Overview of the effects of chemical mixtures with endocrine disrupting activity in the context of real-life risk simulation (RLRS): An integrative approach (Review)

Research over the past years has indicated that chronic human exposure to very low doses of various chemical species in mixtures and administered via different routes (percutaneous, orally, etc.) should be the main focus of new biochemical and toxicological studies. Humans have daily contact with various chemicals, such as food additives, pesticides from fruits/vegetables, antibiotics (and other veterinary drugs) from meat, different types of preservatives from cosmetics, to name a few. Simultaneous exposure to this wide array of chemicals does not produce immediate effects, but summative effect/s over time that may be clinically manifested several years thereafter. Classical animal studies designed to test the toxic outcome of a single chemical are not suitable to assess, and then extrapolate to humans, the effects of a whole mixture of chemicals. Testing the aftermath of a combination of chemicals, at low doses, around or below the no observed adverse effect is stressed by many toxicologists. Thus, there is a need to reformulate the design of biochemical and toxicological studies in order to perform real-life risk simulation. This review discuss the potential use of computational methods as a complementary tool for in vitro and in vivo toxicity tests with a high predictive potential that could contribute to reduce animal testing, cost and time, when assessing the effects of chemical combinations. This review focused on the use of these methods to predict the potential endocrine disrupting activity of a mixture of chemicals.