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Inter-Laboratory Reproducibility and Interchangeability of 3R4F and 1R6F Reference Cigarettes in Mainstream Smoke Chemical Analysis and In Vitro Toxicity Assays

Yuka Sakai
Yuka Sakai
, 
Sakura Mori
Sakura Mori
, 
Miyuki Yanagimachi
Miyuki Yanagimachi
, 
Tomohiro Takahashi
Tomohiro Takahashi
, 
Kaori Shibuya
Kaori Shibuya
, 
Asami Kumagai
Asami Kumagai
, 
Shinkichi Ishikawa
Shinkichi Ishikawa
, 
Shigeaki Ito
Shigeaki Ito
 y 
Toshiro Fukushima
Toshiro Fukushima
   | 31 dic 2020
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Publicado en línea: 31 dic 2020
Páginas: 119 - 135
Recibido: 30 jun 2020
Aceptado: 16 oct 2020
DOI: https://doi.org/10.2478/cttr-2020-0011
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© 2020 Yuka Sakai et al., published by Sciendo
This work is licensed under the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.

Figure 1

Relative differences in the chemical constituents of mainstream cigarette smoke between 3R4F and 1R6F under the ISO standard smoking regimen. Circles and triangles indicate the relative differences in the chemical yields of 1R6F compared with 3R4F in the current and Jaccard studies (12), respectively. The boxes show the critical difference ranges of 3R4F. “Empty” or “filled” symbols indicate whether the relative difference was within or out of the critical difference range, respectively. LOQ indicates the limit of quantitation.
Relative differences in the chemical constituents of mainstream cigarette smoke between 3R4F and 1R6F under the ISO standard smoking regimen. Circles and triangles indicate the relative differences in the chemical yields of 1R6F compared with 3R4F in the current and Jaccard studies (12), respectively. The boxes show the critical difference ranges of 3R4F. “Empty” or “filled” symbols indicate whether the relative difference was within or out of the critical difference range, respectively. LOQ indicates the limit of quantitation.

Figure 2

Relative differences in the chemical constituents of mainstream cigarette smoke between 3R4F and 1R6F under the ISO intense smoking regimen. Circles and triangles indicate the relative differences in the chemical yields of 1R6F compared with 3R4F in the current and Jaccard studies (12), respectively. The boxes show the critical difference ranges of 3R4F. “Empty” or “filled” symbols indicate whether the relative difference was within or out of the critical difference range, respectively. LOQ indicates the limit of quantitation.
Relative differences in the chemical constituents of mainstream cigarette smoke between 3R4F and 1R6F under the ISO intense smoking regimen. Circles and triangles indicate the relative differences in the chemical yields of 1R6F compared with 3R4F in the current and Jaccard studies (12), respectively. The boxes show the critical difference ranges of 3R4F. “Empty” or “filled” symbols indicate whether the relative difference was within or out of the critical difference range, respectively. LOQ indicates the limit of quantitation.

Figure 3

Relative differences between 3R4F and 1R6F in the Ames assay. (A) ISO standard smoking regimen; (B) ISO intense smoking regimen. Circles and triangles indicate the relative differences in the mutagenic slope value of 1R6F compared with 3R4F in the current and Jaccard studies (12), respectively. The boxes show the critical difference ranges of 3R4F. “Empty” symbols indicate the relative difference were within the critical difference ranges. Equivocal indicates there was no reproducible significant increase in revertants over three replicates. Non-mutagenic means there was no significant increase in revertants over three replicates.
Relative differences between 3R4F and 1R6F in the Ames assay. (A) ISO standard smoking regimen; (B) ISO intense smoking regimen. Circles and triangles indicate the relative differences in the mutagenic slope value of 1R6F compared with 3R4F in the current and Jaccard studies (12), respectively. The boxes show the critical difference ranges of 3R4F. “Empty” symbols indicate the relative difference were within the critical difference ranges. Equivocal indicates there was no reproducible significant increase in revertants over three replicates. Non-mutagenic means there was no significant increase in revertants over three replicates.

Figure 4

Relative differences between 3R4F and 1R6F in the MN assay. (A) ISO standard smoking regimen; (B) ISO intense smoking regimen. Circles and triangles indicate the relative difference in the genotoxic logit slope values of 1R6F compared with 3R4F in the current and Jaccard studies (12), respectively. The boxes show the critical difference ranges of 3R4F. “Empty” or “filled” symbols indicate whether the relative difference was within or out of the critical difference range, respectively.
Relative differences between 3R4F and 1R6F in the MN assay. (A) ISO standard smoking regimen; (B) ISO intense smoking regimen. Circles and triangles indicate the relative difference in the genotoxic logit slope values of 1R6F compared with 3R4F in the current and Jaccard studies (12), respectively. The boxes show the critical difference ranges of 3R4F. “Empty” or “filled” symbols indicate whether the relative difference was within or out of the critical difference range, respectively.

Figure 5

Relative differences between 3R4F and 1R6F in the NRU assay. (A) ISO standard smoking regimen; (B) ISO intense smoking regimen. Circles and triangles indicate the relative differences in the IC50 values of 1R6F compared with 3R4F in the current and Jaccard studies (12), respectively. The boxes show the critical difference ranges of 3R4F. “Empty” or “filled” symbols indicate whether the relative difference was within or out of the critical difference range, respectively.
Relative differences between 3R4F and 1R6F in the NRU assay. (A) ISO standard smoking regimen; (B) ISO intense smoking regimen. Circles and triangles indicate the relative differences in the IC50 values of 1R6F compared with 3R4F in the current and Jaccard studies (12), respectively. The boxes show the critical difference ranges of 3R4F. “Empty” or “filled” symbols indicate whether the relative difference was within or out of the critical difference range, respectively.

Figure 6

Dose-response curves in the cell viability assay. Cell viability was measured after 24 h exposure to TPM. The values for the solvent control were set at 100 (%). “Empty” and “filled” symbols represent the means of the viability for 1R6F and 3R4F, respectively. The error bars indicate standard error (n = 3). The solid and dotted lines indicate the dose-response curves for the ISO standard and intense smoking regimens, respectively.
Dose-response curves in the cell viability assay. Cell viability was measured after 24 h exposure to TPM. The values for the solvent control were set at 100 (%). “Empty” and “filled” symbols represent the means of the viability for 1R6F and 3R4F, respectively. The error bars indicate standard error (n = 3). The solid and dotted lines indicate the dose-response curves for the ISO standard and intense smoking regimens, respectively.

Figure 7

Dose-response curves in the GSH/GSSG assay. The intracellular GSH/GSSG ratio was determined after exposure for 2 h to the TPM. “Empty” and “filled” symbols represent the means of the GSH/GSSG ratios of 1R6F and 3R4F, respectively. The error bars indicate standard error (n = 3). The solid and dotted lines indicate the dose-response curve under the ISO standard and intense smoking regimens, respectively.
Dose-response curves in the GSH/GSSG assay. The intracellular GSH/GSSG ratio was determined after exposure for 2 h to the TPM. “Empty” and “filled” symbols represent the means of the GSH/GSSG ratios of 1R6F and 3R4F, respectively. The error bars indicate standard error (n = 3). The solid and dotted lines indicate the dose-response curve under the ISO standard and intense smoking regimens, respectively.

Figure 8

Dose-response curves in the ARE-luciferase reporter assay. Luciferase activity was measured after exposure to the TPM for 24 h to determine ARE gene activity. “Empty” and “filled” symbols represent the means of ARE-luciferase gene activity for 1R6F and 3R4F, respectively. The error bars indicate standard error (n = 3). The solid and dotted lines indicate the dose-response curve under the ISO standard and intense smoking regimens, respectively.
Dose-response curves in the ARE-luciferase reporter assay. Luciferase activity was measured after exposure to the TPM for 24 h to determine ARE gene activity. “Empty” and “filled” symbols represent the means of ARE-luciferase gene activity for 1R6F and 3R4F, respectively. The error bars indicate standard error (n = 3). The solid and dotted lines indicate the dose-response curve under the ISO standard and intense smoking regimens, respectively.

Figure A1

Correlation of the absolute values of the relative differences between 1R6F and 3R4F in chemical analysis. (A) ISO standard smoking regimen; (B) ISO intense smoking regimen. X-axis: relative differences in current study (%), Y-axis: relative differences in Jaccard study (%). The coefficients of determination under the ISO standard and intense smoking regimens were R2 = 0.73 and R2 = 0. 74, respectively.
Correlation of the absolute values of the relative differences between 1R6F and 3R4F in chemical analysis. (A) ISO standard smoking regimen; (B) ISO intense smoking regimen. X-axis: relative differences in current study (%), Y-axis: relative differences in Jaccard study (%). The coefficients of determination under the ISO standard and intense smoking regimens were R2 = 0.73 and R2 = 0. 74, respectively.

Analysis methods used for specific analytes in mainstream cigarette smoke.

Analytes Fraction (smoking machine) Trap Chromatograph, detection Notes Ref.
TSNAs
NNK, NNN, NAB, NAT TPM (RM20Ha) A glass-fiber filter HPLC; Agilent 1290 infinity system c, Triple Quad 4500 MS system d The extract with ammonium acetate solution was syringe filtered. 26
Carbonyls
Formaldehyde, acetaldehyde, acrolein, crotonaldehyde, acetone, propionaldehyde, n-butylaldehyde, MEK WS (SM450RHb) Two impingers with 2, 4-dinitrophenyl-hydrazine solution HPLC; Agilent 1290 Infinity system c, Diode array detection Deribatized solution was stabilized with Tris base. 27
VOCs
1,3-Butadiene, benzene, isoprene, acrylonitrile, toluene GVP (SM450RHb) Two cryogenic impingers with methanol GC/MS; 5975C GC/MSD c, Electron impact ionization – 28
Cyanic compound
HCN GVP TPM (SM450RHb) A glass-fiber filter and an impinger with NaOH solution Continuous flow analyzer; STAT-2000 e The extract with NaOH was syringe filtered. 29
PAH
B[a]P TPM (SM450RHb) A glass-fiber filter HPLC; HPLC-1100 system c, Fluorescence detection The extract with cyclohexane was syringe filtered and purified using SPE by passing through a silica cartridge and an NH2 cartridge, followed by the elution with hexane. 30
Phenols
Hydroquinone, resorcinol, catechol, phenol, o-cresol, m-cresol, p-cresol Ammonia TPM (SM450RHb) A glass-fiber filter HPLC; Agilent 1290 Infinity system c, Fluorescence detection The extract with acetic acid was syringe filtered. 31
Ammonia GVPTPM (RM20Ha) A glass-fiber filter and two impingers with sulfuric acid Cation exchange chromatograph; ICS-3000 f, Suppressed ion conductivity detection The extract with ultrapure water was syringe filtered. 32
NOx
NO, NOx GVP (RM20Ha) – Online gas phase chemiluminescence analyzer; CLD822Mh g – 33
SVOCs
Pyridine, quinoline, styrene GVP TPM (RM20Ha) A glass-fiber filter and two cyrogenic impingers with methanol GC/MS; 5975C GC/MSD c, Electron impact ionization TPM was extracted with the impinger solution. 34
Aromatic amines
1-Aminonaphthalene, 2-aminonaphthalene, 3-aminobiphenyl, 4-aminobiphenyl TPM (RM20Ha) A glass-fiber filter GC/MS; 5975C GC/MSD c, Chemical ionization source (selected ion monitoring) The extract with hydrochloric acid solution was syringe filtered and loaded to the conditioned SPE-I with ammonia solution and methanol, and then loaded to the SPE-II with toluene. The derivatized solution with heptafluorobutyric acid anhydride solution was loaded to SPE-III. 35
Heavy metals
Mercury GVP (RM20Ha) An inpinger with acidified potassium permanganate AAS; FIMS 400 h, cold vapor atomic absorption spectrometry Hydrogen peroxide and ultrapure water were added for microwave digestion. Hydroxlyamine hydrochloride was added. Mercury ions in the sample were reduced by stannous chloride. 36
Arsenic, cadmium, chromium, nickel, lead, selenium, beryllium, cobalt TPM (RM20Ha) Glass electrostatic precipitate tube ICP/MS; Agilent 7500cxc Collected metals with methanol were mixed with Nitric acid solution, TritonX-100 solution by ultrosonication. –

Chemical constituents in the mainstream smoke of 1R6F and 3R4F.

Analyte Unit ISO standard smoking regimen ISO intense smoking regimen
1R6F 3R4F Ratio (1R6F/3R4F) 1R6F 3R4F Ratio (1R6F/3R4F)
mean S.E. mean S.E. mean S.E. mean S.E.
TPM mg/cig 10.5 0.148 9.9 0.389 106 (–) 42.4 1.19 43.3 0.304 97.9 (–)
Nicotine mg/cig 0.720 0.0116 0.700 0.0152 103 (111) 1.92 0.0326 1.97 0.0492 97.5 (95.5)
Carbon monoxide mg/cig 10.0 0.143 10.6 0.371 94.3 (102) 27.5 0.38 30.1 0.622 91.4 (85.9)
TSNAs
NNN ng/cig 100 3.58 116 4.02 86.2 (76.3) 221 5.37 279 4.92 79.2 (68.2)
NAT ng/cig 107 0.894 118 2.68 90.7 (80.9) 253 5.37 291 3.13 86.9 (77.5)
NAB ng/cig 12.9 0.224 15.0 0.224 86.0 (82.7) 29.6 0.626 35.6 0.358 83.1 (76.7)
NNK ng/cig 77.8 2.33 103 3.13 75.5 (74.8) 177 3.58 243 4.92 72.8 (65.1)
Carbonyls
Formaldehyde μg/cig 37.6 1.21 27.3 1.07 138 (136) 134 4.02 106 3.58 126.4 (119)
Acetaldehyde μg/cig 548 9.39 594 11.18 92.3 (89.1) 1570 17.89 1697 14.31 92.5 (87.1)
Acetone μg/cig 179 2.68 202 3.13 88.6 (86.7) 503 3.13 574 5.81 87.6 (84.8)
Acrolein μg/cig 55.9 1.21 50.2 1.12 111 (97.4) 177 1.34 166 0.447 106.6 (96.1)
Propionaldehyde μg/cig 40.3 0.626 42.9 0.805 93.9 (90.9) 115 0.894 124 1.34 92.7 (88.1)
Crotonaldehyde μg/cig 12.2 0.358 11.1 0.358 110 (101) 54.8 0.402 54.9 0.537 99.8 (92.4)
MEK μg/cig 41.8 0.581 48.3 0.894 86.5 (85.3) 119 0.447 143 1.79 83.2 (82.4)
n-Butylaldehyde μg/cig 25.0 0.492 27.5 0.76 90.9 (91.2) 68.1 0.939 77.1 1.3 88.3 (86.3)
VOCs
1,3-Butadiene μg/cig 40.9 0.358 41.5 1.12 98.6 (104) 96.1 1.21 95.2 1.7 100.9 (102)
Isoprene μg/cig 314 3.58 341 8.05 92.1 (99.3) 766 15.21 816 16.1 93.9 (94.1)
Acrylonitrile μg/cig 8.19 0.116 9.39 0.264 87.2 (100) 26.1 0.224 28.9 0.179 90.3 (93.7)
Benzene μg/cig 42.2 0.358 46.1 1.16 91.5 (100) 91.2 0.671 99.4 1.03 91.8 (92.7)
Toluene μg/cig 64.7 0.76 78.6 2.1 82.3 (91.8) 160 1.34 191 1.34 83.8 (86.3)
Cyanic compounds
HCN μg/cig 98.4 1.52 99.2 2.37 99.2 (107) 404 10.29 470 8.94 86.0 (903)
PAH
B[a]P ng/cig 7.51 0.121 6.49 0.17 116 (110) 16.9 0.268 16.9 0.716 100.0 (91.4)
Phenols
Hydroquinone μg/cig 35 0.402 30.4 0.313 115 (113) 87.1 0.984 84.1 0.447 103.6 (108)
Resorcinol μg/cig 0.718 0.0237 0.494 0.0152 145 – 2.15 0.0492 1.6 0.0492 134.4 –
Catechol μg/cig 40 0.313 36.7 0.313 109 (111) 89.3 0.984 88.1 0.537 101.4 (106)
Phenol μg/cig 8.79 0.215 6.69 0.085 131 (131) 12.4 0.224 11 0.179 112.7 (105)
p-Cresol μg/cig 5.09 0.107 4.31 0.0537 118 (115) 8.22 0.157 7.81 0.13 105.2 (100)
m-Cresol μg/cig 2.01 0.0537 1.78 0.0224 113 (115) 3.08 0.085 2.99 0.0894 103.0 (94.6)
o-Cresol μg/cig 2.36 0.0537 2.14 0.0268 110 (111) 3.47 0.112 3.72 0.157 93.3 (85.7)
Other amines
Ammonia μg/cig 8.72 0.13 8.04 0.0581 108 (130) 30.6 0.76 30.4 0.76 100.7 (106)
NOx
Nitric oxide μg/cig 148 5.63 194 7.06 76.2 (67.3) 358.86 15.07 529 20.89 67.9 (69.9)
Nitric oxides μg/cig 163 6.46 217 7.92 75.1 (67.8) 399.08 16.94 589 23.11 67.7 (70.4)
SVOCs
Pyridine μg/cig 7.33 0.112 7.41 0.148 98.9 (91.6) 36.8 0.581 42.1 0.268 87.4 (103)
Quinoline μg/cig 0.273 0.00178 0.228 0.00358 120 (152) 0.546 0.0139 0.53 0.00492 103.0 (105)
Styrene μg/cig 5.68 0.0671 6.79 0.0626 83.7 (76) 23 0.224 27.3 0.134 84.2 (94)
Aromatic amines
1-Aminonaftalene ng/cig 13 0.358 12.9 0.134 101 (97.2) 24.5 0.358 26.9 0.179 91.1 (91.8)
2-Aminonaftalene ng/cig 7.69 0.367 7.82 0.0581 98.3 (122) 15.5 0.581 16.7 0.134 92.8 (89.5)
3-Aminobiphenyl ng/cig 2.04 0.085 2.2 0.0179 92.7 (103) 4.71 0.183 5.21 0.0224 90.4 (82.5)
4-Aminobiphenyl ng/cig 1.41 0.0626 1.54 0.0134 91.6 (96.1) 3.35 0.125 3.71 0.0313 90.3 (80.1)
Heavy metals
Mercury ng/cig 2.33 0.0179 2.58 0.0313 90.3 (93.8) 5.26 0.0268 6.01 0.0537 87.5 (95.1)
Lead ng/cig 11.7 0.268 10.6 0.179 110 (–) 31.1 0.581 33.8 0.626 92.0 (–)
Cadmium ng/cig 36.6 0.671 34.3 0.179 107 (107) 95.3 0.984 114 1.79 83.6 (81.7)
Chromium ng/cig <LOD – <LOD – – (–) <LOD <LOD – – (–)
Nickel ng/cig <LOQ – <LOQ – – (–) <LOQ <LOQ – – (–)
Beryllium ng/cig <LOD – <LOD – – (–) <LOD <LOD – – (–)
Cobalt ng/cig <LOQ – <LOQ – – (–) <LOQ <LOQ – – (–)
Selenium ng/cig <LOQ – <LOQ – – (–) <LOQ <LOQ – – (–)
Arsenic ng/cig 2.41 0.0313 2.56 0.0268 94.1 (–) 6.72 0.152 7.92 0.179 84.8 (–)

IC50 values of 1R6F and 3R4F TPM in the GSH/GSSG assay. IC50 values in the GSH/GSSG assay were calculated by inverse estimation of the effective concentration at which the normalized luminescence was reduced by 50%. S.E. stands for standard error. p values were calculated based on Student's t-test (n = 3).

Smoking regimen 1R6F IC50 (μg/mL) 3R4F IC50 (μg/mL) Relative difference (1R6F/3R4F) p value (t-test)
Mean S.E. Mean S.E. Mean S.E.
Standard 35.0 7.74 40.0 9.36 0.877 0.0128 0.70
Intense 66.5 8.25 73.4 18.9 0.970 0.139 0.76

Characteristics of 1R6F and 3R4F reference cigarettes. The data were obtained from literature (12, 19, 20).

Parameter 3R4F 1R6F
Physical data
Cigarette length (mm) 84 83
Tobacco rod length (mm) 57 56
Filter length (mm) 27 27
Tobacco rod circumference (mm) 24.8 24.6
Cigarette weight (g) 1.1 0.89
Filter ventilation (%) 29 33
Paper permeability (CU) 24 45
Resistance to draw (mm H2O) 128 107
Blend composition
Flue cured (%) 35 34
Burley (%) 22 24
Maryland (%) 1.4 –
Oriental (%) 12 12
Reconstituted (%) 29.6 20
Expanded flue cured (%) – 7
Expanded Burley (%) – 3
Humectants
Glycerol (%) 2.7 1.7
Propylene glycol (%) – 1
Isosweet (%) 6.4 6.3
Yield data from supplier (ISO standard smoking regimen)
Puff count 9.0 7.5
TPM (mg/cig) 11 10
“Tar” (mg/cig) 9.4 8.6
Nicotine (mg/cig) 0.73 0.72
Carbon monoxide (mg/cig) 12.0 10.1
Yield data from supplier (ISO intense smoking regimen)
Puff count a 8.7
TPM (mg/cig) a 46.8
“Tar” (mg/cig) a 29.1
Nicotine (mg/cig) a 1.90
Carbon monoxide (mg/cig) a 28.0

IC50 values of 1R6F and 3R4F TPM in the cell viability assay. The IC50 values were calculated by inverse estimation of the effective concentration at which the normalized fluorescence was reduced by 50%. S.E. stands for standard error. p values were calculated based on Student's t-test (n = 3).

Smoking regimen 1R6F IC50 (μg/mL) 3R4F IC50 (μg/mL) Relative difference (1R6F/3R4F) p value (t-test)
Mean S.E. Mean S.E. Mean S.E.
Standard 75.0 2.44 73.3 2.19 1.02 0.0281 0.62
Intense 79.5 3.98 82.2 4.06 0.975 0.0836 0.67

Genotoxic slope parameters of the logit function of 1R6F and 3R4F TPM in the MN assay.

Smoking regimen Term and S9 metabolic activation 1R6F slope parameter (mg/mL) 3R4F slope parameter (mg/mL) Ratio (1R6F/3R4F)
Mean S.E. Mean S.E. Mean S.E.
Standard “Short” without S9 10.2 1.26 8.11 1.22 1.27 (1.18) 0.0836
Standard “Short” with S9 6.36 1.37 5.67 1.09 1.11 (1.01) 0.520
Standard “Long” without S9 17.8 3.22 15.2 2.22 1.17 (1.05) 0.100
Intense “Short” without S9 7.36 1.10 6.37 1.14 1.17 (1.12) 0.0650
Intense “Short” with S9 4.29 0.850 3.87 0.487 1.09 (1.05) 0.0750
Intense “Long” without S9 13.8 2.11 11.6 2.02 1.21 (0.894) 0.0550

IC50 values of the TPM and GVP of 1R6F and 3R4F in the NRU assay.

Smoking regimen Fraction 1R6F IC50 (μg/mL) 3R4F IC50 (μg/mL) Ratio (1R6F/3R4F)
Mean S.E. Mean S.E. Mean S.E.
Standard TPM 68.6 1.32 70.9 2.67 0.969 (0.979) 0.0221
Standard GVP 101 6.89 95.9 7.11 1.05 (1.18) 0.00707
Intense TPM 94.2 4.84 105 1.97 0.901 (1.05) 0.0429
Intense GVP 104 6.36 107 4.61 0.971 (1.15) 0.0334

Slope values of 1R6F and 3R4F TPM in the ARE-luciferase reporter assay. The slope values in the ARE-luciferase reporter assay were calculated by linear regression analysis over the dose range where cell viability was higher than 50%. S.E. stands for standard error. p values were calculated based on Student's t-test (n = 3).

Smoking regimen 1R6F slope value 3R4F slope value Relative difference (1R6F/3R4F) p value (t-test)
Mean S.E. Mean S.E. Mean S.E.
Standard 0.394 0.0441 0.305 0.0456 1.32 0.133 0.23
Intense 0.377 0.0682 0.266 0.0376 1.46 0.292 0.23

Mutagenic slope values of 1R6F and 3R4F TPM in the Ames assay.

Smoking regimen Strain and S9 metabolic activation 1R6F slope value (Revetants/μg) 3R4F slope value (Revetants/μg) Ratio (1R6F/3R4F)
Mean S.E. Mean S.E. Mean S.E.
Standard TA98 with S9 2.31 0.0748 2.40 0.145 0.966 (0.841) 0.0532
Standard TA98 without S9 equivocal – equivocal – – (1.51) –
Standard TA100 with S9 0.849 0.0430 0.886 0.0509 0.959 (0.902) 0.00907
Standard TA100 without S9 0.354 0.0213 0.298 0.0365 1.23 (–) 0.171
Standard TA1537 with S9 0.300 0.0301 0.305 0.0455 1.00 (1.05) 0.0786
Standard TA1537 without S9 equivocal – equivocal – – (–) –
Standard TA1535 with S9 non-mutagenic – non-mutagenic – – (–) –
Standard TA1535 without S9 non-mutagenic – non-mutagenic – – (–) –
Standard TA102 with S9 non-mutagenic – non-mutagenic – – (–) –
Standard TA102 without S9 non-mutagenic – non-mutagenic – – (–) –
Intense TA98 with S9 1.10 0.0342 1.02 0.0368 1.072 (0.971) 0.0259
Intense TA98 without S9 non-mutagenic euivocal – – (1.18) –
Intense TA100 with S9 0.475 0.0213 0.426 0.0119 1.12 (1.07) 0.0756
Intense TA100 without S9 0.233 0.0178 0.190 0.0115 1.24 (–) 0.136
Intense TA1537 with S9 0.162 0.0258 0.187 9.50E-3 0.864 (0.939) 0.116
Intense TA1537 without S9 equivocal – equivocal – – (–) –
Intense TA1535 with S9 non-mutagenic – non-mutagenic – – (–) –
Intense TA1535 without S9 non-mutagenic – non-mutagenic – – (–) –
Intense TA102 with S9 non-mutagenic – non-mutagenic – – (–) –
Intense TA102 without S9 non-mutagenic – non-mutagenic – – (–) –
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