Fluopicolide (Flupicolide)
CAS No. 239110-15-7

ACTIVITY:Fungicide (acylpicolide)

CAS Name: 2,6-dichloro-N-[[3-chloro-5-(trifluoromethyl)-2-pyridinyl]methyl]benzamide


Adverse Effects:

Boby weight decrease
Developmental: Decreased crown-rump length in fetuses

Regulatory Information
(only comprehensive for the US)
US EPA Registered: On 3-28-07 EPA approved tolerances for imported grape and raisin without US registration
US Tolerances: CFR 180.627
Other Information
Molecular Formula: C14H8Cl3F3N2O
Other Name(s): EXP 11120A
Entry Year: 2004 
Manufacturer: Bayer CropScience
Of special interest:
May 2007. Fluopicolide: summary of toxicology data. California EPA, Department of Pesticide Regulation, Medical Toxicology Branch.
January 27, 2006 - . Valent U.S.A. Corp. has reached an agreement with Bayer Corp. to commercialize and market a new fungicide for vegetables, grapes and turf in the U.S. and Canada... "Valent has entered into an agreement with Bayer Corportion to be the exclusive developer and marketer..."
Ref: Valent, Bayer market new fungicide.
2006. Behaviour of fluopicolide in plants. J. K. Rupprecht. Pflanzenschutz-Nachrichten Bayer 59/2006, 2-3: 261-280.

2006. Fluopicolide: Metabolism in animals. PJ Fisher. Pflanzenschutz-Nachrichten Bayer 59/2006, 2-3: 243-260.

December 2005 - Bayer CropScience received the first registrations for its new downy mildew fungicide fluopicolide in the UK and China... Fluopicolide is the first derivative of the new acylpicolides class of chemicals. Bayer Press Release.

US Federal Register
Date Published Docket Identification
N umber
June 27, 2007 EPA-HQ-OPP-2007-0339

IR-4. Pesticide Petition. PP 7E7172. Proposal to establish a tolerance for residues of the fungicide fluopicolide, in or on food commodities:

Brassica, head and stem, subgroup 5A

This subgroup includes 10 commodities.
broccoli • broccoli, cavalo • broccoli, chinese • brussels sprout • cabbage • cabbage, chinese mustard • cabbage, chinese napa • cauliflower • cavalo broccolo • kohlrabi

5.0 ppm
chive, Chinese, fresh leaves 5.0 ppm
chive, fresh leaves 5.0 ppm
daylily, bulb 5.0 ppm
elegans hosta 5.0 ppm
fritillaria, bulb 5.0 ppm
fritillaria, leaves 5.0 ppm
garlic, serpent, bulb 5.0 ppm
kurrat 5.0 ppm
lady's leek 5.0 ppm
leek, wild 5.0 ppm
lily, bulb 5.0 ppm
onion, Beltsville bunching 5.0 ppm
onion, Chinese, bulb 5.0 ppm
onion, fresh 5.0 ppm
onion, macrostem 5.0 ppm
onion, pearl 5.0 ppm
onion, potato, bulb 5.0 ppm
onion, tree, tops 5.0 ppm
shallot, bulb 5.0 ppm
shallot, fresh leaves 5.0 ppm

vegetable, bulb, group 3

This group includes 15 commodities.
garlic, bulb • garlic, great headed • garlic, great headed, bulb • leek • onion, dry bulb • onion, green • onion, potato • onion, potato, bulb • onion, tree • onion, tree, tops • onion, welsh • onion, welsh, tops • shallot • shallot, bulb • shallot, fresh leaves

5.0 ppm

vegetable, leaves of root and tuber, group 2

This group includes 18 commodities.
beet, fodder, tops • beet, garden, tops • beet, sugar, tops • burdock, edible, tops • carrot, tops • cassava, leaves • chervil, turnip rooted, tops • chicory, tops • dasheen, leaves • parsnip, tops • radish, oriental, tops • radish, tops • rutabaga, tops • salsify, black, tops • tanier, leaves • taro, leaves • turnip, tops • yam, true, leaves

12.0 ppm

Vegetable, root and tuber, group 1

Group 1 includes 83 commodities.

0.2 ppm

A practical analytical method utilizing LC and MSD is available and has been validated for detecting and measuring levels of fluopicolide in and on crops. The validated LOQ is 0.01 ppm.

March 28, 2007 EPA-HQ-OPP-2006-0481

Bayer CropScience AG. Pesticide tolerance. FINAL RULE. Tolerances for residues of fluopicolide in or on imported grape at 2.0 ppm, and grape, raisin at 6.0 ppm with no U.S. registration. Bayer
CropScience AG requested this tolerance. The tolerance petition and data was transferred to Valent U.S.A. Corporation on January 9, 2006.

•• Valent U.S.A. Company submitted the following information in Docket No. EPA-HQ-OPP-2006-0481-0002 on January 1, 2005.

Page 3: Reproductive and developmental toxicity
• In a developmental toxicity study in rats gavage dosed from gestation days 7 to 20 at levels of 0, 5, 60 or700 mg/kg/day, evidence of maternal and fetal toxicity was observed at 700 mg/kg/day, the highest dose tested. The maternal and fetal NOAEL was 60 mg/kg/day based on statistically lower body weights in dams an fetuses, and skeletal findings in fetuses that included delayed ossification of some bones and slight increases in the incidences of various rib and thoracic vertebrae anomalies.

• In a developmental toxicity study with rabbits, pregnant animals were given oral doses of 0, 5, 20 or 60 mg/kg/day on gestation days 6 to 28. At the high dose, 15 animalls were sacrificed following spontaneous abortions and 3 animals were found dead. The few surviving animals in this group had live fetuses at cesarean sectioning but other than lower fetal weight and crown/rump length, no treatment-related findings were observed upon external, visceral and skeletal examinations of these fetuses. The NOAEL for maternal and fetal toxicity was 20 mg/kg/day.

• In a 2-generation reproductive toxicity study, fluopicolide was administered to rats at dietary levels of 0, 100, 500, or 2000 ppm. The NOAEL was 500 ppm (equivalent to 26 and 33 mg/kg/day for males and females respectively) for developing offspring and for parental/systemic toxicity. The LOAEL was 2000 ppm based on decreased body weight and organ weight changes in both F0 anb F1 and F2 pups. The reproductive NOAEL was 2000 ppm.

Page 3-4: Subchronic toxicity.
Ninety-day feeding studies were conducted in dogs, mice and rats.
ii. In 90-day feeding studies in both CD-1 and C57BL/6 mice, liver was the only target organ identified with hepatocellular hypertrophy seen at dietary levels of 320 ppm and higher. The NOAEL in C57BL/6 mice was 200 ppm (equivalent to 37.8 and 52.8 mg/kg/day in males and females, respectively.)
iii. In a 90-day rat study with dietary levels of 100, 1400 and 20,000 ppm, the maximum tolerated dose (MTD) was exceeded at 20,000 ppm based on body weight gain of 30 to 40% below control. The target organs identified in rats were the liver (centrilobular hypertrophy) in both sexes and the kidneys in males (accumulation of hyaline droplets, single cell death at the proximal tubule epithelium, slight foci of basophilic tubules and granular casts) at 1400 ppm and 20,000 ppm. The NOAEL was 100 ppm, equivalent to 7.4 and 8.4 mg/kg/day, in males and females, respectively.
iv. In a subchronic neurotoxicity study, rats were treated with 0, 200, 1400 or 10,000 ppm in the diet for 13 weeks. The NOAEL for systemic toxicity is 1400 ppm (107 mg/kg/day in males and 125 mg/kg/day in females) based on findings in the liver and kidney. There were no neurotoxicity findings.

Page 4: Chronic toxicity
i. Lower body weight gain at the limit dose of 1000 mg/kg/day was the only treatment-related effect noted in a 52-week dog study performed at 70, 300, and 1000 mg/kg/day by gavage.
ii. Chronic toxicity/carcinogenicity was assessed in rats at dietary levels of 50, 200, 750 and 2500 ppm. The NOAEL was 200 ppm (8.4 mg/kg/day in males and 10.8 mg/kg/day in females) based on microscopic changes in the liver and kidneys similar to those observed in the 90-day rat study. No evidence of carcinogenicity was observed in rats up to 2500 ppm.
iii. The oncogenic potential of fluopicolide was investigated in C57BL/6 mice at dietary levels of 0, 50, 400, or 3200 ppm. Significantly lower body weight gain was seen at 3200 ppm in conjunction with a slight decrease in food consumption. Increased liver weight and centrilobular hepatocellular hypertrophy were observed at 400 and 3200 ppm in both sexes. In addition at 3200 ppm, an increased incidence of hepatocellular adenomas was noted in both sexes, but the incidence of hepatocellular carcinomas was not affected. The NOAEL was 50 ppm (equivalent to 7.9 and 11.5 mg/kg/day in males and females, respectively). Subsequent mechanistic work demonstrated a marked transient hepatocellular profileration, whch returned to control levels after 28 days of treatment. This was accompanied by a clear induction of total cytochrome P-450 and related enzymes. These results parallel findings with Phenobarbital, which has a well understood threshold-based mechanism of roden tumor formation commonly known to be of no relevance to humans.

Page 4-5: Metabolite toxicology.
Four metabolites (AEC653711, AEC657188, AEC657378, and AE1344122) were identified as low-level plant and/or soil metabolites of fluopicolide. Several of the metabolites were identified at low levels in the rat following fluopicolide or AEC653711 administration and were therefore covered by the tox studies conducted with the parent molecule. All compounds were tested for acute, subchronic (28-day) and genetic toxicity and AEC653711 and AEC657188 were additionally studied in in vivo ADME studies. All were found to be equally or less toxic than the parent molecule itself. These metabolites are therefore considered not toxicologically relevant to the overall assessment of fluopicolide human health.

uivalen EPA-HQ-OPP-2006-0481 Valent U.S.A. Corporation. Pesticide petition: 5E6903.
Proposal to establish an import tolerance for residues of the fungicide fluopicolide in or on the food commodities
• grape, juice at 2.0 ppm
• grape,wine at 2.0 ppm
• processed commodity grape, raisin at 9.0 ppm.
August 9, 2006 EPA-HQ-OPP-2006-0585 Valent Corporation. Pesticide Products; Registration Applications.
-- File Symbol: 59639-RUN. Product name: V-10161 4SC.
Fungicide. Active ingredient: Fluopicolide at 39.5%. Proposal Classification/Use: For use on outdoor agricultural food crops.
-- File Symbol: 59639-RUR. Flupicolide at 39.5%. Proposal Classification/Use: For use on outdoor ornamentals, turf, and greenhouse grown ornamentals.
-- File Symbol: 59639-RUG. Product name: V-10162 VPP Fungicide. Fungicide. Active ingredient: Fluopicolide and Propamocarb at 5.54%. Proposal Classification/Use: For use on outdoor ornamentals, turf, and greenhouse grown ornamentals.
-- File Symbol: 59639-RGO. Product name: Fluopicolide Technical. Fungicide. Active ingredient: Fluopicolide at 98.8%. Proposal Classification/Use: Manufacturing Use Only.
June 14, 2006 EPA-HQ-OPP-2006-0481

Valent U.S.A. Pesticide petition: PP 5F7016.
in or on food commodities
-- grape at 2.0 ppm
-- raisin at 6.0 ppm
-- potato at 0.02 ppm
-- sweet potato, roots at 0.02 ppm
-- wheat, forage at 0.2 ppm
-- wheat, grain at 0.02 ppm
-- wheat, hay and straw at 0.5 ppm

-- vegetable, leafy (except Brassica) (Group 4) at 20.0 ppm

This group includes 37 commodities.
amaranth, leafy • arugula • cardoon • celery • celery, chinese • celtuce • chervil • chervil, fresh leaves • chrysanthemum, edible leaved • chrysanthemum, garland • corn salad • cress, garden • cress, upland • dandelion, leaves • dock • endive • fennel, florence • fennel, florence, fresh leaves and stalk • kale, sea • lettuce, head • lettuce, leaf • orach • orach, leaves • parsley • parsley, leaves • purslane, garden • purslane, winter • radicchio • rhubarb • spinach • spinach, chinese • spinach, new zealand • spinach, vine • swiss chard • tampala • vegetable, leafy • vegetable, leafy, except brassica, group

-- vegetable, fruiting (Group 8) at 0.8 ppm

This group includes 17 commodities.
chili, postharvest • eggplant • groundcherry • pepino • pepper • pepper, bell • pepper, nonbell • pepper, nonbell, sweet • tomatillo • tomato • tomato, concentrated products • tomato, dried pomace • tomato, paste • tomato, puree • tomato, wet pomace • vegetable, fruiting • vegetable, fruiting, group

-- vegetable, cucurbit (Group 9) at 0.4 ppm

This group includes 19 commodities.
balsam apple • balsam pear • cantaloupe • chayote, fruit • cucumber • cucumber, chinese • cucurbits • gherkin, west indian • gourd, edible • melon • melon, citron • muskmelon • pumpkin • squash • squash, summer • squash, winter • vegetable, cucurbit, group • watermelon • waxgourd, chinese



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