PMID- 35624531
OWN - NLM
STAT- MEDLINE
DCOM- 20220908
LR  - 20220908
IS  - 1477-0393 (Electronic)
IS  - 0748-2337 (Linking)
VI  - 38
IP  - 9
DP  - 2022 Sep
TI  - Exploring structure/property relationships to health and environmental hazards of 
      polymeric polyisocyanate prepolymer substances-2. Dermal sensitization potential 
      in the mouse local lymph node assay.
PG  - 556-577
LID - 10.1177/07482337221089587 [doi]
AB  - The sensitization potencies of twenty custom-designed monomer-depleted polymeric 
      polyisocyanate prepolymer substances and their associated toluene diisocyanate 
      (TDI), methylene diphenyl diisocyanate (MDI), hexamethylene diisocyanate (HDI), 
      and isophorone diisocyanate (IPDI) monomer precursors were investigated by means 
      of the mouse Local Lymph Node Assay (LLNA). These polymeric prepolymers were 
      designed to represent the structural features and physical-chemical properties 
      exhibited by a broad range of commercial polymeric polyisocyanate prepolymers 
      that are produced from the reaction of aromatic and aliphatic diisocyanate 
      monomers with aliphatic polyether and polyester polyols. The normalization of 
      LLNA responses to the applied (15-45-135 mM) concentrations showed that the skin 
      sensitization potency of polymeric polyisocyanate prepolymers is at least 300 
      times less than that of the diisocyanate monomers from which they are derived. 
      The sensitization potency of the prepolymers was shown to be mainly governed by 
      their hydrophobicity (as expressed by the calculated octanol-water partition 
      coefficient, log K(ow)) and surfactant properties. Neither hydrophilic (log K(ow) 
      <0) nor very hydrophobic (log K(ow) >25) prepolymers stimulated lymphocyte 
      proliferation beyond that of the dosing vehicle control. The findings of this 
      investigation challenge the generally held assumption that all isocyanate 
      (-N=C=O) bearing substances are potential skin (and respiratory) sensitizers. 
      Further, these findings can guide the future development of isocyanate 
      chemistries and associated polyurethane applications toward reduced exposure and 
      health hazard potentials.
FAU - West, Robert J
AU  - West RJ
AD  - 550512International Isocyanate Institute, Inc, Mountain Lakes, NJ, USA.
FAU - Burleson, Stefanie
AU  - Burleson S
AD  - Burleson Research Technologies, Morrisville, NC, USA.
FAU - Gulledge, Travis
AU  - Gulledge T
AD  - Formerly Burleson Research Technologies, currently StrideBio Inc, Durham, NC, 
      USA.
FAU - Miller, Jason W
AU  - Miller JW
AD  - 272522Environmental Analytics, Covestro LLC, Pittsburgh, PA, USA.
FAU - Chappelle, Anne H
AU  - Chappelle AH
AD  - 550512International Isocyanate Institute, Inc, Mountain Lakes, NJ, USA.
FAU - Krieger, Shannon
AU  - Krieger S
AUID- ORCID: 0000-0002-4491-2904
AD  - 5470Toxicology and Environmental Research and Consulting, The Dow Chemical 
      Company, Midland, MI, USA.
FAU - Graham, Cynthia
AU  - Graham C
AD  - Huntsman Corp, The Woodlands, TX, USA.
FAU - Snyder, Stephanie
AU  - Snyder S
AD  - 272522Environmental Analytics, Covestro LLC, Pittsburgh, PA, USA.
AD  - Product Safety and Regulatory Affairs, Covestro LLC, Pittsburgh, PA, USA.
FAU - Simon, Glenn
AU  - Simon G
AD  - Simon Toxicology, LLC, Raleigh, NC, USA (Consultant to Vencorex US, Inc.).
FAU - Plehiers, Patrick M
AU  - Plehiers PM
AD  - 550512International Isocyanate Institute, Inc, Mountain Lakes, NJ, USA.
LA  - eng
PT  - Journal Article
DEP - 20220527
PL  - England
TA  - Toxicol Ind Health
JT  - Toxicology and industrial health
JID - 8602702
RN  - 0 (Isocyanates)
RN  - 0 (Polyurethanes)
RN  - 17X7AFZ1GH (Toluene 2,4-Diisocyanate)
SB  - IM
MH  - Animals
MH  - Isocyanates/toxicity
MH  - *Local Lymph Node Assay
MH  - Mice
MH  - Polyurethanes/toxicity
MH  - Respiratory System
MH  - *Toluene 2,4-Diisocyanate/toxicity
OTO - NOTNLM
OT  - Diisocyanates
OT  - OECD 429
OT  - hazard assessment
OT  - local lymph node assay (LLNA)
OT  - prepolymers
OT  - sensitization
EDAT- 2022/05/29 06:00
MHDA- 2022/09/09 06:00
CRDT- 2022/05/28 00:12
PHST- 2022/05/29 06:00 [pubmed]
PHST- 2022/09/09 06:00 [medline]
PHST- 2022/05/28 00:12 [entrez]
AID - 10.1177/07482337221089587 [doi]
PST - ppublish
SO  - Toxicol Ind Health. 2022 Sep;38(9):556-577. doi: 10.1177/07482337221089587. Epub 
      2022 May 27.