Md. Barratt et Jj. Langowski, Validation and subsequent development of the DEREK skin sensitization rulebase by analysis of the BgVV list of contact allergens, J CHEM INF, 39(2), 1999, pp. 294-298
Citations number
27
Categorie Soggetti
Chemistry
Journal title
JOURNAL OF CHEMICAL INFORMATION AND COMPUTER SCIENCES
The DEREK knowledge-based computer system contains a subset of approximatel
y 50 rules describing chemical substructures (toxophores) responsible for s
kin sensitization. This rulebase, based originally on Unilever historical i
n-house guinea pig maximization test data, has been subject to extensive va
lidation and is undergoing refinement as the next stage of its development.
As part of an ongoing program of validation and testing, the predictive, a
bility of the sensitization rule set has been assessed by processing the st
ructures of the 84 chemical substances in the list of contact allergens iss
ued by the BgVV (German Federal Institute for Health Protection of Consumer
s). This list of chemicals is important because the biological data for eac
h of the chemicals have been carefully scrutinized and peer reviewed, a key
consideration in an area of toxicology in which much unreliable and potent
ially misleading data have been published. The existing DEREK rulebase for
skin sensitization identified toxophores for skin sensitization in the stru
ctures of 71 out of the 84 chemicals (85%). The exercise highlighted areas
of chemistry where further development of the rulebase was required, either
by extension of the scope of existing rules or by generation of new rules
where a sound mechanistic rationale for the biological activity could be es
tablished. Chemicals likely to be acting as photoallergens were identified,
and new rules for photoallergenicity have subsequently been written. At th
e end of the exercise, the refined rulebase was able to identify toxophores
for skin sensitization for 82 of the 84 chemicals in the BgVV list.