Development of mechanism-based structural alerts for respiratory sensitization hazard identification.
This study outlines how mechanistic organic chemistry related to covalent bond formation can be used to rationalize the ability of low molecular weight chemicals to cause respiratory sensitization. The results of an analysis of 104 chemicals which have been reported to cause respiratory sensitization in humans showed that most of the sensitizing chemicals could be distinguished from 82 control chemicals for which no clinical reports of respiratory sensitization exist. This study resulted in the development of a set of mechanism-based structural alerts for chemicals with the potential to cause respiratory sensitization. Their potential for use in a predictive algorithm for this purpose alongside an externally validated quantitative structure-activity relationship model is discussed.
School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpool, England L3 3AF. s.j.enoch@ljmu.ac.uk
S J
SJ
Enoch
M J
MJ
Seed
D W
DW
Roberts
M T D
MT
Cronin
S J
SJ
Stocks
R M
RM
Agius
D000485:Allergens / Q000009:adverse effects* / Q000737:chemistry; D006801:Humans; D015394:Molecular Structure; D008970:Molecular Weight; D009930:Organic Chemicals / Q000009:adverse effects* / Q000737:chemistry; D021281:Quantitative Structure-Activity Relationship; D012130:Respiratory Hypersensitivity / Q000139:chemically induced*
D000485:Allergens; D009930:Organic Chemicals