PMID- 12505373
OWN - NLM
STAT- MEDLINE
DCOM- 20030227
LR  - 20201208
IS  - 0300-483X (Print)
IS  - 0300-483X (Linking)
VI  - 184
IP  - 1
DP  - 2003 Feb 14
TI  - Effect of prolonged exposure to low antigen concentration for sensitization.
PG  - 23-30
AB  - The local lymph node assay (LLNA) is an assay in mice to identify potential 
      allergens. Compounds that do not induce a stimulation index (SI)>or=3 are not 
      considered sensitizers. Of the chemicals that do, the SI of 3 is used as a 
      benchmark, and indicates the sensitizing potency of a chemical. Compared to the 
      exposure duration of the LLNA (3 days), real life exposure often lasts for months 
      or years. We therefore investigated whether prolonged exposure to sensitizers at 
      concentrations that do not induce a SI>or=3 in the LLNA, were able to surpass 
      this threshold. Mice were treated for 2 months at 7-day intervals with a range of 
      concentrations of the known allergens ethyl-p-aminobenzoate (benzocaine, BENZ), 
      2,4-dinitrochlorobenzene (DNCB), and tetramethyl thiuram disulfide (TMTD). Both 
      proliferative activity and cytokine production were established at day 60. 
      Neither BENZ nor TMTD showed a significant increase in the proliferation rate 
      compared to vehicle controls. Only DNCB at concentrations originally above the 
      EC(3) a significant increase in proliferation was seen after prolonged exposure. 
      No significant effect on IFN-gamma and IL-4 production was observed for all three 
      compounds compared. These findings indicate that for classification of 
      sensitizers the shorter exposure period employed in the standard LLNA is 
      sufficient, and longer periods of exposure have no bearing on this 
      classification.
FAU - van Och, Francois M M
AU  - van Och FM
AD  - Laboratory for Pathology and Immunobiology, National Institute of Public Health 
      and the Environment (RIVM), PO Box 1, 3720 BA Bilthoven, The Netherlands.
FAU - Vandebriel, Rob J
AU  - Vandebriel RJ
FAU - De Jong, Wim H
AU  - De Jong WH
FAU - van Loveren, Henk
AU  - van Loveren H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Ireland
TA  - Toxicology
JT  - Toxicology
JID - 0361055
RN  - 0 (Allergens)
RN  - 0 (Antigens)
RN  - 0 (Dinitrochlorobenzene)
RN  - 0 (Irritants)
RN  - 0D771IS0FH (Thiram)
RN  - 207137-56-2 (Interleukin-4)
RN  - 82115-62-6 (Interferon-gamma)
RN  - U3RSY48JW5 (Benzocaine)
SB  - IM
MH  - Allergens/*pharmacology
MH  - Animals
MH  - Antigens/*toxicity
MH  - Benzocaine/toxicity
MH  - Cell Division/drug effects
MH  - Dermatitis, Contact/immunology
MH  - Dinitrochlorobenzene/toxicity
MH  - Dose-Response Relationship, Drug
MH  - Female
MH  - Interferon-gamma/biosynthesis
MH  - Interleukin-4/biosynthesis
MH  - Irritants/toxicity
MH  - Lymph Nodes/*drug effects
MH  - Male
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Respiratory Hypersensitivity/immunology
MH  - Stimulation, Chemical
MH  - Thiram/toxicity
EDAT- 2002/12/31 04:00
MHDA- 2003/02/28 04:00
CRDT- 2002/12/31 04:00
PHST- 2002/12/31 04:00 [pubmed]
PHST- 2003/02/28 04:00 [medline]
PHST- 2002/12/31 04:00 [entrez]
AID - S0300483X02005504 [pii]
AID - 10.1016/s0300-483x(02)00550-4 [doi]
PST - ppublish
SO  - Toxicology. 2003 Feb 14;184(1):23-30. doi: 10.1016/s0300-483x(02)00550-4.