PMID- 26168096
OWN - NLM
STAT- MEDLINE
DCOM- 20160620
LR  - 20220311
IS  - 1868-8551 (Electronic)
IS  - 1868-596X (Linking)
VI  - 32
IP  - 4
DP  - 2015
TI  - LLNA variability: An essential ingredient for a comprehensive assessment of 
      non-animal skin sensitization test methods and strategies.
PG  - 379-83
LID - 10.14573/altex.1505051 [doi]
AB  - The development of non-animal skin sensitization test methods and strategies is 
      quickly progressing. Either individually or in combination, the predictive 
      capacity is usually described in comparison to local lymph node assay (LLNA) 
      results. In this process the important lesson from other endpoints, such as skin 
      or eye irritation, to account for variability reference test results - here the 
      LLNA - has not yet been fully acknowledged. In order to provide assessors as well 
      as method and strategy developers with appropriate estimates, we investigated the 
      variability of EC3 values from repeated substance testing using the publicly 
      available NICEATM (NTP Interagency Center for the Evaluation of Alternative 
      Toxicological Methods) LLNA database. Repeat experiments for more than 60 
      substances were analyzed - once taking the vehicle into account and once 
      combining data over all vehicles. In general, variability was higher when 
      different vehicles were used. In terms of skin sensitization potential, i.e., 
      discriminating sensitizer from non-sensitizers, the false positive rate ranged 
      from 14-20%, while the false negative rate was 4-5%. In terms of skin 
      sensitization potency, the rate to assign a substance to the next higher or next 
      lower potency class was approx.10-15%. In addition, general estimates for EC3 
      variability are provided that can be used for modelling purposes. With our 
      analysis we stress the importance of considering the LLNA variability in the 
      assessment of skin sensitization test methods and strategies and provide 
      estimates thereof.
FAU - Hoffmann, Sebastian
AU  - Hoffmann S
AD  - seh consulting + services, Paderborn, Germany.
LA  - eng
PT  - Journal Article
DEP - 20150713
PL  - Germany
TA  - ALTEX
JT  - ALTEX
JID - 100953980
RN  - 0 (Allergens)
SB  - IM
MH  - Allergens/pharmacology
MH  - *Animal Testing Alternatives
MH  - Animals
MH  - Dermatitis, Allergic Contact/prevention & control
MH  - Disease Models, Animal
MH  - Dose-Response Relationship, Drug
MH  - *Local Lymph Node Assay
MH  - Reproducibility of Results
MH  - Risk Assessment
OTO - NOTNLM
OT  - LLNA variability
OT  - skin sensitization
OT  - test method assessment
OT  - test strategy assessment
EDAT- 2015/07/15 06:00
MHDA- 2016/06/21 06:00
CRDT- 2015/07/14 06:00
PHST- 2015/05/05 00:00 [received]
PHST- 2015/07/10 00:00 [accepted]
PHST- 2015/07/14 06:00 [entrez]
PHST- 2015/07/15 06:00 [pubmed]
PHST- 2016/06/21 06:00 [medline]
AID - 10.14573/altex.1505051 [doi]
PST - ppublish
SO  - ALTEX. 2015;32(4):379-83. doi: 10.14573/altex.1505051. Epub 2015 Jul 13.