United States                Prevention, Pesticides          EPA-738-F-95-018
                   Environmental Protection         And Toxic Substances          August 1995
                   Agency	(7508W)	

                   R.E.D.    FACTS
      PGStJCJdG        All pesticides sold or distributed in the United States must be
R0TGClistration   registered by EPA, based on scientific studies showing that they can be used
                   without posing unreasonable risks to people or the environment. Because of
                   advances in scientific knowledge, the law requires that pesticides which
                   were first registered years ago be reregistered to ensure that they meet
                   today's more stringent standards.
                        In evaluating pesticides for reregistration, EPA obtains and reviews a
                   complete set of studies from pesticide producers, describing the human
                   health and environmental effects of each pesticide.  The Agency imposes
                   any regulatory controls that are  needed to effectively manage each
                   pesticide's risks.  EPA then reregisters pesticides that can be used without
                   posing unreasonable risks to human health or the environment.
                        When a pesticide is eligible for reregistration, EPA announces this and
                   explains why in a Reregistration Eligibility Decision (RED) document.  This
                   fact sheet summarizes the information in the RED document for
                   reregistration case 0096, picloram acid and its three derivatives,
                   triisopropanolamine picloram (TIPA-salt), isooctyl/ethylhexyl picloram
                   (IDE), and potassium picloram  (K-salt), referred to collectively as

    USG ProfilG        Picloram is a systemic herbicide used to control deeply rooted
                   herbaceous weeds and woody plants in rights-of-way,  forestry, rangelands,
                   pastures, and small grain crops. It is applied in the greatest amounts to
                   pasture and rangeland, followed by forestry.  Picloram acid is a
                   manufacturing use product with no end uses. The TIPA-salt and K-salt have
                   food and feed uses, and are applied pre- or post-emergence as a ground or
                   aerial broadcast or spot treatment. The IDE derivative is registered for non-
                   food uses only. Picloram products have no household or residential uses.
                        All picloram products are classified as Restricted Use pesticides based
                   on hazard to nontarget plants, and may be applied only by or under the
                   direct supervision of certified applicators.  Use practice limitations for the
                   TIPA-salt include a prohibition against applying through any type of
                   irrigation system, observation of a 30-day preharvest interval for
                   forage/fodder, and observation of a 7-day pregrazing interval.  The IDE
                   includes prohibitions against contaminating water intended for irrigation or
                   domestic purposes,  application to snow or frozen ground, and application

Human Health
near desirable trees if injury from potential transfer through roots cannot be
tolerated.  The K-salt includes prohibitions against application through any
type of irrigation system, grazing or feeding forage from treated areas for 2
weeks after treatment, or harvesting hay from treated grain fields.

      Picloram was first registered as a pesticide in the U.S. in 1964.  EPA
classified picloram as a Restricted Use pesticide in 1978 as a result of
recurring reports of phytotoxicity to economically important crops caused
by contamination of water supplies.
      EPA issued a Registration Standard for  picloram in March 1985
imposing a maximum level of the manufacturing impurity
hexachlorobenzene (HCB) in technical picloram of 200 ppm, and requiring
additional studies including testing for nitrosamines.  The sole registrant
completed this testing; no nitrosamines were detected in picloram products,
and the level  of HCB is certified to  be less than 100 ppm.  EPA issued  a
picloram Final Reregistration Standard and Tolerance Reassessment
document in  May 1988.  Currently, two picloram manufacturing use
products and  seven end-use products are registered.

      In studies using laboratory animals,  picloram generally has been
shown to be of moderate to low acute toxicity.  Picloram and its derivatives
are only slightly toxic by the oral and dermal routes and have been placed in
Toxicity Categories III and IV (the lowest of four categories) for these
effects. However, picloram acid is highly toxic and the three derivatives
are moderately toxic by the inhalation route (Toxicity Categories I and  II).
Picloram and derivatives cause moderate eye  irritation (Toxicity Category
III).  Most are not skin irritants (Toxicity  Category IV, except  IDE in
Category III). The three derivatives are skin sensitizers while picloram acid
is not.
      In a subchronic toxicity study using rats, picloram caused changes in
the liver. A dog dietary study resulted in  decreases in body weight gain,
food consumption, liver weights and several enzymes. In two  dermal
toxicity studies using rabbits, picloram caused skin irritation, redness, and
swelling.  A  study using rats resulted  in increased liver and kidney weights.
A study using rabbits resulted in increases in  levels of several blood
components.  A study using rats resulted in liver effects, increased liver and
kidney effects, and decreased body weight gain.
      A chronic toxicity study using dogs  resulted in increased liver weight.
A chronic/carcinogenicity study using rats resulted in chronic toxicity in
males only and no evidence of carcinogenicity.  A study using  mice  also
resulted in no evidence of carcinogenicity.  Based on these studies, picloram
was classified as a "Group E" chemical—one  showing evidence of non-
carcinogenicity for humans. Subsequently, picloram IDE was  found to bear

structural similarity to di(2-ethylhexyl)phthalate or DEHP, which has been
found to cause cancer in rodents.  EPA included this information in
assessing picloram's risks to workers.
     There is no evidence that picloram and its salts and ester are
associated with significant reproductive or developmental toxicity.  A study
using rabbits resulted in reduced maternal weight gain.  In five studies using
rabbits and rats, there was no evidence of developmental toxicity at any dose
level, though some signs of maternal toxicity were observed.  In a
reproduction study using rats, effects to the kidneys,  urine, and body weight
gain were observed at the high dose. Picloram shows no evidence of
causing mutagenicity.
Dietary Exposure
     People may be exposed to residues of picloram through the diet.
Existing tolerances or maximum residue limits which have been reassessed
and found adequate include grain, forage, and straw of barley, oats, and
wheat;  milk; eggs; fat, meat, kidney,  liver, and meat by-products of
cattle, goats, hogs, horses, and sheep;  and fat, meat,  and meat by-products
of poultry (please see 40 CFR 180.292). Sufficient data also are available
to determine the adequacy of established food/feed additive tolerances for
barley, oat,  and wheat milled fractions (excluding flour) listed in 40 CFR
185.4850 and 40 CFR 186.4850.
     In reassessing picloram tolerances, EPA has found that both an
existing tolerance for forage grasses and a proposed new tolerance for hay
grass need to be raised to a higher level.  A tolerance must be proposed for
wheat grain dust, and established tolerances for flax seed and straw should
be revoked since this use is not registered.  International Codex MRLs are
neither  established nor proposed so compatibility with U.S. tolerances is not
an issue.
     EPA has assessed dietary risks considering chronic dietary exposure
and risk to picloram per se, and to the impurity HCB.  The exposure/risk
estimates for picloram are extremely low. The Anticipated Residue
Concentration (ARC)  for the U.S.  population as a whole represents only
0.5% of the Reference Dose (RfD), an amount believed not to cause adverse
effects if consumed daily over a 70-year lifetime.  The most highly expose
subgroup, non-nursing infants less than one year old,  has an ARC which
represents 1.9% of the RfD.  This low fraction of the allowable RfD is
considered to be an acceptable dietary exposure risk.
     The HCB upper-bound cancer exposure/risk estimate, performed only
for the U.S. population as a whole, produced an ARC risk estimate of 6.7 x
10 7.  This level of risk, which is likely a substantial overestimate, generally
is considered negligible.

Occupational  and Residential Exposure
     Based on current use patterns, handlers (mixers,  loaders, and
applicators)  may be exposed to picloram during applications in agriculture
and forestry, on pastures and rangelands, along rights-of-way, and in other
non-crop areas.  Because of picloram's use patterns, post-application
activities and exposure generally are not expected.  No picloram products
are registered for homeowner use or have residential applications.
     Since there is an exposure risk for handlers of picloram via the dermal
and inhalation routes during normal use, EPA conducted an occupational
exposure assessment.  For the twelve major exposure scenarios identified,
Margins of Exposure (MOEs) for workers range from  111 for
backpack/knapsack application to 42,000 for groundboom application. The
risk to  picloram handlers,  therefore, is considered minimal.
     Due to the HCB impurity in picloram and the structural similarity of
the IDE to DEHP,  EPA also conducted a cancer risk assessment for
picloram handlers.  The estimated excess cancer risk to agricultural workers
from HCB based on picloram use patterns and exposure by the dermal and
inhalation routes is between 4.19 x 10 5 and 1.07 x 10 7. The excess cancer
risk for workers from exposure to the IDE is 8.6 x 10 5.  These estimates
are considered worst-case;  actual exposure and risk may be lower.
     Although entry into  treated areas soon after  application is expected to
be rare given picloram's typical use patterns, EPA has  determined  that entry
should not be permitted immediately following application.  The Agency
therefore is requiring a 12-hour restricted entry interval (REI) for picloram
uses that are within the scope of the Worker Protection Standard for
Agricultural Pesticides (WPS), and a prohibition on entry until sprays have
dried for uses outside the scope of the  WPS.
     Also, the MOEs for handlers are acceptable in some use scenarios
only with chemical-resistant gloves. Therefore, the minimum, baseline
personal protective equipment  (PPE) for all WPS and nonWPS uses of
picloram is chemical-resistant gloves.
Human  Risk Assessment
     Picloram generally is of moderate to low acute toxicity but causes
inhalation toxicity  (Toxicity Category II). Picloram is  classified as a
"Group E" chemical—one  showing evidence of non-carcinogenicity for
humans.  However, it contains the impurity HCB which is classified as a
"B2" probable human carcinogen.  In addition, picloram IDE is structurally
similar to DEHP, which has been found to cause cancer in rodents. EPA
considered this information in assessing picloram's risks.
     People may be exposed to residues of picloram through their diets
since a number of  food and animal feed crop uses are registered.  However,
dietary exposure and risk are extremely low. There is  no reason for
concern regarding  chronic dietary exposure to picloram at this time.

                           Risks to picloram handlers (mixers/loaders/applicators) are considered
                      minimal, and worst-case cancer risks to workers are not unacceptable (in the
                      10 5 to 10 7 range).  To minimize risks to handlers, EPA is requiring use of
                      minimal, baseline PPE (chemical-resistant gloves).  To minimize potential
                      reentry exposure risks, EPA is establishing restrictions on entry to treated
     The principal environmental risks of picloram relate to contamination
of surface and ground water, and damage to nontarget terrestrial plants
including crops adjacent to areas of application via runoff or drift.  Such
damage to plants also may emanate from more distant areas where ground
water is used for irrigation or is discharged into surface water. Nontarget
plants adjacent to areas of application may be exposed to concentrations of
picloram many times the levels  that have been associated with toxic effects.
In addition,  EPA has concerns related to endangered terrestrial mammals
and endangered aquatic animals.
Environmental  Fate
     Picloram is highly soluble in water, resistant to biotic and abiotic
degradation  processes, and mobile under both laboratory  and field
conditions.  It is stable to hydrolysis and anaerobic degradation, and
degrades very slowly with half-lives ranging from 167 to  513 days.  Its
major route  of dissipation appears to be leaching.
     Although no ground water monitoring studies have been submitted to
EPA, available data indicate that picloram has very high potential to leach to
ground water in most soils.  As of 1992, picloram had been detected in
ground water in 10 states,  at concentrations up to 30 ppb.
     Picloram is extremely mobile.  Nearly 100% of the chemical  leached
but none of  it  degraded over a three-year period in a University of Arkansas
study.  Given its high persistence, it appears unlikely that picloram  will
degrade once it reaches ground water, even over  a period of several years.
Environmental  Fate Assessment
     Picloram is among the most mobile of currently registered pesticides.
In some soils,  it is nearly recalcitrant to all degradation processes.  Picloram
has been detected in ground water in 10 states, to date.  However, it
generally does not pose a threat to human health at the levels detected.
     Concerns are related principally to effects on nontarget plants, which
may be exposed to picloram by  drift or runoff from areas of application, or
by irrigation with contaminated surface or ground water.  Aquatic plants
also may be  exposed to picloram via  runoff, drift, or discharge of
contaminated ground water into surface water.
     EPA is concerned about degradation of  water quality in picloram use
areas.  Eventual contamination  of ground water is virtually certain in areas
where picloram residues persist in the overlying soil. Once in ground
water, picloram is unlikely to degrade,  even over a period of several years.

                            Picloram also has a high potential to contaminate surface water by
                      runoff from use areas.  The EPA Office of Drinking Water's STORET
                      database indicates that picloram has been reported in 420 of 744 surface
                      water samples. EPA does not have data from monitoring of picloram in
                      surface water.  However, picloram is regulated by the Safe Drinking Water
                      Act (SDWA) and  water supply systems are required to sample for it.
                      Ecological Effects
                            Picloram and its derivatives are practically nontoxic to birds,
                      mammals, and honeybees on  an acute oral basis.  Picloram acid and the K-
                      salt are moderately toxic to freshwater  fish and slightly toxic to freshwater
                      invertebrates. The TIPA salt is slightly toxic to freshwater fish and
                      marine/estuarine  mollusks and practically nontoxic to marine crustaceans.
                      Picloram salt is slightly toxic to marine/estuarine mollusks and
                      invertebrates. Additional studies are required.
                            Picloram is extremely phytotoxic as well as persistent and prone to
                      leach to ground water in all soil types.  A number of additional  plant, fish,
                      invertebrate, and  marine/estuarine effects studies are required as
                      confirmatory data.
                      Ecological Effects Risk Assessment
                            Picloram poses very significant risks to nontarget plants.  Estimated
                      concentrations of picloram  in the environment are hundreds to thousands of
                      times the "level of concern" at which 25% of seedlings fail  to emerge.
                      Although data requirements are not fulfilled for aquatic plants or animals,
                      estimated picloram  exposures exceed levels of concern for endangered fish
                      and mollusks.  Endangered terrestrial mammals also encounter exposures
                      which are likely to exceed levels of concern.

Risk Mitigation         To lessen risks of picloram to nontarget plants and ground and surface
                      water, EPA  is requiring the following risk mitigation measures and
                      Application Modifications
                      o  EPA is lowering  application rates and imposing limits on the number and
                      frequency of applications for  all use patterns —
                            •  The broadcast rate for range and pasture use and the spot  treatment
                            rate will be lowered.
                            •  The forestry use rate and frequency will be lowered.
                            •  The rights-of-way use rate will be lowered.
                      o  Picloram will remain classified for Restricted Use and may be identified
                      as a candidate for State Management Plans.
                      o  EPA is requiring spray drift mitigation language including an Aerial Drift
                      Reduction Advisory, as well as ground water, surface water, and
                      phytotoxicity advisory language on all picloram product labeling.

                         Monitoring and Other Programs
                         o The registrant, DowElanco, has committed to conduct a state ground
                         water monitoring/surveillance plan.  The results will determine whether
                         additional data are required or appropriate regulatory action is necessary.
                         o The registrant has committed to provide support to the Heritage programs
                         in six states with the highest use of picloram.  These programs map and
                         monitor sensitive habitat in 48 states to help protect endangered species.
                         Registrant Stewardship
                         o The registrant has instituted a strict product distribution system which
                         includes a mandatory training program for all picloram distributors.
                         o EPA conducted a cursory benefits analysis and found that picloram is an
                         extremely effective herbicide at relatively low rates.  To achieve the same
                         control,  a combination of alternatives would have to be used at higher rates.
                         Endangered Species Protection Program
                         o EPA will address picloram's risks to endangered plants, mammals, and
                         aquatic species through the Endangered Species Protection Program, when it
                         goes into effect.

  Additional Data        EPA is requiring the following types of additional generic studies for
          Red UJ r0d   picloram to confirm its regulatory assessments and conclusions. Please see
                         the RED document for a more detailed list.
                               •  Toxicity to marine/estuarine fish, mollusk, and shrimp;
                               •  Early life stage - fish;
                               •  Bluegill and rainbow Acute LD50;
                               •  Invertebrate toxicity  (Daphnia magna);
                               •  Aquatic plant growth (marine diatom, algae);
                               •  Seed germination/emergence;
                               •  Vegetative vigor;
                               •  Estimation of dermal or inhalation  exposure at outdoor sites for
                              mixer/loaders and applicators using the hand cannon or
                              backpack/knapsack equipment;
                               •  Ground water surveillance/monitoring.
                                   The Agency is also requiring product-specific  data including
                              product chemistry and acute toxicity studies, revised Confidential
                              Statements of Formula (CSFs),  and revised  labeling  for reregistration.

Product Labeling        All picloram end-use products must comply with EPA's current
ChanqeS  Required   pesticide product labeling requirements, and with the following labeling
                         requirements.  For the complete text of labeling changes required, please
                         see the picloram RED document.

Reduced Use Rates and Increased Intervals
Labels must be amended to reflect the following changes in maximum
application rates and treatment intervals:
o  Broadcast rate for range and pasture is lowered from current maximum
of 2.0 Ib. to 0.5 acid equivalent per acre (ae/A) for control of broadleaf
weeds and woody plants.  For control of noxious weeds, broadcast
application of up to 1.0 Ib. ae/A may be used annually.  Spot treatment will
be lowered to a maximum of 1.0 Ib ae/A with no more than 50% of an acre
being treated.  Spot treatments and broadcast treatments can be applied
during the same growing season only if the total amount applied  does not
exceed 1.0  Ib.  ae/A per annual growing season.
o  Forestry use rate is  lowered from  maximum of 2.2 Ibs. ae/A to 1.0 Ib.
ae/A for spot and broadcast treatment.  Use is allowed only once every 2
o  Rights-of-way use rate is lowered  from a maximum of 2.2 Ibs. ae/A to 1
Ib. ae/A annually.
Personal Protective Equipment (PPE) for Handlers
The minimum (baseline) handler PPE for all WPS and nonWPS  uses of
picloram is chemical-resistant gloves.  Remaining PPE for handlers is  to be
based on the toxicity of the end-use product.
Entry Restrictions for Occupational-Use Products (WPS Uses)
EPA is establishing a 12-hour restricted entry interval (REI).  PPE required
for WPS-permitted early entry into treated  areas that involves contact with
anything that has been treated, such as plants, soil, or water, is:  coveralls,
chemical-resistant gloves, socks, and shoes.
Entry Restrictions for Occupational-Use Products (NonWPS Uses)
For nonWPS uses of picloram, EPA  is requiring the following:
     "Do not enter or allow others to enter the treated area until sprays
     have dried."
Application Restrictions
     "Do not apply this product in a way that will contact workers or other
     persons,  either directly or through drift. Only protected handlers may
     be in the area during application."
Engineering Controls
     "When handlers use closed systems, enclosed cabs, or aircraft in a
     manner that meets the requirements listed in  the WPS..., the handler
     PPE requirements may be reduced or modified as specified in the
User Safety Requirements
     "Follow  manufacturer's instructions for cleaning/maintaining PPE.  If
     no such instructions exist  for washables, use  detergent and  hot water.
     Keep and wash PPE separately from other laundry."

User Safety Recommendations
      "Users should wash hands before eating, drinking, chewing gum,
      using tobacco, or using the toilet."
      "Users should remove clothing immediately if pesticide gets inside.
      Then wash thoroughly and put on clean clothing."
Precautionary Statements
Because picloram salts and ester are skin sensitizers, the following statement
is required in the  "Hazards to Humans  (and Domestic Animals)" section on
end-use product labeling:
      "Prolonged  or frequent repeated skin contact  may cause allergic
      reactions in some individuals."
If the acute inhalation toxicity of the end-use product is in Category I or II,
a respirator is  required for pesticide handlers.  The following type of
respirator is appropriate to mitigate picloram inhalation concerns:
      "A dust/mist filtering respirator  (MSHA/NIOSH approval number
      prefix TC-21Q."
Spray Drift Labeling
The following language must appear on the label of each product that can be
applied aerially:
      "Avoiding spray drift at the application site is the responsibility  of the
      applicator.   The interaction of many equipment-and-weather-related
      factors determine the potential for spray drift. The applicator and the
      grower are responsible for considering all these factors when  making
      "The following drift management requirements must be followed to
      avoid off-target drift movement from aerial applications to agricultural
      field crops.  These  requirements do not apply to forestry applications,
      public health uses or to applications using dry formulations.
      1.  The distance of the outer  most nozzles on the boom must  not
      exceed 3/4 the length of the wingspan.
      2.  Nozzles must always point backward parallel with the air stream
      and never be pointed downwards  more than 45 degrees."
      "Where  states have more stringent regulations, they should be
      "The applicator should be familiar with and take into account the
      information covered in the Aerial Drift Reduction Advisory."
Aerial Drift Reduction Advisory
Please see the  picloram RED document for the text of this Advisory, which
must be contained in product labeling.

                  Ground Water Advisory Statements
                  The following ground water advisory language must be placed on all
                  picloram labels:
                       "This chemical is known to leach through soil into ground water under
                       certain conditions as a result of agricultural use.  Use of this chemical
                       in areas where soils are permeable, particularly where the water table
                       is shallow, may result in groundwater contamination."
                  Surface Water Advisory Statements
                  The following surface water advisory language must be placed on all
                  picloram labels:
                       "This chemical can contaminate surface water through spray drift.
                       Under some conditions,  picloram may also have a high potential for
                       runoff into surface water (primarily via dissolution in runoff water)
                       for several months post-application. These  include poorly draining or
                       wet soils with readily visible slopes toward adjacent surface waters,
                       frequently flooded areas, areas over-laying extremely shallow ground
                       water, areas with in-field canals or ditches that drain to surface water,
                       areas not separated from  adjacent surface waters with vegetated filter
                       strips, and areas over-laying tile drainage systems that drain to surface
                  Phytotoxicity Advisory Statements
                  The following phytotoxicity advisory language must be placed on  all
                  picloram labels:
                       "This pesticide is toxic to some plants at very low concentrations.
                       Non-target plants may be adversely affected if pesticide is allowed to
                       drift from areas of application."
                  Precautionary Hazard Statement
                  Labeling should include  the following:
                       "Do not apply this product to water, or to areas where surface water is
                       present, or to intertidal areas below the mean high water mark."

                       Picloram and its derivatives can be used without causing unreasonable
                  adverse effects to humans or the environment. Therefore, all uses of
                  products containing picloram acid and  its derivatives are eligible for
                  reregistration, conditional upon implementation of the mitigation measures
                  specified in the picloram RED  document.
                       Picloram products will be reregistered once the required product-
                  specific data, revised Confidential Statements of Formula, and revised
                  labeling are received  and accepted by EPA.
   For MOTG        EPA is requesting public comments on the Reregistration Eligibility
Information   Decision (RED) document for picloram during a 60-day time period, as
                  announced in a Notice of Availability published in the Federal Register.  To

obtain a copy of the RED document or to submit written comments, please
contact the Pesticide Docket, Public Response and Program Resources
Branch, Field Operations Division (7506C), Office of Pesticide Programs
(OPP), US EPA, Washington, DC 20460, telephone 703-305-5805.
     Electronic copies of the RED and this fact sheet can be downloaded
from the Pesticide Special Review and Reregistration Information System at
703-308-7224. They also are available on the Internet on EPA's gopher
server,  GOPHER.EPA. GOV, or using ftp on FTP.EPA.GOV, or using
WWW (World Wide Web) on WWW.EPA.GOV.
     Printed copies of the RED and fact sheet can be obtained from EPA's
National Center for Environmental Publications  and Information
(EPA/NCEPI), PO Box 42419, Cincinnati, OH  45242-0419, telephone
513-489-8190, fax 513-489-8695.
     Following the comment period, the picloram RED document also will
be available from the National Technical Information Service (NTIS), 5285
Port Royal Road, Springfield, VA 22161, telephone 703-487-4650.
     For more information  about EPA's pesticide reregistration program,
the picloram RED, or reregistration of individual products containing
picloram, please contact  the Special Review and Reregistration Division
(7508W), OPP, US EPA, Washington, DC 20460, telephone 703-308-8000.

     For information about the health effects of pesticides, or for assistance
in recognizing and managing pesticide poisoning symptoms, please contact
the National Pesticides Telecommunications Network (NPTN).  Call toll-
free 1-800-858-7378, between 8:00 am and 8:00 pm Eastern Standard
Time, Monday through Friday.