PMID- 34345850
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240403
IS  - 2666-027X (Electronic)
IS  - 2666-027X (Linking)
VI  - 2
DP  - 2021
TI  - Interpretation of murine local lymph node assay (LLNA) data for skin 
      sensitization: Overload effects, danger signals and chemistry-based read-across.
PG  - 53-63
LID - 10.1016/j.crtox.2021.01.004 [doi]
AB  - There is a large body of information on testing of chemicals for skin 
      sensitization in the murine local lymph node assay (LLNA), in which potency is 
      quantified by the EC3 value, derived from dose-response data. This information 
      finds use in risk assessment and regulatory classification, and also in assessing 
      the performance of non-animal methods. However, some LLNA results are not 
      straightforward to interpret, and in some cases published EC3 values are 
      questionable. These cases usually arise where the dose-response does not show a 
      monotonic increasing pattern but is bell-shaped, or shows a decrease in response 
      with increasing dose over the whole dose range tested. By analogy with a 
      long-recognised phenomenon in guinea pig sensitization, this is referred to as 
      the overload effect. Here a mechanistic rationale is presented to explain the 
      overload effect, and at the same time to explain the production of danger signals 
      even when the sensitizer is non-irritant. Some illustrative examples are 
      presented where the overload effect can lead to misinterpretation of LLNA 
      results, and chemistry-based read-across is applied to reinterpret the data.
CI  - (c) 2021 The Author(s).
FAU - Roberts, David W
AU  - Roberts DW
AD  - School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, 
      Byrom Street, Liverpool L3 3AF, England, United Kingdom.
LA  - eng
PT  - Journal Article
DEP - 20210121
PL  - Netherlands
TA  - Curr Res Toxicol
JT  - Current research in toxicology
JID - 101771915
PMC - PMC8320616
OTO - NOTNLM
OT  - Chemistry-based read-across
OT  - Danger signal
OT  - LLNA
OT  - Non-animal methods
OT  - Overload effect
COIS- The author declares that he has no known competing financial interests or 
      personal relationships that could have appeared to influence the work reported in 
      this paper.
EDAT- 2021/08/05 06:00
MHDA- 2021/08/05 06:01
PMCR- 2021/01/21
CRDT- 2021/08/04 07:12
PHST- 2020/12/10 00:00 [received]
PHST- 2021/01/11 00:00 [revised]
PHST- 2021/01/14 00:00 [accepted]
PHST- 2021/08/04 07:12 [entrez]
PHST- 2021/08/05 06:00 [pubmed]
PHST- 2021/08/05 06:01 [medline]
PHST- 2021/01/21 00:00 [pmc-release]
AID - S2666-027X(21)00004-9 [pii]
AID - 10.1016/j.crtox.2021.01.004 [doi]
PST - epublish
SO  - Curr Res Toxicol. 2021 Jan 21;2:53-63. doi: 10.1016/j.crtox.2021.01.004. 
      eCollection 2021.