PMID- 15878228
OWN - NLM
STAT- MEDLINE
DCOM- 20050825
LR  - 20191210
IS  - 0300-483X (Print)
IS  - 0300-483X (Linking)
VI  - 212
IP  - 1
DP  - 2005 Aug 15
TI  - An European inter-laboratory validation of alternative endpoints of the murine 
      local lymph node assay: 2nd round.
PG  - 69-79
AB  - The original local lymph node assay (LLNA) is based on the use of radioactive 
      labelling to measure cell proliferation. Other endpoints for the assessment of 
      proliferation are also authorized by the OECD Guideline 429 provided there is 
      appropriate scientific support, including full citations and description of the 
      methodology (OECD, 2002. OECD Guideline for the Testing of Chemicals; Skin 
      Sensitization: Local Lymph Node Assay, Guideline 429. Paris, adopted 24th April 
      2002.). Here, we describe the outcome of the second round of an inter-laboratory 
      validation of alternative endpoints in the LLNA conducted in nine laboratories in 
      Europe. The validation study was managed and supervised by the Swiss Agency for 
      Therapeutic Products (Swissmedic) in Bern. Ear-draining lymph node (LN) weight 
      and cell counts were used to assess LN cell proliferation instead of [3H]TdR 
      incorporation. In addition, the acute inflammatory skin reaction was measured by 
      ear weight determination of circular biopsies of the ears to identify skin 
      irritation properties of the test items. The statistical analysis was performed 
      in the department of statistics at the university of Bern. Similar to the EC(3) 
      values defined for the radioactive method, threshold values were calculated for 
      the endpoints measured in this modification of the LLNA. It was concluded that 
      all parameters measured have to be taken into consideration for the 
      categorisation of compounds due to their sensitising potencies. Therefore, an 
      assessment scheme has been developed which turned out to be of great importance 
      to consistently assess sensitisation versus irritancy based on the data of the 
      different parameters. In contrast to the radioactive method, irritants have been 
      picked up by all the laboratories applying this assessment scheme.
FAU - Ehling, G
AU  - Ehling G
AD  - Aventis Pharma Deutschland GmbH, ProTox, D-65795 Hattersheim, Germany.
FAU - Hecht, M
AU  - Hecht M
FAU - Heusener, A
AU  - Heusener A
FAU - Huesler, J
AU  - Huesler J
FAU - Gamer, A O
AU  - Gamer AO
FAU - van Loveren, H
AU  - van Loveren H
FAU - Maurer, Th
AU  - Maurer T
FAU - Riecke, K
AU  - Riecke K
FAU - Ullmann, L
AU  - Ullmann L
FAU - Ulrich, P
AU  - Ulrich P
FAU - Vandebriel, R
AU  - Vandebriel R
FAU - Vohr, H-W
AU  - Vohr HW
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Validation Study
DEP - 20050212
PL  - Ireland
TA  - Toxicology
JT  - Toxicology
JID - 0361055
RN  - 0 (Irritants)
SB  - IM
MH  - Animals
MH  - Dermatitis, Allergic Contact/pathology
MH  - Endpoint Determination/*methods/*standards
MH  - Europe
MH  - Irritants/toxicity
MH  - Laboratories/*standards
MH  - *Local Lymph Node Assay
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Skin Tests/methods/standards
EDAT- 2005/05/10 09:00
MHDA- 2005/08/27 09:00
CRDT- 2005/05/10 09:00
PHST- 2004/09/29 00:00 [received]
PHST- 2004/12/30 00:00 [accepted]
PHST- 2005/05/10 09:00 [pubmed]
PHST- 2005/08/27 09:00 [medline]
PHST- 2005/05/10 09:00 [entrez]
AID - S0300-483X(05)00034-X [pii]
AID - 10.1016/j.tox.2004.12.038 [doi]
PST - ppublish
SO  - Toxicology. 2005 Aug 15;212(1):69-79. doi: 10.1016/j.tox.2004.12.038. Epub 2005 
      Feb 12.