PMID- 11526521
OWN - NLM
STAT- MEDLINE
DCOM- 20011018
LR  - 20220311
IS  - 1046-199X (Print)
IS  - 1046-199X (Linking)
VI  - 12
IP  - 3
DP  - 2001 Sep
TI  - Contact allergenic potency: correlation of human and local lymph node assay data.
PG  - 156-61
AB  - BACKGROUND: Effective toxicologic evaluation of skin sensitization requires that 
      potential contact allergens are identified and that the likely risks of 
      sensitization among exposed populations are assessed. By definition, chemicals 
      that are classified as contact sensitizers have the capacity to cause allergic 
      contact dermatitis (ACD) in humans. However, this hazard is not an all-or-nothing 
      phenomenon; clear dose-response relationships can be discerned and thresholds 
      identified for both the induction of sensitization and the elicitation of ACD. 
      Commonly, these parameters are grouped under the heading of potency, the 
      determination of which is vital for risk assessment. Preclinical testing for 
      sensitization potential is critically important for hazard assessment before 
      human exposure. The murine local lymph node assay (LLNA) is the most recently 
      accepted test method for sensitization hazard assessment. OBJECTIVE: The aim was 
      to compare potency estimations derived from LLNA data with clinical 
      determinations of relative potency based on human data. METHODS: No-effect levels 
      (NOELs) for a range of 21 chemicals were determined from nondiagnostic human 
      repeat patch test studies as reported in the literature. These levels were 
      compared with LLNA EC(3) values, the estimated concentration required to produce 
      a 3-fold increase (positive response) in draining lymph node cell (LNC) 
      proliferative activity. RESULTS: Using available human repeat patch test data, 
      together with expert judgment, the compounds were classified as strong, moderate, 
      weak, extremely weak, or nonsensitizing. Additionally, the potency of each 
      chemical was classified independently based on its LLNA EC(3) value. The results 
      show clearly that LLNA EC(3) values are very comparable with the NOELs calculated 
      from the literature. Moreover, the potency rankings based upon LLNA EC(3) data 
      support their human classification. CONCLUSION: The present investigations show 
      that the LLNA can be used to provide quantitative estimates of relative skin 
      sensitizing potency EC(3) values that correlate closely with NOELs established 
      from human repeat patch testing and from our clinical experience.
CI  - Copyright 2001 by W.B. Saunders Company
FAU - Gerberick, G F
AU  - Gerberick GF
AD  - Human and Environmental Safety Division, Procter and Gamble, Cincinnati, OH 
      45252, USA. gerberick.gf@pg.com
FAU - Robinson, M K
AU  - Robinson MK
FAU - Ryan, C A
AU  - Ryan CA
FAU - Dearman, R J
AU  - Dearman RJ
FAU - Kimber, I
AU  - Kimber I
FAU - Basketter, D A
AU  - Basketter DA
FAU - Wright, Z
AU  - Wright Z
FAU - Marks, J G
AU  - Marks JG
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Canada
TA  - Am J Contact Dermat
JT  - American journal of contact dermatitis : official journal of the American Contact 
      Dermatitis Society
JID - 9100472
RN  - 0 (Allergens)
SB  - IM
MH  - Allergens/*adverse effects
MH  - Animals
MH  - Biological Assay
MH  - Dermatitis, Allergic Contact/*diagnosis/etiology
MH  - Humans
MH  - Local Lymph Node Assay
MH  - Lymph Nodes/*drug effects/pathology
MH  - Mice
MH  - Patch Tests/*standards
EDAT- 2001/08/30 10:00
MHDA- 2001/10/19 10:01
CRDT- 2001/08/30 10:00
PHST- 2001/08/30 10:00 [pubmed]
PHST- 2001/10/19 10:01 [medline]
PHST- 2001/08/30 10:00 [entrez]
AID - S1046-199X(01)49486-3 [pii]
AID - 10.1053/ajcd.2001.23926 [doi]
PST - ppublish
SO  - Am J Contact Dermat. 2001 Sep;12(3):156-61. doi: 10.1053/ajcd.2001.23926.