FACT SHEET (New Chemical;
Pymetrozine
r/EPA
United States
Environmental Protection
Agency
Office of Prevention, Pesticides
and Toxic Substances
(7501C)
Pesticide
Fact Sheet
Name of Chemical: Pymetrozine
Reason for Issuance: Conditional Registration
Date Issued: August 2000
I. DESCRIPTION OF CHEMICAL
Generic Name:
Common Name:
Other Name:
Trade Name:
EPA Shaughnessy
(Active Ingredient
Code):
{l,2,4-triazin-3(2H)-one,4,5-dihydro-6-methyl-4-[(3-
pyridinylmethylene) amino]}
Pymetrozine
CGA-215944
Fulfill™, Endeavor™
101103
Chemical Abstracts
Service (CAS) No.: 123312-89-0
Year of Initial
Registration:
Pesticide Type:
1999
Insecticide
Structural Formula:
o
Chemical Family: Pyridine Azomethines
U.S. Producer: Syngenta Crop Protection, Inc. of Greensboro, North Carolina 27419
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FACT SHEET (New Chemical) Page 2 of 22
Pymetrozine
II. REGISTERED PRODUCTS. FORMULATIONS. USE PATTERNS. AND MODE OF
ACTION
Registered Products and
Formulations:
1. Pymetrozine Technical (EPA Reg No. 100-914)
98% Granular Solid
2. Fulfill11 Insecticide (EPA Reg. No. 100-912)
50% Water-Dispersible Granule
3. Endeavor™ Insecticide (EPA Reg. No. 100-913)
50% Water-Dispersible Granule
Use Patterns:
The following table lists the products, type of application, sites, maximum rates, and other
restrictions for pymetrozine.
Table 1. Application Methods, Rates, and Restrictions for Pymetrozine Use
Patterns
Product
Name
Fulfill™
Insecticide
Type of
Application
& Sites
Ground,
Aerial, and
Chemigation
(Foliar)
Potatoes,
Other Tuberous/
Corm Vegetables
Tobacco
Cotton
Cole Crops
Leafy Vegetables
Cucurbits
Fruiting Vegetables
Hops
Maximum Rates
2.75oz product/A per
application
5.5oz product/A per
season
same as above
same as above
same as above
4-6oz product/A per
application
18oz product/A per
season
Other Restrictions
• 2 applications/year
• 7 days between applications
• Last treatment 14 days before
harvest (14 day preharvest
interval or PHI)
• 12 hr before re-entry
• Rotational (Plantback)
Restrictions: all crops (30
days)
same as above but 21 days PHI
same as above but 7 days PHI
same as above but 0 days PHI
3 applications/year
14 days between applications
14 days PHI
12 hr before re-entry
Rotational (Plantback)
Restrictions: 30 days
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FACT SHEET (New Chemical) Page 3 of 22
Pymetrozine
Table 1. Application Methods, Rates, and Restrictions for Pymetrozine Use
Patterns
Product
Name
Endeaver
TM
Insecticide
Type of
Application
& Sites
Pecan
Ground (Foliar)
Ornamentals
Maximum Rates
4oz product/A per
application
8 oz product/A per
season
2. 5 to 10.0 oz/
A per application
48 oz/year-outdoor use
100 oz/y ear-indoor use
(all states but California)
48 oz/year-indoor
use(California only)
Other Restrictions
2 applications/year
7 days between applications
14 days PHI
12 hr before re-entry
Rotational (Plantback)
Restrictions: 30 days
7 Days-severe insect pressure
14 days-normal insect pressure
Mechanism of Pesticidal Action:
The mode of action of pymetrozine in insects has not been precisely determined
biochemically, but it may involve effects on neuroregulation or nerve-muscle interaction.
Physiologically, it appears to act by preventing these insects from inserting their stylus into
the plant tissue.
III. SCIENCE FINDINGS
A. Summary:
Pymetrozine is a new active ingredient from a chemical class (pyridine azomethines) not
previously used as a pesticide. The Agency has reviewed product chemistry, environmental
fate, residue chemistry, toxicology, and ecological effects data. Based on these data,
pymetrozine has been determined to be of low acute toxicity to humans, birds, aquatic
organisms, mammals, and bees. Acute toxicology studies place the technical-grade in
Toxicity Categories III and IV. Dermal Absorption was estimated to be 1%.
Pymetrozine is not mutagenic. It produced some neurotoxic effects, but the frequency and
magnitude were low. It produced developmental effects in pups, but only at levels toxic to
parents. Pymetrozine is not expected to pose a risk of contaminating groundwater. The
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FACT SHEET (New Chemical) Page 4 of 22
Pymetrozine
Agency considers pymetrozine a replacement for organophosphate (OP) pesticides used for
the same use patterns.
The EPA has classified pymetrozine as a "likely" human carcinogen because tumors
occurred in two species (rat and mouse), in two sexes (mouse), and in two types (liver benign
hepatoma and/or carcinoma). Mechanistic arguments have been advanced to explain the
carcinogenicity. However, these have not been sufficient to eliminate the need for
quantitative risk assessment. Because of the limited sites, low use rates, and low exposure,
the risks to humans is below the level of concern.
The environmental fate profile for pymetrozine indicates no major issues in the areas of soil
persistence, mobility, and fish bioaccumulation. Minimal environmental residues of this
chemical in drinking water resources are expected.
The ecological effects data showed that pymetrozine is practically non-toxic to terrestrial and
aquatic vertebrates, and honeybees. In addition, the data showed that this pesticide is only
slightly to moderately toxic to aquatic invertebrates. All of the risk assessments were below
EPA's level of concern. Further, endangered species will not be adversely affected.
B. Chemical Characteristics:
The following table lists the properties of the technical and end-use formulations for
pymetrozine.
Table 2. Properties of Technical and End-Use Formulations for Pymetrozine.
Property
Physical State
Color
Odor
Melting Point
Density
Solubility (Water)
Vapor Pressure
Octanol/Water Partition
Coefficient
PH
Technical
crystalline (granular) solid
white to beige
slightly sweet
217°C (decomp.)
1.36g/mL@23°C
0.29g/L@pH6.4-6.5@25°C
<4xlO-6Pa@25°C
logPow =-0.18
5.6@25C
End-Use
water-dispersible granule
N/A
N/A
N/A
0.479g/cm
N/A
N/A
N/A
7-11 (1% water
dispersion@25C)
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FACT SHEET (New Chemical) Page 5 of 22 Pymetrozine
C. Toxicology Characteristics:
1. Acute Toxicity
Technical pymetrozine has low acute toxicity, being classified as Toxicity Category III
for acute dermal and primary eye irritation studies and Toxicity Category IV for acute
oral, acute inhalation and primary dermal studies. It is a slight sensitizer. Table 3
provides a summary of acute tests.
Table 3. Acute Toxicity of Pymetrozine Technical
Guideline
Number
81-1
81-2
81-3
81-4
81-5
81-6
81-8
Study Type
Acute Oral (rat)
Acute Dermal (rat)
Acute Inhalation
(rat)
Primary Eye
Irritation (Rabbit)
Primary Dermal
Irritation (Rabbit)
Dermal
Sensitization
(Guinea Pig)
Acute
Neurotoxicity (rat)
MRID
Number
44024926
44024928
44024930
44024932
44024934
44024936
44411317
Results
OralLD50: Males: 5693 mg/kg
Females: 5955 mg/kg
Combined: 5820 mg/kg
Dermal LD50: Males: > 2.0 g/kg
Females: > 2.0 g/kg
Inhalation LC50 Males: >1.8 mg/L
Females: > 1.8 mg/L
Combined: > 1.8 mg/L
Is a slight ocular irritant. Primary Irritation
Score (PIS): 12.8 at 1 hour; 1.0 at 72 hours.
Primary Irritation Index (PII): 0.0 Is not a
dermal irritant.
Is a slight dermal sensitizer with intradermal
challenge.
NOAEL (both sexes) < 125 mg/kg (LOT)
LOAEL (both sexes) = 125 mg/kg
Toxicity
Category
IV
III
IV
III
IV
N/A
N/A
2. Subchronic and Chronic Toxicity
Table 4 summarizes the results of the subchronic and chronic toxicity, metabolism, and
dermal penetration studies in animals.
Table 4. Subchronic and Chronic Toxicity, Metabolism, and Dermal Penetration Studies in Animals of
Pymetrozine Technical
Study Type
82- la, Subchronic-Feeding-
Rat
82- Ib, Subchronic -Feeding-
Dog
MRID
No.
44024939
44572201
Results (NOAEL & LOAEL in mg/kg/day)
NOAEL: males = 32.5; females = 33.9
LOAEL: males = 360; females = 370
NOAEL: males =3.12; females = 3. 12
LOAEL: males = 14; females = 14
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FACT SHEET (New Chemical;
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Pymetrozine
Table 4. Subchronic and Chronic Toxicity, Metabolism, and Dermal Penetration Studies in Animals of
Pymetrozine Technical
Study Type
82- Ic, Subchronic-Feeding-
Mouse
82-2, 28-Day Dermal
Toxicity-Rat
82-7, Subchronic
neurotoxicity - rat
83-1, Chronic -Feeding-Dog
83-2, Carcinogenicity-Mouse
83-3a, Developmental
Toxicity-Rat
83-3b, Developmental
Toxicity-Rabbit
83-4, Reproductive Toxicity
-Rat
83-5, Chronic toxicity/
Carcinogenicity-Rat
84-2, Gene Mutation -
Salmonella & E. Coli
84-2, Gene Mutation -
HGPRT with V79 cells
84-2, In vitro cytogenetics
assay in CHO cells
84-2, Micronucleus Assay-
Mice
84-2, Unscheduled DNA
Synthesis-Primary Rat
Hepatocytes
MRID
No.
44024938
44024942
44411318
44024943
44024944
44024948
44024949
44024950
44024951
44024952
44024954
44024953
44024955
44024956
Results (NOAEL & LOAEL in mg/kg/day)
NOAEL: males & females = Not established
LOAEL: males & females = 125 (LOT)
Systemic/Dermal Irritation NOAEL = 1000 (both sexes)
Systemic/Dermal Irritation LOAEL > 1000 (both sexes)
NOAEL: males = 68; females = 81
LOAEL: males = 201; females = 224
NOAEL: males = 5.33; females = 5.33
LOAEL: males = 27.8; females = 27.8
NOAEL: males & females = 12
LOAEL: males & females = 250
liver benign hepatomas and/or carcinomas combined in both
sexes
Maternal NOAEL = 30; Maternal LOAEL = 100
Developmental NOAEL = 100; Developmental LOAEL = 300
Maternal NOAEL = 10; Maternal LOAEL = 75
Developmental NOAEL = 10; Developmental LOAEL = 75
Parental Systemic NOAEL: males = 1.4; females = 1.6
Parental Systemic LOAEL: males = 13.9; females = 16.0
Offspring Syst./Develop. NOAEL: males = 13.9; females =
16.0
Offspring Syst./Develop. LOAEL: males = 136.9; females =
151.6
Reproductive NOAEL: males = 136.9; females = 151.6
Reproductive LOAEL: males > 136.9; females = 151.6 (HOT)
NOAEL: males = 0.377; females = 4.48
LOAEL: males = 3.76; females = 46.26
liver benign hepatomas and/or carcinomas combined in females
Non-mutagenic (±) activation in Salmonella and E. coli.
Non-mutagenic up to the solubility limit (±) activation.
Not clastogenic up to the solubility limit of the test substance.
No clastogenic response at any dose or sacrifice time.
No evidence of induced UDS.
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FACT SHEET (New Chemical;
Page 7 of 22
Pymetrozine
Table 4. Subchronic and Chronic Toxicity, Metabolism, and Dermal Penetration Studies in Animals of
Pymetrozine Technical
Study Type
85-1, Metabolism-Rat
85-3, Dermal absorption
MRID
No.
44024957
44517720
44024958
Results (NOAEL & LOAEL in mg/kg/day)
• Absorption and excretion studies, oral & iv doses.
• Recovered radioactivity 7 days post-dosing: urine (56.3-
80.3%), expired air (0.2-1.4%), tissues (0.3-3.8%), feces
(15.4-38.9%), and cage washes (0.2-0.7%).
• Both sexes excreted more via the kidneys after a high dose
(M/F: 72.5%/78.3%) than low dose (M/F: 56.3%/ 62.1%).
• 12 urinary & fecal metabolites identified after a high dose.
High level of unchanged test material in the urine.
• 3 major metabolic pathways found.
• Max.blood cone.: low dose (15 min, 0.3 ppm) & high dose
(4 hrs (60 ppm).
• Calculated half life: 1 to 2 hours at 0.5 mg/kg dose (both
labels) and from 2 to 1 1 hours (100 mg/kg dose).
• Tissue residue levels (ppm) were highest in the kidneys and
liver. For the low/high doses, the peak kidney levels were
0.6/75 ppm (triazine) and 0.6/101 ppm (pyridine).
The percent of dose absorbed after 10 hour application: 0.01%
(low-dose), 0.01% (mid-dose), and <0.005% (high-dose).
These tests suggest that pymetrozine targets three major areas in the body: the liver, the
hematopoietic system and the lymphatic system. In addition, both the subchronic and chronic
dog studies suggest that this chemical affects muscle tissue, perhaps secondarily. The most
significant effects in these areas are tumors in the livers of mice and rats, necrosis of the liver
of mice and dogs, hyperplasia in the bile ducts of dogs, anemia in dogs, atrophy in the thymus
of young rats and dogs, and myopathy in the muscle of dogs. Hepatocellular hypertrophy is
often related to induction of drug metabolizing enzymes. The red blood cell effects in rats
and mice were somewhat minor.
3. Carcinogenic Effects
The EPA has classified pymetrozine as a "likely" human carcinogen, based on male mouse
liver benign hepatoma and/or carcinoma. Mechanistic arguments have been advanced to
explain the carcinogenicity. However, these have not been sufficient to eliminate the need for
quantitative risk assessment. Because of the limited sites, low use rates, and low exposure,
the actual risks to humans is below the level of concern.
4. Developmental/Reproductive Effects
In the rat, developmental toxicity was observed only at maternally toxic dose levels: (maternal
NOAEL: 30 mg/kg/day, LOAEL: 100 mg/kg/day (reduced body weight gains and food
consumption); developmental NOAEL: 100 mg/kg/day, LOAEL: 300 mg/kg/day (increased
incidence of skeletal anomalies)). In the rabbit, developmental toxicity was also observed
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FACT SHEET (New Chemical) Page 8 of 22 Pymetrozine
only at maternally toxic dose levels: (maternal NOAEL: 10 mg/kg/day, LOAEL: 75
mg/kg/day (reduced body weight gains and reduced food consumption and efficiency);
developmental NOAEL: 10 mg/kg/day, LOAEL: 75 mg/kg/day (increased incidence of
skeletal anomalies)).
In the rat reproduction study, systemic/developmental toxicity for the pups was observed at
parentally toxic dose levels (parental systemic NOAEL: 1.4 mg/kg/day for males, 1.6
mg/kg/day for females, LOAEL: 13.9 mg/kg/day for males, 16.0 mg/kg/day for females (liver
effects in the FO and Fl males); offspring systemic/developmental NOAEL: 13.9 mg/kg/day
for males, 16.0 mg/kg/day for females, LOAEL: 136.9 mg/kg/day for males, 151.6 mg/kg/day
for females (decreased pup weight and delay in eye opening in both Fl and F2 litters)). There
was no reproductive toxicity at dose levels up to 136.9 mg/kg/day for males and 151.6
mg/kg/day for females.
5. Mutagenic Effects
Pymetrozine is not considered to be of mutagenic concern.
6. Neurotoxic Effects
In the acute mammalian neurotoxicity study, there was a transient decrease in the body
temperature and indications of decreased activity in the FOB and motor activity assessments
at a dose level of 125 mg/kg, the lowest dose tested. In the subchronic mammalian
neurotoxicity study, stereotypy in males and tiptoe gate or walking on toes in females were
observed when administered dose levels of 201 mg/kg/day (males) or 224 mg/kg/day
(females). The frequency and magnitude of these effects were low.
D. Toxicological Endpoints and Exposure Doses:
Based on its review of the toxicological data, the Agency selected specific studies, end points
(adverse biological effects), a Lowest Observed Adverse Effect Level (LOAEL), and several No
Observed Adverse Effect Levels (NOAELs), and modified by several safety (SF) or uncertainty
factors (UF), to derive acceptable exposure doses in mg/kg/day for use in acute and chronic risk
assessments. Table 5 lists the studies, endpoints, exposure doses, uncertainty/safety factors, and
exposure profiles that the Agency used in these risk assessments.
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FACT SHEET (New Chemical;
Page 9 of 22
Pymetrozine
Table 5. Summary of lexicological Endpoints for Use in Human Risk Assessment
EXPOSURE
PROFILE
Acute Dietary
Females 13+
Acute Dietary
General
Population
including
Infants and
Children
Chronic Dietary
Short-&
Intermediate
Term
(Dermal)
Short -Term
(Inhalation)a
Intermediate
Term
(Inhalation)"
Long-Term
(Dermal and
Inhalation)
DOSE
(mg/kg/day)
NOAEL= 10
UF = 100
FQPA SF = 3
ENDPOINT
Reduced body weight gain, food consumption
and feed efficiency. Also, increased
incidence of skeletal anomalies in pups.
STUDY
Rabbit Developmental
(MRID No.: 44024949)
Acute RfD (Females 13+) = 0.10 mg/kg
Acute Population- Ad justed Dose (Females 13+) = 0.033 kg/kg
LOAEL = 125
UF = 300
FQPA SF = 3
(Infants,
Children)
Decreased body temperature, decreased motor
activity and FOB parameters associated with
decreased activity.
Acute Neurotoxicity
(MRID No.: 444 113 17)
Acute RfD (General Population) = 0.42 mg/kg
Acute Population-Adjusted Dose (General Population) = 0.42 mg/kg
Acute Population-Adjusted Dose (Infants and Children) = 0.14 mg/kg
NOAEL =
0.377
UF = 100
FQPA SF = 3
(Females 13+,
Infants,
Children)
Liver hypertrophy and pathology supported
by the rat chronic feeding and multigeneration
reproduction studies and dog subchronic and
chronic studies.
Rat Chronic Feeding
(MRID No.: 44024951)
Chronic RfD = 0.0038 mg/kg/day
Chronic Population-Adjusted Dose (General Population) = 0.0038 mg/kg/day
Chronic Population-Adjusted Dose (Females 13+, Infants, Children) = 0.0013 mg/kg/day
NOAEL= 1000
Oral NOAEL =
10
Oral NOAEL =
0.377
No effects at the highest dose tested.
Reduced body weight gain, food consumption
and feed efficiency. Also, increased
incidence of skeletal anomalies in pups.
Liver hypertrophy and pathology supported
by the rat chronic feeding and multigeneration
reproduction studies and dog subchronic and
chronic studies.
Rat Dermal Toxicity
(MRID No.: 44024942)
Rabbit Developmental
(MRID No.: 44024949)
Rat Chronic Feeding
(MRID No.: 44024951)
The current use pattern does not indicate a concern for long-term dermal or inhalation exposure
potential, therefore, these risk assessments are NOT required.
a = Since oral values were selected, 100% inhalation absorption factor (default) value should be used in route-to-
route extrapolation/risk assessment.
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FACT SHEET (New Chemical;
E. Residue Chemistry
Page 10 of 22
Pymetrozine
The pyridine containing metabolites such as nicotinyl alcohol and trigonelline are not of
toxicological concern at the levels observed in tomatoes (ca 0.01-0.1 ppm). This is in part
based on the recommended daily dietary allowance for nicotinic acid being 6-19 mg.
Concentrations of nicotinamide and nicotinic acid compounds in ruminants are similar to
those observed in tomatoes and, therefore, are also not of toxicological concern.
The triazine containing metabolites (CGA-294849 and GS-23199) are likely to be of
toxicological concern. It was noted that these compounds are azapyrimidines and analogs of
thymine and uracil. The uracil analog of GS-23199 is a mutagen. The metabolite GS-23199
can serve as a marker for CGA-215525, CGA-249257, and CGA-294849 for risk assessment
purposes. These compounds are all "azauracils" that may lend to the carcinogenic nature of
pymetrozine.
Tolerances will be set in terms of only the parent compound for enforcement purposes.
Triazine containing metabolites are included in the risk assessment for plants with their levels
estimated using GS-23199 as a marker in field trials. Additionally, the metabolite
CGA-313124 (both free and phosphate-conjugated) would be included in any risk assessment
for livestock commodities due to its structural similarity to pymetrozine.
The Agency has established permanent tolerances for residues of pymetrozine per se in
three Final Rules in the Federal Register on September 29, 1999 (64 FR 52438-50), August 9,
2000 (65 FR 48626-34), and December 27, 2001 (66 FR 66786-94, as indicated in the
following table. The tolerance level and pre-harvest interval (PHI) for each commodity is
expressed in terms of the parent insecticide only, which serves as an indicator of the use of
pymetrozine of these raw agricultural commodities. The following table lists each commodity
and its tolerance level and pre-harvest interval (PHI).
Table 6. Food commodities, Tolerance Levels, Pre-Harvest Intervals for
Pymetrozine.
Commodity
Brassica, head and stem , subgroup
(Crop Subgroup 5 -A)
Brassica, leafy greens, subgroup (Crop
subgroup 5-B)
Cotton gin byproducts
Cotton, undelinted seed
Hops, dry cones
Tolerance
Level (ppm)
0.5
0.25
2.0
0.3
6.0
Pre-Harvest
Interval (PHI)
7
7
21
21
14
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FACT SHEET (New Chemical;
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Pymetrozine
Table 6. Food commodities, Tolerance Levels, Pre-Harvest Intervals for
Pymetrozine.
Commodity
Pecans
Turnip, greens
Vegetable, fruiting, group (Crop Group
8)
Vegetable, cucurbit, group (Crop Group
9)
Vegetable, leafy, except Brassica, group
(Crop Group 4)
Vegetable, tuberous and corm, subgroup
(Crop Subgroup 1-C)
Tolerance
Level (ppm)
0.02
0.25
0.2
0.1
0.6
0.02
Pre-Harvest
Interval (PHI)
14
7
0
0
7
14
Because of a metabolite of concern, the label also includes a plant back restriction of 30 days
for all crops.
F. Human Risk Assessments:
The Agency conducted several acute, chronic, and cancer human risk assessments for different
population subgroups and exposure profiles. These were all below the Agency's level of concern.
The Agency also conducted risk assessments that aggregated (combined) dietary, drinking water,
and residential exposure for acute, chronic, and cancer scenarios. Initially, the aggregate cancer
assessment produced a possible level of concern because of high theoretical levels in drinking
water, resulting in a request for drinking water monitoring data. However, later, the Agency
discovered that the original Cancer Q* value was too high. Once it used the correct value, the
aggregate cancer no longer exceeded its level of concern, and the drinking monitoring studies
were no longer needed. A detailed discussion of the risk assessments may be found in the Final
Tolerance Rules published in the Federal Register on September 29, 1999, August 9, 2000, and
December 27, 2001.
1. Aggregate Risks and Determination of Safety
Tables 7 and 8 show the Drinking Water Levels of Comparison (DWLOC's) for acute and
chronic exposure.
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FACT SHEET (New Chemical;
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Pymetrozine
Table 7. Acute Drinking Water Levels of Comparison for Aggregated Exposures
Scenario/Population
Subgroup
U.S. Population
All Infants (<1 year)
Children (1-6 yrs)
Children 7-12 years
Females 13-50
Males 13-19
Males 20+ years
Seniors 55+
aPAD
mg/kg/day
0.42
0.14
0.14
0.14
0.033
0.42
0.42
0.42
Food
Exposure,
mg/kg/day
0.002119
0.001404
0.003517
0.002615
0.001939
0.001722
0.001807
0.002035
Maximum
Water
Exposure,
mg/kg/day
0.41788
0.13860
0.13648
0.13739
0.031061
0.41828
0.41819
0.41797
SCI-GROW
(groundwater)
ppb
0.02
0.02
0.02
0.02
0.02
0.02
0.02
0.02
PRZM/
EXAMS
(surface water)
ppb
5.23
5.23
5.23
5.23
5.23
5.23
5.23
5.23
DWLOC
*'g/L
15,000
1,400
1,400
1,400
930
15,000
15,000
15,000
DWLOC = Maximum Water Exposure (mg/kg/day) x 1000 • g/mg x body weight (70 kg general population/males 13+, 60 kg
females 13+, 10 kg infants and children) -^ Water Consumption (2 L/day adults, 1 L/day infants and children). The acute EEC is
5.23 • i/L.
Table 8. Chronic Drinking Water Levels of Comparison for Aggregated Exposures
Scenario/Population
Subgroup
U.S. Population
All Infants (<1 year)
Children (1-6 yrs)
Children 7-12 years
Females 13-50
Males 13-19
Males 20+ years
Seniors 55+
cPAD
mg/kg/day
0.0038
0.0013
0.0013
0.0013
0.0013
0.0038
0.0038
0.0038
Food
Exposure,
mg/kg/day
0.000034
0.000018
0.000045
0.000040
0.000029
0.000024
0.000034
0.000036
Maximum
Water
Exposure,
mg/kg/day
0.003766
0.001282
0.001255
0.001260
0.001271
0.003776
0.003766
0.003764
SCI-GROW
(groundwater)
ppb
0.02
0.02
0.02
0.02
0.02
0.02
0.02
0.02
PRZM/
EXAMS
(surface water)
ppb
1.58
1.58
1.58
1.58
1.58
1.58
1.58
1.58
DWLOC*
•g/L
130
13
13
13
38
130
130
130
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FACT SHEET (New Chemical) Page 13 of 22 Pymetrozine
* DWLOC = Maximum Water Exposure (mg/kg/day) x 1000 • g/mg x body weight (70 kg general population/males 13+, 60 kg
females 13+, 10 kg infants and children) -^ Water Consumption (2 L/day adults, 1 L/day infants and children). The chronic and
cancer EEC is 1.58 • g/L.
a. Acute risk.
The Tier 1 exposure estimates provided by the acute dietary analysis are based on the
assumption that tolerance-level residues are present in/on all commodities on which
pymetrozine will be used and that 100% of these commodities are treated. The
exposure estimates are therefore conservative ones. As shown in Table 7, the acute
EECs for pymetrozine are below EPA's level of concern. That is, they are below the
DWLOC values calculated for the various population subgroups. Thus, residues of
pymetrozine in food and drinking water do not exceed EPA's level of concern (100%
of the aPAD) for acute aggregate exposure for any of the population subgroups.
Based on its assumptions and underlying data, this risk assessment is considered
confident, very conservative, and highly protective of human health.
b. Chronic risk.
The Tier 3 exposure estimates provided by the chronic dietary analysis are based on
anticipated residues and projected percent crop treated data. Anticipated residues
(average field trial values) were calculated for the crops. The resulting exposure
estimates are therefore refined ones. The chronic EECs for pymetrozine are below the
Agency's level of concern. That is, as shown in Table 8, they are below the DWLOC
values calculated for the various population subgroups. Thus, residues of pymetrozine
in food and drinking water do not exceed the Agency's level of concern (100% of the
cPAD) for chronic aggregate exposure for any of the population subgroups.
c. Short-term risk
Short-term aggregate exposure takes into account residential exposure plus chronic
exposure to food and water (considered to be a background exposure level). In
aggregating short-term risk, the Agency considered background average dietary
exposure and short-term, non-dietary oral exposure. Non-dietary oral exposure may
occur with toddlers as hand-to-mouth transfer of residues from ornamental plants or
incidental ingestion of treated ornamental plants and/or surrounding soil. The highest
estimated exposure via these routes is 0.0046 mg/kg/day which results from hand-to-
mouth transfer of residues. Combining this exposure with the chronic dietary
exposure estimate of 0.000045 mg/kg/day results in an aggregate exposure of 0.0046
mg/kg/day. In the absence of a short-term oral endpoint, EPA has used the acute
dietary endpoint for infants and children (125 mg/kg/day) to estimate aggregate short-
term risk. Note that this endpoint is based on a LOAEL and therefore has a 300-fold
uncertainty factor associated with it. Combining the exposure estimate with the
toxicological endpoint gives an MOE of 27,000. For this scenario, the Agency would
be concerned with an MOE of less than 900; thus, this exposure is below EPA's level
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FACT SHEET (New Chemical) Page 14 of 22 Pymetrozine
of concern. Aggregated short-term exposure results in a DWLOC of 1400 ppb. This
value is in excess of the peak EEC of 5.23 ppb for pymetrozine. Therefore, the short-
term aggregate risk is below the Agency's level of concern.
d. Intermediate-term risk.
Intermediate-term aggregate exposure takes into account residential exposure plus
chronic exposure to food and water (considered to be a background exposure level).
There are no intermediate-term residential exposure scenarios for pymetrozine based
on the current uses. Therefore, aggregate intermediate-term risks do not exceed the
the Agency's level of concern.
e. Aggregate cancer risk for U.S. population
As with the chronic dietary exposure analysis, the cancer risk assessment is also based
on a Tier 3 estimate of dietary exposure. The cancer aggregate risk consists of chronic
dietary exposure as well as non-occupational exposure resulting from pruning and
planting treated ornamental plants. The sum of the food and residential exposure is
0.000034 (food) + 0.0000012 (residential) = 3.5 x 10'5 mg/kg/day. Assuming a cancer
risk limit of 1 x 10'6, the cancer dose of concern is 8.4 x 10'5 mg/kg/day (0.000001/0^*
= 0.000001/0.0119). As 3.5 x 10'5 mg/kg/day is less than 8.4 x 10'5 mg/kg/day, the
aggregate food and residential exposure is below the level of concern. With respect to
drinking water, the cancer DWLOC is calculated to be 1.7 ppb. The highest EEC for
any of the crops in these petitions is 1.6 ppb (pecans). As a result, the aggregate
cancer risk resulting from use of pymetrozine is below the Agency's level of concern.
f Determination of safety
Based on these risk assessments, EPA concludes that there is a reasonable certainty
that no harm will result to the general population, and to infants and children from
aggregate exposure to pymetrozine residues.
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FACT SHEET (New Chemical) Page 15 of 22
G. Environmental Characteristics:
Pymetrozine
The following table summarizes the results of major environmental fate studies conducted on
pymetrozine.
Table 9. Results of Major Environmental Fate Studies Conducted on Pymetrozine.
Study Type
Hydrolysis (Half Life)
Photolysis in Water (Half Life)
Photolysis on Soil (Half Life)
Aerobic Soil Metabolism (Half Life)
Aerobic Aquatic Metabolism (Half Life)
Anaerobic Aquatic Metabolism (Half
Life)
Mobility- Leaching (Parent)
Mobility- Leaching (Metabolites)
Bioaccumulation
Terrestrial Field Dissipation* (Half
Life)-tests in five locations
Half Life/Other Result
<14 days (pH 5, 25C); >80 days (pH 7)
>86 days (pH 9)
about 2 days (pH 7)
>30 days
Biphasic:
1. primary (0 to 30 days): <1 week
2. secondary (30 days to 357 days): about 1 year
Graphical DT50 = 5 months
4 months
Mobility - negligible (Koc = 7.4 to 38 mL/g)
substantiated in field studies (most residues found
in upper 6-inches of soil)
Mobility - some mobility into upper 12 in of soil,
not environmentally significant because of low
application rate/low concentration of degradates
relative to the parent (<10% in field studies).
Pymetrozine should not significantly
bioconcentrate in fish due to its low octanol/water
parti ti on coeffi ci ent.
Biphasic:
1. Primary (0-14 days): 8 to 138 days, depending
on soil and location.
2. Secondary (14-180 days): 103 to 1269 days
denendine on soil and location
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FACT SHEET (New Chemical) Page 16 of 22
1. Water Resources Assessment
Pymetrozine
Based on the FIRST, SCI-GROW, and PRZM/EXAMS models the estimated environmental
concentrations (EECs) of pymetrozine for acute exposures are estimated to be 5.23 parts per
billion (ppb) for surface water and <0.02 ppb for ground water. The EECs for chronic
exposures are estimated to be 1.58 ppb for surface water and <0.02 ppb for ground water, as
shown in Tables 5 and 6 above. See the December 27, 2001, Final Tolerance Rule (66 FR
66789-90 for a detailed description of the models and have the Agency calculated the EEC
values.
2. Potential to Contaminate Drinking Water
Based upon proposed uses and fate characteristics, EPA does not expect pymetrozine to reach
drinking water resources in significant quantities.
3. Ecological Risk Characterization:
The available data indicate that the use of pymetrozine to control aphids and whiteflies on the
approved sites (food crops, tobacco, and ornamentals) listed under "II" above should not pose
any significant risk concerns to terrestrial plants, aquatic plants, birds, mammals, fish, and
aquatic invertebrates.
4. Endangered Species Concerns
The proposed product labels are not likely to result in any endangered plant species exposed
to pymetrozine.
5. Toxicity to Nontarget Organisms
a. Toxicity to Terrestrial Animals
The following tables summarize the toxicity data for nontarget organisms.
i. Birds, Acute and Subacute
Table 10. Avian Acute Oral Toxicity of Pymetrozine.
Species
Northern
bobwhite quail
(Colinus
virginianus)
%ai
98.0
LD50
(ms/kg)
>2000 '
Toxicity
Category
practically
nontoxic
MRIDNo.
(Author/Year)
440249-08
(Hakin, 1993)
Study
Classification
core
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FACT SHEET (New Chemical;
Page 17 of 22
Pymetrozine
Table 10. Avian Acute Oral Toxicity of Pymetrozine.
Species
Mallard duck
(Anas
platyrhynchos)
%ai
98.0
LD50
(mg/kg)
not
determined
Toxicity
Category
not determined
MRID No.
(Author/Year)
440249-07
(Hakin, 1993)
Study
Classification
supplemental 3
No mortality.
2 One mortality in control group. Vomiting occurred at doses greater than 31 mg/kg; no mortality noted at that level.
3 An LD50 could not be determined because several test birds in the three highest test concentrations
(> 125 mg/kg ) regurgitated within one hour of dosing.
Table 11. Avian Subacute Dietary Toxicity of Pymetrozine.
Species
Northern bobwhite quail
(Colinus virginianus)
Mallard
(Anas platyrhynchos)
%ai
98.0
98.0
1C
^^50
(ppm)
>5130'
>5010'
Toxicity
Category
practically
nontoxic
practically
nontoxic
MRID No.
(Author/Year)
440249-09
(Hakin, 1992)
440249-10
(Hakin, 1992)
Study
Classification
core
core
1 One mortality in the control and one mortality at 2,550 ppm (not considered treatment-related).
2 No mortality.
ii. Birds, Chronic
Table 12. Avian Reproduction Studies for Pymetrozine.
Species/Study
Duration
Northern bobwhite quail
(Colinus virginianus)/
20 weeks
Mallard duck
(Anas platyrhynchos)
%ai
98.5
98.4
NOEC/LOE
C
(ppm)
NOEC = 100
LOEC = 300
N/A
LOEC
Endpoints
14-day old
survivors of
eggs set
N/A
MRID No.
(Author/Year)
440249-11
(Taliaferro &
Brewer, 1996)
444113-04
(Taliaferro, 1997)
Study
Classification
core
invalid '
'The percentage of normal hatching of eggs laid and eggs set in control group were lower than treatment groups.
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FACT SHEET (New Chemical;
Page 18 of 22
Pymetrozine
iii. Mammals, Acute
Table 13. Mammalian toxicitv of Pvmetrozine.
Species/
Study
Duration
Laboratory rat
(Rattus norvegicus)
%
ai
98.0
Test
Type
Acute Oral
Acute
Dermal
Acute
Inhalation
Parental
Offspring
Toxicity
Value
LD50= 5955 mg/kg
LD50= >2000 mg/kg
LC50= 1.8mg/L
NOAEL= 2000 ppm
LOAEL= >2000 ppm
NOAEL= 200 ppm
LOAEL= 2000 ppm
Affected Endpoints
or Toxicity
Category
IV1
in2
IV1
Reproduction
Body weight
MRID No.
440249-26
440249-28
440249-30
440249-50
1 Least toxic and no irritation. Use restriction as on the label
2 Less toxic and can be used for homeowners generally with only restriction as on the label.
iv. Insects
Table 14. Nontarget Insect Acute Contact Toxicity.
Species
Honeybee
(Apis mellifera)
%ai
98.0
LD50
(us/bee)
>200'
Toxicity
Category
practically
nontoxic
MRID No.
(Author/Year)
440249-61
(Decker, 19993)
Study
Classification
Core
1 One mortality at 10 wg/bee (not considered treatment-related).
b. Toxicity to Freshwater Aquatic Animals
i. Fish, Acute
Table 15. Freshwater Fish Acute Toxicitv of Pymetrozine.
Species
Rainbow trout
(Oncorhynchus mykiss/ flow-
through)
Bluegill sunfish
(Lepomis macrochirus/flow-
through)
%ai
98.5
98.5
96-h LC50
(ppm)
>128
(measured)
>134
(measured)
Toxicity
Category
practically
nontoxic
practically
nontoxic
MRID No.
(Author/Yea
r)
440249-13
(Boeri et al.,
1994)
440249-12
(Boeri et al.,
1994)
Study
Classification
Core
Core
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FACT SHEET (New Chemical;
Page 19 of 22
Pymetrozine
ii. Fish, Chronic
Table 16. Freshwater Fish Early Life-Stage Toxicity Study of Pymetrozine.
Species / Test
Conditions
Rainbow trout
(Oncorhynchus
mykiss/flow-through)
%ai
98.5
NOEC/LOEC
(ppm)
NOEC= 11.7
LOEC >1 1.7 2
MATC
(ppm)1
Not
Determine
d
Endpoint
Affected
None
MRIDNo.
(Author/
Year)
440249-18
(Boeri et al.,
1995)
Study
Classification
Supplemental3
1 Maximum Allowed Toxic Concentration, defined as geometric mean of the NOEC and LOEC.
2 Highest test concentration.
3No effects at any test concentrations; MATC could not be determined.
iii. Invertebrates, Acute
Freshwater Invertebrate Acute Toxicity
Table 1 7. Freshwater Invertebrate Acute Toxicity of Pymetrozine.
Species/Test
Conditions
Waterflea (Daphnia
magna/flow-through)
%ai
98.5
48-hour EC50
(ppm)
87.0
(measured)
Toxicity
Category
Slightly Toxic
MRID No.
(Author/
Year)
440249-14
(Boeri et al., 1994)
Study
Classification
Core1
1 Dechlorinated tap water was used.
iv. Invertebrates, Chronic
Table 18. Freshwater Aquatic Invertebrate Life-Cycle Toxicity .
Species / Test
Conditions
Waterflea
(Daphnia magna /
flow-through)
%ai
98.5
21-day
NOEC/LOEC
(ppm)
NOEC = 0.025
LOEC = 0.052
(measured)
MATC
(ppm)1
0.036
Endpoint
Affected
Reproductio
n, Growth,
and Survival
MRIDNo.
(Author/
Year)
440249-19
(Boeri et al.,
1995)
Study
Classification
Core1
1 Maximum Allowed Toxic Concentration, defined as geometric mean of the NOEC and LOEC
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FACT SHEET (New Chemical) Page 20 of 22
c. Toxicity to Estuarine Marine Animals
i. Fish, Acute
Pymetrozine
Table 19. Estuarine/Marine Fish Acute Toxicity of Pymetrozine..
Species / Test Conditions
Sheepshead minnow
(Cyprinodon variegatus)/ 'flow-through
%ai.
98.5
96-h LC50
(ppm)
>117
(measured)
Toxicity
Category
practically
non-toxic
MRID
No.
(Author/Y
ear)
440249-16
(Boeri et al.,
1994)
Study
Classification
Core
ii. Invertebrates, Acute
Table 20. Estuarine/Marine Invertebrate Acute Toxicity of Pymetrozine.
Species
Eastern oyster (shell deposition)
(Crassostrea virginica)/f[ov/-ihrough
Mysid (Americanysisbahia)/f[ov/-
through
%ai.
98.5
98.5
96-hour
EC5/LC50
(ppm)
3.05
(measured)
66.9 2
(measured)
Toxicity
Category
moderately
toxic
slightly toxic
MRID
No.
(Author/Y
ear)
440249-17
(Boeri et al.,
1994)
440249-15
(Boeri et al.,
1994)
Study
Classification
Core
Supplemental1
1 Age of the test mysids was not reported; appeared to be greater than 10 days old.
2 One mortality in control group.
d. Toxicity to Aquatic Plants
i. Terrestrial
Currently, terrestrial plant testing is not generally required for insecticides, unless
there is a known concern about phytotoxicity.
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FACT SHEET (New Chemical;
Page 21 of 22
Pymetrozine
ii. Aquatic Plants
Table 21. Nontarget Aquatic Plant Toxicitv (Tier II) of Pvmetrozine.
Species
%ai
EC5(I (ppm)
NOEC (ppm)
MRID No.
Author/Year
Study
Classification
Vascular Plants
Duckweed
Lemna gibba
98.5
>109
(initial measured)
49
440249-60 (Boeri
et al., 1995)
Supplemental1
Nonvascular Plants
Green algae
Kirchneria subcanitata
98.5
17.0
("initial measured"!
6.28
440249-59
(Boeri et al.. 1995s!
Core
1 Test material was unstable and was not detected by test termination. The test solutions should have been renewed every few
days.
IV. SUMMARY OF REGULATORY POSITION AND RATIONALE
The Agency has established permanent tolerances for residues of pymetrozine per se in the
food crops listed in Table 4 above It most recently published a Final Rule in the Federal Register on
December 27, 2001 (66 FR 66786-94). All of these tolerance will appear in the 2002 version of the
Code of Federal Regulations under 40 CRF 180.556 (Pymetrozine; tolerances for residues). Table 4
of this document lists the commodities and their tolerance levels and pre-harvest intervals (PHI).
Because of a metabolite of concern, the label also includes a plant back restriction of 30 days for all
crops.
Available data provide adequate information to support the conditional registrations of
pymetrozine technical, Fulfill® on food crops and tobacco, and Endeavor® on ornamentals.
V. SUMMARY OF DATA GAPS
Chemistry Data (due December 2000);
• Storage Stability Data
• Corrosion Characteristics Data
Toxicology Data: (due October 2001)
• Developmental Neurotoxicity Study (870-6300 or 83-6)
Environmental Fate Data:
• Drinking water monitoring (originally due October 2002 but the requirement was no longer
applicable after the Cancer Q* was revised downward)
• Photodegredation on Soil (due October 2000)
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FACT SHEET (New Chemical) Page 22 of 22 Pymetrozine
Ecological Effects Data:
• Acute Estuarine/Marine Toxicity (shrimp), 72-3(c), due October 2000
• Avian Reproduction (mallard), 71-4(b), due November, 2003
VI. CONTACT PERSON AND MAILING ADDRESS AT EPA
Dan Peacock
Insecticide-Rodenticide Branch
Registration Division (7504C)
Office of Pesticide Programs
Environmental Protection Agency
401 M Street, SW
Washington, DC 20460
Office Location. Telephone Number. Fax Number, and E-Mail
Room 223, Crystal Mall Building #2
1921 Jefferson Davis Highway
Arlington, VA 22202
Tel: (703) 305-5407
Fax:(703)305-6596
E-Mail: peacock.dan@epa.gov
DISCLAIMER: The information presented in this Pesticide Fact Sheet is for informational purposes
only and may not be used to fulfill data requirements for pesticide registration and reregi strati on.
Disk 74, B:\pymetrozine fact sheet-revised June 25, 2002.wpdJuly 3, 2002 (2:42pm)
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