Table 7.

In vitro animal studies.

Organism	Compound	Dose	Endpoint	Duration	Results	Reference
Review study of in vivo (n = 15) and in vitro (n = 19) 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 μM (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 μg/L	Unscheduled DNA synthesis		No effects observed	Charles et al. [181]
Bacteria	2,4-D acid; salt; ester; 4 other derivatives	10–10000 μg/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 μg/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 μg/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 μg/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 μg/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 μg/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 μM–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 μg/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 μg/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 μM and 23 μM; 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 μg/mL	Intercellular communication	Hours	Colony forming inhibited at 140 μg/mL	Rubinstein et al. [23]