Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2001-4-17
pubmed:abstractText
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0340-5761
pubmed:author
pubmed:issnType
Print
pubmed:volume
74
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
733-44
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:11305775-Administration, Topical, pubmed-meshheading:11305775-Allergens, pubmed-meshheading:11305775-Animals, pubmed-meshheading:11305775-Cell Count, pubmed-meshheading:11305775-Dermatitis, Allergic Contact, pubmed-meshheading:11305775-Dermatitis, Phototoxic, pubmed-meshheading:11305775-Dose-Response Relationship, Drug, pubmed-meshheading:11305775-Ear, External, pubmed-meshheading:11305775-Female, pubmed-meshheading:11305775-Hyperplasia, pubmed-meshheading:11305775-Local Lymph Node Assay, pubmed-meshheading:11305775-Lymph Nodes, pubmed-meshheading:11305775-Lymphocyte Activation, pubmed-meshheading:11305775-Mice, pubmed-meshheading:11305775-Mice, Inbred BALB C, pubmed-meshheading:11305775-Organ Size, pubmed-meshheading:11305775-Reproducibility of Results, pubmed-meshheading:11305775-Specific Pathogen-Free Organisms, pubmed-meshheading:11305775-Time Factors, pubmed-meshheading:11305775-Toxicity Tests
pubmed:year
2001
pubmed:articleTitle
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.
pubmed:affiliation
PCS-Genetic and Experimental Toxicology, Novartis Pharma AG, Basel, Switzerland. peter.ulrich@pharma.novartis.com
pubmed:publicationType
Journal Article, Comparative Study, Validation Studies