United States Office of Pesticide* and Toxic Subttancat
Environmental Protection Office of Pectiade Programs (TS-766C)
Agency Wohington, DC 20460
v°xEPA Pesticide
Fact Sheet
Name Of Chemical: Dimethyl (l,2-Phenylene)-bis (i
Reason for Issuance: thioyl) bis (carbamate)
Date ISSUed: q/Q, Re9lstration Standard
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Fact Sheet Number: 92
DESCRIPTION OF CHEMICAL
Common Name: Thiophanate-inethy 1
Trade Names: NF44, AC 87,844, Topsin M, Cercobin M, Mildothane,
Cycosin, Fungo, Fungo 70, Spot-kleen, TD-1771,
Thiophanate-methyl
Empirical Formula: C\2H14^0482
Chemical Abstracts
Service (CAS) Number: 23564-05-8
Pesticide Chemical Code (Shaughnessy): 102001
Pesticide Type: Systemic fungicide
Chemical Family: Carbamates
U.S. and Foreign
Producers: Agchem Division of the Pennwalt Corporation
USE PATTERNS AND FORMULATIONS
k
Application sites: Thiophanate-methyl is registered for control
of plant diseases on almonds, apples, apricots, bananas, beans,
celery, cherries, cucumbers, melons, nectarines, onions,
ornamentals, pecans, peaches, peanuts, plums, potatoes, pumpkins,
soybeans, squash, strawberries, sugar beets, sugarcane,
turf, and wheat.
Type of formulations: 94.3% technical grade, dusts (2.5, 5%),
granular (1.75, 2.3, 5.5%), wettable powder (l.~75, 15, 24.4,
25, 50, 70%), a 19.65% liquid, and a 46.2% flowable.
Types and methods of applications: End use products are applied
aerially, banded, broadcasted, and applied over-the-top
with ground equipment. Thiophanate-methyl is also used as ^
a post harvest dip for fruits, as a seed piece treatment,
as a soil drench for ornamentals, and as a soil furrow spray.
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Application rates: 0.26 to 2.8 lb ai/A on crop sites, 0.033 to
0.36 lb ai/l000 sq ft on turf, 0.35 to 0.70 lb ai/l00 gal for
post—harvest treatments, and 0.175 to 1.16 lb ai/l00 gal for
seed piece treatments.
Usual carriers: Water, spray oil, or wax.
3. SCIENCE FINDINGS :
Summary science statements: Thiophanate-methyl is readily
absorbed by animals and partly metabolized to methyl-2-ben-
zimidazole carbamate (MBC). Eighty to ninety percent of
thiophanate—methyl orally administered to laboratory animals
is recovered in the excreta within 24 hours as parent compound
and metabolites (including MBC).
Thiophanate-methyl did not show any positive effects in -
ricogenic studies in the rat and mouse. However, the
fungicidal activity of thiophanate—methyl depends on its
c)nversion to MBC in the plants. MBC has been shown to
cause tumors solely in the mouse liver and has been tentatively
classified as a Group C oncogen (possible human oncogen).
No compound—related maternal or fetal effects were observed
- a rat teratology study. A mouse teratology study of
iophanate—methyl is incomplete. Therefore, another
rato1ogy study must be conducted. In a reproduction Study
rats the only signs of toxicity observed were decreased
: -p and litter weights at birth and during lactation for pups
J dams administered the high dose (640 ppm or 32 mg/kg/day).
:- a study with male mice given 5 consecutive oral daily
ioSe3 of 192 mg/kg body weight, there was no indication
Lflat thiophanate—methyl affected the function of the testes
or accesssory sex organs.
;cute toxicity studies of thiophanate—methyl indicate
Toxicity Category III based on dermal toxicity. ThiophanaC e-
methyl is virtually non—toxic to avian species and of low
to moderate toxicity to freshwater fish with the exc ptioii uZ
:atfish. Studies conducted with thiophanate—methyl show
t;— at it is highly toxic to catfish.
Available data are insufficient to fully assess the residues
of thiophanate-methyl and MBC in raw agricultural commodities.
Available data are insufficient to fully assess the environ-
mental fate of thiophanate—methyl.
Chemical characteristics: Thiophanate—methyl is a light—tan
crystalline powder that has a sulfidic odor at room temper-
ature. Its molecular weight is 342.4. It is stable at
neutral pH at 25° C in aqueous solution up to 25 days.
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Toxicological characteristics:
Acute toxicology effects of thiophanate—methyl are as follows:
Acute Oral Toxicity: male: 7,500 mg/kg body weight
(rat) female: 6640 mg/kg body weight
Toxicity category IV
Acute Derrnal Toxicity: >10,000 mg/kg body weight
(rat) Toxicity category III
Derrnal Sensitization: non—sensitizing
(guinea pig)
Subchronic toxicology effects of thiophanate—methyl are as follows:
Subchronic Oral (rats) NOEL = 64 ppm (3 mg/kg/day)
LEL = 320 ppm (16 mg/kg/day)
(decreased body weight gain)
At the highest dose tested (8000 ppm) thyroid histopathology
included decreased coloidal content and epithelial hypertropphy
in the follicles.
Chronic toxicology effects of thiophanate—methyl are as follows:
Thyroid histopathology similar to that observed in the subchronic
rat feeding study was found in the long—term studies in male
rats (32 mg/kg/day) and female dogs (250 mg/kg/day). Decreased
body weight gain in female rats and testicular histopathology
in male rats was noted at the 640 ppm (32 mg/kg/day) diet.
NOEL’S with respect to these effects were 8 mg/kg/day in
rats. A NOEL of 50 mg/kg/day in dogs was based on decreased
weight gain in males and changes in thyroid histology in females.
Oncogenic effects of thiophanate—methyl are as follows:
There were no compound related effects or tumor incidence
in mice after two years of feeding diets containing
0, 40, 160, or 640 ppm (0, 1.5, 6, 24, or 96 mg/kg/day)
Lhiophanate—methyl (a MTD was not reached in this mouse
study). No oncogenic potential was observed in the rat
study at the dietary levels up to 32 mg/kg/day, which did
approach a MTD.
Terat.ogenic effects of thiophanate-methyl are as follows:
No compound—related maternal or fetal effect were observed
in a limited teratology study in rats. In a second study,
pregnant rats received thiophanate—methyl in their diets during
gestation, and no fetal effects were observed. This study was
limited because the palatability of diets containing the
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highest dose was decreased by the fungicide. The highest
dose tested (1000 mg/kg/day) in a mouse study did not cause
toxicity in the dams or their fetuses. However, the report
was incomplete and, therefore, a teratology study in a second
species is needed.
Reproductive effects of thiophanate-methyl are as follows:
In a three—generation reproduction study in rats, there was
no effect on fertility, viability, gestation, or lactation
indices. There was a decrease in pup and litter weights
at the 640 ppm diets. The NOEL for this effect was 8 mg/kg/day.
Mutagenic effects of thiophanate—methyl are as follows:
In mutagenicity tests, thiophanate—methyl did not induce
reverse mutations in bacteria or affect fertility.
Major routes of human exposure:
Dermal, ocular, and inhalation exposures to workers
may occur during application. Exposure from mixing,
handling, and application of the dusts, granulars and
wettable powders is expected to be mainly dermal.
Physiological and biochemical behavioral characteristics:
Translocation: Thiophanate-methyl is mobile in the xylem
and the phloem.
Mechanism of pesticidal action: Thiophanate—methyl inhibits
the growth of plant pathogens.
Environmental characteristics: Available data are insufficient
to fully assess the environmental fate of thiophanate—methyl
and the potential exposure of humans and nontarget organisms.
An aerobic soil metabolism study is the only environmental fate
study available for thiophanate-methyl. In order to assess the
environmental fate and transport of, and the potential exposure
to thiophanate-rnethyl, the Agency is requiring a full range of
environmental ‘fate studies.
Ecological characteristics: Available data indicate that
thiophanate—rnethyl has very low toxicity to birds, is slightly
toxic to sunfish and trout, and very highly toxic to catfish.
MBC has been shown to be highly toxic to fish. Thiophanate—methyl
has been shown to be moderately toxic to aquatic invertebrates.
Aquatic invertebrate toxicity:
Daphnia magna 27 ppm
96 hour fish toxicity:
Bluegill sunfish 15.8 — 58 ppm
Rainbow trout 8.3 — 25.2 ppm
channel catfish 0.030 ppm
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Avian dietary toxicity:
Mallard duck >10,000 ppm
Bobwhite quail >10,000 ppm
Potential problem for endangered species:
A review by the Agency indicates that two endangered
catfish species inhabit areas where soybeans are grown
and which may be treated with thiophanate—methyl.
Tolerance Reassessment :
Listed below are tolerances which have been established for
residues of thiophanate—methyl on a wide range of raw agricultural
products listed in 40 CFR 180.371.
The most appropriate NOEL’s for this tolerance reassessment
are those from the chronic and reproduction studies in rats
(160 ppm or 8 mg/kg/day). There were no effects in any other
study that evaluated doses at or below that NOEL. Using a safety
factor of 100 and the 8 mg/kg/day NOEL, the ADI for humans was
calculated as 0.08 mg/kg/day. The maximum permissible intake
(MPI) for a 60 kg adult is 4.8 mg/l.5 kg diet.
To date the tolerances granted have accounted for approximately
22.85% of the acceptable daily intake with a theoretical maximum
residue contribution (TMRC) to the daily diet of 1.0969 mg/day
(for an average 1.5 kg daily diet).
Commodity Tolerance (ppm )
Almonds pre—H 0.2
Almonds (hulls) pre—H 1.0
Apples (pre— and post—H) 7.0
Apricots (pre— and post—H) 15.0
Bananas (pre—H) 2.0
Bananas, pulp (pre—H) 0.2
Beans (snap and dry) pre—H 2.0
Bean (forage and hay) pre—H 50.0
Cattle, fat 0.1
Cattle, kidney 0.2
Cattle, liver 2.5
Cattle, meat byproducts
(exc. kidney and liver) 0.1
Cattle, meat 0.1
Celery (pre-H) 3.0
Cherries (pre— and post—H) 15.0
Cucumbers 1.0
Eggs 0.1
Goats, fat 0.1
Goats, kidney 0.2
Goats, liver 2.5
Goat, meat byproducts
(exc. kidney and liver) 0.1
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Commodity Tolerance (ppm)
Goat, meat 0.1
Hogs, fat 0.1
Hogs, liver 1.0
Hogs, meat byproducts(exc. liver) 0.1
Hogs, meat 0.1
Horses, fat 0.1
Horses, liver 1.0
Horses, meat byproducts (exc. liver) 0.1
Horses, meat 0.1
Melons 1.0
Milk 1.0
Nectarines (pre— and post—H) 15.0
Onion, dry 3.0
Onion, green 3.0
Pecans (pre—H) 0.2
Peaches (pre— and post—H) 15.0
Peanuts pre—H 0.2
Peanuts (hulls) pre—H 2.0
Peanuts (forage and hay) pre—H 15.0
urns (pre— and post—H) 15.0
.otatoes (seed treatment) 0.05
Poultry, fat 0.1
cu:Ltry, liver 0.2
“Ltry meat byproducts (cxc. liver) 0.1
Itry, meat 0.1
r nes (pre— and post—H) 15.0
Pumpkins 1.0
fat 0.1
Sheep, kidney 0.2
Sheep, liver 2.5
Sheep, meat byproducts
(exc. kidney and liver) 0.1
‘heep, meat 0.1
;oybeans (pre—H) 0.2
..quash 1.0
Strawberries (pre—H) 5.0
Sugar beets (roots pre—H) 0.2
sugar beets (tops pre—l-1) 15.0
-Zu jarcane (seed piece treatment pre—H) 0.1
Wheat, grain 0.05
;heat, hay 0.1
wheat, straw 0.1
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Problems known to have occurred with use:
The Pesticide Incident Monitoring System (PIMS) did not
identify any incidents involving agricultural/domestic uses
of thiophanate—methyl from 1966 to present.
4. SUMMARY OF REGULATORY POSITION AND RATIONALE :
Based on the review and evaluation of all available data and other
relevant information on thiophanate-methyl, the Agency has
made the following determinations:
a. The Agency will not place thiophanate—methyl and its metabolite
MBC into Special Review [ Section 162.11(a) of CFR 401
Thiophanate-rnethyl was previously placed in Special Review
by the Agency in December, 1977, because of its potential
adverse effects on nontarget organisms and because its
metabolite, MBC, had the potential to cause mutagenic -
effects. It was removed from the special review process
in October, 1982 because it was determined that the risks
were not unreasonable and were exceeded by the benefits
associated with the use of thiophanate—methyl products.
MBC has been classified as a Group C oncogen (possible human
oncogen). The current risk analysis performed for thiophanate—
methyl, based on its metabolite MBC, is of the same order
of magnitude as those calculated in the PD 4 for benomyl
(i.e. 10 4 to iO ).
Although MBC is associated with liver tumors in Swiss and Swiss
derived mice (CD—i), MBC is not associated with liver tumors in
NMRKf strain of mouse , which has a low background incidence of
liver tumors. MBC was not oncogenic in the rat and only
weakly mutagenic as a possible result of inhibition of the
cellular spindle apparatus rather than direct gene mutation
or alteration of DNA repair.
The Agency has concluded that the risks to humans posed by
thiophanate—methyl are minimal and of the same magnitude as
estimated in the 1982 decision. The Agency has also reviewed
the benefits of thiophanate—methyl and has concluded that the
benefits have not changed significantly since the 1982
decision. The benefits of thiophanate—methyl outweigh its
risks with the protective measures on the label. Hence
inititation of an additional special review is not necessary
at this time.
h. The Agency does not intend to establish new food additive
regulations pursuant to Section 409 of the Federal, Food,
Drug, and Cosmetic Act (FFDCA). The Agency is deferring
action on the presently established food additive regulations
until receipt and evaluation of comments in response to a
Federal Register notice discussing this issue. This notice
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C. The Agency is not requiring a reentry interval for currently
registered uses of thiophanate—methyl. The acute toxicity
for thiophanate—methyl is low (Category IV) except for
dermal irritation (Category III). Additionally, exposure
and the resultant risks to field workers are not expected
to be significant because thiophanate—methyl is expected
to be poorly absorbed dermally. The SAP is being asked
if a dermal absorption study should be required.
d. The Agency is imposing labeling restrictions on rotational
crops. The extent of the restrictions will be reconsidered
when additional data are submitted and reviewed. The
restrictions will serve to protect the public from
impermissable residues in food and feed. In addition
this restriction will protect subsequent planted crops
from possible effects due to persistent residues of
thiophanate-methyl in the soil.
e. The Agency has determined that the available data are
insufficient to fully assess the environmental fate of
thiophanate-methyl. Preliminary laboratory data show that
thiophanate—methy]. and its degradate MBC are moderately
mobile in Lakeland sand and Sultan silt loam columns.
The Agency determined that two endangered catfish species
inhabit areas where soybeans may be grown. To protect
Lhese species, endangered species labeling is required.
Site: The Agency has not proposed changes in thiophanate-
methyl’s uses.
‘ cci.fic Label Warning Statements:
‘he following required label statements must appear on the labels
f all products in channels of trade within two years [ April
‘0, 19881 of issuance of this Standard. After review of data
to be submitted under this Standard, the Agency may impose
additional label requirements or take further regulatory actions
. ; necessary.
1. Manufacturing—Use Product Statements
: ii products intended for formulation into EPs must bear
Lhe following environmental hazard statement:
“Do not discharge effluent containing this ptodu& directly
into lakes, streams, ponds, estuaries, oceans or public
waters unless this product is specifically identified and
addressed in a National Pollutant Discharge Elimination System
(NPDES) permit. Do not discharge effluent containing this
product into sewer systems without previously notifying the
sewage treatment plant authority. For guidance, contact your
State Water Board or Regional Office of the Environmental
Protection Agency.”
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2. End—Use Product Statements
The following environmental hazard statement must appear
on all EP’s:
“This pesticide is toxic to catfish. Do not apply directly
to water or wetlands (swamps, bogs, marshes, and pot holes)
Drift and runoff from treated areas may be hazardous to
catfish in adjacent areas. Do not contaminate water by
cleaning of equipment or disposal of wastes.”
——for granular products add “cover or incorporate spills.”
Restrictions on Rotational Crops
“Do not plant food or feed crops in thiophanate—methyl
treated fields for 18 months after the last application unless
thiophanate—methyl is registered for use on those crops.”
Endangered Species Information for use on Soybeans
The following must appear on all EP’s registered for use
on Soybeans:
“ ENDANGERED SPECIES RESTRICTIONS
The use of any pesticide in a manner that may kill or other-
wise harm an endangered or threatened species or adversely
modify their habitat is a violation of federal laws. The
use of this product is controlled to prevent death or harm
to endangered or threatened species that occur in the fol-
lowing counties or elsewhere in their range.
STATE
Species
COUNTY
OHIO
Scioto madtom
CHAMPAGNE
FRANKLIN
LOGAN
MADISON
PICKAWAY
UNION
TENNESSEE
Yellowf in madtom
CLAIBORNE
HANCOCK
VIRGINIA
Yellowfin madtom
LEE
RUSSELL
SCOTT
S
Before using this pesticide in these counties you must obtain
the EPA Cropland Endangered Species Bulletin (EPA/ES—CROP).
The use of this pesticide is prohibited in these counties
unless specified otherwise in the Bulletin. The EPA Bulletin
is available from either your County Agricultural Extensid n
Agent, the Endangered Species Specialist in your State
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Wildlife Agency Headquarters, or the appropriate Regional
Office of either the U.S. Fish and Wildlife Service (Fws)
or the U.S. Environmental Protection Agency (EPA). THIS
BULLETIN MUST BE REVIEWED PRIOR TO PESTICIDE USE. ”
5. SUMMARY OF MAJOR DATA GAPS :
The toxicological studies are required on the following dates:
January
January
January
April 30
June 30,
April 30,
April 30,
April 30,
31, 1987
31, 1987
31, 1987
1987
1990
1987
1987
1987
The environmental fate data are required on the following dates:
Hydrolysis
Photodegradation in water and on soil
Anaerobic Soil
Leaching and Adsorption/Desorption
Volatility (lab)
(field)
Soil dissipation
Accumulation — rotational crops (confined)
— rotational crops (field)
— fish
January 31, 1987
January 31, 1987
July 31, 1988
April 30, 1987
April 30, 1987
July 31, 1987
July 31, 1989
July 31, 1989
June 30, 1990
April 30, 1987
The ecological effects data are required on the following dates:
Acute Avian Oral Toxicity
Avian Subacute Dietary Toxicity — waterfowl
Acute Toxicity to Aquatic Invertebrates
January
January
January
31 , 1987
31, 1987
31, 1987
The residue chemistry data are required on the following dates:
Nature of residue (animal metabolism)
Residue Analytical Methods
Storage Stability Data
Residue studies on crops, processed
food/feed commodities
Acute Inhalation Toxicity — rat
Eye Irritation — rabbit
Derinal Irritation — rabbit
Teratogenicity
Oncogeriicity — mouse
Structural Chromosomal Aberration
Mechanisms of Mutagenicity
Dermal Absorption Study
October 31, 1987
October 31, 1987
July 31, 1987
A ril 30, 1988
Product chemistry data required within a year of issuance of
standard.
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6. CONTACT PERSON AT EPA
Henry M. Jacoby, PM 21
Office of Pesticide Programs, EPA
Registration Division (TS—767C)
Fungicide-Herbicide Branch
401 M Street., 20460
(703) 557—1900
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 reregistration.
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