PMID- 19207375
OWN - NLM
STAT- MEDLINE
DCOM- 20090529
LR  - 20151119
IS  - 1600-0536 (Electronic)
IS  - 0105-1873 (Linking)
VI  - 60
IP  - 2
DP  - 2009 Feb
TI  - Nothing is perfect, not even the local lymph node assay: a commentary and the 
      implications for REACH.
PG  - 65-9
LID - 10.1111/j.1600-0536.2008.01444.x [doi]
AB  - For many regulatory authorities, the local lymph node assay (LLNA) is the 
      preferred assay for the predictive identification of skin-sensitizing chemicals. 
      It is the initial requirement for sensitization testing within the new REACH 
      (Registration, Evaluation, Authorization and Restriction of Chemical substances) 
      regulations in the European Union. The primary reasons for the preferment of the 
      LLNA are the animal welfare benefits it provides compared with traditional 
      guinea-pig methods (refinement and reduction of animal usage) and the general 
      performance characteristics of the assay with regard to overall reliability, 
      accuracy, and interpretation. Moreover, a substantial published literature on the 
      LLNA is available making it appropriate for use as a benchmark against which new 
      approaches, including in vitro alternatives, can be evaluated and validated. 
      There is, therefore, a view that the LLNA represents the 'gold standard' for skin 
      sensitization testing. However, although this is probably correct, it is 
      important to recognize and acknowledge that in common with all other predictive 
      tests (whether they be validated or not), the LLNA has limitations, in addition 
      to strengths, some of which were mentioned above. Arguably, it is the limitations 
      (e.g., the occurrence of false positive and false negative results) of test 
      methods that are most important to understand. With respect to the LLNA, these 
      limitations are similar to those associated with guinea-pig skin sensitization 
      methods. Among these are the occurrence of false positive and false negative 
      results, susceptibility of results to changes in vehicle, and the possibility 
      that interspecies differences may confound interpretation. In this commentary, 
      these issues are reviewed and their impact on the utility of the LLNA for 
      identification, classification, and potency assessment of skin sensitizers are 
      considered. In addition, their relevance for the future development and 
      validation of novel in vitro and in silico alternatives is explored.
FAU - Basketter, David A
AU  - Basketter DA
AD  - St John's Institute of Dermatology, St Thomas Hospital, London, UK. 
      david.basketter@ukonline.co.uk
FAU - McFadden, John F
AU  - McFadden JF
FAU - Gerberick, Frank
AU  - Gerberick F
FAU - Cockshott, Amanda
AU  - Cockshott A
FAU - Kimber, Ian
AU  - Kimber I
LA  - eng
PT  - Journal Article
PL  - England
TA  - Contact Dermatitis
JT  - Contact dermatitis
JID - 7604950
RN  - 0 (Allergens)
SB  - IM
MH  - Allergens
MH  - Animal Welfare
MH  - Animals
MH  - Dermatitis, Allergic Contact/*classification/*diagnosis
MH  - *Disease Models, Animal
MH  - Dose-Response Relationship, Drug
MH  - Dose-Response Relationship, Immunologic
MH  - European Union
MH  - False Negative Reactions
MH  - False Positive Reactions
MH  - Guinea Pigs
MH  - Humans
MH  - *Local Lymph Node Assay
MH  - Mice
EDAT- 2009/02/12 09:00
MHDA- 2009/05/30 09:00
CRDT- 2009/02/12 09:00
PHST- 2009/02/12 09:00 [entrez]
PHST- 2009/02/12 09:00 [pubmed]
PHST- 2009/05/30 09:00 [medline]
AID - COD1444 [pii]
AID - 10.1111/j.1600-0536.2008.01444.x [doi]
PST - ppublish
SO  - Contact Dermatitis. 2009 Feb;60(2):65-9. doi: 10.1111/j.1600-0536.2008.01444.x.