In silico methodology in toxicology – software for toxicity predictions

Abstract

For over a century, one of the main toxicologists’ goals was finding the relationship between the chemical structure and toxicity. The development of computer technologies has lead to the production of software models that could be applied for this purpose. However, use of in silico methodology in toxicology is very complex. Having in mind that toxic effect occurs through multiple mechanisms on different tissues and organs, creating software that can make reliable toxicity predictions is very complicated. In silico methods found the application in toxicity assessment of substances for which data obtained from traditional toxicity tests is lacking (metabolites, drug impurities, etc.). Also, in silico methods can be used in the process of chemical synthesis, with the aim of designing safer chemicals. Currently, in silico methods for toxicity predictions are most commonly used along with standard toxicological tests, with a tendency to replace in vitro and in vivo toxicity tests in the future. This paper will present the strengths and limitations of commonly used software in in silico toxicology (OECD QSAR Toolbox, Derek Nexus, ToxTree i MultiCASE).

Već više od sto godina jedan od glavnih ciljeva toksikologa je povezivanje hemijske strukture supstanci sa njihovom toksičnošću. Progres u razvoju kompjuterskih tehnologija omogućio je kreiranje softverskih modela za ovu namenu. Međutim, primena in silicometodologije u toksikologiji je veoma složena. Kako se toksični efekat može ostvariti preko više mehanizama na različitim tkivima i organima, veoma je kompleksno kreirati softvere kojima se može dovoljno pouzdano predvideti toksičnost ispitivane supstance. Upotreba in silico metoda našla je primenu u proceni toksičnosti onih supstanci za koje ne postoji dovoljno podataka dobijenih tradicionalnim testovima toksičnosti (metaboliti, nečistoće u lekovima, itd.). Takođe, in silico metode se mogu koristiti u procesu sinteze hemikalija, sa ciljem dobijanja bezbednijih hemikalija, dajući uvid u strukturne karakteristike odgovorne za toksičnost. In silicometode za predviđanje toksičnosti trenutno se najčešće koriste uz standardna toksikološka ispitivanja, dok je tendencija da u budućnosti zamene deo in vitro i in vivo testova toksičnosti. U ovom radu biće prikazane mogućnosti i ograničenja najčešće korišćenih softvera u in silico toksikologiji (OECD QSAR Toolbox, Derek Nexus, ToxTree i MultiCASE).