PMID- 36652206
OWN - NLM
STAT- MEDLINE
DCOM- 20230223
LR  - 20230318
IS  - 1520-5010 (Electronic)
IS  - 0893-228X (Print)
IS  - 0893-228X (Linking)
VI  - 36
IP  - 2
DP  - 2023 Feb 20
TI  - Nature-Derived Epoxy Resin Monomers with Reduced Sensitizing 
      Capacity horizontal line Isosorbide-Based Bis-Epoxides.
PG  - 281-290
LID - 10.1021/acs.chemrestox.2c00347 [doi]
AB  - Epoxy resin systems (ERSs) are a class of thermosetting resins that become 
      thermostable and insoluble polymers upon curing. They are widely used as 
      components of protective surfaces, adhesives, and paints and in the manufacturing 
      of composites in the plastics industry. The diglycidyl ether of bisphenol A 
      (DGEBA) is used in 75-90% of ERSs and is thus by far the most used epoxy resin 
      monomer (ERM). Unfortunately, DGEBA is a strong skin sensitizer and it is one of 
      the most common causes of occupational contact dermatitis. Furthermore, DGEBA is 
      synthesized from bisphenol A (BPA), which is a petroleum-derived chemical with 
      endocrine-disruptive properties. In this work, we have used isosorbide, a 
      renewable and nontoxic sugar-based material, as an alternative to BPA in the 
      design of ERMs. Three different bis-epoxide isosorbide derivatives were 
      synthesized: the diglycidyl ether of isosorbide (1) and two novel 
      isosorbide-based bis-epoxides containing either a benzoic ester (2) or a benzyl 
      ether linkage (3). Assessment of the in vivo sensitizing potency of the 
      isosorbide bis-epoxides in the murine local lymph node assay (LLNA) showed that 
      all three compounds were significantly less sensitizing than DGEBA, especially 2 
      which was nonsensitizing up to 25% w/v. The peptide reactivity showed the same 
      order of reactivity as the LLNA, i.e., 2 being the least reactive, followed by 3 
      and then 1, which displayed similar peptide reactivity as DGEBA. Skin permeation 
      of 2 and 3 was compared to DGEBA using ex vivo pig skin and static Franz cells. 
      The preliminary investigations of the technical properties of the polymers formed 
      from 1-3 were promising. Although further investigations of the technical 
      properties are needed, all isosorbide bis-epoxides have the potential to be less 
      sensitizing renewable replacements of DGEBA, especially 2 that had the lowest 
      sensitizing potency in vivo as well as the lowest peptide reactivity.
FAU - Karlsson, Isabella
AU  - Karlsson I
AUID- ORCID: 0000-0002-5924-6123
AD  - Department of Environmental Science, Exposure and Effect, Stockholm University, 
      SE-106 91Stockholm, Sweden.
FAU - Ponting, David J
AU  - Ponting DJ
AUID- ORCID: 0000-0001-6840-2629
AD  - Department of Chemistry and Molecular Biology, Dermatochemistry and Skin Allergy, 
      University of Gothenburg, SE-412 96Gothenburg, Sweden.
FAU - Ortega, Miguel A
AU  - Ortega MA
AD  - Department of Chemistry and Molecular Biology, Dermatochemistry and Skin Allergy, 
      University of Gothenburg, SE-412 96Gothenburg, Sweden.
FAU - Niklasson, Ida B
AU  - Niklasson IB
AD  - Department of Chemistry and Molecular Biology, Dermatochemistry and Skin Allergy, 
      University of Gothenburg, SE-412 96Gothenburg, Sweden.
FAU - Ndreu, Lorena
AU  - Ndreu L
AUID- ORCID: 0000-0003-1567-4262
AD  - Department of Environmental Science, Exposure and Effect, Stockholm University, 
      SE-106 91Stockholm, Sweden.
FAU - Steen, E Johanna L
AU  - Steen EJL
AUID- ORCID: 0000-0002-8707-7574
AD  - Department of Chemistry and Molecular Biology, Dermatochemistry and Skin Allergy, 
      University of Gothenburg, SE-412 96Gothenburg, Sweden.
FAU - Seifert, Tina
AU  - Seifert T
AD  - Department of Chemistry and Molecular Biology, Medicinal Chemistry, University of 
      Gothenburg, SE-412 96Gothenburg, Sweden.
FAU - Luthman, Kristina
AU  - Luthman K
AD  - Department of Chemistry and Molecular Biology, Medicinal Chemistry, University of 
      Gothenburg, SE-412 96Gothenburg, Sweden.
FAU - Karlberg, Ann-Therese
AU  - Karlberg AT
AUID- ORCID: 0000-0003-2691-3644
AD  - Department of Chemistry and Molecular Biology, Dermatochemistry and Skin Allergy, 
      University of Gothenburg, SE-412 96Gothenburg, Sweden.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230118
PL  - United States
TA  - Chem Res Toxicol
JT  - Chemical research in toxicology
JID - 8807448
RN  - F3XRM1NX4H (2,2-bis(4-glycidyloxyphenyl)propane)
RN  - MLT3645I99 (bisphenol A)
RN  - 0 (Epoxy Resins)
RN  - WXR179L51S (Isosorbide)
RN  - 0 (Benzhydryl Compounds)
RN  - 0 (Epoxy Compounds)
SB  - IM
MH  - Animals
MH  - Mice
MH  - Swine
MH  - *Epoxy Resins/chemistry
MH  - *Isosorbide
MH  - Benzhydryl Compounds
MH  - Epoxy Compounds/chemistry
PMC - PMC9945177
COIS- The authors declare no competing financial interest.
EDAT- 2023/01/19 06:00
MHDA- 2023/02/25 06:00
PMCR- 2023/02/22
CRDT- 2023/01/18 11:29
PHST- 2023/01/19 06:00 [pubmed]
PHST- 2023/02/25 06:00 [medline]
PHST- 2023/01/18 11:29 [entrez]
PHST- 2023/02/22 00:00 [pmc-release]
AID - 10.1021/acs.chemrestox.2c00347 [doi]
PST - ppublish
SO  - Chem Res Toxicol. 2023 Feb 20;36(2):281-290. doi: 10.1021/acs.chemrestox.2c00347. 
      Epub 2023 Jan 18.