Limitations and Modifications of Skin Sensitization NAMs for Testing Inorganic Nanomaterials
Abstract
:1. Introduction
2. Materials and Methods
2.1. Nanomaterials
2.2. Test Substance Preparation
2.3. Test Concentrations
2.4. Direct Peptide Reactivity Assay (DPRA)
2.5. LuSens Assay
2.6. h-CLAT Assay
2.7. Defined Approach
3. Results and Discussion
3.1. DPRA
3.2. LuSens
3.3. h-CLAT
3.4. Assessment of the Skin Sensitization Potential with DAs
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Test Substance | CAS-Number | Physicochemical Properties | Skin Sensitization Potential |
---|---|---|---|
CeO2 NM-212 | 1306-38-3 | 40 nm (SEM) very low water solubility (<0.001 wt.%) # | Cerium oxide is reported non-sensitizing in the GPMT [33] |
BaSO4 NM-220 | 7727-43-7 | 25 nm (SEM) # low water solubility (<0.05 wt.%) # | bulk material was reported non-sensitizing in the LLNA 1 |
SiO2 Levasil 200 (40%) | 7631-86-9 | 5–50 nm (REM/TEM) * soluble in water | reported non-sensitizing in the GPMT * and the LLNA 1 |
Quartz SiO2 DQ12 | n.a. | 500–750 nm * crystalline quartz practically insoluble * | reported non-sensitizing in the LLNA 1 |
SiO2 Aerosil R972 | 68611-44-9 | 16 nm + hydrophobized colloidal silica water solubility > 1 mg/L * | Aerosil R812 and R 8200 were reported non-skin sensitizing in the GPMT 1 |
SiO2 Aerosil 200 | 7631-86-9 | 9 nm (TEM/SEM) [25] hydrophilic fumed silica water solubility > 1 mg/L * | bulk material was reported non-sensitizing in the LLNA 1 |
TiO2 NIST® SRM® | 13463-67-7 | 19–37 nm + very low water solubility (0.001 g/L) * | reported non-sensitizing in the LLNA * |
TiO2 P25 Aeroxide | 13463-67-7 | 21 nm * hydrophilic titanium dioxide | reported non-sensitizing in the patch test and the GMPT * |
ZnO Z-Cote HP1 | 1314-13-2 | 190 nm [34] | ZnO nanomaterials were reported as non-sensitizing in patch test 1 |
Mean Peptide Depletion [%] | C-Peptide Depletion [%] 1 | Reactivity | Evaluation |
---|---|---|---|
>42.47 | >98.24 | high reactivity | positive |
>22.62; ≤42.47 | >23.09; ≤98.24 | moderate reactivity | positive |
>6.38; ≤22.62 | >13.89; ≤23.09 | low reactivity | positive |
>4.94; ≤8.32 | >10.55; ≤18.47 | borderline 2 | inconclusive |
≤6.38 | ≤13.89 | minimal or no reactivity | negative 3 |
Mean Fold Induction | Reactivity | Evaluation |
---|---|---|
>1.76 | activates keratinocytes | positive 1 |
>1.28; ≤1.76 | borderline 2 | inconclusive |
≤1.28 | does not activate keratinocytes | negative 3 |
Mean RFI (CD86) | Mean RFI (CD54) | Reactivity | Evaluation |
---|---|---|---|
>184 | >255 | activates dendritic cells | positive 1 |
>121; ≤184 | >156; ≤255 | borderline 2 | inconclusive |
≤121 | ≤156 | does not activate dendritic cells | negative 3 |
Test Substance | K-Peptide Depletion [%] | C-Peptide Depletion [%] | Mean Depletion [%] 1 | Result 2 |
---|---|---|---|---|
CeO2 NM-212 | 0.60 ± 0.46 | 3.28 ± 0.94 | 1.94 | negative 3 |
BaSO4 NM-220 | 0.00 ± 0.24 | 1.96 ± 0.82 | 0.98 | negative 3 |
SiO2 Levasil 200 (40%) | 0.25 ± 0.80 | −0.36 ± 0.28 | 0.12 | negative 3 |
SiO2 DQ12 | −0.41 ± 0.97 | −0.20 ± 0.64 | 0.00 | negative 3 |
SiO2 Aerosil R972 | −0.30 ± 0.63± | −2.00 ± 1.01 | 0.00 | negative 3 |
SiO2 Aerosil 200 | −0.55 ± 0.33 | −0.88 ± 1.44 | 0.00 | negative 3 |
TiO2 NIST® SRM® | −2.62 ± 0.84 | −1.67 ± 2.67 | 0.00 | negative 3 |
TiO2 P25 Aeroxide | −2.91 ± 0.39 | 1.16 ± 2.53 | 0.58 | negative 3 |
ZnO Z-Cote HP1 | −3.09 ± 2.75 | −6.76 ± 0.42 | 0.00 | negative 3 |
Test Substance | CV75 [µg/mL] | Imax | EC 1.50 [µg/mL] | Result |
---|---|---|---|---|
CeO2 NM-212 | 532 | 0.71 | n.a. 1 | negative |
BaSO4 NM-220 | n.a. 1 | 1.41 | n.a. 1 | inconclusive 2 |
Levasil 200 (40%) | 61.5 | 2.77 | 33 | positive |
SiO2 DQ12 | 498 | 3.32 | <179 3 | positive |
SiO2 Aerosil R972 | n.a. 1 | 1.81 | n.a. 1 | inconclusive 2 |
SiO2 Aerosil 200 | 15 | 1.85 | n.a. 1 | negative |
TiO2 NIST® SRM® | 351 | 1.01 | n.a. 1 | negative |
TiO2 P25 Aeroxide | 222 | 0.89 | n.a. 1 | negative |
ZnO Z-Cote HP1 | 13.7 | 5.17 | <7 3 | positive |
Test Substance | EC150 (CD86) | Imax (CD86) | EC200 (CD54) | Imax (CD54) | Evaluation |
---|---|---|---|---|---|
CeO2 NM-212 | n.a. | 140 | n.a. | 100 | negative/borderline for CD86 in one run 1 |
BaSO4 NM-220 | n.a. | 121 | n.a. | 97 | negative |
SiO2 Levasil 200 (40%) | n.a. | 87 | n.a. | 201 | inconclusive 2 |
SiO2 DQ12 | n.a. | 176 | <144 µg/mL | 970 | positive |
SiO2 Aerosil R972 | n.a. | 138 | n.a. | 120 | inconclusive 2 |
SiO2 Aerosil 200 | n.a. | 171 | n.a. | 235 | inconclusive 3 |
TiO2 NIST® SRM® | n.a. | 128 | n.a. | 132 | negative/borderline for CD86 in one run 1 |
TiO2 P25 Aeroxide | <357 µg/mL | 213 | n.a. | 152 | positive |
ZnO Z-Cote HP1 | n.a. | 163 | <144 µg/mL | 2585 | positive |
Test Substance | DPRA 1 | LuSens 2 | h-CLAT | Evaluation 2o3 5 |
---|---|---|---|---|
CeO2 NM-212 | n 1 inconclusive | n | n/br inconclusive | non sensitiser 5 inconclusive |
BaSO4 NM-220 | n 1 inconclusive | inconclusive 2 | n | non sensitiser 5 inconclusive |
SiO2 Levasil 200 (40%) | n 1 inconclusive | p | inconclusive 3 | inconclusive |
SiO2 DQ12 | n 1 inconclusive | p | p | sensitiser |
SiO2 Aerosil R972 | n 1 inconclusive | inconclusive 2 | inconclusive 3 | inconclusive |
SiO2 Aerosil 200 | n 1 inconclusive | n | inconclusive 4 | non sensitiser 5 inconclusive |
TiO2 NIST® SRM® | n 1 inconclusive | n | n/br inconclusive | non sensitiser 5 inconclusive |
TiO2 P25 Aeroxide | n 1 inconclusive | n | p | non sensitiser 5 inconclusive |
ZnO Z-Cote HP1 | n 1 inconclusive | p | p | sensitiser |
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Wareing, B.; Aktalay Hippchen, A.; Kolle, S.N.; Birk, B.; Funk-Weyer, D.; Landsiedel, R. Limitations and Modifications of Skin Sensitization NAMs for Testing Inorganic Nanomaterials. Toxics 2024, 12, 616. https://doi.org/10.3390/toxics12080616
Wareing B, Aktalay Hippchen A, Kolle SN, Birk B, Funk-Weyer D, Landsiedel R. Limitations and Modifications of Skin Sensitization NAMs for Testing Inorganic Nanomaterials. Toxics. 2024; 12(8):616. https://doi.org/10.3390/toxics12080616
Chicago/Turabian StyleWareing, Britta, Ayse Aktalay Hippchen, Susanne N. Kolle, Barbara Birk, Dorothee Funk-Weyer, and Robert Landsiedel. 2024. "Limitations and Modifications of Skin Sensitization NAMs for Testing Inorganic Nanomaterials" Toxics 12, no. 8: 616. https://doi.org/10.3390/toxics12080616