PMID- 11305775
OWN - NLM
STAT- MEDLINE
DCOM- 20010712
LR  - 20191210
IS  - 0340-5761 (Print)
IS  - 0340-5761 (Linking)
VI  - 74
IP  - 12
DP  - 2001 Feb
TI  - Intralaboratory validation of alternative endpoints in the murine local lymph 
      node assay for the identification of contact allergic potential: primary ear skin 
      irritation and ear-draining lymph node hyperplasia induced by topical chemicals.
PG  - 733-44
AB  - We validated a two-tiered murine local lymph node assay (LLNA) with a panel of 
      standard contact (photo)allergens and (photo)irritants with the aim of improving 
      the discrimination between contact (photo) allergenic potential and true skin 
      (photo)irritation potential. We determined ear weights to correlate 
      chemical-induced skin irritation with the ear-draining lymph node (LN) activation 
      potential. During tier I LLNAs, a wide range of concentrations were applied on 
      three consecutive days to the dorsum of both ears. Mice were exposed to UVA light 
      immediately after topical application to determine the photoreactive potential of 
      some test chemicals. Mice were killed 24 h after the last application to 
      determine ear and LN weights and LN cell counts. It was possible to classify the 
      tested chemicals into three groups according to their threshold concentrations 
      for LN activation and skin irritation: (1) chemicals with a low LN activation 
      potential and no or very low skin irritation potential; (2) chemicals with a 
      marked LN activation potential higher than a distinct skin irritation potential; 
      and (3) chemicals with LN activation potential equal to or lower than their skin 
      irritation potential. Group 1 consisted only of contact allergens, indicating 
      that LN activation in the absence of skin irritation points to a contact 
      allergenic activity. Since groups 2 and 3 comprised irritants and contact 
      allergens, a tier II LLNA protocol was used to finally differentiate between true 
      irritants and contact allergens. Briefly, mice were pretreated with mildly to 
      moderately irritating concentrations of the chemical to the shaved back and after 
      12 days were challenged on the ears as described above in order to elicit a 
      contact allergenic response in the ear skin and the ear-draining LN. With this 
      approach, tier II LLNAs have to be conducted only in cases for which skin 
      irritation potential is in the range of LN activation potential and no 
      structure-activity relationship data indicating a contact allergenic hazard are 
      available.
FAU - Ulrich, P
AU  - Ulrich P
AD  - PCS-Genetic and Experimental Toxicology, Novartis Pharma AG, Basel, Switzerland. 
      peter.ulrich@pharma.novartis.com
FAU - Streich, J
AU  - Streich J
FAU - Suter, W
AU  - Suter W
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Validation Study
PL  - Germany
TA  - Arch Toxicol
JT  - Archives of toxicology
JID - 0417615
RN  - 0 (Allergens)
SB  - IM
MH  - Administration, Topical
MH  - Allergens/classification/*toxicity
MH  - Animals
MH  - Cell Count
MH  - Dermatitis, Allergic Contact/*etiology/immunology/pathology
MH  - Dermatitis, Phototoxic/*etiology/immunology/pathology
MH  - Dose-Response Relationship, Drug
MH  - Ear, External/drug effects/pathology
MH  - Female
MH  - Hyperplasia
MH  - *Local Lymph Node Assay
MH  - Lymph Nodes/*drug effects/immunology/pathology
MH  - Lymphocyte Activation/drug effects
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Organ Size/drug effects
MH  - Reproducibility of Results
MH  - Specific Pathogen-Free Organisms
MH  - Time Factors
MH  - Toxicity Tests
EDAT- 2001/04/18 10:00
MHDA- 2001/07/13 10:01
CRDT- 2001/04/18 10:00
PHST- 2001/04/18 10:00 [pubmed]
PHST- 2001/07/13 10:01 [medline]
PHST- 2001/04/18 10:00 [entrez]
AID - 10.1007/s002040000192 [doi]
PST - ppublish
SO  - Arch Toxicol. 2001 Feb;74(12):733-44. doi: 10.1007/s002040000192.