Organism Compound Dose Endpoint Duration Results Reference Review study of in vivo (
) and in vitro (
) studies of mutagenicity and genotoxicity MCPA Review and meta-analysis Mutagenicity and genotoxicity Many 6 equivocal positive results in vitro at highest dose; 6 weakly positive (borderline statistical significance, etc.) in vivo Elliott [20 ] Chinese hamster ovary 2,4-D acid; MCPA (pure compound and commercial herbicide) 100, 150, and 200 mg/kg oral gavage CHO/HGPRT assay 2 weeks 5 days/wk No increase in SCE from 2,4-D; significant increase in SCE from MCPA Linnainmaa [19 ] Male Wistar rat liver 2,4-D acid 0, 200, and 500 μ M (44, 110 ppm) Liver mitochondrial bioenergetics Not specified depressed membrane polarization at highest concentration; no effect on ATP synthetase Palmeira et al. [159 –162 ]
Male Fischer 344 rat hepatocytes 2,4-D acid; salt; ester; 4 other derivatives 2–350 μ g/L Unscheduled DNA synthesis No effects observed Charles et al. [181 ] Bacteria 2,4-D acid; salt; ester; 4 other derivatives 10–10000 μ g/plate Ames test No evidence of mutagenic activity in any tester strain across 2,4-D or any derivative either in the presence or absence of S9 Charles et al. [181 ] 3–5/dose/sex/group ICR and CD-1 mice 2,4-D acid; salt; ester; 4 other derivatives 40, 130, and 400 ppm Mouse bone marrow micronucleus test No significant increases in the incidence of micronucleated polychromatic erythrocytes (MN-PCE) Charles et al. [185 ] Sprague Dawley rat blood 2,4-D 2-butoxyethyl ester, and 2,4-D isopropylamine salt, 2,4-D triisopropanolamine salt Up to 1400 μ g/mL plate Rat lymphocyte chromosomal aberration test 48 hr No clastogenic response Gollapudi et al. [18 ] Chinese hamster ovary 2,4-D 2-butoxyethyl ester, 2,4-D isopropylamine salt, 2,4-D triisopropanolamine salt up to 1400 μ g/mL plate CHO/HGPRT assay 48 hr No increase in SCE Gollapudi et al. [18 ] Chinese hamster ovary 2,4-D acid; salt 2–10 μ g/mL SCGE (Comet) 90 m/36 hr Statistically significant increases in DNA damage up to 100% González et al. [186 ] Chinese hamster ovary 2,4-D acid; salt 2–10 μ g/mL Cell cycle progression, mitotic index, and replicative index 90 m/36 hr No effect on cell cycle progression or replicative index; reductions in mitotic index González et al. [186 ] Chinese hamster ovary 2,4-D acid; salt 2–20 μ g/mL Chromosomal aberrations 90 m/36 hr Significant dose- dependent increase in SCE González et al. [186 ] Chinese hamster ovary 2,4-D acid; salt 200 μ M–4 mM SCGE (Comet) 24 hr No effects observed Sorensen et al. [187 ] Syrian hamster embryo 2,4-D salt 1, 2.5, and 5 μ g/mL SCGE (Comet) 5 hr/24 hr Increase in DNA damage Maire et al. [188 ] Syrian hamster embryo 2,4-D salt 1, 2.5, and 5 μ g/mL Morphological transformation 5 hr/24 hr Percentage of morphologically transformed colonies increased in a dose-dependent manner to up to 2.4% and 3.8% at 11.5 μ M and 23 μ M; significant upregulation of c-Myc RNA. No induction of apoptosis Maire et al. [188 ] Chinese hamster ovary cells 2,4-D 1 mM Polyamine biosynthesis 24 hr Significant decrease in polyamine metabolism Rivarola and Balegno [189 ]; Rivarola et al. [190 ] Chinese hamster (lung) V79 cells 2,4-D acid 20, 50, 75, 100, 120, and 140 μ g/mL Intercellular communication Hours Colony forming inhibited at 140 μ g/mL Rubinstein et al. [23 ]
