ACTIVITY:Fungicide
(acylpicolide)
CAS Name:
2,6-dichloro-N-[[3-chloro-5-(trifluoromethyl)-2-pyridinyl]methyl]benzamide
Structure:
Adverse
Effects:
Boby
weight decrease
Bone
Developmental: Decreased crown-rump length in fetuses
Kidney
Liver |
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
V10161 |
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 |
Details |
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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