Chemical Diversity Approach for Evaluating Mechanistic Relatedness Among Toxicological Phenomena
作者:
N. Pollack,
A.R. Cunningham,
G. Klopman,
H.S. Rosenkranz,
期刊:
SAR and QSAR in Environmental Research
(Taylor Available online 1999)
卷期:
Volume 10,
issue 6
页码: 533-543
ISSN:1062-936X
年代: 1999
DOI:10.1080/10629369908033222
出版商: Taylor & Francis Group
关键词: Structure-activity relationship;SAR;CASE/MULTICASE;eye irritation;mechanis
数据来源: Taylor
摘要:
The CASE/MULTICASE structure-activity relationship (SAR) system was used to assess a new procedure to investigate the mechanistic relatedness of various toxicological endpoints. The method consisted of predicting the activity of 10,000 randomly selected chemicals using validated and characterized SAR models from a variety of biological and toxicological endpoints. The prevalence of chemicals predicted to possess the ability to induce two or more toxicological effects simultaneously should provide a measure of the mechanistic relatedness of these phenomena. Eight toxicological endpoints were predicted and the results were compared to predictions based on an eye irritation SAR model. Allergic contact dermatitis demonstrated a 29.6% greater than expected overlap between expected and observed results (p< 0.001). Similar results were seen for respiratory hypersensitivity (33.1%), sensory irritation (28.9%), cell toxicity (25.9%), and Ah receptor binding (19.8%). A lesser degree of overlap was seen between eye irritation andSalmonellamutagenicity (11.5%) and the inhibition of gap junction intercellular communication (6.7%). Moreover, a negative overlap, suggesting possibly an antagonistic phenomena, was observed between eye irritation and α2μ-induced nephropathy. These results indicate that this method can provide a useful tool to investigate mechanistic relatedness between diverse toxicological endpoints.
点击下载:
PDF (599KB)
返 回