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EXTOXNET PIP-2,4-D Page 2 of 4 v � o Acute toxicity: The acid form is of slight to moderate toxicity. The oral LD50 of 2,4-D ranges from 375 to 666 mg/kg in the rat, 370 mg/kg in mice, and from less than 320 to 1000 mg/kg in guinea pigs. The dermal LD50 values are 1500 mg/kg in rats and 1400 mg/kg in rabbits, respectively [1,5,7]. In humans,prolonged breathing of 2,4-D causes coughing,burning, dizziness, and temporary loss of muscle coordination [1]. Other symptoms of poisoning can be fatigue and weakness with possible nausea. On rare occasions following high levels of exposure, there can be inflammation of the nerve endings with muscular effects [25]. o Chronic toxicity: Rats given high amounts, 50 mg/kg/day, of 2,4-D in the diet for 2 years showed no adverse effects. Dogs fed lower amounts in their food for 2 years died, probably because dogs do not excrete organic acids efficiently. A human given a total of 16.3 g in 32 days therapeutically, lapsed into a stupor and showed signs of incoordination, weak reflexes, and loss of bladder control [1,5,7]. • Reproductive effects: High levels of 2,4-D (about 50 mg/kg/day) administered orally to pregnant rats did not cause any adverse effects on birth weights or litter size. Higher doses (188 mg/kg/day) resulted in fetuses with abdominal cavity bleeding and increased mortality [1,5,7]. DNA synthesis in the testes was significantly inhibited when mice were fed large amounts (200 mg/kg/day) of 2,4-D [7]. The evidence suggests that if 2,4-D causes reproductive effects in animals, this only occurs at very high doses. Thus reproductive problems associated with 2,4-D are unlikely in humans under normal circumstances. e Teratogenic effects: 2,4-D may cause birth defects at high doses. Rats fed 150 mg/kg/day on days 6 to 15 of pregnancy had offspring with increased skeletal abnormalities, such as delayed bone development and wavy ribs [7]. This suggests that 2,4-D exposure is unlikely to be teratogenic in humans at expected exposure levels. e Mutagenic effects: 2,4-D has been very extensively tested and was found to be nonmutagenic in most systems. 2,4-D did not damage DNA in human lung cells. However, in one study, significant effects occurred in chromosomes in cultured human cells at low exposure levels [26]. The data suggest that 2,4-D is not mutagenic or has low mutagenic potential. • Carcinogenic effects: 2,4-D fed to rats for 2 years caused an increase in malignant tumors [7]. Female mice given a single injection of 2,4-D developed cancer(reticulum-cell sarcomas) [7]. Another study in rodents shows a low incidence of brain tumors at moderate exposure levels (45 mg/kg/day) over a lifetime [1,7]. However, a number of questions have been raised about the validity of this evidence and thus about the carcinogenic potential of 2,4-D. In humans, a variety of studies give conflicting results. Several studies suggest an association of 2,4-D exposure with cancer. An increased occurrence of non-Hodgkin's lymphoma was found among a Kansas and Nebraska farm population associated with the spraying of 2,4-D [25,27]. Other studies done in New Zealand, Washington,New York, Australia, and on Vietnam veterans from the U.S. were all negative. There remains considerable controversy about the methods used in the various studies and their results [28]. Thus,the carcinogenic status of 2,4-D is not clear. . Organ toxicity: Most symptoms of 2,4-D exposure disappear within a few days,but there is a report of liver dysfunction from long-term exposure [1,25]. . Fate in humans and animals: The absorption of 2,4-D is almost complete in mammals after ingestion and nearly all of the dose is excreted in the urine. The compound is readily absorbed through the skin and lungs. Men given 5 mg/kg excreted about 82% of the dose as unchanged 2,4- D. The half-life is between 10 and 20 hours in living organisms. There is no evidence that 2,4-D accumulates to significant level in mammals or in other organisms [20]. Between 6 and 8 hours after doses of 1 mg/kg,peak concentrations of 2,4-D were found in the blood, liver,kidney, lungs, and spleen of rats. There were lower levels in muscle and brain. After 24 hours, there were no detectable tissue residues. Only traces of the compound have been found in the milk of lactating animals for 6 days following exposure. 2,4-D passes through the placenta in pigs and rats. In rats, about 20%was detected in the uterus,placenta, fetus, and amniotic fluid [27]. Chickens given moderate amounts of 2,4-D in drinking water from birth to maturity had very low levels of the http://extoxnet.orst.edu/pips/24-D.htm 5/8/2008