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Test system | Compound | Concentration | Number | Endpoint | Results | Reference | Effect |
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In vitro human lymphocytes | 2,4-D acid | 0.2, 10, 20, 30, 40, 50, and 60 μg/mL for 48–52 h | NA | SCE and chromosomal aberrations | Statistically significant increase in SCE at all doses (but less at highest dose); deletions and gaps above 50 ug/mL | Korte and Jalal [191] | ++ |
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in vitro human lymphocytes | 2,4-D acid | 50, 100, and 250 μg/mL for 72 h | NA | SCE | Significant increase in SCE at lowest dose but not at higher doses; weak effect | Turkula and Jalal [192] | + |
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In vitro human lymphocytes | 2,4-D acid; DMA salt (commercial product) | 0.125, 0.25, 0.5, 1.0, and 1.25 mM | NA | Chromosomal aberrations | Statistically significant increases in breaks at 0.5 (but not gaps) only in commercial mixture (not pure product) | Mustonen et al. [193] | + |
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Human fibroblasts | 2,4-D acid; DMA salt (commercial product) | 18 mM 2,4-D; 5 mM U 46 D Fluid | NA | Colony-forming ability | No effect of 2,4-D; reduced colony-forming ability of U 46 D Fluid at 5 mM | Clausen et al. [194] | + |
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Human fibroblasts | 2,4-D acid; DMA salt (commercial product) | 18 mM 2,4-D; 5 mM U 46 D Fluid | NA | Single-strand DNA breaks | No effect of 2,4-D; increased strand breaks of U 46 D Fluid (0.1 strand breaks/10 mM) | Clausen et al. [194] | + |
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Human fibroblasts | U 46 D Fluid (commercial product) | 1 mM–10 mM | NA | Unscheduled DNA synthesis | No effect | Jacobi and Witte [195] | − |
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Human fibroblasts | U 46 D Fluid (commercial product) | 1 mM–10 mM | NA | Colony forming ability | No effect | Jacobi and Witte [195] | − |
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In vitro human erythrocytes | 2,4-D salt; 2,4-DP; MCPA | 100; 500; 1000 ppm for 1, 3, and 24 h | NA | Catalases in human blood | Small decrease in catalase activity at 1000 ppm | Bukowksa et al. [169] | + |
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In vitro human erythrocytes | MCPA-NA; 2,4-DMP | 10–500 ppm | NA | Effect on glutathione (GSH and GSSG), glutathione peroxidase (GSH-Px), glutathione transferase (GST), and adenine energy charge (AEC) | MCPA decreased GSH at 250 ppm (not statistically significant); no effect on GSSG, GSH-Px, GST, and AEC | Bukowska et al. [158] | + |
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In vitro human erythrocytes | 2,4-D-NA; MCPA-NA; 2,4-DCP | 1–1000 ppm | NA | AChE activity (indicator of membrane damage) | One hour incubation of erythrocytes showed no statistically significant changes in AChE activity except for highest dose of 2,4-D (1000 ppm) | Bukowska and Hutnik 2006 [196] | − |
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In vitro human erythrocytes | 2,4-D; MCPA | 1, 2, and 4 mM | NA | –SH groups (membrane protein damage) | Membrane damage at 2 and 4 mM | Duchnowicz et al. [165] | |
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In vitro human erythrocytes | 2,4-D; MCPA | 1, 2, 4 mM | NA | ATPase | Increase in ATPase at 1mM; decrease at 2 and 4 mM | Duchnowicz et al. [165] | + |
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In vitro human erythrocytes | 2,4-D-NA; MCPA-NA | 0.045 mM to 2.25 mM | NA | | 2,4-D-NA induced H2DCF oxidation, but not MCPA-NA. Neither denatured hemoglobin | Bukowska et al. [168] | − |
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In vitro human lymphocytes | 2,4-D salt | 1–3 mM | NA | Apoptosis | Significant increase in apoptosis but only at 660 ppm | Kaioumova et al. [170] | + |
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In vitro HepG2 cells | 2,4-D | 4, 8, and 16 mM | NA | Apoptosis | Significant increase in apoptosis above 884 ppm | Tuschl and Schwab [197] | + |
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In vitro human blood/lymphocytes from 5 individuals | Commercial product | 0.001–1.0 mM | NA | Peripheral blood lymphocyte proliferation (RI); micronuclei frequency (MN) | Minimal increase in MN frequency at cytotoxic level, decreased RI with high dose | Holland et al. [21] | + |
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In vitro human lymphocyte from 15 healthy male smoker/nonsmokers | 2,4-D | 221–2,221 μg/mL | 8 healthy nonsmokers, 7 healthy smokers | SCGE (comet) | No effects observed in nonsmokers; smokers only at the highest concentration | Sandal and Yilmaz [198] | − |
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In vitro human lymphocytes | Deherban A (commercial 2,4-D product) | 0.4 and 4 μg/mL | healthy, young nonsmokers | SCE | Statistically significant increase in chromatid and chromosome breaks, number of micronuclei and number of nuclear buds | Zeljezic and Garaj-Vrhovac [199] | ++ |
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In vitro whole blood culture | 2,4-D acid; salt | 10, 25, 50, and 100 μg/mL | 6 healthy individuals | SCE | Statistically significant increase in SCE at all doses; not at lowest dose for salt | Soloneski et al. [22] | ++ |
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In vitro plasma leukocyte culture | 2,4-D acid; salt | 10, 25, 50, and 100 μg/mL | 6 healthy individuals | SCE | No effect | Soloneski et al. [22] | − |
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In vivo |
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Blood from in vivo exposed workers | 2,4-D acid; commercial product | Sprayed 333 g/L 2,4-D; 167 g/L MCPA between 6–28 days | 19 exposed sprayers | Chromosomal aberrations | No effects observed | Mustonen et al. [193] | − |
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Blood from in vivo exposed workers | 2,4-D acid; MCPA | 12–155 kg sprayed | 10 farmers | Immunological variables | Small,statistically significant reduction in immunological variables 1–12 d but not 50–70 d following exposure. Increased CD8-DR | Faustini et al. [200] | + |
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Blood from in vivo exposed workers | 2,4-D acid | Not given; based on urinary concentrations (12–1285 ppb) | 13 exposed sprayers | Peripheral blood lymphocyte proliferation (RI); micronuclei frequency (MN) | Small, statistically significant increase in RI not in MN related to urinary levels of 2,4-D but not statistically significant | Figgs et al. [201] | + |
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Isolated lymphocytes from in vivo exposed workers | 2,4-D acid; commercial product | Exposure based on urinary levels of 2,4-D | 12 exposed sprayers | Peripheral blood lymphocyte proliferation (RI); micronuclei frequency (MN) | No effect on MN, increased RI | Holland et al. [21] | + |
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