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Environmental Protoaion Office of Pwcicid* Piuy«tin (TS-7SaC)
Agency Wtahlnfton. DC 20490
540/FS-88-133
&EPA Pesticide
Fact Sheet
Name of Chemical:
Reason for Issuance: Registration Standard
Date Issued: October 24, 1988
Fact Sheet Number: 48.1
1. Description of Chemical
Chemical Name: 4-amino-3,5,6-trichloropicolinic acid
Common Name: picioram
OPP Chemical Code: 005101
Chemical Abstracts Service (CAS) Number: 1918-02-1
Year of Initial Registration: 1964
Pesticide Type: Herbicide
Chemical Family: Picolinic acid
U.S. Producer: Dow Chemical, U.S.A.
Chemical Name: Potassium salt of 4-amino-3,5,6-trichloropicolinic
acid
Common Name: Picioram, Potassium (K) salt
OPP Chemical Code: 005104
CAS No.: 2545-60-0
Chemical Name: Isooctyl ester of 4-amino-3,5,6-trichloropicolinic
acid
Common Name: Picioram, Isooctyl ester (IOE) of picioram
OPP Chemical Code: 005103
Chemical Name: Triisopropanolamine salt of 4-amino-3,5,6-trichloro-
picolinic acid
Common Name: Picioram, TIPA salt
OPP Chemical Code: 005102
Chemical Name: Triethylamine salt of 4-amino-3,5,6-trichloropicolinic
acid
Common Name: Picioram, TEA salt
OPP Chemical Code: 005105
Chemical Name: Isopropanolamine salt of 4-amino-3,5,6-trichloropico-
linic acid
Common Name: Picioram, IPA salt
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2. Use Patterns and Formulations
Application Sites:
Picloran, potassiun salt: Terrestrial food crop use on small grains,
flax, pastures and rangeland grasses; Terrestrial noncrop use
\ on noncrop agricultural areas and rights-of-way; Forestry use on
forest lands site preparation.
Picloram, isooctyl ester: Terrestrial noncrop use on industrial
sites and rights-of-way; Forestry use on forest trees site
preparation.
Picloram triisopropanplamine salt: Terrestrial food crop use on
small grains and pastures and rangeland; Terrestrial nonfood crop
use on uncultivated agricultural areas, rights-of-way, and industrial
sites; Aquatic noncrop use on drainage ditch banks; Forestry
use on forest trees.
Picloram, triethylamine salt: Terrestrial food crop use on pastures
and rangelands.
Types and Methods of Application: By ground: broadcast or spot
treatment as foliar or soil spray; as a basal spot treatment,
broadcast as pelletized spray; as tree injection, as frill treat-
ment; as a stump treatment, as basal bark treatment, as a wick
application, and as a low-volume dormant stem spray. By air:
broadcast and low-volume dormant spray.
Pests Controlled: Broadleaf weeds and woody plants.
Application fetes: (Section 3 registrations)
Picloram, TIPA salt: 0.27 to 3.00 pounds acid equivalent (Ib ae)
per acre (A)
Picloram, IDE: 0.5 to 3.0 Ib ae/A(mixtures or MAP)
Picloram, K salt: 1.0 to 8.5 Ib ae/A
Picloram, TEA salt: 0.25 to 1.0 Ib ae/A(SLNS)
Types of Formulations: [represented Sec 3 registrations of the potassium
salt(K)]: Formulation Intermediate: 30% ae or 34.7% acvtive
ingredient (ai), Pelleted: 2% ae or 2.3 ai, 5 ae or 5.855 ai, 1Q% ae
or 11.6 ai; Soluble Concentrate, Liquid: 2 Ib ae or 2^% ai, 2**.^
ai or 29.9% ai
Usual Carrier: Water
3. Science Findings
Summary Science Statement: Technical picloram is in Toxicity
Category I with respect to acute inhalation and Categories III and
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IV with respect to other acute toxicities. Picloram has been clas-
sified as Group D Oncogen (not classifiable to human carcinogenicity).
Repeat oncogenicity, teratology, and reproduction studies are
being required. Picloram does not appear to be mutagenic based
on available data.
Picloram is stable to hydrolysis, does not photodegrade under light,
and is relatively stable in anaerobic loam soils and under anaerobic
aquatic conditions and does not accumulate in fish. Picloram is
intermediately to very mobile in soils ranging in texture from
clay to loam. Picloram has been identified as a chemical with a
potential to contaminate groundwater.
The Agency is requiring that residue data depicting residues of HCB
in plant and animal commodities be submitted.
Picloram is practically nontoxic to avian species, slightly to
moderately toxic to freshwater fish, and slightly toxic to freshwater
invertebrates.
Chemical Characteristics:
Technical Picloram (Acid):
Color: White
Physical State: Powder
Odor: Chlorine like
Melting Point: 215 °C (decomposes)
Bulk Density: 19.7 Ib/cu ft
Solubility at 25 °C:
0.043 g/100 mL - Water
0.55 g/100 mL - Isopropanol
1.05 g/100 mL - Ethanol
1.98 g/100 mL - Acetone
0.12 g/100 mL - Diethyl ether
0.16 g/100 mL - Acetonitrile
1.85 g/100 mL - Methanol
0.06 g/100 mL - Methylene dichloride
0.02 g/100 mL - Benzene
0.001 g/100 mL - Kerosene
Vapor Pressure: 6.16 x 10~? millimeters (mm) Hg at 35 °C
1.07 x ID"6 mm Hg at 45 °C
Storage Stability: Stable under normal conditions.
Picloram, Potassium (K) Salt (34.7% ai)
Color: Dark brown
Physical State: Liquid
Odor: Alcoholic
Bulk Density: 1.320 at 20 °C
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Toxicology Characteristics;
Existing data are all based on picloram (technical) or K salt.
Rirther data are requested for the IOE, TIPA salt, TEA salt, and
IPA salt.
Acute Toxicology - Technical (Acid);
o Acute Oral Toxicity (Rats): Greater than (» 5000 ing/kg body
wsight for males - Toxiclty Category IV; = 4012 mg/kg for
females - Toxicity Category III
o Acute Dermal Toxiclty (Rabbits): > 2000 mg/kg for males and
females, Toxicity Category III
o Acute Inhalation (Rat): > 0.035 mg/L for males and fanales,
Toxicity Category I
o Primary Eye Irritation (Rabbit): Moderate eye irritation,
Toxicity Category III
o Primary Dermal Irritation (Rabbit): Not an irritant, Toxicity
Category IV
o Dermal Sensitization (Guinea Pig): Not a skin sensitizer
Acute Toxicology (K Salt);
o Acute Oral Toxicity (Rat): > 5000 mg/kg for males,
Toxicity Category IV; = 3536 mg/kg for females, Toxiclty
Category II
o Acute Dermal Toxicity (Rabbit): > 2000 mg/kg for males and
females, Toxicity Category III
o Acute Inhalation Toxicity (Rat): > 1.5 mg/L for males and
females, Toxicity Category II
o Primary Eye Irritation (Rabbit): Moderate eye irritation,
Toxiclty Category III
o Primary Dermal Irritation (Rabbit): Not a skin irritant,
Toxicity Category IV
o Dermal Sensitization (Guinea Pig): Skin Sensitizer*
•Requires statement for skin Sensitization: "May Cause
Allergic Skin Reaction."
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Acute Toxicology (IOE);
o Acute Oral Toxlclty (Rat): > 3500 rag/kg for males and females,
Tbxicity Category III
o Acute Dermal Toxicity (Rabbit): > 2000 mg/kg for males and
females, Tbxicity Category III
o Acute Inhalation Tbxicity (Rats): > 0.35 mg/L for males and
females, Tbxicity Category II
o Primary Eye Irritation (Rabbits): Moderate eye irritation,
Toxicity Category III
o Primary Dermal Irritation (Rabbit): Mild skin irritation,
Tbxicity Category III
Subchronic Toxicology Studies;
An acceptable 13-week subchronic feeding study in rats is available
for picloram. The no-observed-effect level (NOEL) for this study
was 50 mg/kg. A dose dependent increase in absolute and relative
liver weights was seen at 150 mg/kg.
An acceptable 6-month feeding study with dogs is available for
picloram. The NOEL for this study was 7 mg/kg. A decrease in
food consunption and increase in liver weights was noted at the
highest dose.
No subchronic feeding studies are available for the TIPA, TEA, IPA, or
IOE forms of picloram. Subchronic feeding studies are required in
a rodent and a nonrodent for each form of picloram.
A 21-day subchronic dermal study is not available for picloram. This
study is required for all forms of picloram.
Chronic Feeding Studies:
An acceptable 2-year chronic feeding study with rats is available for
picloram. An increase in size and altered tinctorial properties
of centrilobular hepatocytes occurred in males and females at the
high (200 mg/kg/day) and mid (60 mg/kg/day) dose resulting in a
NOEL of 20 mg/kg/day for this study.
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A chronic feeding study in nonrodents is not available for picloram
and is required.
Oncoqenicity Studies:
The available oncogenic data for picloram include mouse and rat
studies performed by the National Toxicology Program (NTP) and a
rat study performed by Dow Chemical U.S.A.
An oncogenic effect (neoplastic nodules) was seen in female rats at
the highest dose in the NTP study. This study was unacceptable
based on experimental design (too short exposure limit, insuffi-
cient information to determine if a maximum tolerated dose [MTD]
was attained).
No oncogenic effects were noted in either the mouse study done by NTP
or the rat study done by Dow. These studies were not acceptable
because the available information was insufficient for determining
if an MTD had been reached.
The test material in all of these studies contained the contaminant
hexachlorobenzene (HCB), which is classified by the Agency as a
Group B2 oncogen (probable human carcinogen). Picloram was clas-
sified as a Group D oncogen (not classifiable as to human carcino-
genicity). The Agency is requiring that both the mouse and rat
oncogenicity studies be repeated.
Teratoqenicity and Reproduction:
A teratogenicity study in rabbits is available for picloram. A small
number of fetuses showed abnormalities such as missing ribs,
omphalocele, and hypoplastic tail. Historical control data are
required to evaluate the observed abnormalities.
A teratology study in rats is available for picloram. No teratogenic
effects were noted. Some fetotoxicity was present at the lowest
dose. Because a NOEL cannot be set for the study a repeat
teratology study in rats is required.
A multigeneration reproduction study in rat is available for picloram.
No reproductive effe:ts were observed however, too few test animals
were used and no toxicity was observed at the highest dose.
Therefore, a 2-generation reproduction study is required for
picloram.
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No teratology or reproduction studies are available for the ester and
amine forms of picloram. Teratology studies in rats and rabbits
are required for all ester and amine forms of picloram. Reproduction
studies are not required at this time.
Mutagenicity;
Picloram did not show evidence of chromosomal changes in a cytogenetlc
bone marrow study exposing rats up to 2000 mg/kg of picloram.
No other acceptable mutagenicity studies are available for picloram,
its salt, ester, or amine forms. Additional mutagenicity data are
required for picloram, its esters, and its amines.
Metabolism;
Available rat metabolism data are not adequate to fulfill Guideline
requirements; therefore, additional studies are required.
Manufacturing Contaminants;
Technical picloram is contaminated with HOB, classified as a probable
human carcinogen (Group B2). Dietary and nondietary risk assess-
ments were performed by the Agency. Ihe Agency considered the
dietary and nondietary risk from HOB to be acceptable at this
time.
Nitrosoamines are a potential contaminant of tertiary amines (TEA)
and alkanolamines (TIPA) forms of picloram. Testing is required
to show that the level of 1 ppm nitrosoamine contamination is not
exceeded.
Physiological and Biochemical Characteristics;
Foliar Absorption and Translocation: Picloram translocates from both
the roots and leaves of plants and accumulates in the new growth.
Picloram is both foliar-absorbed and root-absorbed.
Mechanism of Pesticldal Action: Alters nucleic acid and protein
synthesis.
Metabolism and Persistence in Plants: Available plant metabolism
data indicate that picloram degrades to CC>2, oxalic acid, and
the metabolites 4-amlno-2,3,5-trichloropyridlne and 4-amlno-3,5-
dichloro-6-hydroxypicolinic acid.
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Metabolism and Persistence in Animals: Available metabolism data
indicate that animals excrete 82 to 98 percent of the [14C]picloram
used in dosing the animals as picloram.
Environmental Characteristics;
Absorption and Leaching in Basic Soil Types: Available data indicate
that picloram was intermediately mobile to very mobile in soils
ranging in texture from clay to loam. Adsorption of picloram
pH. Addition of inorganic salts to the soil did not affect
adsorption of picloram.
Microbial Breakdown: Picloram degraded with half-lives of 100 to
200 days in loam soil, 200 to 300 days in silt loam soil, and
greater than 300 days in loamy sand, commerce loam, clay, and
sandy loam soils under aerobic conditions. Picloram was rela-
tively stable in anaerobic loam soil under anaerobic aquatic
soil conditions.
Loss from Photodecomposition: Does not degrade.
Bioaccumulation in Fish: Does not accumulate in fish.
Potential to Contaminate Groundwater: Picloram has been previously
identified as a pesticide with a propensity to leach into ground-
water. Picloram has been reported as detected in seven States.
Picloram is persistent and mobile and has a high potential to
reach groundwater.
Exposure to Humans: Based on available acute toxicology data the
major routes of exposure appear to be through inhalation and
dermal sensitization. Although technical picloram (free acid) is
in Toxicity Category I based on inhalation, there is little chance
of exposure to mixer/loaders or applicators because there are
currently no products registered containing the free acid form of
picloram.
Risk to Humans: The major risk to humans appears to be from the
contaminant HCB. Both dietary and nondietary risk assessments
were performed. The dietary exposure to HCB occurs from the use
of pesticides containing picloram on small grains and secondary
residues on animal commodities. The oncogenic risk for the U.S.
population based on dietary exposure was calculated to be 6. x
10-7.
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Potential nondietary exposure to HCB is to workers, mixer/loaders
and applicators from use of picloram on wheat, forests, rights-
of-way, and pasture/rangeland. The estimated nondietary risk
to mixer/loaders and applicators ranged from 5.0 x 10-5 to
10-8.
Reentry: Reentry intervals are not required because cultural practices
for existing uses indicate little likelihood that field workers
would be exposed to acutely toxic levels of picloram from agricultural
applications.
Efcoloqical Characteristics:
Avian Acute Oral Toxicity (Technical): Bobwhite quail > 2250 mg/kg/day;
K Salt: Bobwhite quail > 2510 mg/kg/day
Avian Subacute Dietary Toxicity (Technical): Bobwhite quail > 5000 ppm,
mallard duck > 5000 ppm; K Salt, bobwhite quail > 5620 ppm; IDE,
bobwhite quail > 5620 ppm
Acute Toxicity to Freshwater Fish (Technical): Rainbow trout = 4.3
to 19.3 ppm, bluegill sunfish = 14.5 to 23.0 ppm; K Salt, rainbow
trout = 13 ppm, catfish = 14 ppm, bluegill sunfish = 24 ppm; IOE,
rainbow trout =4.0 ppm, catfish =1.4 ppm, bluegill sunfish =
6.3 ppm
Fish Embryolarvae Study: Rainbow trout with a maximum acceptable
threshold concentration (MATC) = 0.55 < MATC < 0.88 mg/L
Acute Toxicity to Freshwater Invertebrates Studies: (Daphnids,
Gammarus, Pteronarcella, and Pteronarcys) = 10 to 68.3 ppm
Chronic Aquatic Invertebrate Study (Daphnids): 11.8 < MATC
< 18.1 "mg/L
Acute Toxicity to Honey Bees (Technical): = 14.5 micrograms per bee
Technical picloram appears to be moderately to slightly toxic to
freshwater fish, slightly toxic to aquatic invertebrates, and
practically nontoxic to birds. Chronic fish testing showed that
picloram caused a reduction in rainbow trout larval survival at
2.02 mg/L and a reduction in growth at 0.88 mg/L. Picloram
affected the growth and survival in cutthroat trout at 0.29 mg/L.
The isooctyl ester form of picloram is moderately toxic to fish, and
practically nontoxic to birds.
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The potassium salt of picloram appears to be slightly toxic to
freshwater fish and practically nontoxic to birds.
Phytotoxicity and Endangered Species
Picloram has been shown to be a highly phyotoxic herbicide.
Because of picloram1s demonstrated toxicity to nontarget plant species
and its intended use pattern, picloram has been identified as
being likely to jeopardize endangered plant species when used on
pastures/rangeland and forests. A program is being developed by
the Agency to reduce or eliminate exposure to these species to a
point where use does not jeopardize these species.
Tolerance Assessment:
Tolerances are established under 40 CFR 180.292 for residues of the
picloram. Food and Feed additive tolerance are established
under 40CFR 185.4580 and 40 CFR 186.4580. These replace old
Section 21 CFR 183.350 and 21 CFR 561.305.
The Agency has established a R.F.D or a provisional acceptable daily
intake at 0.07 mg/kg/day based on a 6-month dog feeding study
(NOEL of 7.0 mg/kg/day) using a safety factor of 100. The the-
oretical maximum residue contribution (TMRC) is calculated to
be 0.001847 mg/kg/day, which utilizes 2.6 percent of the PADI.
The tolerance assessment indicated that additional residue data are
needed for wheat grain, wheat forage, wheat straw, pasture, range-
land grasses, and flax. Data are required depicting residues of
HCB in or on wheat grain, wheat straw, pasture and rangeland
grasses, flax seed, and flax straw. Additional plant and animal
metabolism data are needed.
Reported Pesticide Incidents
Most of the reported pesticide incidents involve crop damage and
damage to other nontarget plants resulting from drift and from
soil contaminated with picloram.
4. Summary of Regulatory Position and Rationale
A review of available data indicates that none of the risk criteria
listed in 40 CFR 154.7 have been exceeded. Therefore, no referral
to Special Review is being made at this time.
The Agency will continue to require that EPS containing picloram
retain the "Restricted use" classification and the groundwater
advisory against the use of picloram on well-drained soils.
The Agency is requiring that the rat and mouse oncogenicity studies
be repeated using Osborne-Mendel rats and BgC3Fi mice of both
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sexes using a commercially available technical grade plcloram
uncontaminated with potentially tumorigenlc levels of HCB.
The Agency has determined that basic toxicology studies are needed
for the organic esters and amines of picloram in addition to the
complete toxicological testing of the acid and/or K salt.
The Agency will continue to require manufacturers to limit the level
of HCB in the technical to a maximum of 200 ppm.
The Agency is requiring nitrosamine testing for the tertiary amlne
and alkanoloamlne forms of picloram. The level of nitrosoamines
permitted in these forms is a maximum of 1 ppm.
The Agency is requiring that a prospective groundwater monitoring
study be submitted for picloram.
The Agency is requiring that Tier II phytotoxicity testing be performed
with the technical picloram, its salts, ester, and amine forms.
The Agency is requiring that droplet size spectrum and drift field
evaluation data be submitted for picloram.
The Agency is requiring that additional residue data be submitted for
wheat grain, wheat forage, wheat straw, pasture and rangeland
grasses, and flax. The data must include residues of HCB and the
results of analysis for HCB levels.
The Agency is requiring that additional plant metabolism data be
submitted providing complete identification and quantitation of
all terminal residues.
The U. S. Pish and Wildlife Service has determined that picloram
is likely to jeopardize endangered plant species when used on
rangeland/pastureland and forests. The Agency is developing a
program to reduce or eliminate exposure of this chemical to these
species. After the program is developed, notification of any
additional labeling requirements will be made.
The Agency is requiring that the labels of products containing
picloram determined to be skin sensltlzers include the state-
ment "May cause allergic skin reaction after multiple exposure"
on the labels
The Agency will not approve any significant new food uses for picloram
while major data gaps exist. When additional data are evaluated
the Agency will determine whether significant new uses may he-
established.
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5. Summary of Data Gaps
Requirements Due Dates
Product Chartistry 6 to 15 months
Residue Data 6 to 24 months
Toxicology Data 9 to 40 months
Environmental Fate 9 to 39 months
Groundwater Monitoring 9 months
Plant Protection 9 months
6. Contact Person at EPA
Robert J. Taylor
Product Manager 25
Fungicide-Herbicide Branch
Registration Division (TS-767C)
Office of Pesticide Programs
Environmental Protection Agency
401 M Street SW.
Washington, DC 20460
Phone: (703) 557-1800
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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&EPA
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