PMID- 16283904
OWN - NLM
STAT- MEDLINE
DCOM- 20060207
LR  - 20191210
IS  - 0105-1873 (Print)
IS  - 0105-1873 (Linking)
VI  - 53
IP  - 5
DP  - 2005 Nov
TI  - Predictive identification of human skin sensitization thresholds.
PG  - 260-7
AB  - For years, methods have been available for the predictive identification of 
      chemicals that possess the intrinsic potential to cause skin sensitization. 
      However, many have proven less suitable for the determination of relative 
      sensitizing potency. In this respect, the local lymph node assay (LLNA) has been 
      shown to have a number of important advantages. Through interpolation of LLNA 
      dose-response data, the concentration of a chemical required to produce a 
      threshold positive response (a 3-fold increase in activity compared with 
      concurrent vehicle controls, the EC3 value) can be measured. The robustness of 
      this parameter has been demonstrated rigorously in terms of inter- and 
      intralaboratory reproducibility. Additionally, the relationship between potency 
      estimates from the LLNA and an appreciation of human potency based on clinical 
      experience has been reported previously. In the present investigations, we have 
      sought to consolidate further our understanding of the association between EC3 
      values and human skin-sensitization potency by undertaking a thorough and 
      extensive analysis of existing human predictive assays, particularly where 
      dose-response information is available, from historical human repeated insult 
      patch tests (HRIPTs). From these human data, information on the approximate 
      threshold for the induction of skin sensitization in the HRIPT was determined for 
      26 skin-sensitizing chemicals. These data were then compared with LLNA-derived 
      EC3 values. The results from each assay, expressed as dose per unit area 
      (microg/cm(2)), revealed a clear linear relationship between the 2 values, 
      thereby substantiating further the utility of LLNA EC3 values for prediction of 
      the relative human sensitizing potency of newly identified skin sensitizers.
FAU - Basketter, David A
AU  - Basketter DA
AD  - Unilever, Colworth House, Sharnbrook, Bedfordshire, UK. 
      david.basketter@unilever.com
FAU - Clapp, Catherine
AU  - Clapp C
FAU - Jefferies, Donna
AU  - Jefferies D
FAU - Safford, Bob
AU  - Safford B
FAU - Ryan, Cindy A
AU  - Ryan CA
FAU - Gerberick, Frank
AU  - Gerberick F
FAU - Dearman, Rebecca J
AU  - Dearman RJ
FAU - Kimber, Ian
AU  - Kimber I
LA  - eng
PT  - Comparative Study
PT  - Evaluation Study
PT  - Journal Article
PL  - England
TA  - Contact Dermatitis
JT  - Contact dermatitis
JID - 7604950
RN  - 0 (Allergens)
RN  - 0 (Organic Chemicals)
SB  - IM
MH  - Allergens/*adverse effects/immunology
MH  - Animals
MH  - Confidence Intervals
MH  - Dermatitis, Allergic Contact/immunology/*prevention & control
MH  - Dose-Response Relationship, Immunologic
MH  - Humans
MH  - Linear Models
MH  - *Local Lymph Node Assay
MH  - Mice
MH  - Mice, Inbred CBA
MH  - Organic Chemicals/*adverse effects/immunology
MH  - Patch Tests
MH  - Risk Assessment
EDAT- 2005/11/15 09:00
MHDA- 2006/02/08 09:00
CRDT- 2005/11/15 09:00
PHST- 2005/11/15 09:00 [pubmed]
PHST- 2006/02/08 09:00 [medline]
PHST- 2005/11/15 09:00 [entrez]
AID - COD707 [pii]
AID - 10.1111/j.0105-1873.2005.00707.x [doi]
PST - ppublish
SO  - Contact Dermatitis. 2005 Nov;53(5):260-7. doi: 10.1111/j.0105-1873.2005.00707.x.