Simple stochastic fingerprints towards mathematical modeling in biology and medicine. 3. Ocular irritability classification model.
MARCH-INSIDE methodology and a statistical classification method--linear discriminant analysis (LDA)--is proposed as an alternative method to the Draize eye irritation test. This methodology has been successfully applied to a set of 46 neutral organic chemicals, which have been defined as ocular irritant or nonirritant. The model allow to categorize correctly 37 out of 46 compounds, showing an accuracy of 80.46%. Specifically, this model demonstrates the existence of a good categorization average of 91.67 and 76.47% for irritant and nonirritant compounds, respectively. Validation of the model was carried out using two cross-validation tools: Leave-one-out (LOO) and leave-group-out (LGO), showing a global predictability of the model of 71.7 and 70%, respectively. The average of coincidence of the predictions between leave-one-out/leave-group-out studies and train set were 91.3% (42 out of 46 cases)/89.1% (41 out of 46 cases) proving the robustness of the model obtained. Ocular irritancy distribution diagram is carried out in order to determine the intervals of the property where the probability of finding an irritant compound is maximal relating to the choice of find a false nonirritant one. It seems that, until today, the present model may be the first predictive linear discriminant equation able to discriminate between eye irritant and nonirritant chemicals.
Cruz-Monteagudo
Maykel
M
Applied Chemistry Research Center, Central University of Las Villas, Santa Clara, 54830, Cuba.
González-Díaz
Humberto
H
Borges
Fernanda
F
González-Díaz
Yenny
Y
D000465:Algorithms; D000826:Animal Testing Alternatives / Q000379:methods; D000818:Animals; D005131:Eye Injuries / Q000139:chemically induced*; D005189:False Positive Reactions; D006801:Humans; D007509:Irritants / Q000737:chemistry / Q000145:classification* / Q000633:toxicity; D008390:Markov Chains; D008954:Models, Biological; D009930:Organic Chemicals / Q000145:classification* / Q000633:toxicity; D011336:Probability; D021281:Quantitative Structure-Activity Relationship; D012372:ROC Curve; D023382:Toxicity Tests, Acute
D007509:Irritants; D009930:Organic Chemicals