United States Environmental Protection Agency Office of

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Chemical Class Anthranilic diamide insecticide, Mode of Action Interruption of normal muscle contraction. Pesticide Type Insecticide,U S Technical Registrant DuPont Crop Protection. P O Box 30,Newark DE 19714 0030,Chemical Structure. 2 USE PATTERNS AND FORMULATIONS, Registered Uses pome fruit crop group 11 stone fruit crop. group 12 leafy vegetables crop group 4,Brassica leafy vegetables crop group 5.
cucurbit vegetables crop group 9 fruiting,vegetables crop group 8 cotton grapes. potatoes rice and ornamentals and turf,grass growing in residential commercial. and public landscaped areas, Pests Application Sites moths beetles caterpillars etc. Application Rates Seasonal Maximum,Food Crops 0 2 lb a i acre. rice 0 13 a i acre year,Turf Grass 0 5 lb a i acre.
Ornamentals highly variable range,between 0 33 to 0 5 lb. Types of Formulations,Product Names Technical,DuPont Rynaxypyr Technical 95 3 a i. End Use Agricultural Uses,DuPont Coragen,18 4 a i suspension concentrate. DuPont Altacor,35 a i water dispersible granule,End Use Turf and Ornamental Uses. DuPont E2Y45 SC Insecticide,18 4 a i suspension concentrate.
DuPont E2Y45 0 33G Insecticide,0 33 a i granular,DuPont E2Y45 0 16G Insecticide. 0 16 a i granular,DuPont E2Y45 0 133G Insecticide,Fertilizer. 0 133 a i granular,Manufacturing Concentrate 35 a i. 3 SCIENCE FINDINGS,Physical and Chemical Characteristics. Available product chemistry data supporting the use of chlorantraniliprole are. summarized below in Tables 1 and 1 1,Table 1 Chlorantraniliprole Nomenclature.
Chemical structure HN,Common name Chlorantraniliprole. Company experimental name DPX E2Y45, IUPAC name 3 Bromo N 4 chloro 2 methyl 6 methylcarbamoyl phenyl 1 3 chloro 2. pyridine 2 yl 1H pyrazole 5 carboxamide, CAS name 3 Bromo N 4 chloro 2 methyl 6 methylamino carbonyl phenyl 1 3 chloro 2. pyridinyl 1H pyrazole 5 carboxamide,CAS registry number 500008 45 7. Table 1 1 Physiochemical Properties of the Technical Grade Test. Parameter Value,Melting point range C 200 202 95 9 208 210 99 2.
pH 5 77 0 087 at 20 C,Relative Density 1 5189 95 9 1 507 99 2 at 20 C. Table 1 1 Physiochemical Properties of the Technical Grade Test. Parameter Value,Water solubility 20 C Deionized Water 1 023 mg L. pH 4 0 972 mg L,pH 7 0 880 mg L,pH 9 0 971 mg L,Solvent solubility 20 C Acetone 3 446 0 172 g L. Acetonitrile 0 711 0 072 g L,Ethyl Acetate 1 144 0 046 g L. Dichloromethane 2 476 0 058 g L,Dimethylformamide 124 4 g L.
n Octanol 0 386 0 01 g L,Methanol 1 714 0 057 g L,n Hexane 0 0001 g L. o Xylene 0 162 0 01 g L, Vapor pressure 6 3 x 10 12 Pa 20 C 2 1 x 10 11 Pa 25 C. Dissociation constant pKa 10 88 0 71,Octanol water partition Deionized Water 589. coefficient KOW 20 C pH 4 588, UV visible absorption max pH 2 no absorption max 200 nm at 290. pH 7 no absorption max 200 nm at 290 4185,pH 10 absorption max at 320 nm which may be.
due to decomposition of DPX E2Y45 at 290,Metabolism Assessment. The nature of the residue in plants and livestock is adequately understood Very. little degradation was observed in primary and rotational crops Unchanged parent. chlorantraniliprole was the major identified residue in primary and rotational crops The. metabolism of chlorantraniliprole in livestock was extensive and followed the major steps. similar to those observed in rice i hydroxylation of the N methyl group to IN H2H20. or hydroxylation of the tolyl methyl group to IN HXH44 ii cyclization with loss of. water to a quinazolinone derivative IN EQW78 and iii N demethylation via IN. H2H20 to IN F9N04,Hazard Characterization,Toxicology Requirements. The toxicology requirements 40 CFR 158 340 for a food use for. chlorantraniliprole are in Table 2,Table 2 Toxicology Data Requirements. Test Technical,Required Satisfied,870 1100 Acute Oral Toxicity yes yes. 870 1200 Acute Dermal Toxicity yes yes,870 1300 Acute Inhalation Toxicity yes yes.
870 2400 Primary Eye Irritation yes yes,870 2500 Primary Dermal Irritation yes yes. 870 2600 Dermal Sensitization yes yes,870 3100 Oral Subchronic rodent yes yes. 870 3150 Oral Subchronic nonrodent yes yes,870 3200 21 Day Dermal yes yes. 870 3250 90 Day Dermal no,870 3465 90 Day Inhalation no. 870 3700a Developmental Toxicity rodent yes yes, 870 3700b Developmental Toxicity nonrodent yes yes.
870 3800 Reproduction yes yes,870 4100a Chronic Toxicity rodent yes yes. 870 4100b Chronic Toxicity nonrodent yes yes,870 4200a Oncogenicity rat yes yes. 870 4200b Oncogenicity mouse yes yes,870 4300 Chronic Oncogenicity yes yes. 870 5100 Mutagenicity Gene Mutation bacterial yes yes. 870 5300 Mutagenicity Gene Mutation mammalian yes yes. 870 5385 Mutagenicity Structural Chromosomal Aberrations yes yes. 870 5395 Mutagenicity Micronucleus yes yes,870 6100a Acute Delayed Neurotox hen no. 870 6100b 90 Day Neurotoxicity hen no, 870 6200a Acute Neurotox Screening Battery rat yes yes.
870 6200b 90 Day Neuro Screening Battery rat yes yes. 870 6300 Develop Neuro no,870 7485 General Metabolism yes yes. 870 7600 Dermal Penetration no,Special Studies,28 day immunotoxicity rat yes. 28 day immunotoxicity mouse yes,Acute Toxicity, Chlorantraniliprole Technical is toxicity category IV for all routes of exposure. and is a non sensitizer Table 3, Table 3 Acute Toxicity of Technical Chlorantraniliprole. Guideline Study Type MRID No Results Toxicity,No Category.
870 1100 Acute oral toxicity 46889112 LD50 5000 mg kg bw IV. 870 1200 Acute dermal toxicity 46889113 LD50 5000 mg kg bw IV. 870 1300 Acute inhalation 46889121 LC50 5 1 mg L IV. 870 2400 Acute eye irritation 46889115 Iritis score of 1 in 1 3 rabbits conjuctival IV. redness score of 1 in 2 3 rabbits All eyes,returned to normal after 72 hours. 870 2500 Primary skin irritation 46889114 No dermal irritation clinical signs or body IV. weight loss, 870 2600 Dermal sensitization 46889221 Not a dermal sensitizer Negative. Subchronic Chronic and Other Toxicity, In short term studies the most consistent effects are those associated with non. adverse pharmacological response to the xenobiotic induction of liver enzymes and. subsequent increase in liver weights Chlorantraniliprole is not genotoxic neurotoxic. immunotoxic carcinogenic or teratogenic Overall chlorantraniliprole exhibits minimal. mammalian toxicity after long term exposure The only consistent observation in the. mammalian toxicology studies is an increased degree of microvesiculation of the adrenal. cortex after dermal or dietary administration of chlorantraniliprole Based on the lack of. adverse effect on the function of the adrenal gland this observation was considered. treatment related but not adverse, Table 4 Subchronic Chronic and Other Toxicity Profile. STUDY DOSES NOAEL LOAEL,SPECIES mg kg day mg kg day mg kg day.
14 day Oral 0 25 100 1000 1000 Not No adverse effects Weak inducer of cytochrome. Gavage rat established P450 3A at all dose levels with statistical. significance at 100 and 1000 mg kg day, 28 Day Oral 0 20 7 106 and 584 male Not No adverse effects Slight increase in liver weight. feed rat 584 male 0 24 and 675 established at 128 and 675 mg kg day in females and minimal. 128 and 675 female hepatocellular hypertrophy at 675 mg kg that is. female attributed to enzyme induction characterized by. increased amount of eosinophilic cytoplasm with,hepatocytes but no histomorphologic evidence of. hepatocellular damage In 128 and 675 mg kg, females a statistically significant increase in UDP. GT activity was observed in HDT female rats with,a similar increase in males These changes are. consistent with a pharmacological response and,were not considered adverse.
28 Day Oral 0 52 182 538 and 1443 male Not No adverse effects Slight increase in liver wt in. feed mouse 1443 male 0 64 and 1524 established 658 and 1524 mg kg day females corresponded. 206 658 and 1524 female with a mild increase in cytochrome P450 enzyme. female activity No histopathological evidence of liver. toxicity was observed,A reduction in body weight gain was observed in. HDT males 52 but not in females No, statistically significant decrease in absolute body. weight was observed therefore this effect was not,considered adverse. 28 day Oral 0 300 1000 1000 Not No adverse effects Induction of cytochrome P450. capsule established enzyme activity 58 in both males and females at. Dog 1000 mg kg day specifically 1A1 and 2B1 2 at 300. and 1000 mg kg day, 28 day Oral 0 26 138 266 1302 male Not No adverse effects Food consumption generally. feed dog 797 and 1302 and 1240 established increased as the study progressed with males. Palatability male 0 28 138 female generally demonstrating the highest food. study 298 888 and 1240 consumption when fed the HDT. 28 day 0 100 300 and 1000 Not No adverse effects Reductions in mean body. Table 4 Subchronic Chronic and Other Toxicity Profile. STUDY DOSES NOAEL LOAEL,SPECIES mg kg day mg kg day mg kg day.
Dermal rat 1000 established weight gain 22 and 19 for males and females. and food efficiency 19 and 17 for males and,females over the 28 day at the HDT. Increased microvesiculation of adrenal cortex in, males only with no light or electronic microscopic. evidence of adrenal cellular degeneration or,toxicity No effect on the capacity of the adrenal. gland to produce corticosterone under either basal. or following ACTH stimulation Therefore these,effects were not considered adverse. 90 day Oral 0 36 9 120 359 1188 male Not No adverse effects A slight increase in liver. feed rat 1188 male 0 47 and 1526 established weight at HDT females and reduction in bilirubin. 157 460 1526 female in females at 157 mg kg day with no. female corresponding histopathological evidence of liver. 90 day Oral 0 32 6 115 345 1135 male Not No adverse effects Hyperactivity and. feed mouse 1135 male 0 and 1529 established hyperreactivity in females were observed near the. 40 7 158 422 female end of the study and one male in the upper mid. 1529 female dose had convulsions but these effects were. considered spurious as they were not reproducible,in the 18 month mouse study with a FOB.
A slight increase in liver weight at the HDT males. and females with no corresponding,histopathological evidence of liver toxicity. 90 day Oral 0 32 2 119 303 1163 male Not No adverse effects A mild increase in liver weight. feed dog 1163 male 0 and 1220 established was observed in males at 1163 mg kg day with no. 36 5 133 318 female corresponding histopathological evidence of liver. 1220 female toxicity, 52 week 0 32 112 317 1164 male Not No adverse effects A mild increase in liver weight. Oral 1164 male 0 34 and 1233 established in HDT males and females and increase in alkaline. feed dog 113 278 1233 female phosphatase in HDT males with no corresponding. female histopathological evidence of liver toxicity. Body weight gain increase in HDT males for weeks,8 9 compared to controls with an increase in food. efficiency in week 9, 2 Year Oral 0 7 71 39 156 805 male Not No evidence of carcinogenicity and no adverse. feeding rat 805 male 0 and 1076 established findings Increased adrenal cortical. 10 9 51 212 1076 female microvesiculation due to lipid was present in the. female zona fasciculata region of the adrenal gland of. some male rats in all dose groups in both the one,year and main studies This finding was considered.
test substance related but was not considered, adverse as the adrenal morphology was generally in. the range of what was observed in control rats and. the finding was not associated with any indication. of cytotoxicity or other evidence of structural or. functional impairment of the adrenal gland, 18 Month 0 2 6 9 2 26 1 158 male 935 male No evidence of carcinogenicity Eosinophilic foci. Oral 158 935 male 0 and 1155 no LOAEL accompanied by hepatocellular hypertrophy and. feeding 3 34 11 6 32 9 female established increased liver weight form the bases for the male. Mouse 196 1155 female for female LOAEL of 935 mg kg day. Two 0 200 1000 1199 male Not A slight increase in mean liver weights in P1. generation 4000 20000 and 1594 established and F1 males and females at 238 318 9. oral ppm female mg kg day and above slight increase in mean. study rat mg kg bw d adrenal weight at 238 318 9 mg kg day and. Table 4 Subchronic Chronic and Other Toxicity Profile. STUDY DOSES NOAEL LOAEL,SPECIES mg kg day mg kg day mg kg day. equivalents 1199 1594 mg kg day P1 and F1 males and. pre mating females Mean body weight of 1199 1594, P1 m 0 12 60 mg kg day F1 pups was slightly reduced on. 238 1199 lactation days 7 14 and 21 No effects on F2. F1 m 0 18 89 offspring weights during lactation, P1 f 0 16 78 Minimal to mild increase in adrenal cortical.
318 1594 microvesiculation in P1 adult males and F1. F1 f 0 20 104 adult males and females P1 adult at 60 4 77 8. 406 2178 mg kg day and greater F1 adult males at 12. gestation mg kg day and greater These effects were not. P1 f 0 14 68 observed in weanlings No cytotoxicity or. 278 1373 abnormal cellular structures were observed. F1 f 0 14 71 under light or electron microscopy,P1 f 0 32 162. F1 f 0 35 183,Develop 0 20 100 300 1000 Not No adverse effects. 1 United States Environmental Protection Agency Office of Prevention Pesticides and Toxic Substances 7505P

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