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EX roXNE,"r PIP - IMIDnCLOPRID <br />http:,/'ace.orst.edu/cgi-bin/mt's/01/pips/iiiiidaclo.htili <br />that resulted in mortality to half of the test animals (LD50) is 450 mg/kg body weight in rats (223), <br />and 131 mg/kg in mice (1). The 24-hour dermal LD50 in rats is >5,000 mg/kg. It is considered <br />non -irritating to eyes and skin (rabbits), and non -sensitizing to skin (guinea pigs) (1). Some <br />granular formulations may contain clays as inert ingredients that may act as eye irritants. In acute <br />inhalation toxicity tests with rats, the airborne concentration of imidacloprid that resulted in <br />mortality to half of the test organisms (LC50) is > 69 mg/meters cubed air in the form of an aerosol, <br />and >5323 mg/meters cubed air in the form of dust. These values represent the maximum attainable <br />airborne concentrations (1). <br />• Signs and Symptoms of Poisoning: Although no account of human poisoning was found in the <br />literature, signs and symptoms of poisoning would be expected to be similar to nicotinic signs and <br />Symptoms. including fatigue, twitching, cramps, and muscle weakness including the muscles <br />necessary for breathing (330). <br />• Chronic Toxicity: A 2 -year feeding study in rats fed up to 1,800 ppm resulted in a No Observable <br />Effect Level (NOEL) of 100 ppm (5.7 mg/kg body weight in males and 7.6 mg/kg in females). <br />Adverse effects included decreased body weight gain in females at 300 ppm, and increased thyroid <br />lesions in males at 300 ppm and females at 900 ppm. A 1 -year feeding study in dogs fed up to 2,500 <br />ppm resulted in a NOEL of 1,250 ppm (41 mg/kg). Adverse effects included increased cholesterol <br />levels in the blood, and some stress to the liver (measured by elevated liver cytochrome p-450 <br />levels) (331). <br />• Reproductive Effects: A three generation reproduction study in rats fed up to 700 ppm <br />imidacloprid resulted in a NOEL of 100 ppm (equivalent to 8 mg/kg/day) based on decreased pup <br />body weight observed at the 250 ppm dose level (331). <br />• Teratogenic Effects: A developmental toxicity study in rats given doses up to 100 ppm by gavage <br />on days 6 to 16 of gestation resulted in a NOEL of 30 mg/kg/day (based on skeletal abnormalities <br />observed at the next highest dose tested of 100 ppm) (329). In a developmental toxicity study with <br />rabbits given doses of imidacloprid by gavage during days 6 through 19 of gestation, resulted in a <br />NOEL of 24 mg/kg/day based on decreased body weight and skeletal abnormalities observed at 72 <br />mg/kg/day (highest dose tested) (331). <br />• Mutagenic Effects: Imidacloprid may be weakly mutagenic. In a battery of 23 laboratory <br />mutagenicity assays, imidacloprid tested negative for mutagenic effects in all but two of the assays. <br />It did test positive for causing changes in chromosomes in human lymphocytes, as well as testing <br />positive for genotoxicity in Chinese hamster ovary cells (331). <br />• Carcinogenic Effects: Imidacloprid is considered to be of minimal carcinogenic risk, and is thus <br />categorized by EPA as a "Group E" carcinogen (evidence of noncarcinogenicity for humans). There <br />were no carcinogenic effects in a 2 -year carcinogenicity study in rats fed up to 1,800 ppm <br />imidacloprid (328). <br />• Organ Toxicity: In short-term feeding studies in rats, there were thyroid lesions associated with <br />very high doses of imidacloprid (331). <br />• Fate in Humans and Animals: Imidacloprid is quickly and almost completely absorbed from the <br />gastrointestinal tract, and eliminated via urine and feces (70-80% and 20-30%, respectively, of the <br />96% of the parent compound administered within 48 hours). The most important metabolic steps <br />include the degradation to 6-chloronicotinic acid, a compound that acts on the nervous system as <br />described above. This compound may be conjugated with glycine and eliminated, or reduced to <br />guanidine (1). <br />ECOLOGICAL EFFECTS <br />• Effects on Birds: Imidacloprid is toxic to upland game birds. The LD50 is 152 mg/kg for bobwhite <br />quail, and 31 mg/kg in Japanese quail (223, 1). In studies with red -winged blackbirds and <br />brown -headed cowbirds, it was observed that birds learned to avoid imidacloprid treated seeds after <br />- of 4 5111100 4:22 PM <br />