United States
Environmental Protection
Agency
Office of
Pesticides and Toxic Substances
Washington DC 20460
Sepwmber 1980
•"esticides
x»EPA
2-chloro-N-(2-ethyl-6-methylphenyl
-N-(2-methoxy-1-methylethyl)
acetamide Metolachlor
Pesticide Registration
Standard
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METOLACHLOR
2-~chloro-~N-'(2~ethyl~6-methylphenyl)
•~N— (2-*methoxy-il-rnethylethyl acetamide
Pesticide Registration Standard
David Gettman, Project Manager (SPRD)
Bill Audia, Plant Sciences Specialist (BFSD)
William Boodee, Residue Chemist (BED)
Larry Chitlick, Toxicologist (HED)
Harry Craven, Wildlife Ecologist (HED)
Carolyn Gregorio, Toxicologist (HED)
Samuel Howard, Environmental Chemist (HED)
Alfred Smith, Residue Chemist (HED)
James Stone, Technical Product Manager (RD)
September, 1980
OFFICE OF PESTICIDES AND TOXIC SUBSTANCES
ENVIRONMENTAL PROTECTION AGENCY
401 M STREET S.W.
WASHINGTON, DC 20460
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TABLE OF CONTENTS
I-fow to Register Under a Registration Standard
Organi zation of the Standard 7
Purpose of the Standard • 7
Requirement to Re-register Ihder the Standard 9
"Product Specific" Eata and "Generic" Data 9
Data Compensation Requirements under FIFRA 3(c) (1) (D) 11
Obtaining Eata to Fill "Eata Gaps"; FIFRA 3(c) (2) (B) 12
Amendments to the Standard 12
Requirements for Metolachlor Products 15
Technical Metolachlor 16
Emulsif iable Concentrate Metolachlor 19
Use Profile 27
Product Chemistry
Introduction 29
Topical Discussions
Chemical Identity 29
Manufacturing Process 31
Percentages of Components in Pesticide Products 31
Product Analytical Methods and Eata 32
Physical/Chemical Properties 32
Disciplinary Review
Chemistry Profile '. 35
Product Specific Data Gaps 35
Suggested Labeling 36
Bibliography 37
Environmental Fate
Topical Discussions
Physico-Chemical Transformation 39
Soil Metabolism 41
Microbial Metabolism 42
Mobility 43
Spray Drift 44
Field Dissipation 44
Accunulation 44
Disciplinary Review
Environmental Fate Profile 49
Exposure Profile 51
Generic Data Gaps , 53
Suggested Labeling 53
Bibl iography 55
Toxicology
Topical Discussions
Metabolism and Pharmacodynamics 57
Acute Effects and Neurotoxicity 58
Local Irritation , 59
Subchronic Effects and Neurotoxicity 60
Sensitization 61
Chronic Effects 62
Cncogenicity 52
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Mutagenicity . . 63
Teratology 63
Reproductive Effects 64
Disciplinary Review
Toxicology Profile 65
Toxicology Hazard Assessment . 66
Generic Data Gaps « 68
Product Specific Data Gaps 68
Suggested Labeling 68
Bibliography . • 69
Residue Chemistry
Topical Discussions
Metabol ism in Plants 73
Metabolism in Animals . 75
Analytical Methodology 75
Residue Data 78
Present Tolerances .. 83
Disciplinary Review
Residue Chemistry Profile 85
Tolerance Reassessment 87
Generic Data Gaps 89
Suggested Labeling 89
Bibl iography „ 91
Ecological Effects
Topical Discussions
Microbes 95
Algae .... .... 97
Aquatic Macrophytes 97
Terrestrial Plants . 97
Bi rds ... 97
Wild Mammals ..... 99
Aquatic Invertebrates .. 99
Fish 100
Ecosystem Effects 101
Disciplinary Review
Ecological Effects Profile 102
Ecological Effects Hazard Assessment 103
Generic Data Gaps 103
Suggested Labeling 104
Bibl iography 105
Regulatory Rationale
Technical Metolachlor 107
The Delimitation of Risks to Hunans 107
The Delimitation of Risks to Wildlife . 108
Emulsifiable Concentrates of Metolachlor 109
The Delimitation of Risks to Humans 110
The Delimitation of Risks to Wildlife 113
Append ix
Chemical Data Sheets 117
Bibliography • 147
Guide to the Use of This Bibliography 149
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HOW TO REGISTER
UNDER A REGISTRATION STANDARD
Organization of the Standard
Purpose of the Standard
Requirement to Re-register Lhder the Standard
"Product Specific" Data and "Generic" Data
Data Compensation Requirements under FIFRA 3(c) (1) (D)
Obtaining Data to Fill "Data Gaps"; FIFRA 3(c) (2) (B)
Amendments to the Standard
Organization £f the Standard
This first chapter explains the purpose of a Registration Standard and
summarizes the legal principles involved in registering or re-registering under
a Standard. The second chapter sets forth the requirements that must be met to
obtain or retain registration for products covered by this particular
Registration Standard. In the remaining chapters, the Agency reviews the
available data by scientific discipline, discusses the Agency's concerns with
the identified potential hazards, and logically develops the conditions and
requirements that would reduce those hazards to acceptable levels.
Purpose o_f the Standard
Section 3 of the Federal Insecticide, Fungicide, and Fbdenticide Act
(FIFRA) provides that "no person in any State may distribute, sell, offer for
sale, hold for sale, ship, deliver for shipment, or receive (and having so
received) deliver or offer to deliver, to any person any pesticide which is not
registered with the Administrator [of EPA]." Tb approve the registration of a
pesticide, the Administrator must find, pursuant to Section 3(c) (5) that:
"(A) its composition is such as to warrant the proposed claims for it;
(B) its labeling and other material required to be submitted comply with
the requirements of this Act;
(C) it will perform its intended function without unreasonable adverse
effects on the environment; and
(D) when used in accordance with widespread and commonly recognized
practice it will not generally cause unreasonable adverse effects on
the environment."
In making these findings, the Agency reviews a wide range of data which
registrants are required to submit, and assesses the risks and benefits
associated with the use of the proposed pesticide. But the established
approach to making these findings has been found to be defective on two counts:
First, EPA and its predecessor agency, the Lhited States Department of
Agriculture (USDA) , routinely reviewed registration applications on a 'product
by product1 basis, evaluating each product-specific application somewhat
independently- In the review of products containing similar components, there
was little opportunity for a retrospective review of the full range of
pertinent data available in Agency files and in the public literature. Thus
the 'product by product' approach was often inefficient and sometimes resulted
in inconsistent or incomplete regulatory judgments.
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Second, over the years, as a result of inevitable and continuing advances
in scientific knowledge, methodology, and policy, the data base for many
pesticides came to be considered inadequate by current scientific and
regulatory standards. Given the long history of pesticide regulation in
several agencies, it is even likely that materials may have been lost from the
data files. When EPA issued new requirements for registration in 1975 (40 CFR
162) and proposed new guidelines for hazard testing in 1978 (43 FR 29686, July
10, 1978 and 43 FR 37336, August 22, 1978), many products that had already been
registered for years were being sold and used without the same assurances of
human and environmental safety as was being required for new products. Because
of this inconsistency, Cbngress directed EPA to re-register all previously
registered products, so as to bring their registrations and their data bases
into compliance with current requirements [See FIFRA Section 3(g) ] .
Facing the enormous job of re-reviewing and calling-in new data for the
approximately 35,000 current registrations, and realizing the inefficiencies of
the 'product by product1 approach, the Agency decided that a new, more
effective method of review was needed.
A new review procedure has been developed. UYider it, EPA publishes
documents called Registration Standards, each of which discusses a particular
pesticide active ingredient. Each Registration Standard summarizes all the
data available to the Agency on a particular active ingredient and its current
uses, and sets forth the Agency's comprehensive position on the conditions and
requirements for registration of all existing and future products which contain
that active ingredient. These conditions and requirements, all of which must
be met to obtain or retain full registration or re-registration under Section
3(c)(5) of FIFRA, include the submission of needed scientific data which the
Agency does not now have, compliance with standards of toxicity, composition,
labeling, and packaging, and satisfaction of the data compensation provisions
of FIFRA Section 3(c) (1) (D) .
The Standard will also serve as a tool for product classification. As part
of the registration of a pesticide product, EPA may classify each product for
"general use" or "restricted use" [FIFRA Section 3(d)]. A pesticide is
classified for "restricted use" when some special regulatory restriction is
needed to ensure against unreasonable adverse effects to man or the
environment. Many such risks of unreasonable adverse effects can be lessened
if expressly-designed label precautions are strictly followed. Thus the
special regulatory restriction for a "restricted use" pesticide is usually a
requirement that it be applied only by, or under the supervision of, an
applicator who has been certified by the State or Federal government as being
competent to use pesticides safely, responsibly, and in accordance with label
directions. A restricted-use pesticide can have other regulatory restrictions
[40 CFR 162.11(c)(5)] instead of, or in addition to, the certified applicator
requirement. These other regulatory restrictions may include such actions as
seasonal or regional limitations on use, or a requirement for the monitoring of
residue levels after use. A pesticide classified for "general use," or not
classified at all, is available for use by any individual who is in compliance
with State or local regulations. The Registration Standard review compares
information about potential adverse effects of specific uses of the pesticide
with risk criteria listed in 40 CFR 162.11(c), and thereby determines whether a
product needs to be classified for "restricted use." If the Standard does
classify a pesticide for "restricted use," this determination is stated in the
second chapter.
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Requirement _tp_ Re-register Under the Standard
FIFRA Section 3(g), as amended in 1978, directs EPA to re-register all
currently registered products as expeditiously as possible. Congress also_
agreed that re-registration should be accomplished by the use of Registration
Standards.
Each registrant of a currently registered product to which this Standard
applies, and who wishes to continue to sell or distribute his product in
commerce, must apply for re-regisration. His application must contain proposed
labeling that complies with this Standard.
EPA will issue a notice of intent to cancel the registration of any
currently registered product to which this Standard applies if the registrant
fails to comply with the procedures for re-registration set forth in the
Guidance Package which accompanies this Standard.
"Product Specific" Data and "Generic" Data
In the course of developing this Standard, EPA has determined the types of
data needed for evaluation of the properties and effects of products to which
the Standard applies, in the disciplinary areas of Product Chemistry,
Environmental Fate, Tbxicology, Residue Chemistry, and Ecological Effects.
These determinations are based primarily on the data Guidelines proposed in
1978 (43 FR 29686, July 10, 1978, and 43 FR 37336, August 22, 1978), as applied
to the use patterns of the products to which this Standard applies. Where it
appeared that data from a normally applicable Guidelines requirement was
actually unnecessary to evaluate these products, the Standard indicates that
the requirement has been waived. Cn the other hand, in some cases studies not
required by the Guidelines may be needed because of the particular composition
or use pattern of products the Standard covers; if so, the Standard explains
the Agency's reasoning. Data guidelines have not yet been proposed for the
Residue Chemistry discipline, but the requirements for such data have been in
effect for some time and are, the Agency believes, relatively familiar to
registrants. Data which we have found are needed to evaluate the
registrability of some products covered by the Standard may not be needed for
the evaluation of other products, depending upon the composition, formulation
type, and intended uses of the product in question. The Standard states which
data requirements apply to which product categories. (See the second chapter.)
The various kinds of data normally required for registration of a pesticide
product can be divided into two basic groups:
(A) data that is "product specific," i.e., data that relates only to
the properties or effects of a product with a particular composition
(or a group of products with closely similar composition) ; and
(B) "generic" data that pertains to the properties or effects of a
particular ingredient, and thus is relevant to an evaluation of the
risks and benefits of all products containing that ingredient (or all
such products having a certain use pattern), regardless of any such
product's unique composition.
The .Agency requires certain "product specific" data for each product to
characterize the product's particular composition and physical/chemical
properties (Product Chemistry), and to characterize the product's acute
toxicity (which is a function of its total composition) . The applicant for
registration or re-registration of any product, whether it is a manufacturing-
use or end-use product, and without regard to its intended use pattern, must
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submit or cite enough of this kind of data to allow EPA to evaluate the
product. For such purposes, "product specific" data on any product other than
the applicant's is irrelevant, unless the other product is closely similar in
composition to the applicant's, (Wiere it has been found practicable to group
similar products for purposes of evaluating, with a single set of tests, all
products in the group, the Standard so indicates.) "Product specific" data on
the efficacy of particular end-use products is also required where the exact
formulation may affect efficacy and where failure of efficacy could cause
public health problems.
All other data needed to evaluate pesticide products concerns the
properties or effects of a particular ingredient of products (normally a
pesticidally active ingredient, but in some cases a pesticidally inactive, or
"inert," ingredient), Some data in this "generic" category are required to
evaluate the properties and effects of all products containing that ingredient
[e.g., the acute LD-50 of the active ingredient in its technical or purer
grade; see proposed 40 CFR 163. 81-1 (a) , 43 FR 37355].
Other "generic" data are required to evaluate all products which both
contain a particular ingredient and are intended for certain uses (see, e.g.,
proposed 40 CFR 163.82-1, 43 FR 37363, which requires subchronic oral testing
of the active ingredient with respect to certain use patterns only) . Where a
particular data requirement is use-pattern dependent, it will apply to each
end-use product which is to be labeled for that use pattern (except where such
end-use product is formulated from a registered manufacturing-use product
permitting such formulations) and to each manufacturing-use product with
labeling that allows it to be used to make end-use products with that use
pattern. Thus, for example, a subchronic oral dosing study is needed to
evaluate the safety of any manufacturing-use product that legally could be used
to make an end-use, food-crop pesticide. But if an end-use product's label
specified it was for use only in ways that involved no food/feed exposure and
no repeated human exposure, the subchronic oral dosing study would not be
required to evaluate the product's safety; and if a manufacturing-use
product's label states that the product is for use only in making end-use
products not involving food/feed use or repeated hunan exposure, that
subchronic oral study would not be relevant to the evaluation of the
manufacturing-use product either.
If a registrant of a currently registered manufacturing-use or end-use
product wishes to avoid the costs of data compensation [under FIFRA Section
3(c)(l)(D)] or data generation [under Section 3(c)(2)(B)] for "generic" data
that is required only with respect to some use patterns, he may elect to delete
those use patterns from his labeling at the time he re-registers his product.
An applicant for registration of a new product under this Standard may
similarly request approval for only certain use patterns.
®^± Compensation Requirements under FIFRA 3(c) (1) (D)
Lhder FIFRA Section 3(c) (1) (D) , an applicant for registration, re-
registration, or amended registration must offer to pay compensation for
certain existing data the Agency has used in developing the Registration
Standard. The data for which compensation must be offered is all data which is
described by all the following criteria:
(1) the data were first submitted to EPA (or to its predecessor agencies,
USDA or FE&) , on or after January 1, 1970;
(2) the data were submitted to EPA (or USDA or EER) by some other
applicant or registrant in support of an application for an
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experimental use permit, an amendment adding a new use to a
registration, or for re-registration, or to support or maintain in
effect an existing registration;
(3) the data are relevant to the Agency's decision to register or re-
register the applicant's product under the Registration Standard,
taking into account the applicant's product's composition and intended
use pattern(s);
(4) the data are determined by EPA to be valid and usable in reaching
regulatory conclusions; and
(5) the data are not those for which the applicant has been exempted by
FIFRA Section 3(c) (2) (D) from the duty to offer to pay compensation.
(This exemption applies to the "generic" data concerning the safety of
an active ingredient of the applicant's product, not to "product
specific" data. The exemption is available only to applicants whose
product is labeled for end-uses for which the active ingredient in
question is present in the applicant's product because of his use of
another registered product containing that active ingredient which he
purchases from another producer.)
An applicant for re-registration of an already registered product under
this Standard, or for registration of a new product under this Standard,
accordingly must determine which of the data used by EPA in developing the
Standard must be the subject of an offer to pay compensation, and must submit
with his application the appropriate statements evidencing his compliance with
FIFRA Section 3(c)(1)(D).
An applicant "would never be required to offer to pay for "product specific"
data submitted by another firm. In many, if not in most cases, data which are
specific to another firm's product will not suffice to allow EPA to evaluate
the applicant's product, that is, will not be useful to the Agency in determin-
ing whether the applicant's product is registrable. There may be cases, how-
ever, where because of close similarities between the composition of two or
more products, another firm's data may suffice to allow EPA to evaluate some or
all of the "product specific" aspects of the applicant's product. In such a
case, the applicant may choose to cite that data instead of submitting data
from tests on his own product, and if he chooses that option, he would have to
comply with the offer-to-pay requirements of Section 3(C) (1) (D) for that data.
Each applicant for registration or re-registration of a manufacturing-use
product, and each applicant for registration or re-registration of an end-use
product, who is not exempted by FIFRA Section 3(c) (2) (D) , must comply with the
Section 3(c)(1)(D) requirements with respect to each item of "generic" data
that relates to his product's intended uses.
A detailed description of the procedures an applicant must follow in
applying for re-registration (or new registration) under this Standard is found
in the Guidance Package for this Standard.
Obtaining Data ^o Fill "Data Gaps"; FIFRA 3(c)(2)(B)
Some of the kinds of data EPA needs for its evaluation of the properties
and effects of products to which this Standard applies have never been
submitted to the Agency (or, if submitted, have been found to have deficiencies
rendering them inadequate for making registrability decisions) and have not
been located in the published literature search that EPA conducted as part of
preparing this Standard. Such instances of missing but required data are
referred to in the Standard as "data gaps".
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FIFRA Section 3(c) (2) (B) , added to FIFRA by the Gbngress in 1978,
authorizes EPA to require registrants to whom a data requirement applies to
generate (or otherwise produce) data to fill such "gaps" and submit those data
to EPA. EPA must allow a reasonably sufficient period for this to be
aceonplished. If a registrant fails to take appropriate and timely steps to
fill the data gaps identified by a section 3(c)(2)(B) order, his product's
registration may be suspended until the data are submitted. A mechanism is
provided whereby two or more registrants may agree to share in the costs of
producing data for which they are both responsible.
The Standard lists, in its summary second chapter, the "generic" data gaps
and notes the classes of products to which these data gaps pertain. The
Standard also points out that to be registrable under the Standard, a product
must be supported by certain required "product specific'- data. In some cases,
the Agency may possess sufficient "product specific" data on one currently
registered product, but may lack such data on another. Chly those Standards
which apply to a very small number of currently registered products will
attempt to state definitively the "product specific" data gaps on a 'product by
product' basis. (Although the Standard will in some cases note which data that
EPA does possess would suffice to satisfy certain "product specific" data
requirements for a category of products with closely similar composition
characteristics.)
As part of the process of re-registering currently registered products, EPA
will issue Section 3(c) (2)(B) directives requiring the registrants to take
appropriate steps to fill all identified data gaps — whether that data in
question is "product specific" or "generic" — in accordance with a schedule.
Persons who wish to obtain registrations for new products under this
Standard will be required to submit (or cite) sufficient "product specific"
data before their applications are approved. Upon registration, they will be
required under Section 3(c) (2) (B) to take appropriate steps to submit data
needed to fill "generic" data gaps. (Vfe expect they will respond to this
requirement by entering into cost-sharing agreements with other registrants who
previously have been told they must furnish the data.) The Guidance Package
for this Standard details the steps that must be taken by registrants to comply
with Section 3(c) (2) (B) .
Amendments _to the Standard
Applications for registration which propose uses or formulations that are
not presently covered by the Standard, or which present product compositions,
product chemistry data, hazard data, toxicity levels, or labeling that do not
meet the requirements of the Standard, will automatically be considered by the
Agency to be requests for amendments to the Standard. In response to such
applications, the Agency may request additional data to support the proposed
amendment to the Standard, or may deny the application for registration on the
grounds that the proposed product would cause unreasonable adverse effects to
the environment. In the former case, when additional data have been
satisfactorily supplied, and providing that the data do not indicate the
potential for unreasonable adverse effects, the Agency will then amend the
Standard to cover the new registration.
Each Registration Standard is based upon all data and information available
to the Agency's reviewers on a particular date prior to the publication date.
This "cut-off" date is stated at the beginning of the second chapter. Any
subsequent data submissions and any approved amendments will be incorporated
into the Registration Standard by means of addenda, which are available for
inspection at EPA in Washington, B.C., or copies of which may be requested from
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the Agency. When all the present "data gaps" have been filled and the
submitted data have been reviewed, the Agency will revise the Registration
Standard. Thereafter, when the Agency determines that the internally
maintained addenda have significantly altered the conditions for registration
under the Standard, the docunent will be updated and re-issued for publication.
While the Registration Standard discusses only the uses and hazards of
products containing the designated active ingredient(s), the Agency is also
concerned with the potential hazards of some inert ingredients and impurities.
Independent_of the development of any one Standard, the Agency has initiated
the evaluation of some inert pesticide ingredients. Where the Agency has
identified inert ingredients of concern in a specific product to which the
Standard applies, these ingredients will be pointed out in the Guidance Package.
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REQUIREMENTS FOR METQLACHLOR PRODUCTS
Tne following is the Agency's position on the present requirements for
registration and re-registration under this Metolachlor Registration Standard,
including: (1) what 'standards' of composition, acute toxicity, physical and
chemical properties, use, labeling, and packaging will ensure the safe use of
the pesticide active ingredient Metolachlor; and (2) what studies are needed
to retain existing registrations and to complete the data base that will
support future registrations under the Metolachlor Standard. There are
different 'standards' and data requirements for technical (manufacturing-use)
Metolachlor and for emulsifiable concentrate (end-use) Metolachlor. Producers
who use an 'integrated formulation system' to manufacture a Metolachlor end-use
product are responsible for the data required for both a manufacturing-use and
an end-use product.
This Registration Standard is based on all pertinent data and information
on Metolachlor available to the Agency's reviewers as of June 30, 1980.
Metolachlor
'Metolachlor' [2-chloro-N-(2-ethyl-6-methylphenyl)-N-(2-methoxy-l-
methylethyl)acetamide] is a selective herbicide used as either a pre-plant
incorporated or pre-emergence surface applied treatment for the control of most
annual grasses and certain broadleaf weeds in field corn (except fresh corn and
popcorn), soybeans, peanuts, and grain sorghum.
There is presently only one registrant and data submitter for pesticide
products containing Metolachlor: Ciba-Geigy Corporation (Agricultural
Division, P.O. Box 11422, Greensboro, ttorth Carolina, 27409).
The three presently registered products containing Metolachlor as the sole
active ingredient are a manufacturing-use "technical1 and two emulsifiable
concentrate formulations, one containing 8 pounds of active ingredient per
gallon, and the other containing 6 pounds per gallon. The formulation contain-
ing 6 pounds active ingredient per gallon is not presently in production,
although a small quantity remains on the market for 1980. Metolachlor is also
marketed in a package mix with each of two other herbicides, 'Atrazine1 and
1 Propazine', and is often mixed by the applicator with other herbicides to
provide a broader spectrun of weed control. However, please note that this
Metolachlor Standard will only consider the registration of products which
contain Metolachlor as the sole active ingredient, and will only consider
those potential hazarxfs which arise from Metolachlor applied alone.
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TECHNICAL METOLACHLOR
In order to be registrable under this Standard, a Technical Mstolachlor
product must comply with the following standards of composition, purity, and
toxicity: A Technical Metolachlor should contain at least 90 % (by weight) the
active ingredient ' Matolachlor", i.e. 2-chloro-N- (2-^thyl-6-methylphenyl) -N- (2-
methoxy-1-methylethyl) acetamide. If the manufacturing process submitted is
found by the Agency to be substantially different from the one used to produce
the presently registered Technical Mstolachlor, a theoretical discussion
concerning the formation of unintentional ingredients will have to be submitted
to attest that potentially harmful impurities will not result (see Proposed
Guidelines 163.61-5). The "product specific" acute toxicology testing on a
Technical Metolachlor (or on a "substantially similar" Technical Metolachlor)
must demonstrate that it falls into Tbxicity Categories which are the same as
or numerically higher than the following:
Acute Oral Tbxicity: Category III
Acute Eermal Tbxicity: Category III
Acute Inhalation Tbxicity: Category III
Primary Eye Irritation: Category III
Primary Dermal Irritation: Category III
The following 'Sample Label1 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 from the handling, transport,
re-formulation, storage, or disposal of Technical Metolachlor. In order to be
registered under this Standard, therefore, a Technical Metolachlor must meet
the following standard for labeling by submitting a label which includes
these statements in an appropriate format. [Consult the Proposed Guidelines
Section 162.10 for more complete directions on formats for labeling.]
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PRODUCT NAME
For Formulation of Herbicides Chly
Active Ingredient:
Metolachlor: 2-chloro-N-(2-ethyl-6-methylphenyl)-
N-(2-methoxy-l^nethylethyl)acetamide %
Inert Ingredients: %
Tbtal: 100%
CAUTION
PRECAUTIONARY STATEMENTS:
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. Wash thoroughly after
handling. Remove and wash contaminated clothing before re-use.
Statement of Practical Treatment: If swallowed, drink one or two
glasses of water. Induce vomiting by placing finger in back of
throat. Call a physician. Never give anything by mouth to an
unconscious person. If in eyes or on skin, flush with plenty of
water. If irritation persists, call a physician.
Hazards to Wildlife: Do not discharge into lakes, streams, ponds,
or publicTwaters unless in accordance with an NPDES permit. For
guidance, contact your regional office of EPA.
DIRECTIONS FOR USE
Refer to technical bulletin. It is a violation of federal law to
use this product in a manner inconsistent with its labeling.
STORAGE AND DISPOSAL
For bulk shipments in holding tanks, tank cars, storage tanks, etc.:
Do not contaminate water, food, or feed by storage or disposal.
Open dumping or open burning is prohibited. Pesticide or
rinsate that cannot be used, recycled, or chemically reprocess-
ed and tanks that cannot be re-used should be disposed of in
a landfill disposal site approved for pesticides. Thoroughly
clean containers before re-use. Consult federal, state, or
local disposal authorities for approved alternative measures.
For metal drums, cans, etc.:
Do not contaminate water, food, or feed by storage or disposal.
Open dumping or open burning is prohibited. Re-seal container
and offer for re-conditioning; or triple rinse (or equivalent)
and offer for recycling or re-conditioning. Pesticide or
rinsate that cannot be used, recycled, or chemically re-process-
ed, and containers that cannot be re-used or recycled should
be disposed of in a landfill disposal site approved for
pesticides. Consult federal, state, or local disposal
authorities for approved alternative measures.
Note _to Formulators: formulators are responsible for providing data
to support the registration of products formulated from this Technical.
EPA Registration No. Net Wt. or Measure
Establishment No. '
Name and Address of the producer, registrant, or person for whom produced.
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Finally, in order to re-register Technical I^fetolachlor under this
each registrant is required to submit or cite all the data below. The product
Chemistry data are "product specific" studies specific to the currently
registered Technical Metolachlor; the Environmental Fate, Toxicology, and
Ecological Effects data are "generic" studies that would test the active
ingredient or a typical formulation in order to assess the hazards due to end-
uses. After each is listed the section in the Proposed Guidelines (43 FR
29686, July 10, 1978, and 43 FR 37336, August 2, 1978) which describes that
type of data and what test substances should be used.
Product Chemistry
163. 61-8 (c) 6
163.61.8(c)13
163.61-8(c)14
163.61-3(0)15
163.61-8(c)17
163.61-8(0)18
1) Octanol/Ufeter Partition Coefficient;
2) Flammability;
3) Oxidizing or Reducing Action;
4) Explosiveness;
5) Viscosity;
6) Corrosion Characteristics;
7) (and, if Technical Metolachlor is shown to
produce genetic effects in future testing:)
An analytical method (or reference 163.61-7
to a method) for detecting and measuring
each identifiable impurity (associated with
the manufacturing of the Technical) in the
formulated products of Metolachlor;
Environmental Fate
8) Adsorption/desorption studies;
9) Actual field-use residue monitoring
studies at two watershed sites to be
approved by the Agency;
10) Accumulation studies on rotational
crops for small grains, root crops,
and leafy vegetables;
Toxicology
IT)Subchronic Oral Losing - Pathological
evaluation for both the rat and dog;
12) Chronic Feeding - A chronic feeding
study on laboratory rat;
13) Oncogenicity - Completion of the mouse
study; and testing on a mammal other than
the mouse (the laboratory rat is preferred),
or an oncogenic evaluation for the chronic
feeding study [see (12) above];
14) Teratology - A teratology study in a
mammalian species other than the rat;
15) Reproduction - A multi^generation
reproduction study on one mammalian
species (preferably the laboratory rat)
Ecological Effects
I6~) Activated sludge metabolism study;
17) The avian acute oral LE>-50 for ona
species of waterfowl (preferably the
mallard) or one species of upland game
bird (preferably the bobwhite quail); the
species must be one of those for which an
LC-50 was determined under FR 163.71-2.
163.62-9
(not discussed
in the Proposed
Guidelines)
163.61-11(b)
163.82-1
163.83-1
163.83-2
163.33-3
163.83-4
163.62-8(g)
163.71-1
18
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EMULSIFIABLE CONCENTRATE METOLACHLOR
In order to be registrable under this Registration Standard, an end-use
pesticide product containing ffetolachlor must contain fetolachlor as the sole
pesticide active ingredient. The only end-use Metolachlor formulations
registrable under this Standard are Emulsifiable Concentrates of Mstolachlor,
which are liquids consisting of the active ingredient suspended or dissolved in
one or more water-insoluble organic solvents, and if necessary, stabilized by
an emulsifying agent. Tne strength of each i^tetolachlor Emulsifiable
Concentrate must be stated in pounds Matolachlor per gallon liquid.
In order to registrable under this Standard, the "product specific" acute
toxicology testing on a Metolachlor Emulsifiable Concentrate (or a
"substantially similar" one) must demonstrate that it falls into Toxicity
Categories which are the same as or numerically higher than the following:
Acute Oral Toxicity: Category II
Acute Dermal Toxicity: Category III
Acute Inhalation Toxicity: Category II
Primary Eye Irritation: Category I
Primary Eermal Irritation: Category II
In order to be registrable under this Standard, the "product specific"
product chemistry testing on a Metolachlor Emulsifiable Concentrate must show
that it has physical/chemical properties which fall within the limits listed
below. For physical/chemical properties which are not shown below (see
the Product Chemistry chapter), no Standard has been set.
Physical State: liquid at room temperature
Vapor Pressure: between 0.05 and 1.0 mm Hg at 20 C
pH: between 6 and 8
Flammability: flashpoint above 80 F
Explosiveness: does not form explosive mixtures and is
not shock sensitive
Corrosiveness: must be no more than slightly corrosive to
steel or tin
These acute toxicity and physical/chemical properties tests need not be
performed for a proposed Emulsifiable Concentrate if it is substantially
similar to a previously registered Mstolachlor Emulsifiable Concentrate. The
applicant may request the Agency, in writing, to consider, by examination of
the statements of formula, whether the proposed product qualifies as
'substantially similar' to a previously registered product.
19
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In order to be registrable under this Standard, a Metolachlor Emulsi
Concentrate product must bear labeling in compliance with the following,
where appropriate, with label statements which are correctly correlated with
the product's toxicity categories or physical/chemical properties. [Consult
40 CFR Section 162.10 for more complete directions on formats for labeling = ]
1) The PRODUCT NAME at the top of the front panel;
2) Beneath the name, the product type "Herbicide";
3) A general statement of the product's use: "Fbr weed control in field
corn (except fresh corn and popcorn), soybeans, grain sorghun, and
peanuts", or any one or combination of these crops;
4) A front panel statement of the ingredient percentages:
Active Ingredient:
Metolachlor: 2-chloro-N-(2-ethyl-6-methylphenyl)-
N-(2-methoxy-l-methylethyl)acetamide ..... %
Inert Ingredients: ..... %
Total: 100%
5) Directly below the ingredient statement, the statement "PRODUCT NAME
contains ( ) pounds active ingredient per gallon";
6) A human hazard signal word on the front panel, selected as follows:
If the Primary Eye Irritation is Category I: DANGER
If the highest Toxicity Category is II: WARNING
If the highest Toxicity Category is III or IV: CAUTION
7) Just above the signal word, the statement "Keep out of reach
of children".
8) Under the heading, "PRECAUTIONARY STATEMENTS", (preferably on front
panel, but if not, then print on front panel, below the signal word:
"See side panel for additional precautionary statements"):
Under the heading, "Hazards to Hunans and Domestic Animals":
The human hazard signal word [same as (6) above] ;
Fbr acute oral toxicity,
if Category II: "May be fatal if swallowed."
if Category III: "Harmful if swallowed."
if Category IV: no statement required
Bbr acute dermal toxicity,
if Category III: "Harmful if absorbed through skin.
Avoid contact with skin or
clothing."
if Category IV: no statement required
For acute inhalation toxicity,
if Category II: "May be fatal if inhaled. Do not
breathe vapors or spray mist."
if Category III: "Harmful if inhaled. Avoid breathing
vapors or spray mist."
if Category IV: no statement required
Fbr primary eye irritation,
if Category I: "Corrosive, causes eye damage. Do not
get in eyes. Vvear goggles or face
shield when handling."
if Category II: "Causes eye irritation. Do not get
in eyes."
20
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if Category III: "Avoid contact with eyes. In case of
contact immediately flush eyes or
skin with plenty of water. Get
medical attention if irritation
persists."
if Category IV: no statement required
For primary dermal irritation,
if Category II: "Causes skin irritation. Do not get on
skin or on clothing."
if Category III: "Avoid contact with skin or
clothing. In case of contact,
immediately flush skin with plenty of
water. Get medical attention if
irritation persists."
if Category IV: no statement required
For dermal sensitization,
"May cause skin sensitization. Wear gloves and
protective clothing while handling or using this
product. Wash thoroughly after handling. Remove and
wash contaminated clothing before re-use."
Under the heading, " Environmental Hazards":
"Avoid direct application to any body of water. Eb not apply
where runoff is likely to occur. Co not contaminate water by
cleaning of equipment or disposal of wastes. Eb not apply
when weather conditions favor drift from target area."
Ihder the heading, "Physical/Chemical Hazards" : Q
For flammability, if the flash point is above 80 F and
not over 150°F, the statement: "Do not use or
store near heat or open flame".
For corrosiveness, if corrosive to steel or tin, the
statement: "Eb not place in unlined metal containers
or tanks."
And beside the heading, "First Aid":
If the formulation has greater than 10% by weight petroleum
distillates, and has Category IV Acute Oral Tbxicity:
"In case of contact with eyes, immediately flush with
plenty of water for at least 15 minutes. Call a
physician. If inhalation occurs, the victim should be
moved to fresh air, and medical attention should be
sought. If swallowed contact your local Poison Control
Center, hospital, or physician immediately. If patient
is unconscious, maintain breathing and heartbeat (CPR:
cardiopulmonary resuscitation) . Eb not induce vomiting!
[Note to Physician: If swallowed, there is no
specific" antidote. The use of emesis and/or lavage
should be weighed against the possibility of a chemical
pneunonitis as this product contains petroleum
distillates. Treat symptomatically! The use of an
aqueous slurry of activated charcoal (such as ISbrit A)
and a saline cathartic should be considered.]"
If the formulation has greater than 10% by weight petroleum
distillates, and has Category II or III Acute Oral Tbxicity:
"In case of contact with eyes, immediately flush with
plenty of water for at least 15 minutes. Call a
physician. If inhalation occurs, the victim should be
21
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moved to fresh air, and medical attention should be
sought. If swallowed contact your local Fbison Control
Center, hospital, or physician immediately ..." [The
remainder of this First Aid statement, which will
concern the use of emesis and/or lavage, will be
determined at the time of (re-) registration, and will
be based on the precise quantitative toxicity of the
formulation. See the NOTE below.]
If the formulation contains, by weight, 10% or less (or does
not contain) petroleum distillates:
"In case of contact with eyes, immediately flush with
plenty of water for at least 15 minutes. Gall a
physician. If inhalation occurs, the victim should be
moved to fresh air, and medical attention should be
sought. If swallowed, contact your local R>ison Gbntrol
Center, hospital, or physician immediately. If patient
is unconscious, maintain breathing and heartbeat (CPR:
cardiopulmonary resuscitation) . If patient is
conscious, induce vomiting (syrup of ipecac; if not
available, stimulate back of throat with finger).
Never give anything by mouth to an unconscious person!
[Note to Physician: If swallowed, there is no
specific" antidote. Induce emesis and lavage stomach.
Treat symptomatically! The use of an aqueous slurry of
activated charcoal (such as Norit A) and a saline
cathartic should be considered.]
9) After precautionary statements, under "DIRECTIONS FOR USE":
The statement:
"It is a violation of Federal law to use this product in
a manner inconsistent with its labeling."
The statement (required for agricultural-use pesticides):
"This product must be applied in accordance with 40 CFR
Part 170."
"Under the heading, "General Information":
"PRODUCT NAME [( ) Ibs. a.i./gal.] is a selective herbicide
recommended as a preplant incorporated or pre-emergence
surface-applied treatment in water or fluid fertilizer for
control of most annual grasses and certain broadleaf weeds
in corn grown for grain (except popcorn), soybeans, peanuts,
and grain sorghum", or any one or combination of these
crops. When corn is listed as one of these crops, "Do not
use on sweet corn or popcorn." Also, the statement:
"Failure to follow all precautions on this label may result
in poor ,veed control, crop injury, or illegal residues."
Also include, where spraying equipment if discussed:
"Use conventional ground sprayers or center pivot irrigation
application" and any additional directions or precautions
for using these methods of application.
10) Under the heading, "PRODUCT NAME Applied Alone":
If for use on corn, under the heading, "Corn":
Directions should specify all application methods and
rates. All applications must be pre-emergence. to rate
in excess of 6 pounds active ingredient per acre may be
recommended.
22
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If for use on soybeans, under the heading, "Soybeans":
Directions should specify all application methods and
rates. All applications must be pre-emergence. No rate
in excess of 3 pounds active ingredient per acre may be
rec arm ended.
If for use on peanuts, under the heading, "Peanuts":
Directions should specify all application methods and
rates. All applications must be pre-emergence. No rate
in excess of 3 pounds active ingredient per acre may be
recommended.
If for use on sorghum, under the heading, "Grain Sorghum":
Directions should specify all application methods and
rates. All applications must be pre-emergence. No rate
in excess of 2-1/2 pounds active ingredient per acre may be
recommended. (If the product will severely injure the
crop when the sorghum seed is not pre-treated, it is
advisable to include a statement to this effect.)
(When application methods and rates are the same for two or more
crops, these directions may be listed under a combined heading
such as "Corn and Soybeans".)
Under the heading,- "Rotational Crops":
"1) If crop treated with PRODUCT NAME is lost, corn,
soybeans, peanuts, or grain sorghum may be replanted
immediately. Do not make a second application of PRODUCT
NAME. If the original application was banded, and the second
crop is planted in the untreated row middles, a second
banded treatment may be applied. 2) Small grains may be
planted 4-1/2 months following treatment. Field corn (except
fresh corn and popcorn) , cotton, soybeans, peanuts, sorghum,
root crops, and small grains may be planted in the spring
following treatment. Do not graze or feed forage or fodder
from cotton or small grains to livestock. All other rota-
tional crops may be planted 18 months after application."
11) Under the heading, "STORAGE AND DISPOSAL":
Concerning disposal,
"Open dumping or open burning is prohibited. Do not re-use
empty container; triple rinse or equivalent. Pesticide or
rinsate that cannot be used, recycled, or chemically
reprocessed, and triple-rinsed containers with their
rinsate, should be disposed of in a landfill disposal site
approved for pesticides. Consult federal, state, or local
disposal authorities for approved alternative procedures."
Concerning storage,
the statement: "Keep out of reach of children";
if the flash point is above 80°F and not over 150°F, the
statement: "Do not store near heat or open flame.";
if the product is corrosive to steel or tin, the statement:
"Do not store in unlined containers or tanks.";
12) The label must also bear the 'EPA Registration Number1, the "Net
Weight or Measure" of the contents of the container, and the Name and
Address of the producer, registrant, or person for whom the product
was produced. Finally, the "Establishment Number" should appear on
either the label or the container.
23
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NOTE: Concerning labeling for products containing petroleum distillates,
proper emergency medical treatment for the ingestion of petroleun
distillates is a controversial subject. Two significant risks must be
weighed in reaching a decision on whether or not to induce emesis or
perform gastric lavage: If emesis is induced, or gastric lavage is
performed, petroleun distillates may be aspirated, possibly resulting in
fatal chemical pneunonitis. However, retaining a highly toxic pesticide in
the stomach even for a short period of time may also prove fatal.
The Agency has contacted a nunber of authorities both within and
outside EPA. Tnere is no general agreement on how this problem may best be
solved. In reaching a decision on appropriate labeling policy for
products, the Agency considers the toxic properties of the active
ingredients, inerts, and impurities. Thus, labeling requirements may
differ for chemicals and products addressed in these Standards.
In establishing a policy, the Agency has considered that emergency
treatment may not be readily available, and that first aid will usually be
administered by a member of the general public who has little or no medical
training.
In general the Agency believes that the best advice is to seek medical
help immediately and to keep the patient breathing until medical help
arrives. The Agency believes the following labeling is appropriate for all_
products which contain more than 10% by weight petroleum distillates:
(1) "If patient is unconscious, maintain breathing and heartbeat
(CPR: cardiopulmonary resuscitation) . Cbntact your local Poison
Control Center, hospital, or physician immediately."
Pesticides in Acute Oral Toxicity Category I have an acute LD-50 of
less than or equal to 50 mg/kg, and a seriously toxic dose of such a
pesticide could readily be swallowed by both a 70 kg adult (a dose of 3*5
gm) and a 12 kg child (a dose of 0.6 gm). Thus for all products that con-
tain more than 10% by weight petroleum distillates and are in Oral Toxicity
Category I, it is prudent to recommend in addition to Statement (1) :
"If patient is conscious, induce vomiting (syrup of ipecac; if
not available, stimulate back of throat with finger). Never give
anything by mouth to an unconscious person!"
Pesticides in Acute Oral Toxicity Category IV have an acute LD-50 of
greater than 5 g/kg , and a seriously toxic dose could not readily be
swallowed by either a 70 kg adult (a dose of 350 gm) or a 12 kg child (a
dose of 60 gm) . Thus, because the risk of chemical pneumonitis following
emesis is greater than the risk of allowing the pesticide to remain in the
system, for all products which contain more than 10% by weight petroleum
distillates and are in Oral Toxicity Category IV, the label should say in
addition to Statement (1) :
"Do not induce vomiting!"
Products in Oral Toxicity Categories II and III, which could have an
acute LD-50 anywhere between 50 and 5000 mg/kg, will be dealt with on a
product by product basis at the time of registration or re-registration,
and label statements will be based on a review of the toxicity of active
ingredient(s) , inerts, and impurities.
4
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The Agency has determined that the above 'Standards' adequately limit the
acute hazards of Bnulsifiable Concentrate tetolachlor for agricultural workers
and others not directly involved in the application, and that therefore no re-
entry interval has been established for Emulsifiable Concentrate ffetolachlor.
Nevertheless, users should be aware that the "application of a pesticide in
such a manner as to directly or through drift expose workers or other persons
except those knowingly involved in the application" is expressly prohibited
under 40 CFR 170.3. Registrants may amplify the statement on labels or
labeling to "apply in a accordance with 40 CFR Fart 170" by stating the
requirements of 40 CFR Part 170 or additions thereto if they so choose.
Finally, the following are "product specific" studies needed to complete
the data base which will support the re-registration of currently registered
Emulsifiable Concentrates under this Standard. In order to re-register the
following Mstolachlor Emulsifiable Concentrates under this Standard, each
registrant is required to submit or cite these data. After each requirement is
listed the section in the Proposed Guidelines which describes that type of data
and what test substances should be used.
For currently registered Bnulsifiable Concentrate Mstolachlor of
six (6) pounds active ingredient per gallon:
Product Chemistry
I) Color 163.61-8(c)l
2} Cdor 163.51-8(0)2
For currently registered Emulsifiable Concentrate Matolachlor of
eight (8) pounds active ingredient per gallon:
Product Chemistry
Tj" Color 163.61-8(0)1
2) Cdor 163.61-8 (c) 2
3) Ebcplosiveness 163.61-8 (c) 15
Toxicology
4) Acute inhalation toxicity study. 163.81-3
25
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USE PROFILE
The currently registered end-use formulations of Metolachlor are two
Emulsifiable Gbncentrates, one at six pounds active ingredient per gallon, the
other at eight pounds per gallon. Metolachlor is a selective herbicide, used
either as a pre-plant incorporated or pre-emergence surface-applied treatment
in water or fluid fertilizer for the control of most annual grasses and certain
broadleaf weeds in field corn (except fresh corn and popcorn) , soybeans,
peanuts, and grain sorghum. This Registration Standard for Metolachlor only
considers the risks that arise from the use of Metolachlor alone, and not when
it is formulated or tank mixed with other pesticides. Application for
Metolachlor alone is performed as follows for presently registered products:
pre-plant incorporated - 1.5 to 3.0 pounds active ingredient per acre
(1.5 to 2.5 Ibs. ai/acre for grain sorghum) (depending upon soil type),
used when field has furrow irrigation, or when a period of dry weather is
expected. fourteen 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 by
conventional ground sprayer (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 (1.5 to 2.5 Ibs. ai/acre for grain sorghum) (depending upon soil
type), applied by conventional ground sprayer (or center pivot irrigation
system) during planting (behind the planter), or after planting but before
weeds or crop emerge.
The directions for application to sorghum fields require that grain sorghum be
treated with Mstolachlor alone only when the seed have been pre-treated with
'Goncep' (registered trademark of CIBA-GEIGY) at 8 oz./100 Ibs. of seed,
which blocks the herbicidal action of Metolachlor on sorghum.
The registered rotational crops restriction is: small grains may be
planted 4-1/2 months following treatment; field corn (except fresh corn and
popcorn), soybeans, cotton, peanuts, grain sorghun, root crops, and small
grains may be planted the spring following treatment; do not graze or feed
forage or fodder from small grains to livestock; all other crops may be planted
18 months after application without restriction.
Studies which examine the use of a pesticide in integrated pest management
(IPM) schemes may suggest ways of reducing application rates or frequency for
pesticide chemicals, without reducing the degree of pest control achieved. IPM
schemes may put the reduced use of a chemical in conjunction with one or more
of the following biological and cultural methods of control: the development
of resistant varieties of host plants and animals, the introduction of natural
enemies, adjustments in crop rotations, cropping systems and planting time,
water management and tillage practices, and the diagnostic techniques for
evaluating the degree of pest infestation so that the chemical is used only
when needed. Information about the use of Metolachlor in IPM schemes is
expected to become available as more IPM weed control schemes are developed,
and the Standard for Matolachlor will then consider the degree to which hazards
are lowered by these alternative, but equally effective, uses of the chemical.
27
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PRODUCT CHEMISTRY
INTRODUCTION
FIFRA 3(c)(2)(A) requires the Agency to establish guidelines for
registering pesticides in the United States. The Agency requires registrants
to provide quantitative data on all added ingredients, active and inert, which
are equal to or greater than 0.1% of the product by weight.
To establish the composition of products proposed for registration, the
Agency requires not only data and information on the manufacturing and
formulation processes, but also a discussion on the formation of manufacturing
impurities and other product ingredients, intentional and unintentional.
Further, to assure that the composition of the product as marketed will not
vary from the composition evaluated at the time of registration, applicants are
required to submit a statement certifying upper and lower composition limits
for the added ingredients, or only upper limits for some unintentional
ingredients. Subpart D suggests specific precision limits for ingredients
based on the percentage of ingredient and the standard deviation of the
analytical method.
In addition to the data on product composition, the Agency also requires
data to establish the physical and chemical properties of both the pesticide
active ingredient and its formulations (FR 163.61-10). For example, data are
needed concerning the identity and physical state of the active ingredient
(e.g., melting and boiling point data, vapor pressure, and solubility) . Data
are also required on the properties of the formulated product to establish
labeling cautions (e.g., flammability, corrosivity, and storage stability).
The Agency uses these data to characterize each pesticide and to determine its
environmental and health hazards.
TOPICAL DISCUSSIONS
Corresponding to each of the Topical Discussions listed below is the nunber
of the section in the 'Proposed Guidelines for Registering Pesticides' of July
10, 1978 (FR Part 163), which explains the data that the Agency will need in
order to assess Matolachlor's Product Chemistry.
Guidelines Section
Chemical Identity 163.61^3
Manufacturing Process 163.61-4
Percentages of Components in Pesticide Products 163.61-6
Product Analytical Methods and Data 163.61-7
Physical/Chemical Properties 163.61-8
Chemical Identity
'Metolachlor1 is the acceptable common name for 2-chloro-N-(2-«thyl-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 Matolachlor in the United States, has
assigned Metolachlor the experimental number 'CGA-24705' (for the active
ingredient) , and the trade name 'Dual1. The name 'Metolachlor' will be
used in the Standard in place of the trade name or the chemical name.
29
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METOLACHLOR AND RELATED
HERBICIDES
Metolachlor
Alachlor
.e
Butachlor
o
Acetochlor
Terbuciilor
Diethathyl-ethyl
CH-CSCH
Prynachlor
1
l-C-CH-O.
Allidochlor
FIGURE 1.1
Propachlor
30
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Metolachlor is both a 2-chloroacetamide and a 2-chloroacetanilide._ Figure
1.1 shows the relationship between ftetolachlor and other pesticide active
ingredients similar in chemical structure. See the 'Chemical Data Sheet' on
'CCM-0011 in the Appendix for a complete chemical characterization of the
active ingredient Metolachlor.
Manufacturing Process
Although specific manufacturing information is withheld, the publicly-
available U.S. Patent for the synthesis of Metolachlor shows that it may be
produced by reacting the N-substituted aniline above with a chloroacetylating
agent, preferably an anhydride or halide of chloroacetic acid. The general
process is shown in Figure 1.2 below, which is taken from Vogel and Aebi, U.S.
Patent 3,937,730 (1975) and German Patent 2,328,340 (1973).
CICHj.-C-N-CH-
Figure 1.2
Percentages of Components _rn Pesticide Products
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 or contaminant, reaction
product, and degradation product which is known to be present or which might
reasonably be identified.
Although the Agency has been supplied with all this information for
Technical Metolachlor, the manufacturer has claimed that the identity of
impurities or contaminants can indirectly disclose details about the
manufacturing process, and that the identity of Metolachlor impurities is
therefore Confidential Business Information. The Agency agrees that one can
sometimes extrapolate part of the manufacturing process from the identity of
impurities or contaminants. The identity of the impurities in Technical
Metolachlor is thus not reported in this discussion, but is instead retained
by the Agency for internal reference. (Accordingly, in the Appendix, the
Chemical Data Sheets for components CCM-002 through CCM-011 are also withheld
from publication.) The Agency does not presently have any reason for concern
about the nature of the identified impurities for Technical Metolachlor.
31
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Cnly the percentage of active ingredient has been supplied for the
presently registered formulated end-use products containing Metolachlor.
Technical Metolachlor (manufacturing-use preparations)
1 presently registered: Technical Metolachlor is comprised of minimum
90 to 95 % (by weight) the active ingredient
'Metolachlor1, i.e., 2-chloro-N-(2-ethyl-6-
methylphenyl) -N- (2-methoxy-l-methylethyl)
acetarnide.
Emulsifiable Concentrate Metolachlor (end-use pesticide)
2 presently registered: (a) EmulsiFiable Concentrate with six pounds of
active ingredient per gallon is comprised of
68.5% the active ingredient 'Metolachlor' and
31.5 % inerts.
(b) Qnulsifiable Concentrate with eight pounds of
active ingredient per gallon is comprised of
86.4% the active ingredient 'Metolachlor' and
13.6 % inerts.
Product Analytical Methods and Data
Methods for detecting and measuring the Matolachlor compound in its
registered formulations have been submitted (Itelseth and Cole, 1973) . Though
all the non-Metolachlor components of the Technical product have been
identified by its manufacturer (Ciba-Geigy Corporation, 1974) , methods have
not been reported for determining or measuring any of the impurities in
Metolachlor products. This analytical method would only be required if a
definite positive response were observed in genetic toxicological tests
performed on the Technical. (See the Toxicology chapter for a discussion of
genetics effects testing requirements.)
Physical/Chemical Properties
Colo_r: Technical Metolachlor is white to tan. The color of each
Emulsifiable Concentrate was not reported.
Odor: Technical Mstolachlor is odorless. The odor of each Bnulsifiable
Concentrate was not reported.
Solubulity: The solubility of Technical Metolachlor was reported to be:
~~ In water - 530 ppm 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-dichloroethane (ethylene dichloride)
Miscible with cyclohexanone
32
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Stability: Ebr Technical Metolachlor, the half-life of a 0.25% aqueous
solution at 100°C is 30 hours at pH 3, 18 hours at pH 7, and 1.5
hours at pH 10.
Cctanol/Water Partition Coefficient: ND octanoI/water partition
coefficient has been reported for Technical Mstolachlor.
Physical State: Both Technical and Emulsifiable Concentrate Mstolachlor
products are in liquid form at room temperature.
Specific Gravity; The specific gravity of Technical Mstolachlor is 1.085
H7- 0.005) at 20 C. The specific gravity of the six pound active
ingredient per gallon Emulsifiable Concentrate is 1.04 (+/- 0.005) at
20 C, and the specific gravity of the eight pound ger gallon
Emulsif iable Concentrate is 1.11 (+/- 0.005) at 20 C.
Boiling Point; At 0.001 urn Kj, the boiling point of Technical
ffiitolachlor is 100 C. Ebr the six pound per gallon Emulsifiable
Concentrate (EC) , it is 118 C, and for the eight pound per gallon,
it is 140 to 160 C.
Vapor Pressure: Ebr the Technical, the vapor pressure is about 10 mm
Hg at 20 C. Ebr the six pound per gallon EC, the vapor pressure was
reported to be 0.05 to 1.0 rrm Hg at 20 C, and for the eight pound
per gallon EC, it was 0.05 urn Hg at 20°C.
pH: The pH of a 10% solution of six pound active ingredient per
gallon Emulsifiable Concentrate is between 7 and 8, and that of an
eight pound per gallon EC is between 6 and 8.
Storage Stability: Results of ongoing studies show that Technical
Metolachlor is stable for a minimum of one year at room temperature.
The shelf life of both concentrations of the Emulsifiable Concentrate
is estimated to be a minimum of 5 years.
Flammability: No data were available on the flammability of the
Technical. The flash point of £he six pound per gallon Emulsifiable
Concentrate was found to be 118 F (Setaflash C.C.T.) , and that of
the eight pound per gallon was found to be 185 (+/- 5)°F (TCC) .
Oxidizing or Reducing Action; isb data were available for the Technical,
but th"i~ Emulsifable Concentrates were reported to be clearly non-
reactive.
Explosiveness: Again no data were available about the Technical. A
study on the explosiveness of the six pound per gallon Emulsifiable
Concentrate has shown that the material is thermally stable at
200°C, can be processed or handled at temperatures 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: Both Emulsifiable Concentrate formulations form a stable
emulsion with water.
33
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Viscosity: ND data were available on the viscosity of the Technical.
The six pound per gallon Hnulsifiable Concentrate has a viscosity of
15.6 (+/- 0-3) CS at 25 C. The eight pound per gallon, a viscosity
of 120 (+/- 5) CD at 25 C.
Corrosion Characteristics; Isb data were available on the corrosiveness
of the Technical."for the Bnulsifiable 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.
Dielectric Breakdown Voltage: As long as Mstolachlor is not registered
~ for""industrial weed control, it will not be used around high power
electrical machinery, and a dielectric breakdown voltage test will not
be needed.
34
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DISCIPLINARY REVIEW
Chemistry Profile
Product Specific Eata Caps
Suggested labeling
Chemistry Profile
The technical material for a pesticide is the toxicant in pure form
(usually more than 90 % the active ingredient) as it is manufactured by a
chemical company prior to being formulated into an end-use pesticide product,
Technical Metolachlor, which is at least 90 to 95 % 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 Matolachlor is a 'manufacturing-use product1. The
physical/chemical properties which have so far been determined for the
Technical do not suggest any imminent hazards from the handling of the
Technical product.
An emulsifiable concentrate is an end-use pesticide product, consisting of
a toxicant 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.
Two strengths of Emulsifiable Concentrate Mstolachlor are currently
registered: six pounds active ingredient per gallon and eight pounds per
gallon. These are somewhat 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 two warnings on the
labels of emulsifiable concentrates: due to the vapor pressure and high
flammability of the solvent in the six pound per gallon formulation, the user
should keep any six pounds or less per gallon formulation away fron 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 tanks and storage containers that are protectively lined.
Product Specific Data Gaps
The following are "product specific" data gaps for Product Chemistry which
need to be filled in order to maintain in effect current registrations under
this Standard. After each gap is listed the section in the Proposed Guidelines
(July 10, 1978, FR Part 163) which describes that type of data and when it is
required.
For Technical Mstolachlor:
1) Octanol/Water Partition Coefficient 163.61-8(c)6
2) Flammability 163.61-8(c)13
3) Oxidizing or Reducing Action 163.61-8 (c) 14
4) Explosiveness 163.61-8(c)15
35
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5) Viscosity 163.61-8(c)17
6) Corrosion Characteristics 163.61-8(c)18
7) [and, if the Technical is found to produce
genetic effects (see Toxicology chapter) :]
An analytical method (or reference 163.61-7
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 Bnulsifiable Concentrate tetolachlor (6 Ibs. ai/gallon) :
1) Color 163.61-8(c) 1
2) Cdor 163.61-8(c)2
For Snulsifiable Concentrate Metolachlor (8 Ibs. ai/gallon) :
1) Color 163.61-8(c)l
2) Cdor 163.61-8(c)2
3) Explosiveness 163.61-3(c)15
Suggested Labeling
The ingredient statement for Metolachlor products should list the
active ingredient 'Metolachlor' as:
"Pfetolachlor: 2-chloro-N- (2-ethyl-6-methylphenyl) -N- (2-methoxy-l-
methylethyl) ace tarn ide"
36
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BIBLIOGRAPHY
Each of the following studies contributed useful information to the
Agency's review of the product chemistry of Metolachlor, and is considered part
of the data base supporting registrations under this Standard.
American National Standards Institute (1976). American National Standard ANSI
K62.198-1976. Common name for the pest control chemical 2-chloro-N-(2
methoxy-1-methylethyl) acetamide: "metolachlor". New York, N.Y.
Ciba-Geigy Corporation (1974) Section A, CGA-24705: Name, Chemical Identity
and Composition of CGA-24705. (Unpublished study; received Sep 26,
1974 under 100-EUP-44; CDL:96505:A)
Ciba-Geigy Corporation (1975h) Section A, CGA-24705: Name, Chemical Identity,
and composition of CAG-24705. Received Nov 25, 1976 under 6G1708.
(Unpublished study; CDL:96439-A)
Ciba-Geigy Corporation (1976a) CGA-24705: Name, Chemical Identity, and
Composition of CGA-24705. Received Nov 23, 1976 under 100-587.
(Unpublished study prepared by Ciba-Geigy Corp., Greensboro, N.C.;
CDL:226955-A)
Ciba-Geigy Corporation (1977) Aerial Application. Received Feb 18, 1977
under 100-583. (Unpublished study that includes studies ID-9D with a
summary; CDL:228101-F; 228122)
Ciba-Geigy Corporation (1977ba) Section A General Chemistry. (Unpublished
study; received Jan 19, 1977 under 7F1913; CDL:95764-A)
Ciba Geigy Corporation (1977b) Aerial Application. Received Jun 20, 1977.
(Unpublished study containing studies ID-10D with a summary; CDL:230672-D,
230683)
Helseth, J. ; Cole, G. (1973) The Determination of CGA-24705 in Hnulsifiable
Concentrates by Gas Liquid Chromatograpy. Method PA-9 dated Nov 14,
1973. Received Sep 26, 1974 under 5G1553. (Unpublished report
prepared by Ciba-Geigy Corp., Greensboro, N.C.; CDL:96666-A)
Vogel, C.; Aebi, R., inventors; Ciba-Geigy Corp., assignee (1976) Plant growth
regulating agent. U.S. patent 3,937,730. Eeb 10: 8p. Int CI . C07G
103.34.
Vogel, C.; Aebi, R., inventors; Ciba-Geigy Corp., assignee (1973)
Haloacetanilides acting on plant growth. German patent 2,328, 340.
Dae 20: 50p. Int. CI. C07C 103.38.
37
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ENVIRONMENTAL FATE
TOPICAL DISCUSSIONS
Corresponding to each of the Topical Discussions listed below is the nunber
of the section(s) in the 'Proposed Guidelines for Registering Pesticides' of
July 10, 1978 (40 FR Part 163) which explain(s) the data that the Agency will
need in order to assess Matolachlor's Environmental Fate.
Physico-Chemical Transformation
Soil Metabolism
Microbial Metabolism
Mobility
Spray Drift
Field Dissipation
Accumulation
Guidelines Section
153752^7
163.62-8
163.62-8
163.62-9
163.126-2, -3, and/or -4
163.62-10
163.62-11
Physico-Chemical Transformation
Hydrolysis
Metolachlor in buffer pH 5, 7, and 9 at 30 , was respectively 97,
100, and 96% stable for 28 days (Burkhard 1974) . From rate constants,
Arrhenius parameters for each pH value were calculated. Using the
Arrhenius parameters, half-lives for Mstolachlor at 20 C were calculated
to be greater than 200 days in 0.1N HQ (pH 1) and in buffer pH 5, 7, and
9. In 0.1N NaOH (pH 13), the calculated half-life was 97 days. Hydrolysis
of Metolachlor in 0.1N NaOH at 30 C yields N-(2 'methoxy-1 -methyl-ethyl) -
2-ethyl-6-methyl hydroxyacetanilide. In 0.1N HC1 at 70 C, Metolachlor
hydrolyzed to 4-(2-methyl-6-ethyl-phenyl)-3-methyl-morpholinone-5.
These data were sufficient to show that hydrolysis products are not of
envirormental concern because Mstolachlor is considered to be stable in the
natural environment.
Photolysis
Because Matolachlor is used on outdoor crops, studies on photolysis
in both soil and water are needed. Because an assessment 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
MetolacHlor 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, accounting 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.
39
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Qie 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, Matolachlor
in aqueous solution was approximately 69% degraded in 15 days (Aziz
and Kahrs 1974). Five photoproducts comprising 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-
methylmorpholine (MET-009) , N=(2-hydroxyacetyl-N-methoxyprop-2-yl) 2-
ethyl-6=methylaniline (MET-001), and N-chloroacetyl-2-ethyl-6-methyl-
aniline (MET-010). (See the Appendix for identities of chemicals
referred to by MET nunbersc) Photolysis products in the aqueous
phase amounted to 23% of the activity* Chloroform soluble products
which stayed at the origin on thin layer chromatography (TLC),
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 TLC with a developer of chloroform and methanol
(9:1) and chronotropic acid, methanolic sodiun hydroxide, and
diaaonium fluoroborate as specific spray reagents. With this TLC
system, at least seven photolysis products were separated. None
represented more than 4% of the original C activity. These polar
products did not contain hydroxyl, aldehyde, or N-hydroxynethyl
groups as judged from tests with the specific chromogenic agents.
Based upon the data discussed in this section, Metolachlor is
considered to be stable in aqueous solution under natural sunlight.
photolysis in Soil
~ Studies~brr~soil slides were performed by Aziz (1974) . Lhder
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-1-
ol~2-yl-N-chloroacetyl-2~jnethyl-6-ethylaniline, and three unknowns
accounted for 7«7%o ESich unknown was less than 10% of the applied
activity. Non-extractable C-activity in soil amounted to 39% of
the applied activity, \folatiles accounted for 10.5% of the applied
activity, of which 5.2% was determined to be parent.
Uider artificial sunlight conditions, Metolachlor on soil slides
was approximately 52% degraded in 7 days. Activity in the chloroform
extract amount 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 comprised of 3
unknowns. (Each unknown was less than 10% of the applied activity.)
Nonextractable " C-residue in soil amounted to 39%. \blatiles
accounted for 6.8% of applied activity, of which 4.12% was determined
to be parento
Though either study would 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 Metolachlor in soil.
40
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Soil Metabolism
Elleghausen (1976a and b) studied the degradation of Matolachlor in soil
under sterile aerobic, nonsterile aerobic, and nonsterile aerobic followed by
nonsterile anaerobic conditions. Uhder sterile aerobic conditions, at the end
of 12 weeks, 30% of the reductively dechlorinated analog of Metolachlor (MET-
005) was found. No other metabolite could be detected. The remaining
radioactivity existed as undegraded Metolachlor.
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-02S» Another 10%
MET-005
MET-025
of the initially applied radioactivity was found as polar, water soluble
products. They were inseparable by TLC, but could be methylated with
diazomethane to form three distinct components, separable by gas liquid
chronatography (GDC). The investigator considers these to be ring
hydroxylated analogs of MET-025. A CH-CL--soluble nonpolar metabolite,
representing about 5% of•initial radioactivity was compared, by TLC and GLC co-
chromatography, to 26 model Metolachlor metabolites with no identity fit.
Small amounts of MET-005 as well as unidentifiable polar and nonpolar
extractables were also found.
Sumner, Szqlics, and Gassidy (1976) studied the products of degradation of
ring labeled C Matolachlor in silt loam treated at an exaggerated rate
(100 ppm) and incubated out-of-doors in open bottomed containers. Besides
41.7% of total initial radioactivity found as Metolachlor, 0.9% of MET-001 and
0.1% MET-008 were fbind. Additionally, an oxalic acid derivative was
tentatively identified as MET-025. Chemicals contained in the leachate from
this study were qualitatively similar, as determined by comparative radioassay
of various TLC R~ zones.
Concurrently, Sumner, Szolics, and Cassidy (1976) conducted a field plot
study of silt loam soil treated at 2 Ibs active ingredient per acre (a.i./A)
41
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and aged 12 months. This study yielded in addition to MET-001, MET-008, and
MET-025, the additional compounds MET-003 and MET-026.
MET-003
All metabolites in both substudies were less than 1% of total
radioactivity, except MET-001 in the leachate, which reprosented 2.5% of total
radioactivity. Two TLC spots, representing metabolites less polar than MET-
003 were also noted, both at the 1% level, in the extracts from the field
experiment; the two spots as well as a spot near the TIC plate origin
represented 6.4% of the total radioactivity.
Sunner and Cassidy (1975a) showed that under field conditions, over a one
year period, the relative percentage of unextractable residues reached a
steady state (ca. 80% of total). During the latter stages of the test, the
relative amount of extractable residue in the organic fulvic and humic acid
fractions decreased with a concomitant increase in the amount remaining in
H_0 soluble and mineral fractions. The fractionation procedure used was
described by Sunner (1974).
Dupre (1974a) conducted an anaerobic soil metabolism study as described in
the Agency'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-conditioning aerobic period, as compared to the character of degradates
during a similar period of continued aerobic metabolism.
Evidence is provided by Sunner and Cassidy (1975a) that nonextractable
bound residues of Metolachlor and its metabolites are in dynamic equilibrium
with soluble forms and that the nonextractable portion may therefore serve as
a long term reservoir for extractable residues.
When viewed as a composite, these tests satisfy the soil metabolism data
requirement for Metolachlor. (The following additional studies contain
information related to metabolic transformation in soil but did not by
themselves supply adequate information about soil metabolism: I&iser 1974,
Sunner and Cassidy 1974g, k, 1, m, f, and e) .
Microbial Metabolism
Three microbial metobolism studies were available. Cne was conducted
according to the alternative pure or mixed culture technique and two were
conducted by the sterile and non-sterile soil approach.
In the pure and mixed culture study (MrGahen and Tiedje) , American Type
Culture Collection nunber 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 Metolachlor exhibited substantial
degradation with only 55% of Mstolachlor 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.
42
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MET-009, MET-003, MET-018 and MET-019 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 from the ring, although it
dehydrogenated the ethyl moiety 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 gm of soil (40 ppm) (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
Metolachlor). This study is not considered acceptable for the purpose of
describing the effects.
In another sterile and non-sterile soil study (Ellgehausen, 1976b,c), a
clay loam (Stein, Switzerland) which was treated with ring-labeled Metolachlor
at a concentration of 1 mg/232 gm of soil (ca. 4 ppm) and a control sample
(autoclaved soil) were monitored for degradation. After a short lag phase, a
slow but steady evolution of C0_ was evolved in the non-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 compound versus 65% Metolachlor in the sterile soil.
Cn the basis of these studies, a general microbial transformation scheme
can be postulated vtfiich 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 compound in the
presence of microbes, but it is not a significant route of degradation.
The studies by McGahen and Tiedje and by Ellgehausen followed acceptable
protocols, and are sufficient to support this facet of the fate assessment for
the present uses of Metolachlor.
Mobility
Leaching
Data on leaching have been developed by Eupre (1974c) and HDUseworth
(1973b). Parent Metolachlor leaches readily in sandy loam and sandy soils
low in organic matter. Twenty to 33% of the applied Metolachlor leaches
more than 12 inches in the above soils when an equivalent of 20 inches of
rainfall are applied to a soil colunn overlayered with Metolachlor.
Cbnversely, insignificant leaching is expected in muck soils high in
organic matter. Field studies (Ballantine, 1975) showed substantial
leaching into the 6"-12" soil horizon in 5 different states with various
soil types. Metolachlor 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 Metolachlor.
Adsorption
A laboratory adsorption/desorption study using four concentrations of
radiolabeled or non-radiolabeled pesticides and the same soil as used for
the leaching study is not presently available for Metolachlor. This
constitutes a data gap.
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Spray Drift
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. Subpart J of the
Proposed Guidelines, which will cover drift as it relates to phytotoxic
effects, has not yet been accepted for regulatory use. Because Metolachlor is
a herbicide which may potentially damage an adjacent crop or neighboring flora,
when these Guidelines do go into effect, drift studies may be required.
Field Dissipation
Field dissipation studies were conducted by Ballantine (1975) on five
different soil types representing five geographical locations. The following
conclusions were drawn from the studies: 1) Approximately 10% of applied
Metolachlor was found in the upper 12 inches of Mississippi loam after 60 days
for both. 2 and 4 Ibs. active ingredient per acre (a.i./A) application rates.
2) In bfebraska silt loam, approximately 10% of applied Metolachlor was found
in the upper 12 inches after 162 days for both 2 and 4 Ibs. a.i./A application
rates. 3) In tew York, 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 Ibs. a.i./A application rates.
These field dissipation studies under actual use conditions are sufficient
to show that Metolachlor, applied alone, dissipates to approximately 10% of
the applied amount 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 additional field
dissipation tests, at the proposed rates, would be needed.
Accumulation
Rotational Crops
~Oats in the greenhouse, and carrots and soybeans in the field, were
grown as rotational crops to corn 9 months after soil treatment at 2 Ibs/
acre using C-ring labeled Metolachlor. Low levels of residues ranging
from 0.02 to 0.27 ppm, expressed as Metolachlor, were found in different
portions of the various crops (Sumner and Cassidy 1974e; Sumner and
Cassidy 1974f; Sunner and Cassidy 1974g). The preponderance of
extractable residues were polar in nature (partition into H«0/MeOH vs.
CHCL.J and the two major fractions constituting these polar residues
were neutral and acidic in nature, as determined by ion exchange
chronatography. A typical analysis of such plant residues is provided by
the following example for oat straw derived from oats grown as a
rotational crop to corn where Metolachlor was applied at a rate of 2 Ibs/
acre (Sumner and Cassidy, 1974f).
Calculated ppm
,. as Metolachlor
1) Total C activity = 0.27 ppm
2) H-O/MeOH extractable, % of total activity = 67% -18
-Tfeutral Fraction, % of total activity = 19% -05
- Acidic Fraction, % of total activity = 45% -12
3) CHCL extractable, % of total activity = 7.0% -02
44
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The text of the review by Marco (1974) of metabolism studies with
Metolachlor in corn implies that only highly polar acid metabolites, such
as conjugates involving the N-acetyl group of Metolachlor are present.
However, the data presented in Table IV of Marco (1974) show that the
relative amounts 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 From Table IV, Marco-1974)
Ionic Characterization of Radioactive Metabolites in Polar
Fraction of Cbrn Treated with 2 Ib. ai/A 14C Metolachlor
Ionic Charge «•-.-, 14,
Location
weeks after treatment
Percent of Total C in Plant
Greenhouse
Field
Neutral
Acid
Base
Zwitterion
Neutral
Acid
Base
Zwitterion
8_
7.0
73.1
0.6
6.2
7.4
68.2
1.7
2.7
12
7.9
53.6
0.9
21.4
10.8
70.4
1.2
8.4
16 (mature forage)
a
a
a
a
7.3
26.3
1.0
15.3
(a = sample
decomposed
in shipment)
Marco (1975) , and Sunner and Cassidy (1975) , argue that the metabolic
pathways in rotational carrots and soybeans are qualitatively similar
based on a comparison of the ionic and TLC comparative characteristics of
acidic constitutents. While it is conceded the conjugated metabolites of
Metolachlor in corn grain may be the only ones worthy of consideration,
the same is not necessarily true with rotational crop uptake. Compounds
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-001 and HP-002. (Aziz and Ftass, 1975).
,CH
This method will not detect MET 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 could form oxo-neutral
45
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conjugates 0 Again, using the oat (straw) example, cited above, one can
conclude that the entire neutral fraction of the H_0/MeOH extractables
equaling 0,05 ppn could be a mixture of MET 002, 004, 008, 009, and 010
(or other degradates of a similar nature) and would not be detectable by
the method of Balasubramanian, Aziz, and Ross (1975). Such compounds
should ba readily amendable to GLC and TLC separation Rf zone and
retention time comparisons with model compounds.
Based on information submitted by Ballantine (1975), the roots of root
crops, grain of small grains, and oil from oil seed crops (such as cotton
seed) can reasonably be expected to contain little, if any, residue of
Metolaehlor per se or its metabolites hydrolyzable to HP-001 or HP-002
using the method of Balasubramanian, Aziz, and Ross (1975). All residue
analyses for MET-007 were 0.03 ppn or less and were 0.10 ppn or less for
MET-015. The question as to whether this regulatory method for corn-
related products is applicable to rotational crops is moot and must await
further elucidation of the nature of the neutral polar metabolites in
rotational crops.
The studies cited above show that levels of Metolachlor-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,
1975o
Lettuce was grown outdors as a rotational crop to soybeans in the fall
and spring, 14 and 41 weeks respectively, after soil was treated at 2 Ibs.
a.i./acre with C-ring labeled Metolachlor« The residue level,
expressed as Metolachlor, found in the 26-week old fall planting of
lettuce, was 0*025 ppm. The levels observed in the second crop (spring
planting) were 0*144 ppn in the 13-week old sample and 0.062 ppn in the 15-
week old sample (final harvest).
Oily the 54-week lettuce sanple (second crop, spring sample) was
considered to contain a sufficiently high level of residues for further
characterization, which consisted of partitioning the radioactivity into
organic, polar, and non-extractable fractions. The fractions contained
21%, 73%, and 12% of the activity, respectively. No further identification
was attempted„
The data on rotational crop residues are deficient in two respects:
first, acceptable data are not available on residues in small grains, root
crops, or leafy vegetables to establish an interval between ffetolachlor
treatment and the planting of rotational crops so that carry-over residues
into rotational crops are prevented; second, although it is agreed that
present day analytical technology is not easily adapted to the task, the
extractable non-polar metabolites in rotational crops were not sufficiently
characterized to dispel concern over their potential contamination of the
food web =
The registered rotational crops restriction provides that: "Snail
grains may be planted 4-1/2 months following treatment. Field corn (except
fresh corn and popcorn) , cotton, soybeans, peanuts, sorghum, root crops,
and snail grains may be planted in the spring following treatment. Do not
graze or feed forage or fodder from cotton or small grains to livestock.
All other rotational crops may be planted 18 months after application."
However, the Agency has a new policy on rotational crops: EPA will
now accept petitions for "rotational crop tolerances' for rotated crops,
and where necessary, for meat, milk, and eggs. When the rotational crop
restrictions that would ensure the absence of residues in rotated crops are
not practical for the grower, tolerances may be set for residues in
46
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specific rotated crops, and an earlier planting of those rotated crops may
be allowed. In brief, the registrant now has the optionf for each rotated
crop, of: (1) accepting a crop rotation restriction interval (not to
exceed 18 months) which is sufficient to ensure that residues are not
present in the rotated crop; or (2) petitioning for a 'rotational crop
tolerance1 for that crop, which may allow for an earlier rotation.
Studies in which Metolachlor was applied in accord with existing
usage showed residues, and the need for tolerances for these residues, in
the forage and fodder of small grains, in the tops of sugar beets and
carrots, and in lettuce. Uider the new policy, because there is no
'rotational crop tolerance' for residues in the forage and fodder of small
grains, for residues in the tops of sugar beets and carrots, or for
residues in rotated lettuce (or other leafy vegetables), crops in these
crop groupings should not be rotated in MBtolachlor-treated fields before
18 months. Cotton for cottonseed would be an exception to this
restriction, because the data for rotational soybeans showed that the
mature soybean contained either non-detectable or very small amounts of
Metolachlor residues. Higher levels were found in soybeans foliage.
Therefore it may be extrapolated that cotton foliage, but not cottonseed,
will contain detectable levels of residues when cotton is grown as a
rotational crop in the spring following the treatment of corn, soybeans,
peanuts, or sorghun with Mstolachlor. Because cotton foliage would be
expected to contain residues of Metolachlor, it should not be fed to
livestock.
Thus, unless additional data are submitted to demonstrate intervals
(less than 18 months) after which no residues will occur in rotational
crops, or unless tolerances are established for those rotated crops which
would contain residues, the label on any product formulated with
Metolachlor and intended for use on food or feed should carry the following
rotational crops restrictions: "Field corn (grown for grain, except
popcorn) , cotton, soybeans, peanuts, and grain sorghum may be planted in
the spring following treatment. CD not rotate other crops until 18 months
after application. Eb not graze or feed forage or fodder from cotton to
livestock." In the meantime, in accordance with the conditional
registration policy authorized by Section 3(c) (7) of FIFRA and implemented
under 40 CFR 162.18, this Standard will retain the existing rotational crop
restrictions and simply state the data requirement for additional
rotational crop data for small grains, root crops, and leafy vegetables.
Fish Accumulation
Elleghausen (1977) tested the uptake, transfer and degradation of
Metolachlor by algae, daphnia, and catfish. After 90 minutes exposure to
0.1 ppm Mstolachlor, algae accumulated 10.4 ppm. Bfowever, following 2
hours depuration, less than 2 ppm remained in the cells. Daphnia, exposed
for 24 hours to 0.1 ppm, accunulated 0.60 ppm. Eight hours depuration was
needed to achieve a 50% loss. Daphnids accunulated only 20% more when
exposed to both algae with 10.4 ppm Matolachlor and water containing 0.1
ppm Metolachlor as compared to fortified water in the absence of algae.
Catfish, exposed to 0.1 ppm C Metolachlor accunulated 1.20 ppm
Metolachlor in their tissues after 96 hours. However, a plateau was not
reached.
Metabolites of Metolachlor were noted but not identified in the
algae, daphnids, and catfish. At the end of the 96-hour catfish study,
only 1/2 of the C-activity remaining in the water was Metolachlor.
The remainder was present as 3 unidentified degradation products. The
theoretical basis for the model system used was discussed in another paper
47
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(Elleghausen, 1976b) . 3nith (1977) conducted a 30-day catfish exposure
study in a soil/water/fish ecosystem. At an average concentration of 0.08
ppn in the water, bioaccunulation factors were 6*5 - 9.0 for edible
portions of the fish and 55.0 - 92.4 in the viscera. After 14 days of
withdrawal, residue levels in the edible portion declined from a maximum
exposure value of 0*72 ppm to 0.03 ppn, and levels in the viscera declined
from a maximum exposure value of 7.39 ppn to 0.18 ppm. The accumulated
residues in the edible portions remained relatively constant in terms of
extractable vs. nonextractable (about 8:1) . Cn days 1 and 30 there was 16
times more organically soluble activity than aqueous soluble (ethyl acetate-
water system). A cysteine conjugate of Metolachlor was identified as a
metabolite and reached a high of 12.8% of total C activity in the
edible tissue on day 14. Smaller amounts of other metabolites were found
in edible and/or visceral tissues but were not identified.
N-(2'hydroxy-l'-methylethyl)-2-ethyl-6-methyl chloroacetanilide (MET-
003), N-2(2-hydroxy acetyl)-N-(l-methyl propane-2-yl)-2-ethyl-6-!nethyl
aniline, and a cysteine metabolite of Metolachlor were all found in water
along with three other unidentified degradation products.
Barrows (1974) reported on a bluegill sunfish flow-through study at
C P-fetolachlor exposure levels of 10 and 1000 ug/liter. Bioaccunulation
levels at the 1000 ug/liter exposure level reached 28 ppn in edible tissues
and 702 ppn in the nonedible tissues. Existence of a plateau could not be
established. After 28 days depuration, residues in edible portions of fish
decreased to 0.08 ppn for the 10 ug/liter C Pfetolachlor exposure and to
11.7 ppn for the 1000 ug/liter exposure. The chemical nature of the fish
residues was not defined. Mien the above studies are considered as a
composite, they are sufficient to adequately characterize the fish
accumulation characteristics of Mstolachlor.
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DISCIPLINARY REVIEW
Environmental Fate Profile
Exposure Profile
Generic Eata Gaps
Suggested Labeling
Environmental Fate Profile
Mstolachlor is applied at a rate of 1.5 to 3.0 pounds active ingredient per
acre to soil where corn (excluding popcorn), soybeans, peanuts, or grain
sorghun 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 estimated half-life is 200 days over this entire pH range) .
Photolysis appears to be a more significant degradation pathway, as
approximately 50% was found to have degraded on sunlit soil over a period of
eight days. However, if Metolachlor is applied and incorporated into the top 2
inches of soil, then degradation by photolysis is expected to be minimal. Soil
metabolism, by both aerobic and anaerobic microorganisms, would also play an
important role in the degradation of Mstolachlor in the soil (MrGahen and
Tiedge, 1978) .
About 30% of the photoproducts were represented by MET-009 and MET-001.
(See the Chemical Fact Sheets in Appendix A for characterizations of these
and other metabolites.) Another 30% was represented by CHCL-, and water-
soluble polar metabolites. Indirect evidence obtained from analysis of
aqueous photoproducts produced by artificial light of <280 nm suggests that
the polar products, both aqueous soluble and CHC1., soluble, are not ,.
aldehydes or phenolic in nature (Aziz and Kahrs , 1975). Exposure of C
Metolachlor treated soil thin layers to natural sunlight (Aziz, 1974) resulted
in gradual photolysis to MET-003 and three unidentified products. Two
unidentified products have moderate polarity and one was relatively high in
polarity. After 8 days exposure, about 1/2 of the initially applied dose had
decomposed .
Soil metabolism of Mstolachlor appears to proceed 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 -C3 -CH.
r-lnj doSUJTB
?3
K^a^
R-C-OI^ °
II
Q
[Elleghausen, 1976a and 1976b;
Sumner and Cassidy, 1974 and 1975)
I
SrC-C-CH
0 0
Sunner, Szolics, and Cassidy 1976;
49
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.•-retook of the benzenoid portion of the molecule to form phenolic metabolites
"as speculated but not proven (Elleghausen, 1976b). The likelihood of such
ring attack is contraindicated by the following observations: (1) Evidence is
provided by Sumner and Cassidy (1974) that non-extractable bound residues of
Metolachlor are in dynamic equilibrium with soluble forms, (2) unextractable
residues represented by fulvic and hunic acid fractions decrease with
increased aging. Incorporation of polyphenolic metabolites into the soil
organic matrix veuld mitigate against both of the above findings.
Studies were also available on Metolachlor's environmental mobility.
feuseworth (1973b) , in a laboratory column leaching study, using a wide range
of soil types, stowed 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 sands and sandy loams having organic
contents of 2% or less. Residues of aged C-Metolachlor were also found
•r.o leach extensively in sandy loam soil (Dupre, 1974). Based on incremental
1 C activity at different soil depths, several discrete chemicals of
different mobilities were probably involved. A runoff study by Dupre (1974c)
showed that Metolachlor can be expected to move from agricultural sites of
application both by sheet erosion and leaching.
Field dissipations studies confirmed Metolachlor's potential for
significant movement in the soil, but left open the question of whether
i'-fetolachlor may sometimes persist undegraded. Skipper, Cbssett, and 9nith
(1976), in field dissipation tests, concluded that extensive leaching was the
major cause of dissipation from the upper 3-inch soil horizon in two different
plots containing sandy loam soils. Field dissipation studies of Mstolachlor
applied at up to 4 Ibs. a.i./acre (pre-emergent) showed residues generally less
than 10% of the amount originally applied over time spans ranging between 107
and 162 days» A total of 5 states representing continental -USA climate
extremes were involved. But absolute losses of Metolachlor between the day of
application and final sanpling were not always so great. Ebr example, in a
Nebraska study, residues declined only 44% over a 107-day time span. In sane
cases, substantial residues were found in the 6" to 12" soil horizon
suggesting extensive leaching. This high soil mobility, in combination with a
'potential for long-term environmental stability, may prove to be significant
concern in projecting potential exposures to Metolachlor residues.
Additional studies were performed to estimate the possibility of
Metolachlor bioaccunulation« KLuegill sunfish exposed for 70 days to a mean
level of 1=2 ppm ~ C Matolachlor accumulated 18 ppm of C activity
(expressed as Metolachlor) in their edible tissues and 486 ppm in non-edible
tissues. After a 28-day depuration, the residue levels decreased to 12 and 13
ppm respectively. The chemical nature of the residues was not investigated
(Barrows, 1974). A catfish study (Smith, 1977) involving aged Metolachlor on
sandy loam soil resulted in an accumulation of 0.53 ppm in edible catfish
tissue at the end of 30-day exposure. After 14 days of depuration, the level
decreased to 0.03 ppm. values for viscera at the end of the 30 day exposure
and after 14 days depuration were 4.4 and 0.18 ppm, 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 Mstolachlor-treated soil. Roots of root crops, grain of
small grains, and oil from oil seed crops, grown as rotational crops to corn in
a Metolachlor-treated field, were shown to have little, if any, residues of
Metolachlor, as analyzed by the officially accepted regulatory method for corn
grain, forage, and fodder (Balasubramanian, Aziz, and Ross 1975; Ballantine
1975). This method will detect Metolachlor per se and a series of sugar and
50
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glutathione conjugates which can form .after 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, would not 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 Ftoss (1975): carrot tops, soybean
stalks, sugar beet tops, and wheat straw. Finally, lettuce rotated on a
soybean plot treated with C-Metolachlor contained detectable residues in
samples of spring and fall seedlings, 41 and 56 weeks after treatment,
respectively (Newby, 1979).
Exposure Profile
Technical Metolachlor; For persons involved in the handling, storage, or
shipment 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 hunan
exposure is a repeated dermal exposure, and occasionally, by accident, an
occular exposure.
The fate data have indicated the relative stability of Metolachlor to
hydrolysis and metabolic degradation, and its high mobility in the
terrestrial environment. Thus, for wildlife in the proximity of Technical
Metolachlor manufacture, storage, shipping, or disposal, if significant
amounts of the chemical were spilled, drained, discharged, or disposed of
in the natural environment, it is possible that exposure could occur to
various species, but particularly aquatic species, and perhaps to
carnivores feeding on contaminated fish. Also, considering Metolachlor1s
potential for rotational crop uptake, plants growing on contaminated soil
could pass on residues to herbivores, including birds.
Qnulsifiable Concentrate Metolachlor: Though all pesticide products, but
particularly those mixed with seed or foodstock before application, present
some possibility of accidental ingestion, for persons involved in the
dilution, mixing, and application of Metolachlor 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 in diluting and
tank mixing, and in the loading of spray equipment. The vapors from
the Emulsifiable Concentrates are limited by the vapor pressure and the
viscosity of the solutions, thus limiting the chance of inhalation
exposure during mixing or loading. But the spray droplets generated by the
application of end-use Matolachlor may result in an inhalation and/or
dermal exposure for applicators and for agricultural workers or livestock
who may be in direct proximity to the spraying.
As concerns the possibility of wildlife exposures from Metolachlor's
end-uses, several aspects of Mstolachlor's fate combine to suggest that
Metolachlor may have a potential to contaminate natural freshwater
habitats. This suspicion is supported by the following test findings:
laboratory column leaching studies, using a wide range of soil types, show
that Metolachlor per _se is subject to extensive leaching when applied to
soils having a low organic content; field tests designed to show
dissipation and mobility concluded that extensive leaching was the major
cause of dissipation in soil, with residues found to a depth of 12 inches
below the surface; runoff studies showed that Metolachlor can move from
agricultural sites of application both by sheet erosion and leaching;
51
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Metolachlor is stable to hydrolysis over the environmental pH range of 5
to 9; the estimated half-life for Matolachlor in water is over 200 days;
loss due to photolysis is minimal (6% over one month) ; and Metolachlor can
be resistant to microbial degradation, with soil half-lives reported to be
greater than 107 days, and anaerobic degradation rates observed to be
slower and even non-existent. It is thus concluded that Metolachlor"s end-
uses may have the potential to contaminate groundwater via leaching and
possibly by surface contamination (at the well head), thereby exposing
freshwater fish and other freshwater plants and animals, animals which
drink the contaminated water, or carnivores which feed on contaminated
fish. Also, because of Metolachlor's demonstrated uptake by rotational
crops, it may be assumed that some aquatic or terrestrial plants may either
suffer phytotoxic exposures or pass Metolachlor residues on to herbivores,
including birds.
Because there is a concern that residues may migrate to and persist in
aquatic habitats, there is a need to quantitatively determine potential
aquatic exposures, so that these potential exposures can be compared with
toxic levels for sensitive species. Fbr this purpose, the Agency will
require that residue monitoring be performed after actual applications
at several sites selected for their ability to demonstrate the potential
for aquatic contamination. The Agency has identified, in a three-step
process of selection, two watersheds which have been determined
appropriate for Mstolachlor field monitoring: first, the Agency identified
the regions of the United States in which the most corn? soybeans, peanuts,
and grain sorghum are grown; secondly, the Agency found six watersheds
within these potential Metolachlor use regions which have terrain and soil
types that could promote the contamination of freshwater by leaching or
runoff (i.e., a relatively low organic content and flat terrain for
leaching, and a high organic content and hilly terrain for runoff) (Radtke,
1980) ; finally, the Agency selected the two watersheds which provided the
best delimitation of variables to allow for the clearest interpretation of
results. The two sites which the Agency thereby selected as appropriate
for watershed residue monitoring are: one watershed just south of Treynor
in Fbttawattamie Cbunty, Iowa; and the Little River experimental watershed
near Tifton, Georgia.
The possibility for Matolachlor residues to occur in food or feed,
which may result in dietary exposures to hunans, livestock, or domestic
animals, is discussed in the 'Residue Chemistry1 chapter.
52
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Generic Data Gaps
The following are gaps in the Environmental Fate data base vtfiich will be
used to support registrations under this Metolachlor Standard. Opposite each
gap is given the section in the Proposed Guidelines of July 10, 1978 (FR Fart
163) which describes that type of data and when it is required.
1) Adsorption/desorption studies 163.62-9
2) Accumulation studies on rotational crops 163.61-ll(b)
for small grains, root crops, and leafy
vegetables.
3) Actual field residue monitoring studies (no guidelines)
at two watershed sites to be approved by
the Agency.
Suggested Labeling
There are no environmental fate labeling requirements for manufacturing-
use Metolachlor labels.
Conditional upon the registrant's agreement to provide the supporting
rotational crops data, Emulsifiable Concentrate Metolachlor should carry
the following rotational crops restriction on its label:
"9nall grains may be planted 4-1/2 months following treatment. Field
corn (except fresh corn and popcorn) , cotton, soybeans, peanuts,
sorghun, root crops, and anall grains may be planted in the spring
following treatment. Eb not graze or feed forage or fodder from cotton
or anall grains to livestock. All other rotational crops may be
planted 18 months after application."
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BIBLIOGRAPHY
Each of the following studies contributed useful information to the
Agency's review of the environmental fate of Metolachlor, and is considered
part of the data base which supports registrations under this Standard.
Aziz, S.A. (1974) Photolysis of CGA-24705 on Soil Slides under Natural and
Artificial Sunlight Conditions: GAAC-74102. Received Mar 26, 1975 under
5F1606. (Unpublished study prepared by Ciba-Geigy Corp., Greensboro, N.C.;
CDL:94385-J)
Aziz, S.A.; Kahrs, R.A. (1974) Photolysis of CGA-24705 in Aqueous Solution
under Natural and Artificial Sunlight Conditions: GAAC-74041. Received Sept
26, 1974 under 5G1553. (unpublished study prepared by Ciba-Geigy Corp.,
Greensboro, N.C.; CDL:94222-A)
Aziz, S.A.; Kahrs, R.A. (1975) Photolysis of CGA-24705 in Aqueous Solution —
Additional Information: GAAC-75021. Received Mar 26, 1975 under 5F1606.
(Unpublished study prepared by Ciba-Geigy Corp., Greensboro, N.C.;
CDL:94385-M)
Burkhard, N. (1974) Hydrolysis of CGA-24705 Under Laboratory Conditions,
PP #5G1553, 'Vblime 2, AC 25.53; SPR 2/74. (Unpublished report prepared by
CIBA-GEIGY ltd., Basle, Switzerland; CDL: 94222-H)
14
Dupre, G.D. (1974a) Abbreviated Anaerobic Metabolism of C-CGA-24705 in
Silt Loam Soil under Greenhouse Conditions: Report No. 73019-3. Received Sep
26, 1974 under 5G1553. (Unpublished study prepared by Bio/dynamics Inc. for
Ciba-Geigy Corp., Greensboro, N.C. CDL:94222-B)
Ellegehausen, H. (1976a) Project. Report 4/76: A Madel system for Estimating
the Uptake, Transfer and Degradation of Agrochemicals by Aquatic Organisms.
AC 2.52. Received Feb 6, 1978 under 100-583- (Unpublished study prepared by
Ciba-Geigy Ltd., Basle, Switzerland; CDL:232789-B)
Ellegehausen, H. (1976b) Project Report 4/76: Degradation of CGA 24705 in
Aerobic, Anaerobic and Autoclaved Soil. AC 2.52. Received Feb 6, 1978 under
100-583. (Unpublished study 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 CGA 24705 in Aerobic, Anaerobic and Autoclaved Soil. AC
2.52. Received Feb 6, 1978 under 100-583. (Unpublished study prepared by
Ciba-Geigy Ltd., Basle, Switzerland; CDL:232789-E)
Ellegehausen, H. (19771. Project Report 3/77: Uptake, Transfer and Degradation
of CGA 24705 (Dual1 ') by Aquatic Organisms. AC 2.52. Received Feb 6, 1978
under 100-583. (Unpublished study prepared by CIBA-GEIGY Ltd., Basle,
Switzerland; CDL:232789-C)
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L.D. (1973b) Report on Parent teaching Studies for CGA-24705:
Report No. 1. Received Sep 26, 1974 under 5G1553. (Unpublished study
prepared by University of Missouri—Columbia, Department of Plant Pathology
for Ciba-Geigy Cbrp., Greensboro, N.C.; CDL:94222-E)
Marco, G. (1974) Summary of Section D: CGA-24705-Gom: Residues Cbserved and
Metabolism Data Including the Analytical Methods Used: GAAC-74062. Received
Sep 26, 1974 under 5G1553. (Unpublished study prepared by Ciba-Geigy Corp.,
Greensboro, N.C. that includes studies AG-A-2929, AG-A-2969, AG-A-2973, AG-A-
3105, AG-A-3133; CDL:94217-A; 94222)
McGahen, L. L.; Tiedje, J.M. (1978). Metabolism of two new acylanilide
herbicides, Antor Herbicide (H-22234) and Dual (Metolachlor) by the soil
fungus Chactomium globosum. Journal of Agricultural Food Chemistry
26(2):414-419.
Smith, K.S. (1977) Report: Catfish Bioaccunulation Study Following Exposure to
C-Metolachlor in a Soil/Water/Fish Ecosystem. 7E-6506; Received Feb 6,
1978 under 100-583. (Unpublished study prepared by Cannon Laboratories, Inc.
for Ciba-Geigy Corp., Greensboro, N.C.; CDL:232789-U)
Sunner, D.D.; Cassidy, J.E. (1975a) The Degradation of CGA-24705 in a Field
Soil: GAAC-75022. Received Mar 26, 1975 under 5F1606. (Unpublished study
prepared by Ciba-Geigy Corp., Greensboro, N.C.; CDL:94385-M)
Sumner, D.D., Szolics, I.M.; Cassidy, J.E. (1976) Degradation of CGA-24705 in
Soil. ABR-76057. Received Feb 6, 1978 under 100-583. (Unpublished study
prepared by Ciba-Geigy Corp., Greensboro, N.C.; CDL:232789-V)
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TOXICOLOGY
TOPICAL DISCUSSIONS
Corresponding to each of the Topical Discussions listed below is the nunber
of the section(s) in the 'Proposed Guidelines' of August 22, 1978 (FR Part 163)
which explain(s) the data that the Agency will need in order to assess
Matolachlor's Toxicology.
Guidelines Section(s)
Metabolism and Fharmacodynamics 163.85-1:
Acute Effects and Neurotoxicity 163.81-1, -2, -3, and -7
local Irritation 163.81-4 and 163.81-5
Subchronic Effects and Naurotoxicity 163.82-1, -2, -4, -5, and -6
Sensitization 163.81-6
Chronic Effects 163.83-1
Chcogenicity 163.83-2
Mutagenicity 163.84-2, -3, and -4
Teratology 163.83-3
Reproductive Effects 163.83-4
Metabolism and Pharmacodynamics
Metabolism studies on Metolachlor (Hambock, 1974a,b) demonstrated that:
(a) Most orally administered Metolachlor is rapidly absorbed,
metabolized, and excreted.
(b) The urine and faces of treated animals contained a complex pattern
of metabolites; each metabolite accounted for less than 5% of the
administered dose. No unchanged drug was detected in urine or feces
samples.
(c) Approximately half the urinary and fecal radioactivity was
extractable with organic solvents.
(d) No glucuronide or sulfate conjugates were found in the excreta.
(e) Several excreted metabolites were tentatively identified and
appear to result from dechlorination, 0-methylation, N-dealkylation,
and side chain oxidation in the rat.
In an additional study (Hambock, 1974c) , male rats were treated with C
Metolachlor (approximately 31mg/kg, p.o.), and urine and feces were collected
for 48 hours. The urine and feces contained 21.5% and 51.4% of the
administered dose, respectively, and the halflife was determined to be
approximately 28 hours. TLC, GLC, HVE (high voltage electrophoresis) , colunn
chronatography, gel permeation chrcmatography, and enzynatic hydrolysis were
adequately utilized to identify radioactive metabolites, which were identified
as 2-ethyl-6-methylhydroxyacetanilide (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 contained 1, 15, and 22% of the administered
dose as MET-002, MET-004, and MET-003 respectively. (See the Appendix for
Chemical Data Sheets on MET-002, MET-003, and MET-004.)
These studies demonstrate the relatively rapid metabolism and excretion of
Metolachlor, and are sufficient to fulfill the requirement for this type of
information.
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Acute Effects and Neurotoxicity
Acute Oral Toxicity
The minimun testing needed on acute oral toxicity is one test on the
laboratory rat for each technical and formulation.
Ebr Technical I«tetolachlor, the acute oral LD-50 in the laboratory
rat is 2,780 mg/kg with 95% confidence limits of 2,180-3,545 rag/kg (Bathe
1973). Technical Mstolachlor in corn oil has been shovai 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 were also done on the two Bnulsifiable Gbncentrate formulations.
In a test involving a 6-pound per gallon E.G. formulation, the acute oral
LD-50 was found to be more than 2,000 mg/kg but less than 5,000 mg/kg in
the rat (Affiliated' fkdical Research, Incorporated, 1974d) . In a test
involving an 8-pound per gallon E.G. 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 tferrison, 1977a). A related study (Affiliated
Msdical Research, incorporated, 1974f) established that the 'emetic dose
50' in dogs to a 6-pound per gallon E.G. was 24.5 (+/- 9.2) mg/kg. Based
on the above data, it is anticipated that E.G. formulations of IVfetolachlor
as high as 8-pounds per gallon can be expected to produce an oral LD-50 of
not less than approximately 1,890 mg/kg in the rat. The available data,
then, places both existing E.G. formulations in Category III with regard
to acute oral toxicity„
Acute Dermal Toxicity
The minimum testing needed on acute dermal toxicity is one test,
preferably on the albino rabbit, for each technical and formulation.
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. The above
information is sufficient to meet the requirsnent for acute dermal toxicity
data on intact skin. The uiabraded dermal test results place the Technical
in Category III with respect to acute dermal toxicity.
In a test involving a 6-pound per gallon E.G. formulation, the acute
dermal LD-50 to the tew Zealand rabbit was found to be greater than 10,000
mg/kg by the intact dermal route (Affiliated ffedical Research Incorporated,
1974b). For an 8-pound per gallon E»C. formulation, it was established
that the acute dermal LD-50 to the Wsw Zealand rabbit is greater than
3,038 mg/kg via the intact denaal route (Nham and Eferrison 1977b). A
related study (Tryzna and Rsa, 1976) determined that the acute dermal LD~
50 of a 1 to 10 dilution of a 6-pound per gallon E.G. formulation was
greater than 16f000 mg/kg via the intact dermal route. The available
data, then? places both existing E*Co formulations 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 mamnalian species, preferably the albino
rat, for each technical and formulation.
Acute inhalation toxicity for the Technical was tested by Sachsse and
ULlman (1974a). In that test there were no deaths in albino rats at the
maximun achievable level of exposure (1.752 mg/1 with four hours of
exposure). This study is adequate to establish a Category IV toxicity with
regard to inhalation exposure for Technical Mstolachlor.
In a test involving a 6 pouid per gallon E.G. formulation, the acute
inhalation LC-50 was found to be greater than 257 mg/1 of air (with four
hours of exposure) in the albino rat (Affiliated Msdical Research,
Incorporated 1974c) . However, in the test for acute inhalation LC-50 for
an 8 pounds per gallon E.G. formulation, the gross pathology raw data
indicate that the test material had an observable effect at both dosage
levels in producing areas of consolidation on the lobes of the lungs. But
the failure of this Study to provide data on particle size distribution
invalidates the study, and it cannot be used to determine the acute
inhalation toxicity category for the 8 pounds per gallon E.G. The
available data, then, places the existing E.G. formulation of 6 Ibs. par
gallon or less in Category IV with regard to acute inhalation toxicity»
The inhalation LC-50 for the 8 pounds per gallon is a data gap.
Acute Delayed Neurotoxicity
This type of data is needed only if the active ingredient or any of
its metabolites, degradation products, or impurities cause esterase
depression or are structurally related to a substance that induces the
specific neuropathy, delayed neurotoxicity. ftetolachlor is a
chloroacetanilide herbicide and is not expected to cause esterase
depression or delayed neurotoxicity. Therefore, this test is not required
for Technical Metolachlor.
Local Irritation
Primary Eye Irritation
The minimun testing needed to evaluate eye irritation potential is one
test for each technical and formulation, conducted on the albino rabbit*
A study of eye irritation for the Technical was conducted 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 Craiza
(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 Ketolachlor is non-irritating to the
rabbit eye (Category IV) .
In a test involving a 6-pound per gallon E.G. formulation, the data
indicates that this formulation is a severe irritant which can cause
irreversible corneal opacity in the unrinsed albino rabbit eye (Affiliated
Medical Research, Incorporated, 1974i) . In a study involving an 8-pound
per gallon E.G. formulation (Scribor and Ffestri , 1977a): the results from
tests conducted with unrinsed eyes showed moderate corneal opacity
(reversed in 7 days) and conjunctival effects (partially reversed in 7
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days) ; the results from tests on rinsed eyes showed slight iris and
moderate conjunctival effects (reversed in 3 days). The available data,
then, places existing E.G. formulations in Category I (for 6 Ibs.) or
Category II (for 8 Ibs.) 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 two formulations, the degree of eye irritation produced by
Matolachlor formulations appears to be directly dependent upon the type and
amount of inert formulants used.
Primary Dermal Irritation
The minimum testing needed to determine the potential for primary
dermal irritation is one test conducted on a maximal, preferably the albino
rabbit, for each technical and formulation.
Sachsse (1973b) 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
Metolachlor is non-irritating to rabbit skin (Category IV) .
In a test involving a 6-pound per gallon E.G. formulation, the primary
irritation index was determined to be 1.62 (Affiliated Medical Research
Incorporated, 1974h) . In a test involving an 8-pound per gallon E.G.
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.G. formulations of Matolachlor 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, places existing E.G. formulations in
Category II (for 8 Ibs.) or Category IV (for 6 Ibs.) with regard to primary
dermal irritation. As with eye irritation, the degree of dermal irritation
appears to be dependent upon the type of inert components used in the
formulations rather than on the concentration of the active ingredient,
Metolachlor.
Subchronic Effects and Neurotoxicity
Subchronic Oral Dosing
Testing should be performed in at least 2 mammalian species. Cne
species should be a generally recognized strain of laboratory rat while
the second species should be a non-rodent.
Three-month feeding studies were performed with Sprague-Dawley rats
(Coquet, Galland, Guyot, Fbuillet, and Ftouaud, 1974d) and with beagle dogs
(Coquet, Galland, Guyot, Fbuillet, and Fbuaud, 1974c) . The Agency
determined that the histopathology evaluations for both the rat and the
dog study were not performed by a pathologist. Subsequently, the
histopathology from the 90-day dog study was re-read by a qualified
pathologist, and this re-evaluation of histopathology was submitted to the
Agency, allowing this study to fulfill the Guideline's requirement for non-
rodent subchronic oral dosing.
Because a two-year rat chronic feeding study was initiated in support
of tolerance petitions (see discussion below under 'Chronic Effects'),
the Agency decided to waive the need for a re-evaluation of the
histopathology of the other 90-day feeding study - the one on rats (Coquet
et al, 1974d) . However, because that two-year rat feeding study was
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subsequently found to be invalid (again see discussion below under
'Chronic Effects'), the Agency presently requests (as an interim
requirement until the two-year chronic feeding study on rats is re-done)
the additional re-evaluation of the histopathology for the subchronic
feeding study on rats by Gbquet et al (1974d). This histopathology review
for the subchronic feeding study on rats thus presently constitutes a data
gap for Mstolachlor.
A six-month (180 day) dog study (IRDC, 1979) was performed in support
of certain tolerance petitions in lieu of adequate chronic data. Various
questions about this study's methodology and statistical calculations have
now been answered, and the Agency concludes that the 'no observed effect
level' (NOEL) in the study was 100 ppm.
Subchronic 21-Day Dermal
The minimum testing needed is one study in one mammalian species.
Although no data is presently available on Technical ftetolachlor, a 21-day
dermal study was performed using Metolachlor 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 Matolachlor per kilogram, per
day. At 1080 mg Metolachlor per kilogram, per day, the only indication of
systemic effects was decreased body weight gain.
Subchronic 90-Day Dermal
This study is not needed because the existing acceptable end-uses
should not result in repeated hunan 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 Neurotoxicity
Metolachlor is a chloroacetanilide and is related in structure to
registered chemicals 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
The minimum data needed to assess dermal sensitization can be provided by
an intradermal test on one mammalian species, preferably the male albino
guinea pig. The first evaluation of dermal sensitization was conducted by
Affiliated Medical Ftesearch, 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
6 1
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guinea pigs. Positive reaction was demonstrated in animals injected with
Technical tetolachlor dissolved in the vehicle; there was no 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. Though there are no studies available in which the E.G.
formulations were directly tested, it is anticipated that E.G. formulations of
6 or 8 Ibs. ai/gal will also cause skin sensitization in guinea pigs.
Chronic Effects
Chronic testing should be available on at least one mammalian species.
The species should normally be a generally recognized strain of the laboratory
rat, and the route of admnistration should be through the animals' diet.
Cne two-year feeding study on the rat was performed (Kennedy, 1976b) , but
the Agency found the study to be invalid because of several deficiencies in
protocol, including the fact that dose levels were not verified by an analysis
of the diet. The study does offer supplementary information on Metolachlor's
potential oncogenicity (see below) . Because this study thus cannot be used to
fulfill the guidelines requirement, the rat chronic feeding study for
Matolachlor is currently a data gap.
Cncogenicity
For the adequate assessment of oncogenicity, studies are needed in two
mammalian species: normally, the mouse and the laboratory rat.
A mouse study was conducted with Charles River CD-I albino mice (50 of each
sex) at levels of 0, 30, 1,000, and 3,000 ppn fed in the diet. The duration of
the study was 18 months for males and 20 months for females. It was conducted
by Industrial Bio-Test laboratories (IBT) and validated by Ciba-Geigy
Corporation (Gesme, Albanese, Marias, and Arceo, 1977). Because EPA suspected
that sane of the toxicology studies performed by IBT were deficient to the
point of not being valid for the support of pesticide registrations, Ciba-
Geigy initiated a new mouse oncogenicity study, ffcwever, the Agency's
subsequent in-depth evaluation of the IBT study found that, despite certain
deficiencies in good laboratory practices and animal husbandry techniques, the
raw data supported the reported negative results. The IBT study therefore
satisfies the requirement for mouse oncogenicity testing, and the Agency
concludes from it that Metolachlor is not oncogenic to mice at the given
dietary dosages. Although the additional mouse data is not required, the
second mouse oncogenicity study is still underway and the Agency will evaluate
the results if and when they are submitted.
Though the two-year chronic feeding study on rats discussed in the 'Chronic
Effects' section above) (Kennedy, 1976b) was not valid for the fulfillment of
the chronic feeding data requirement, it did offer supplementary information
for oncogenicity by reporting no evidence that Metolachlor is oncogenic.
Nsvertheless, this study does not fulfill the guideline requirement for an
oncogenicity test in the rat, and this constitutes a data gap. An oncogenic
evaluation performed on the animals in the required two-year rat chronic
feeding study would suffice for this requirement on oncogenicity in the rat.
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Mutagenicity
The following studies represent only the minimum requirements for data on
the potential heritable effects of a pesticide: (1) a mammalian in vitro point
mutation test; (2) a sensitive sub-mammalian point mutation test~~(bacteria,
fungi, insect); (3) a primary ENA damage test (i.e., sister chromatid exchange
or unscheduled ENA synthesis; and (4) a mammalian in vitro cytogenetics test.
If the last test suggests a positive result, a dominant lethal or heritable
translocation test may be required.
After results from these test systems and other toxicology disciplines have
been considered, additional testing may be required to further characterize or
quantify the potential genetic risks. Although the Agency's mutagenic testing
requirements are not final, the standards for these tests should be based on
the principles set forth in the Proposed Guidelines (FR 43, No. 163, August 22,
1978). Protocols and choices of test systems should be accompanied by a
scientific rationale. Substitution of test systems for those listed above will
be considered after discussion with the Agency.
These requirements should be considered an interim guide and not final
Agency policy. However, the Agency has considered the above testing scheme to
be a reasonable minimum requirement.
In accordance with the fact that the above policy on mutagenicity testing
is an interim one, the minimum testing presently being required to assess
mutagenicity for Nbtolachlor is testing in only two experimental systems. The
potential of Metolachlor to cause genetic changes has been tested for in a
bacterial system utilizing activation by mammalian microsomes (Arni and Muller,
1976), and in an _in vivo system to test the effect on developing sperm in the
mouse (Ciba-Geigy Limited, 1976a) .
The bacterial (Salmonella) 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. Isbr were there any
effects noted, in the mouse 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. From these two studies,
which are presently sufficient for mutagenicity testing, no evidence arose
to suggest that Metolachlor has any mutagenic potential. Further mutagenicity
testing on ffetolachlor may later be required when a final policy on
mutagenicity testing has been established.
Teratology
The minimum data needed to evaluate the potential fetotoxic or teratogenic
effects of a pesticide are tests in two mammalian species. A study of the
teratogenic effects of Technical Mstolachlor on rats was conducted by Fritz
(1976) . The study found that doses of either 0, 60, 180, or 360 mg/kg/day
during 6 to 15 days of gestation did not effect the offspring of female
Sprague-Cawley rats. ND fetotoxic effects of the compound were observed.
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 mammal, and does not show
any evidence of a teratogenic hazard for Nfetolachlor. Data is still needed
on a second mammalian species.
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Reproductive Effects
The minimun data needed for measuring reproductive effects can be
provided by one rat study lasting two generations. The one available study
(3nith and Adler, 1978) had significant deficiencies including problems in
animal husbandry, mating performance and success (possibly caused by poor
animal health), and observation records, which cause the Agency to consider
its conclusions as only 'supplementary' information. The study suggests no
reproductive effects, but Metolachlor still requires a satisfactory multi-
generation reproduction study.
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DISCIPLINARY REVIEW
•toxicology Profile
Toxicology tezard Assessment
Generic Data Gaps
Product Specific Eata Gaps
Suggested Labeling
Toxicology Profile
Technical Metolachlor: 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 hunans. Eermally, at least in the
rabbit, Metolachlor does not appreciably penetrate intact skin. Ebses of
up to 10,000 mg/kg caused no signs of toxicity and little irritation.
Pending receipt of data on abraded skin, it would appear that Metolachlor
would' not be readily absorbed through human skin. The lack of toxic signs
or irritation from high acute dermal exposure in test animals indicates
that Technical Metolachlor has a low dermal toxicity to hunans. Testing of
acute inhalation toxicity in rats failed to elicit any deaths at the
maximum achievable concentration (1.752 mg/1 for 4 hours exposure), and so
a low inhalation toxicity to humans for manufacturing-use Metolachlor 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 observed. 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.
Metolachlor should therefore be considered a potential skin sensitizer in
hunans.
A six-month dog study indicated an oral 'no observed effect level1
(NOEL) of 100 ppn, and this is presently the only NOEL value available for
tolerance setting. (See Residue Chemistry 'Tolerance Reassessment1.) The
one available chronic (two year) feeding study was not valid, though it
offered evidence to support the conclusion of the one oncogenicity study in
mice that Metolachlor is not oncogenic by the dietary levels tested.
Though data on a second species will be needed, there was one study of
teratogenic effects in rats, and it reported no teratogenic or fetotoxic
effects due to Metolachlor at the doses tested. Metolachlor has been
tested in two systems for mutagenicity: a bacterial system, and an in vivo
system in the mouse. No evidence is presented in either study to sugge'sl;
that Metolachlor has any mutagenic potential.
The currently registered Metolachlor Technical product falls into the
following 'Tbxicity Categories' [see 40 CFR 162.10 (h)(l)]:
Acute Oral Tbxicity: Category III
Acute Dermal Toxicity: Category III
Acute Inhalation Toxicity: Category IV
Primary Eye Irritation: Category IV
Primary Dermal Irritation: Category IV
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Emulsifiable Concentrate; For the E.G. formulations of 6 and 8 Ibs,
aT7gallon, the" repTrtlcTvalues of 1,890 mg/kg or higher indicate a
relatively high acute oral LD-50 in rats, implying a low acute oral
toxicity for huaans. Dennally, at least in the rabbit, the two existing
B.C. formulations of ffetolachlor do not appreciably penetrate intact skin,
and doses of up to 3,038 mg/kg produced no signs of toxicity in the !few
Zealand rabbit, From existing data, it can thus be assumed that the E.G.
formulations of 6 and 8 Ibs. ai/gallon present a low overall acute toxicity
to humans via the intact dermal route. The test on acute inhalation was
only available for the six pound per gallon E.G., and demonstrated a very
low acute inhalation toxicity. A test for the eight pounds per gallon
EoC, is required because of the difference in volatile inerts.
The potential for local irritation and sensitization appears to be
significant.. Based on the albino rabbit as an indicator species, the 8
Ibs. ai/gallon formulation will produce moderate erythma, edema, and second
degree burns (severe irritation). A dermal sensitization study in guinea
pigs indicated that two registered E.G. formulations are also potential
skin sensitizers in humans„ In a primary eye irritation study conducted on
the albino rabbit, the 6 Ibs. ai/gallon formulation of Metolachlor was
fo'jid to cause irreversible corneal opacity and severe irritation in
uisrinsed eyes, which indicates a potential for serious hunan eye irritation
due to that formulation„
The currently registered Mstolachlor Emulsifiable Concentrate Products
fsll into the following "Ibxicity Categories' [see 40 CFR 162.10 (h) (1) ] :
Snulsifiable Cbncentrate (6 Ibs, active ingredient per gallon):
Acute Oral Tbxicity: Category III
Acute Dermal Tbxicity: Category III
Acute Inhalation Tbxicity: Category IV
Primary Eye Irritation: Category I
Primary Dermal Irritation: Category IV
Briulsifiable Cbncentrate (8 Ibs. active ingredient per gallon):
Acute Oral Ibxicity: Category III
Acute normal Tbxicity: Category III
Acute Inhalation Tbxicity: undetermined
Primary Eye Irritation: Category II
Primary Dermal Irritation; Category II
Tojdcology Hazard Assessment
Technical tetolachlor; Considering first the potential for human (or
domestic animal)"'exposure to manufacturing-use Matolachlor, 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 necessarily viscous
liquid, there is also little chance of inhalation exposure. The most
likely type of exposure for persons involved in the handling, storage,
shipment, or re-formulation of Technical ffetolachlor is a repeated dermal
exposure.
Because of Technical Fetolachlor's low acute oral toxicity, and very
low inhalation toxicity, we may dismiss these unlikely exposure routes as
significant sources of hazard. The occasional occular exposure is also
not of serious concern,, as no eye irritation effects would be expected.
ait with respect to dermal exposures, although it has been shown that
i-etolachlor is not readily absorbed by the skin, the likelihood of repeated
dermal exposure raises tv*o concerns: first, Metolachlor has been observed
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to^elicit a dennal sensitization reaction; second, although no positive
evidence of general chronic, teratogenic, fetotoxic, oncogenic, or
mutagenic effects has so far been presented, the available information is
presently insufficient to satisfy all the Agency's requirements for the
study of chronic effects. Thus the risks to hunans caused by repeated
dermal exposures to a Technical Metolachlor solution cannot be concluded at
this time, and the only presently known hazard of manufacturing-use
Mstolachlor is the potential for dermal sensitization for factory,
transport? or re-formulation workers.
anulsifiable Concentrate; The hazards to humans and domestic animals
that may arise from the "end-use of an agricultural pesticide are of three
kinds: those hazards to humans which arise in the tank mixing, dilution,
application, storage, or disposal of the end-use chemical; those hazards
to humans and domestic animals which arise as a result of ambient
residues from pesticide application, storage, or disposal, including
residues in air, water, and edible wildlife; and, finally, those hazards
to hunans or domestic animals which may arise as a result of anticipated
residues in harvested food or feed. The first two kinds are considered
here in the Toxicology chapter. The last kind will be considered in the
Residue Chemistry chapter.
As was stated in the Exposure Profile, there is little chance for
accidental oral exposure to a soil-sprayed pesticide that is not mixed
with foodstuffs before application. But there is a chance for dennal and
eye exposure for chanical applicators who are tank mixing, diluting, or
loading. There is also a chance of inhalation exposure for applicators,
agricultural workers, and livestock in the proximity of the spraying.
Though spray drift properties of Metolachlor applications have not been
established, and Metolachlor may therefore not be applied aerially, ambient
air residue exposures may conceivably occur to persons or livestock outside
the ground-spray area. Due 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 persons ingesting contaminated fish or
water.
The routine outdoor agricultural field use of Metolachlor could
directly result in a number of minor hazards for hunans. The data show
that it is possible for a Metolachlor formulation to cause irreversible
corneal opacity and severe iritation to an applicator whose eyes are
unprotected during mixing, loading, or diluting. Similarly, an applicator
with unprotected hands or face could run an acute risk of erythrna, edema,
and second degree burns due to contact with certain formulations. If
dermal exposures to any Matolachlor formulation are repeated, there is a
risk of a sensitization reaction. Finally, though the active ingredient
is not readily absorbed through the skin, various chronic or reproductive
effects from a repeated dermal or inhalation exposure to a Metolachlor
formulation cannot presently be ruled out.
Anbient residues from the ground-spray application of a Metolachlor
formulation may present parallel, though significantly lesser, hazards to
persons or livestock outside the spray area. Of potential concern are the
long-term, repeated exposures for livestock or hunans drinking contaminated
water or feeding on nearby aquatic and plant life, possibly resulting in
undetermined chronic effects.
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Generic Data Gaps
The following are gaps in the Toxicology data base which will be used to
support registrations under this Metolachlor Standard. After each gap is
listed the section in the Proposed Guidelines of August 22, 1978 (FR Part 163)
which describes that type of study and when it is required.
1) Subchronic Oral Dosing - Acceptable pathology 163.82-1
evaluation is required for the rat study.
2) Chronic Feeding - A chronic feeding study using 163.83-1
the laboratory rat is required.
3) Oncogenicity - An oncogenic evaluation performed 163.83-2
for the chronic feeding study [see (2) above] , or
an oncogenicity study in a mammalian species other
than the mouse (preferably the laboratory rat) .
The Agency is also awaiting the results of the
second mouse study.
4) Teratology - A teratology study in a mammalian 163.83-3
species other than the rat is required.
5) Reproduction - A multi-generation reproduction 163.83-4
study on one mammalian species (preferably the
laboratory rat).
Product Specific Data Gaps
The following is a "product specific" data gap for Toxicology which
needs to be filled in order to maintain in effect a current registrations under
this Standard. After the gap is the section in the Proposed Guidelines
(August 22, 1978, FR Part 163) which describes that type of data and when it
is required.
For Bnulsifiable Concentrate Mstolachlor (8 Ibs. ai/gallon):
1) Acute inhalation toxicity study. 163.81-3
Suggested Labeling
See the tetolachlor Standard's 'Regulatory Rationale' for a discussion of
the levels of acute toxicity which the Agency will consider acceptable, and the
second chapter of the Standard for a listing of the specific label statements
appropriate to the acceptable 'Tbxicity Categories.' Section 162.10 of the CFR
40 explains the Agency's established toxicity labeling requirements as they
relate to the "Ibxicity Categories'.
The only toxicology labeling suggested by the available data that does not
follow directly from ftetolachlor' s "Ibxicity Categories' is a precaution
concerning dermal sensitization: "my cause skin sensitization. Wear gloves
and protective clothing while handling or using this product. Wash thoroughly
after handling. Remove and wash contaminated clothing before re-use."
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BIBLIOGRAPHY
Each of the following studies contributed useful information to the
Agency's review of the toxicology of Metolachlor, and is considered part of the
data base which supports registrations under this Standard.
Affiliated Medical Research, Incorporated (1974a) Acute Dermal LDv,, of CGA-
24705 - Technical in Rabbits: Contract ND. 120-2255-34. Received Sep 26,
1974 under 5G1553. (Unpublished study prepared for Ciba-Geigy Corp.,
Greensboro, N.C.; CDL:112840-E)
Affiliated Medical Research, Incorporated (1974e) Emetic Ebse 50 in Beagle
Dogs with CGA-24705-Technical: Contract No. 120-2255-34. Received Sep 26,
1974, Greensboro, N.C.; CDL:112840-C)
Affiliated Medical Research, Incorporated (1974f) Twenty-one Day Repeated
Dermal Tbxicity of CGA-24705-6E in Rabbits: Contract No. 120-2255-34.
Received Sep 26, 1974 under 561553. (Unpublished study prepared for Ciba-
Geigy Corp., Greensboro, N.C.; CDL: 112840-Q)
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. Received Sep 26, 1997 under 5G1553.
(Unpublished reportprepared for Ciba-Geigy Corp., Greensboro, N.C.;
CDL: 11284 0-K)
Arni, P.; Muller, D. (1976) Salmonella/Mammalian-Microsome Mutagenicity Test
with CGA 24705 (Test for Mutagenic Properties in Bateria): PH 2.632.
Received Jan 19, 1977 under 7F1913. (Unpublished study prepared by Ciba-
Geigy, Ltd., Basle, Switzerland; CDL:95768-B)
Bathe, R. (1973) Acute Oral LD^ of Technical CGA-24705 inthe Rat: Project
No. Siss 2979. Received SSp 26, 1974 under 5G1553. (Unpublised study
prepared by Ciba-Geigy Corp., Ltd., Basle, Switzerland; CDL:112840-A)
Ciba-Geigy Limited (1976a) Dominant Lethal Study on CGA 24705 Technical: Mouse
(Test for Cytotoxic or Mutagenic Effects on Male Germinal Cells) PH 2.632.
Received Jan 18, 1978 under 7F1913. (Unpublished study including
Addendum; CDL:96717-C; 96717-D)
Ciba-Geigy Limited (1976b) Reproduction Study CGA 24705 Tech.: Rat: Seg. II
(Test for Teratogenic or Embryotoxic Effects) PH 2.632. Received Jan 18,
1978 under 7F1913. (Unpublished study including Addendum; CDL:96717-A;
96717-B)
Ciba-Geigy Limited (1977) Skin Sensitizing (Contact Allergenic) Effect in
Guinea Pigs of Technical CGA 24705: Siss 5726. Received Jan 18, 1978
under 7F1913. (Unpublished study; CDL:96717-E)
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Cbquet, B.; Galland, L.; Guyot, D.; Ebuillet, X.; Rouanud, J. L. (1974a) Essai
de Tbxicite de 3 Mois chez Le Chien par Mbie Orale du Produit CGA 24 705.
[Three-Month Oral Tbxicity Trial of CGA 24 705 in Cog]: IC-DREB-R-740119.
Received Sep 26, 1974 under 5G1553. (Unpublished study prepared by the
Chcins Research and Breeding Center for Ciba-Geigy Corp., Greensboro, N.C.;
CDL:94223-B)
Coquet, B.; Galland, L.; Guyot, D.; Fouillet, X.; Fbuaud, J. L. (1974b) Essai de
Tbxicite de 3 Mois chez Le Rat par Voie Orale du Produite CGA 24 705.
[Three month oral ToxicityTrial of CGA 24 705 in Rats]: IC-DREB-R-740120.
Received Mar 1, 1974 under 5G1553. (Unpublished study prepared bythe
Cncins Research and Breeding Center for Ciba-Geigy Corp., Greensboro, N.C.;
CDL:94219-B)
Coquet, B.; Galland, L.; Guyot, D.; Fouillet, X.; Rouanud, J. L. (1974c) Three-
Month Oral Toxicity Test of CGA 24 705 in Dog. A translation of: Essai de
Toxicite de 3 Mois chez Le Chien par ^ie Orale du Produit CGA 24 705: IC-
EREB-R-740119. Received Sep 26, 1974 under 5G1553. (Ihpublished study
prepared by the Chcins Research and Breeding Center for Ciba-Geigy Corp.,
Greensboro, N.C.; CDL:94223-A)
Coquet, B.; Galland L.; Guyot, D.; Fouillet, X.; Fbuaud, J. L. (1974d) Three-
Month Oral Toxicity Test of CGA 24 705 in Rats. A translation of: Essai
de Toxicite de 3 Mois chez te Pat par \foie Orale du Produit CGA 24 705: IC-
EREB- R-740120. Received Mar 1, 1974 under 5G1553. (Unpublished study
prepared by the Cncins Research and Breeding Center for Ciba-Geigy Corp.,
Greensboro, N.C.; CDL:94219-A)
Draize, J.H. (1959) The Appraisal of Chemicals in Food, Drugs, and Cosmetics.
Association of Food and Drug Officials of the United States. Austin, Texas.
Fritz, H. (1976) Reproduction Study CGA 24705 Tech. Pat: Sag. II: (Test for
Teratogenic or Qnbryotoxic Effects): PH 2.632. Received Jan 19, 1977
under 7F1913. (Unpublished study prepared by Ciba-Geigy Ltd., Basle,
Switzerland; CDL:95768^)
Gesme, J.; Albanese, E.; Marias, A.J. (1977) Report to Ciba-Geigy Corporation:
Carcinogenicity Study with CGA-24705 Technical in Albino Mice: IBT ND. 622-
07925 (8532-07925). Received Jan 18, 1978 under 7F1913. (Unpublished
study prepared by Industrial Bio-Test Laboratories, Inc. for Ciba-Geigy
Corp.; including* Validation report prepared by Ciba- Geigy Corp.,
Greensboro, N.C.; CDL:96719^; 96720-^A; 96720-B)
Gfeller, W. (1974) Tolerability Trial in Milk Cows with CGA-24705: 14, 21, and
28 day Feeding Study: AC 9.26; T73/23. Received Sep 26, 1974 under
5G1553. (Unpublished study prepared by Ciba-Geigy Lt., St. Aubin,
Switzerland; CDL:94216-F)
Bambock, H. (1974a) Project ND . 7/74: Metabolism of CGA 24 705 in the Pat.
(Status of Results Gathered up to June 10, 1974): AC 2.52. Received Sep
26, 1974 under 5G1553. (Unpublished report prepared by Ciba-Geigy Ltd.,
Basle, Switzerland; CDL:94217-L)
7 0
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Hambock, H. (1974b) Project Report 12/74: Addendum to Project Report 7/74:
Metabolism of CGA 24 705 in the Rat: AC 2.52; Received Nov. 25, 1975 under
631708. (Unpublished report prepared by Ciba-Geigy Ltd., Basle,
Switzerland; CDL:94984-P)
Hambock, H. (1974c) Project Report No. 1/74: Distributions, Degradation and
Excretion of CGA 24 705 in the Rat. Received Sep 26, 1974 under 5G1553.
(Unpublished report prepared by Ciba-Geigy Ltd., Basle, Switzerland;
CDL:94217-K)
Kennedy, G. L. (1975) 28-Day Mouse Pilot Study with CGA-24705 (Technical).
Received Feb 16, 1978 under 100-583: dated Nov 21. 1975; 1ST No. 622-
07857. (Unpublished study prepared by Industrial Bio-Test Laboratories,
Inc. for Ciba- Gaigy Corp., Greensboro, N.C.; CDL-232855-B)
Kennedy, G. L. (1976a) Letter dated Dec 10, 1976, relative to the results of
the first generation of a three-generation reproduction study in albino
rats with the chemical CGA 24705 (IBT No. 8533-079280] to George Rolofson.
Received Jan 19, 1977 under 7F1913. (Unpublished study prepared by
Industrial Bio-Test Laboratory, Inc., for Ciba-Geigy Corp., Greensboro,
N.C.; CDL:95768-E)
Kennedy, G. L. (1976b) Letter [dated Dec 13, 1976, interim reporton IBT No. 8531-
07926, 2-year chronic toxicity of CGA 24705 in albino rats] to George
Rolofson. Received Jan 19, 1977 under 7F1913. (Unpublished study prepared
by Industrial Bio-Test Laboratories, Inc., for Ciba-Geigy Corp.,
Greensboro, N.C.; CDL:95768-D)
Kennedy, G. L. (1976c) Letter [dated Dec 13, 1976, relative to the 2-year
carcinogenicity study of CGA 24705 in albino mice (IBT Isb. 8531-07925)] to
George Rolofson. Received Jan 19, 1977 under 7F1913. (Unpublished study
prepared by Industrial Bio-Test laboratories, Inc., for Ciba-Geigy Corp.,
Greensboro, N.C.; CDL:95768-C)
Cncins Research and Breeding Center (1974) Three-Month Dietary Feeding Study in
Rats: CGA 24 705. A translation of: Toxicite de 3 Mois chez le Rat par
A/bie Orale du Produit CGA 24 705, translated by F. Roulet: IC-DREB-R
741009. Received Mar 26, 1975 under 5F1606. (Unpublished study prepared
by Ciba-Geigy Corp., Greensboro, N.C.; CDL:94377-B)
Sachsse, K. (1973a) Irritation of Technical CGA-24705 in the Rabbit Eye:
Project No. Siss 2979. Received Sep 1974 under 5G1553. (Unpublished
report prepared by Ciba-Geigy Ltd., Basle, Switzerland; CDL:112840-G)
Sachsse, K. (1973b) Skin Irritation in the Rabbit after Single Application of
Technical CGA-24705: Project No. Siss 2979. Received Sep 26, 1974 under
5G1553. (Unpublished study prepared by Ciba-Geigy Ltd., Basle,
Switzerland; CDL:112840-1)
Sachsse, K.; Ullman, L. (1974a) Acute Inhalation Toxicity of Technical CGA-
24705 in the Rat: Project No. Siss 3516. Received Sep 26, 1974 under
5G1553. (Unpublished study prepared by Ciba^3eigy Ltd., Basle,
Switzerland; CDL:112840-L)
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Sachsse, K. (1977) Skin Sensitizing (Cbntact Allergenic)Effect in Guinea Pigs
of Technical CGA-24705. Project No. Siss 5726. Received October 17,
1977. [Unpublished study prepared by Ciba-Geigy Ltd., Basle, Switzerland]
Smith, S.H.; Adle'r", G. L. (1978) Final Report to Ciba-Geigy Cbrp.: Three-
Generation Reproduction Study with CGA-24705 Technical in Albino Rats: IBT
No. 8533-07928. Received Jan 18, 1978 under 7F1913. (Unpublished study
prepared by Industrial Bio-Test Laboratories, Inc. for Ciba-Geigy Corp.
Greensboro, N.C.; CDL:96718-A; 96718-B)
Sunner, D.D. (1978a) Audit Report CQted Nov 21, 1975: 28-Eay touse Pilot Study
with CGA-24705 (Technical). Received Feb 16, 1978 under 100-583; IBT No.
622-07857. (Lhpublished study prepared by Ciba-Geigy Corp., Greensboro,
N.C.; CDL:232855-C)
Sumner, D.D. (1978b) Addendum to Audit Report Dated Jan 12, 1978:
Carcinogenic Study with CGA-24705 Technical in Albino Mice. Received Feb
16, 1978 under 100-583; IBT No. 622-07925. (Unpublished study prepared by
Ciba-Geigy Corp., Greensboro, N.C.; CDL.-232855-A)
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RESIDUE CHEMISTRY
TOPICAL DISCUSSIONS
Metabolism in Plants
Matabolism in Animals
Analytical Methodology
Residue Data
Present Tolerances
Metabolism in Plants
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 (Sunner and Cassidy, 1975).
Ring-labeled Metolachlor was applied as a pre-emergence treatment at 2 Ibs.
ai/acre. For corn, it was dissolved in nutrient solution at a concentration of
approxiornately 2 ppm and applied to field and greenhouse soils. For soybeans,
it was added to soil and plantings were incubated in the greenhouse. The
maximum levels of residues found in the various plant parts, based on total
radioactivity, were as follows: corn grain, greenhouse and field, 0.05 ppn
and 0.02 ppm, respectively; corn forage, greenhouse and field, 0.72 and 0.17
ppji, respectively; soybeans 0.17 ppm, soybean hay 2.66 ppm, soybean oil 0.01
ppm and soybean meal 0.14 ppm. These data show that the total residues in
soybeans are higher than those in corn.
The metabolism of Metolachlor by corn plants consists of a major and a
minor pathway. The figure in the 'Disciplinary Review1 at the end of this
chapter depicts these pathways for both corn and soybeajj4plants (Marco 1975) .
When corn plants were grown in soil treated with fi- C-Metolachlor at 2
Ibs. ai/acre (Sunner 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
Metolachlor. More than 80% of the remaining activity was found in the polar
fraction. TLC 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 amino acids, sugars, or sugar acids (Sumner and Cassidy,
1974C).
One metabolic pathway in the corn plants involves conjugation of
Metolachlor with glutathione (Sunner and Cassidy, 1974b). Fourteen percent of
the radioactive Metolachlor recovered from corn leaves was found conjugated
with glutathione. It appears that degradation occurs through a thio-ether
bond forming a glutathione conjugate via the reactive chloroacetyl moiety of
Metolachlor.
Metabolites, which upon hydrolysis, produce 2-[(2-ethyl-6-methylphenyl)
amino]-1-propanol (HP-001) and 4-(2-ethyl-6-methylphenyl)-2-hydroxy-5-methyl-3-
morpholinone (HP-002) were found to be common in plants and in animals, from
high level feedings of Metolachlor (Hambock, 1974a,b,c; Mattson, 1975). When
partly purified plant conjugates were cleaved by a reduction reaction with
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Raney nickel, which breaks thio-ether bonds (Gross, 1974a and Gross, 19745} ,
tvo compounds, M- (2-ethyl-6-methylphenyl) -N- (2-methoxy-l-methylethyl) acetamide
(MET-005) , and N-(2-ethyl-6-methylphaiyl)-N-(2-hydroxy-l-methylethyl)acetanide
(MET-006) ware produced, indicating that these compounds were moieties of
sulfur-bonded conjugates. These two compounds represent 80% of the
radioactivity extracted from the corn leaves. They were positively identified
by GLC <-iT:d mass spectrcmetry,,
Further residue characterization, involving rigorous HQ hydrolysis
(Sunner,, Thomas, and Cassidy, 1975), showed the presence of either 2-[ (2-ethyl-
6-methyIphenyl)amino]-l-propanol (HP-001) or 4-(2-^thyl-6-methylphenyl) -2-
hydroxy-5-methyl=3-morpholinone (HP-002). These data suggest that the
compounds present before hydrolysis are predominantly alpha-thioglycoside
metabolites and the alpha-oxygen glycoside analogues. The relative amounts of
the compounds indicate that the major pathway of metabolism involves
conjugation with glutathione, breakage of the thio- bond to form the
rnercaptan, conjugation of mercaptan with glucuronic acid, hydrolysis of methyl
ether, and conjugation of the alcohol with a neutral sugar. A minor pathway
assumes chloro replacement by hydroxyl. The same pathway may also involve
direct conjugation with glucuronic acid, followed by demethylation and
conjugation of the hydroxyl with a neutral sugar, all forming oxo- conjugates.
When radiolabeled 0- C-Metolachlor was applied to growing soybeans
(Summer and Cassidy, 1975b), characterization of the extracted residues
indicated that the metabolic pathways in soybeans are similar to 'those
observed in corn. Thin-layer chronatography and partitioning data indicated
that higher concentrations of less polar metabolites will occur in soybeans
when compared to corn grain.
Because it has been suggested that the chloroacetyl group could split off
as monochloroacetic acid and occur as part of the terminal residue, Tbxicology
reviewers expressed concern about the possible presence of monochloroacetic
acid as a component of the residues of Metolachlor, resulting from metabolism
or degradation of the parent compound. However, Residue Chemistry reviewers
can find no reason to expect monochloroacetic acid to occur as a residue
following the use of Metolachlor. While there is no definitive data on the
matter, the Agency has postulated, based upon the unique chemical and
biological stability of the amide bond and the relatively unstable carbon-
chlorine bond in Metolachlor, that any hydrolysis of the amide would be
preceded by displacement of the chlorine. Consequently, the presence of
monochloroacetic acid as a product of metabolism is not likely to occur.
The above studies adequately define the fate of Metolachlor in soybeans
and corn for the purposes of establishing tolerances. " : ~~~
Though no studies were available for peanuts or sorghum, the metabolism
studies for corn and soybeans are adequate to reflect the nature of Metolachlor
residues in peanuts and sorghum. In other words, the Agency is taking the
position that the nature of the residues in peanuts and sorghum is similar to
that of corn and soybeans. ND metabolism studies are yet available for root
crops such as potatoes. Because the residue in root crops may differ from
that of non-root crops, we are unable to apply the data on corn and soybeans to
root crops such as potatoes. If. a tolerance is to be established root crops,
root crop metabolism data will be needed.
7 4
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1'ietabollsm In Animals
Matolachlor is rapidly metabolized and almost totally eliminated in the
urine and feces of runinants (goats), non-runinants (rats), and poultry (Roger
and Cassidy, 1974a; Hambock, 1974a- Guth, 1974). These findings ware made in
studies using both unlabeled and C-ring-labeled Metolachlor. Matolachlor
per se was not detected in any of the excreta or tissues.
Additional studies with goats (Cbunselman and Fbger, 1973; Fbger and
Cassidy, 1974a,b) confirmed the finding that the urine and feces contain
almost all the metabolized products.
In animals, trace amounts of metabolized Matolachlor were found in kidneys,
liver, blood, and milk (Biouetric Itesting Incorporated, 1973; Hambock, 1974a,
b,c; Schenker, 1975a) .
No residues were found in eggs, meat, or fat samples of laying chickens.
The only metabolite found, in the liver (at 0.02 - 0.03 ppm), was the one
which upon hydrolysis yields HP-001 (Mattson, 1974, 1975). ND precursor of
the hydrolysis product HP-002 was found in the liver (Oath, 1974).
When C-labeled metabolites of Metolachlor, bio-synthesized in corn,
were fed to goats, no parent Metolachlor nor any metabolites were found in the
animals' tissues or milk (Ciba-Geigy Limited, 1973; Schenker, 1974, 1975b).
It is concluded that the metabolism of Metolachlor in animals appears to be
similar to and as complex as that in plants. Whereas plants retain their
metabolic products, animals eliminate their Metolachlor metabolic ..products
almost entirely. Various studies with unlabeled Nfetolachlor and C-ring
labeled Metolachlor fed to different animals indicate clearly the identity and
the amounts 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
Matolachlor in animals for the purposes of establishing tolerances for corn
grain and soybeans. (Ebr an evaluation of rat metabolism data, please see
Ibxicology Chapter.)
Analytical Methodology
Metolachlor in Corn and Soybeans
The reslcfue data submitted for corn were obtained by the use of
methods AG-265 (Balasubramanian, Gold, and Ross, 1974) and AG-277
(Balasubramanian, Aziz, and Ross, 1975). The residue data for soybeans
were obtained by Method AG-286 (Aziz and Ross, 1975) . Most of the corn
residue data were obtained by Method AG-265. This method utilizes HQ to
hydrolyze Metolachlor and those metabolites which are capable of
conversion to 2-[(2-ethyl-6-methylphenyl)amino]-1-propanol (HP-001).
In Method AG-265, fifty grams of ground or chopped sample is refluxed
with 250 ml of 6N HO. for 16 hours. The aqueous extract is filtered off,
neutralized, and made basic with NaOH solution and extracted twice with
hexane. The combined hexane extracts are chromatographed on an alunina
colunn. The residues of HP-001 are eluted using 5% ether in hexane. The
eluate is evaporated and the residues are taken up in 0.5 ml of benzene.
An aliquot of the sample solution is injected into a gas chromatograph
equipped with a Gbulson eletrolytic conductivity detector, mown amounts
of HP-001 are used for standardization. Peak heights are compared with
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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-001; (2) fortification
parent Metolachlor, (CCM-001) ; and (3) comparison of GLC analyses 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 ppm with HP-001 averaged 81%. All control samples were
determined to have <0.03 ppm (the method sensitivity). Ebrtification
studies using parent Metolachlor averaged 63% for levels of 0.05-0.2 ppm
in stover. ,.
The total C-activities in samples of corn plants taken from both
the field and greenhouse studies were determined by combustion (Hermes,
1972). The combustion technique determined all residues (both extractible
and nonextractible) after conversion to CO-. The residues
(expressed as CCM-001) determined by Chemical Method AG-265 ranged from
12% (mature crop) to 27% (immature forage or silage) of the total residues
found by combustion techniques. Comparisons were also made of the total
extractible residues by the chemical method vs. the C-combustion
method using two extraction solvent systems, HQ, and combined chloroform-
methanol solvent. .About 50-60% of the C-residues in mature corn were
extractable using either method. The chemical method determined 20-30%
of the total extractable C-residues.
Except as stated directly below, method AG-265 (Balasubramanian, Gold,
and Ross, 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-(thiocyanomethylthio)-benzotriazole. An alternate column liquid
phase is available and provides additional specificity for residues of
Metolachlor.
Method AG—277 (Balasubramanian, Aziz, and Fbss, 1975) is a
modification of AG-265 which includes partitioning, clean-up,
derivatization, and micro-coulometric GLC steps determining two hydrolysis
products: 2-[ (2-^thyl-6-methylphenyl)amino]-l-propanol (HP-001) and 4-(2-
ethyl-6-methylphenyl)-2-hydroxy-5-methyl-3-morpholinone (HP-002).
Residues of Metolachlor (CCM-001) in corn grain, ears, forage, fodder
and stover are converted to a mixture of HP-001 and HP-002 by refluxing 16
hours with 6N HQ. The filtered acid extract is partitioned with
dichloromethane to extract the HP-002 into the organic phase. The aqueous
phase containing HP-001 is made strongly basic with 50% sodium hydroxide
and subjected to distillation-partition into isooctane using a Bleidner
apparatus. The isooctane phase containing HP-001 is cleaned up by using
an alunina colurm. HP-001 is determined with a gas chromatograph equipped
with a Coulson electrolytic conductivity nitrogen detector. It is
quantified by comparing it with the peak height of a standard amount of HP-
001 and then calculated as CCM-001 using the 1.47 equivalence factor.
The dichloromethane phase containing HP-002 is washed with 5% sodium
carbonate solution and further cleaned up using an alunina colunn. The
chloroethanol derivative of HP-002 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
alunina columns. A gas chromatograph equipped with Dohrmann
76
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microcoulonetric chloride detector is used for analysis. For
quantification, the peak area is compared to that of peak areas of
derivatized standard HP-002. Residues are calculated as CCM-001 using
the conversion factor 1.13.
Controls for HP-001 usually ranged from less than 0.02 ppm to 0.05
ppm. In some 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 from 57-115% with an
average of 65%. Typical recovery data residues of HP-002 for samples
fortified at 0.05-0.20 ppm ranged from 45-102% with an average of 62%.
The method sensitivity is considered to be 0.10 ppm for HP-002 when
calculated as CCM-001.
The method used for the soybean residue data is Method AG-286 (Aziz
and Ross, 1975). This method, "Analytical Method for the Determination of
Residues of Metolachlor Soybean Metabolites (as HP-001 and HP-002) by Acid
Hydrolysis," is the method for regulatory enforcement which will be
incorporated in the FDA pesticide Analytical Methods, Mbl. 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
de te rm ina t ive steps.
The analytical methods are also adequate for the enforcement of
tolerances on peanuts and sorghun. However, the absence of data indicating
the significant components of residues in root crops precludes valid
conclusions on the adequacy of these methods for the determination of
Metolachlor residues in root crops for enforcement purposes.
Metolachlor _in Animal Tissues
Analyses~~of meat, milk, and egg samples were conducted by methods
reported in Basle REM 5/74 (Hermann, Guth, Ebrmica, and Schenker, 1974)
and Basle REM 2/75 (Ramsteiner and Karlhuber, 1975). Analytical method
(REM 2/75) accounts for "combined residues" of Matolachlor, determined as
HP-001 and HP-002.
In the first method (REM 5/74), the herbicide and the potential
metabolites and/or conjugates in animal products are subjected to acidic
hydrolysis. The resulting solution is made alkaline before steam-
distillation; extraction of residues into isooctane is effected by means
of a steam distillation-extraction head. The HP-001 fraction is cleaned
up by using an alunina column and, if necessary, by TLC.
The HP-001 "residues" are detected by gas chromatography/mass
spectrometry. This method is a minor modification of AG-265 and was used
for the gas chromatographic analysis of milk, blood, meat, fat, liver,
kidney, egg white and egg yolk. The limits of detection for HP-001 are
0.006 ppm for milk, 0.015 ppm for eggs and chicken tissues, and 0.02 ppm
for cow tissues.
The second method (REM 2/75) determines all residues which are
hydrolyzed by acid to HP-001 and HP-002. HP-002 is converted to a
derivative which is determined by gas chromatography. This method for
animal tissues involves minor modifications of Method AG-286. The
reported limits of detectibility are 0.01 ppm in milk, and 0.04 in for
77
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meat, liver, and kidney.
F^fethod REM 2/75, CCM-001, "Determination of Total Residues in Material
of Animal Origin" (Ramsteiner and PSrlhuber, 1975), was tried on beef
liver in one of EPA's laboratories. Samples fortified in duplicate with
HP-001 gave 99% and 100% recovery. Samples fortified in duplicate with HP-
002 showed 43% and 45% recovery.
Methods AG-286 and REM 2/75 were found to have adequate specificity
and are judged satisfactory for enforcement purposes.
Residue Data
Field residue data for Metolachlor should reflect the use with respect to
dosage, mode of application, number 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 growing
season as well as analyses of the harvested grain.
The analytical methods used to generate the residue data involve a
conversion of residues of Metolachlor and its metabolites (through hydrolysis)
to 2-[(2-ethyl-6-methylphenyl)amino]-l-propanol (HP-001) and 4-(2^athyl-6-
methylphenyl)-2-hydroxy-5-methyl-3-fnorpholinone (HP-002) . The resulting
residues from the application of Metolachlor are accordingly expressed as HP-
001 and HP-002, or combined as 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 Yahrs, 1975b). Samples of corn fodder and corn
grain were fortified with Metolachlor at 1.0 ppm and 0.2 ppm, respectively.
The samples were kept frozen at -15 C and analyzed at pre-determined
intervals up to 13 months after storage. The recoveries for the corn
fodder ranged from 92-115% of the fortified amount and the corn grain samples
ranged from 92-119%.
Several samples of field-treated corn fodder were also monitored during the
13-month storage period. Residues in one sample varied from 0.43-0.39 ppm and
residues in another sample ranged from 0.29-0.26 ppm 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 submitted regarding the composition of 250 E.G. formulation.
The residues of CCM-001 in these studies are determined as HP-001 alone.
The HP-002 breakdown product was not determined. These studies were
performed in 9 states (Nebraska, Mississippi, Illinois, New York, Texas,
Chio, California, Wisconsin, Indiana) . (Tweedy, 1974; Ttoeedy and Mattson,
1974; Mattson and Kahrs, 1975b.) (Only studies performed with Metolachlor
alone are considered here.)
Nine studies with field corn, at 2 Ibs. and 4 Ibs. ai/acre of 250
E.G., reported residues less than 0.03 ppm of Metolachlor (as HP-001) in
grain at intervals of 111-162 days between pre-emergent application and
harvest. Three studies with sweet corn at 2 Ibs. and 4 Ibs. ai/acre of
250 E.G. reported residues of Metolachlor (as HP-001) in ears as less than
0.03 ppm at 61, 67, and 138 days after the pre-emergent application. Two
additional studies with field corn and one with sweet corn using the 5E
formulation (at 3 and 6 Ibs. ai/acre ) indicated no detectable combined
-------
residues of HP-001 (as Metolachlor) (less than 0.03 ppm) 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 two additional studies at 2
Ibs. and 4 Ibs.ai/acre of 250 E.G. formulation on sweet corn were
performed. No detectable residues of Metolachlor as HP-001 (less than
0.03 ppn) or HP-002 (less than 0.10 ppn) were found in the fresh ear
sample at 60 and 67 days after the application.
Seventeen residue studies where Nfetolachlor was measured as HP-001
show forage residues were less than 0.03 ppm at intervals of 34 and 72
days following 1.5 Ibs. ai/acre. Residues resulting from 2 Ibs. and 3
Ibs. ai/acre applications (at 26 to 72 days) range from less than 0.03 to
0.14 ppm, and less than 0.03 to 0.10 ppm, respectively. At intervals of
26 to 64 days, 4 Ibs. ai/acre resulted in residues of less than 0.03 to
0.43 ppm; 6 Ibs. ai/acre rates showed HP-001 residues at 0.03 to 0.19 ppm.
Silage stage forage residues of Metolachlor (measured as HP-001)
resulting from 2 Ibs. and 4 Ibs. ai/acre range from less than 0.03 ppm to
0.16 ppm, and less than 0.03 ppm to 0.43 ppm, respectively, at intervals
from 71 to 112 days after application.
Mature fodder and stover residues ranged from less than 0.03 ppm to
0.44 ppn (measured as HP-001) for both the 2 Ibs. and 4 Ibs. ai/acre rates.
Eleven studies in which Metolachlor was later measured as combined
residues of HP-001 and HP-002 show residues in early forage of less than
0.03 ppn to 0.24 ppm and less than 0.03 ppn to 0.08 ppn for 2 Ibs. and 3
Ibs. ai/acre treatments, respectively; 4 Ibs. and 6 Ibs. ai/acre
applications resulted in forage residues ranging from 0.04 ppn to 0.64 ppn
and 0.03 to 0.19 ppn, respectively.
Silage stage forage showed combined HP-001 and HP-002 residues (as
Metolachlor) of 0.08 to 0.14 ppn, 0.04 ppn to 0.12 ppn, and 0.05 ppn to
0.28 ppn for treatments at 1.5 Ibs., 2.0 Ibs., and 3.0 Ibs., respectively.'
Combined residues from 4 Ibs. and 6 Ibs. ai/acre treatments were 0.14 to
0.63 ppn and 0.13 to 0.34 ppn, respectively.
Ebdder and stover residues for 1.5 Ibs., 2.0 Ibs., and 3.0 Ibs., ai/
acre treatments were less than 0.03 to 0.06 ppn, less than 0.03 to 0.23
ppn, and 0.07 to 0.30 ppn.
Combined residues of HP-001 and HP-002 (as Mstolachlor) in mature
fodder and stover reported in six studies at 4 Ibs. ai/acre ranged from
0.07 ppn to 0.90 ppn. Three studies at 6 Ibs. ai/acre reported combined
residues in fodder ranging from 0.14 to 0.53 ppn.
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-lEEree residue studies were performed in eight states
representing the major soybean growing areas. (Again, only studies
performed with Matolachlor alone are considered here.) Application rates
were from 2 to 6 Ibs. ai/acre (Mattson and Rolla, 1975; Texas A & M
Cottonseed Products Research Laboratory, 1966; Houseworth and Rolla, 1976).
Analyses involved the determination of both HP-001 and HP-002. No
detectable residues (less than 0.05 ppn) of HP-002 were found in any of
the soybean samples. Residues of HP-001 in the soybeans which ranged from
less than 0.03 to 0.09 ppn resulted from application rates of up to 5 Ibs.
ai/acre; the maximum reported residue was from a 3 Ib. ai/acre
application. At 5 Ibs. ai/acre, residues of HP-001 ranged from less than
79
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0.33 to 0.21 ppm.
Three fractionation studies showed no detectable residues of HP-001
(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
Ibs. ai/acre. At 6 Ibs. 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-001 from
treatment rates of 2.5 and 5 Ibs. ai/acre.
Total residues (sun of residues converted to HP-001 and HP-002) of
Metolachlor in soybean forage ranged from 0.20 to 0.36 ppn at a 2 Ibs. ai/
acre application rate. Total residues in soybean forage at the 3 Ibs. ai/
acre ranged from 0.15 to 1.01 ppm. At exaggerated rates of 4 Ibs. and 6
Ibs. ai/acre, total residues ranged from 0.34 to 1.76 ppm. These residue
studies represented pre-harvest intervals of 30-92 days.
Total residues in soybean hay at pre-harvest intervals of 122-194 days
ranged from less than 0.10 to 0.84 ppm at rates of up to 3 Ibs. ai/acre.
At exaggerated rates of 4 to 6 Ibs. ai/acre, total residues ranged from
0,14 to 2.46 ppm.
The above residue data for soybeans allows for an adequate range of
geographical variation.
Residues _in or on Sorghum
Forty^fTveTesidue studies were performed in seven states representing
the major sorghum growing areas. Application rates were 2 to 5 Ibs.
ai/acre. Analyses involved the determination of both HP-001 and HP-002 in
silage stage forage, harvest fodder, and mature grain.
Residues of HP-001 in the silage stage forage (sampled at 55 to 111
days after treatment) were 0.05 to 0.56 ppm due to a rate of 2 Ibs.
ai/acre; less than 0.03 to 0.34 ppm due to 2.5 Ibs. ai/acre; and, 0.14
to 0.51 ppm due to a rate of 5 Ibs. ai/acre (two times the maximum
proposed rate) . Residues of HP-002 in the silage stage forage were less
than 0.05 to 0.43 ppm due to a rate of 2 Ibs. ai/acre; less than or
exactly 0.05 to 0.11 ppm due to a rate of 2.5 Ibs. ai/acre; and less than
0.05 to 0.46 ppm due to a rate of 5 Ibs. ai/acre.
Samples of mature grain and harvest fodder were collected at intervals
of 85 to 169 days after treatment and analyzed. Resides of HP-001 in the
harvest fodder were 0.06 to 0.96 ppm due to a 2 Ibs. ai/acre application
rate; 0.06 to 1.90 ppm due to a 2.5 Ibs. ai/acre rate; and 0.14 to 0.99
ppm due to a 5 Ibs. ai/acre rate. Residues of HP-002 in the harvest fodder
were less than 0.05 to 0.20 ppm due to a 2 Ibs. ai/acre rate; less than
0.05 to 1.29 ppm due to a 2.5 Ibs. ai/acre rate; and, 0.07 to 0.45 ppm due
to a 5 Ibs. ai/acre rate.
Residues of HP-001 in sorghum grain were less than 0.03 to 0.11 ppm
due to the 2 Ibs. ai/acre application rate; less than 0.03 to 0.18 ppm due
to the 2.5 Ibs. ai/acre rate; and less than 0.03 to 0.37 ppm due to -the 5
Ibs. ai/acre rate. ND detectable residues of HP-002 (less than 0.05 ppm)
were noted in sorghum grain from any application rate.
Two processing studies were performed on sorghum grain. The grain was
obtained from crops treated at 2 Ibs. ai/acre and harvested at intervals of
114 to 146 days after treatment. The grain had HP-001 residues of less
than 0.03 to 0.09 ppm, but no HP-002 residues were detected (less than 0.05
ppm) . The bran had 0.03 ppm HP-001 residues. However, no residues of HP-
001 (less than 0.03 ppm) or HP-002 (less than 0.05 ppm) were detected in
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the flour or shorts.
These residue data are sufficient to reflect residues of Mstolachlor
and its metabolites in sorghun grain and its processing fractions (bran,
flour, and shorts) and in sorghun forage and fodder.
Residues in or on Peanuts
Seventy^six~residue studies were performed in 5 major peanut growing
areas of the United States. Application rates were 3 Ibs. ai/acre and 6
Ibs. ai/acre. Analyses involved the determination of both HP-001 and HP-
002 in peanuts, peanut hulls, peanut forage, and peanut hay. The peanuts,
hulls, and hay were sampled st intervals of 128 to 159 days after
treatment. The peanut forage was sampled at intervals of 56 to 69 days
after treatment.
The peanuts had no detecable residues of either HP-001 (less than 0.03
ppm) or HP-002 (less than 0.05 ppm) due to the 3 Ibs. ai/acre application
rate. At the 6 Ibs. ai/acre rate, HP-001 residues were less than 0.03 to
0.05 ppm, and HP-002 residues were less than 0.05 to 0.10 ppn.
The peanut hulls had HP-001 residues of 0.06 to 0.24 ppm and HP-002
residues of less than 0.05 to 0.45 ppm due to the 3 Ibs. ai/acre
application rate. Residues due to the 6 Ibs. ai/acre rate were 0.07 to
0.74 ppn for HP-001 and 0.06 to 1.3 ppn for HP-002.
The peanut forage had 0.09 to 1.7 ppn HP-001 residues and 0.12 to 1.2
ppn HP-002 residues due to the 3 Ibs. ai/acre application rate. Residues
due to the 6 Ibs. ai/acre rate were 0.12 to 3.0 ppn HP-001 and 0.14 to 1.6
ppn HP-002.
The peanut hay had 0.26 to 1.5 ppn HP-001 residues and 0.17 to 1.1 ppn
HP-002 residues due to the 3 Ibs. ai/acre application rate. From the 6
Ibs. ai/acre rate, HP-001 residues were 0.46 to 3.0 ppn and HP-002 residues
were 0.26 to 2.9 ppn.
Treated peanuts were processed to peanut cake (or, peanut meal), crude
oil, refined oil, and soapstock. Processing was performed by either
mechanical extraction or solvent extraction of the oil. The peanut cake
(or meal) and the crude and refined oil had no detectable residues of HP-
001 (less than 0.03 ppn) due to the 3 or 6 Ibs. ai/acre rates. The
soapstock had no detectable HP-001 residues due to the 3 Ibs. ai/acre rate,
but at the 6 Ibs. ai/acre rate, the soapstock had HP-001 residues of less
than 0.03 to 0.04 ppn. ND detectable residues of HP-002 (less than 0.05
ppn) were noted in the crude or refined oil, or the soapstock due to either
the 3 or 6 Ibs. ai/acre rates. The peanut cake (or meal) had no detectable
residues of HP-002 (less than 0.05 ppn) due to the 3 Ibs. ai/acre rate, but
at the 6 Ibs. ai/acre rate, the peanut cake had HP-002 residues of less
than 0.05 to 0.07 ppn.
These residue data are sufficient to reflect residues of Metolachlor
and its metabolites in peanuts, peanut forage, peanut hay, and peanut by-
products (meal, oil, and soapstock).
Residues in or on Potatoes
Residue~data were available for the root crop, potatoes. Eighty-four
residue studies were performed in seven states representing potato growing
areas. Application rates were 3 Ibs. ai/acre and 6 Ibs. ai/acre. Analyses
involved the determination of both HP-001 and HP-002 in immature (48 to 84
days after treatment) and mature (57 to 135 days after treatment) potatoes.
Residues of HP-001 in immature or mature potatoes due to the 3 Ibs.
81
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ai/acre rate were less than 0.03 to 0.05 ppm. Residues of HP-002 in
immature and mature potatoes were less than 0.05 to 0.07 ppm due to the 3
Ibs. ai/acre application rata. From the 6 Ibs. ai/acre rate, residues of
HP-001 in immature potatoes ware less than 0.03 to 0.22 ppm and less than
0.03 to 0.05 ppm in mature potatoes. Residues of HP-002 were less than
0.03 to 0.28 ppm in immature potatoes and less than 0.05 to 0.06 ppm in
mature potatoes.
We have concluded (see the discussion on 'Metabolism in Plants') that
the absence of metabolism studies on root crops precludes an understanding
of the nature of the residues in potatoes. Therefore, valid conclusions
about these reported residue levels in potatoes cannot be determined.
Residues _in Meat, Milk, Poultry, and Eggs
Residues in meat and milk were studied in a three-level feeding study
(Mattson, 1975). In this study, eleven cows were fed unlabeled Metolachlor
at levels of zero, 0.02 ppm, 1.0 ppm, and 5.0 ppm of the total diet. Milk
samples were collected at zero, 1, 2, 7, 14, 21, and 28 days. Animals were
sacrificed and samples of tissues taken at 14, 21, and 28 days. Oily milk
and tissue samples from the two highest feeding levels (1.0 and 5.0 ppm)
were analyzed.
In this study, the analytical method determined "total" residues of
Metolachlor, (i.e., parent compound and all metabolites yielding HP-001
and HP-002 after hydrolysis with 6N HCL) . All residues in milk samples
were less than the method sensitivity of 0.006 ppm for HP-001 and 0.01 ppm
for HP-002. All residues in the muscle, fat, kidney, and liver were less
than the method sensitivity of 0.02 ppm for HP-001 and 0.04 ppm for HP-002.
Tbtal C-residues (calculated as Metolachlor) were determined in
the goat metobolism study where 4.7 ppm of C-labeled Metolachlor was
fed for 10 days (Fbger and Cassidy, 1974a). Activity levels were
equivalent to 0.01 ppm in milk, 0.003 ppm in kidney, 0.07 ppm in liver,
and less than0.006 POT.in other tissues. The activity was not
characterized. When C-labeled corn biosynthesized metabolites were
fed to goats, no detectable C-residues resulted in milk or tissues
(Fbger and Cassidy, 1974b) .
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 ppm in the dry diet. Egg
samples were taken on days 1, 3, 7, 10, 14, and 21. Birds were sacrificed
after 7, 14, 21, and 28 days for tissue analysis. Cnly tissue and eggs
samples from the two highest feeding levels (0.5 and 2.0 ppm) were
analyzed. Residues as HP-001 in eggs, muscle, and fat were reported as
less than 0.02 ppm. Residues of 0.02 ppm and 0.03 ppm as HP-001 were
reported for the livers from birds fed at 0.5 and 2.0 ppm feeding levels,,
respectively. ND detectable residues (less than 0.04 ppm) of HP-002 were
found in eggs nor Jin any tissues.
From the feeding of soybean meal, hulls, and soap-stock bearing
residues of 0.1 ppm, the dietary residue level could approach 0.04 ppm for
cattle and 0.03 ppm for poultry. The feeding levels at which barely
detectable residues were found in the feeding studies represent
exaggerations of ca. 100x for cows 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 and cattle except for the fractions of soybeans. Although the
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livestock feed use of soybean fractions may lead to small residues in
meat, milk, poultry, and eggs, these residues, if present, would be at
levels below the sensitivity of the analytical methods.
Present Tolerances
In 1976, Matolachlor was registered for use on corn grain, and a permanent
tolerance of 0.1 ppm in corn grain (except popcorn) was established for
residues of Mstolachlor and its metabolites pursuant to 40 CFR 180.368 (FR
41:178, 9/13/76). Since then, Metolachlor has been conditionally registered
for use on soybeans, sorghun, and peanuts, 'conditional' upon the accepted
fulfillment of the following Tbxicology data requirements: a two-year rat
chronic feeding study, a new mouse oncogenic study, a rat oncogenic evaluation,
a teratology study in a species other than the rat, and a rat multi-generation
reproduction study. Tb accompany the registered use on soybeans and the
conditionally registered uses on sorghum and peanuts, permanent tolerances wsre
established for residues of Metolachlor and its metabolites at: 1.0 ppm for
corn forage and fodder; 0.1 ppn for soybeans; 2.0 ppm for soybean forage and
fodder; 0.02 ppn for meat, eggs, poultry, fat, meat by-products, and milk;
0.3 ppn for sorghum grain; 2.0 ppm for sorghum forage and fodder; 0.1 ppn for
peanuts; 1.0 ppn for peanut hulls; and 3.0 ppn for peanut forage and hay.
The permanent tolerances for ffetolachlor and its metabolites of 0.02 ppm for
eggs, milk, meat, fat, and meat by-products are enforced for the following
animals: cattle, goats, hogs, horses, poultry, and sheep.
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DISCIPLINARY REVIEW
Residue Chemistry Profile
Tolerance Reassessment
Generic Eata Gaps
Suggested Labeling
Residue Chemistry Profile
When Matolachlor was applied as a pre-emergence treatment at 2 Ibs./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 metabolites
conjugated with polar plant molecules such as amino acids or sugars. The
major pathway of metabolism appears to be conjugation with glutathione,
breakage of the thioglycoside bond 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 observed in corn, and pathways in peanuts and sorghum are also expected
to be similar.
The metabolism of Metolachlor in animals appears to be similar to and as
complex as that in plants. But whereas plants retain their metabolic
products, animals eliminate their Mstolachlor metabolic products almost
completely. The parent compound was rapidly metabolized and almost totally
eliminated in the urine and feces of goats, rats, and poultry, and no 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 ppm in the liver of
chickens.
Adequate ffetolachlor-specific and metabolite-specific analytical methods
are available for the detection of residues in com, soybeans, peanuts,
sorghum, meat, milk, and eggs, and data were available on actual residues in
these commodities. Residue data were also available for the root crop
potatoes.) No detectable residues were found in corn grain, and less than 1.0
ppn were found corn fodder, forage, and stover as a result of applying as much
as 6 Ibs. ai/acre. Residue data for soybeans was adequate to allow for the
wide range in the geographical characteristics of the U.S. soybean crop.
Eetectable residues in the beans, soybean meal, hulls, forage, and hay showed
that an exaggerated rate of 6 Ibs. ai/acre resulted in as much as 2.46 ppm in
hay and 0.21 ppm in the soybeans. But residues from treatments of up to 3
Ibs. ai/acre were all less than 2.0 ppm for hay and forage and 0.1 ppm for the
beans. Residue data on sorghum grain, including its processing fractions, and
sorghum forage and fodder, showed that application rates of 2 Ibs. ai/acre
resulted in combined residues which did not exceed 2.0 ppm in forage or fodder
or 0.3 ppn in grain, while a rate of 5 Ibs. ai/acre resulted in as much as 0.37
ppm in grain, and a rate of 2.5 Ibs. ai/acre resulted in as much as 3.19 ppm in
harvest fodder. Eata for peanuts showed that 3 Ibs. ai/acre was the maximum
application rate which did not cause residues in excess of 0.1 ppm in peanuts,
1.0 ppm in peanut hulls, and 3.0 ppm in peanut forage and hay. £n application
rate of 6 Ibs. ai/acre resulted in as much as 2.04 ppm combined residues in
peanut hulls, 5.9 ppm in peanut hay, and 4.6 ppm in peanut forage. 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, and
85
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METABOLIC PATHWAYS OF METOIACHEOR
IN CORN AND SOYBEANS
Metolachlor
Major path
g lucur onie
-glueuronic
-g lueuronic
86
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fat. The feeding levels at which barely detectable residues were found
represent exaggerations of about 100 times for cows and 25 times for
poultry. Finally, the absence of metabolism studies on root crops precluded
the regulatory evaluation of levels observed for potatoes.
Metolachlor has permanent tolerances of 0.1 ppm in corn grain (except
popcorn) , 1.0 ppm for corn forage and fodder, 0.1 ppm for soybeans, 2.0 ppm
for soybean forage and fodder, 0.02 ppm for meat, eggs, poultry, fat, meat by-
products, and milk, 0.3 ppm for sorghum grain, 2.0 ppm for sorghum forage and
fodder, 0.1 ppm for peanuts, 1.0 ppm for peanut hulls, and 3.0 ppm for peanut
forage and hay. The permanent tolerances for Nfetolachlor and its metabolites
of 0.02 ppm for eggs, milk, meat, fat, and meat by-products are enforced for
the following animals: cattle, goats, hogs, horses, poultry, and sheep.
Tolerance Reassessment
The only presently available 'no observed effect level1 (NOEL) on which to
base a re-assessment of Mstolachlor's established tolerances is given by a six-
month dietary study on dogs, which indicated a NOEL of 100 ppm (see the
'Tbxicology1 chapter). The following set of calculations re-assesses the
acceptability of the established tolerances for Metolachlor, that is, the
degree of hazard presented to the general population by dietary exposures to
Mstolachlor resulting from its registered end-uses.
1) The first step in the tolerance re-assessment is the calculation of a
level of Metolachlor and metabolite residues which, on the basis of
available animal studies, can probably be ingested by the general
human population without the occurrence of toxicological effects in
any individual. The only available animal study which can be used to
estimate this level was a six-month feeding study on dogs, which
demonstrated a 'no observed effect level' (NOEL) of 100 ppm in dogs.
In the context of the dog study, a dietary exposure of 100 parts
Metolachlor per million parts food is equivalent to 2.5 mg Metolachlor
per kg of dog per day. That is, the NOEL of 100 ppm is equivalent to
a NOEL of 2.5 mg/kg/day. The translation of a level which caused no
toxicological effects in animals to a level safe for humans usually
takes into account a safety factor of at least 100x, to allow for a
10x greater sensitivity of humans over test animals, and to allow for
the possibility of an individual who is 10x more sensitive than the
average person. But because of the numerous chronic data gaps for
Metolachlor, a safety factor of 2000 times is recommended. Thus, the
dog study allows us to calculate an 'allowable daily intake1 (ADI) of
2.5 mg/kg/day divided by 2000 = 0.0013 mg/kg/day
0.0013 mg/kg/day for humans. Ebr the average human, who weighs
approximately 60 kilograms, the 'maximum permissable intake1 (MPI) is
0.0013 mg/kg/day x 60 kg = 0.0750 mg/day
thus 0.0750 mg/day. This safe daily level of dietary exposure, the
MPI, will be compared to the total residue intake permitted by the
tolerances for Metolachlor.
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2)
3)
The maximum total residue intake permitted by established tolerances
is then calculated in three steps: (a) by multiplying the tolerance
level (in mg/kg) for a particular commodity by the percentage of the
total aggregate Anerican diet supplied by that commodity ('Food
Factor'); (b) then converting that value into the total mg of residue
in an individual's daily diet contributed by that commodity (where the
average human daily diet is taken to be 1.5 kg food); (c) and finally
summing the total mg of residue in an individual's daily diet from all
possible food sources„ These calculations are performed in the table
below for each of ftetolachlor's established tolerances:
Commodity Tolerance Food Factor Maximum Residue Contribution
corn (grain)
soybeans
meat, poultry
milk, dairy
eggs
sorghum
peanuts
0.10 mg/kg
0.10
0.02
0.02
0.02
0.30
0.10
1.00
0.92
13.85
28.62
2.77
0.03
0.36
0.00150 mg/day/1.5 kg diet
0.00138
0.00415
0.00858
0.00083
0.00014
0.00054
Ibtal Maximum Residue Contribution = 0.01712 mg/day/1.5 kg diet
We see that the total maximum residues (TMRC) of Metolachlor and
metabolites, from all potentially contaminated dietary sources, that
may be ingested in 1.5 kg of food each day, is 0.0171 mg.
The percentage of the toxicologically-determined 'maximum permissable
intake' (MPI) [from step (1) above] supplied by the 'total maximum
residue contribution1 (TMRC) [from step (2) above], is an indication
of the degree to which the present tolerances ensure against human
effects due to dietary exposure. For Metolachlor, the maximum
TMRC divided by the MPI x
100
0.0171 mg/day
0.0750 mg/day
%_ MPI in human diet
12TF2 %
possible residues in the average 1.5 kg daily diet is only 22.82 % of
the level which has been determined safe for the average 60 kg person
on the basis of a 2000X safety factor. This suggests that the present
tolerances are more than adequate for ensuring against the potential
hazards of human dietary exposure to Metolachlor. It also suggests
that additional dietary sources of residues may be added to the
present ones - that is, additional similar tolerances may be
established for Metolachlor - without exceeding the safe dietary level
(the MPI) .
The established tolerances for Matolachlor on corn grain, soybeans,
peanuts, sorghum, and meat, poultry, milk, and eggs have been re-assessed to be
sufficient to protect against adverse human effects with a margin of safety of
more than 2000X. Although the approval and establishment of tolerances
requires other information, calculations also indicate that certain additional
tolerances could be accommodated without exceeding the 'maximum permissable
intake' for Metolachlor in the daily diet.
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Generic Data Gaps
If a permanent tolerance is to be considered for Ntetolachlor in root crops, a
root crop plant metabolism study will be needed.
Suggested Labeling
none
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BIBLIOGRAPHY
Each of the following studies contributed useful information to the
Agency's review of the residue chemistry of Metolachlor, and is considered part
of the data base which supports registrations under this Standard.
Aziz, S.A; Ross, J.A. (1975) Analytical Method for the Determination of
Residues of CGA-24705 Soybean Metabolites as CGA-37913 and CGA-49751 by Acid
Hydrolysis. Method AG-286 dated Jun 10, 1975. Received Nov 6, 1975 under
4G1469. (Unpublished report prepared by Ciba-Geigy Cbrp., Greensboro, N.C.;
CDL:95190-E)
Balasubramanian, K.; Aziz, S.A.; RDSS, J.A. (1975) Analytical Method for the
Determination of Residues of CGA-24705 Corn Metabolites as CGA-37913 and CGA-
49751 by Acid Hydrolysis. Method AG-277 dated Jan 9, 1975. Received Mar
26, 1975 under 5F1606. (Unpublished report prepared by Ciba-Geigy Corp.,
Ardsley, N.Y.; CDL:95190-D)
Balasubramanian, K.; Gold, B.; Ross, J.A. (1974) Validation of Method AG-265
for the Determination of CGA-24705 Metabolites Which are Converted to the
CGA-37913 Moiety: GACC-74043. Received Sep 26, 1974 under 5G1553.
(Unpublished report prepared by Ciba-Geigy Corp., Greensboro, N.C. ;
CDL:94216-1)
14
Biometric Testing Incorporated (1973) Metabolism C-CGA-24705 Corn
Biosynthesized Metabolites in a Lactating Goat: A-1004. Received Sep 26f
1974 under 5G1553. (Unpublished report prepared for Ciba-Geigy COrp.,
Greensboro, N.C.; CDL:94217-J)
Ciba-Geigy Limited (1973?) CGA 24 705 Feeding Study in Milk Cows: Methods.
Received Sep 26, 1974 under 5G1553. (Unpublished report; CDL:94216-G)
Counselmanr ,C.J.; Roger, J.C. (1973) Biological Report, Goat Metabolism Study
with 0- C-CGA-24705 and 16- C-CGA-17020. Received NDV 25, 1975
under 6G1708. (Unpublished report prepared by Ciba-Geigy Corp., Greensboro,
N.C.; CDL:94984-K)
Gold, B.; Kahrs, R.A. (1975b) Freeezer Storage Stability of CGA-24705 Residues
in Com Fodder and Grain: GAAC-75062. Received Nov 25, 1975 under 6G1708.
(Unpublished report prepared by Ciba-Geigy Corp., Greensboro, N.C.;
CDL:94877-Y)
Gross, D. (1974a) Project Report ND . 8/74: Uptake, Translocation and
Degradation of CGA 24 705 in Com Grown under Controlled Conditions.
Received Sep 26, 1974 under 5G1553. (Unpublished report prepared by
Ciba-Geigy Corp., Greensboro, N.C.; CDL:94217-F)
91
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Gross, D. (1974b) Project Report to. 13/74: Addendum to Project Report No. 8/
74: Uptake, Translocation and Degradation of CGA 24 705 in Corn Grown under
Controlled Conditions: AC 2.52. Received Mar 26, 1975 under 5F1606.
(Unpublished report 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. Received Sep 26, 1974 under 5G1553. (Unpublished report
prepared by Ciba-Geigy Ltd., Basle, Switzerland; CDL:94216-D)
Hambock, H. (1974a) Project to. 7/74: Metabolism of CGA 24 705 in the Rat.
(Status of Results Gathered up to JUne 10, 1974): AC 2.52. Received Sep 26,
1974 under 5G1553. (Unpublished report prepared by Ciba-Geigy Ltd., Basle,
Switzerland; CDL:94217-L)
Bambock, H. (1974b) Project Report 12/74: Addendum to Project Report 7/74:
Metabolism of CGA 24 705 in the Rat: AC 2.52; Received Nov 25, 1975 under
6G1708-, (Unpublished report prepared by Ciba-Geigy Ltd., Basle, Switzerland;
CDL:94984-P)
Hambock, H. (1974c) Project Report to. 1/74: Distribution, Degradation and
Excretion of CGA 24 705 in the Rat. Received Sep 26, 1974 under 5G1553.
(Unpublished report prepared by Ciba-Geigy Ltd., Basle, Switzerland;
CDL:94217-K)
Helseth, J.; Cole, G. (1973) The Determination of CGA-24705 in Emulsifiable
Concentrates by Gas Liquid Chrcmatography. Method PA-9 dated Nov 14, 1973.
Received Sep 26, 1974 under 5G1553. (Unpublished report prepared by
Ciba-Geigy Corp., Greensboro, N.C.; CDL:96666^A)
Itennes, P. (1972) Biphasic Extraction of Radioactive Metabolites from Treated
Biological Material. Method AG-214 dated Aug 15, 1972. Received Sep 26, 1974
under 5G1553. (Unpublished report prepared by Ciba^eigy Corp., Ardsley,
N.Y.; CDL:94216-M)
Hormann, W.D. ; Guth, J.A.; Ebrmica, G. ; Schenker, M. (1974) CGA 24705: Gas
Gnrcmatographic Determination of Total Residues in Material of Animal
Origin. (Provisional): AC 2.53; REM 5/74. Received Sep 26, 1974 under
5G1553. (Unpublished report prepared by Ciba-Geigy Ltd., Basle, Switzerland;
CDL.-94216-E)
Bousevvorth, L.D. and Rolla, H. (1976) Residues from Metolachlor Alone and in
Tank Mix with Linuron, Metribuzin, and Liquid Fertilizer in Soybeans: ABR-
76077. (Unpublished study received Jan 19, 1977 under 7F1913; prepared by
Ciba-Geigy Corp., Greensboro, N.C.; CDL-95767-A)
Marco, G. (1974) Summary of Section D: CGA-24705-Corn: Residues Observed and
Metabolism Data Including the Analytical Methods Used: GAAC-74062. Received
Sep 26, 1974 under 5G1553. (Unpublished report prepared by Ciba-Geigy Corp.,
Greensboro, N.C. that includes studies AG-A-2929, AG^V-2969, AG-A-2973, AG-A-
3105, AG-A-3133; CDL:94217-A; 94222)
92
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Marco, G. (1975) Suimary of Section D: CGA-24705 Corn: Residues Observed and
Metabolism Data Including the Malytical Methods Used: GAAC-75001. Received
Mar 26, 1975 under 5F1606. (Lhpublished report prepared by Ciba-Gaigy Corp.,
Greensboro, N.C.; CDL.-94378-A)
Mattson, A.M. (1974) CGA-24705 Residues in Milk, Meat, Eggs and Chickens
(Three Level Feeding Studies): GAAC-74064. Received Sep 26, 1974 under
5G1553. (Unpublished report prepared by Ciba-Geigy Corp., Greensboro, N.C.;
CDL:94216-B)
Mattson, A.M. (1975) CGA-24705 Resideues in Milk, Meat, Eggs and Chickens
(Three Level Feeding Studies): GAAC-75059. Received Nov 25, 1975 under
6G1708. (Unpublished report prepared by Ciba-Geigy Corp., Greensboro, N.C.;
CDL:94878-A)
Mattson, A.M.; Fahrs, R.A. (1975b) Residues in Field Grown Corn Following Use
of CGA-24705 Determined as CGA-37913 and CGA-49751: GAAC-75015. Received Mar
26, 1975 under 5F1606. (Unpublished report prepared by Ciba-Geigy Corp.,
Greensboro, N.C. that includes studies AG-A-2967, AG-A-2982, AG^-3255, AG-A-
3289, AG-A-3299, AG-A-3328, AG-^-3383, AG-A-3501, AG-A-3005, AG-A-3153, AG-A-
3446; CDL:94379-B)
Mattson, A.M.; Rolla, H. (1975) Summary of Section D: CGA-24705-Soybeans:
Residues Observed and Metabolism Data Including the Analytical Methods Used:
GAAC-75057. Received NDV 25, 1975 under 6G1708. (unpublished report prepared
by Ciba-Geigy Corp., Greensboro, N.C. that includes studies AG^-3268, AG-A-
3466, AG-A-3523, AG-A-3570, AG-A-3650 I & II, AG-^A-3702, AG-A-3724, AG-A-
3743, AG-A-3776, AG-A-3780, AG^-3803; CDL:94984-A; 94878)
Ramsteiner, K; Karlhuber, B. (1975) CGA-24705: Determination of Total Residues
in Material of Animal Origin: AC 2.53; REM 2/75. Received Mar 26, 1975 under
5F1606. (Unpublished report prepared by Ciba-Geigy Ltd., Basle, Switzerland;
CDL:94379-I)
14
Roger, J.C.; Cassidy, J. E. (1974a) Metabolism and Balance Study of C-
CGA-24705 in a Lactating Goat: GAAC-74020. Received Sep 25, 1974 under
5G1553. (Unpublished report prepared by Ciba-Geigy Corp., Greensboro, N.C.;
CDL:94217-G)
14
Roger, J.C.; Cassidy, J.E. (1974b) Metabolism and Balance Study of j6- C-
CGA-24705 Corn Biosynthesized Metabolites in a Goat: M6-68-2A: GAAC-74046.
Received Sep 26, 1974 under 5G1553. (Unpublished report prepared by Ciba-
Geigy Corp., Greensboro, N.C.; CDL:94217-1)
Schenker, M. (1974) CCA 24705: Tbtal Residues in Milk and Tissues of Swiss
Cows: Switzerland 1973: AC 2.53 RVA 81/74. Received Jan 19, 1977 under
7F1913. (Unpublished report prepared by Ciba-Geigy Ltd., Basle,
Switzerland; CDL:95747-F)
93
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Schenker, M, (1975a) CGA 24705: Determination of the Degradation Product CGA
49751 in'thicken Liver: Switzerland 1973: RVA 02/75. Received Jan 19,
1977 under 7F1913. (Unpublished report prepared by Ciba-Geigy Ltd., Basle,
Switzerland; CDL:95747-1)
Sunner, D.D.; Cassidy, J.E. (1974b) The Metabolism of CGA-24705 in Cbrn: GAAC-
74050. Received Jan 19, 1977 under 7F1913. (Unpublished report prepared by
Ciba-Geigy Corp., Greensboro, N.C.; CDL:95750-C)
14
Sumner, D.D.; Cassidy, J.E. (1974c) The Uptake and Distribution of?* C-
CGA-24705 from Soil in Greenhouse Grown Corn: GAAC-74015. Received Jan 19,
1977 under 7F1913. (Unpublished report prepared by Ciba-Geigy Corp.,
Greensboro, N.C.; CDL:95750-A)
14
Sumner, D.D.; Cassidy, J.E. (1974d) The Uptake and Distribution of & C-CGA-
24705 in Field Grown Corn: GAAC-74022. Received Mar 26, 1975 under 5F1606.
(Unpublished report prepared by Ciba-Geigy Corp., Greensboro, N.C.;
CDL:94385-C)
14
Sumner, D.D.; Cassidy, J.E, (1975b) The Uptake and Distribution of j3- C
CGA-24705 from Soil in Greenhouse Grown Soybeans: GAAC-75039. Received Nbv
26, 1975 under 6G1708. (Unpublished report prepared by Ciba-Geigy Corp.,
Greensboro, N.C.; CDL:94984-G)
Sumner, D.D.; Thomas, R.D.; Cassidy, J.E. (1975) Structure Elucidation of the
Metabolites of CGA-24705 in Com:GAAC-75012. Received Mar 26, 1975 under
5F1606. (Unpublished report prepared by Ciba-Geigy Corp., Greensboro, N.C.;
CDL:94378-F)
Tweedy, B.B. (1974) CGA-24705-Corn: Summary of Ftesidues Observed and
Analytical Methods Used: GAAC-74061. Received Sep 26, 1974 under 5G1553.
(Unpublished report prepared by Ciba-Geigy Corp., Greensboro, N.C., that
includes tests number AG-A 2967, AG-A 2982. AG-A 3132, AG-A 2972, AG-A
3057, AG-A 3005, AG-A 3083, AG-A 3153, AG-A 3141, AG-A 3103, AG-A 3137, AG-A
3070, AG-A 3255, AG-A 2974, AG-A 3057 II, AG-A 3288, AG-A 3289, AG-A 3327,
AG-A 3328; CDL:94216-A)
Tweedy, B.C.; Mattson, A.M. (1974) CGA-24705: Corn Summary of Residues
Observed and Malytical Methods Used: GAAC-74067. Received Mar 26, 1975
under 5F1606. (Unpublished report prepared by Ciba-Geigy Corp., Greensboro,
N.C. that includes studies AG-A-2967, AG-A-2972, AG-A-2982, AG-A-3057, AG-A-
3103, AG-A-3132, AG-A-3137, AG-A-3141, AG-A-3255, AG-A-3289, AG-A-3299, AG-A-
3327, AG^A-3005, AG-A-3083, AG-A-3153, AG-A-2974, AG-A-3057 II, AG^A-3070,
AG^-3288, AG-A-3298, AC-^A-3325, AG-A-3326, AG-A 3406; CDL:94379-A)
94
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ECOLOGICAL EFFECTS
TOPICAL DISCUSSIONS
Corresponding to each of the Tbpical Discussions listed below is the nunber
of the sections in the 'Proposed Guidelines' of July 10, 1978 (FR Part 163)
which explain the data that the Agency will require in order to assess
Matolachlor's Ecological Effects.
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)*
Birds 163.70-1, .71-1, .71-2, .71-4, and .71-5
Wild Mammals 163.70-1, .71-3, and .71-5
Aquatic Invertebrates 163.70-1, .72-2, .72-4a(l), .72-5, and .72-6
Fish 163.72-1, .72-4, .72-5, and .72-6
Ecosystem Effects 163.71-5 and 163.72-6
* Subpart j of the Proposed Guidelines, which will
cover phytotoxic effects, has not yet been
published as final rulemaking.
Microbes
Data on the effects of pesticides on microbes are obtained from laboratory
studies employing non-radioisotopic analytical techniques. These studies
determine effects on either microbial functions or microbial populations.
The study of effects on microbial functions constitutes a more direct
approach, but some effects cannot be measured directly and population studies
may be the only recourse. Studies should be conducted over a long enough
period to demonstrate whether there is a temporary or long-lasting effect on
microbes. Three studies were submitted for Metolachlor. Two of the studies
used the population approach and one used the functional approach.
In the first population study (Bbuseworth, 1973a) , reviewers noted
variations in tabulated results, and raised questions about the aggregation,
dilution, dispersal, enumeration, and identification of selected soil
microorganisms (such as Bacillus, pseudomonas, Arthrobacter, Cellulomonas,
Cytophaga, Flavobacterium, Achromopacter, Aspergillus, Chaetomium, Fusarium
and Penicillium).These issues will require clarification before this study
can be used to support regulatory decisions.
In the other population approach study (Ercegovich, Bogus, and Buly, 1978),
a diverse selection of microorganisms with 27 species representing the family
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Actinomycetes and the following genera: Bacillus, Cellulomonas, Cytophaga,
Flavobacterium, Pseudomonas, Archromobacter, Aspergillus, ChaetomTum,
Fusarium, Penicillium, and Trlcoderma, were evaluated against three
concentrations of f-fetolachloT;5, 25, and 125 ppm. At 5 ppm, 6 of 27; at 25
ppn, 9 of 27; and at 125 ppm, 19 of 27 species were inhibited with a static
(but not cidal) effect showi. At 5 ppm, 4 of 27 species had increased counts
and 1 species did not show any effect at all three concentrations. Potential
degraders could be estimated and 10 of 27 species could have this potential.
Eata for oxygen consumption, carbon dioxide evolution, nitrogen cycling,
dehydrogenase activity, and phosphatase activity were not supplied. Because
application rates normally used for I^fetolachlor are 1-3 Ibs ai/A, the slight
inhibitory/static effect on soil commensal populations would not be as
significant as the laboratory study indicates, would be alleviated with time,
and would allow populations to recover. The effect would 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 ppm concentrations of Mstolachlor was evaluated on the soil
function processes of nitrification in two soil types: Morrison sandy loam and
Bagerstown silt loam. Morrison sandy loam did not show any inhibitory effects
at any of the three concentrations evaluated. Ragerstovvn silt loam did not
show any inhibitory effects at 5 or 25 ppm, but did show an inhibitory effect
at 125 ppm. 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 two soils varied considerably.
Ihough this latter study does not by itself fully explore the potential
effects of Mstolachlor 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
Metolachlor 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 aquatic environment, but it may also impede the
degradation of other toxics that are disposed of in sewer system drains.
A laboratory study of the effects of Metolachlor on activated sludge
metabolism is not presently available for Technical Metolachlor, and this
constitutes a data gap.
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Studies on Nfetolachlor's toxicity to algae are not presently available.
But because residues of Mstolachlor are expected to reach the freshwater
aquatic environment, if such studies were available, they would be reviewed
and assessed for information on potential effects to freshwater aquatic
ecology. The Agency will not presently require data on Nfetolachlor's effects
on algae because Subpart J of the Proposed Guidelines, which will cover
phytotoxic effects, has not yet been published as final rulemaking.
Aquatic Macrophytes
Studies about Metolachlor's effect on aquatic plants are not available.
But because residues of Matolachlor are expected to reach the freshwater
aquatic environment, if such studies were available, they would be reviewed and
assessed for information on potential effects to freshwater aquatic habitats.
The Agency will not presently require data on Matolachlor1s effects on aquatic
macrophytes because Subpart J of the Proposed Guidelines, which will cover
phytotoxic effects, has not yet been published as final rulemaking.
Terrestrial Plants
Studies on the ecological effects of Mstolachlor on non-target terrestrial
plants are not presently available. The Agency will not now require data on
Matolachlor1s effects on terrestrial plants because Subpart J of the Proposed
Guidelines, which will cover phytotoxic effects, has not yet been published as
final rulemaking.
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
intended effects has a direct impact on public health, efficacy data was not
reviewed for the Matolachlor Standard.
Birds
The minimum data required for establishing the acute and subacute toxicity
of Metolachlor to birds are the results from two 8-day dietary studies and one
oral study with technical Metolachlor. Two types of birds - waterfowl
(preferably mallard duck) and upland game (preferably bobwhite quail) are to be
tested as per the specifications in FR 163.71-1 and 163.71-2.
Five studies of technical Metolachlor's effects on birds were available for
evaluation, all performed by Fink: two studies performed in 1974, one in 1976,
and two in 1978.
Fink's 1976 study reported data on the effects of single oral doses of
technical Matolachlor to avian wildlife: the acute LD-50 for mallards (Anas
platyrhynchos) was 4640 (3000-7200, 95% confidence limits) mg/kg, indicating
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that fetolachlor is practically non-toxic, acutely, to waterfowl. But due to
deviations from recommended protocols, such as discrepancies in body weights,
this study is unacceptable for use in the regulatory process. M avian single
dose oral LD-50 determination is thus a data gap for ffetolachlor.
Acceptable data on the dietary DC-50 of technical Matolachlor for avian
wildlife are reported on the mallard (Anas platyrhynchos) (Fink, 1974a),
and the bobwhite quail (Colinus virgimanus](Fink, 1974b). The 5-day
dietary LC-50 (with 3 days observation) for both species was greater than
10,000 ppm, indicating that technical ffetolachlor is practically non-toxic,
subacutely, to upland gamebirds and waterfowl. These two studies meet the
guidelines requirement for avain dietary testing.
Because, as was seen in the Environmental Fate chapter, technical
Metolachlor is persistent under certain conditions and is stored in plant and
rotational crop tissue, information on avian reproduction effects was also
needed. In 1978, Fink performed two studies of technical Mstolachlor1 s effects
on avian reproduction.
The first reproduction study (Fink, 1978a) tested the bobwhite quail with
seventeen (17) weeks of dietary exposure during mating, egg laying, and egg
hatching. In comparison with the controls, bobwhite quail exposed to 10, 300,
and 1000 ppn Technical Mstolachlor for 17 weeks produced significantly fewer
chicks surviving to 14 days. (See table 1.)
table !_
Summary of Reproductive Success of Quail Bcposed to IVtetolachlor for 16 Ufeeks
Pesticide Percent, Chi- _ Significance
Concentration Survival Square DF Level
Control 58.8% - ~ -
10 ppm 47.0% 22.35 1 >0.001
300 ppn 37.0% 62.4 1 >0.001
1000 ppm 41.5% 44.5 1 >0.001
The number of chicks surviving to age 14 days expressed as
2 a percentage of the eggs laid.
Chisquare calculated by 2x2 Contingency Table analysis of
treatment versus control group survival.
Although the subacute dietary LC-50 to quail was shown to be greater than
10,000 ppn, there appeared to be a dose response for mortality among the
females subjected to a dietary exposure for seventeen weeks, as seen in table 2
below*
table 2
Bctowhite Quail Dosed wrth"Metolachlor for 17 Weeks
dietary dose number of female deaths
0 pptf~( control) 2
10 ppm 1
300 ppm 4
1000 ppm 7
The other reproduction study (Fink, 1978b) was performed on the mallard duck,
using the same dietary dose levels for the same 17 weeks. In comparison with
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the controls, mallard ducks exposed to 10 and 1000 ppm Technical Metolachlor
for 17 weeks produced significantly fewer chicks surviving to 14 days. (See
table 3 below.)
table _3
Summary of Reproductive Success of Mallards Exposed to Mstolachlor for 16 Weeks
Pesticide Percent, Chi- ~ Significance
Concentration Survival Square DF Level
Control 57.0% - ~ ^~~
10 ppm 48.0% 11.29 1 >0,001
300 ppn 57.6% 0.053 1 NS
1000 ppm 51.0% 5.26 1 >0.025
The number of ducklings surviving to age 14 days expressed as
_ a percentage of the eggs laid.
Chisquare calculated by 2x2 Contingency Table analysis of
treatment versus control group survival.
But the female ducks suffered no dose-related mortality, as seen in table 4
below. The one duck mortality at 300 ppm was attributed to an impacted
table _4
Mallard Duck Dosed with Metolachlor for; 17 Weeks
dietary dose number £f female deaths
0~ppn (control)0
10 ppm 0
300 ppn 1
1000 ppm 0
oviduct, rather than to a chemical-related effect. These two 1978 studies by
Fink are sufficient to satisfy the guideline requirements for avian
reproductive testing.
In sunmary, all guideline data requirements for avian effects are fulfilled
except the acute oral LD-50, which is presently a data gap for Metolachlor.
Cn the basis of available data, this Standard will not require precautionary
labeling addressing toxicity to birds.
Wild Mammals
Mammalian toxicity data are not needed for MBtolachlor because the data on
laboratory animals reviewed in the Toxicology Chapter are generally sufficient
for an estimation of toxicity to wild mammals. Based on the data in
Metolachlor's Tbxicology review, there does not appear to be any unusual
toxicity, and therefore, no special precautions need be recommended.
Aquatic Invertebrates
The minimum data required for an outdoor use pesticide to establish its
acute toxicity to aquatic invertebrates is the result of one 48 or 96 hour
study using the technical, as described in FR 163.72-2. Cne such study
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by Vilkas (1976) was available for Mstolachlor. Vilkas exposed water fleas
(Daphnia magna Straus) to technical Metolachlor for 48 hours. The 48-hour
no-effect level was 5.6 ppn. The 48-hour LC-50 at 95% confidence limits is
25.1 (21.6-29.2) ppn. These data satisfy the guidelines requirement for
aquatic invertebrate testing and are sufficient to characterize Ntetolachlor as
being slightly toxic to aquatic invertebrates.
Fish
A determination of the 96-hour LC-50 of the technical compound for one
cold-water fish species (preferably rainbow trout) and one warm-water fish
species (preferably bluegill) is required for all outdoor use pesticides. The
acute' toxicity of technical Metolachlor to freshwater fizh was reported in two
studies conducted by Buccafusco (1978a, 1978b), one study by Sachsse and
LTLlman (1974) , and one study by Dionne (1978) . As shown in the following
table, some of these tests could be used to satisfy Agency data requirements,
while others, although they also offered useful information, were not directly
applicable to the data requirements.
Satisfies EPA
Species 96 hr LC-50 Author Date Data Requirements
Bluegill sunfish 10.0 ppn
Buccafusco 1978
Rainbow trout
Fathead minnow
Fathead minnow
Crucian Carp
Channel Catfish
Guppy
3.9 ppm
11.0 ppn (static)
9.2 ppn (flow)
4.9 ppn
4.9 ppn
8.6 ppn
Buccafusco
Dionne
Dionne
Sachsse
Sachsse
Sachsse
1978
1978
1978
1974
1974
1974
yes
yes
no
no
no
no
no
These tests provide sufficient information to characterize I^fetolachlor as
moderately toxic to both warm-water and cold-water fish. The guidelines
requirement for LC-50's for both types of fish has been satisified.
As was seen in the Bivironmental Fate chapter, Pfetolachlor is resistant to
hydrolysis and metabolism in soil, and has a tendency to leach. With this
potential for residues to migrate to freshwater aquatic habitats, a chronic
fish study, as described in FR 163.72-4, was required.
Che such study was available. It was performed by Dionne (1978), and
tested the effects of 97.4% Metolachlor on the reproduction of the Fathead
minnow (Pimephales promelas) . When the minnows were exposed to a measured
concentration of > 1.60 ppn, significantly (p=0.05) fewer first and second
generation fry survived. The majority of mortalities occurred during the 4th
week of exposure. The 'maximum acceptable toxicant concentration1 (MATC) , the
concentration below which no effects were observed, was reported to be between
0.78 and 1.60 ppn.
The ratio of the mTC to the LC-50 for the same species is called the
'application factor1 (AF) . Because the AF is essentially a property of the
pesticide (i.e., its acute versus its chronic mode of action) , the AF can be
used to calculate an estimated MATC for any fish species for which one knows
the 96-hour LC-50. Dividing the minnow mTC values of 0.78 and 1.60 by the 96-
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hour flow-through LC-50 for minnows (9.2 ppm) , the application factor (AF) for
Metolachlor was calculated to be between 0.08 and 0.17. This AF for
Mstolachlor was then used to calculate an estimation of the MATC for other fish
species :
estimated
species 96-hour LC-50 max acceptable tox cone (MATC)
Bluegill sunfish 10.0 ppm 0.8 ppm to 1.7 ppm
Rainbow trout 3.9 ppm 0.3 ppm to 0.7 ppm
Crucian Carp 4.9 ppm 0.4 ppm to 0.8 ppm
Channel Catfish 4.9 ppm 0.4 ppm to 0.8 ppm
Guppy 8.6 ppm 0.7 ppm to 1.5 ppm
The 1978 minnow reproduction study by Dionne satisfies the requirement for a
study of technical Metolachlor's chronic effects on a freshwater fish species,
and allows an estimation of potentially hazardous residue levels for several
other species.
Cn the basis of available acute and chronic toxicity information, which
indicates a moderate toxicity to fish, the following precautionary labeling
appears appropriate. For the technical: "Do not discharge into lakes,
streams, ponds, or public waters unless in accordance with an NPDES permit."
And for the emulsifiable concentrate: "Avoid direct application to any body of
water. Eb not apply where runoff is likely to occur. Eb not contaminate water
by cleaning of equipment or disposal of wastes."
Ecosystem Effects
The need for studies of ecosystem effects, including such field studies as
those described in FR 163.71-5 and 163.72-6, cannot presently be determined
because the available laboratory data have not yet been correlated with an
estimation of potential 'environmental concentrations'. If fate or monitoring
information suggest the potential for chronic adverse effects to fish or birds,
the Agency will consider imposing a requirement for field data.
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DISCIPLINARY REVIEW
Ecological Effects Profile
Ecological Effects tezard Assesanent
Generic Data Gaps
Suggested Labeling
Ecological Effects Profile
Technical Metolachlor: Scientifically sound data on the toxicity of
Metolachlor to wildlife are available on a wide range of non-target
organisms. Fish appear to be the most sensitive class tested.
A diverse selection of soil microorganisms were evaluated against
three concentrations of Metolachlor: 5f 25, and 150 ppm. Oily static, not
cidal, effects were noted (Ercegovich, Bogus, and Buly, 1978). Another
study using the same concentrations showed no effects on nitrification at
the two lower levels, and only temporary inhibition at the high level
(Ercegovich, Vallejo, and Bogus, 1978). Effects on wastewater treatment
microorganisms have not yet been investigated.
Subacute dietary studies on the mallard duck and bobwhite quail, as
well as an acute oral test on the mallard duck, indicate that Metolachlor
is practically non-toxic to birds, tfcwever, in reproduction studies,
Bobwhite Quail and Mallard ducks fed 10 ppm in their diet for 17 weeks
experienced significant (p<0.001) reproductive impairment: fewer chicks
surviving to 14 days. Ten parts per million was the lowest of three
concentrations tested, and therefore a "no observed effect level1 has not
been established.
Based on data reviewed in the Tbxicology chapter, Metolachlor appears
to present a low toxicity to wild mammals. Eata on the acute toxicity of
Mstolachlor to the water flea show that the herbicide is slightly toxic to
aquatic invertebrates, with a 48-hour LC-50 of 25.1 ppm»
Fish were clearly the most acutely sensitive of the organisms tested.
The cold-water fish Rainbow trout had an LC-50 of 3.9 ppm, and the warm-
water Bluegill sunfish had an LC-50 of 10.0 ppm, indicating that
Metolachlor is likely to be moderately toxic to both cold and warm water
species. Indeed, tests on additional warmwater species, including the
Crucian carp, Channel catfish, Guppy, and Fathead minnow showed comparable
LC-50's ranging between 4.9 and 11.0 ppm. In a fish reproduction study on
the Fathead minnow, fry of both the F,. and F. generations suffered
significant mortality at levels greater than 1.6 ppm. The MATC was
estimated for the various fish species, and ranged from 0.3 to 1.7 ppm.
Emulsifiable Concentrate Matolachlor: Information on the toxicity of
the Emulsifiable Concentrate to non-target wildlife organisms is
effectively supplied by the studies on the Technical chemical.
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Ecological Effects Hazard Assessment
Technical Metolachlor: Ebr non-target organisms 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 wall as unintentional discharges, such
as by spillage or fire, could result in fish and wildlife exposure. Though
•unintentional discharges could result in a risk to fish and birds in the
contaminated area, the Agency does not perceive unintentional discharges to
be any more likely with Technical Mstolachlor than with any other technical
chemical. As concerns the disposal of wastes or factory effluent,
Ecological Effects data are available to EPA officials responsible for
issuing a discharge permit should one become necessary, and to EPA
officials responsible for regulating the handling of hazardous wastes.
Emulsifiable Concentrate: As was pointed out in the Exposure Profile in
the Environmental Fate chapter, because of the relative stability of
Matolachlor to hydrolysis, its high mobility in the terrestrial
environment, and its potential resistance to metabolic degradation, it is
anticipated that the spraying of Metolachlor on certain terrains and soil
types, and in certain types of weather, may result in the contamination of
aquatic sites adjacent to treated fields. It is possible that fish can
be exposed to levels of Mstolachlor that would cause significant mortality
to fry, although the presently available exposure information does not lead
the Agency to suspect significant acute effects on freshwater fish.
Other non-target organisms of potential concern include microbes,
non-target plants, soil and surface invertebrates, mammals, and birds.
Soil microbes and the nitrification process do not appear to be threatened,
and mammalian wildlife do not appear threatened by acute effects. Cata are
not presently available on toxicity to non-target plants nor to soil and
surface invertebrates. Metolachlor's resistance to hydrolysis and
metabolism, and the possibility of non-target plant uptake, suggest that
birds may be exposed to residues in non-sensitive weeds, crops, or soil
organisms from the pre-emergent application of Metolachlor to soil. (If
Matolachlor is applied post-emergent or to non-tilled fields, a higher
dietary exposure WDuld be expected to occur to birds.) Because of
Metolachlor's low acute toxicity to birds, the acute risk to birds is
minimal. However, as concerns reproductive effects to birds, data have
indicated reproductive effects at 10 ppn dietary exposure. The presently
available exposure information is not sufficient to conclude that a harmful
exposure level will occur in Metolachlor treated fields.
Generic Data Gaps
The following are gaps in the Ecological Effects data base which will be
used to support registrations under this Matolachlor Standard. After each gap
is listed the section in the Proposed Guidelines of July 10, 1978 (FR Part 163)
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which describes that type of test and when it is required. The following
studies would test the Technical in order to assess the hazard associated with
the use of the Emulsifiable Concentrates.
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 quail). The species must be
one of those for which an LC-50 was
determined under FR 163.71-2 (see the
discussion on 'Birds') .
Suggested Labeling
For Technical Mstolachlor:
"Do not discharge into lakes, streams, ponds, or public waters unless in
accordance with an NPDES permit. Ebr guidance, contact your• regional
office of EPA."
For Emulsifiable Cbncentrate Mstolachlor:
"Avoid direct application to any body of water. ED not apply where runoff
is likely to occur. ED not contaminate water by cleaning of equipment or
disposal of wastes. ED not apply when weather conditions favor drift from
target area."
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BIBLIOGRAPHY
Each of the following studies contributed useful information to the
Agency's review of the ecological effects of Metolachlor, and is considered
part of the data base which supports registrations under this Standard.
Buccafusco, Robert J. (1978a). Acute Tbxicity Test Results of CGA-24705 to
Bluegill Sunfish (Lepomis macrochirus) . Report #BW-78-181. Received
July 13, 1978 under 100.597. (Unpublished study prepared by EG&G,
Bionimics; Submitted by Ciba-Geigy Corp., Greensboro, N.C.; GEL:234396)
Buccafusco, Robert J. (1978b). Acute toxicity Test Results of CGA-24705 to
Rainbow Trout (Salmo gairdneri) . Report #BW-78-6-186. Received July
13, 1978 under 100-597. (Unpublished study prepared by EG&G, Bionomics;
Submitted by Ciba-Geigy Corp., Greensboro, N.C.; CEL:234396)
Dionne, E. (1978). Chronic Tbxicity of CGA-24705 to the Fathead Minnow
(Pimephales promelas); received 12-13-78 under 100-587, (Prepared
by EG&G Bionomics for Ciba-Geigy Corporation, Greensboro, N.C.;
CDL:236620)
Ercegovich, C.D. ; Bogus, E.R. ; Buly, R. L. (1978) The Effects of 5, 25, and 125
PPM of Metolachlor, [2-Chloro-N-(2-ethyl-6-methylphenyl)-N-(2-metnoxy-l-
raethylethyl) acetamide] on Actinomycetes, Bacteria and Fungi in Laboratory
Culture Tests. E-2/1-CG78. Received Feb 6, 1978 under 100-583. (Uipublishe
report prepared by Pesticide Research Lab., Pennsylvania State University
for Ciba-Geigy Corp., Greensboro, N.C.; CDL:232789-F)
Ercegovich, C.D. ; Vallejo, R.P. ; Bogus, E.R. (1978). The Effects of 5, 25, and
125 PPM of Mstolachlor, [2-Chloro-N-(2-ethyl-6-methylphenyl) -N-(2-methoxy-l-
methylethyl) acetamide], on Soil Nitrification. E-3/2-CG78. Received Feb 6,
1978 under 100-583. (Unpublished study prepared by Pesticide Research Lab.,
Pennsylvania State University for Ciba-Geigy Corp., Greensboro, N.C.;
CDL:232789-G)
Fink, R. (1974a) . Eight-Day Dietary LC-50 — Mallard Ducks Technical CGA-
24705: Project No. 108-111. Received September 26, 1974 under 5G1553.
(Unpublished study by Truslow Farm, Inc. for Ciba-Geigy Corp., Greensboro,
N.C.; CDL: 112840-0)
Fink, R. (1974a) . Eight-Day Dietary LC-50 — Bobwhite Quail Technical CGA-
24705: Project No. 108-111. Received September 26, 1974 under 5G1553.
(Unpublished study by Truslow Farm, Inc. for Ciba-Geigy Corp., Greensboro,
N.C. ; CDL:112840-P)
Fink, R. (1976). Acute Oral LD-50 -Mallard Duck: CGA-24705 Technical: Final
Report. Received November 23, 1976 under 100-587. (Unpublished study
prepared by Truslow Farm, Inc. for Ciba-Geigy Corp., Greensboro, N,C.;
CDL:226955-D)
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Fink, Ro (1978a) . Che-Generation Reproduction Study - Bobwhite Quail
CGA-24750 technical Final Report; received 12-13-78 under 100-587,
(Unpublished report prepared by Wildlife International Ltd. for Ciba-Geigy
Corp., Greensboro, N.C.; GEL:236620)
Fink, R0 (1978b). Che-Generation Reproduction Study - Mallard Duck
CGA-24705 technical Final Report; received 12-13-78 under 100-587,
(Unpublished report prepared by Wildlife International Ltd. for Ciba-Geigy
Corp., Greensboro, N.C.; GEL:236620)
Ebuseworth, L.D. (1973a) Effect of CGA-24705 on Microbial Populations in Two
Soils: Report ND . 2. Received Sep 26, 1974 under 5G1553. (unpublished study
prepared by University of Missouri—Columbia, Department of Plant Pathology
for Ciba-Geigy Corp., Greensboro, N.C.; CEL:94222-F)
Sachesse, K.; ULlman, L. (1974b). Acute Toxicity to Rainbow Trout, Crucian
Carp, Channel Catfish, Bluegill, and Guppy of Technical CGA-24705: Project
tto. Siss 3516. Received September 26, 1074 under 5G1553. (Unpublished
study prepared by Ciba-Geigy Ltd., Basle, Switzerland, that includes a
cable from Ciba-Geigy Corp., Greensboro, N.C. on fish name change;
CrL:112840-N)
Vilkas, A.Go (1976). Acute Toxicity of CGA-24705 Technical to the Water Flea
Daphnia magna. Received isbvember 23, 1976 under 100-587. (unpublished
study prepared by Aquatic Environmental Sciences, Union Carbide Corp. for
Ciba-Geigy Corp., Greensboro, N.C.; CEL:226955-C)
10 6
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REGULATORY RATIONALE
TECHNICAL METOLACHLOR
The risks which determine the conditions of a technical chemical's
registrability are those risks which arise in handling, storing, shipping,
re-formulating, and disposing of it - that is, in the various aspects of its
disposition as a manufacturing-use chemical. Technical Metolachlor, at least
ninety percent the pure compound, is an off-white, odorless liquid, soluble in
water, and miscible with several organic solvents.
The Delimitation of Risks to Humans
To review~our Toxicology findings, Technical Mstolachlor1 s acute
toxicity to hunans appears to be mild: it has a low acute oral toxicity,
it is not readily absorbed by the skin, it has a very low inhalation
toxicity, and no eye irritation effects are observable. The only
significant short-term effect is skin sensitization. Once an exposure
occurs, Metolachlor is rapidly metabolized and excreted. Although the
available chronic effects studies were not sufficient to satisfy all the
Agency's requirements for such testing, the data that were available showed
no evidence of general chronic, teratogenic, fetotoxic, oncogenic, or
mutagenic effects.
The Exposure Profile pointed out that for persons involved in the
handling, storage, shipment, or re-formulation 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 repeated dermal exposure,
and occasionally, by accident, an occular exposure.
In sun, the acute risks of handling the presently registered
Technical Metolachlor are minimal, and the currently available studies
show no evidence of general chronic, oncogenic, mutagenic, fetotoxic, or
teratogenic effects due to Matolachlor. Available studies only suggest
a potential dermal sensitization problem for factory, transport, or re-
formulation workers.
For the professional handling of a manufacturing-use chemical by
factory, transport, or re-formulation workers, acute risks higher than
those found for Technical Matolachlor are normally acceptable,- because the
Agency expects members of such occupations to be responsive to a chemical's
accompanying label precautions. However, because it is evidently possible
to manufacture a Technical Matolachlor with a mild acute toxicity, the
Agency should only register Technical Metolachlor products that fall into
'Toxicity Categories' IjT"or~IV"for each of the Tive acute tests: acute
oral toxicity, acute~dermaT~tox'i'cTty, acute InHalation toxicity, primary
eye irritation, and 'primary dermal iTritation^ Technical Matolachlor
products that faTT~into numerically lower "Ibxicity Categories' are likely
to be substantially different in either impurities or inerts from the
chemical on which this Standard is based, and so a proposal to amend the
Standard should accompany the application for their registration.
The Agency considers the dermal sensitization risk to be acceptable
in the case of Technical Matolachlor because two reasonable regulatory
actions are available for helping to preclude repeated dermal exposures:
a label warning that the chemical "May cause skin sensitization" which will
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alert handlers to the possibility of the effect; and a label direction to
"Wear protective clothing (coveralls and gloves) while handling _o_£ using
this product".(Jhless the absence of dermal sensitization effects can be
demonstrated by the appropriate toxicology study, these two requirements
should be applied to the registration of any Technical Metolachlor product.
Because the most likely route of long-term exposure to a Technical
Metolachlor is by repeated dermal contact, the above actions which help
limit dermal exposures also serve to render more acceptable the potential
for the as-yet-undetermined risk of chronic effects, at least until
adequate long-term studies have been completed.
The Delimitation of Risks to Wildlife
To review~our Ecological Effects findings, the available wildlife
studies suggested several potential hazards for wildlife. Though the
toxicity of Technical Metolachlor to birds was showi to be low in one
dietary LC-50 test, a several month dietary exposure of 300 ppn was shown
to produce reproductive effects in upland game birds. Fish were the most
sensitive species tested, with relatively low L£-50's and a high mortality
for fry in the presence of concentrations less than 2 ppm. Aquatic
invertebrates have a lesser, though still significant, sensitivity.
As stated in our Exposure Profile, for wildlife in the proximity of
Technical Metolachlor manufacture, handling, storage, shipping,- re-
formulation, or disposal, intentional discharges of the chemical into the
environment, such as by disposal or drainage, as well as unintentional
discharges, such as by spillage or fire, could conceivably result in
wildlife exposures. But the pathway of exposure which is the most direct
concern is the discharge of effluent or the disposal of Matolachlor wastes
into freshwater aquatic habitats. The organisms that may be exposed by
route of freshwater aquatic discharge are fish, aquatic invertebrates, and,
because of plant uptake, local avian or mairmalian herbivores.
Thus, if the Technical chemical or effluent from its manufacture or
re-formulation were disposed of or allowed to drain into freshwater aquatic
habitats, the stability of the Matolachlor compound to hydrolysis and its
potential resistance to metabolic degredation, together with its moderate
acute and serious chronic toxicity for fresh water fish and their fry,
indicate a potential long-term risk for fish. Further, birds continually
feeding on contaminated leaves or seeds could conceivably suffer
reproductive effects, and aquatic invertebrates, integral to the watershed
ecology, could possibly suffer a small population reduction. The suggested
label precaution, "Do not discharge into lakes, streams, ponds, or public
waters unless Jji accordance with an NPDES permit" is therefore necessary to
help control contamination of the~quatic environment.
As concerns storage and disposal, it should be noted that soil
injection, landspreading, and any unauthorized land disposal would not be
acceptable for Technical Matolachlor because of its demonstrated mobility
in soil and resistance to metabolic degradation. Metolachlor's stability
to extremes of pH preclude acid or alkalai hydrolysis as a technique for
disposal or container decontamination. Further, data are not presently
available to demonstrate the effectiveness or safety of incineration or
open burning, nor the degree of potential damage to activated sludge water
treatment processes caused by disposal into a sewage system. Thus the only
disposal practice that the Agency can recommend at this time is to place
Technical Metolachlor _in_ a_ landfill disposal site approved for pesticides.
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Until the risks, particularly for fish and birds, are quantified by
the comparison of toxic concentrations with anticipated 'environmental
concentrations' resulting from measured applications to use sitas, the
potential for hazard to wildlife cannot be quantified. Nevertheless, bar-
ring a severe concentrated spill, and providing that discharge and disposal
practices are appropriately controlled, the Agency does not perceive an
imminent hazard to wildlife from the handling or manufacturing use of
Technical Matolachlor. Lhtil these risks are quantified, the Agency should
presune that as concerns Ecological Effects, a Technical Metolachlor
product will be registrable if it bears the following warnings:
Ihder 'hazards to wildlife1: "Do not discharge into lakes, streams,
ponds, ££ public waters, unless in accordance with an NPDES permit. For
guidanceT contact your Regional Office of EPA.11' OnHer 'storage and
disposal1 directions: "Open dumping or~open burning is prohibited.
Thoroughly clean containers "or tanks before re-use, o~re-seal and offer
for recycling or reconditioning". Pesticide or rinsat~that cannot be
used, recycled~or chemically reprocessed, and tanks or other containers
that cannot be refused or recycled; should~~be disposed"^ in a landfill'
approved for pesticide's. Consult federal, "state, o r lo^al'~d'i's'posaT
authorities for approved' alternative procedures."
Section 162.11(a) of 40 CFR states that the Agency shall presune against
the registration of a pesticide product which meets or exceeds certain specific
risk criteria set forth therein. Because the available data on potential
effects to man or the environment do not indicate that any of these risk
criteria would be met or exceeded for a Technical Metolachlor which meets all
the 'standards' suggested above, the Agency shall presume that such Technical
Metolachlor is registerable for sale, distribution, and re-formulation in the
In i ted States.
EMULSIFIABLE CONCENTRATES of METOEACHLOR
This Standard will presently only cover 'emulsifiable concentrate1 type
formulations of Metolachlor, because the hazards due to other formulation types
such as granulars or dusts, and the significantly different application methods
they would require, are not adequately considered by the data available on the
presently registered formulations. Additional data pertaining to the product
chemistry, environmental fate, toxicology, residue chemistry, and ecological
effects of new formulation types and their application methods would be needed
to evaluate the registrability of such products.
Emulsifiable Concentrate formulations containing Metolachlor alone are
appropriate for the control of weeds in non^kmestic, outdoor, terrestrial food-
crop fields. When not 'tank mixed' with other herbicides, the Emulsifiable
Concentrates should be applied by conventional ground spray or through center
pivot irrigation systems before, during, or after planting, but always before
the emergence of the crop seedlings. The applications must be pre-emergence
because residue data are not available to show that tolerances will not be
exceeded by post-emergence applications, and because the ecological effects of
a post-harvest application have not been determined, particularly for birds.
The establishment of tolerances for agricultural-use pesticides requires
certain residue chemistry data. Occasionally, sufficient residue chemistry
data are available for several crops within a crop grouping (e.g., 'grain
crops', 'leafy vegetables', or 'root crop vegetables') so that the Agency can
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establish a toleranca for other crops in the grouping without requiring
additional data. For Matolachlor, however, the presently available residue
data are only sufficient to support tolerances for, and thereby enable the use
of Emulsifiable Cbncantrate Matolachlor on: corn grown for grain (excluding
popcorn), soybeans, (Concep-treated) grain sorghun, and peanuts. Presently
available residue data show that Metolachlor Emulsifiable Concentrate can be
applied pre-emergence to corn fields at a rate of up to 6 Ibs. ai/acre, to
soybean fields at a rate of upTo 3 J5s.~ai/acre, _to grain sorghum fields _at
rates of up to ~2=l72 Ibs .~i7acre',~and to_ peanuts ~at_ _up _to 3 Ibs. ai/acre,
withou~e3cceearing the established tolerances.
If the crop treated with the Bnulsifiable Concentrate is lost, it may be
replanted immediately with com, soybeans, peanuts, or (Concap-treated) grain
sorghum without a second treatment.
The recommended rotational crop restriction (conditional upon an agreement
to generate the required data as specified) is as follows: Small grains may be
planted 4-1/2 months following treatment. Field corn (except fresh corn and
popcorn), cotton, soybeans, peanuts, sorghum, root crops, and small grains may
be planted in the spring following treatment. Do not graze or feed forage o_r
fodder EronTco'tto'n or small grains to livestockT" All other rotational crops
may be planted 18 months after application.
The Delimitation of Risks _to Humans
It may be~recalled~from our Tbxicology review that the presently
registered Emulsifiable Concentrate formulations of Metolachlor have sane
potential for serious acute effects. The eight pounds per gallon
formulation could produce severe irritation and burns on contact. The six
pounds per gallon formulation can cause serious eye irritation, including
irreversible corneal opacity. Like the active ingredient, any Emulsifiable
Concentrate may produce skin sensitization with repeated exposures.
The Ekposure Profile determined that for an outdoor agricultural
ground spray, there is a possibility of dermal and eye exposure from the
splashing that may occur while diluting and tank mixing, and in the loading
of spray equipment. If an Emulsifiable Concentrate has a high vapor
pressure, as do most products with organic solvents, an unprotected mixer
or diluter who is handling an open container without adequate ventilation
may be exposed to funes. Also of concern are the spray droplets generated
by the application of a ground-sprayed agricultural pesticide, which could
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 are expected to occur at finite
levels, due to residues on food (and in animal products from livestock fed
Metolachlor-treated plant parts) which will be less than the established
tolerances.
The Agency concludes that there is presently no evidence of general
chronic, teratogenic, fetotoxic, oncogenic, or mutagenic effects due to
end-use of Metolachlor. Miown chronic dietary hazards for the general
population were estimated to be avoidable at exposures less than 0.0750 mg
per day. But there may be acute risks involved in the end-use of
Bnulsifiable Concentrate formulations. The acute risks to hunans caused by
the handling of these Emulsifiable Concentrate formulations consist
primarily in the potential for skin and eye burns from accidental
splashing, the potential for skin sensitization from repeated dermal
contact, the danger of fune inhalation from mixing or loading in a poorly
ventilated area, and the danger of spray inhalation near the point of
ground spray application. Except for the skin sensitization hazard, the
severity of these hazards from the use of a particular formulation depends
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upon its acute toxicity and irritation categories. The sensitization
hazard depends directly upon the concentration of the active ingredient.
First we will consider the acceptability of the various acute risks.
As concerns acute oral toxicity, because Mstolachlor is not intended
for domestic use, and is not mixed with seeds or foodstuffs before
application, there is very little chance of accidental oral exposure, and
the Agency should accept Metolachlor formulations with an acute oral
toxicity as high~as Category II. A Category I would not~be acceptable
unless the formulation were classified for restricted use by certified
applicators.
As concerns acute dermal toxicity, because even with appropriate label
precautions there1 is still a reasonable chance for occasional accidental
dermal exposures in mixing, diluting, loading, or spraying, the Agency
should not accept a Metolachlor formulation with an acute dermal~boxicity
higher than Category III.~
As concerns acute inhalation toxicity, although Matolachlor is an
outdoor use pesticide and is commonly mixed, diluted, and loaded outdoors,
because most Emulsifiable Concentrates have a high volatility, a high
inhalation exposure could even occasionally occur outdoors. The actual
spraying could also result in inhalation exposures for those nearby.
Nevertheless, because the loading and mixing do commonly occur outdoors,
because the spraying is limited to ground spraying, and because the
accompanying warning "Do not breathe vapors" would be reasonably effective
with even untrained applicators, a Category II inhalation toxicity should
be acceptable. A formulation with a Category I inhalation toxicity,
however, would require sane protective apparatus, and without restricting
the chemical to use by trained applicators, the Agency cannot be assured
that such equipment would be consistently used. An additional limit that
will not affect efficacy can be put on the exposure to vapors by limiting
the physical/chemical property -vapor pressure1 to less than 1.0 mm Hg.
The Agency will thus find acceptable a Matolachlor formulation with an
acute inhalation toxicity as high but no higher than a_ Category II, and a
vapor pressure between 0.03~and 1.0 mm Hg.
With the above limitations on th~e~ 3e~rmal and inhalation hazards, the
Agency does not see the need to prescibe a re-entry interval for
Metolachlor. Nevertheless, users should be aware that the "application of
a pesticide in such a manner as to directly or through drift expose workers
or other persons except those knowingly involved in the application" is
expressly prohibited under 40 CFR 170.3.
As concerns primary eye irritation, the classification guidelines
suggest that any Category I toxicity rating should imply a restriction of
the product's use to certified applicators, unless some aspect of
"formulation, packaging, or method of use of the product (which) can
reasonably be expected to eliminate the route of exposure" is available and
is likely to be effective [162.11 (c)(2)]. In the case of Metolachlor as
an agricultural-use crop field spray, the requirement to "Wear goggles or_
face shield when handling" which accompanies a Category I formulation can
be expected to be complied with by even untrained agricultural workers or
applicators, and it may be assumed that such protective equipment as
goggles are conmonly available to pesticide applicators. This assurance
allows the Agency to accept a_ Metolachlor formulation with _a primary eye
irritation as high~as Category ^.
As concerns primary dermal~irritation, because of the likelihood of
accidental dermal exposures, the Agency should not accept £ formulation
with a dermal irritation higher~than Category II. (Category II is
acceptable for dermal irritation, but not for dlFrmal toxicity, because sane
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high concentration accidental dermal exposures are certain to occur, and a
high exposure to a Category II dermal toxicity solution brings the user too
close to a risk of whole body poisoning, including death, while a Category
II dermal irritation could at worst result in local dermal injury.) The
Agency can further delimit the risk of dermal irritation, without affecting
efficacy, by limiting the physical/chemical property 'pli' _to the relatively
neutral range of pH 6 _to pH _8.
Th~e Agency consTders~~Ehe dermal sensitization risk to be acceptable in
the case of Emulsifiable Concentrates of Metolachlor because two reasonable
regulatory actions are available for helping to preclude repeated dermal
exposures: a label warning that "The active ingredient, metolachlor, may
cause skin sensitization", which will alert handlers to the possibility of
the effect;and label directions to "Wear gloves and protective clothing
when handling", "Wash thoroughly after handling", and "Remove and wash"
contaminated clothing before re-use". Even though applicators and
agricultural workers who may cone in contact with the chemical might be
untrained in the handling of pesticide chemicals, the Agency can reasonably
assune that the simple and unencumbering direction to wear gloves or other
protective clothing will be obeyed most of the time. Even if, as stated
above, occasional accidental dermal exposures are highly likely, only a
continous series of repeated exposure could lead to dermal sensitization.
Three additional physical/chemical properties of concern for their
potential health effects are flammability, explosiveness, and
corrosiveness. Because Emulsifiable Concentrate Metolachlor will be
handled by untrained applicators and is likely to be used or mixed near
combustion engines and other machinery, it should not be "flammable" by
Agency standards, which means that its flashpoint should be above 80°F.
Because the solvents, however, are likely to bring the flashpoint Below
150 F, users should be warned: "Do not use or store near heat or open
flame" in both the 'Precautionary Statements''" and 'Storage and~Disposal'
sections of the label. Second, because it would require special training
for safe handling, no Matolachlor Emulsifiable Concentrate should be
explosive or shock sensitive. Third, a corrosive pesticide might Horn
though application tanks or storage containers, potentially resulting in
harmful skin or eye exposures. But a slight corrosiveness to steel or tin
is acceptable if the warning "Do not store in unlined containers or tanks"
appears in both the 'Precautionary Statements"1 and Storage and Disposal'
sections of the label.
Finally, because without protective clothing the most likely route of
long-term exposure for applicators is the dermal route, the above actions
which help limit dermal exposures also serve to render more acceptable the
potential for the as-yet-undetermined risks of chronic effects, at least
until adequate long-term studies have been completed. The known chronic
risks of a dietary exposure for the general public are limited by the
fact that residues resulting from acceptable use patterns will not exceed
established tolerances for the crops to which the formulations are applied
and for products from animals which are fed these crops. Because the
chronic effects data base is not yet complete, the Agency will presently
consider additional food uses for Metolachlor on an incremental risk and
benefits assessment basis. The established tolerances provide a more than
2000 fold safety factor between the highest potential human dietary
exposure and the "no observed effect level" from a valid six-month feeding
study on dogs.
112
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The Delimitation of Risks to Wildlife
The potential effects to wildlife due to Pfetolachlor exposures
resulting from the use of the formulations are estimated in toxicity
studies on the Technical. To review our Ecological Effects findings for
the Technical, the available wildlife studies suggested several potential
hazards for wildlife. Though the toxicity of Technical f-fetolachlor to
birds was shown to be low in one dietary LC-50 test, a several month
dietary exposure of 10 ppm was shown to produce reproductive effects in
upland game birds. Fish were the most sensitive species tested, with
relatively low LC-50's and a high mortality for fry in the presence of
concentrations less than 2 ppm. Aquatic invertebrates have a lesser,
though still significant, sensitivity to Nfetolachlor.
As stated in our Exposure Profile, several aspects of Metolachlor's
fate, including its tendency to leach or runoff, its stability to
hydrolysis, and its resistance to microbial degradation, combine to suggest
that the end-use application of Metolachlor formulations could contaminate
surface and groundwater, thereby exposing fish, freshwater plants and
animals, animals which drink the contaminated water, or carnivores which
feed on the contaminated fish. Further, because of Metolachlor's
demonstrated uptake by rotational crops, it may be assumed that some
aquatic or terrestrial plants may either suffer phytotoxic exposures or
pass Matolachlor residues on to herbivores, including birds.
Thus, several concerns about wildlife risks arise from the suspicion
that Pfetolachlor residues will migrate to and persist in aquatic habitats.
The most notable of these potential, but as yet unquantified, risks is that
to the fry of freshwater fish. Lesser but potentially serious risks may
exist for adult fish, nesting herbivorous birds, or aquatic invertebrates,
the last of which can be integral to the ecology of terrestrial watersheds.
Uhtil the Agency compares toxic concentrations with the as yet
undetermined 'environmental concentrations' resulting from measured
applications to use sites, the potential for hazard cannot be quantified.
But unless the formulated pesticide is directly applied to or disposed of
into water, heavily applied in an area of hilly terrain with soils of a
high organic content, or applied when weather conditions favor drift to
aquatic sites, the Agency does not forsee an immanent risk to wildlife from
the routine use of Mstolachlor formulations. Thus, the Agency considers
these as yet unquantified risks to be temporarily acceptable, at least
until a quantification becomes possible, if the labels for Mstolachlor
formulations present the following statements under 'hazards to wildlife':
"Avoid direct application _to any body ^f water. Do not apply where runoff
is likely to occur. Do not~~contaminate water by cleaning of equipment or
disposal o~F~wastes. Do not apply when weatHer~conditions Tavor drift from
areas tr'eaTed."
As with the Technical, disposal practices involving soil injection,
landspreading, hydrolysis, incineration, open burning, or discharge into a
sewage system are not supported by the current (fata. Disposal should thus
be limited to landfill disposal sites approved for pesticides: "Open
dumping or_ open burning _is prohibited. Do not re-use empty container;
triple rinse or equivalent. Pesticide or rinsate that cannot _be used,
recycled, or cHemically reprocessed, an? triple-rinsed containers with
their rinsaTeTshould be disposed of _in a landfill approved for
pesticIcTes. Consult federal, state, or local disposal autHonties for
approved alternative procedures."
113
-------
Section 162.11(c) of 40 CFR states .that the Agency may classify for
•general use1 , that is, for purchase and use by any member of the general
public, any end-use pesticide product which meets certain specific criteria
set forth therein, or else has a formulation, package, or method of use which
can reasonably be expected to eliminate the route of exposure for each hazard
which exceeds a criterion [162.11 (c)(2)]. The available data on potential
effects to man and the environment show that all of these criteria, except for
eye irritation, would be met for an Hnulsifiable Concentrate Mstolachlor which
was in accord with all the 'Standards' suggested in the above discussions;
and eye exposure can be effectively eliminated by the requirement to "Wear
goggles or face shield when handling". An Emulsifiable Concentrate Metolachlor
which meets all the Standards suggested in the above discussions is therefore
classified for 'general use'.
114
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APPENDIX
115
-------
CHEMICAL DATA SHEETS
Chemical Data Sheets have been prepared for the components, hydrolysis
products, and known metabolites of manufacturing-use Metolachlor. The Data
Sheets are divided into Components COM001 through COM011, Hydrolysis Products
HP001 and HP002, and Metabolites MET001 through MET024. Chemical Data Sheets
are not available for MET025 and MET026, though their structures are given in
the Environmental Fate chapter.
117
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COMPONENT NUMBER COM001
01. Chemical Abstracts Chemical names;
01 Acetamide, 2-chloro-N-(2-ethyl-6-raethylphenyl)-N-(2-methoxy-l-
methylethyl) - (CA9)
02 o-Acetotoluidide, 2-chloro-6 ' -ethyl-N- (2-methoxy-l-methylethyl) -
(CAS)
02. Other Chemical Names;
01 2-Chloro-N- (2-ethyl-6-methylphenyl) -N- (2' -methoxy-1' -methylethyl) -
acetamide
02 Acetanilide, 2-chloro-2'-ethyl-N-(2-methoxy-l^nethylethyl)-6'-methyl-
03 N- (2' -Methoxy-1' -methylethyl) -2-ethyl-6-methyl-chloroacetanilide
04 N- (Chloroacetyl) -6-ethyl-N- (2-methoxyisopropyl) -o-toluidine
03. Structural Formula;
^^NTT*
04. Molecular (Empirical) Formula;
C 15H22C1N°2
05. Chemical Abstracts (CAS) Registry Number;
06. Approved Common Name;
01 Metolachlor
07. Other Common Names, Trade Names, or Codes;
01 Dual
02 CGA No. 24705
119
-------
Chemical Data Sheets COM-002 through COM-011 have been
emitted in this Sample Registration Standard because of
confidentiality claims by the manufacturer.
120
-------
HYDRQLYTIC PRODUCT NUMBER HP001
01. Chemical Abstracts Chemical Names;
01 1-Propanol, 2-[(2-ethyl-6-inethylphenyl)amino]- (CA9)
02 1-Propanol, 2-(6-ethyl-o-toluidino)- (CAS)
02. Other Chemical Names;
01 1-Propanol, 2-(2-ethyl-6-methylanilino)-
02 2-[(2-Ethyl-6-methyl)amino]-1-propanol
03. Structural Formula;
04. Molecular (Empirical) Formula;
05. Chemical Abstracts (CAS) Registry Number;
06. Approved Common Name; None
07. Other Common Names, Trade Names, or Codes;
01 CGA NO. 37913
02 PHP (Propanol hydrolytic product)
121
-------
HYDRDLYTIC PRODUCT NUMBER HP002
01. Chemical Abstracts Chemical Names;
01 3-Morpholinone, 4~(2-ethyl~6-methylphenyl)-2-hydroxy-5-roethyl-
02 3-Morpholinane, 4-(6-ethyl-2-tolyl)-2-hydroxy-5-roethyl-
02. Other Chemical Names;
01 4-(2-Ethyl-6-methylphenyl)~2-hydroxy-5~roethyl-3-morpholinone
03. Structural Formula;
04. Molecular (Empirical) Formula?
05. Chemical Abstracts (GAS) Registry Number?
06o Approved Correnon Name? None
07. Other Common Names, Trade Names, or Cedes;
01 CGA No. 49751
02 MHP (iRorpholinone hydrolytic product)
122
-------
METABOLITE NUMBER MET001
01. Chemical Abstracts Chemical Names;
01 Acetamide, N-(2-ethyl-6-methylphenyl)-2-hydroxy-N-(2-methoxy-l-
methylethyl)- (CA9)
02 o-Acetotoluidide, 6'-ethyl-2-hydroxy-N-(2-methoxy-l-methylethyl)-
(CA8)
02. Other Chemical Names;
01 Acetanilide, 2'-ethyl-2-hydroxy-N-(2-methoxy-l-methylethyl)-6'-methy1-
02 N- (2-Ethyl-6-methylphenyl)-2-hydroxy-N-(2-methoxy-l-
methylethyl )acetamide
03. Structural Formula;
04. Molecular (Empirical) Formula;
C15H23N03
05. Chemical Abstracts (CAS) Registry Number;
06. Approved Conroon Name; None
07. Other Common Names, Trade Names, or Codes;
01 CGA NO. 40172
123
-------
METABOLITE NUMBER MET002
01. Chemical Abstracts Chemical Names;
01 Acetamide, N-(2-ethyl-6-methylphenyl)-2-hydroxy- (CA9)
02 o-Acetotoluidide, 6'-ethyl-2-hydroxy-(CA8)
02. Other Chemical Names;
01 Acetanilide, 2'-ethyl-2-hydroxy-6'-methyl-
02 N-(2-Ethyl-6-methylphenyl)-2-hydroxyacetamide
Structural Formula;
04. Molecular (Empirical) Formula;
05. Chemical Abstracts (CAS) Registry Number;
06. Approved Common Name; None
07. Other Common Names, Trade Names, or Codes;
01 CGA No. 37735
124
-------
METABOLITE NUMBER MET003
01. Chemical Abstracts Chemical Names;
01 Acetamide, 2-chloro-N-(2-ethyl-6-methylphenyl)-N-(2-hydroxy-l-
raethylethyl)- (CA9)
02 o-Acetotoluidide, 2-chloro-6'-ethyl-N-(2-hydroxy-l-methylethyl)-
(CA8)
02. Other Chemical Names;
01 Acetanilide, 2-chloro-2l-ethyl-N-(2-hydroxy-l-methylethyl)-6'-nethyl-
02 2-Chloro-N- (2-ethyl-6-methylphenyl)-N- (2-hydroxy-l-
methylethyl)acetamide
03. Structural Formula;
\ ^CH-CM-
ct
04. Molecular (Empirical) Formula;
C14H20C1N02
05. Chemical Abstracts (CAS) Registry Number;
06. Approved Cannon Name; None
07. Other Common Names, Trade Names, or Codes;
01 CGA No. 41638
125
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METABOLITE NUMBER MET004
01. Chemical Abstracts Chemical Names;
01 DL-Alanine, N-(2-ethyl-6-methylphenyl)-N-(hydroxyacetyl)- (CA9)
02 DL-Alanine, N-(6-ethyl-o-tolyl)-2-(hydroxyacetyl)- (CAS)
02. Other Chemical Names;
01 Propanoic acid, 2-[N-(2^thyl-6-methylphenyl)-2-hydroxyacetamido]
02 Propionic acid, 2-[N-(6-ethyl-o-tolyl)-2-hydroxyacetamido]-
03 N- (2-Ethyl-6-methylphenyl)-N-(hydroxyacetyl)alanine
03. Structural Formula;
\ xCH— COOH
04. Molecular (Empirical) Formula;
C14H19N03
05. Chemical Abstracts (CAS) Registry Number;
06. Approved Common Name; None
07. Other Common Names, Trade Names, or Codes;
01 CGA No. 46129
126
-------
METABOLITE NUMBER MET005
01. Chemical Abstracts Chemical Names;
01 Acetamide, N-(2-ethyl-6-methylphenyl)-N-(2-^nethoxy-l-methylethyl)'
(CA9)
02 o-Acetotoluidide, 6'-ethyl-N-(2-methoxy-l-methylethyl)- (CAS)
02. Other Chemical Names;
01 Acetanilide, 2'-ethyl-N-(2-methoxy-l-methylethyl)-6I-methyl-
02 N-(2-Ethyl-6-methylphenyl) -N-(2-methoxy-l-methylethyl)acetamide
03. Structural Formula;
04. Molecular (Empirical) Formula;
C15H23ira2
05. Chemical Abstracts (CAS) Registry Number;
06. Approved Common Name; None
07. Other Common Names, Trade Names, or Codes;
01 Dechlorometolachlor
02 CGA No. 41507
127
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METABOLITE NUMBER MET006
01. Chemical Abstracts Chemical Names;
01 Acetamide, N-(2-ethyl-6-methylphenyl)-N-(2-hydroxy-l-methylethyl)•
(CA9)
02 o-Acetotoluidide, 6'-ethyl-N-(2-hydroxy-l-methylethyl)- (CA8)
02. Other Chemical Names;
01 Acetanilide, 2'-ethyl-N-(2-hydroxy-l-methylethyl)-6'-methy1-
02 N-(2-Ethyl-6-methylphenyl)-N-(2-hydroxy-l-methylethyl)acetamide
03. Structural Formula;
r
-CHjOH
v-wnj
'V
-------
METABOLITE NUMBER MET007
01. Chemical Abstracts Chemical Names;
01 Acetamide, N-(2-ethyl-6-methylphenyl)- (CAS)
02 o-Acetotoluidide, 6'-ethyl- (CAS)
02. Other Chemical Names;
01 Acetanilide, 2'-e thy 1-6'-me thy 1-
02 &-(2-Ethyl-6-methylphenyl)acetamide
03. Structural Formula;
04. Molecular (Empirical) Formula;
05. Chemical Abstracts (CAS) Registry Number;
06. Approved Common Name; None
07. Other Common Names, Trade Names, or Codes;
01 CGA No. 42444
129
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METABOLITE NUMBER MET008
01. Chemical Abstracts Chemical Names;
01 3-Morpholinone, 4-(2-ethyl-6-methylphenyl)-5-methyl- (CAS)
02 3-Morpholinone, 4-(6-ethyl-o-tolyl)-5-methyl- (CAS)
02. Other Chemical Names;
01 4-(2-Ethyl-6-methylphenyl)-5-methyl-3-morpholinone
03. Structural Formula;
04. Molecular (Empirical) Formula;
05. Chemical Abstracts (CAS) Registry Number;
06. Approved Common Name; None
07. Other Common Names, Trade Names, or Codes;
01 CGA No. 40919
130
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METABOLITE NUMBER MET009
01. Chemical Abstracts Chemical Names;
01 Acetamide, 2-chloro-N-(2-ethyl-6-methylphenyl)- (CA9;
02 £-Acetotoluidide, 2-chloro-6'-ethyl- (CAS)
02. Other Chemical Names;
01 Acetanilide, 2-chloro-2'-ethy1-6'-methyl
02 2-Chloro-N- (2-ethyl-6-methylphenyl) acetamide
03. Structural Formula;
04. Molecular (Empirical) Formula;
05. Chemical Abstracts (CAS) Registry Number;
06. Approved Common Name; None
07. Other Common Names, Trade Names, or Codes;
01 CGA No. 13656
131
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METABOLITE NUMBER MET010
01. Chemical Abstracts Chemical Names;
01 Benzenamine, 2-ethyl-N-(2-methoxy-l-raethylethyl)-6-methyl- (CA9]
02 oj-Toluidine, 6-ethyl-N-(2-methoxy-l-methylethyl)- (CAS)
02. Other Chemical Names;
01 Aniline, 6-ethyl-N-(2-methoxy-l-methylethyl)-6-^nethyl-
0 2 2-Ethyl-N_- (2-methoxy-l-methylethyl) -6-methylbenzenamine
03. Structural Formula;
04. Molecular (Empirical) Formula;
05. Chemical Abstracts (CAS) Registry Number;
06. Approved Common Name; None
07. Other Common Names, Trade Names, or Codes;
01 CGA No. 38502
132
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METABOLITE NUMBER MET011
01. Chemical Abstracts Chemical Names;
01 Acetamide, N-(2-ethyl-6-methylphenyl)-2-mercapto-N-(2-methoxy-l-
methylethyl)-,S-conjugate with Glutathione
02 o-Acetotoluidide, 2'-ethyl-2-mercapto-N-(2-methoxy-l^nethylethyl)-,
S-conjugate with Glutathione
02. Other Chemical Names;
01 Acetanilide, 2'-ethyl-2-inercapto-N-(2-methoxy-l-methylethy)-6'-
methy1-,S-conjugate with Glutathione
02 Glutathione, sulfide with 2-chloro-N-(2-ethyl-6-methylphenyl)-N-
(2-methoxy-l-methylethyl)acetamide
03 Glutathione, sulfide with 2-chloro-6'-ethyl-N-(2-methoxy-l-
methylethyl)-o-acetotoluidide
03. Structural Formula;
04. Molecular (Empirical) Formula;
05. Chemical Abstracts (CAS) Registry Number;
06. Approved Camon Name; None
07. Other Common Names, Trade Names, or Codes;
01 Metolachlor glutathione conjugate
02 CGA No. 43826
133
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METABOLITE NUMBER MET012
01. Chemical Abstracts Chemical Names;
01 Acetamide, N-(2-ethy1-6-methyIphenyl)-2-mercapto-N-(2-methoxy-l-
methylethyl)-, S-con jugate with Glucuronic acid (CA9)
02 o-Acetotoluidide, 2'-ethyl-2-mercapto-N-(2-methoxy-l^nethylethyl)-,
S-conjugate with Glucuronic acid (CAS)
02. Other Chemical Names;
01 Acetanilide, 2'-ethyl-2-mercapto-N-(2-methoxy-l-methylethyl) -6' -
methyl-,S-conjugate with Glucuronic acid
02 Glucuronic acid, 1-S-[[[(2-ethy1-6-methyIphenyl)(2-methoxy-l-
methylethyl )-amino]carbonyl]methyl]-1-thio-
03 Glucuronic acid, 1-S-[[(6-ethyl-o-tolyl)(2-methoxy-l-methylethyl)
carbamoyl]methyl]-1-thio-
03. Structural Formula;
04. Molecular (Empirical) Formula;
C21H30"°8S
05. Chemical Abstracts (CAS) Registry Number;
06. Approved Common Name; None
07. Other Common Names, Trade Names, or Codes;
01 Metolachlor glucuronic acid conjugate
02 Compound N
134
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METABOLITE NUMBER MET013
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 pj-Acetotoluidide, 6'-ethyl-N-(2-hydroxy-l-methylethyl)-2-mercapto-,
0-glucoside, S-conjugate with Glucuronic acid (CAS)
02. Other Chemical Names;
01 Acetanilide, 2'ethyl-N-(2-hydroxy-l-methylethyl)-2-mercapto-6'-
methyl-, 0-glucoside, S-conjugate with Glucuronic acid
02 Glucuronic acid, 1-S-[[(6-ethyl-o-tolyl)(2-glucosyl (1) -1-
methylethyl)carbamoyl]methyl]-1-thio-
03 Glucuronic acid, 1-S-[[[(2-ethyl-6-methylphenyl)(2-glucosyl(1)-1-
methylethyl)amino]carbonyl]methyl]-1-thio-
03. Structural Formula;
,CH
04. Molecular (Empirical) Formula;
05. Chemical Abstracts (CAS) Registry Number;
06. Approved Common Name; None
07. Other Common Names, Trade Names, or Codes;
01 Compound No. 0
135
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METABOLITE NUMBER MET014
01. Chemical Abstracts Chemical Names;
01 Acetamide, N-(2-ethyl-6-methylphenyl)-N-(2-hydroxy-l-methoxyethyl)-2-
mercapto-, S-conjugate with Glucuronic acid (CA9)
02 o-Acetotoluidide, 2'-ethyl-N-(2-hydroxy-l-methylethyl)-2-mercapto-,
S-conjugate with Glucuronic acid (CAS)
02. Other Chemical Names;
01 Acetanilide, 2'-ethyl-N-(2-hydroxy-l-methylethyl)-2-mercapto-6I-
methyl-, S-conjugate with Glucuronic acid
02 Glucuronic acid, 1-S-[[[(2-ethyl-6-methylphenyl)(2-hydroxy-l-
methylethyl)amino]carbonyl]methyl]-1-thio-
03 Glucuronic acid, 1-S-[[(6-ethyl-o-tolyl)(2-hydroxy-l-
methylethyl)carbamoyl]methyl]-1-thio-
03. Structural Formula;
04. Molecular (Empirical) Formula;
C2QH28N08S
05. Chemical Abstracts (CAS) Registry Number;
06. Approved Common Name; None
07. Other Common Names, Trade Names, or Codes;
01 Eemethyimetolachlor glucuronic acid conjugate
136
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METABOLITE NUMBER MET015
01. Chemical Abstracts Chemical Names;
01 Acetamide, N-(2-ethyl-6-methylphenyl)-2-hydroxy-N-(2^nethoxy-l-
methylethyl)-, O-conjugate with Glucuronic acid (CA9)
02 o-Acetotoluidide, 2'-ethyl-2-hydroxy-N-(2-fnethoxy-l-methylethyl)-,
O-conjugate with Glucuronic acid (CAS)
02. Other Chemical Names;
01 Acetanilide, 2'-ethyl-2-hydroxy-N-(2-methoxy-l-methylethyl)-6'-
methyl-, O-conjugate with Glucuronic acid
02 Glucuronic acid, 1-0-[[[(2-ethyl-6-methylphenyl)(2-methoxy-l-
me thy lethyl )amino] carbony]methyl]-
03 Glucuronic acid, 1-0-[[(6-ethyl-o-tolyl)(2-methoxy-l-methylethyl)-
carbamoy 1 ] me thy 1 ] -
03. Structural Formula;
Ctl,
-------
METABOLITE NUMBER MET016
01. Chemical Abstracts Chemical Names;
01 Acetamide, N-(2-ethyl-6-methylphenyl)-2-hydroxy-N-(2-hydroxy-l-
methylethyl)-, O-conjugate with Glucuronic acid
02 £-Acetotoluidide, 2'-ethyl-2-hydroxy-N-(2-hydroxy-l-methylethyl)-,
O-conjugate with Glucuronic acid
02o Other Chemical Names;
01 Acetanilide, 2'-ethyl-2-hydroxy-N-(2-hydroxy-l-methylethyl)-6'-methyl-,
O-conjugate with Glucuronic acid
02 Glucuronic acid, 1-0-[[[(2-ethyl-6-methylphenyl)(2-hydroxy-l-
methylethyl )amino] carbonyl]methyl]-
03 Glucuronic acid, 1-0-[[(6-ethyl-o-tolyl)(2-hydroxy-l-methylethyl)-
carbamoyl]methyl]-
03,, Structural Formula;
COOM
04. Molecular (Empirical) Formula;
C20H29I:D9
05. Chemical Abstracts (CAS) Registry Number;
06o Approved Cannon Name; None
07. Other Common Names, Trade Names, or Codes;
01 Desmethylmetolachlor glucuronic acid conjugate
138
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METABOLITE NUMBER MET017
01. Chemical Abstracts Chemical Names;
01 Acetamide, N-(2-ethy1-6-methyIphenyl)-2-hydroxy-N-(2-hydroxy-l-
methy lethyl)-, 0-glucoside, 0-conjugate with Glucuronic acid (CA9)
02 £-Acetotoluidide, 6'-ethyl-2-hydroxy-N-(2-hydroxy-l-methylethyl)-,
O-glucoside, O-conjugate with Glucuronic acid (CAS)
02. Other Chemical Names;
01 Acetanilide, 2'-ethyl-2-hydroxy-N-(2-hydroxy-l-methylethyl)-6'-
methyl-,0-glucoside, O-conjugate with Glucuronic acid
02 Glucuronic acid, 1-0-[[(6-ethyl-o-tolyl)(2-glucosyl(1)-1-
methylethyl)-carbamoyl]methyl]
03 Glucuronic acid, 1-0-[[[((2-ethyl-6-methylphenyl)(2-glucosyl(1)-1-
methylethyl)amino]carbonyl]methyl]-
03. Structural Formula;
04. Molecular (Empirical) Formula;
C26H39ig°14
05. Chemical Abstracts (CAS) Registry Number;
06. Approved Common Name? None
07. Other Common Names, Trade Names, or Codes; None
139
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METABOLITE NUMBER: 018
01. Chemical Abstracts Chemical Names:
01 Quinoline, N-(2-methoxy-l-methylethyl)-8-
ethyl-3-hydroxy-2-oxo-l,2,3,4-tetrahydro-
02. Other Chemical Names:
01 8-Ethyl-3-hydroxy-N-(2-methoxy-l-methylethyl)
2-oxo-l,2,3,4-tetrahydroquinoline
03. Structural Formula:
04. Molecular (Empirical) Formula:
05. Chemical Abstracts (CAS) Registry Number:
06. Approved Common Names, Trade Names, or Codes:
140
-------
METABOLITE NUMBER: 019
01. Chemical Abstracts Chemical Names:
01 Acetamide, 2-hydroxy-N-(2-methyl-6-vinylphenyl)
N-(2-methoxy-l-methylethyl)-
02. Other Chemical Names:
01 2-hydroxy-N-(2-mothy1-6-vinylphenyl)-N-
(2^nethoxy-l-methylethyl) acetamide
03. Structural Formula:
04. Molecular (Empirical) Formula:
05. Chemical Abstracts (CAS) Registry Number:
06. Approved Common Names: None
07. Other Common Names, Trade Names, or Codes:
141
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METABOLITE NUMBER: 020
01. Chemical Abstracts Chemical Names:
01 Quinoline, 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:
04. Molecular (Empirical) Formula:
05. Chemical Abstracts (CAS) Registry Number:
06. Approved Cortmon Names: None
07. Other Common Names, Trade Names, or Codes:
142
-------
METABOLITE NUMBER: 021
01. Chemical Abstracts Chemical Names:
01 Quinoline, 8-methyl-N-(2-methoxy-l-methylethyl)-2-
oxo-1,2,3,4-tetrahydro
02. Other Chemical Names:
01 8-Methyl-N-(2-methoxy-l-methylethyl)-2-oxo
1,2,3,4-tetrahydroquinoline
03. Structural Formula:
04. Molecular (Empirical) Formula:
05. Chemical Abstracts (CAS) Registry Number:
06. Approved Common Names: None
07. Other Common Names, Trade Names, or Codes:
143
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METABOLITE NUMBER: 022
01. Chemical Abstracts Chemical Names:
01 Aniline, N-(2-methoxy-l-methylethyl)-2-methyl-6-vinyl-
02. Other Chemical Names:
01 N-(2-methoxy-l-methylethyl)-(2-methyl-6-vinyl)
aniline
03. Structural Formula:
04. Molecular (Empirical) Formula:
05. Chemical Abstracts (CAS) Registry Number:
06. Approved Common Names: None
07. Other Common Names, Trade Names, or Codes:
144
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METABOLITE NUMBER: 023
01. Chemical Abstracts Chemical Names:
01 Indole, 2,3-dihydro-N-(2-methoxy-l-methylethyl)-7-methyl-
02. Other Chemical Names:
01 N- (2-methoxy-l-methylethyl) -7-methyl-2,3-dihydroindole
aniline
03. Structural Formula:
-OH—OHa
04. Molecular (Empirical) Formula:
C13H19NO
05. Chemical Abstracts (CAS) Registry Number:
06. Approved Common Names: None
07. Other Common Names, Trade Names, or Codes:
145
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METABOLITE NUMBER: 024
01. Chemical Abstracts Chemical Names:
01 Quinoline, N-(l-hydroxyethyl)-8-methyl-2-oxo-l,2,3,4-tetrahydro-
02. Other Chemical Names:
01 8-Methyl-N-(1-hydroxyethyl)-2-oxo-l,2,3,4-tetrahydrcquinoline
03. Structural Formula:
04. Molecular (Empirical) Formula:
05. Chemical Abstracts (CAS) Registry Number:
06. Approved Common Names: None
07. Other Common Names, Trade Names, or Codes:
146
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BIBLIOGRAPHY
147
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GUIDE TO THE USE OF THIS BIBLIOGRAPHY
Content of_ the Bibliography
This bibliography contains citations of all the studies reviewed by EPA in
arriving at the positions and conclusions stated elsewhere in this Standard.
The two primary sources for these studies were: (a) the body of data submitted
to EPA and its predecessor agencies in support of pest regulatory decisions on
pesticide registration, and (b) published technical literature. The
bibliography cites and distinguishes between three types of studies:
(1) Studies which were found to contribute useful information to the
Agency's review of Mstolachlor and are considered part of the data
base which supports registrations under this Standard. (Each of these
studies also appears in one or more of the Disciplinary Chapter
bibliographies.) These studies are identified by an asterisk (*)
placed beside their citation.
(2) Studies which were examined and judged to be inappropriate for use in
developing the Standard. These studies do not have any mark placed
beside their citation.
(3) Standard reference materials. These materials are identified by a
small circle (o) placed beside their citation.
Units of_ Entry
The unit of entry in this bibliography is called a "study". In the case of
published materials, this corresponds closely to an article. In the case of
unpublished materials submitted to the Agency, we have sought to identify
documents at a level parallel to a published article from within the typically
larger volunes in which they were submitted. The resulting "studies" generally
have a distinct title (or at least a single subject), can stand alone for
purposes of review, and can be described with a conventional bibliographic
citation. We have also attempted to unite basic documents and commentaries
upon them, treating them together as a single study.
Form _of the Entry
The entries in the bibliography are sorted by author, date of the
document, and title. Each entry consists of a bibliographic citation
containing standard elements. In the case of materials submitted to EPA, these
elements are followed by a description of the earliest known submission. The
bibliographic conventions used reflect the standards of the American National
Standards Institute (ANSI), explanded to provide for special needs. Some
explanatory notes of specific elements follow:
(a) Author. Whenever we could confidently identify one, we have chosen
to show a personal author. When no individual was identified, we have
shown an identifiable laboratory or testing facility as author. As a
last resort, we have shown the first known submitter as author.
(b) Document Date. When the date appears as four digits with no
question marks, we took it directly from the document. When a four
digit date is followed by a question mark, the bibliographer deduced
the date from evidence in the document. When the date appears (19??),
we were unable to determine or estimate the date of the document.
149
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(c) Title. This is the third element in the citation. In some cases it
has been necessary for our bibliographers to create or enhance a
document title. Pny such editorial insertions are contained between
square brackets.
(d) Trailing Parentheses. Ebr studies submitted to us in the past, the
trailing parentheses include (in addition to any self-explanatory
text) the following elements describing the earliest known submission:
(1) Submission Date. Immediately following the word
'received1 appears the date of the earliest known
submission.
(2) Administrative Number. The next element, immediately
following the word 'under', is the registration number,
experimental permit number, petition number, or other
administrative number associated with the earliest known
submission.
(3) Preparer and/or Submitter. Fbllowing the phrase 'prepared
by' is the name of the facility which conducted the study or
reported its results, and following the phrase 'prepared
for1 is the name of the submitter who submitted the data to
support some application or petition.
(4) Volume Identification. The final element in the trailing
parentheses identifies the EPA accession number of the
volime in which the original submission of the study
appears. The six-digit accession number follows the symbol
'CDL', which stands for "Company Data Library." This
accession number is in turn followed by an alphabetic suffix
which shows the relative posiution of the study within the
volume. Fbr example, within accession number 123456, the
first study \vould be 123456-A; the second, 123456-B; the
26th, 123456-Z; and the 27th, 123456-AA.
150
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* Affiliated Medical Research, Incorporated (1974a) Acute Dermal LDsn of CGA-
24705 - Technical in Rabbits: Contract No. 120-2255-34. (Unpublished study
received Sep 26, 1974 under 5G1553; prepared for Ciba-Geigy Corp.,
Greensboro, N.C.; CDL:112840-E)
Affiliated Medical Research, Incorporated (1974b) Acute Dermal LDsn of CGA-
24705-6E: Contract No. 12-2255-34. Unpublished study received Sep 26,
1974 under 5G1553; prepared for Ciba-Geigy Corp., Greensboro, N.C.;
CDL:112840-F)
Affiliated Medical Research, Incorporated (1974c) Acute Inhalation Study of CGA-
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:112840-M)
Affiliated Medical Research, Incorporated (1974d) Acute Oral Toxicity in Rats
of CGA-24705-6E: Contract tto. 121-2255-34. (Unpublished study received
Sep 26, 1974 under 5G1553; prepared for Ciba-Geigy Corp., Greensboro, N.C.;
CDL:112840-B)
* Affiliated Medical Research, Incorporated (1974e) Emetic 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) Emetic 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:112840-K)
Affiliated Medical Research, Incorporated (1974h) Primary Dermal 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:112840-J)
Affiliated Medical Research, Incorporated (19741) 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:112840-H)
Affiliated Medical Research , Incorporated (1974J) Twenty-One Day Repeated
Dermal Toxicity of CGA-24705-6E in Rabbits: Contract No. 120-2255-34.
(Unpublished study received Sep 26, 1974 under 5G1553; prepared for Ciba-
Geigy Corp., Greensboro, N.C.; CDL:112840-Q)
151
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Ahrens, J.F.; Cubanski, M. (1977) Herbicides for hemlock seedbeds. Pages 315-
319, In Proceedings of the Thirty-First Annual Meeting of the Northeastern
Weed Science Society; Jan 4-6, 1977, Baltimore, Maryland. Salisbury, Md.:
[University of Maryland?].
American Institute of Biological Sciences, Aquatic Hazards of Pesticides Task
Group (1978) Criteria and Rationale for Decision Making in Aquatic Hazard
Evaluation: Report to the Environmental Protection Agency. Washington,
D.C.: U.S. E.P.A. (EPA Contract No. 68-01-2457)
o American National Standards Institute (1976). Common name for the pest control
chemical 2-chloro-N-(2-ethyl-6-methylphenyl)-N-(2-methoxy-l-methylethyl)
acetamide "metolachlor." In American National Standard: ANSI K62,198-1976.
New York: ANSI.
Anon. (1976) 2-Chloro-N-(2-ethyl-6-methylphenyl)-N-(2-methoxy-l-methylethyl)
Acetamide: Tolerances for Residues. Federal Register 41(226):51400.
* Ami, P.; Miller, D. (1976) Salmonella/Mammalian-Microsonie Mutagenicity Test
with CGA 24705 (Test for Mutagenic Properties in Bacteria): PH 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, Md: University of Maryland, Vegetable Research Farm.
* Aziz, S.A. (1974) Photolysis of CGA-24705 on Soil Slides under Natural and
Artificial Sunlight Conditions: GAAC-74102. (Unpublished study received
Mar 26, 1975 under 5F1606 prepared by Ciba-Geigy Corp., Greensboro, N.C.;
CDL:94385-J)
* Aziz, S.A.? Kahrs, R.A. (1974) Photolysis of CGA-24705 in Aqueous Solution
under Natural and Artificial Sunlight Conditions: GAAC-74041.(Unpublished
study received Sep 26, 1974 under 5G1553; prepared by Ciba-Geigy Corp.,
Greensboro, N.C.; CDL:94222-A)
* Aziz, S.A.; Kahrs, R.A. (1975) Photolysis of CGA-24705 in Aqueous Solution —
Additional Information: GAAC-75021. (Unpublished study received Mar 26,
1975 under 5F1606; prepared by Ciba-Geigy Corp., Greensboro, N.C.;
CDL.-94385-M)
* Aziz, S.A; Ross, J.A. (1975) Analytical Method for the Determination of
Residues of CGA-24705 Soybean Metabolites as CGA-37913 and CGA-49751 by Acid
Hydrolysis. Method AG-286 dated Jun 10, 1975. (Unpublished study received
Nov 6, 1975 under 4G1469; prepared by Ciba-Geigy Corp., Greensboro, N.C.;
CDL:95190-E)
Aziz, S.A.; Ross, J.A. (1976) Specificity of Analytical Method AG-286 for the
Determination of Residues of Metolachlor and Its Metabolites in Soybeans:
ABR-76083. (Unpublished study received Jan 19, 1977 under 7F1913; prepared
by Ciba-Geigy Corp., Greensboro, N.C.; CDL:95748-AC)
152
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Bailey, G.W.; Leonard, R.A.; Livank, R.R., Jr. (1976) Land Application of Waste
Materials: Transport, Detoxification, Fate, and Effects of Pesticides in
Soil and Water Environment. Ankeny, Iowa: Soil Conservation Society of
America, (p.48-78)
Balasubramanian, K.; Aziz, S.A.; Ross, J.A. (1975) Analytical Method for the
Determination of Residues of CGA-24705 Corn Metabolites as CGA-37913 and CGA-
49751 by Acid Hydrolysis. Method AG-277 dated Jan 9, 1975. (Unpublished
study received Nov 6,1975 under 4G1469; prepared by Ciba-Geigy Corp.,
Ardsley, N.Y.; CDL:95190-D)
Balasubramanian, K.; Gold, B.; Ross, J.A. (1973?) Gas Chromatographic
Determination of Residues of CGA-24705 Metabolites in Corn as CGA-37913.
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.; Ross, J.A. (1974) Validation of Method AG-265
for the Determination of CGA-24705 Metabolites Which are Converted to the
CGA-37913 Moiety: GACC-74043. (Unpublished study received Sep 26, 1974
under 5G1553; prepared by Ciba-Geigy Corp., Greensboro, N.C.; CDL:94216-I)
Ballantine, L.G. (1975) CGA-24705: Environmental Impact Statement: GAAC-75011.
(Unpublished study that includes studies AG-A 2929 I-IV 1st Rept., Ag-A 2929
I-IV 2nd Rept., AG-A 2969 I-III 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-II,
AG-A 3244 II, AG-A 3282 I (2nd)-II, AG-A 3554; received Mar 26, 1975 under
5F1606; prepared by Ciba-Geigy Corp., Greensboro, N.C. CDL:94385-A, 94376)
Ballantine, L.G. (1976a) 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-II; 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, MO.] for
Ciba-Geigy Corp., Greensboro, N.C.; CDL:95763-A]
Ballantine, L.G. (1978) Metolachlor: Update of Environmental Impact Statement.
ABR-78011. Unpublished study that includes studies AG-A 2929 I-IV 1st
Rept., AG-A 2969 I-III 1st Rept., 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, N.C. CDL:232789-A, 232789-N,
232789-0, 232789-P, 232789-Q, 232789-R, 232789-S, 232789-T)
153
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Ballantine, LoG.; Herman, M.M. (1977a) Metalochlor Plus Atrazine Plus Paraquat
Tank Mix Soil Dissipation: ABR-77068. (Unpublished study containing
studies Ortho T-4QS8, Ortho T-4089, AG-A 4084 I-IV, AG-A 4085 I-IV; received
Nov 8, 1977 under 100-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-III, AG-A 4156 I-IV, Craven Lab 76-1-D; CDL:232193-A, 232193-D,
232193-E, 232193-F) received Nov 8, 1977 under 100-EUP-59 prepared by Ciba-
Geigy Corp,, Greensboro, N.C.;
14
Barrows. M.E. (1974) Exposure of fisjj to C-CGA-24705. Accumulation
Distribution, and Elimination of C Residues. Report No.:73019-3.
(Unpublished study received Mar 27, 1975 under 5F1606; prepared by
Bionomics E G & G Environmental Consultants for Ciba-Geigy Corp.,
Greensboro, N«Co; CDL:94376-E)
Bathe, R. (1973) Acute Oral LD,-0 of Technical CGA-24705 in the Rat: Project
No. Siss 2979. (Unpublished study received Sep 26, 1974 under 5G1553;
prepared by Ciba-Geigy Corp., Ltd., Basle, Switzerland; CDL:112840-A)
Bayer, G.H. (1977) Herbicide combinations for soy, snap, and kidney beans in
Hew York. Pages 34-38, _In Proceedings of the Thirty-First Annual Meeting of
the Northeastern Weed Science Society; Jan 4-6, 1977, Baltimore, Maryland.
Salisbury Md; [University of Maryland.]
Bing, Ac (1977) 1976 pre-emergence 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, Baltimore, Maryland. Salisbury, Md.
[University of Maryland?]
14
Biometric Testing Incorporated (1973) Metabolism 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, NoC,; CDL;94217-J)
Bleidner, W.E.? Baker, H.M.; Levitsky, M.; Lowen, W.K. (1954) Determination of
3-(p-chlorophenyl)-l, 1-dimethylurea in soils and plant tissues. Journal of
Agricultural and Food Chemistry 2(9): 476-479. (Also In unpublished study
received Sep 26, 1974 under 5G1553; prepared by Ciba-Geigy Corp.,
Greensboro, N.C.s CDL;94221-A)
Bonn, J.A.? Price, J*H,; Rieck, C.E. (1976). Comparison of the herbicidal
activity of chloro-acetamides. Pages 30- , Page 150, _In Proceedings of
the North Central Weed Control Conference; December 9-11, 1975, Milwaukee,
Wisconsin, Gnaha, Neb.; by Stauffer Chemical Company 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 Texas cotton: Abstract. In Proceedings
of the 29th. Annual Meeting of the Southern Weed Science Society; Jan 27-29,
1976, Dalles,, 'Itexas< Raleigh, N.C.: Glover Printing for the Southern Weed
Science Society
154
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Buccafusco, Robert J. (1978a) Acute Toxicity Test Results of CGA-24705 to
Bluegill Sunfish (Lepomis macrochirus): Report #BW-78-6-181.
(Unpublished study received Jul 13, 1978 under 100.597; prepared by E G &
G,Bionomics, Submitted by Ciba-Geigy Corp., Greensboro, N.C.; CDL:234396)
Buccafusco, Robert J. (1978b) Acute Toxicity Test Results of CGA-24705 to
Rainbow Trout (Salmo gairdneri): Report #BW-78-6-186. (Unpublished
study received Jul 13,1978 under 100-597; prepared by E.G. & G., Bionomics,
submitted by Ciba-Geigy Corp., Greensboro, N.C.; CDL:234396)
Buckhard, N. (1974) CGA-24705: Hydrolysis of CGA 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.: Hofberg, A. (1972) Analysis of Water in Soils and Column
Adsorbants 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:94216-K)
Centre de Recherche et d'Elevage des Oncins (1974) Toxicite De 3 Mois chez le
Rat par Voie Orale du Produit CGA 24 705. [Three-Month Dietary Feeding Study
in Rats: CGA 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 immunosuppressive drug
Azathioprine. Biochemical Pharmacology 23: 1891-1901. (Also In unpublis
report received Mar 27, 1975 under 5F1606; prepared by Ciba-Geigy Corpc,,
Greensboro, N.C.; CDL:94382-A)
Ciba-Geigy Corporation (1974) Section A, CGA-24705: Name, Chemical Identity and
Composition of CGA-24705. (Unpublished study? received Sep 26, 1974 under
100-EUP-44; CDL:96505:A)
Ciba-Geigy Corporation (1975a) CGA-24705 Efficacy and Crop Safety Summary; 1973-
1974. (Unpublished study that includes efficacy and crop safety reports 1-51
and rotational bioassay reports 52-71; received Mar 27, 1975 under 5F1606;
CDL; 94383-A, 94384)
TM
Ciba-Geigy Corporation (1975b) Biological Summary: Dual 6EC Applied Alone.
(Unpublished study that includes reports 1-99; received Nov 25, 1975
under 100-EUP-43; CDL:94832-A; 94831)
Ciba-Geigy Corporation (1975c) Biological Summary: Dual 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 Summary: Dual 6EC + Sencor 50% W.P.
or Lexone Tank Mix. (Unpublished study that includes reports 1-49; received
Nov 25, 1975 under 100-EUP-43; CDL:94832-C; 94830)
155
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Ciba-Geigy Corporation (1975e) Efficacy and Crop Safety Summary GA-2-686 15G
Herbicide for Corn. (Unpublished study including summary tables and
efficacy tests 1-6, 8-14L; received Feb 9, 1976 under 100-EUP-44;
CDL:96496-B)
Ciba-Geigy Corporation (1975f) Name, Chemical Identity and Composition of CGA-
24705, (Unpublished study received Nov 25, 1975 under 100-EUP-43;
CDL:94879-A)
TM 1M
Ciba-Geigy Corporation (1975g) Results of Dual 6E and Cycle SOW
Experimental Permits. (Unpublished study; received Dec 29, 1975 under 100-
EUP 36; CDL:95053-A)
* Ciba-Geigy Corporation (1975?h) Section A, CGA-24705: Name, Chemical Identity
and composition of CGA-24705. (Unpublished study; received Nov 25, 1975
under 6G1708; CDL:96439-A)
* Ciba-Geigy Corporation (1976a) CGA-24705: Name, Chemical Identity and
Composition of CGA-24705. (Unpublished study received Nov 23, 1976 under 100-
587; prepared by Ciba-Geigy Corp., Greensboro, N.C.: CDL:226955-A)
»
Ciba-Geigy Corporation (1976b) Aerial Application. (Unpublished study that
includes reports Dual/PPI, Dual/PRE, Dual & Lorox, III.l - III.10; received
Jan 19, 1977 under 100-583; CDL:95738-E; 95757)
/ o \ / -p \
Ciba-Geigy Corporation (1976c) Dual + Sencor Pre-emergence.
(Unpublished study that includes reports I.I - 1.78 with a summary, II.1 -
11.62 with a summary and III.l - III.33 with a summary, and received Jan 19,
1977 under 100-583; CDL:95738-C:95744; 95765; 95756; 95769; 95741)
/ -p \ I TD \
Ciba-Geigy Corporation (1976d) Dual 6E + Lorox Pre-emergence.
(Unpublished study that includes reports I.I - 11.27 with a summary, and
III.l - III.28 with a summary; received Jan 19, 1977 under 100-583;
CDL:95738-D; 95740; 95760; 95759; 95758)
Ciba-Geigy Corporation (1976e) Dual^R) 6E Preemergence. (Unpublished study
that includes reports I.I - 1.139 with a summary, II.1-II.94 with a summary,
and III.l - III.33 with a summary; received Jan 19, 1977 under 100-583;
CDL;95738-B; 95742; 95766; 95743; 95752; 95751; 95762; 95761)
Ciba-Geigy Corporation (1976f) Dual(R' 6E Preplant Incorporated. (Unpublished
study that includes reports I.I - 1.40 with a summary, II.1-II.21 with a
summary and 111.1-111,19 with a summary; received Jan 19, 1977 under
100-583; CDL:95738-A; 95755; 95754; 95753)
Ciba-Geigy Corporation (1976g) Compatibility of Dual^R) 6E with Fertilizers
and Other Herbicides. (Unpublished study received Jan 19, 1977 under 100-
583; CDL:95738-H)
Ciba-Geigy Corporation (1976h) Liquid Fertilizer. (Unpublished study that
includes reports Dual/PPI, I.I - 1.8, III.1-III.5; Dual/PRE, I.I -1.4,
III.l - III.5: received Jan 19, 1977 under 100-583; CDL:95738-F; 95746)
156
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Ciba-Geigy Corporation (19761) Rotational Crops. (Unpublished study that
includes reports Dual/PRE, I. - 1.48 with a summary; DUAL/PPI, I.I - I.11
with a summary; Dual + Sencor/PRE, I.1-1.9 with a summary; Dual + Lorox/PRE,
I.I - 1.5 with a summary; received Jan 19, 1977 under 100-583; CDL:95738-G;
95745; 95739)
* Ciba-Geigy Corporation (1977a) Aerial Application. (Unpublished study that
includes reports ID-9D with a summary? received Feb 18, 1977 under 100-
583; CDL:228101-F;228122)
* Ciba-Geigy Corporation (1977b) Aerial Application. (Unpublished study
containing reports ID - 10D with a summary; 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 (1977d) Application in Liquid Fertilizers. (Unpublished
study that includes reports 1-18 with a summary; received Feb 18, 1977 under
100-583; CDL:228101-E; 228121)
Ciba-Geigy Corporation (1977e) Application in Liquid Fertilizers. (Unpublished
study containing reports 1-9 with a summary, ID - 4D with a summary;
received Jun 20, 1977 under 100-590; CDL:230672-C, 230682)
Ciba-Geigy Corporation (1977f) Application in Fertilizers. (Unpublished study
received Nov 8, 1977 under 100-EUP-59; CDL:232194-F)
Ciba-Geigy Corporation (1977g) 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 (19771) Ciba-Geigy Rating System. (Unpublished study
received Nov 1, 1977 under 100-583; CDL:232134-C)
( R} (Rl
Ciba-Geigy Corporation (1977J) Dual 6E + AAtrexv —Preemergence.
(Unpublished study that includes reports 1-35 with a summary and 1C-32C with
a summary; received Feb 18, 1977 under 100-583; CDL:228101-C; 228114? 228115)
Ciba-Geigy Corporation (1977k) Dual(R) 6E + AAtrex(R) —Preplant
Incorporated. (Unpublished study that includes reports 1-96 with a summary,
1C-32C with a summary, and 1D-10D with summary; received Feb 18, 1977 under
100-583; CDL:228101-D; 228116; 228117; 228118; 228119; 228120)
Ciba-Geigy Corporation (19771) Dual 6E Alone —Preemergence. (Unpublished
study that includes reports 1-139 with a summary, 1C-70C with a summary, and
1D-12D with summary; received Feb 18, 1977 under 100-583; CDL;228101-A:
228102; 228103; 228104; 228105; 228106; 228107; 228108)
157
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Ciba-Geigy Corporation (1977m) Dual^ ^ 6E Alone — Preplant Incorporated.
(Unpublished study that includes reports 1-82 with a summary, 1C-52C with a
summary, and 1D-11D with summary; received Feb 18, 1977 under 100-583;
CDL:228101-B; 228109; 228110; 228118; 228111; 228112; 228113)
( R} ( R}
Ciba-Geigy Corporation (1977n) Dual 8E + AAtrex^ 4- Paraquat or
Roundup. (Unpublished study containing reports 1-22 with a summary, 1C-27C
with a summary; received Nov 8, 1977 under 100-EUP-59; CDL:232194-D, 232200,
232201)
Ciba-Geigy Corporation (1977o) Dual(R) 8E -t- AAtrex(R) Early Post.
(Unpublished study containing reports 1-47 with a summary, 1C-15C with a
summary; received Nov 8, 1977 under 100-EUP-59; CDL:232194-E, 232202, 232203)
(R)
Ciba-Geigy Corporation (1977p) Dual 8E Alone. (Unpublished study
including reports 1-43 with a summary; received Nov 8, 1977 under 100-EUP-
59; CDL:232194-A, 232195)
(R)
Ciba-Geigy Corporation (1977q) Dualv '8E Alone. (Unpublished study that
includes reports 1-32 with a summary; received Nov 14, 1977 under 100-EUP-
61; CDL:96624-A; 96618)
(R ]
Ciba-Geigy Corporation (1977r) Dual /Atrazine Prepack: Chemistry Data
Section. (Unpublished study; received June 20, 1977 under 100-590;
CDL:230686-A)
Ciba-Geigy Corporation (1977s) Dual 8E + Banvel( . (Unpublished study
containing reports 1-21, with a summary, 1C-9C with a summary; received
Nov 8, 1977 under 100-EUP-59; CDL:232194-C, 232198, 232199)
Ciba-Geigy Corporation (1977t) Dual(R) 8E + Bladex^R). (Unpublished study
containing reports 1-37 with a summary, 1C-10C; received Nov 8, 1977 under
100-EUP-59; CDL:232194-B, 232196, 232197)
Ciba-Geigy Corporation (1977u) Dual + Lorox PRE. (Unpublished study received
Nov 1, 1977 under 100-583; CDL:232134-P)
Ciba-Geigy Corporation (1977v) Dual + Lorox — Soybeans Preemergence: Phyto
Summary or 1/13/77 Submission. (Unpublished study received Nov 1, 1977
under 100-583; CDL:232134-Q)
Ciba-Geigy Corporation (1977w) Dual + Lorox — Soybeans Preemergence: Phyto
Summary of 1/13/77 Submission. (Unpublished study; received Nov 1, 1977
under 100-583; CDL:232134-R)
Ciba-Geigy Corporation (1977x) Dual + Lorox PRE Yield Data. (Unpublished
study; received Nov 1, 1977 under 100-583; CDL:232134-T)
Ciba-Geigy Corporation (1977y) Dual Preemergence. (Unpublished study; received
Nov 1, 1977 under 100-583; CDL:232134-D)
158
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Ciba-Geigy Corporation (1977z) Dual(R) PRE Yields. (Unpublished study;
received Nov 1, 1977 under 100-583; CDL:232134-G)
Ciba-Geigy Corporation (1977aa) Dual PRE Yield Data (1977). (Unpublished
study; received Nov 1, 1977 under 100-583; CDL:232134-H)
Ciba-Geigy Corporation (1977ab) Dual(R) PRE Yield Questions. (Unpublished
study; received Nov 1, 1977 under 100-583; CDL:232134-I)
Ciba-Geigy Corporation (1977ac) Dual(R) + Lorox(R) Yields. (Unpublished
study; received Nov 1, 1977 under 100-583; CDL:232134-S)
Ciba-Geigy Corporation (1977ad) Dual + Lorox Yields. (Unpublished study;
received Nov 1, 1977 under 100-583; CDL:232134-U)
Ciba-Geigy Corporation (1977ae) Dual Preplant Incoroporated . (Unpublished
study; received Nov 1, 1977 under 100-583; CDL:232134-J)
Ciba-Geigy Corporation (1977af) Dual(R)PPl Yields. (Unpublished study;
received Nov 1, 1977 under 100-583; CDL:232134-M)
Ciba-Geigy Corporation (1977ag) Dual PPI Yield Data. (Unpublished study;
received Nov 1, 1977 under 100-583; CDL:232134-N)
Ciba-Geigy Corporation (1977ah) Dual^R' PPI Yield Questions. (Unpublished
study; received Nov 1,1977 under 100-583; CDL:232134-O)
Ciba-Geigy Corporation (1977ai) Dual + Sencor PRE. (Unpublished study;
received Nov 1, 1977 under 100-583; CDL:232134-V)
Ciba-Geigy Corporation (1977aj) Dual + Sencor/Lexone — Soybeans Preemergence :
Phyto Summary of 1/13/77 Submission. (Unpublished study; received Nov 1,
1977 under 100-583; CDL:232134-W)
Ciba-Geigy Corporation (1977ak) Dual + Sencor/Lexone — Soybeans Preemergence:
Phyto Summary of 1/13/77 Submission. (Unpublished study; received Nov 1,
1977 under 100-583; CDL:232134-X)
Ciba-Geigy Corporation (1977al) Dual + Sencor PRE Yield Data. (Unpublished
study; received Nov 1, 1977 under 100-583; CDL:232134-Z)
( R)
Ciba-Geigy Corporation (1977am) Dual^ + Sencor Yields. (Unpublished
study; received Nov 1, 1977 under 100-583; CDL:232134-Y)
/ T5 \ f ~D\
Ciba-Geigy Corporation (1977an) Dual^ + Sencorv 'Yields. (Unpublished
study; received Nov 1, 1977 under 100-583; CDL:232134-AA)
Ciba-Geigy Corporation (1977ao) Dual - Soybeans Preemergence Phyto and Yield
review of 1/13/77 Submission. (Unpublished study; received Nov 1, 1977
under 100-583; CDL:232134-E)
159
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Ciba-Geigy Corporation (1977ap) Dual - Soybeans Preemergence Phyto and Summary
of 1/13/77 Submission. (Unpublished study; received Nov 1, 1977 under 100-
583; CDL:232134-F)
Ciba-Geigy Corporation (1977aq) Dual — Soybeans Preplant Incorporated: Phyto
Summary of 1/13/77 Submission. (Unpublished study; received Nov 1, 1977
under 100-583; CDL:232134-K)
Ciba-Geigy Corporation (1977ar) Dual — Soybeans Preplant Incorporated: Phyto
Summary 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 summary; received Nov 1, 1977 under
100-583; CDL:232134-A)
Ciba-Geigy Corporation (1977at) M+A 4.5L - Preemergence. (Unpublished study
containing reports 1-71 with a summary, 1C-12C with a summary, and ID -16D
with a summary; 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 summary, 1C-9C with a summary, and 1D-
12D with a summary; received Jun 20, 1977 under 100-590; CDL:230672-B,
230678, 230679, 230680, 230681)
Ciba-Geigy Corporation (1977av) Response to EPA Comments,Concerning Marginal
Soybean tolerance to Dual^ PPI or PRE, Dual + Dorox^ or Dual +
Sencor Application. (Unpublished study; received Nov 1, 1977 under
100-583; CDL:232134-B)
Ciba-Geigy Corporation (1977aw) Rotational Crops. (Unpublished study
containing reports 1-13 with a summary; received Jun 20, 1977 under 100-590;
CDL:230672-E 230684)
Ciba-Geigy Corporation (1977ax) Rotational Crops. (Unpublished study including
reports Vol. 2 - Report 40 and Vol. 9 - Report 46; received Nov 8, 1977
under 100-EUP-59; CDL:232194-H, 232195, 232202)
Ciba-Geigy Corporation (1977ay) Tank Mixtures. (Unpublished study; received
Nov 14, 1977 under 100-EUP-61; CDL:96624-B)
Ciba-Geigy Corporation (1977az). Rotational Crops. (Unpublished study that
includes reports 1-49 with a summary, 1-39 with a summary; 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:94216-G)
160
-------
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) Dominant Lethal Study on CGA 24705 Technical: Mouse
(Test for Cytotoxic or Mutagenic Effects on Male Germinal Cells) PH 2.632.
(Unpublished study including Addendum; received Jan 18, 1978 under 7F1913;
CDL:96717^2; 96717-D)
Ciba-Geigy Limited (1976b) Reproduction Study CGA 24705 Tech.: Rat: Seg. II
(Test for Teratogenic or Embryotoxic Effects) PH 2.632. (Unpublished study
including Addendum; 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 CGA 24705: Siss 5726. (Unpublished study; received
Jan 18, 1978 under 7F1913; CDL:96717-E)
Coquet, B.; Galland L.; Guyot, D.; Fouillet, X.; Rouaud, J.L. (1974a) Essai de
Toxicite de 3 Mois chez Le Chien par Voie Orale du Produit CGA 24 705.
[Three-Month Oral Toxicity Trial of CGA 24 705 in Dog]: IC-DREB-R-740119.
(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.; Guyot, D.; Fouillet, X.; Rouaud, J.L. (1974b) Essai de
Toxicite de 3 Mois chez Le Rat par Voie Orale du Produit CGA 24 705. [Three
month oral Toxicity Trial of CGA 24 705 in Rats]: IC-DREB-R-740120.
(Unpublished study received Mar 1, 1974 under 5G1553; prepared by the Oncins
Research and Breeding Center for Ciba-Geigy Corp., Greensboro, N.C.;
CDL:94219-B)
Coquet, B.; Galland L.; Guyot, D.; Fouillet, X.; Rouaud, J.L. (1974c) Three-
Month Oral Toxicity Test of CGA 24 705 in Dog. A translation of: Essai de
Toxicite de 3 Mois chez Le Chien par Voie Orale du Produit CGA 24 705: IC-
DREB-R-740119. (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.; Guyot, D.; Fouillet, X.; Rouaud, J.L. (1974d) Three-
Month Oral Toxicity Test of CGA 24 705 in Rats. A translation of: Essai de
Toxicite de 3 Mois chez Le Rat par Voie Orale du Produit CGA 24 705: IC-DREB-
R-740120. (Unpublished study received Mar 1, 1974 under 5G1553; prepared by
the Oncins Research and Breeding Center for Ciba-Geigy Corp., Greensboro,
N.C.; CDL:94219-A)
161
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Counselman,4C.J.; Roger, J.C. U973) Biological Report, Goat Metabolism Study
with f6~~ C-CGA-24705 and
-------
* Dupre, G.D. (1974a) Abbreviated Anaerobic Metabolism of 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 Corp., Greensboro, N.C. CDL:94222~B)
Dupre, G.D. (1974b) Leaching Characteristics of 14C-CGA-24705 and its
Degradation Products Following Aging in Sandy Loam Soil under Greenhouse
Conditions: Report no. 73021-6. (Unpublished study received by Sep 26.. 1974
under 5G1553; prepared by Bio-dynamics Inc. for Ciba-Geigy Corp.,
Greensboro, N.C.; CDL:94222-C)
Dupre, G.D. (1974c) Runoff Characteristics of 14C-CGA-24705 Applied to
Sandy Loam Soil under Greenhouse Conditions: Report no. 73022-1.
(Unpublished study received Sep 26, 1974 under 5G1553; prepared by Bio-
dynamics Inc. for Ciba-Geigy Corp., Greensboro, H.C.; CDL:94222-D)
Elkins, D.M.; Vandeventer, J.W.; Briskovich, M.A. (1977). Effect of chemical
growth retardants on turfgrass morphology. Agronomy Journal 69(3): 458-461.
* Ellegehausen, H. (1976a) Project Report 48/76: A Model system for Estimating
the Uptake, Transfer and Degradation of Agrochemicals 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. (1976b) 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 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-E)
* Ellegehausen, H. (1977) Project Repor^Project Report 32/77: Uptake, Transfer
and Degradation of CGA 24705 (Dual1 j) 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)
Environmental Protection Agency (1977) 2-Chloro-N-(2-ethyl-6-methylphenyl)-K-(2-
methoxy-1-methylethyl-acetamide): Extension of Temporary Tolerances.
Federal Register 42 (67): 18426.
* Ercegovich, C.D.; Bogus, E.R.; Buly, R.L. (1978) The Effects of 5, 25, and 125
PPM of Metolachlor, [2-Chloro-N-(2-ethyl-6-methylphenyl)-N-(2-methoxy~l-
methylethyl) acetamide] on Actinomycetes, 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:232789-F)
* Ercegovich, C.D.; Vallejo, R.P.; Bogus, E.R. (1978) The Effects of 5, 25, and
125 PPM of Metolachlor, [2-Chloro-N-(2-ethyl-6-methylphenyl)-N-(2-methoxy-l-
methylethyl) acetamide], on Soil Nitrification. E-3/2-CG78. (Unpublished
study received Feb 6, 1978 under 100-583; prepared by Pesticide Research
Lab., Pennsylvania State University for Ciba-Geigy Corp., Greensboro, N.C.;
CDL:232789-G)
163
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Eschiapati, D.; Dachler, C. (1976) Metetilachlor + Atrazine, a new herbicide
for corn crops. Resumes XI Seminario Brasileiro de Herbicidas e Ervas
Daninhas, Londrma, 1976: 44-45.
Fink, R. (1974a) Eight-Day Dietary LCSQ — Mallard Ducks Technical CGA-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. (1974b) Eight-Day Dietary LCSO~ Bobwhite Quail Technical CGA-24705:
Project No. 108-111. (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,n - Mallard Duck: CGA-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)
Fink> R- (1978a) .. Qie-Generatiorr Reproduction. Study - Bobwhite- Quail
CGA-24750 technical Final Report; received 12-13-78 under 100-587,
(Unpublished report prepared by Wildlife- International Ltd.. for; Ciba-Geigy
Corp.,. Greensboro,. N.C,,- CDEi236620)
Finkv R_ (1978b) » One-Generation- Reproduction Study — MaHard Dude
CG&-24705 technical Final Report; received 12.-13-78 under 100-587,
(Unpublished, report prepared by Wildlife: International. Ltd- for Coba-Gsigy
.r- Greensboro r N.C.? CHLi23662Cl)
Frans, R.E.; Richardson, J.T.; Gordon, E.C. (1977) Herbicide Field Evaluation
Trials on Field Crops, 1976. Fayetteville, Ark.: University of Arkansas,
Department of Agronomy. (Arkansas Agricultural 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,
Department of Agronomy. (Arkansas Agricultural Experiment Station,
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Fritz, H. (1976) Reproduction Study CGA 24705 Tech. Rat: Seg. II: (Test for
Teratogenic or Embryotoxic 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.; Ebner, L. (1974) CGA 24705, A new grasskiller
herbicide. Pages 787-794, In Proceedings of the 12th British Weed Control
Conference; Nov 18-12, 1974 Brighton, England. Begbroke Hill, Oxford,
England: ARC Weed Research Organization.
Gesme, J.; Albanese, E.; Marias, A.J. (1977) Report to Ciba-Geigy Corporation:
Carcinogenicity Study with CGA-24705- Technical in Albino Mice: IBT No. 622-
07925 (8532-07925). (Unpublished study received Jan 18, 1978 under 7F1913;
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)
164
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Gfeller, W. (1974) Tolerability Trial in Milk Cows with CGA 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. Aubin, Switzerland;
CDL:94216-F)
Gold, B.; Kahrs, R.A. (1975a) DC-200: An Alternate Gas Chronatographic Column
for the Determination of CGA-37913: GAAC-75026. (Unpublished study received
Mar 26, 1975 under 5F1606; 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 6G1708; prepared by Ciba-Geigy Corp., Greensboro, N.C.; CDL:94877-
Gross, D. (1974a) Project Report No. 8/74: Uptake, Translocation and
Degradation of CGA 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 CGA 24 705 in Corn Grown under
Controlled Conditions: AC 2.52. (Unpublished study received Mar 26, 1975
under 5F1606; 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 systems
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: Metabolism of CGA 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. (1974b) Project Report 12/74: Addendum to Project Report 7/74:
Metabolism of CGA 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 5G1553; prepared by Ciba-Geigy Ltd., Basle, Switzerland; CDL:94217-K)
Harrison, W.A.; (1975) Report to Ciba-Geigy Corporation: Acute Toxicity Studies
with CGA 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)
1 6 5
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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 100-EUP-44; prepared
for Ciba-Geigy Corp., Greensboro, N.C.; CDL:96496-C)
Heinrichs, L. (1975) Determination of CGA-24705 and Procyazine in GA-2-686 15G
by Gas Chromatography: Method PA-71 T dated Oct 9, 1975. (Unpublished
study received Feb 9, 1976 under 100-EUP-44; prepared by Ciba-Geigy Corp.,
Greensboro, N.C.; CDL:96496-A)
/ TJ \
Heinrichs, L. (1976) The Determination of Metolachlor in Dual 6E by Gas
Liquid Chromatography. Method PA-9A dated Dec 16, 1976. (Unpublished study
received Nov 14, 1977 under 100-EUP-61; prepared by Ciba-Geigy Corp.,
Greensboro, N.C.; CDL:96623-A)
* Helseth, J.; Cole, G. (1973) The Determination of CGA-24705 in Emulsifiable
Concentrates by Gas Liquid Chromatography. Method PA-9 dated Nov 14, 1973.
(Unpublished study received Sep 26, 1974 under 5G1553; prepared by Ciba-
Geigy Corp., Greensboro, N.C.; CDL:96666-A)
Hermes, P. (1970) Extraction of Radioactive Metabolites from Sorghum Treated
with C GS-13529. Method AG-141 dated Jun 23, 1970. (Unpublished study
received Mar 26, 1975 under 5F160; prepared by Ciba-Geigy Corp., Greensboro,
N.C.; CDL:94380-A)
* Hermes, P. (1972) Biphasic Extraction of Radioactive Metabolites from Treated
Biological Material. Method AG-214 dated Aug 15, 1972. (Unpublished study
received Sep 26, 1974 under 5G1553; prepared by Ciba-Geigy Corp., Ardsley,
N.Y.; CDL:94216-M)
14
Hermes, P. (1973) Radioassay of C in Biological Materials by Combustion
using the Harvey Biological Material Oxidizer (BMO). Method AG-252 dated
Aug 14, 1973. (Unpublished study received Sep 26, 1974 under 5G1553.;
prepared by Ciba-Geigy Corp., Ardsley, N.Y.; CDL:94216-R)
Higgins, E.R.; Schnappinger, M.G.; Pruss, S.W. (1975) Yellow nutsedge control
with CGA-24705 in corn and soybeans. Pages 9-16, In Proceedings of the
Twenty-Ninth Annual Meeting of the Northeastern Weed Science Society;
Jan 7-9, 1975; New York City. Salisbury, Md.: University of Maryland,
Vegetable Research Farm.
Higgins, E.R.; Schnappinger, M.G.; Pruss, S.W. (1976) CGA-24705 plus atrazine
yellow nutsedge control in corn. Pages 65-70, Jin Proceedings of the
Thirtieth Annual Meeting of the Northeastern Weed Science Society; Jan 6-8,
1976; Boston, Massachusettes. Salisbury, Md.: University of Maryland,
Vegetable Research Farm.
Hofberg, A.; Balu, K. (1972a) Preparation of a Model System to Study Aqueous
Solution Photolysis in a Laboratory Environment. Method AG-208 dated Aug
11, 1972. (Unpublished study received Sep 26, 1974 under 5G1553; prepared
by Ciba-Geigy Corp., Ardsley, N.Y.; CDL:94216-L)
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Hogenboom, P.M. (1976) Metetilachlor - a new grass herbicide. Resumas XI
Seminario Brasileir de Herbicidas e Eruas Daininhas, Londrina, 1976: 127-
128.
Holliday, W.K. (1975) Report to Ciba-Geigy Corporation: Acute Aerosol
Inhalation Toxicity Study with CGA-24705 + Atrazine (2.5:2.0) 4.5F in Albino
Rats: IBT No. 633-07540. (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-C)
Hermann, W.D.; Guth, J.A.; Formica, G.; Schenker, M. (1974) CGA 24705: Gas
Chromatographic Determination of Total Residues in Material of Animal
Origin. (Provisional): AC 2.53; REM 5/74. (Unpublished study received Sep
26, 1974 under 5G1553; prepared by Ciba-Geigy Ltd., Basle, Switzerland;
CDL:94216-E)
Houseworth, L.D. (1973?a) Effect on CGA-24705 on Microbial Populations in Two
Soils: Report No. 2. (Unpublished study received Sep 26, 1974 under 5G1553;
prepared by University of Missouri—Columbia, Department of Plant Pathology
for Ciba-Geigy Corp., Greensboro, N.C.; CDL:94222-F)
Houseworth, L.D. (1973?) Report on Parent Leaching Studies for CGA-24705:
Report No. 1. (Unpublished study received Sep 26, 1974 under 5G1553;
prepared by University of Missouri—Columbia, Department of Plant Pathology
for Ciba-Geigy Corp., Greensboro, N.C.; CDL:94222-E)
Houseworth, L.D. (1977) Residues of Metolachlor and Atrazine in or on Corn
Grain Resulting from Preemergence and Preplant Incorporated Application of a
Liquid Prepack Formulation of Metolachlor and Atrazine with and without
Liquid Fertilizer. (Unpublished study including reports AG-A-3298 II,
III, AG-A-3325 II, AG-A-3326 II, AG-A-3372 II, AG-A-3406 II, AG-A-3674 II,
III, AG-A-3745 I, II, III, with a summary ABR-77028; received Jun 20, 1977
under 100-590; prepared by Ciba-Geigy Corp.; Greensboro, N.C.; CDL:230685-A)
Houseworth, L.D. (1977) Residues of Metolachlor and Dicamba in or on Corn Grain
Resulting from Preemergence Tank Mix Applications: ABR-77071. (Unpublished
study containing reports AG-A 4253, AG-A 4264, AG-A 4270 received Nov 8,
1977 under 100-EUP-59; prepared by Ciba-Geigy Corp., Greensboro, N.C.;
CDL:232192-A)
Houseworth, L.D.; Rolla, H. (1976) Residues from Metolachlor Alone and in Tank
Mix with Linuron, Metribuzin and Liquid Fertilizer in Soybeans: ABR-76077.
(Unpublished study received Jan 19, 1977 under 7F1913; prepared by Ciba-
Geigy Corp., Greensboro, N.C.; CDL:95767-A)
Houseworth, L.D.; Rolla, H. (1977a) Residues of Metolachlor and Atrazine in or
on Corn Grain Resulting from Tank Mix Applications with and without Liquid
Fertilizer-Preplant Incorporated and Preemergence Applications: ABR-77017.
(Unpublished study that includes studies AG-A-3325 II, AG-A-3406 II, AG-A-
3672 II-III, AG-A-3673 I, II, III, AG-A-3704 I, II, AG-A-3735 I, II, III, AG-
A-3799 II, III, AG-A-3858 with a summary; received Feb 18, 1977 under 100-
583; prepared by Ciba-Geigy Corp., Greensboro, N.C., CDL:228126-A)
167
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Houseworth, L.D.; Rolla, H. (1977b) Residues of Metolachlor in or on Sorghum
Resulting from Preplant Incorporated and Preemergence Applications: ABR-
77086. (Unpublished study, that includes studies AG-A-4413, AG-A-4418, AG-A-
4503, and AG-A-4753, received Nov 14, 1977 under 8G2019; prepared by Ciba-
Geigy Corp., Greensboro, N.C.; CDL:96625, 96626-A, 96626-B, 96626-C, 96626-D)
Iggo, G.A. (1975) Results of screening preemergence herbicides for sugarcane.
Pages 11-14, _ln Proceedings of the South African Sugar Technologists'
Association Forty-Ninth Meeting; Jun 30-Jul 4, 1975; Durban, South Africa.
Durban, South Africa: Hayne and Gibson Ltd. for the Society and the South
African Sugar Association Experiment Station:
Industrial Bio-Test Laboratories, Incorporated (1975) Report to Ciba-Geigy
Corporation: Acute Dust Inhalation Toxicity Study with CGA-24705 + CGA-18762
(1:1) 15G(FL-751873) in Albino Rats: 1ST No. 663-07826. (Unpublished study
received Feb 9, 1976 under 100-EUP-44; prepared for Ciba-Geigy Corp.,
Greensboro, N.C.; CDL:96495-B)
Industrial Bio-Test Laboratories, Incorporated (1975) Report to Ciba-Geigy
Corporation: Acute Toxicity Studies with CGA-24705 + CGA-18762 (1:1) 15G:
IBT No. 601-07825. (Unpublished report received Feb 9, 1976 under 100-EUP-
44; prepared for Ciba-Geigy Corp., Greensboro, N.C.; CDL:96495-A)
Jagschitz, J.A. (1976) Response of Kentucky bluegrass to growth retardant
chemicals. Pages 327-333, In Proceedings of the Thirtieth Annual Meeting of
the Northeastern Weed Science Society; Jan 6-8, 1976; Boston,
Massachusettes. Salisbury, Md. University of Maryland, Vegetable Research
Farm.
Jordan, L.; Harvey, G. (1976) Comparison of acid aralid herbicides for canning
pea weed control. Page 30, In Proceedings of the North Central Weed
Control Conference; December 9-11, 1975; Milwaukee, Wisconsin. Omaha,
Neb.; by Stauffer Chemical Company for the North Central Weed Control
Conference.
Jooste, J. v.d. W.; Van Biljon, J.J. (1976). Metolachlor + Atrazine a
combination pre-emergence herbicide for broad spectrum weed control in
maize. Gewasproduksie/crop production 5:85-90.
Kahrs, R.A. (1977) Tank Mixes of Metolachlor Plus Atrazine Plus Paraquat -
Corn: No and Minimum Tillage Applications: Summary of Residue Data: ABR-
77074. (Unpublished study containing reports AG-A-4167 II, AG-A-4187 II,
III, AG-A-4198 II, III, AG-A-4247 II, III, AG-A-4288 I, II received Nov 8,
1977 under 100-EUP-59; prepared by Ciba-Geigy Corp., Greensboro, N.C.;
CDL:232192-H)
Kaiser, F. (1974) Soil Degradation Study of Ciba-Geigy 14C-CGA-24705.
(Unpublished study received Mar 27, 1975 under 5F1606; prepared by
Analytical Biochemistry Laboritories, Inc., Submitted by Ciba-Geigy Corp.,
Greensboro, N.C.; CDL: 94376-A)
16
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Karlhuber, B.; Ramsteiner, K. (1973) CGA 24705: Gas Chromatographic Residue
Determination in Plant Material, Grains and Soil. (Provisional): AG 2.53;
REM 2/73. (Unpublished study received Sep 26, 1974 under 5G1553; prepared
by Ciba-Geigy Ltd., Basle, Switzerland; CDL:94222-G)
Keezer, W. (1971) Ion-Exchange Characterization of Metabolites of Radioactive
Pesticides. Method AG-156 dated Mar 3, 1971. (Unpublished study received
Mar 26, 1975 under 5F1606; prepared by Ciba-Geigy Corp., Greensboro, N.C.;
CDL:94380~C)
* Kennedy, G.L. (1975) 28-Day Mouse Pilot Study with CGA-24705 (Technical).
dated Nov 21. 1975; IBT No. 622-07857. (Unpublished study received Feb 16,
1978 under 100-583; prepared by Industrial Biotest Laboratories, Inc. for
Ciba-Geigy Corp., Greensboro, N.C.; CDL-232855-B)
* Kennedy, G.L. (1976a) Letter [dated Dec 10, 1976, relative to the results of
the first generation of a three generation reproduction study in albino rats
with the chemical CGA 24705 (IBT No. 8533-07928)] to George Rolofson.
(Unpublished study received Jan 19, 1977 under 7F1913; prepared by
Industrial Bio-Test Laboratory, Inc., for Ciba-Geigy Corp., Greensboro,
N.C.; CDL:95768-E)
* Kennedy, G.L. (1976b) Letter [dated Dec 13, 1976, interim report on IBT No.
8531-07926, 2 year chronic toxicity of CGA 24705 in albino rats] to George
Rolofson. (Unpublished study received Jan 19, 1977 under 7F1913; prepared
by Industrial Bio-Test Laboratory, Inc. for Ciba-Geigy Corp., Greensboro,
N.C.; CDL:95768-D)
* Kennedy, G.L. (1976c) Letter [dated Dec 13, 1976, relative to the 2 year
carcinogenicity study of CGA 24705 in albino mice (IBT No. 8531-07925)] to
George Rolofson. (Unpublished study received Jan 19, 1977 under 7F1913;
prepared by Industrial Bio-Test Laboratories, Inc., for Ciba-Geigy Corp.,
Greensboro, N.C.; CDL:95768-C)
Knaak, J.B.; Tallant, M. J.; Bartley, W.J.; Sullivan, L.J. (1965) The
metabolism of carbaryl in the rat, guinea pig, and man. Journal of
Agricultural and Food Chemistry. 13(6): 537-542. (Also In unpublished
report received Sep 26, 1974 under 5G1553; prepared by Ciba-Geigy Corp.,
Greensboro, N.C.; CDL:94221-C)
Kurtz, L.; Stroube, W. (1976). Control of yellow nutsedge by various
herbicides. Page 59, _In Proceedings of the North Central Weed Control
Conference; December 9-11, 1975; Milwaukee, Wisconsin. Cmaha, Neb.; by the
Stauffer Chemical Company for the North Central Weed Control Conference.
Lazzara, K.; Paa, H. (1975) Report to Ciba-Geigy Corporation: Acute Dermal
Toxicity Study with 1:4 Aqueous Suspension of CGA-24705 + Atrazine (2.5:2.0)
4.5L in Albino Rabbits: IBT No. 601-08061. (Unpublished study received Jun
20, 1977 under 100-590; prepared by Ciba-Geigy Corp., Greensboro, N.C.;
CDL:230687-B)
169
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Lee, T,; Kaldon, H. (1974) [Tank-Mix Compatabilities Test Report for CGA-24705-
GE. GA-2-621, with other Herbicides]: AG Request No. 4349. (Unpublished
study received Mar 26, 1975 under 5F1606; prepared by Ciba-Geigy Corp.,
Greensboro, NoC.; CDL:94384-A)
Lcrensi, H.J. (1976J). Herbicide tests on corn crops. Resumes XI Seminario
Braslieiro de Herbicidas e Eruas Daninhas, Londrina, 1976: 38:39
naher, 0\; Heinrichs, L. (1975a) Analysis of Atrazine and CGA-24705 in GA-2-622
4,5 L Formulation. Method Pa-72-T dated Oct 9, 1975. (Unpublished study
received Dec 29, 1975 under 100-EUP-45.; prepared by Ciba-Geigy Corp.,
Greensboro, N.C.; CDL:224074-A)
Maher, J.^-Heinrichs, L. (1975b) Analysis of Atrazine and CGA-24705 in
Ultrex 4.5L Formulation by Gas Chromatography. Method PA-72-T dated Oct
9, 1975. (Unpublished study received Jun 20, 1977 under 100-590; prepared
by Ciba-Geigy Corp., Greensboro, N.C.; CDL:230686-B)
Marco, G. (1974) Summary of Section D: CGA-24705-Corn: Residues Observed and
Metabolism Data Including the Analytical Methods Used: GAAC-74062.
(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-
Geigy Corp., Greensboro, N.C. CDL:94217-A; 94222)
Marco, G, (1975) Sumtnary of Section D: CGA-24705 Corn: Residues Observed and
Metabolism Data Including the Analytical Methods Used: GAAC-75001.
(Unpublished study received Mar 26, 1975 under 5F1606; prepared by Ciba-
Geigy Corp., Greensboro, N.C.; CDL:94378-A)
Mattson, A.M. (1969) Quantitative Determination of Triazine Herbicides in Soils
by Chemical Analysis: GAAC-69014. (Unpublished study received Feb 18, 1977
under 100-583; prepared by Ciba-Geigy Corp., Greensboro, N.C.; CDL:228125-B)
Mattson, A.M. (1974) CGA-24705 Residues in Milk, Meat, Eggs and Chickens
(Three Level Feeding Studies): GAAC-74064. (Unpublished study received Sep
26, 1974 under 5G1553; prepared by Ciba-Geigy Corp., Greensboro, N=C«;
CDL:94216-8)
Mattson, A»M. (1975) CGA-24705 Residues in Milk, Meat, Eggs and'Chickens
(Three Level Feeding Studies): GAAC-75059. (Unpublished study received Nov
25, 1975 under 6G1708; prepared by Ciba-Geigy Corp., Greensboro, N.C.;
CDL:94878-A)
Mattson, A.M.; Kahrs, R.A. (1969) Quantitative Determination of Triazine
Herbicides in Soils by Chemical Analysis: GAAC-69014. (Unpublished study
received ttov 8, 1977 under 100-EUP-59; prepared by Ciba-Geigy Corp.,
Greensboro, N.C.; CDL:232193-H)
Mattson, A.M.; Kahrs, R.A. (1975a) Procyazine — Corn: Tank Mixes with CGA-
24705 with and without Fertilizers, Preemergence and Preplant Incorporated
Applications: Procyazine Plus CGA-24705-15% Granule: GAAC-75077.
17 0
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(Unpublished study that includes reports AG-A-3638, AG-A-3671, AG-A-3716, AG-
A-3731, AG-A-3741, AG-A-3798, AG-A-3703, AG-A-3726, AG-A-3784, AG-A-3817;
received itov 26, 1975 under 4G1469; prepared by Ciba-Geigy Corp.,
Greensboro, N.C. CDL:95190-A)
Mattson, A.M.; Kahrs, R.A. (1975b) Residues in Field Grown Corn Following Use
of CGA-24705 Determined as CGA-37913 and CGA-49751: GAAC-75015.
(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-3501, AG-A-3005, AG-A-3153, AG-
A 3446; received Mar 26, 1975 under 5F1606; prepared by Ciba-Geigy Corp.,
Greensboro, N.C. CDL:94379-B)
Mattson, A.M.; Kahrs, R.A. (1975c) Summary of Residue Data CGA-24705TAtrazine
Combinations as Corn Herbicides Tank Mixes-Dual 6EC Plus AAtrex^ ' SOW
or AAtrex 4L Flowable Combination Formulation-GA-2-6-622 4.5L
Preemergence and Preplant Incorporated Applications: GAAC-75081.
(Unpublished study including reports AG-A-2974; AG-A-3057; AG-A-3070; AG-A-
3288; AG-A-3298; AG-A-3325; AG-A-3326; AG-A-3372; AG-A-3406; received Dec
29, 1975 under 100-EUP-45; prepared by Ciba-Geigy Corp., Greensboro, N.C.;
CDL:224074-D)
Mattson, A.M.; Rolla, H. (1975) Summary of Section D: CGA-24705-Soybeans:
Residues Observed and Metabolism Data Including the Analytical Methods Used:
GAAC-75057. (Unpublished study that includes reports AG-A-3268, AG-A-3466,
AG-A-3523, AG-A-3570, AG-A-3650 I & II, AG-A-3702, AG-A-3724, AG-A-3743, AG-
A-3776, AG-A-3780, AG-A-3803; received Nov 25, 1975 under 6G1708; prepared
by Ciba-Geigy Corp., Greensboro, N.C. CDL;94984-A; 94878)
Mattson, A.M.; Kahrs, R.A.; Schneller, J. (1965) Use of Microcoulonetric gas
chromatograph for triazine herbicides. Journal of Agricultural and Food
Chemistry 13(2): 120-122. (Also In unpublished study received Feb 18, 1977
under 100-583; prepared by Ciba-Geigy Corp., Greensboro, N.C.; CDL:228126-K)
McCohen, L.L.; Tiedje, J.M. (1978). Metabolism of two new acylanilide
herbicides, Antor Herbicide (H-22234) and Dual (Metolachlor) by the soil
fungus Chaetomium globosum. Journal of Agricultural and Food Chemistry
26(2):414-419.
McGahen, L.L.; Tiedje, J.M. (1978). Metabolism of two new acylanilide
herbicides, Antor Herbicide (H-22234) and Dual (Metolachlor) by the soil
fungus Chaetomium globosum. Journal of Agricultural Food Chemistry 26(2):
414-419.
Mclaughlin, J.P.; Hartwig, N.L. (1976) Yellow nutsedge control in conventional,
minimum, and no-tillage corn, Pages 711-76, In Proceedings of the
Thirtieth Annual Meeting of the Northeastern Weed Science Society? Jan 6-8,
1976; Boston, Massachusettes. Salisbury, Md: University of Maryland,
Vegetable Research Farm.
Michieka, R.W.; Ilnicki, R.D.; Somody, J. (1976). The response of corn and
annual weeds to some new herbicides used alone and in combination with
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171
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Michieka, R.W.: Ilnicki, R.D.: Somody, J. (1977). Weed control in potatoes
wiuh preplant incorporated herbicides applied alone, in combination, and
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Northeastern Weed Science Society.
Miyazaki, S. (1976) Gas Chromatographic Residue Determination of CGA-24705 in
Soil. Method AG-303 dated Oct 15, 1976. (Unpublished study received Jan 19,
1977 under 100-583; prepared by Ciba-Geigy Corp., Greensboro, H.C.;
CDL:95763-B)
Miyazaki, S. Kahrs; R.A. (1974) Specificity of the Residue Determination of
CGA-24705 Metabolic Residues in Corn (AG-265): GAAC-74063. (Unpublished
study received Sep 26, 1974 under 5G1553; prepared by Ciba-Geigy Corp.,
Greensboro, N.C.; CDL:94216-J)
Miyazaki, S.; Kahrs, R.A. (1975) Specificity of the Residue Determination of
CGA-24705 Residues in Corn (AG-277): GAAC-75014. (Unpublished study
received Mar 26, 1975 under 5F1606; prepared by Ciba-Geigy Corp.,
Greensboro, N.C.; CDL:94380-W)
Murphy, H.J.; Gajewski, T. (1977). Effect of several herbicides applied
preemergence, at drag-off and layby on weed control in white potatoes.
Pages 176-179, _In Proceedings of the Northeastern Weed Science Society.
Murphy, H.J.; Goven, M.J. (1976). A comparison of AC 92,553, CGA-24705, and
FMC 25213 in combination with metribuzin for weed control in potatoes.
Pages 256-261, _In Proceedings of the Northeastern Weed Science Society.
Nham, Dan; Harrison, W.A. (1977a) Report to Ciba-Geigy Corporation: Acute Oral
Toxicity Study with Dual1 ; 8E in Albino Rats: IBT No. 8530-10822.
(Unpublished study received Nov 8, 1977 under 100-EUP-59; prepared by
Industrial Bio-Test Laboratories, Inc. for Ciba-Geigy Corp., Greensboro,
N.C., including Addendum A — Validation by Ciba-Geigy Corp.; CDL:232191-A)
Nham, Dan; Harrison, W.A. (1977b) Report to Ciba-Geigy Corporation: Acute
Dermal Toxicity Study with Dual1 ' 8E in Albino Rabbits: IBT 8530-10822.
(Unpublished study received Nov 8, 1977 under 100-EUP-59; prepared by
Industrial Bio-Test Laboratories, Inc. for Ciba-Geigy Corp., Greensboro,
N.C.; including Addendum B—Validation by Ciba-Geigy Corp; CDL:232191B)
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Norton, J.A. (1978) Letter Sent to George LaRocca data Aug 28, 1978. Dual 8E
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(Submitted by Ciba-Geigy Corp., Greensboro, N.C.)
(R}
Norton, J.A. (1978) [Letter on Dual^ 6E Herbicide -EPA Reg. No. 100-583
Ciba-Geigy follow-up to requests from Mr. James Skaptason, Metolachlor
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172
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letter from the files of the Office of Pesticide Programs, Technical
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Norton, J.A. (1977) Letter sent to Henry Jacoby dated May 20, 1977. [Relative
to the May 17, 1977, meeting between H. Craven, R. Felthausen, and H. Jacoby
of EPA and J. Barnett, L. Newly, and J. Norton of Ciba-Geigy. Conclusions
reached on text protocols, data requirements, and timetables relating both
to Ciba-Geigy's petition for residue tolerances for metolachlor in soybeans
and to its application for registering Dual 6E for selective weed control].
(Submitted by Ciba-Geigy and on file in Generic Standards Branch, OPP)
Norton, J.A. (1978) Letter sent to Henry Jacoby dated March 23, 1978. [Dual 6E
Herbicide - Follow-up to questions raised by Mr. Harry. Craven, Efficacy and
Ecological Effects Branch, During Reviews for Metolachlor Generic Standard.]
Received May 1978 under 100-583. (Submitted by Ciba-Geigy Corp.,
Greensboro, N.C., and on file in Generic Standards Branch, OPP)
Norton, J.A. (1978) Letter sent to Henry Jacoby dated February 3, 1978. [Dual
6E Herbicide - Binomial Nomenclature - Channel Catfish.] Received Feb 27,
1978 under 100-583. (Submitted by Ciba-Geigy Corp., Greensboro, N.C. and on
file in Generic Standards Branch, OPP)
Norton, J.A. (1978) Letter sent to Henry Jacoby dated March 8, 1978. [Dual 6E
Herbicide - Regarding Norton's February 3, 1978 Letter on Binomial
Nomenclature for Channel Catfish]. Received Mar 1978 under 100-853.
(Submitted by Ciba-Geigy Corp., Greensboro, N.C. and on file in Generic
Standards Branch, OPP)
* Oncins Research and Breeding Center (1974) Three-Month Dietary Feeding Study in
Rats: CGA 24 705. A translation of: Toxicite de 3 Mois chez le Rat par Voie
Orale du Produit CGA 24 705, translated by F- Roulet: IC-DREB-R 741009.
(Unpublished study received Mar 26, 1975 under 5F1606; prepared by
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Paa, H. (1976a) Report to Ciba-Geigy Corporation: Acute Dermal Toxicity Study
with an Aqueous Herbicide,Use Dilution Containing a Combination of Dual
6EC (FL-760205) and Lorox1 ' 50 W (FL-761533) in Albino Rabbits: IBT No.
8530-09780. (Unpublished study received Jan 19, 1977 under 7F1913; prepared
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Paa, H. (1976b) Report to Ciba-Geigy Corporation: Acute Dermal Toxicity Study
with an Aqueous Herbicide Use Dilution Containing a Combination of Dual
6EC (FL-760205) and Sencor( SOW (FL-761088) in Albino Rabbits: IBT No.
8530-09781. (Unpublished study received Jan 19, 1977 under 7F1913; prepared
by Industrial Bio-Test Laboratory Inc. for Ciba-Geigy Corp., Greensboro,
N.C.; CDL:95768-H)
Parker, C.; Dean, M.L. (1976) Control of wild rice in rice. Pesticide Science
7(4):403-416.
173
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Parochetti, J.V. (1975) Weed control in soybeans with rrtetribuzin and
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1975; New York City. Salisbury, Md: University of Maryland, Vegetable
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Parochetti, J.V. (1977). Herbicides for no-tillage double cropped soybeans,
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Parochetti, J.V. ; Burt, G.W. ; Bell, A.W. (1976). Triazines, acetanilides, and
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of Maryland Vegetable Research Farm.
( R)
Peek, J. W. (1976) Dual Experimental Use Permit for Weed Control in
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1-38 with sunmary; CDL:229062-A; 229063)
Peek., J.W. (1977X,Biological Research Report on Herbicide Efficacy and Crop
Safety: Bicep 4.5 L Experimental Use Permit for Weed Control Evaluation
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prepared by Ciba-Geigy Corp., Greensboro, N.C.; including studies 1-8 with a
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Peters, R.A. ; Dest, W.M. (1975) Evaluation of herbicides for use on no-tillage
corn in a rye cover crop. Pages 74-77, _In Proceedings of the Twenty-Ninth
Annual Meeting of the Northeastern Weed Science Society; Jan 7-9, 1975; New
York City. Salisbury, Md: University of Maryland, Vegetable Research Farm.
Pillai, G.G.P., Davis, D.E. (1975) Mode of action of CGA-18762, CGA-17020, and
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Southern Weed Science Society.
Pillai, C.G.P., Davis, D.E., Truelove, B. (1976) CGA-24705 effects on
germination, growth, leucine uptake, and incorporation: Abstract. Page 403,
_In Proceedings of the Twenty-Ninth Annual Meeting of the Southern Weed
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Pillai, G.G.P., Davis, D.E., Truelove, B. (1977) Site of uptake and mode of
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Plant Sciences Branch, BFSD, EPA. Contract No. 68-01-5155
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triazine herbicides for annual grass and broadleaf weed control in corn.
Pages 40-45r _ln Proceedings of the Thirtieth Annual Meeting of the
Northeasten Weed Science Society; Jan 6-8, 1976; Boston, Massachusettes.
Salisbury, Md.: University of Maryland Vegetable Research Farm.
Ramsteiner, K; Karlhuber, B. (1975) CGA-24705: Determination of Total Residues
in Material of Animal Origin: AC 2.53; REM 2/75. (Unpublished study
received Mar 26, 1975 under 5F1606; prepared by Ciba-Geigy Ltd., Basle,
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Remos, M. (1976). Chemical weed control in growing soybeans planted with
minimum soil preparation. Resumes XI Seminario Brasileiro de Herbicidas e
Ervas Daninhaus, Londrina, 1976: 91-92.
Richter, W.; Alt, K.O.; Blum, W.; Winkler, T. (1974) Structure Elucidation of
'Metabolite X', a Degradation Product of CGA 24705: AC 2.53. (Unpublished
study received March 26, 1975 under 5F1606; prepared by Ciba-Geigy Ltd.,
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Robbins, J.D.; Bakke, J.E. (1967) Sheep4and goat metabolism unit for the
collection of excreta and expired C 0 . Journal of Animal Science
26(2): 424-429. (Also In unpublished report received Sep 26, 1974 under
5G1553; prepared by Ciba-Geigy Corp., Greensboro, N.C.; CDL:94221-E)
14
Roger, J.C. (1973) Addendum to AG-218 — Total Organic C Contents in
Rumen and Intestinal Wash Using Lindberg Combustion Furnace. Method AG-251
dated Aug 16, 1973. (Unpublished study received Mar 26, 1975 under 5F1606;
prepared by Ciba-Geigy Corp., Greensboro, N.C.; CDL:94380-K)
14
Roger, J.C.; Cassidy, J.E. (1974a) Metabolism and Balance Study of fir- C-
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14
Roger, J.C.; Cassidy, J.E. (1974b) Metabolism and Balance Study of $- C-
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14
Roger, J.C. (1973?) Radioassay of C 02 by Acid Neutralization and
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14
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14
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14
Sumner, D.D.; Cassidy, J.E. (1974d) The Uptake and Distribution of fi- C-
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14
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14
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*U S GOVERNMENT PRINTING OFFICE: I960 341-085/3949
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