Acute, Pharmacokinetic, and Subchronic Toxicological Sudies of 2,4-Dichlorophenoxyacetic Acid

Synergistic Effects of Copper and Butylic Ester of 2,4-Dichlorophenoxyacetic Acid (Esternon Ultra) on Amphibian Embryos

“…For copper, the LC 50 24 and 168 hr were 0.12 and 0.05 mg Cu 2+ /L respectively. The LCs are within the range obtained in previous studies [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21]. The LC 10 for 168 hr resulted in 0.022 mg/L.…”

“…In addition, the fact that the Xenopus laevis study was conducted with FETAX [25], a different toxicity test, could also explain at least partially this difference by taking into account: i) the high salinity of the solution employed in FETAX test which usually reduce toxic effects [16]; ii) FETAX is a 96 hr test conducted at 24±2°C while the AMPHITOX test employed is for 168 hr at 20±1°C. In mammals, different formulations of 2,4-D administered in unique oral doses, result in a LD 50 of 553-1090 mg/kg depending on its chemical form, while the NOEL value was 15 mg/kg/day [6]. As a whole, for Bufo arenarum, the results point out that copper is very significantly more toxic than 2,4-D (for example, 60 times at 168 hr of exposure).…”

“…Although its higher toxicity is on autotrophyc organisms there are numerous reports of adverse effects on a wide diversity of heterotrophyc species [2]. Gorzinski et al showed a significant diminution in the gain weight and functional and structural alterations of kidneys of rats subchronically treated with 2,4-D (15-150 mg/kg/day for 13 days) [6], and it was also reported that different 2,4-D formulations produce neurotoxic effects such as ataxia and failures in neuromuscular coordination [7,8] probably related to changes in various neurotransmitter systems, such as serotonin and dopamine [9]. Its oxidative stress effects were reported as the diminution of glutathion and thiol-proteins, lipoperoxidation [10], increases in superoxide dismutase activity, changes in catalase, glutathione peroxidase and Glutathione S-transferase activities [11].…”

Weight-of-the-evidence evaluation of 2,4-D potential for interactions with the estrogen, androgen and thyroid pathways and steroidogenesis

“…2,4-D clearly exhibits species-, dose-and sex-dependent nonlinear TK in animal test species (Gorzinski et al 1987;Van Ravenswaay et al 2003;Timchalk 2004;Saghir et al 2006;. The non-linear TK is directly and primarily attributable to high-dose saturation of a renal anion transporter, OAT-1, that is responsible for rapid renal clearance of 2,4-D (Hasegawa et al 2003;Saghir et al 2013).…”

“…The transporter does not effectively function in dogs. Studies in rats indicate the renal clearance of 2,4-D is clearly saturated at oral [gavage] dose levels of 50 mg/kg, resulting in nonlinear increases in 2,4-D blood concentrations at this dose and above (Gorzinski et al 1987;Van Ravenswaay et al 2003). Given this non-linear behavior, saturation of 2,4-D renal clearance at 50 mg/kg suggests that animal toxicity findings observed at this dose level and higher overestimate potential human risks.…”