PMID- 36647556
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230131
IS  - 2332-1512 (Print)
IS  - 2332-1539 (Electronic)
IS  - 2332-1512 (Linking)
VI  - 8
IP  - 4
DP  - 2022 Dec 1
TI  - Application of Defined Approaches to Assess Skin Sensitization Potency of 
      Isothiazolinone Compounds.
PG  - 117-128
LID - 10.1089/aivt.2022.0014 [doi]
AB  - INTRODUCTION: Isothiazolinones (ITs) are widely used as antimicrobial 
      preservatives in cosmetics and as additives for preservation of consumer and 
      industrial products to control bacteria, fungi, and algae. Although they are 
      effective biocides, they have the potential to produce skin irritation and 
      sensitization, which poses a human health hazard. In this project, we evaluated 
      nonanimal defined approaches (DAs) for skin sensitization that can provide 
      point-of-departure estimates for use in quantitative risk assessment for ITs. 
      MATERIALS AND METHODS: The skin sensitization potential of six ITs was evaluated 
      using three internationally harmonized nonanimal test methods: the direct peptide 
      reactivity assay, KeratinoSens, and the human cell line activation test. Results 
      from these test methods were then applied to two versions of the Shiseido 
      Artificial Neural Network DA. RESULTS: Sensitization hazard or potency 
      predictions were compared with those of the in vivo murine local lymph node assay 
      (LLNA). The nonanimal methods produced skin sensitization hazard and potency 
      classifications concordant with those of the LLNA. EC3 values (the estimated 
      concentration needed to produce a stimulation index of three, the threshold 
      positive response) generated by the DAs had less variability than LLNA EC3 
      values, and confidence limits from the DAs overlapped those of the LLNA EC3 for 
      most substances. CONCLUSION: The application of in silico models to in chemico 
      and in vitro skin sensitization data is a promising data integration procedure 
      for DAs to support hazard and potency classification and quantitative risk 
      assessment.
CI  - Copyright 2022, Mary Ann Liebert, Inc., publishers.
FAU - Strickland, Judy
AU  - Strickland J
AUID- ORCID: 0000-0002-4112-7484
AD  - Inotiv, Inc., Morrisville, North Carolina, USA.
FAU - Allen, David G
AU  - Allen DG
AD  - Inotiv, Inc., Morrisville, North Carolina, USA.
FAU - Germolec, Dori
AU  - Germolec D
AD  - Division of Translational Toxicology, National Institute of Environmental Health 
      Sciences, Research Triangle Park, North Carolina, USA.
FAU - Kleinstreuer, Nicole
AU  - Kleinstreuer N
AD  - National Toxicology Program Interagency Center for the Evaluation of Alternative 
      Methods, National Institute of Environmental Health Sciences, Research Triangle 
      Park, North Carolina, USA.
FAU - Johnson, Victor J
AU  - Johnson VJ
AD  - Burleson Research Technologies, Inc., Morrisville, North Carolina, USA.
FAU - Gulledge, Travis
AU  - Gulledge T
AD  - Burleson Research Technologies, Inc., Morrisville, North Carolina, USA.
FAU - Truax, Jim
AU  - Truax J
AD  - Inotiv, Inc., Morrisville, North Carolina, USA.
FAU - Lowit, Anna
AU  - Lowit A
AD  - United States Environmental Protection Agency, Office of Pollution Prevention and 
      Toxics, Washington, District of Columbia, USA.
FAU - Dole, Timothy
AU  - Dole T
AD  - United States Environmental Protection Agency, Office of Pesticide Programs, 
      Washington, District of Columbia, USA.
FAU - McMahon, Timothy
AU  - McMahon T
AD  - United States Environmental Protection Agency, Office of Pesticide Programs, 
      Washington, District of Columbia, USA.
FAU - Panger, Melissa
AU  - Panger M
AD  - United States Environmental Protection Agency, Office of Pesticide Programs, 
      Washington, District of Columbia, USA.
FAU - Facey, Judy
AU  - Facey J
AD  - United States Environmental Protection Agency, Office of Pesticide Programs, 
      Washington, District of Columbia, USA.
FAU - Savage, Stephen
AU  - Savage S
AD  - United States Environmental Protection Agency, Office of Pesticide Programs, 
      Washington, District of Columbia, USA.
LA  - eng
PT  - Journal Article
DEP - 20221216
PL  - United States
TA  - Appl In Vitro Toxicol
JT  - Applied in vitro toxicology
JID - 101692723
PMC - PMC9814110
OTO - NOTNLM
OT  - LLNA
OT  - artificial neural network
OT  - nonanimal methodology
OT  - point of departure
OT  - risk assessment
OT  - skin sensitization
COIS- D.G.A., J.S., and J.T. are employed by Inotiv, Inc. V.J.J. is employed by 
      Burleson Research Technologies, Inc. T.G. was employed by Burleson Research 
      Technologies, Inc., at the time of the in vitro laboratory work and is now 
      employed by Torque Bio, Inc. The remaining authors, A.L., D.G., T.D., J.F., M.P., 
      T.M., N.K., and S.S., declare that the research was conducted in the absence of 
      any commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2023/01/18 06:00
MHDA- 2023/01/18 06:01
PMCR- 2022/12/16
CRDT- 2023/01/17 01:47
PHST- 2023/01/17 01:47 [entrez]
PHST- 2023/01/18 06:00 [pubmed]
PHST- 2023/01/18 06:01 [medline]
PHST- 2022/12/16 00:00 [pmc-release]
AID - 10.1089/aivt.2022.0014 [pii]
AID - 10.1089/aivt.2022.0014 [doi]
PST - ppublish
SO  - Appl In Vitro Toxicol. 2022 Dec 1;8(4):117-128. doi: 10.1089/aivt.2022.0014. Epub 
      2022 Dec 16.