Un ited States
Environmental Protection
Agency
Office of
Pesticides and Toxic Substances
Special Pesticide Review Division
March 1980
Washington, DC 20460
Pesticide
Metolachlor
Pesticide Registration
Standard
'».
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MFTOIACHLOR
~T
A Sample Pesticide Registration Standard
March, 1980
Special Pesticide Review Division
Office of Pesticides and Toxic Substances
Environmental Protection Agency
401 'M' Street, S.W.
Washington, D.C. 20460
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TABLE OF CONTENTS
‘eface •, ,.• . ..... Vii
Product Chemistry
Introduction . . 1
‘Itpica]_ Discussions . . 1
cheinicai. Identity . . 1
Manufacturing Process . . . . . . . . . . . 3
Percentages of Canponents in Pesticide Products ... 3
Product Analytica].. Methods and I)ata . 4
Physical/Chemical Properties . .. 5
Disciplinary Review . . . . . . . 8
Ch nistry Profile 8
Generic I)at.a Gaps •... . 9
Suggestec. L.abeling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9
B ibliograliy (Reserved) . . 10
Environmental Fate
Introduction 11
‘Ibpical Discussions . . . . . . . . 11
Use Patterns and Restrictions . 11
Physico—Chemical Transformation ... 12
Soil Metatxlisxn 14
Aquatic Metabolism . . . . . . . . . . . . . 16
Micrcbial Metabolisin .. .... 17
r4obility .. 18
Sç ray Drift 19
Field Dissipation 19
Bi cc u1ation ... 20
Contamination and Control . 24
A lternativePestManagementPractices ...... 24
Disciplinai:y Review 25
Environmental Fate Profile . . 25
sure Profile 27
Generic Data Gaps . 28
suggested Labeling . * 28
Bibliography (R eserved) 29
¶ftxico logy
Introduction . . . •... 31
‘DDplca]. Discussions . . . . . . . . . 31
Metakxl isin and Pharmaccxlynamics . . . . . . . . . . . . . . 32
A .cuteEffectsandNeurotoxiC ] . .ty .... 33
L ca]. Irritation 35
Subchronic Effects and Neurotoxicity . 37
Sensitization 38
Chronic Effects 38
Biological Parameters of Specific Effects ................ 39
()ncogenicity .... . 40
Genetic Effects .... 41
q rato1c gy .. .. .. .. . . .. ... 41
productive Effects . . . 42
Clinical Experience . . . . . . . . . . . . . . . . . . . . . . 43
Prevention and Treatment of Intoxication . 43
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Disciplinary Review . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45
T)xic lc)gy Profile . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45
1 It)xicc)log j Hazard Asses nent . . . . . . . . . . . . . . . . . . . . . * . . . . . . . 46
Generic Data Gaps . . . . . . . . . . . . . . . . . 47
Registration Requirements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 48
Suggested t..a.beling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49
Bib1i ra y (I sercred) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 52
Residue Ch nistry
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 53
¶Itpical Discussions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 53
Me tacli n in Plants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 53
Metabo]_isti in Annnals . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55
Analytical MetJ.-icx3ology . . . . . . . . . . . . . . . . . . . . . . . . . . . . 56
Residue Data . . . . . . . . . . , . . . • . . . • . . . . . . . . . . . , , . . • 59
Present ¶Lblerances . . . . . . . . . . . . . . • • • • • . • . . • • . 63
R ulatory Incidents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63
Disciplinary Review . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 64
Residue Chemistry Profile . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 64
‘It)lerarlce Reasses nent . . . . . . . . . • • • • • • • • • • • • • , • • . • • . . . . . . . 66
Generic Data Gaps . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 66
Registration i quireuients . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 66
Suggested Labeling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 66
Bibli ra y (Reserved) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 67
Ecological Effects
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 69
Ikpical Discussions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 69
Microbes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 70
Algae . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1 quatic Macrhytes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 72
¶irestria.l Plants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 72
Soil arxl Surface Invertebrates ....•• ..••••.••••.••.•••• .. 73
Bi s . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Amphibians and Reptiles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 74
Wild Maxru.nals . . . . . . . . . . . . . . . . . . . * . . . . . . . . . . . . . . . . . . . . . . . . . 75
1- uatic Invertebrates . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 75
Fish . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Es tuarin.e and Marine CYrgani ns . . . . . . . . . . . . . . . . . . . . . . . . . . . 77
Nonbiological Canporients of the Envirorinent .. .... ........ 77
Ecosystem Effects . . . * . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 78
Disciplinary Review . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 79
Ecological Effects Profile . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 79
Ecological Effects Hazard Assesanent ..................... 79
Generic Data Gaps . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 81
Suggested L.abelxng . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 82
Bibl ogr y (Reserved) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 83
Regulatory Ratic iale . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 85
Technical Metolachlor
The Mitigation of Hazards to Humans ...................... 85
The Mitigation of Hazards to Wildlife .................... 86
Dnulsifiable C ncentrates of Metolachlor
The Mitigation of Hazards to Humans ...................... 86
The Mitigation of Hazards to Wildlife .................... 88
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Regulatory Position (including Sample Labels) ..................... 89
Technicai. Metclachlor . . . . . • . . . , . . . . . . . . . • . . . . . . . . . . 89
DnulsifiableConcentratesofMetolachlor ...................... 91
Registration Under this Standard
I g istration Procedures . . . . . . . . . . . . . . . . . . . . . . 97
Generic 1)ata Requirements . . . . . . . . . . . . . . . . . . . . . . . . . . 98
Amending the Standard . . . . . . . . . . . . . . . . . . . . . . . . . . . . 99
l˝ endices . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 101
A • C iaiu.cal I)ata Sheets . . . . . . . . . . . . . • . . . . . . • . . . . • . . • . . 103
B. Significant Historical Events ............................. 133
C.IndexofAcceptableUses(Reserved) .•.... . 134
D. Index of ‘Ik)lerances •.. •.... .. .......S........ ... .. 135
E.cai panyDatachrono1ogy(Reserved) ........................ 136
F. Analytical Methods (Reserved) . . • . . . . . . . • . . . . . . . . . . . . . . . • . . 137
G. Information Search Strategy- . . . . . . . . . . . 138
H. Treatment of Chemical Intoxication (Reserved) • . . •... ....... 139
I. Management of Environmental Contamination (Reserved) ...... 140
J. Disposal Information (Reserved) ........................... 141
B li ra y . . • . . . . . . • . . . . . . . . . . . . . . . . . . . . • . . . . . • . . . . . • . . . . . . . . . • 143
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PREFACE
This is a Sample Registration Standard, designed to demonstrate the
Agency’s proposed implementation of Section 3(c)(2)(C) of the Federal
Insecticide, Fungicide, and Rodenticide Act (FIFRP ), which calls for a
simplified procedure for the registration of pesticides. The new procedure
being proposed by the Agency is based on the use of ‘Registration Standards’,
publicly available regulatory position—documents for pesticide active
ingredients. The function of a Registration Standard is to determine, through
the review of all relevant scientific data, ‘standards’ of ccanposition,
packaging, toxicity, labeling, arid data requirements that together ensure the
safe use of a pesticide chemical. The ‘standards’ for a particular active
ingredient are the conditions which each product containing that active
ingredient must meet if it is to be registered for use in the United States.
There are three ways in which this Sample Registration Standard differs
fran an actual Registration Standard.
First, though the herbicide ‘Metolachlor’ is an actual pesticide currently
registered with the EPA, this Sample Registration Standard does not have any
regulatory status bearing on that registration; it is intended merely as an
informational publication. The way in which this Sample Standard’s scientific
issues are resolved in a ‘Regulatory Position’ should therefore rot be
construed as a precedent for regulatory actions involving similar situations
with other pesticide chemicals.
Second, the scientific review presented in this Sample Standard does rot
consider certain recent studies suixuitted in suçport of the actual re-
registration of Metolachior. Because the scientific camitunity is constantly
testing and re—testing chemicals, the data base used to support any one
Registration Standard will be canprised of only those relevant studies which
were available as of a certain cut—off date. F r an actual Registration
Standard, this cut—off date will be within no more than a few months of the
publication date, arid at least one updating will occur before publication.
For Metolachlor, the body of studies row available has grown considerably
since the original writing of this Sample Standard, and no updating has been
performed. Thus the ‘data gaps’ identified in the body of this Sample
Standard are by no means the actual gaps currently pending for the re-
registration of the herbicide ‘Metolachior’. All Registration Standards will
be updated periodically through reviews of the latest available scientific
data.
Third, because this is an informational publication, a great deal of
explanatory text is provided throughout the document. This text, which you
will find set in ‘Italics’, will be used in actual Registration Standards only
when atypical circumstances call for sane explanation or qualification.
Further, to demonstrate the wide spectrum of information that the Agency
considers in the regulation of pesticides, the explanatory text provided in
this Sample Standard covers the full range of issues that might potentially be
discussed with regard to pesticide safety. In an actual Registration
Standard, the Agency will discuss only those issues which are relevant to the
safety of the one particular chemical.
Though this Sample Standard is meant to inform the public about the
Agency’s present intentions, it is also to serve as a tool for modifying and
ref ining these intentions to meet public needs. As was explained in the
Federal Register notice (0PP—30032) making this Sample Standard available,
your caitnents, criticisms, and suggestions are encouraged. Please direct your
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cannents to the general regulatory concepts illustrated by the discussions and
to the format and principles of the presentation, and rot to the specific
scientific issues that have been portrayed for the herbicide ‘Metolachior’.
We suggest that you read this sample document through frc*ii front to back,
as there is a logical developuent to the discussions, which lead through a
consideration of available information, to an assessment of potential hazard,
to a consideration of regulatory means of delimiting those hazards, and
finally to a regulatory position. We also suggest, for persons interested in
data requirements for registration, that you have at hand the ‘Proposed
Guidelines’ for hazard evalution testing (40 CFR Part 163: Federal Register
notices of July 10, 1978 and August 22, 1978), so that you can read in more
detail about the nature of the Agency’ s mininun data requirements and when
they apply to particular types of pesticide products or uses.
The consideration of available information and the assessment of potential
hazard are accanplished in five separate ‘disciplinary chapters’, each
specializing in sane aspect of hazard evaluation, and each building on the
conclusions of the previous chapters.
First, in the Product Chemistry chapter, the scope of the Standard is
determined in a review of the canpositia-i and chemical nature of the pesticide
and the products which contain it. The physical/chemical properties that are
discussed in this chapter sanetimes indicate hazards for those who handle the
products.
The Envirorinental Fate chapter then examines the chemical’ s tranf ormat ion,
degradation, movement, and potential accumulation after it is applied
according to label directions. The Exposure Profile in the Environmental Fate
chapter extrapolates fran the fate information to estimate who or what ron—
target organisms may be exposed to the chemical as a result of its manufacture,
handling, and application. For those organisms which are expected to bear
significant exposures, an attempt is made to quantify the level of these
exposures.
In the I xicology chapter, an evaluation is made of the effects that could
potentially occur in humans or danestic animals as a result of certain levels
of exposure. With these potential effects and the Exposure Profile in mind, a
“Ibxicolcxgy Hazard Assessment’ is performed to point out potential problems for
handlers of pesticide products, for applicators, and for rkers or
danesticated animals in the vicinity of the application.
Next, in the Residue Chemistry chapter, the level of residues and the
nature of the metabolites to be expected in food or feed is determined, and the
currently allowable levels of residues are cxznpared to the potentially harmful
dosage level s identified in the ¶L xicology Chapter.
In the last disciplinary chapter, the Ecological Effects chapter, an
evaluation is made of the potential effects which may occur to microorganisms,
non—target plants, and wildlife species as a result of certain levels of
exposure, and the potential damage that these effects might have on vital
ecological balances. As in the ¶Ltxicology Chapter, an ‘Ecological Effects
Hazard Assessment’ is performed using the estimations in the Exposure Profile,
and potential hazards to the specific species or to the general ecology are
identified.
Then, in the Regulatory Rationale, means of preventing or mitigating the
potential hazards identified in the “Ibxicology Hazard Assessment’ and the
‘Ecological Effects Hazard Assessment’ are discussed. Finally, the regulatory
actions recannended by the Rationale are brought into effect in the Regulatory
Iksition, and a sample label is constructed for each type of product, bearing
ail the required restrictions and precautions.
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Until the Agency begins to routinely inform registrants, in advance of
initiating the building of a Standard, that certain data required under the
authority of the ‘Proposed Guidelines’ have not been supplied, most early
Standards will be ‘Conditional Standards’, with their regulatory positions
conditional upon the generation of the missing data. When these data are later
supplied by registrants seeking registration or re—registration, the hazards
will be re—assessed and the regulatory position will be changed to reflect the
new information.
‘lb aid present and potential registrants in using the Standard to register
or re—register their products, a section will be provided at the end of each
Standard called ‘Registration Under this Standard’. This section will
list the data requirements which must be filled to turn the Conditional
Standard into a Final Standard, the tests needed to demonstrate that the
cxxnposition of the proposed product falls within the scope of the Standard, the
procedure used to petition the Agency to amend the Standard to include product
caapositions or uses not presently covered, and the routine procedure to be
used for registration and re—registration.
The disciplinary chapters and the Regulatory Rationale, by making explicit
the thinking behind the Agency’s decision-making, should be of help to public
interest groups and environmental interest groups in evaluating the efficiency
and thoroughness of the Agency’ s protection of the public health and the
natural environment. Though representatives of the pesticide chemical industry
will be most interested in what is required of them in order to accat pl ish
registration or re-registration, they too will have the opportunity to see how
those requirements and any accanpanying regulatory restrictions were derived in
a clear and logical manner fran the available information on the potential
hazards of the pesticide.
In addition to providing a simplified means of pesticide registration, the
goal of the Registration Standards process is to give the Agency’s decisions a
broader scientific base and to open the Agency’ s decision-making to public
scrutiny. ¶lbgether this will ensure that the Agency’s regulatory decisions on
pesticides afford an effective protection of man and the environment as well as
a fair and equitable treatment of pesticide producers and users.
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wcr a EMIsmY
INTRODUCTION
The Product C zemistry chapter begins our review of the information about
the chemical and its pesticide products by discussing the chemical’s
identity, how it is manufactured, and how it may be detected or measured, and
by sunvnarizing data iich reports characteristic physical/chemical properties.
‘IOPICAL DISCUSSIONS
Corresponding to each of the 9xpical Discussions listed below is the number
of the section in the ‘Proposed Guidelines for Registering Pesticides’ of July
10, 1978 (40 CFR Part 163), which explains the minimum data that the Agency
usually requires in order to adequately assess a pesticide’s Product Chemistry.
Guidelines Section
Chemical Identity 163.61—3
Manufacturing Process 163.61—4
Percentages of Cauponents in Pesticide Products 163.61—6
Product Analytical Methods and Data 163 . 61-7
Physical/Chemical Properties 163 .61—8
Chemical Identity
A definition of Metolachlor’s chemical identity is necessary as the
starting point in the Standard for three reasons: to locate relevant
scientific sources, to make clear ?Iaich pesticide products come under the
regulatory authority of the Standard, and to identify the essential compounds
to be studied in the evaluation of pesticide hasards.
In general, a chemical’s identity is defined by names, numbers, and
symbols. This can include convnon names, chemical names, representative trade
names, names of manufacturers, molecular formulas and structures, CAS numbers,
S zaughnesey numbers, or other alpha/numeric codes.
Beyond a list of synonyms, the identity of the generic chemical may need
qualification in two additional ys. First, the Standard may discuss as one,
several stereoisomers of a single molecule, several distinct molecules z ich
occur simultaneously, or various complex molecules of indeterminate structure.
Secondly, a single Standard rIrLy encc. npass several distinct derivatives of an
active ingredient vinich are asswned to have similar behavior and effects, as
may often be the case with various salts and esters of an acid.
‘Metolachlor’ is the acceptable azTitcn name for 2—chloro--N--(2—ethyl—6—
methylphenyl) -N- (2-methoxy-l--methylethyl ) acetamide as determined by the
American National Standards Institute (1975). Ciba—Geigy Corporation,
presently the sole manufacturer of Metolachlor in the United States, has
assigned Metolachior the experimental number ‘CGk-24705’ (for the active
ingredient), and the trade name ‘I al’. The name ‘Metolachlor’ will be
used in the Standard in place of the nore cxznplex chemical name or trade name.
Metolachior is both a 2—chioroacetamide and a 2—chloroacetanilide. Figure
1.1 shows the relationship between Metolachlor and other pesticide active
ingredients similar in chemical structure. See the ‘Chemical Data Sheet’ for
‘Cct4—00l’ in Appendix A for a cxrnplete chemical characterization of Metolachior.
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METOLAQILOR AND RELATED
HERBI CIDES
cs
0— II& •O Cp I
Ace toch br
Terbuchior
Diethatby1—ethY]
Prynachior
c !1. C4I_ cI!%),4_ .. c*i ci
Allidochior
FIGURE 1.1
Propachior
Metolachior
Alachior
Butachior
—çss,
—c”&—c&.
DelacMor
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Manufacturing Process
The chemical reactions employed in the synthesis and/or purification of
the active ingredient may suggest the presence of potentially harmful
unpurities and can serve as a verification of product ccwiposition. Because
it is considered ‘Confidential Business Information’, a discussion of the
specific procedures, equipnent, and conditions required for comnercial
manufacture will not be published in the body of a Registration Standard.
Though specific manufacturing information is withheld, the publicly-
available U.S. Patent for the synthesis of Metolachior shows that it may be
produced by reacting the N—substituted aniline below with a chioroacetylating
agent, preferably an anhydride or halide of chioroacetic acid. The general
process is shown in Figure 1.2 below, which is taken fran Vogel and Aebi, U.S.
Patent 3,937,730 (1975) and German Patent 2,328,340 (1973).
CH p
C CH -C-N--cH- CH - O-CM
HsC J fCH3 + _•)
Figure 1.2
Percentages of Ccxnponents in Pesticide Products
The Registration Standard will describe the composition of the technicals,
manufacturing-use, and/or end—use formulations vihich contain the active
ingredient. This information is needed to define the acceptable ranges of
concentration alloz xzble in registered products, to prescribe appropriate test
material concentrations in hazard evaluation testing, and later, to estimate
likely exposures to each component resulting from the handling or use of the
products thich contain it. Information on the identity and quantity of
components which is claimed to be Confidential Business Information is
normally to be withheld from publication.
For all pesticide products, the Agency requires a listing of the upper and
lower limit established (by the producer or formulator) for each active
ingredient, and the upper limit for each impurity, reaction product, and
degradation product which is kix,wn to be present or which might reasonably be
identified.
Though the Agency has been supplied with all this information for Technical
Metolachlor, the manufacturer has claimed that the identity of impurities can
indirectly disclose details about the manufacturing process, and that the
identity of Metolachior impurities is therefore Confidential Business
Information. The identity of impurities is thus r t reported in this
discussion, but is instead recorded in a ‘Confidential Discussion Appendix’ to
be retained by the Agency for internal reference. (Accordingly, in Appendix A,
the Chenical Data Sheets for ccznponents OJM-002 through O 4—0fl are also
withheld fra u publication and are included instead in the Agency’s internally
used ‘Confidential Discussion Appendix’.)
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Only the percentage of active ingredient has been supplied for the
presently registered fornulated end-use products containing Metolachior.
Technical Metolachior (manufacturing—use preparations)
1 presently registered: Technical Metolachior is cal1prised of 95 to 100%
the active ingredient ‘Metolachior’, i.e., 2—
chloro—N- ( 2—ethyl-6--methylphenyl) -N- ( 2-methoxy--l-
methylethyl) acetamide.
Thus, one condition that manufacturing-use Metolachor preparations must
meet in order to be registered under this Standard is that they must
contain at least 95% the active ingredient ‘Metolachior’ as defined in the
¶ pical Discussion on ‘Ch nica1 Identity’.
E nulsifiable Concentrate Metolachior (end—use pesticide)
2 presently registered: (a) E nulsifiable Concentrate with six pounds of
active ingredient per gallon is c nprised of
68.5% the active ingredient ‘Metolachior’ and
31.5 % inerts.
(b) uulsifiable Concentrate with eight pounds of
active ingredient per gallon is cx iprised of
86.4% the active ingredient ‘Metolachior’ and
13.6 % inerts.
Thus, one condition that formulated end-use products containing
Metolachlor must meet in order to be registered under this Standard is
that they must be enulsifiable concentrates containing 86.4% or less of the
active ingredient ‘Metolachior’ as defined in the ‘lbpical Discussion on
th nical Identity’.
Product Analytical Methods and Data
F i ret, in order to ensure that products contain only those percentages of
active ingredient which they pro perly claim to contain, it is necessary to
have available analytical methods which may be Used to determine the
concentration of active ingredient in each formulation.
Second, the commercial production of pesticide chemicals, reactions
between pesticide ingredients, reactions with packaging materials, as well as
degredation during the long period over which some products may be stored
before use, can result in the formation of chemical impurities. Because of
the potential toxicity of impurities, analytical methods must be provided for
their detection, both to improve the reliability of the en’s hazard
assessment and to ensure that marketed products conform to the standards of
purity agreed upon by the pesticide producer.
Methods for detecting and measuring the Metolachior canpound in its
registered formulations have been sukinitted (Belseth and Cole, 1973). ¶L xngh
all the ixxi-Metolachlor cx nponents of the Technical product have been
identified by its manufacturer (Ciba—Geigy Corporation, 1974), methods have
r t been reported for determining or measuring any of the impurities in
Metolachior products. The lack of analytical methods for impurities
constitutes a data gap in the information needed to support this Standard.
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Physical/Chemical Pr erties
Physical/chemical properties can serve as a means of chemical
identification: for instance, as an emergency means of identifying displaced
or unlabeled pesticides, or as a confirmation of the reliability of other
composition data. Physical/chemical properties can also disclose a direct
hasard potential in the storage, mixing, dilution, or use of pesticide
chemicals, and can indirectly indicate the chemical ‘s environmental fate, or
determine the c npatibility of the cc nponents of a proposed formulation or
tank mix. Because these properties vary with chemical composition, each
technical and formulation type will have its own unique characteristics.
Color : the color of a pesticide chemical may be helpful to medical
personnel in identifying the causative agent in accidental
poisonings, and can be used in identifying particular formulation
types of an active ingredient.
Technical Metolachior is white to tan. The color of each
Emulsifiable Concentrate was not reported.
odor : a pesticide’s characteristic odor may also give clue to the
identity of the ingredients in emergency situations or under re—entry
conditions, and may give an indication of the palatability of
residues in the diet.
Technical Metolachior is odorless. The odor of each Emulsifiable
Concentrate was not reported.
Solubility : the solubility of technical products in various solvents
factors in an estimation of the mobility of the pesticide chemical
from the site of application, and provides one basis for considering
the suitability of various solvents for formulation.
The solubility of Techni 8 al Metolachlor was reported as follows:
In water — 530 p n at 20 C
In organic solvents —
Insoluble in 1,2—ethanediol (ethylene glycol)
Insoluble in 1,2-propanediol (propylene glycol)
Miscible with dimethylbenzene (xylene)
Miscible with methylbenzene (toluene)
Miscible with N,N-dimethylformamide
Miscible with 2—methoxyethanol (methyl cellosolve)
Miscible with 2--butoxyethanol (butyl cellosolve)
Miscible with 1,2—dichioroethane (ethylene dichioride)
Miscible with cyclohexanone
Stability : the stability of the technical products suggests the rate of
decc.in position of the pesticide chemical so that environmental
chemists can estimate the accompanying change in hazard potential.
For Technigal Metolachior, the half—life of a 0.25% aqueous
solution at 100 C is 30 hours at 1 3, 18 hours at pH 7, and 1.5
hours at pH 10.
Octanol /Water Partition Coefficient : this coefficient, derived from
tests on technical products, is a theoretical indicator of the
relative potential of a pesticide chemical to accumulate in fatty
tissue.
t coefficient has been reported for Technical Metolachior.
5
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Physical State : the physical state of a technical, manufacturing-use
product, or formulated product is correlated to the types of studies
thich will be required to evalivite its potential hazards.
Both Technical and Dnulsifiable Concentrate tolach1or products
are in liquid fotm at roan tauperature.
Specific Gravity : the density of pesticide products helps confirm their
chemical compositions, and may be a factor in the Agency’s
assessments of the hazard involved with such application methods as
aerial spraying.
he specific gravity of Technical Metolachior is 1.085 (+1— 0.005)
at 20 C. The specific gravity of the six pound active ingred ,ent
per gallon nulsifiable Concentrate is 1.04 (+1— 0.005) at 20 C,
and the specific gravity of the eight 0 pound per gallon E nulsifiable
Concentrate is 1.11 (+1— 0.005) at 20 C.
Boiling Point : the boiling points of liquid—form pesticide products helps
to confirm their identity. Deviations from a standard boiling point
may suggest the presence of impurities.
At 0.001 nm Hg, the boiling point of Technical Metolachior is
100 0 C. Fbr six pour per gallon E nulsifiable Concentrate, it is
118 C, and for eight pound per gallon, it is 140 to 160 C.
Vapor Pressure : the vapor pressures of pesticide products are indicative
of inhalation hazards that may be encountered in their pockaging,
handling, and application, and is an important factor in the
assessment of volatility.
For the Technical, the vapor pressure is about 10 nm Hg at
20 C • r the six poun per gallon 0 EC, the vapor pressure was
reported to be 0. OSxlO m Hg 1 at 20 C, an for the eight pound
per gallon EC, it was 0.5xlO nm Hg at 20 C.
: the pH’s of those pesticides which can be diluted or dispersed with
vxzter, directly indicate hazards resulting from high corrosiveness
and from the mixing of pH-incomrxztible products.
The i of a 10% solution of six pound active ingredient per
gallon E tulsifiable Concentrate is between 7 and 8, and that of an
eight pound per gallon EC is between 6 and 8.
Storage Stability : the stability of the manufacturing-use or end-use
formulations of a pesticide, when stored under typical conditions, Ł8
the basis for assessing reasonable efficacy—related expiration dates,
and for assessing changes over time of such physical/chemical
properties as pH, viscosity, color, odor, and density, as well as of
the ‘effective’ concentration of the active ingredient.
Results of ongoing studies show that Technical Metolachlor is
stable for a minimun of or year at roan temperature. The shelf life
of both cxncentrations of the E nulsifiable Concentrate is estimated
to be a minimun of 5 years.
FlaiTmability : this determines whether labels of pesticide products should
bear an appropriate ‘flai7vnability’ iurning.
No data were available on the oathustability of the Technical.
The flash point of he six pound per gallon E nulsiflable Concentrate
was found to be 118 F (Setaflash C.C.T.), an that of the eight
pound per gallon was found to be 185 (+1— 5) F (TCC).
6
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Oxidizing or Reducing Action : the oxidation/reduction reactivity of each
pesticide product must be determined to prohibit the hazardous
mixing of incompatible product types.
No data were available for the Technical, but the Emulsifable
Concentrates were reported to be clearly non—reactive.
Explosiveness : the safe packaging, transport, storage, and application of
pesticide products is clearly dependent upon an understanding of
their impact explosion characteristics.
Again no data were available about the Technical. A study on the
explosiveness of the six pound per gallon Emulsifiable 0 Concentrate
has shown that the material is thermally stabl 8 at 200 C, can be
processed or handled at t nperatures up to 150 C, (under normal use
and application practices) does not form (nor does its vapor form)
explosive mixtures, and is not shock sensitive. The study on the
eight pound per gallon EC is currently in progress.
Miscibility : some end—use pesticide products may separate out from their
solvents when diluted in accordance with label directions, and this
may decrease the product’s efficacy and may make the distribution of
the active ingredient on the application site dangerously uneven.
The suitability of various solvents may hereby be brought into
question.
Both Dnulsifiable Concentrate formulations form a stable emulsion
with water.
Viscosity : special concerns in mixing and diluting either the
manufacturing—use or the end—use formulations, and in applying the
end—use formulations of a pesticide, may be suggested by an
examination of the viscosity of the solutions.
No data were available on the viscosity of the Technical. The
six pound per gallon Dn 8 lsifiable Concentrate has a viscosity of
15.6 (+1— 0.3) CS at 25 0 C. The eight pound per gallon, a viscosity
of 120 (+1— 5) CD at 25 C.
Corrosion Characteristics : to prevent the accidental leakage of those
pesticide chemicals which are packaged in or applied from metal
containers, an assessment must be made of each chemical’s corrosion
potential.
Again no data were available on the Technical. For the
E nulsifiable Concentrates, however, it was discovered that the six
pound per gallon formulation was not corrosive to steel or tin, while
the eight pound per gallon did show a slight corrosiveness. Lined
containers are therefore a itu st for the eight pound per gallon EC.
Dielectric Breakdown Voltage : if a chemical is applied around electrical
equipnent, such as telephone poles or tranforner stations, then it is
necessary to determine the dielectric breakdown voltage so that risks
of electrical shock to applicators can be appropriately assessed.
Metolachior is not registered for industrial weed control and so
will not be used around high power electrical machinery.
7
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DISCIPLINARY IEVIEW
Chemistry Profile
Generic Data Gaps
Suggested Labeling
Chemistry Profile
The technical material for a pesticide is the toxicant in pure form
(usually 95 to 100% active ingredient) as it is manufactured by a chemical
caupany prior to being formulated into an end-use pesticide product.
Technical Metolachior, which is 95 to 100% active ingredient, is an off—white,
odorless liquid, soluble in water, and miscible with several organic
solvents. Because it is intended only for re—formulation into the end—use
pesticide, Technical Metolachlor is a ‘manufacturing—use product’. The
physical/chemical properties which have so far been determined for the
Technical do rot suggest any ii ininent hazards to packagers, shippers, or
formulators — the only intended users of the Technical product. In order to
be reg isterable under this Standard, a Technical Metolachlor product
must have between 95 and 100% the Metolachior active ingredient, identifiable
non—Metolachlor cxiilponents, and physical/chemical properties equivalent to or
less hazardous than those reported above.
An emulsifiable concentrate is an end—use pesticide product, consisting of
a tox icant suspended or dissolved in a water— insoluble organic solvent,
stabilized by an emulsifying agent. The strength of an emulsifiable
concentrate is usually stated in pounds toxicant per gallon concentrate. The
only formulated end-use products containing Metolachlor which are considered
req isterable under this Standard are emulsifiable concentrates of eight pounds
or less Metolachlor active ingredient per gallon (86.4% Metolachior or less),
with identifiable non-Metolachior canponents, and with physical/chemical
properties equivalent to or less hazardous than those reported above.
¶ [ strengths of E nulsifiab1e Concentrate Metolachlor are currently
registered: six pounds active ingredient per gallon and eight pounds per
gallon. These are sai ewhat viscous liquids, miscible with water, and having a
slightly greater density than water. The physical/chemical properties which
have so far been determined for these emulsifiable concentrates indicate a few
notable characteristics, due primarily to the presence of the organic
solvents: a significant vapor pressure, a relatively low flash point
temperature, and a slight corrosiveness to metal containers for the eight pound
per gallon. These properties suggest the need for t warnings on the labels
of emulsifiable concentrates: due to the vapor pressure and high flalTinability
of the solvent in the six pound per gallon formulation, the user should keep
any six pounds or less per gallon formulation away fran open flame or high
heat; to prevent potential leaks of the eight pound per gallon formulation due
to its slight corrosiveness, it should be placed only in application equipitent
tanks that are protectively lined.
8
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Generic Data Gaps
The following tests or determinations are gaps in the Product Chemistry
data base needed to adequately su ort a Registration Standard for Metolachior.
After each gap is listed the section in the Proposed Guidelines (July 10, 1978
40 CFR Part 163) which describe that type of data and when it is required.
For Technical Metolachior:
1) Octanol/Water Partition Coefficient
2) Flanlnability
3) oxidizing or Reducing Action
4) Explosiveness
5) Viscosity
6) Corrosion Characteristics
7) An analytical method (or reference
to a method) for detecting and
measuring each identifiable impurity
(associated with the manufacturing
of the technical grade of the active
ingredient) in the formulated
products of Metolachlor.
For Emulsifiable Concentrate (6 lbs./gallon):
1) Color
2) Odor
For Emulsifiable Concentrate (8 lbs./gallon):
1) Color
2) Odor
3) Explosiveness
Suggested Labeling
Ingredient Statement : The ingredient statement for manufacturing—use
Metolachior will list the active ingredient ‘Metolachlor’ as:
“Metolachior: 2-chloro-N- (2-ethyl-6-methylphenyl ) -N- (2-methoxy-l-
methy lethy l)acetamide ”
Physical Hazard Precautionary Labeling : The labels of the Emulsifiable
Concentrates should bear the following:
For 6 lbs.(or less)/gallon EC:
“Do not use or store near heat or open flame.”
For the 8 lbs./gallon EC only:
“Do not place in unlined metal antainers or tanks.”
l63.6l—8(c)6
l63.6l—8(c)13
163.61—8(c)14
163.6l—8(c)15
163.6l—8(c)17
163.6l—8(c)18
163.61—7
163.61—8(c)l
l63.6l—8(c)2
163.61—8(c)l
l63.6l—8(c)2
163.61—8(c)15
9
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BIBLIOGRA 1Y
(Reserved)
In order for the provisions of FIERA concerning data compensation (Section
3(c)(1)(d)) to be effective wider Registration Standards, data used in direct
support of the Standard for each type of product must be accurately listed,
enabling applicants and their arbitrators to determine zuhat data do and do not
support the registrations of individual pesticide products. ThUs, for each
disciplinary chapter, studies used to evaluate hazard and establish Standards
for the manufacturing-use chemical and for each type of end-use formulation
wz il be listed separately.
‘lb protect present and potential a licants for the registration or re-
registration of products xxttaining Metolachlor, the citations appropriate to
each disciplinary chapter will not be published in this Sarr le Standard, though
a cxznplete Bibliography is provided at the end of the docunent.
10
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E VIRJNMENTAL FATE
INTRODUCTION
‘Environmental fate’ studies are used to predict and estimate the presence
of potentially ha nful pesticide residues in the man-made and natural
environment. A pesticide chemical released into the environment may be
transformed by chemical or photocheinical reaction, be metabolized by living
organisms, or persist unaltered. Some degradation and transformation
products can be hazardous in their own right. The goal of an environmental
fate review is to identify the d minant xzthz iy8 by izich a pesticide chemical
degrades, dissi pates, and ace uinulates, and then to relate this behavior to
various chemical, physical, and biological conditions.
When the pesticide, its degradation products, or its metabolites reaches a
non- target organism, an ‘exposure’ has occurred, with the potential of causing
adverse effects. Our undertanding of a pesticide’s likely fate in the
environment can be used to infer ?izat organisms (including man) may be
inadvertently exposed to the chemicals, by what route, how often, and in what
concentrations.
¶LOPICAL DISCUSSIONS
Corresponding to each of the ‘1 pical Discussions listed below is the number
of the section(s) in the ‘Proposed Guidelines for Registering Pesticides’ of
July 10, 1978 (40 CFR Part 163) which explain(s) the minimum data that the
Agency usually requires in order to adequately assess a pesticide’s
Environmental Fate. Where ro section number is listed, a minimum requirement
has riot been set for such information.
Guidelines Section
Use Patterns and Restrictions
Physico-Chemical Transformation 163.62—7
Soil Metabolism 163.62—8
Aquatic Metabolism 163 .62—8
Microbial Metabolism 163.62 -S
Mobility 163.62—9
Spray Drift 163.126—2, —3, and/or —4
Field Dissipation 163.62—10
Bioaccumulation 163.62—11
Contamination and Control
Alternative Pest Manag nent Practices
Use Patterns and Restrictions
The environmental fate of a pesticide depends upon the formulation type,
initial concentrations, and method of application, as well as the
environmental conditions of the application site. Environmental conditions
are those relating to the climate and geology of representative application
locations. Initial concentrations depend upon dosage rates and dilutions,
label and packaging information, methods of mixing and loading, application
techniques, application schedules, the ciinount of area treated, common safety
practices, and pounds used in a typical application.
11
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Dvatinctly different use patterns may result in significantly different
patterns of chemical behavior. It may someti..mes be necessary to discuss
separately the environmental fate resulting from each significantly
different type of application or use pattern.
The currently available end—use formulations of Metolachior are t
anulsifiable Concentrates, one at six pounds active ingredient per gallon, the
other at eight pounds per gallon. Metolachior is a selective herbicide, used
either as a pre—plant incorporated or pre—emergence surface—applied treatment
for the control of host annual grasses and certain broadleaf weeds in corn
(grown for grain only [ excluding popcorn]) and soybean fields:
p -plant incorporated — 1.5 to 3.0 pounds active ingredient per acre
(depending upon soil type), used when field has furrow irrigation, or when
a period of dry weather is expected. E urteen days before planting, (but
after bed formation if the corn or soybeans are to be planted on beds),
the chemical is diluted appropriately with water or fluid fertilizer,
applied to the soil with conventional ground sprayers (or center pivot
irrigation system) and incorporated, into the top 2 inches of soil. A
finishing disc, harrow, rolling cultivator, or similar implement is used
to provide a uniform 2 inch incorporation.
pre-emergence surface—applied — 1.5 to 3.0 pounds active ingredient per
acre (depending upon soil type), applied with conventional ground sprayer
(or center pivot irrigation system) during planting (behind the planter),
or after planting but before weeds or crop emerge.
Present use restrictions include: for rotational crops on a treated corn or
soybean field, rotational crops other than corn or soybeans may not be
planted earlier than 18 nonths after application; should rot be used i
sweet or popcorn; should not graze or feed corn forage and fodder to
livestock or use for silage; should not graze or feed soybean hay or forage
treated with Metolachlor alone or with tank mixes containing Metolachior.
The restrictions against: (1) the grazing or feeding of corn forage, corn
fodder, (2) the use for silage, (3) the grazing or feeding of soybean hay or
forage, were needed because their feed uses were classified as Section
180.6(a) (2), CFR 40. Feeding restrictions for soybeans were required because
no permanent tolerances have been set for soybean forage or for its hay
(including the fodder or straw left after harvesting the beans).
The U.S. Department of griculture Crop 1 porting Board in June 1975 listed
77,527,000 acres of corn planted in 1975 (Ciba—Geigy Corp., 100—EUP—38,1975).
Seven mid—western states (South Dakota, Nebraska, Minnesota, Iowa, Illinois,
Indiana, and Ohio) produce four fifths of the corn crop. Within this region,
the usual planting dates are between April 20 and May 9.
Phys icc-Chemical Transformation
Chemicals introduced into the environment can react with any number of
other chemicals already present in the air, water, or soil These reactions
can be dependent upon such factors as pH, concentration, the nature of the
eubstance8 present, or temperature. Reactions with water itself, in bodies of
water and in soil, are of particular importance with pesticides released into
the natural environment. The importance of hydrolysis as a dc ninant pathway
for pesticide degradation can be determined quantitatively from data on the
rate of hydrolysis, and the identity, quantity, and persistence of hydrolysis
products.
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In addition to reacting with other chemicals, a pesticide in the air,
adsorbed on soil surfaces, or in the water, may undergo transformation by
direct photolysis in sunlight. Photolysis reactions vary with the intensity
and wavelength of radiation, the physical or chemical state of the pesticide,
the matrix (air, soil, or water) in which the pesticide resides, and the
presence of other reactants. The importance of photolysis by sunlight as a
transfor,nation pathway of a pesticide chemical can be established through a
study of the rate of photolysis, and the identity, quantity, and persistence
of photolysis products.
Hydrolysis
Metolachior in buffer H 5, 7, and 9 at 30 , was respectively 97,
100, and 96% stable for 28 days (Burkhard 1974). Frcnt rate constants,
Arrhenius parameters for each pH value were calculatedó Using the
Arrhenius parameters, ha1 lives for Methlachlor at 20 C were calculated
to be greater than 200 days in 0.1N HC1 (pH 1) and in buffer pH 5, 7, and
9. In 0.lN NaOH (pH 13), the calculated hal —1ife was 97 days.
Hydrolysis of Metolachior in 0.1N NaOH at 30 C yields N-(2’ methoxy-1 5
methyl—ethyl)—2—ethyl—6—niethyl hydroxyacetanilide. In 0.1N HC1 at 70 C,
Metolachlor hydrolyzed to 4- ( 2—me thyl—6—e thyl-phenyl) -3—methyl—
morphol inone—5.
These data were sufficient to show that hydrolysis products are not of
environmental concern because Metolachior is considered to be stable. The
extreme basic and acidic conditions which caused the hydrolysis of
Metolachior are not likely to occur in the natural environment.
Photolysis
Because Metolachlor is used on outdoor crops, studies on photolysis
in both soil and water are needed. Because an asses iient of re—entry
hazard is not required for any of the proposed uses of products containing
Metolachlor, a study on photolysis in the vapor phase is not necessary.
Photolysis in Aqueous Solution
Metolachior was found to be relatively stable in aqueous
solution under natural sunlight (Aziz and Kahrs 1975). Approximately
6.6% was photolyzed in 30 days, which was less than 10% of the
exposed activity. Five photoproducts, accountir for about 4.7% of
the activity, were found in the chloroform soluble fraction. One
photoproduct was identified as 4—(2-methyl—6-ethylphenyl)-5—
methylmorpholine. Four of the photoproducts were not identified.
One unknown was found in the aqueous fraction and amounted to about
1.9% of total activity. These photoproducts do not need to be
identified because they represent less than 10% of the exposed
activity.
Under high intensity artificial sunlight conditions, Metolachior
in aqueous solution was approximately 69% degraded in 15 days (Aziz
and Kahrs 1974). Five photoproducts cx prising about 13% of total
radioactivity were found in the chloroform soluble fraction. Three
of the products were identified as 4-(2—methyl—6—ethylphenyl)-5-
methylmorphol me (MET—009), N— (2_hydroxyacetyl-N-methOXyProp- 2 -yl) 2—
ethyl—6—methylaniline (ME r—00l), and N—chloroacetyl—2—ethyl—6—
methylaniline (MET—OlO). (See Appendix A for identities of chemicals
referred to by MET nnmbers.) Photolysis products in the aqueous
phase amounted to 23% of the activity. Chloroform soluble products
which stayed at the origin on thin layer chranatography (TLC),
13
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amounted to 17.2% of the activity. Mass spectroscopy and TLC
analyses of this activity indicated that at least five major products
were present. Further efforts were taken to separate and identify
these products using mc with a developer of chloroform and methanol
(9:1) and chrariotropic acid, methanolic sodiun hydroxide, and
diazonium fluoroborate as specific spray reagents. With this TLC
system, at least seven photolysis product 4 were separated. None
represented more than 4% of the original c activity. These polar
products did not contain hydroxyl, aldehyde, or N-hydroxymethyl
groups as judged fran tests with the specific chrctnatographic
agents.
Based upon the data discussed in this section, Metolachior is
considered to be stable in aqueous solution under natural sunlight.
Photolysis in Soil
Studies on soil slides re performed by Aziz (1974). Under
natural sunlight conditions, Metolachlor on soil slides was
approximately 50% photolyzed in 8 days. Activity in chloroform
extract amounted to 44.9% of the applied radioactivity, of which
32.7% was determined to be parent, 3.9% was identified as N—propen-l—
ol—2—yl—N—chloroacetyl—2—methyl—6—ethylan ii me, and three unknowns
accounted for 7.7%. Each u nown was less than 10% of the applied
activity. Non—extractable c—activity in soil amounted to 39% of
the applied activity. Volatiles accounted for 10.5% of the applied
activity, of which 5.2% was determined to be parent.
Under artificial sunlight conditions, Metolachior on soil slides.
was approximately 52% degraded in 7 days. Activity in the chloroform
extract anount to 47.1% of the applied activity, of which 24.1% was
determined to be parent, 5.6% was identified as N—propen-l--ol—2—yl-N—
chloroacetyl—2--methyl—6—ethylaniline, and 16.4% was canprised of 3
unknowns. (Eac 4 unkr jn was less than 10% of the applied activity.)
Nonextractable c—residue in soil amounted to 39%. Volatiles
accounted for 6.8% of applied activity, of which 4.12% was determined
to be parent.
Though either study u1d have been adequate alone, these
studies, the one conducted under natural sunlight and the other under
simulated sunlight, provide sufficient information about the
photodegradation of Metolachior in soil. -
Soil Metabolism
A chemical in the environment can also be transformed by the metabolic
activity of biological systems, including microbes, plants, and anvnals.
Biodegradation is an important degradative patJm ay for organic compounds in
nature, in terms of mass of material transformed and e rtent of breakdown.
Microbes, because they need not absorb what they metabolize, and because of
their widespread occurrence in soil, are the primary organisms responsible for
biodegradation on land.
The rate, rxith zy, and degree of pesticide degradation by soil microbes
varies most significantly with moisture, temperature, soil chemistry,
soil composition, and soil aeration. Because microbes that require oxygen may
have different metabolic paths frccn those that function without it, metabolism
studies should be performed under both aerobic and anaerobic conditions. One
may also observe different effects in specifically cultured soil mediums.
14
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Elleghausen (1976a and b) studied the degradation of Metolachior in soil
under sterile aerobic, nonsterile aerobic, and nonsterile aerobic followed by
nonsterile anaerobic conditions. Under sterile aerobic conditions, at the end
of 12 weeks, 30% of the reductively dechlorinated analog of Metolachior (MET—
005) was found. No other metabolite could be detected. The remaining
radioactivity existed as undegraded Metolachior.
Also at a time interval of 12 weeks, both the aerobic nonsterile and
aged aerobic/anaerobic nonsterile tests resulted in a degradation pattern
wherein about 18% of the radioactivity was identified as MET—025. Another 10%
/ CM - Ci-4 0 C H,
\ - -
U
00
MET—025
of the initially applied radioactivity was found as polar, water soluble
products. They were inseparable by TLC, but could be methylated with
diazcinethane to form three distinct cx*nponents, separable by gas liquid
chranatography (GLC). The investigator considers these to be ring
hydroxylated analogs of ME r-025. A G1CL —soluble nonpolar metabolite,
representing about 5% of initial radioactivity was canpared, by TLC and GLC co—
chrcxnatography, to 26 model Metolachlor metabolites with no identity fit.
nall amounts of MET-005 as well as unidentifiable polar and nonpolar
extractables were also found.
Sumner, S lics, and Cassidy (1976) studied the products of degradation of
ring labeled C Metolachior in silt loam treated at an exaggerated rate
(100 ppn) and incubated out—of—doors in open bottaned containers. Besides
ç44 5
MET—OOl MET—008
41.7% of total initial radioactivity found as Metolachior, 0.9% of MET—OOl and
0.1% MET—008 were found. P 3ditionally, an oxalic acid derivative was
tentatively identified as MET-025. Chemicals contained in the leachate fran
this study were qualitatively similar, as determined by canparative radioassay
of various PLC Rf zones.
Concurrently, Sumner, Szolics, and Cassidy (1976) conducted a field plot
study of silt loan soil treated at 2 lbs ai/A and aged 12 months. This study
yielded in addition to MET—OOl, MET—008, and ME I’ —025, the additional cartpounds
MET—003 and MET—026.
MET—005
‘C H;
15
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) Ct4 H;
H-ckz-OM
\ 2Hs <
MET—003 MET—026
All metabolites in both substudies were less than 1% of total
radioactivity, except ME r—O0l in the leachate, which represented 2.5% of total
radioactivity. T TIC spots, representing metabolites less polar than MET—
003 were also noted, both at the 1% level, in the extracts fraii the field
experiment; the t spots as well as a spot near the TIC plate origin
represented 6.4% of the total radioactivity.
Sumner and Cassidy (1975a) showed that under field cx)nditions, over a one
year period, the relative percentage of unextractable residues reached a
steady state (ca. 80% of total). txiring the latter stages of the test, the
relative anount of extractable residue in the organic fulvic and humic acid
fractions decreased with a concx nitant increase in the anount remaining in
H.)O soluble and mineral fractions. The fractionation procedure used was
d scribed by Sumner (1974).
I)ipre (1974a) conducted an anaerobic soil metabolism study as described in
the l gency’ s Proposed Guidelines for testing and found that the gross character
(extractable polar, extractable nonpolar, or nonextractable) of soil
metabolites did not change over a 60-day anaerobic period following a 30—day
pre—cond itioning aerobic period, as aznpared to the character of degradates
during a similar period of continued aerobic metabolism.
Evidence is provided by Sumner and Cassidy (1975a) that nonextractable
bound residues of Metolachior and its metabolites are in dynamic equilibrium
with soluble forms and that the ronex tractable portion may therefore serve as
a long term reservoir for extractable residues.
When viewed as a ccinposite, these tests are sufficient to meet the needs of
the rqency’s interests in soil metabolism for Metolachlor. (The following
additional studies contain information related to metabolic transformation in
soil but di 5 not by themselves snpply adequate information about soil
metabolism: Kaiser 1974, S nnner and Cassidy 1974g, k, 1, m, f, and e).
P uatic Metabolism
The rate, pathway, and degree of pesticide biodegradation in the aquatic
environment may vary with the pH and other chemical properties of water,
oxygen content, organic content, and the type of sedvnent present. As
with terrestrial biotransformation studies, one should observe the different
effects under anaerobic or aerobic conditions, and may attempt to observe the
effects of specifically cultured water mediums. Pesticide degradation and
trc.nsfonnation must be studied to detennine the dc ninant pathways of
breakdown, so that a pesticide ‘5 fate can be related to the environmental
conditions at its site of application. Also, pesticide transformation
products, w 1 zether caused by aquatic metabolism, terrestrial metabolism, or
physico—chemical reaction, may themselves be as hazardous, or even more
hazardous, than the parent ccm pounds.
16
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Neither aerobic nor anaerobic aquatic metabolism studies are ordinarily
needed to assess the environmental fate of pesticides intended solely for
terrestrial uses, and no products formulated with 1 tolachlor have yet been
proposed for any uses other than the protection of corn and soybean fields.
Microbial Metabolism
In order to refine our understanding of how a pesticide may actually be
tranfor’ined by specific kinds of microorganisms, or by the microorganisms that
populate a specific type of soil or aquatic habitat, it may he useful to
measure the direct impact of microbes on pesticide transformation. This may
be done by a cccnparison of metabolic effects under sterile and non-sterile
conditions, or by the use of specifically pure cultures.
Three studies of this sort were subnitted. One was conducted according to
the alternative pure or mixed culture technique and tv were conducted by the
sterile and ron—sterile soil approach.
In the pore and mixed culture study (McGahen and Tiedje), Pmerican Type
Culture Collection number 34507, identified as Chaetomium globosum , a soil
fungus, was used in resting cell experimentation at 0.035 mM concentrations of
Metolachlor including control flasks without Metolachlor and without
C. globosum . Control flasks did not exhibit any degradation for 144
hours. Flasks with C. globosum and Metolachior exhibited substantial
degradation with only 55% of Metolachior remaining after 5—7 days. An
adaptive lag period of approximately 20 hours was observed. A total of at
least eight extractable products were identified or tentatively identified.
MET—009, MET—003, ME’r—0l8 and MET—0l9 were firmly identified. Identifications
of MET—020, MET—021, MET—022, MET—023, and MET—024 were tentative. The
formation of the oxoquinoline is unique to pesticide metabolism, with the three
quinolines of Metolachlor unique to Metolachlor itself. It is apparent that
the fungus did not remove any group fran the ring, although it dehydrogenated
the ethyl noiety to form a vinyl on the ring.
Kaiser, using labeled Metolachlor (position of label unspecified) added
Metolachlor to both sterilized and unsterilized sandy loam soil at a
concentration of 10 mg/250 gin of soil (40 p n) (Kaiser, 1974). Essentially no
loss of total activity was noted in either sterile or non-sterile soil (5—15%
of the residual activity was found to be degradation products of Metolachior).
This study is not considered acceptable for the p..irpose of describing the
effects.
In another sterile and ron-sterile soil study (Ellgehausen, l976b,c), a
clay loam (Stein, Switzerland) which was treated with ring—labeled Metolachior
at a concentration of 1 mg/232 gin of soil (ca. 4 ppn) and a control sample
(autoclaved soil) were monito d for degradation. After a short lag phase, a
slow but steady evolution of CO 2 was evolved in the ron-sterile soil
reaching 4.8% of the applied dose after 12 weeks. Analysis of the soils after
12 weeks indicated that 10% of the residual activity in the non-sterile soil
was parent cxinpound versus 65% Metolachlor in the sterile soil.
On the basis of these studies, a general microbial transformation scheme
can be postulated which involves dehalogenation, dehydrogenation, dealkylation,
ring formation, and oxidation of the acetyl group and/or ring oxidation. Ring
oxidation apparently results after extended incubation of the a npound in the
presence of microbes, but it is not a significant route of degradation.
The studies by McGahen and Tiedje and by Eligehausen followed acceptable
protocols, and are sufficient to support this facet of the fate assessment for
the present uses of Metolachior.
17
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Mobility
The movement of a pesticide chemical away frc n its si te of application may
transfer its hazardous effects to non- target organisms, may contaminate the
air, Water, and soi. l phases of the environment, causing loss of usable land
and Water resources to man and loss of habitat to wildlife, may infiltrate food
webs including non-target crops, and may result in a loss of effectiveness
against the target pest. Where a chemical goes in the environment is directly
dependent upon how it moves.
Different types of pesticide products and applications will bring into play
different mechanisms of movement • For example, pesticides applied by plane
will be subject to aerial drift, systemic pesticides will be removed from the
the soil by plant uptake, and surface applications will runoff more easily
than soil incorpo rations. However, the most ccqnmon pathways for pesticide
mobility in the environment are:
1) Leaching , which is the movement of a pesticide through soil,
usually by a mass transport process, which varies with the soil ‘s
adsorption potential, rainfall, flow rate, diffusion and dispersion, and
pesticide solubility, and which possibly results in a contwnination of
groundwater or drainage effluent; and Surface Runoff , which is the
Washing of a pesticide over the surface of the soil by rain;
2) Volatility , which determines the availability of residues to the
atmosphere, which is affected by surface type, soil particle size,
interaction with envirownental substrates or product ingredients, vapor
pressure, soil moisture, and climate, and the rate of which depends
upon the moisture conditions at the soil surface, because a surface layer
of dry soil can act as a barrier to volatilization;
3) Adsorption to and desorption from various types of soil, sediments,
and particulate matter, which helps determine the availability of
residues to the aqueous phase of the environment, and varies with soil
composition, particle size, moisture content, water solubility, and the
length of time that the pesticide has remained in contact with soil;
4) Water Dispersal , which is determined by measuring residue
concentrations in Water at selected distances from a point of release, and
which is of particular interest with pesticides discharged directly into
bodies of water.
The importance of each of these mechanisms as a dominant pathway for pesticide
movenent should be established quantitatively. Predictions may then be made
about how much, there, and at that rate a pesticide may move wider particular
environmental conditions.
Leaching
Data on leaching have been developed by Exipre (1974c) and House rth
(l973b). Parent Metolachlor leaches rea3ily in sandy loan and sandy soils
low in organic matter. Twenty to 33% of the a lied Metolachlor leaches
nore than 12 inches in the above soils when an equivalent of 20 inches of
rainfall are applied to a soil cxltxnn overlayered with tolachlor.
Conversely, insignificant leaching is expected in nuck soils high in
organic matter. Field studies (Ballantine, 1975) showed substantial
leaching into the 6 —l2” soil horizon in 5 different states with various
soil types. tolachlor residues, aerobically aged for 30 days in soil,
will also leach in soils low in organic matter. These data are sufficient
to assess leaching potential for b tolachlor.
18
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Volatility
A volatility study, which is conducted on the end—use formulations of
a pesticide, is not currently available for the Emulsifiable Concentrates
of tolachlor.
Adsorption
An adsorption/desorpt ion study using four concentrations of
radiolabeled active ingredient in a soil sediment representative of the
proposed use area is not presently available for Matolachior.
pray Drift
Spray drift may result in a significant exposure to non-target organisms
when pesticides are applied by aircraft, air carriers (mistblowers), or ground
application equipnent such as overhead sprinklers, and sprayers for rights-of-
way. lkvnage from drift has been demonstrated at distances up to several miles
from the site of application. Studies conducted under actual field conditions
or under simulated conditions in wind tunnels can determine the probable drift
potential, (i.e. the greatest volz&ne of droplets less than 100 un in
dwijneter), under various conditions. The parameters that may significantly
alter droplet volwne spectra include nozzle types and cores, pressure
settings, discharge orientations, wind speeds, temperature, and relative
hiinidity. The physical properties of different formulations, such as surface
tension, viscosity, density, and vapor pressure and the use of diluents,
adjuvants, and tank mixes may also alter the hazard associated with swath
displacement.
Information on the likelihood or extent of spray drift for Emulsifiable
Concentrate Metolachlor when conventional ground sprayers are used is not
presently available, except for what is generally understood about the spray
drift behavior of similar agricultural chemical preparations.
Field Dissipation
By delimiting the variables of a chemical’s behavior, laboratory studies on
transformation and mobility can determine the dominant pathways by which
pesticides may dissipate in the environment. But field studies introduce
important new variables, such as the presence of a crop, and allow all
variables to operate simultaneously, thus verifying laboratory predictions of
primary mechanisms. Residue decline curves obtained under field conditions
are directly used to estimate the duration of residues in the environment.
This allows the direct estimation of potential exposures, including those
which might be suffered by agricultural workers re-entering a treated area, by
the general public ingesting rotated crops, by wildlife consi ning residues
through the food web, or by any organisms making use of treated or
contaminated land or water resources.
Field dissipation studies were conducted by Ballantine (1975) on five
different soil types representing five geographical locations. The following
conclusions were drawn fran the studies: 1) Approximately 10% of applied
Metolachior was found in the upper 12 inches of Mississippi loam after 60 days
for both 2 and 4 lbs. ai/A application rates. 2) In Nebraska silt loam,
approximately 10% of applied Metolachior was found in the upper 12 inches after
162 days for both 2 and 4 lbs. ai/A application rates. 3) In New York,
19
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California, and Illinois, soils that were not analytically characterized,
Metolachlor dissipated to about 10% of the applied in 60 to 150 days for both
2 and 4 lbs. ai/A application rates.
These field dissipation studies under actual use conditions are sufficient
to sIx i that Metolachior, applied alone, dissipates to approximately 10% of the
applied anount in 60 to 160 days in each soil type tested, and that it leaches
to approximately 12 inches in loam and silky loam soils. If uses were proposed
at greater than 4.0 pounds ai/A pre—emergent, then a5ditional field dissipation
tests, at the proposed rates, would be needed.
Ccmbination and Tank Mix Dissipation
Because t tolachlor may be applied in xxnb mat ion or tank mixes
with other pesticides or with fertilizers, a study is also needed that
canpares the dissipation characteristics of each active ingredient of the
mixture when applied to the soil as a mixture, with the separate
dissipation characteristics of each active ingredient in soil when applied
individually. Ballantine (1976a) conducted field studies to detei:mine
the canparative persistence of !.‘ to1achlor and Atrazine in silty clay loam
(Illinois) and sand soil (Florida). Rates were the maxirrnin specified in
the presently proposed labeling. Samples were collected fran the 0—6 inch
soil depth at 0.2, 4, 8, and 12 ironths.
The study was sufficient to conclude that there are no significant
differences in the dissipation rates of the chemicals when applied
individually. Metolachior dissipated to less than 0.05 p xn in eight nonths
in Illinois and one year in Florida. But the study was not sufficient to
evaluate the dissipation characteristics of each active ingredient of the
mixture when applied as a mixture.
Bioaccumulation
Dissipation is the study of the disappearance of a chemical in the
environment. Bioaccwnulation is concerned with the concentration of a
pesticide or its transfomzation products in living organis7ns. There are four
stages through bii2ich bioaccunulation may proceed:
1) Some pesticide chemicals may be very Blow to break down, and so could
be absorbed or adsorbed by living organisms.
2) Organisms can attempt to metabolize the chemical. The chemical may be
completely metabolized to simple, naturally—occurring compounds, or
partly metabolized to potentially toxic compounds.
3) If the compound or its metabolites are fat—soluble and are stored in
fatty tissue they may be released very slowly, as fat is burned off.
If the compounds or its metabolites are vxLter soluble, they may sometimes
be stored as carbohydrates.
4) These plants and animals may in turn be eaten by other animals,
including man. Where a pesticide compound is stored by populations of
organisms, each successively higher member in their food chain may
accumulate greater amounts of residues.
Bioaccwnulation studies can examine the rate and degree of each of these
stages. First, residue levels in rotational crops can suggest safe rotation
intervals and crop selection for hztmaan food sources, and can also suggest the
extent of plant uptake from the soil. Second, studies on irrigated crops do
the came for uptake from ?,nter sources. Third, the accwnulation of residues
in non-target organisms, and particularly in aquatic organisms such as fish,
can provide a useful indication of general food web contamination.
20
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Rotational Crops
Oats in the greenhouse, and carrots and soybeans in the field, were
grown as ro tional crops to corn 9 months after soil treatment at 2 lbs/
acre using C—ring labeled Metolachior. Low levels of residues ranging
fran .02 to .27 ppn, expressed as Metolachior, were found in different
portions of the various crops (Sumner and Cassidy 1974e; Sumner and Cassidy
l974f; Sumner and Cassidy 1974g). The preponderance of extractable
residues were polar in nature (partition into H 2 0/MeOH vs. CHC1 3 ) and
the two major fractions constituting these polar residues were neutral and
acidic in nature, as determined by ion exchange chranatography. A typical
analysis of such plant residues is provided by the following example for
oat straw derived fran oats grown as a rotational crop to corn where
Metolachior was applied at a rate of 2 lbs/acre (Sumner and Cassidy
1974f).
The text of the review by Marco (1974) of metabolism studies with
Metolachior in corn implies that only highly polar acid metabolites, such
as conjugates involving the N—acetyl group of Metolachlor are present.
lbwever, the data presented in Table IV of Marco (1974) show that the
relative ajiounts of polar neutral and polar acidic constituents in
extracts of mature stalks differ by about 4 to 1. These data support the
contention that TLC characterization of the polar neutral constituents
should be possible. Sumner and Cassidy (1974d) did not adequately
characterize the polar neutral constituents, though the very low levels of
radioactive content in these fractions made further characterization
difficult by means of present—day technology.
(adapted Frau Table IV, Marco-1974)
Ionic Characterization of E dioactive fr tabolites in lar
Fraction of Corn Treated with 2 lb. ai/A 14 C Metolachlor
________ Ionic Charge Percent of Total 14 C in Plant
weeks after treatment 8 12 16 (mature forage)
Marco (1975), and Sumner and Cassidy (1975), argue that the metabolic
pathways in rotational carrots and soybeans are qualitatively similar
based on canparison of the ionic and mc canparative characteristics of
acidic constitutents. While it is conceded the conjugated metabolites of
21
1) Total 14 C activity
2) H.)O/MeOH extractable, % of total activity
—‘Neutral Fraction, % of total activity
— Acidic Fraction, % of total activity
3) CHC1 3 extractable, % of total activity
Calculated pn
as Metolachlor
= 0.27 pçm
= 67%
= 19%
= 45%
= 7.0%
.18
.05
.12
.02
Location
Greenhouse
Field
Neutral
7.0
7.9
a
(a
= sample
Acid
73.1
53.6
a
decc*nposed
Base
0.6
0.9
a
in
shi nent)
Zwitterion
6.2
21.4
a
Neutral
7.4
10.8
7.3
Acid
68.2
70.4
26.3
Base
1.7
1.2
1.0
Zwitterion
2.7
8.4
15.3
-------
Metolachior in corn grain may be the only ones worthy of consideration,
the same is not necessarily true with rotational crop uptake. Oxipounds
unable to readily form sugar and/or S-glutathione conjugates may be taken
up by rotational crops and exist as discrete residues. These may therefore
be worthy of individual consideration by the toxicologists.
Also, it should be noted that the official regulatory method for
Metolachlor and its metabolites in corn is based on an acid hydrolysis
which forms HP—00l and HP —002. (Aziz and Ross 1975).
_____1#,cn p’
-c on / \ flC l&N
‘-C i ?
HP—002
This n thod will rot detect ME’r 002, 004, 008, 009, or 010, all of which
are postulated degradation products of Metolachlor (Marco 1974), and none
of which can readily ,form the conjugates, but only oxo-neutral conjugates.
1 gain, using the oat (straw) example, cited above, one can conclude that
the entire neutral fraction of the H. ,O/MeC* extractables equaling 0.05
n could be a mixture of MET 002, 004, 008, 009, and 010 (or other
degradates of a similar nature) and would rot be detectable by the method
of Balasubramanian, 1 ziz, and Ross (1975). Such canpounds sIx)uld be
readily amendable to GLC and ThC separation Rf zone and retention time
canparisons with nodel canpounds.
Based on information su xnitted by Ballantine,(1975) the roots of root
crops, grain of amall grains and oil frau oil seed crops can reasonably
be expected to contain little, if any, residue of tolach1or per se or
its metabolites hydrolyzable to HP-OOl or HP-002 using the method of
Balasubramanian, Aziz and Ross (1975). All residue analyses for MET—007
were .03 in or less and were 0.10 ppu or less for MET—015. The question
as to whether this regulatory method for corn-related products is
applicable to rotational crops is noot and must await further elucidation
of the nature of the neutral polar metabolites in rotational Crops.
The studies cited above si-ow that levels of Metolachior-derived
residues in other plant portions of these crops (carrot tops, soybean
stalks, sugar beet tops and wheat straw) may at times be expected to
exceed this analytical “baseline” level when grown as rotational crops to
corn and analyzed by the procedure of Balasubramanian, Aziz, and Ross,
1975.
The data on rotational crop residues are deficient in two respects:
first, data are not available on residues in leafy vegetable, rotational
crops; second, though it is agreed that present analytical technology is
not easily adapted to the task, the extractable nonpolar metabolites
in rotational crops were not sufficiently characterized to dispel concern
over their potential toxicity. Until these probl are resolved, any
product formulated with t tolach1or awl intended for use on food crops
should carry: a label restriction that calls for an 18—nonth interval
between application time awl the planting of rotational crops, to allow for
a caaplete degradation of residues; and also a warning against using corn
forage or fodder for silage or to graze or feed livestock, to prevent
uncharacterized residues fran being passed on to h inan constiners.
HP—O Ol
22
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Irrigated Crops
An irrigated crop residue study under actual field use conditions
is needed only when a pesticide is used in holding ponds or effluent and
other discharged sources used to irrigate crops.
No such aquatic uses have been proposed for tolachlor.
Fish Accumulation
Elleghausen (1977) tested the uptake, transfer and degradation of
Metolachlor by algae, daphnia, arid catfish. After 90 minutes exposure to
0.1 ppm Metolachior, algae accumulated 10.4 ppm. However, following 2
hours depuration, less than 2 ppm remained in the cells. Daphnia, exposed
for 24 hours to 0.1 ppm, accumulated 0.60 ppm. Eight hours depuration was
needed to achieve a 50% loss. Daphnids accumulated only 20% more when
exposed to both algae with 10.4 ppm Metolachior arid water containing 0.1
ii Metolachior as canpared fortified water in the absence of algae.
Catfish, exposed to 0.1 ppm C Metolachlor incorporated 1.20 ppm
Metolachior in their tissues after 96 hours. However, a plateau was not
reached.
Metabolites of Metolachlor were roted but not identified in the
algae, daphnids, lr catfish. At the end of the 96—hour catfish study,
only 1/2 of the C—activity remaining in the water was Metolachior.
The remainder was present as 3 unidentified degradation products. The
theoretical basis for the model system used was discussed in another paper
(Elleghausen l976b). 9iiith (1977) conducted a 30—day catfish exposure
study in a soil/water/fish ecosystem. At an average concentration of 0.08
pn in the water, bioaccumulation factors were 6.5 — 9.0 for edible
portions of• the fish and 55.0 — 92.4 in the viscera. After 14 day
withdrawals, these values dropped to 0.03 and 0.18 ppm, respectively,
corresponding to a bioaccumulation factor of less than 1. The accumulated
residues in the edible portions remained relatively constant in terms of
extractable vs. nonextractable (about 8:1). On days 1 and 30 there was 16
times more organically soluble activity than aqueous soluble (ethyl
acetate—water system). A cysteine conjugate of Metol h1or was identified
as a metabolite and reached a high of 12.8% of total C activity in the
edible tissue on day 14. Snaller amounts of other metabolites were found
in edible and/or visceral tissues but were rot identified.
N— (2 ‘hydroxy—l’-methylethyl ) —2—ethyl—6—methyl chloroacetanil ide (MET-
003), N—2(2 --hydroxy acetyl)—N—(l--methyl propane—2—yl)-2-ethyl—6—methyl
aniline, arid a cysteine metabolite of Metolachlor were all found in water
along with three other unidentified degradation products.
14 Barrows (1974) reported on a bluegill sunfish flow—through study at
C Metolachior exposure levels of 10 and 1000 ug/liter.
Bioaccumulation levels at the 1000 ug/liter exposure level reached 28 ppm
in edible tissues and 702 ppm in the ronedible tissues. Existence of a
plateau could not be established. After 28 days depuration, resid s in
edible portions of fish decreased to 0.08 ppm for the 10 ug/liter C
Metolachior exposure arid to 11.7 ppm for the 1000 ug/liter exposure. The
chemical nature of the fish residues was rot defined. When the above
studies are considered as a canposite, they are sufficient to adequately
characterize the fish accumulation characteristics of Metolachior.
23
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Contamination and Control
The prevailing fate of a pesticide chemical, and any resulting exposure to
non-target populations, can be si..gnificantly affected by certain safety-
related practices. First, pesticide chemicals may be unintentionally released
into the environment by means other than intended applications, such as
imprv per disposal or storage, accidental spillage, container leakage, fire,
explosion, factory mishap, leaching from landfill sites, or misuse. Second,
the fate of pesticide chemicals having already entered the environment can be
significantly controlled by Various intentional practices and precautions,
such as by land management techniques to reduce runoff, environmental
decontamination techniques, and various monitoring systems. Third, particular
ecological habitats and populations can be protected from exposure to stray
pesticide chemicals by certain equipment and techniques for applicators, re-
entry intervals, water quality standards, and various forms of safety
packaging.
Information about the prevalence, effects, or importance of any such
practices which either precipitate or mitigate pesticide chemical
displacement, could naturally be of direct importance in an assessment of the
overall fate of pesticide chemicals.
Because such information is not yet available for th1achlor, the P gency
can only offer sai cam n precautions with regard to the prevention and
mitigation of unintentional environmental contamination: Rr disposal
purposes, open duiipir should be prohibited, and pesticide, spray mixture, or
rinsate that cannot be used or chemically reprocessed should be disposed of in
a landfill approved for pesticides or buried in a safe place away fran water
supplies.
Alternative Pest Management Practices
Studies which examine the use of a pesticide in integrated pest management
schemes may suggest ways of reducing exposure to toxic chemicals, without
reducing the degree of pest control achieved. 1PM schemes may rely on the use
of a chemical in conjunction with some of the following biological and
cultural methods of control: the developnent of resistant varieties of host
plants and animals, the introduction of natural enemies, adjust ments in crop
rotations, cropping systems and planting time, water management and til lage
practices and the identification of pest population levels at which chemical
control is called for.
Information about the use of t tolachlor in 1PM or diagnostic weed control
progr ns is not presently available, tIxx h information is expected to becane
available as nore 1PM schemes are developed that require the use of herbicides
in ca bination with alternative weed control methcx5s.
24
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DISCIPLINARY REVIEW
Environmental Fate Profile
Exposure Profile
Generic Data Gaps
Suggested Labeling
Environmental Fate Profile
Metolachlor is applied at a rate of 1.5 to 3.0 pounds active ingredient per
acre to soil where corn arid soybeans are to be grown. Normally, the chemical
is sprayed on the soil during or soon after planting, before sprouts emerge.
However, when dry weather is expected, or if furrow irrigation is being used,
the chemical is sprayed on the soil before planting, and incorporated into the
top 2 inches of soil.
Metolachlor is quite stable to hydrolysis over the environmental pH range
of 5 to 9 (the half—life is 200 days over this entire pH range). Photolysis
appears to be a ITore significant degradation pathway, as approximately 50% was
found to have degraded in sunlit soil over a period of eight days. Soil
metabolism, by both aerobic and anaerobic microorganisms, s uld also play an
important role in the degradation of Metolachlor in the soil (McGahen and
Tiedge, 1978).
About 30% of the photoproducts were represented by MET-009 and MET—OOl.
(See the Chemical Fact Sheets in the Appendix for characterizations of these
and other metabolites.) Another 30% was represented by CHC1 3 arid water-
soluble polar metabolites. Indirect evidence obtained frcm analysis of aqueous
photoproducts produced by artificial light of <280 mm suggests that the polar
products, both aqueous soluble arid CHCl soluble, are ro 4 a1dehydes or
phenolic in nature (Aziz and Kahrs, 1975). Exposure of C Metolachior
treated soil thin layers to natural sunlight (Aziz, 1974) resulted in gradual
photolysis to MEr—003 and three unidentified products. ‘I unidentified
products have n derate polarity arid one was relatively high in polarity. After
8 days exposure about 1/2 of the initially applied dose had decomposed.
Soil metaboli n of Metolachior appears to proceed initially by hydrolytic
cleavage of the N—alkyl terminal constituents followed by oxidation and/or ring
closure. The following reactions were found to occur on the N—alky groups:
1) R - > R-O
2) R-C-c -C1
3)
B.- C-. r r c1cs e
0
(Elleghausen 1976a arid l976b; Sumner, Szolics, and Cassidy 1976;
Sumner arid Cassidy 1974 and 1975)
Attack of the benzenoid portion of the nolecule to form ptienolic metabolites
was speculated but not proven (Elleghausen 1976b). The likelihood of such ring
attack is contraindicated by the following observations: (1) Evidence is
0
I ,
1
•0
00
25
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provided by Sumner and Cassidy (1974) that non—extractable bound residue:
Metolachior are in dynamic equilibrium with soluble forms, (2) unextractable
residues represented by fulvic and humic acid fractions decrease with increased
aging. Incorporation of polyphenolic metabolites into the soil organic matrix
u1d mitigate against both of the above findings.
Studies were also available cri Metolachlor’s environmental nobility.
Houseworth (l973b), in a laboratory column leaching study, using a wide range
of soil types, showed that Metolachlor per se is subject to extensive leaching
when applied to soils having low organic content. Extensive leaching can thus
be expected in soils such as agricultural s ds and sandy loairis having organic
contents of 2% or less. 1 sidues of aged C—Metolachlor were also four 4 to
leach extensively in sandy loam soil (rxipre 1974). Based on incremental C
activity at different soil depths, several discrete chemicals of different
mobilities were probably involved. A runoff study by flipre (l974c) showed that
Metolachior can be expected to move fran agricultural sites of application both
by sheet erosion and leaching.
With the stability to hydrolysis and the likelihood of leaching,. we should
consider in more detail the potential for Metolachlor residues in the aquatic
environment. Metolachlor residues will be contained in runoff (soil and water)
fran adjacent corn fields. firing the midspring and early suiner months when
corn fields contain little or no vegetation to reduce runoff, more than 30% of
the erosive rainfall occurs. The average monthly rainfall during April, May
and June is approximately 3 inches (USD , YearBook, 1941). This results in
greater than 40% of the annual runoff and causes a range fran 1 inch to 3
inches of water in most of the cornbelt; parts of Southern Illinois, however,
lose up to 7 inches of runoff water (EPA—600/2—75—026 a, 1975). A runoff study
by txipre (1974) demonstrated that three simulated rainfalls (totaling 1.5
inches) r oved 3.2% of the applied Metol ch1or in runoff water and 1.4% in
soil, fran an experimental plot with an 8 slope. This study suggests that
individual rainfall events of 0.5—3.0 inches may move 1.5% to 2.5% of soil—
incorporated Metolachlor fran a treated field (Personal cmnunication with
Enviromental Fate Branch, 1978). If Metolachior is sprayed on the soil
surface and rot incorporated, the percentage of residues in runoff is expected
to be greater than 2.5% for 2.5—3.0 inches of rain. This range of values
appears to be reasonable in light of levels observed in field studies for
various pesticides (Bailey, Leonard, and Swank, 1976). Both the 6E and 8E
formulations of Metolachior are registered for ground application at a maxinuin
rate of 3 lb. ai ./acre. Assuming field application and climatic conditions
result in a loss of 2.5% of the applied Metolachlor, then each acre of treated
field uld contribute 0.075 lbs. to an adjacent aquatic sIte. This amount of
active ingredient in an acre foot of water uld yield Metalochlor residues of
.055 n in 6 inches of water and .0176 r m in 12 inches of water.
Field dissipations studies confirmed Metolachior’ s potential for
significant movement in the soil, but left open the question of whether
Metolachlor may sanetimes persist undegraded. Skipper, Gossett, and &nith
(1976), in field dissipation tests, concluded that extensive leaching was the
major cause of dissipation fran the çer 3—inch soil horizon in t different
plots containing sandy loam soils. Field dissipation studies of Metolachlor
applied at up to 4 lbs. ai/acre (pre—emergent) showed residues generally less
than 10% of the amount originally applied over tine spans ranging between 107
and 162 days. A total of 5 states representing continental LiSA climate
extremes were involved. But absolute losses of Metolachlor between the day of
application and final sampling were rot always so great. F r example, in a
Nebraska study, residues declined only 44% over a 107-day tine span. In sane
cases, substantial residues were found in the 6” to 12” soil horizon suggesting
26
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extensive leaching. This high soil nobility, in caT bination with a potential
for long—term environmental stability, may prove to be of significant concern in
projecting potential exposures to Metolachlor residues.
Additional studies were performed to estimate the possibility of
Metolachior bioac mu1ation. Bluegill sunfish exposed r 70 days to a mean
level of 1.2 ppii C Metolachlor accumulated 18 pç n of C activity
(expressed as Metolachior) in their edible tissues and 486 in non—edthle
tissues. After a 28—day depuration, the respective residue levels decreased to
12 and 13 ppn respectively. The chemical nature of the residues was not
investigated (Barrows, 1974). A catfish study (Smith, 1977) involving aged
Metolachlor on sandy loam soil sediments resulted in an accumulation of 0.53
ppn in edible catfish tissue at the end of 30—day exposure. After 14 days of
depuration, the level decreased to 0.03 ppn. Respective values for viscera at
the end of the 30 day exposure and after 14 days depuration were 4.4 and .18
çr xn, respectively. The major identified metabolite found in the edible tissues
was CGA—46576.
Though the available data do not indicate significant long—term
accumulation in fish, there is a possibility that residues may result in
rotated crops grown on Metolachlor—treated soil. 1 ots of root crops, grain of
5nall grains, and oil fran oil seed crops, grown as rotational crops to corn in
a Metolachlor—treated field, were shown to have little, if any, residues of
metabolites, as analyzed by the officially accepted regulatory method for corn
grain, forage, and fodder (Balasubrarnanian, Aziz, and Ross 1975; Ballantine
1975. This method will detect Metolachlor per se and a series of sugar and
glutathione conjugates which can form 1 fter hydrolysis of the N-alkyl groups of
Metolachlor to terminal OH groups.) C studies on rotational crops to corn,
however, gave evidence of other possible metabolites which, if present in a
rotational crop, s uld rot be detected by the official regulatory method for
corn products. Also, the following types of rotational crop products were
found to contain finite residues in one or more samples collected for analysis
by the method of Balasubramanian, Aziz, and I ss (1975): carrot tops, soybean
stalks, sugar beet tops, and wheat straw.
Exposure Profile
Technical Metolachlor : For persons involved in the manufacture,
handling, storage, or shiçment of Technical Metolachlor, there is little
likelihood of oral exposure, and because of the low vapor pressure of the
viscous liquid, there is also little chance of inhalation exposure. The
most likely human exposure is a i peated dermal exposure, and occasionally,
by accident, an occular exposure.
For wildlife in the proximity of Technical Metolachlor manufacture,
storage, shipping, or disposal, because of the relative stability of
Metolachlor to hydrolysis, its high nobility in the terrestrial
environment, and its potential resistance to metabolic degradation, there
is a significant potential for exposure to occur to various species, but
particularly aquatic species. Should significant amounts of the chemical
be spilled, drained, discharged, or disposed of in the natural environment,
aquatic life in drainage waters, or in bodies of water adjacent to
contaminated soil, v uld be likely to receive a long—term exposure, though
the chemical uld not be expected to bioaccumulate in aquatic or
terrestrial food chains. Considering Metolachlor 1 s potential for
rotational uptake, however, plants growing on contaminated soil could well
pass on residues to herbivores in that habitat.
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Emulsifiable Concentrate Metolachior : Though all chemical products
present sai possibility of accidental ingestion, for persons involved in
the dilution, mixing, and application of Metolachior formulations, there is
little chance of oral exposure. But there is a significant possibility of
dermal and eye exposure frcin the splashing that may occur in diluting and
tank mixing, and in the loaiing of spray equi ment. While the vapors frc*n
the Emulsifiable Concentrates are limited by the vapor pressure and the
viscosity of the solutions, the spray droplets generated by the application
of end—use Metolachior may result in an inhalation exposure for
applicators, and for agricultural workers or livestock who may be in the
proximity of the spraying.
Though ‘spray drift’ has rot been studied for Metolachior, we should
assure that terrestrial non-target plants and animals may occasionally be
subjected to a single direct exposure fr a nearby spraying. But more
importantly, the relative stability of Metolachlor to hydrolysis, its high
mobility in the terrestrial environment, and its potential resistance to
metabolic degra ation, together suggests that more significant, and longer—
term exposures may be expected for fresh-water aguatic plants and animals
in low-lying streams or ponds near the fields where Metolachlor is applied.
The Environmental Fate Profile estimates this potential aguatic exposure to
be near .055 ppxt in 6 inches of water or .0176 ppu in 12 inches of water.
As with the Technical, Metolachior’ s potential for rotational uptake
suggests that plants growing on contaminated soil could pass on residues to
herbivores in that habitat.
Because Metolachlor is applied primarily in seven midwestern states,
once annually, usually between the dates of April 20 and May 9, nontarget
terrestrial and aguatic organisms in those regions that may encounter
residues frait a pre-planting or a pre-energent application of Metolachior
will suffer the highest exposure between April and June (USDa *283, 1972).
The possibility for Metolachlor residues to occur in food or feed,
which may result in dietary exposures to the general p iblic, is discussed
in the ‘Residue Ch nistry’ chapter.
Generic Data Gaps
The following is a gap in the Environmental Fate data base needed to
alequately support a Registration Standard for Metolachlor. C posite the gap
is given the section in the Pr osed Guidelines of July 10, 1978 (40 CFR Part
163) which describes that type of data and when it is required.
For Technical Metolachlor:
1) Msorption/desorption studies 163.62—9
For flailsifiable Concentrate Metolachior: none
Suggested Labeling
There are no environmental fate labeling requirements for manufacturing-
use Metolachlor labels.
Emulsifiable Concentrate Metolachlor should carry the following
statanents on its label: the requiresent of an 18—month interval before
planting rotational cro , and a warning against the using of corn forage
or fodder for silage or to graze or feed livestock.
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BIBLIOGRP .RW
(Reserved)
In order for the provisions of FIFRA concerning data compensation (Section
3(c)(1)(d)) to be effective under Registration Standards, data used in direct
support of the Standard for each type of product must be accurately listed,
enabling applicants and their arbitrators to determine at data do and do not
sUpport the registrations of individual pesticide products. Thus, for each
disciplinary chapter, studies used to evaluate hasard and establish Standards
for the manufacturing—use chemical and for each type of end-use formulation
will be listed separately.
To protect present and otential a licants for the registration or re-
registration of products containing Metolachior, the citations appropriate to
each disciplinary chapter will r t be p.iblished in this Saniple Standard, though
a canpiete Bibliography is provided at the end of the docuiient.
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‘ IoxIcoIAJGy
INTRODUCTION
The chapter on Environmental Fate has explored the routes and mechanisms
by which Metolachior may be transformed and dis placed frc n the point of its
release into the environment, and the possibility of exposure for organisms
other than the target pests.
Because man applies pesticides where he lives and w ’rks, and to the crops
and livestock that he uses for food, he and his domesticated animals are
particularly susceptible to wiintentional exposure. This exposure may come as
food, feed, or water residues, surface or airborne traces, poisonings or
misapplications, or occupational exposures for pesticide applicators and
agricultural workers.
Studies of the toxic effects that may result from such exposures usually
fall into five categories: metabolism and pha-r nacodyno nics studies, which
detail the fate of a pesticide within a manvnalian body; dose-response
studies, which disclose the observable effects that can be tied to particular
ranges and conditions of exposure; studies that investigate the biological
variables influencing specific toxicological effects; reproduction studies,
which examine effects upon multi—generation reproductive viability for both
cells and organisms; and clinical reports, which discuss experiences with
actual human or domestic animal exposures.
WPICPL DISCUSS ICt IS
Corresponding to each of the Tbpical Discussions listed below is the number
of the section(s) in the ‘Proposed Guidelines’ of August 22, 1978 (40 CFR Part
163) which explain(s) the minimum data that the Agency usually requires in
order to adequately assess a pesticide’s ‘Ibxicology. Where no section nuiTber
is listed, a minimum requirement has not been set for such information.
Metabolism and Phauitaxdynamics
Acute Effects and Neurotoxicity
Local Irritat ion
Subchronic Effects and Neurotoxicity
Sensitization
Chronic Effects
Biological Parameters of Specific Effects
Q icogenicity
Genetic Effects
ratology
I productive Effects
Clinical Experience
Prevention and Treatment of Intoxication
Guidelines Section(s )
163.85—1
163.81—1, —2, —3, and —7
163.81—4 and 163.81—5
163.82—1, —2, —4, —5, and —6
163.81—6
163.83—1
163.83—2
163.84—2, —3, and —4
163.83—3
163.83—4
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Metabolism and Pharmacodynamics
Just as environmental chemists investigate the fate of a pesticide
chemical in the environment to estimate the potential for non-target
exposures, so may toxicologists investigate the fate of the chemical in the
body, to see that form it may take, how long it may stay, and that organs,
tissues, or functions may be affected by it. The term ‘metabolism’ refers to
the effect of an organism on the chemical structure of a foreign compound;
‘phannacodynarnics’ is here used to encompass the other aspects of a chemical ‘s
fate in the body - its adsorption, distribution, storage, and excretion. The
degree to which a pesticide chemical can penetrate the body by
gastrointestinal, respiratory, or dermal absorption can be measured by
comparisons with intravenous injection, by remainder analysis, or by direct
detection in blood, lynph, tissue, or zxwte. Once a compound is absorbed,
biochemical mechanisms of transport in the blood, such as binding to plasma
proteins, will enable its distribution to other tissues. Initial distribution
is directed mainly by the rate of blood flow to a particular tissue; final
distribution is dependent upon the inherent affinity of various tissues for
the compound.
As a chemical is distributed, it can also undergo metabolic
transformation, which generally occurs in at least one of three phases: the
first involves oxidations, reductions, and hydrolyses; the second involves
synthesis or conjugation of the foreign cc.!npound with a normal metabolite of
the body to form a more bxLter’—soluble, and therefore more readily excreted,
product; further chemical changes have been traced to micr’osomal ens ynee,
especially in the liver. Though metabolic transformation often results in an
expedited excretion, at least some storage of the chemical is likely to
occur. The storage of pesticides or their metabolites is effectively just
that portion of the dosage which has not been eliminated, and so it can be
measured and simply expressed as a concentration in particular tissues. But
the dynamics of storage can constitute a complex mathematical study, involving
time, steady states, and half—lives, as determined by the biology of tissue
binding, detoxification, and excretion. In any chronic exposure, if the rate
of administration exceeds the rate of elimination from the body, the toxic
substance will accumulate in the body until a steady state is reached, at
which point the rate of elimination will become equal to the rate of
administration. The elimination of absorbed compounds may occur by x y of
expired air, urine, feces, milk, and dermal secretions, and can often be
impeded by toxicological damage to the excretory organs themselves.
The sum of all these functions should account for all the chemical
absorbed. A ‘balance study’ is sometimes attempted to describe the long—term
equilibriwn of a pesticide’s metabolic fate.
Metabolism studies on Metolachior (Haithock 1974 a,b) demonstrated that:
(a) ? st orally administered Metolachlor is rapidly absorbed,
metabolized, ar 1 excreted.
(b) The urine ar 3 feces of treated animals contained a cai plex pattern
of metabolites; each metabolite accounted for less than 5% of the
administered dose. No unchanged chemical was detected in urine or feces
samples.
(c) A ç)roxiiuate1y half the urinary arx5 fecal radioactivity was
extractable with organic solvents.
(d) No glucuronide or sulfate conjugates ware four 1 in the excreta.
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(e) Several excreted metabolites were tentatively identified and
appear to result from dechlorination, O-methylation, N—dealkylation,
and side chain oxidation in the rat. 14
In additional studies (Hambock, 1974c), male rats were treated with C
Metolachior (approximately 31 mg/kg, p.o.), and urine and feces were collected
for 48 hours. The urine and feces cxntained 21.5% and 51.4% of the
administered dose, respectively, and the half life was determined to be
approximately 28 hours. TLC, GLC, HVE (high voltage electrophoresis), colunn
chromatography, gel permeation chromatography, and enzymatic hydrolysis were
adequately utilized to identify radioactive metabolites, which were identified
as 2—ethyl-6—methylhydroxyacetanil ide (MET—002) and N— ( 2-ethyl-6—methylphenyl)-
N—(hydroxyacetyl)—DL-alanine (MET—004) in the urine and 2-chloro-N—(2-ethyl-6-
methylphenyl)—N—(2--hydroxy—l—methylethyl)acetamide (MET—003) and MET—004 in the
feces. The 48 hour excreta xnthined 1, 15, and 22% of the administered dose
as MET—002, MEr_004, and ME’r—003 respectively. (See Appendix A for Chemical
Data Sheets on MET—002, MET—003, and MET—004.)
These studies denonstrate the relatively rapid metaboli n and excretion of
Metolachlor, and are sufficient to fulfill the requirement for this type of
information.
Acute Effects and Neurotoxicity
The a cutefles8 or chronicity of a toxicological effect is indicated by the
degree of its reversibility, and the occurrence of certain damages, especially
scarring and atrophy. By ‘acute’ effects we will here mean not only those
iizich are reversible, but also those effects, including death, which can occur
by means of a single exposure.
The ‘single-dose ED—50’, the dosage (milligram toxin per kilogram animal)
at which fifty percent of the subjects experience a toxic effect, is the
primary z4xzy of expressing the acute effects of one—exposure contaminations.
An LD—.50 is a special case of the ED—50, in which the effect measured is
death. The E’D—SO or LD— .50 values permit useful comparisons between the acute
effects of different cc, npounds or of the same compound by different routes.
The dosage—response relationship is the most fundamental principle in
toxicology. It can extend to all kinds of injurious effects, but in the case
of this topic, applies to acute systemic or whole—body effects such as changes
in behavior, histo pathology, irmiunology, body weight, and mortality, as well
as delayed systemic effects resulting from a single exposure, such as acute
delayed neurotoxicity. It can also extend to all routes of exposure, but for
pesticides we emphasize the oral, dermal, and inhalation routes.
The hazard evaluation of pesticides has three direct uses for acute
toxicity data. First, the dosage—response relationship implies the existence
of a threshold dosage for each compound, below which, under defined
conditions, no harmful effect is observed. Such a ‘no observable effect’
level is often used as a basis for estimating a value considered safe under
more varied conditions, including exposure of another species, especially
man. Second, acute effects levels can be used as an indication of eu-i-table
dosages for long—term or chronic studies. Thi .rd, acute oral, dermal, and
inhalation toxicity data are used directly for a number of regulatory
purposes, including pesticide classification, labeling, and packaging
specifications.
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Acute Oral Toxicity
The mininun testing needed on acute oral toxicity is one test on the
laboratory rat for each registered product.
For Technical Metolachior, the acute oral LD-50 in the laboratory
rat is 2,780 mqjkg with 95% confidence limits of 2,180—3,545 mg/kg (Bathe
1973). Technical Metolachior in corn oil has been shown to be emetic in
beagle dogs to an extent that precludes the establishment of an oral LD-50
in dogs (Affiliated Medical Research, Incorporated, 1974e). The study did,
however, establish the ‘emetic dose 50’ to be 19.0 (+/— 9.7) mg/kg. The
Technical therefore falls into Category III with regard to acute oral
toxicity.
Tests ware also done on the t E nulsifiab1e Concentrate formulations.
In a test involving a 6—pound per gallon E.C. formulation, the acute oral
LD-50 was found to be nore than 2,000 mg/kg but less than 5,000 mg/kg in
the rat (Affiliated Medical Research, Incorporated, 1974d). In a test
involving an 8—pound per gallon EC formulation, the acute oral LD—50 in
the laboratory rat was 2,530 mg/kg with 95% confidence limits of 1,890—
3,400 mg/kg (Nham and Harrison, l977a). A related study (Affiliated
Medical Research, Incorporated, l974f) established that the ‘emetic dose
50’ in dogs to a 6—pound per gallon E .C. was 24.5 (+1— 9.2) mg/kg. Based
on the above data, it is anticipated that E.C. formulations of Metolachlor
as high as 8-pounds per gallon can be expected to produce an oral LD-50 of
not less than approximately 1,890 mqjkg in the rat. The available data,
then, place existing E.C. formulations of 8 lbs. per gallon or less in
Category III with regard to acute oral toxicity.
Acute Dermal Toxicity
The mininun testing needed on acute dermal toxicity is one test,
preferably on the albino rabbit, for each registered product. This test
should be conducted on both intact and abraded skin.
Affiliated Medical Research, Incorporated (1974a) established that
the LD-50 of the Technical to the New Zealand rabbit is greater than
10,000 mg/kg when tested by the unabraded dermal route. ¶L1 ough the above
information is sufficient to meet the requirement for acute dermal
toxicity data on intact skin, data are not available on the acute dermal
toxicity to abraded rabbit skin. The unabraded dermal test results place
the Technical in Category III with respect to acute detmal toxicity.
In a test involving a 6-pound per gallon E .C. formulation, the acute
detmal ID-SO to the New Zealand rabbit was found to be greater than 10,000
mg/kg by the intact dermal route (Affiliated Medical Research Incorporated,
1974b). For an 8—pound per gallon E .C. formulation, it was established
that the acute dermal LD-50 to the New Zealand rabbit is greater than
3,038 nq/kg via the intact dermal route (Nhan and Harrison l977b). A
related study (Tryzna and Paa, 1976) determined that the acute dermal LID-SO
of a 1 to 10 dilution of a 6—pound per gallon E.C. formulation was greater
than 16,000 mg/kg via the intact dermal route.
Based on the above data, it is anticipated that E.C. formulations of
Metolachlor as high as 8-pounds per gallon can be expected to produce an
intact dermal LD-50 of not less than 3,038 mg/kg in the New Zealand rabbit.
The available data, then, place existing E.C. formulations of 8 lbs. per
gallon or less in Category III with respect to acute dermal toxicity.
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Acute Inhalation Toxicity
The minimum data needed on acute inhalation toxicity is One
inhalation LC—50 test, using one maimnalian species, preferably the albino
rat.
Acute inhalation toxicity was tested by Sachsse and Uliman (1974a).
In that test there were no deaths in albino rats at the maximum achievable
level of exposure (1.752 mg/i with four hours of exposure). This study is
adequate to establish a Category IV toxicity with regard to inhalation
exposure for Technical Metolachior.
In a test involving a 6 pound per gallon E.C. formulation, the acute
inhalation LC—50 was found to be greater than 247 mg/i of air (with four
hours of exposure) in the albino rat (Affiliated Medical Research,
Incorporated 1974c). The acute inhalation LC—50 for an 8 pound per gallon
E.C. formulation was determined to be greater than .94 mg/i of air (with
four hours of exposure) in the albino rat (Dreier 1977).
Based on these tests, it is anticipated that EC formulations of
Metolachlor as high as 8 pounds per gallon can be expected to produce an
inhalation LC—50 of rot less than .94 mg/i of air, in the albino rat • The
available data, then, place existing E.C. formulations of 8 lbs. per
gallon or less in Category II (for 8 lbs.) or Category IV (for 6 lbs.)
with regard to acute inhalation toxicity.
Acute Delayed Neurotoxicity
This type of data is needed only if the active ingredient or any of
its metabol ites, degradation products, or impurities cause esterase
depression or are structurally related to a substance that induces the
specific neuropathy, delayed neurotoxicity. Metolachlor is a
chioroacetanil ide herbicide and is rot expected to cause esterase
depression or delayed neurotoxicity. Therefore, this type of data is not.
required for Metolachior.
Local Irritation
Systemic effects like those observed in tests of acute toxicity can only
occur vihere there has been a significant absorption of the pesticide chemical
into the body. But !i2ether an exposure is absorbed or not, harm may be done
to that part of the body which suffered the initial contact, resulting in a
localized, though sometimes debilitating irritation. The eyes, skin, and
lungs are particularly susceptible to damage on contact with many compounds
and their solvents.
Frequently, toxicity manifested at the site of exposure is the result of
the caustic or corrosive nature of the chemical or its solvents. Such agents
are commonly referred to as ‘primary irritants’ because their action is non-
specific and can occur on all cells regardless of type. Damage done by these
compounds is usually directly related to the exposure concentration. Some
other agents, such as gases r ihich are converted to acids on contact with
bxzter, may have a more specific action on certain tissues, and may be
especially harmful to mucous membranes.
The dosage-response relationship that governs localized irritation can be
quantified through the use of irritation scores, and qualified by observations
of the reversibility of the effects.
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Primary Irritation
The minimum testing needed to evaluate eye irritation potential is one
test for each pesticide product, conducted on the albino rabbit.
A study of eye irritation for the Technical was cx)nducted by Sachsse
(1973a) on the New Zealand rabbit. In that study 0.1 ml of Technical
Metolachlor was used. The test was evaluated using the system of Draize
(1959) and produced the following eye irritation and indices at 24 hours
and 7 days:
Cornea: 0
Iris: 0
Conj unctivae: 0
This study establishes that Technical Metolachlor is non-irritating to the
rabbit eye.
In a test involving a 6—pound per gallon E.C. formulation, the data
indicates that this formulation is a severe irritant which can cause
irreversible corneal c acity in the unrinsed albino rabbit eye (Affiliated
Medical I search, Incorporated, 1974i). In a study involving an 8—pound
per gallon E .C. formulation (Scribor and Mastri, 1977a): the results frau
tests conducted with unrinsed eyes showed moderate corneal opacity
(reversed in 7 days) and conjunctival effects (partially reversed in 7
days); the results frau tests on rinsed eyes showed slight iris and
moderate conjunctival effects (reversed in 3 days).
Based on the above data, it is anticipated that E.C. formulations of
Metolachior as high as 8-pounds per gallon can be expected to produce a
reversible primary eye irritation, no more than a n x3erate corneal opacity,
and at least partially reversible conjunctival effects in unrinsed eyes.
Primary eye irritation, involving slight iris and moderate conjunctival
effects (reversed in 3 days) in rinsed eyes can be expected to occur fran
E.C. formulations of 8 pounds per gallon. The available data, then, place
existing E C. formulations of 8 lbs. per gallon or less in Category I (for
6 lbs.) or Category II (for 8 lbs.) with regard to primary eye irritation.
Considering the lack of irritation effects due to the active ingredient
alone (in the Technical), and the difference in eye irritation effects
between the t formulations, the degree of eye irritation produced by
Metolachlor formulations appears to be directly dependent upon the type and
amount of inert formulants used.
Primary Dermal Irritation
The minimun testing needed to determine a pesticide’s potential for
primary dermal irritation is one test conducted on a inaninal, preferably
the albino rabbit. Sachsse (l973b) evaluated the dermal irritation of
Technical Metolachlor on the New Zealand rabbit. The test was evaluated
using the system of Draize (1959) and resulted in a primary irritation
index of 0.1. This information is sufficient, and it establishes that
Technical Metolachior is non-irritating to rabbit skin.
In a test involving a 6—pound per gallon E.C. formulation, the primary
irritation index was determined to be 1.62 (Affiliated Medical Research
Incorporated, l974h). In a test involving an 8—pound per gallon E .C.
formulation, the dermal irritation was described as: moderate erythma,
edema, and second degree burns at 72 hours (Scribor, 1971). Based on the
above data, it is anticipated that E.C. formulations of Metolachior as high
as 8 pounds per gallon can be expected to produce not less than a primary
irritation index value of 1.62 (mild irritation) in the albino rabbit.
The available data, then, place existing E .C. formulations of 8 lbs. per
gallon or less in Category II (for 8 lbs.) or Category IV (for 6 lbs.)
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with regard to primary dermal irritation. As with eye irritation, the
degree of dermal irritation appears to be dependent upon the type of inert
canponents used in the formulations rather than on the concentration of
the active ingredient, Metolachior.
Subchronic Effects and Neurotoxicity
Sing le-dose toxicity studies are sometimes only fact-finding experiments
whereby an evaluation of biological effect is made that can be applied to
more prolonged repeated—dose studies on the compound. A study of suLichronic
effects is a multiple—dose schedule carried out for a period equivalent to
about ten percent of the life—span of the animal. Because of the duration of
the exposures., dosages to be used are more critical, and can be based upon
zthat has been learned from the single—dose studies. In prolonged toxicology
tests, experimenters usually use the route of administration (oral, der,nal, or
inhalation) corresponding to the route ‘of exposure that is most likely to
result from the actual use of the pesticide.
An evaluation of subchronic toxicity in turn helps to set the dosage levels
and suggests target organs of interest for long—term, chronic studies yet to
be done. Or it can serve as the definitive test for agents that are not to be
subjected to chronic tests because their pattern of use is such as to preclude
the possibility of life—span exposures. The shorter—term subchronic studies
have a nwnber of advantages over the Longer-term chronic studies, apart from
decreased time and expense. Often, the pathological damages due to subchronic
exposure are more clear-cut because they are occurring more quickly with
larger doses, becauae they are not obscured by natural chronic changes such as
aging, and because some toxic effects are overcome by long-term physiological
adaptations.
Subchronic Oral Dosing
Testing should be performed in at least 2 marrnialian species. One
species should be a generally recognized strain of laboratory rat while
the second species should be a non—rodent.
Three—m nth feeding studies were performed with Sprague—Dawley rats
(Coquet, Galland, Guyot, Ruillet, and Rouaud l974d) and with beagle dogs
(Coquet, Galland, Guyot, Fbuillet, and 1 uaud 1974c). It has been
determined that the histopathology evaluations for both the rat and the
dog study were not performed by a pathologist. These studies cannot serve
in support of this Standard, until the histopatholoqy evaluations are
properly made and subnitted. Therefore, data on subchronic oral dosing in.
t mammalian species is currently a data gap.
Subchronic 21-Day Dermal
The minimum testing needed is one study in one mammalian species.
Although no data is presently available on Technical Metolachior, a 21—day
detmal study was performed using Metolachior 6E (68.5% active ingredient)
and is considered to provide sufficient information (Affiliated Medical
Research Inc., 1974f). The study reported no significant evidence of
systemic effects at a dose level of 540 mg Metolachior per kilogram, per
day. At 1080 mg Metolachior per kilogram, per day, the only indication of
systemic effects was decreased body weight gain.
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Subchronic 90-Day Dermal
This study is not needed because the existing acceptable end—uses
should not result in repeated h an skin contact for this long a period.
Subchronic Inhalation
The existing acceptable end uses should also not result in repeated
inhalation exposure at a concentration which is likely to be toxic as
determined by an acute inhalation test. Therefore, this study is not
needed.
Subchronic Neurotoxici ty
Metolachior is a chioroacetanilide and is related in structure to
registered ch aicals that have not induced neuropathy nor delayed
neurotoxicity, as evidenced by the results of an acute test. This type
of data is therefore not needed.
Sensitization
In addition to oubchroni..c effects on histo logy, blood chemistry,
neurological functions (such as cholinesterase inhibition), excretion
functions normal tissue growth, body weight, and ens yne functions, short-term
multiple—dose exposure can lead to sensitization of the invnune system. The
sensitization response is a multiple—dose reaction because it is caused by the
gradual incitement of the body to produce antibodies specific to the compound
tested. It can be observed as a dei,nal irritation resulting from repeated
local exposure.
The minimiju data needed to assess dermal sensitization can be provided by
an intradermal test on one maninal ian species, preferably the male albino guinea
pig. The first evaluation of dermal sensitization was conducted by Affiliated
Medical Research, Incorporated (1974g). Inappropriate methodology (the patch
test) and the lack of sensitization in a positive control invalidate this study
and preclude its use in the regulatory process. A second study (Sachsse, 1977)
used the intradermal injection method: Technical Metolachlor dissolved in the
vehicle (propylene glycol) and the vehicle alone (negative control) were
intradermally injected into the skin of Pilbright guinea pigs. tk)sitive
reaction was denonstrated in animals injected with Technical Metolachior
dissolved in the vehicle; there was to reaction in animals injected with the
vehicle alone. Based on this second study, which is sufficient, it is
established that Technical Metolachlor is a skin sensitizer in guinea pigs.
Thongh there are to studies available in which the E .C. formulations were
directly tested, it is anticipated that E.C. formulations of 8 lbs. per gallon
or less will also cause skin sensitization in guinea pigs.
Chronic Effects
The basis for the chronic study is the contention that nothing less than a
life—span observation is adequate to assess the hazard of potentially life-
long exposures to a toxic agent. With pesticides, only those chemicals v*ich
may be expected to leave residues in food, feed, or potable ?Xzter, or those
zich may result in occupational exposure, will be likely to present the
possibility of lifetime exposure for man or domestic mamnals. This is thy the
chronic study is usually performed as a chronic ‘feeding’ study.
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the basis of acute effects and subchronw studies, dosage levels are
convnonly selected to include a ‘no observable effect’ level, another that
is clearly toxic, and at least one dosage that falls between these two
reference points. Mortality, life-span, gro h rate, food consumption, and
the gross appearance and behavior of the animal are routine observations
in chronic studies. Other measures of toxicity, such as pharmacology,
h-tsto pathology, hematology, blood chemistry, neurotoxicology, residue
analys-i s, body—weight changes, neo plasm and lesion counts, are also commonly
recorded. It t s frequently useful to obtain evidence regarding the reversible
nature of chronwally i..nduced toxicities by discontinuing administration for
select dosage groups, and observing final differences. 4ll animals in chronic
toxicity studies are eventually subjected to complete pathological evaluation.
Chronic testing should be available on at least one manTualian species.
The species should normally be a generally recognized strain of the laboratory
rat. 1 b chronic study is currently available for Metolachlor, aud this
constitutes a data gap.
Biological Parameters of Specific Effects
The tests on dose—response relationships may reveal the need for further
studies to investigate specific effects of particular concern. These studies
may be suggested by the analyses of histo pathology, hematology, body weight
changes, and lesions, routinely conducted In the investigations of dose-
response relationships. Studies on specific effects either Investigate the
chemical or biological conditions that influence the effect, or else attempt
to isolate and characterize the effect by experimental modeling.
There are a wide range of potential effects iiiich may be investigated in
this manner, and different types of effects will be subjected to different
sorts of investigations.
Some toxicological injuries affect all cells equally, but are highly
specific in their mode of action. An example of this is the universal
inhibition of mitochondrial respiration by the cyanide ion. In vitro studies
of such universal cellular effects are often useful indicators of in vivo
toxicity. With universal cellular effects, isolated cells and intact
orgcrnisms will be affected in a parallel zany.
Other effects on cells may be more specific to a particular type of cell,
(i.e. a tissue), or may involve interference with the biochemical interactions
between types of cells, as with the inhibition of acetyicholinesterase.
Toxic compounds that significantly interfere with the ‘integration’ of
cellular activity into essential bodily functions are said to be toxic at the
‘systemic’ level.
Systemic effects may be further divided Into ‘biochemical’ ones and
‘physiological’ ones. &rainples of ‘biochemical’ lesions include: the
inhibition of critical enzymes, such as SH—enzymes, acetyicholinesterase, and
cytochrane oxidase; the inactivation of critical transfer molecules, such as
hemoglobin; and bindings to membranes izich might affect membrane
permeabilities, such as the sodiwn and potassium gates of the nerve axon.
Specific ‘physiological’ effects on tissues and organs might include:
alterations in the function of the blood and lymph vessels, including abnormal
constriction and sensitivities to temperature; mild lesions in the
hypothalamus, such as to cause changes in body weight or appetite; fibrosis of
the lungs; maladies of muscles and supportive tissues such as the pericardium;
necrosis in the liver and kidney, which because of their importance in
39
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biotransformation and excretion often suffer high concentrations of toxins or
their metabolities; injuries to the central and peripheral nervous system
i nducements of cataracts and retinal damage in the eye; histological
alterations in the endocrine glands, such as to cause diabetes by danage to
the pancreas; and epithelial injuries, as in the digestive or respiratory
tracts.
Studies on the chemical and biological pre—conditions and co—conditions
that influence the rate, severity, and nature of specific cellular, systemic
bwchemwal, or systemic physiological toxic effects, can be instructive about
both the toxicology of the chemical and the facet of hunan physiology which it
alters or impacts.
The currently available dose—response studies on Metolachior do not
suggest any specific toxicological effects which necessarily require further
investigation, nor are any such studies currently available for Metolachlor.
Oncogenicity
Certain chemical substances appear to have the effect of causing cells to
reproduce uncontrollably, which in turn n iy produce lesions, twnors, or other
neoplasms, or physiological chaos in the blood, l ,mph, or immune systems. The
ch nical—induced formation of neoplasms - ‘oncogenesis’, and the continued
uncontrolled multiplication of cells - ‘carcinogenesis’, differ from other
toxicological effects in three xzys: the action is usually residual and
irreversible; single doses that have no detectable effect may nevertheless act
in an additive manner to initiate a serious pathology; and synergistic effects
with other environmental factors are of vital importance in determining
whether an effect occurs at all. The essential relationship between
oncogenicity and carcinogenicity is that oncological neoplasms, though they
rtuy appear to have limits in growth, have a greater likelihood of beccining
cancerous than most naturally occurring tissues.
Scrne carcinogens appear to have their primary effect at the point of
application to animals. These ‘direct-acting’ agents do not commonly require
metabolic activation but appear to be subject to detoxification and
excretion. Other carcinogens seem to have their primary effect on specific
tissues regardless of the route of application. These ‘procarcinogens’ must
undergo some type of metabolic activation, but also may be subject to
detoxification. A third type of cancer—causing agent is the ‘cocarcinogen’,
which is not significantly carcinogenic alone, but dramatically potentiates
the effect of other carcinogens.
For the adequate assessment of oncogenicity, studies are needed in t
maninal ian species: normally, the laboratory rat and the mouse. A mouse study
was conducted with (tharles River CD-i albino mice (50 of each sex) at levels
of 0, 30, 1,000, and 3,000 ç in fed in the diet. The duration of the study was
18 nviiths for males and 20 months for females. It was conducted by Industrial
Bio— st Laboratories and validated by Ciba—Geigy Corporation (Ge3ne,
Albanese, Marias, and Arceo, 1977). The P ency is currently evaluating the
significance of saI flaws in the experimental procedures and seeking
additional information fran Ciba-Geigy Corporation. Although the available
data s1u , no oncogenic potential associated with Metolachior, the use of this
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study in the regulatory process depends upon the resolution of the unsettled
technical issues. Along with testing on another marrinal, preferably the
laboratory rat, this present lack of t oncogenicity studies constitutes a
data gap.
Genetic Effects
In addition to aberrations in the rate of celL. reproduction, other cellular
reproductwe effects, such as spindle poisoning or mutations, may also result
from exposure to pesticide chemicals. Mutations are aberrations in the
genetic material transmitted from p2rent cell to offspring, and when the cell
is a gamete, from parent animal to offspring.
Genetic effects at the cellular level are of interest for two reasons.
First, because a cell’s genetic material is partially responsible for the
control of cell reproduction, mutagenic agents may also have a carcinogenic
effect. Second, alterations specifically in the inheritable genetic material
of the paternal or maternal gametocyte may result in birth defects. 1too major
kinds of genetic change in the gametes are recognized: a ‘point mutation’,
which involves a single gene (a change in as many as three DNA base pairs),
and which, because it does not interfere otherwise with the integrity of the
chromosome of which the gene is a part, may be reversible; and a ‘chromosome
aberration’, which includes chromosome loss or non-separation in cell
division, segment changes, inversions, or translocations. It is not clear
whether an increased rate in genetic change is caused by direct action on
genetic material, or is the indirect effect of injury to normal repair
mechaniems.
Point mutations, chromosome aberrations, and specific functional effects
such as on DNA repair and s jnthesie, can be tested for separately by a variety
of means in various experimental systems.
The minimum testing needed to assess mutagenicity is testing in ts’ )
experimental systems. The potential of Metolachior to cause genetic changes
has been tested for in a bacterial system utilizing activation by man nalian
microsanes (Arni and Muller, 1976), and in an in vivo system to test the effect
on developing sperm in the nouse (Ciba-Geigy Limited, 1976a).
The bacterial ( Salnonella ) system was tested for base substitutions and
point mutations at various ranges (10, 100, 1,000 and 10,000 ug/plate). No
increase in background mutation rates was observed. Nor were there any
effects noted, in the nouse study, on fertility rates, or on zygote or embryo
survivals, after single oral doses of 100 and 300 mg/kg. Also, no
malformations of resulting embryos were reported. Fran these t stud ies,
which are sufficient for mutagenicity testing, no evidence is presented which
suggests that Metolachlor has any mutagenic potential.
Teratology
While a fetus may be misdirected in its developnent by chemically induced
damages to its genetic foundation, its health, growth, and maturation may also
be directly affected by the presence of certain chemicals in the body of its
mother.
‘Fetotoxicity’ refers to any detrimental effect upon the health of a
fetus. For chemical doses which produce sublethal effects in the pregnant
mother, it is often not possible to distinguish between direct effects of the
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chemical upon the fetus, and effects on the fetus due to the impaired health
of the mother. Thus maternal toxicity should alvxzys be noted in observations
of fetotoxic effects. ‘Fetotoxic’ effects include degenerative changes in any
anatomic, physiologic, or biochemical system that has already been formed,
even though the formation may not yet be cc nplete.
‘Teratogenicity’ refers more specifically to aberratwn6 in the growth and
developnent of the fetus. Most teratogenic malformations which begin during
early embryonic developnent are made clearly visible by the subsequent growth
of the organ or tissue affected.
Though either fetotoxic or teratogenic effects may sometimes be termed
‘congenital’ because they were discovered at birth, an ex vnination of when
certain exposures occurred, and how the observed effects may have developed,
can help distinguish genetically determined maladies frc n those induced during
fetal developnent. Experimental teets for teratogenicity do not usually
schedule dosages for the female animal until after confirmed conception.
The major factors influencing chemical fetotoxicity and teratogenicity
include dosage, genetic background of the mother, genotype of the embryo, and
the embryo’s stage of developnent. The effective dosage of teratogens is far
less in the first third of gestation because malformations of the early
embryo are more pervading and irreparable. The effective dosage for general
fetotoxirw, notably antichoiinesterases, is less during the latter two—thirds
of gestation, because the critical injury is not to individual cells or
tissues, but to their functional integration. A significant factor for any
chemically induced fetal effect is the function of placental metabolism and
transfer, Izich matures with the embryo and fetus.
The minimiin testing needed to evaluate the potential fetotoxic or
teratogenic effects of a pesticide are tests in t mamaliari species. A study
of the teratogenic effects of Technical Metolachior on rats was conducted by
Fritz (1976). The study fourx5 that doses of either 0, 60, 180, or 360 ing/kg/
day during 6 to 15 days of gestation did not affect the offspring of f ale
Sprague-Dawley rats • fetotoxic effects of the cx npound were obsetved. The
only possible effect on the rats was a decrease in food consumption at the
highest dose during the first 1/3 of the experiment which may indicate that
this was the beginning of toxic maternal doses. This study is sufficient for
the assessment of teratology in one species of maninal, and does not show any
evidence of a teratogenic hazard for Metolachior. Data is still needed on a
second maninal ian species.
Reproductive Effects
The health and developnent of the fetus is just one phase in a complex
series of interrelated functions necessary to successful maninalian
reproduction. These include the general health of the adults, including the
health of the mother during pregnancy, the fertility of the male and female,
gametogenesis, implantation, nutritional supplies to the developing fetus,
parturition, lactation, and the health, growth, developnent, and sexual
maturation of the young.
Of special interest amongst potential multigeneration effects is the degree
to which the young have an enhanced susceptibility to pesticide toxicity.
Pesticide metabolism, distribution, storage, and excretion may be
significantly different in younger bodies, and tissues which are changing and
developing may have special sensitivities to the presence of toxic chemicals.
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Infants and children may be affected in health, growth, and developnent by
exposure to, and early storage of, pesticide residues in mother’s milk and
co,mnercial foods, on disinfected surfaces, and ingested accidentally.
The minimum data needed for measuring reproductive effects can be provided
by one study with rats lasting t generations. Diets containing up to
1,000 pfxn Metolachior did not affect reproduction during a three-generation, 2
litters per generation, reproductive study in the rat ( nith and Adler 1978).
These data are sufficient to satisfy the minimum needed for Metolachior.
Clinical Experience
Of all the factors that quantitatively and qualitatively determine toxic
response, ‘species tested’ is second only to ‘dosage’ in importance. Thus the
best subject for the study of toxic effects to man, is man himself, and for
the study of effects to dc neatic animals, is the species of concern.
Information about the effects of a pesticide chemical to man can be obtained
in three situations: cases of poisoning; the use of the compound as a drug;
and actual-use experience, especially that involving occupational exposure.
Cases of poisoning constitute our only source of information on
syinptomology and the approximate dosages of pesticides required to produce
illness in hunans. Dosage range is more established in studies of the medical
uses of certain pesticide compounds, some of iiich are applied directly to the
body for the control of internal and external parasites, others of which
simply have medically useful effects in humans, such as antibiotic or
anaesthetic effects. ‘Actual-use experience’ studies vuld include any
retrospective clinical measures of residues in a particular environment, and
the comparison of those findings with symptoms, deaths, or residues in tissues
or excreta. Most such information centers around studies with workers and the
workplace, because of the greater knowledge the investigator can have about
dosage, schedules and length of exposure, residue samples, and the dynamics of
the occupational enviro rment.
Though information Ercin clinical studies may be useful to the assessment
of a pesticide’s toxicology, the 1 gency does not routinely require such data.
A review of Piency pesticide accident records and a survey of poison control
centers failed to turn up any data on accidents involving Metolachior.
Neither have any data fros occupational exposures, epidemiological studies, or
clinical trials been reported for Metolachior.
Prevention and Treatn nt of Intoxication
Responsibility for the possible adverse effects of pesticide use must
accompany the introduction of these chemicals into the home, factory,
hospital, or field. As has been stressed so far in this Standard, measures
for preventing and alleviating injury by pesticides must be based on a finn
knowledge of their physical, chemical, and biological properties.
Should accidental poisoning occur, we must also be prepared to correctly
diagnose and treat the victim before the onset of serious effects. Of
interest to clinicians in this regard would include: studies about diagnostic
techniques, such as epidemiological analyses of cause and effect, patient
histories, case studies, laboratory teats for residues or secondary
pharmacological effects, and symptomologies; and studies about treatment,
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inti luding the removal of poison by emesis, gastric aspiration, lavage, and
z xiahing, the temporary support of the victim by artificial respiration and the
maintenance of the air x y, and curative therapy, including oxygen therapy,
infusions and transfusions, sedatives, stimulants, antiemetics, steroids,
antibiotics, and antidotes.
Though the l gency does riot routinely require studies to be perfotmed
on the prevention and treatment of intoxication, it is critical to the
registerability of a pesticide that an effective first aid treatment be
available for the treatment of accidental exposures [ see 40 CFR 162.11 (a)(3)
(iii)].
In first aid treatments for accidental ingestion, vaniting should be
induced only for chemical preparations which do not contain petroleum
distillates, or if they do, also have a very high acute oral toxicity.
Technical Metolachior does rot contain petroleum distillates, and so the
inducement of vaniting is an appropriate first aid for accidental ingestion of
the Technical. The presently registered E nulsifible Concentrates, however, do
contain petroleum distillates, but do riot have a high enough acute oral
toxicity (Category III) to risk the lung damage that may result if sane of the
chemical is breathed in when vaniting.
The first aid treatment rexirmerx3ed for Technical Metolachior, or any
formulation of Metolachior which does not contain petroleum distillates, is as
follows: ‘If iithalat ion exposure occurs, the victim should be noved into fresh
air, and medical attention should be imnediately sought. If Metolachlor is
swallowed, vaiiiting should be induced. If contact is made with eyes and/or
skin, the exposed area should be flushed with water.’
The first aid treatment for formulations of Metolachior which do contain
petroleum distillates is as follows: ‘If inhalation occurs, the victim should
be noved into fresh air, and medical attention should be iniiiediately sought.
If contact is made with eyes or skin, the exposed area should be flushed with
water, and medical attention should be sought. If swallowed, prcii ptly drink
egg white or gelatin solutions; or if these are not available, water. Call a
physician iirntediately. [ Note to Physician : If swallowed, there is rio
specific antidote. i not induce emesis as a chemical pneumonitis may occur if
aspirated. Lavage stanach. Deposit 50 grams of activated charcoal in a water
slurry in the stanach. Give a saline laxative and supportive therapy as
needed.]’
A iiore c xiiiplete account of an effective medical treatment for intoxication
with pesticide products containing Metolachlor is currently in preparation.
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DISC IPLINARY PEVIEW
Toxicology Profile
Toxicology Hazard Assessment
Generic Data Gaps
Registration Requirements
Suggested Labeling
Toxicology Profile
Technical Metolachior : Sufficient data were available to support
an assessment of the Technical’s acute toxicity. The relatively high
acute oral LD—50 in rats (2780 mg/kg) and the emetic effects in dogs
indicate a low acute oral toxicity to humans. Dermally, at least in the
rabbit, Metolachlor does rot appreciably penetrate intact skin. D3ses of
up to 10,000 mg/kg caused no signs of toxicity and little irritation.
Pending receipt of data on abraded skin, it i uld appear that Metolachior
v uld not be readily absorbed through human skin. The lack of toxic signs
or irritation from high acute dermal exposure in test animals indicates
that manufacturing—use Metolachlor has a law dermal toxicity to humans.
Testing of acute inhalation toxicity in rats failed to elicit any deaths
at the maximum achievable concentration (1.752 mg/l for 4 hours exposure),
and so a very low inhalation toxicity to humans for manufacturing—use
Metolachior may be expected.
Information was also available on the irritation and sensitization
potential of Technical Metolachlor. In a primary eye irritation study
conducted on albino rabbits, no signs of irritation were cbserved. Based
on the rabbit as an indicator species, Metolachlor is not expected to be
irritating to human eyes. A dermal sensitization study in guinea pigs
indicated that Metolachlor was a skin sensitizer to that species.
Metolachior should therefore be considered a potential skin sensitizer in
humans.
Adequate chronic toxicity data were rot available for Metolachlor. No
study on chronic feeding has yet been subaitted; oncogenicity data are not
currently usable. Though data on a second species will be needed, there
was one study of teratogenic effects in rats, and it reported no
observations of teratogenic or fetotoxic effects due to Metolachior. The
one available test of reproductive effects in the rat showed no effects on
reproduction through three generations. Metolachior has been tested in
t systems for mutagenicity: a bacterial system, and an in vivo system
in the nouse. No evidence is presented in either study to suggest that
Metolachior has any mutagenic potential.
Emulsifiable Concentrate : F r E.C. formulations of less than or equal
to 8 lbs. per gallon, the reported values of 1,890 mg/kg or higher
indicate a relatively high acute oral LD-50 in rats. This relatively
high value implies a low acute oral toxicity to humans for EC.
formulations of 8 lbs. per gallon or less. Dermally, at least in the
rabbit, existing E.C. formulations of Metolachlor of 8 lbs. per gallon
or less do not appreciably penetrate intact skin, and doses of up to 3,038
mg/kg produced no signs of toxicity in the New Zealand rabbit. Pending
receipt of data on abraded skin, it wuld appear that E.C. formulations of
8 lbs. per gallon or less uld not be readily absorbed through human
skin. From existing data, it can thus be assumed that E.C. formulations
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of 8 lbs. per gallon or less present a low overall acute toxicity to
humans via the intact dermal mute. While the oral and dermal mutes
presented a relatively low toxicity, the inhalation route resulted in a
more significant effect. Testing of acute inhalation toxicity in rats
elicited LC—50 values of not less than .94 mg/i of air for existing E.C.
formulations of less than or equal to 8 lbs. per gallon. This cxnstitutes
a high toxicity fran inhalation exposure.
The potential for local irritation and sensitization also appears to
be significant. Based on the albino rabbit as an indicator species,
existing E.C. formulations of 8 lbs. per gallon or less will produce
n derate erythma, edema, and second degree burns (severe irritation). A
dermal sensitization study in guinea pigs indicated that E .C. formulations
are also potential skin sensitizers in humans. In a primary eye
irritation study conducted on the albino rabbit, E.C. formulations of
Metolachior of 8 lbs. per gallon or less were found to cause irreversible
corneal c acity and severe irritation in unrinsed eyes. The potential
effects on the h .maan eye are expected to be as serious.
Toxicology Hazard Assessn nt
Technical Metolachior : Considering first the potential for human (or
danestic animal) exposure to manufacturing—use Metolachior, it was stated
in the Exposure Profile that there is little likelihood of oral exposure,
and that because of the low vapor pressure of the viscous liquid, there is
also little chance of inhalation exposure. The most likely type of
exposure for persons involved in the manufacturing, handling, storage, or
shipnent of Technical Metolachior is a repeated dermal exposure, and
occasionally, by accident, a single occular exposure.
Because of Technical Metolachlor’ s low acute oral toxicity, and very
low inhalation toxicity, we may di niss these unlikely exposure routes as
significant sources of hazard • The occasional occular exposure is also
not of serious concern, as no eye irritation effects uld be expected.
But with respect to dermal exposures, though it has been shown (pending
receipt of data on abraded skin) that Metolachlor is not readily absorbed
by the skin, the likelihood of repeated dermal exposures raises t
significant concerns: first, Metolachlor has been observed to elicit a
dermal sensitization reaction; second, though no evidence of teratogenic,
fetotoxic, reproductive, or mutagenic effects have so far been presented,
the available information is presently insufficient to be certain of the
absence of chronic effects. Thus the risks to humans caused by repeated
dermal exposures to a Technical Metolachior solution cannot be concluded,
and the only presently krx n hazard of manufacturing-use Metolachior is the
potential dermal sensitization problem for factory, transport, or re—
formulation rkers.
milsifiable Concentrate : The hazards to hwnans and dc nestic animals
that may arise from the end—use of an agricultural pesticide are of three
kinds: those hazards to hwnans which arise in the tank mixing, dilution,
application, storage, or disposal of the end-use chemical; those hazards
to hz.mans and danestic animals which arise as a result of ambient
residues from pesticide application, storage, or disposal, including
residues in air, z iter, and edible wildlife; and, finally, those hazards
to humana or domestic animals which may arise as a result of anticipated
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residues in harvested food or feed. The first two kinds are considered
here -in the To icolog j chapter. The last kind will be considered in the
‘Tolerance Reassessment’ section of the Residue Chemistry chapter.
As was stated in the Exposure Profile, there is little chance for oral
exposure to E.C. Metolachlor, except by accidental ingestion. But there
is a significant chance for dermal and eye exposure for chemical
applicators who are tank mixing, diluting, or loading. There is also a
significant chance of inhalation exposure for applicators, agricultural
workers, and livestock in the proximity of the spraying. Though spray
drift properties of Metolachior applications have not been established,
ambient air residue exposures may cx)nceivably occur to persons or
livestock outside the spray area. aie to leaching and a stability to
hydrolysis, residues may also be found in nearby freshwater streams or
ponds, thus posing the threat of repeated exposures to livestock drinking
the water or grazing on nearby plants, or to person’s ingesting contaminated
fish.
Accidental oral exposures, because of the E.C. s relatively low acute
toxicity, do not present an unusually serious accidental poisoning hazard.
However, the routine use of E.C. tolachlor directly results in a n .nnber
of significant hazards. Eye exposures can be seriously damaging, and the
applicator whose eyes are unprotected during mixing, loading, or diluting,
runs a significant risk of irreversible corneal opacity and severe
irritation. Similarly, the applicator with unprotected hands or face runs
an acute risk of erythma, edema, and second degree burns, and if the
exposures are repeated, a risk of a sensitization reaction. Thirdly, a
significant acute toxicity risk is borne by applicators whose respiration
is unprotected during spraying. ? jricu1tural workers or dcmestic
animals in the inutediate proximity of this spraying are similarly
endangered. Finally, though tolachlor is not readily absorbed through
the skin, chronic effects fran a repeated dermal exposure or inhalation
exposure to E.C, tolachlor cannot presently be ruled out.
Ambient residues fran the application of EC. r4etolachlor will present
parallel, though lesser, hazards to persons or livestock outside the spray
area. The ii st significant acute hazard fran ambient residues would be an
inhalation hazard. Of potential concern are the long-term, repeated
exposures for livestock and hunans feeding on nearby aquatic and plant
life, possibly resulting in undetermined chronic effects.
Generic Data Gaps
The following are gaps in the ‘Ibxicology data base needed to adequately
support a Registration Standard for Metolachior. After each gap is listed the
section in the Proposed Guidelines of August 22, 1978 (40 CFR Part 163) which
describe that type of test and when it is required.
For Technical Metolachlor:
1) Subchronic Oral Dosing — Acceptable pathology 163.82-1
evaluation is required for both the rat and
dog studies.
2) Oncogenicity — Completion of the nouse study 163.83—2
and testing on a mammal other than the nouse
(the laboratory rat is preferred) is required.
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3) Chronic Feeding — A chronic feeding study using 163.83—1
the laboratory rat is required.
4) Teratology — A teratology study in a marrinalian 163.83—3
species other than the rat is required.
For Emulsifiable Concentrate t4etolachlor: none
Registration Requirements
In order to ensure that their products fall under the regulatory authority
of this Registration Standard, and in order to ensure that the parameters of
potential hazard presented in this Standard are rot exceeded, certain data
sutinissions pertaining to ¶Ltxicology are required of each individual applicant
for the registration of the manufacturing and end—use formulations of
Metolachior. General Itxico1ogy requirements for registration are outined
and discussed in the Proposed Guidelines for Registration of August 22, 1978
(40 CFR Part 163). Special hI xicology requirements for pesticide products
containing Metolachior are listed below.
For both Technical and Emulsifiable Concentrate Metolachior:
Dermal Sensitization (Guidelines Section 163.81—6) — Applicants
for registration of Technical or Emulsifiable Concentrate
Metolachior will be required to docui ent the lack of dermal
exposure in manufacturing facilities or to nonitor and sutinit
skin sensitization data fran such exposure.
For Emulsifiable Concentrate Metolachlor (8 lbs./gallon or less):
So as to establish the chemical equivalency (the same active
and inert constituents in equivalent percentages) of a proposed
product to the cxinposition of the pesticide formulations on
which this Standard is based, each applicant must sutinit or cite
data that demonstrate that the proposed product is within the
established range for each of the following properties. In the
event that the result of any of the required tests is outside the
established range, the applicant must successfully petition the
Agency to amend the Standard to include the wider range prior to
seeking registration. (See Section 162.10 of the CFR 40 for an
explanation of ‘Ibxicity Categories I through IV.)
1. Acute Oral Ltxicity
Any E .C. Metolachior of 8 pounds per gallon or less which
falls into Category III or Category IV will be considered
within the scope of this Standard with regard to acute oral
toxicity.
2. Acute Dermal ‘DDxicity
Any E.C. Metolachior of 8 pounds per gallon or less which
falls into Category III or Category IV will be considered
within the scope of this Standard with regard to acute
dermal toxicity.
3. Acute Inhalation ‘l xicity
Any E.C. formulation Metolachlor of 8 pounds per gallon or
less which falls into Category II or a nixnerically higher
category will be considered within the scope of this
Standard with regard to acute inhalation toxicity.
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4. Primary Eye Irritation
Any E.C. ? tolachlor of 8 pounds per gallon or less which
falls into Category I or a numerically higher category will
be cx,nsidered within the scope of this Standard with regard
to primary eye irritation.
5. Primary Dermal Irritation
Any E.C. formulation tolachlor of 8 pounds per gallon or
less which falls into Category II or a numerically higher
category will be cxxisidered within the scope of this
Standard with regard to primary dermal irritation.
Suggested Labeling
See Section 162.10 of the CFR 40 for an explanation of the Agency’s
established toxicity labeling requirements.
For Technical Metolachior:
The required signal word is “CAtJPION” followed by “Keep out of
reach of children.”
¶IkD reduce the risk frau oral exposure, the Category Iii
statement, “Harmful if swallowed ,“ is required. Technical Metolachior
is in Category IV with regard to inhalation exposure, therefore, no
inhalation hazard precautionary labeling is required. Except for the
risk of skin sensitization, the Technical is in Category IV with
regard to dermal exposure; therefore, no dermal hazard precautionary
labeling is required other than the following derinal sensitization
warning: “May cause skin sensitization, Wear protective clothing
while handling or using this product.” Technical Metolachior is in
Category IV with regard to eye irritation, therefore, no eye hazard
precautionary labeling is required.
The required first aid statement for manufacturing—use
Metolachior is: “If swallowed, induce vauiting. Flush exposed eyes
and skin with water.”
For E uulsifiable Concentrate Metolachior (8 lbs./gallon or less):
The required signal word for E.C. formulations varies as a
function of the numerically lowest toxicity category assigned as a
result of the five ‘r gistration Requirements’ tests performed on the
particular formulation: If the lowest toxicity category assigned is
Category I, then the Category I signal word “Danger” followed by “Keep
out of reach of children” shall be r ployed. In aldition if the
Category I requirements have been satisfied for oral, inhalation, or
dermal toxicity, the word “Poison” shall appear in proximity to a
skull and cross bones. If the lowest toxicity category assigned is
Category II, then the Category II signal word “Warning” followed by
“Keep out of reach of children” shall be employed. If the lowest
toxicity category assigned is Category III or IV, then the Category
III/IV signal word “Caution” followed by “Keep out of reach of
children” shall be employed.
Products with a demonstrated oral LD-50 in rats of 500—5,000 mg/
kg must bear the Category III labeling precaution “Harmful if
swallowed”, to reduce the risk of hazard fran oral exposure.
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Products with a demonstrated oral LD—50 in rats of greater than 5,000
(Category IV) are rot required to bear precautionary labeling with
regard to oral exposure.
Products with a demonstrated intact dermal LD-50 in New Zealand
rabbits of 2,000—20,000 nq/kg must bear the Category III labeling
precaution “Avoid contact with skin”, to reduce the risk of hazard
fran dermal exposure. Products with a demonstrated intact dermal LD-
50 in New Zealand rabbits of greater than 20,000 mg/kg (Category IV)
are rot required to bear precautionary labeling with regard to dermal
exposure.
Products with a demonstrated inhalation LC—50 in albino rats of
.2-2 mg/i of air must bear the Category II labeling precaution “to not
breathe vapors”, to reduce the risk of hazard fran inhalation
exposure. Products with a demonstrated inhalation LC-50 in albino
rats of 2—20 mg/i of air (Category III) must bear Category III
labeling precaution “Avoid breathing vapors”, to reduce the risk of
hazard fran inhalation exposure. Products with a demonstrated
inhalation LC-50 in albino rats of greater than 20 mqjl (Category IV)
are not required to bear precautionary labeling with regard to
inhalation exposure.
Products with a demonstrated primary eye irritation effect of
severe irritation in unrinsed eyes or irreversible corneal opacity
must bear the Category I label precaution “Corrosive, causes eye
damage. Wear goggles or face shield when handling” to reduce the risk
of hazard fran eye exposure. Products with a demonstrated primary eye
irritation effect of reversible corneal opacity (7 days) and
conjunctival effects (partly reversible in 7 days) in unrinsed eyes,
and slight iris and moderate conjunctival effects (reversed in 3 days)
in rinsed eyes must bear the Category II label precaution “Causes eye
irritation” to reduce the risk of hazard fran eye exposure. Products
with a demonstrated primary eye irritation effect of reversible
irritation (7 days) must bear the Category III label precaution “Avoid
contact with eyes” to reduce the risk of hazard. Products with no
d ionstrated primary eye irritation probl are not required to bear
precautionary labeling with regard to primary eye irritation.
Products with a demonstrated primary dermal irritation effect
described as severe irritation or as moderate erythma, edema, and 2nd
degree burns at 72 hours must bear the Category II label precaution
“Causes skin irritation” to reduce the risk of hazard fran dermal
exposures. Products with a demonstrated primary dermal irritation
effect described as moderate irritation at 72 hours must bear the
Category III label precaution “Avoid contact with skin” to reduce the
risk of hazard fcun dermal exposures. Products with a primary dermal
irritation effect described as mild or slight at 72 hours, or as
possessing a primary irritation index of 1.62, are rot required to
bear precautionary labeling with regard to dermal exposure.
Products with a demonstrated ability to cause dermal
sensitization must bear the label precaution “May cause skin
sensitization. Wear protective clothing while handling this product”
to reduce the hazard.
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The required first aid statement for E.C. formulations
(containiug petroleiin distillates) is: “If inhalation occurs, the
victim should be uoved into fresh air, and medical attention should be
inmediately sought. If contact is made with eyes or skin, the exposed
area should be flushed with water, and medical attention should be
sought. If swallowed, prcinptly drink egg white or gelatin solutions;
or if these are not available, water. Call a physician iiiiiiediately.
[ Note to Physician : If swallowed, there is no specific antidote.
n notTnduce emesis as a chemical pneurronitis may occur if
• Lavage stcknach. t posit 50 grams of activated charcoal in a
water slurry in the stanach. Give a saline laxative and supportive
therapy as needed .1
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BIBLIOGRAWY
(Reserved)
In order for the provisions of FIFRA concerning data cc npensation (Section
3(c)(1)(d)) to be effective under Registration Standards, data used in direct
support of the Standard for each type of product must be accurately listed,
enabling applicants and their arbitrators to determine z iat data do and do not
support the registrations of individual pesticide products. Thus, for each
disciplinary chapter, studies used to evaluate hazard and establish Standards
for the manufacturing—use ch nical and for each type of end-use formulation
will be listed separately.
¶I protect present and potential arclicants for the registration or re-
registration of products containing Metolachior, the citations appropriate to
each disciplinary chapter will rot be published in this Sample Standard, though
a ccxrtplete Bibliography is provided at the end of the document.
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RESItUE CHEMISTRY
INTRODUCTION
For any pesticide thich has uses that may directly result in residues on
food or feec4 the Agency sets an allowable resi4ue level for each conmodity on
which it may occur. An allowable residue level for a particular chemical on a
particular con nodity is a function of the chemical ‘s toxicity, the percentage
of an average daily diet comprised by the commodity, and the amount of residue
that can be expected to occur on that coninodity at the maximwn directed rate
of application. The total crinount of chemical to which a person may be exposed
from all sources should always be less than the toxicological estimate of a
safe ‘Allowable r ily Intake.’
¶LDPICP L DISCUSSIONS
Metabolism in Plants
Metabolism in Animals
Analytical Methods
Residue Data
Present ‘Iblerances
Regulatory Incidents
Metabolism in Plants : (Corn and Soybeans)
In addition to that may remain of an original application of the chemical,
residues may also consist of the chemical’s metŕbolites, a formed by the
plant crop thick it was applied to protect. The major and minor pathways of
thechemical’s absorption, transfor ,nation, and distribution can be deduced
experimentally from the analysis of r’adiolabeled applications. Applications
by various routes, for example to the roots or leaves, will show differences
in absorption rates. The distribution of the chemical and its metabolites can
be examined by measuring the radioactivity present in various plant
fractions. Isolated metabolites can then be characterized by chromatography,
partitioning, or electroplioresis. Metabolic transformations often result in
the polarization of the foreign chemical to facilitate elimination.
Metabolitee characterized as highly polar may have undergone conjugation with
naturally occurring amino acids, sugars, or sugar acids. Further chemical
analysis can help identify the exact nature of the conjugations. Other
possible major transformations can occur by hydrolysis, oxidation/reductions,
or the breaking of unstable bonds. The absorption, distribution, and
metabolic fate of the chemical determine the potential quantity and identity
of pesticide residues in plants used for food or feed.
The absorption, distribution, and metabolic fate of Metolachlor were
investigated in corn plants grown under field and greenhouse conditions
(Sumner and Cassidy, 1974c,d) and in soybeans grown under greenhouse
conditions only (Sumner and Cassidy, 1975).
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Ring—labeled Metolachlor was applied as a pre—emergence treatment at 2 lbs.
ai/acre. For corn, it was mixed with soil to result in a concentration of
approxianately 2 ppn and applied to field and greenhouse soils. For soybeans,
it was added to soil and plantings ware incubated in the greenhouse. The
maximum levels of residues found in the various plant parts, based on total
rai ioactivity, ware as follows: corn grain, greenhouse and field, 0.05 PrITL and
0.02 çin, respectively; corn forage, greenhouse and field, 0.72 and 0.17 ppn,
respectively; soybeans 0.17 n, soybean hay 2.66 prIn, soybean oil 0.01 p xn and
soybean meal 0.14 rp . These data show that the total residues in soybeans are
higher than those in corn.
The metabolism of to1ach1or by corn plants consists of a major and a
minor pathway. The Figure in the Residue Chemistry Disciplinary Review
depicts these pathways for both corn and soybean plants 1 Marco 1975).
When corn plants ware grown in soil treated with 0- C-Metolachlor at 2
lbs. ai/acre (Sumner and Cassidy 1974d), extracts of 4—week old corn plants
contained less than 10% of the extractable radioactivity present in the
organic fraction. Very little, if any, of the activity was present as parent
Metolachior. tbre than 80% of the remaining activity was found in the polar
fraction. UC characterization indicated the presence of at least 10
metabolites. The highly polar nature of these metabolites indicated
conjugation of the parent and/or its metabolites had occurred with natural
products such as anino acids, sugars, or sugar acids (Sumner and Cassidy,
1974c).
One metabolic pathway in the corn plants involves conjugation of
Metolachlor with glutathione (Sumner and Cassidy, l974b). Fourteen percent of
the radioactive Metolachior recovered fran corn leaves was found conjugated
with glutathione. It appears that degradation occurs through a thio-ether
bond forming a glutathione conjugate via the reactive chioroacetyl noiety of
Meto lachlor.
Metabolites, which upon hydrolysis, produce 2— [ (2—ethyl-6--methylphenyl)
aninoj -1-propanol (HP-001) and 4- (2-ethyl-6-methylphenyl ) -2-hydroxy-5-niethyl-3-
iwrpholinone (HP-002) were found to be aiiuon in plants and in animals, fran
high level feedings of Metolachior (Hambock, l974a ,b,c; Mattson, 1975). When
partly purified plant conjugates ware cleaved by a reduction reaction with
Raney nickel, which breaks thio-ether bonds (Gross, 1974a and Gross, l974b),
t canpounds, N- (2-ethyl-6-methylphenyl ) -N- ( 2-methoxy-l-methylethyl) acetamide
(MET-QOS), and N— (2-ethyl-6-methylphenyl ) -N- ( 2-hydroxy-l-methylethyl ) acetamide
(MET—006) ware produced, indicating that these npounds ware i oieties of
sulfur—bonded conjugates. These t x canpounds represent 80% of the
radioactivity extracted fran the corn leaves. They ware positively identified
by GLC and mass spectranetry.
Further residue characterization, involving rigorous HC1 hydrolysis
(Sumner, Thanas, and Cassidy, 1975), showed the presence of either 2— [ (2—ethyl—
6—methyiphenyl ) anino] —1—propanol (HP—001) or 4- (2—ethyl—6—methylphenyl ) —2-
hydroxy—5-methyl—3—norpholinone (HP—002). These data suggest that the
canpounds present before hydrolysis are predcminantly aipha-thioglycoside
metabolites and the alpha-oxygen glycoside analogues. The relative arr unts of
the cxiiçounds indicate that the major pathway of metabolism involves
conjugation with glutathione, breakage of the thio- bond to form the
mercaptan, conjugation of mercaptan with glucuronic acid, hydrolysis of methyl
ether, and conjugation of the alcohol with a neutral sugar. A minor pathway
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involves chioro replacement by hydroxyl and/or direct conjugation with
glucuronic acid, followed by demethylation and conjugation of the hydroxyl with
a neutral sugar, all forp. ng oxo—conjugates.
When radiolabeled - C-Metolachlor was applied to growing soybeans
(Sumner and Cassidy 1975b), characterization of the extracted residues
indicated that the metabolic pathways in soybeans are similar to those
observed in corn. Thin-layer chranatography and partitioning data indicated
that higher concentrations of less polar rnetabolites will occur in soybeans
when ccinpared to corn grain.
¶I xicology reviewers expressed concern about the possible presence of
monochloroacetic acid as a canponent of the residues of Metolachior, resulting
frcxn metabolism or degradation of the parent canpound. ‘])Dxicology postulated
that the chloroacetyl group could split of f as nonochioroacetic acid and occur
as part of the terminal residue. However, r sidue Chemistry reviewers can
find no reason to expect itonochloroacetjc acid to occur as a residue following
use of Metolachior. While there is no definitive data on the matter, the
conclusion is based upon the unique chemical and biological stability of the
amide bond and the relatively unstable carbon-chlorine bond in Metolachior.
Thus, it is postulated that any hydrolysis of the amide uld be preceded by
displacement of the chlorine. Consequently, the presence of nonochioroacetic
acid as a product of metabolism is not likely to occur.
The above studies adequately define the fate of Metolachior in soybeans and
corn for the purposes of establishing tolerances.
Metabolism in Animals
The identity of residues in animal prod ucts used for food may, as with
plants, be largely determined by the metabolic fate of the chemical in the
living organism. Of livestock that may ingest chemicals through treated feed
or forage, or that are treated directly with dips or sprays, ruminants or cud-
chewing animals (such as cattle and goats) may produce a different metabolic
effect than non-ruminants, and poultry may produce a third type of effect.
Gastrointestinal absorption, biotransformation, and body distribution are
usually studied by the feeding of animals with the vnlabeled or radiolabeled
chemical. The degree to which the parent cc npound and its plant metabolities
are absorbed or excreted can often vary with the forage or fodder crop on.
which the chemical i s administered, and so actual feeding practices are
usually approximated. Residues in exereta, blood, milk, eggs, or tissue are
then measured and characterized. Where the chemical identity of the
metabolites is inaccessible to simple analysis, the subjection of these
residues to further controlled reactions, such as acid hydrolysis, may itself
yield identifiable products. These products can then serve as a reference for
the original residue, so that other residue analyses can be performed to test
for its presence.
Metolachlor is rapidly metabolized and almost totally eliminated in the
urine and feces of rtxninants (goats), non-ruminants (rats), and poultry (1 ger
and Cassidy, 1974a; Hambock, l974 4 Qith, 1974). These findings were made in
studies using both unlabeled and C—ring—labeled Metolachlor. Metolachlor
per sewas not detected in any of the excreta or tissues.
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i 3ditional studies with goats (Counselman and Roger, 1973; Roger and
Cassidy, 1974a,b confirmed the finding that the urine and feces contain
almost all the metabolized products.
In animals, trace 1ounts of metabolized Metolachior were found in kidneys,
liver, blood, and milk (Bianetric Testing Incorporated, 1973; Hambock, 1974a,
b,c; Schenker, 1975a).
No residues were found in eggs, meat, or fat samples of laying chickens.
The only metabol ite found, in the liver (at 0.02 — 0.03 pçm), was the one
which upon hydrolysis yields HP—00l (Mattson, 1974, 1975). No precursor of the
hydro1ysi 4 product HP—002 was found in the liver (Guth, 1974).
When C—labeled netabolites of Metolachior, bio-synthesized in corn,
were fed to goats, no parent Metolachior nor any inetabolites were found in the
animals’ tissues or milk (Ciba—Geigy Limited, 1973; Schenker, 1974, l975b).
It is concluded that the metabolism of Metolachior in animals appears to be
similar to and as c nplex as that in plants. Whereas plants retain their
metabolic products, animals eliminate their Metolachior metabolic 1 roducts
alnost entirely. Various studies with unlabeled Metolachlor and C—ring
labeled Metolachior fed to different animals indicate clearly the identity and
the aiounts of the metabolites which result as residues in the excreta,
tissues, milk, and eggs.
Although the exact metabolic pathway of Metolachlor in animals is not
known, the available metabolic studies adequately delineate the fate of
Metolachlor in animals for the purposes of establishing tolerances for corn
grain and soybeans. (For an evaluation of rat metabolism data, please see
¶L’bxicology Chapter.)
Analytical Methodology
There must be available, before a tolerance may be granted, practicable
analytical methods for the detection and measurement of the residue and
its metabolites. Every coninodity considered for a tolerance must have some
applicable method. Such methods are often published and widely used; others
may involve adaptations of coninon analytical procedures. In general, any
analytical method suggested for consideration must be characterized in four
ys: first, there should be scine assurance as to the efficiency of the
extraction procedure, so that the analysis is not carried out on partial
samples; second, the method should afford a measure of the ‘total toxic
residue’, including toxic degradation, metabolic, or other conversion products;
third, the method must be thoroughly vaiidated by analyses of representative
samples in cc nparison to blank values significantly lower than the pro posed
tolerance; fourth, the validation should conclude with an estimate of
sensitivity, i.e., the least concentration of pesticide iich can be detected
with a reasonable degree of assurance.
At least one method must be suitable as a regulatory enforcement method, in
that it does not require the use of untreated crop samples for blanks, that it
is rapid, that it makes use of commonly available equipment and reagents, and
that it is sufficiently specific to identify and measure a specific pesticide
in the presence of other residues likely to occur on the same commodity.
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Metolachior in Corn and Soybeans
The residue data sutinitted for corn were obtained by the use of
Methods AG—265 (Balasubramanian, Gold, and 1 ss, 1974) and AG—277
(Balasubramaniari, Aziz, and Ross, 1975). The residue data for soybeans
were obtained by Method AG-286 (Aziz and } ss, 1975). st of the corn
residue data v re obtained by Method AG—265. This method utilizes HC1 to
hydrolyze Metolachior and those metabolites which are capable of
conversion to 2- [ (2-ethyl-6--methylphenyl)aminol —1--propanol (HP—001).
In Method AG—265, fifty grams of ground or chopped sample is ref luxed
with 250 ml. of 6N HC1 for 116 hours. The aqueous extract is filtered off,
neutralized, and made basic with NaOH solution and extracted twice with
hexane. The xxnbined hexane extracts are chranatoqraphed on an alumina
column. The residues of HP—OOl are eluted using 5% ether in hexane. The
eluate is evaporated and the residues are taken up in 0.5 ml of benzene.
i- n aliquot of the sample solution is injected into a gas chrcinatograph
equipped with a Coulson eletrolytic conductivity detector. Known amounts
of Hp—OOl are used for standardization. Peak heights are compared with
those of the standard for quantification. Residues are expressed as parent
Metolachlor equivalents using the 1.47 factor.
The method was validated by the petitioner in three ways: (1)
fortification with the determined compound, HP—00l; (2) fortification 1 ith
parent Metolachlor, (CCM—001); and (3) comparison of GLC a lyses of C—
labeled residues from metabolism study samples with total C—combustion
analyses of duplicate samples.
Recovery for samples of grain, forage, silage, and stover fortified at
levels of 0.05—2.0 pp*n with HP—OOl averaged 81%. All control samples were
determined to have <0.03 ppni (the method sensitivity). Fortification
studies using parent Metolachlor averaged 63% for levels of 0.05—0.2 ppn
in stover. 14
The total C-activities in samples of corn plants taken fran both
the field and greenhouse studies were determined by combustion (Hermes,
1972). The combustion technique determi d all residues (both extractible
and nonextractible) after conversion to CO . The residues
(expressed as COM—00l) determined by Chemica Method AG—265 ranged from
12% (mature crop) to 27% (ir unature forage or silage) of the total residues
found by ccmbustion techniques. Comparisons were al made of the total
extractible residues by the chemical method vs. the C—combustion
method using t extraction solvent sys ms, HC1, and combined chloroform—
methanol solvent. About 50—60% of the C—residues in mature corn were
extractable using either p thod. The chemical method determined 20—30%
of the total extractable C—residues.
Except as stated directly below, method AG—265 (Balasubramanian, Gold,
and 1 ss, 1974) was found to be specific in the presence of other
pesticides with established tolerances on corn. Six pesticides were not
available for testing: EPN, Vegadex, Avadex, Landrin, 4—amino pyridine,
and 2—( thiocyananethylthio)—benzotriazole. P n alternate column liquid
phase is available and provides additional specificity for residues of
Metolachlor.
Method AG—277 (Balasubramanian, Aziz, and Ross, 1975) is a
modification of AG—265 which includes partitioning, clean-up,
derivatization, and micro—coulanetric GLC steps determining t hydrolysis
products: 2— [ (2—e thyl—6- -methylpbenyl ) amino] —1—propanol (HP-00l) and 4— (2-
ethyl_6_methylphenyl)_2_hydroxy —5-methyl—3-llorphOlinOne (HP-002).
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Residues of Metolachior (ca4—0O1) in corn grain, ears, forage, fodder
and stover are converted to a mixture of HP-00l and HP-002 by refluxing 16
hours with 6N HC1. The filtered acid extract is partitioned with
dichioranethane to extract the HP-002 into the organic phase. The agueous
phase containing HP-00l is m 1e strongly basic with 50% sodiun hydroxide
and subjected to distillation—partition into isooctane using a Bleidner
apparatus. The isooctane phase containing HP—00l is cleaned up by using
an alunina cohinn. HP-0Ol is determined with a gas chrcmatograph equipped
with a Coulson electrolytic conductivity niltogen detector. It is
quantified by canparing it with the peak height of a standard anount of HP —
001 and then calculated as COM—00l using the 1.47 equivalence factor.
The dichloranethane phase containing HP-002 is washed with 5% sodium
carbonate solution and further cleaned up using an altiuina oolunn. The
chloroethaixil derivative of HP-00 is formed by reaction with boron
trichloride/2—chloroethanol at 90 C for 15 minutes. The derivative is
partitioned into hexane and an aliquot is cleaned up using silica gel and
a1t uina colunns. A gas chranatograph equipped with Dohrmann
microcoulanetric chloride detector is used for analysis. For
quantification, the peak area is cx npared to that of peak areas of
derivatized standard HP—002. Residues are calculated as CC14—OOl using
the conversion factor 1.14.
Controls for HP—001 usually ranged fra u less than 0.02 ppm to 0.05
*n. In sane samples, the controls ranged up to 0.1 ppm due to an
interfering peak. We consider the sensitivity of the method for HP-001 to
be 0.05 ppm or less. Recoveries for 69 samples of fodder, forage, grain,
or ears, fortified at 0.02 and 0.20 ppm, ranged fran 57—115% with an
average of 65%. Typical recovery data residues of HP—002 for samples
fortified at 0.05-0.20 ppm ranged fran 45—102% with an average of 62%. The
method sensitivity is considered to be 0.10 zn for HP—002 when calculated
as (ThI-00l.
The method used for the soybean residue data is Method AG—286 (Aziz
and I ,ss, 1975). This method, “Analytical Method for the Determination of
Residues of t tolach1or soybean Metabolites (as HP-OOl and HP-002) by Acid
Hydrolysis,” is the method for regulatory enforc uent which will be
incorporated in the FI pesticide Analytical Methods, Vol. II. Method AG-
286 was tried out in one of EPA’ s laboratories and found to be
acceptable.
Method AG—286 was tested for specificity with 54 of the 58 pesticides
registered on soybeans. DC-200 and Carbowax 20 M are available as
alternate liquid phases to enhance the specificity of the GLC determinative
steps.
Metolachlor in Animal Tissues
Analyses of meat, milk, and egg samples re conducted by methods
reported in Basle RE24 5/74 (Hormann, Gith, Formica, and Schenker, 1974) and
Basle RE 4 2/75 (Ramsteiner and Karlhuber, 1975). Analytical method (RE74 2/
75) accounts for “caiibined residues” of Metolachlor, determined as HP—OOl
and HP—002.
In the first method (RE74 5/74), the herbicide and the potential
metabolites and/or conjugates in animal products are subjected to acidic
hydrolysis. The resulting solution is m 1e alkaline before steam-
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distillation; extraction of residues into isooctane is effected by means
of a steam distillation—extraction head. The HP—OOl fraction is cleaned
up by using an alumina column and, if necessary, by TLC.
The HP—OOl “residues” are detected by gas chranatography/mass
spectralletry. This method is a minor modification of AG—265 and was used
for the gas chranatographic analysis of milk, blood, meat, fat, liver,
kidney, egg white and egg yolk. The limits of detection for HP—00l are
0.006 p xn for milk, 0.015 p n for eggs and chicken tissues, and 0.02 pp n
for a tissues.
The second method (REN 2/75) determines all residues which are
hydrolyzed by acid to HP—0O1 and HP—002. HP—002 is converted to a
derivative which is determined by gas chrcinatography. This method for
animal tissues involves minor n,3difications of Method AG—286. The
reported limits of detectibility are 0.01 p u in milk, and 0.04 in for
meat, liver, and kidney.
Method REM 2/75, (X 4—001, “Determination of Ibta1 Residues in Material
of nimal origin” (Ramsteiner and Karihuber, 1975), was tried on beef liver
in one of EPA’S laboratories. Samples fortified in duplicate with HP—00l
gave 99% and 100% recovery. Samples fortified in duplicate with HP—002
showed 43% and 45% recovery.
Methods PA3—286 and REM 2/75 were found to have 3equate specificity
and are judged satisfactory for enforcanent purposes.
Residue Data
In addition to provisions for analytical methodology, a second
prerequisite to the granting of tolerances is the generation of supporting
data. Residue experiments generally consist of:
2) Data about the stability of extracted residues wider storage;
2) An examination of raw consumable commodities for residues of the
pesticide chemical after treatment corresponding to the proposed
uses.
These commodities should include both the treated organism and city plants,
livestock, or consumable wildlife that may be expected to acquire residues by
feed, forage, or unintentional exposure. Where residues are likely to occur
in plant parts which are used for animal feeds, it is necessary to have
experimental evidence that such levels in feeds do not contribute non-
tolerated residue6 to meat, poultry, eggs, or milk. Information about the
fate and persistence of the pesticide in representative soil types would
determine whether a residue could exist when ‘rotational’ crops are
subsequently planted in treated fields. And information about the general
environmental fate of the pesticide would ensure against non-tolerated
residues in such conswnable wildlife forms as fish and estuarine mollusks.
Residue data generally disclose: the nature of the residue (i.e., parent
compound or transformation product); the level of the residue as it occurs i n
the whole raw agricultural commodity, the commodity being in the form in which
it moves in interstate commerce; the di6tribution of the residue in the
cani-nodity; and sometimes also the effect on the residue caused by the
processing of the commodity for consumption, including wishing, brushing,
trirnning, curing, drying, cooking, or caiming. Some data may be available
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com xzring various methods for the intentional removal of residues. Residue
data can be obtained by field experiments, by animal treatment studies, by
soil persistence studies, or by the monitoring of actual residues in marketed
food or feed products, by whieh toieranr es can be enforced or reassessed.
Field residue data for Metolachlor should reflect the proposed use with
respect to dosage, mode of application, nunber and timing of treatments,
formulations used and geographical areas represented. Pre-plant soil
treatments for grain crops should include examination of foliar parts of the
plant during the grc ing season as well as analyses of t e harvested grain.
The analytical methods used to generate the residue data involve a
conversion of residues of Metolachlor and its metabol ites (through hydrolysis)
to 2— t (2—ethyl—6--methylphenyl) amino] —l—propanol (HP-0Ol) and 4— ( 2-ethyl—6—
methylphenyl ) —2—hydroxy—5—methyl—3—uorphOlinOne (HP—002). The resulting
residues fran the application of r. tolachlor are accordingly expressed as HP-
001 and HP--002, or cathined as the total residue and calculated as Metolachlor.
A storage stability study of Metolachlor residues in corn fodder and grain
was performed to ensure that results obtained for samples stored prior to
analysis are valid (Gold and Kahrs, l975b). Samples of corn fodder and corn
grain were fortified with Metolachl 8 r at 1.0 pç n and 0.2 p zn, respectively.
The samples were kept frozen at —15 C and analyzed at pre-determined
intervals i p to 13 months after storage. The recoveries for the corn
fodder ranged fran 92—115% of the fortified amount and the corn grain samples
ranged fran 92—119%.
Several samples of field—treated corn fodder were also monitored during the
13—month storage period. Residues in one sample varied fran 0.43—0.39 pçin and
residues in another sample ranged fran 0.29-0.26 ppn over the 13-month period.
Residues in Corn
The majority of the residue studies on field and sweet corn were
performed by the use of a formulation of Metolachlor called 250 EC. No
data were sukinitted regarding the (xlnrx)sition of 250 E.C. formulation. The
residues of Ctt4—OOl in these studies are determined as HP—OOl alone.
The HP—002 breakdown product was not determined. The studies were
performed in 13 states representing major corn-producing areas. (Tweedy,
1974; Tweedy and Mattson, 1974; Mattson and Kahrs, l975b).
Nine studies with field corn, at 2 lbs. and 4 lbs. ai/acre of 250
E .C., reported residues less than 0.03 zn of Metolachior (as HP-OOl) in
grain at intervals of 111—162 days between pre—emergent application and
harvest. Three studies with sweet corn at 2 lbs. and 4 lbs. ai/acre of 250
E .C. reported residues of Metolachlor (as HIP—OOl) in ears as less than 0.03
zn at 61, 67, and 138 days after the pre-emerqent application. ‘1
additional studies with field corn and one with sweet corn using the 6E
formulation (at 3 and 6 lbs. ai/acre ) indicated no detectable canbined
residues of HP-00l (as Metolachlor) (less than 0.03 p n) and HP—002 (less
than 0.10 ppn) in the grain and fresh ears respectively 62, 92 and 129 days
after the application. At a later date t additional studies at 2 lbs.
and 4 lbs.ai/acre of 250 E.C. formulation on sweet corn were performed. No
detectable residues of Metolachior as HP—OOl (less than 0.03 m) or HP—002
(less than 0.10 çin) were found in the fresh ear sample at 60 and 67 days
after the application.
Seventeen residue studies where Metolachior was measured as HP—OOl
show forage residues were less than 0.03 ppn at intervals of 34 and 72 days
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following 1.5 lbs. ai/acre. Residues resulting fran 2 lbs. and 3 lbs. ai/
acre applications (at 26 to 72 days) range fran less than 0.03 ppm to 0.14
ppm, and less than 0.03 ppm to 0.10 ppm, respectively. At intervals of 26
to 64 days, 4 lbs. ai/acre resulted in residues of less than 0.03 to 0.43
p 1l; 6 lbs. al/acre rates showed HP—OOl residues were 0.03 ppm to 0.19 ppm.
Silage stage forage residues of Metolachior (measured as HP—00l)
resulting fran 2 lbs. and 4 lbs. ai/acre range fran less than 0.03 ppm to
0.16 p in, and less than 0.03 ppm to 0.43 ppm, respectively, at intervals
fran 71 to 112 days after application.
Mature fodder and stayer residues ranged fran less than 0.03 ppm to
0.44 ppm (measured as HP—00l) for both the 2 lbs. and 4 lbs. ai/a re rates.
Eleven studies in which tolachlor was later measured as canbined
residues of HP—001 and BP—002 show residues in early forage of less than
0.03 ppm to 0.24 ppm and less than 0.03 ppm to 0.08 ppm for 2 lbs. and 3
lbs. ai/acre treatments, respectively; 4 lbs. and 6 lbs. ai/acre
applications resulted in forage residues ranging fran 0.04 ppm to 0.64 ppm
and 0.03 to 0.19 ppm, respectively.
Silage stage forage showed xitibined HP—00l and HP-002 residues (as
Metolachlor) of 0.08 to 0.14 n, 0.04 ppm to 0.12 ppm, and 0.05 ppm to
0.28 ppm for treatments at 1.5 lbs., 2.0 lbs., and 3.0 lbs., respectively.
Combined residues f ran 4 lbs. and 6 lbs. ai/acre treatments were 0.14 to
0.63 ppm and 0.13 to 0.34 ppm, respectively.
Fodder and stover residues for 1.5 lbs., 2.0 lbs., and 3.0 lbs., a i/
acre treatments were less than 0.03 to 0.06 ppm, less than 0.03 to 0.23
çin, and 0.07 to 0.30 ppm.
Combined residues of HP—001 and HP—002 (as Metolachior) in mature
fodder and stover reported in six studies at 4 lbs. ai/acre ranged f ran
0.07 n to 0.90 ppm. Three studies at 6 lbs. ai/acre reported canbined
residues in fodder ranging fran 0.14 to 0.53 ppm.
Because no detectable residues were found in corn grain, no residue
data are needed for corn grain by—products (corn oil, corn meal, etc.).
Residues in or on Soybeans
Twenty—three residue studies were performed in ten states representing
the major soybean growing areas. Application rates were fran 2 to 6 lbs.
ai/acre (Mattson and I lla, 1975; xas A & M Cottonseed Products
Research Laboratory, 1966; Houseworth and 1 11a, 1976).
Analyses involved the determination of both HP-OOl and HP-002. No
detectable residues (less than 0.05 ppm) of HP—002 were found in any of
the soybean samples. Residues of HP—001 in the soybeans which ranged f ran
less than 0.03 to 0.09 ppm resulted frau application rates of up to 5 lbs.
ai/acre; the nuaxiinum reported residue was fran a 3 lb. ai/acre
application. At 6 lbs. al/acre, residues of HP—001 ranged fran less than
0.03 to 0.21 ppm.
Three fractionation studies showed no detectable residues of HP-OOl
(less than 0.03 ppm) or HP—002 (less than 0.05 ppm) in any fraction (meal,
crude and refined oil, soapstock) from soybeans treated at rates of 2 to 5
lbs. al/acre. At 6 lbs. ai/acre, the only finite residue was found in
the soybean meal where 0.04 ppm HP—001 was detected.. In one of the three
tests, soybean hulls (pods) contained 0.03 and 0.06 ppm HP—OOl fran
treatment rates of 2.5 and 5 lbs. al/acre.
¶ [ ttal residues (sum of residues converted to HP—001 and HP—002) of
Metolachlor in soybean forage ranged fran 0.20 to 0.36 ppm at a 2 lbs. ai/
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acre application rate. ¶L tal residues in soybean forage at the 3 lbs. ai/
acre ranged fran 0.15 to 1 • 01 ppn. At exaggerated rates of 4 lbs. and 6
lbs. al/acre, total residues ranged fran 0 • 34 to 1.76 u. These residue
studies represented pre—harvest intervals of 30—92 days.
I tal residues in soybean hay at pre—harvest intervals of 122-194 days
ranged fran less than 0.10 to 0 • 84 ppn at rates of up to 3 lbs. al/acre.
At exaggerated rates of 4 to 6 lbs. a i/acre, total residues ranged fran
0.14 to 2.46 xn.
The above residue data for soybeans allow for an adequate range of
geographical variation.
Residues in Meat, Milk, Poultry , and Eggs
For this Bection, data shou12T how viiether residues will result in
meat (muscle, liver, kidney, fat), poultry, eggs, or milk. The toxicant
fed should correspond to the aged residues found in the item of feed,
& ich may or may not be the parent pesticide. The studies should be
performed at several dosage levels, including exaggerated dosages,
preferably threefold cmd tenfold.
Residues in meat and milk were studied in a three—level feeding study
(Mattson, 1975). In this study, eleven a ,s were fed unlabeled Metolachlor
at levels of zero, 0.02 çin, 1.0 n, and 5.0 iu of the total diet. Milk
samples were xllected at zero, 1, 2, 7, 14, 21, and 28 days. nimals
were sacrificed and samples of tissues taken at 14, 21, and 28 days. Only
milk and tissue samples fran the t highest feeding levels (1 .0 and 5.0
xn) were analyzed.
In this study, the analytical metlcd determined “total” residues of
Metolachlor, (i.e., parent canpound and all metabolites yielding HP—OOl
and HP—002 after hydrolysis with 6N MCi). All residues in milk samples
were less than the method sensitivity of 0.006 ppn for HP-001 and 0.01 p tn
for HP—002. All residues in the nuscie, fat, kidney, and liver were less
than the me od sensitivity of 0.02 n for HP—00l and 0.04 ppu for HP—002.
ta1 C-residues (calculated as Metoj chlor) were determined in
the goat metabolism study where 4.7 p in of C—labeled Metolachlor was
fed for 10 days (I ger and Cassidy, l974a). Activity levels were
equivalent to 0.01 pçiu in milk, 0.003 ppn in kidney, 0.07 pçzn in liver,
and less than .006 4 in other tissues. The activity was r t
characterized. When C—lab ed (X)rfl biosynthesized metabolites were
fed to goats, rx detectable C—residues resulted in milk or tissues
(1 er and Cassidy, l974b).
Residues in poultry and eggs were determined in a feeding study
involving 112 laying hens (Mattson, 1975). The birds were fed unlabeled
Metolachlor at levels of zero, 0.1, 0.5, and 2.0 p xn in the dry diet. Bgg
sanpies were taken on days 1, 3, 7, 10, 14, and 21. Birds were sacrificed
after 7, 14, 21, and 28 days for tissue analysis. Only tissue and eggs
samples frau the t highest feeding levels (0.5 and 2.0 pun) were
analyzed. I sidues as HP-00l in eggs, muscle, and fat were reported as
less than 002 ,jin. I sidues of 0.02 p xu and 0.03 n as HP-00l were
reported for the livers fran birds fed at 0.5 arid 2.0 p zn feeding levels,
respectively. 1 b detectable residues (less than 0.04 p in) of HP—002 were
found in eggs r r in any tissues.
Frau the feeding of soybean meal, hulls, arid soap-stock bearing
residues of 0.1 n, the dietary residue level cxxild approach 0.04 zn for
cattle arid 0.03 pçin for poultry. The feeding levels at which barely
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detectable residues were found in the feeding studies represent
exaggerations of ca. lOOx for axis and 25x for poultry.
A restriction against the feeding of soybean forage or hay, including
the fodder or straw from the bean harvest, precludes dietary residues for
poultry arx i cattle except for the fractions of soybeans. Although the
livestock feed use of soybean fractions may lead to snail residues in
meat, milk, poultry, and eggs, these residues, if present, would be at
levels below the sensitivity of the analytical methods.
Present Tolerances
A permanent tolerance of 0.1 ppu in corn grain (except popcorn) has been
established for residues of Metolachlor and its metabolites pursuant to 40 CFR
180.368 (FR 41:178, 9/13/76). Temporary tolerances were granted on 4/23/76
for residues of Metolachior arid its metabolites at 0.1 ppn for soybeans, 1.25
ppit for soybean hay and forage, and 0.02 ppm for meat, eggs, poultry, and
milk. (These were renewed on 2/9/78.)
Presently there is a proposal pending for a permanent tolerance of 0.1 ppn
for residues of Metolachior arid its metabolites in soybeans. A restriction
against the feeding or grazing of soybean hay or forage is on the label. The
t porary tolerances for Metolachlor arid its metabolites of 0.02 ppn for eggs,
milk, meat, fat, and meat by—products are enforced for the following animals:
cattle, goats, hogs, horses, poultry, and sheep. The permanent petition for
these tolerances, in aId it ion to the tolerance of 0.1 ppmn in soybeans, is
presently in abeyance because ftxicology reviewers are requiring additional
toxicology studies as a prerequisite for permanent tolerances for meat, milk,
eggs, arid poultry.
Regulatory Incidents
Though EPA sets tolerances for pesticides, it is up to the Food and Drug
Administration to enforce them. When reviewing Residue Chemistry for
Registration Standards, EPA will routinely search regulatory records for
incidents in z ihich the tolerances for the chemical under review were
exceeded. Such incidents can indicate problems in either the practicability
of the tolerances or in the accurate detection of residues, and may suggest
the re—evaluation of current tolerances.
First, EPA has record in their files concerning any regulatory action
taken by FE1Z with respect to the registered uses of Metolachior. Second,
Metolachlor is a relatively new amnpound, and the method for regulatory
compliance has not yet been edited arid incorporated into the PAM II.
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Disciplinary Review
Residue chemistry Profile
Tolerance Reassessment
Generic Data Gaps
Registration Requirements
Suggested Labeling
Residue Chemistry Profile
When Metolachlor was applied as a pre—emergence treatment at 2 lbs ./acre to
corn and soybeans, total residues later found in plants parts were higher in
soybeans than in corn • In corn, the residues were primarily metabol ites
conjugated with polar plant molecules such as amirx acids or sugars. The
major pathway of metabolism appears to be conjugation with glutathione,
breakage of the thioglycos ide borxl to form mercaptan, conjugation of mercaptan
with glucuronic acid, hydrolysis of methyl ether, and conjugation of the
alcohol with a neutral sugar. Metabolic pathways in soybeans were similar to
those dserved in corn.
The metabolism of Metolachior in animals appears to be similar to and as
ocn lex as that in plants. But whereas plants retain their metabolic
products, animals el ijuinate their Metolachior metabolic products almost
canpietely. The parent ca ourw3 was rapidly metabolized and almost totally
eliminated in the urine arK] feces of goats, rats, and poultry, and ro residues
or only trace amounts could be detected in the tissues, kidneys, liver, blood,
or milk of animals, or in the eggs, meat, or fat samples of laying chickens.
The most significant residue detected was 0.02 to 0.03 ppu in the liver of
chickens.
Adequate tolachlor-specif ic and metabol ite-specific analytical methods
are available for the detection of residues in corn, soybeans, meat, milk, and
eggs, and data were available on actual residues in these cxiiucdities. No
detectable residues were found in corn grain, though small amounts of residues
were found in corn forage, fodder, and stover. Residue data for soybeans were
aiequate to allow for the wide rar e in the geographical characteristics of
the U.S. soybean crop, and detectable residues were found in the beans,
soybean meal, hulls, forage, and hay, though all were in small quantities.
The highest soybean residues (0.14 to 2.46 n) were in hay fran plants treated
with exaggerated rates of 4 lbs. and 6 lbs. ai/acre. Residues at just above
or below the sensitivity of the analytical method were reported for cattle
meat and milk, for goat meat and milk, and for poultry eggs, meat, arK] fat.
The feeding levels at which barely detectable residues were found represent
exaggerations of approximately 100 times for cows and 25 times for poultry.
Present tolerances for Metolachior are set permanently for corn grain at
0.1 PP11, arK] temporarily at 0.1 p rn for soybeans, 1.25 ppu for soybean hay and
forage, and 0.02 pn for meat, eggs, poultry, and milk. There are ro records
of regulatory incidents involving the enforcement of these tolerances.
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METABOLIC PATEWAYS OF METOIACBWR
IN CORN AND SO ANS
eto].acli]or
cu 3
cQ( y - -
j. OCH3
SglucurQnic acid
acid
/ NfO-sugar
f* s_ 1ucuronic acid
Minor path
glucurenic
1a o: path
4,
/L ..O_suga
lucuronic
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Tolerance Reassessment
The e.xposure of humans to pesticide residues fr’c. n r’eg ’z.stered U688 and via
the food chain is a function of several factors:
a) The established tolerance for a coninodity (in ppm).
b) The percentage of a commodity in the daily diet.
c) The assumed amount of food conszinption by an average person, which
is i. 5 kg per day.
d) The assumed body weight of an average person, thich is 60 kg.
When these factors are substituted into a toxicological formula
[ i.e., (a x b x c) divided by dJ, the human exposure to those pesticide
residues in a coriinodity is found in terms of mg of pesticide per kg of body
weight per day.
A tolerance is re—assessed by comp ’zring this potential daily exposure with
an ‘Allowable Duly Intake’, which is set on the basis of a toxicological ‘No
Observable Fiffect Level’, plus a margin of safety factor’ of lOOx, to allow for
a lox greater sensitivity of humans over test animals, and to allow for the
possibility of an individzeul who is lOx more sensitive than the average
person. In order to determine the ‘No Observable Effect Level’ for a
pesticide chemical, the Toxicology reviewers must have a full complement of
acute and chronic studies.
For M to1achlor the following tolerances have been established: A
permanent tolerance of 0.1 pn in corn grain, and temporary tolerances of 0.1
ppn for soybeans, 1.25 n in soybean hay, and 0.02 pçxn in meat, milk,
poultry, and eggs. Based on these established permanent and temporary
tolerances, the theoretical huuan exposure to tolachlor residues is
calculated to be <.0003 n Jkg/day. But because certain necessary chronic
studies are not presently available (see Toxicology (lapter) a Tolerance
Reasses9uent is rot possible at this t ine, and will instead be performed when
the chronic data have been su pl ied and reviewed;
Generic Data Gaps
none
Registration Requirements
The proposed guidelines for Residue themistry have rot been piblished, and
accordingly, there are no citations for Guidelines corresponding to the types
of Residue themistry data normally required to support individual
registrations. In general, lu!ever, the Residue Chemistry reviewers must have
enough data for each proposed product to be assured that the residues of the
parent chemical and its metabolites have been adequately identified,
quantitatively arx qualitatively.
Suggested Labeling
For F nulsifiab1e Concentrate ! tolachlor (8 lbs. or less per gallon):
for corn: 1x rot graze or feed forage and fodder to
- livestcck or use for silage.
for soybeans: L X ) rot graze or feed soybean hay or forage.
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BIBLIOGRAPHY
(Reserved)
In order for the provisions of FIFRA concerning data cc’ npensation (Section
3(c)(1)(d)) to be effective under Registration Standards, datci used in direct
support of the Standard for each type of product must be accurately listed,
enabling applicants and their arbitrators to determine what data do and do not
support the registrations of individual pesticide products. Thus, for each
disciplinary chapter, studies used to evaluate hazard and establish Standards
for the manufacturing—use chemical and for each type of end-use formulation
will be listed separately.
¶I protect present and pztential a 1icants for the registration or re-
registration of products containing Metolachior, the citations appropriate to
each disciplinary chapter will not be published in this Sample Standard,
though a canpiete Bibliography is provided at the erx of the document.
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EODtAJGIC1 L EFFECTS
INTRODUCTION
The environment as a biaole is a closed system that uses energy from the sun
to constantly recycle its water, air, mineral, plant, and animal resources.
Natural mechanisms recognized by ecologists to be essential to this system
i .nclude: biogeochemical cycling, host/parasite relations, competition for
ha bi-t at and food, predator/prey relationships, food chains, symbioses,
coninunity diversity and succession, and natural selection.
Man’s activities form a significant subsystem of the earth’s overall
environment. When man utilizes the power of technology to support, defend, or
enrich his existence, his activities can have a great enough impact to
significantly disrupt ecological mechanisms, or to deplete and dconage
ecological resources. Sometimes the depleted resources are ones that man
values for his oz n use, such as sport and con,nercial fisheries, shellfish
populations, recreational areas, or agricultural land. Other times, there
occurs a depletion of natural resources which man does not utilize directly,
but thich form an integral part of the ongoing process of ecological recycling.
As a technological intervention of significant magnitude, the release of
pesticides into the environment influences both natural and man-modified
ecosystems. The study of pesticide effects on ecological systems is difficult
to carry out because of the complexity of the interactions involved. Testing
begins with a selection of biological ‘indicators’, including single species
of microbes, vertebrates, invertebrates, and plants, that provide for wide
taxonrxiic representation and include a range of biological processes. Then,
if single species show effects, true ‘ecological effects’ are determined by
systemic studies of the environment’s natural mechanisms.
‘IOPICAL DISCUSSIONS
Corresponding to each of the pical Discussions listed below is the number
of the sections in the ‘Proposed Guidelines’ of July 10, 1978 (40 CFR Part
163) which explain the minimum data that the Agency usually requires in order
to equately assess a pesticide’ s Ecological Effects. Where no section
number is listed, a minimum requirement has not been set for such information.
Guidelines Sections
Microbes 163 .62—8(f) and (g)
Algae 163.122—2, .123—2. .124—2, and .125—4
Aquatic Macrophytes 163.122—2, .123—2, .124—2, and .125—4
Terrestrial Plants 163.121—1, .122—1, .123—1, .124—1, and .125
Soil and Surface Invertebrates
Birds 163.70—1, .71—1, .71—2, .71—4, and .71—5
Reptiles and Amphthians
Wild Mairinals 163.70—1, .71—3, and .71—5
Aquatic Invertebrates 163.70—1, .72—2, .72—4a(1), .72—5, and .72—6
Fish 163.72—1, .72—4, .72—5, and .72—6
Estuarir and Marine Organisms 163.72—3, .72—5, and .72—6
Effects on Nonbiological Canponents of the Environment
Ecosystem Effects 163.71—5 and 163.72—6
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Microbes
Bacteria and fungi are among the principal agents of decay and
transformation, reducing plant, animal, and other organic remains to their
component compounds. Cellulose decomposition by microbes forms nutrient-rich
humus from decomposing plants on the soil surface, recycling large cnnoie2ts of
organically bound carbon. Microorganisms are also the primary actors in the
nitrogen cycle, fixing gaseous nitrogen, and causing the cmvnonification of
organically bound nitrogen, which reintroduces the element into the soil from
protein wastes and remains. Sulfur salts from volcanic rock and hydrogen
sulfide from the anaerboic microbial decomposition of plant and animal wastes
are oxidized by other microorganisms to sulfates, which are taken up by plants
as primary nutrients. The cyclic movements of chemical elements such as
carbon, nitrogen, and sulfur through soil, air, and living tissue could not
proceed without microbes, and the effect of pesticides on microbes is a
potential impiir nent of these most basic ecological cycles.
Effects on microbes can also have serious consequences for resources used
or modified by man. The fertility of natural farmland depends upon the
presence of nitrogen-fixing bacteria as well as microorganisms which can
degrade dead plant material. Re4uctions in pirticular populations of microbes
might even interfere with the degradation of other pesticides applied to the
some area. Some pesticides, which may be rinsed off into drains or sewer
waters, can end up harming the populations of microorganisms responsible for
normal wastewater treatment.
Data on the effects of pesticides on microbes are obtained frcx laboratory
studies employing non-r lioisotopic analytical techniques. These studies
determine effects on either microbial functions or microbial populations.
The study of effects on microbial functions constitutes a irore direct
approach, but sane effects cannot be measured directly and population studies
may be the only recourse. Studies should be conducted over a long enough
period to dancmstrate whether there is a temporary or long—lasting effect on
microbes. Three studies were sutinitted for Metolachior. Tc’ of the studies
used the population approach and one used the functional approach.
In the first population study (}buse rth, l973a), reviewers noted
variations in tabulated results, and raised questions about the aggregation,
dilution, dispersal, enisneration, and identification of selected soil
microorganisms (such as Bacillus, Pseudcxtonas, Arthrobacter, Ceflulatonas,
Cytcçhaga, Flavobacterium, Achrcirobacter, Aspe 9 illus, Chaetomium, Fusarium and
Penicillium) . These issues will require clarification before this study can
be used to support regulatory decisions.
In the other population a proach study (Ercegovich, &gus, and Buly, 1978),
a diverse selection of microorgani with 27 species representing the family
Actincinycetes and the following genera: Bacillus, Cellulaionas, ytophaga,
Flavobacteritin, Pseudanonas, Archraw bacter, Asperg illus, Chaetanit un,
Fusarium, Penicillium , and Tr ccderma , were evaluated against three
concentrations of Metolachior; 5, 25, and 125 ppB. At 5 p *u, 6 of 27; at 25
9 of 27; and at 125 p xn, 19 of 27 species were inhibited with a static
rot cidal effect si-own. At 5 ppn, 4 of 27 species hal increased counts and 1
species did not show any effect at all three concentrations. Pztential
degralers could be estimated and 10 of 27 species could have this potential.
Data for oxygen consumption, carbon dioxide evolution, nitrogen cycling,
dehydrogenase activity, and phosphatase activity were not supplied. Because
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application rates normally used for tv tolachlor are 1—3 lbs ai/A, the slight
inhibitory/static effect on soil ccmnensal populations v uld not be as
significant as the laboratory study indicates, uld be alleviated with
time, and uld allow populations to recover. The effect uld be further
minimized by reduction of the pesticide concentration by physico—chemical
means, of which photolysis is a major pathway. Based on these actions, the
fact that dehydrogenase or phosphatase activity data were not submitted does
not invalidate the use of this study.
In a study by Ercegovich, Vallejo, and Bogus (1978), the effect of
5, 25, and 125 ppit concentrations of Metolachior was evaluated on the soil
function processes of nitrification in t soil types: Morrison sandy loam and
Hagerstown silt loam. Morrison sandy loam did not show any inhibitory effects
at any of the three concentrations evaluated. Hagerstown silt loam did not
show any inhibitory effects at 5 or 25 ppn, but did show an inhibitory effect
at 125 ppi . The rate of nitrification was inhibited for seven weeks, with a
recovery starting at eight weeks and continuing until the end of the
experiment (at ten weeks). Rates between the t soils varied considerably.
Though this latter study does not by itself fully explore the potential
effects of to1ach1or on microbial functions (for example, effects on the
degredation of cellulose, starch, and protein), it does support the data in
Ercegovich, Bogus, and Buly (1978), and together these studies provide
sufficient information about potential effects on naturally occurring
microorganisms.
The activated sludge process used in wastewater treatment plants utilizes
the metabolic degredation activity of certain microbes to break down raw
sewage into a form acceptable for discharge in environmental waters. Because
Metolachior rinsate or irrigation mix may inadvertently make its way into
municipal sewage systems, studies on its potential effects on wastewater
treatment microorganisms is important. Not only may this cause unprocessed
sewage to be released into the &juatic environment, but it may also impede the
degradation of other toxics that are disposed of in sewer system drains.
Activated sludge metabolism data are rot presently available for
Metolachlor.
Algae
As aquatic plants utilizing light energy for photosynthesis, algae
function as the primary aquatic producers of biomass upon which the higher
levels of food chain are dependent. Inhibition of algal growth can reduce
available biomass, while changes in algal size, content, or nutritive content
can make it less accessible to higher—level feeders. The artificially
stunulated growth of an algal population can suffocate a body of z zter by
eutrophication. Info nation about the inhibition or stimulation of natural
algal growth thus indicates the extent to which a chemical substance may
interfere with such essential ecological functions as primary productivity,
nitrogen fixation, oxygen production, and nutrient cycling in lakes, streams,
estuaries, and oceans.
The atmospheric oxygen produced by marine algae is of course of direct
importance to all animal life, including man. Algae are also a major source
of food for zooplankton, which are fed upon by commercially and recreationally
important fish and shellfish.
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Studies on tolachlor’ s toxicity to algae are rot presently available.
But because residues of Metolachior are expected to reach the freshwater
aquatic environment, if such studies were available, they uld be reviewed and
assessed for information on potential effects to freshwater aquatic ecology.
aquatic Macrophytes
Like algae, aquatic macro phytes transform light energy and simple
molecules into biomass for conewners in the aquatic food chain. Decaying
aquatic plants form a large part of fish and shellfish diets. Aquatic
macro phytee also provide important microhabitats for aquatic organisms.
Pesticides viaich can impair the growth of higher plants may shift relative
populations of macrophytea and algal species, thus altering community
can poBition, possibly upsetting habitat, food—chain, and productivity
balances.
In addition to their contribution to aquatic microhabitats thus alive and
their contribution to the detritus food web upon decomposition, aquatic
macrophytes may also participate in nutrient recycling. Aquatic plants iz*jCh
are rooted in aquatic sediment are particularly active in recycling nutrients
from settled and decaying biomass and aquatic-bed minerals. These plants may
unfortunately also face a greater exposure to pesticide residues sorbed to
soil or organic matter, then this material enters bodies of iter and settles
to the bottom.
Studies about Metolachior’ s effect on aquatic plants are rot available.
But because residues of Metolachior are expected to reach the freshwater
aquatic environment, if such studies were available, they s uld be reviewed and
assessed for information on potential effects to freshwater aquatic ecology.
T rrestrial Plants
One of the primary concerns of an Ecological Effects assessment,
particularly for agricultural—use pesticides, is the toxicity of the che nical
to non-target plants. This includes those plants within the pesticide
application area thick are subject to direct exposure, such as crop plants,
as well as plants outside the target area thick may be exposed to residues,
such as adjacent crop plants, ornamentals, wildlife food and cover species,
forests, and marshland plants. The potential risk to terrestrial plants is
first an ecological threat, and secondly an economic threat.
The ecological impact of phytotoxicity ranges from soil disruptions to
bioaccwnulation. Because both roots and aerial plant parts contribute to soil
structure and nutrient retention, toxic effects on terrestrial plants, either
wiid or cultivated, annual or perennial, may cause erosion, destabilizing
terrestrial and aquatic ecosystems. Paytotoxic effects to forest vegetation
can cause nutrient loss, the erosion of forest soils, and loss of wildlife
habitat. C zemicals that do not visibly affect the nornal growth, developnent,
and reproduction of plants may, nevertheless, bioaccumulate to a degree that
bx)uid cause hazard to primary or secondary conewners.
Thytotoxic effects of economic importance to man primarily concern the
impaired growth of crop plants, and adverse effects to plants capable of
nitrogen fixation, upon thich crop plants depend. Diminished terrestrial
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plant grcmfth can sometimes lead to erosion into r’ .vers and streams, which can
in turn greatly diminish the useful life of dams, degrade the waters impounded by
them and disable agricultural irrigation systems. If widespread, the
inadvertent destruction of terrestrial plants can lead to the loss of forest
and agricultural land by desertification.
Studies on the ecological effects of Metolachior on non—target terrestrial
plants are riot presently available. However, efficacy tests which examine the
effects of an herbicide on protected crops can often supply sufficient
information to conduct an ecological effects review of phytotoxicity.
Nevertheless, in accordance with present Agency policy, which requires an
efficacy review for pesticides only when the chemical’ s use has a direct impact
on public health, efficacy data was not reviewed for the Metolachior Standard.
Soil and Surface Invertebrates
Soil and surface invertebrates such as arthro pods and earthwor ns play a
number of important ecological roles, but are especially vital to the
stability of the artificial ecosystems induced by agriculture.
In the natural environment, many species of mammals, birds, reptiles, and
con phibians depend upon terrestrial invertebrates for their food supply, and
their numbers may be adversely affected by reductions in invertebrate
populations. The use of pesticides, especially insecticides, can subject non—
target invertebrates to unnatural selection pressures and can create shifts in
predator/prey relationships. Pesticide use may also result in a loss of
insects important to flowering-plant pollination and soil aeration.
In an agricultural ecosystem, these effects may be manifested in the
development of pesticide-resistant strains of insects, in a reduction in the
number of parasitic and predaceous arthro pods such as spiders, mites, and
centipedes (which can exert a natural control over injurious insect
populations), and in outbreaks of secondary pests. Likewise, pesticide use
may result in a reduction in populations of earthwo ns, nematodes, insect
larvae, and other organisms which are important in improving soil fertility
through aeration and nutrient cycling. Finally, the use of certain pesticides
may adversely affect such insects as honey bees, wild bees, silkwo ne, or lac
insects, which perform functions directly useful to man.
Studies concerning Metolachior’ s effects on soil arid surface invertebrates
are riot presently available. Though the Agency does riot routinely require
these data, because tolachlor is applied to arid mixed with the soil, if such
studies were available, they v uld be reviewed and assessed for information on
potential effects to terrestial invertebrates which affect the fertility of
agricultural soil, arid which keep potential insect pests in ecological check.
Birds
Both the ecological and econccnic importance of birds are partially
dependent upon their functions as predators and prey. Birds may be exposed to
pesticide chemicals by feeding on contaminated plants or anvnals, and by
de-mnal contact and inhalation then in the proximity of outdoor sprays and
dusts. A coninon route of exposure is the ingestion of contami nated water,
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plants, seeds, invertebrates, fish, or rodents. Higher food chain carnivores,
w zich include many endangered bird species, may be particularly susceptible to
poisoning by pesticide chemicals zthich enter the enviro,vnent at low
concentrations but which are bic nagnified through aquatic and terrestrial food
chains. Also, birds themselves may bioaccwnulate, and then pass on their
stored residues to other predators. And as has been discovered in connection
with certain now cancelled pesticides, chemicals that may be innocuous in
tenns of direct mortality may nevertheless threaten the survival of a bird
population by impairing reproductive success.
Pesticide effects on birds as predators may have direct consequences for
rmm. Insectivorous birds often help control insect populations which consume
crops, while carnivorous birds such as owls help regulate rodent populations.
In addition, birds are of aesthetic and recreational value, and nvi iy are
considered to be significant food sources and popular targets for game.
r ta on the effects of single oral doses of Metolachlor to avian
wildlife are reported by Fink (1976): the acute LD-50 for mallards ( Arias
platyrhynchos ) was 4640 (3000—7200, 95% confidence limits) n j/kg, indicating
that Metolachior is practically non—toxic, acutely, to waterfowl. But due to
deviations fran reocimnended protocols, such as discrepancies in body weights,
these data are unacceptable for use in the regulatory process. An avian single
dose oral LC—S0 determination is thus a data gap for Metolachior.
}k qever, acceptable data on the dietary 1C—50 of Metolachior for avian
wildlife are reported on the mallard ( Anas platyrhynchos ) (Fink, 1974a),
and the bobwhite qj.iail ( Colinus virginianus ) (Fink, 1974b). The 5—day
dietary LC—50 (with 3 days observation) for both species was greater than
10,000 irxl icating that Metolachior is practically non-toxic, subacutely,
to upland gamebirds and waterfowl.
Because, as was seen in the Enviror nental Fate chapter, Metolachlor is
persistent under certain conditions and is stored in plant and rotational crop
tissue, information on avian reproduction effects is needed. Avian
reproduction studies are not presently available for Metolachior, which
constitutes a data gap.
An hibians and Reptiles
As with birds, amphibians and reptiles can function as natural or
introduced regulators of insect and rodent populations. Amphibians and
reptiles most susceptible to pesticide residue exposure are those such as
smakee, turtles, frogs, and lizards, which live near the shallow margins of
streams and ponds, and those which live on the exposed surface of the ground.
SzaUow waters often collect residues from runoff without adequately diluting
them, and some oil—based pesticides tend to concentrate at the water surface,
where amphibians can be repeatedly exposed. S’nakes which themselves feed on
amphibians may be subject to poisoning by bioaccunuiation.
Studies concerning Metolachlor’ s potential effects on amphibians or
reptiles are rot presently available. 1 ugh the N ency does not routinely
require these tests, because residues of Metolachior are expected to reach
the freshwater aquatic habitats of certain snakes, frogs, and lizards, if such
studies ware available, they xu1d be reviewed and assessed for information on
potential hazards to these species or to freshwater ecology.
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Wild Maiwnals
Wild maninal food habits are extemely diverse, ranging from grazing on fiel-d
plants to seed gathering to predation. Manvnals such as ground squirrels,
rabbits, racoons, bobcats, deer, and moose may be exposed to pesticide
residues in food and forage as well as on plant surfaces. Occasionally such
CX OBUP5 may result in acute poisoning and death, though more connionly the
hazard i.-s chronic or indirect, due to such effects as a toxic bioaccumulation
of residues, an increased susceptibility to capture by predators, lowered
resistance to weather and disease, loss of food supply or inability to reach
it, abandonment of habitat, bacterial upset in ruminants, or widespread
population effects. For man, these effects can mean a loss of game, fur-
bearing, and aesthetic resources.
These data are rot needed for tolachlor because the data on laboratory
animals reviewed in the Toxicology Chapter are generally sufficient for an
estimation of toxicity to wild mamals. Based on the data in Metolachior’ s
Toxicology review, there do not appear to be any unusual hazards to wild
nianinals that arise with the use of the herbicide, and SD no special
precautions need be recaiinended.
P uatic Invertebrates
Aquatic invertebrates, including crustaceans, zooplankton, and aquatic
insect larvae, take a wide variety of forms in the aquatic environment, and
occupy most of the vital niches of the food web. Many invertebrate species
function as primary consumers, as predators and even as decom posers. In their
role as primary conewners, herbivorous zoo plankton conswne phyto plankton thich
have converted solar energy into chemical energy.
Zooplankton are in turn conswned by higher animals and are thus the link
between phyto plankton, the chemical energy base of aquatic ecosystems, and
higher aquatic animals. Because invertebrates are so basic to ecosystem
function, impacts on invertebrate populations can have major effects on the
stability and viability of the aquatic ecosystem as a ?ii.ole. The effects of
pesticides on aquatic invertebrates is therefore a good indicator of the
possibility of broader effects on the aquatic ecology.
Data are available on the acute toxicity of Metolachior in the water flea
( Daphnia magna Straus) (Vilkas 1976). The 48—hour no-effect level was
5.6 jçzn. The 48—hour LC—50 at 95% confidence limits is 25.1 (21.6—29.2) ppn.
These data are sufficient to characterize Metolachior as being slightly toxic
to aquatic invertebrates, but less than to fish. ? b precautionary labeling
regarding aquatic invertebrates appears necessary.
Fish
Fieh may be exposed to pesticide active ingredients or solvents by the
migration of residues from terrestrial sites, by accumulation in the aquatic
invertebrates they feed upon, by effluent discharge, or by di rect pestwi de
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applications. Toxic effects to fish may include changes in behavior,
physiology, and reproduction. Adult fish and fry are susceptible to poisoning
by several routes of exposure, including ingestion, direct adsorption from
water, and gill absorption. Fry are susceptible to poisoning by the
absorption of a yolk sac carrying accumulated lipid soluble residues from the
f nale ‘5 ovum. Because aquatic food chains have many links, and because fish
at all levels tend to accumulate lipid soluble chemicals, some poisoning to
fish and fish conszcners m zy occur by bioaccwnulation. As predators or
grazers, fish aid in controlling the populations of organisms at lower trophic
levels. As prey, they are crucial to the survival of various birds,
terrestrial mcmvnals, and other fish. The role of fish as predators, grazers,
and prey can be significantly affected by pesticide poisoning. With
ecological damage irizy come a threat to the economic uses of fish as food and
recreational resources for man, either by population losses or through
contamination.
The acute toxicity of to1ach1or to fish is examined in t studies
cxuiucted by Buccafusco (1978), and in a study by Sachsse and Uliman (1974).
Cold—Water Fishes
t*ie to various deviations fran the proposed recannended protocol, the data
by Sachsse and Uliman are not adequate for regulatory use in establishing a
96—hour LC—50 to rainbow trout. Buccafusco (1978b) d nonstrated a 96—hour
LC—50 at 95% confidence limits of 3.9 (3.3—4.6) pj u. The acceptable
rainbow trout study indicates that to1achlor is n derately toxic to cold
water fish.
Warn Water Fishes
Sachsse and Uliman tested four species of warm water fish to determine
their respective 96—hour LC—50’s for Metolachior.
Species 96—Hour 95% Confidence
LC-50 (ppn) Lim ts
Crucian Carp ( Carassius carasius ) 4.9 3.6 — 6.8
Channel Catfish ( Ictaluris punctatus ) 4.9 3.6 — 6.8
Bluegill ( L 1 epcwnis macrochirus ) 15.0
Guppy ( Lebistes reticulatus ) 8.6 7.4 — 10.5
Buccafusco (1978a) derived a bluegill 96-hour LC—50 at 95% confidence
limits of 10 (8.6—12) n. The acute LC—50 data fran both studies are
adequate to establish that Metolachior is n derately toxic to warm water
fish.
CWt the basis of available acute toxicity information, no precautionary
labeling regarding hazards to fish appears necessary. But as was seen in the
Envirorinental Fate chapter, t to1ach1or is resistant to hydrolysis and
metaboli&n in soil, and has a tendency to leach. Because of this significant
potential for residues to migrate to freshwater a4uatic habitats, a chronic
fish study was recaiinended, and is currently underway, though it was initiated
prior to a satisfactory “state of the art” success with the fish thryo1arvae
bioassay.
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Estuarine and Marine Organisiris
Marine and estuarine organisms, including clams, oysters, shrimp, crabs,
seals, and gulls, have well—recognized economic and recreational importance,
but also serve essential functions in coastal habitats. Coastal organisms are
adapted to constantly changing climatic and tidal conditions. In the coastal
food chain, clams, oysters, and other shellfish are filter feeders that
extract nutrients and plankton from water passed through their gills. Cr’abs
may feed on small fish and marine invertebrates. Fish, birds, and crabs
search out the soft immature forms of oysters and clams. Seals and other
marine mammals feed upon fis i and invertebrates. And various marine
invertebrates break down wastes from these higher organisms.
Coastal marine and estuarine organisms also protect themselves and each
other against turbulence in tide or weather by physical modifications of the
environment. Oyster beds are formed because the soft immature forms of these
animals need the hard surface offered by the adults before they can mature.
The calcareous secretions of many coastal invertebrates are also known to
build up rock—like barriers ?izich protect other organisms from extremes of
weather.
The introduction of pesticide chemicals into the coastal or estuarine
environment from terrestrial residue runoff and drift, direct discharge, waste
disposal, or industrial spills, can have an adverse effect upon any of these
organisms and their ecological functions. Filter feeders may filter out
residues, while birds and seals may be indirectly exposed by the ingestion of
other contaminated organisms.
Data on tolachlor’s inpact on estuarine and marine organisms are not
presently available, and need not be provided, considerir its present arid
proposed uses, which provide for application primarily in inland regions, and
not near coastal or estuarine waters.
Nonbiological Cai onents of the EnvironiT nt
Studies of ecological effects must also focus on the non—living components
of the environment. The abiotic portion of the natural biosphere corn be
divided into the solid earth or lithosphere, liquid water or hydrosphere, and
the atmosphere.
Bodies or currents of writer can be contaminated by spill, runoff, or direct
discharge, rendering them toxic to man, plants, animals, or microorganisms.
An ecosystem’s water phase can also be modified by the presence of a foreign
chemical so as to alter water’s unique ecologically important properties, such
as its viscosity, its thermal properties, its latent heat of evaporation or
fusion, its properties as a solvent, or its surface tension.
An ecosystem can also be threatened by pesticide chemicals affecting
sediments and soils. This can occur by the reaction of chemicals with
minerals and nutrients, by reactions that inhibit the normal weathering of
rocks, by effects on the lichens that help break rock down into soils, and by
chemical effects upon the permeability and absorption potential of soils.
The troposphere is the segment of the earth’s atmosphere upon winch li.-v ng
organisms most depend, for it is the medium of our weather, the medium in
which animals or microorganisms fly or float, and the medium which supplies
life with its gaseous nutrients. The presence of certain chemicals in
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significant concentrations could conceivably have an impact upon any of these
functions. But the higher strata of the atmosphere also has certain features
which, if altered by chemical reaction, could adversely affect the ecosystem.
For instance, the ozone layer is of vital importance because its absorption of
ultraviolet radiation prevents the latter from reaching the surface of the
earth, zthere it vxuld be lethal to most living organisms.
ThDugh the J qency does not routinely require information about the effects
of a pesticide information on the nonbiological xniponents of the environment,
such information may be available in the open literature or through research
involving the non-pesticidal aspects of the themical. l such data were
found in the rld—wide literature search for Metolachior.
Ecosystem Effects
An understanding of how the presence of a pesticide chemical may affect
the operation of natural ecosystems often requires a systemic approach, in
which the emphasis is placed on the z ny in which the various components of the
ecosystem operate together as a unit. An alteration produced in any part of
the ecosystem may have repercussions throughout the entire system as it
responds and adapts to the change.
Several methods have been devised to create experimental ‘microcosms’, or
assemblages of organisms and abiotic components that approximate a particular
ecosystem. One method is to take into the laboratory a small functional
se nent of a natural setting, such as a soil core with its natural
stratification preserved, or a sample of pond x ter, including some of the
bottom sediment and macroorganiwne. Another method vxuld recreate simple food
chains under controlled and monitorable conditions. But because microcosms
are isolated, they are subject to a restricted capacity for the exchange of
energy and materials, and therefore cannot consistently model the behavior of
actual ecosystems.
Another approach to the study of ecosystem effects involves the monitoring
of a measured test substance applied to an actual field site, and the
correlation of the presence of the substance with observations of organism
toxicity, reproductive success, predator/prey relationships, competition for
food and habitat, symbioses, community diversity, and biogeochemical cycling.
Observations of animal behavior can indicate ecological perturbations that may
otherwise remain hidden. &zny species of invertebrates, birds, mc nmals, and
fish possess highly for nalized behavioral repertoirea. Changes in feeding,
defense, mating, grooming, and nest building can disrupt the life-cycles of
individual species, but may also indicate the need for a more detailed
assessment of the effects of sublethal concentrations.
A third approach to the study of ecosystem functions and reactions is the
developnent of computer models that mathematically simulate energy and
material flows and exchanges. Though such models study enviro,vnental
manipulations through many generations or seasonal cycles without additional
risk or expense, the effects observed can only occur along the parameters and
functions already anticipated by the progranvner.
data on ecosystem effects are presently available for Metolachlor,
though the results of ecological effects studies yet to be performed may later
suggest the need for field tests under actual use conditions.
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DISCIPLINARY REVIEW
Ecological Effects Profile
Ecological Effects Hazard Assessment
Generic Data Gaps
Suggested Labeling
Ecological Effects Profile
Technical Metolachior : The available studies suggest that Technical
Metolachior’s toxicity toinicrobes and acute toxicity to certain species
of wildlife is relatively mild. Of the organisms tested, only fish appear
susceptible to adverse effects.
A diverse selection of soil microorganisms were evaluated against
three concentrations of Metolachior: 5, 25, and 150 w . Only static, not
cidal, effects were noted (Ercegovich, Bogus, and Buly, 1978). Another
study using the same concentrations showed no effects on nitrification at
the tw lower levels, and only temporary inhibition at the high level
(Ercegovich, Vallejo, and Bogus, 1978). Effects on wastewater treatment
microorganisms has not yet been investigated.
The toxicity of Technical Metolachlor to birds was shown to be low in
one dietary LC—50 test, though adequate data were not available to
determine single—dose toxicity nor reproductive effects. Based on the data
reviewed in the It)xicology Chapter, Metolachior appears to present a low
toxicity to wild mann a1s. Metolachlor is slightly toxic to aquatic
invertebrates, but less so than to fish. Both cold water and warm water
fishes showed iw derate toxic effects, and a chronic fish study is
forthcaning.
Emulsifiable Concentrate Metolachior : Because wildlife is not expected
to sustain significant direct exposure to the Emulsifiable Concentrate, but
only occasional exposures to residues of the active ingredient or its
degradation products and metabolites, information on the toxicity of the
Emulsifiable Concentrate to non—target wildlife organisms is effectively
supplied by the studies on the Technical chemical.
Ecological Effects Hazard Assessment
Technical Metolachlor : Fbr wildlife in the proximity of Technical
Metolachlor manufacture, storage, shipping, or disposal, intentional
discharges of the chemical into the environment, such as by the disposal or
drainage of effluent, as well as unintentional discharges, such as by
spillage or fire, could result in significant wildlife exposures. Because
of the stability of Metolachlor to hydrolysis and its potential resistance
to metabolic degredation, and because of the noderate sensitivity of fish
to Metolachior poisoning, the hazard to fish is the nost serious in this
regard. Considering Metolachior’ s potential for rotational uptake, a
secondary exposure could conceivably result for herbivores in areas
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proximate to the aquatic habitats contaminated with effluent, but the
studies in the lbxicology chapter suggest that acute effects frau such
small exposures s.xuld be highly unlikely.
Ecological Effects data are available to EPA officials responsible for
issuing a discharge permit should one becane necessary.
Enulsifiable Concentrate : According to tolachlor’ s caiu n use patterns,
certain non—target terrestrial and aquatic organisms in midwestern
agricultural regions may be expected to encounter finite residues, between
April and June of each year, frau the pre-plantirYg or pre-emergent
application of E.C. t’ tolachlor (USD #283, 1972).
We will consider first the hazard to aquatic organisms. As was
discussed in the Fate Profile of the Environmental Fate chapter, assimuing
field application and climatic conditions result in a loss of 2.5% of
Metolachior applied at the maximua rate of 3 lbs. ai/acre, each acre of
treated field uld contribute 0.075 lbs. to an jacent aquatic site.
This tount of active ingredient in an acre foot of water u1d yield
Metolachior residues of .055 ppn in 6 inches of water and .0176 ppu in 12
inches of water. The lowest LC—50 to aquatic organisms was 3.9 ppn to
rainbow trout; therefore, each treated acre within a watershed potentially
contributes 1/70 of the LC—50 to an 1jacent aquatic site which remains at
an area of 1 acre and a depth of six inches of water regardless of the
amount of runoff in one incident. Because 0.075 lbs ai. in a 6 inches acre
of water is less than 1/10 the LC—50, E .C. Metolachlor is not considered an
acute hazard to aquatic organisms which requires any restriEEion of use.
However, the persistence of Metolachior in water will vary principally
with micr ial activity, as the canpound has a hydrolysis half life of 200
days at 20 C and çtiotodegredation rate of less than 10% in 30 days.
Metolachior’s potential for persistence suggests the need for a chronic
aquatic organism study (Criteria and Rationale for Decision making in
Aquatic Hazard Evaluation, 1978), and indeed, as has been mentioned, a
chronic fish study is presently underway.
The wildlife hazard assessment could also benefit fra n more precise
information on Metolachlor’ s persistence in the aquatic environment.
First, should the estimated environmental concentration residues levels due
to a particular use pattern be equal to or exceed 1/10 of the ‘no effect
level’ in the chronic study, aquatic field monitoring weuld be necessary to
determine if the use pattern was acceptable. Secondly, there are
approximately 40 species of fish within the 48 continental States listed as
Federal Endangered Species. The future intent of EPA (in conjunction with
USD1) will be to determine if any of these species are potentially exposed
to residues of at least 1/10 the LC—l0 of rainbow trout. The LC—lO value
for Metolachlor is 2.6 pn (Buccafusco, l978b). Therefore, the critical
residue level uld be 0.26 n. Theoretically, an endangered species in
an acre foot of water, receiving runoff fran five acres of Metolachlor-
treated land, could receive this amount of residue, resulting in a
potentially hazardous condition.
Other non-target organisms of potential concern include microbes,
plants, soil and surface invertebrates, maimials, amphibians and reptiles,
and birds. Soil microbes and the nitrification process do rot appear to
be threatened. Despite the resistance of Metolachlor to hydrolysis and
metabolism, and the possibility of plant tptake with later ingestion by
herbivores, the application of E.C. Metolachior should pose no, or at
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most a highly unlikely, acute hazard to maimT alian i1d1ife. Data are
presently unavailable on toxicity to non-target plants themselves, to
soil and surface invertebrates, and to aiT hibians and reptiles. As
concerns the potential hazard to birds, taking into account E.C.
Metolachlor’ s acreptable uses, its environmental fate, its metabolism, its
persistence in soil under certain conditions, and its uptake by rotational
crops, a long—term exposure of birds to finite levels of tolachlor is
expected. Yet considering Metolachior’s low dietary toxicity to birds, the
acute hazard to birds is minimal, though the long—term effect of
Metolachlor—use on avian wildlife cannot be determined until an acceptable
avian reproduction study hasT been sut nitted and reviewed *
In conclusion, the rtost serious wildlife concern for Metolachior was
with uatic organisms, and it is determined that presently registered use
patterns of F nulsifiable Concentrate Metolachior do not appear to pose an
acute hazard to non—endangered uatic species. Further investigation will
be required to determine if target fields located in drainage basins,
bordering streams inhabited by endangered aquatic species, should be
prohibited fran being treated with Metolachior at any application rate.
Finally, Metolachior’s quantified potential for persistence in the aguatic
envirornnent, and for causing chronic effects to aquatic organisms, have yet
to be determined.
Generic Data Gaps
The following are gaps in the Ecological Effects data base needed to
adequately support a Registration Standard for Metolachior. After each gap is
listed the section in the Proposed Guidelines of July 10, 1978 (40 CFR Part
163) which describes that type of test and when it is required. The following
studies s uld test the Technical in order to assess the hazard associated with
the use of the F nulsifiable Concentrates.
For Technical Metolachior:
1) Activated sludge metabolism study. 163.62—8(g)
2) The avian acute oral LD—50 for one species 163.71—1
of waterfowl (preferably the mallard) or
one species of upland game bird (preferably
the bobwhite, other native quail, or the
ring—necked pheasant).
3) Avian reproduction studies on bobwhite quail 163.71—4
and mallard ducks.
4) A freshwater fish (fathead minnow, preferably) 163.72—4
life—cycle test.
For Dnulsifiable Concentrate Metolachlor (8 lbs./gallon or less): none
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Suggested Labeling
In order to reduce the risk of the chemical reaching aquatic sites when
an effluent occurs during the manufacturing of Metolachior, or when Metolachior
is ar.plied in the field, the following precautionary labeling is required:
For T chnical Metolachior:
“Do rot discharge into lakes, streams, ponds, or public waters
unless in accordance with an NPDES peimit. For guidance, contact
your I gional Office of the EPA.”
For flttulsifiable Concentrate Metolachior:
“Avoid direct application to any body of water. Do rot apply
where runoff is likely to occur. Do not contaminate water by cleaning
of equi xnent or disposal of wastes • Do rot apply when weather
conditions favor drift fran target area.”
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BIBLIOGRAPHY
(Reserved)
In order for the provisions of FIFRA concerning data compensation (Section
3(c)(1)(d)) to be effective znder Registration Standards, data used in direct
support of the Standard for each type of product must be accurately listed,
enabling applicants and their arbitrators to determine what data do and dt not
support the registrations of individual pesticide products. Thus, for each
di-sciplinary chapter, studies used to evaluate hazard and establish Standards
for the manufacturing-use chemical and for each type of end—use formulation
will be listed separately.
Tb protect present ar 5 potential applicants for the registration or re—
registration of products containing Metolachlor, the citations appropriate to
each disciplinary chapter will not be published in this Sample Standard, though
a canpiete Bibliography is provided at the end of the doc ent.
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REGULT )RY R1 TION LE
The purpose of the ‘Regulatory Rationale’ is to swnmav’ize the salient
factors supporting the Agency’s regulatory decisions, and to show how the
regulatory position is logically derived from the evaluation of hazard in the
Disciplinary Chapters. Because a manufacturing—use pesticide product presents
different hazards from an end-use pesticide product, and because different
types of end—use products can themselves present different hazards, each will
have its own ‘regulatory rationale’. The discussions are further divided
between hazards to man and hazards to wildlife. The goal of each discussion
is to determine how hazards may be lessened, mitigated, or prevented by
regulatory actions which are appropriate to the severity of the problem and
which preserve, to the greatest extent possible, the efficacy and benefits of
the pesticide.
TECHNIC1 L ME’lDIACHLOR
The only risks used to determine the conditions of a technical chemical’ s
registerability are those which arise in the production, packaging, shipping,
handling, re-formulating, and disposing of the chemical - that is, in the
various aspects of its manufacture as a pesticide active ingredient.
Technical Metolachior, at least ninety—five percent the pure ccinpound, is
an off—white, odorless liquid, soluble in water, and miscible with several
organic solvents.
The Mitigation of Hazards to Humans
Technical Metolachlor’ s acute toxicity to humans appears to be mild:
it has a low acute oral toxicity, it is not re iily absorbed by the skin,
it has a very low inhalation toxicity, and no eye irritation effects are
observable. The only significant acute effect is skin sensitization. once
an exposure occurs, Metolachior is rapidly absorbed, metabolized, and
excreted. Though the available oncogenicity and chronic feeding studies
were not aiequate for a caiiplete evaluation of these effects in humans, the
long-term tests that were available showed no evidence of teratogenic,
fetotoxic, reproductive, or mutagenic effects.
For persons involved in the manufacture, handling, storage, or
shipment of Technical Metolachior, there is little likelihood of oral
exposure, and because of the low vapor pressure of the viscous liquid,
there is also little chance of inhalation exposure. The nost likely human
exposure is a repeated dermal exposure, and occasionally, by accident, an
occular exposure.
Though there is presently no evidence of teratogenic, fetotoxic,
reproductive, or mutagenic effects due to Metolachlor, the chronic hazard
to humans caused by repeated dermal exposure to a Technical Metolachior
solution cannot be concluded, for lack of sufficient chronic studies.
Available studies do indicate a potential dennal sensitization problem for
factory, transport, or re—formulation workers.
‘i regulatory actions are available for helping to preclude repeated
dermal exposures: a label warning to “Wear protective clothing while
handling or using this product”; and a registration requirement for
manufacturers that calls for the documentation of the lack of dermal
exposures in manufacturing facilities or the nonitoring and suthassion of
skin sensitization data frau such exposure.
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For a Technical Metolachior with a ‘Category IV’ toxicity by oral,
dermal, arx3 inhalation routes, and a ‘Category IV’ rating with regard to
eye irritation, the label need only bear the following precautions:
“CPtJrICtV’, followed by “Keep out of reach of children”, “Harmful if
swallowed”, and the first—aid statement, “If swallowed, induce vaniting.
Flush exposed eyes and skin with water.”
The Mitigation of Hazards to Wildlife
The available wildlife studies suggested similarly mild ecological
hazards. The toxicity of Technical Metolachior to birds was shown to be
low in one dietary LC—50 test, though adequate data were rot available to
determine single—dose toxicity nor reproductive effects. The data used to
evaluate htxnan acute toxicity were sufficient to indicate a low acute
toxicity to wild maiwnals. Though the chronic fish study has not yet been
canpleted, Technical Metolachlor was shown to have a moderate acute
toxicity to cold and warm water fishes, and a sa what lower acute toxicity
to aquatic invertebrates.
For wildlife in the proximity of Technical Metolachlor manufacture,
storage, shi çing, or disposal, intentional discharges of the chemical into
the envirot ent, such as by disposal or drainage, as well as unintentional
discharges, such as by spillage or fire, could result in significant
wildlife exposures The pathway of exposure which is the most direct
concern is the discharge of effluent into freshwater aquatic habitats. The
organisms nost susceptible to exposure by route of freshwater aquatic
discharge are fish, amphibians, and, because of plant uptake, certain local
mauinalian herbivores.
The stability of the Metolachlor axnpound to hydrolysis and its
potential resistance to metabolic degredation, together with its moderate
toxicity to both cold and warm water fishes, indicates a potential hazard
to fish, if the Technical chemical or effluent fran its manufacture
were disposed of, spilled, or allowed to drain into freshwater aquatic
habitats. Ibxicity to maninals is low enough that an occasional exposure for
matinalian herbivores is rot of concern. ‘Itxicity to amphibians is rot
known, aid testing on amphibians aid reptiles is not usually required.
Though the required long—term studies on fish and birds, and the acute oral
test for waterfowl, may later disclose a greater wildlife sensitivity
to exposure, in the meantime, the label for Technical Metolachlor should
bear the precaution: “D not discharge into lakes, streams, ponds, or
piblic waters unless in accordance with NPDES permit. For guidance,
contact your I gional Office of EPA.”
4ULSIFIABLE Q) ICEN RKI S of ME’IOIACHIDR
The only forniilations of Metolachlor which are registered, and which
therefore provide the standards of formulation for this chemical, are t
milsifiable Concentrates: one formulated with six pounds active ingredient
per gallon; and the other with eight pounds per gallon. Thus this Standard
will cover all E tvlsifiable Concentrates with eight pounds per gallon or less
of the active ingredient. The currently registered products are in the form of
viscous liquids of neutral The more concentrated formulation is more
viscous aid slightly corrosive to steel and tin.
The Mitigation of Hazards to Humans
The FinulsiTiable Concentrate formulations with eight pounds active
ingredient per gallon have the potential for relatively serious acute
86
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effects. Though they would not be readily absorbed through human skin,
they could produce severe irritation and burns on contact, and like the
active ingredient, may produce skin sensitization with repeated exposures.
The formulations also have a moderate inhalation toxicity, and can cause
serious eye irritation, including irreversible corneal opacity.
Though all chemical products present sane possibility of accidental
ingestion, for persons involved in the dilution, mixing, and application of
Metolachior formulations, there is little chance of oral exposure. But
there is a significant possibility of dermal and eye exposure from the
splashing that may occur while diluting and tank mixing, and in the loading
of spray equip iient. ixie to the Dnulsifiable Concentrate’s high vapor
pressure, an unprotected mixer or diluter who is handling an open container
without adequate ventilation will be subject to fumes. Of greater concern
is that the spray droplets generated by the application of end—use
Metolachior may result in an inhalation exposure for applicators and other
agricultural workers who may be in the proximity of the spraying. Chronic
dietary exposures for the general population, due to residues on food (and
in feed given to livestock subsequently consumed by humans), are expected
to occur at finite levels determined by the temporary tolerances.
Though there is presently no evidence of teratogenic, fetotoxic,
reproductive, or mutagenic effects due to Metolachior, chronic hazards to
humans cannot be determined until further studies on the chronic effects of
Metolachlor are cxiupleted. But we can presently conclude that there are
acute hazards involved in the end—use of nulsifiable Concentrate
formulations of eight pounds or less active ingredient per gallon. The
acute hazards to humans caused by the pre—application handling of these
E iiulsifiable Concentrate formulations consist primarily in the potential
for skin and eye burns from accidental splashing, the potential for skin
sensitization f ran repeated dermal contact, and the danger of fume
inhalation from mixing or loading in a closed area. All of these ‘risks’
are routine safety considerations that arise in the mixing and loading of
many an agricultural chemical, and do not suggest that Metolachior is an
unusually hazardous one, but only that a on safety practices are in
order. The greatest risk arising from the actual application of these
formulations is the potential for toxic effects from the inhalation of
spray droplets, and this too is a ‘risk’ that with proper safety
precautions would be unlikely to occur.
There are several general label requirements that are routinely
imposed to help ensure proper safety practices and thereby reduce the acute
end—use risks of agricultural pesticides. To ‘Keep out of reach of -
children’ is the most effective prevention of accidental poisonings from
ingestion. Certain signal words, such as ‘Danger’,, ‘Warning’, and
‘Caution’, when used to reflect the level of a chemical’ s toxicity, can
incite the user of a chemical product to follow written intructions more
precisely so as to avoid accidental exposures. When accidental exposures
do occur, their effects can often be diminished with appropriate first
aid. In the case of E.C. Metolachior, the first aid statement should
instruct: ‘If swallowed, promptly drink egg white or gelatin solutions; or
if these are not available, water. Call a physician iirinediately. Do not
induce emesis as a chemical pneumonitis may occur if aspirated.’
Other more specific label requirements, with stronger warnings
for the more toxic formulations, are available to modify the user’s
behavior and thereby reduce the risks by particular routes of exposure:
‘Harmful if swallowed’ for oral exposure; ‘Avoid contact with skin’,
‘Causes skin irritation’, and/or ‘May cause skin sensitization. Wear
protective clothing when handling this product’ for dermal exposure; ‘Do
87
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not breathe vapors’ or ‘Avoid breathing vapors’ and ‘t)z rot apply when
weather conditions favor drift fran target area’ for inhalation exposure;
‘Corrosive, causes eye damage. Wear goggles or face shield when handling’,
Causes eye irritation’, or ‘Avoid contact with eyes’ for occular
exposure. E nulsifiab1e Concentrates with acute hazards equivalent to or
less than those set out by this Standard, as determined by the toxicity
categories into which they fall, can generally be made safer for use by
means of the appropriate statements of precaution, as set forth in the
Agency’ s regulations on labeling (40 CFR 162.10).
Until nore chronic data becane available for the assessment of the
hazards of a dietary exposure to tolachlor, the temporary tolerances
granted for Metolachior will not be re-assessed. Because there are
presently no tolerances for Metolachior on them, corn forage or fodder
or soybean hay or forage treated with Metolachior should not be grazed or
fed to livestock or used for silage.
The Mitigation of Hazards to Wildlife
The potential hazards to wildlife posed by the use of the Emulsifiable
Concentrates arise fra u the toxicity of the active ingredient rather than
the toxicity of any particular formulation, and the toxicity of the active
ingredient is approximated in the toxicity studies on the Technical. ‘1
repeat the results of those studies: the toxicity of Technical Metolachior
to birds was s1 n to be low in one dietary L 1 C-50 test, but adequate data
were rot available to determine single-dose toxicity nor reproductive
effects. The data used to evaluate h inan acute toxicity were sufficient to
indicate a low acute toxicity to wild mamals. Though the chronic fish
study has not yet been canple ted, Technical Metolachior was shown to have
a noderate acute toxicity to cold and warm water fishes, and a sanewbat
lower acute toxicity to aquatic invertebrates.
As was discussed in the Ecological Effects Hazard Assessment, the
0.075 lbs. active ingredient that ould collect in a 6 inches acre of water
as a result of a normal application rate of 3 lbs. ai/acre uld not pose
an acute hazard to aquatic organisms. However, until the results of the
chronic fish study are in, to reduce the chance of harm to an Endar ered
Species of freshwater fish, to help protect untested species such as
amphibians and local herbivores, and to ensure that sludge treatment
microbes are not affected, every effort should be made to keep the ccxr ound
out of the natural aquatic envirorEnent and the sewer system, and the
following label restrictions are recaiinended: “Avoid direct application to
any body of water. I not apply where runoff is likely to occur. I
not contaminate water by cleaning of equipuent or disposal of wastes.”
‘lb help protect other organisms which still require testing,
particularly birds, fran potential harmful exposures, the following
additional label statement is recaiinended: “1X not apply when
weather conditions favor drift fran target area.”
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REGUL1 LORY POSITION
The ‘Regulatory Position’ represents the Agency’s final decision on how to
best mitigate the hazards to hunans and the envirovvnent which may arise as the
result of the proposed uses of the pesticide chemical. It is based on the
full consideration of all the available hazard information as presented in the
Disciplinary Chapters, on the means for hazard mitigation discussed in the
Regulatory Rationale, and on the public comments received in the course of the
development of the Standard. The ‘Position’ may be expected to comply with
the rules and regulations (40 CFR Parts 162.10 and 162.11) used to
implement the Federal Insecticide, Fungicide, and Rodenticide Act, and with
the Agency’s present regulatory policies. The ‘Regulatory Position’ is a
primary output of the ‘standard-setting’ function of a Registration Standard
in that it represents the ‘standards’ of packaging, labeling, and usage which
help to ensure the safe use of the pesticide chemical.
A separate position is reached for the manufacturing-use chemical and for
each type of end—use formulation which presents a significantly different set
of hazards.
Technical Metolachior
Section 162.11(a) of the Regulations states that the Agency shall presume
against the registration of a pesticide product which meets or exceeds certain
specific risk criteria set forth therein. Because the available data do not
ir icate that any of these risk criteria have been met or exceeded for
Technical Metolachlor, the Agency shall presume that the Technical Metolachior
described in this Standard is conditionally registerable for sale,
distribution, and reformulation in the United States.
The following ‘Sample Label’ includes all those labeling statements which
the Agency has determined will provide an adequate mitigation of those hazards
to man and the environment which may result frau the manufacture, packaging,
transport, handling, reformulation, storage, or disposal of Technical
Metolachior.
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• PIODUCP NNIE
• For Formulation of Herbicides Only
• Active Ingredient:
• Metolachior: 2—chloro—N—(2—ethyl—6—methylphenyl)—
• N— ( 2—methoxy—l—methylethyl ) acetamide %
• Inert Ingredients: ______
• ‘DDtal: 100%
CAUTION
Keep Out of ach of Children
PPECAJJI I(] IARY STPtTE 4E IS:
• Hazards to Humans and Domestic Animals
• Harmful if swallowed. May cause skin sensitization. Wear
• protective clothing (coveralls and gloves) while handling and
• using this product. If swallowed, induce vaniting. Flush
• exposed eyes and skin with water.
Hazards to Wildlife
Do not discharge into lakes, streams, ponds, or public waters
unless in accordance with an NPDES permit. F r guidance, contact
your regional office of EPA.
Directions for Use
It is a violation of federal law to use this product in a manner
inconsistent with its labeling. Refer to technical bulletin.
• Storage and Disposal
For bulk shipments — holding tanks, tank cars, storage tanks, etc.:
Do rot contaminate water, food, or feed by storage or disposal.
• Open dumping is prohibited. Pesticide or rinsate that cannot
• be used or chemically re—processed should be disposed of in a
• landfill approved for pesticides or buried in a safe place
• away frcin water supplies. Thoroughly clean container before
• re—use. Consult federal, state, or local disposal authorities
• for approved alternative measures.
Fbr metal drums, cans, etc.:
• Do not contaminate water, food, or feed by storage or disposal.
• Open dumping is prohibited. Pesticide or rinsate that cannot
be used or chemically re-processed should be disposed of in a
• landfill approved for pesticides or buried in a safe place away
• fran water supplies. Re—seal container and offer for
• re—conditioning; or triple rinse (or equivalent) and offer for
recycling, re-conditioning, or disposal in aWroved landfill;
• or bury in a safe place. Consult federal, state, or local
• disposal authorities for approved alternative procedures.
Note to Formulators : formulators are responsible for providing data
to support the registration of products formulated fran this Technical.
• EPA Registration No. ___________ Net Wt. or Measure _______________
Establishment No. ____________
Name and J ddress of the producer, registrant, or person for whan produced.
. . . . . . . . . .
90
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Emulsifiable Concentrates of Metolaáhlor
(In order to be registerable under this i gistration Standard, an end—use
pesticide product containing Metolachior must contain Metolachlor as the sole
pesticide active ingredient. End—use products containing other pesticide
active ingredients in addition to Metolachior must be registered under a
separate Registration Standard that covers the mixture. A Standard on a
mixture of active ingredients will not routinely be set until the Agency has
caupleted a Registration Standard for each of the active ingredients alone.)
Section 162.11(a) of the Regulations states that the Agency shall presume
against the registration of a pesticide product which meets or exceeds certain
specific risk criteria set forth therein. Because the available data do not
indicate that any of these risk criteria have been met or exceeded for the
proposed uses of Emulsifiable Concentrate Metolachior of eight pounds per
gallon or less, the Agency shall presume that the Emulsifiable Concentrates of
Metolachior described in this Standard are conditionally req isterable for sale,
distribution, and use in the United States.
Section 162.11(c) of the Regulations states that the Agency may classify
for ‘general use’, that is, for use by any member of the general public, any
end—use pesticide product which meets certain specific criteria set forth
therein. An end—use pesticide product which does not meet all these criteria
is considered a candidate for ‘restricted use’, that is, for use only by
certified applicators. Because the available data adequately demonstrate that
these criteria have been met for the Emulsifiable Concentrates of Metolachior
of eight pounds per gallon or less, the Agency shall conditionally classify for
‘general use’ the Emulsifiable Concentrates of Metolachlor described in this
Standard.
The following t ‘Sample Labels’ are for Emulsifiable Concentrates of
Metolachlor: the first ‘Sample Label’ is for an Emulsifiable Concentrate
Metolachlor of six pounds per gallon, and the second is for one of eight pounds
per gallon. These ‘Sample Labels’ include all those statements which the
Agency has determined will provide an adequate mitigation of those hazards to
man and the environment which may result fran the packaging, handling,
transport, application, storage, or disposal of the currently registered
formulations, as investigated in the disciplinary chapters.
In order to be registered under this Standard, an Emulsifible Concentrate
of eight pounds or less Metolachlor per gallon must be shown to have acute
hazards which fall in the same or numerically higher toxicity categories (see
the chart in 40 CFR 162.10) than those identified in the ftxicology chapter,
and equivalent or lesser wildlife hazards than those identified in the
Ecological Effects chapter. Thus, no end—use Emulsifiable Concentrate
Metolachior product may be registered under this Standard if its toxicity
to humans or wildlife requires more stringent precautions than those appearing
in either of the ‘Sample Labels’ that follow. Or in other rds, the following
‘Sample Labels’ contain, between them, the most stringent precautions that will
be needed for any end—use product req isterable under this Standard.
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• S • • S • • • • S • • S S S • • • • • . . S • •
• iooucr NAME
.
• P1OWC NAME contains 6 lbs.
• active ingredient per gallon
.
Ftr weed control in soybeans
and in corn grown for grain (excluding popcorn)
Active Ingredient:
• Metolachlor: 2-chloro-N- ( 2-ethyl-6-methylphenyl ) -
• N—(2—methoxy—l—methylethyl)acetajujde 6 8.5 %
• Inert Ingredients: 3 1.5 %
• ¶Ibtal: 100%
.
• DANGER
• Keep C .it of 1 ach of Children
• See additional danger statements on ____ side of container.
PRECAIJTICt ARY SI’A’I 1ENIS:
• Hazards to Humans and Dat stic Animals
• Corrosive — causes eye damage. Wear goggles or face shield
• when handling. Do not get on clothing. Harmful if swallowed.
• The active ingredient, metolachior, may cause skin
• sensitization reactions in certain individuals. Wear
• protective clothing when handling, and wash thoroughly after
• handling. Avoid contamination of food. 1 move and wash
• contaminated clothing before re-use.
.
• FI AID: In case of contact with eyes, ixrrnediately flush with
• plenty of water for at least 15 minutes. Call a physician. If
• inhalation occurs, the victim should be noved to fresh air, and
medical attention should be iirrnediately sought. If swallowed,
p x* t1y drink egg white or gelatin solutions; or if these are
not available, water. Call a physician irrtnediately. ( Note to
physician : if swallc d, there is no specific antidote. Do rot
• induce emesis as a chemical pneuionitis may occur if aspirated.
• Lavage stczuach. Deposit 50 grams of activated charcoal in a water
• slurry in the stanach. Give a saline laxative and supportive
• therapy as needed.)
• Hazards to Wildlife
• Avoid direct application to any tody of water. Do not apply where
• runoff is likely to occur. Do not contaminate water by cleaning
• of & uipnent or disposal of wastes • Do not apply when weather
• conditions favor drift fran target area.
Physical/Chemical Hazards
Do not use or store near heat or open flame.
(sample label continued)
92
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(sample label continued)
Directions for Use
PR)LiJCT NAME (6 lbs. ai/gal..) is a selective herbicide
recarrnended as a preplant incorporated or preemergence surface—
applied treatment for control of riost annual grasses and certain
broadleaf weeds.
Corn : Use only on corn grown for grain. tO rot
use on sweet corn or popcorn. Do not graze
or feed forage and fodder to livestock
or use for silage.
Soybeans : to not graze or feed soybean hay or
forage.
It is a violation of federal law to use this product in a manner
inconsistent with its labeling.
I tational Crops
1) If corn treated with PIODUC NAME (6 lbs. aijgal.) is
lost due to poor germination, hail, flood, insects, etc.,
corn may be replanted iitinediately. Lb rot make a second
broadcast application. If the original application was banded
arx3 the second crop is planted in the untreated row middles,
a second band treatment may be applied. 2) Do not plant
rotational crops other than corn or soybeans within 18 nonths
after application.
Storage and Disposal
Do not contaminate water, food, or feed by storage or disposal.
C en dumping is prohibited. Pesticide, spray mixture, or
rinsate that cannot be used or chemically reprocessed should be
disposed of in a landfill approved for pesticides or buried in
a safe place away frc*it water supplies. Triple rinse (or
equivalent) empty containers, re—seal, and offer for recycling,
re—conditioning, or disposal in an approved landfill or bury in
a safe place. Consult federal, state, or local disposal
authorities for approved alternative procedures.
EPA Pegistration No. ___________ Net Wt. or Measure _______________
• Establishment No. ____________
Name and Address of the producer, registrant, or person for whom produced.
93
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S • • S • . . S S •
• PFOWCP NAME
.
P1O1X)CP NAME contains 8 lbs.
active ingredient per gallon.
For weed control in soybeans
and in corn grown for grain (excluding popcorn)
Active Ingredient: :
Metolachior: 2-chloro-N— (2—ethyl--6—methylphenyl ) -
N—(2—methoxy—l—methylethyl)acetamide 8 6.4 %
Inert Ingredients: 1 3.6 %
i tal: 100%
.
WARNING
• Keep c t of leach of children
See additional danger stat nts on ____ side of container.
.
PRECATJPICt ARY SIWIEIENIS:
• Hazards to Humans and Dat stic Animals
• Causes eye irritation. Do rot get in eyes or on clothing.
Causes skin irritation. Wear gloves and protective clothing
• when handling. Harmful if swallowed. Do rot breathe vapors.
The active ingredient, metolachlor, may cause skin sensitization
in certain individuals. Wash thoroughly after handling. Avoid
contamination of food. Ratove and wash contaminated clothing
before re—use.
• FII AID: In case of contact with eyes, iim ediately flush with
plenty of water for at least 15 minutes. Call a physician. If
inhalation occurs, the victim should be noved to fresh air, and
• medical attention should be imnediately sought. If swallowed,
pratptly drink egg white or gelatin solutions; or if these are
• rot available, water. Call a physician ininediately. ( Note to
Physician : If swallowed, there is no specific antidote. Do rot
induce sines is as a chsinical pneuionitis may occur if aspirated.
Lavage stanach. I posit 50 grams of activated charcoal in a water
slurry in the stanach. Give a saline laxative and supportive
therapy as needed.)
Hazards to Wildlife
Avoid direct application to any body of water. Do rot apply where
runoff is likely to occur. Do rot contaminate water by cleaning
of uipnent or disposal of wastes. Do rot apply when weather
• conditions favor drift fran target area.
Ph ’sica1/Chemical Hazards
Do rot place in unlined metal containers or tanks.
(sample label continued)
94
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(sample label continued)
.
Directions for Use
PFOWCr NN4E (8 lbs. ai/gal.) is a selective herbicide
recanmended as a preplant incorporated or preemergence surface—
• applied treatment for control of most annual grasses and certain
• broa:]leaf weeds.
• Corn : Use only on corn grown for grain. E not
• use on sweet corn or popcorn. Dz not graze
• or feed forage and fodder th livestock
• or use for silage.
• Soybeans : L X ) rot graze or feed soybean hay or
• forage.
• It is a violation of federal law to use this product in a manner
• inconsistent with its labeling.
I p
• Rotational Crops
• 1) If corn treated with PFOtXJCr NN4E (8 lbs. ai/gal.) is
• lost due to poor germination, hail, flood, insects, etc.,
• corn may be replanted ininec3iately. DD rot make a second
• broadcast application. If the original application was banded
• and the second crop is planted in the untreated row middles,
• a second band treatment may be applied. 2) DD not plant
• rotational crops other than corn or soybeans within 18 months
• after application.
.
• Storage and Disposal
• LX) not contaminate water, food, or feed by storage or disposal.
• Open dumping is prohibited. Pesticide, spray mixture, or
• rinsate that cannot be used or chemically reprocessed should be
• disposed of in a landfill approved for pesticides or buried in
• a safe place away fran water supplies. Triple rinse (or’
equivalent) empty containers, re—seal, and offer for recycling,
• re—conditioning, or disposal in an approved landfill or bury in
a safe place. Consult federal, state, or local disposal
• authorities for approved alternative procedures.
EPA I gistration No. ___________ Net Wt. or asure _______________
• Establishment No. ____________
• Name and Mdress of the producer, registrant, or person for whc*n produced.
• . I I . I • I • •
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REGISThATIC UNDER ThIS STANDARD
Registration Procedures
For a full understanding of pesticide testing guidelines and registration
procedures, please refer to 40 CFR 162.1 — 162.23 and 40 CFR 162.40 — 162.96.
Briefly, however, to register or re—register a pesticide product under this
Registration Standard for Metolachlor, an applicant must su iiiit the appropriate
application forms and other information, as specified below, to the following
address:
Registration Division (WH—567)
Office of Pesticide Programs
Environmental Protection Agency
Washington, D.C. 20460
(All forms may be obtained by request from the same address. Please request
forms with EPA Form Numbers by the number, and all other forms by title.)
I. Your application must include the following forms:
EPA Form Number
1) Application for (Re—)Registration 8570—1
2) Confidential Statement of Formula 8570—4
3) Label Technical Data 8570—10
4) Offer to Pay Statement
5) Certification Statement
II. Your application must also include:
1) Certification of Upper and Lower Limits of Components
(See 40 CFR 163.61—6(a))
2) Proposed Label (2 copies) (see ‘Sample La1 1s’ in ‘Regulatory
Position’)
3) Detmal Sensitization Data (see 40 CFR 163.81—6) — Applicants
are required to document the lack of dermal exposure in
manufacturing facilities or to monitor and subnit skin
sensitization data from such exposure.
III. In order to establish the equivalence of the composition of a proposed
formulation to the composition of formulations covered by the
Standard, applicants for the registration or re-registration of
F iu1sifiable Concentrate (8 lbs. or less/gallon) must also supply
or cite Acute ‘Poxicology Data which demonstrate that the proposed
product meets the following criteria:
1. Acute Oral Toxicity
Any E.C. Metolachlor of 8 pounds or less per gallon
which falls into Category III or Category IV will be
considered within the scope of this Standard with
regard to acute oral toxicity.
2. Acute Dermal Toxicity
Any E.C. Metolachlor of 8 pounds or less per gallon
which falls into Category III or Category IV will be
97
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considered within the scope of this Standard with
regard to acute dermal toxicity.
3. Acute Inhalation ‘Ibxicity
Any E.C. Metolachlor of 8 pounds or less per gallon
which falls into Category II or a numerically higher
category will be considered within the scope of this
Standard with regard to acute inhalation toxicity.
4. Primary Eye Irritation
My E.C. Metolachior of 8 pounds or less per gallon
which falls into Category I or a numerically higher
category will be considered within the scope of this
Standard with regard to primary eye irritation.
5. Primary t nnal Irritation
My E.C. Metolachior of 8 pounds per gallon or less
which falls into Category II or a numerically higher
category will be considered within the scope of this
Standard with regard to primary dermal irritation.
Generic Data Requirements
This document is currently a Conditional Registration Standard. That is,
the registerability of a pesticide product under this Standard is ‘conditional’
upon each applicant’s agreement to generate, or canpensate other applicants
for generating, certain missing but required data, within a specific schedule
to be determined by the Agency at the time of application. Registrations or re-
registrations which take place under this ‘Conditional Standard’ are termed
‘conditional registrations’. When this required data is supplied to the
Agency and has been determined to be sufficient for the support of a Final
Registration Standard, the potential hazards will be re-assessed, the
appropriate Disciplinary Chapters will be revised, and the regulatory position
(and labels) will be ncdified to reflect the new information.
The data which are currently required in order to adequately support a
Final Registration St pdard for Metolachior are listed belc . After each
requirement is listed the section in the Proposed Guidelines (40 CFR) which
describes that type of data and when it is required.
For Technical Metolachior :
Product Chemistry
1) Octanol/water partition coefficient
2) Flaninability
3) Oxidizing or reducing action
4) Explosiveness
5) Viscosity
6) Corrosion characteristics
7) An analytical method (or reference
to a method) for detecting and
measuring each identifiable impurity
(associated with the manufacturing
of the technical grade of the active
ingredient) in the forimilated
products of Metolachior.
Envirorinental Fate
8) Msorptio desorption studies
163.6l—8(c)6
163 .61—8 ( C) 13
163.61—8(c)14
163 .6l—8(c)15
163.61—8(c)l7
163.6 1—8(c)18
163.61—7
163.62—9
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Toxicology
9) Subchronic Oral ODsing — Acceptable 163.82—1
pathology evaluation is required for
both the rat and dog studies.
10) Oncogenicity — CaTipletion of the mouse 163.83—2
study and testing on a manunal other
than the mouse (the laboratory rat is
preferred) is required.
11) Chronic Feeding — A chronic feeding 163.83—3
study using the laboratory rat is
required.
Ecological Effects
12) Activated sludge metabolism study 163.62—8(g)
13) The avian acute oral LD—50 for one 163.71—1
species of waterfowl (preferably
the mallard) or one species of upland
game bird (preferably the bobwhite,
other native quail, or the ring—necked
pheasant).
14) Avian reproduction studies on bobwhite 163.71—4
quail and mallard ducks.
15) A freshwater. fish (preferably the 163.72—4
fathead minnow) life-cycle test.
For Emulsifiable Concentrate Metolachior (6 lbs./gallon) :
Product Chemistry
1) Color 163.6l—8(c)1
2) Odor 163.6 1—8(c)2
For Emulsifiable Concentrate Metolachlor (8 lbs./gallon) :
Product Chemistry
1) Color 163.6l—8(c)1
2) Odor 163.6l—8(c)2
3) Explosiveness 163.61—8(c)15
Amending the Standard
Applicants for the registration of a pesticide product which contains
Metolachior as the sole pesticide active ingredient, but which does not fall
within the parameters of product cariposition, use, or toxicity as defined in
this Standard, must petition the Agency to ‘amend the Standard’. The Agency
will consider the petition, and determine what studies are needed to assess the
potential adverse effects of this new canposition, new use, or higher toxicity
to man or the environment. When the applicant has satisfactorily upplied the
needed data, and providing that the data do not indicate the potential for
unreasonable a3verse effects, the Agency will then consider amending the
Standard to cover the new type of product. Amendments to the Standard will
involve the incorporation of the new information into the Disciplinary
Chapters, the appropriate revision of the Regulatory Rationale and Position,
and any needed modification of Registration Procedures.
The actual procedure to be used for petitioning the Agency to amend a
Registration Standard will be forthcaning in future Regulations.
99
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APPENDICES
101
-------
APPENDIX A. CHEMICAL DATA SHEETS
Chemical Data Sheets have been prepared for the ca’nponents, hydrolysis
products, and known metabolites of manufacturing—use Metolachlor. The Data
Sheets are divided into Ccraponents COMOO1 through COMO11, Hydrolysis Products
HPOO1 and HPOO2, and Metabolites METOO1 through METO24. Chemical Data Sheets
are not available for METO25 and METO26, though their structures are given in
the Environmental Fate chapter.
103
-------
COMEONENT NUMBER (DM001
01. Chemical Abstracts Chemical names;
01 Acetamide, 2—chloro—N-- ( 2-ethyl—6-methylphenyl ) —N-- ( 2-methoxy-1-
methylethyl ) - (C1 9)
02 o—Acetotoluidide, 2—chloro—6’ —ethyl—N— ( 2—methoxy-1—methylethyl ) —
(CAB)
02. Other Chemical Names;
01 2-Chloro—N—(2--ethyl—6—methylphenyl)-N—(2’ —methoxy-1 ‘—methylethyl)-
acetamide —
02 1 etani1 ide, 2—chloro-2’—ethyl-N- ( 2—methoxy-l-methylethyl ) -6 ‘-methyl-
03 N— (2’ —Methoxy—1 ‘—methylethyl ) -2—ethyl—6-inethyl-chloroacetanilide
04 N—(Chloroacetyl)—6—ethyl—N—(2—methoxyisopropyl)-o—toluidine
03. Structural Formula;
0
I
çCCHrCL
0—cs , 3
CH 3
04. t 1ecu1ar (Empirical) Formula;
C 15 H 22 C1N0 2
05. Chemical Abstracts (CAS) 1 egistry Number;
06. Approved Cci non Name;
01 Metolachior
07. Other Corrii n Names, Trade Names, or Codes;
01 IXial
02 CGA t . 24705
105
-------
Ch nica1 Data Sheets (X 4—0O2 through (t 4—Oll have been
cinitted in this Sample Registration Standard because of
confidentiality claims by the manufacturer.
106
-------
HYD )L? IC P1 )WCP NUMBER HPOO1
01. Chemical Abstracts Chemical Names;
01 1—Propanol, 2- [ (2-ethyl-6-methylphenyl )amino] - (CA9)
02 1—Propanol, 2—(6—ethyl—o—toluidino)— (CAB)
02. Other Chemical Names;
01 1—Propanol, 2— (2—ethyl—6—methylanil mo ) —
02 2— [ (2—Ethyl—6-methyl ) amino] —1—propanol
03. Structural Formula;
04. Molecular (flupirical) Formula;
C 12 H 19 N0
05. Chemical Abstracts (CAS) Registry Number;
06. Approved CarEnon Name; None
07. Other Coiruon Names, Trade Names, or Codes;
01 CG1 No. 37913
02 PUP (Propanol hydrolytic product)
107
-------
H))LYTIC P1 )WCT NUMBER HPOO2
01, Chemical Abstracts Chemical Names;
01 3-Morpholinone, 4- (2-ethyl-6-methylphenyl ) -2-hydroxy- 5-nE thyl-
02 3-Morpholinone, 4- ( 6—ethyl-o-tolyl ) -2-hydroxy-5-methyl-
02. Other Chemical Names;
01 4- ( 2—Ethyl-6-methylphenyl ) -2-hydroxy-5-nethyl-3-irorphol inone
03. Structural Formula;
/S f ’s
1 \ ir tx
‘ -Ci -?
04. Łblecular (E npirical) Formula;
C 14 H 19 3
05. th aica1 Abstracts (CAS) Registry Nunter;
06. Ajj.proved Camon Name; None
07. Other Ca cn Names,’ Trade Names, or Codes;
01 CG No. 49751
02 PUlP (nx)rpholinone hydrolytic product)
108
-------
ME I’I BOLITE NUMBER METOO1
01. Chemical P bstracts Chemical Names;
01 k etamide, N- ( 2—ethyl—6—methylphenyl ) —2—hydroxy-N- ( 2—methoxy-l—
methylethyl)- (CA9)
02 o-Acetotoluidide, 6 ‘—ethyl—2—hydroxy—N— ( 2-methoxy—1-methylethyl ) -
(Cl 8)
02. Other Chemical Names;
01 Acetanilide, 2 ‘—ethyl—2—hydroxy—N— ( 2—methoxy—1-methylethyl ) -6’ -methyl—
02 N— ( 2—Ethyl—6--methylphenyl ) —2—hydroxy—N-- (2-me thoxy-l-
methylethyl ) acetamide
03. Structural Formula;
___ CH&
/ \ ,, H—ctlIL-o _cN$
04. Molecular (flupirical) Formula;
C 15 H 23 I D 3
05. Chemical Abstracts (CAS) Registry Number;
06. Approved Ccxri n Name; None
07. Other Cc tm n Names, Trade Names, or Codes;
01 CG1 No. 40172
109
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METIBOLITE NUMBER METOO2
01. Chemical 1 bstracts Chemical Names;
01 2 cetarnide, N- ( 2-ethyl-6-methylphenyl ) -2-hydroxy- (CA9)
02 o-1 cetoto1uidide, 6’ -ethyl-2-hydroxy— (CM)
02. Other Chemical Names;
01 etani1ide, 2’-ethyl—2—hydroxy—6 ‘—methyl—
02 N- (2—Ethyl-6--methylphenyl ) -2—hydroxyacetamide
Structural Formula;
c44$
04. 1ecular (E npirica1) Formula;
C 11 H 15 F1J 2
05. themical bstracts (CAS) Registry Number;
06. Apprcwed Cart n Name; None
07. Other Ccnicn Names, Tr& e Names, or Ccdes;
01 CGA No. 37735
110
-------
METABOLITE NUMBER METOO3
01. Chemical 1 bstracts Chemical Names;
01 ?cetamide, 2—chloro—N— ( 2—ethyl—6—methylphenyl ) —N— ( 2—hydroxy—l—
methylethyl)- (CA9)
02 o-Acetotoluidide, 2—chloro-6 ‘-ethyl—N—(2—hydroxy-l-methylethyl)-
(CA8)
02 • Other Chemical Names;
01 1 etani1ide, 2—chloro--2 ‘—ethyl—N—(2—hydroxy-1--methylethyl)-6 ‘-methyl-
02 2-Chloro-N-- ( 2—ethyl—6-methylphenyl ) -N— ( 2-hydroxy-1-
methylethyl ) acetamide
03. Structural Formula;
04. Molecular (E npirical) Formula;
C 14 H 20 C1N0 2
05. Chemical Abstracts (CAS) Registry Number;
06. Approved Coint n Name; None
07. Other Catuon Names, Trade Names, or Codes;
01 CG No. 41638
111
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MErABOLITE NUMBER METOO4
01. Chemical Ithstracts Chemical Names;
01 DL-Alanine, N- ( 2-ethyl-6-uethylphenyl ) -N- (hydroxyacetyl ) - (CA9)
02 DL-Alanine, N- ( 6-ethyl-o-tolyl )-2- (hydroxyacetyl ) - (CAB)
02. Other Chemical Names;
01 Propanoic acid, 2— [ N— ( 2-ethyl—6--methylphenyl )—2—hydroxyacetamido] —
02 Propionic acid, 2- [ N- ( 6-ethyl-o-tolyl ) -2-hydroxyacetamido] -
03 U- (2—Ethyl—6-methylphenyl )-N-- (hydroxyacetyl )alanine
03. Structural Formula;
04 • tiblecular (E npirica1) Formula;
C 14 H 19 ) 3
05. (i emical lths tracts (CAB) Beg is try Number;
06. A ç rwed Caoi n Name; Norm
07. Other Oxmon Names, Trade Names, or CA des;
01 GA . 46129
112
-------
METABOLITE NUMBER METOO5
01. Chemical Abstracts Chemical Names;
01 1 etamide, N— ( 2—ethyl—6—methylphenyl )—N— ( 2—methoxy—1—methylethyl ) -
(CA9)
02 o—Acetotoluid ide, 6 ‘—ethyl—N— ( 2—methoxy—1--methylethyl ) — (CA8)
02. Other Chemical Names;
01 I cetani1 ide, 2’ —ethyl—N— ( 2—methoxy--1—methylethyl ) —6’ —methyl—
02 N— ( 2—Ethyl—6—methylphenyl ) —N— ( 2—methoxy—1—inethylethyl )acetainide
03. Structural Formula;
p ,C.i —CH 1 OCI4 3
04. M 1ecular (Empirical) Formula;
C 15 H 23 N0 2
05. Chemical Abstracts (CAS) Registry Number;
06. Approved Cannon Name; None
07. Other Conuon Names, Trade Names, or Codes;
01 DechloranetOlachlOr
02 CGA No. 41507
113
-------
M ABOLITE NUMBER METOO6
01. Chemical Abstracts Chemical Names;
01 Ace tamide, N- ( 2-ethyl—6—irethylphenyl ) —N- ( 2-hydroxy—l--methylethyl ) -
(CA9)
02 o-Acetotoluidide, 6’ -ethyl—N—(2—hydroxy—1—methylethyl )— (CA8)
02. Other Chemical Names;
01 Acetanilide, 2 ‘—ethyl—N—(2—hydroxy—1—methylethyl)—6 ‘-methyl-
02 N- (2—Ethyl—6--methylphenyl ) —N— ( 2—hydroxy—1-methylethyl ) acetainide
03. Structural Formula;
—CW 1 OH
04. tblecular (Empirical) Formula;
C 14 H )
05 • th nica1 Abstracts 4 CAS) Req is try Number;
06. AL pro ,ed Cati n Name; None
07 • Other Cariion Names, Tr e Names, or Ccdes;
01 cGA No. 42446
114
-------
M BOLITE NUMBER METOO7
01. Chemical l˝bstracts Chemical Names;
01 Acetamide, N- ( 2-ethyl—6—methylphenyl ) — (C 9)
02 o—Acetotoluidide, 6’—ethyl— (CA8)
02. Other Chemical Names;
01 Acetanilide, 2’—ethyl—6’—methyl--
02 N— ( 2—Ethyl—6—methylphenyl ) acetamide
03. Structural Formula;
04. M 1ecu1ar (E npirica1) Formula;
C 11 H 15 N0
05. Chemical Abstracts (CAS) Registry Number;
06. Appro ied Caimn Name; None
07. Other Cc mon Names, Trade Names, or Codes;
01 CGA No. 42444
115
-------
METABOLIT! !Y&JMBER METOO8
01. Ch nical Abstracts Chemical Names;
01 3- rpho1 inone, 4- ( 2-ethyl-6-nethylphenyl ) -5-methyl- (CA9)
02 3— rpho1 iixne, 4- ( 6-ethyl--o--tolyl ) -5—methyl- (CAB)
02. Other Chemical Names;
01 4— (2—Ethyl—6 -methylphenyl ) -5—methyl— 3—nirphol inone
03. Structural Formula;
04. tblecular (E npirica1) Formula;
C 14 H 19 ND 2
05. themical Abstracts (CAS) Registry nber;
06. A}jçrcwed CaIITcn Name; None
07, Other Cmt Names, Tr e Names, or Codes;
01 cGA No. 40919
116
-------
ME FABOLITE NUMBER ME’r009
01. Chemical Thstracts Chemical Names;
01 1 cetamide, 2-chloro-N- ( 2-ethyl-6--methylphenyl. ) - (CA9)
02 o-Acetotoluidide, 2—chloro-6 ‘—ethyl— (CAB)
02. Other Chemical Names;
01 Acetanil ide, 2—chloro--2 ‘-ethyl—6’ —methyl
02 2-Chloro-N-- ( 2—ethyl-6-methylphenyl ) acetamide
03. Structural Formula;
04. Molecular (flupirical) Formula;
C 11 H 14 C1 )
05. (lemical Abstracts (CAS) Pegistry Number;
06. Approved Ccitn on Name; None
07. Other Carton Names, Trade Names, or Codes;
01 CG1 No. 13656
117
-------
M ABOLITE NUMBER METO1O
01. Ch nica1 Abstracts Ct nica1 Names;
01 Benzenamine, 2-ethyl-N- ( 2-methoxy-1-methylethyl ) -6-methyl- (CA9)
02 o-lbluidine, 6-ethyl—N-- ( 2-methoxy-1—methylethyl )- (CAB)
02. Other C mica1 Names;
01 Aniline, 6-ethyl-N- (2-metl xy--l-methylethy1 ) -6-methyl-
02 2-Ethyl-N- ( 2-met1- xy-l-methylethyl ) -6--me thylbenzenamine
03. Structural Formula;
04 • ?blecular (Dapirical) Formula;
C 13 H 21 t )
05. th nica1 Abstracts (CAS) Registry &unber;
06. A ,rcw Caiu n Name; None
07. Other Caii cn Names, Trade Names, or Codes;
01 CGA No. 38502
118
-------
MET2ABOLITE NUMBER ME’rOll
01. Chemical 1 bstracts Chemical Names;
01 ? cetamide, N- ( 2-ethyl-6-methylphenyl ) -2—mercapto-N- ( 2-methoxy-l-
methylethyl)-,S-conjugate with Glutathione
02 o—Acetotoluid ide, 2’ —ethyl-2-mercapto-N- ( 2-u thoxy-1-methylethyl ) —,
S—conjugate with Glutathione
02. Other Chemical Names;
01 P cetani1 ide, 2’ -ethyl—2--mercapto-N— ( 2-niethoxy—l-methylethy) —6’-
methyl-, S-conjugate with Glutathione
02 Glutathione, sulfide with 2-chloro-N- ( 2-ethyl-6--methylphenyl ) -N-
(2—rae thoxy— 1-me thylethyl ) acetamide
03 Glutathione, sulfide with 2—chloro-6 ‘-ethyl—N- ( 2—methoxy- -l-
methylethyl ) -o—acetotoluid ide
03. Structural Formula;
04. t.tlecular (Dnpirical) Formula;
C 25 H 38 N 4 0 8 S
05. Chemical Abstracts (CAS) Registry Number;
06. Approved Cc inon Name; None
07. Other O mion Names, Trade Names, or Codes;
01 MetolachlOr glutathione conjugate
02 CGA No. 43826
119
-------
ME’rABOLITE NUMBER ME 012
01. Ch uica1 I bstracts CI aica1 Names;
01 etamide, N- ( 2-ethyl-6-methylphenyl ) -2--mercapto-N- (2-me thoxy—1-
methy1ethyl)—,S- njugate with Glucuronic acid (CA9)
02 o—1 cetoto1uidide, 2’ —ethyl-2-mercapto-N- (2—me thoxy—1-methylethyl ) -,
—xnjugate with Glucuronic acid (CAB)
02. Other Chenical Names;
01 ? etani1 ide, 2 ‘-ethyl-2-mercapto --N- ( 2-methoxy-1-methylethyl ) -6 ‘-
methyl-,S-cxnjugate with Glucuronic acid
02 Glucuronic acid, 1—S-- [ [ [ (2-ethyl—6—methylphenyl) (2-me thoxy—1—
methylethyl )-amino] carbonyl] methyl] -l-thio-
03 Glucuronic acid, 1—S— [ [ (6—ethyl—o-tolyl) (2—me thoxy—1—methylethyl)
carbamyl] methyl] -1-thio-
03. Structural Formula;
04. Molecular (flupirical) Formula;
C 21 H 30 I D 8 S
05. th nical Thstracts (CAS) 1 gistry I &unber;
06. A roved Cam n Name; Norm
07 • Other Qzuon Names, Tr e Names, or Codes;
01 Metolachlcx glucuronic acid xnjugate
02 CanpourKi N
120
-------
METABOLITE NUMBER METO13
01. Chemical Abstracts Chemical Names;
01 Acetamide, N— (2—ethyl—6—methylphenyl ) —N-- ( 2-hydroxy—l—methylethyl ) -2-
mercapto—, 0—glucoside, S—conjugate with Glucuronic acid (CA9)
02 0—Ace totoluid ide, 6 ‘-ethyl-N— ( 2-hydroxy—l-methylethyl ) -2-mercapto-,
0—glucoside, S—conjugate with Glucuronic acid (CM)
02. Other Chemical Names;
01 Acetanilide, 2’ethyl—N—(2—hydroxy—l—methylethyl)—2—mercapto--6 I—
methyl—, 0—glucoside, S-conjugate with Glucuronic acid
02 Glucuronic acid, 1—S— [ [ (6—ethyl-o—to lyl) (2 —gluoosyl(1)—l—
methylethyl ) carbanoyl] methyl] -l-thio-
03 Glucuronic , l—S— [ [ [ (2—ethyl—6--methylphenyl) (2-glucosyl(1)—1-
methylethyl ) amino] carbonyl] methyl] -1-thio-
03. Structural Fbrmula;
04. Molecular (Empirical) Formula;
C 26 H 39 t O 13 S
05. Chanical Abstracts (CAS) Registry Number;
06. A roved Ccimion 1 ame; None
07. Other Convon Names, Trade Names, or Codes;
01 Canpourx No. 0
N
121
-------
MF ABOLITE NUMBER METO14
01. Chemical 1 bstracts Chemical Names;
01 Pee tamide, N- ( 2-ethyl-6-methylphenyl ) -N- ( 2-hydroxy-1-methoxyethyl ) -2-
mercapto-, S—conjugate with Glucuronic acid (Cl 9)
02 o-Acetotoluidide, 2’ -ethyl-N- ( 2—hydroxy-1-methylethyl ) -2-mercapto-,
S—conjugate with Glucuronic acid (C1 8)
02. Other Chemical Names;
01 Acetanilide, 2 ‘—ethyl—N— ( 2—hydroxy—l—methylethyl )—2—mercapto-6’ -
methyl—, S—conjugate with Glucuronic acid
02 Glucuronic acid, 1—S— [ [ [ (2—ethyl—6—methylphenyl) (2—hydroxy—l—
methylethyl )aminoj carbonyll methyl] -1-thio-
03 Glucuronic acid, 1—S— I ((6—ethyl—o-tolyl) (2—hydroxy—1—
methylethyl ) carbai oy1] methyl] -lirthjO-
03 • Structural Fbrmula;
04. Molecular (E npirical) Formula;
C 20 H 1 I) 8 S
05 • Chemical Abstracts (CAS) Registry ! &jmber;
06. A .pro ed Coum n Name; None
07. Other Caim n Names, Trade Names, or Codes;
01 t methy1meto1ach1or glucuronic acid conjugate
c$ -CH
, II
122
-------
METABOLITE NUMBER METO15
01. Chemical Abstracts Chemical Names;
01 1 etamide, N- ( 2—ethyl—6—methylphenyl ) —2—hydroxy—N- (2—me thoxy-1-
methylethyl)—, 0-conjugate with Glucuronic acid (C 9)
02 o-Acetotoluid ide, 2’ —ethyl—2—hydroxy—N— ( 2—rnethoxy--1—methylethyl ) —,
0—conjugate with Glucuronic acid (CAB)
02. Other Chemical Names;
01 Acetanilide, 2 ‘—ethyl—2—hydroxy—N—(2-inethoxy-l—methylethyl)-6 ‘-
methyl—, 0—conjugate with Glucuronic acid
02 Glucuronic acid, 1—0— [ [ [ (2—ethyl—6—methylphenyl) (2—methoxy—1—
niethylethyl)aminoj carbony] methyl] -
03 Glucuronic acid, 1—0— [ ((6—ethyl-o-tolyl) (2—methoxy-1—methylethyl )—
carbamoylimethyl] —
03. Structural Ebnnula;
04. Molecular (fl’rtpirical) Formula;
C 21 H 31 J 9
05. Chemical Abstracts (CAS) P. gistry Number;
06. Approiied CcxrmDn Name; None
07. Other Cc T n Names, Trade Names, or Codes;
01 MetolachiOr glucuroniC acid conjugate
—C .,)
123
-------
M P1 BOLITE NUMBER METO16
01. Chemical /thstracts Chmlical Names;
01 Acetamide, N- ( 2-ethyl-6-methylphenyl ) -2-hydroxy-N- ( 2-hydroxy-1-
methylethyl)-, 0-conjugate with Glucuronic acid
02 o-Acetotoluidide, 2’ -ethyl-2-hydroxy-N- ( 2-hydroxy-1-methylethyl ) -,
s-conjugate with Glucuronic acid
02. Other Chemical Names;
01 Ace tanilide, 2 ‘-ethyl—2-hydroxy-N- ( 2-hydroxy-1-methylethyl ) -6 ‘—methyl-,
0-conjugate with Glucuronic acid
02 Glucuronic acid, 1-0— LEE ( 2-ethyl-6-methylphenyl) (2-hydroxy-l-
methylethyl ) amir ] carbonyl] methyl] -
03 Glucuronic acid, 1-0-1 [ (6-ethyl-o-tolyl) (2-hydroxy—1-methylethyl ) -
carbauoy l]methy l]-
03 • Structural E rmula;
+0N1
44f
coo.”
04. Molecular (Ekupirical) Formula;
C 20 H 29 ND 9
05. Chemical Abstracts (CAS) Registry Nauber;
06. AL croved Cam n Name; None
07. Other Camion Names, Trade Names, or Ccdes;
01 Desmethylmetolachlx glucuronic acid conjugate
124
-------
METABOLITE NUMBER METO17
01. Chemical Abstracts Chemical Names;
01 Pee tamide, N— ( 2—ethyl—6—methylphenyl ) —2—hydroxy—N— ( 2-hydroxy—1-
methylethyl ) —, 0—glucoside, 0—conjugate with Glucuronic acid (CA9)
02 0-Ace totoluid ide, 6’ —ethyl—2—hydroxy—N— ( 2—hydroxy-1—methylethyl ) -,
0—glucoside, 0—conjugate with Glucuronic acid (CAB)
02 • Other Chemical Names;
01 Acetanil ide, 2 ‘ —ethyl—2—hydroxy—N— ( 2—hydroxy—1-methylethyl )—6 ‘-
methyl—,0—glucoside, 0-conjugate with Glucuronic acid
02 Glucuronic acid, 1—0— [ [ (6—ethyl—o—tolyl) (2—glucosyl(1)—1—
methylethyl ) -carbanoyl] methyl]
03 Glucuronic acid, 1—0— [ 1 [ ((2—ethyl—6--methylphenyl) (2-glucosyl(1)—l—
methylethyl)amino] carbonyl]methyl]-
03. Structural Formula;
04. Molecular (flapirical) Formula;
C 26 H 39 1 O 14
05. Chemical Abstracts (CAS) I gistry Number;
06. Approved CQtEnon Name; None
07. Other Ca on Names, Trade Names, or Codes; None
H
125
-------
ME1!ABOLITE JMBER: 018
01. Ch nica1 abstracts Chemical Names:
01 iirx1ine, N-( 2—methoxy--1--methylethyl ) -8-
ethyl-3-hydroxy-2-oxo-1 ,2,3, 4-tetrahydro-
02. Other Chemical Names:
01 8—Ethyl-3-hydroxy-N- ( 2-methoxy-1-methylethyl ) -
2—oxo—1 ,2 ,3 ,4—tetrahydroquinoline
03. Structural Fornuila:
— ctl—çH 2 —OCH 3
04. !etlecular (F npirical) rnLila:
C 15 H 21 ? ) 3
05. Chemical Abstracts (CAS) Registry imber:
06. Approved Ccmt n Names, Trade Names, or Codes:
126
-------
METABOLITE NUMBER: 019
01. Chemical Abstracts Chemical Names:
01 Acetamide, 2—hydroxy—N- ( 2—methyl—6—vinylphenyl ) -
N- ( 2-methoxy-1-methylethyl ) -
02. Other Chemical Names:
01 2—hydroxy-N- (2-mothyl-6—vinylphenyl)-N-
(2—methoxy--1—methylethyl) acetamide
03. Structural Formula:
04
__,h Gi
/ ,is4 -c* 1 -o-cIĽ
04. Molecular (Dupirical) rmula:
C 15 H 21 N3 3
05. Chemical Abstracts (CAS) Registry Number:
06. Approved Ccxriton Names: None
07. Other Ccimnon Names, Trade Names, or Codes:
127
-------
METABOLI’1 NUMBER: 020
01. Chemical Abstracts Chemical Names:
01 iino1 me, N- isopropyl-8-ethyl-3-hydroxy-2-oxo-
1,2,3 ,4,—tetrahydro—
02. Other Chemical Names:
01 8—Ethyl—3—hydroxy—N— isopropyl—2-oxo-l , 2,3,4—
tetrahydroquinoline
03. Structural Formula:
ç - 1 CH3
04. tblecular (Dnpirical) Fornula:
C 14 H 19 1 .D 2
05. Chemical Abstracts (CAS) Registry N.imber:
06. Approved Catuon Names: ne
07. Other Catiton Names, Tr ie Names, or Codes:
128
-------
METABOLITE NUMBER: 021
01. Chemical Abstracts Chemical Names:
01 iino1 me, 8—methyl-N- ( 2-inethoxy-1-methylethyl ) -2-
oxo—1 ,2 ,3 ,4—tetrahydro
02. Other Chemical Names:
01 8-Methyl-N— (2-methoxy-1-methylethyl ) -2-oxo
1,2,3, 4—tetrahydroquinoline
03. Structural Formula:
04. Molecular (E pirica1) Forrrula:
C 14 H 19 ND 2
05. Chemical Abstracts (CAS) Registry Number:
06. Approved Cannon Names: ne
07. Other Ccxm n Names, Trade Names, or Codes:
-o.
129
-------
METABOLIIE NUMBER: 022
01. Ch nical Thstracts Ch nica1 Names:
01 Aniline, N- ( 2-methoxy—1-methylethyl ) -2-methyl—6—vinyl—
02. Other Ch nica1 Names:
01 N- ( 2—methoxy-1--methylethyl ) - ( 2-methyl—6-vinyl)
aniline
03. Structural Formula:
04. Molecular ( npirica1) Formula:
C 13 H 19 N3
05. (i nical bstracts (CAS) Registry iither:
06. pproved Ccmtcn Names: ne
07. Other Ccm n Names, Th 1e Names, or Codes:
130
-------
METABOLITE NUMBER: 023
01. Chemical Abstracts Chemical Names:
01 Indole, 2, 3—dihydro-N— (2—methoxy—1—methylethyl ) —7—methyl—
02. Other Chemical Names:
01 N- ( 2—methoxy—1—methylethyl ) —7—methyl—2 , 3—dihydroindole
aniline
03. Structural Formula:
CHCH 2 0CH 3
04. Molecular (E npirica1) Fornula:
C 1 3 H 19 1 )
05. Chemical Abstracts (CAS) Registry Number:
06. Approved Cannon Names: Nune
07. Other Cawnon Names, Trade Names, or Codes:
131
-------
METABOLflE NUMBER: 024
01. Ch nica1 Abstracts Ch nica1 Names:
01 ()iirxline, N— (1—hydroxyethyl ) —8—methyl—2—oxo--1 ,2,3 , 4—tetrahydro-
02. Other Ch nica1 Names:
01 8—Methyl--N— ( l—hydroxyethyl ) —2—oxo-1 ,2,3, 4—tetrahydroquinol me
03. Structural Formula:
05. th nica1 Abstracts (CAS) Registry Number:
06. Approved Cczmon Names: 3Dne
07. Other CaTiron Names, Trade Names, or Codes:
04. tblecular (Dnpirical) Formula:
C 12 H 15 2
132
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APPENDIX B. SIGNIFICANT HIS IORICAL EVEN
March, 1975 Receipt of application for pesticide
registration.
May, 1977 Registration of Technical Metolachlor.
133
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APPENDIX C. INDEX OF ACCEPTABLE USES
RESE 1ED
134
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APPENDIX D. INDEX OF ‘IOLERANCES
(as of February 9, 1978)
Chemical Cairnod ity PPM
Metolachior Corn Grain (except popcorn) 0.1
Soybeans 0.1 (temporary)
Soybean Hay and Forage 1.25 (temporary)
Meat, Eggs, Poultry, Milk 0.02 (temporary)
(for cattle, goats, hogs,
horses, poultry, and sheep)
135
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APPENDIX E. CCt4PANY W TA QU OIL)GY
RESERVED
136
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APPENDIX F. ANALYTICAL METHODS
RESERVED
137
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APPENDIX G. INOMATIC1 SEARCH STR1 TEGY
Technical literature used in the ccxnpilatiicn of this starkiar was derived fran
an exhaustive search of rld—wide literature sources using both manual and on—
lire autanated search techniques.
Search cx np1etion date: venter 1977
date performed: N. A.
Ch nica1 identification profile:
R 51218—45—2
1 55762—76—0
tXial
Metolachior
GA 24705
CGA24705
CGA—24705
Name Fragments
Acetamide and ch.loro and ethyl and methylphenyl and methoxy and methylethyl
Lata bases searched
Autanated (on-line) search
Aqrix la
1 uatic Abstracts
Bios is Previews
CAB Abs tracts
Cancerline (NU4)
Cancerproj (NLI4)
Ch nical Abstracts 1970—1977
Dissertation Abstracts
Envirolire
Epilepsy (NL14)
Hayes (W EPA)
Medline/Medback (NTJ4)
NTIS ( t pt. Qxrin.)
eanic Abstracts
Pe ticides Abstracts (U.S. EPA)
Pollution Abstracts
RIECS (1 gistry of Ibxic Effects of th idcal Substances) (NIOSH)
Scisearch
lbxl ine/Ibxback (N114)
USI CRIS
Manual Search
Biological Abstracts 1950—1970
Ch ica1 Abstracts 1950—1970
Excerpta Med ica:
Pharmacol. Ibxicol. 18:1965—41 (2):1977
Cancer 1:1953—35 (10:1977
Devel. Biol. 1:1961—17 (7):1977
138
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APPENDIX H. TREAThENT OF CHEMICAL INWXICATION
PESE WED
139
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APPENDIX I. MANAGE 4ENT OF E VII M 2AL DNTAMINATIC
RESERVED
140
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P PPENDIX 3 • DISBDSAL INFOI 4hTION
I ESERVED
141
-------
BIBLIcx3pJ y
143
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Affiliated Medical Research, Incorporated (l974a) Acute Dermal LI).- of CG1 —
24705 — Technical in Rabbits: Contract No. 120—2255—34. (Unp8Elished study
received Sep 26, 1974 under 5G1553; prepared for Ciba—Geigy Corp.,
Greensboro, N.C.; CDL:112840—E)
Affiliated Medical Research, Incorporated (l974b) Acute Dermal LI) of CG —
24705—6E: Contract No. 12—2255—34. Unpublished study receive °Sep 26,
1974 under 5Gl553; prepared for Ciba—Geigy Corp., Greensboro, N.C.;
CDL: 112840—F)
Affiliated Medical Research, Incorporated (1974c) Acute Inhalation Study of CGPr-
24705—6E for Albino Rats: Contract No. 121—2253—34. Unpublished study
received Sep 26, 1974 under 5G1553; prepared for Ciba—Geigy Corp.,
Greensboro, N.C.; CDL:1l2840—M)
Affiliated Medical Research, Incorporated (1974d) Acute Oral ¶Ibx icity in Rats
of CGA—24705—6E: Contract No. 121—2255—34. (Unpublished study received
Sep 26, 1974 under 5Gl553; prepared for Ciba—Geigy Corp., Greensboro, N.C.;
CDL: 112840—B)
Affiliated Medical Research, Incorporated (1974e) flnetic Dose 50 in Beagle Dogs
with CGA—24705—Technical: Contract No. 120—2255—34. (Unpublished study
received Sep 26, 1974 under 5G1553; prepared for Ciba-Geigy Corp.,
Greensboro, N.C.; CDL:112840—C)
Affiliated Medical Research, Incorporated (1974f) anetic Dose 50 in Beagle Dogs
with CGA—24705—6E: Contract No. 121—2255—34.(Unpublished study received
Sep 26, 1974 under 5G1553; prepared for Ciba—Geigy Corp., Greensboro, N .C •;
CDL: 112840—D)
Affiliated Medical Research, Incorporated (1974g) Evaluation of CGA—24705
Technical (FL740408) as a Potential Skin Sensitizer in the Guinea Pig:
Contract No. 120—2255—34. (Unpublished study received Sep 26, 1977 under
5G1553; prepared for Ciba—Geigy Corp., Greensboro, N.C.; CDL:ll2840—K)
Affiliated Medical Research, Incorporated (1974h) Primary Derinal Irritation of
CGA—24705—6E in Albino Rabbits: Contract No. 121—2255—34. (Unpublished
study received Sep 26, 1974 under 5Gl553; prepared for Ciba—Geigy Corp.,
Greensboro, N.C.; CDL:1l2840—J)
Affiliated Medical Research, Incorporated (1974i) Primary Eye Irritation of CGA—
24705—6E in Albino Rabbits: Contract No. 121—2255—34. (Unpublished study
received Sep 26, 1974 under 5G1553; prepared for Ciba—Geigy Corp.,
Greensboro, N.C.; CDL:112840H)
Affiliated Medical Research , Incorporated (1974j) Twenty-One Day Repeated
Dermal Toxicity of CG1 —24705—6E in Rabbits: Contract No. 120—2255—34.
(Unpublished study received Sep 26, 1974 under 5Gl553; prepared for Ciba—
Geigy Corp., Greensboro, N.C.; CDL:112840-Q)
145
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Abrens, J.F.; Cubanski, M. (1977) Herbicides for h n1ock seedbeds. Pages 315—
319, In Proceedings of the Thirty-First Annual Meeting of the Northeastern
Weed Science Society; Jan 4—6, 1977, Ba1tii re, Maryland. Salisbury, !tL:
[ University of Maryland?].
American Institute of Biological Sciences, uatic Hazards of Pesticides Task
Group (1978) Criteria and Rationale for Decision Making in uatic Hazard
Evaluation: Report to the Enviromental Protection 2 ency. Washington,
D.C.: U.S. E.P.A. (EPA Contract No. 68—01—2457)
American National Standards Institute (1976). Caiion name for the pest control
ch nica1 2-chloro-N- ( 2-ethyl-6--methylphenyl ) -N- ( 2-methoxy-l-methylethyl)
acetamide “metolachlor. In American National Starx 1ard: ANSI K62,198—1976.
w York: ANSI.
Ancn. (1976) 2-Chloro-N- ( 2—ethyl-6-methylphenyl ) —N- ( 2-n ethoxy-1-methylethyl)
Acetamide: l’blerances for Residues. Federal Register 4l(226):51400.
Arni, P.; Miller, D. (1976) Salnonella/)iamalian—Microscne Mutagenicity Test
with CG 24705 (Test for Mutagenic Properties in Bacteria): I 1 2.632.
(Unpublished study received Jan 19, 1977 under 7F1913; prepared by Ciba—
Geigy, Ltd., Basle, Switzerland; CDL:95768—B)
Ashley, R.A. (1976) Varietal response of sweet corn to Procyazine and CGA-
24705. Pages 193—196, In Proceedings of the Thirtieth Annual Meeting of
the Northeastern Weed Science Society; Jan 6-8, 1976, Boston, Massachusetts
Salisbury, ?tI: Lk iversity of Maryland, Vegetable Research Farm.
Aziz, S.A. (1974) Photolysis of CGA—24705 on Soil Slides under Natural and
Artificial Sunlight Conditions: GMC—74102. (Unpublished study received
Mar 26, 1975 under 5F1606 prepared by Ciba—Geigy Corp., Greensboro, N. C.;
1L:94385—J)
Aziz, S.A.; Kahrs, R.A. (1974) Ptotolysis of CXA—24705 in 1 ueous Solution
under Natural and Artificial Sunlight Conditions: GAAC—74041. (Unpublished
study received Sep 26, 1974 under 5 ( 31553; prepared by Ciba-Geigy Corp.,
Greensboro, N.C.; CDL:94222—A)
Aziz, S.A.; Kahrs, R.A. (1975) Photolysis of (XA—24705 in 2 ueous Solution —
Mditional Information: GMC—75021. (Unpublished study received Mar 26,
1975 under 5F1606; prepared by Ciba—Geigy Corp., Greensboro, N.C.;
CDI.: 94385—M)
Aziz, S.A; ss, l.A. (1975) Analytical Method for the Determination of
Residues of CG1 -24705 Soybean Metabolites as CGA-37913 and CG -4975l by Acid
Hydrolysis. Method AG—286 dated Jun 10, 1975. (Unpublished study received
No , 6, 1975 under 4(31469; prepared by Ciba—Geigy Corp., Greensboro, N • C.;
CDL: 95190—E)
Aziz, S.A.; kss, J .A. (1976) Specificity of Analytical Method —286 for the
Determination of Residues of Metolachlor and Its Metabolites in Soybeans:
ABR—76083. (Unpublished study received Jan 19, 1977 under 7Fl9l3; prepared
by Ciba-Geigy Corp., Greensboro, N.C.; CDL:95748-AC)
146
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Bailey, G.W.; Leonard, R.A,; Livank, R.R., Jr. (1976) Land Application of Waste
Materials: Thansport, Detoxification, Fate, and Effects of Pesticides in
Soil and Water Environment. 2˝nkeny, Iowa: Soil Conservation Society of
America. (p.48—78)
Balasubramanian, K.; Aziz, S .A.; Rss, J .A. (1975) Analytical Method for the
Determination of Residues of CGA—24705 Corn Metaboljtes as CGA—37913 and CGA-
49751 by Acid Hydrolysis. Method AG—277 dated Jan 9, 1975. (Unpublished
study received v 6,1975 under 4G1469; prepared by Ciba—Geigy Corp.,
Ardsley, N.Y.; CDL:95190—D)
Balasubramanian, K.; Cold, B.; 1 ss, J.A. (1973?) Gas Chrcxuatographic
Deterniinaticn of Residues of CGA—24705 Metabolites in Corn as CGA—379l3.
Method AG—265 undated. (Unpublished study received Mar 26, 1975 under
5F1606; prepared by Ciba—Geigy Corp., Ardsley, N.Y.; CDL:94380—P)
Balasubramanian, K.; Gold, B.; ss, J.A. (1974) Validation of Method AG—265
for the Determination of CGA—24705 Metabolites Which are Converted to the
CG1 —37913 Moiety: G1 CC—74O43. (Unpublished study received Sep 26, 1974
under 5G1553; prepared by Ciba—Geigy Corp., Greensboro, N.C.; CDL:942l6—I)
Ballantine, L.G. (1975) CGA—24705: Environmental Impact Statement: GMC—75011.
(Unpublished study that includes studies AG—A 2929 I—IV 1st Rept., Ag—A 2929
I—IV 2nd Rept., AG—A 2969 I—Ill 1st Rept., AG—A 2969 I—IV 2nd Rept., AG—A
2973, AG—A 3105, AG—A 3133 1st Rept., Ag—A 3133 2nd Rept., AG—A 3150 I—Il,
AG—A 3244 II, AG—A 3282 I (2nd)—II, AG—A 3554; received Mar 26, 1975 under
5Fl606; prepared by Ciba—Geigy Corp., Greensboro, N .C. CDL: 94385—A, 94376)
Ballantine, L.G. (l976a) Metolachlor plus Atrazine Tank Mix Soil Dissipation:
ABR—76076. (Unpublished study that includes the reports AG-A 3493 I—IV, and
AG—A 3573 I—Il; received Feb 18, 1977 under 100—583; prepared by Ciba Geigy
Corp.; CDL: 228125—A
Ballantine, L.G. (1976b) Metolachlor plus Linuron Tank Mix Soil Dissipation:
ABR—76079. (Unpublished study that includes AG-A 3706 I—V, AG-A 3719 I—IV,
and AG—A 4139 I, II; received Jan 19, 1977 under 100—583; prepared by Ciba—
Geigy Corp., Greensboro, N.C.; CDL:95763—D)
Ballantine, L.G. (1976c) Metolachlor plus Metribuzin Tank Mix Soil
Dissipation: ABR—76092. (Unpublished study that includes studies AG—A 3807
I—V, AG—A 3722 I—IV, and AG—A 4140; prepared by Ciba—Geigy Corp. and studies
no. 50842 and 50843 received Jan 19, 1977 under 100—583; prepared by
Chemagro Agricultural Division, Mobay Chemical Corp. [ Kansas City, *).] for
Ciba—Geigy Corp., Greensboro, N • C.; CDL: 95763—A]
Ballantine, L.G. (1978) Metolachlor: L4xlate of Environmental Impact Statement.
ABR—78011. Unpublished study that includes studies AG-A 2929 I—IV 1st
Pept., AG—A 2969 I—Ill 1st Pept., AG—A 3133 1st Rept., AG—A 3706 I—V, AG—A
3707 I—V, AG—A 3722 I—IV, AG-A 4140; received Feb 6, 1978 under 100—583;
prepared by Ciba-Geigy Corp., Greensboro, NC. CDL:232789—A, 232789—N,
232789—0, 232789—P, 232789—Q, 232789—R, 232789—S, 232789—T)
147
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Ballantine, L.G.; Herman, M.M. (l977a Metalochior Plus Atrazine Plus Paraquat
Tank Mix Soil Dissipation: ABR—77068. (Unpublished study containing
studies Orttx) T-4088, Ortho T—4089, Na—A 4084 I—IV, Nj—A 4085 I—IV; received
Nov 8, 1977 under l00—EUP—59; CDL:232193—G, 232193—J, 232193—K, 232193—L,
232193—M)
Ballantine, L.G.; Herman, M.M. (1977b) Metolachlor Plus Dicamba Tank Mix Soil
Dissipation Studies: ABR—77067. (Unpublished study including studies AG—A
4141 I—Ill, AG—A 4156 I—IV, Craven Lab 76—l—D; CIL:232193—A, 232193—D,
232l93—E, 232193—F) received Nov 8, 1977 under 100—EUP—59 prepared by Ciba—
Geigy Corp., Greensboro, N .C.;
Barrows. M.E. (1974) Exposure of fi to 14 C—CGA—24705. Accunulation
Distribution, and Elimination of C E sidues. 1 port No • :73019—3.
(Unpublished study received Mar 27, 1975 under 5Fl606; prepared by
Bior ics E G & G E ivirorinenta1 Consultants for Ciba-Geigy Corp.,
Greensboro, N.C.; CDL:94376—E)
Bathe, R. (1973) Acute Oral LD of ‘I chnical CGl -24705 in the Rat: Project
No. Siss 2979. (Unpub1ishe study received Sep 26, 1974 under 5Gl553;
prepared by Ciba-Geigy Co rp, Ltd., Basle, Switzerland; CDL: 112840—A)
Bayer, G.M. (1977) Herbicide cxxnbinations for soy, snap, and kidney beans in
New York. Pages 34—38, In Proceedings of the Thirty—First Annual Meeting of
the Northeastern Weed Sci nce Society; Jan 4-6, 1977, Baltimore, Maryland.
Salisbury Pti: [ University of Maryland .1
Big, A. (1977) 1976 pre- nerger weed control in nursery liners. Pages 320—
325, In Proceedings of the Thirty-First Annual Meeting of the Northeastern
Weed Science Society; Jan 4-6, 1977, Baltiixre, Maryland. Salisbury, tt].
[ University of Maryland?]
Bianetric sting Incorporated (1973) Metabolism 14 C—CGA—24705 Corn
Biosynthesized Metabolites in a Lactating Goat: A—1004. (Unpublished
study received Sep 26, 1974 under 5G1553; prepared for Ciba-Geigy Corp.,
Greensboro, N.C.; CDL:94217-J)
Bleidner, W.E.; Baker, H.M.; Levitsky, M.; Lowen, W.K. (1954) DeterminatiOn of
3—(p-ch1oro henyl)-l, 1-dimethylurea n soils and plant tissues. Journal of
Agricultural and Food Ch nistry 2(9): 476—479. (Also In unpublished study
received Sep 26, 1974 under 5G1553; prepared by Ciba—Geigy Corp.,
Greensboro, N.C.: aL:94221—A)
Bohn, J.A.; Price, J.H.; RJeck, C.E. (1976). Canparison of the herbicidal
activity of ch1oro-acet nides. Pages 30— , Page 150, In Proceedings of
the North Central Weed Control Conference; December 9-11, 1975, Milwaukee,
Wisconsin. Quaha, Neb.; by Stauffer Cbanical Ca pany for the North Central
Weed Control Conference:
Brashears, A. D.; Abernathy, J .R.; Schrib, J .V. (1976) An evaluation of yellow
nutsedge control techniques in West 1 xas cotton: Abstract. In Proceedings
of the 29th Annual Meeting of the Southern Weed Science Society; Jan 27-29,
1976, t llas, 1 xas. Raleigh, N.C.: Glover Printing for the Southern Weed
Science Society:
148
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Buccafusco, Robert J. (1978a) Acute ¶L xicity Test Results of CG1 —247O5 to
Bluegill Sunfish ( L pctnis macrochirus) : Report # —78—6—l8l.
(Unpublished study received Jul 13, 1978 under 100.597; prepared by E G &
G,Bionanics, Sutinitted by Ciba-Geigy Corp., Greensboro, N.C.; CDL:234396)
Buccafusco, Robert 3. (1978b) Acute ¶Ibxicity Test Results of CG1 —247O5 to
Rainbow Trout ( SainD gairdneri) : Report #BW—78—6—l86. (Unpublished
study received Jul 13,1978 under 100—597; prepared by E.G. & G., Bionanics,
sutinitted by Ciba—Geigy Corp., Greensboro, N.C.; CDL:234396)
Buckhard, N. (1974) CGA—24705: Hydrolysis of CG Under Laboratory Conditions:
AC 2.5.53; SPR 2/74. (Unpublished study received Sep 26, 1974 under 5G1553;
prepared by Ciba—Geigy Ltd., Basle, Switzerland; CDL:94222-H)
Cannizzaro, R.D.: Ibfberg, A. (1972) Analysis of Water in Soils and Colunn
Aisorbants Using the Aquatest II Electronic Karl—Fischer Titration System.
Method AG—192 dated Mar 9, 1972. (Unpublished study received Sep 26, 1974
under 5G1553; prepared by Ciba—Geigy Corp., Ardsley, N.Y.; CDL:942l6—K)
Centre de Pecherche et d’Elevage des C)ncins (1974) Toxicite De 3 Mois chez le
Rat par Voie Orale du Produit CG 24 705. [ Three—Month Dietary Feeding Study
in Rats: CG1 24 705]: IC—DREB—R 741009. (Unpublished study received Mar 26,
1975 under 5F1606; prepared for Ciba—Geigy Corp., Greensboro, N • C •;
CDL: 94377—C)
Chalmers, A.H. (1974) Studies on the mechanism of formation of 5—mercapto-l—
methyl—4—nitroimidazole, a metabolite of the imnunosu ressive drug
Azathioprine. Biochemical Pharmacology 23: 1891-1901. (Also In unpublis
report received Mar 27, 1975 under SF1606; prepared by Ciba—Geigy Corp.,
Greensboro, N.C.; CDL:94382—A)
Ciba—Geigy Corporation (1974) Section A, CGA -24705: Name, Chemical Identity and
Canposition of CGA—24705. (Unpublished study; received Sep 26, 1974 under
lOO—EUP—44; CIL: 96505 :A)
Ciba—Geigy Corporation (1975a) CG —24705 Efficacy and Crop Safety Sunluary: 1973-
1974. (Unpublished study that includes efficacy and crop safety reports 1—51
and rotational bioassay reports 52—71; received Mar 27, 1975 under SF1606;
CIL; 94383—A, 94384)
Ciba—Geigy Corporation (1975b) Biological Sumary: Deal 6EC Applied Alone.
(Unpublished study that includes reports 1—99; received Nov 25, 1975
under 100—ELJP—43; CDL:94832—A; 94831)
Ciba—Geigy Corporation (1975c) Biological Sumriary: Deal 6EC + Lorox Tank Mix.
(Unpublished study that includes reports 1—21; received Nov 25, 1975 under
100—EUP—43; CDL:94832—B; 94829)
Ciba-Geigy Corporation (1975d) Biological Sunmary: Deal 6EC + Sencor 50% W.P.
or Lexone Tank Mix. (Unpublished study that includes reports 1-49; received
Nov 25, 1975 under lOO—EUP—43; CDL:94832—C; 94830)
149
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Ciba—Geigy Corporation (1975e) Efficacy and Crop Safety Sumary GA—2—686 15G
I rbicide for Corn. (Unpublished study inc1udir sunmary tables and
efficacy tests 1—6, 8—14L; received Feb 9, 1976 under 100—EUP—44;
CDL: 96496—B)
Ciba-Geigy Corporation (197Sf) Name, Chemical Identity and Canposition of CGA—
24705. (Unpublished study received 1 v 25, 1975 under l0O—EUP--43;
CDL: 94879—A)
Ciba-Geigy Corporation (1975g) Results of IulalTh 6E and Cycle tm 8(
Experimental Permits. (Unpublished study; received Dec 29, 1975 under 100—
EtJP 36; CIL:95053—A)
Ciba—Geigy Corporation (1975?h) Section A, CG1 —24705: Name, Chemical Identity
and canposition of CGA—24705. (Unpublished study; received ? bv 25, 1975
under 6Gl708; CtL:96439—A)
Ciba—Geigy Corporation (1976a) CGk-24705: Name, Chemical Identity and
Canposition of CGk24705. (Unpublished study received v 23, 1976 under 100—
587; prepared by Ciba-Geigy Corp., Greensboro, N.C.: CDL:226955-A)
Ciba—Geigy Corporation (1976b) Aerial A 1ication. (Unpublished study that
includes reports lXial/PPI, Dial/PRE, Dial & Lorox, 111.1 — 111.10; received
Jan 19, 1977 urxler 100—583; CDL:95738—E; 95757)
Ciba—Geigy Corporation (1976c) Dia1 + Senxr Pre—eme ence.
(Unpublished study that includes reports 1.1 — 1.78 with a sumary, 11.1 —
11.62 with a sutinary and 111.1 — 111.33 with a sumary, and received Jan 19,
1977 under 100—583; CDL:95738—C:95744; 95765; 95756; 95769; 95741)
Ciba—Geigy Corporation (1976d) 1 (R) 6E + iorox Pre—emergence.
(Unpublished study that includes reports I .1 — 11.27 with a sumary, and
111.1 — 111.28 with a s .zhInary; received Jan 19, 1977 under 100—583;
CDL:95738—D; 95740; 95760; 95759; 95758)
Ciba-Geigy Corporation (1976e) Dial (R) 6E Preemergence. (Unpublished study
that includes reports 1.1 — 1.139 with a sumary, 11.1—11.94 with a suuii ary,
and 111.1 — 111.33 with a suninary; received Jan 19, 1977 under 100—583;
CIL:95738—B; 95742; 95766; 95743; 95752; 95751; 95762; 95761)
Ciba—Geigy Corporation (1976f) Dial 6E Preplant Incorporated. (Unpublished
study that includes reports 1.1 — 1.40 with a sumary, 11.1—11.21 with a
s inu-y and 111.1—111.19 with a s%xtmary; received Jan 19, 1977 under
100—583; CDL:95738—A; 95755; 95754; 95753)
Ciba—Geigy Corporation (l976g) Canpatibility of flial 6E with Fertilizers
and Other Herbicides. (Unpublished study received Jan 19, 1977 under 100—
583; CIL:95738—H)
Ciba—Geigy Corporation (1976h) Liquid Fertilizer. (Unpublished study that
includes reports IXial/PPI, 1.1 — I .8, 111.1—Ill • 5; Dual/PRE, 1.1 —I .4,
111.1 — 111.5: received ,Jan 19, 1977 under 100—583; C]L:95738—F; 95746)
150
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Ciba—Geigy Corporation (1976 i) Rotational Crops (Unpublished study that
includes reports Illal/PRE, I. — 1.48 with a suninary; t JA1/PPI, 1.1 — 1.11
with a Suirinary; LXial + Sencor/PRE, 1.1—1.9 with a sumary; tXial + Lorox/PRE,
1.1 — 1.5 with a sumary; received Jan 19, 1977 under 100—583; CDL:95738—G;
95745; 95739)
Ciba—Geigy Corporation (1977a)
includes reports ID-9D with
583; CDL: 228l0l—F;228122)
Ciba—Geigy Corporation (l977b) Aerial Application. (Unpublished study
containing reports ID — 1OD with a suninary; received Jun 20, 1977;
CDL: 230672—D, 230683)
Ciba-Geigy Corporation (1977c) Aerial Application. (Unpublished study
received Nov 8, 1977 under 100—EUP—59; CDL:232194—G)
Ciba—Geigy Corporation (l977d)
study that includes reports
100—583; CDL:228101—E; 228121)
Ciba—Geigy Corporation (l977e) Application in Liquid Fertilizers. (Unpublished
study containing reports 1—9 with a suninary, ID - 4D with a suninary;
received Jun 20, 1977 under 100—590; CDL:230672—C, 230682)
Ciba—Geigy Corporation (l977f) Application in Fertilizers. (Unpublished study
received Nov 8, 1977 under 100—EUP—59; CDL:232194—F)
Ciba—Geigy Corporation (l977g) Application in Fertilizers. (Unpublished study
received Nov 14, 1977 under 100—EUP—61; CDL:96624—C)
Ciba—Geigy Corporation (1977h) Application—to—Planting interval. (Unpublished
study received Nov 1, 1977 under 100—583; CDL:232134—BB)
Ciba-Geigy Corporation (1977i) Ciba-Geigy Rating System. (Unpublished study
received Nov 1, 1977 under 100—583; CDL:232l34—C)
Ciba—Geigy Corporation (1977j) IXial R) 6E + 1 trex —Preemergence.
(Unpublished study that includes reports 1—35 with a suninaty and 1C—32C with
a suninary; received Feb 18, 1977 under 100—583; CDL:228101—C; 228114; 228115)
Ciba—Geigy Corporation (19771) Dial 6E Alone ——Preemergence. (Unpublished
study that includes reports 1—139 with a suninary, lC—70C with a suninary, and
1D—12D with surrinary; received Feb 18, 1977 under 100—583; CDL;22810l—A:
228102; 228103; 228104; 228105; 228106; 228107; 228108)
Aerial Application.
a sultinary; received
(Unpublished study that
Feb 18, 1977 under 100—
Application in Liquid Fertilizers. (Unpublished
1—18 with a suninary; received Feb 18, 1977 under
Ciba—Geigy Corporation (1977k) tXiai 6E
Incorporated. (Unpublished study that
lC—32C with a sumary, and 1D-1OD with
100—583; CDL:228l01—D; 228116; 228117;
+ 1 trex —Preplant
includes reports 1—96 with a suimiary,
suntnary; received Feb 18, 1977 under
228118; 228119; 228120)
151
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Ciba—Geigy Corporation (1977m) Lxia1 6E Alone — Preplant Incorporated.
(Unpublished study that includes reports 1—82 with. a suninary, 1C-52C with a
suninary, and iD-liD with sunn ary; received Feb 18, 1977 under 100—583;
CDL:228101—B; 228109; 228110; 228118; 228111; 228112; 228113)
Ciba-Geigy Corporation (1977n) 1 (R) 8E ÷ i4.1 trex + Paraquat or
I undup. (Unpublished study containing reports 1—22 with a suninary, 1C—27C
with a suninary; received Nov 8, 1977 under 100—EUP—59; CDL:232194—D, 232200,
232201)
Ciba-Geigy Corporation (19770) Dia1 1 8E + Jv trex Early st.
(Unpublished study containing reports 1—47 with a suninary, 1C-15C with a
suninary; received Nov 8, 1977 under 100—EUP—59; CDL:232194—E, 232202, 232203)
Ciba-Geigy Corporation (1977p) 8E Alone. (Unpublished study
including reports 1—43 with a suninary; received Nov 8, 1977 under 100—EUP--
59; CIL:232194—A, 232195)
Ciba-Geigy Corporation (1977q) Dial 8E Alone. (Unpublished study that
includes reports 1—32 with a suninary; received Nov 14, 1977 under 100—EUP—
61; C1L:96624—A; 96618)
Ciba-Geigy Corporation (l977r) flial /Atrazine Prepack: Chemistry I ta
Section. (Unpublished study; received June 20, 1977 under 100—590;
CDL: 230686—A)
Ciba—Geigy Corporation (1977s) 1 (R) 8E + anvei(R). (Unpublished study
containing reports 1-21, with a sunnary, lC-9C with a suiwnary; received
Nov 8, 1977 under 100—EUP—59; CIL:232194—C, 232198, 232199)
Ciba—Geigy Corporation (1977t) Dia1 1 8E + B1adex . (Unpublished study
containing reports 1-37 with a suninary, lC—1OC; received 8, 1977 under
100—EUP--59; CJL:232194—B, 232196, 232197)
Ciba—Geigy Corporation (1977u) Dial + Lorox PRE. (Unpublished study received
Nov 1, 1977 under 100—583; CIL:232l34—P)
Ciba-Geigy Corporation (1977v) Dial + Lorox — Soybeans Preemergence: Phyto
Sutrnary or 1/13/77 Subaission. (Unpublished study received Nov 1, 1977
under 100—583; CDL:232134—Q)
Ciba-Geigy Corporation (1977w) Dial + torox — Soybeans Preemergence: Phyto
Suninary of 1/13/77 Sutinission. (Unpublished study; received Nov 1, 1977
under 100—583; CII: 232134—R)
Ciba—Geigy Corporation (1977x) Dial + torox PRE Yield I ta. (Unpublished
study; received Nov 1, 1977 under 100—583; CDL:232134—T)
Ciba-Geigy Corporation (1977y) Dial Preanergence. (Unpublished study; received
Nov 1, 1977 under 100—583; CDL:232l34—D)
152
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Ciba—Geigy Corporation (1977z) 1 (R) pi Yields. (Unpublished study;
received Nov 1, 1977 urxler 100—583; CDL:232134—G)
Ciba—Geigy Corporation (1977aa) Dual PRE Yield Data (1977). (Unpublished
study; received Nov 1, 1977 urrier 100—583; CDL:232134—H)
Ciba—Geigy Corporation (1977ab) Dual PRE Yield Questions. (Unpublished
study; received Nov 1, 1977 urxier 100—583; CDL:232134—I)
Ciba—Geigy Corporation (1977ac) tX al + I.orox Yields. (Unpublished
study; received Nov 1, 1977 ur er 100—583; CDL:232l34—S)
Ciba—Geigy Corporation (1977ad) Dual + torox Yields. (Unpublished study;
received Nov 1, 1977 urx er 100—583; CDL:232134—U)
Ciba—Geigy Corporation (1977ae) Dual Preplant Incoroporated. (Unpublished
study; received Nov 1, 1977 ur er 100—583; CDL:232l34—J)
Ciba—Geigy Corporation (1977af) 1 (R) 1 Yields. (Unpublished study;
received Nov 1, 1977 urx ier 100—583; CDL:232134—M)
Ciba—Geigy Corporation (l977ag) Dual PPI Yield Data. (Unpublished study;
received Nov 1, 1977 ur ier 100—583; CDL:232134—N)
Ciba—Geigy Corporation (l977ah) Dual PPI Yield Questions. (Unpublished
study; received Nov 1,1977 uuder 100—583; CDL:232134—O)
Ciba—Geigy Corporation (1977ai) Dual + Sencor PRE. (Unpublished study;
received Nov 1, 1977 urxier 100—583; CDL:232l34—V)
Ciba-Geigy Corporation (l977aj) Dual + Sencor/Lexone - - Soybeans Preemergence:
Phyto Suninary of 1/13/77 Suthiission. (Unpublished study; received Nov 1,
1977 urvier 100—583; CDtj:232134—W)
Ciba-Geigy Corporation (l977ak) Dual + Senoor/Lexone -- Soybeans Preexnergence:
Phyto Suninary of 1/13/77 Suiinission. (Unpublished study; received Nov 1,
1977 urvler 100—583; CDL:232134—X)
Ciba-Geigy Corporation (1977a1) Dual + Sencor PRE Yield Data. (Unpublished
study; received Nov 1, 1977 urxier 100—583; CDL:232l34—Z)
Ciba—Geigy Corporation (l977am) Dual + Sencor Yields. (Unpublished
study; received Nov 1, 1977 ur ier 100—583; CDL:232l34—Y)
Ciba-Geigy Corporation (l977an) 1 (R) ÷ Sencor Yields. (Unpublished
study; received Nov 1, 1977 ur er 100—583; CDL:232l34—AA)
Ciba-Geigy Corporation (1977ao) Dual — Soybeans Preemergence Phyto arx 1 Yield
review of 1/13/77 Sukinission. (Unpublished study; received Nov 1, 1977
ur er 100—583; CDL:232134—E)
15 3
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Ciba—Geigy Corporation (1977ap) Exial - Soybeans Preemergence Phyto and Sumary
of 1/13/77 Sutinission. (Unpublished study; received Nov 1, 1977 under 100—
583; CIL:232134—F)
Ciba—Geigy Corporation (1977aq) aial -- Soybeans Preplant Incorporated: Phyto
S xm ary of 1/13/77 Sulinission. (Unpublished study; received Nov 1, 1977
under 100—583; CDL:232l34—K)
Ciba—Geigy Corporation (l977ar) 1)ial —- Soybeans Preplarit Incorporated: Phyto
S i inaxy of 1/13/77. (Unpublished study; received Nov 1, 1977 under 100—
583; CDL:232134—L)
Ciba—Geigy Corporation (1977as) Foxtail Millet. (Unpublished study that
includes 3, 7, 8, 19, 35, and 52 with a suninary; received Nov 1, 1977 under
100—583; CDL 1 :232134—A)
Ciba—Geigy Corporation (1977at) M+A 4.5L — Preemergence. (Unpublished study
containing reports 1—71 with a suninary, 1C—12C with a suirmary, and lD -16D
with a suninary; received Jun 20, 1977 under 100—590; CDL:230672—A, 230673,
230674, 230675, 230676).
Ciba—Geigy Corporation (1977au) M+A 4.5L — Preplant Incorporated. (Unpublished
study containing reports 1-50 with a suninary, lC-9C with a sumary and it)—
l2D with a suninary; received Jun 20, 1977 under 100—590; CDL:230672—B,
230678, 230679, 230680, 230681)
Ciba—Geigy Corporation (l977 Response to EPA Caiinents ncerning Marginal
Soybean, 1erance to aia1’ PPI or PRE, Dial + torox or Dial +
Sencvr ‘ Application. (Unpublished study; received Nov 1, 1977 under
100—583; CDL: 232134—B)
Ciba-Geigy Corporation (1977aw) I tationa1 Crops. (Unpublished study
containing reports 1-13 with a suninary; received Jun 20, 1977 under 100—590;
CDL: 230672—E 230684)
Ciba—Geigy Corporation (1977ax) 1 tationa1 Crops. (Unpublished study including
reports Vol. 2 - Report 40 and Vol. 9 — Report 46; received Nov 8, 1977
under 100—EUP—59; CIL:232194—H, 232195, 232202)
Ciba-Geigy Corporation (197 7ay) Tank Mixtures. (Unpublished study; received
Nov 14, 1977 under i00—EUP—6l; CDL:96624—B)
Ciba—Geigy Corporation (1977az). ktational Crops. (Unpublished study that
includes reports 1—49 with a sl.mnary, 1—39 with a suuinary; received Feb 18,
1977 under 100—583; CDL:228101—G; 228123; 228124)
Ciba—Geigy Corporation (1977ba) Section A General Chemistry. (Unpublished
study; received Jan 19, 1977 under 7F1913; CDL:95764—A)
Ciba—Geigy Limited (1973?) CGA 24 705 Feeding Study in Milk Cows: Methods.
(Unpublished study; received Sep 26, 1974 under 5G1553; CDL:942l6—G)
154
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Ciba—Geigy Limited (1973?) CGA 24 705 Feeding Study in Milk Cows: Methods.
(Unpublished study prepared by Ciba—Geigy Ltd.; St. Aubin, Switzerland;
received Nov 14, 1977 under 8G2019; CDL:96626—C)
Ciba—Geigy Limited (1974) CGA 24705: Hydrolysis of CGA—24705 under Laboratory
Conditions. AC 2.53/NB/cr; SPR 2/74. (Unpublished study; received Mar 27,
1975 under 5F1606; CDL:94376—J)
Ciba—Geigy Limited (1976a) Daninant Lethal Study on CGA 24705 Technical: Mouse
(Test for Cytotoxic or Mutagenic Effects on Male Genninal Cells) PH 2.632.
(Unpublished study including l˝idendum; received Jan 18, 1978 under 7F1913;
CDL: 96717—C; 96717—D)
Ciba—Geigy Limited (1976b) Reproduction Study CGl s. 24705 Tech.: Bat: Seg. II
(Test for Teratogenic or Eithryotoxic Effects) PH 2.632. (Unpublished study
including kidendum; received Jan 18, 1978 under 7F1913; CDL: 96717—A; 96717—
B)
Ciba—Geigy Limited (1977) Skin Sensitizing (Contact Allergenic) Effect in
Guinea Pigs of Technical CG 24705: Siss 5726. (Unpublished study; received
Jan 18, 1978 under 7F1913; CDL:96717—E)
Coquet, B.; Galland L.; Guyot, D.; Fouillet, X.; I uaud, J.L. (1974a) Essai de
‘Ibxicite de 3 Mois chez Le Chien par Voie Orale du Produit CGA 24 705.
[ Three—Month Oral ¶L xicity Trial of CG1 24 705 in Dzg]: IC—DREB—R—7401l9.
(Unpublished study received Sep 26, 1974 under 5G1553; prepared by the
Oncins Research and Breeding Center for Ciba—Geigy Corp., Greensboro, N.C.;
CDL: 94223—B)
Coquet, B.; Galland L.; Olyot, D.; Fouillet, X.; 1 uaud, LL. (l974b) Essai de
Toxicite de 3 Mois chez Le Rat par Voie Orale du. Produit CG1 24 705. [ Three
month oral Toxicity Trial of CGA 24 705 in Rats]: IC—DREB—R—740120.
(Unpublished study received Mar 1, 1974 under 5Gl553; prepared by the Oncins
Research and Breeding Center for Ciba—Geigy Corp., Greensboro, N .C.;
CDL: 94219—B)
Coquet, B.; Galland L.; Oiyot, D.; Fouillet, X.; 1 uaud, J.L. (1974c) Three—
Month Oral Toxicity Test of CGA 24 705 in L g. A translation of: Essai de
Toxicite de 3 Mois chez Le Chien par Voie Orale du Produit CGA 24 705: IC—
DREB—R—740fl9. (Unpublished study received Sep 26, 1974 under 5G1553;
prepared by the Oncins Research and Breeding Center for Ciba-Geigy Corp.,
Greensboro, N .C •; CDL; 94223—A)
Coquet, B.; Galland, L.; Qiyot, D.; Fouillet, X.; 1 uaud, J.L. (1974d) Three—
Month Oral Toxicity Test of CGA 24 705 in Rats. A translation of: Essal de
¶ft)xicite de 3 Mois chez Le Rat par Voie Orale du Produit CG1 24 705: IC—DREB—
R—740120. (Unpublished study received Mar 1, 1974 under 5Gl553; prepared by
the Oncins Research and Breeding Center for Ciba-Geigy Corp., Greensboro,
N.C.; CDL:94219A)
155
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Counselman 14 C.J.; Boger, J.C. j 973) Biological Report, (bat Metabolism Study
with 0- C—CGA—24705 and 0- C-CG —l7020. (Unpublished study
received Nov 25, 1975 under 6Gl708; prepared by Ciba—Geigy Corp.,
Greensboro, N.C.; CDL:94984—K)
Cullen, T.; Balu, K. (1973) Determination of CGk-18762 Residues in Corn Forage,
Stayer, and Grain by Microcoulanetric Gas Chratiatography. Method 1 G-249
dated Jun 20, 1973. (Unpublished study received Nov 6, 1975 under 4G1469;
prepared by Ciba—Geigy Corp., Ardsley, N.Y.; CDL:95190—B)
Davis, T.W. (1976) Report to Ciba—Geigy Corporation: Eye Irritation Test with
CGA—24705 + Atrazine (2.5:2.0) 4.5L:IBT No. 601—08061. (Unpublished study
received Jun 20, 1977 under 100—590; prepared by Industrial Bio-Test
Laboratories, Inc. for Ciba—Geigy Corp.; Greensboro, N .C •; CDL: 230687-A)
Derot, P. (1976) Desherbage du maise: L’ association rr tet1i1ach1or +
atrazine. [ Weed control in maize: A mixture of metetilachlor (CGA24705) and
atrazine] La Defense des Vegetaux 30(177): 39—48.
Dest, W.M.; Peters, R.A., Barrett, M. (1976) The control of crabgrass and
redroot pigweed in the silage corn. Pages 55-58, In Proceedings of the
Thirtieth Annual Meeting of the Northeastern Weed Science Society; Jan 6-8,
1976, Boston, Massachusettes. Salisbury, Mi.: University of Maryland,
Vegetable Research Farm:
Dietz, W.P.; Jennings, V.M. (1976) 1975 tb—till corn herbicide results in
northeast Iowa. Pages 151-152, In Proceedings of the North Central Weed
Control Conference; Deceither 9-11, 1975, Milwaukee Wisconsin. Quaha, Neb.;
by the Stauffer Chemical Canpany for the North Central Weed Control
Conference:
Diner, A.M.; Davis, D.E.; 1 e1ove, B. (1977) Absorption and translocation of
root and foliar-applied C-metolachlor in soybean: Abstract. Pages -
In Proceedings of the Thirtieth Meeting of the Southern Weed Science
Society; Jan 19-21, 1977, Dallas, Texas. Raleigh, N .C.: Glover Printing
for the Southern Weed Science Society.
lXnald A. Willigan, Incorporated (1975) Supplementary Report to Contract No.:
120-2255—34: Histcpathological Evaluation: enty-Qie day Repeated Dermal
ItAxicity of CG 24705—6E in Rabbits. (Unpublished study received Mar 26,
1975 under SF1606; prepared by Affiliated Medical Research, Inc., Princeton,
N.J. for Ciba-Geigy Corp., Greensboro, N.C.; CDL:94377—A)
Draize, J.H. (1959) The appraisal of Chemicals in Food, Drugs, and Cosmetics.
Austin, Texas: Association of Food and Drug Officials of the United States.
Dreier, H. (1977) Report to ba-Geigy Corporation: Acute P erosal Inhalation
‘Ibxicity Study with flia1 ‘8E (FL- 770350) in Albino Pats: JB 8562—10823.
(UnE*lblished study received Nov. 8, 1977 under l00—EUP—059; prepared by
Industrial Bio—Test Laboratories, Inc. for Ciba-Geigy Corp., Greensboro,
N.C., including Mdendtin C — Validation by Ciba—Geigy Corp.; CDL:232191—C)
156
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Ilipre, G.D. (1974a) Abbrevjatej Anaerobic Metabolism of 14 C —CGA—24705 in
Silt Loam Soil under Greenhouse Conditions: Report No. 73019—3.
(Unpublished study received Sep 26, 1974 under 5G1553; prepared by
Bio/dynamics Inc. for Ciba—Geigy rp, Greensboro, N .C. CDL:94222—B)
1)ipre, G.D. (1974b) Leaching Characteristics of 14 C—CGA—24705 and its
Degradation Products Following ing in Sandy Loam Soil under Greenhouse
Conditions: Report no. 73021—6. (Unpublished study received by Sep 26, 1974
under 5Gl553; prepared by Bio-dynamics Inc. for Ciba—Geigy Corp.,
Greensboro, N.C.; CDL:94222—C)
Dupre, G.D. (1974c) Runoff Characteristics of ‘ 4 C—CG —24705 Applied to
Sandy Loam Soil under Greenhouse Conditions: Report no. 73022—1.
(Unpublished study received Sep 26, 1974 under 5Gl553; prepared by Bio-
dynamics Inc. for Ciba—Geigy Corp., Greensboro, N.C •; CDL: 94222—D)
Elkins, D.M.; Vandeventer, J.W.; Briskovich, M.A. (1977). Effect of chemical
growth retardants on turfgrass morphology. Agronany Journal 69(3): 458-461.
Ellegehausen, H. (1976a) Project Report 48/76: A t&del system for Estimating
the Uptake, Transfer and Degradation of rochemica1s by Aquatic Organisms.
AC 2.52. (Unpublished study received Feb 6, 1978 under 100—583; prepared by
Ciba—Geigy Ltd., Basle, Switzerland; CDL:232789—B)
Ellegehausen, H. (l976b) Project Report 4/76: Degradation of CGA 24 705 in
Aerobic, Anaerobic and Autoclaved Soil. AC 2.52. (Unpublished study received
Feb 6, 1978 under 100—583; prepared by Ciba—Geigy Ltd., Basle, Switzerland;
CDL: 232789—D)
Ellegehausen, H. (1976c) Project Report 5/76: Addendum to Project Report 4/76:
Degradation of CG1 24 705 in Aerobic, Anaerobic and Autoclaved Soil. AC
2.52. (Unpublished study received Feb 6, 1978 under 100—583; prepared by
Ciba—Geigy Ltd., Basle, Switzerland; CDL:232789—E)
Ellegehausen, H. (1977) Project Repor roject Report 32/77: Uptake, Transfer
and Degradation of CGP 24705 (Dual ) by Aquatic Organisms. AC 2.52.
(Unpublished study received Feb 6, 1978 under 100—583; prepared by Ciba
Geigy Ltd., Basle, Switzerland; CDL:232789—C)
Envirorunental Protection Aqency (1977) 2-Chloro-N— ( 2—ethyl—6--methylphenyl ) -N— (2-
methoxy—l—methylethyl—acetamide): Extension of Temporary ‘Iblerances.
Federal Register 42 (67): 18426.
Ercegovich, C.D.; Bogus, E.R.; Buly, R.L. (1978) The Effects of 5, 25, and 125
PP?4 of Metolachlor, [ 2-Chloro-N— ( 2—ethyl-6-methylphenyl ) -N— (2-me thoxy-1-
methylethyl) acetainide] on Actincinycetes, Bacteria and Fungi in Laboratory
Culture Tests. E—2/1—CG78. received Feb 6, 1978 under 100—583; (Unpublished
report received Feb 6, 1978 under 100—583; prepared by Pesticide Research
Lab., Pennsylvania State University for Ciba—Geigy Corp., Greensboro, N • C.;
CDL: 23 789—F)
Ercegovich, C.D.; Vallejo, R.P.; Bogus, E.R. (1978) The Effects of 5, 25, and
125 PR4 of Metolachior, [ 2-Chloro-N— ( 2—ethyl—6--methylphenyl ) —N-- ( 2-methoxy-l-
157
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methylethyl) acetamide], on Soil Nitrification. E—3/2—CG78. (Unpublished
study received Feb 6, 1978 urxler 100—583; prepared by Pesticide Research
Lab., Pennsylvania State University for Ciba-Geigy Corp., Greensboro, N • C.;
CDL: 232789—G)
Eschiapati, D.; Duchier, C. (1976) Metetilachior + Atrazine, a new herbicide
for corn crops. Resumos X I S uinario Brasileiro de Herbicidas e Ervas
Daninhas, Londrina, 1976: 44—45.
Fink, R. (l974a) Eight—Day Dietary LC 5 —Mallard Ducks Technical CGŕ—24705:
Project No. 108—111’. Received Sep 26, 1974 under 5G1553. (Unpubli
report Truslow Farm Inc. for Ciba-Geigy Corp., Greensboro, N.C.;
CDL: 112840—0)
Fink, R. (l974b) Eight—Day Dietary IC 5 —Bobwhite Quai1 Technical CGPr-24705:
Project No. 108—ill. (Unpublished study received Sep 26, 1974 under
5G1553.; Truslow Farm Inc. for Ciba—Geigy Corp., Greensboro, N .C.;
CDL: 112840—P)
Fink, R. (1976) Acute Oral LD — Mallard Duck: CGk-24705 Technical: Final
Report. (Unpublished study received Nov 23, 1976 under 100—587; prepared by
Truslow Farms Inc. for Ciba-Geigy Corp., Greensboro, N. C.; CDL: 226955-D)
Frans, R.E.; Richardson, J.T.; Cordon, E.C. (1977) Herbicide Field Evaluation
Trials cx i Field Crops, 1976. Fayettevifle, Ark.: University of Arkansas,
Department of / gro4xwy. (Arkansas 1 ricu1thral Experiment Station,
Mimeograph Series 249)
Frans, R.E.: Blythe, T.O.; Richardson,•J.T. (1976). Herbicide Field Evaluation
Trials on Field Crops, 1975. Fayetteville, Ark.: University of Arkansas,
Departuent of 1 grcx xny. (Arkansas gricu1thral Experiment Station,
Mimeograph Series, 240)
Fritz, H. (1976) Reproduction Study CGh 24705 Tech. Pat: Seq. II: (Test for
Teratogenic or Extryotc cic Effects): PH 2.632. (Unpublished study received
Jan 19, 1977 under 7F1913; prepared by Ciba—Geigy Ltd •, Basle, Switzerland;
CDL: 95768—A)
Gerber, H.R.; Mueller, G.; thner, L. (1974) CG 24705, A new grasskiller
herbicide. Pages 787—794, In Proceedings of the 12th British Weed Control
Conference; Nov 18—12, l97tsrighton, England. Begbroke Hill, Oxford,
England :AW Weed Research Organization.
Gesme, J.; Albanese, E.; Marias, A.J. (1977) Report to Ciba—Geigy Corporation:
Carcincgenicity Study with CG1 —24705 Technical in A1bir Mice: iwr No. 622—
07925 (8532—07925). (Unpublished study received Jan 18, 1978 under 7Fl9l3;
prepared by Industrial. Bio-Test Laboratories, Inc. for Ciba-Geigy Corp.;
including Validation report prepared by Ciba-Geigy Corp., Greensboro, N • C.;
CDL:96719—A; 96720-A; 96720—B)
158
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Gfeller, % . (1974) Tolerability Trial in Milk Cows with CG1 24 705: 14, 21 and
28 day Feeding Study: AC 9.26; T73/23. (Unpublished study received Sep 26,
1974 under 5G1553; prepared by Ciba—Geigy Ltd., St. L4Ubin, Switzerland;
CDL: 94216—F)
Gold, B.; Kahrs, R.A. (1975a) 1X—200: An Alternate Gas Chranatographic Column
for the Determination of CGA—37913: GAAC—75026. (Unpublished study received
Mar 26, 1975 under SF1606; prepared by Ciba—Geigy Corp., Greensboro, N.C.;
CDL: 94380—X)
Gold, B.; Kahrs, R.A. (1975b) Freeezer Storage Stability of CGA—24705 Residues
in Corn Fodder and Grain: GAAC—75062. (Unpublished study received Nov 25,
1975 under 6Gl708; prepared by Ciba—Geigy Corp., Greensboro, N.C.; CDL:94877-
Y)
Gross, D. (l974a) Project Report No. 8/74: Uptake, Translocation and
Degradation of CG 24 705 in Corn Grown under Controlled Conditions.
(Unpublished study received Sep 26, 1974 under 5G1553; prepared by Ciba—
Geigy Corp., Greensboro, N.C.; CDL:94217—F)
Gross, D. (1974b) Project Report No. 13/74: Addendum to Project Report No. 8/
74: Uptake, Translocation and Degradation of CGT 24 705 in Corn Grown under
Controlled Conditions: AC 2.52. (Unpublished study received Mar 26, 1975
under 5Fl606; prepared by Ciba—Geigy Ltd., Basle, Switzerland; CDL:94378—H)
Guth, J.A. (1974) CGA 24705: Total Residues in Chicken Tissues and Eggs, 1974:
AC 2.53; RVA 88/74. (Unpublished study received Sep 26, 1974 under 5G1553;
prepared by Ciba—Geigy Ltd., Basle, Switzerland; CDL:94216—D)
Hack, H., Schmidt, R. R. (1976). Use of Metamitron in weed control syst s
in sugar beets. Pages 197—204, In Proceedings 1976 British Crop
Protection Conference, Bayer AG, Pflanzenschutz Anwendunstechnik,
Leverkusen, Federal Republic of Germany.
Hambock, H. (1974a) Project No. 7/74: Metabo1i n of CG1 24 705 in the Rat.
(Status of Results Gathered up to June 10, 1974): AC 2.52. (Unpublished
study received Sep 26, 1974 under 5G1553; prepared by Ciba—Geigy Ltd.,
Basle, Switzerland; CDL:94217—L)
Hambock, H. (l974b) Project Report 12/74: Addendum to Project Report 7/74:
Metabo1i n of CG1 24 705 in the Rat: AC 2.52; (Unpublished study received
Nov 25, 1975 under 6G1708; prepared by Ciba—Geigy Ltd., Basle, Switzerland;
CDL: 94984—P)
Hambock, H. (1974c) Project Report No. 1/74: DistributiOn, Degradation and
Excretion of CGa 24 705 in the Rat. (Unpublished study received Sep 26, 1974
under 5Gl553; prepared by Ciba—Geigy Ltd., Basle, Switzerland; CDL:94217—K)
Harrison, W.A.; (1975) Report to Ciba—Geigy Corporation: Acute Toxicity Studies
with CGI 24705 + Atrazine: IBT No. 601—07539. (Unpublished study received
Dec 29, 1975 under 100—EUP—45; prepared by Industrial Bio—Test Laboratories,
Inc., For Ciba—Geigy Corp., Greensboro, N.C.; CDL:224074—B; 231913)
159
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Harvey, R.G.; Baker, C.R. (1974?) Annual Weed Control in Corn Study: Project
No. 755. (Unpublished study received Feb 9, 1976 under l00—EUP—44; prepared
for Ciba—Geigy Corp., Greensboro, N .C •; CDL: 96496-C)
Heinrichs, L. (1975) Determination of CG1 —24705 and Procyazine in G —2—686 15G
by Gas Chranatography: Method PA—71 T dated Oct 9, 1975. (Unpublished
study received Feb 9, 1976 under l00—EIJP—44; prepared by Ciba-Geigy Corp.,
Greensboro, N.C.; CDL:96496 —A)
Heinricbs, L. (1976) The Determination of Metolachior in Deal 6E by Gas
Liquid Chranatography. Method PA—9A dated Dec 16, 1976. (Unpublished study
received Nov 14, 1977 under lOO—EUP—61; prepared by Ciba—Geigy Corp.,
Greensboro, N.C.; CDL:96623—A)
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160
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Hormann, W.D.; Guth, J.A.; Formica, G.; Schenker, M. (1974) CGA 24705: Gas
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Houseworth, L.D. (1973?) Report on Parent Leaching Studies for CGA—24705:
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Liquid Fertilizer. (Unpublished study including reports AG—A—3298 II,
III, AG—A—3325 II, PL3—A—3326 II, AG—A—3372 II, AG—A—3406 II, AG—A—3674 II,
III, AG—A—3745 I, II, III, with a suimtary ABR—77028; received Jun 20, 1977
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3672 lI—Ill, AG—A—3673 I, II, III, AG—A—3704 I, II, AG—A—3735 I, II, III, AG—
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163
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Lee, T.; Kaldon, H. (1974) [ Tank—Mix Catipatabilities ¶L st Ičport for CGk-24705—
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(Unpublished study that includes reports AG—A—2929, AG—A—2969, AG—A—2973, AG—
A—3105, AG—A—3133; received Sep 26, 1974 under 5G1553; prepared by Ciba—
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Mattson, A.M. (1974) CGA—24705 Residues in Milk, Meat, E gs and Chickens
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Mattson, A.M. (1975) CGAr247OS Residues in Milk, Meat, D gs and Chickens
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Mattson, A.M.; Kahrs, R.A. (1969) Quantitative Determination of Triazine
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Mattson, A.M.; Kahrs, R.A. (1975a) Procyazine — Corn: 1 nk Mixes with CGA-
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164
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(Unpublished study that includes reports AG—A—3638, G—A—3671, AG—A—3716, G—
A—3731, AG—A—3741, AG—A—3798, AG—A—3703, AG—A—3726, AG—A—3784, AG—A—38l7;
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(Unpublished study that includes reports AG—A—2967, AG—A—2982, AG—A—3255, AG—
A—3289, AG—A—3299, AG—A—3328, AG—A—3383, AG—A—350l, AG—A—3005, AG—A—3153, AG—
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Mattson, A.M.; Kahrs, R.A. (l975c) Summary of Resi e Data CG1 _24705T razine
Canbinati?P as Corn Herbicides Tank Mixes—Deal 6EC Plus Mtrex 80W
or AAtrex 4L Flowable Ccinbination Forinulation—G1 —2—6—622 4.5L
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(Unpublished study including reports ?˝G—A—2974; AG—A—3057; AG—A—3070; AG—A—
3288; AG—A—3298; AG—A—3325; AG—A—3326; AG—A—3372; A&-A—3406; received Dec
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Mattson, A.M.; R11a, H. (1975) Summary of Section D: CGA—24705—Soybeans:
Residues Cbserved and Metabolism Data Including the Analytical Metbods Used:
GAAC—75057. (Unpublished study that includes reports AG—A—3268, AG—A—3466,
AG—A—3523, 1˝G-A—3570, AG—A—3650 I & II, AG—A—3702, AG—A—3724, AG—A—3743, AG—
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Michieka, R.W.: Ilnicki, R.D.: Sa 1y, J. (1977). Weed control in potatoes
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Norton, J.A. (1978) [ Letter on 1 (R) 6E Herbicide —EPA Reg. No. 100—583
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166
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letter fran the files of the Office of Pesticide Progran s, Technical
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Received May 1978 under 100—583. (Submitted by Ciba—Geigy Corp.,
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Norton, J.A. (1978) Letter sent to Henry Jacoby dated March 8, 1978. [ Dual 6E
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Oncins Research and Breeding Center (1974) Three—Month Dietary Feeding Study in
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8530—09781. (Unpublished study received Jan 19, 1977 under 7Fl9l3; prepared
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16 7
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U.S. G0VERNN {T F8INTING OFFICE 1980 0—311-726/3862
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