PMID- 19025322
OWN - NLM
STAT- MEDLINE
DCOM- 20090106
LR  - 20190518
IS  - 0261-1929 (Print)
IS  - 0261-1929 (Linking)
VI  - 36
IP  - 5
DP  - 2008 Nov
TI  - Application of a systems biology approach to skin allergy risk assessment.
PG  - 521-56
AB  - We have developed an in silico model of the induction of skin sensitisation, in 
      order to characterise and quantify the contribution of each pathway to the 
      overall biological process. This analysis has been used to guide our research on 
      skin sensitisation and in vitro test development programmes, and provides a 
      theoretical rationale for the interpretation and integration of non-animal 
      predictive data for risk assessment (RA) purposes. The in vivo mouse Local Lymph 
      Node Assay (LLNA) is now in widespread use for the evaluation of skin 
      sensitisation potential and potency. Recent changes in European Union (EU) 
      legislation (i.e. the 7th Amendment to the EU Cosmetics Directive) have made the 
      development of nonanimal approaches to provide the data for skin sensitisation RA 
      a key business need. Several in vitro predictive assays have already been 
      developed for the prediction of skin sensitisation. However, these are based on 
      the determination of a small number of pathways within the overall biological 
      process, and our understanding of the relative contribution of these individual 
      pathways to skin sensitisation induction is limited. To address this knowledge 
      gap, a "systems biology" approach has been used to construct a computer-based 
      mathematical model of the induction of skin sensitisation, in collaboration with 
      Entelos, Inc. The biological mechanisms underlying the induction phase of skin 
      sensitisation are represented by nonlinear ordinary differential equations and 
      defined by using information from over 500 published papers. By using the model, 
      we have identified knowledge gaps for future investigative research, and key 
      factors that have a major influence on the induction of skin sensitisation (e.g. 
      TNF-alpha production in the epidermis). The relative contribution of each of 
      these key pathways has been assessed by determining their contributions to the 
      overall process (e.g. sensitiser-specific T-cell proliferation in the draining 
      lymph node). This information provides a biologically-relevant rationale for the 
      interpretation and potential integration of diverse types of non-animal 
      predictive data. Consequently, the Skin Sensitisation Physiolab (SSP) platform 
      represents one approach to integration that is likely to prove an invaluable tool 
      for hazard evaluation in a new framework for consumer safety RA.
CI  - 2008 FRAME.
FAU - Maxwell, Gavin
AU  - Maxwell G
AD  - Unilever Safety & Environmental Assurance Centre (SEAC), Sharnbrook, 
      Bedfordshire, UK. gavin.maxwell@unilever.com
FAU - Mackay, Cameron
AU  - Mackay C
LA  - eng
PT  - Journal Article
PL  - England
TA  - Altern Lab Anim
JT  - Alternatives to laboratory animals : ATLA
JID - 8110074
SB  - IM
MH  - Animal Testing Alternatives
MH  - Animals
MH  - Dermatitis, Allergic Contact/*etiology
MH  - Humans
MH  - Local Lymph Node Assay
MH  - Risk Assessment/*methods
MH  - Systems Biology/*methods
MH  - T-Lymphocytes/immunology
EDAT- 2008/11/26 09:00
MHDA- 2009/01/07 09:00
CRDT- 2008/11/26 09:00
PHST- 2008/11/26 09:00 [pubmed]
PHST- 2009/01/07 09:00 [medline]
PHST- 2008/11/26 09:00 [entrez]
AID - 10.1177/026119290803600510 [doi]
PST - ppublish
SO  - Altern Lab Anim. 2008 Nov;36(5):521-56. doi: 10.1177/026119290803600510.