A Systematic Review of Carcinogenic Outcomes and Potential Mechanisms from Exposure to 2,4-D and MCPA in the Environment

Table 8

Studies in human cell cultures in vitro or humans exposed in vivo.

Test system	Compound	Concentration	Number	Endpoint	Results	Reference	Effect
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]	++
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]	+
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]	+
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]	+
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]	+
Human fibroblasts	U 46 D Fluid (commercial product)	1 mM–10 mM	NA	Unscheduled DNA synthesis	No effect	Jacobi and Witte [195]	−
Human fibroblasts	U 46 D Fluid (commercial product)	1 mM–10 mM	NA	Colony forming ability	No effect	Jacobi and Witte [195]	−
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]	+
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]	+
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]	−
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]
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]	+
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]	−
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]	+
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]	+
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]	+
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]	−
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]	++
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]	++
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]	−
In vivo
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]	−
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]	+
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]	+
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]	+

Notes. ⁻No effect observed; ⁺weak effect (not statistically significant or at conentrations exceeding systemic toxicity); ⁺⁺statistically significant strong effect.