antioxidants that act as one of the first lines of cell defense. Therefore, the discoveries on the intracellular antioxidant activity of polyphenols as a plant supplement have contributed significantly to the improvement of antioxidant activity, as polyphenols prevent oxidative stress damage and eliminate excessively produced free radicals. To achieve animal welfare, reduce stress and the need for medicines, and increase the quality of food of animal origin, the addition of polyphenols to research and breeding can be practised in part with a free-choice approach to animal nutrition.

In this work, a dataset of more than 200 nitroaromatic compounds is used to develop Quantitative Structure–Activity Relationship (QSAR) models for the estimation of in vivo toxicity based on 50% lethal dose to rats (LD50). An initial set of 4885 molecular descriptors was generated and applied to build Support Vector Regression (SVR) models. The best two SVR models, SVR_A and SVR_B, were selected to build an Ensemble Model by means of Multiple Linear Regression (MLR). The obtained Ensemble Model showed improved performance over the base SVR models in the training set (R2 = 0.88), validation set (R2 = 0.95), and true external test set (R2 = 0.92). The models were also internally validated by 5-fold cross-validation and Y-scrambling experiments, showing that the models have high levels of goodness-of-fit, robustness and predictivity. The contribution of descriptors to the toxicity in the models was assessed using the Accumulated Local Effect (ALE) technique. The proposed approach provides an important tool to assess toxicity of nitroaromatic compounds, based on the ensemble QSAR model and the structural relationship to toxicity by analyzed contribution of the involved descriptors.

The feeding of domestic animals with diets in which polyphenols are present is increasingly attracting the attention of nutritionists and scientists. This review summarizes the knowledge regarding polyphenols’ possible positive and negative effects and their bioavailability. The bioavailability of substances is a prerequisite for any postabsorption effect in vivo. Positive and negative properties have been confirmed in previous studies on the diets of domestic animals rich in polyphenols, such as secondary metabolites of plants. Free radicals are formed in every organism, leading to oxidative stress. Free radicals are highly reactive molecules and can react in cells with macromolecules and can cause damage, including in reproductive cells. Some polyphenols at specific concentrations have antioxidant properties that positively affect animal reproduction by improving the quality of male and female gametes. The intake of phytoestrogens that mimic estrogen function can induce various pathological conditions in the female reproductive tract, including ovarian, fallopian, and uterine dysfunction. The metabolism of genistein and daidzein yields the metabolites equol and p-phenyl-phenol, leading to a decline in cow fertilization. The findings so far confirm that numerous questions still need to be answered. This review points out the importance of using polyphenols that have both benificial and some unfavorable properties in specific diets.

The CompTox Chemistry Dashboard (ToxCast) contains one of the largest public databases on Zebrafish (Danio rerio) developmental toxicity. The data consists of 19 toxicological endpoints on unique 1018 compounds measured in relatively low concentration ranges. The endpoints are related to developmental effects occurring in dechorionated zebrafish embryos for 120 hours post fertilization and monitored via gross malformations and mortality. We report the predictive capability of 209 quantitative structure–activity relationship (QSAR) models developed by machine learning methods using penalization techniques and diverse model quality metrics to cope with the imbalanced endpoints. All these QSAR models were generated to test how the imbalanced classification (toxic or non-toxic) endpoints could be predicted regardless which of three algorithms is used: logistic regression, multi-layer perceptron, or random forests. Additionally, QSAR toxicity models are developed starting from sets of classical molecular descriptors, structural fingerprints and their combinations. Only 8 out of 209 models passed the 0.20 Matthew’s correlation coefficient value defined a priori as a threshold for acceptable model quality on the test sets. The best models were obtained for endpoints mortality (MORT), ActivityScore and JAW (deformation). The low predictability of the QSAR model developed from the zebrafish embryotoxicity data in the database is mainly due to a higher sensitivity of 19 measurements of endpoints carried out on dechorionated embryos at low concentrations.