PMID- 15135206
OWN - NLM
STAT- MEDLINE
DCOM- 20040923
LR  - 20220311
IS  - 0273-2300 (Print)
IS  - 0273-2300 (Linking)
VI  - 39
IP  - 3
DP  - 2004 Jun
TI  - Quantitative relationship between the local lymph node assay and human skin 
      sensitization assays.
PG  - 245-55
AB  - The local lymph node assay (LLNA) is a new test method which allows for the 
      quantitative assessment of sensitizing potency in the mouse. Here, we investigate 
      the quantitative correlation between results from the LLNA and two human 
      sensitization tests--specifically, human repeat insult patch tests (HRIPTs) and 
      human maximization tests (HMTs). Data for 57 substances were evaluated, of which 
      46 showed skin sensitizing properties in human tests, whereas 11 yielded negative 
      results in humans. For better comparability data from mouse and human tests were 
      transformed to applied doses per skin area, which ranged over four orders of 
      magnitude for the substances considered. Regression analysis for the 46 human 
      sensitizing substances revealed a significant positive correlation between the 
      LLNA and human tests. The correlation was better between LLNA and HRIPT data 
      (n=23; r=0.77) than between LLNA and HMT data (n=38; r=0.65). The observed 
      scattering of data points is related to various uncertainties, in part associated 
      with insufficiencies of data from older HMT studies. Predominantly negative 
      results in the LLNA for another 11 substances which showed no skin sensitizing 
      activity in human maximization tests further corroborate the correspondence 
      between LLNA and human tests. Based on this analysis, the LLNA can be considered 
      a reliable basis for relative potency assessments for skin sensitizers. Proposals 
      are made for the regulatory exploitation of the LLNA: four potency groups can be 
      established, and assignment of substances to these groups according to the 
      outcome of the LLNA can be used to characterize skin sensitizing potency in 
      substance-specific assessments. Moreover, based on these potency groups, a more 
      adequate consideration of sensitizing substances in preparations becomes 
      possible. It is proposed to replace the current single concentration limit for 
      skin sensitizers in preparations, which leads to an all or nothing classification 
      of a preparation as sensitizing to skin ("R43") in the European Union, by 
      differentiated concentration limits derived from the limits for the four potency 
      groups.
FAU - Schneider, K
AU  - Schneider K
AD  - Forschungs-und Beratungsinstitut Gefahrstoffe (FoBiG) GmbH, Werderring 16, 
      D-79098 Freiburg, Germany. klaus.schneider@fobig.de
FAU - Akkan, Z
AU  - Akkan Z
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - Regul Toxicol Pharmacol
JT  - Regulatory toxicology and pharmacology : RTP
JID - 8214983
RN  - 0 (Allergens)
SB  - IM
MH  - Allergens/administration & dosage/classification/*toxicity
MH  - Animals
MH  - Dermatitis, Allergic Contact/etiology
MH  - Disease Models, Animal
MH  - Dose-Response Relationship, Drug
MH  - Dose-Response Relationship, Immunologic
MH  - European Union
MH  - Government Regulation
MH  - Humans
MH  - Hypersensitivity/etiology
MH  - *Local Lymph Node Assay
MH  - Mice
MH  - *Patch Tests
MH  - Predictive Value of Tests
MH  - Regression Analysis
MH  - Reproducibility of Results
EDAT- 2004/05/12 05:00
MHDA- 2004/09/24 05:00
CRDT- 2004/05/12 05:00
PHST- 2003/11/18 00:00 [received]
PHST- 2004/05/12 05:00 [pubmed]
PHST- 2004/09/24 05:00 [medline]
PHST- 2004/05/12 05:00 [entrez]
AID - S0273230004000121 [pii]
AID - 10.1016/j.yrtph.2004.02.002 [doi]
PST - ppublish
SO  - Regul Toxicol Pharmacol. 2004 Jun;39(3):245-55. doi: 10.1016/j.yrtph.2004.02.002.