SUBSTITUTE CHEMICAL PROGRAM
         INITIAL  SCIENTIFIC
    MINIECONOMIC REVIEW
                     MARCH 1975
         U.S. ENVIRONMENTAL PROTECTION AGENCY
               OFFICE OF PESTICIDE PROGRAMS
            CRITERIA AND EVALUATION DIVISION
                   WASHINGTON, D.C. 20460

                       EPA-540/1-75-006

-------

-------
This report has been compiled by the Criteria
and Evaluation Division, Office of Pesticide
Programs, EPA in conjunction with other sources
listed in the Preface.  Contents do not
necessarily reflect the views and policies of
the Environmental Protection Agency, nor does
mention of trade names or commercial products
constitute endorsement or recommendation for
use.

-------
                                 PREFACE
     The Alternative (Substitute) Chemicals Program was initiated under
Public Law 93-135 of October 24, 1973, to "provide research and testing
of substitute chemicals."  The legislative intent is to prevent using
substitutes, which in essence are more deleterious to man and his environ-
ment, than a problem pesticide (one that has been suspended, cancelled,
deregistered or in an "internal review" for suspected "unreasonable
adverse effects to man or his environment").  The major objective of the
program is to determine the suitability of substitute chemicals which now
or in the future may act as replacements for those uses (major and minor)
of pesticides that have been cancelled, suspended, or are in litigation
or under internal review for potential unreasonable adverse effects on
man and his environment.

     The substitute chemical is reviewed for suitability considering all
applicable scientific factors such as:  chemistry, toxicology, pharma-
cology and environmental fate and movement; and socio-economic factors
such as:  use patterns and costs and benefits.  EPA recognizes the fact
that even though a compound is registered it still may not be a practical
substitute for a particular use or uses of a problem pesticide.  The -
utilitarian value of the "substitute" must be evaluated by reviewing its
biological and economic data.  The reviews of substitute chemicals are
carried out in two phases.  Phase I conducts these reviews based on data
bases readily accessible at the present time.  An Initial Scientific
Review and Minieconomic Review are conducted simultaneously to determine
if there is enough data to make a judgment with respect to the "safety
and efficacy" of the substitute chemical.  Phase II is only performed if
the Phase I reviews identify certain questions of safety or lack of benefits.
The Phase II reviews conduct in-depth studies of these questions of safety
and cost/benefits and consider both present and projected future uses of
the substitute chemicals.

     The report summarizes rather than interprets scientific data reviewed
during the course of the studies.  Data is not correlated from different
sources.  Opinions are not given on contradictory findings.

     This report contains the Phase I Initial Scientific and Minieconomic
Review of Bromacil (5-bromo-3-sec-butyl-6-methyluracil).  Bromacil was
identified as a registered substitute chemical for certain cancelled and
suspended uses of 2,4,5-T.  Where applicable, the review also identifies
areas where technical data may be lacking so that appropriate studies may
be initiated to develop desirable information.

     The review covers all uses of bromacil and is intended to be adaptable
to future needs.  Should bromacil be identified as a substitute for a problem
pesticide other than 2,4,5-T, the review can be updated and made readily
available for use.  The data contained in this report was not intended to be
                                    iii

-------
complete In all areas.  Data-searches ended in December, 1974.  The review
was coordinated by a team of EPA scientists in the Criteria and Evaluation
Division of the Office of Pesticide Programs.  The responsibility of the team
leader was to provide guidance and direction and technically review information
retrieved during the course of the study.  The following EPA scientists were
members of the review team:  Fumihiko Hayashi, Ph.D.  (Team Leader); Carroll
Collier (Chemistry); William Burnam  (Pharmacology and Toxicology); John Bowser
(Fate and Significance in the Environment); John Leitzke (Fate and Significance
in the Environment); Richard Petrie  (Registered Uses); Jeff Conopask (Economics),

     Data research, abstracting and  collection were primarily performed by
Midwest Research Institute, Kansas City, Missouri (EPA Contract #68-01-2448).
RvR Consultants, Shawnee Mission, Kansas,  under a subcontract to Midwest
Research, assisted in data collection.  E. I. du Pont de Nemours and Company,
a manufacturer of bromacil, made certain comments and additions to this report.
                                      iv

-------
                           GENERAL CONTENTS


                                                                  Page

List of Figures   	   vi


List of Tables	vii


Fart    I.         Summary	    1


Part   II.         Initial Scientific Review	   10
       Subpart A.    Chemistry  	   10
       Subpart B.    Pharmacology and Toxicology  	   25
       Subpart C.    Fate and Significance in the Environment . .   39
       Subpart D.    Production and Use	   55
Part  III.         Minieconomic Review	   70

-------
                                 FIGURES








No.                                                               Page






 1    Production Schematic for Bromacil  ..... 	 .     13

-------
                                 TABLES
No.                                                               Page

 1    Weight Losses on Combustion of a Commercial Bromacll
        Formulation (percent)  	    20

 2    Consumption of Bromacll  	    27

 3    Mortality of Rats Consuming Bromacll 	    28

 4    Results of Multiple Oral Dosing of Bromacll In Cattle,
        Sheep, and Chickens	    31
 5    Bromacil 80Z Wettable Powder (Hyvar^X) Label	    58

 6    Estimated Uses of Bromacll In the U.S. by Regions and
        Categories, 1972   	    64

 7    Bromacll Uses in California by Major Crops and Other
        Uses, 1970-1973	    66

 8    Use of Bromacil in California in 1972 by Crops and Other
        Uses, Applications, Quantities, and Acres Treated  ...    68

 9    Use of Bromacil in California in 1973 by Crops and Other
        Uses, Applications, Quantities, and Acres Treated  ...    69
                                    vii

-------
                            PART I.   SUMMARY
                                CONTENTS
Production and Use
Toxicity and Physiological Effects . . .






Food Tolerances and Acceptable Intake  .






Environmental Effects  	






Limitations in Available Scientific Data






Efficacy and Cost Effectiveness  ....
                                                                  Faze

-------
     This section contains a brief summary of the "Initial Scientific
 and Minieconomic Review" on bromacil.  The section summarizes rather
 than intreprets data reviewed.

 Production and Use

     Bromacil (5-bromo-3-sec-butyl-6-methyluracil)  is  one of a  family
 of substituted uracils used  as  herbicides.   Three  reactions  are required
 for its  manufacture:
see-but ylamine
                COC12

              phosgene
                                                                     2HC1
                                                  sec-butylurea  (I)
(I)  +  CH,COCH9C09C9H«
          j    /  / ^ :

        ethyl acetoacetate
                                                               H20
                                                               ethanol
                              sec-C
               Br2
                                         3-sec-butyl-6-methyluracil  (II)
                                                HBr
                                        Bromacil
     The only domestic manufacturer of bromacil and other substituted
uracils is E. I. du Pont de Nemours and Company, Inc.  Their produc-
tion facility, which is located in La Porte, Texas, has an estimated
capacity of 20 million pounds per year of total uracils.

     The chemistry of bromacil reported in available literature primarily
concerns degradation reactions.  Bromacil  is  reported  to  be slowly  de-
composed in strong acid, but  is stable  in  water,  aqueous  base,  common
organic solvents, and at temperatures up to  its melting point  (158  to
159° C).  Degradation by ultraviolet  radiation has also been reported.

-------
     Bromacil is a broad-spectrum herbicide used for control of annual
and perennial grasses and broadleaf weeds,  for nonselective weed and
brush control on noncropland, and for selective weed control on a limited
number of crops.  Bromacil is commercially available in formulation as
a single active ingredient, and in combination with diuron, sodium meta-
borate, and sodium chlorate.

     An estimated 3 million pounds of bromacil active ingredient (AI)
were used domestically in 1972.  Of that quantity, about 400,000 Ib AI
were used for agricultural purposes (primarily for weed control in citrus
groves located in the Southwestern states,  and in pineapple fields in
Hawaii); 2,300,000 Ib AI were used by industrial and commercial organi-
zations; and about 300,000 Ib AI by government agencies.  Bromacil is
not registered for home and garden use.

     Estimated 1972 regional uses of bromacil are:  South Central states—
about 25%, Southwestern states—about 20%,  Southeastern states—about
20%, North Central states—13%, and the Northeastern and Northwestern
states—less than 10% each.

Toxicity and Physiological Effects

     No data was found on effects of bromacil on humans, either on an
acute basis or under field conditions or in the manufacturing processes.
Bromacil, however, is not a highly toxic compound.  The spectrum of its
toxicity as evaluated in rats is as follows:

Acute oral toxicity - LD5Q = 5,200 mg/kg.

Acute inhalation toxicity - No deaths occurred after 4 hr in a 4.8 mg/liter
environment.

Subacute oral toxicity (10-day study) - No deaths occurred after 10 daily
doses of 650 mg/kg, and five out of six animals survived 10 daily doses
of 1,035 mg/kg.  In contrast, four out of five animals died after five
doses of 1,500 mg/kg.  At both the 650 and 1,035 mg/kg doses, pathological
changes were observed in the liver immediately after the final (10th) dose.
No pathological changes were observed in the livers, after a 14-day
recovery period.

-------
Chronic oral toxicitv  (2-year study) - Female rats on the highest dose
level tested (1,250 ppm) suffered weight retardation during first and
second years.  There were no clinical signs of toxicity.  No unusual
alterations were observed during hematological, urinalysis, and clinical
chemistry evaluations.  There were no gross pathological lesions.  There
appeared to be a dose-related effect on the thyroid.  Slight hyperplasia
of the thyroid was noted at the highest dose level.

     An acute oral toxicity evaluation could not be obtained in dogs
because of ernes is.  Five grains per kilogram, as a single dose or as
divided doses, produced excessive ernesis.  Emesis was still observed at
the 200 to 250 mg/kg level.  Signs of toxicity in dogs were salivation,
weakness, loss of coordination, excitability, diarrhea and nydriosis.
In long term studies with rats, bromacil did not appear to accumulate
in tissues.

     In a 2-year chronic oral toxicity test, groups of dogs were
maintained on 0.005, 0.025, and 0.125% bromacil in the diet.  Only one
death occurred, and that dog was on the 0.005% diet; the cause of death
was not associated with the compound.  A loss in weight was noted at the
high dose at the beginning of the experiment.

     Bromacil is moderately toxic to ruminants.  Cattle suffered weight
loss and were poisoned with a single dose at 250 mg/kg.  Sheep were also
poisoned and had a weight loss after three 250 mg/kg doses of bromacil
were given by drench or capsule; a dose (drench) of 100 mg/kg also caused
poisoning and weight loss.  None of the ruminants died.

     In ±a vitro tests, bromacil reduced the amount of dry matter digested
by rumen bacteria.  Bromacil did not effect volatile fatty acid production.
A decrease in the number of ciliated protozoa in rumen fluid in the
presence of bromacil was noted.

     Chickens appear to tolerate a dose of 500 mg/kg.  There was a sig-
nificant reduction in weight gain at this level.

-------
     The effect of bromacil on the reproduction of rats was evaluated
in a three-generation study.  Addition of 0.025% bromacil to the diet
did not markedly effect the reproductive performance; no deformed
young were produced.

     Very little information exists as to the site of bromacil metabo-
lism, distribution or retention, the enzymes involved, and the cofactor
requirements.

     Bromacil is metabolized and excreted as six metabolites by rats,
one being 5-bromo-3-8ec-butyl-6-hydroxymethyluracil.  In cases of
human industrial exposure, bromacil and its primary metabolite, 5-bromo-
3-sec-butyl-6-hydroxymethyluracil was detected in urine.

     No gross manifestations of teratogenic effects were observed in
the fetuses of pregnant rabbits consuming as much as 250 ppm from the
eighth day of pregnancy to the 16th day.

     There is no Indication from the literature review that bromacil
produces oncogenic effects.

Food Tolerances and Acceptable Intake

     Bromacil has not been reported as a significant residue in any
class of food, but is not necessarily detected by the analytical system
routinely used to monitor pesticide residues in food.

     Tolerances have been established for bromacil on only two crops
in the United States, citrus fruits and pineapples.  Both tolerances
have been set at 0.1 ppm.

     An acceptable daily intake (ADI) has not been established for
bromacil.  An ADI has not been considered by the Food and Agricultural
Organization/World Health Organization (FAO/WHO).

-------
 Environmental Effects

      Brotnacil displayed a low order of toxicity to six fish species
 as well  as  tadpole, crawfish and waterflea.  The eight-day dietary
 LCso  for both the mallard duck and the bobwhite quail was? 10,000 ppm.
 Bromacil was tested as a spray at 10,000 ppm against housefly, roach
 aphid (systemic) and mite and was found to be totally lacking in
 insecticidal or acaricidal activity.

      Stains of Euglena. an aquatic algae, were not affected by 40 ppm
 bromacil, and were only partially Inhibited by 100 ppm.  One wild strain
 of Euglena. however, was markedly inhibited by 2 ppm and completely
 inhibited by 10 ppm (none of the strains were affected by bromacil in
 the dark).


     A number of soil fungi have shown uninhibited growth with bromacil.
Ten soil fungi (Aspergillus tamarii, A. niger. A. flavus. A.  oryzae.
 Curvularla  lunata. Mucor pusillus. Trichoderma vlride. Penicillium
 funiculosum. £. brevicompactum. and Myrothecium verucaria) were  cultured
 on liquid broth media with bromacil levels  from 250  to 5,000  ppm for
 5 days.  Bromacil, up to 2,000 ppm did not  inhibit the growth of the
 fungi; except A. niger. which was inhibited by bromacil  levels less than
 1,500 ppm.

     No  statistically significant differences were found in the  ammonium
and nitrate nitrogen contents of, nor in the amounts of  carbon dioxide
evolved from untreated sandy loam and that  from loam treated  with 4 ppm
bromacil (twice the application rate recommended for this type of soil).

     The available data indicates that certain soil microorganisms are
 capable of degrading bromacil, and that normal bromacil concentrations
 in the soil, i.e., those that might be expected from its use in accord-
ance with label directions, do not appear to adversely affect the soil
microflora.

     Available data indicates that bromacil is not strongly adsorbed on
soil colloids.

-------
     Bromacil residues In the soil appear to be quite persistent.  In
one test, the half-life of a A Ib Al/acre application to the surface of
& Butlertown silt loam was found to be about 5 to 6 months.  At higher
application rates, the herbicidal activity of brotnacil seemed to persist
for two or more seasons.

     Other investigations involving the application of 1 and 4 Ib of
bromacil per acre to six California locations found bromacil to be
persistent.  One year after application (for both application rates)
plots remained toxic to barley, milo, sugar beets, alfalfa, tomatoes,
and wheat.

     In vitro studies show that some microorganisms have the ability
to metabolize bromacil.  The solubility of bromacil in water could be
resulting rainfall being a factor in soil persistence.

     Regarding bromacil residues in air, one study showed that the rate
of bromacil volatilization in an air circulation oven maintained at 120°F
was less than 0.1%/week.  Other studies indicated that bromacil is very
stable to phctodecomposition.

Limitations in Available Scientific Data

     The review of scientific literature was based on available sources
given limitations of time and resources.  Data was not found in a
number of pertinent areas.

      1.  The effect of bromacil on humans.

      2.  Intraperitoneal and intravenous 11*50 values on at least one
          species.

      3.  Inhalation data on more species than the rat.

      4.  A long-term (2 years) study in rats at a dose level higher
          than 0.125%.

      5.  Data related to behavioral effects and the effects on tissue
          culture growth and viability.

      6.  Field data on effects on fish.

      7.  Field data on effects of wildlife.

      8.  Additional data on the effects on the soil microflora and on
          effects on soil microfauna.

-------
       9.  Data from national or regional soil monitoring studies  on
           pesticide residues.

      10.  Laboratory or field data on effects on lower aquatic organisms.

      11.  Additional information on the presence,  fate,  and persistence
           of bromacil residues in water, sediment, or other elements of
           the aquatic ecosystem.

      12.  Additional data on the presence,  fate, or persistence of
           bromacil residues in air.

      13.  Data on the possible bioaccumulation or biomagnification  of
           bromacil.

      14.  Specific data on the environmental transport mechanisms of
           bromacil.

      Bromacil is used primarily as a nonselective industrial herbicide
 on noncropland,  and  limitations in environmental data should be evaluated
 in terms of this use pattern.

 Efficacy and Cost Effectiveness

      Bromacil is used as a broad-spectrum herbicide to control annual
 and perennial grasses and brush in pineapple and citrus  orchards, along
 railroads and highway right-of-ways,  around utility poles,  and along
 drainage ditches,  canals and fences.

      Bromacil has effectively controlled Bermuda grass,  Vasey  grass,
 nutsedge, crabgrass,  Bahia grass and  sweetgrass.  It also controls  willow,
 cottonwood,  water locust,  post oak, blackjack oak,  hickory,  maple,  wild
 cherry,  sweet gum, elm and a wide variety of other brush.

      The economic benefit from using  bromacil on oranges was determined
 from one experiment  in Florida.   At a rate  of 3.5  Ib/acre,  the economic
 benefit  amounted to  $27.25/acre from  the increased yield of  oranges (based
 on  1972  cost  data).   No other economic benefit data was  found.

      Economic benefits from noncrop applications (e.g.,  grass  and brush
 control  along highways,  utility lines,  and  railroads)  are best  measured
 by  an alternative  costing  method.  Alternative methods to chemical  con-
 trol  include  mechanical control  such  as mowing,  discing, bulldozing and
 the use  of brush cutting machines.  Hand labor is  often  required  for
mowing around trees,  poles  and  other  objects  and for weeding or cutting
brush.   In some cases  burning for  control of  grasses along canal banks
 is an alternative.

-------
     The true economic benefits cannot be measured because much of the
noncrop weed control is for aesthetic reasons such as beautification of
highways.  It is also a form of preventative maintenance to keep fires
from causing damage when grasses are dry.  Therefore, the cost of the
chemical control should be subtracted from the alternative control cost,
such as hand labor or mechanical control, to determine the economic
benefit from the use of bromacil.

     Selected tests comparing the use of chemical treatment to alterna-
tive methods such as mechanical or hand labor control for noncrop weed
and brush removal showed economic benefits ranging from a decreased cost
of $6.50/acre for chemical control of weeds and brush along irrigation
ditches in California, to a $175.00/acre cost reduction for treatment of
flood control dikes in West Springfield, Massachusetts.  However, a more
accurate assessment of economic benefits would require cost data over at
least a 3-year period because initial costs of chemical treatment are
much higher than subsequent chemical treatment costs.

-------
                  PART  II.   INITIAL SCIENTIFIC REVIEW


                         SUBPART A.   CHEMISTRY


                               CONTENTS



                                                                    Page

 Synthesis and Production Technology 	     11

 Physical Properties of Bromacil 	     12

 Analytical Methods.	     14

 Composition and Formulation 	     17

 Chemical Properties, Degradation and Decomposition Processes. .  .     17

  Photochemical Decomposition 	     18
  Degradation in  Soil	     19
  Thermal Decomposition  	     19
  Other Decomposition Processes 	     21

Occurrence of Bromacil Residues in Food and Feed Commodities. .  .     21

Acceptable Daily  Intake  	     21

Tolerances	     22

References	     23
                                      10

-------
     This section reviews available data on bromacil's chemistry and presence
in foods.  Eight subject areas have been examined:  Synthesis and Production
Technology; Physical Properties of Bromacil; Composition and Formulation;
Chemical Properties, Degradation and Decomposition Processes; Occurrence and
Residues in Food and Feed Commodities; Acceptable Daily Intake; and Tolerances.
The section summarizes rather than interprets scientific data reviewed.
Synthesis and Production Technology

     Bromacil is one of a. family of substituted uracils used as herbi-
cides.  The production steps are similar for all members of the family,
the differences being primarily in the starting materials.   The chemical
synthesis of bromacil is as follows (von Rumker et al., 1974)I/:
                    COC12    +    NH3 	>  C4HgNHCONH2    +    2HC1   (1)

sec-butylamine     phosgene     ammonia       sec-butylurea



                                      'sec-C^  j}^                ,     (2)
                                                           H20 + C2H5OH
sec-butylurea      ethyl acetoacetate
                                             r* ••  "r»«^   ^TT
                                                                ethanol
                                       3-sec-butyl-6-methyluracil
 3-sec-butvl-6-methyluracil                     Bromacil
 I/  von Rumker,  R.,  E.  W.  Lawless,  and A. F. Meiners, "Production, Dis-
       tribution, Use and Environmental Impact Potential of Selected
       Pesticides," Final Report, Contract No. EQC-311, for Council on
       Environmental Quality, Washington, D.C. (1974).


                                   11

-------
      E. I. du Pont de Nemours and Company is the  only manufacturer of
 bromacil.  The manufacturing plant is located in  La Porte, Texas and
 has an estimated total capacity of 20 million pounds per year for all
 substituted uracils.

      A proposed schematic for bromacil production is  shown in Figure  1.

      A series of substituted uracils is covered by U.S.  Patent  No.
 3,235,357 (Loux, 1966)!/, but this is primarily a use  patent and  the
 method suggested for preparing bromacil is a laboratory  method.

      The preparation of bromacil is described as  follows:

      "A solution of 182 parts of 3-sec-buty1-6-methyluracil  in
      700 parts of acetic acid containing 82 parts of  sodium acetate
      was treated with 160 parts of bromine.  After standing  over-
      night,  the mixture, which contained some solid, was evaporated
      to a solid under reduced pressure.  The solid was recrystallized
      from an ethanol-water mixture to give, as a  white crystalline
      solid,  2-sec-butyl-5-br6mo-6-methyluracil melting at 157.5 to
      160°C."

 Physical Properties of Bromacil

 Chemical name:   5-bromo-3-sec-butyl-6-methvluracil

 Common  name:   Bromacil

 Trade name:   Hyvar® X

 Pesticide  class:   Herbicide;  substituted  uracil

 Structural formula:                 H
                                    u
                             Br-C.    N-CH-CH2-CH3
                                   I    **

Empirical formula:  CgHj^Br^C^
I/  Loux, H. M. (to E. 1. du Pont de Nemours and Company, Inc.), U.S.
      Patent No. 3,235,357  (February 15, 1966).
                                   12

-------
f—
Sec - Butylamine—^

M I"M i th


I
Urea Unit


I
Purification
~ ~l
1
1
1
|
1
	 J
th. IMiif"!

Sec-C4H9NHCONH2
1
Ethyl 	 ^
Acetoacetate
Ki..r^ii 1^.

Uracil Unit
\
Purification
Aqueous
Waste
Na Salt of
3 -Butyl ,6- Methyl Uracil
I
i
H^SO'j » Neutralization _ Ku««n. ^
«2:)U4 + Separation
Bromine 	 ^
H^O ih.
NaOH
Stream
j
Bromacil
Unit


Source: von Rlimker et al.f op
^^ Filtrqtion
Drying
i >
1
Bromacil
. cit. (1974).

Biological
Treatment
r
^ Disposal
at Sea
NaBr
Stream
                                                          •Discharge
Figure 1.  Production schematic for bromacil.
                      13

-------
 Molecular weight:  261.1

 Analysis:  C - 41.37%; H - 5.02%; Br - 30.61%; N - 10.73%;  0 - 12.26%

 Physical state:  White, odorless, crystalline solid

 Melting point:  158-159°C

 Vapor pressure:  8 x 10~4 mm Hg at 100°C

 Stability:  Temperature stable up to melting point, but slowly sublimes
               at temperatures just below melting point.

 Specific gravity:  1.55  25/25°C

 Solubility at 25°C:       Solvent          g/100 ml

                      Absolute ethanol       13.4
                      Acetone                16.7
                      Acetonitrile            7.1
                      Sodium hydroxide
                        (3% aqueous)          8.8
                      Water                   0.0815 (= 815  ppm)
                      Xylene                  3.2

 Analytical Methods

      This subsection reviews analytical methods  for bromacil.  The review
 describes multi-residue methods,  residue analysis principles,  and formula-
 tion analysis principles.   Information on the sensitivity and  selectivity
 of  these methods is also presented.

 Multi-Residue Methods - Multi-residue methods for detecting bromacil are not
 found in either the Association of Official  Analytical Chemists methods
 manuall/ or the Pesticide  Analytical Manual.  Volume I  (PAM  1971).?J  Bromacil
 has  not  been reported as a significant residue in any  class of food nor is it
 routinely searched  for in  the FDA multi-residue  analytical  system which is
 used to  monitor pesticide  residues in food.   Adequate  individual compound
 methods  exist for measuring bromacil residues.   The apparent reason for the
 absence  of  bromacil  residue data  is  that the pesticide is not  widely used on
 food and feed items.   The  absence of bromacil residue  data  does not mean that
 it could not  be present  in food.
I/  Association of Official Analytical Chemists, Official Methods of Analysis
      of the Association of Official Analytical Chemists, llth ed., Washington,
      D.C. (1970).
21  U.S. Department of Health, Education and Welfare, Food and Drug
      Administration, Pesticide Analytical Manual, Vol. I (1971).
                                       14

-------
Residue Analysis Principles - Volume II of the Pesticide Analytical Manual
(PAM, 1971)i/ lists two methods of residue analysis for bromacil.   The first
is the method described by Pease (1966).I/  This method can be used for soil,
fruits, vegetables, animal tissue, grain and seed.   The sample is  first
extracted with sodium hydroxide; the extract is acidified with sulfuric acid,
and the bromacil is then extracted into chloroform.  The chloroform portion is
separated and the solvent is evaporated.  The residue is redissolved in aqueous
sodium hydroxide, acidified, and the bromacil is reextracted into  ethyl acetate.
The solvent is again evaporated and the residue is finally dissolved in nitrq-
methane.  The final determination is made using gas chromatography and a micro-
coulometric detector.  The recoveries are greater than 85%, and the sensitivity
is about 0.04 ppm.

     The second PAM method is described in Jolliffe et al. (1967)!/.  The
method employs a relatively short (13 in.) gas chromatography column and
an electron-capture detector.  The authors claim the method is simple and
fast, but maintains sensitivity and reproducibility.  The procedure for
the analysis of soils is slightly different from that for leaves or fruit.
For both procedures, the initial extraction is performed with an aqueous
solution of ammonium sulfate and sodium hydroxide.   In soil analysis, the
recoveries are 90 to 110%, and sensitivity is about 0.01 ppm.  For leaves
or fruit, the method is not as accurate; recovery is about 60 to 85%, and
sensitivity is 0.1 ppm.

     Zweig and Sherma (1972)A/ discuss two additional methods.  One is
described by Bevenue and Ogata (1970).!.'   This method uses gas chromatog-
raphy with an electron-capture detector and is applicable to plant material,
soil and water.  Sample preparations are similar to those used by Pease  (1966)
and Jolliffe et al.  (1967).  The method differs from that of Pease  (1966)—a
microcoulometric titrating system is not needed.  The method also differs from
that of Jolliffe et al. (1967)—a short gas chromatograph is not used.
Recoveries of bromacil were 85 to 89%, and the limits of detectability were
0.005 ppm.  The second method is that of Gutenmann and Lisk  (1968) .6/  Their
method for bromacil was tested only on residues in soil.  The residue was
extracted directly into ethyl acetate.  The herbicide was then isolated  by
evaporative co-distillation.  Electron affinity detection was employed in the
gas chromatographic procedure.  Recoveries of bromacil in the 0.04  to 0.4 ppm
range ranged from 72 to 90%.
I/  U.S. Department of Health, Education and Welfare, Food and Drug
      Administration, Pesticide Analytical Manual. Vol. II (1971).
2J  Pease, H. L., "Determination of Bromacil Residues," J. Agr. Food Chem.,
      14(l):94-96 (1966).
.37  Jolliffe, V. A., B. D. Day, L. S. Jordan, and J. D. Mann, "Method  of
      Determining Bromacil in Soils and Plant Tissues, "J. Agr. Food Chem..
      15(l):174-77  (1967).
kj  Zweig, G. and J. Sherma, Analytical Methods for Pesticides and Plant
      Growth Regulators. Vol. VI; Gas Chromatographic Analysis, p. 603,
      Academic Press, New York, New York  (1972).
5_/  Bevenue, A. and J. N. Ogata, "Determination of Bromacil by Gas Chroma-
      tography ," J_i_J]hromatog>., 46(1): 110-11  (January 1970).
6J  Gutenmann, W. H. and D. J. Lisk, "Estimation of Residues  of Uracil
      Herbicides by Gas Chromatograjphy After  Evaporative  Co-Distillation,"
      J. Assoc. Offie. Anal. Chem.. 51(3):688-90  (1968).
                                      15

-------
 Formulation Analysis Principles - Pease and Deye (1967)—/ explain the basis
 for formulation analysis as follows:

      "Bromacil exhibits the properties of a weak acid.   It forms water-
 soluble alkali salts and can be extracted from aqueous  acid into nonpolar
 organic solvents.  The material can thus be separated,  purified, and  con-
 centrated by appropriate extraction techniques.

      "The isolated material is most accurately determined by a differential
 infrared analysis at 13.02 pm, the absorption maximum arising from the
 uracil configuration of the molecule.   Bromacil is too  weakly acidic  for
 titration in water, but can conveniently and easily be  assayed with good
 precision by nonaqueous titration.

      "Ultraviolet analysis of the extracted material is impractical because
 of interferences.  Gas chromatographic methods are accurate but generally
 lack the precision of the differential infrared and nonaqueous titration
 methods."

      Pease and Deye (1967) then explain the principle of the differential
 infrared method:

      "The active  ingredient,  5-bromo-3-sec-butyl-6-methyluracil. is isolated
 by extraction with ethyl ether and is  determined by differential infrared
 analysis.   In the differential infrared method, a solution of known concen-
 tration of pure bromacil is placed in  the reference beam of the infrared
 spectrophotometer,  and its absorbance  is compared with  that of a solution
 of the unknown placed in the  sample beam.  To assure maximal precision,
 the solution is scanned three times at slow speed and high gain, and  the
 average absorbance reading is used."

      The  standard deviation of this method is approximately 1% in the 40
 to 60% concentration of bromacil range,  provided there  are no extractable
 ingredients that  absorb at the analytical wavelengths.

      The principle  of the nonaqueous titration method is explained by Pease
 and  Deye  (1967):

      "The  active  ingredient,  5-bromo-3-sec_-butyl-6-methyluracil,  after
 isolation  from possible interfering formulating ingredients,  is dissolved
 in acetone and titrated with  tetrabutylammonium hydroxide.   The titration
 is followed potentiometrically with a  high impedance pH meter using a
 glass-modified calomel  electrode system."

     The precision  of this  method is i 0.3%.   Other weakly acidic materials
may interfere.
I/  Pease H. L. and J. F. Deye, "Bromacil," Analytical Methods for Pesti-
      cide. Plant Growth Regulators, and Food Additives. Vol. V; Additional
      Principles and Methods of Analysis, G. Zweig  (ed.), Academic Press,
      New York (1967).
                                       16

-------
Composition and Formulation

     Bromacil is available in five formulations from the manufacturer:

      1.  Hyvarfe/X bromacil weed killer, a wettable powder containing
          80% bromacil.

      2.  HyvarOPx-L bromacil weed killer, a water-soluble liquid
          containing 2 Ib bromacil per gallon (present as lithium salt).
      3.  Hyvar®X-P brush killer, pellets containing 10% bromacil.
      4.  KrovarUivi weed killer, a wettable powder containing 40% bromacil
          and 40% diuron.

      5.  KrovarUxII weed killer, a wettable powder containing 53% bromacil
          and 27% diuron.

     Commercial femulators prepare other formulations, including some which
contain other pesticides.

Chemical Properties, Degradation and Decomposition Process

     Bromacil is a herbicide of a family called substituted uracils.
Many members of this family are strong photosynthesis inhibitors.

     Bromacil has been, shown to be an inhibitor of photosynthesis in many
laboratory systems, and this effect is the probable cause of its herbicidal
activity.  (Hoffmann et al.i/, Hilton et al..£/).

     The lack of activity on nonphotosynthesizing plant tissue was confirmed
by Jordan et al.^.'.  They found that bromacil had no effect on the dark growth
of tobacco callus tissue supplied with an organic energy source, except at
much greater concentrations than required for inhibition of photosynthesis.

     Couchz/ found that one ppm of bromacil reduced photosynthesis ^C02 -
fixation in corn (Zea mays), cotton (Gossypium hirsutum), and soybeans
(Glycine Max).
I/  Hoffmann, C. E., J. W. McGahen, and P. B. Sweetser, "Effect of Substituted
      Uracil Herbicides on Photosynthesis", Nature. 202 (4932):577-8  (1968).
21  Hilton, J. L., T. J. Monaco, D. E. Moreland, and W. A. Centner, "Mode
      of Action of Substituted Uracil Herbicides," Weeds. 112:129-131  (1964).
3f  Jordan, L. S., T. Murashige, J. D. Mann, and B. E. Day, "Effect of
      Photosynthesis - Inhibiting Herbicides on Nonphotosynthetic Tobacco
      Callus Tissue." Weeds. 14(2):134-6  (1966).
47  Couch, R. W. and D. Davis, "Effect of Atrazine, Bromacil and Diquat  on
      14-CO£ - Fixation in corn, cotton, and soybeans", Weeds, 14(3):
      251-5 (1966).
                                   17

-------
      The chemical name of 5-bromo-3-sec-butyl-6-methyluracil was origi-
 nally used by Chemical Abstract Services (CAS), and is the one accepted
 for use on the pesticide label ingredient statement (Caswell, 1972)i/.
 CAS now uses the name 5-bromo-6-methyl-3-(l-methylpropyl)-2,4(lH.3H)-
 pyrimidinedione.

 Photochemical Decomposition - Several investigations have been made of
 the ef|ect of ultraviolet (UV) radiation on herbicides.  Jordan et al.
 (1965)—' subjected samples of several herbicides to various sources of
 UV radiation.  Three sources of UV radiation were used:  far UV (wavelength
 range, 240 to 260 nm, peak at 253.7 nm) ; middle UV (275 to 375 nm, peak
 at 311 ran); and near UV (320 to 450 nm, peak at 360 nm).  The lamps emitted
 approximately 15 w at the peak wavelength.  The samples were prepared by
 allowing solutions (1 x 10"^ molar) to evaporate on 1-in. diameter alum-
 inum planchets.  The samples were placed 1 ft from the UV sources.

      The results showed that the most extensive decomposition of bromacil
 was caused by far UV radiation.  However, a thin layer of decomposed
 product  apparently protected the lower layers, indicating that very
 little protection is required to prevent photodecomposition.  The author
 noted that far UV radiation does not occur in natural sunlight.  Signifi-
 cant UV  radiation above 290 nm occurs in sunlight and the photodecomposi-
 tion mechanism may be the same at all UV wavelengths, although the rate
 may vary.   Wright (1967)  2/ also found that far UV radiation produces more
 rapid decomposition of bromacil than middle or near UV radiation.
\J  Caswell, R. L., D. E. Johnson,  and C. Fleck, Acceptable  Common Names
      and Chemical Names for the Ingredient Statement  on  Pesticide Labels
      (2nd ed.), Environmental Protection Agency, Washington, D.C. (June
      1972).
2/  Jordan, L. S., J. D. Mann, and B. E.  Day, "Effects of Ultraviolet
      Light on Herbicides," Weeds,  13(l):43-46 (January 1965).

3/  Wright, W. L., "Photochemical Breakdown of Herbicides,"  (Abstract),
      Proceedings, 20th Southern Weeds Conference,  20:391 (1967).
                                       18

-------
     Hill (1971)I/ reported that, in exposure tests in sunlight and in
several practical field tests, bromacil did not appear to be affected
adversely by sunlight.  However, he presented no details of the analy-
tical method or the extent of exposure.

     Kearney et al. (1969)27 obtained results showing that ultraviolet
radiation can greatly reduce the phytotoxicity of bromacil.  In seeking
a method to decontaminate water supplies, he irradiated various solu-
tions of pesticides in water with a 450-w Hanovia lamp.  This lamp is
an intense source of UV radiation and emits strongly in the far, middle
and near UV.  The initial concentration of bromacil was 1 ppm.  Kearney
used a bioassay for bromacil, but did not report any products formed from
the implied photodecomposition.

Degradation in Soil - Zimdahl (1968)-' studied the kinetics of the degrada-
tion of various herbicides in soil.  Nine different herbicides were
applied at 8 ppm, and temperatures were maintained at either 13.2°C or
31.2°C.  Moisture was maintained at about 507. of field capacity, and
monthly samples of the soil were analyzed.   The following conclusions were
reported:

      1.  The rate of degradation followed a first order rate law.

      2.  The degradation was probably nonenzymatic.

      3.  The herbicides appeared to be attacked by chemical hydrolysis
          at the halogen substitutent.  (This conclusion was apparently
          based upon kinetic data, not analytical data, and no hydrolysis
          products were reported.)
Thermal Decomposition - Bromacil is stable up to its melting point of
158 to 159°C.  However, it begins to sublime at temperatures below its
melting point (du Font, April, 1972)^./.   Bromacil apparently begins to
I/  Hill, G. D., "Characteristics of Herbicides by Chemical Groups,"
      Proceedings. 23rd Annual California Weed Conference (January  1971).
21  Kearney, P. C., E. A. Woolson, J. R. Plimmer, and A. R. Isensee,
      "Decontamination of Pesticides in Soils," Residue Rev.. 29:137-
      149 (1969).
3/  Zimdahl, R. L., "A Kinetic Analysis of Herbicide Degradation in Soil,"
      Piss. Abstr. Int.. 29:849-B (1968).
tj  E. I. du Pont de Nemours and Company, Inc., Bromacil Technical  Data
      Sheet, Wilmington, Delaware (April 1972).
                                    19

-------
decompose  above its  melting point,  but,  according to Kennedy et al.  (1969}—
the  decomposition is not total even up to temperatures as high as  1000°C.
Table  1  shows  weight losses of a commercial formulation of bromacil  heated
to various temperatures (the exact  nature of the formulation was not dis-
closed) .

         Table 1. WEIGHT LOSSES ON COMBUSTION OF A COMMERCIAL
                     BROMACIL FORMULATION (PERCENT)
600CC
88.8
700° C
89.1
800°C
89.4
900°C
90.5
1000° C
91.3
Source:   Kennedy et al.. op.  cit. (1969).

      The data in Table I  is not  only an  indication of volatalization
but  also an indication of  the decomposition of  inorganic carriers or
fillers  in the formulation.  Kennedy et  al.  (1969) apparently used a
solid commercial formulation containing  80% bromacil.  Under experi-
mental conditions,  the bromacil  would most likely volatilize completely,
although the contact times were  not  given.

      Kennedy et al.  (1972)A/»1/  identified the  volatile products of the
combustion of analytical  grade bromacil  at 900°C as carbon monoxide and
carbon dioxide;  however,  they noted  that there  were several unidentified
products.   The sample gas  was specifically analyzed for hydrogen bromide,
but  It was not detected.

      In  other experiments  at the same laboratories, Stojanovlc et al.
(1972)4/ subjected various pesticides to thermoshocking, or partial
degradation at temperatures below that required for complete destruction.
At the temperature employed for  bromacil, 250°C for 30 min, the breaking
I/  Kennedy, M. V., B. J. Stojanovic, and F. L. Shuman, Jr., "Chemical
      and Thermal Methods for Disposal of Pesticides," Residue Rev.. 29:
      89-104 (1969).
2j  Kennedy, M. V., B. J. Stojanovic, and F. L. Shuman, Jr., "Chemical
      and Thermal Aspects of Pesticide Disposal," J. Environ. Quality,
      1(1):63-65 (1972).
3/  Kennedy, M. V., B. J. Stojanovic and F. L. Shuman, Jr. "Analysis of
      Decomposition Products of Pesticides" J. Agr. Food Chem., 20(2):
      341-3 (1972).
4/  Stojanovic, B. J., Fay Hutto, M. V. Kennedy, and F. L. Shuman, Jr.,
      "Mild Thermal Degradation of Pesticides," J. Environ. Quality.
      1(4):397-401 (1972).
                                      20

-------
 of carbon-carbon bonds appeared to be minimal.  The authors found that
 bromacil turned black, and lost 342 of its weight.  The remaining product
 was believed to be 3-sec-butyl-o-methyluracil (infrared spectral analysis).
 The formation of this product indicates that the bromine substituent was
 lost.

 Other Decomposition Processes - Kennedy et al. (1972) reported that con-
 centrated sulfuric acid was effective in bringing about changes in bromacil
 but did not elaborate on what the changes were.  This is in agreement with
 the manufacturer's information that bromacil decomposes slowly in strong
 acid, but is stable in water, aqueous bases, and common organic solvents
 (du Pont, April, 1972).

      Hill (1971) reported the results of a volatilization test.  Bromacil
 was held in an air circulation oven at 120°F for 2 weeks.  Losses were
 less than O.lZ/week.

 Occurrence of Bromacil Residues in Food and Feed Commodities

     The Food and Drug Administration (FDA)  monitors pesticide residues
in the nation's food supply as part of two programs—a "total diet:
program and a "market basket" study.   Much of the data obtained is
published, and the literature is voluminous.  However, published data
reveals that bromacil has not been reported as a significant residue
in any food class, nor is it routinely searched for in the FDA's multi-
residue analytical system which monitors pesticide residue in food.
Adequate individual compound methods exist for measuring bromacil residues.
The apparent reason for the absence of bromacil residue data is that the
pesticide is not widely used on major food and feed items.  The absence
of bromacil residue data does not necessarily mean that it could not be
present in food.

 Acceptable Daily Intake

      The acceptable daily intake  (ADI) is  defined  as the daily  Intake
 which, during an entire  lifetime, appears  to be without appreciable
 risk on  the basis of  all known  facts at  the time of  evaluation  (Lu,
 1973)A/-  It is expressed in milligrams  of the chemical per  kilogram
 of body weight  (mg/kg).
  I/  Lu,  F.  C.,  "Toxlcologlcal  Evaluation  of  Food  Additives  and Pesticide
        Residues  and  Their  'Acceptable  Daily Intakes'  for Man:   The Role
        of WHO, in Conjunction with FAO," Residue Rev..  45:81-93 (1973).
                                      21

-------
      The ADI is established only by the FAO/WHO.   Since bromacil is
 used on so few food crops,  the FAO/WHO has not yet determined an ADI
 for bromacil.

 Tolerances


      Tolerances for bromacil are within the purview of tolerance
 procedures for pesticide chemicals established under the Food, Drug,
 and Cosmetic Act, as amended.  Bromacil is primarily a monagricultural
 herbicide.  Most of its uses are commercial and industrial.   Only two
 crop sectors in the United States, citrus fruits and pineapple,  have
 bromacil tolerances.  The tolerance for both is 0.1 ppm.i/
I/  Code of Federal Regulations. "USDA Summary of Registered Agricultural
      Pesticide Chemical Uses," (Vol. I, 1970), Title 40, Part 180,210.
                                  22

-------
References

Association of Official Analytical Chemists,  Official Methods of Analysis
  of the Association of Official Analytical Chemists, llth ed.,  Washington
  D.C. (1970).

Bevenue, A. and J. N. Ogata, "Determination of Bromacil by Gas Chromatog-
  raphy," J. Chromatog.. 46(1):110-11 (January 1970).

Caswell, R. L., D. E. Johnson, and C. Fleck,  Acceptable Common Names and
  Chemical Names for the Ingredient Statement on Pesticide Labels (2nd ed.),
  Environmental Protection Agency, Washington, D.C.  (June 1972).

Code of Federal Regulations. "USDA Summary of Registered Agricultural
  Pesticide Chemical Uses" (Vol. I, 1970), Title 40, Part 180,210.

Couch, R. W. and D. Davis, "Effect of Atrazine, Bromacil, and Diquaton
  14-C02 - Fixation in Corn, Cotton and Soybenas," Weeds. 14:(3):251-255.

E. I. du Pont de Nemours and Company, Inc., Bromacil Technical Data Sheet,
  Wilmington, Delaware (April 1972).

Gutenmann, W. H. and D. J. Lisk, "Estimation of Residues of Uracil Herbi-
  cides by Gas Chromatography After Evaporative Co-Distillation," J. Assoc.
  Offie. Anal. Chem.. 51 (3):688-90 (1968).

Hill, G. D., "Characteristics of Herbicides by Chemical Groups," Proceedings.
  23rd Annual California Weed Conference (January 1971).

Hilton, J. L., T. J. Monaco, D. E. Moreland,  and W.  A. Gentner, "Mode of
  Action of Substituted Uracil Herbicides," Weeds. 112:129-131  (1964).

Hoffmann, C. E., J. W. McGahen, and P. B. Sweetser,  "Effect of Substituted
  Uracil Herbicides on Photosynthesis", Nature. 202(4932):577-8 (1968).

Jolliffe, V. A., B. D. Day, L. S. Jordan, and J. D.  Mann, "Method of Deter-
  mining Bromacil in Soils and Plant Tissues," J. Agr. Food Chem.. 15(1):
  174-77  (1967).

Jordan, L. S., J. D. Mann, and B. E. Day, "Effects of Ultraviolet Light
  on Herbicides," Weeds. 13(l):43-46  (January 1965).

Jordan, L. S., T. Murashige, J. D. Mann, and B. E. Day, "Effect of
  Photosynthesis - Inhibiting Herbicides on Nonphotosynthetic Tobacco
  Callus Tissue," Weeds. 14(2):134-6  (1966).

Kearney, P. C., E. A. Woolson, J. R. Plimmer, and A. R. Isensee,
  "Decontamination of Pesticides in Soils," Residue Rev.. 29:137-149  (1969).

Kennedy, M. V., B. J. Stojanovic, and F. L. Shuman, Jr., "Chemical  and
  Thermal Methods for Disposal of Pesticides," Residue Rev.. 29:89-104  (1969)

Kennedy, M. V., B. J. Stojanovic, and F. L. Shuman, Jr., "Chemical  and
  Thermal Aspects of Pesticide Disposal," J. Environ. Quality.  l(l):63-65
  (1972).
                                     23

-------
Kennedy, M. V., B. J. Stojanovic and F. L. Shuman, Jr. "Analysis of
  Decomposition Products of Pesticides" J. Agr. Food Chem.. 20(2):341-3 (1972),

Loux, H. M. (to E. I. du Pont de Nemours and Company, Inc.), U.S. Patent
  No. 3,235,357 (15 February 1966).

Lu,  F.  C.,  "lexicological  Evaluation of Food Additives and Pesticide
  Residues  and Their  'Acceptable Daily Intakes' for Man:  The Role of
  WHO,  in Conjunction with FAO," Residue Rev.. 45:81-93  (1973).

Pease,  H. L., "Determination of Bromacil Residues," J. Agr. Food Chem.
  14(1):94-96  (1966).

Pease,  H. L., and J.  F. Deye, "Bromacil," Analytical Methods for Pesti-
  cides. Plant Growth Regulation,  and  Food Additives. G.  Zweig  (ed.),
  Academic  Press, New York (1967).

Stojanovic, B. J., Fay Hutto, M. V. Kennedy, and F. L. Shuman, Jr., "Mild
  Thermal Degradation of Pesticides,"  J. Environ. Quality. 1(4):397-401
  (1972).

U.S. Department of Health, Education,  and Welfare, Food and Drug
  Administration, Pesticide Analytical Manual. Vol. II (1971).

von Rumker, R., E. W. Lawless, and A.  F. Meiners, "Production, Distribu-
  tion, Use and Environmental Impact Potential of Selected Pesticides,"
  Final Report, Contract No. EQC-311,  for Council on Environmental
  Quality, Washington, D.C. (1974).

Wright, W. L., "Photochemical Breakdown of Herbicides," (Abstract),
  Proceedings. 20th Southern Weeds Conference. 20:391 (1967).

Zimdahl, R. L., "A Kinetic Analysis of Herbicide Degradation in Soil,"
  Piss. Abstr. Int.. 29:849-B (1968).

Zweig,  G. and J.  Sherma, Analytical Methods for Pesticides and Plant
  Growth Regulators.. Vol.  VI; Gas Chromatographic Analysis, p. 603,
  Academic Press,  New York (1972).
                                     24

-------
             SUBPART II. B.    PHARMACOLOGY AND TOXICOLOGY


                               CONTENTS



                                                                    Page

Acute, Subacute and Chronic Toxicity 	    26

  Acute Oral Toxicity - Rats	    26
  Acute Inhalation Toxicity - Rats	    26
  Subacute Oral Toxicity - Rats	    26
  Chronic Oral Toxicity - Rats	    27
  Acute Oral Toxicity - Dogs	    29
  Chronic Oral Toxicity - Dogs	    29
  Other Toxicological Evaluations	    29

    Dermal - Acute Toxicity - Rabbits	    29
    Dermal - Sensitization Test - Guinea Pigs	    30
    Eye Irritation	    30

  Toxicity to Domestic Animals 	    30
  Symptomalogy and Pathology Associated with Mammals 	    32

Metabolism	    33

  Absorption	    33
  Excretion	    33
  Biotransformation	    33

Effect on Reproduction  	    34

Teratogenic Effects	    34

Behavioral Effects 	    35

Toxicity Studies with Tissue Culture 	    35

Mutagenic Effects	    35

Oncogenic Effects	    36

Effect on Humans	    36

References	    37
                                       25

-------
     This  section reviews pharmacological and  toxicological data on bromacil.
Subsections present  information  on  acute, subacute and chronic studies in
different  species of laboratory  and domestic animals by various routes of
administration.  Information  is  reviewed concerning effects on reproduction
and mutagenic effects.   There was little available data on behavioral effects,
tissue culture studies,  oncogenlc effects and  the effect on humans.  The
section  summarizes rather than Interprets scientific data reviewed.

Acute. Subacute and  Chronic Toxicity

Acute Oral Toxicity  - Rats -  The LD50 value for bromacil (as active ingre-
dient in 80% wettable powder) in male rats has been reported in petition
data (Zapp, 1965, EPA Pesticide  Petition No. 6F0499 Vol. II, and Edson et
al., 1965)I/>!/ to be 5,200 mg/kg (95% confidence limits 5,024 mg—5,330
mg/kg).  Another reported LDso value was 5,175 mg/kg based on active
ingredient (Sherman  et al.).!'.

Acute Inhalation Toxicity - Rats -  In each test bromacil was atomized into
an inhalation chamber at levels of  2.1 mg/liter and 4.8 mg/liter for 4 hr.
There were four test animals  for each exposure and the animals were observed
for 14 days post exposure.  All  the animals survived.  The symptoms displayed
during exposure were rapid and deep respiration and ruffled fur.  One of the
animals  in the 4.8 mg/litter  exposure had dried blood around the nose and
mouth (Zapp, 1965).

Subacute Oral Toxicity - Rats -  Bromacil (80%  wettable powder) was given to
male rats  by intubation  as a  15% aqueous suspension five times a week for 2
weeks.   Five out of  six  animals  survived 10 daily doses of 1,035 mg/kg of
body weight.  Four out of six animals died after four to five doses of 1,500
mg/kg/day  whereas there were no  deaths when 10 daily doses of 650 mg/kg of
bromacil were administered.   The 650 mg/kg and the 1,035 mg/kg levels did
produce  some pathological changes in the livers (focal cell hypertropy and
hyperplasia) of animals which were  sacrificed  after 10 days exposure to the
pesticide.  These symptoms were  no  longer evident in animals after a 14-day
recovery period (Zapp, 1965).
I/  Zapp,  J. A.,  Jr.,  Report on Bromacil,  EPA Pesticide Petition No.  6F0499,
      Vol.  II,  1965.
2J  Edson,  E. F.,  D. M.  Sanderson,  and D.  N.  Noakes,  "Acute Toxicity Data
      for  Pesticides  (1964)." World Rev. Pest Con..  4:36-41 (1965).
3/  Sherman, H.,  et al.,  Report 12-66, EPA Pesticide  Petition No.  6F0499,
      Vol.  I  (1963).
                                     26

-------
Chronic Oral Toxlclty - Rats - Bromacil (80% wettable powder containing
83.0% AI) was fed to rats for a 2-year period (Sherman, et al., 1963).
            Group Number

            I (control)
            I-A (control)
            II
            III
            IV
                        Level of
                     Bromacil in Diet
                CPUS/  + 1%
                GPLC +  1% Co
                GPLC +  1% Co + 0.005% (50 ppm)
                GPLC +  1% Co + 0.025% (250 ppm)
                GPLC +  1% Co + 0.125% (1,250 ppm)
          ja/Ground Purina Laboratory Chow.
          b/  Corn oil.
     Hematology examinations and urinalysis were run on six males and six
females once a month for the first 3 months and every 3 months thereafter.
Biochemical tests of six males and six females of each group were run at
the end of 1, 3, 6, 9, 12 and 24 months.  At the end of 3, 6 and 12 months
of feeding, the number of animals of each sex was reduced to 32, 30 and
24, respectively.  The brain, heart, lung, liver, spleen, kidney, testis,
stomach, adrenals and pituitary were weighed and pathological examinations
were made on 26 other body tissues.  The daily dosage for male rats ranged
from 154.2 to 38.7 ppm (4:1) and for female rats 143.3 to 39.3 ppm  (3.6:1).
It is normal for dosage to decrease since rats consume less per body weight
as they grow larger.                                                    J

     The actual amounts of bromacil ingested in  the various diets  are  shown
in Table 2.  Mortalities which occurred within the group  are  shown in  Table
3.

     The female rats on the 0.125% bromacil diet suffered weight retarda-
tion for the first and second year.  There were  no clinical signs  of  toxi-
city.  During the first year, three control animals died  and  there were
three deaths in the treated groups.

         Table 2.   CONSUMPTION OF BROMACIL
 Days of test

 0.7
 105-112
 203-210
 490-504
 602-616
 714-728
0.005%
fag/kg)
   08
   27
   83
   55
   46
 1.37
0.025%
(mg/kg)

  30.2
  11.3
   9.6
   8.0

   6.56
0.125%
(mg/kg)
154.2
 56.4
 47.6
 39.7
 37.9
 38.7
 Source:  Sherman, et al., op. cit.  (1963),
                                    27

-------
            Table 3.  MORTALITY OF RATS CONSUMING BROMACIL
Dietary
 level
 Killed by       Killed          Found
  design        extremis          dead	
Male  Female   Male  Female    Male  Female
                                        Survived
                                        24 months
                                        Male  Female
  0
  0
  0.005
  0.025
  0.125
 11
 10
 12
 12
 12
12
12
12
11
12
2
6
8
3
8
8
8
6
8
3
14
 9
 8
 9
 8
3
6
9
5
4
 9
11
 8
12
10
13
10
 9
12
17
  Source:   Sherman et al.  op.  cit.  (1963).
  There were no unusual  alterations  in  the hematology, urinalysis and
  clinical chemistry evaluations.  No gross pathological lesions were
  observed.   There appeared  to be  a  dose-related effect on the thyroid.
  Focal light cell hyperplasia and focal  follicular cell hyperplasia were
  noted somewhat in controls but observed slightly more often in the 'hyroids
  of  rats  at the high dose.   One follicular cell adenoma occurred in a
  female rat at the highest  dose level.   There were no excessive accumula-
  tions of residues in the tissues.

       Another investigation (Zapp,  1965) involved a  90-day oral toxicity
  test  of  bromacil in rats.   Ten male and 10  female rats were placed in
  each  group.   The dosages were as follows:
                                               Dietary level
                                                                      •a/
  Group Number

      1
      2
      3
      4

      4A
      4B
                             Ppm

                            0
                           50
                          500
                        2,500  (0-6 weeks)
                        5,000  (7-10 weeks)
                        5,000  (11-13 weeks)
                        6,000  (llth week)
                        7,500  (12-13 weeks)
                                         Estimated-'
                                          (mg/kg)
                                             2.5
                                            25.0
                                           125.0
                                           250.0
                                           250.0
                                           300.0
                                           375.0
  a/  Estimation by reviewer based  on  a  500-g  rat  consuming 25 g of
        diet a day.
                                     28

-------
     No deaths occurred and no signs of toxiclty were observed.  The male
rats in Groups 4A and 4B exhibited a reduced growth rate during the last
3 weeks of the test.  The hematology and urinalysis values were within
normal limits.  There were no pathological changes of significance in the
groups receiving 50 and 500 ppm of bromacil.  For the groups receiving
5,000 ppm and above, there were microscopic changes in the thyroids,
suggestive of increased glandular activity.

Acute Oral Toxiclty - Dogs - An attempt was made to determine the acute
oral toxiclty of bromacil in dogs (Hazelton Laboratories, 1966).i'  Bromacil
(80% wettable powder) as a massive dose (5 g/kg) was given by capsule to a
dog.  The dog exhibited excessive emesis, copious salivation, weakness, loss of
coordination, excitability, diarrhea and mydriasis.  Forty-eight hr
later, six divided doses were given and repeated emesis, salivation,
mydriasis and sanguineous diarrhea occurred.

     The second dog was given two oral doses of bromacil 5 days apart (200
and 250 mg/kg); each dose evoked repeated emesis.  A lethal dose was not
obtained in the dog because of emesis.

Chronic Oral Toxicity - Dogs - A 2-year feeding study of bromacil in dogs
was also conducted.^/  Six dogs (three male and three female) in each of
four groups received the following dosages of dietary bromacil:

                        Group 1     0.0% (Control)
                              2     0.005%
                              3     0.025%
                              4     0.125%

     The dogs in the 0.125% level declined in weight at the start of the
experiment and then weights stabilized between 1 to 1.5 kg lower than the
other dogs in the test.  Throughout the duration of the test, clinical
signs, such as appearance, rectal temperature, pulse and respirationi
appeared to be normal.

     The only death loss was an animal on the 0.005% dosage level.  Illness
and death were judged not to be associated with the test compound.  A
subdural hemorrage was observed in the spinal column.  Throughout the
course of the study, there were no significant alterations in hematology,
urinalysis and blood chemistry.  There was no effect on organ weight and
no significant pathology occurred at the microscopic level.  There was
no evidence of excessive accumulation of residues in the tissues.

Other Toxicologlcal Evaluations -

     Dermal - Acute Toxicity - Rabbits - An acute skin absorption toxicity
tept was made on rabbits.  Bromacil was applied  to the intact  skin  (clipped)
of three male rabbits.  A 70% aqueous paste was made up to supply 5,000 mg/kg.
The contact period was 24 hr and the animals were observed for 14 days.  There
were no signs of toxicity or gross pathological  changes.  The  approximate
lethal dose  (AID) was estimated to be greater than 5,000 mg/kg (Zapp,  1965).
I/  Hazelton Laboratories, Report on Bromacil, EPA Pesticide  Petition No.
      6F0499, Vol.  II, 1966.
J2/  Bromacil Report, EPA Pesticide Petition No.  6F0499,  Section C.

                                     29

-------
      Dermal - Sensitization Test - Guinea Pigs - Ten guinea pigs were
 prepared by clipping fur and abrading the skin.  A 50% suspension of
 bromacil in 1% aqueous Duponal PT was applied to these areas for 24 hr.
 Animals with abraded skin were exposed 3 times a week for 3 weeks.  They
 were reexposed after 2 or 3 weeks rest.  There appeared to be no induced
 skin sensitivity.  The skin of the younger animals was mildly irritated
 (Zapp, 1965).


      Eye Irritation - Ten milligrams of bromacil  (0.1 ml of a 10% suspension
 in mineral oil) was placed on the surface of two rabbits' eyes.  One eye of
 each rabbit was then washed for 1 minute with tap water, starting 20 seconds
 after contact.  The other eye of each rabbit was not washed.  A mild temporary
 conjunctivitus was observed in both washed and unwashed eyes.  No corneal
 damage was observed in either washed or unwashed eyes.  The experiment was
 repeated as above, with identical results, using 50% wettable powder (Zapp,1965).


 Toxicity to Domestic Animals - Palmer and Radeleff (1969).i/ have evaluated
 the toxicity of multiple-dosing of bromacil in cattle, sheep, and chickens.
 The results of these tests are given in Table 4.

      One dose (250 mg/kg)  administered to a yearling calf produced poison-
 ing with survival and a 14% weight loss.

      The results with sheep were varied.   A dose  of 50 mg/kg given 10 times
 by drench produced no effect.   When the dosage was given by capsule, the
 animal was poisoned,  survived  and sustained an 8% weight loss.   A 100 mg/kg
 dosage in capsule form had no  observable  effects, while a drench produced
 poisoning.   At the 250 mg/kg level,  poisoning occurred after the third dose,
 and,  by  capsule, eight doses were consumed before poisoning occurred.

      Chickens  appeared to  tolerate  a dose of 500  mg/kg.   However, there
 was  a significant reduction in weight gain.   Weight gain was also reduced
 slightly at the  250 mg/kg  level.

      The authors commented that bromacil  application rates range from 1.6
 to 20 Ib/acre.   They  felt  that a rate of  20 Ib/acre would not be hazardous
 to cattle  or chickens,  but rates  of  application in excess of 5  Ib/acre
 would be hazardous to  sheep.

      Palmer  (1964)—/  reported  that  the  administration of five doses  of 250
 mg/kg each  to sheep of  bromacil produced  tympany  and stilted gait within 4
 hr after administration of  the  first  dose.   After five doses of  bromacil the
 animal slowly recovered and had marked  lameness.   When the  dosage was
 reduced  to  100 mg/kg,  the  administration  of  11  treatments  produced no
 clinical symptoms  but  there was an 11%  weight loss.
I/  Palmer, J. S., and R. D. Radeleff, "The Toxicity of Some Organic
      Herbicides to Cattle, Sheep, and Chickens," USDA Prod. Res.. Report
      No. 106; 1-26 (1969).
2f  Palmer, J. S., "Toxicity of Methyluracil and Substituted Urea and Phenol
      Compounds to Sheep," Amer. Vet. Med. Assoc. J.. 145:787-789 (1964).
                                     30

-------
              Table 4. RESULTS OF MULTIPLE ORAL  DOSING  OF
                        IN CATTLE, SHEEP, AND  CHICKENS^'

Animal
and dosage
received
(me/ke)
Cattle:
100
100
250

Sheep :
25
50

50
100
100

250

250

Chickens!/
100
250
500
Controls


Doses
Number
10
10
10


10
10

10
10
10

5

10


10
10
10


Means of
dosing

Drench
Capsule
Capsule


Drench
Capsule

Drench
Capsule
Drench

Drench

Capsule


Capsule
Capsule
Capsule



Results and remarks

NH£/
NIE
Poisoned after one dose and
survived, 14% weight loss

NIE
Poisoned and survived,
8% weight loss
NIE
NIE
Poisoned and survived,
97. weight loss ,
Poisoned after three doses
survived, 97. weight loss
Poisoned after eight doses
survived, 87. weight loss

49% weight gain
397. weight gain
24% weight gain
48% weieht train
a/Hyvar®X, 80% wettable powder.
b/  Adapted from Palmer and Radeleff  (1969).
£/  NIE indicates no ill effects apparent.
d_/  Average results of five treated chickens.
                                      31

-------
      Tympanites is  commonly encountered  in cattle  and  sheep dosed with
 bromacil.   Williams et al.  (1963)!/  found that  certain chlorinated hydro-
 carbons,  organophosphates,  and  carhamate compounds stimulate gas produc-
 tion in vitro by rumen holotrich protozoa whereas  these compounds had no
 appreciable effect  when rumen bacteria inoculum was used.  In  these
 experiments total gas  production was measured by manometric techniques.
 No  attempt  was made to determine the chemical composition of the gases
 produced.   Kutches  et  al.  (1970)^.' studied the  effect  of a number of
 insecticides and herbicides on  in vitro  rumen fermentation.  The parameters
 of  investigation included dry matter disappearance, volatile fatty acid
 production, and changes in  protozoal numbers.   With dosages of 0.0, 100,
 250,  500, 750, and  1,000 ppm, the respective values for percent in vitro
 dry matter  disappearance were:   28.5,  28.4, 27.7,  25.0, 22.8 and 18.5.
 The volatile fatty  acid production was not affected by 1,000 ppm of
 bromacil.   The numbers of ciliated protozoa increased  slightly in the
 presence  of 100 ppm bromacil but decreased sharply as  the bromacil con-
 centration  exceeded 500 ppm.

      The  results indicated  that high concentration of  bromacil (1,000 ppm)
 significantly affected rumen microbial processes.   No  significant effects
 in  in vitro forage  digestability were  noted at  lower concentrations (250
 ppm and below).   Since feedstuff contamination  is  usually less than 250 ppm,
 it  was  concluded that  bromacil  would have negligible affect on rumen
 digestability or other associative rumen function.

 Symptomalogy and Pathology  Associated  with Mammals - In the dog, massive
 doses of bromacil caused excessive emesis,  copious salivation, weakness,
 lack of coordination,  excitability,  diarrhea, and  mydriasis (Hazelton
 Laboratories,1966).  In the rat, a near-toxic dose of  bromacil caused an
 initial weight loss  of the  animal.   In acute toxicity  cases the respiration
 rate  became very rapid.  Discomfort, prostration,  salivation and lack of
 coordination occurred  (Zapp,  1965).

      In cattle and  sheep, bromacil poisoning caused a  weight loss, anorexia
 and depression,  tympanites,  and incoordinated gait (Palmer, 1964; Palmer
 and Radeleff,  1969).
I/  Williams, P. P., J. D. Bobbins, J. Gutienez, and R. E. Davis, "Rumen
      Bacterial and Protozoal Responses to Insecticides Substrates,"
      Appl. Microbiol.. 11:517-522 (1963).
2J  Kutches, A. J., D. C. Church, and F. Duryee, "lexicological Effects of
      Pesticides on Rumen Function in Vitro." J. Agr. Food Chem.. 18(3):
      430-433 (1970).
                                     32

-------
Metabolism

Absorption - Brotnacil is apparently not excreted via the gastrointestinal
tract of cows, since Gutenmann and Lisk (1970)i/ found no bromacil in feces
of cows fed 5 and 30 ppm bromacil in the feed for 4 days.

Excretion - Gardiner et al. (1969)!/ found that rats fed 1,250 ppm bromacil
for 1 month excreted five to six metabolites in the urine, the main one
being 5-bromo-3-sec_-butyl-6-hydroxymethyluracil.  5-Bromouracil was not
found as a product of bromacil metabolism.

     Urine samples from workers at two different locations in a bromacil
production plant were analyzed for bromacil and its metabolites.  The
results indicated that bromacil was metabolized by man in a manner similar
to that in rats (bromacil was found and 5-bromo-3-sec-butyl-6-hydroxymethyl-
uracil was found to be the principal metabolite).  No 5-bromouracil was
found in either hvdrolyzed or nonhydrolyzed urine samples from humans
(Du Pont, 1966) .!'

Biotransformation - Gardiner et al. (1969) found six metabolites of bromacil
in the urine of rats fed 1,250 ppm bromacil for 1 month.  The primary
metabolite, 5-bromo-3-sec-butyl-6-hydroxymethyluracil was present in the
urine as a conjugate which was hydrolyzed with /0"~glucuronidase-arylsulfatase
enzyme solution.

     Additional metabolites found in lesser quantities were 5-bromo-3-
(2-hydroxy-l-methylpropyl)-6-methyluracil, 5-bromo-3-(2-hydroxy-l-
methylpropyl)-6-hydroxy-methyluracil, 3-sec-butyl-6-hydroxymethyluracil,
5-bromo-3-(3-hydroxy-l-methylpropyl)-6-methyluracil, 3-sec-butyl-6-
methyluracil, and an unknown bromine-containing compound of mol. wt 339.

     McGahen and Hoffmann (1963a)—' found that bromacil was not incorporated
into Escherichia coli DNA.  These authors reported  (1963b)5/ similar findings
in mice.
17  Gutenmann, W. H., and D. J. Lisk, "Metabolism and Excretion of  Bromacil
      in Milk of Dairy Cows," J. Agr. Food Chem.. 18(1):128-129 (1970).
2J  Gardiner, J. A., R. W. Reiser, and H. Sherman, "Identification  of  the
      Metabolites of Bromacil in Rat Urine," J. Agr. Food Chem..  17(5):
      967-973 (1969).
_3/  Du Pont de Nemours Co., Supplementary Report on Bromacil, EPA Pesticide
      Petition No. 6F0499 (1966).
4/  McGahen, J. W., and C. E. Hoffmann, "Action of 5-Bromo-3-sec-butyl-
      6-methyluracil on Escherichia coli 15T," Nature.  200(4906):571-572
      (1963a).
5/  McGahen, J. W., C. E. Hoffmann, "Action of 5-Bromo-3-sec-butyl-6-
      methyluracil as Regards Replacement of Thymine in Mouse DNA,"
      Nature. 199(4895):810-811  (1963b).
                                     33

-------
 Effect  on Reproduction

      The  effect  of  bromacil  on reproduction in the rat has been reported.
 During  a  2-year  chronic toxicity study,  12  male and  12 female rats each
 were  allowed  to  continue their regular feeding regimin and reproduce.  One
 of  the  groups continued to be  fed the control  diet.  The test group
 continued to  consume  0.025%  bromacil in  the diet.  The original rats were
 called  the FQ generation.  The first litter produced from this group became
 the Fia generation  and the second mating produced the FU, generation.  The
 Fib litter was maintained on the same diet  and at 100 days of age they were
 mated to  yield the  F2a and F£b litters.
      There were  no marked  differences  between  the reproductive performance
 of  the  control and test  animals.   There were no deformed young.  The
 fertility, gestation, viability and  lactation  indices were not significantly
 different.   Furthermore, there were  no gross or microscopic pathological
 differences. I/

 Teratogenic  Effects

      There were  no deformities  found in  the previously  cited  reproductive
 study on rats.

      A  study was made of the effects of bromacil on reproduction in the
 rabbit  (Paynter, 1966) ,2J   Bromacil  (80%  wettable powder) was fed  to New
 Zealand white rabbits that had  an initial weight of 3.0 to 4.7 kg.  The
 groupings and dosages were as follows:


                                       Number of      Dietary  level of
                    Group  number       rabbits        bromacil (ppm)

                      1  (Control)           9                  0
                      2                     9                50
                      3                     8               250

     The  females were bred and the above  dosages were administered starting
with the  eighth  day of pregnancy  and continuing through the 16th day.  The
does were returned to the  untreated  basal diet on the 17th day.  On the
28th or 29th day after breeding,  three does each from both the control and
50 ppm diet groups were sacrificed.  Four does on the 250 ppm diet were
killed.   After parturition,  all the  remaining does  were killed and one-
third of  the young was prepared for  tissue clearing to  observe any skeletal
defects.

     No gross manifestations  of teratogenic effect  were observed in the
fetuses and there were no  abnormal bone structures.
I/  Bromacil Report, EPA Pesticide Petition No. 6F0499, Section C.
2J  Paynter, 0. E., Hazleton Report, Ref. Mro-879, 1966, EPA Pesticide
      Petition No. 6F0499, Vol. II.
                                    34

-------
Behavioral Effects

     No studies were found in the literature concerning the behavioral
effects of bromacil.

Toxicity Studies with Tissue Culture

     No information was found on toxicity studies with tissue cultures.

Mutagenic Effects

     Because of the possibility that bromacil (5-bromo-3-sec-butyl-6-
methyluracil) could be metabolized in vivo to the potent mutagen,
5-bromouracil, experiments have been conducted to determine if bromacil
yields mutagenic effects in laboratory animals and to determine whether
5-bromouracil can be detected as a bromacil metabolite.

     No 5-bromouracil was detectable in either urine from bromacil produc-
tion plant works (Du Pont, 1966) or in urine of rats fed bromacil (Gardiner
et al., 1969).

     McGahen and Hoffmann (1963b) could not detect bromacil in mouse DNA.
These same authors evaluated the action of bromacil on Escherichia coli
15T using labeled bromacil.  In growth experiments, bromacil was not
inhibitory to E. coli 1ST.  Escherichia coli 1ST is a thymine-requiring
mutant.  E. coli 15T cells in the log phase were exposed to 10 microcuries
of labeled bromacil for various periods, chilled and harvested.  The cells
were washed with water and cold 5% trichloroacetic acid.  Bromacil was
readily washed from the cells.  Furthermore, no radioactivity was detected
in the DNA of cells exposed to bromacil.

     McGahen and Hoffman  (1966)—' further examined the mutagenic effects
of bromacil on bacteriophage.  From their earlier work it was not com-
pletely ruled out that there may be indirect mutagenic effect.  They used
mutant AP72, E. coli B and E. coli K12 (X) organisms in a back mutation
rate study,  fney observed no mutagenic effect of bromacil.  The other
substituted 5-bromouracils did not appear to be mutagenic.  The explanation
was given that the alkyl substitution prevents incorporation of bromacil
into DNA or the precursors.

     Andersen et al. (1972)—' has evaluated 110 herbicides for their ability
to induce point mutations in one or more of four different microbial systems.
In one test utilizing eight histidine requiring mutants of Salmonella
typhimurium, bromacil tested negative to reversion to histidine independence.
The effect of bromacil in the induction of the r II mutants of T4 bacteri-
ophage was not different from the control.  An evaluation was also made on
I/  McGahen, J. W., and C. E. Hoffman, "Absence of Mutagenic Effects of 3-
      and 6-Alkyl-5-bromouracil Herbicides on a Bacteriophage," Nature
      (London), 209(5029): 1241-1242 (1966).
2J  Andersen, K. J., E. G. Leighty, and M. T. Takahashi, "Evaluation of
      Herbicides for Possible Mutagenic Properties," J. Agr. Food Chem..
      20(3):649-656 (1972).

                                     35

-------
the reversion of the guanine-cytosine transition r II mutant AP72.  In
general, the herbicides evaluated were not mutagenic in this test system.

     Siebert and Lemperle  (1974)i' found that bromacil did not induce mitotic
gene conversion in a diploid  strain of the ascomycete Saccharomyces
cerevisiae heteroallelic at two  loci in a test which reacts very sensitively
to compounds that induce base-pair substitution as well as frame-shift
mutations.

     Epstein et al. (1972)2/  found that bromacil in the dominant lethal
assay  in mice, when administered either by intraperitoneal injection as a
single dose of 150 mg/kg or by gavage for five successive doses of 750 mg/kg
and 1,000 mg/kg, was not mutagenic.

     Ficsor and Nil Lo Piccolo (1972)3/ found bromacil was not mutagenic by
the Bacterial-plate assay method.  It was inactive in its ability to revert
two E._ coli lac - amber mutants  to the lactose - fermenting phenotype and a
cys -  and two len - auxotrophs to prototrophy.

Oncogenic Effects

     A follicular cell adenoma was found in  a female rat that was retained
on a long-term study consuming 0.125% bromacil in the diet (Lawless),^/
During the 2-year chronic  toxicity studies in dogs and rats, discussed
previously, no evidence of oncogenic effects due to bromacil administration
was observed in any of the test  animals (Sherman, et al., 1966; Zapp, 1965).

Effect on Humans

     No information was found on the effect  of bromacil to humans on an
acute  basis, under field conditions, or in the manufacturing process.
I/  Siebert, D. and E. Lemperle, "Genetic Effects of Herbicides: Induction
      of Mitotic Gene Conversion in Saccharomyces cerevisiae," Mutation
      Research,(22):111-120  (1974).
2J  Epstein, S. S., et. al., "Detection of Chemical Mutagens by the Dominant
      Lethal assay in the Mouse," Toxicol. Appl. Pharmacol..(23);288-325
      (1972).
3/  Ficsor, G. and G. M. Nii Lo Piccolo, "Survey of Pesticides for Mutageni-
      city by the Bacterial - Plate Assay Method," Newslett. Environ.
      Mutagen Society.(6);6-8 (1972).
4/  Lawless, E. W., Report on Bromacil, EPA Pesticide Petition No. 6F0499,
      Vol. I.
                                    36

-------
References

Andersen, K. J., E. G. Leighty, and M. T. Takahashi, "Evaluation of Herbicides
  for Possible Mutagenic Properties," J. Agr. Food Chem., 20(3):648-656 (1972).

Bromacil Report, EPA Pesticide Petition Ho. 6F0499, Section C.

Du Pont de Nemours and Co., Supplementary Report on Bromacil, EPA Pesticide
  Petition No. 6F0499 (1966).

Edson, E. F., D. M. Sanderson, and D. N. Noakes, "Acute Toxicity Data for
  Pesticides (1964)." World Rev. Pest Con.. 4:36-41 (1965).

Epstein, S. S., et. al., "Detection of Chemical Mutagens by the Dominant
  Lethal Assay in the Mouse," Toxicol. Appl. Pharmacol.. 23: 288-325 (1972).

Fiacor, G., and G. M. Nil Lo Piccolo, "Survey of Pesticides for Mutagenlcity
  by the Bacterial - Plate Assay Method," Newslett. Environ. Mutagen Society,
  (6): 6-8  (1972).

Gardiner, J. A., R. W. Reiser, and H. Sherman, "Identification of the
  Metabolites of Bromacil in Rat Urine," J. Agr. Food Chem.. 17(5):967-973
  (1969).

Gutenmann, W. H., and D. J. Lisk, "Metabolism and Excretion of Bromacil in
  Milk of Dairy Cows," J. Aer. Food Chem.. 18(1);128-129 (1970).

Hazelton Laboratories, Report on Bromacil, EPA Pesticide Petition No. 6F0499,
  Vol. II,  (1966).

Kutches, A. J., D. C. Church, and F. Duryee, "lexicological Effects of
  Pesticides on Rumen Function in Vitro," J. Agr. Food Chem., 18(3):430-
  433 (1970).

Lawless, E. W., Report on Bromacil, EPA Pesticide Petition No. 6F0499,
  Vol. I.

McGahen, J. W., and C. E. Hoffmann, "Absence of Mutagenic Effects of 3- and
  6-Alkyl-5-bromouracil Herbicides on a Bacteriophage," Nature (London),
  209(5029):1241-1242 (1966).

McGahen, J. W., C. E. Hoffmann, "Action of 5-Bromo-3-sec-butyl-6-methyluracil
  as Regards Replacement of Thymine in Mouse DNA," Nature. 199(4895):
  810-811  (1963b).                                 	

McGahen, J. W., and C. E. Hoffmann, "Action of 5-Bromo-3-sec-butyl-6-methyl-
  uracil on Escherichia coli 15T." Nature. 200(4906):571-572 (1963a).

Palmer, J. S., "Toxicity of Methyluracil and Substituted Urea and Phenol
  Compounds to Sheep," Amer. Vet. Med. ABSOC. J.. 145:787-789 (1964).
                                     37

-------
Palmer, J. S. and R. D. Radeleff, "The Toxicity of Some Organic Herbicides
  to Cattle, Sheep, and Chickens,"   USDA Prod. Res., Report No. 106;1-26
  (1969).

Paynter, 0. E., Hazleton Report, Ref. Mro-879, 1966, EPA Pesticide
  Petition No. 6F0499, Vol. II.

Sherman, H., et al., Report 12-66, EPA Pesticide Petition No. 6F0499,
  Vol. I   (1963).

Siebert, D. and E. Lemperle, "Genetic Effects of Herbicides:  Induction of
  Mitotic Gene Conversion in Saccharomyces cerevisiae." Mutation Research,
  22:111-120 (1974).

Williams, P. P., J. D. Robbins, J. Gutienez, and R. E. Davis, "Rumen
  Bacterial and Protozoal Responses to Insecticides Substrates," Appl.
  Microbiol.. 11:517-522 (1963).

Zapp, J. A., Jr., Report on Bromacil, EPA Pesticide Petition No. 6F0499,
  Vol. II, (1965).
                                     38

-------
      SUBPART II.  C.   FATE AND SIGNIFICANCE IN THE ENVIRONMENT
                                CONTENTS
Effects on Aquatic Species
                                                                    Page
  Fish ..............................    40
  Lower Aquatic Organisms ............ • ........    40

Effects on Wildlife ........................    41

Effects on Insects ........................    41

Effects and Residues in the Soil .................    41

  Interactions with Lower Terrestrial Organisms ..........    41
  Residues in Soil/Laboratory Studies ...............    44
  Residues in Soil/Field Studies .................    46
  Monitoring Studies .......................    49

Residues in Water .........................    49

Residues in Air ..........................    50

Effects and Residues in Nontarget Plants .............    50

Bioaccumulation, Biomagnification .................    51

Environmental Transport Mechanisms ................    51

References ............................    52
                                      39

-------
      This section contains data on the environmental effects  of  bromacil,
 including effects on aquatic species,  wildlife,  beneficial insects,  soil,
 water, air, and nontarget plants.   The section summarizes  rather than  inter-
 prets data reviewed.

 Effects on Aquatic Species

 Fish - TLm values for Bluegill sunfish,  Rainbow  trout,  and carp,  based on
 an 80% formulation, indicate a low order of fish toxicity:.!/


                     Bluegill sunfish

                       TLm for 24 hr. - 103 ppm
                       TLm for 48 hr. -  71 ppm

                     Rainbow trout

                       TLm for 24 hr. - 102 ppm
                       TLm for 48 hr. -  75 ppm
                       TLm for 72 hr. -  38 ppm
                       TLm for 24 hr.  - 164 ppm
                       TLm for 48 hr.  - 164 ppm

     Yoshida  and  Nishiuchi£'  list the 48  hour  TLm values  for  carp, Jap-
 anese  goldfish and  killifish  as  10-40 ppm in each instance.   The 48 hour
 TLm value  for loach is>40 ppm and for tadpole,  230  ppm.   The 72 hour value
 for crawfish  is 40  and the 3  hour value for the  waterflea is^40.  Data on
 the effects of bromacil to fishes under field  conditions  appears to be non-
 existent.  Registered  labels  of  bromacil-containing  commercial pesticides
 do  not carry  any  warning or caution statements regarding  fish toxicity.

 Lower  Aquatic Organisms - Hoffman (1973),!/ in a report on the mode of action
 of  bromacil and related uracils, stated that a monuron-reslstant strain of
 Euglena showed similar resistance to  Bromacil; the resistant  strain was not
 affected by bromacil at 40 ppm,  and only  partially inhibited  at 100 ppm.
 By  comparison,  a  wild  strain  of  Euglena was markedly inhibited at 2 ppm and
 completely inhibited at 10 ppm.   Neither  strain  was  affected  by bromacil in
 the dark, indicating that inhibition  of photosynthesis is one of the mechanisms
 of  phytotoxic actions  of bromacil.  No other data was found on the interactions
 between bromacil  and lower aquatic  organisms.
_!/  E. I. du Pont de Nemours and Company,  Inc., Personal  communication
       (1974).
21 Yoshida, K., and Y. Nishiuchi,  "Toxicity of Pesticides  to Some Water
     Organism" Bull of Agr. Chem Inspect.  Stn. (Tokyo)12:  122-128 (1972).
3j Hoffman, C. E., "The Mode of Action of  Bromacil and Related Uracils,"
     Second International Conference of Pesticide Chemical Proceedings.
     (1971).  In:  Ashton and Crafts, Mode of Action of Herbicides. John
     Wiley & Sons, pp. 430-431 (1973).
                                       40

-------
Effects on Wildlife

     No data was found regarding laboratory experiments on the toxicity
of bromacil to wildlife, or the effects of bromacil to wildlife under
field conditions.  E. I. du Pont de Nemours (1974) reported that the eight-
day dietary LCso of Bromacil for both the mallard duck and the bobwhite
quail is greater than 10,000 ppm.

     The Handbook of Toxicity of Pesticide to Wildlife (Tucker and
Crabtree, 1970)i/ contains no entries on bromacil.

     Pimentel's summary on "Ecological Effects of Pesticides on Nontar-
get Species" (1971)1/ does not include any data on the effects of bromacil
on wildlife or other nontarget species.

Effects on Insects

     Bromacil was tested as a spray at 10,000 ppm against housefly, roach,
aphid  (systemic) and mite and was found to be totally lacking in insecticidal
and acaricidal activity Anderson et al.,  (1971).I/

     In laboratory and field studies  (mostly spraying) on the effects  of
honey  bees, Aphis mellifera L., conducted in California between 1950 and  1971,
bromacil  (Hyvar(S& was listed as a "relatively non-toxic" herbicide  (Anderson
et al., 1971).  Atkins et al.  (1973)A/ also reported that bromacil  (HyvarvB/ X)
is a relatively nontoxic pesticide with a 1.20% mortality at 193.38 micro-
grams  per honey bee.

Effects and Residues in the Soil

Interactions with Lower Terrestrial Organisms - Torgeson and Mee  (1967)1.'
studied the microbial degradation of bromacil.  In laboratory  tests,  soils
having no history of exposure to bromacil were treated either with  40  ppm
of bromacil in a soil perfusion system, or by mixing bromacil at rates
up to  200 Ib Al/acre.  After incubation, fungi and bacteria were isolated
from the  treated soil by use of a dilution plate technique.  Fifty-five
 I/   Tucker,  R. K., and D. G. Crabtree, Handbook of Toxicity  of  Pesticides
       to Wildlife. Bureau of Sport Fisheries and Wildlife, Denver Wildlife
       Research Center, Resource Publication No. 84  (1970).
 2J   Pimentel, D.,  "Ecological Effects of Pesticides on Nontarget Species,"
       Executive  Office of the President, Office of Science and  Technology,
       Superintendent  of Documents, U.S. Government Printing  Office,  Washington,
       D.C.  (1971).
 3/   Anderson, L. D.,  E. L. Atkins Jr., H. Nakakihara  and  E.  A.  Greywood,
       Toxicity of  Pesticides and Other Agricultural Chemicals to Honeybees.
       U.S.  Department of Agriculture, Agricultural Extension Service Report,
       University of California Press, Berkeley, Calif.  (1971).
 kj   Atkins,  E. L., E. A. Greywood, and R. L. Macdonald, Toxicity of  Pesticides
       and other  Agricultural Chemical to Honeybees. U.S.  Department  of
       Agriculture, Agricultural Extension Service Report, University of
       California Press, Berkeley, Calif.  (1973).
 5/   Torgeson, D. C.,  and H. Mee, "Microbial Degradation of Bromacil,"
       Northeastern Weed Control Conference Proceedings. 21:584  (1967).


                                        41

-------
 fungal  and  73  bacterial  cultures were  studied  in regard to their ability
 to  degrade  bromacil by growing  them in a Czapek-Dox broth containing 20
 ppm of  bromacil.   The amount  of bromacil remaining was periodically de-
 termined by a  bioassay technique sensitive  to  less than 1 ppm of bromacil,
 using buckwheat  as the test organism.   None of the bacteria degraded
 bromacil;   but four of the fungi exhibited  this capability.  The most active
 of  these, Penicillium paraherquei.  was studied further.  No signigicant
 amounts of  bromacil were detectable 15 to 20 days after Czapek-Dox broth
 containing  20  ppm of the herbicide  had been inoculated with this fungus.

     Sterile soil treated with  bromacil at  the rate of 3.1 Ib Al/acre
 was still toxic  to buckwheat  after  56  days.  No herbicidal effects were
 detected 21 days  after treatment with  6.2 Ib Al/acre, or 28 days after
 treatment with 12.5 Ib Al/acre  in sterile soil inoculated with I>. para-
 herquei.  The  herbicidal effectiveness of bromacil applications at 25
 and 50  Ib Al/acre was reduced to 50 and 80%, respectively, after 56 days.

     In liquid and solid Czapek-Dox media,  P_.  paraherquei grew normally
 at  concentrations of bromacil up to 200 ppm.   At higher concentrations
 of  bromacil, growth of the fungus was  slower and abnormal in appearance.
 The organism failed to grow in  a liquid mineral salts medium containing
 bromacil as the sole carbon and nitrogen source.  A variant of f_. para-
 herquei isolated  from liquid  media  containing  800 to 1,000 ppm of broma-
 cil appeared to be capable of growing  slowly on bromacil as the sole sub-
 strate.

     Pancholy and  Lynd (1969)—'  studied the  interactions between bromacil
 and plants,  cultures of  fungi,  and  nitrification in the laboratory.  In
 Eufaula sand,  bromacil reduced  the  growth of oat seedlings at concentra-
 tions of  0.25  to  1.0 ppm, and the growth of  sorghum seedlings at concen-
 trations of  1.0 to  4.0 ppm.   Organic matter  amendments added to the sand
 at  rates of  1, 2,  and 4  ppm significantly reduced the phytotoxicity of
 bromacil  to both  oats and sorghum.   Oats were  more sensitive than sorghum;
 at  0.25 ppm, the  growth  of sorghum  was not  adversely affected by bromacil.

     Ten soil  fungi (Aspergillus tamarii, A. niger, A. flavus, A. oryzae,
 Curvularia  lunata,  Mucor pusillus.  Trichoderma viride, Penicillium
 funiculosum, £. brevicompactum. and Myrothecium verucaria) were cultured
 on  liquid broth media with bromacil levels  of  0, 250, 500, 1,000, and
 5,000 ppm for  5 days  at  22 to 28°C.  Bromacil  up to 2,000 ppm did not in-
hibit the growth  of  the  fungi,  except  A. niger, which was inhibited by
bromacil levels less  than 1,500 ppm.   This  fungitoxic effect was par-
 tially offset  by  increasing the inorganic nitrogen levels to 500 ppm,
and/or by 1,000 ppm of presynthesized  growth factor additive (cyanoco-
balamin, yeast extract,  peptone). Bromacil  at  100 ppm reduced nitrifi-
cation temporarily.
I/  Pancholy, S. K., and J. Q. Lynd, "Bromacil Interactions in Plant
      Bioassay, Fungi Cultures, and Nitrification," Weed Sci.. 17(4):
      460-463 (1969).
                                    42

-------
     Wehr and Klein  (1971)1/ studied the effects of bromacil and other
herbicides on Bdellovibrio bacteriovorus parasitism of a soil pseudomonad.
]5. bacteriovorus, a  small endoparasitic bacterium indigenous to soil, mud
and  sewage can attack and penetrate other susceptible gram-negative bacteria,
causing host lysis and release of parasite progeny into the surrounding
environment. Bromacil showed only a slight inhibition against a Bdellovibrio
strain and its Pseudomonas species host using disc assay techniques.

     Using three types of soil from Puerto Rico, Liu and Cibes-Viade (1972)2J
studied the effects of bromacil and several other herbicides on the respira-
tion of soil microorganisms.   At 10 ppm (equivalent to an application of
4 Ib Al/acre), most of the herbicides tested including bromacil, inhibited
oxygen consumption slightly in Goto clay soil.  None of the herbicides inhibited
oxygen consumption noticeably in Fraternidad clay at 10 ppm, but at 100 ppm,
oxygen uptake was generally inhibited.   In San Anton sandy loam, bromacil
and most of the other herbicides tested increased oxygen consumption at 10 ppm,
and the respiration rate at 100 ppm.


     Steyn and Wolff  (1969)—'  investigated  the influence of bromacil on the
nitrifying and respiratory capacities of soil.   Sandy loam was treated with
an 80% wettable powder formulation of bromacil at the rate of 4 ppm, which
is twice the application rate recommended for this  type of soil.  No statis-
tically significant differences  were  found  in the ammonium and nitrate nitrogen
contents, nor in the  amounts  of  carbon  dioxide evolved from treated as compared
to untreated soils.   Those authors noted that according to the literature,
nitrification organisms are relatively  sensitive to soil-applied chemicals
and are therefore useful indicator organisms.  They concluded that the use of
bromacil in accordance with the  specified label directions would have no
statistically significant detrimental effect  on the soil microflora.

     Kutches et al.  (1970)A'  studied  the effects of bromacil and several other
pesticides on the microbial activity  of sheep rumen liquor in vitro.  Dry
matter disappearance, volatile fatty  acid production, and alterations in
rumen ciliated protozoa numbers  were  the criteria measured.  Relat-ively high
concentrations (500 pg/ml) of bromacil  (and of the  other pesticides) were
tolerated by rumen microorganisms without deleterious effects on rumen function
I/  Wehr, N., D. Klein, "Herbicide Effects on Bdellovibrio Bacteriovorus
      Parasitism of a Soil Pseudomonad", Soil Biol. Biochem.. 3(2)1 143-9  (1971)
2J  Liu, L. C., and H. R. Cibes-Viade, "Effect of Various Herbicides on
      the Respiration of Soil Microorganisms," J. Agr. Univ. P.R.. 56(4):
      417-425  (1972).
3/  Steyn, P.L., and S. W. Wolff, "The Influence of 5-Bromo-3-secondary
      butyl-6-methyluracil on the Nitrifying and Respiratory Capacities
      of Soil." Phytophylactica. 1:157-160 (1969).
4/  Kutches, A. J., D. C. Church, and F. L. Duryee, "lexicological Ef-
      fects of Pesticides on Rumen Function In Vitro," J. Agr. Food
      Chem.. 18(3):430-433 (1970).
                                       43

-------
 as measured by the three aforementioned parameters.  The authors concluded
 that the concentrations of bromacil  (and of the other pesticides studied)
 that might be ingested by ruminents by way of contaminated feedstuffs would
 have no, or negligible, effects on rumen digestibility or other rumen
 functions.  Pesticide residues that might be found on contaminated feed-
 stuffs would be expected to be much lower than those studied.

      The reports reviewed in this subsection indicate that certain soil
 microorganisms are capable of degrading bromacil, and that bromacil concen-
 trations in the soil that might be expected from its use in accordance with
 label directions do not appear to effect soil microflora adversely.

      No reports were found on the effects of bromacil on the soil microfauna.
 Laboratory Studies - Gardiner et al. (1969)i/ synthesized ^C - labeled
 bromacil for disappearance and metabolism studies.  This molecule
 was labeled in the 2-position so that the l^C - label would be retained
 by all metabolites in which the uracil ring had not been degraded.  In
 laboratory studies, soil samples were treated with bromacil at a rate
 equivalent to 20 Ib Al/acre.  Of the bromacil applied, 25.3% was decomposed
 to l^C-labeled carbon dioxide in nine weeks.

      Zimdahl et al. (1970) 2/ investigated the degradation of bromacil and
 several other herbicides in Chehalis loam soil in the laboratory.  Bromacil
 was added to this soil at the rate of 8 ppm (by weight).  The treated soil
 was stored at two different temperatures, i.e., 13.2 and 31.2°C.  The degra-
 dation of bromacil followed a first order rate law with no induction period.
 Evaluation of the rate constants at the two temperatures permitted calculation
 (from the Arrhenius equation) of an energy of activation of 3.0 kcal/mole for
 bromacil degradation.   Decomposition of bromacil appeared to occur by breakage
 of the carbon-halogen bond.

      Dowler (1969).3/ used a cucumber bioassay test to determine the persist-
 ence of soil residues  of bromacil and several herbicides.  Cucumber plants
 were grown in steam-sterilized sand to which the herbicides were added at
 concentrations ranging from 0.001 to 2.187 ppm weight.  Concentrations of
 bromacil as low as 0.001 to 0.027 ppm weight could be detected by this method.
 This paper provides details of the bioassay method, but not persistence data.
I/  Gardiner,  J.  A.,  R.  C.  Rhodes,  J.  B.  Adams Jr.,  and E.  J.  Soboczenski,
      "Synthesis  and  Studies with 2-l^C-labeled Bromacil and Terbacil,"
      J. Agr.  Food  Chem.. 17(5):980-986 (1969).
2J  Zimdahl, R. L., V. H. Freed,  M.  L.  Montgomery, and W. R. Furtick,
      "The Degradation on Triazine  and  Uracil Herbicides in Soil," Weed
      Res.. 10:18-26  (1970).
_3_/  Dowler, C. C.,  "A Cucumber Bioassay Test  for the Soil Residues of
      Certain  Herbicides,"  Weed Sci., 17(3):309-310  (1969).
                                      44

-------
     Rhodes et al. (1970)!/ studied the mobility and adsorption of broma-
cll and several other pesticides on soils in the laboratory.  2-1*0
bromacil at concentrations ranging from 1 to 20 ppm was added to four
agricultural soils from different locations, selected to represent a
variety of soil types.  Soil pH ranged from 5.4 to 6.7; organic matter
content from 0.7 to 83.5%.  The Freundlich isotherm constants were de-
termined, and the mobility of the test compounds was evaluated by pre-
paring radioautograms of soil thin-layer chromatographic plates.  In
each of the four different soils, bromacil was relatively more mobile
than the other four chemicals studied.  Bromacil also showed greater
lateral diffusion than the less mobile materials.

     Haque and Coshow (1971)2/ studied the adsorption of bromacil from
aqueous solutions onto mineral surfaces including illite, montmorillon-
ite, silica gel, humic acid, and kaolinite surfaces.  Freundlich-type
Isotherms best represented the adsorption process.  The humic acid
surface adsorbed considerably more chemical than other surfaces.  Montmo-
rillonite and kaolinite showed a concave-type, humic acid a convex-type
adsorption.  From the adsorption data at two temperatures, the isosteric
heats of adsorption in relation to the amount of chemical sorbed were
calculated.  The results suggested that for most of the surfaces, the
adsorption occurs through physical forces.  At very low surface coverage,
some hydrogen-bond formation was noticed.

     Volk (1972)!/ studied the physicochemical aspects of the interac-
tions between bromacil (and several other pesticides) and soil.  Cation
saturation and time of exposure did not appreciably affect the adsorption
of bromacil on montmorillonlte.  In another test series, an aqueous solu-
tion of bromacil  (0.1 meq) was titrated with 0.1 N HC1 or NaOH.  No
inflection points were obtained, indicating that bromacil cannot be titrated
in an aqueous solution.  However, titration in nonaqueous media indicated
that it is weakly acidic.
If  Rhodes, R. C., I. J. Belasco, and H. L. Pease, "Determination of
      Mobility and Adsorption of Agrichemicals on Soils," J. Agr. Food
      Chem.. 18(3):524-528  (1970).
2]  Haque, R., and W. R. Coshow, "Adsorption of Isocil and Bromacil
      from Aqueous Solutions onto Some Mineral Surfaces," Environ. Sci.
      Technol.. 5(2):139-141 (1971).
I/  Volk, V. V., "Physico-Chemical Relationships of Soil-Pesticide Inter-
      actions," Oreg. State Univ. Environ. Health Sci. Cent. Annu.
      Progr. Rep., pp.  186-199  (1972).
                                       45

-------
 Residues  in  Soil/Field  Studies  -  Gardiner  et al.  (1969) also studied the
 disappearance  of  2-l^C-labeled  bromacil applied at the rate of 4 Ib AI/
 acre  to the  surface  of  a  Butlertown  silt loam.  Sections of 4-in. diameter
 stainless steel tubes were  driven into the ground to isolate undistrubed
 columns of soil.  About 1.5 in. of each cylinder was left protruding above
 the ground surface.  The  radiolabeled bromacil was applied to the soil
 surface and  watered  into  the soil with five separate rinses, which in
 total were equivalent to  about  0.25  in. of rain.  The half-life of broma-
 cil was about  5 to 6 months.  After  1 year, about 75% of the total radio-
 activity  applied  had disappeared.  Bromacil constituted, about 90% of the
 remaining residues,  indicating  that  there  was little accumulation of
 unknown metabolites.  No  5-bromouracil was formed as a metabolite, though
 5-bromo-3-sec-butyl-6-hydroxymethyl  uracil and a few related minor metabolites
 have  been identified as metabolites  of bromacil in soil.  Evaluation of thin-
 layer chromatography radioautograms  of soil extracts indicated that one
 mode  of degradation  of  bromacil proceeds through hydroxylation of the side
 chain alkyl  groups,  presumably  followed by ring opening and complete metab-
 olism to  carbon dioxide,  ammonia,  and hydrobromic acid.

      Tucker  and Phillips  (1970)!/ studied  the movement and degradation of
 bromacil  (and  several other pesticides) in Florida citrus soil which had
 been  treated repeatedly with these herbicides for up to 5 years.  Soil
 samples were obtained from  experimental plots and commercial citrus groves
 from  different areas in Florida.   Samples  were taken at depths up to 18 in.
 from  the  middle of tree rows and  kept in frozen storage until analyzed.
 Bromacil  content  was determined by gas chromatography.  From a total amount
 of 100 Ib Al/acre of bromacil applied in Leon Immokalee fine sand over a
 5-year period  at  the rate of 20 Ib Al/acre annually, approximately 1.0 Ib
 AI was present in the soil  (0-  to 18-in. depth) 13 months after the last
 application.  This represents a 99%  loss over the 5-year period.

      Bromacil residues  were found throughout the 18-in. layer of soil.
 Its movement into the lower soil  layers was shown to be a function of
 the chemical's water solubility,  its adsorption on soil colloids, and soil
 type.   Factors affecting  soil persistence  include microbial degradation,
 rainfall,  and the degree  of uptake by plants.  Bromacil is quite water soluble,
 and may be leached into deeper  soil  layers in sandy soils.  The authors
 concluded  that their results  "preclude the possibility of any toxicity
 (phytotoxicity) to citrus trees due  to a buildup of bromacil in the soil
 following  repeated applications at recommended rates."
I/  Tucker, D. P., Jr., and R. L. Phillips, Jr., "Movement and Degrada-
      tion of Herbicides in Florida Citrus Soil," Citrus Ind., 51(3):
      11-13 (1970).
                                      46

-------
     Lange et al. (1968)i/ studied residues of bromacil and other herbi-
cides remaining in California soils following use under typical field
conditions at six locations.   Bromacil, applied at 1 and 4 Ib Al/acre,
was among the most persistent of 13 herbicides tested.   One year after
application, both rates were  still toxic to barley,  milo, sugar beets,
alfalfa, tomato, and wheat.   Among these plants, alfalfa was most sensi-
tive, followed by wheat and tomato.  Phytotoxicity was  still evident in
the bromacil-treated plots 24 and 30 months after the initial applica-
tion.  Among the 13 herbicides tested,  bromacil generally lasted the
longest.  At every test location, the bromacil plots were visibly obvious.
The authors point out that bromacil is  a long-term,  broad-spectrum soil
sterilent, and that it will find little, if any, use as a selective herbi-
cide on annual crops because  of its long-lasting residual effects.

     The authors do not provide disaggregate information on the properties
of the soils in which these studies were conducted.   The organic matter
content of the soils ranged from 1.3 to 12.6%; sand, from 24 to 607.;
silt, from 27 to 56%; and clay, from 9  to 32%.  The  amount of moisture
received was approximately 30 to 45 in.

     Tucker and Phillips (1970) do not  provide data  on  rainfall, and
neither Lange et al. (1968) nor Tucker  and Phillips  (1970) provide data
on soil temperatures, soil pH, or other parameters that might help to
explain their seemingly divergent observations concerning the persistence
of bromacil residues.

     Weber and Best (1972)!/  studied the activity and movement of broma-
cil and 12 other soil-applied herbicides as influenced  by soil reaction.
Broadleaf weeds were more prevalent in  neutral (pH 7) than in acid soils
(pH 5).  The opposite was true for grass weeds.  Bromacil was the second
\J  Lange, A., B. Fischer, W. Humphrey, W.  Seyman, and K. Baghott,
      "Herbicide Residues in California Agricultural Soils," California
      Agr.. pp. 2-4 (August 1968).
2J  Weber, J. B., and J. A. Best, "Activity  and Movement of 13 Soil-
      Applied Herbicides as Influenced by Soil Reaction," Proc. S. Weed
      Sci. Soc.. 25:403-413 (1972).
                                   47

-------
most active herbicide against broadleaf weeds and was the most active against
the grass weeds.   Its activity  appeared to be unaffected by soil pH.  When
the relative mobilities  of  the  herbicides were measured by their movement
over the soil surface into  adjacent untreated areas, bromacil was very
mobile.  It also was the most persistent of all herbicides studied.

     Stecko (1970)!/ studied the persistence and vertical movement of
bromacil in clay and sandy  soils in field tests in Sweden.  Herbicides
were applied to the surface of  the test soils at 2.7, 5.3, and 10.7 Ib
Al/acre.  The herbicides were not incorporated into the soil.  Soil samples
were taken from six different layers ranging from 0 to 9.4 in., and the
residual toxicity  was determined by bioassay with white mustard and oats.
Within 120 days after treatment, bromacil had moved downwards beyond the
9.4-in. level.  Bromacil persisted longer in the sandy soil than in the clay
soil, and its phytotoxic residues disappeared more rapidly from the upper
than from the lower soil layers.

     Stecko states that  it  is difficult to explain why bromacil disappeared
more rapidly from  the clay  than from the sandy soil.  He suggests that
there may have been differences in the populations of microorganisms in the
two soil types.  Another explanation might be that during the summer, the
microbial activity in the clay  soil was inhibited due to drought.

     Horowitz (1969).2/ evaluated the persistence of bromacil and nine other
herbicides in soil in the greenhouse, using an oat bioassay test.  Bromacil
was applied at concentrations ranging from 0.4 to 12.8 ppm weight.  Under
these conditions,  bromacil  was  rated as "moderately persistent," its
residual activity  decreased rather slowly.  In general, four triazines and
bromacil were the  most active among the 10 herbicides studied.
_!/  Stecko, V., Jr.,  "Comparison of the Persistence and the Vertical
      Movement of the Soil-Applied Herbicides Simazine and Bromacil,11
      10th British Weed  Control Conference Proceedings, 1:303-306 (1970).
2J  Horowitz, M., "Evaluation of Herbicide Persistence in Soil," Weed
      Res., 9(4):314-321 (1969).
                                     48

-------
     The data reviewed in this subsection on the behavior and  persistence
of bromacil in the soil indicated that it is not strongly adsorbed  on soil
colloids.  Bromacil appears to be more mobile (both laterally  and verti-
cally) in the soil than most other herbicides.   Bromacil residues in the
soil are moderately persistent.  Microbial activity as well as nonbiological
factors appear to contribute to its degradation in the soil.   In one test,
the half-life of a 4 Ib Al/acre application of  bromacil was about 5 to 6
months.  When applied at higher rates, the herbicidal activity of bromacil
seems to persist for two or more seasons.

Monitoring Studies - None of the published reports from the National Soils
Monitoring Program for pesticides include data  on reported uses of  broma-
cil, or records of detection of bromacil residues.  Reports scanned in this
regard include those by Stevens et al. (1970),I/  Crockett et  al, (1970)-£'
and Wiersma et al (1972) .I/

     Since the results of the 1972 National Soils Monitoring Program were not
published at the time of review, data from this source is not  included.

Residues in Water

     A technical data sheet on bromacil (E. I.  du Pont de Nemours and
Company, Wilmington, Delaware)states that the water solubility of bromacil
is 815 ppm at 25°C, and that it is stable in water and aqueous bases.


     Davis and Rahn (1970)—' investigated the possible contamination of
surface water following the use of bromacil for nonselective weed control.
Surface runoffs from an industrial site treated with bromacil  were  collected
and analyzed by gas chromatography.  Insignificant amounts of  bromacil were
found in surface water from the bromacil-treated industrial site following
heavy rains within 2 to 4 weeks after application.  These amounts were far
below levels reported to be injurious to animal or plant life.

     No additional reports were found on the presence (or absence)  of bro-
macil residues in water, sediment, or other elements of aquatic ecosystems.
i/  Stevens, L. J., C. W. Collier, and D. W. Woodham, "Monitoring Pesticides
      in Soils from Areas of Regular, Limited, and No Pesticide Use,"
      Pest. Monit. J..  4(3):145-164 (1970).
2/  Crockett, A. B., G. B. Wiersma, H. Tai, W. G. Mitchell, and P. J. Sand,
      "National Soils Monitoring Program for Pesticide Residues - FY 1970,"
      U.S. Environmental Protection Agency, Techinical Services Division,
      unpublished manuscript (1970).
3/  Wiersma, G. B., H. Tai, and P. F. Sand, "Pesticide Residue Levels in
      Soils, FY 1969-National Soils Monitoring Program," Pest. Monit. J..
      6(3):194-201  (1972).
4/  Davis, W. A., and E. M. Rahn, "Atrazine, Trifluralin and Bromacil in
      Surface Water from Selected Agricultural and Industrial Sites,"
      Northeastern Weed Control Conference Proceedings. 24:283  (1970).
                                      49

-------
  Residues  in Air

       Hill (1971)i/ reported  that the rate  of volatilization of bromacil
  was  measured for weeks  at 120°F in air  circulation  oven.  Losses were
  less than 0.1%/week.

       Bingetnan et al.  (1962)J?/  reported  that  (based  on  tests at elevated
  temperatures and with long exposures to sunlight) loss of bromacil from
  soil by volatilization  and photodecomposition  is negligible.

       Moilanen and Crosby  (1974).-L/ investigated the  action of sunlight
  on dilute (1 to 10 ppm) aqueous solutions  of bromacil.  Even upon pro-
  longed  irradiation, only  very  low yields of the one detectable photo-
  product (5-bromo-6-methyluracil)  were obtained.  The starting material
  was  recovered almost  quantitatively.  The  results indicate that bromacil
  is very stable  toward sunlight and undergoes only N-dealkylatlon.  The
  slow breakdown  of bromacil in  sunlight  indicates that photodecomposition
  probably  makes  only a minor  contribution to the environmental disappearance
  of this herbicide.

       No additional reports were found within the time frame allocated for
  this review on  the presence, fate or  persistence of bromacil residues in air.
  The  data  reviewed indicates  that  bromacil  does not  volatilize from treated
  soil to any appreciable extent and that it is  stable to photodecomposition
  in sunlight.

  Effects and Residues  in Nontarget Plants

       Since  bromacil is primarily  a broad-spectrum nonselective herbicides,
  there are no  "nontarget"  higher plants  per se.  However, two noteworthy
  reports were  found on "nontarget" higher plants.

      Sterret et al. (1972)_L/ studied antagonistic effects between bromacil
 and another herbicide  (picloram) on oats.  It was observed that field appli-
 cations  of combinations  of picloram and bromacil in pellet form were less
 effective in controlling broomsedge (Andropogon virginicus),  dallisgrass
 (Paspalum dilatatum),  and several panicums (Panicum sp.)  than was bromacil
 alone.  Further experiments were conducted on oats  in soil in the greenhouse
 and in nutrient solution in controlled environment  chambers  to study this
 apparent interaction.  When oats were grown in soil treated with combinations
 of picloram (5 or 10 Ib  Al/acre) and bromacil (10 Ib Al/acre),  there was less
 I/   Hill,  G.  D.,  "Characteristics of Herbicides by Chemical Groups. II.
       Hyvar X Bromacil," California Weed Conference Proceedings.  23:171-174
       (1971).
 2J   Bingeman,  C.  W.,  G.  D.  Hill,  R. W.  Varner, and T.  A. Weidenfeller,
       North Central Weed Control  Conference Proceedings. 19:42-43 (1962).
       In:  Herbicide Handbook of the Weed Science Society of America.
       3rd  ed., p.  68  (1974).
 3/   Moilanen,  K.  W.,  and D.  G.  Crosby,  "The Photodecomposition of Bromacil,"
      Arch, of Environ.  Contain, and Toxicol..   2(1):3-8 (1974).
^/   Sterrett,  J.  P.,  J.  T. Davis,  and W.  Hurtt, "Antagonistic Effects
      Between  Picloram and Bromacil with Oats," Weed Sci.,  20(5):440-444
       (1972).
                                      50

-------
plant Injury than in plants treated with bromacil alone.   The higher rate of
picloram in combination with bromacil resulted in an almost twofold decrease
in response as compared to plants treated with bromacil alone.  In nutrient
culture experiments, it was found that the uptake of 14C-labeled bromacil
alone by oats was nearly double that of ^C-bromacil combined with picloram.
Thin-layer chromatographic analyses showed that 47% of the radioactivity from
bromacil in the oat was intact bromacil, and 70% of the labeled activity from
picloram was unaltered picloram.  Roots of oats treated with picloram alone
or picloram and bromacil in combination were significantly shorter than the
roots of untreated plants, or of plants treated with bromacil alone.  Reduction
of root length by picloram could be responsible for the reduction in adsorption
of bromacil.

     Hiranpradit and Foy (1973)J^ found that soil applications of subtoxic
levels of bromacil (0.03 to 0.09 ppm) markedly retarded the senescence of
corn leaves.  Plants treated with bromacil showed increased chlorophyll reten-
tion and incorporation.  The authors point out that bromacil does not contain
a purine ring, yet it exhibited a cytokinin-like effect of retarding leaf
senescence.

Bioaccumulation, Biomagnification

     There were no reports found on the possible bioaccumulation or biomag-
nification of bromacil.

Environment Transport Mechanisms

     According to Hill (1971), bromacil has relatively low solubility in water
(0.08 or 815 ppm) and a K value (Freundlich constant) of 1.5 on a Keyport
silt loam.  This combination of water solubility and low soil adsorption
results in considerable mobility of bromacil in soil profiles.

     In a recent review, Helling et al. (1971)—'  ranked a number of pesti-
cides by their relative mobility in soils by mobility classes from 1 (immobile)
to 5 (very mobile).  In this scheme, bromacil was placed in Class 4.  Of
82 pesticides included in this tabulation, bromacil was among the 14 materials
(mostly herbicides) rated most mobile in the soil.

      This data, along with those reviewed in the preceding subsections,
indicate that bromacil is relatively stable in the soil, subject to leaching
and surface transport via runoff, not strongly adsorbed on soil solids,
and not subject to significant volatization from treated soil.
JL/  Hiranpradit, H., and C. L. Foy, "Retardation of Leaf Senescence in
      Maize by Subtoxic Levels of Bromacil, Fluometuron, and Atrazine,"
      Botanical Gazette. 134(1):26-31 (1973).
2]  Helling, C. S., P. C. Kearney, and M. Alexander, "Behavior of Pesti-
      cides in Soils," Advances in Agronomy.  23:147-240(1971).
                                    51

-------
References

Anderson, L. D., E. L. Atkins Jr., H. Nakakihara,  and  E. A. Greywood, Toxicity
  of Pesticides and Other Agricultural Chemicals to Honeybees. U. S. Department
  of Agriculture, Agricultural Extension Service Report, University of Calif-
  ornia Press, Berkeley, Calif. (1971).

Atkins, E. L., E. A. Greywood, and R. L. Macdonald, Toxicity of Pesticides and
  Other Agricultural Chemical to Honeybees.  U.  S.  Department of Agriculture,
  Agricultural Extension Service Report, University of California Press, Berkeley,
  Calif. (1973).

 Bingeman,  C. W., G. D. Hill, R. W. Varner,  and T. A.  Weidenfeller,  North
   Central Weed Control Conference Proceedings. 19:42-43  (1962).   In:
   Herbicide Handbook of the Weed Science Society of America,  3rd ed.,
   p.  68 (1974).

Crockett, A. B.,  G. B. Wiersma, H. Tai, W.  G.  Mitchell, and P. J. Sand,
   "National Soils Monitoring Program for Pesticide Residues - FY 1970,"
  U.S.  Environmental Protection Agency, Technical Services Division,
  unpublished manuscript  (1970).

Davis,  W. A., and E.  M. Rahn, "Atrazine, Trifluralin  and  Bromacil in
  Surface Water from Selected Agricultural  and Industrial Sites," North-
  eastern Weed  Control Conference Proceedings, 24:283 (1970).

Dowler, C.  C.,  "A Cucumber Bioassay Test for the  Soil Residues of Cer-
  tain  Herbicides," Weed_§£ii,  17(3):309-310 (1969).

E. I. du Pont de Nemours and Company, Inc.,  Personal communication   (1974).

Gardiner, J. A.,  R.  C. Rhodes,  J.  B. Adams,  Jr.,  and  E. J. Soboczenski,
  "Synthesis and  Studies with 2-lAC-Labeled Bromacil  and  Terbacil," J^
  Agr. Food  Chem..  17(5):980-986  (1969).

Haque, R., and W.  R.  Coshow,  "Adsorption of Isocil and Bromacil  from
  Aqueous Solution onto Some  Mineral  Surfaces," Environ.  Sci. Techno1.,
  5(2):139-141  (1971).

Helling, C.  S., P.  C.  Kearney,  and M.  Alexander,  "Behavior of Pesticides
  in Soils," Advances  in Agronomy.  23:147-240  (1971).

Hill, G. D., "Characteristics of  Herbicides by Chemical Groups.  II.
  Hyvar X Bromacil,"  California Weed Conference Proceedings, 23:171-174
  (197n-

Hiranpradit, H., and  C. L. Foy, "Retardation of Leaf  Senescence  in Maize
  by Subtoxic Levels of Bromacil,  Fluometuron,  and Atrazine," Botanical
  Gazette. 134(1):26-31 (1973).

                                     52

-------
Hoffman, C, E., "The Mode of Action of Bromacil and Related Uracils,"
  Second International Conference of Pesticide Chemical Proceedings.
  (1971).  In:   Ashton and Crafts, Mode of Action of Herbicides. John
  Wiley & Sons, pp. 430-431 (1973).

Horowitz, M., "Evaluation of Herbicide Persistence in Soil." Weed Res,,
  9(4):314-321  (1969).

Kutches,  A. J., D. C. Church, and F. L. Duryee, 'lexicological Effects
  of Pesticides on Rumen Function In Vitro.11 J. Agr. Food Chem. t 18(3):
  430-433 (1970).

Lange, A., B. Fischer, W. Humphrey, W. Seyman, and K. Baghott, "Herbi-
  cide Residues in California Agricultural Soils," California Agr.,
  pp. 2-4 (August 1968).

Liu, L. C., and H. R. Cibes-Viade, "Effect of Various Herbicides on the
  Respiration of Soil Microorganisms." J. Agr. Univ. P.R.. 56(4):417-
  425 (1972).

Moilanen, K. W., and D. G. Crosby, "The Photodecomposition of Bromacil,"
  Arch, of Environ. Contain, and Toxicol.. 2(1):3-8 (1974).
Pancholy, S. K., and J. Q. Lynd, "Bromacil Interactions in Plant Bio-
  assay, Fungi Cultures, and Nitrification," Weed Sci.. 17(4):460-463
  (1969).

Pimentel, D., "Ecological Effects of Pesticides on Nontarget Species,"
  Executive  Office of the President, Office of Science and Technology,
  Superintendent of Documents, U.S. Government Printing Office,
  Washington, D.C. (1971).

Rhodes, R. C., I. J. Belasco, and H. L. Pease, "Determination of Mobility
  and Adsorption of Agrichemicals on Soils," J, Agr. Food Chem., 18(3):
  524-528 (1970).

Stecko, V.,  Jr., "Comparison of the Persistence and  the Vertical Movement
  of the Soil-Applied Herbicides Simazine and  Bromacil," 10th British Weed
  Control Conference Proceedings. 1:303-306 (1970).

Sterrett, J. P., J. T. Davis, and W. Hurtt, "Antagonistic  Effects Between
  Picloram and Bromacil with Oats," Weed Sci.  20(5):440-444  (1972).

Stevens, L.  J., C. W. Collier, and D. W. Woodham,  "Monitoring Pesticides
  in Soils from Areas of Regular, Limited, and No  Pesticide  Use," Pest.
  Monit. J..  4(3):145-164 (1970).
                                     53

-------
 Steyn,  P.  L.,  and S.  W.  Wolff,  "The  Influence  of 5-Bromo-3-secondary-
   butyl-6-methyluracil on the Nitrifying  and Respiratory  Capacities of
   Soil," Phytophylactica. 1:157-160  (1969).

 Torgeson,  D. C.,  and  H.  Mee, "Microbial Degradation  of  Bromacil," North-
   eastern  Weed Control Conference  Proceedings,  21:584 (1967).

 Tucker, D. P., Jr., and  R. L. Phillips, Jr., "Movement  and Degradation
   of Herbicides in Florida Citrus  Soil,"  Citrus  Ind.. 51 (3):11-13 (1970).

Tucker, R. K., and D. G.  Crabtree, Handbook of Toxicity of Pesticides to
  Wildlife. Bureau of Sport Fisheries and Wildlife, Denver Wildlife
  Research Center, Resource Publication No. 84  (1970).

Volk, V. V., "Physico-chemical Relationships of  Soil-Pesticide Interac-
  tions," Oreg. State Univ. Environ. Health Sci. Cent. Annu. Progr. Rep..
  pp. 186-199  (1972).

Weber, J. B., and J. A. Best, "Activity and Movement of 13 Soil-Applied
  Herbicides as Influenced by Soil Reaction," Proc. S. Weed Sci. Soc.,
  25:403-413 (1972).

 Wehr, N.,  and  D.  Klein,  "Herbicide Effects on Bdellovibrio bacteriovorus
   Parisitism of a Soil Pseudomonad." Soil Biol.  Biochem.. 3(2):143-149
   (1971).

 Wiersma, G. B., H. Tai,  and P. F.  Sand, "Pesticide Residue Levels in
   Soils, FY 1969-National Soils Monitoring Program," Pest. Monit. J..
   6(3):194-201  (1972).

Yoshida, K., and Y. Nishiuchi, "Toxicity of Pesticides to Some Water
  Organism," Bull, of Agr. & Chem  Inspect. Stn.  (Tokyo) 12:122-128 (1972)

Zimdahl, R. L., V. H. Freed, M. L. Montgomery, and W. R. Furtick, "The
  Degradation of Triazlne and Uracil Herbicides  in Soil," Weed Res..
  10:18-26 (1970).
                                      54

-------
                  SUBPART II.  D.   PRODUCTION AND USE


                                CONTENTS



                                                                  Page

Registered Uses of Bromacil	    56

  Federally Registered Uses  	    56
  State Regulations	    57

Production and Domestic Supply 	    57

  Volume of Production   	    57
  Imports	    61
  Exports	    61
  Domestic Supply  	    62
  Formulations	    62

Use Patterns of Bromacil in the United States	    63

  General	    63
  Agricultural Uses of Bromacil	    63
  Nonagricultural Uses of Bromacil 	    65
  Bromacil Uses in California	    65

References	  .    75
                                     55

-------
      This section contains data on the registered uses, and on the pro-
 duction, domestic supply, and use patterns of bromacll.  The section
 summarizes rather than interprets scientific data reviewed.

 Registered Uses of Bromacil

 Federally Registered Uses - Bromacil is a broad-spectrum general herbi-
 cide.   It controls a wide range of annual and perennial grasses and
 broadleaf weeds.  Annual weeds are controlled at lower rates, perennial
 weeds  (including grasses) and brush at higher rates.

      Bromacil is registered and reconmended for nonselective weed and
 brush control on noncropland, and for selective weed control on a few
 crops.

      Commercially available bromacil formulations are discussed below
 in the subsection on production and domestic supply.

      Bromacil is currently registered in the United States for the fol-
 lowing major uses:

      1.  Nonselective weed and brush control on noncropland areas including
          railroad, highway and pipeline right-of-ways; petrochemical tanks;
          lumber yards; storage areas; industrial plant sites; and drainage
          ditches using the following applications, as found on registered
          use labels:

          a.   2.4 to 4.8 Ib Al/acre for the control of annual weeds and
              grasses;

          b.   5.6 to 9.6 Ib Al/acre for the control of perennial weeds and
              grasses;

          c.   12.0 to  24.0 Ib Al/acre for the control of Johnson grass and
              other hard-to-kill perennial weeds and grasses;

          d.   5.6 to 24.0 Ib Al/acre (broadcast treatment)  for the control
              of  undesirable woody plants (rate of application dependent
              upon suspectibility of target brush and soil  adsorptivity;
              higher rates required on adsorptive soils);

          e.   2.0 Ib AI in 5 gal.  of water for basal (spot)  treatment, to be
              applied  at the rate of 1 to 2 fluid ounces/stem, 2 to 4 in. in
              basal diameter.

      2.   Selective weed control in crops using the following applications:—'

          a.   1.6 to 6.4 Ib Al/acre for the control of annual and perennial
              weeds in  citrus  plantings (oranges, grapefruit, lemons), to be
              applied as a band or broadcast treatment beneath and/or between
              trees, lower rates for the control of annual  weeds and on light
              soils; higher rates  against perennial weeds,  especially grasses,
              and on silt  and  clay loams.   Do not plant treated areas to any
  	crop within  two  years of last treatment.
T7U.S.  Environmental  Protection Agency,  EPA Compendium of Registered
    Pesticides. Vol. I  (1970).

                                     56

-------
          b.  1.6 to 4.8 Ib Al/acre (restricted  to Hawaii)  for  the  control of
              seedling weeds In pineapple,  for broadcast  application  immediately
              after planting and before the planting material begins  to  grow.
              A second application of  1.6 Ib Al/acre may  be made  prior to
              differentiation,  If needed, as a directed interline spray.   Do not
              replant to any crop other than pineapple within two years  of last
              application.

          c.  0.6 to 3.2 Ib Al/acre (restricted  to Puerto Rico) at  planting time
              is recommended on pineapple.   Single overall  application immedi-
              ately after planting. Do not replant  to any  crop other than
              pineapple within two years of last application.

     For further details on these registered uses of bromacil,  including
necessary use precautions, specific weeds controlled at  different rates,
retreatment, moisture requirements, type and duration of  efficacy,  and
other directions to users see Table 5, illustrating a commercial  label
for bromacil 802 wettable powder (Trademark: Hyvar^X).

     Registered uses of bromacil on crops  (i.e., citrus  and pineapple),
established tolerances, dosage rates,  and use limitations are tabulated
in the EPA Compendium of Registered Pesticides.   Tolerances established
for bromacil residues on raw agricultural commodities are recorded in the
Code of Federal Regulations Jy

     Bromacil is also registered and recommended for use in combination
with diuron.  Two wettable powder formulations containing different ratios
of these two herbicides are commercially available under the trademark
"Krovar."  These products are registered and used for the same weed con-
trol purposes as formulations containing only bromacil.

State Regulations - In a number of states, the sale and use of pesticides
is subject to state pesticide laws and regulations, in addition  to Federal
laws and regulations.  For instance, in  the State of California, 42  spe-
cific pesticides have been designated as "injurious or restricted materi-
als."  The use of pesticides in this category is subject to special  re-
strictions under regulations administered by the California State Department
of Agriculture.  Bromacil has not been designated as an "Injurious or re-
stricted" pesticide.  As far as could be determined, bromacil  is not subject
to intrastate use restrictions in any  state.
Production and Domestic Supply

Volume of Production - Accordii
and 1973 final reports!/ on synthetic organic chemicals, there has been
Volume of Production - According to United States Tariff Commission's 1972
                     si/ on (
T7Code of Federal Regulations. "USDA Summary of Registered Agricultural
      Pesticide Uses," (Vol. I, 1970), Title 40, Part 180-210, p.  22.
2J  U.S. Tariff Commission, Synthetic Organic Chemicals. U.S. Production
      and Sales. T. C. Publication 681 (1972, 1973).
                                    57

-------
               Table  5.   BROMACIL  807. WETTABLE POWDER

                           (HWAR® X)  LABEL

 V.to observe the following: Do not apply (exeep    ,.,,,„„„.     ...  ,	
  equipment on or near desirable trees or other plant}, eronl Mitt whsra their roots may <
  In Ittiitloiw where the chemical may be washet^jOfInured Wp(pr.Ud tottHtyelr —'
  •use cr. lawns, walks, driveways, tennis wurto, of ilmflar attj»$. P.«yent,drfftof <    —,..,..
 i j spray to desirable plnrrts. Do not contaminate; » tracos'of, "HyVar", X fronj applfcatjoi:
  E. I. cfy Pont de
[ Biochemlcals DepartrhehtVVIlrnl
   Source:  Label  for HYVAR*'X bromacil  weed killer 807. wettable

               powder, 4-lb bag,  EPA Registration No.  352-287.
                                   58

-------
                        Table   5.     (Continued)
                                     NON-CROP USE
WEED CONTROL
To control most w»edi lor in extended period of lima on non-cropland area* fuch as RAILROAD, HIGH-
WAY and PIPELINE RIGHT OFAVAYS. PETROLEUM TANK FARMS. LUMBERYARDS. STORAGE AREAS and
INDUSTRIAL PLANT SITES:    l
Apply 3 to C Ibs. per acr* to control ANNUAL WEEDS and GRASSES such » foxtail, ryegrats. wild oats,
crabgrass. cheatgrass. bromegrass. ragweed, lambsquarters. puncturevine and turkey mullein. When applied
fust prior to or attar •mergence of annuals, rain ai low ai 2 Ibs. par acre control many annual weeds and
(raises In low rainfall areas and give short-term control In higher rainfall areas.
Apply 7 to 12 Ibs. per acre to control PERENNIAL WEEDS and GRASSES such as smooth brome. Bahla-
grass, bluegrass, redtop. purpletop. quackgrass, broomsedge,  aster, dandelion, dog fennel, goldenrod.
plantain and wild carrot. In areas with low or seasonal rainfall, rates as low as 5 Ibs. per acre control many
perennial weeds and grasses.
Apply IS to 30 Ibs.  per acre to control  JOHNSONGRASS; use at the same rate for OTHER HARD-TO-
KILL PERENNIAL WEEDS and  GRASSES  such as Bermudagrass, Dallisgrass, nutgrass. vaseygrass, salt-
grass, bouncingbet, dogbane, bracken fern and horsetail. Where limited rainfall (usually less than 4 inches)
occurs during the active growth period, such as some areas of Ihe West, "Hyvar" X usually will not provide
satisfactory control of hard-to-kill, deep-rooted perennial weeds such as Johnsongrass.
Hole-Use the higher levels of the dosage ranges on adsorptive soils (those high in organic matter or carbon).
Retnetment-Apply 2 to 6 Ibs. per acre  when annual weeds and grasses reappeer on sites where weed
growth has been controlled.
For Small Anus-V* cupful of "Hyvar" X per  250 sq. ft. Is approximately IS Ibs. per acre.
BRUSH  CONTROL
To control undesirable woody plants on non-cropland areas such as RAILROAD RIGHT-OF-WAYS, STORAGE
AREAS. INDUSTRIAL PLANT SITES, and DRAINAGE DITCHES:
Apply In  spring or summer as a broadcast or basal (spot) treatment; for use on drainage ditches, apply
•s a basal (spot) treatment only. Note: For effective brush control and prevention of damage to desirable
vegetation: do not apply to brush standing In water; do not use water from treated ditches for irrigation;
do not use in Irrigation ditches nor on  right-of-ways or other sites where marketable timber or other
desirable trees or shrubs are immediately adjacent to the treated area.
Broadcast Treatment-Apply 7 to 12 Ibs. per acre to control oak, willow, sweet gum, and pine; apply 15
to 30 Ibs. per acre to control brush such as American elm, winged elm. haekberry, sumac, and cotton-
wood. Use the higher levels of the dosage ranges on adsorptive soils (those high in organic matter or carbon).
Basal (Spot) Treatment-Mix 2V, Ibs. in 5 gals, of water and apply at the rate of  I to 2 fl. oz. per stem 2"
to 4" In basal diameter; wet base of stem to run-off. Treatment controls woody plants such as cottonwood,
haekberry. maple, oak. poplar, red  bud. sweet gum. wild cherry, willow, and winged elm.

                              SELECTIVE USE IN CROPS                 i
    "Hyvar" X should be used only in accordance with recommendations on this label, or in separate
    Du Pont bulletins available through local dealers.
All dosages of "Hyvar" X are expressed as broadcast rates. For band treatment, use proportionately less;
for example, use H of the broadcast rate when band treating V> of the area.
Moisture is necessary to activate the chemical; best results are obtained if moisture is supplied by rainfall
or irrigation within two weeks after application.
                           CITRUS (Oranges, Grapefruit, Umons)
Apply as a band or broadcast treatment beneath and/or between trees. Avoid contact of foliage and fruit
with spray or mist. Temporary yellowing of citrus leaves may occur fallowing treatment.
Because Injury to citrus trees may result: do not use on soils low in organic matter (less than 1%) nor on
poorly drained soils; do not apply more than 8 Ibs. per acre per yean do  not treat trees planted in Irriga-
tion furrows: do not treat diseased trees such as those with foot rot. Do  not use in citrus orchards inter-
planted with other trees or desirable plants, nor m home citrus plantings  or in areas where roots of other
valuable plants or trees  may extend  as plant injury may result. Treated  areas may be planted to citrus
trees one year after last application; do not replant to other crops within  2 years after last application as
plant injury may result.
Trees Established  for Four Years or More
Annual Weedt-lncluding crsbgrass. crowfoot. Coloradograss. natalgrass  (red top), barnyardgrass (water-
grass), sandspur.  purslane. Florida pusley. sprangietop,  puneturevme. mustard, lambsquarters. henbit,
annual sedge and turkey mullein, apply 2 to 4 Ibt  per acre. Apply anytime ol the year, preferably shortly
before or after weed growth begins when adequate moisture is available.
Perennial Weeds-Best results are obtained if application is made shortly before or shortly after weed
growth begins: if dense growth is present, remove lops and spray the ground. Effects on perennial weeds
are slow to appear, usually progressing over a period of several months.
Make a single application per year during the period from winter to early summer; use at the following rates:

           20" J»f»                                                  Uw. "Hyvar" X Per Acre
           Sand, loamy sand	4 to 5
           Sandy loam   	5 to 6
           Silt team, day loam  	               6 to 8
Alternatively, make two applications of 3 to 4 Ibs. "Hyvar" X per acre  per year, lii Florida, Tent, and
Louisiana, apply in spring and summer, in California and Arizona, apply in tell and  soring.
                                             59

-------
                          Table  5.    (Continued)
NeU— Partial control  usually occur* with  •
single treatment; repeat applications art re-
quired to control perennials. "Hyvar" X con-
trols the following:
Bermudagrass	All areas U.S.
Torpedograss. paragrass.
  pangolagrass,
  Bahiagrass	Florida
Johnsongrass	  Texas
Nutsedge	Texas. California
Control of perennials may be Improved by cul-
tivation prior to treatment:  otherwise, avoid
working the soil  as long as weed control  con-
tinues or else effectiveness of the treatment
may be reduced.

Torpedogftss Control-Barrier Strip Treatment
For control of torpedograss adjacent to citrus
graves to prevent spread of the weed  Into
groves, apply 30 IDS. per acre. Treat  a border
strip 10 to 20 ft wide adjacent to the citrus
grove, but not closer than 10 ft. to the drip-
line  of  citrus trees.  Examine treated  area
every four months after application and spot-
treat Invading or surviving  torpedograss at
30 IDS. per acre (11 oz. per 1000 sq. ft.). For
best result* apply in late winter or early spring
after the torpedograss has broken dormancy
and Is  actively  growing.  For later season
application where growth Is rank,  mow or
disc the area prior to  treatment.

               PINEAPPLE
Do not replant  treated areas  to  any  crop
other than pineapple within 2 years after last
application  as  injury to subsequent crops
may result.
Hawall-For control of seedling weeds such as
crabgrass, wiregrass,  foxtail, chloris. Hlaloa,
Flora's paintbrush,  balsam apple and Amar-
•nthus, apply 2  to 6 Ibs. per acre broadcast
Immediately  after planting  and before the
planting material  begins to grow.  Use the
lower rates in  low rainfall  areas  (5 to 10
Inches annually) and  on clean-culture fields;
use the higher  rates  in high rainfall areas
(above  10 inches annually) and for trash-
mulch  fields.  An  additional application of
2 Ibs.  per acre  may  be  made  prior to dif-
ferentiation, if needed, as a directed interline
•pray. Do  not spray over top of plants.
Puerto Rlco-For control of seedling weeds
such as crabgrass. goosegrass,  jungle  rice,
pigweed, and purslane, apply 2  to 4 Ibs. per
acre broadcast  immediately after  planting
and before planting material begins to grow.

          NOTICE TO BUYER
Seller warrants  that this product conforms
to the chemical description on the label thereof
and is reasonably fit for purposes stated on
such label only when used in accordance with
directions under normal use conditions.  This
warranty does not extend to use of this prod-
uct contrary to label use directions, or under
abnormal  use conditions,  or under condi-
tions not  reasonably foreseeable to seller;
buyer assumes all risk of any such use. Seller
makes no other warranties, express or implied.
    Made in U.S.A.    Printed In U.S.A.
     GENERAL INFORMATION

Du Pont "Hyvar" X Bromadl Weed Killer Is a
wettable  powder to be mixed in water and
applied as a spray for control of weeds and
brush. It  I* non-corrosive to equipment,  non-
flammable and non-volatile.

"Hyvar' X Is an effective general herbicide for
the control of many annual weeds at low rates
and perennial weeds and brush at higher rates
and Is particularly useful for control of peren-
nial grasses. It may be used on non-cropland
for non-selective weed and brush control and
for selective weed control In certain crops.

Effects are stow to appear and may not become
apparent until the chemical has bean carried
Into the root zone of the weeds by moisture.
The  degree of  control and duration of affect
will vary with the amount of herbicide applied.
soil type, rainfall, and other conditions.
             DIRECTIONS

Apply "Hyvar" X as a spray just before or dur-
ing the period of active growth of plants to be
controlled. If dense growth is present, results
will be Improved If vegetation Is removed bat ore
treatment. Do not apply when ground Is frozen.

Before spraying, calibrate equipment to deter-
mine quantity of water necessary to uniformly
cover measured area to be treated. Weigh the
proper amount  of "Hyvar" X and mix Into
necessary volume of water.

For crop use, apply with a fixed-boom power
sprayer property calibrated to a constant spaed
and rate  of delivery. For calibration instruc-
tions, see Du Pont Bulletin, "Instructions for
Applying  Du Pont Weed Killers for Selective
Weed Control In Crops". Use sufficient water
(min. 40  gals, per acre) to provide thorough
and uniform coverage of  the ground. Spray
booms must be shut off while starting, turn-
ing, slowing or stopping, or Injury to the crop
or successive crops may result.

For non-crop use, application also may be made
with a hand-gun sprayer  using at least 200
gals, spray per acre to Insure uniform cover-
age. For small areas, a hand sprayer or sprink-
ling can may be used.

Nozzle screens should be 50 mesh or larger.
Continuous agitation In the spray tank is re-
quired to keep the material in suspension.
Agitate by mechanical or  hydraulic means In
the  spray tank. If by-pass or return  line Is
used,  it should terminate at bottom of tank
to minimize foaming. Do not use air agitation.
                                             60

-------
one major producer of bromacil in the United States,  du Pont.   The
moat recent issues of the Farm Chemicals Handbook!/ (1973,  1974)
list only du Font as basic producer of bromacil.

     In the Tariff Commission pesticide reports, the  production and
sale volumes of bromacil are not reported individually.  Bromacil is
included in a large category "all other cyclic herbicides and  plant
hormones" which includes, in addition to bromacil,  all other cyclic
herbicides and plant hormones except maleic hydrazide and the  dimethy-
lamine salt of 2,4-D.  This group includes such large-volume herbicides
as:  atrazine and other triazines; 2,4-D acid, esters, and  salts;
amiben esters and salts; trifluralin; dimethylurea  compounds;  and many
other specified and unspecified herbicides.  The reported production
volumes for this composite category was 344,789,000 Ib AI in 1972 and
357,310,000 Ib in 1973.

     In comparison to many other herbicides in this category,  the pro-
duction and sales volume of bromacil is so small that it is difficult
to make quantitative estimates on bromacil.  However, based on studies
by Midwest Research Institute and R.V.R. Consultants!./ it is estimated
that in 1972, the volume of production of bromacil  in the U. S. was
approximately 4 million pounds AI.

Imports - Imports of pesticides that are classified as benzenoid chemicals
(this group includes bromacil) are reported in a U.S. Tariff Commission
annual report .27

According to the report  there were no  imports  of bromacil  into the
United States in 1972.

Exports - Pesticide exports are reported in a Bureau of  the Census annual
report.

     Technical  (unf emulated) bromacil is cited in the report .A/   In
addition to bromacil, a number of other specified synthetic organic  her-
bicide active ingredients are included.
   Farm Chemicals Handbook. Meister Publishing Co.,  Willoughby, Ohio,
      1973, 1974.
   von Rumker, R., E. W. Lawless, and A. F. Meiners, "Production, Distri-
      bution, Use and Environmental Impact Potential of Selected Pesticides,"
      Final Report, Contract No. EQC-311, for Council on  Environmental
      Quality, Washington, D. C.  (1974).
   U. S. Tariff Commission, Imports of benzenoid Chemicals  and Products.
      T.C. Publication 601, (1973).
   U. S. Bureau of the Census, U. S. Exports. Schedule B. Commodity by
      Country. Section 512.0629, Report FT 410.
                                   61

-------
      Formulations of bromacil are also Included.—'   In addition  to several
 specified bromacil-containing formulations,  a number of other  formulated
 herbicides are included.

      Total exports of herbicides  for 1972 were reported as  34,796,185 Ib
 for technical herbicides  and 38,967,237 Ib for herbicidal preparations.

      The Foreign Trade Division reports indicate  that both  technical and
 formulated bromacil are being exported from  the United States.   However,
 bromacil exports represent only a small share of  the total  volume of ex-
 port of  technical and formulated  herbicides,  respectively.  Therefore, the
 export statistics provide only minimal help  in estimating the  export volume
 of  bromacil.   However, based on information  obtained from pesticide trade
 sources  and overseas pesticide markets, it is estimated that the 1972
 export volume of bromacil was 0.5 to 1.0 million  pounds AI, probably closer
 to  1.0 million pounds AI.

 Domestic Supply - Subtracting estimated exports from estimated total pro-
 duction  and assuming no imports,  it  is estimated  that about 3 million pounds
 of  bromacil AI were used  domestically in 1972.

     A comparable estimate for 1973  cannot be made  at this  time  because
 all necessary U.S.  Tariff Commission and Bureau of  the Census Pesticide
 Reports  for 1973 were not available  at the time of  review.

 Formulations  - The  following bromacil formulations  are commercially available
 in  the United States:

     1.  Hyvar ® X bromacil weed killer, a wettable powder containing 80%
         bromacil.

     2.   Hyvar ® X-L bromacil weed killer, a water soluble-liquid containing
         2 Ib bromacil per gallon (present as lithium salt).

     3.   Hyvar ® X-P brush killer, pellets containing 10% bromacil.

     4.   Krovar ® I weed killer,  a wettable powder containing 40% bromacil
         and 40% diuron.

     5.   Krovar ® II weed killer, a wettable powder containing 53% bromacil
         and 27% diuron.

In addition, formulators  offer  combination formulations  containing bromacil,
including the following:

     1.   1.5% bromacil +  66.5%  sodium metaborate  tetrahydrate +  30.0 %
           sodium chlorate  (UreaborUv), applicable in dry form or as an
           aqueous spray.
\J  U. S. Bureau of the Census, U. S. Exports, Schedule B. Commodity
      by Country.  Section 599,2080, Report FT 410.
                                      62

-------
      2.  4.0% bromacil + 64.0% sodium metaborate tetrahydrate + 30.0%
            sodium chlorate (Hibor®), applicable in dry form or as an
            aqueous spray.

      3.  4.0% bromacil + 94.0% sodium metaborate tetrahydrate
            applicable in dry form or as an aqueous spray.

Use Patterns of Bromacil in the United States

General - As discussed in the subsection on the registered uses of
bromacil in the United States, this product is a broad-spectrum herbicide
for nonselective control of many annual and perennial grasses and broad-
leaf weeds, including brush, on noncropland; and (at lower rates of appl-
ication) for selective control of annual and perennial weeds in citrus
groves, and for the control of seedling weeds in pineapple,  Bromacil is
primarily an Industrial herbicide; agricultural uses comprise only 10 to
15% of its estimated domestic consumption.

     The herbicidal potential of bromacil was first recognized and described
in the early 1960's.  Bromacil has been in commercial use in the United
States since the mid-1960's, and its use volume appears to be still on the
increase.  Data on the uses of bromacil by industrial, commercial and
institutional organizations, and by government agencies was obtained by the
Midwest Research Institute (von Rumker et al., 1974).  In the same project,
RvR Consultants obtained information on the farm uses of bromacil from the
following sources:

     1.  Survey of the Federal/State Cooperative Extension Services in all
         50 states and in Puerto Rico  (conducted in 1973);

     2.  Analyses of state pesticide use recommendations;

     3.  Pesticide use reports from the states of Arizona and California;

     4.  Data on pesticide uses supplied by the EPA Community Pesticide
         Studies Project in Arizona, Hawaii and Texas;

     5.  Estimates and information obtained from basic producers  of bro-
         macil and other pesticides, and from pesticide  trade sources;

     6.  Agricultural Statistics, an annual publication  of  the  U.S.
         Department of Agriculture.

     Information on the uses of bromacil from all of  these  sources were
utilized in arriving at the estimates summarized in Table 6  and discussed
below.

Agricultural Uses of Bromacil - Midwest Research Institute  estimates  that  in
1972 about 400,000 Ib of bromacil AI were used for agricultural purposes in the
U.S., primarily in the Southwestern states for weed control in  citrus groves
                                    63

-------
                          Table 6.  ESTIMATED USES OF BROM&CIL IN THE U.S.
                                   BY REGIONS AND CATEGORIES, 1972

Category
Region
Agri-
culture
Industrial/
commercial
Sub-
totals
Government
agencies^'
Home
and
garden
Total,
all
categories
Northeast^/
Southeast^,/
North central^/
South central—'
Northwest6./
Southwest!/

 Total,  all regions
    40

Neglected

   360

   400
  200
  500
  400
  800
  200
  200

2,300
(Thousands  of pounds  AI)

     200
     540
     400
     800
     200
     560
   2,700
300
None
  200
  540
  400
  800
  200
  560

3,000
al  New England  States,  New York,  New Jersey, Pennsylvania.
b/  Maryland,  Delaware,  Virginia,  West Virginia,  North  Carolina, South Carolina, Georgia, Florida.
£/  Ohio,  Indiana,  Illinois, Michigan, Wisconsin,  Minnesota,  Iowa, Missouri, North Dakota, South
      Dakota,  Nebraska,  Kansas.
d/  Kentucky,  Tennessee, Arkansas, Louisiana, Mississippi, Alabama, Oklahoma, Texas.
e/  Montana,  Idaho, Wyoming, Colorado, Utah, Washington, Oregon, Alaska.
f/  New Mexico,  Nevada,  Arizona,  California, Hawaii.
&/  No regional  breakdown available.
Sources:   MRI-RvR estimates.   See text.

-------
and in pineapple fields  in Hawaii.  It is also estimated that a small quantity
of bromacil (approximately 40,000 Ib) was used on the same crops in the South-
eastern states and in Puerto Rico, and an even smaller amount on citrus in Texas.

     There were no other major agricultural uses of bromacil in the United
States in 1972.  However, California data suggests other uses.

Nonagricultural Uses of  Bromacil - It is estimated that in 1972 about 2,300,000
Ib of bromacil AI were used by industrial and commercial organizations, and
about 300,000 Ib by government agencies.  Bromacil is not registered or rec-
ommended for any home garden uses.

     In the industrial/commercial weed control sector, the largest quan-
tity of bromacil, about 800,000 Ib, was used in the South Central states
in 1972; followed by the Southeastern states, 500,000 Ib; the North Central
states, 400,000  Ib; and the Northeastern, Northwestern, and Southwestern
states, about  200,000 Ib each.   This estimated distribution pattern corre-
sponds largely to the length and intensity of weed infestation pressure
on noncropland areas as determined primarily be the climate in these
regions.

     Government  agencies, including federal,, state, county, and local
government units, highway departments, etc., used an. estimated 300,000
Ib of bromacil in 1972  nationwide.  No regional breakdown is available
for this estimate.

     Thus, considering  all domestic uses of bromacil combined (Table 6),
Midwest Research Institute estimates indicate that slightly more than 25%
of the total  quantity used in 1972 was used in the South Central states;
about 13%  in  the North  Central states; the balance (less than 10% each) in
the Northeastern and Northwestern states.
 Bromacil Uses  in  California - The State keeps detailed records of pesticide
 uses by crops  and commodities.  These reports are published  quarterly  and
 summarized annually.  Table 7 summarizes the uses of bromacil in California
 by major crops and other uses for the 4-year period 1970 to  1973.
      In California,  bromacil is not subject to the special restrictions
 and  reporting requirements imposed upon the sale and use of pesticides
 designated  as "injurious or restricted materials."  For this reason, the
 percentage  of bromacil use reported to the State Department of Agricul-
                                    65

-------
         Table 7.   BROMACIL  USES  IN CALIFORNIA BY MAJOR
                CROPS AND OTHER  USES,  1970-1973

Crop/use

1973
Year
1972

1971

1970
Citrus

Other fruit and
  nut crops—
Vegetable and
   field  crops—'

All other uses—'
Total, all uses
                           (Thousands of pounds AI)

                       16.3       20.7      16.4
 0.4


 0.6


64.9

82.2
  0.6


  0.4


131.5

153.2
 0.3


 0.4


48.0

65.1
   9.4

Neglected


  None


  79.6

  89.0
a/  Includes almonds, avocados, grapes, plums, nectarines, peaches,
      strawberries  (bromacil not registered or recommended for use
      on any of these crops).
b/  Includes cauliflower, broccoli, melons, corn, cucumbers, lettuce,
      potatoes, tomatoes, cotton, alfalfa  (bromacil not registered
      or recommended for use on any of these crops).
£/  Includes Federal, state, county and city agencies; the University
      of California; irrigation, flood control, water resource, and
      vector control districts or agencies; school districts: resi-
      dential, structural and turf uses; and uses on industrial and
      other nonagricultural areas.
Source:   California Department of Agriculture,  Pesticide
           Use Reports for 1970, 1971, 1972 and 1973.
                                66

-------
ture (and included in its statistics)  is probably lower than the percent-
age for restricted use pesticides.   However,  the State Department of
Agriculture and others familiar with pesticides uses in California be-
lieve that the department's statistics do include a high percentage of
the actual uses of nonrestricted pesticides,  and that these statistics
are representative of the use patterns by crops and other uses in
California.

     According to the California State Pesticide Use Reports (Table 7),
the use of bromacil in California for  all purposes varied between 65,100
Ib in 1971 and 153,200 Ib in 1972,  with the quantities used in 1970 and
1973 within that range.

      The use of bromacil on citrus  fruits during  this period varied from
 a low of 9,400 Ib in 1970 to a high of  20,700  Ib  in 1972.

      In each of the 4 years covered in Table 7, the largest share of the
 total bromacil volume used in California (about 75 to 907.) was used by
 Federal, state, county, and city agencies; irrigation, flood control,
 water, and vector control districts and agencies; school districts; and
 for weed control on industrial and other nonagricultural sites.

      Tables 8 and 9 present the bromacil uses in California by crops and
 other uses, number of applications, pounds AI, and numbers of acres treated,
 for 1972 and 1973, the two most recent years for which data is avail-
 able.  These tables provide a detailed breakdown of the bromacil uses
 summarized in Table 7 for the years 1972 and 1973.
                                  67

-------
    Table 8.  USE OF BROMACIL IN CALIFORNIA IN 1972 BY CROPS AND OTHER USES,
                   APPLICATIONS, QUANTITIES,  AND ACRES TREATED

Commodity
Alfalfa
Almond
Avocado
Cauliflower
Citron, melon
Citrus
City agency
Corn--sweet
County agricultural commissioner
County or city parks
County road
Crucifer
Cucumber or pickle
Federal agency
Fallow (open ground)
Flood control
Grapefruit
Grape
Industrial areas
Irrigation district
Lemon
Lettuce/head
Lime
Nonagricultural areas
Orange
Other agencies
Plum
Potato
Reclamation district
Residential control
School district
Soil (fumigation only)
State highway
Structural control
Tangelo
Tomato
Turf
University of California
Vector control
Water areas
Water resources
Applications^/
1
1
4
1
1
129

1



1 CR
2

8

20
3
2

94
15
2
132
327

1
5



1


1
11
2


46

Lb
13.33
117.60
411.20
2.40
42.90
4,185.46
1,541.15
15.10
6,222.26
69.60
4,827.87
57.60
6.70
146.90
115.82
2,933.30
408.57
46.20
25.60
3,347.44
5,498.03
76.50
14.40
4,087.49
10,584.68
93,018.93
1.60
64.02
52.00
3,546.75
45.38
14.40
1,124.40
34.00
16.00
122.19
13.40
739.20
1,164.87
1,907.80
5,608.08
Acres
100.00
49.00
136.00
6.00
5.50
2,628.40

38.00



24.00
57.00

49.50

516.00
43.00
10.50

2,873.65
309.00
4.50
987.04
7,747.43

10.00
197.00



1.50


20.00
409.00
5.00


394.95

                            Total
809
152,155.92     16,573.97
til  Only agricultural  applications are tabulated in this  column.
Source:  California Department of Agriculture Pesticide Use
            Report 1972.
                                     68

-------
   Table 9.  USE OF BROMACIL IN CALIFORNIA IN 1973 BY CROPS AND OTHER USES,
                  APPLICATIONS, QUANTITIES, AND ACRES TREATED

Commodity
Alfalfa
Alfalfa fur seed
Almond
Apricot
Avocado
Citrus
City agency
Cotton
County agricultural commissioner
County or city parks
County road
Federal agency
Fallow (open ground)
Flood control
Flowers
Grapefruit
Crape
Industrial areas
Irrigation district
Lemon
Lettuce/head
Line
Nectarine
Nonagricultural areas
Nursery stock
Orange
Ornamentals
Ornamental bedding plants
Other agencies
Peach
Potato
Reclamation district
Residential control
School district
Soil (fumigation only)
Squash, summer
State highway
Strawberry
Structural control
Tangerine
Tomato
Turf
University of California
Vector control
Water areas
U-Water areas*-/
Water resources
Applications^/
8
1
1
1
8
61

1




5

3
54
2
8

151
2
1
3
132
1
400
1 CR
1

1
2



8
1

6

1
7
3


22
1

Lb
248.46
50.00
18.00
24.00
269.00
2,455.11
812.48
52.99
5,632.10
20.29
1.489.80
176.74
30.24
3.008.00
6.00
776.05
34.80
77.92
2,453.74
4,106.39
14.76
2.00
7.60
2,155.03
18.52
8,921.63
5.83 CR
1.40
36,084.84
31.80
192.92
73.60
4,025.75
131.09
21.21
0.80
1,260.80
32.37
16.80
5.92
59.14
10.79
350.40
1,287.71
3,738.99
32.00
1,947.15
Acres
390.50
40.00
30.00
40.00
134.50
1,915.50

300.00




20.23

30.00
787.50
29.00
39.00

2,577.90
45.00
1.00
24.00
513.09
1.93
7,463.34
22.00 C
7.00

40.00
182.00



9.93
4.00

132.00

4.00
155.55
3.00


320.25
0.01

                           Total
895
82,161.30
                                                                      15,218.22
a/  Only agricultural applications are tabulated  in this  column.
b/  0 • miscellaneous units.
Source:  California- Department of Agriculture', Pesticide Use
            Report 1973.

                                         69

-------
                     PART-III.   MINIECONOMIC REVIEW


                                CONTENTS



                                                                  Page

Introduction	    71

Citrus	    73

  Efficacy Against Pest Infestation	    74
  Cost Effectiveness of Pest Control	    74

Noncrop Brush and Weed Control	    75

  Efficacy Against Pest Infestation   	    75
  Cost Effectiveness of Pest Control	    76

References	    78
                                    70

-------
     This section contains a general assessment  of the  efficacy and cost
effectivensss of bromacil.  Data on the production of bromacil in the
United States as well as an analysis of its use  patterns at  the regional
level and by major application are conducted as  part of  the  Scientific
Review (Part II) of this report.   The section  summarizes rather  than
interprets scientific data reviewed.
Introduction

     The efficacy and cost effectiveness of a specific pesticide should
be measurable in terms of the increased yield or improved quality of a
treated crop which would result in a greater income or lower cost than
would be achieved if the pesticide had not been used.  Thus, one should
be able to pick an isolated test plot of a selected crop, treat it with
a pesticide, and compare its yield with that of a nearby untreated test
plot.  The difference in yield should be the increase due to the use of
the pesticide.  The increased income (i.e., the yield multiplied by the
selling price of the commodity) less the additional cost (i.e., the
pesticide, its application and the harvesting of the increased yield)
is the economic benefit due to the use of the pesticide.

     Unfortunately, this method has many limitations.  The data derived
is incomplete and should be looked on with caution.   Review of the
literature and EPA registration files revealed that experimental tests
comparing crops treated with specific pesticides to the same crop with-
out treatment are conducted by many of the state agricultural experimental
stations.  Only a few of these, however, have attempted to measure
increased yield and most of this effort has been directed toward just a
few crops such as cotton, potatoes, and sorghum.  Most other crop tests
measure the amount of reduction in pest levels which cannot be directly
related to yield.
     Even the test plot yield data are marginally reliable, since these
tests are conducted under actual field conditions that may never be
duplicated again and are often not representative of actual field use.
Thus, yield is affected by rainfall, fertilizer use, severe weather  con-
ditions, soil type, region of the country, pesticide infestation  levels
and the rate, frequency and method of pesticide application.

     Because of these factors, yield tests at different  locations and
in different years will show a wide variance ranging from a yield de-
cline to significant increases.  For example, in a year  of heavy pest
infestation, frequent pesticidal use can  result in a high yield increase
                                    71

-------
 because the crop from the untreated test plot is practically destroyed.
 Conversely, in a year of light infestation,  the yield increase will be
 slight.

      The use of market price to estimate the value received by the pro-
 ducer also has its limitations.  If the use  of the pesticide increases
 the yield of a crop and the national production is increased, then the
 market price should decline.  According to J. C. Headley and J.  N. Lewis
 (1967),A/ a 1% increase in quantity marketed has at times resulted in a
 greater than 1% decrease in price.   Thus, the marginal revenue from the
 increased yield would be a better measure of value received.

      A third limitation to the quantification of the economic costs and
 benefits is the limited availability of data on the quantities of the
 pesticide used by crop or pest, the acres treated, and the number of
 applications.   In most cases the amount of bromacil used on each crop
 (or noncrop) application is not available.

      As a result  of these limitations an overall economic benefit by
 crop or pest cannot be determined.   This review presents a range of the
 potential economic benefits derived from the use of bromacil  for control
 of  a specific  pest on a specific crop.   This economic benefit or loss
 is  measured in dollars per acre for the highest and lowest yield developed
 from experimental  tests conducted by the pesticide producers  and the state
 agricultural experimental stations.   The high and low yield increases are
 multiplied  by  the  price of the  crop  and reduced by the cost of the broma-
 cil applied to  generate the range of economic benefits in dollars per
 acre.

      Economic benefits from noncrop  applications (e.g.,  grass and brush
 control  along highways,  utility lines,  and railroads)  are best measured
 by  an alternative  costing method.  Alternative  methods to  chemical con-
 trol  include mechanical  control such as  mowing,  discing,  bulldozing and
 the use  of  brush cutting  machines.   Hand labor  is  often required for
mowing around trees, poles  and  other objects  and for weeding or  cutting
 brush.   In  some cases  burning for control of  grasses  along canal banks
 is an alternative.
\J  Headley, J. C., and J. N. Lewis, The Pesticide Problem;  An Economic
      Approach to Public Policy, Resources for the Future, Inc., pp.
      39-40 (1967).
                                   72

-------
     The true economic benefits cannot be measured because much of the
noncrop weed control is for aesthetic reasons such as beautification of
highways.  It is also a form of preventative maintenance to keep fires
from causing damage when grasses are dry.  Therefore, the cost of the
chemical control should be subtracted from the alternative control cost,
such as hand labor or mechanical control, to determine the economic
benefit from the use of bromacil.

     Bromacil is a broad-spectrum pesticide used as a herbicide and soil
sterilant.  It controls a wide variety of annual and perennial grasses
such as Johnson grass, Bermuda grass, nutsedge and dallisgrass.  Brush
such as blackjack and post oak, hackberry, maple, oak, poplar, sweet
gum, wild cherry and others are also controlled.

     Bromacil is a relatively new herbicide having been introduced dur-
ing the past decade*  Although there is a significant number of references
relating to the efficacy of bromacil, little is available regarding the
economics of its use.  This latter situation arises from the difficulty
in measuring its true economic value; bromacil often takes two to three
years to control vegetation effectively,  but the quantity needed to
maintain control declines after the initial application .

     Most of the bromacil is used to control grass and brush along rail-
roads, utility lines, roads, fences, buildings, and other noncrop areas.
It is used for beautification of.the area by removal of the weeds, but
may be used to prevent fires along railways, or because of federal or
state requirements for weed and brush control.

     The only registered crop uses are for control of weeds and grasses
in pineapple and citrus groves.

     The following subsection summarizes  available literature on the
efficacy and cost effectiveness of bromacil.

Citrus

     Bromacil is recommended for control  of annual  and  perennial grasses
in citrus groves.  Control of grasses can promote  faster tree growth by
reducing the competition for water.   It  also  improves spraying effective-
ness and yields.
                                   73

-------
 Efficacy Against Pest Infestation

      Only one reference was found in the literature which relates  broma-
 cil use' to improved yields.  Tucker et al.  (1971)i/ initiated experiments
 in Florida in 1967 to evaluate several soil residual herbicides  over  a
 3-year period.  These herbicides were tested on oranges and tangelos.

      The results showed that bromacil consistently proved to be  the most
 wide-spectrum herbicide and provided the best control over the 4-month
 period at all locations.  Its "burndown" action was good without a sur-
 factant and its residual control was satisfactory.  Bermuda grass  was
 the main grass controlled.  Spanish needles, pigweed and Vasey grass  be-
 came a problem in some of the plots.  Control of weeds by bromacil
 averaged from 75 to 907. in the four counties under test.

      Tree growth varied in each county and  was usually faster with the
 bromacil treatment.  Tree growth was associated with degree of weed re-
 moval and depth of tree feeder roots.   Mechanical hoeing severely  pruned
 the feeder roots in some areas limiting growth.

      The influence of bromacil on fruit yield and quality was measured
 in one test.   With bromacil applied at a rate of 3.5 Ib/acre, the  yields
 compared to a mechanically hoed check increased from 200 boxes/acre to
 225 boxes/acre.

 Cost Effectiveness  of  Pest Control

      The price of oranges in 1972 averaged  $2.42/box (Agricultural
 Statistics 1973)—', and the cost of  bromacil averaged  $9.50/lb of active
 ingredient (Bost,  1974)!/.

      Using the above prices and costs the increased income for the 25-
 box yield increase  would be $60.50/acre,  Bromacil costs at an applica-
 tion rate of  3.5 Ib/acre would be $33.25.  This would result in  an eco-
 nomic benefit  of $27.25/acre based  upon this test.
I/  Tucker, D. P. H.,  and R. L. Phillips,  "Weed Control Demonstrations
       in Florida  Citrus Groves,"  Southern  Weed Science Society Proceed-
       ings. 24:235-240 (1971).
£/  United States Department of Agriculture (1973).  Agricultural
"~      Statistics 1973.
3i/  Bost, W. M., Director, Cooperative  Extension Service,  Mississippi
*~      State, Mississippi, personal letter  to  D.  F.  Hahlen  (1974).
                                    74

-------
     The actual economic benefits for this test would be greater
since the yield comparisons were made with a mechanically hoed test
plot.  A completely untreated  field could have produced a much
lower yield than the hoed plot.

Noncrop Brush and Weed Control

Efficacy Against Pest Infestation

     Bromacil  is used for a wide variety of weed and brush control ap-
plications by  industry, commercial firms and local governments.  It is
used along railroad  right-of-ways, in drainage ditches, around utility
poles and  lines, on  farm fence rows and along embankments.  It controls
a wide number  of grasses and woody plants.  Walls (1971)-i/ evaluated
bromacil for control of highway weeds in Georgia, North Carolina, and
South Carolina, and found that bromacil controlled 1007. of the annual
weeds and  grasses, 60% of perennial weeds, 107. of Bermuda grass and 307.
of the nut sedge when applied  at a rate of 4 Ib/acre.  Almost 1007. con-
trol was achieved  when applied with 2,4-D and 2,4,5-T amine  and Dowpon C.

     Rogers (1967)2.7 tested bromacil for control of brush in drainage
ditches  in the south and achieved 957. control of willow, cottonwood, and
water locust with  doses ranging from 7.5 to 15 Ib Al/acre.  Persimmons,
American elm,  green  ash and hackberry were 957. controlled with 15 to 20
Ib Al/acre.

     Lewis (1968)2/   tested several soil sterilants on sand  soil  in West
Florida  for control  of annual grasses and weeds  such  as Bahia, spurge,
pokeweed,  Bermuda  grass, vasey grass, nutsedge,  crabgrass, and smut
grass.   He concluded that bromacil had the longest residual action
and  was  most effective at 10  or 20 Ib/acre.
 I/   Walls,  C.  E.,  "Post-Emergence Control of Vegetation in Asphalt
       Highway  Shoulders,"  Southern Weed Conference Society Proceedings,
       24:308-309 (1971).
 2/   Rogers, A. G.,  "Bromacil Effective for Control of Willow and
       Cottonwood in Drainage Ditches," Southern Weed Science Society
       Proceedings.  20:218-220 (1967).
 3_/   Lewis,  W.  F.,  "Test of Soil Sterilants in West Florida on Sand
       Soil," Southern Weed Science Society Proceedings. 22:273-274
       (1968).
                                    75

-------
      Peevy (1973)JV evaluated bromacil and picloram for control of south-
 ern hardwoods.  Bromacil-treated plots showed a crown reduction after 17
 months of 98% for post oak, 93% for blackjack oak, and 89% for hickory
 when applied at 5 to 10 Ib/acre.  It was much less effective against
 huckleberry (16%), American beauty berry (34%) and sassafras (48%).
 Similar results were achieved by Peevy (1971)2/ for control of black-
 jack and post oak.

      Harris et al. (1971)V reported on tests to control woody plants in
 Ohio, Michigan, Indiana, and Kentucky in 1968.  At applications of
 7 ounces/stem, 100% root kill was achieved on maple, sweet gum, box elder,
 wild cherry, oak, sumac, white ash, elm, sassafras, hackberry, red bud,
 dogwood, poison ivy, winged elm, willow and cottonwood.

      Dunn (1967)ft/ evaluated sterilants for control of grasses and trees
 on riprap along Lake Pontchartrain levees in New Orleans.  He found broma-
 cil the most suitable herbicide for control of false willow, tallow,
 Bermuda and Vasey grasses when applied at rates of 12 to 16 Ib/acre.

 Cost Effectiveness of Pest Control

      The economic benefits of the  use  of bromacil will  vary  depending
 upon the system being controlled,  the  degree  of  control and  the cost of
 alternate treatment.   Data that  compared the  costs  of alternate methods
 of control is  summarized here.
     The  town of West Springfield,  Massachusetts (Chemical Brush Program,
 1973)JL/ estimated a cost  of $300.00 to $400.00/acre for cutting and
 chopping  small trees and  dense brush thickets along flood control dykes.
 A program of chemical control using bromacil cut this figure in half
 resulting in economic benefits of $150.00 to $200.00/acre.
I/  Peevy, F. A., "Bromacil  and  Picloram Under Southern  Upland Hardwoods,"
      Weed Sci.. 21:54-56  (1973).
2f  Peevy, F. A., "Application Data and Dosage Influence Kill of Hard
      woods by Soil Application  of Bromacil, Fenuron,  and  Picloram,"
      Southern Weed Science  Society Proceedings.  24:271-273  (1971).
3/  Harris, C. B., Jr., and  Turney J. Hernandez,  "Basal  Stem Soil Appli-
      cations of Bromacil  for Woody Plant  Control,"  Southern Weed Science
      Society Proceedings, 24:321-322 (1971).
I\J  Dunn, C. R., "Riprap Test Work on Lake Pontchartrain Levees,"
      Southern Weed Science  Society Proceedings,  20:207-211  (1967).
5_/  "Chemical Brush Program  Helps Guard a  City,"  Reprinted from Public
      Works, 104:3 (March  1973).
                                    76

-------
     Offutt (1967)!/ compared mechanical and chemical weed control meth-
ods for the lower Tule River irrigation district.  Mechanical control
cost $134.00/mile or $34.00/acre.  Chemical control costs averaged
$324.00/mile the first year but were projected at an average of $110.007
mile or $27.50/acre for future control.  This would result in an economic
benefit of $6.50/acre, assuming that bromacil use averaged 1 Ib/acre/year
and application was 2 Ib/acre every 2 years or 3 Ib/acre every 3 years.

     In evaluating the economic benefits of chemical weed control, initial
costs are often high, because high dosage rates are usually required for
initial applications of bromacil, but subsequent applications for main-
tenance of the area require significantly less chemical.  Therefore, tests
should cover at least a 3-year period and projections of future costs to
maintain the area should be taken into consideration when evaluating
chemical control.
I/  Offutt, J. R.,  "Chemical Weed  Control Replaces Mechanical Weed
      Control in Ditch Maintenance,"  California Weed Conference
      ProrP-edingSj  19:32-37  (1967).
                                       77

-------
 References

 Boat, W. M., Director, Cooperative Extension Service, Mississippi State,
   Mississippi, Personal Letter to D. F. Hahlen (1974).

 "Chemical Brush Program Helps Guard a City," Reprinted from Public Works,
   104:3 (March 1973).

 Dunn, C. R., "Riprap Test Work on Lake Pontchartraln Levees," Southern
   Weed Science Society Proceedings. 20:207-211 (1967).

 Farm Chemicals Handbook. Meister Publishing Co.,  Willoughby, Ohio, 1973,
   1974.

 Harris, C. B., Jr., and T. J. Hernandez, "Basal Stem Soil Applications
   of Bromacil for Woody Plant Control," Southern Weed Science Society
   Proceedings. 24:321-322 (1971).

 Head ley, J. C., and J. M. Lewis, The Pesticide Problem;  An Economic
   Approach to Public Policy, Resources for the Future, Inc., pp.  39-40
   (1967).

 Lewis,  W.  F., "Test of Soil Sterilants in West Florida on Sand Soil,"
   Southern Weed Science Society Proceedings, 22:273-274 (1968).

 Offutt, J. R., "Chemical Weed Control Replaces Mechanical Weed Control
   in Ditch Maintenance," California Weed Conference Proceedings,  19:
   32-37 (1967).

 Peevy,  F.  A., "Application Date and Dosage Influence Kill of Hardwoods
   by Soil  Application of Bromacil, Fenuron, and Picloram," Southern
   Weed  Science Society Proceedings. 24:271-273 (1971).

 Peevy,  F.  A., "Bromacil and Picloram Under Southern Upland Hardwoods,"
   Weed  Sci..  21:54-56 (1973).

 Rogers,  A.  G.,  "Bromacil Effective for Control of Willow and Cotton-
   wood  in  Drainage Ditches," Southern Weed Science Society Proceedings,
   20:218-220  (1967).

 Tucker,  D.  P.  H.,  and R.  L.  Phillips, "Weed Control Demonstrations in
   Florida  Citrus Groves," Southern Weed Science Society Proceedings,
   24:235-240  (1971).

U.S. Bureau of  the Census,  U.S.  Exports, Schedule B,  Commodity by
   Country,  Report  FT  410.

U.S. Department of Agriculture,  Agricultural Statistics 1973.

U.S. Environmental Protection Agency,  EPA Compendium of Registered
  Pesticides, Vol.  I.
                                       78

-------
U.S. Tariff Conies ion, Imports of Benzeooid Cheaicals and Products,
  TC Publication 601 (1973).

Walla, C. E., "Poat-Eaergence Control of Vegetation in Aaphalt Highway
  Shoulders," Southern Weed Conference Society Proceedings. 24:308-
  309 (1971).
                                   79

-------