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<br />simazine in rats and mice is >5000 mg/kg [6,15]; its dermal LD50 is 3100 mg/kg in rats and >
<br />10,000 mg/kg in rabbits [6.15]. The 4 -hour inhalation LC50 in rats is greater than 2 mg/L (6). The
<br />formulated products, in most cases, are less toxic via all routes [15]. Simazine is nonirritating to the
<br />skin and eyes of rabbits except at high doses [3]. Patch tests on humans have shown that simazine is
<br />not a skin irritant, fatiguing agent, or sensitizer [3]. However, rashes and dermatitis from
<br />occupational exposure to simazine have occurred [3]. The triazine herbicides disturb energy
<br />metabolism (thiamin and riboflavin functions). Symptoms include difficulty in walking, tremor,
<br />convulsions, paralysis, cyanosis, slowed respiration, miosis (pinpoint pupils), gut pain, diarrhea,
<br />and impaired adrenal function [3]. No cases of poisoning in humans have been reported from
<br />ingestion of simazine [3]. Rats given an oral dose of 5000 mg/kg exhibited drowsiness and irregular
<br />breathing. In another study, a single oral dose of 4200 mg/kg produced anorexia, weight loss, and
<br />some deaths in rats within 4 to 10 days [26]. For unknown reasons, sheep and cattle are especially
<br />susceptible to poisoning by simazine. Doses of 500 mg/kg were fatal in sheep with death delayed
<br />for 5 to 16 days. Symptoms exhibited by poisoned sheep included lower food intake, higher water
<br />intake, incoordination, tremors, and weakness, especially in the hindquarters [3].
<br />• Chronic toxicity: Some 90 -day feeding studies showed reduced body weight at 67 to 100
<br />mg/kg/day [10]. This same effect and kidney toxicity were seen in rats at doses of 150 mg/kg/day
<br />[10]. In 2 -year chronic oral feeding studies in which rats were given daily dosages of 5 mg/kg/day
<br />of simazine in the diet, no gross or microscopic signs of toxicity were seen [3]. When rats were
<br />given repeated doses of 15 mg/kg/day, some liver cells degenerated during the first 3 days, but the
<br />condition did not progress. Instead, the liver adapted and the compound was metabolized [3]. Othcr
<br />effects observed in test animals include tremors, damage to the testes, kidneys, liver, and thyroid,
<br />disturbances in sperm production, and gene mutations [10].
<br />• Reproductive effects: No adverse effects on reproductive capacity or development were observed
<br />in a three -generation study of rats fed 5 mg/kg/day simazine [101. High rates of fetotoxicity and
<br />decreased birth weight were noted in the fetuses of pregnant rabbits fed 75 mg/kg/day [26].
<br />Reproductive effects are not likely in humans under normal circumstances.
<br />• Teratogenic effects: No dose-related teratogenic effects were observed when rabbits were given
<br />daily doses of 5, 75, or 200 mg/kg for days 7 through 19 of pregnancy [26]. Chronic inhalation of a
<br />cumulative dose of 0.3 mg/L for 8 days in pregnant rats resulted in no treatment-related
<br />developmental abnormalities [10]. Simazine does not appear to be teratogenic.
<br />• Mutagenic effects: Simazine has shown negative results in a variety of mutagenicity tests on
<br />bacterial cultures [10]. Tests on human lung cell cultures have produced both positive and negative
<br />results [10]. When injected into adult male fruitflies, simazine increased the frequency of
<br />sex-linked lethal mutations, but failed to do so when fed to larvae. Other tests for mutagenicity in
<br />fruitflies were negative [3]. It is likely that simazine is either nonmutagenic or weakly mutagenic.
<br />• Carcinogenic effects: Simazine was not tumorigenic in mice at the maximum tolerated dose of 215
<br />mg/kg/day over an 18 -month period [10]. In other studies, doses as low as 5 mg/kg/day produced
<br />excess tumors (thyroid and mammary) in female rats [3,10]. Because of inconsistencies in the data,
<br />it is not possible to determine simazine's carcinogenic status.
<br />• Organ toxicity: Damage to the testes, kidneys, liver, and thyroid has been observed in test animals
<br />[3,10].
<br />Fate in humans and animals: Studies in rats, goats, and sheep reveal that 60 to 70% of the
<br />ingested dose may be absorbed into the system [10], with approximately 5 to 10% distributed
<br />systemically to tissues. The remainder is eliminated via urine within 24 hours [6]. Distribution led
<br />to detectable levels in red blood cells (highest), liver, kidney, fat, bone, and plasma [10]. When a
<br />cow was fed 5 ppm for 3 days, no simazine was found in the cow's milk during the next 3 days. It
<br />has been reported that simazine residues were present in the urine of sheep for up to 12 days after
<br />administration of a single oral dose. The maximum concentration in the urine occurred from 2 to 6
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