PMID- 18830887
OWN - NLM
STAT- MEDLINE
DCOM- 20081222
LR  - 20191210
IS  - 1547-6901 (Electronic)
IS  - 1547-691X (Linking)
VI  - 5
IP  - 3
DP  - 2008 Jul
TI  - Use of an ex vivo local lymph node assay to assess contact hypersensitivity 
      potential.
PG  - 271-7
LID - 10.1080/15376510802311961 [doi]
AB  - The local lymph node assay (LLNA) is used to assess the contact hypersensitivity 
      potential of compounds. In the standard assay, mice are treated topically with 
      test compound to the dorsum of both ears on Days 1-3. The induction of a 
      hypersensitivity response is assessed on Day 6 by injecting [(3)H]-thymidine into 
      a tail vein and measuring thymidine incorporation into DNA of lymph node cells 
      draining the ears. The ex vivo LLNA is conducted similarly except lymphocyte 
      proliferation is assessed after in vitro incubation of lymph node cells with 
      [(3)H]-thymidine, which significantly reduces the amount of radioactive waste. 
      The current study tested the use of this approach for hazard assessment of 
      contact hypersensitivity and to estimate allergenic potency. Female BALB/c mice 
      were treated on Days 1-3 with two nonsensitizers (4' -methoxyacetophenone, 
      diethyl phthalate), three weak sensitizers (hydroxycitronellal, eugenol, citral), 
      one weak-to-moderate sensitizer (hexylcinnamic aldehyde), two moderate 
      sensitizers (isoeugenol, phenyl benzoate), and one strong sensitizer 
      (dinitrochlorobenzene). On Day 6, isolated lymph node cells were incubated 
      overnight with [(3)H]-thymidine and thymidine incorporation was measured by 
      liquid scintillation spectrophotometry. The ex vivo LLNA accurately distinguished 
      the contact sensitizers from the nonsensitizing chemicals, and correctly ranked 
      the relative potency of the compounds tested. The EC3 values, i.e., the effective 
      concentration of test substance needed to induce a stimulation index of 3, were 
      as follows: 4' -methoxyacetophenone (> 50%), diethyl phthalate (> 50%), 
      hydroxycitronellal (20.4%), eugenol (13.6%), citral (8.9%), isoeugenol (3.8%), 
      hexylcinnamic aldehyde (2.7%), phenyl benzoate (2%), and dinitrochlorobenzene 
      (0.02%). In addition, low inter-animal and inter-experiment variability was seen 
      with 25% hexyl-cinnamic aldehyde (assay positive control). The results of the ex 
      vivo LLNA in the current study were consistent with published reports using the 
      standard LLNA and provided further evidence that supports the use of this 
      alternative approach to assess the skin sensitization potential of test 
      compounds.
FAU - Piccotti, Joseph R
AU  - Piccotti JR
AD  - Drug Safety Research & Development, Pfizer Global Research and Development, Ann 
      Arbor, Michigan, USA. joseph.piccotti@spcorp.com
FAU - Kawabata, Thomas T
AU  - Kawabata TT
LA  - eng
PT  - Evaluation Study
PT  - Journal Article
PL  - England
TA  - J Immunotoxicol
JT  - Journal of immunotoxicology
JID - 101201960
RN  - 0 (Organic Chemicals)
SB  - IM
MH  - Animals
MH  - Dermatitis, Contact/*immunology
MH  - Female
MH  - *Local Lymph Node Assay
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Organic Chemicals/*adverse effects/classification/immunology
MH  - Sensitivity and Specificity
EDAT- 2008/10/03 09:00
MHDA- 2008/12/23 09:00
CRDT- 2008/10/03 09:00
PHST- 2008/10/03 09:00 [pubmed]
PHST- 2008/12/23 09:00 [medline]
PHST- 2008/10/03 09:00 [entrez]
AID - 903265506 [pii]
AID - 10.1080/15376510802311961 [doi]
PST - ppublish
SO  - J Immunotoxicol. 2008 Jul;5(3):271-7. doi: 10.1080/15376510802311961.