['lifetime', 'cancer', 'risk', 'that', 'is', 'greater', 'than', 'approximately', 'one', 'in', 'a', 'million,', 'EPA', 'attempts', 'to', 'derive', 'a', 'more', 'accurate', 'exposure', 'estimate', 'for', 'the', 'pesticide', 'by', 'evaluating', 'additional', 'types', 'of', 'information', '(anticipated', 'residue', 'data', 'and/or', 'percent', 'of', 'crop', 'treated', 'data)', 'which', 'show,', 'generally,', 'that', 'pesticide', 'residues', 'in', 'most', 'foods', 'when', 'they', 'are', 'eaten', 'are', 'well', 'below', 'established', 'tolerances.', 'II.', 'Aggregate', 'Risk', 'Assessment', 'and', 'Determination', 'of', 'Safety', 'Consistent', 'with', 'section', '408(b)(2)(D),', 'EPA', 'has', 'reviewed', 'the', 'available', 'scientific', 'data', 'and', 'other', 'relevant', 'information', 'in', 'support', 'of', 'the', 'existing', 'uses', 'of', 'spinosad.', 'EPA', 'had', 'sufficient', 'data', 'to', 'assess', 'the', 'hazards', 'of', 'spinosad', 'and', 'to', 'make', 'a', 'determination', 'on', 'aggregate', 'exposure,', 'consistent', 'with', 'section', '408(b)(2),', 'for', 'tolerances', 'for', 'residues', 'of', 'spinosad', 'for', 'those', 'uses.', "EPA's", 'assessment', 'of', 'the', 'dietary', 'exposures', 'and', 'risks', 'associated', 'with', 'establishing', 'the', 'existing', 'tolerances', 'follows.', 'ane', 'A.', 'Toxicological', 'Profile', 'EPA', 'has', 'evaluated', 'the', 'available', 'toxicity', 'data', 'and', 'considered', 'its', 'validity,', 'completeness,', 'and', 'reliability', 'as', 'well', 'as', 'the', 'relationship', 'of', 'the', 'results', 'of', 'the', 'studies', 'to', 'human', 'risk.', 'EPA', 'has', 'also', 'considered', 'available', 'information', 'conceming', 'the', 'variability', 'of', 'the', 'sensitivities', 'of', 'major', 'identifiable', 'subgroups', 'of', 'consumers,', 'including', 'infants', 'and', 'children.', 'The', 'nature', 'of', 'the', 'toxic', 'effects', 'caused', 'by', 'spinosad', 'are', 'discussed', 'below.', '1.', 'Acute', 'toxicity', 'studies', 'with', 'technical', 'spinosad', '(88%', '-', '90.4%):', 'Oral', 'LD[50]', 'in', 'the', 'rat', 'is', '>', '5,000', 'milligram/kilogram', '(mg/kg)', 'for', 'males', 'and', 'females', '-', 'Toxicity', 'Category', 'IV;', 'dermal', 'LD[50]', 'in', 'the', 'rat', 'is', '>', '2,800', 'mg/kg', 'for', 'males', 'and', 'females', '-', 'Toxicity', 'Category', 'III;', 'inhalation', 'LC[50]', 'in', 'the', 'rat', 'is', '>', '5.18', 'mg/L', '-', 'Toxicity', 'Category', 'IV;', 'primary', 'eye', 'irritation', 'in', 'the', 'rabbit', '(slight', 'conjunctival', 'irritation)', '-', 'Toxicity', 'Category', 'IV;', 'primary', 'dermal', 'irvitation', 'in', 'the', 'rabbit', '(no', 'erythema', 'and', 'edema)', '-', 'Toxicity', 'Category', 'IV.', 'Spinosad', 'is', 'not', 'a', 'sensitizer.', '2.', 'Acute', 'toxicity', 'studies', 'with', 'the', 'end-use', '(44%', 'formulation)', 'product', 'for', 'spinosad:', 'Oral', 'LD[50}', 'in', 'the', 'rat', 'is', '>', '5,000', 'mg/kg', 'for', 'males', 'and', 'females', '-', 'Toxicity', 'Category', 'IV;', 'dermal', 'LD[50]', 'in', 'the', 'rat', 'is', '>', '2,800', 'mg/kg', 'for', 'males', 'and', 'females', '-', 'Toxicity', 'Category', 'III;', 'inhalation', 'LC[50}', 'in', 'the', 'rat', 'is', '>', '5', 'mg/L', '-', 'Toxicity', 'Category', 'IV;', 'primary', 'eye', 'irritation', 'in', 'the', 'rabbit', '(slight', 'conjunctival', 'irritation)', '-', 'Toxicity', 'Category', 'IV;', 'primary', 'dermal', 'irritation', 'in', 'the', 'rabbit', '(slight', 'transient', 'erythema', 'and', 'edema)', '-', 'Toxicity', 'Category', 'IV;', 'not', 'a', 'sensitizer.', '3.', 'Ina', 'subchronic', 'feeding', 'study', 'in', 'rats,', 'the', 'no-observed', 'adverse', 'effect', 'level', '(NOAEL)', 'was', '33.9', 'and', '38.8', 'mg/kg/day', 'for', 'mates', 'and', 'females,', 'respectively.', 'The', 'lowest', 'observed', 'effect', 'level', '(LOEL)', 'was', '68.5', 'and', '78.1', 'mg/kg/day', 'for', 'males', 'and', 'females,', 'respectively', 'based', 'on', 'decreased', 'body', 'weight', 'gain,', 'anemia,', 'and', 'vacuolation', 'in', 'multiple', 'organs', '(kidney,', 'liver,', 'heart,', 'spleen,', 'adrenals,', 'and', 'thyroid).', '4,', 'Ina', 'subchronic', 'feeding', 'study', 'in', 'mice,', 'the', 'no', 'observed', 'effect', 'level', '(NOEL)', 'was', '7.5', 'mg/kg/day', 'and', 'the', 'LOEL', 'was', '22.5', 'mg/kg/day', 'based', 'on', 'cytoplasmic', 'vacuolation', 'in', 'multiple', '[*43632]', 'organs', '(kidney,', 'liver,', 'heart,', 'stomach,', 'lymphoid', 'organs,', 'and', 'ovary).', '5.', 'In', 'a', 'subchronic', 'feeding', 'study', 'in', 'dogs,', 'the', 'NOEL', 'was', '4.89', 'and', '5.38', 'mg/kg/day', 'for', 'males', 'and', 'females,', 'respectively.', 'The', 'LOEL', 'was', '9.73', 'mg/kg/day', 'and', '10.5', 'mg/kg/day', 'based', 'on', 'decreased', 'mean', 'body', 'weights', 'and', 'food', 'consumption,', 'and', 'anemia.', '6.', 'Ina', '21-day', 'dermal', 'study', 'in', 'rats,', 'the', 'NOEL', 'for', 'systemic', 'effects', 'was', '>', '1,000', 'mg/kg/day', '(limit', 'dose).', 'No', 'systemic', 'toxicity', 'was', 'observed', 'at', 'any', 'dose', 'tested.', '7.', 'Ina', 'chronic', 'feeding', 'study', 'in', 'dogs,', 'the', 'NOEL', 'was', '2.68', 'mg/kg/day.', 'The', 'LOEL', 'was', '8.22', 'mg/kg/day', 'based', 'on', 'increased', 'liver', 'enzymes', '(ALT,', 'AST),', 'triglycerides;', 'vacuolated', 'cells', '(parathyroid),', 'and', 'arteritis.', '8.', 'In', 'an', 'carcinogenicity', 'study', 'in', 'mice,', 'the', 'NOEL', 'was', '11.4', 'mg/kg/day.', 'The', 'LOEL', 'was', '50.9', 'mg/kg/day', 'based', 'on', 'decreased', 'body', 'weight', 'gains,', 'increased', 'mortality,', 'hematologic', 'effects,', 'increased', 'thickening', 'of', 'the', 'gastric', 'mucosa,', 'and', 'histologic', 'changes', 'in', 'the', 'stomach', 'of', 'males.', '9.', 'In', 'a', 'chronic', 'feeding/carcinogenicity/neurotoxicity', 'study', 'in', 'rats,', 'the', 'NOEL', '(systemic)', 'was', '9.5', 'and', '12.0', 'mg/kg/day', 'for', 'males', 'and', 'females,', 'respectively.', 'The', 'LOEL', '(systemic)', 'was', '24,1', 'and', '30.3', 'mg/kg/day', 'for', 'males', 'and', 'females,', ' ', '1gzZ9', 'BST?S']