United States               Prevention, Pesticides         EPA-738-F-98-018
             Environmental Protection       And Toxic Substances         December 1998
             Agency	(7508C)	

             R.E.D.    FACTS
            Alachlor
PGStJCJdG       All pesticides sold or distributed in the United States must be 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 before November 1, 1984, be reregistered to ensure that they meet
            today's more stringent safety standards.

                 Under the Food Quality Protection Act of 1996, EPA must consider the
            increased susceptibility of infants and children to pesticide residues and
            determine the need for an additional safety factor for the protection of infants
            and children.  When establishing or reassessing tolerances, the  Agency must
            also consider aggregate exposures to a pesticide, that is, combining the
            exposures that result from consuming pesticide residues in food and water, or
            using pesticide products in and around the home. Additionally, the Agency
            must assess the cumulative effect of pesticides and other chemicals that
            demonstrate a common mechanism of toxicity. Mechanism of toxicity is
            defined as the steps leading to an adverse health effect following exposure to a
            chemical. A common mechanism of toxicity occurs when two or more
            chemicals produce the same adverse health effect by the same sequence of
            steps.

                 In evaluating pesticides for reregi strati on, the pesticide producers submit
            to EPA a complete set of studies describing the human health and
            environmental effects of each pesticide. Agency scientists review the
            submitted studies to determine if the studies are scientifically valid.  These
            studies are the basis for the Agency's risk assessment. The Agency then
            develops any mitigation measures or regulatory controls needed to effectively
            reduce each pesticide's risks, and then reregisters those pesticides and/or uses
            that can be used without posing unreasonable risks to human health or the
            environment.

                 When a pesticide is eligible for reregistration, EPA explains the basis for
            its decision in a Reregistration Eligibility Decision (RED) document. This fact
            sheet summarizes the information in the RED document for reregistration case
            0063, alachlor.

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Use Profile
     Alachlor is a herbicide used for weed control on corn, soybeans,
sorghum, peanuts, and beans. There are liquid, dry flowable,
microencapsulated, and granular formulations. The timing of applications is
preplant, pre-emergent, at plant for corn and soybeans, post-transplant, post-
emergent,  and at ground crack for peanuts only. Alachlor is applied by ground,
aerial, and chemigation equipment.  It can also be mixed with dry bulk
fertilizer.
  Regulatory        Alachlor was first registered in 1969 as a selective herbicide for control
      History  of broadleaf weeds and grasses. Alachlor is produced by the Monsanto
                Company in the US.

                      A Registration Standard was issued for alachlor on November 20, 1984.
                The Registration Standard involved a thorough review of the scientific data
                base underlying pesticide registrations and an identification of essential, but
                missing, studies.  The Registration Standard (1) stated that alachlor was
                classified as an oncogen, (2) required additional data on the leaching and
                mobility of alachlor to examine the potential of alachlor to contaminate ground
                and surface water, (3) required a monitoring study of ground and surface water
                were required, and required additional data in the areas of toxicology, product
                chemistry, and residue chemistry.

                      On January 9, 1985, the Agency published a Notice of Initiation of
                Special Review of Registrations of Pesticide Products Containing Alachlor
                (Federal Register. Volume 50, No. 1115) and the Alachlor Position Document
                (PD-1) that detailed the basis for the Special Review.  The Special Review was
                initiated  under the Federal Insecticide, Fungicide, and Rodenticide Act
                (FIFRA) because pesticide products containing alachlor met or exceeded the
                Agency's  oncogenicity criteria.

                      Following the review of public comments and additional information
                received in response to the Notice of Initiation of Special Review and the
                Alachlor PD-1, EPA issued a Notice of Preliminary Determination on October
                8, 1986 (Federal Register. Volume 51, No. 36106). In this notice the Agency
                proposed to allow the continued use of alachlor products subject to
                modifications of the terms and conditions of registration .
                      Following review of comments and additional information received in
                response to the Preliminary Notice, EPA issued a notice entitled "Alachlor;
                Notice of Intent to Cancel Registrations, Conclusion of Special Review on
                December  31, 1987 (Federal Register. Volume 52, No. 49480). This notice is

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                    also known as Alachlor Position Document 4 (PD-4).  The PD-4 concluded the
                    Special Review and stated that EPA would cancel the registrations and deny
                    applications for registration of products containing alachlor that did not
                    comply with the modified terms and conditions of registration set forth in this
                    notice. The PD-4 stated that tolerances would be rewritten once all residue
                    data required by the Registration  Standard were received and evaluated.  The
                    PD-4 required the following label amendments: Restricted Use due to
                    Oncogenicity, a tumor hazard warning, use of a mechanical transfer system to
                    be used by mixer/loaders and/or applicators who treat 300 or more acres
                    annually, and human flaggers were prohibited for aerial application. Additional
                    ground water monitoring data were required.  Labeling bearing required
                    changes was submitted and  accepted in early  1988.

Human  Health   Toxicity
  Assessment         Data from acute toxicity studies serve as the basis for labeling and
                    packaging requirements. In studies using laboratory animals, alachlor generally
                    has been shown to be of low acute toxicity. All acute studies have been
                    classified as either Category III or IV, the two lowest classifications.

                          Alachlor has been evaluated for carcinogenic activity in rats and mice.  In
                    accordance with the 1996 EPA proposed Guidelines for Carcinogen Risk
                    Assessment, alachlor was classified as "likely" to be a human carcinogen at
                    high doses, but" not likely" at low  doses. Based on numerous studies
                    submitted by the registrant that were reviewed by Agency scientists, as well as
                    an external peer review panel, it was agreed that a margin of exposure (MOE)
                    approach (indicative of a non-linear dose response) should be used for the risk
                    assessment.

                          The scientific validity of the MOE approach has been documented by
                    various review panels, such  as the FIFRA Scientific Advisory Panel, and the
                    Cancer Review Committee.  However, the policy implications, methodology,
                    and appropriateness of using an MOE approach in regulatory decision making
                    have not yet been fully developed by the Agency.   Perhaps, the most critical of
                    the decision criteria to develop are those for determining the appropriate
                    regulatory level.  While informed by the science, this determination is
                    ultimately a risk management decision.  Once this methodology has been
                    developed, then the  available chemical-specific data would be used to
                    determine whether or not the MOEs identified in the risk assessment constitute
                    acceptable risks.

                          For now, the regulatory decision for alachlor will be based on both the
                    Qj* approach and the MOE  approach for the evaluation of carcinogenic
                    potential.  These are not directly comparable approaches. The  Qt* approach

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is indicative of a linear approach and reflects the assumption that any exposure
to alachlor could cause cancer.  The MOE approach is indicative of a non-
linear approach and reflects the assumption that there is an exposure dose
below which tumor formation is not likely to occur.  Thus, the risk numbers do
not translate from one approach to the other. Each approach must be
considered separately.

      The alachlor database for pre-and post-natal effects is complete based on
current requirements.   The Agency has reviewed two developmental toxicity
studies: one in rats, and one in rabbits. Developmental studies are designed to
identify possible adverse effects on the developing organism during pre-natal
development, which may result from the mother's exposure to the pesticide.
For alachlor, there is also a multi-generation rat reproduction study. A
reproduction study is designed to provide general information concerning the
effects of a test substance on mating begavior, conception, parturition,
lactation, weaning, and growth and development of the offspring.

      Review by Agency scientists indicates no evidence of increased
susceptibility of rats or rabbits to m utero and/or early postnatal exposure to
alachlor. Based on this conclusion, as well as additional information on
exposure to alachlor in food and water, the Agency has concluded that the
additional safety factor, as required by FQPA for the protection of infants and
children, can be removed.  Therefore, this safety factor need not be applied to
the alachlor risk assessment.

      The toxicological effects of a pesticide can vary with different exposure
durations and routes. For example, an individual may be exposed throughout
their lifetime to pesticide residues in the food and water consumed, but a farm
worker could also be exposed for several days or a month to pesticide
formulations that can enter the body through the skin, or be inhaled.  The
Agency considers the entire toxicity database and, based on the effects  seen for
different durations and routes of exposure, determines which risk assessments
are necessary to insure that the public is adequately protected from any
pesticide exposure.

      The alachlor reregi strati on eligibility review considered the following
assessments to be appropriate:

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Assessment
Acute
Chronic
(non-carcinogenic)
Short-Term
Occupational
Intermediate-Term
MOE Approach5
Carcinogenic
MOE Approach
Carcinogenic
Occupational
Qj* Approach6
Carcinogenic
Residential
Exposure Route
Dietary
(food and water)
Dietary
(food and water)
Dermal + Inhalation
Dermal + Inhalation
Dietary
(food and water)
Dermal + Inhalation
Dietary
(food and water)
Dermal + Inhalation
NOEL1 for Use in
Estimating Risk
Not required - no evidence
of significant toxicity from
a one day or single event
exposure by the oral route
RfD2'3 = 0.01 mg/kg/day
NOEL= 150 mg/kg/day
Use of dermal absorption
factor (0.24) required.4
NOEL = 50 mg/kg/day
Use of dermal absorption
factor not required since
NOEL is from a dermal
study.4
NOEL = 0.5 mg/kg/day
(nasal)
NOEL = 14 mg/kg/day
(stomach)
Not appropriate - Exposure
assessment does not
indicate that use is long-
term and continuous.
Qt* = 0.08 (mg/kg/day)-1
Not appropriate - The
Agency has not identified
any alachlor products that
are intended for home use,
or uses in/around schools,
parks or other public areas.
1 A NOEL (no observed effect level) is the dose at which no effects were
observed in the test animals.
2 The chronic Reference Dose (RfD) is the traditionally selected endpoint
for chronic dietary risk. The RfD represents the quantity of a substance
which if absorbed on a daily basis over a lifetime, is not expected to pose
significant risk of adverse health effects.
Acceptable risk is less than 100% of the RfD.

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4    Acceptable risk results in a MOE that is greater than 100.
5    Acceptable risk has not been determined.
6    Acceptable risk is 1 x 10"6, or lower.

Dietary Risk (Food Only)
     People may be exposed to small amounts of alachlor through the
consumption of food containing residues of alachlor.  Tolerances are pesticide
residue levels that should not be exceeded in or on a raw agricultural
commodity in the channels of interstate commerce when the pesticide is
applied according to label directions. Tolerances have been established (see 40
CFR 180.249) for residues of alachlor in/on a variety of food and feed
commodities:
•    beans, which includes dry beans, lima beans, forage and fodder;
•    corn, fresh sweet, and forage, fodder, and grain;
     eggs;
•    milk;
     peanuts, forage, hay, and hulls;
     sorghum, fodder, forage, and grain;
•    soybeans, forage, and hay;
•    meat and meat byproducts of cattle, goats, hogs, poultry and horses.

     Sufficient data are available to determine the adequacy of most
established tolerances. Based on this data, some tolerances need to be
revoked, and some need to be increased. The reassessed tolerances for
alachlor will range  from 0.02 to 10 ppm.

     EPA has also assessed the chronic (non-carcinogenic) dietary risk posed
by alachlor. Using refinements to the dietary assessment process and
considering all food uses recommended  through reregi strati on, the Anticipated
Residue Concentration (ARC) for the overall U.S. population represents less
than 1% of the chronic Reference Dose  (RfD), the amount believed not to
cause adverse effects if consumed daily over a 70-year lifetime. The most
highly exposed subgroup, non-nursing infants less than one year old, has an
ARC which also represents less than 1% of the chronic RfD.  This low fraction
of the allowable RfD is considered to be an acceptable dietary risk.

     EPA has assessed the total carcinogenic dietary risk posed by alachlor by
both the Qj* approach and the MOE approach. Both approaches are discussed
below in the Aggregate Dietary Discussion.

Dietary Risk (Drinking Water Only)

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     People may be exposed to small amounts of alachlor through the
consumption of water containing residues of alachlor. Alachlor residues in
drinking water are regulated under the SDWA (Safe Drinking Water Act).
The MCL (Maximum Contaminant Level), set by the Agency, for alachlor is 2
ppb.  An MCL is the maximum permissible level of a contaminant in drinking
water that is delivered to any user of a public water supply system. For
alachlor, there is extensive monitoring data for both ground and surface water
sources.

     EPA has assessed the chronic (non-carcinogenic) drinking water risk
posed by alachlor. Using the monitoring data for alachlor only and Agency
assumptions on the amount of water consumed, the estimated exposure
represents less than  1% of the chronic Reference Dose (RfD), for adult males,
adult females, and children (1-6 years) sub-population groups. This is
considered to be  an acceptable drinking water risk.

     EPA has assessed the carcinogenic drinking water risk posed by  alachlor,
using water monitoring data and Agency assumptions on the  amount of water
consumed, for both the Qt* approach and the MOE approach. Both approaches
are discussed below in the Aggregate Dietary Discussion.

Aggregate Dietary  Risk (Food and Drinking Water)
     FQPA requires that the Agency consider aggregate risk, that is,  exposure
from all food, water, and residential (non-occupational, non-dietary) exposures
when making a safety determination. Since there are no residential uses of
alachlor, the aggregate exposure is for food and water only.  The highest
chronic risk is 4% of the chronic RfD which represents the sub-population
children (1-6 years).  This was calculated considering both food  and water
containing residues of alachlor as well as consumption of water containing
residues of the alachlor ESA degradate. The Agency considers this to be an
acceptable risk.

     The aggregate carcinogenic risk using the Qt* approach considers
exposures from both food and water. For adult males and adult females
carcinogenic risks range from 7.8 x 10"7 to 1.4 x 10"6. These risks are
consistent with the carcinogenic level (1 x 10"6 ) that the Agency considers to
be negligible.

     The aggregate carcinogenic MOEs (food and drinking water) for adult
males and adult females vary from 29,000 to 1,400,000. At this time,  the
Agency is not making any conclusions regarding the adequacy of these
calculated MOEs for carcinogenic  dietary risk. This is due to the fact  that the
Agency has not yet made a final decision  as to the appropriate uncertainty

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factors which would be adequately protective of a carcinogenic endpoint
regulated using a non-linear approach. However, given that the cancer risk
using the Qt* approach is acceptable and that the magnitude of the calculated
MOEs is quite large, the Agency believes that the dietary cancer risk from the
use of alachlor is not of concern.

Occupational Exposure
     Based on current use patterns, handlers (mixers, loaders, and applicators)
may be exposed to alachlor during normal use of granular, liquid, and dry
flowable formulations.  No protective equipment is required for the granular
formulations. For worker protection, the Agency will require the use of
additional protective equipment (chemical resistant gloves, apron, and chemical
resistant shoes) when handling liquid and dry flowable formulations for
workers supporting groundboom applications. For workers supporting aerial
applications, closed (mechanical transfer) systems will be required  for liquid
formulations. Monsanto will be required to develop water soluble packaging
for dry flowable formulations for aerial applications.  Closed (mechanical
transfer)systems will be required for the dry bulk fertilizer impregnation
process.

     The levels of protection required were based on the intermediate-term
exposure (one week to several months) scenario.  As previously stated, the
exposure assessment indicated that use of alachlor is an intermittent exposure
(not long-term and continuous.) The carcinogenic MOE approach  is not
appropriate for  an occupational risk  assessment for alachlor, because the
exposure is not of sufficient duration (i.e., chronic) to produce tumors.

     Unlike the MOE approach to carcinogenic risk assessment, the Qt*
approach assumes that any exposure could result in tumor formation. Thus,
this type of assessment could be performed for an intermittent exposure.
However, the scientific validity of the MOE approach for carcinogenic risk
assessment of alachlor has been documented. Alachlor was classified as
"likely" to be a carcinogen at high doses, but "not likely" at low doses.  It is
only the policy  on determining an appropriate regulatory level that has not been
fully developed by the Agency.  Since, performing a carcinogenic MOE risk
assessment for the occupational scenario is not appropriate, a Qt* carcinogenic
occupational assessment for comparison  purposes is not necessary.

     The potential for post-application worker exposure is negligible,
provided the Restricted Entry Interval of 12 hours is observed. This is due to
the timing of applications. Alachlor is applied to the soil  and/or soil
incorporated preplant, and pre-emergent. Thus the application of alachlor to

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                     emerging plants, well before the plants are mature, mitigates the potential for
                     post-application exposure.

Environmental   Environmental Fate
   AsSGSSrnGnt        The Environmental Fate Assessment shows that:
                          Alachlor has a low affinity to adsorb to soils and is expected to be highly
                          mobile.
                          Alachlor is moderately persistent and dissipates primarily by aerobic soil
                          metabolism processes with a half-life of 2-3 weeks.
                     •     The major acid degradates of alachlor are very mobile and appear to be
                          persistent.
                     •     Field dissipation studies confirm this fate profile (half-life of 6-11 days;
                          leaching through 42-48 inches in one of the studies).

                     Water Resources Assessment
                          The Water Resources Assessment concludes that:
                     •     Alachlor is highly mobile and moderately persistent. These two
                          characteristics are generally observed in chemicals that reach ground
                          water and surface water.
                     •     Alachlor presents a clear hazard to groundwater quality.  Reliable
                          monitoring studies have demonstrated that alachlor, even when used
                          according to label directions, results in significant groundwater
                          contamination.  Alachlor use also results in groundwater in the use areas
                          being contaminated with degradation products, which are also very
                          mobile and persistent.
                     •     Monitoring studies show that alachlor levels in surface water result in
                          effects on aquatic plants and indirectly on aquatic animals.
                     •     Available information indicates that (surface) drinking water supply
                          systems will usually comply with the SDWA.

                     Ecological Effects
                          The available toxicity data for alachlor indicate that alachlor is:
                          Slightly to practically non-toxic to birds on an  acute oral basis (LD50 of
                          1500mg/kg).
                     •     Slightly toxic to mammals, based on a rat study (LD50 of 930 mg/kg).
                     •     Slightly toxic to honey bees (LD50 >36 ug/bee).
                          Slightly to moderately toxic on an acute basis to freshwater fish (LC50 1-
                          33 ppm).
                     •     Highly to moderately toxic to freshwater fish on a chronic basis
                          (NOEC>0.1 ppm, LOEC>0.2 ppm).

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                        •     Moderately toxic to saltwater fish (3.9 ppm), moderately toxic to
                              saltwater mysid (2.4 ppm) and moderately toxic to shellfish (1.6 ppm).
                        •     Highly toxic to aquatic plants (based on a single species tested:
                              NOEL=0.35 ppb, LOEL=0.69 ppb, EC50=1.64ppb).
                              Therefore, a potential risk to nontarget terrestrial and aquatic plants, and
                        endangered plant species  exists. The available information on the major
                        alachlor degradates indicates that the degradates appear to be less toxic to
                        aquatic organisms than the parent.

                        Ecological Risk Assessment
                              An evaluation of the risk to nontarget organisms from the use  of alachlor
                        products, combining toxicity data with potential exposure, indicates that:
                        •     Alachlor poses a potential risk to terrestrial animals on a chronic basis.
                              Additional information are required to confirm this assessment.
                        •     The granular formulations and high use rate pose the greatest risk to
                              nontarget organisms.
                              Alachlor levels observed in surface water monitoring studies could result
                              in extensive adverse effects on aquatic plants.
                              Aquatic animals are not at acute risk due to exposure to alachlor, but
                              chronic effects may be observed under certain circumstances.

   Risk Mitigation         To lessen the human health, ecological, water and food quality risk
                        posed by alachlor, the registrant has voluntarily agreed to reduce the maximum
                        single application rate from 6 Ib to 4 Ib ai/acre, and to classify alachlor as a
                        restricted use pesticide (RUP) for groundwater concerns. EPA is requiring
                        additional mitigation measures that will:  protect non-target species, control
                        surface water and ground water contamination, and protect workers.
  Additional Data         EPA is requiring the following additional generic studies for alachlor to
          Required   confirm its regulatory assessments and conclusions:
                        •     avian reproduction
                        •     aquatic plant studies
                        •     analytical methodologies
                              handler exposure studies

                              The Agency also is requiring product-specific data including product
                        chemistry and acute toxicity studies, revised Confidential Statements of
                        Formula (CSFs), and revised labeling for reregi strati on.

Product Labeling         All alachlor end-use products must comply with EPA's current pesticide
                        product labeling requirements. The following label changes are required: (For

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ChangGS RGCjUirGd   a comprehensive list of labeling requirements, please see the Alachlor RED
                          Document, Table 78.)

                          •    Classify alachlor as a Restricted Use Pesticide (RUP) for ground water
                               concerns.
                          •    Label language regarding mixing/loading setbacks must appear in
                               Precautionary Statements in the Environmental Hazards Section.
                               Groundwater advisory language.
                               Surface water advisory language.
                          •    Advisory statement in the Environmental Hazards Section of toxicity to
                               terrestrial and aquatic plants, fish, and aquatic invertebrates.
                               Advisory statement for granular products.
                               Spray Drift Labeling Language.
                          •    For liquid (emulsifiable concentrate) formulations or dry flowable
                               formulations require that mixers, loaders, and persons cleaning
                               equipment must wear long-sleeved shirt, long pants, chemical-resistant
                               gloves, chemical-resistant footwear, and chemical-resistant apron for
                               those workers supporting groundboom application.
                               For workers supporting aerial applications and chemigation, for liquid
                               (emulsifiable concentrate) formulations require that mixers, and loaders,
                               must wear  long-sleeved shirt, long pants, and chemical-resistant gloves,
                               and the use of closed (mechanical transfer) systems.
                               For workers supporting aerial applications and chemigation, for dry
                               flowable formulations require that Monsanto develop water soluble
                               packaging.
                          •    For impregnating dry bulk fertilizer with alachlor require the use  of
                               closed mixing systems.
                          •    A 12 hour  restricted entry interval (REI) is required for uses within the
                               scope of the WPS.  The PPE required for early entry is coveralls,
                               chemical-resistant gloves, and shoes plus socks.
          Regulatory        EPA has determined that the reassessed tolerances for alachlor meet the
         Conclusion   safety standard under the FQPA, and that there is a reasonable certainty that no
                          harm will result to infants and children or to the general population from
                          aggregate exposure to alachlor residues.  The use of currently registered
                          products containing alachlor in accordance with approved labeling will not
                          pose unreasonable risks or adverse effects to humans or the environment.
                          Therefore, all uses of these products are eligible for reregistration. Alachlor
                          products will be reregistered once the required product-specific data, revised
                          Confidential Statements of Formula, and revised labeling are received and
                          accepted by EPA.

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   For MorG        EPA is requesting public comments on the Reregi strati on Eligibility
Information   Decision (RED) document for alachlor 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 Information and Records Integrity
                 Branch, Information Resources and Services Division (7502C), Office of
                 Pesticide Programs (OPP), US EPA, Washington, DC 20460, telephone
                 703-305-5805.

                      Electronic copies of the RED and this fact sheet are available on the
                 Internet. See http://www.epa.gov/REDs.

                      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  45242-2419, telephone 1-800-
                 490-9198;  fax 513-489-8695.

                      Following the comment period, the Alachlor RED document also will be
                 available from the National Technical Information Service (NTIS), 5285 Port
                 Royal Road, Springfield, VA 22161, telephone 703-605-6000.

                      For more information about EPA's pesticide reregi strati on program, the
                 Alachlor RED, or reregi strati on of individual products containing alachlor
                 please contact the Special Review and Reregi strati on Division (7508C), 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 Pesticide Telecommunications Network (NPTN).  Call toll-free 1-
                 800-858-7378, from 6:30 am to 4:30 pm Pacific Time, or 9:30 am to 7:30 pm
                 Eastern Standard Time, seven days a week.  Their website address is
                 ace.orst.edu/info/nptn/.
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