PMID- 19125718
OWN - NLM
STAT- MEDLINE
DCOM- 20090505
LR  - 20131121
IS  - 1600-0536 (Electronic)
IS  - 0105-1873 (Linking)
VI  - 60
IP  - 1
DP  - 2009 Jan
TI  - Read-across to rank skin sensitization potential: subcategories for the Michael 
      acceptor domain.
PG  - 21-31
LID - 10.1111/j.1600-0536.2008.01473.x [doi]
AB  - BACKGROUND: Eliminating animal testing for skin sensitization is a significant 
      challenge in consumer safety risk assessment. To be able to perform resilient 
      risk assessments in the future, one will need alternative approaches to fill the 
      data gaps. OBJECTIVES: To this end, we propose a subcategory-based read-across 
      approach to estimate and rank skin sensitization potential of chemicals. The 
      example described here is for the mechanism of Michael-type nucleophilic addition 
      with subcategories being limited to carbonyl-containing compounds. 
      PATIENTS/METHODS: In this approach, in silico tools based on structural alerts 
      were used to determine both the mechanism of protein binding and the relative 
      subcategories within that mechanism. RESULTS: Fifty compounds previously 
      evaluated in the in vivo mouse local lymph node assay (LLNA) were placed in 10 
      subcategories defined by their polarized alpha,beta-unsaturated substructure. To 
      offset the limitations and skewness of the published in vivo data, in chemico 
      glutathione (GSH) depletion data also were included. CONCLUSIONS: It was shown 
      that the read-across approach can be successfully used to rank qualitatively skin 
      sensitization potential of an untested carbonyl-containing Michael acceptor 
      chemical by using subcategories. Moreover, the use of the more resilient in 
      chemico GSH depletion data added further support to the read-across result.
FAU - Schultz, Terry Wayne
AU  - Schultz TW
AD  - Department of Comparative Medicine, College of Veterinary Medicine, The 
      University of Tennessee, 2407 River Drive, Knoxville, TN 37996-4543, USA.
FAU - Rogers, Kathryn
AU  - Rogers K
FAU - Aptula, Aynur Osman
AU  - Aptula AO
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PL  - England
TA  - Contact Dermatitis
JT  - Contact dermatitis
JID - 7604950
RN  - 0 (Irritants)
RN  - GAN16C9B8O (Glutathione)
SB  - IM
MH  - Animal Testing Alternatives/*methods
MH  - Animals
MH  - Catalytic Domain
MH  - Dermatitis, Allergic Contact/diagnosis/immunology
MH  - Dermatitis, Irritant/diagnosis/*immunology
MH  - Disease Models, Animal
MH  - Glutathione/immunology/toxicity
MH  - Guinea Pigs
MH  - Humans
MH  - Immunization/methods
MH  - Irritants/*toxicity
MH  - Local Lymph Node Assay
MH  - Mice
MH  - Models, Chemical
MH  - Protein Binding/immunology
MH  - Risk Factors
MH  - Sensitivity and Specificity
MH  - Severity of Illness Index
MH  - Skin Irritancy Tests/*methods
MH  - Toxicity Tests/*methods
RF  - 35
EDAT- 2009/01/08 09:00
MHDA- 2009/05/06 09:00
CRDT- 2009/01/08 09:00
PHST- 2009/01/08 09:00 [entrez]
PHST- 2009/01/08 09:00 [pubmed]
PHST- 2009/05/06 09:00 [medline]
AID - COD1473 [pii]
AID - 10.1111/j.1600-0536.2008.01473.x [doi]
PST - ppublish
SO  - Contact Dermatitis. 2009 Jan;60(1):21-31. doi: 10.1111/j.1600-0536.2008.01473.x.