Structure–activity relationships for skin sensitization: recent improvements to Derek for Windows

Derek for Windows (DfW) is a knowledge‐based expert system that predicts the toxicity of a chemical from its structure. Its predictions are based in part on alerts that describe structural features or toxicophores associated with toxicity. Recently, improvements have been made to skin sensitization alerts within the DfW knowledge base in collaboration with Unilever. These include modifications to the alerts describing the skin sensitization potential of aldehydes, 1,2‐diketones, and isothiazolinones and consist of enhancements to the toxicophore definition, the mechanistic classification, and the extent of supporting evidence provided. The outcomes from this collaboration demonstrate the importance of updating and refining computer models for the prediction of skin sensitization as new information from experimental and theoretical studies becomes available.

[1]  K Enslein,et al.  A quantitative structure-toxicity relationships model for the dermal sensitization guinea pig maximization assay. , 1997, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[2]  D. Roberts,et al.  Structure‐activity relationships in the murine local lymph node assay for skin sensitization: α,β‐diketones , 1999, Contact dermatitis.

[3]  Philip N. Judson,et al.  Using Argumentation for Absolute Reasoning about the Potential Toxicity of Chemicals , 2003, J. Chem. Inf. Comput. Sci..

[4]  I. Kimber,et al.  Dendritic cells and skin sensitisation hazard assessment. , 2004, Toxicology in vitro : an international journal published in association with BIBRA.

[5]  D A Basketter,et al.  An expert system rulebase for identifying contact allergens. , 1994, Toxicology in vitro : an international journal published in association with BIBRA.

[6]  G. Patlewicz,et al.  Further evaluation of quantitative structure–activity relationship models for the prediction of the skin sensitization potency of selected fragrance allergens , 2004, Contact dermatitis.

[7]  R. Rietschel.  Human and economic impact of allergic contact dermatitis and the role of patch testing. , 1995, Journal of the American Academy of Dermatology.

[8]  M D Barratt,et al.  Development of an expert system rulebase for the prospective identification of photoallergens. , 2000, Journal of photochemistry and photobiology. B, Biology.

[9]  M. D. Barratt,et al.  Validation and Subsequent Development of the Derek Skin Sensitization Rulebase by Analysis of the BgVV List of Contact Allergens , 1999, J. Chem. Inf. Comput. Sci..

[10]  B. R. Alexander.  An assessment of the comparative sensitization potential of some common isothiazolinones , 2002, Contact dermatitis.

[11]  M. Bruze,et al.  Chloroatranol, an extremely potent allergen hidden in perfumes: a dose‐response elicitation study , 2003, Contact dermatitis.

[12]  G. Patlewicz,et al.  Skin‐sensitization structure‐activity relationships for aldehydes , 2001, Contact dermatitis.

[13]  A. Goossens,et al.  Contact allergy to oak moss: search for sensitizing molecules using combined bioassay-guided chemical fractionation, GC-MS, and structure-activity relationship analysis , 2003, Archives of Dermatological Research.

[14]  Jean-Pierre Lepoittevin,et al.  Studies of chemical selectivity of hapten, reactivity, and skin sensitization potency. 3. Synthesis and studies on the reactivity toward model nucleophiles of the 13C-labeled skin sensitizers, 5-chloro-2-methylisothiazol-3-one (MCI) and 2-methylisothiazol-3-one (MI). , 2003, Chemical research in toxicology.

[15]  Manuela Pavan,et al.  The Characterisation of (Quantitative) Structure-Activity Relationships: Preliminary Guidance , 2005 .

[16]  G. Patlewicz,et al.  Structure–activity relationships for selected fragrance allergens , 2002, Contact dermatitis.