United Stitaj Office of Pesticide) and TOXK Sufa*tanc«i
Environmental Protection Office of Pentad* Programs (TS-766C)
Agency Washington. DC 20460
c/EPA Pesticide
Fact Sheet
Name of Chemical: Lactofen
Reason for Issuance: New Chemical Registration
Date Issued: March 18, 1987
Fact Sheet Number: 128
1. Description of Chemical
Generic Nane: l-(<»rboethoxy)ethyl-5-[2-chloro--4-(trifluoro-
methyl )Fhenoxy]-2-nitrbbenzoate
Gorrmon Name: Lactofen
Trade Nanes: Cobra", PPG-844
EPA Shaughnessy Code: 128885
Chemical Abstracts
Service (CAS) Number: 77501-63-4
Year of Initial
Registration: 1987
Pesticide Type: Herbicide
Chemical Family: Diphenyl ethers
Producer: PPG Industries, Inc.
2. Use Patterns and Formulations
Application sites: Used for postemergent control of broadleaf weeds
on the terrestrial food crop - soybeans.
Types of formulations: Manufacturing-use product containing 60%
active ingredient (ai). End-use product containing 23.2% ai formulated
as an enulsifiable concentrate.
Ususal carrier: Water. Crop oil concentrates and surfactants may
also be used with the agricultural use formulation.
Types and methods of application: Lactofen is applied by both ground
and aerial application.
-------
—2—
Application rates: Application rates for soybeans range from 10 to
12.5 fluid ounces per acre (0.16 to 0.2 lb/aiiM depending on the
target weed species.
3. Science Findinqs
SuJTm ary Science Statement: Lactofen has been found to be oncogenic
in mice and rats and has been classified as a Group 82 oncogen (Probable
Human Carcinogen). A quantitative risk estimate has been conducted for
the use of lactofen on soybeans. Based on a Q* = 1.7 x l0 1 (m /kg/day)l
and using a Theoretical Maxinum Residue Contribution (TMRC) of 0.000017
rrqlkg (1.5 kg diet) the “worst case” dietary risk was calculated to be
2.9 incidences in a million (2.9 x 10—6). Using the TMRC provides a
conservative estimate since it does not consider the effect of
processing on residue levels in the raw agricultural con iodity, that
actual residue levels will be lower than the tolerance level (0.05 ppm),
and that less than 100 percent of the crop is treated. The 0.05 ppm
level is based on a conservative assun tion that lactofen and its four
metabolites could each be theortically present in an amount just below
the level of dectection of the individual coirpounds (0.01 ppm).
Based on exposure estimates for use of lactofen on soybeans and the Q*,
the following ranges in risk numbers were calculated:
Private Applicators
Ground boom application:
Low l0—
Mean
High l0— to l0—
Mixing, loading, and spraying:
Open loading system i0 to 10
Closed loading system i0
Coemerical Applicators
Aerial application
- Pilots: i0 5 to 10—6
Flaggers: l0—
Mixing/loadinqjaerial application:
Open loading system l0— to l0—
Closed loading system i0
Ground Boom application
Mixing loading and spraying
Open loading system l0
Closed loading system l0 to l05
-------
—3—
These estimates assume that workers are wearing long—sleeved shirts,
long pants, and shoes; protective gloves are worn during mixing and
loading, and 10 percent dermal absorption.
Lactofen is not considered to be teratogenic and the chemical did not
significantly impair reproductive ability in a two—generation
reproductive effects study in rats. Pour rrutagenicity studies with
lactofen were negative. A second Ames test was positive.
Lactofen is not acutely toxic to humans or avian species. The
pesticide is highly toxic to fish and moderately toxic to aquatic
invertebrates. Environmental fate studies sh i that lactofen does
not persist significantly in the environment, that it is relatively
iui&bile, and therefore should not pose a risk of leaching to ground
water.
An applicator carcinogenic warning and fish toxicity statements are
reguired to appear on the product’s labeling.
Chemical Characteristics :
Physical state: White crystalline solid (Pure Grade Active Ingredient
(PGAII)
Molecular forirula: C19 H 15 Cl F 3 N07
Molecular weight: 461.8
Odor: Very faint aromatic
Solubility: 96 ppb (22 °C) in water
(l i solubility)
Melting point: 43.9 — 45.5 °C (PGAI)
vapor pressure: 8 x i0 9 rI11 Hg at 25 °C (extrapolated)
(nonvolatile)
Toxicoloqical characteristics :
Acute oral toxicity (rat): 5960 rrEg/kg
(relatively nontoxic)
Acute dermal toxicity (rabbit): Greater than 2000 mg/kg
(moderately toxic)
Acute Inhalation: Greater than 6.3 mg/L
(moderately toxic)
Dermal sensitization: Nonsensitizing
Primary Dermal Irritation: Very slight erythema subsiding within 76
hours.
-------
—4—
Prin ry Eye Irritation: Redness of iris and redness and che Tosis of
the conjunct iva disappearing by 72 hours post—
administration.
Subdironic Effects: In a 90-day feeding study in the rat at doses
of 40, 200 and 1000 ppm, the no—observed—effect
level (NOEL) is 200 ppm (10 mg/kg/day) and
lc iest—observed—effect level (LOEL) is 1000 ppm
(50 nq/kqjday).
Chronic effects :
Chronic Feeding!
Oncogenicity: An 18-uonth oncogenicity study in CD-i mice at doses
of 10, 50, and 250 ppm in the diet was positive for
oncogenic response. A statistically significant
increased combined incidence of liver adenomas and
carcinanas was observed at 250 ppm in both sexes.
The lc iest dose, 10 ppm (1.5 m/kg/day), was the
WEL with increased liver weight and hepatocylomegally.
A 2-year chronic feeding/oncogencity study in Sprague—
Dawley rats at doses of 500, 1000, and 2000 ppm in the
diet was positive for oncogenic response. A statistically
significant increase of liver neoplastic nodules and
foci of cellular alteration was observed in both sexes
at 2000 ppm. The systemic NOEL is 500 ppm (25 mg/kg/day)
and the LOEL is 1000 ppm (50 mg/kg/day) based on
kidney and liver pigmentation.
In a 1—year feeding study with beagle dogs, the
NOEL is 200 ppm (5 mg/kg/day) and the LOEL is
1000/3000 ppm (25/75 mg/kg/day) based on renal
dysfunction, and decreased Hgb, Hct, RBC and cholesterol.
Mutagenicity: Unscheduled DNA synthesis, chrorrcsomal aberration, DNA
repair assay, and one Ames Study are negative. A
second Ames test in strain TA 1538 of Sa1n ne1la
typhinurium at 5000 and 7500 g/p1ate (precipitates
formed in plates) is positive.
Two-Generation Reproduction (rat): Charles River CD rats were dosed
with 0, 50, 500, and 2000 ppm
lactofen in the diets. The
reproductive NOEL is 50 ppm
(2.5 nujkqjday) and the WEL is 500
ppm (25 mg/kg/day) based on
reduced mean pup weight, and
increased pup heart and liver
weight.
-------
—5—
Developnental Toxicity: Sprague —Dawley rats were dosed with 0, 15,
50, and 50 mg/kg/day lactofen in the diet.
The maternal and developnental toxicity NOEL
is 50 mg/kg and the LOEL is 150 mgj’kg/day
based on maternal post inpiantat ion loss and
reduced body weight and fetal bent ribs.
New Zealand White rabbits were dosed with 0,
1, 4, and 20 mg/kg/day lactofen in the diet.
The NOEL is 4 rrq/kg/day and the LOEL is 20
mg/kg/day based on reduction in maternal
food consumption with no developnental toxicity
occurring at any dose level tested.
Physioloqical and Biochemical Behavior Characteristics :
Foliar absorption: Contact activity results in relatively rapid
krlockdcNri of weeds.
Translocation: In presence of rainfall, plants absorb lactofen from
soil by root uptake.
Environmental Characteristics :
Lactofen is relatively stable to hydrolysis at 25 °C in H 5 and pH 7
but rapidly hydrolyzes in pH 9 solutions. Lactofen was found to
degrade quickly under aerobic soil conditions and degrades under
anaerobic conditions. Lactof en half—life under photolysis conditions
was 23 days. Lactofen was found to be immobile in soil. Degradation
products are highly mobile in sandy soils and have moderate to lc i
nobilities in soils that have a high silt and clay content. H ever, in
an aged column leaching study total radioactivity found in the leachate
comprised only 0.27 percent of that applied and was determined to be
extensively degraded products. Lactofen was found to have a field
dissipation rate of less than or equal to 7 days in a variety of
soils. Field rotational crop data indicate residues are not taken up
by grains, leafy vegetable, or root crops. Lactofen was found to
accu,rulate in bluegill sunfish with a bioaccunlilation factor of 380X
for whole fish after 30 days. Depuration was rapid.
Ecoloqical Characterisics :
Avian acute oral toxicity:
Bot jhite quail > 2510 mg/kg
(Practically nontoxic)
Avian dietary toxicity:
Mallard duck and bo hite quail > 5620 ppm
(Practically nontoxic)
-------
—6—
Freshwater fish acute toxicity
Blugill sunfish: > 100
(Highly toxic)
RainbcM trout: > 100 ppbi/
0.81 ppm /
(Highly toxic)
Freshwater fish 7—day fl i—through: > 100 ppb /
k uatic invertebrate acute toxicity
Daphnia maqna : > 100 ppb /
2.0 ppm (I AI above solubility)
4.8 ppmY
(Moderately toxic)
Hon ’ Bee acute contact toxicity: > 160 ug/bee
(Practically nontoxic)
Fish early life stage toxicity
(Sheepshead minn .i): Maximum acceptable toxicant
concentration > 0.78 < 1.6 ppm.
These data indicate that lactof en is essentially nontoxi.c to avian
species and bees; and that it is highly toxic to fish and noderately
toxic to aquatic invertebrates. Based on the acute and chronic data
no significant problems to nontarget organisms are expected from
lactof en’s use on soybeans.
4. Tolerance Assessment
Tolerances have been established for the combined residues of lactofen
and its metabolites containing the diphenyl ether linkage in or on
the foll ing raw agricultural caiuirdity (40 CFR 180. ):
- ConiT odity Tolerance (p )
Soybeans 0.05
There are no international tolerances/residue limits for lactofen.
i/Maximum solubility of technical grade active ingredient (TGAI)
Expressed as active ingredient derived from studies conducted with
end—use product.
-------
—7--
There are sufficient residue chemistry data available to support this
tolerance, including plant and animal metabolism, storage stability
(for both the parent compound and its metabolites), field residue
studies, and analytical methods. Cattle and poultry feeding studies
were not submitted. H ’jever, under the proposed conditions of use,
measurable residues are not expected to be found in the raw agricultural
ccmuxxlities or fractions. These data are therefore not n ’i necessary.
The Acceptable Daily Intake (ADI) and the Maximum Permissible Intake
(MPI) are two ways of expressing the anount of a substance that the
Agency believes, on the basis of the results of data from 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 (mg/kg/day). The MPI, a
related figure, is obtained by assuming a human body weight of 60 kg,
and is expressed in terms of mg of substance per day (mg/day).
The Agency has calculated an ADI for lactofen of 0.0015 irg/kqjday,
based on a WEL of 1.5 mg/kg/day in the n use oncogenicity study
and a thousandfold safety factor. The MPI for a 60 kg person is 0.09
mg/day. These tolerances have a theoretical maximum residue contribution
(TMRC) of 0.000017 mg/day in a 1.5 kg diet and would utilize 1.13 percent
of the ADI.
5. Contact Person At EPA
Richard F. Mountfort
U.S. Environmental Protection Agency
TS-767C
401 M Street, SW.
Washington, D.C. 20460
DISCLkIMER: The information presented in this Pesticide Fact Sheet is
for informational purposes only and may not be used to fulfill data
reguirements for pesticide registration and reregistration.
------- |