PMID- 16898167
OWN - NLM
STAT- MEDLINE
DCOM- 20070808
LR  - 20220311
IS  - 0960-3271 (Print)
IS  - 0960-3271 (Linking)
VI  - 25
IP  - 7
DP  - 2006 Jul
TI  - The local lymph node assay in practice: a current regulatory perspective.
PG  - 387-94
AB  - Following the formal acceptance of the local lymph node assay (LLNA) as an 
      Organization for Economic Cooperation and Development (OECD) guideline in April 
      2002, the UK Health and Safety Executive (HSE) informed notifiers that this was 
      now the method of choice for the assessment of skin sensitization potential under 
      the EU notification scheme for new industrial chemicals (NONS). This paper 
      summarizes the experience of the HSE for the 2-year period immediately following 
      the issuing of this statement, during which 48 LLNA study reports were assessed 
      for notification purposes. The issues discussed here include adherence to the 
      OECD guideline, interpretation of results, and classification outcomes. 
      Generally, notifying laboratories followed the OECD guideline successfully, with 
      regard to the sex/ strain/numbers of mice used, the precise process used for 
      measurement of cell proliferation, and the use of recommended vehicles and 
      positive controls. Initially, use of the individual animal approach (measuring 
      the cell proliferation in each animal rather than for a pooled dose group) 
      highlighted problems caused by technical inexperience, but these were overcome by 
      practice. Toxicity or irritation were found to be minor factors in dose 
      selection; more important was the choice of vehicle to correctly maximize the 
      test substance concentration, while maintaining appropriate application 
      properties. Contrary to concerns that the LLNA would prove to be less sensitive 
      or more sensitive than the traditionally used Guinea Pig Maximization Test 
      (GPMT), the proportion of new substances classified as skin sensitizers was 
      within the range observed in previous years. Although the sample size is 
      relatively small, the experience of the HSE indicates that the LLNA is 
      satisfactory for routine regulatory use.
FAU - Cockshott, A
AU  - Cockshott A
AD  - Health and Safety Executive, Bootle, UK. amanda.cockshott@hse.gsi.gov.uk
FAU - Evans, P
AU  - Evans P
FAU - Ryan, C A
AU  - Ryan CA
FAU - Gerberick, G F
AU  - Gerberick GF
FAU - Betts, C J
AU  - Betts CJ
FAU - Dearman, R J
AU  - Dearman RJ
FAU - Kimber, I
AU  - Kimber I
FAU - Basketter, D A
AU  - Basketter DA
LA  - eng
PT  - Journal Article
PL  - England
TA  - Hum Exp Toxicol
JT  - Human & experimental toxicology
JID - 9004560
RN  - 0 (Irritants)
SB  - IM
MH  - Animals
MH  - Cell Proliferation
MH  - Dermatitis, Contact/etiology
MH  - Dose-Response Relationship, Drug
MH  - Female
MH  - *Guideline Adherence
MH  - *Guidelines as Topic
MH  - Irritants/classification/toxicity
MH  - *Local Lymph Node Assay
MH  - Lymph Nodes/cytology/drug effects
MH  - Male
MH  - Mice
MH  - Mice, Inbred CBA
MH  - Reproducibility of Results
MH  - Risk Assessment/methods
MH  - United Kingdom
EDAT- 2006/08/11 09:00
MHDA- 2007/08/09 09:00
CRDT- 2006/08/11 09:00
PHST- 2006/08/11 09:00 [pubmed]
PHST- 2007/08/09 09:00 [medline]
PHST- 2006/08/11 09:00 [entrez]
AID - 10.1191/0960327106ht640oa [doi]
PST - ppublish
SO  - Hum Exp Toxicol. 2006 Jul;25(7):387-94. doi: 10.1191/0960327106ht640oa.