United States
Environmental Protection
Agency
Office of Prevention, Pesticides
and Toxic Substances
(7501C)
Pesticide
Fact Sheet
Name of Chemical:
Reason for Issuance:
Date Issued:
Famoxadone
New Chemical
July, 2003
Description of Chemical
Chemical Name:
Common Name:
Trade Name:
Chemical Class:
EPA Chemical Code:
3-anilino-5-methyl-5-(4-phenoxyphenyl)-l,3-oxazolidine-2,4-
dione (IUPAC)
Famoxadone
Famoxate™ Technical
Oxazolidinedione
113202
Chemical Abstracts
Service (CAS) Number: 131807-57-3
Year of Initial Registration: 2003
Pesticide Type: Fungicide
U.S. Producer:
E.I. DuPont Nemours and Company
DuPont Agricultural Products
P.O. Box 30
Newark, DEI 9711-3 507
Use Pattern and Formulations
Famoxadone is used in the U.S. in combination with cymoxanil in the formulated product
Tanos DF (water dispersible granules with 25% Famoxadone/25% cymoxanil) for the control of
1
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various fungal diseases on fruiting vegetables, tomatoes, potatoes, curcurbits, head lettuce and
imported grapes, including raisins. For example, the uses of Tanos 50DF include treating downy
mildew on curcurbits and head lettuce and early and late blight on potatoes and fruiting
vegetables.
Famoxadone belongs to the oxazolidinedione class of chemicals and is highly active
against spore germination and mycelial growth of sensitive fungi. The biochemical mechanism
of action of famoxadone is inhibition of the fungal mitochondrial respiratory chain at Complex
III, resulting in a decreased production of ATP by the fungal cell.
SUMMARY OF SCIENCE FINDINGS
Acute Toxicity: Technical grade famoxadone has minimal to moderate acute toxicity in acute
oral, dermal and inhalation tests, it is moderately irritating to the eyes and skin, and is not a
dermal sensitizer.
Subchronic Toxicity: In subchronic feeding studies in rats, mice, and dogs, famoxadone
generally caused decreased body weights and body weight gains that were often accompanied by
decreased food consumption and food efficiency. A mild regenerative hemolytic anemia was
regularly observed. Secondary effects of the anemia were frequently observed in the spleen,
bone marrow and liver. Famoxadone frequently induced a mild hepatotoxicity in treated animals
characterized by elevated levels of clinical chemistry enzymes indicative of liver damage and/or
by histopathological lesions in the liver. Adaptive hepatocellular responses indicating
stimulation of the liver microsomal/peroxisomal enzyme system were also regularly observed,
but were not considered to be adverse effects. Both the anemia and the hepatotoxicity were mild
and did not significantly compromise the overall health status of the treated animals. In a
subchronic dermal study in rats, the systemic effects were similar to those observed in oral
studies in rats. No dermal irritation was observed. Additional treatment-related effects were
observed in dogs, but were not observed in other species. In a subchronic feeding study,
myotonic twitches were noted in male and female dogs at the highest dose tested starting on day
21 and continuing throughout the remainder of the study. Lens lesions (cataracts) were observed
in dogs at the end of the 90-day study.
Chronic Toxicity: In chronic feeding studies in rats, dogs, Cynomolgus monkeys (gavage
study) and mice, famoxadone generally caused decreased body weights and body weight gains
that were often accompanied by decreased food consumption and food efficiency. A mild
regenerative hemolytic anemia was regularly observed. Secondary effects of the anemia were
frequently observed in the spleen, bone marrow and liver. Famoxadone frequently induced a
mild hepatotoxicity in treated animals characterized by elevated levels of clinical chemistry
enzymes indicative of liver damage and/or by histopathological lesions in the liver. Adaptive
hepatocellular responses indicating stimulation of the liver microsomal/peroxisomal enzyme
system were also regularly observed, but were not considered to be adverse effects. In a 1-year
chronic feeding study in dogs, famoxadone induced treatment-related cataracts in the lens in
male and female dogs. Treatment-related cataracts in the lens of the eye were not observed in
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the chronic feeding study in rats or in the 1-year gavage study in Cynomolgus monkeys or in the
carcinogenicity study in mice. Both the anemia and the hepatotoxicity were mild and did not
significantly compromise the overall health status of the treated animals.
Carcinogenicity: In carcinogenicity studies in rats and mice, famoxadone did not demonstrate
evidence of carcinogenic potential. Famoxadone is classified as "not likely to be carcinogenic to
humans."
Developmental Toxicity: In a developmental toxicity study in rats, no developmental toxicity
was observed. In a developmental toxicity study in rabbits, an increased incidence of abortions
was observed. The does which aborted also had markedly decreased body weight, body weight
gain and food consumption. Since it could not be determined whether the abortions were due to
maternal toxicity or due to an effect on reproductive/developmental mechanisms, the does and
fetuses were considered to be equally sensitive to the test material. There was also an equivocal
increase in % postimplantation loss and mean number of resorptions per doe in this study. The
results in the two developmental toxicity studies demonstrated no quantitative or qualitative
evidence of increased susceptibility of fetuses or pups as compared to adults.
Reproductive Toxicity: In a 2-generation reproduction study in rats, decreased body weights for
FI and F2 pups were observed throughout lactation, but no reproductive toxicity was observed.
The LOAEL for offspring toxicity was determined to be 800 ppm (44.7 mg/kg/day for males and
53.3 mg/kg/day for females), while a LOAEL for reproductive performance was not observed.
The NOAEL for reproductive performance is 800 ppm. The results in the reproduction study
demonstrated no quantitative or qualitative evidence of increased susceptibility of fetuses or
pups as compared to adults.
Neurotoxicity: In an acute neurotoxicity study in rats, equivocal evidence of a possible slight
neurotoxic effect at the limit dose of 2000 mg/kg was observed. In this study, an increased
incidence of palpebral (eyelid) closure in the 13-week feeding study in dogs of myotonic
twitching in the high dose level male and female animals. In none of the other toxicity studies
with famoxadone, including a subchronic neurotoxicity study in rats, were there any
lexicologically significant evidence of treatment-related neurotoxicity.
Mutagenicity: Famoxadone may have a weak mutagenic potential, but this is not considered to
be lexicologically significant. In three gene mutation studies, results were negative. In three
chromosome aberration studies, a weak clastogenic effect was observed in two in vitro
chromosome aberration studies in human lymphocytes, but in an in vivo micronucleus study in
mice using bone marrow cells, the results were negative. In four unscheduled DNA synthesis
(UDS) studies, although a positive response was observed in an in vitro unscheduled DNA
synthesis (UDS) assay in primary rat hepatocyte cultures, results in two repeat studies were
negative. Also, results in an in vivo/in vitro UDS assay in primary rat hepatocyte cultures
derived from male rats given oral doses of famoxadone were negative.
Chronic Reference Dose (cRfD) In a 13-week subchronic oral study famoxadone was
administered by diet to 4 beagle dogs/sex/group at doses of 0, 40, 300, or 1000 ppm (equal to 0,
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1.3/1.4, 10.0/10.1, or 23.8/23.3 mg/kg/day in males/females). The dose and endpoint for
establishing the cRfD is based on a LOAEL of 1.4 mg/kg/day, based on treatment-related
microscopic lens lesions (cataracts) in eyes of female dogs. A NOAEL could not be determined.
Uncertainty Factor(s): 1000 (10X for inter-species extrapolation, 10X for intra-species variation;
and an additional 10X for the use of a LOAEL and the use of a subchronic study. This endpoint
is based on an oral study, which is the route of interest for a dietary risk estimate. This study and
endpoint were selected because they would address the concerns for toxic effects observed in all
the other available studies for this chronic risk assessment.
Chronic RfD =
1.4 mg/kg/dav (LOAEL) =
0.0014 mg/kg/day
1000 (UF)
Physical/Chemical Properties
TABLE 1. Physicochemical Properties of Famoxadone
Parameter
Color/Physical state
Molecular Structure
Melting point/range
pH of 1% aqueous suspension
Density or specific gravity
Water solubility (20°C)
Value
Pale cream powder
rY"Oi>-x
^ ° \-Q
140.3- 141. 8°C
6.56at20°C
D204= 1.310g/mL
EH iig/L
unbuffered 52
2 143
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TABLE 1. Physicochemical Properties of Famoxadone
Parameter
Solvent solubility (20°C)
Octanol/water partition
coefficient (Kow)
Vapor pressure at 20°C
Henry's Law Constant
Dissociation constant (pKa)
Value
3 191
5 243
7 111
9 38
Solvent g/L
acetone 274
acetonitrile 125
dichloromethane 239
ethyl acetate 125
hexane 0.0476
methanol 10.0
1-octanol 1.87
toluene 13.3
pH Log Knw + SD
3.0 4.59 ± 0.06
5.0 4.80 ±0.13
7.0 4.65 ± 0.40
9.0 5.55 ± 0.26
6.4x1 0'4 mPa(4.8xlO-9mmHg)
4.6xlO'3Pam3mor1, pH 7
Expected to be weakly basic. The dissociation constant
could not be measured or inferred from solubility or
octanol water partition coefficient.
Toxicological Characteristics:
Table 2. Acute Toxicity of Famoxadone Technical (Selected Studies)
Guideline No. /Study Type
870.1100
Acute oral, rats
870.1200
Acute dermal, rabbits
870.1300
Acute inhalation, rats
870.2400
Primary eye irritation, rabbits
MRIDNo.
44302407
44302409
44302410
44302411
Results
M: LD50 = >5000 mg/kg
F: LD50 = >5 000 mg/kg
M: LD50 = >2000 mg/kg
F: LD50 = >2000 mg/kg
M:LC50 = >5.3mg/L
F: LC50 = >5.3mg/L
Moderately irritating
Toxicity
Category
IV
III
IV
III
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870.2500
Primary skin irritation, rabbits
870.2600
Dermal sensitization, guinea pig
44946205
44302413
Moderately irritating
Non-sensitizer
III
NA
Table 3 Toxicity Profile of Famoxadone Technical (Selected Studies)
Guideline No./Study
Type
870.3100
90-Day oral toxicity,
rats
Results
NOAEL = M: 3.3 mg/kg/day. F: 4.2 mg/kg/day.
LOAEL = M: 13.0 mg/kg/day based on mild hemolytic anemia and
decreased glucose. F: 16.6 mg/kg/day based on decreased body
weight gain, food consumption, and food efficiency; mild hemolytic
anemia and decreased globulin.
870.3100
90-Day oral toxicity,
mice
NOAEL = M: 62.4 mg/kg/day. F: 79.7 mg/kg/day.
LOAEL = M: 534 mg/kg/day based on mild hemolytic anemia with
secondary responses in spleen and mild hepatotoxicity in the liver.
F: 757 mg/kg/day based on mild hemolytic anemia with secondary
responses in spleen and mild hepatotoxicity in the liver.
870.3150
90-Day oral toxicity,
dogs
NOAEL = M: 1.3 mg/kg/day. F: <1.4 mg/kg/day.
LOAEL = M: 10.0 mg/kg/day based on lens cataracts in eyes. At
23.8/21.2 mg/kg/day, also myotonic twitches (starting on day 21);
decreased body weight, body weight gain, food consumption, and
food efficiency; slight anemia and hyperkalemia. F: 1.4 mg/kg/day
based on lens cataracts in eyes. At 10.1 mg/kg/day, no additional
effects. At 23.3/20.1 mg/kg/day, same effects as for males at
23.8/21.2 mg/kg/day.
870.3200
28-Day dermal
toxicity, rats
NOAEL = M: 250 mg/kg/day. F: 1000 mg/kg/day.
LOAEL = M: 500 mg/kg/day based on increased alkaline
phosphatase, alanine aminotransferase and sorbitol dehydrogenase;
and mild hepatotoxicity in the liver. F: none ( >1000 mg/kg/day).
No dermal irritation in M or F.
870.3700a
Prenatal developmental
toxicity, rats
Maternal NOAEL = 250 mg/kg/day.
LOAEL = 500 mg/kg/day based on transient decreased body weight
gain and food consumption.
Developmental NOAEL = 1000 mg/kg/day.
LOAEL = none (>1000 mg/kg/day).
870.3700b
Maternal NOAEL = 350 mg/kg/day.
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Prenatal developmental
toxicity, rabbits
LOAEL = 1000 mg/kg/day based on abortions; decreased body
weight, body weight gain, and food consumption; and abnormal
stools.
Developmental NOAEL = 350 mg/kg/day.
LOAEL = 1000 mg/kg/day based on abortions and equivocal
increases in postimplantation loss and mean resorptions per doe.
870.3800
Reproduction and
fertility effects, rats
Parental/Systemic NOAEL = M/F: 11.3/14.2 mg/kg/day.
LOAEL = M/F: 44.7/53.3 mg/kg/day based on decreased body
weight, body weight gain, and food consumption; and
hepatotoxicity in the liver.
Reproductive NOAEL = M/F: 44.7/53.3 mg/kg/day.
LOAEL = M/F: none (>44.7/53.3 mg/kg/day).
Offspring NOAEL = M/F: 11.3/14.2 mg/kg/day.
LOAEL = M/F: 44.7/53.3 mg/kg/day based on decreased body
weights for FI and F2 pups throughout lactation.
870.4100b
Chronic toxicity,
dogs
NOAEL = M: 1.2 mg/kg/day. F: 1.2 mg/kg/day.
LOAEL = M: 8.8 mg/kg/day based on lens cataracts in eyes.
F: 9.3 mg/kg/day based on lens cataracts in eyes. No other adverse
effects were observed in M or F.
870.4100
Chronic toxicity,
Cynomolgus monkeys
(1-year gavage study)
NOAEL = M: 100 mg/kg/day. F: 100 mg/kg/day.
LOAEL = M: 1000 mg/kg/day based on mild hemolytic anemia
with secondary responses in spleen, liver and kidney; and sinus
dilatation in spleen. F: 1000 mg/kg/day based on mild hemolytic
anemia with secondary responses in spleen, liver and kidney; and
sinus dilatation in spleen.
No evidence of lens cataracts in eyes of M or F.
870.4200b
Carcinogenicity,
mice
NOAEL = M: 96 mg/kg/day. F: 130 mg/kg/day.
LOAEL = M: 274 mg/kg/day based on slight hepatotoxicity in the
liver; no anemia. F: 392 mg/kg/day based on amyloidosis and slight
hepatotoxicity in the liver; no anemia.
No evidence of carcinogenicity in M or F.
870.4300
Combined chronic
toxicity/carcinogenicit
y, rats
NOAEL = M: 8.4 mg/kg/day. F: 2.2 mg/kg/day.
LOAEL = M: 16.8 mg/kg/day based on slight hemolytic anemia
with compensatory erythropoiesis and secondary responses in
spleen and bone marrow; and mild hepatotoxicity in the liver. F:
10.7 mg/kg/day based on decreased body weight gain and slight
hemolytic anemia. At 23.0 mg/kg/day, also secondary responses to
anemia in spleen, bone marrow and/or liver; and mild hepatotoxicity
in the liver.
No evidence of carcinogenicity in M or F.
870.5100
Negative without and with S-9 activation up to limit dose of 5000
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Reverse gene mutation
(S. typhi./E. coli)
ug/plate.
870.5300
Forward gene mutation
(CHO/HGPRT locus)
Negative without and with S-9 activation up to the limit of
solubility (in DMSO) of 30 ug/mL.
870.5300
Forward gene mutation
(CHO/HGPRT locus)
Negative without and with S-9 activation up to cytotoxic
concentrations (>200 ug/mL without S-9 and >150 ug/mL with
S-9).
870.5375
Chromosome
aberration (human
lymphocytes)
Positive (weak clastogenic effect) without S-9 activation.
Statistically significant increases in percentage of aberrant cells at
several dose levels ranging from 5-15 ug/mL. Cytotoxicity was
observed at 10-18 ug/mL. Negative with S-9 activation.
870.5375
Chromosome
aberration (human
lymphocytes)
Positive (weak clastogenic effect) without S-9 activation.
Statistically significant increases in percentage of aberrant cells at
several dose levels ranging from 15-30 ug/mL. Cytotoxicity was
observed at 20-30 ug/mL. Negative with S-9 activation.
870.5395
Micronucleus assay
(mouse bone marrow)
Negative at single oral doses of up to limit dose of 5000 mg/kg.
870.5550
Unsched. DNA
synthesis
(prim, rat hepatocytes)
Positive response (increased net nuclear grain counts) observed at
several treatment levels ranging from 0.05-10 ug/mL. Cytotoxicity
was observed at 10 ug/mL.
870.5550
Unsched. DNA
synthesis (prim, rat
hepatocytes)
Negative at treatment levels up to 10 ug/mL. Cytotoxicity was
observed at 10 ug/mL.
870.5550
Unsched. DNA
synthesis (prim, rat
hepatocytes)
Negative at treatment levels up to 5.0 ug/mL. Cytotoxicity was
observed at 2.5 and 5.0 ug/mL.
870.5550
Unsched. DNA
synthesis (hepatocytes
derived from male rats
given Famoxadone)
Negative at single oral doses of up to 2000 mg/kg. No marked
increases in net nuclear grain counts or percentage of cells in repair
in hepatocyte cultures.
870.6200a
Acute neurotoxicity
screening battery,
NOAEL = M: 1000 mg/kg. F: 2000 mg/kg.
LOAEL = M: 2000 mg/kg based on decreased body weight gain and
food consumption (on days 1-2); and palpebral (eyelid) closure (on
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rats
day 1 only). F: none (>2000 mg/kg).
870.6200b
Sub chronic
neurotoxicity screening
battery, rats
NOAEL = M: 11.7 mg/kg/day. F: 14.4 mg/kg/day.
LOAEL = M: 47 mg/kg/day based on decreased body weight, body
weight gain, food consumption and food efficiency.
F: 59 mg/kg/day based on decreased body weight, body weight
gain, food consumption and food efficiency. No evidence of
neurotoxicity in M or F.
Occupational and Residential Exposure and Risk Characterization.
Chemical-specific data for assessing human exposures during pesticide handling activities
were not submitted for famoxadone. Therefore, the Agency used Pesticide Handlers Exposure
Database (PFtED V 1.1) to assess handler exposure. Based on the application rates and uses,
exposures are expected to be short- and intermediate-term in duration. Since both dermal and
inhalation endpoints were based on the same toxicological effects for short- and intermediate-
term exposures, the route-specific MOEs were combined into a total MOE. All MOEs for
handlers were greater then the target MOEs of 100 (short term) and 300 (intermediate-term) and
therefore do not exceed the Agency's level of concern. The Agency is imposing a re-entry
interval of 12 hours for the Tanos 50DF product. The Agency will also be requiring on product
labels personal protective equipment (PPE) required by the Worker Protection Standard (WPS).
For short-term (1-30 days) occupational dermal and inhalation exposures, the toxicology
endpoint was selected from the subchronic feeding study in dogs in which myotonic twitches
were observed in male and female dogs at the highest dose tested (23 mg/kg/day) starting on day
21. The next lower dose in this study (10 mg/kg/day) was the dose selected for the short-term
risk assessments. The cataracts observed in the eyes of dogs in this study and in the chronic
feeding study in dogs did not occur until after 8 weeks (56 days) of exposure and therefore were
not an appropriate endpoint on which to base a short-term (1-30 days) risk assessment. For short-
term exposures, the target Margin of Exposure (MOE) is 100. For intermediate-term (1-6
months) and long-term (>6 months) occupational dermal and inhalation exposures, the toxicology
endpoint was selected from the same subchronic feeding study in dogs, but was based on
microscopic lens lesions (cataracts) observed in the eyes of female dogs at the LOAEL of 1.4
mg/kg/day. This dose/endpoint/study was also selected for long-term dietary risk assessment.
For intermediate-term exposures, the target MOE is 300. This MOE includes the conventional
factor of 100 and an additional factor of 3 since a LOAEL, rather than a NOAEL, was selected for
risk assessments. For long-term exposures, the target MOE is 1000. This MOE includes the
conventional factor of 100 and an additional factor of 10 for the use of the LOAEL and dose from
a subchronic study for long-term risk assessment. For dermal exposures, a 5% dermal absorption
factor was used. For inhalation exposures, a 100% inhalation absorption factor (default value)
was used.
At this time, only agricultural uses have been proposed for famoxadone. There are no
uses that would result in residential or recreational exposures. Assessments addressing residential
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and recreational risks are not warranted at this time.
Aggregate Exposure and Risk Characterization.
The currently proposed uses for famoxadone encompass only agricultural use sites.
Therefore, when addressing aggregate exposures, only the dietary pathways of food and drinking
water were considered. No appropriate endpoint attributable to a single oral dose was identified
in the available toxicology studies on famoxadone. Therefore, an acute aggregate risk assessment
for famoxadone is not warranted.
Dietary exposure and risk estimates were evaluated using Dietary Evaluation Model,
Version 1.3 (DEEM-FCID). These exposure estimates are based on average field trial residues
but retain the conservative assumption of 100% crop treated and should be considered moderately
refined.
For considering exposure to residues of famoxadone in drinking water, the Agency has
calculated Drinking Water Levels of Comparison (DWLOCs). These values are the maximum
concentration of a chemical that occur in drinking water after taking into account exposures to
residues from other pathways and sources. The DWLOCs are compared against the modeled
estimated environmental concentrations (EECs). DWLOC values that are greater than the EECs
indicate that aggregate exposures are unlikely to exceed the Agency's level of concern.
As shown in Table 4, the DWLOCs for the general U.S. population and all of the
representative population subgroups modeled by DEEM-FCID are greater than both the surface
water and ground water EECs.
Famoxadone has been classified as not likely to be carcinogenic to humans. As such, a
cancer aggregate risk assessment is not warranted.
Table 4. Chronic DWLOC Calculations.
Population
Subgroup
General U.S.
Population
All Infants,
(< 1 year old)
cPAD
mg/kg/da
y
0.0014
0.0014
Food Exp
mg/kg/day
0.000505
0.000175
Max Water
Exp
mg/kg/daya
0.000895
0.001225
Ground
Water
EEC
(Hg/L)
0.23
0.23
Surface
Water
EEC
(Hg/L)
0.47
0.47
DWLOC
(Mg/L)b
31
12
10
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Table 4. Chronic DWLOC Calculations.
Population
Subgroup
Children,
1-2 years old
cPAD
mg/kg/da
y
0.0014
Food Exp
mg/kg/day
0.001057
Max Water
Exp
mg/kg/daya
0.000343
Ground
Water
EEC
(Hg/L)
0.23
Surface
Water
EEC
(Hg/L)
0.47
DWLOC
(Mg/L)b
3.4
a Maximum water exposure (mg/kg/day) = [(chronic PAD (mg/kg/day) - food exposure
(mg/kg/day)]
b DWLOC(//g/L) = [maximum water exposure (mg/kg/day) x body weight (kg)] +• [water
consumption (L) x 10"3 mg///g]. Consumption = 1 L/day for populations <13 years old and 2
L/day for populations > 13 years old. Default body weights = 70 kg for males > 13 years old
and general U.S. population, 60 kg for females > 13 years old, and 10 kg for all others.
Values are rounded to 2 significant figures.
Human health aggregate risk assessments have been conducted for acute aggregate
exposure (food + drinking water) and chronic aggregate exposure (food + drinking water). Short-
, intermediate-, and long-term aggregate assessments were not performed, since there are no
registered or proposed residential uses. A cancer risk assessment was not performed, because the
Agency classified famoxadone as "not likely to be carcinogenic to humans." All aggregate
exposure and risk estimates are below the Agency's level of concern for the scenarios listed
above.
Ecological Effects/Environmental Fate Characteristics:
Hydrolysis
The half-life for famoxadone is 31 - 41 days in pH 5 solution, 2 - 2.7 days in pH 7
solution, and 1.55 - 1.8 hours in pH 9 solution (in the dark at 25°C, sterile aqueous buffered
solutions). Hydrolysis of the parent compound is pH dependent and the rate of degradation
increases with increasing pH. Under neutral to basic conditions hydrolysis would likely be a
significant route of degradation.
Aqueous Photolysis
The half-life for famoxadone in irradiated solution (pH 5) is 1.1 - 1.9 days (equivalent to
2.6 - 4.6 days of natural sunlight) and in the dark control is 41 days.
Soil Photolysis
The half-life for famoxadone in irradiated soil is 3.3 - 4.9 days (after correction for dark
11
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controls, equivalent to 9.5 - 16.2 days of natural sunlight).
Mobility
Famoxadone is of slight mobility using the general classification scheme of McCall. The
mobility of famoxadone, at nominal concentrations of 5.0, 10.0, and 25.0 ng/mL, was investigated
in three soils (sand, sandy loam, and sandy clay loam). Kd values ranged from 71.3 - 109.8 for the
sand soil (2.29% o.c.); 33.9 - 51.9 for the sandy loam soil (1.34% o.c.), and 16.5 - 29.4 for the
sandy clay loam soil (0.58% o.c.); 1/n values ranged from 0.737 to 0.831. Following adsorption,
Koc values were 3890 for the sand soil, 3300 for the sandy loam soil, and 4030 for the sandy clay
loam soil.
Field Dissipation
In four different Terrestrial Field Dissipation Studies (three U.S. studies, one Canadian
study), famoxadone had dissipation half-lives ranging from 6.5 - 32.9 days. Famoxadone was not
detected (detection limit - 0.007 ppm) below the 15-cm soil depth at any of the sites.
Bioaccumulation
The accumulation of famoxadone in two different (14C labeled in different ring positions)
juvenile bluegill sunfish indicated bioconcentration factors of 971X - 1286X for the edible tissue,
3327X - 3608X for the nonedible tissue, and 2434X - 3425X for the whole fish tissues.
Depuration was rapid with 50% of the total residues accumulated by exposure day 28 eliminated
by day 2 of the depuration period. Because of the rapid depuration of famoxadone,
bioaccumulation is not expected to be a significant concern.
Spray Drift
No famoxadone-specific studies were reviewed. Droplet size spectrum (201-1) and drift
field evaluation (201-2) studies are required since famoxadone may be applied aerially. The
registrant, E.I. DuPont de Nemours is a member of the Spray Drift Task Force (SDTF), a
membership of U.S. pesticide registrants. The Agency has been working with the SDTF, EPA
Regional Offices and State Lead Agencies for pesticide regulation and other parties to develop
the best spray drift management practices. The Agency has completed its evaluation of the data
base submitted by the SDTF and is developing a policy on how to appropriately apply the data
and the AgDRIFT computer model to its risk assessment for pesticides applied by air, orchard
airblast and ground hydraulic methods. After the policy is in place, the Agency may impose
further refinements in the spray drift management practices to reduce off-target drift and risks
associated with aerial as well as other application types where appropriate. Due to risks
associated with exposures via spray drift, product labels should include a strong enforceable
statement to avoid off-target spray drift.
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ECOLOGICAL CHARACTERISTICS
Acute Freshwater Fish
Bluegill 96-hr LC50 = 13 (9.3, 21) //g/L NOAEC = 9.3 //g/L
Rainbow trout 96-hr LC50 = 12 (5.2, 72) //g/L NOAEC = 5.2 //g/L
Acute Estuarine/Marine Fish
Sheepshead minnow 96-hr LC50 = 49.4 (44.1, 56.1) //g/L NOAEC = 27.7 //g/L
Chronic (Early-Life) Freshwater Fish
Rainbow trout NOAEC 1.4//g/L LOAEC = 4.1 //g/L
Chronic (Early-Life) Estuarine/Marine Fish
Sheepshead minnow NOAEC 5.6 //g/L LOAEC = 11.2 //g/L
Acute Freshwater Invertebrates
Daphnia magna 48-hr EC50 = 11.8 (10.1, 14.5) //g/L NOAEC = 3.5 //g/L
Chironomus riparius Pore water concentrations:
28-day EC50 = 15 (12.7, 18.2) mg/L NOAEC < 0.55 mg/L
Sediment concentrations.
28-day EC50 = 2.4 (2.0, 2.8) mg/kg NOAEC <0.07 mg/kg
Acute Estuarine/Marine Invertebrates
Eastern oyster (Shell deposition) 96-hr EC50 = 1.6 (1.0, 2.7) //g/L NOAEC < 1.10 //g/L
Mysid shrimp 96-hr EC50 = 3.8 (2.2, 4.9) //g/L NOAEC = 2.2 //g/L
Chronic (Life-Cycle) Freshwater Invertebrate
Daphnia magna NOAEC = 0.085 //g/L LOAEC = 0.29 //g/L
Chronic (Life-Cycle) Estuarine/Marine Invertebrate
Mysid shrimp NOAEC = 0.83 //g/L LOAEC = 1.72 //g/L
Aquatic Plants
Lemna gibba 14-day EC50 >81 //g/L NOAEC = 8 l//g/L
Skeletonema costatum 120-hr EC50 >75 //g/L NOAEC = 75 //g/L
Selenastrum capricornutum 120-hr EC50 = 23 (12, 29) //g/L NOAEC = 3.9//g/L
Naviculapelliculosa 120-hr EC50 =13 (9.6, 19.0) //g/L NOAEC <9.87//g/L
Anabaenaflos-aquae 120-hr EC50 >84.3 //g/L NOAEC =42.6 //g/L
Avian Acute Single Oral Dose
Bobwhite quail LD50 > 2250 mg/kg-bw NOAEC = 2250 mg/kg-bw
Bobwhite quail LD50 > 511 mg/kg-bw NOAEC = 66 mg/kg-bw
Avian Acute Dietary
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Bobwhite quail LC50 > 5620 mg/kg-diet NOAEC = 5620 mg/kg-diet
Mallard duck LC50 > 5620 mg/kg-diet NOAEC = 5620 mg/kg-diet
Avian Chronic
Bobwhite quail NOAEC = 46 mg/kg-diet LOAEC = 252 mg/kg-diet
Mallard duck NOAEC = 46 mg/kg-diet LOAEC = 252 mg/kg-diet
Earthworm
Eisenia fetida andrei 14-day LCso = 470 mg/kg-soil NOAEC < 62.5 mg/kg-soil
Terrestrial Plants
Species studied were: common onion, corn, winter wheat, sorghum, sugar beat, soybean, pea,
tomato, rape, cucumber. For all endpoints in the emergence study and the vegetative vigor study,
the EC25 > 0.187 Ib/acre and the NOAEC = 0.187 Ib/acre.
Environmental Risk Summary:
Agency analysis indicates that famoxadone presents the greatest risks to fish and aquatic
invertebrates through spray drift and runoff in the dissolved phase as compared to the other
taxonomic groups evaluated in this assessment.
For aquatic and terrestrial plants, LOCs are not exceeded for the proposed uses of
famoxadone. In this risk assessment, modeling results did not indicate potential concerns for
aquatic or terrestrial plants.
ENVIRONMENTAL RISK MITIGATION
The Agency has conducted a screening level analysis to assess potential ecological risks
posed by famoxadone. The exceedance of a RQ does not necessarily indicate "high risk" to a
species as the RQ is not an absolute estimate of the likelihood, magnitude, or severity of risk.
Inputs into this screening level assessment were designated to overestimate likely exposures and
effects of famoxadone. Given the slight exceedences of the RQs and the risk mitigation that will
be imposed for famoxadone, the Agency, believes that potential ecological risks are low.
FRESHWATER FISH/INVERTEBRATES: Based on a screening level analysis, the Endangered
Species LOG and Acute Restricted Use LOG for freshwater fish and invertebrates are slightly
exceeded. Acute Fish RQs and Acute Invertebrate RQs ranged from 0.04 - 0.24. Chronic Fish
RQs ranged from 0.08 - 0.24, while Chronic Invertebrates RQs ranged from 2.47 - 8.35.
ESTUARINE/MARINE FISH/INVERTEBRATES: Based on a screening level analysis, the
Endangered Species LOG for estuarine/marine fish was exceeded for Florida tomatoes, Florida
peppers, and Maine potatoes. The Endangered species LOG and Acute Restricted Use LOG for
estuarine/marine invertebrates was exceeded in all scenarios; however, there are currently no
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federally listed endangered estuarine invertebrates. RQs ranged from 0.01 - 1.81. Chronic RQs
ranged from 0.02-0.86.
AVIAN: Based on a screening level analysis, Chronic RQs for herbivorous birds, insectivorous
birds and herbivorous mammals exceeded the LOCs from exposure to famoxadone residues in
wildlife food items indicating potential for chronic risks. Chronic RQs ranged from 0.3 - 4.7 at
the estimated maximum residue levels, and ranged from 0.1 to 1.70 at the predicted mean residue
levels. Short grass eating birds had the highest RQs of 1.7 at the estimated mean residues level
and 4.7 at the estimated maximum residue level, these are the only exceedances of the Avian
Chronic LOG. For chronic exposure the predicted mean residue is the appropriate level for risk
assessment. The only Endangered species that feeds exclusively on short grasses is native to
Hawaii and the commodities that famoxadone is registered for use on are generally not grown in
that area.
MAMMALS: RQs were not calculated to evaluate potential acute risks to mammals because of
the low toxicity to mammals (LDso >5000 mg/kg). Acute risk is low at the proposed application
rates. Chronic effects are not expected for mammals using anticipated mean residue levels, which
is the appropriate level for use in a chronic analysis.
BENEFICIAL INSECTS: Famoxadone may have negative effects on beneficial insects (e.g.,
hoverfly and green lacewing). The Agency has concerns with the potential for negative impacts
on endangered insects.
ENVIRONMENTAL RISK MITIGATION: The Agency believes that famoxadone presents the
greatest risk to fish and aquatic invertebrates through spray drift and runoff in the dissolved
phase. In order to mitigate this risk the Agency will be requiring use limitations, label warning
statements and/or restrictions on the end-use product label:
** Maximum number of use per season - The Agency is restricting the maximum number
of applications per season to six and limiting the maximum seasonal use rate.
**
The Agency will require spray drift language on all end use products.
** The Agency will also require a beneficial insect warning statement on all end use
products.
In addition, the Agency will be requiring a 25-foot vegetative buffer strip around treated
fields. While the Agency cannot quantify the reduction in risk to non-target/endangered species
resulting from this restriction on the use, it should significantly reduce the potential for spray drift
and/or runoff, which are the major concerns. The Agency also notes that this product has a
relatively low seasonal maximum use rate compared to current alternatives.
Famoxadone is an alternative to other fungicides some of which may have higher seasonal
use rates, a different maximum number of applications, or shorter re-treatment intervals. Thus
while the Agency cannot strictly compare the RQs from those various fungicides the Agency does
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note that the issues with this fungicide are similar and that the RQ for the same use site are
comparable. The Agency believes that by restricting the maximum seasonal use rate and by
employing the use of vegetative buffer strips, actual ecological risks are significantly lower than
model estimates.
The Agency notes that DuPont is a member in the FIFRA Endangered Species Task Force.
SUMMARY OF DATA GAPS
Environmental Fate and Effects Data Requirements:
835.1220 163-1 Leaching/Adsorption/Desorption (one additional soil type which should be
finer-grained than those previously tested - which were sand, sandy/loam, and
sandy/clay/loam)
850.1075 72-1 Acute freshwater fish (Rainbow trout) guideline study using the end-use
product
850.1735 Whole sediment acute toxicity invertebrates, freshwater (chironomids, the 28-day
test
850.3020 Honey-bee acute contact with the end-use product
850.3030 Honey Bee Toxicity of residues on foliage with the end-use product
Contact person at USEPA
Mailing address:
Cynthia Giles-Parker
Product Manager (22)
Environmental Protection Agency
Office of Pesticide Programs
Registration Division (7505C)
Fungicide Branch
1200 Pennsylvania Avenue, NW
Washington, D.C. 20460
Office location and telephone number:
Room 249, Crystal Mall #2
1921 Jefferson Davis Highway
Arlington, VA 22202
703-308-7740
DISCLAIMER: The information in this Pesticide Fact Sheet is for information only and is not to be used to satisfy
data requirements for pesticide registration. The information is believed to be accurate as of the date on the
document.
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