Flonicamid
CAS No. 158062-67-0
US Federal Register
 
 

Return to
Index Page
Adverse Effects

ACTIVITY: Insecticide (pyridinecarboxamide)

CAS Name: N-(cyanomethyl)-4-(trifluoromethyl)-3-pyridinecarboxamide

Structure:

US Federal Register
Date published Docket Control No. Brief review
June 27, 2007 EPA-HQ-OPP-2007-0338

IR-4. Pesticide Petition. PP 6E7081. Proposal to establish a tolerance for combined residues of the insecticide flonicamid and its metabolites TFNA [4-trifluoromethylnicotinic acid], TFNA-AM [4-trifluoromethylnicotinamide], TFNG [N-(4-trifluoromethylnicotinoyl)glycine] in or on food commodities:

Brassica, leafy greens (subgroup 5B)

This subgroup includes 8 commodities.
broccoli raab • cabbage, chinese bok choy • collards • kale • mizuna • mustard greens • mustard spinach • rape greens

16.0 ppm
hop 7.0 ppm
okra 0.4 ppm
radish, tops 16.0 ppm
turnip greens 16.0 ppm

vegetables, tuberous and corm, (subgroup 1C)

This subgroup includes 22 commodities.
arracacha • arrowroot • artichoke, chinese • artichoke, jerusalem • canna, edible • cassava • chayote root • chufa • dasheen • ginger • leren • potato • potato culls • potato granules flakes • potato peel, wet • potato processed potato waste • potato, specialty • sweet potato • tanier • turmeric • yam bean • yam, true

0.2 ppm

Vegetables, root, except sugarbeet, (subgroup 1B)

This subgroup includes 19 commodities.
beet, garden • burdock, edible • carrot • carrot culls • celeriac • chervil, turnip rooted • chicory root • ginseng • horseradish • parsley, turnip rooted • parsnip • radish • radish, oriental • rutabaga • salsify • salsify, black • salsify, spanish • skirret • turnip

0.45 ppm

Analytical methodology has been developed to determine the residues of flonicamid and its three major metabolites (TFNA, TFNG, and TFNA-AM) in various crops. The residue analytical method for the majority of crops includes an initial extraction with acetonitrile/deionized water (ACN/DI), followed by a liquid/liquid partition with ethyl acetate. The residue method for wheat straw is similar, except that a C18 solid phase extraction (SPE) is added prior to the liquid/liquid partition. The final sample solution is quantitated using LC equipped with a reverse phase column and a triple quadruple mass spectrometer (MS/MS).

March 29, 2006 EPA-HQ-OPP-2004-0132

ISK Biosciences. Pesticide Tolerance. FINAL RULE.
This regulation establishes a tolerance for combined residues of flonicamid and its metabolites
TFNA [4-trifluoromethylnicotinic acid],
TFNA-AM [4-trifluoromethylnicotinamide]
TFNG [N-(4-trifluoromethylnicotinoyl)glycine]

in or on

Commodity
Parts per million

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

1.5
Mustard greens
11

This Rule refers to the Final Rule of August 31, 2005 (see below) for
• toxicological endpoints for flonicamid used for human risk assessment
• dietary exposure from drinking water
• the nature of the toxic effects caused by flonicamid and its metabolites as well as the no observed adverse effect level (NOAEL), and
• the lowest observed adverse effect level (LOAEL) from the toxicity studies.

In that document, first-time tolerances were approved for food and EPA stated
• Suggestive evidence of carcinogenic potential (Lung and Nasolacrimal duct)

August 31, 2005 OPP-2005-0217

ISK Biosciences. Pesticide tolerances. FINAL RULE.
First-time tolerances for food
Cancer. Suggestive evidence of carcinogenic potential (Lung and Nasolacrimal duct)
The FQPA Safety Factor is reduced to 1X
EPA received one comment from the National Cotton Council, which stated that it supports ISK Bioscience's request for the establishment of tolerances in the listed food and feed items.

Section 180.613 is added to read as follows:
Sec. 180.613 Flonicamid; tolerances for residues.
(a) General. (1) Tolerances are established for the combined residues of flonicamid [N-(cyanomethyl)-4-(trifluoromethyl)-3-pyridinecarboxamide]
and its metabolites
TFNA [4-trifluoromethylnicotinic acid], TFNA-AM [4-trifluoromethylnicotinamide]
TFNG [N-(4-trifluoromethylnicotinoyl)glycine]
in or on the following raw agricultural commodities:
Commodity Parts per million
Cotton, gin byproducts 6.0
Cotton, hulls 2.0
Cotton, meal 1.0
Cotton, undelinted seed 0.50

Fruit, pome, group 11

This group includes 10 commodities.
apple • apple, dried pomace • apple, juice • apple, wet pomace • crabapple • fruit, pome • loquat • mayhaw • pear • pear, oriental • quince

0.20

Fruit, stone, group 12

This group includes 14 commodities.
apricot • cherry, sweet • cherry, tart • fruit, stone • fruit, stone, except plum, prune, dried • nectarine • peach • plum • plum, chickasaw • plum, damson • plum, japanese • plum, prune • plum, prune, dried • plum, prune, fresh

0.60
Potato 0.20
Potato, granular/flakes 0.40
Spinach 9.0
Tomato, paste 2.0
Tomato, puree 0.50

Vegetable, cucurbit, group

This group (group 9) 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

0.40

Vegetable, fruiting, group

This group (group 8) 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

0.40

Vegetable, leafy except Brassica group 4, except spinach

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

4.0

(2) Tolerances are established for combined residues of flonicamid
[N-(cyanomethyl)-4-(trifluoromethyl)-3-pyridinecarboxamide],
and its metabolites
TFNA [4-trifluoromethylnicotinic acid],
TFNA-AM [4-trifluoromethylnicotinamide]
in or on the following raw agricultural commodities:
Commodity Parts per million
Cattle, fat 0.02
Cattle, meat 0.05
Cattle, meat byproducts 0.08
Egg 0.03
Goat, fat 0.02
Goat, meat 0.05
Goat, meat byproducts 0.08
Horse, fat 0.02
Horse, meat 0.05
Horse, meat byproducts 0.08
Milk 0.02
Poultry, fat 0.02
Poultry, meat byproducts 0.02
Sheep, fat 0.02
Sheep, meat 0.05
Sheep, meat by products 0.08
July 7, 2004 OPP-2004-0132

ISK Biosciences. Pesticide tolerance petition PP 4F6832; by establishing tolerances for the combined residues of the insecticide
flonicamid (N-(cyanomethyl)-4-trifluoromethyl)-3-pridinecarboxamide
(CA) or N-cyanomethyl-4- trifluoromethylnicotinamide (IUPAC) and its
metabolites, TFNA
[4-trifluoromethylnicotinic acid, TFNA-AM (4-
trifluoromethylnicotinamide) and TFNG N-(4-trifluoromethylnicotinoyl)-
glycine) in or on the raw agricultural commodities:

Brassica, head and stem, subgroup 5-A, at 1.5 ppm and
Mustard greens at 11 ppm.

Acute toxicity. In an acute neurotoxicity study, the no observed adverse effect levels (NOAELs) for neurotoxicity were 600 milligrams/kilogram (mg/kg) in males and 1,000 mg/kg in female highest doses tested (HDT). The systemic NOAELs were
600 mg/kg in males and 300 mg/kg in females.

Reproductive and developmental toxicity
-- A developmental toxicity study in rats resulted
in the maternal and developmental no observed effect levels (NOELs) of 100 mg/kg/day. The maternal lowest observed effect level (LOEL) was 500 mg/kg/day based on the treatment-related effects observed on the liver and kidney of the dams in the highest dose group. The developmental LOEL was 500 mg/kg/day based on the increases in placental weights and incidences of fetal skeletal variations seen only at maternally toxic doses of 500 mg/kg/day.
-- In the rabbit developmental toxicity study, the maternal and
developmental NOELs were 7.5 mg/kg/day and 25 mg/kg/day HDT,
respectively. The maternal LOEL was 25 mg/kg/day based on
decreased body weights and food consumption ...
-- In the multigeneration rat reproduction study, the NOAEL was 300 ppm for both parental animals (13.5-32.8 and 16.3-67.0 mg/kg/day, respectively, for males and females) and their offspring. The effects at the highest dose of 1,800 ppm included the following: Increased kidney weights and gross and histopathological alterations in the kidney. Findings noted in the top dose females included delayed vaginal opening and increased liver, kidney and spleen weights in the F1 generation and reduced ovary and adrenal weights in the parental generation and decreased uterine weights in the F1 female weanlings. There was an increase in the follicle stimulating hormone (FSH) and luteinizing hormone (LH) levels in F1 females tested for these endpoints.
• Subchronic toxicity.
-- In a 90-day rat feeding study the NOAEL was established at 200 ppm
(12.11 mg/kg/day) for males and 1,000 ppm (72.3 mg/kg/day) for females. The NOAELs were based on effects on hematology, triglycerides, and pathology in the liver and kidney.
-- In a 13-week mouse study, the NOAEL was 100 ppm (15.25 mg/kg/day in males and 20.1 mg/kg/day in females). The LOAEL is 1,000 ppm (153.9 mg/kg/day in males and 191.5 mg/kg/day in females) based on hematology effects and changes in glucose, creatinine, bilirubin, sodium, chloride and potassium levels, increased liver and spleen weights and histopathology findings in the bone marrow, spleen and kidney.
-- In a subchronic toxicity study in dogs with capsule administration, the NOAEL was 20 mg/kg/day based on findings of severe toxicity at a dose exceeding the maximum tolerated dose; symptoms included collapse, prostration and convulsions leading to early sacrifice at the LOAEL of 50 mg/kg/day.
-- In a subchronic neurotoxicity study in rats, the NOAEL for dietary
administration was 1,000 ppm (67 mg/kg/day in males and 81 mg/kg/ day in females) for systemic toxicity based on body weight and food
consumption effects
.
Chronic toxicity.
-- In the chronic dog study with administration via using capsules, the NOEL was 8 mg/kg/day. The LOAEL was 20 mg/kg/
day based on
reduced body weights in females and effects on the
circulating red blood cells.

• In a rat 24-month combined chronic and oncogenicity study,
flonicamid technical was not carcinogenic in rats. The NOAEL was 200
ppm (7.32 mg/kg/day) for males
and 1,000 ppm (44.1 mg/kg/day) for
females.
The LOAEL was 1,000 ppm for males and 5,000 ppm for females based on histopathology in the kidney, hematology effects, hepatic effects including changes in biochemical parameters, increased organ weights, and histopathological changes. Atrophy of striated muscle fibers, cataract and retinal atrophy observed in the high dose females were considered to be due to acceleration of spontaneous age-related lesions.
-- In the 18-month mouse study, effects were observed in the lung,
liver, spleen and bone marrow at 250 ppm or highe
r. Findings included
centrilobular hepatocellular hypertrophy, extramedullary hematopoiesis
and pigment deposition in the spleen and decreased cellularity
(hypocellularity) in the bone marrow.
There were statistically
significant increases
in the incidence of alveolar/bronchiolar adenomas
in both sexes of treated groups with hyperplasia/hypertrophy of
epithelial cells in terminal bronchioles. There was a statistically
significant increase
in the incidence of alveolar/bronchiolar
carcinomas in males at 750 ppm and 2,250 ppm and in females at 2,250
ppm only.
Mechanism-of-action studies have indicated that
the lung effects are unique to the mouse and are not likely to
translate to other species including the rat.

-- A second 18-month mouse study was conducted in CD-1 mice at dose levels ranging from 10 to 250 ppm to establish a NOAEL for hyperplasia/hypertrophy of epithelial cells in terminal bronchioles and for the incidence of alveolar/bronchiolar adenomas and carcinomas in both sexes. There was a statistically significant increase in the incidence of alveolar/bronchiolar adenomas in males at 250 ppm. In females, there was no statistically significant increase in the incidence of pulmonary neoplastic lesions at any dose level. The incidence of hyperplasia/hypertrophy of epithelial cells lining the terminal bronchioles of the lungs was statistically increased at 250 ppm in both sexes.

June 1, 2004 OPP-2004-0153 ISK and FMC. Pesticide Product Registrations; Conditional Approval.
This notice announces Agency approval of applications
submitted by ISK Biosciences Corporation and FMC Corporation, to conditionally register the pesticide products Technical Flonicamid
Insecticide and F1785 GH 50 WG Insecticide containing a new active ingredient not included in any previously registered products.
-- A paper copy of the fact sheet, which provides more detail on this registration, may be obtained from the National Technical Information Service (NTIS), 5285 Port Royal Rd., Springfield, VA 22161.

-- A conditional registration may be granted under section 3(c)(7)(C)
of FIFRA for a new active ingredient where certain data are lacking, on
condition that such data are received by the end of the conditional
registration period and do not meet or exceed the risk criteria set
forth in 40 CFR 154.7; that use of the pesticide during the conditional
registration period will not cause unreasonable adverse effects; and
that use of the pesticide is in the public interest. The Agency has
considered the available data on the risks associated with the proposed
use of flonicamid, and information on social, economic, and
environmental benefits to be derived from such use. Specifically, the
Agency has considered the nature and its pattern of use, application
methods and rates, and level and extent of potential exposure. Based on
these reviews, the Agency was able to make basic health and safety
determinations which show that use of flonicamid during the period of
conditional registration will not cause any unreasonable adverse effect
on the environment, and that use of the pesticide is in the public
interest.
May 28, 2003 OPP-2003- 0174

ISK and FMC - Pesticide Products; Registration Applications.
--
File Symbol: 71512-O. Applicant: ISK Biosciences Corporation 7470 Auburn Road, Suite A, Concord, OH 44077. Product Name: Flonicamid 50 WG. Insecticide. Active ingredient: Flonicamid at 50%. Proposed classification/Use: None. For use on potatoes, pome fruit, cotton, stone fruit, fruiting vegetables, cucurbits, and leafy vegetables.
-- File Symbol: 279-GETT. Applicant: FMC Corporation 1735 Market Street, Philadelphia, PA 19103. Product Name: F1785 N 50 WG. Insecticide. Active ingredient: Flonicamid at 50%. Proposed classification/Use: None. For ornamental uses in nurseries and landscapes.

May 23, 2003 OPP-2003-0172

ISK BIOSCIENCES - Petition for pesticide tolerances;

-- for the combined residues of the insecticide flonicamid and its metabolites, TFNA, (4-trifluoromethylnicotinic acid), TFNA-AM, (4- trifluoromethylnicotinamide) and TFNG, (N-(4- trifluoromethylnicotinoyl)-glycine) in or on the raw agricultural commodities:
-- Celery, at 1.2 ppm
-- cotton, at 0.5 ppm;
-- cotton, gin trash, at 6.0 ppm;
-- cotton, hulls, at 1.0 ppm;
-- cotton, meal, at 1.0 ppm;
-- fruit, pome, group 11, at 0.2 ppm;
-- fruit, stone, group 12, except plum and
-- fresh prune plum, at 0.7 ppm;
-- lettuce, head, at 1.0 ppm;
-- lettuce, leaf, at 4.0 ppm;
-- plum, at 0.1 ppm;
-- potato, at 0.2 ppm;
-- potato, flakes, at 0.4 ppm;
-- prune, fresh, at 0.1;
-- spinach, at 9.0 ppm;
-- tomato, paste, at 2.0 ppm;
-- tomato, puree, at 0.5 ppm;
-- vegetable, cucurbit, group 9, at 0.4 ppm;
-- vegetable, fruiting, group 8, at 0.4 ppm;
-- by establishing tolerances for the combined residues of the insecticide flonicamid and its metabolite TFNA-AM, (4-trifluoromethylnicotinamide) in animal tissues and poultry meat byproducts:
-- FAT: Cattle,Goat, Hog, Horse, Poultry, Sheep, at 0.01 ppm;
-- MEAT: Cattle, Goat, Horse, Sheep, at 0.04 ppm;
-- MEAT: Hog, Poultry, at 0.01 ppm;
-- eggs, at 0.02 ppm;
-- milk, at 0.02 ppm;
-- poultry, meat byproducts, at 0.01 ppm.
-- by establishing tolerances for the combined residues of the insecticide flonicamid and its metabolites TFNA and TFNA-AM in the animal meat byproducts:
-- MBYP: Cattle,Goat, Horse, Sheep, at 0.06 ppm;
-- Hog, meat byproducts, at 0.01 ppm.

-- In an acute neurotoxicity study, the no observed adverse effect levels (NOAELs) for neurotoxicity were 600 milligrams/kilogram (mg/kg) in males and 1,000 mg/kg in female (highest doses tested). The systemic NOAELs were 600 mg/kg in males and 300 mg/kg in females.
-- In a 90-day rat feeding study the NOAEL was established at 200 ppm (12.11 mg/kg/day) for males and 1,000 ppm (72.3 mg/kg/day) for females. The NOAELs were based on effects on hematology, triglycerides, and pathology in the liver and kidney.
-- In a 13-week mouse study, the NOAEL was 100 ppm (15.25 mg/kg/day in males and 20.1 mg/kg/day in females). The LOAEL is 1,000 ppm (153.9 mg/kg/day in males and 191.5 mg/kg/day in females) based on hematology effects and changes in glucose, creatinine, bilirubin, sodium, chloride and potassium levels, increased liver and spleen weights and histopathology findings in the bone marrow, spleen and kidney.
-- In a rat 24-month combined chronic and oncogenicity study, flonicamid technical was not carcinogenic in rats. The NOAEL was 200 ppm (7.32 mg/kg/day) for males and 1,000 ppm (44.1 mg/kg/day) for females. The LOAEL was 1,000 ppm for males and 5,000 ppm for females based on histopathology in the kidney, hematology effects, hepatic effects including changes in biochemical parameters, increased organ weights, and histopathological changes. Atrophy of striated muscle fibers, cataract and retinal atrophy observed in the high dose females were considered to be due to acceleration of spontaneous age-related lesions.
-- In the 18-month mouse study, effects were observed in the lung, liver, spleen and bone marrow at 250 ppm or higher. Findings included, centrilobular hepatocellular hypertrophy, extramedullary hematopoiesis and pigment deposition in the spleen and decreased cellularity (hypocellularity) in the bone marrow. There were statistically significant increases in the incidence of alveolar/bronchiolar adenomas in both sexes of treated groups with hyperplasia/hypertrophy of epithelial cells in terminal bronchioles There was a statistically significant increase in the incidence of alveolar/bronchiolar carcinomas in
males at 750 ppm and 2,250 ppm and in females at 2,250 ppm only.
-- Reproductive and developmental toxicity. A developmental toxicity study in rats resulted in the maternal and developmental no observed adverse effect levels (NOAELs) of 100 mg/kg/day. The maternal lowest observed adverse effect level (LOAEL) was 500 mg/kg/day based on the treatment-related effects observed on the liver and kidney of the dams in the highest dose group. The developmental LOAEL was 500 mg/kg/ day based on the increases in placental weights and incidences of fetal skeletal variations seen only at maternally toxic doses of 500 mg/kg/ day.
-- In the rabbit developmental toxicity study, the maternal and developmental NOAELs were 7.5 mg/kg/day and 25 mg/kg/day highest dose tested (HDT), respectively. The maternal LOAEL was 25 mg/kg/day based on decreased body weights and food consumption.
-- In the multi-generation rat reproduction study, the NOAEL was 300 ppm for both parental animals (13.5-32.8 and 16.3-67.0 mg/kg/day, respectively, for males and females) and their offspring. The effects at the highest dose of 1,800 ppm included the following: increased kidney weights and gross and histopathological alterations in the kidney. Findings noted in the top dose females included delayed vaginal opening and increased liver, kidney and spleen weights in the F1 generation and reduced ovary and adrenal weights in the parental generation and decreased uterine weights in the F1 female weanlings. There was an increase in the FSH and LH levels in F1 females tested for these endpoints.
-- In a subchronic toxicity study in dogs with capsule administration, the NOAEL was 20 mg/kg/day based on findings of severe toxicity at a dose exceeding the maximum tolerated dose; symptoms included collapse, prostration and convulsions leading to early sacrifice at the LOAEL of 50 mg/kg/day.
-- Chronic toxicity. In the chronic dog study with administration via using capsules, the NOAEL was 8 mg/kg/day. The LOAEL was 20 mg/kg/ day based on reduced body weights in females and effects on the circulating red blood cells.
-- In the 18-month mouse study, effects were observed in the lung, liver, spleen and bone marrow at 250 ppm or higher. Findings included, centrilobular hepatocellular hypertrophy, extramedullary hematopoiesis and pigment deposition in the spleen and decreased cellularity (hypocellularity) in the bone marrow. There were statistically significant increases in the incidence of alveolar/bronchiolar adenomas in both sexes of treated groups with hyperplasia/hypertrophy of epithelial cells in terminal bronchioles. There was a statistically significant increase in the incidence of alveolar/bronchiolar carcinomas in males at 750 ppm and 2,250 ppm and in females at 2,250 ppm only.
-- Endocrine disruption.
No special studies investigating potential estrogenic or other endocrine effects of flonicamid have been conducted. Some suggestions of possible endocrine effects were reported at the highest dose tested (1,800 ppm) in the multi-generation reproduction study which showed increased FSH and LH levels, a delay in the time to vaginal opening in the F1 generation, and reduced ovary and adrenal weights in the parental generation.

July 10, 2002 OPP-2002-0119

FMC and ISK - Registration applications for two pesticide products:

File Symbol: 279-GEAU. Applicant: FMC Corporation, Agricultural Products Group, 1735 Market Street, Philadelphia, PA 19103. Product name: F1785 GH 50 WG Insecticide. Insecticide. Active ingredient: Flonicamid at 50%. Proposed classification/Use: None. For greenhouse use.

File Symbol: 71512-T. Applicant: ISK Biosciences Corporation, 7470 Auburn Road, Suite A, Concord, OH 44077. Product name: Technical Flonicamid Insecticide. Insecticide. Active ingredient: Flonicamid at 98.4%. Proposed classification/Use: None. For manufacturing use only.

 
Fluoride Action Network | Pesticide Project | 315-379-9200 | pesticides@fluoridealert.org