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;XTOXNET PIP-2,4-D h"p://ace,ace.orst.cdu/info/extoxnct/pips/24-I).htm <br /> - Acute toxicity: The acid form is of slight to moderate toxicity. The oral LD50 of 2,4-D ranges from <br /> 375 to 566 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 /> temporary 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-D in 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 <br /> in the testes was significantly inhibited when mice were fed large amounts (200 mg/kg/day) of <br /> j 2,4-D [7]. The evidence suggests that if 2,4-D causes reproductive effects in animals, this only <br /> occurs at very high doses. Thus reproductive problems associated with 2,4-D are unlikely in <br /> humans under 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 /> kFemale 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 variety 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 /> e Organ toxicity: Most symptoms of 2,4-D exposure disappear within a few days, but there is a <br /> report 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 <br /> 2,4-D. 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 <br /> 2,4-D in drinking water from birth to maturity had very low levels of the compound in eggs [7]. <br /> i <br /> �t 4 1/26/00 9:00 AM <br />