United States Office of Pesticides and Toxic itos ances
Environmental Protection Office of Pesticide Programs (TS-756C)
Agency Washington. DC 20460
x°/EPA Pesticide
Fact Sheet
Name Of Chemical: Sodium Salt of Fomesafen
Reason for Issuance: *» chanical
Date Issued: April 1937
Fact Sheet Number:
132
1. Description of Chemical
Generic Name: Sodium Salt of 5-[2-Chloro-4-(trifluoromethyl)-
phenoxy]-N-(methylsulfonyl)-2-nitrobenzamide
Common Name: Sodium Salt of Fomesafen
Trade Name: Reflex, Flex
EPA Shaughnessy Code: 123802
Chemical Abstracts
Service (CAS) Number: 72178-02-0
Year of Initial Registration: 1987
Pesticide type: Herbicide
Chemical Family: Diphenyl ethers
U.S. and Foreign
Producers: ICI Americas Inc.
New Murphy Road & concord Pike .
Wilmington, DE 19897
2. use Patterns and Formulations:
Application Sites: Fomesafen is proposed for use on soybeans.
Types of formulations: 21.7% Liquid Concentrate End-Use Product
Types and methods of application: End-use product is applied
postemergence by ground application. Contact activity results
in relative rapid knockdown of weeds in 3 to 5 days. Residual
activity may result through root uptake from the soil if rainfall
occurs soon after application.
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Application rates: The proposed maxini im application rate is
0.375 lb/ai/acre with one application per gra iing season.
Usual carrier: Water
3. Science FindinqS
SUITEnarY Science Statement :
Fomesafen has been found to be oncogenic in mice and has been classified
as a Group C oncogen (possible human carcinogen). A quantitative risk
estimate has been conducted for the use of fomesafen on soybeans.
Based on a Q* = 1.9 x 10—1 (rrq/kqjday) and using a Theoretical Maxinum
Residue Contribution (TMRC) of 0.0000115 in/ kg (1.5 kg diet) the “worst
case” dietary risk was calculated to be 2.2 incidences in a million
(2.2 x l0 ). Using the ThRC provides a conservative estimate since it
does not consider the effect of processing on residue levels in the raw
agricultural connodity, that actual residue levels will be l er than
the level of detectiOn (0.05 ppm), and that less than 100 percent of
the crop is treated.
Based on exposure estimates for use of forriesafen on soybeans and the
Q*, the foll iing ranges in risk numbers were calculated:
Private applicators:
Farmers in South 1Cr 5
Farmers in North Central i0 to i0
CT C 3l & o1icators:
In South
In North Central i0
These estimates assume that workers are wearing long—sleeved shirts,
long pants, and shoes; protective gloves are worn during mixing,
loading, and application; and 10 percent dermal absorption.
Fomesafen is not considered to be teratogenic and the chemical did
not significantly inpair reproductive ability in a two-generation
reproductive effects study in rats. Four mutageniCitY studies with
fomesaf en were negative. Two rat bone marr J cytogenic tests were
positive.
Fomesafen is not acutely toxic to humans, avian species, freshwater
fish and invertebrates, honey bees or marine species. The pesti-
cide is slightly toxic to marine invertebrates. A mininum adverse
effect is expected on nontarget organisms. Fomesafen is relatively
stable to hydrolysis, moderately to very mobile in some soils and
may persist at si 9 nificant levels beyond 1 year; it may contaminate
ground water.
An applicator carcinogenic warning, ground water advisory, and crop
rotation restrictions are required to appear on the product’s labeling.
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Che ica1 Characteristics :
Color: White (PGAI)
Physical State:
Aqueous paste (technical)
Solid (PGAI)
Odor: Faint, sweet
Melting point: 220—221 °C PGAI
Specific gravity: 1.28 PGAI
Solubility:
1120 — 50 mg/L
Acetone — 300 g/L
Methanol — 25 g/L
Xylene — 1.9 qjL
Hexane — 0.5 g/L
Cyclohexane 150 g/L
Stability: > 6 months at 50 °C
Toxicoloqy Characteristics:
Acute effects 11 :
Acute oral toxicity (rat):
1,250—2000 mg/kg (males);
1,595—5,203 mg/kg (females);
Toxicity Category III
acute derr l toxicity: > 780 mg/kg
Primary eye irritation (rabbit): Corneal opacity, iritis and
coajunctLVitls witn rer.ass oa before icn .ay;
Toxicity Category II
-rirr.3r/ skin irritation (rab ,irj:
Slight erythema graded PIS = 0.58
Toxicity Category III
Dermal Sensitization: Acid form produced dermal sensitization.
Sodium salt produced no sensitization.
Subchronic effects :
Subchronic oral toxicity studies in the rat and the dog
show that the liver is the primary - qe’ ‘f toxicity in
both sexes. Rats were dosed at 1, 5, 100, and LOGO ppm in
the diet. The lowest-observed-effect level (LOEL) in this
: dy was 100 ppm (5 nrg/kqjday) and the no-observed—effect
level (NOEL) was 5 ppm (0.25 mg/kg/day). The dogs were dosed
at 0.1, 1, and 25 rrq/kqjday. The WEL in this study was
25 mg/kg/day and the NOEL was 1 mg/kg/day.
i 21—day subchronic dermal toxicity study in the rabbit, at
doses of 10, 100, and 1000 mg/kg/day, showed moderate to
severe skin irritation at the application site but no
1/ See 40 CFR 162.10 for discussion of toxicity categories and companion
labeling requirements.
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cystemic effects at doses up to 1000 ny/kg/day. The LOEL
for skin irritation was 100 fTq/kg/day and the NOEL was 10
rrq/kqjday.
Chronic-effects :
chronic FeedinajOncogenicity — A 2—year feeding study in
Wistar albino SPF rats at doses of 1, 5, 100, and 1000 ppm
in the diet also identified the liver as the target organ.
The WEL in this study was 100 ppm based on increased
hylinization of liver cells and pigmentation of Kupffer
cells at 100 ppm in males, and the NOEL is 5 ppm. No
evidence of oncogenicity was reported in this study.
The 2—year feeding study in Charfes River CD-i mice, at
doses of 1, 5, 10, 100, and 1000 ppm in the diet, was posi-
tive for oncogenic response. A statistically significant
increased incidence of liver adenonas were observed in
males at 1, 100, and 1,000 ppm and females at 100 and 1000
ppm. A statistically significant increased incidence of
liver carcinomas in both sexes was observed at 1000 ppm.
Developmental toxicity :
Rats were dosed with 0, 50, 100, and 200 ny/kg/day fomesafen
in the diet and in a second study the same strain of rats
at the same laboratory were dosed with 0, 1.0, 7.5, and 50
rrg/kglday fomesafen. In the first scu y a1teration of tn
14th rib and increased ossific ticn of the heel bone were
observed only at. O rri ,’ky,’day. es ef re not
repeated in the second study. The NOEL is 7.5 i /kg/day.
The maternal WEL is 200 ne/kg/day with increased post-
iuplantation loss and decreased body weight. No terata
were observed under conditions of the studies.
Rabbits were dosed with 0, 2.5, 10, and 40 n g/kg/day
fomesafen in the diet. The NOEL is 10 ny/kg/day and
there were no adverse effects on offspring under
conditions of the study.
Two-Generation reproduction — rat :
wistar-derived rats (30/sex/dose) were dosed with 0, 50,
250, and 1000 ppm fomesafen in the diet. Significant
effects in survival index and litter weight gain at the
1000 ppm were seen. The NOEL for this study is the mid—
dose 25 ppm. No meaningful effects were seen at 50 ppm.
Mutaqenici y :
Gene .niitation tests in Salmonella and hamater kidney
fibroblasts were negative. In vivo chromosomal aberration
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studies in the rat bone marr i were considered positive.
Physioloqi.cal and biochemical characteristics :
Foliar absorption: Contact activity results in relatively rapid
knockd in of weeds in 3 to 5 days.
TranslOcatiOn: In the presence of rainfall, plants absorb
fomesafen from the soil by root uptake.
Environmental characteristics :
Persistence:
Fomesafen is relatively stable to hydrolysis. The half—life was
estimated to be about 3 years at 25 °C and does not appear to be
pH dependent. In Northern aerobic soils the half—life is approxi-
mately 1 year. In Southern anaerobic soils fomesafen’s half—life
is less than 5 weeks. Laboratory data indicate rapid degradation
of parent corrpound under anaerobic conditions, but degradates
were not adequately identified, and where identified, were not
monitored in field studies. Therefore, half—lives in Southern
anaerobic soils do not provide an accurate estimate of total
soil residues.
P bsorption and leaching:
Fomesafen aged residues are moderately mobile in loains and clay
1oa s, cbile in sands. and vet’.’ nc’bi1 in coarse sands. The
only resioue ioentif ied w par€: . z :r r diolc . . le
residues at 20 to 30 cm depth of the coarse sand were
unidentified.
Bioaccum.llatiOfl:
( 14 C)Pomesafen residues have a l i potential for bioaccuriulation
in bluegill sunfish exposed in a flc ithrough system. Maxinurn
bioconcentratiOn factors of < 6X occurred in viscera after 7 and
14 days of exposure to ( 14 C fomesaf’?n at 1 ppm. Accunulated resi-
dues were depurated rapidly; < 50% of the residues in viscera were
eliminated after 1 day of deputation.
Crop rotation:
Confined and field rotation studies with wheat are conflicting.
Significant uncharacterized residues are present in wheat chaff
and straw at about a 1—year rotation interval, but in the field
study where only, parent was analyzed, no residues were present.
Lack of confirmation that parent represents 25 percent of residues
in the confined study preclude acceptance of the field data.
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Environmental fate and surface and ground water contamination
concerns:
Fomesafen may possibly contaminate ground water. Additional
data are required before the Agency can fully assess the poten-
tial for. ground water contamination.
Ecoloqical tharacteristics :
Avian acute oral toxicity
(Mallard duck): > 5000 1mg/kg
Avian subacute dietary toxicity
(Mallard duck and bo hite quail): > 2Q,000 ppm
Freshwater fish acute r. oxicicy —
Rainbow trout: 680 ppm
Bluegill sunfish: 6030 ppm
Freshwater invertebrate acute
toxicity (Daphnia): 330 ppm
Marine fish acute toxicity
(Sheepshead minnow): > 163 ppm
Marine invertebrate acute toxicity —
Fiddler crab: > 163 ppm
?1n shriirç: > 212 pm
‘arine e: icur..e tcxici: ’
(Pacific oyster): > 96.6 ppm
Marine invertebrate acute toxicity
(Mysid shrifrç)): 22.1 ppm
Beneficial insects acute oral and
contact toxicity (honey bees): > 50 ug/bee
- — -
Mallard c c %: NOEL = 46 ppm
Bo hite quail: NOEL = 50 ppm
Fish early life stage toxicity
(Sheepshead minnow): 54-89 ppm
Freshwater invertebrate life-cycle
(Daphnia): Maxinum Acceptable Toxic
Concentration (MATC) =
50-100 ppm
Marine invertebrate life—cycle
(Mysid shrirrç): MATC = 0.69—1.71 ppm
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Field chronic effects for soil
annelida (earthworm): NOEL (—1 yr) = 5 kg/ha
Field chronic effects for micro-
arthropods (mites, collent)ola): NOEL (—2 yr) = 5 kg/ha
These data indicate that fomesaf en is essentially nontoxic to avian,
freshwater fish, and invertebrate species and bees; and that it is
slightly toxic to aquatic invertebrates. Based on the acute and
chronic data no significant probleus to nontarget organisus are
expected from fomesaf en’s use on soybeans.
4. Benefits
Fomesafen is one of a nurrber of postemergent h rbicides recently
registered, or for which registration is pending, for soybeans.
Projecting use of these herbicides is difficult due to lack of data
on distribution of various weeds controlled, co parative efficacy
and lack of information on the failure of preemergent herbicides to
provide adequate weed control. Based on the reasonable assumption
that 30 percent of soybeans will be treated with postemergent herbi-
cides, lc ier chemical cost, and on estimated market penetration,
benefits range from $10 million to $15 million per year.
Registration of fomesafen would also provide another postemergent
herbicide which would increase competition resulting in l er prices.
These 1G.zer prices could result in benefits up to $30 million per year.
If additio’al weed control were to r ult ir r a1 yield increases
cr preve :t so et d ro n beco ir:g p cble s i.i f t re, fur r::
benefits would occur. HcMever, no data exist to justify such a
prediction, or quantify it at this time.
5. Tolerance Assessment
Tolerances have been established for residues of the sodium salt of
fomesafen in or on the foll iing raw agricultural a)nlnodity (40 CFR
180. ):
Cotimodity Tolerance (ppm )
Soybeans 0.05
There are no international tolerances/residue limits for fomesafen.
There are sufficient residue chemistry data avail?ble to supoort this
tolerance, including plant and animal metabolism, storage stability
(for both the parent coirpound and its metabolites), field residue
studies, and analytidal methods- Cattle and poultry feeding studies
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were not submitted. However, under the proposed conditions of use,
measurable residues are not expected to be found in the raw agricul-
tural cc mod1ties or fractions. These data are therefore not now
necessary.
The Acceptable t ily Intake (ADI) and the Maxlinim Permissible Intake
(MPI) are two ways of expre8slng the amount of a aub8tance that the
Agency believes, on the basis of the results of data fran animal
studies and the application of “safety” or “uncertainty” factors,
nay safely be ingested by humans without risk of’ adverse health
effects. The ADI is expressed in terms of milligrams (mg) of the
substance per kilogram (kg) of body weight per day (mgJkg/day). The
MPI, a related figure, is obtained by assuming a human body weight of
60 kg, and is expressed in terms of n,g of substance per da’y (mg/day).
The Agency has caicuieted an ADI for f’anesafen of u.uuc 5 mg/xg/day,
based on a ? )EL of 0.25 mg/kgJday in the rat oncogenicity study and a
hundredfold safety factor. The MPI for a 60 kg person is 0.15 mg/day.
These tolerances have a theoretical maxinaim residue contribution (ThRC)
of 0.0000115 mg/day in a 1.5 kg diet and would utilize 0. i6 percent of
the ADI.
6. Sumary of Major Data Gaps
Data required:
Time Generally Allowed for
uice1.. e uinber Study Fespoiise to Data heque :
:...
161-2 Photodegradatlon — water 9 months
161—3 Photodegradatlon — soil 9 months
162—2 Anaerobic soil metabolIsm 27 months
163-1 LeachIng (degradates) 12 months
16 1 1 —i Soil field dissipatIon 27 months
165—1 RotatIonal crops
(confined) 39 months
Ground water monitoring 27 months
Interim reports due
at 6 months and 18
months
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Contact Person at EPA :
Richard F. Mountfort
Product Manager (23)
Registration Division (TS-767C)
F viromenta1 Protection Agency
zeol M Street S11.
Washington, D.C. 201460
(703) 557—1830
DISCLATh1 : The Information pres ted in this Pesticide Fact eet
is for Infon tional purp es only and n y not be u ed to fulfill data
requir nents for pesticide registration and reregistration.
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