UMHd Swt             OH1 of ftctlcad* nt Toxk
                    Environmental Protoaion      Office of Pwcicid* Piuytin (TS-7SaC)
                    Agency                Wtahlnfton. DC 20490
&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
     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
     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
     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


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

    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


   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

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

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."


   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.


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

 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.


 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.


 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

 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

 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

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.


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

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

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

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

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.


    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


   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-


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.

   U.S. Environrnental Protection Agency
   Office of Pesticide Program (TS-757C)
   PMSD, Information Services Branch
   401 M Street, S.W.
   Washington, D.C. 20460

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