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