PMID- 9561969
OWN - NLM
STAT- MEDLINE
DCOM- 19980430
LR  - 20191102
IS  - 1528-7394 (Print)
IS  - 0098-4108 (Linking)
VI  - 53
IP  - 7
DP  - 1998 Apr 10
TI  - Assessment of the skin sensitization potential of topical medicaments using the 
      local lymph node assay: an interlaboratory evaluation.
PG  - 563-79
AB  - The murine local lymph node assay (LLNA) is a method for the predictive 
      identification of chemicals that have a potential to cause skin sensitization. 
      Activity is measured as a function of lymph node cell (LNC) proliferative 
      responses stimulated by topical application of test chemicals. Those chemicals 
      that induce a threefold or greater increase in LNC proliferation compared with 
      concurrent vehicle controls are classified as skin sensitizers. In the present 
      investigations we have evaluated further the reliability and accuracy of the 
      LLNA. In the context of an international interlaboratory trial the sensitization 
      potentials of six materials with a history of use in topical medicaments have 
      been evaluated: benzoyl peroxide, hydroquinone, penicillin G, streptomycin 
      sulfate, ethylenediamine dihydrochloride, and methyl salicylate. Each chemical 
      was analyzed in the LLNA by all five laboratories. Either the standard LLNA 
      protocol or minor modifications of it were used. Benzoyl peroxide and 
      hydroquinone, both human contact allergens, elicited strong LLNA responses in 
      each laboratory. Penicillin G, another material shown previously to cause 
      allergic contact dermatitis in humans, was also positive in all laboratories. 
      Streptomycin sulfate induced equivocal responses, in that this material provoked 
      a positive LLNA response in only one of the five laboratories, and then only at 
      the highest concentration tested. Ethylenediamine dihydrochloride dissolved in a 
      3:1 mixture of acetone with water, or in 4:1 acetone:olive oil (one laboratory), 
      was uniformly negative. However, limited further testing with the free base of 
      ethylene diamine yielded a positive LLNA response when applied in acetone:olive 
      oil (AOO). Finally, methyl salicylate, a nonsensitizing skin irritant, was 
      negative at all test concentrations in each laboratory. Collectively these data 
      serve to confirm that the local lymph node assay is sufficiently robust to yield 
      equivalent results when performed independently in separate laboratories and 
      indicate also that the LLNA is of value in assessing the skin sensitization 
      potential of topical medicaments.
FAU - Kimber, I
AU  - Kimber I
AD  - Zeneca Central Toxicology Laboratory, Macclesfield, Cheshire, UK. 
      IAN.KIMBER@APVXCI.ZENECA.COM
FAU - Hilton, J
AU  - Hilton J
FAU - Dearman, R J
AU  - Dearman RJ
FAU - Gerberick, G F
AU  - Gerberick GF
FAU - Ryan, C A
AU  - Ryan CA
FAU - Basketter, D A
AU  - Basketter DA
FAU - Lea, L
AU  - Lea L
FAU - House, R V
AU  - House RV
FAU - Ladics, G S
AU  - Ladics GS
FAU - Loveless, S E
AU  - Loveless SE
FAU - Hastings, K L
AU  - Hastings KL
LA  - eng
PT  - Journal Article
PL  - England
TA  - J Toxicol Environ Health A
JT  - Journal of toxicology and environmental health. Part A
JID - 100960995
SB  - IM
MH  - Administration, Topical
MH  - Animals
MH  - Data Interpretation, Statistical
MH  - Dermatitis, Contact/*pathology
MH  - Drug Hypersensitivity/*pathology
MH  - Female
MH  - Lymph Nodes/*drug effects
MH  - Mice
MH  - Mice, Inbred CBA
MH  - Predictive Value of Tests
EDAT- 1998/04/30 00:00
MHDA- 1998/04/30 00:01
CRDT- 1998/04/30 00:00
PHST- 1998/04/30 00:00 [pubmed]
PHST- 1998/04/30 00:01 [medline]
PHST- 1998/04/30 00:00 [entrez]
AID - 10.1080/009841098159141 [doi]
PST - ppublish
SO  - J Toxicol Environ Health A. 1998 Apr 10;53(7):563-79. doi: 
      10.1080/009841098159141.