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I;XFOXNF F PIP-SIMAZING http://ace.orst.cdu/cgi-bin/int's/01/pips/simazine.hnn
<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]. Other
<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 [10]. 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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