TY - JOUR
T1 - Identification of structural alerts for liver and kidney toxicity using repeated dose toxicity data
AU - Pizzo, Fabiola
AU - Gadaleta, Domenico
AU - Lombardo, Anna
AU - Nicolotti, Orazio
AU - Benfenati, Emilio
PY - 2015/12/1
Y1 - 2015/12/1
N2 - Background: The potential for a compound to cause hepatotoxicity and nephrotoxicity is a matter of extreme interest for human health risk assessment. To assess liver and kidney toxicity, repeated-dose toxicity (RDT) studies are conducted mainly on rodents. However, these tests are expensive, time-consuming and require large numbers of animals. For early toxicity screening, in silico models can be applied, reducing the costs, time and animals used. Among in silico approaches, structure-activity relationship (SAR) methods, based on the identification of chemical substructures (structural alerts, SAs) related to a particular activity (toxicity), are widely employed. Results: We identified and evaluated some SAs related to liver and kidney toxicity, using RDT data on rats taken from the hazard evaluation support system (HESS) database. We considered only SAs that gave the best percentages of true positives (TP). Conclusions: It was not possible to assign an unambiguous mode of action for all the SAs, but a mechanistic explanation is provided for some of them. Such achievements may help in the early identification of liver and renal toxicity of substances.
AB - Background: The potential for a compound to cause hepatotoxicity and nephrotoxicity is a matter of extreme interest for human health risk assessment. To assess liver and kidney toxicity, repeated-dose toxicity (RDT) studies are conducted mainly on rodents. However, these tests are expensive, time-consuming and require large numbers of animals. For early toxicity screening, in silico models can be applied, reducing the costs, time and animals used. Among in silico approaches, structure-activity relationship (SAR) methods, based on the identification of chemical substructures (structural alerts, SAs) related to a particular activity (toxicity), are widely employed. Results: We identified and evaluated some SAs related to liver and kidney toxicity, using RDT data on rats taken from the hazard evaluation support system (HESS) database. We considered only SAs that gave the best percentages of true positives (TP). Conclusions: It was not possible to assign an unambiguous mode of action for all the SAs, but a mechanistic explanation is provided for some of them. Such achievements may help in the early identification of liver and renal toxicity of substances.
KW - In silico
KW - Kidney
KW - Liver
KW - Mechanism of action
KW - Structural alerts
KW - Toxicity
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U2 - 10.1186/s13065-015-0139-7
DO - 10.1186/s13065-015-0139-7
M3 - Article
AN - SCOPUS:84946569574
VL - 9
SP - 1
EP - 11
JO - Chemistry Central Journal
JF - Chemistry Central Journal
SN - 1752-153X
IS - 1
ER -