United Stat**
Environmental ProtBCTron
A#«nev
Off ica of
PanicidM and Tonic SuMMncoi
Wathtngton OC 20480
PMtmdw
2-chloro-N-(2-ethyl-6-methylphenyi
-N-(2-methoxy-1-methylethyl)
acetamide Metolachlor
Pesticide Registration
Standard
£P#/Sf£l>- So/sJ.O
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50?73-ini
3. Recipient's Accession No
m 1238 2 0
REPORT DOCUMENTATION
PAGE
1. REPORT
£.PA^j&^80/52 0
4. Title and Subtitle
Metolachlor: Pesticide Registration Standards
5. Report Date
5/80
7. AuthOr(s)
9. Performing Organization Name and Address
Environmental Protection Agency
Special Pesticide Review Division
Crystal Mall #2
Arli ngton , VA 22202
ft. Performing Organization Rept. No.
10. Project/Task/Woe* Unit No.
I
12. Sponsoring Organization Name and Address
Environmental Protection Agency
401 M St. S.W.
Washington, D.C. 20460
11. ContractCC) or Grant(G) No.
CC)
13- Type of Report & Period Covered
14.
IS. Supplementary Notes
16. Abstract (Limit: 200 words)
A comprehensive statement of the Agency's regulatory position
on all pesticide products containing the same active ingredient
The document discribes the data upon which the regulatory
position is based, provides the rationale for the position
and states the conditions which must be met to register a
product under a standard.
17. Document Analysis a. Descriptors
0504,0606,0703
b. Identifiers/Open-Ended Terms
c. COSATI Field/Group
18. Availability Statement
U n1i m i ted
19. Security Dams (This Report)
Unclassified
20. Security Class Chla Page)
llnrl a^ci fi prl
21. No. of Pages
22. Price
(See ANSI-Z3918) See Instructions on Reverse OPTIONAL FORM 272 «-77)
(Formerly NTIS-35)
Department of Commerce
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NOTICE
THIS DOCUMENT HAS BEEN REPRODUCED
FROM THE BEST COPY FURNISHED US BY
THE SPONSORING AGENCY. ALTHOUGH IT
IS RECOGNIZED THAT CERTAIN PORTIONS
ARE ILLEGIBLE, IT IS BEING RELEASED
IN THE INTEREST OF MAKING AVAILABLE
AS MUCH INFORMATION AS POSSIBLE.
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METOLACHLOR
2-chloro-N~(2-ethyl-6~methylphenyl)
~N~ (2-methoxy-il-methylethyl acetamide
Pesticide Registration Standard
David Gettman, Project Manager (SPRD)
Bill Audia, Plant Sciences Specialist (BFSD)
William Boodee, Residue Chemist (HED)
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-bw to Register Ihder a Registration Standard
Organization of the Standard 7
Purpose of the Standard 7
Requirement to Re-register Ihder the Standard 9
"Product Specific" Data and "Generic" Eata 9
Data Compensation Requirements under FIFRA 3(c)(1)(D) 11
Cbtaining Data to Fill "Data Gaps"; FIFRA 3(c)(2)(B) 12
Amendments to the Standard 12
Requirements for Metolachlor Products 15
Technical Xetolachlor 16
Ehulsifiable Concentrate ftetolachlor 19
Use Profile 27
Product Chemistry
Introduction 29
Tbpical Discussions
Chemical Identity 29
ffenufacturing Process 31
Ffercentages of Components in Ftesticide 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
Tbpical Discussions
Physico-Chemical Transformation. 39
Soil Metabolism 41
Microbial Metabolism 42
Mability 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
Bibliography 55
Tbxicology
Tbpical Discussions
Metabolism and Pharmacodynamics 57
Acute Effects and Neurotoxicity 58
local Irritation 59
Subchronic Effects and Neurotoxicity 60
Sensitization 61
Chronic Effects 62
Oncogenicity 62
Preceding page blank
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Mutagenicity 63
Teratology 63
Reproductive Effects . 64
Disciplinary Review
Ibxicology Profile . 65
toxicology Bazard Assesanent .. 66
Generic Data Gaps 68
Product Specific Data Gaps 68
Suggested labeling . ... 68
Bibliography .................. 69
Residue Charustry
topical Discussions
Metabolism in Plants 73
Metabolism in Animals 75
Analytical Methodology . 75
Residue Data 78
Present tolerances 83
Disciplinary Review
Residue Chemistry Profile 85
tolerance Reassesanent 87
Generic Esta Gaps .... 89
Suggested Labeling .' 89
Bibliography ;,v ¦.... 91
Efcological Effects
topical Discussions
Microbes 95
Algae 97
Aquatic i^fecrophytes 97
Terrestrial Plants 97
Birds ... 97
Wild Mammals 99
Aquatic Invertebrates .... 99
Fish ... 100
Ecosystem Effects 101
Disciplinary Review
Ecological Effects Profile 102
Ecological Effects Hazard Assesanent 133
Generic Ceta Gaps 133
Suggested labeling 104
Bibliography ¦ 105
Regulatory Rationale
Technical Metolachlor 107
The Eel imitation of Risks to Hihans ; 107
The Delimitation of Risks tc Wildlife 108
Etnulsif iable Concentrates of Metolachlor 109
The Delimitation of Risks to Humans 110
The Delimitation of Risks to Wildlife 113
Append ix
Chemical E&ta Sheers 117
Bibliography - 147
Guide -o the Use of This Bibliography 149
_ _ IO
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HOW TO REGISTER
UNDER A REGISTRATION STANDARD
Organization of the Standard-
Purpose of the Standard
Requirement to Re-register Ihder ..the Standard
"Product Specific" Eata and "Generic" Cata
Data Cbmpensation Requirements under FIFRA 3(c) (1) (D)
Obtaining Eata to Fill "Eata Gaps"; FIFRA 3(c) (2) (B)
^endments to the Standard
Organization of the Standard
Ibis 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 of the Standard '
Section 3 of the Ebderal Insecticide, F\jngicide, and Rodenticide 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]." lb 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 sutmitted 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, EI& and its predecessor agency, the ..Ihited States Department of
Agriculture (USDA) , routinely reviewed registration applications on a 'product
by product' 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.
7
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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 cane 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 2PA issued new requirements for registration in 1975 (40 CFR
162) and proposed new guidelines for hazard testing in 1978 (43 FR 29686, July
10, 1973 and 43 FR 37336, August 22, 1978), many products that had already been
registered for ^ars were being sold and used without the same assurances of
human and environmental safety as was being required for new products.. 3ecause
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 oy product1 approach, the Agency decided that a new, mora
effective method of review was needed.
A new review procedure has been developed. Under it, 2PA publishes
docunencs 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 ana requirem&nts, 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, ana 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 seme special regulatory restriction is
needed to ensure against unreasonable adverse effects to man or the
enviroiment. Many such risxs 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
[4E 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.
8
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Requirement to 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.
EFft 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 F&ckage 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,
EJrvironmental E&te, Tbxicology, Residue Chemistry, and Ecological Effects.
These determinations are based primarily on the data Qiidelines proposed in
1979 (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 frcm a normally applicable Guidelines requirement was
actually unnecessary to evaluate these products, the Standard indicates that
the requirement has been waived- Ch the other hand, in sane 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. Eata 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.)
Ihe 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 affects 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
9
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submit or cits 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. (Where 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 scne 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 37 3 5 5J.
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 nanufacturing-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 'aqs 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 human 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)(1)(D)] or data generation 'under Section 3(c)(2)(E)] for "generic" data
that is required only with respect to sane use patterns, he may elect to delete
those use patterns from his labeling at the time he re-registers his product.
M applicant for registration of a new product under this Standard may
similarly request approval for only certain use patterns.
Data 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 ERA (or to its predecessor agencies,
USDA or FDA) , on or after January 1, 1970;
(2) the data were submitted to EPA (or USDA or FEA) by some other
applicant or registrant in support of an application for an
10
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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 "produce
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.)
to 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 «*ould 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 EFft 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.
Efcch 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 oy 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 Ffcckage for this Standard.
Obtaining Data to Fill "Data Gaps"; FIFRA 3(c)(2)(B)
Sane of the kinds of data EPA needs for its evaluation of the properties
and effects of products to which this Standard applies have never teen
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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PIFRA Section 3(c) (2) (B), added to FIKRA 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. ERA muse allow a reasonably sufficient period for this to be
accomplished. 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 wiereby two or more registrants may agree to share in the costs of
producing data for vtfiich they are both responsible.
The Standard lists, in its sunmary 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 sane cases,
the Agency may possess sufficient "product specific" data on one currently
registered product, but may lack such data on another. Oily those Standards
which apply to a very anall nimber 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 aider Section 3(c) (2) (B) to take appropriate steps to sufcmit data"
needed to fill "generic" data gaps. (Wfe 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 Ftegistration 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 sufcmissions and any approved amendments will be incorporated
into the Ftegistration Standard by means of addenda, which are available for
inspection at EPA in Washington, D.C., or copies of which may be requested frcm
1 o
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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. Ihereafter, wen the Agency determines that the internally
maintained addenda have significantly altered the conditions for registration
under the Standard, the document 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 FQckage.
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REQUIREMENTS FOR METOLACHLOR PRODUCTS
The following is the Agency's position on the present requirements for
registration and re-reqistration under this r-tetolachlor Registration Standard,
including: (1) what 'standards' of canposition, acute toxicity, physical and
chemical properties, use, labeling, and packaging will ensure the safe use of
the pesticide active ingredient f-tetolachlor; and (2) what studies are needed
to retain existing registrations and to complete the data base chat will
support future registrations under the Metolachlor Standard. Ihere 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 ail pertinent data and information
on Metolachlor available to the Agency's reviewers as of June 30, 1930.
Metolachlor
'Metolachlor1 [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-energence 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 subnitter for pesticide
products containing Metolachlor: Ciba-Geigy Corporation (Agricultural
Division, P.O. Box 11422, Greensboro, Marth Carolina, 27409).
The three presently registered products containing Metolachlor as the sole
active ingredient are a manufacturing-use 'technical' and two emulsifiable
concentrate formulations, one containing 3 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 ana11 quantity remains on the market for 1930. tetolachlor is also
marketed in a package mix with each of two other herbicides, 'Atrazine' and ^
1 Propazine' , ar.d is often mixed by die applicator with other herbicides to
provide a broader spectrur. 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 hazaTas which arise from Metolachlor applied alone.
Preceding page blank
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TECHNICAL METOLACHLOR
In order to be registrable under this Standard, a Technical Xetolachlor
product must comply with the following standards of composition, purity, and
toxicity: A Technical Mstolachlor should contain at least 90 % (by weight) the
active ingredient ' Mstolachlor', i.e. 2-chloro-N-(2-ethyl-6-methylphenyl)-N-(2-
methoxy-l-methylethyl)acetamide. If the manufacturing process submitted is
found by the Agency to be substantially different frcm the one used to produce
the presently registered Technical ivetolachlcr, 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 153.51-5). The "product specific" acute toxicology testing on a
Technical Mstolachlor (or on a "substantially similar" Technical Metolachlor)
.must demonstrate that it falls into Ibxicity Categories 'which are the same as
or nunerically higher than the following:
A^ute Oral Ibxicity: Category III
Acute Eermal Ibxicity: Category III
Arute Inhalation Ibxicity: Category III
Primary Eye Irritation: Category III
Primary Dermal Irritation: Category III
Hie following 'Sample Label' includes all those labeling statements which
the Agency has determined will provide an adequate mitigation of those hazards
to man and the environment 'which may result from the handling, transport,
re-formulation, storage, or disposal of technical ffetolachlor. In order to be
registered under this Standard, therefore, a .^technical .Vetolachlor 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.]
16
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PRODUCT NAME
Ebr Fbrmulation of Herbicides Oily
Active Ingredient:
Metolachlor : 2-chloro-N-(2-ethy1-6-methylphenyl)-
N- (2-methoxy-l-methylethyl)acetamide %
Inert Ingredients: %
"total: 1 0 0 %
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 vcmiting 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 public waters unless in accordance with an NPDES permit. Ebr
guidance, contact your regional office of EFft.
DIRECTIONS FOR USE
Refer to technical bulletin. It is a violation of federal law to
use thTs 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.
Cpen 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 druns, cans, etc.:
Do not contaminate water, food, or feed by storage or disposal.
Cpen dumping or open burning is pronibited. Re-seal container
and offer for re-conditioning; or triple rinse (or equivalent)
and offer for recycling or re-conditioning, ftesticide or
rinsate that cannot be used, recycled, or chemically re-process-
ed, ana containers that cannot be re-used or recycled should
be disposed of in a landfill disposal site approved for
pesticides. Cbnsult 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 Regiseracion to. tot Wt. or Measure
Escablishment to.
t^iame and Address of the producer, registrant, or person for whan produced.
1 7
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Finally, in order to re-recister Technical Metolachlor under this Standard,
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 ffetolachlor; the Environmental F^te, "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
29636, July 10, 1973, ar.d 43 FR 37336, August 2, 1973) which describes that
type of data and what test substances should be used.
Product Chemistry
IT Cctanol/Watar Partition Coefficient; 163.61-3(c)6
2) Flarnmability; 163.61.3(c) 13
3) Oxidizing or Reducing Action; 163.61-8 (c) 14
4) Ekplosiveness; 163.61-3 (c) 15
5) Viscosity; 163.61-8(c)17
6) Corrosion Characteristics; 163.61-3(c)13
7) (and, if Tbchnicai Metolachlor is show to
produce genetic effects in future testing:)
Pn 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
3) Ad sorption/resorption studies; 163.62-9
9) Actual field-use residue monitoring (not disrussed
studies at two watershed sites to be in the Proposed
approved by the Agency; Guidelines)
10) Accumulation studies on rotational 163.61-11(b)
crops for ana 11 grains, root crops,
and leafy vegetables;
Toxicology
11) Subchronic Oral Ebsing - FSthological 163.82-1
evaluation for both the rat and dog;
12) Chronic Feeding - A chronic feeding. 163.83-1
study on laboratory rat;
13) Oncogenicity - Completion of the mouse 163.33-2
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 163.33-3
marrmalian species other than the rat;
15) Reproduction - A multi-generation 163.33-4
reproduction study on one mammalian
species (preferably the laboratory rat);
Ecological Effects
IF) Activated sludge metabolism study; 163.62-3 (g)
17) The avian acute oral LD-50 for ona 163.71-1
species of waterfowl (preferably the
mallard) or one species of upland game
bird (preferably the bobwfriite quail) ; the
species must be one of those for v^hich an
LC-50 was determined under FR 163.71-2.
18
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£MUL3 IF IABLE CONCENTRATE METOLACHLOR
In order to be registrable under this Registration Standard, an end-use
pesticide product containing Metolachlor must contain f»tetolachlor as the sole
pesticide active ingredient. The only end-use Metolachlor formulations
registrable under.this Standard are Bnulsif iable. Cbncentrates of Metolachlor,
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. The strength of each Metolachlor Bnulsifiable
Concentrate must be stated in pounds Mstolachlor'per gallon liquid.
In order to registrable under this Standard, the "product specific" acute
toxicology testing on a Metolachlor Bnulsifiable Gbncentrate (or a .
"substantially similar" one) must demonstrate that it falls into Tbxicity
C&tegories which are the same as or numerically higher than the following:
Acute Oral Tbxicity: Category II
£cute Dermal Tbxicity: Category III
Acute Inhalation Tbxicity: Category II
Primary Eye Irritation:' category I
Primary Dermal Irritation: Category II
In order to be registrable mder this Standard, the "product specific"
product chemistry testing on a Metolachlor Eltiulsif iable Cbncentrate must show
that it has physical/chemical properties which fall within the limits listed
below. For physical/chemical properties which are not show below (see
the Product Chemistry chapter), no Standard has been set.
Physical State: liquid at room temperature
Vapor Pressure: between 0.35 and 1.0 iron Hg at 20 C
pH: between 6 and 8
Flammability: flashpoint above 30 F
Ekplosiveness: 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 Bnulsif iable Gbncentrate if it is substantially
similar to a previously registered Metolachlor Bnulsifiable Cbncentrate. The
applicant may request the Agency, in writing, to consider, by examination of
che 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 .Ntetolachlor chulsifiable
Concentrate product must bear labeling in compliance with the following, and
where appropriate, with label statements which are correctly correlated with
the product's toxicity categories or physical /'chemical properties. (Consult
40 CFR Section 162.13 for more complete directions on formats for labeling.]
1) PRODUCT NAME at the top of the front panel;
2) Beneath the name, the product type "Pterbicide";
3) A ganeral statement of the product's use: "rbr weed control in field
corn (except fresh corn and popcorn), soybeans, grain sorghum, ana
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-etnyl-6-.methylphenyl) -
N-(2-methoxy-l-methylethyl)acetamide %
Inert Ingredients: ..... %
Tbtal: 10 0%
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 Ibxicity Category is II: WARNING
If the highest Toxicity Category is III or IV: CAUTION
7) Just above the signal vcrd, 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 v*ord :
"See side panel for additional precautionary statements"):
Lhder the heading, "ffezards to Hunans and Dcmestic r^nimals":
The human hazard signal word [same as (6) above] ;
Fbr acute oral toxicity,
if Category II: "May be fatal if swallowed."
j if Category III: "Hamful if swallowed."
if Category IV: no statement required
Fbr 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: "Ptoy be fatal if inhaled. CD 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. Eb not
get in eyes, '.fear goggles or face
shield viien handling."
if Category II: "Causes eye irritation. Da not get
in eyes."
2 0
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if Category III: "Avoid contact with eyes. In case cf
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. Eb not gee on
skin or on clothing."
if Category III: "Avoid contact with skin or
clothing. In case cf contact,
immediately flush skin with plenty of
"water. Get medical attention if
irritation persists."
if Category IV: no statement required
For dermal sensitization,
"Ntey cause s.
-------
moved to frash air, and medical attention should be
sought-. If swallowed contact your local Ebison Cbntrol
Center, hospital, or physician immediately ..." [The
ranainder of this First Aid statement, which will
concern the use of araesis 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 Fbison Cbntrol
Center, hospital, or physician immediately. If patient
is unconscious, maintain breathing and heartbeat (CPR:
cardiopulmonary resuscitation) . If patient is
conscious, induce vaniting (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 enesis and lavage stanach.
TVeat symptomaticallyi The use of .an aqueous slurry of
activated charcoal (such as Itorit A) and -a saline
cathartic should be considered.]
9) After precautionary statements, aider "DIRECTIONS FOR USE':
Ihe 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 43 CFR
Part 170."
"Under the heading, "General Information":
"PRODUCT NAME [( ) lbs. 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 broadle_af Vveeds
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, "Dd not
use on sweet corn or popcorn." Also, the statement:
"Failure to follow all precautions on this label may result
in poor ^eed control, crop injury, or illegal residues."
Also include, *here spraying equipnent if discussed:
"Use conventional groixid sprayers or center pivot irrigation
application" and any additional directions or precautions
for using these methods of application.
10) Ihder the heading, "PRODUCT NAME Applied Alone":
If for use on corn, under the heading, "Cbrn":
Directions should specify all application methods and
rates. All applications must be ore-emergence. Nb rate ¦
in excess of 6 pounds active ingredient per acre may be
recommended.
0 0
-------
If for use on soybeans, under the heading-., "Soybeans":
Directions should specify all application methods ana
rates. All applications must be pre-emergenca. to rate
in excess of 3 pounds active ingredient per acre may be
r.ec amended. *
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-energence. No rate
in excess of 2-1/2 pounds active ingredient per acre may be
recommended. (If the product will severely injure the
crop vvhen the sorghun seed is not pre-treated, it is
advisable to. include a statement to this effect.)
(When application methods and rates are zhe same for two or more
crops, rhese directions may be listed under a combined heading
such as "Cbrn and Soybeans".)
Lhder the heading, "Fbtational Crops":
"1) If crop treated with PRODUCT NAME is lost, corn,
soybeans, peanuts, or grain sorghum may be replanted
irrmediately. Eb 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 he applied. 2) Small grains may be
planted 4-1/2 months following treatment. Field corn (except
fresh corn and popcorn), cotton, soybeans, peanuts, sorghun,
root crops, and snail grains may be planted in the spring
following treatment. Do not graze or feed forage or fodder
fran cotton or ana11 grains to livestock. All other rota-
tional crops may be planted 18 months after application."
11) lhder the heading, "STORAGE AND DISPOSAL":
Concerning disposal,
"Qpen dumping or open burning is prohibited, not re-use
enpty container; triple rinse or.equivalent. Efesticide 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, (insult federal, state, or local
disposal authorities for approved alternative procedures."
Cbncerni.ng storage, .
the statement: "Keep out of reach of children"; o
if rhe flash point is above 80 F and not over 150 F, che
statement: "Dd 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 Number', 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, -he "Establishment Number" should appear on
either the label or the container.
2 3
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NOTE: Concerning labeling for products containing petroleum distillates,
proper artergency medical treatment for the ingestion of petroleum
distillates is a controversial subject. T\*
-------
The Agency has determined that the above "Standards' adequately limit the
acute hazards of Ebulsifiable Concentrate Mstolachlor for agricultural workers
and others not directly involved in the application, and that therefore no re-
entry interval lias been established for Bnulsifiable Concentrate Mstolachlor.
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 E&rt 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
Bnulsifiable Concentrates under this Standard. In order to re-register the
following Mstolachlor Bnulsifiable 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 vhat test substances should be used.
Fbr currently registered Bnulsifiable Concentrate ^fetolachlor of
six (6) pounds active ingredient per gallon:
Product Chemistry
iy £olor
2) Cdor
163.61-8 (c) 1
163.51-8(c)2
For currently registered Bnulsifiable Concentrate Mstolachlor of
eight (8) pounds active ingredient per gallon:
Product Chemistry
1) Color
2) Cdor
3) Explosiveness
163.61-8(c)1
163.61-3(c) 2
163.61-8 (c) 15
Toxicology
51 Acute inhalation toxicity study.
163.81-3
25
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USE PROFILE
The currently registered end-use formulations of Metolachlor are two
Ehiulsifiable Cbncentrates, one at six pounds active ingredient per gallon, the
other at eight pounds per gallon. Matolachlor 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 waeds in field corn (except fresh corn and popcorn), soybeans,
peanuts, and grain sorghun. This Registration Standard for Metolachlor only
considers the risks that arise from the use of Matolachlor 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 ir*gredient per acre
(1.5 to 2.5 lbs. ai/acre for grain sorghum) (depending upon soil type),
used itfien field has furrow irrigation, or when a period of dry weather is
expected. Eburteen 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 lbs. 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
weds or crop emerge.
The directions for application to sorghun fields require that grain sorghun be
treated with Metolachlor alone only when the seed have been pre-treated with
'Cbncep' (registered trademark of CIRA-GEIGY) at 8 oz./100 lbs. of seed,
vtoich blocks the herbicidal action of Metolachlor on sorghum.
The registered rotational crops restriction is: snail 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 snail
grains may be planted the spring following treatment; do not graze or feed
forage or fodder from anall 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,
vster 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 beccme available as more IPM weed control schanes are developed,
and the Standard for ftetolachlor will then consider the degree to which hazards
are lowered by these alternative, but equally effective, uses of the chemical.
' Preceding page blank I
' " 2 7
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PRODUCT CHEMISTRY
INTRODUCTION
FIFRA 3(c) (2) (A) requires the Agency to establish guidelines for
registering pesticides in the Ihited 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 veight.
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 inintentional.
Further, to assure that the composition of the product as marketed will not
vary frcm 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 sane 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). Fbr 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 ibpical Discussions listed below is the nunber
of the section in the 'Proposed Guidelines for Registering Efesticides' of July
10, 1978 (EH Part 163), which explains the data that the Agency will need in
order to assess Metolachlor's Product Chemistry.
Chemical Identity
'Metolachlor1 is the acceptable common name for 2-chloro-N-(2-ethyl-6-
methylphenyl)-N-(2-methoxy-l-methylethyl)acetamide as determined by the
Anerican h&tional Standards Institute (1975). Ciba-Gaigy Cbrporation,
presently the sole manufacturer of Metolachlor in the united States, has
assigned Mstolachlor the experimental nunber 'CGA-24705' (for the active
ingredient), and the trade name 'Dual'. Ihe name 'Metolachlor' will be
used in the Standard in place of the trade name or the chenical name.
Guidelines Section
Chemical Identity
Manufacturing Process
fercentages of Components in Pesticide Products
Product Analytical Methods and Data
Physical/Chemical Properties
TbX6l^r
163." 61-4
163.61-6
163.61-7
163.61-8
Preceding page blank
29
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METOLACHLOR AND RELATED
HERBICIDES
^8
V*
% c-c^cu.
o
Metolachlor
Q<
CM-- O-C*.
Alachlor
O-
Butachlor
,V*
o-<
c-cH^-a.
<**% I
Acetochlor
CHj
0~"
/VQ-^t
'W
Texbuciilor
fiH
-------
Metolachlor is both a 2-chloroacetanide and a 2-cnloroacetanilide. Figure
1.1 shows the relationship between Mstolachlor and other pesticide active
ingredients similar in chanical structure. See the '.Chenical Data Sheet' on
'CCM-001' in the Appendix for a complete chemical characterization of the
active ingredient Metolachlor.
Nknufacturing Process
Although specific manufacturing information is withheld, the publicly-
available U.S. Statent 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. Ihe general
process is shown in Figure 1.2 below, which is taken from Vogel and Aebi, U.S.
Patent 3,937,730 (1975) and Gsrman fttent 2,328,340 (1973).
Percentages of Components in Pesticide Products
Ebr all pesticide products, the Agency requires a listing of the upper and
lover limit established (by the producer or fomulator) Cor each active
ingredient, and the upper limit for each impurity or contaninant, reaction
product, and degradation product which is knpwn 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
scmetimes extrapolate part of the manufacturing process from the identity of
impurities or contaminants. Ihe 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.
Figure 1.2
31
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Oily 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 Matolachlor 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)
acetamide.
Elnulsifiable Concentrate Metolachlor (end-use pesticide)
2 presently rag istered: (a) Eftiulsif iable Cbncentrate with six pounds of
active ingredient per gallon is comprised of
68.5% the active ingredient 'Metolachlor' and
31.5 % inerts.
(b) Elnulsif iable Concentrate with eight poinds of
active ingredient per gallon is comprised of
35.4% 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 (Hslseth and Gole, 1973) . Thouqh
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 Tbxicology chapter for a discussion of
genetics effects testing requirements.)
Phys i ca1/Chemi ca1 Properties
Color: Technical Metolachlor is white to tan. The color of each
Elnulsifiable Concentrate was not reported.
Odor: technical Metolachlor is odorless. The odor of each Bnulsifiable
Cbncentrate was not reported.
Solubulity: The solubility o£ technical Metolachlor was reported to be:
In water - 530 ppn at 20 C
In organic solvents -
Insoluble in'1,2-ethanediol (ethylene glycol)
Insoluble in 1,2-propanediol (propylene glycol)
Miscible with dimethylbenzene (xylene) 1
Miscible with methylbenzene (toluene)
Miscible with N,N-dimethylformanide
Miscible with 2-methoxyethanol (methyl cellosolve)
Miscible with 2-butoxyethanol (butyl cellosolve)
Miscible with 1,2-dichloroethane (ethylene dichloride)
Miscible with cyclohexanone
32
f
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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.
Octanol/Water Partition Coefficient: Na octanol/water partition
coefficient has been reported for "technical Metolachlor.
Physical State: Both technical and Bnulsifiable Cbncentrate i^fetolachlor
products are in liquid form at room temperature.
Specific Gravity: "Iheospecif ic gravity of technical Metolachlor is 1.085
W- (3.005) at 20 C. The specific gravity of the six pound active
ingredient per gallon Bnulsifiable Cbncentrate is 1.04 (+/- 0-005} at
20 C, and the specific gravity of the eight poind ger gallon
Bnulsifiable Cbncentrate is 1.11 (+/- C.005) at 20 C.
3oilinq Point: At 0.00^ mm Hg, the boiling point of "technical
Rstolachlor is 100 C. Ebr the six pound per gallon Ehiulsif iable
Cbncentrate (EC), it is 118 C, and for the eight pound per gallon,
it is 140 to 160 C.
Vapor Pressurg: Fbr the Technical, the vapor pressure is about 10
at 20 C. Fbr the six poind per gallon EC, the vapor pressure was
reported to be 0.05 to 1.0 ran Hg at 20 C, and for the eight poind
per gallon EC, it was 0.05 rrrn Hg at 20 C.
pH: The pH of a 10% solution of six pound active ingredient per
gallon Bnulsifiable Cbncentrate is between 7 and 8, and that of an
eight poind per gallon EC is between 6 and 8.
Storage Stability: Results of ongoing studies show that "technical
Mstolachlor is stable for a minimun of one year at room temperature.
Hie shelf life of both concentrations of the Bnulsifiable Cbncentrate
is estimated to be a minimum of 5 years.
Flaimability: ffc> data were available on the flammability of the
"technical. Hie flash point of the six pound per gallon Bnulsifiable
Cbncentrate was found to tie 118 F (Setaflash C.C.T.) , and that of
the eight poind per gallon was foind to be 185 (+/- 5) F (TCC) .
Oxidizing or Reducing Action: No data ware available for the technical,
but tHe Bnulsifable Cbncentrates were reported to be clearly non-
reactive.
Bxplosiveness: Again no data ware available about the technical. A
study on the explosiveness of the six pound per gallon Bnulsifiable
Cbncentrate has shown that the material is thermally stable gt
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 riot shock sensitive. The
study on the eight pound per gallon EC is currently in progress.
Miscibility: Both Bnulsifiable Cbncentrate formulations form a stable
emulsion with water.
-------
Viscosity: No data were available on the viscosity of the Technical.
The six pound per gallog Enulsifiable 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. Fbr the Etaulsifiable 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-wee3 control, it will not be used around high power
electrical machinery, and a dielectric breakdown voltage test will not
be needed.
34
-------
DISCIPLINARY REVIEW
Giemistry Profile
Product Specific Lata Gaps
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 Metolachlor is a 'manufacturing-use product'. The
physical/chenical 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 anulsifying agent. The strength of an emulsifiable
concentrate is usually stated in poinds toxicant per gallon concentrate.
TVo strengths of Snulsifiable Concentrate Metolachlor are currently
registered: six pounds active ingredient per gallon and eight pounds per
gallon. These are someviiat viscous liquids, miscible with water, and having a
slightly greater density than vater. 'Die 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
tanperature, 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 fran open flame
or high heat; to prevent potential leaks of the eight pound per gallon
formulation due to its slight corrosiveness, it should be placed only in
application 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 Jfart 163) which describes that type of data and when it is
required.
Fbr technical Metolachlor:
1) Octanol/Vteter sortition Cbefficient
2) Flanmability
3) Oxidizing or Reducing Artion
4} EJcplosiveness
163. 61-8 (c) 6
163.61-8(c)13
163.61-8(c) 14
163.61-8(c)15
35
-------
5) Viscosity 163.51-8(c)17
6) Corrosion Characteristics 163.61-8(c)18
7) [and, if the Technical is found to produce
genetic effects (see Tbxicology 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 Mstolachlor.
Ebr Ebulsifiable Concentrate Mstolachlor (6 lbs. ai/gallon):
1) Color 163.61-8(c)1
2) Cdor 163.61-8(c)2
For Elnulsifiable Concentrate ffetolachlor
1) Color
2) Cdor
3) feplosiveness
(8 lbs. ai/gallon):
163.61-8(c)1
163.61-8(c)2
163.61-8(c)15
Suggested Labeling
The ingredient statement for Mstolachlor products should list the
active ingredient • Mstolachlor' as:
"Mstolachlor: 2-chloro-N-(2-ethyl-6-methylphenyl)-N-(2-methoxy-l-
methylethyl)acetan ide"
36
-------
BIBLIOGRAPHY
Each of the following studies contributed useful information to the
Agency's review of the produce chemistry of Metolachlor, and is considered part
of the data base supporting registrations under this Standard.
American National Standards Institute (1976). Anerican National Standard ANSI
K62.198-1976. Common name for the pest control chemical 2-chloro-N-(2
methoxy-l-methylethyl) acetamide: "nietolachlor". New York, N. Y.
Ciba-Geigy Cbrporation (1974) Section Af CGA-24705: Name/ Chanical Identity
and Composition of CGA-24705. .(Unpublished study; received Sep 26,
1974 under 100-SUP-44; CDL:96505:A)
Ciba-Geigy Cbrporation (1975h) Section A, CGA-24705: Name, Onanical Identity,
and ccmposition of CAG-24705. Fteceived Nov 25, 1976 under 6G1708.
(Unpublished study; CDL:96439-A)
Ciba-Geigy Cbrporation (1976a) CGA-24705: Name, Chanical Identity, and
Ccmposition of CGA-24705. fteceived Nov 23, 1976 under 100-587.
(Unpublished study prepared by Ciba-Geigy Osrp., Greensboro, N.C.;
CDL: 226955-A)
Ciba-Geigy Corporation (1977) Aerial Application. Received F^b 18, 1977
under 100-583. (Unpublished study that includes studies ID-9D with a
sunmary; CDL: 228101-F; 228 122)
Ciba-Geigy Corporation (1977ba) Section A General Chemistry. (Unpublished
study; received Jan 19, 1977 under 7F1913; CDL:95764-A)
Ciba Geigy ODrporation (1977b) Aerial Application. Received Jun 20, 1977.
(Unpublished study containing studies 3D-10D with a sutmary; CDL:230672-D,
230683)
Helseth, J.; Gole, G. (1973) The Determination of CGA-24705 in Qnulsifiable
Oancentrates by Gas Liquid Chrcmatograpy. 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)
\fogel, C.; Asbi, R., inventors; Ciba-Geigy Cbrp., assignee (1976) Plant growth
regulating agent. U.S. patent 3,937,730. Eteb 10: 3p. Int CI . C07G
103.34.
Vbgel, C.; Aebi, R., inventors; Ciba-Geigy Obrp., assignee (1973)
Haloacetanilides acting on plant growth. German patent 2,328, 340.
Dec 20: 50p. Int. CI. C07C 103.38.
37
-------
ENVIRONMENTAL FATE
TOPICAL DISCUSSIONS
Corresponding to each of the Tbpical Discussions listed below is the nunber
of the section(s) in the 'Proposed Guidelines for Registering Pesticides' of
July 10, 1978 (40 FR Pact 163} which explain(s) the data that the Agency will
need in order to assess Metolachlor*s Ehvirormental Ffete.
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 i^tetolachlor at 22 C were calculated
to be greater than 200 days in 0.1N HQ (pH 1) and in buffer pH 5, 7, and
9. to 0.1N NaOH (pH 13), the calculated half-life was 97 days. Hydrolysis
of Metolachlor in 0.1N NaCH at 30 C yields N-(2'methoxy-1-methyl-ethyl)-
2-ethyl-6-methyl hydroxyacetanilide. Ih 0.1N HQ 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
environmental concern because Metolachlor is considered to be stable in the
natural environment.
Photolysis
Because ftetolachlor 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
Mstolachlor, a study on photolysis in the vapor phase is not necessary.
Photolysis in Aqueous Solution
MetolacKlor was found to be relatively stable in aqueous
solution under natural sunlight (Aziz and tehrs 1975). Approximately
6.6% was photolyzed in 30 days, which was less than 10% of the
exposed activity. Five photo products, accounting for about 4.7% of
the activity, were fouid in the chloroform soluble fraction. Che
photoproduct was identified as 4-(2-methyl-6-ethylphenyl)-5-
methylmorpholine. Ebur of the photo products ware not identified.
Guidelines Section
Fhysico-Chanical Transformation
Soil Metabolisn
Microbial Metabolisn
Mobility
Spray Drift
Field Dissipation
Accumulation
163.62-8
163-62-8
163.62-9'
163.126-2, -3, and/or -4
163.62-10
163.62-11
Preceding page blank
39
-------
Che in known 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,
Lhder high intensity artificial sunlight conditions, Metolachlor
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 numbers.) Photolysis products in the aqueous
phase anounted 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 product^were separated, tone...
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, Matolachlor is
considered to be stable in aqueous solution under natural sunlight.
Photolysis in Soil
Studies on soil slides were performed by Aziz (1974). Ihder
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-methyl-6-ethylaniline, and three unknowns
accounted for 7.7%. Each unknown was less than 10% of the applied
activity, ton-extractable C-activity in soil amounted to 39% of
the applied activity. Vblatiles accounted for 10.5% of the applied
activity, of which 5.2% was determined to be parent.
thder 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-yi-N-
chloroacetyl-2-methyl-6-ethylaniline, and 16.4% was comprised of 3
unknowns. (Each.unknovji was less than 10% of the applied activity.)
Nbnextractable C-residue in soil amounted to 39%. \folatiles .
accounted for 6.8% of applied activity, of which 4.12% was determined
to be parent.
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
-------
Soil Metabolism
Elleghausen (1976a and b) studied the degradation of Mstolachlor in soil
under sterile aerobic, nonsterile aerobic, and nonsterile aerobic followed by
nonsterile anaerobic conditions. Uider sterile aerobic conditions, at the end
of 12 weeks, 30% of the reductively dechlorinated analog of Metolachlor (MET-
005) vas found, other metabolite could be detected. The remaining
radioactivity existed as undegraded Matolachlor.
Also at a time interval of 12 weeks, 'both the aerobic nonsterile and
aged aerobic/anaerobic nonsterile tests resulted in a degradation pattern
wherein about 18% of the radioactivity was identified as MET-025. Another 10%
Vs
MET-005
(
ch3
I
CH-CHjQCH^
> r - Cl - <
"C-C-OH
II ll
o o
MET-025
of the initially applied radioactivity was found as polar, water soluble
products. They were inseparable by TDC, but could be methylated with
diaaDmethane to form three distinct components, separable by gas liquid
chromatography (GLC). The investigator considers these to be ring
hydroxylated analogs of MET-025. A nonpolar metabolite,
representing about 5% of initial radioactivity was compared, by TLC and GLC co-
chromatography, to 26 model Mstolachlor metabolites with no identity fit.
3nall amounts of MET-005 as well as unidentifiable polar and nonpolar
extractables were also fornd.
Sumner, Szglics, and Cassidy (1976) studied the products of degradation of
ring labeled C Mstolachlor in silt loam treated at an exaggerated rate
(100 ppm) and incubated out-of-doors in open bottoned containers. Besides
CM
* ,c*s
\c-
MET-001
MET-008
41.7% of total initial radioactivity foind as Metolachlor, 0.9% of MET-001 and
0.1% MET-008 were focnd. Additionally, an oxalic acid derivative was
tentatively identified as MET-025. Chatticals contained in the leachate from
this study ware qualitatively similar, 'as determined by comparative radioassay
of various TLC Rc zones.
Concurrently, Sumner, Szolics, and Cassidy (1976) conducted a field plot
study of silt loam soil treated at 2 lbs active ingredient per acre (a.i./A)
41
-------
and aged 12 months. This study yielded in addition to MET-00I, ME7T-008, and
MET-025, the additional compounds MET-003 and KET-026-
All metabolites in both substudies were less than 1% of total,
radioactivity, except MET-001 in the leachate, which represented 2.5% of total
radioactivity. TVo 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 TLC plate origin
represented 6.4% of the total radioactivity.
Sunner and Cassidy (1975a) showed that inder 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 aid humic acid
fractions decreased with a concomitant increase in the amount remaining in
ctions. The fractionation procedure used was
IXipre (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 metabolian.
Evidence is provided by Sunner and Cassidy (1975a) that nonex tractable
bound residues of Metolachlor and its metabolites are in dynanic equilibrium
with soluble fonns and that the nonextractable portion may therefore serve as
a long term reservoir for extractable residues.
When viewed as a canpDSite, these tests satisfy the soil metabolism data
requirenent for Metolachlor. (The following additional studies contain
information related to metabolic transformation in soil but did not by
themselves supply adequate information about soil metabolian: teiser 1974,
Sumner and Cassidy 1974g, k, 1, m, f, and e) .
Microbial Metabolism
Three microbial metobolisra studies «ere available. Che was conducted
according to the alternative pure or mixed culture technique and tv*o were
conducted by the sterile and non-sterile soil approach.
In the pure and mixed culture study (MrGahen and Tiedje) , Anerican Type
Culture Cbllection 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% ot Metolachlor ranaining after 5-7 days, fln
adaptive lag period of approximately 20 hours was observed. A total of at
least eight extractable products were identified or tentatively identified.
C-CWiQM
MET-003
MET-026
42
-------
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.
IGiiser, using labeled Metolachlor (position of label unspecified) added
Metolachlor to both sterilized and unsterilized sandy loam soil at a
concentration of 10 rag/250 gra of soil (40 ppra) (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 monitoi^jd for degradation. After a short lag phase, a
slow but steady evolution of CC>2 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.
Ch the basis of these studies, a general microbial transformation schane
can be postulated v»tiich 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 compoind 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 assesanent for
the present uses of Metolachlor.
Mobility
Leaching
Data on leaching have been developed by Dupre (1974c) and fbusevorth
(1973b) . Ffcrent 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 vtfien an equivalent of 20 inches of
rainfall are applied to a soil colunn overlayered with Metolachlor.
Conversely, insignificant leaching is expected in muck soils high in
organic matter. Field studies (Ballantine, 1975) shoved 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 tetolachlor.
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 Matolachlor. This
constitutes a data gap.
43
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Spray Drift
Information on the likelihood or extent of spray drift for Ehalsifiable
Concentrate Metolachlor when conventional ground sprayers are used is not
presently available, accept for what is generally understood about the spray
drift behavior of similar agricultural chemical preparations. Subpart J of the
Proposed Guidelines, '«hich will cover drift as it relates to phytotoxic
effects, has not yet been accepted for regulatory use. Because Metolachlor is
a herbicide vAiich 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 v«re conducted by Bailantine (1975) on five
different soil types representing five geographical locations. The following
conclusions were drawn from the studies: 1) Approximately 13% of applied
Metolachlor was found in the upper 12 inches of Mississippi loam after 60 days
for both 2 and 4 lbs. active ingredient per acre (a.i./A) application rates.
2) In Nebraska silt loam, approximately 10% of applied Metolachlor was foind
in the upper 12 inches after 162 days for both 2 and 4 lbs. a.i./A application
rates. 3) In tew York, California, and Illinois, soils that were not
analytically characterized, Metolachlor dissipated to about 10% of che applied
in 60 to 150 days for both 2 and 4 lbs. 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 thac 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 lbs/
acre using C-ring labeled Metolachlor. Low levels of residues ranging
frcm 0.02 to 0.27 ppn, 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 ^O/MeCH vs.
CHG.^) and the two major fractions constituting these polar residues
were neutral and acidic in nature, as determined by ion exchange
chromatography. A typical analysis of such plant residues is provided by
the following example for oat straw derived from oats growi as a
rotational crop to corn where Metolachlor was applied at a rate of 2 lbs/
acre (Sumner and Cassidy, 1974f).
Calculated ppn
. as Metolachlor
1) Ttotal C activity =0.27 ppm
2) HjyMeOH extractable, % of total activity = 67% .18
-Tfeutral Fraction, % of total activity. = 19% .05
- Acidic Fraction, % of total activity = 45% .12
3) extractable, % of total activity =7.0% .02
44
-------
The text of the review by Pterco (1974) of metabolian studies with
Matolachlor in corn implies that only highly polar acid metabolites, such
as conjugates involving the N-acetyl group of Metolachlor are present.
HDVsever, the data presented in T&ble 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. Sunner 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 IVf Marco-1974)
Ionic Characterization of Radioactive Metabolites in Ftolar
Fraction of Cbrn Treated with 2 lb. ai/A 14C Metolachlor
Location
Ionic Charge
14
Percent of Total C
in Plant
weeks after
treatment
8
12
16 (mature forage)
Greenhouse
Neutral
7.0
7.9
a
(a » sample
£cid
73.1
53.6
a
decomposed
Base
0.6
0.9
a
in shipnent)
Zwitterion
6.2
21.4
a
Field
Meutral
7.4
10.8
7.3
A^id
68.2
70.4
26.3
Base
1.7
1.2
1.0
Zwitterion
2.7
8.4
15.3
Marco (1975), and Suaner 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
tetolachlor in corn grain may be the only ones worthy of consideration,
the same is not necessarily true with rotational crop uptake. GampDunds
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 Fbss, 1975).
HP-002
CH
HP-001
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
-------
conjugates* Again, using the oat (straw) example, cited above, one can
conclude that the entire neutral fraction of the H-C/MeOH extractables
equaling 0.05 ppn could be a mixture of MET 302, 004, 308, 009, and 010
(or other degradates of a similar nature) and would not be detectable by
the method of 3alasubramanian, Aziz, and Fbss (1975). Such compounds
should be readily amendable to GLC and TLC separation zone and
retention time can pari sons with model con pounds .
Based on information submitted by Ballantine (1975), the roots of root
crops, grain of anall grains, and oil frcm oil seed crops (such as cotton
seed) can reasonably be expected to contain little, if any, residue of
Metolachlor per se or its metabolites hydrolyzable to HP-001 or HP-302.
using the method of Ealasubramanian, Aziz, and Fbss (1975). All residue
analyses for MET-007 were 0.33 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 v^ieat 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 Fbss,
1975.
Lettuce was grown outdors as a rotational crop to soybeans in the fall
and spring, 14 ^rjd 41'weeks respectively, after soil was treated at 2 lbs.
a A./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 ppn. The levels observed in the second crop (spring
planting) were 0.144 ppm in the 13-week old sample and 0.062 ppm in the 15-
week old sample (final harvest) .
Oily the 54-week lettuce sample (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 anall grains,, root
crops, or leafy vegetables to establish an interval between Metolachlor
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 wre not sufficiently
characterized to dispel concern over their potential contamination of the
food web.
Tne registered rotational crops restriction provides that: "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. Da 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."
However, the Agency has a new policy on rotational crops: EPA will
now accept petitions for 1 rotational crop tolerances' for rotated crops,
and vrfnere 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
4 6
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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 option, 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
tolerance' for that crop, which may allow for an earlier rotation.
Studies in which Metolachlor was applied in accord with existing
usage shoved residues, and the need for tolerances for these residues, in
the forage and fodder of anall 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 anall
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 ?fetolachlor-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 anall 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 growi as a
rotational crop in the spring following the treatment of corn, soybeans,
peanuts, or sorghun with ftetolachlor. 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 in less tolerances are established for those rotated crops which
wuld contain residues, the label on any product formulated with
Mstolachlor 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 sorghun may be planted in
the spring following treatment. 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 anall 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
3.1 ppn Metolachlor, algae accumulated 10.4 ppn. ftowaver, following 2
hours depuration, less than 2 ppn remained in the cells. Daphnia, exposed
for 24 hours to 0.1 ppn, accumulated 0.63 ppn. Eight hours depuration was
needed to achieve a 50% loss. Eaphnids accumulated only 20% more when
expDsed to both algae with 10.4 ppm Metolachlor and water containing 0.1
ppn Metolachlor as compared to fortified water in the absence of algae.
Catfish, exposed to 0.1 ppn C Metolachlor accumulated 1.20 ppn
Metolachlor in their tissues after 96 hours. Hawever, a plateau was not
reached.
Metabolites of Jfetolachlor were noted but not identified in the
algae, daphnids,^|nd 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 ppn. The accimulated
residues in the edible portions remained relatively constant in terns of
extractable vs. nonextractable (about 8:1). Ch 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 1 C activity in the
edible tissue on day 14. 3naller amounts of other metabolites were found
in edible and/or visceral tissues but v^ers not identified.
M-^'hydroxy-l'-methylethyl) -2-ethyl-6-methyl chloroacetanilide (MET-
003), N-2(2-hydroxy acetyl)-N-(l-methyl propane-2-yl)-2-ethyl-6-methyl
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 Metolachlor 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 ppm in the nonedible tissues. Existence of a plateau could not be
established. After 23 days depuration, residues in edible portions of fish
decreased to 3.08 ppn for the 10 ug/liter C Mstolachlor exposure and to
11.7 ppn for the 1000 ug/liter exposure. The chemical nature of the fish
residues was not defined. When the above studies are considered as a
ccmposite, they are sufficient to adequately characterize the fish
accunillation characteristics of Metolachlor.
48
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DISCIPLINARY REVIEW
Environmental Pate Profile
Exposure Profile
Generic lata Gaps
Suggested Labeling
Environmental Fate Profile
Metolachlor is applied at a rate of 1.5 to 3.0 poinds active ingredient per
acre to soil where corn (excluding popcorn), soybeans, peanuts, or grain
sorghum are to be growi. Normally, the chemical is sprayed on the soil during
or soon after planting, before sprouts anerge. 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. fbwever, if Metolachlor is applied and incorporated into the top 2
inches of soil,, then degradation by photolysis is expected to be. minimal. Soil
metabolian, by both aerobic and anaerobic microorganisms, would also play an
important role in the degradation of Metolachlor in the soil (McGahen and
Tiedge, 1978) .
About 30% of the photoproducts were represented by MET—309 and MET-001.
(See the Chemical r^ct Sheets in Appendix A for characterizations of these
and other metabolites.) Another 30% was represented by CHC1, and water-
soluble polar metabolites. Indirect evidence obtained from analysis of
aqueous photoproducts produced by artificial light of <280 rm 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. TVo
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 Metolachlor appears to proceed by hydroiytic cleavage
of the N-alkyl terminal constituents followed by oxidation and/or ring
closure. The following reactions -were found to occur on the N-alkv groups:
R-C- (3> 0
ring .closure
0 0
S-C-C-CH
¦ •
0 0
tl
q
(Elleghausen, 1976a and 1976b; Sumner, Szolics, and Cassidy 1976;
Sumner and Cassidy, 1974 and 1975)
4 9
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Attack of the 'oenzenoid portion of the molecule to form phenolic metabolites
was speculated but not proven (Elleghausen, 1976b). The likelihood of such
ring attack is contraindicated by the following observations: (1) B/idence is
provided by Sumner and Gassidy (1974) that non-extractable bound residues of
Metolachlor are in dynamic equilibrium with soluble foms, (2) unextractable
residues represented by fulvic and humic acid fractions decrease with
increased aging. Incorporation of polyphenols metabolites into the soil
organic matrix would mitigate against both of the above findings.
Studies were also available on Metolachlor1s environmental mobility.
Houseworth (1973b) , in a laboratory colunn 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 ^nds and sandy loams having organic
contents of 2% or less. Residues of aged C-Metolachlor wre also found
leach extensively in sandy loam soil (Eupre, 1974). Based on incremental
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 Metolachlor5s potential for
significant movement in the soil, but left open the question of whether
Metolachlor 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 Metolachlor
applied at up to 4 lbs. a.i./acre (pre-anergent) 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 LEA climate
extranes were involved. But absolute losses of Metolachlor between the day of
application and final sampling were not alvrays so great. Fbr 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. Tnis 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 bioacc^^nulation. Bluegill sunfish exposed J^r 70 days to a mean
level of 1.2 ppm C Metolachlor accumulated 18 ppn 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 1-2 and 13
ppn respectively. The chenical nature of the residues was not investigated
(Barrows, 1974). A catfish study (Smith, 1977) involving aged Matolachlor on
sandy loam soil resulted in an accumulation of 3.53 ppm in edible catfish
tissue at the end of 30-day exposure. After 14 days of depuration, the level
decreased to 3.03 ppn. Values for viscera at the end of the 30 day exposure
and after 14 days depuration were 4.4 and 0.18,-Ppn, 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
anall grains, and oil fran oil seed crops, grown as rotational crops to com in
a Mstolachlor-treated field, vere shown to have little, if any, residues of
Metolachlor, as analyzed by the officially accepted regulatory method for corn
grain, forage, and fodder (Balasubiramanian, 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 forn^after hydrolysis ,of the N-alkyl groups of
Mstolachlor 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
com 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 Balasubrananian, Aziz, and Ross (1975): carrot tops, soybean
stalks, sugar beet tops, and Vvheat 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: Ebr persons involved in the handling, storage, or
shipnent 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.
Ihe fate data have indicated the relative stability of Mstolachlor 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 envirorment, it is possible that exposure could occur to
various species, but particularly aquatic species, and perhaps to
carnivores feeding on contaminated fish. Also, considering Mstolachlor's
potential for rotational crop uptake, plants growing on contaminated soil
could pass on residues to herbivores, including birds.
Bnulsifiable 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 fran the splashing that may occur in diluting and
tank mixing, and in the loading of spray equipment. The vapors from
the Bnulsifiable Cbncentrates 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 Nfetolachlor 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 fran Mstolachlor'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 Mstolachlor per se is subject to extensive leaching i^ien 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 Mstolachlor can move from
agricultural sites of application both by sheet erosion and leaching;
-------
Metolachlor is stable to hydrolysis over the environmental pH range of 5
to 9; the estimated half-life for fetolachlor 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 v^ater, or carnivores which feed on contaminated
fish. Also, because of Metolachlor's demonstrated uptake by rotational
crops, it may be assuned 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. Pbr 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. Hie Agency has identified, in a three-step
process of selection, two watersheds which have been determined
appropriate for ffetolachlor field monitoring: first, the Pgency identified
the regions of the ihited .States in which the most com, soybeans, peanuts,
and grain sorghun are growi; 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 rmoff) (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 v^tershed residue monitoring are: one watershed just south of Treynor
in Rittawattamie Cbunty, Ibwa; and the Little River experimental watershed
near Tifton, Georgia.
The possibility for ffetolachlor residues to occur in food or feed,
which may result in dietary exposures to hunans, livestock, or domestic
animals, is discussed in the 'Residue Qianistry' chapter.
5 2
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Generic Data Gaps
The following are gaps in the Ehvironmental Fate data base which will be
used to support registrations under this Metolachlor Standard. Opposite each
gap is given the section in the Proposed Qaidelines of July 10, 1978 (FR Efert
163) which describes that type of data and when it is required.
1) Adsorption/desorption studies 163.62-9
2) Ascunulation studies on rotational crops ' 163.61-ll(b)
for anall grains, root crops, and leafy
vegetables.
3) Actual field residue monitoring studies (no guidelines)
at two watershed sites co 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, Bnulsifiable Concentrate Metolachlor should carry
the following rotational crops restriction on its label:
"anall 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. 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."
53
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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 Cbnditions: GAAC-74102. Fteceived Mar 26, 1975 under
5F1606. (LhDublisned study prepared by Ciba-Geigy Corp., Greensboro, N.C.;
CDl:94385-J)*
Aziz, S.A.; tehrs, 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 Gbrp.f
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, VDlune 2, AC 25.53; SR 2/74. (Unpublished report prepared by
CIBA-GEIGY ltd., Basle, Switzerland; CDL: 94222^1)
Hjpre, G.D. (1974a) Abbreviated Anaerobic Mstabolism of "^C-CGA-24705 in
Silt Loam Soil under Greenhouse Gonditions: 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:94222-3)
Ellegehausen, H. (1976a) Project Report 4/76: A Madel system for Estimating
the Uptake, Transfer and Degradation of Agrochetiicals by Aquatic Organisns.
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 24705 in
Aerobic, Anaerobic and Autoclaved Soil. AC 2.52. Received Fteb 6, 1978 under
100- 583. (Unpublished study prepared by Ciba-Geigy Ltd., Basle,
Switzerland; CDL:232789-D)
Ellegehausen, H. (1976c) Project Report 5/76: Pddendun to Project Report 4/76:
Degradation of CGA 24705 in Aerobic, Anaerobic and Autoclaved Soil. AC
2.52. Iteceived Feb 6, 1978 under 100-583. (Unpublished study prepared by
Ciba-Gaigy Ltd., Basle, Switzerland; CDL:232789-E)
Ellegehausen, H. (19771. Project Report 3/77: Uptake, Transfer and Degradation
of CGA 24705 (Dualv ') by ?quatic Organisms. AC 2.52. Received Feb 6, 1978
under 100-583. (Unpublished study prepared by CIBA-GEIGY Ltd., Basle,
Switzerland; CDL:232789-C)
; Preceding page blank
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Fbuseworth, L.D. (1973b) Report on Ferent leaching Studies for CGA-24735:
Report Mo. 1. Fteceived Sep 26, 1974 under 5G1553. (llhpublished study
prepared by University of Missouri—Golumbia, Department of Plant ethology
for Ciba-Geigy Cbrp., Greensboro, N.C.; CDL:94222-E)
Marco, G. (1974) Surrmary of Section D: CGA-24705-Gom: Residues Cbserved and
Metabolism Data Including the Analytical ."Methods Used: GAAC-74062. Fteceived
Sep 26, 1974 under 5G1553. (Lhpublished study prepared by Ciba-Geigy Corp.,
Greensboro, N.C. that. incl'jdes 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 acvlanilide
herbicides, Antor Herbicide (H-22234) and Dual (Metolachlor) by the soil
fungus Chactomium globosum. Journal of Agricultural Fbod Chemistry
26(2):414-419.
9nit^, K.S. (1977) Report: Catfish Bioaccunulation Study following Exposure to
C-Metolachlor in a Soil/Water/Fish Efcosysten. 7E-6506; Fteceived Ebb 6,
1978 under 100-583. (lhpublished study prepared by Cannon Laboratories, Inc.
for Ciba-Geigy Cbrp., Greensboro, N.C.; CDL:232739-U)
Sunner, D.D.; Cassidy, J. E. (1975a) The Degradation of CGA-24705 in a Field
Soil: GAAC-75022. Fteceived fflr 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 CCft-24705 in
Soil. ABR-76057. Fteceived Ffeb 6, 1978 under 100-583. (Unpublished study
prepared by Ciba-Geigy Cbrp., Greensboro, N.C.; CDL:232789-V)
56
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TOXICOLOGY
TOPICAL DISCUSSIONS
Corresponding to each of the Tbpical Discussions listed below is the number
of the section(s) in the 'Proposed Guidelines' of August 22, 1978 (FR Fart 163)
vhich explain(s) the data that the Agency will need in order to assess
Metolachlor's "toxicology.
Metabolism and Pharmacodynamics
Metabolian studies on Jfetolachlor (Hambock, 1974a,b) demonstrated that:
(a) Most orally administered Matolachlor is rapidly absorbed,
metabolized, and excreted.
(b) Hie urine and feces of treated animals contained a complex pattern
of metabolites; each metabolite accounted for less than 5% of the
administered dose, bb unchanged drug v*as detected in urine or feces
sanples.
(c) Approximately half the urinary and fecal radioactivity was
extractable with organic solvents.
(d) Mo glucuronide or sulfate conjugates «ere found in the excreta.
(e) Several excreted metabolites were tentatively identified and
appear to result from dechlorination, O-methylation, N-dealkylation,
and side chain oxidation in the rat. ^
In an additional study (Hambock, 1974c), male rats were treated with C
Matolachlor (approximately 31 mg/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) , colimn
chromatography, gel permeation chromatography, and enzynatic hydrolysis were
adequately utilized to identify radioactive metabolites, which were identified
as 2-ethyl-6-methylhydroxyacetanilide (MET-002) and N-(2-ethy1-6-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 danonstrate the relatively rapid metabolian and excretion of
Metolachlor, and are sufficient to fulfill the requirement for this type of
information.
Metabolisn and Pharmacodynamics
Acute Effects and Neurotoxicity
Local Irritation
Subchronic Effects and Neurotoxicity
Sensitization
Chronic Effects
Oncogenicity
Mutagenicity
Teratology
Reproductive Effects
Guidelines Section(s)
153.85=1
163.81-1, -2, -3, and -7
163.81-4 and 163.81-5
163.82-1, -2, -4, -5, and -6
163.81-6
163.83-1
163.83-2
163.84-2, -3, and -4
163.83-3
163.83-4
5 7
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Acute Effects and Neurotoxicity
Acute Oral Toxicity
The minimum testing needed on acute oral toxicity is one test on the
laboratory rat for each technical and formulation.
For "technical Mstolachlor, the acute oral LD-50 in the laboratory
rat is 2,780 mg/kg with 95% confidence limits of 2,180-3,545 mg/kg (Bathe
1973). Technical Mstolachlor in corn oil has been showi to be emetic in
beagle dogs to an extent that precludes the establishnent of an oral LD-50
in dogs (Affiliated Medical Research, Incorporated, 1974e) . The study
did, however, establish the 'anetic dose 50' to be 19-0 (+/- 9.7) rag/kg*
The Ttechnical therefore falls into category III with regard to acute oral
toxicity.
Ttests were also done on the two Bnulsifiable Cbncentrate formulations.
In a test involving a 6-pound per gallon E.C. 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 Medical Research, Incorporated, 1974d). Hi a test
involving an 8-pound per gallon E.C. 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 f&rrison, 1977a). A related study (Affiliated
Medical Research, Incorporated, 1974f) established that the 'emetic dose
50' in dogs to a 6-pound per gallon E.C. vras 24.5 (+/- 9.2) mg/kg. Based
on the above data, it is anticipated that E.C. formulations of Mstolachlor
as high as 8-poinds 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.C. 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 Ttechnical to the >few Zealand rabbit is greater than
10,000 mg/kg when tested by the unabraded dermal route, 'lie above
information is sufficient to meet the requirenent for acute dermal toxicity
data on intact skin. The unabraded dermal test results place the Ttechnical
in Category III with respect to acute dermal toxicity.
In a test involving a 6-pound per gallon E.C. formulation, the acute
dermal LD-50 to the New Zealand rabbit was found to be greater than 10,000
mg/kg by the intact dermal route (Affiliated Medical fesearch Incorporated,
1974b). Ebr an 8-pound per gallon E.C. formulation, it was established
that the acute dermal LD-50 to the New Zealand rabbit is greater than
3,338 mg/kg via the intact dermal route (Miam and Harrison 1977b). A
related study (Tryzna and Faa, 1976) determined that the acute dermal LD-
50 of a 1 to 10 dilution of a 6-pound per gallon E.C. formulation was
greater than 16,000 itg/kg via the intact dermal route. The available
data, then, places both existing E.C. formulations in Category III with
respect to acute dermal toxicity.
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Acute Inhalation Toxicity
Hie minimum data needed on acute inhalation toxicity is one
inhalation LC-50 test, using one mammalian species, preferably the albino
rat, for each technical and formulation.
.Acute inhalation toxicity for the Technical was tested by Sachsse and
LUlman (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 pound per gallon E.C. formulation, the acute
inhalation LC-50 was found to be greater than 257 rtq/1 of air (with four
hours of exposure) in the albino rat (Affiliated Msdical Research,
Incorporated 1974c). Hswever, in the test for acute inhalation LC-50 for
an 8 pounds per gallon E.C. 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.C. The
available data, then, places the existing E.C. formulation of 6 lbs. per
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. Metolachlor is a
chloroacetanilide herbicide and is not expected to cause esterase
depression or delayed neurotoxicity. Therefore, this test is not required
for Ttechnical Mstolachlor.
Local Irritation
Primary Eye Irritation
The minimum 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 >tew Zealand rabbit. In that study 0.1 ml of Technical
Metolachlor was used. The test ms evaluated using the system of Draize
(1959) and produced the following eye irritation and indices at 24 hours
and 7 days:
Cornea: 0
Iris: 0
Conj unctivae: 0
This study establishes that Technical Metolachlor is non-irritating to the
rabbit eye (Category IV).
In a test involving a 6-pound per gallon E.C. formulation, the data
indicates that this formulation is a severe irritant which can cause
irreversible corneal opacity in the unrinsed albino rabbit eye (Affiliated
.¦fedical Research, Incorporated, 1974i) . In a study involving an 8-pound
per gallon E.C. formulation (Scribor and f-festri , 1977a): the results from
tests conducted with unrinsed eyes showed moderate corneal opacity
(reversed in 7 days) and conjunctival effects (partially reversed in 7
-------
days) ; the results from tests on rinsed ayes showed slight iris and
moderate conjunctival effects (reversed in 3 days). The available data,
then, places existing E.C.- fomulations in Category I (for 6 lbs.) or
Category II (for 8 lbs.) with regard to primary eye irritation.
Considering the lack of irritation effects due to the active ingredient
alone (in the Technical), and the difference in eye irritation effects
between the two formulations, the degree of eye irritation produced by
Metolachlor formulations appears to be directly dependent upon the type and
anount of inert formulants used.
Primary Dermal Irritation :
fFe minimun testing needed to determine the potential for primary
dermal irritation is one test conducted on a mairmal, 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 vas evaluated using the
system of Craize (1959) and resulted in a primary irritation index of 0.1.
This information is sufficient, and it establishes that Technical
Mstolachlor is non-irritating to rabbit s*in (Category IV) .
In a test involving a 6-pound per gallon E.C. formulation, the primary
irritation index was determined to be 1.62 (Affiliated Medical Research
Incorporated, 1974h). In a test involving an 8-pound per gallon E.C.
formulation, the dermal irritation was described as: moderate erytfrna,
edema, and second degree burns at 72 hours (Scribor, 1971). 3ased on the
above data, it is anticipated that E.C. formulations of Mstolachlor 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.C. formulations in
category II (for 8 lbs.) or category IV (for 6 lbs.) with regard to primary
dermal irritation. As with eye irritation, the degree of dermal irritation
appears to be dependent upon the type of inert canponents used in the
formulations rather than on the concentration of the active ingredient,
Metolachlor.
Subchronic Effects and Neurotoxicity
Subchronic Oral Dosing
Testing should be performed in at least 2 mammalian species. Che
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-Cawley rats
(Cbquet, CSlland, Guyot, fbuillet, and Fbuaud, 1974d) and with beagle dogs
(Cbquet, Galland, Guyot, fbuillet, and Rouaud, 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 9&-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 (Cbquet
et al, 1974d). However, because that two-year rat feeding study was
60
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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 Metolachlor.
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 ppn.
Subchronic 21-Day Dermal
The minimum testing needed is one study in one manualian species.
Although no data is presently available on Technical Metolachlor, 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 Metolachlor 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
iEi" 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 rainimixn 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 ftedical 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) wsre intradermally injected into the skin of Pilbright
6 1
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guinea pigs. Positive reaction-was demonstrated in animals injected with
Technical Metolachlor dissolved in the vehicle; there was no reaction in
animals injected' with the vehicle alone. Based on this second study, wnicn 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.C.
fomulations were directly tested, it is anticipated chat E.C. formulations of
o or 8 lbs. ai/gal will also cause skin sensitization in guinea pigs.
Chronic Effects
Chronic testing should be available on at least one manmalian 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.
Che 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 dieto The study does offer supplementary information on tetolachlor's
potential oncogenicity (see below) . Because this study thus cannot be used to
fulfill the guidelines requirement, the rat chronic feeding study for
Metolachlor is currently a data gap.
Oncogenicity
For the adequate assessment of oncogenicity, studies are needed in two
manmalian 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, 1,300, 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-Ttest 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 beirq valid for the support of pesticide registrations, Ciba-
Cteigy initiated a new mouse oncogenicity study, rtowever, 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 I3T 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 ffetolachlor is oncogenic.
Nevertheless, this study does not fulfill the guideline requirement for an
oncogenicity test in the rat, and this constitutes a data gap. Pn oncogenic
evaluation performed on the animals in the required tvvo-year rat chronic
feeding study would suffice for this requiranent on oncogenicity in the rat.
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Mutagenicity
The following studies represent only the minimun requirements for data on
the potential heritable effects of a pesticide: (1) a mammalian in vitro point
mutation test; (2) a sensitive sub-manmalian point mutation test-(bacteria,
fungi, insect); (3) a primary ENA damage test (i.e., sister chromatid exchange
or unscheduled ENA synthesis; and (4) a manmalian 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
requiranents 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 minimun requirement.
In accordance with the fact that the above policy on mutagenicity testing
is an interim one, the minimun testing presently being required to assess
mutagenicity for Nfetolachlor 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 maimalian microsomes (Arni and Miller,
1976), and in an in vivo system to test the effect on developing sperm in the
mouse (Ciba-Gaigy 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).
Isb increase in background mutation rates was observed. Nor 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,
vdiich are presently sufficient for mutagenicity testing, no evidence arose
to suggest that Metolachlor has any mutagenic potential. Further mutagenicity
testing on Mstolachlor may later be required when a final policy on
mutagenicity testing has been established.
Teratology
The minimun data needed to evaluate the potential fetotoxic or teratogenic
effects of a pesticide are tests in two manmalian species, A study of the
teratogenic effects of Technical Mstolachlor on rats v*as 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-Dawley rats. No fetotoxic effects of the can pound 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 assessnent of teratology in one species of mamnal, 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 minimum data needed for measuring reproductive effects can be
provided by one rat study lasting t'wo generations. The one available study
(3nith and Ailer, 1973) 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.
6 4
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DISCIPLINARY REVIEW
Toxicology ftrofile
Ibxicology ffczard Assesanent
Generic Eata Gaps ,
Product Specific Data Gaps
Suggested labeling
Toxicology Profile
Technical Metolachlor: Sufficient data were available to support
an assesanent of the technical's acute toxicity. Hie relatively high
acute oral LI>-50 in rats (2780 mg/kg) and the emetic effects in dogs
indicate a low acute oral toxicity to hunans. Dsrmally, at least in the
rabbit, Metolachlor does not appreciably penetrate intact skin. Doses 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 ftetolachlor
would not be readily absorbed through hunan 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
maximun achievable concentration (1.752 mg/1 for 4 hours exposure), and so
a low inhalation toxicity to hunans for manufacturing-use Nfetolachlor 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 vere observed. Based
on the rabbit as an indicator species, Nbtolachlor is not expected to be
irritating to hunan eyas. A dermal sensitization study in guinea pigs
indicated that Metolachlor was a skin sensitizer to that species,
tetolachlor should therefore be considered a potential skin sensitizer in
hunans.
A six-month dog study indicated an oral 'no observed effect level'
(NOEL) of 100 ppn, and this is presently the only NOEL value available for
tolerance setting. (See Ftesidue Chemistry "Iblerance ^assessment'.) 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. Nd evidence is presented in either study to suggesf
that Metolachlor has any mutagenic potential.
The currently registered Metolachlor technical product falls into the
following 'Toxicity Categories' [see 40 CFR 162.10 (h)(1)]:
Scute Cral Tbxicity: Category III
Acute Dermal Toxicity: Category III <
£eute Inhalation "toxicity: Category IV
Primary Eye Irritation: Category IV
Primary Dermal Irritation: Category IV
65
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Emulsifiable Concentrate: Pbr the E.C. formulations of 6 and 8 lbs,
ai/gallon, the reported values of 1,890 mg/kg or higher indicate a
relatively high acute oral LD-50 in rats, implying a low acute oral
toxicity for hunans. Etermally, at least in the rabbit, the two existing
E.C. formulations of Metolachlor 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.C.
formulations of 6 and 8 lbs. ai/gallon present a low overall acute toxicity
to hunans via the intact dermal route. The test on acute inhalation was
only available for the six pound per gallon E.C., and demonstrated a very
low acute inhalation toxicity. A test for the eight pounds per gallon
E.C. 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
lbs. ai/gallon formulation will produce moderate erythma, edema, and second
degree burns (severe irritation). A dermal sensitization study in guinea
pigs indicated that tWD registered E.C. formulations are also potential
skin sensitizers in hunans. In a primary e^ irritation study conducted on
the albino rabbit, the 6 lbs. ai/gallon formulation of Metolachlor was
foLnd to cause irreversible corneal opacity and severe irritation in
unrinsed eyes, which indicates a potential for serious human eye irritation
due to that formulation.
The currently registered Metolachlor Bnulsifiable Cbncentrate Products
fall into the following :Tbxicity Categories' [see 40 CFR 162.10 (h)(1)]:
Bnulsifiable Cbncentrate (6 lbs. active ingredient per gallon):
A:ute Cral Toxicity: Category III
Acute Dermal "toxicity: Category III
Arute Inhalation Tbxicity: Category IV
Primary Eye Irritation: Category I
Primary Dermal Irritation: Category IV
Elnulsifiable Gbncentrate (8 lbs. active ingredient per gallon) :
Pcute Oral Tbxicity: Category III
Acute Dermal Tbxicity: Category III
/cute Inhalation Tbxicity: undetermined
Primary Eye Irritation: Category II
Primary Dermal Irritation: Category II
Toxicology Hazard Assessment
Technical Metolachlor: Considering first the potential for human (or
domestic animal) exposure to manufacturing-use Metolachlor, 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 Metolachlor is a repeated dermal
exposure.
Because of Technical Mstolachlor1s low acute oral toxicity, and very
low inhalation toxicity, we may dianiss these inlikely 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.
But with respect to dermal exposures, although it has been shown that
Metolachlor is not readily absorbed by the skin, the likelihood of repeated
dermal exposures raises tWD concerns: first, Metolachlor has been observed
66
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to elicit a dermal sensitization reaction? second, although no positive
evidence of general chronic, teratogenic, fetotoxic, oncogenic, or
mutagenic effects lias 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 humans caused by repeated
dermal exposures to a "technical ftetolachlor solution cannot be concluded at
this time, and the only presently known hazard of manufacturing-use
Metolachlor is the potential for dermal sensitization for factory,
transport, or re-formulation workers.
\
Qriulsifiable 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 hunans which arise in the tank mixing, dilution,
application, storage, or disposal of the end-use chenical; those hazards
to humans and domestic animals which arise as a result of ambient
residues frati pesticide application, storage, or disposal, including
residues in air, water, and edible wildlife; and, finally, those hazards
to humans 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 Tbxicology 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 dermal and
eye exposure for chemical 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 >ater 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 erytiwa, edema,
and second degree burns due to contact with certain formulations. If
dermal exposures to any Metolachlor 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.
Mbient 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.
6 7
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Generic Data Gaps
The following are gaps in the Tbxicology 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
evaluation is required for the rat study.
2) Chronic Eteeding - A chronic feeding study using
the laboratory rat is required.
3) Oncogenicity - An oncogenic evaluation performed
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 manmalian
species other than the rat is required.
5) Reproduction - A multi-generation reproduction
study on one manmalian species (preferably the
laboratory rat) .
Product Specific Data Gaps
The following is a "product specific" data gap for Tbxicology 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 Fart 163) which describes that type of data and when it
is required.
For Ehmlsifiable Cbncentrate Mstolachlor (8 lbs. ai/gallon) :
1) A^ute inhalation toxicity study. 163.81-3
Suggested Labeling
See the Pfetolachlor 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 "Ibxicity 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 fran Metolachlor's "Ibxicity categories' is a precaution
concerning dermal sensitization: "May cause skin sensitization. Wear gloves
and protective clothing while handling or using this product. Wash thoroughly
after handling. Itemove and vesh contaminated clothing before re-use."
6 8
163.82-1
163.83-1
163.83-2
163.83-3
163.83-4
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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 Cemal LD5(, of CGA-
24705 - Technical in Rabbits: Gontract No. 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) Qnetic Dose 50 in Beagle
Cogs with CGA-24705-1technical: Contract No. 120-2255-34. Received Sep 26,
1974, Greensboro, N.C.; CDL:112840-C)
Affiliated Medical Research, Incorporated (1974f) Twenty-one Cay Repeated
Dermal Tbxicity of CGA-24705-6E in Rabbits: Gontract No. 120-2255-34.
Received Sep 26, 1974 under 561553. (Unpublished study prepared for Ciba-
. Geigy Cbrp., 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:
Gontract Ito. 120-2255-34. Received Sep 26, 1997 under 5G1553.
(Unpublished reportprepared for Ciba-Geigy Cbrp., Greensboro, N.C.;
CDL: 1123 4 0-K)
Arni, P.; Muller, D. (1976) Salmonella/Mammalian-Microsome Mutagenicity Tfest
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' LD5_ of Itechnical CGA-24705 inthe Rat: Project
No. Siss 2979. Received Sep 26, 1974 under 5G1553. (Uhpublised study
prepared by Ciba-Geigy Corp., Ltd., Basle, Switzerland; CDL: 1128 4 0-^A)
Ciba-Geigy Limited (1976a) Dominant Lethal Study on CGA 24705 Technical: Mouse
(Test for Cytotoxic or Mutagenic Effects on Pfele Germinal Cells) FH 2.632.
Received Jan 18, 1978 under 7F1913. (Unpublished study including
Mdendum; CDL:96717-C; 96717-D)
Ciba-Geigy Limited (1976b) Reproduction Study CGA 24705 Tfech.: Rat: Seg. II
(Test for Teratogenic or Embryotoxic Effects) 2.632. Received Jan 18,
1978 under 7F1913. (Unpublished study including A3dendun; CDL:96717-A;
96717-B)
Ciba-Geigy Limited (1977) Skin 'Sensitizing (Gontact Allergenic) Effect in
Guinea Pigs of Technical CGA 24705: Siss 5726. Received Jan 18, 1978
under 7F1913. (Unpublished study; CDL:96717-E)
69
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Cbquec, B.; Galland, L.; Guyot, D.; Ebuillet, X.; Fbuanud, J. L. (1974a) Essai
de Tbxicite de 3 Mois chez Le Chien par \fc>ie Orale du Produit CCA 24 735.
[Three-Month Oral Tbxicity Trial of CGA 24 705 in Ebg] : IC-DRE3-R-740119.
Received Sep 26, 1974 under 5G1553. (Unpublished study prepared by the
Chcins Research and Breeding Center for Ciba-Geigy Cbrp., Greensboro, N.C.;
CDL:94223-B)
Coquet, 3.; C^lland, L.; Guyot, D.; Fouiliet, X.; Fbuaud, J. L. (1974b) Essai de
Tbxicite de 3 fois chez La Rat par Vbie Orale du Produite CGA 24 705.
[Three month oral TbxicityTrial of CGA 24 705 in Rats]: IC-DRE3-R-740120.
Fteceived Mar 1, 1974 under 5G1553. (Unpublished study prepared bythe
Cncins Ftesearch and Breeding Center for Ciba-Geigy Gorp., Greensboro, N.C.;
CDL:94219-B)
Coquet, B.; Galland, L.; Guyot, D.; Ebuillet, X.; Ftouanud, J. L. (1974c) Ihree-
Month Oral Tbxicity Ttest of CGA 24 705 in Dog. A translation of: Essai de
Tbxicice de 3 Mois chez Le Qnien par TJbie Orale du Produit CGA 24 705: IC-
DREB-R-740119. Fteceived Sep 26, 1974 under 5G1553. (Unpublished study
prepared by the Chcins Ftesearch and Breeding Center for Ciba-Geigy Cbrp.,
Greensboro, N.C.; CDL:94223-A)
Coquet, B.; Galland L.; Guyot, D.; Fouiliet, X.; Fbuaud, J. L. (1974d) Three-
>bnth Oral Tbxicity Ttest of CGA 24 705 in Rats. A translation of: Essai
de Tbxicite de 3 Mois chez le Rat par \bie Crale du Produit CGA. 24 705: IC-
EREB- R-740120. Received Mar 1, 1974 under 5G1553. (Unpublished study
prepared by the Cncins Ftesearch and Breeding Center for Ciba-Geigy Cbrp.,
Greensboro, N.C.; CDL:94219-A)
Draize, J.H. (1959) The Appraisal of Chemicals in Fbod, Drugs, and Cosmetics.
Association of Food and Erug Officials of the United States. Austin, Tfexas.
Fritz, H. (1976) Reproduction Study Cffl 24705 Tfech. tec: Seg. II: (Test for
Teratogenic or Bnbryotoxic Effects): PH 2.632. Fteceived Jan 19, 1977
under 7F1913. (Uhpublished study prepared by Ciba-Geigy Ltd., Basle,
Switzerland; CDL:95768-A)
Gesme, J.; Albanese, E.; Marias, A.J. (1977) Report to Ciba-Geigy Cbrporation:
Carcinogenicity Study with CGA-24705 Ttechnical in Albino Mice: IBT Ms. 622-
07925 (8532-07925). Received Jan 18, 1978 under 7F1913. (Unpublished
study prepared by Industrial Bio-Test Laboratories, Inc. for Ciba-Geigy
Cbrp.; including Validation report prepared by Ciba- Geigy Corp.,
Greensboro, N.C.; CDL:96719-A; 96720-A; 96720-B)
Gfeller, W. (1974) Tblerability 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)
Hambock, H. (1974a) Project I>b. 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)
r
7 0'
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f&mbock, H. (1974b) Project Report 12/74: Mdendun to Project Report 7/74:
Metabolism of CGA 24 705 in the Rat: AC 2.52; Received tov. 25, 1975 under
631708. (Unpublished report prepared by Ciba-Geigy Ltd., 3asler
Switzerland; CDL:94984-P)
Hambock, H. (1974c) Project Iteport to. 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 Ms use Pilot Study with CGA-24705 (Technical).
Received Feb 16, 1978 under 100- 583: dated Nov 21. 1975; IBT to. 622-
B7857. (Unpublished study prepared by Industrial Bio-Test laboratories,
Inc. for Ciba- Gaigy Cbrp., Greensboro, N.C.; CDL-232855-8)
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 die chemical CGA 24705 (X3T to. 8533-079280] to George Fblofson.
Received Jan 19, 1977 under 7F1913. (Unpublished study prepared by
Industrial Bio-Test laboratory, Inc., for Ciba-Geigy Cbrp., Greensboro,
N.C.; CDL:95768-E)
Kennedy, G.L. (1976b) Letter [dated Dsc 13, 1976, interim reporton IBT to. 3531-
37926, 2-year chronic toxicity of CGA 24705 in albino rats] to George
Rolofson. Fteceived Jan 19, 1977 under 7F1913. (Unpublished study prepared
by Industrial Bio-Ttest Laboratories, Inc., for Ciba-Geigy (brp.,
Greensboro, N.C.; CDL:95768-D)
Kennedy, G.L. (1976c) Letter [dated Dsc 13, 1976, relative to the 2-year
carcinogenicity study of CGA 24705 in albino mice (IBT to. 8531-07925)] to
George Fblofson. Received Jan 19, 1977 under 7F1913. (Unpublished study
prepared by Industrial Bio-Test laboratories, Inc., for Ciba-Geigy Cbrp.,
Greensboro, N.C.; CDL:95768-C)
Chcins Research and Breeding Center (1974) Three-Month Dietary Feeding Study in
Rats: -CGA 24 705. A translation of: Ibxicite de 3 Mois chez le Rat par
\foie Orale du Pro'duit CGA 24 705, translated by F. Rsulet: IC-DREB-R
741009. Received Mar 26, 1975 under 5F1606. (Unpublished study prepared
by Ciba-Geigy Cbrp., Greensboro, N.C.; CDL:94377-B)
Sachsse, K. (1973a) Irritation of Ttechnical CGA-24705 in the Rabbi't Eye:
Project to. Siss 2979. Received Sep 1974 under 5G1553. (Unpublished
report prepared by Ciba-Geigy Ltd., Basle, Switzerland; CDL: 11284 0-G)
Sachsse, K. (1973b) Skin Irritation in the Rabbit after Single Application of
Technical CGA-24705: Project to. Siss 2979. Fteceived Sep 26, 1974 under
5G1553. (Unpublished study prepared by Ciba-Geigy Ltd., Basle,
Switzerland; CDL:112840-1)
Sachsse, K.; Ullman, L. (1974a) Acute Inhalation Tbxicity of Tfechnical CGA-
24705 in the Rat: Project to. Siss 3516. Received Sep 26, 1974 under
5G1553. (Unpublished study prepared by Ciba-Geigy ltd., Basle,
Switzerland; CDL:112840-L)
-------
Sachsse, K. (1977) Skin Sensitizing (Contact Allergenic) Effect in Guinea Pigs
of Technical CGA-24705. Project >to. Siss 5726. Received October 17,
1977. [Unpublished study prepared by Ciba-Geigy Ltd., Basle, Switzerland]
Smith, S.H.; /^dlet*", G. L. (1978) Final Report to Ciba-Geigy Cbrp.: Ihree-
Generation Reproduction Study with CGA-24705 Technical in Albino Rats: I3T
No. 9523-07923. Received Jan 13, 1978 under 7F1913. (Unpublished study
prepared by Industrial Bio-Test Laboratories, Inc. for Ciba-Geigy Cbrp.
Greensboro, N.C.; CDL:967—8^A; 96718—3) ,
Sunner, D.D. (1978a) Audit Report Dated Nov 21, 1975: 28-Cay Nbuse Pilot Study
with CGA-24705 (Technical) . Received Feb 16, 1978 under 100-583; BT No.
622-07857. (Unpublished study prepared by Ciba-Geigy Corp., Greensboro,
N.C.; CDL:232855-C)
Sumner, D.D. (1978b) ^ddendun to Audit Report Cated Jan 12, 1978:
Carcinogenic Study with CGA-24705 Technical in Albino Mice. Received Feb
16, 1973 under 100-583; IBT Nb. 622-07925. (Unpublished study prepared by
Ciba-Geigy Corp., Greensboro, N.C.; CDL:2328 5 5-A)
7 2
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RESIDUE CHEMISTRY
TOPICAL DISCUSSIONS
Metabolism in Plants
Metabolism in Animals
Analytical Methodology
Residue Cata
Present Tblerances
Metabolism in Plants
The absorption, distribution, and metabolic fate of Metolachlor vere
investigated in com plants grown under field and greenhouse conditions
(Sunner and Cassidy, 1974c,d) and in soybeans grow under greenhouse
conditions only (Sumner and Cassidy, 1975).
Ring-labeled Metolachlor was applied as a pre-emergence treatment at 2 lbs.
ai/acre. Ebr corn, it was dissolved in nutrient solution at a concentration of
approximately 2 ppm and applied to field and greenhouse soils. Fbr soybeans,
it was added to soil and plantings were incubated in the greenhouse. The
maximun levels of residues fouid 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
ppn, respectively; soybeans 0.17 ppn, soybean hay 2.66 ppn, soybean oil 0.01
ppn and soybean meal 0.14 ppn. These data show that the total residues in
soybeans are higher than those in com.
The metabolism of Metolachlor by com plants consists of a major and a
minor pathvay. The figure in the 'Disciplinary Review' at the end of this
chapter depicts these pathways for both corn and soybean.plants (terco 1975).
When corn plants were grov*n in soil treated with j&- C-Metolachlor at 2
lbs. 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. Msre than 80% of the remaining activity vas foind 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) .
Che metabolic pathway in the corn plants involves conjugation of
Metolachlor with glutathione (Sunner and Cassidy, 1974b). Eburteen 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)
snino]-l-propanol (HP-001) and 4-(2-ethyl-6-methylphenyl) -2-hydroxy-5-methyl-3-
morpholi.none (HP-002) ware 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
73
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Raney nickel, which breaks thio-ether bonds (Gross, 1974a and Gross, 1974b),
two compounds, N-(2-ethyl-6-nethylphenyl) -N-(2-methoxy-l-methylethyl) acetamide
(MET-005) , and N- (2-ethyl-6-!n ethyl phenyl) -N- (2-hydroxy-l-methylethyl)acetanide
(MET-006) were produced, indicating that these compounds were moieties of
sulfur-bonded conjugates. These two ccmpounds represent 80% of the
radioactivity extracted from the corn leaves. They wre positively identified
by GLC and mass spectranetry.
Further residue characterization, involving rigorous HQ hydrolysis
(Sumner, Thomas, and Cassidy, 1975), showed the presence of either 2-•;^-ethyl-
s-methyl phenyl) amino]-1-propanol (HP-001) or 4-(2-ethyl-6-methylphenyl)-2-
hydroxy-fHnethyl-3-morpholinone (HP-002) . These data suggest that tha
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
mercaptan, conjugation of mercaptan with glucuronic acid, hydrolysis of methyl
ether, and conjugation of the alcohol with a neutral sugar. A minor pathway
assunes chloro replacement by hydroxyl. The same pathway may also involve
direct conjugation with glucuronic acid, followed by dsnethylation and
conjugation of the hydrowl wich a neutral sugar, all forming oxo- conjugates.
When radiolabeled 0- C-Metolachior was applied to growing soybeans
(Suuner and Cassidy, 1975b), characterization of the extracted residues
indicated that the metabolic pathways in soybeans are similar to those
observed in corn. Thin-layer chranatography and partitioning data indicated
that higher concentrations of less polar metabolites will occur in soybeans
when can pa red 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 frcn metabolism
or degradation of the parent compound. However, Ftesidue 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 chmical 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
monochloroacecic acid as a producr of metabolism is not likely to occur.
The above studies adequately define the fate of ffetolachlor 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 sorghun. In other words, the Agency is taking the
position that the nature of the residues in peanuts and sorgnun is similar to
that of corn and soybeans, to 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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Metabolism _in Animals
Metolachlor is rapidly metabolized arid almost totally eliminated in the
urine and feces of ruminants (goats), non-ruminants (rats), and poultry (Roger
and Cassidy, 1974a; ffembock, 1974a; Guth, 1974). These findings were made in
studies using both unlabeled and C-ring-labeled Metolachlor. Metolachlor
per se was not detected in any of the excreta or tissues.
Additional studies with goats (Qounselman and Roger, 197 3; 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 Metolachlor >*ere found in kidneys,
liver, blood, and milk (Bicmetric Ttesting incorporated, 1973; Hambock, 1974a,
b,c; Sshenker, 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 (ftettson, 1974, 1975). precursor of
the hydrolysis product HP-002 was found in the liver (Guth, 1974).
When C-labeled metabolites of Metolachlor, bio-synthesi2ed in corn,
were fed to goats, no parent Mstolachlor nor any metabolites were Sound in the
animals' tissues or milk (Ciba-Geigy Limited, 1973; Sshenker, 1974, 1975b).
It is concluded that the raetabolisn 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 Metolachlor and C-ring
labeled Metolachlor fed to different animals indicate clearly the identity and
the amounts of the metabolites vduch result as residues in the excreta,
tissues, milk, and eggs.
Although the exact metabolic pathway of Metolachlor in animals is not
knovn, the available metabolic studies adequately delineate the fate of
Metolachlor in animals for the purposes of establishing tolerances for corn
grain and soybeans. (For an evaluation of rat metaboliati data, please see
Tbxicology Chapter.)
Analytical Methodology
Metolachlor in Corn and Soybeans
The residue 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 HO. 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 mi of QJ HQ for 16 hours. Ihe 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 alumina
column. 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 chranatograph
equipped with a Cbulson eletrolytic conductivity detector. Itaovn amounts
of HP-001 are used for standardization. Baak heights are compared with
7 5
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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,with
parent Metolachlor, (CCM-001); and (3) comparison of GLC arj|lyses of C-
labeled residues from metabolism study samples with total C-combustion
analyses of duplicate sanples.
Recovery for samples of grain, forage, silage, and stover fortified at
levels of 0.05-2.0 ppri with HP-001 averaged 81%. All control samples were
determined to have <0.03 ppm (the method sensitivity). fortification
studies using parent Nfetolachlor 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). Ihe combustion technique determined all residues (both extractible
and nonextractible) after conversion to CCL. The residues
(expressed as CCM-001) determined by Chsnical Method AG-265 ranged from
12% (mature crop) to 27% (immature forage or silage) of the total residues
found by combustion techniques. Can pari sons were al^ made of the total
extractible residues by the chanical method vs. the C-combustion
method using two extraction solvent systans, HCL, and combined chloroform-
methanol solvent. £bout 50-60% of the C-residues in mature corn were
ex tractable using either nj^thod. The chemical method determined 20-30%
of the total extractable C-residues.
Ekcept as stated directly below, method AG-265 (3alasubramanian, Gold,
and Rdss, 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, Ai/adex, Landrin, 4-amino pyridine,
and 2-(thiocyanomethylthio)-benzotriazole. 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 GDC steps determining two hydrolysis
products: 2- [ (2-ethyl-6-methylphenyl) amino]-1-propanol (HP-001) and 4—(2—
ethyl-6-methyl phenyl)-2-hydroxy-5-rnethyl-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. Hie 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 alumina column. HP-001 is determined with a gas chromatograph equipped
with a Cbulson 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 alumina column. The
chloroethanol derivative of HP-00^ is formed by reaction with boron
trichloride/2-chloroethanol at 90 C for 15 minutes. The derivative is
partitioned into hexane and an aliquot is cleaned up using silica gel and
alumina columns. A gas chromatograph equipped with Cohrmann
76
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iriicrocoulcmetric chloride detector is used for analysis, rbr
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
ppn. In seme samples, the controls ranged up to 0.1 ppn due to an
interfering peak. V»fe consider the sensitivity of the method for HP-001 to
be 0.35 ppn br less. Recoveries for 69 samples of fodder,, forage, grain,
or ears, fortified at 0.02 and 0.20 ppn, 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 3.10 ppn for HP-002 wnen
calculated as CCM-001.
The method used for the soybean residue data is tethod AG-286 (Aziz
and Ross, 1975). This method, "Analytical Method for the Determination of.
Residues of Metolachlor Soybean ffetabolites (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-, "\fcl. II. Method AG-
286 was tried out in one of SPA's laboratories and found to be
acceptable.
Method AG-286 was tested for specificity with 54 of the 58 pesticides
registered on soybeans. EC-200 and Carbowax 20 M are available as
alternate liquid phases to enhance the specificity of the GDC
determinative steps.
The analytical methods are also adequate for the enforcement of
tolerances on peanuts and sorghun. ttawever, 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, Fbrmica, and Schenker, 1974)
and Basle REM 2/75 (Ramsteiner and Karlhuber, 1975). Analytical method
(REM 2/75) accounts for "combined residues" of Metolachlor, 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 colunn and, if necessary, by Tl£.
•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 ppn for milk, 3.015 ppm for eggs and chicken tissues, and 3.02 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 Mefthod 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, arid kidney.
Method REM 2/75, CQM-001, "Determination of Tbtal Residues in i^aterial
of Animal Origin" (Ramsteiner and Karlhuber, 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 shov
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residues of HP-001 (as ffetolac'nlor) (less than 0.03 ppm) arid HP-002 (less
than 3.10 ppn) in the grain and fresh ears respectively 62, 92 and 129
days after the application. At a later date tw additional studies at 2
lbs. and 4 lbs .ai/acre of 250 S.C. formulation on sweet corn *>ere
performed. No detectable residues of Metolachlor as HP-001 (less than
0.03 ppn) or HP-002 (less than 0.10 ppm) were found in the fresh ear
sample at 60 and 67 days after the application.
Seventeen residue studies v^ere Macolachlor was measured as'HP-001
show forage residues were less than 0.03 ppm at intervals of 34 and 72
days following 1.5 lbs. ai/acre. Residues resulting from 2 lbs. and 3
lbs. ai/acre applications (at 26 to 72 days) range fran less than 0.03 to
0.14 ppn, and less than 0.03 to 0.10 ppm, respectively. At intervals of
26 to 64 days, 4 lbs. ai/acre resulted in residues of less than 0.03 to
0.43 ppm; 6 lbs. ai/acre rates shoved HP-001 residues at 0.03 to 0.19 ppm.
Silage stage forage residues of Metolachlor (measured as HP-001)
resulting from 2 lbs. and 4 lbs. ai/acre range from less than 3.03 ppn to
0.16 ppn, and less than 0.03 ppn to 0.43 ppn, 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 lbs. and 4 lbs. 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 3.24 ppn and less than 0.03 ppm to 0.08 ppn for 2 lbs. and 3
lbs. ai/acre treatments, respectively; 4 lbs. and 6 lbs. ai/acre
applications resulted in forage residues ranging from 0.04 ppn to 0.64 ppm
and 0.03 to 0.19 ppn, respectively.
Silage stage forage showed combined HP-001 and HP-002 residues (as
Matolachlor) of 0.03 to 0,14 ppn, 0.04 ppn to 0.12 ppn, and 0.05 ppn to
3.28 ppm for treatments at 1.5 lbs., 2.0 lbs., and 3.0 lbs., respectively.'
Combined residues from 4 lbs. and-6 lbs. ai/acre treatments were 0.14 to
0.63 ppn and 0.13 to 0.34 ppn, respectively.
Fbdder and stover residues for 1.5 lbs., 2.0 lbs., and 3.0 lbs., ai/
acre treatments ware less than 0.03 to 0.06 ppn, less than 0.03 to 0.23
ppn, and 0.07 to 3.30 ppn.
Combined residues of HP-001 and HP-002 (as Metolachlor) in mature
fodder and stover reported in six studies at 4 lbs. ai/acre ranged from
0.07 ppn to 0.90 ppn. Three studies at 6 lbs. 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.).
' iC
Residues in or on Soybeans
TVenty-tEree residue studies v«re performed in eight states
representing the major soybean growing areas. (Again, only studies
performed with Metolachlor alone are considered here.) Application rates
were from 2 to 6 lbs. ai/acre (ftettson and Ftolla, 1975; Itexas A & M
Cottonseed Products ftesearch Laboratory, 1966; Ibuseworth and Rolla, 1976)
Analyses involved the determination of both HP-001 and HP-002. No
detectable residues (less than 3.05 ppn) of HP-302 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 lbs.
ai/acre; the maximim reported residue was from a 3 lb. ai/acre
application. At 6 lbs. ai/acre, residues of HP-001 ranged from less than
-------
0.03 to 0.21 ppn.
Three fractionation studies.showed no detectable residues of HP-001
(less than 0.03. ppn) or HP-002 (less than 0.0 5 ppn) in any fraction (meal,
crude and refined oil, soapstock) from soybeans treated at rates of 2 to 5
lbs. ai/acrs. At 5 lbs. ai/acre, the only finite residue was found in
the soybean meal where 0.34 ppn HP-001 was detected. In one of the three
tests, soybean hulls (pods) contained 3.03 and 0.36 ppn HP-331 from
treatment'rates of 2.5 and 5 lbs. ai/acre.
Tbtal residues (sum of residues converted to HP-001 and HP-002) of
Matolachlor in soybean forage ranged from 0.20 to 0.36 ppn at a 2 lbs. ai/
acre application rate. Tbtal residues in soybean forage at the 3 lbs. ai/
acre ranged from 0.15 to 1.01 pcm. At exaggerated rates of 4 lbs. and 6
lbs. ai/acre, total residues ranged from 0.34 to 1.76 ppn. These residue
studies represented pre-harvest intervals of 30-92 days.
Tbtal residues in soybean hay at pre-harvest intervals of 122-194 days
ranged from less than 3.10 to 0.84 ppn at rates of up to 3 lbs. ai/acre.
At exaggerated rates of 4 to 6 lbs. ai/acre, total residues ranged frcm
0.14 to 2.46 ppn.
The above residue data for soybeans allows for an adequate range of
geographical variation.
Residues in or on Sorghum
Forty^fTve-residue studies were performed in seven states representing
the major sorghun growing areas. Application rates were 2 to 5 lbs.
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 lbs.
ai/acre; less than 0.03 to 3.34 ppn due to 2.5 lbs. ai/acre; and, 0.14
to 0.51 ppn due to a rate of 5 lbs. ai/acre (two times the maximun
proposed rate) . Residues of HP-002 in the silage stage forage were less
than 0.05 to 3.43 ppn due to a rate of 2 lbs..ai/acre; less than or
exactly 0.05 to 0.11 ppn due to a rate of 2.5 lbs. ai/acre; and less than
0.35 to 0.46 ppn due to a rate of 5 lbs. ai/acre.
Samples of mature grain and harvest fodder were collected at intervals '
of 35 to 169 days after treatment and analyzed. Resides of HP-001 in the
harvest focder were 0.06 to 0.96 ppn due to a 2 lbs. ai/acre application
rate; 0.06 to 1.90 ppn due to a 2.5 lbs. ai/acre rate; and 3.-14 to 0.99
ppn due to a 5 lbs. ai/acre rate. Residues of HP-002 in the harvest fodder
were less than 0.35 to 0.20 ppm due to a .2 lbs. ai/acre rate; less than
0.05 to 1.29 ppn due to a 2.5 lbs. ai/acre rate; and, 0.07 to 0.45 ppn due
to a 5 lbs. ai/acre rate.
Residues ,of HP-C01 in sorghum grain were less than 0.03 to 0.11 pcm
due to the 2 lbs. ai/acre application rate; less than 0.03 to 3.18 ppn due
to the 2.5 lbs. ai/acre rate; and less than 0.03 to 0.37 ppn due to the 5
lbs. ai/acre rate. No detectable residues of HP-002 (less than 0.05 ppm)
ware noted in sorghun grain from any application rate.
TV/o processing studies were performed on sorghun grain. The grain was
obtained from crops treated at 2 lbs. ai/acre and harvested at intervals of
114 to 146 days after treatment. The grain had HP-001 residues of less
than 3.03 to 0.09 ppn, but no HP-002 residues '.«ire detected (less than 0.05
ppn) . The bran had 0.03 ppn HP-001 residues. However, no residues of HP-
001 (less than 0.03 ppn) or HPr002 .(less than 0.05. ppn) were detected in
8 0
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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 sorghum forage and fodder.
Residues in or on Peanuts
Seventy-six residue studies were performed in 5 major peanut growing
areas of the thited States. Application rates were 3 lbs. ai/acre and 6
lbs. ai/acre. Analyses involved the determination of both HIH301 and HP-
002 in peanuts, peanut hulls, peanut forage, and peanut hay. The peanuts,
hulls, and hay vere 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 r» detecable residues of either HP-001 (less than 0.03
ppn) or HP-002 (less than 0.05 ppn) due to the 3 lbs. ai/acre application
rate. At the 6 lbs. ai/acre rate, HP-001 residues were less than 0.03 to
0.05 ppn, 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 ppn due to the 3 lbs. ai/acre
application rate. Residues due to the 6 lbs. 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 lbs. ai/acre application rate. Residues
due to the 6 lbs. ai/acre rate vere 0.12 to 3.0 ppn HP-001 and 0.14 to 1.6
ppn HP-002.
Ihe 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 lbs. ai/acre application rate. From the 6
lbs. ai/acre rate, HP-001 residues v^re 0.46 to 3.0 ppm 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 lbs. ai/acre rates. The
soapstock had no detectable HP-001 residues due to the 3 lbs. ai/acre rate,
but at the 6 lbs. ai/acre rate, the soapstock had HP-001 residues of less
than 0.03 to 0.04 ppn. Ma detectable residues of HP-002 (less than 0.05
ppn) ware noted in the crude or refined oil, or the soapstock due to either
the 3 or 6 lbs. ai/acre rates. The peanut cake (or meal) had no detectable
residues of HP-002 (less than 0.05 ppn) due to the 3 lbs. ai/acre rate, but
at the 6 lbs. 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
Resi3ue~Uata ware available for the root crop, potatoes. Eighty-four
residue studies were performed in seven states representing potato growing
areas. Application rates were 3 lbs. ai/acre and 6 lbs. ai/acre. Analyses
involved the determination of both HP-001 and HP-002 in iinnature (48 to 84
days after treatment) and mature (57 to 135 days after treatment) potatoes.
Residues of HP-001 in iirmature or mature potatoes due to the 3 lbs.
8 1
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ai/acre rata were less than 0.03 to 0.35 ppn. Residues of HP-002 in
immature and mature potatoes were less than 0.05 to 0.07 ppn due to the 3
lbs. ai/acre application rata. From the 6 lbs. ai/acre rate, residues of
HP-001 in immature potatoes -were less than 0.03 to 0.22 ppn and less than
3.33 to 0.05 ppn in mature potatoes. Residues of HP-002 were less than
0.33 to 0.28 ppn in immature potatoes and less than 0.05 to 0.06 ppn in
nature potatoes.
We have concluded (see the discussion on 'Metabolism in Plants') that
the absence of metabolian 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 vere fed unlabeled Metolachlor
at levels of zero, 0.02 ppn, 1.0 ppn, and 5.0 ppn of the total diet. Milk
samples were collected at zero, 1, 2, 7, 14, 21* and 23 days. Mimals were
sacrificed and samples of tissues taken at 14, 21, and 28 days. Chly milk
and tissue samples from the two highest feeding levels (1.0 and 5.0 ppn)
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 pan for HP-001 and 0.01 ppn
for HP-002. All residues in the muscle, fat, kidney, and liver were less
than the method sensitivity of 0.02 ppn for HP-001 and 0.04 ppn for HP-002.
Ibtal C-residues (calculated as Metolachlor) were determined in
the goat metobolian study where 4.7 ppn of C-labeled Metolachlor was
fed for 10 days (Roger 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 pp^^in other tissues. The activity was not
characterized. When C-lab^ed corn biosynthesized metabolites were
fed to goats, no detectable C-residues resulted in milk or tissues
(Roger 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 ppn in the dry diet. 3jg
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. Chly tissue and eggs
samples from the two highest feeding levels (0.5 and 2.0 ppn) were
analyzed. Residues as HP-001 in eggs, muscle, and fat were reported as
less than 0.02 ppn. Residues of 0.02 ppn and 0.03 ppn as HP-001 were
reported for the livers from birds fed at 0.5 and 2.0 ppn feeding levels,
respectively. No detectable residues (less than 0.04 ppn) of HP-002 were
found in eggs nor 'in any tissues.
From the feeding of soybean meal, hulls, and soap^-stock bearing
residues of 0.1 ppn, the dietary residue level could approach 0.04 ppn for
cattle and 3.03 ppn 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
82
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livestock feed use of soybean fractions may lead to anall residues in
meat, milk, poultry, and eggs, these residues, if present, vould be at
levels below the sensitivity of the analytical methods.
Present Tolerances
In 1976, Nfetolachlor was registered for use on corn grain, and a permanent
tolerance of 0.1 ppn in corn grain (except popcorn) was established for
residues of Metolachlor and its metabolites pursuant to 40 CFR 180-368 (TR
41:178, 9/13/76). Since then, Metolachlor has been conditionally registered
for use on soybeans, sorghum, 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, lb accompany the registered use on soybeans and the
conditionally registered uses on sorghun and peanuts, permanent tolerances wre
established for residues of Metolachlor and its metabolites at: 1.3 ppn for
corn forage and fodder; 0.1 ppn for soybeans; 2.0 ppn for soybean forage and
fodder; 0.02 ppn for meat, eggs, poultry, fat, meat by-products, and milk;
0.3 ppn for sorghun grain; 2.0 ppn for sorghum forage and fodder; 0.1 ppn for
peanuts; 1.0 ppn for peanut hulls; and 3.0 ppn for peanut forage ana hay.
The permanent tolerances for Matolachlor and its metabolites of 0.02 ppn for
eggs, milk, meat, fat, and meat by-products are enforced for the following
animals: cattle, goats, hogs, horses, poultry, and sheep.
83
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DISCIPLINARY REVIEW
Residue Chemistry Profile
Tblerance Fteassesanent
Generic Lata Gaps
Suggested Labeling
Residue Chemistry Profile •
When ftetolachlor was applied as a pre-emergence treatment at 2 lbs./acre to
corn and soybeans, total residues later found in plants parts were higher in
soybeans than in corn. In corn, the residues w^re 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 sorghun are also expected
to be similar.
Ihe metabolism of Metolachlor in animals appears to be similar to and as
canplex as that in plants. But whereas plants retain their metabolic
products, animals eliminate their Pfetolachlor metabolic products almost
canpletaly. The parent ccmpoirsd 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.
Ihe most significant residue detected was 0.02 to 3.03 ppn in the liver of
chickens.
Mequate tetolachlor-specific and metabolite-specific analytical methods
are available for the detection of residues in corn, soybeans, peanuts,
sorghum, meat, milk, and eggs, and data v^re available on actual residues in
these conroodities. 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 lbs. ai/acre. Residue data for soybeans was adequate to allow for the
wide range in the geographical characteristics of the U.S. soybean crop.
Detectable residues in the beans, soybean meal, hulls, forage, and hay showed
that an exaggerated rate of 6 lbs. ai/acre resulted in as much as 2.46 ppm in
hay and 0.21 ppn in the soybeans. 3ut residues from treatments of up to 3
lbs. ai/acre were all less than 2.0 ppn for hay and forage and 0.1 ppn for.the
beans. Residue data on sorghum grain, including its processing fractions, and
sorghun forage and fodder, showed that application rates of 2 lbs. 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 lbs. ai/acre resulted in as much as 0.37
ppm in grain, and a rate of 2.5 lbs. ai/acre resulted in as much as 3.19 ppn in
harvest fodder. Eata for peanuts showed that 3 lbs. 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 3-3 ppn in peanut forage and hay. Pn application
rate of 6 lbs. ai/acre resulted in as much as 2.04 ppn combined residues in
peanut hulls, 5.9 ppn 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
| Preceding page blank
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metabolic pathways op mbtoiacheor
IN CORN AND SOYBEANS
MetoLachlor
ten
cl
lutas.'iione
i
\^OH
-glucuronic ac,
I
M/
/''Ssw-0-suvir
n
\glucuronic acid
ii J ^
0
>
\l/
'r— N
>
l-i
X^-O-g iucurcnic
0'
i
i
\1/
I
/"-v^o-sugar
J
lucuronic
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 metabolian 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 ppn for corn forage and fodder, 0.1 ppm for soybeans, 2.0 ppn
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 ppm for peanut
forage and hay. The permanent tolerances for Mstolachlor and its metabolites
of 0.02 ppn for eggs, milk, meat, fat, and meat by-products are enforced for
the following animals: cattle, goats, hogs, horses, poultry, and sheep.
Tolerance Reassessment
The only presently available 'no observed effect level' (NOEL) on which to
base a re-assesanent of Metolachlor's established tolerances is given by a six-
month dietary study on dogs, which indicated a NOEL of 100 ppn (see the
"Ibxicology' 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
Metolachlor resulting from its registered end-uses.
1) The first step in the tolerance re-assesanent 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 v*as 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 ppn 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
'13x greater sensitivity of hunans over test animals, and to allow for
the possibility of an individual who is I0x more sensitive than the
average person. But because of the numerous chronic data gaps for
Mstolachlor, a safety factor of 2000 times is recormended. Thus, the
dog study allows us to calculate an 'allowable daily intake' (ADI) of
2.5 mg/kg/day divided by 2000 = 0.0013 mg/kg/day
0.0013 mg/kg/day for humans. Fbr the average human, who weighs
approximately 60 kilograms, the 'maximum permissable intake' (MPI) is
0.3013 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. 1
8 7
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2) The maximum total residue intake permitted by established tolerances
is then calculated in three steps: (a) by multiplying the tolerance
level (in ng/kg) for a particular commodity by the percentage of the
total aggregate American diet supplied by that commodity ('Food
Factor'); (b) then converting that value into the total rrq 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
simming 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 Matolachlor's established tolerances:
Commodity
Tolerance
Food Factor
Maximum Residue Contribution
corn (grain)
0.10 mg/kg
1.00 %
3.30150 mg/day/1.5 kg diet
soybeans
0.10
0.92
0.00138
meat, poultry
0.02
13.85
0.00415
milk, dairy
0.02
28.62 •
0.00858
eggs
0.02
2.77
0.00083
so rghum
0.30
0.33
0.00014
peanuts
0.10
0.36
3.30054
Tbtal Maximum Residue Contribution = 3.31712 rag/day/1.5 kg diet
We see that the total maximun residues (TMRC) of Metolachior and
metabolites, fran all potentially contaminated dietary sources, that
may be ingested in 1.5 kg of food each day, is 0.0171 mg.
3) The percentage of the toxicologically-determined 'maximum pecnissable
intake' (MPI) [from step (1) above] supplied by the 'total maximum
residue contribution' (TMRC) [frcm step (2) above], is an indication
of the degree to which the present tolerances ensure against hunan
effects due to dietary exposure. Fbr Metolachior, the maximum
TMRC divided by the MPI x 130 % = % MPI in human diet
0.0171 mg/day 0.0750 mg/day "22.82 %
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 hunan dietary exposure to .'•fetolachlor. 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 Metolachior - without exceeding the safe dietary level
(the MPI) .
The established tolerances for fetolachlor on corn grain, soybeans,
peanuts, sorghun, 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 accomodated without exceeding the •maximum permissable
intake' for Nfetolachlor in the daily diet.
88
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Generic Data Gaps
If a permanent tolerance is to be considered for Metolachlor in root crops, a
root crop plant metabolisn study will be needed.
Suggested Labeling
none
8 9
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BIBLIOGRAPHY
Each of the following studies contributed useful information to the
Agency's review of the residue chanistry of Metolachlor, and is considered part
of the data base which supports registrations under this Standard.
Aziz, S.A; Fbss, J.A. (1975) Analytical Method for the Determination of
Residues of CGA-24705 Soybean ffetabolites as CGA-37913 and CGA-49751 by teid
Hydrolysis. Method AG-286 dated Jun 10, 1975. Received Nov 6, 1975 under
431469.'(Unpublished report prepared by Ciba-Geigy Gbrp., Greensboro, N.C.;
CDL:95190-E)
Balasubramanian, K.; Aziz, S.A.; Fbss, J.A. (1975) .Analytical Method for the
Determination of Residues of CGA-24705 Corn Metabolites as CGA-37913 and CGA-
49751 by Pcid Hydrolysis. Method AG-277 dated Jan 9, 1975. Fteceived Mar
26, 1975 under 5F1606.,(Unpublished report prepared by Ciba-Geigy Gorp.,
Ardsley, N.Y.; CDL:95190-D)
Balasubramanian, K.; Gold, B.; Fbss, J.A. (1974) Validation of f>tethod AG-265
for the Determination of CGA-24705 Metabolites Which are Converted to the
CGA-37913 Moiety: GACC-74043. fteceived Sep 26, 1974 under 5G1553.
(Unpublished report prepared by Ciba-Geigy Corp., Greensboro, N.C. ;
CDL:94216-1)
14
Bionetric Ttesting Incorporated (1973) Metabolism C-CGA-24705 Corn
Siosynthesized Metabolites in a Lactating G^at: A-1004. Fteceived Sep 26,
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.
Iteceived Sep 26, 1974 under 5G1553. (Uipublished report; CDL:94216-G)
Counselmanj.C.J.Fbger, J.C. (}973) Biological Report, Cbat Metabolism Study
with CCGA-24705 and C-CGA-17020. Received Nov 25, 1975
under 6G1708. (Unpublished report prepared by Ciba-Geigy Cbrp., Greensboro,
N.C.; CDL:94984-K)
Gold, B.; Kahrs, R.A. (1975b) Freeezer Storage Stability of CG\-24705 Residues
in Cbm Ebdder and Grain: GAAC-75062. Iteceived Nov 25, 1975 under 6G1708.
(Unpublished report prepared by Ciba-Geigy Cbrp., Greensboro, N.C.;
CDL:94877-Y)
Gross, D. (1974a) Project Fteport No. 8/74: Uptake, Translocation and
Degradation of CGA 24 705 in Gom Grown under Controlled Conditions.
Received Sep 26, 1974 under 5G1553. (Unpublished report prepared by
Ciba-Geigy Cbrp., Greensboro, N.C.; CDL:94217-F)
Preceding page blank ' 91
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Gross, D. (1974b) Project Report Ms. 13/74: Addend un to Project Report No. 8/
74: Uptake, Translocation and Degradation of CGA 24 705 in Cbrn Grow under
Controlled Conditions: AC 2.52. Received tor 26, 1975 under 5F1606.
(Unpublished report prepared by Ciba-Geigy Ltd., 3asle, Switzerland;
CDL:94378-H)
Guth, J.A. (1974) CGA 24705: Tbtal Residues in Chicken Tissues and 2ggs, 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 Ftesults Gathered up to JUne 10, 1974): AC 2.52. Fteceived Sep 26,
1974 under 5G1553. (Unpublished report prepared by Ciba-Geigy Ltd., Basle,
Switzerland; CDL:94217-L)
Hambock, H. (1974b) Project Pteport 12/14: Addendun to Project feport 7/74:
Metabolian 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)
ftambock, H. (1974c) Project Ffeport Ifo. 1/74: Distribution, Eegradation and
Excretion of CCA 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.; Gole, G. (1973) The Extermination of CGA-24705 in Ehiulsifiable
Concentrates by Gas liquid Chranatography. Method PA-9 dated Nov 14, 197 3.
Received Sep 26, 1974 under 5G1553. (Unpublished report prepared by
Ciba-Geigy Cbrp., Greensboro, N.C.; CDL:96666-A)
Hermes, P. (1972) Biphasic Extraction of radioactive Metabolites from Treated
3iological Material. Method AG-214 dated Aug 15, 1972. Received Sep 26, 1974
under 5G1553. (Unpublished report prepared by Ciba-Geigy Cbrp., Ardsley,
N.Y. ; C2L:94216-M)
Hormann, W. D.; Guth, J.A.; rboiica, G.; Schenker, M. (1974) CCA 24735: Gas
Chromatographic Determination of Tbtal Residues in Material of Animal
Crigin. (Provisional): AC 2.53; RM 5/74. Received Sep 26, 1974 under
5G1553. (Unpublished report prepared by Ciba-Geicry Ltd., Basle, Switzerland;
CDL:94216-E)
Housevcrth, L.D. and Rolla, H. (1976) Residues from Metolachlor Alone and in
TSnk Mix with Linuron, Metribuzin, and Liquid Fertilizer in Soybeans: ABR-
76377. (Unpublished study received Jan 19, 1977 under 7F1913; prepared by
Ciba-Geigy Oorp., Greensboro, N.C.; CDL-95767-A)
Marco, G. (1974) Summary of Section D: CCA-24705-Corn: Ftesidues Cbserved and
Metabolian cata Including the Analytical Methods Used: GAAC-74062. Fteceived
Sep 26, 1974 under 5G1553. (Unpublished report prepared by Ciba-Geigy Cbrp.,
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)
92
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Marco, G. (1975) Surmary of Section D: CGA-24705 Cbrn: Residues Cbserved and
f-tetabolism Eata Including the /Vialytical Nfethods Lteed: GAAC-75001. Fteceived
Mar 26, 1975 under 5F1606. (Unpublished report prepared by Ciba-Geigy Corp.,
Greensboro, N.C.; CDL:9437S-A)
Mattson, A.M. (1974) CG^-24705 Residues in Milk, Nteat, Eggs and Chickens
{Three Level Feeding Studies): GAAC-74064. Received Sep 26, 1974 under
5G1553. (Unpublished report prepared by Ciba-Geigy Cbrp., Greensboro, N.C.;
CDL:94216-B)
Mattson, A.M. (1975).CGA-24705 Resideues in Milk, Meat, E^gs and Chickens
(Three Level Feeding Studies): GAAC-75059. Received Nov 25, 1975 under
5G1708. (Unpublished report prepared by Ciba-Geigy Cbrp., Greensboro, N.C.;
CDL:94878-A)
Mattson, A.M.; Kahrs, R.A. (1975b) Residues in Field Growi Cbrn .following Use
of CGA-24735 Determined as CGA-37913 and CGA-49751: GAAC-75015. Received Mar
26, 1975 under 5F1606. (Unpublished report prepared by Ciba-Geigy Cbrp.,
Greensboro, N.C. that includes studies AG^-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; CDL.-94379-B)
Mattson, A.M.; Rolla, H. (1975) Summary of Section D: CGA-24705-Soybeans:
Residues Cbserved and Mstabolian Data Including the Analytical Methods Used:
GAAC-75057. Fteceived Ndv 25, 1975 under 6G1708. (Unpublished report prepared
by Ciba-Gsigy Corp., Greensboro, N.C. that includes studies 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-^-3780, AG-A-3803; CDL:94984-A; 94878)
Ramsteiner, K; Karlhuber, B. (1975) CGA-24705: Datermination of Tbtal Residues
in Material of Animal Origin: AC 2.53; REM 2/75. Fteceived 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 or C-
CGA-24705 in a Lactatirq Goat: GAAC-74020. Fteceived Sep 25, 1974 under
5G1553. (Unpublished report prepared by Ciba-Geigy Cbrp., Greensboro, N.C.;
CDL.-94217-G)
14
Roger, J.C.; Cassidy, J.E. (1974b) Metabolism and Balance Study of 0- C-
CGA-24705 Gam Biosynthesized Metabolites in a Goat: M6-68-2A: GAAC-74046-
Fteceived Sep 26, 1974 under 5G1553. (Uhpublished report prepared by Ciba-
Gaigy Gorp., Greensboro, N.C.; CDL:94217-I)
Schenker, M. (1974) CGA 24705: Tbtal Residues in Milk and Tissues of S^iss
Cbws: 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, Mf (1975a) CGA 24735: Determination of the Degradation Product CGA
49751 in'*thicken Liver: Switzerland 1973: R"^ 02/75. Fteceived Jan 19,
1977 under 7F1913- (Ihpublished report prepared by Ciba-Geigy Ltd., Basle,
Switzerland; CDL:95747-1)
Sumner, D.D.; Gassidv, J.E. (1974b) The Metabolism of. CGA-24705 in Cbrn: GAAC-
74050. Received Jan 19, 1977 under 7F1913. (Unpublished report prepared by
Ciba-<3eigy Gsrp., Greensboro ,¦ N.C.; CDL:95750-C)
14
Sumner, D.D.; Cassidy, J.E. (1974c) The Uptake and Distribution ofjzf C-
CGA-24705 frcm Soil in Greenhouse Grown Qarn: GAAC-74015. Fteceived Jan 19,
1977 under 7F1913. (Unpublished report prepared by Ciba-Geigy Gorp.,
Greensboro, N.C.; CDL:95750^A)
14
Sumner, D.D.; Cassidy, J.E. (1974d) Hie Uptake and Distribution of ^ C-CGA-
24735 in Field Grov»n Cbm: GAAC-74022. Fteceived Mar 26, 1975 under 5F1606.
(Unpublished report prepared by Ciba-Geigy Cbrp., Greensboro, N.C.;
CDL:94385-C)
14
Sumner, D.D.; Cassidy, J.E. (1975b) The Uptake and Distribution of 0- C
CGA-24705 from Soil in Greenhouse Grown Soybeans: GAAC-75039. Fteceived btov
26, 1975 under 5G1708. (Unpublished report prepared by Ciba-Geigy Cbrp.,
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 Gom:GA2C-75012. Received Mar 26, 1975 under
5F1606. (Unpublished report prepared by Ciba-Geigy Cbrp., Greensboro, N.C.;
CDL:94378-F)
IVveedy, B.B. (1974) CGA-24705-Corn: Summary of Ftesidues Observed and
Analytical Methods Used: GAAC-74061. Fteceived Sep 26, 1974 under 5G1553.
(Unpublished report prepared by Ciba-Geigy Cbrp., Greensboro, N.C., that
includes tests nuober AG-A 2967, AG-A 2982. AG-A 3132, AG-A 2972, AG-A
3057, AG-rA 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 3323; CDL:94216-A)
TV/eedy, B.G.; Mattson, A.M. (1974) CGA-24705: Cbrn Summary of Ftesidues
Cbserved and Analytical Methods Lfeed: GAAC-74067. Fteceived Mar 26, 1975
under 5F1606. (Unpublished report prepared by Ciba-Geigy Cbrp.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-A-3288, AG-A-3298, AG-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 aumber
of the sections in the 'Proposed Guidelines1 of July 10, 1978 (FR fart 163)
which explain the data diat the Agency will require in order to assess
Mstolachior's Efcological Effects.
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 oyer a long enough
period to demonstrate whether there is a temporary or long-lasting effect on
microbes. Ihree studies were submitted for Mstolachlor. Two of the studies
used the population approach and one used the functional approach.
In the first population study (Hauseworth, 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, Flavobacteriurn, Achromobacter, Aspergillus, Chaetomium, Fusariun
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 microorganisns with 27 species representing the family
Microbes
Algae
Aquatic tecrophytes
Terrestrial Plants
Birds
Wild Manmals
Aquatic Invertebrates
Fish
Ecosystem Effects
Guidelines Sections
163.62-8(f) and (g)
(163.122-2, .123-2, .124-2, and .125-4)*
(163.122-2, .123-2, .124-2, and .125-4)*
(163.121-1, .122-1, .123-1, .124-1, and .125)*
163.70-1, .71-1, .71-2, .71-4, and .71-5
163.70-1, .71-3, and .71-5
163.70-1, .72-2, .72-4a(l), .72-5, and .72-6
163.72-1, .72-4, .72-5, and .72-6
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
9 5
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Actinomycetes and the following genera: 3aciliusf Cellulomonas, Cytophaga,
Flavobacterium, Pseudomonas, Archromobacter, Aspergillus, Chaetomium,
Fusarium, Penicillium, and Tricodema, were evaluated against three
concentrations of Metolachlor; 5, 25, and 125 ppn. At 5 ppn, 5 of 27; at 25
ppn, 9 of 27; and at 125 ppn, 19'of 27 species were inhibited with a static
(but not cidal) effect shown. At 5 ppn, 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.
Cata for oxygen consumption, carbon dioxide evolution, nitrogen cyrling,
dehydrogenase activity, and phosphatase activity were not supplied. Because
application rates normally used for Mstolachlor are 1-3 lbs ai/A, the slight
inhibitory/static effect on soil camiensal populations wauld 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. Eased 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, V&llejo, and Bogus (1978), the effect of
5, 25, and 125 ppn concentrations of Metolachlor was evaluated on the soil
function processes of nitrification in two soil types: Morrison sandy loam and
Hagerstown silt loam. f
-------
Algae
Studies on Metolachlor's toxicity to algae are not presently available.
But because residues of Metolachlor 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 ffetolachlor's effects
on algae because Sikpart 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 Metolachlor 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 J^fetolachlor's 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 Metolachlor on non-target terrestrial
plants are not presently available. Ihe Agency will not now require data on
Metolachlor's 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 chanical's
intended effects has a direct impact on public health, efficacy data was not
reviewed for the Metolachlor Standard.
Birds
The minimim data required for establishing the acute and subacute toxicity
of Metolachlor to birds are the results frcra two 8-day dietary studies and one
oral study with technical Metolachlor. TVo 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 Metolachlor to avian wildlife: the acute LD-50 for mallards (Anas
platyrhynchos) was 4640 (3000-7200, 95% confidence limits) mg/kg, indicating
9 7
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that Metolachlor 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. An avian single
dose oral LD-50 determination is thus a data gap for >fetolachlor.
Acceptable data on the dietary LC-50 of technical Matolachlor for avian
wildlife are reported on the mallard (Anas platyrhynchos) (Fink, 1974a),
and the bobwnite quail (Colinus virginianusl (Fink, 1974b). The 5-day
dietary LC-50 (with 3 days observation) £or both species -was greater than
10,000 ppn, indicating t±ac technical Matolachlor is practically non-toxic,
subacutely, to upland gamebirds and veterfowl. These two studies meet the
guidelines requirement for avain dietary testing.
Because, as was seen in the Qrvirormental 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 tvo studies of technical Metolachlor's effects
on avian reproduction.
Ihe first reproduction study (Fink, 1978a) tested the bobvtfiite 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 1003 ppn Technical Matolachlor for 17 weeks produced significantly fewer
chicks surviving to 14 days. (See table 1.)
table _1
Sunmary of reproductive Success of Cuail Ekposed to Metolachlor for 16 V\feeks
Pesticide Percent^ Chi- ^ Significance
Concentration Survival Square DF Level
Cbntrol 58.3% - ~ ~
10 ppn 47.0% 22.35 1 >0.001
300 ppn 37.0% 62.4 1 >0.001
1000 ppn 41c5% 44.5 1 >0.001
^Tne nunber 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
Bobwhite Quail Dosed with Metolachlor for 17 Weeks
dietary dose number of female deaths
0 ppn (control) 2
10 ppn 1
300 ppn 4
1000 ppm 7
The other reproduction study (Fink, 1978b) was performed on the mallard duck,
using the sane dietary dose levels for the same 17 weeks. In comparison with
98
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the controls, mallard duc!0.331
300 ppm 57.6% 0.353 1 NS
1000 ppn 51.0% 5.26 1 >0.025
^Ihe number of ducklings surviving to age 14 days expressed as
? a percentage of the eggs laid.
"Chisquare calculated by 2x2 Contingency Tkble 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 mortalityTt 300 ppn was attributed to an impacted
table _4
Mallard Duck Dosed with Metolachlor for 17 Weeks
dietary dose number of female deaths
0 ppm (control) 0
13 ppn 0
300 ppn 1
1000 ppn 3
oviduct, rather than to a chanical-related effect. These two 1978 studies by
Fink are sufficient to satisfy the guideline requirements for avian
reproductive testing.
In summary, all guideline data requirements for avian effects are fulfilled
except the acute oral LD-50, which is presently a data gap for Metolachlor.
Qi 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 Nfetolachlor because the data on
laboratory animals reviewed in the "toxicology Gnapter are generally sufficient
for an estimation of toxicity to wild manmals. Based on the data in
Metolachlor's Tbxicology review, there does not appear to be any musual
toxicity, and therefore, no special precautions need be recommended.
Aquatic Invertebrates
The minimun 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 ER 163.72-2. Che such study
-------
by Vilkas (1976) was available for Metolachlor. 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 lijnits is
25.1 (21.6-29.2) ppn. These data satisfy the guidelines requirement for
aquatic invertebrate testing and are sufficient to characterize Matolachlor as
being slightly toxic to aquatic invertebrates.
Fish
A determination of the 96-hour [£-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 Matolachlor to freshwater firh was reported in two
studies conducted by Buccafusco (1978a, 1978b) , one study by Sachsse and
Ullman (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
Date Data Requirements
1978 yes
1978 yes
1978 no
1978 no
1974 no
1974 no
1974 no
These tests provide sufficient information to characterize Metolachlor 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 Brviroomental Ekte chapter, Metolachlor 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 ware 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 /"RTC to the LC-50 for the same species is called the
'application factor' (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 fWTC values of 0.78 and 1.60 by the 96-
Species
96 hr LC-50
Author
Bluegill sunfish
F!airtbow trout
Fathead minnow
Fathead minnow
Crucian Carp
Channel Catfish
Guppy
10.0 ppn
3.9 ppn
11.0 ppn (static)
9.2 ppn
4.9 ppn
4.9 ppn
8.6 ppn
(flow)
Buccafusco
Buccafusco
Dionne
Dionne
Sachsse
Sachsse
Sachsse
10 0
-------
hour flow-through [£-50 for minnows (9.2 ppm), the application factor. (AF) for
fetolachlor was calculated to be between 0.08 and 0.17. This AF for
ffetolachlor was then used to calculate an estimation of the MATC for other fish
species:
The 1978 minnow reproduction study by Dionne satisfies the requirement for a
study of technical Mstolachlor's chronic effects on a freshwater fish species,
and allows an estimation of potentially hazardous residue levels for several
other species.
Qi the basis of available acute and chronic toxicity information, which
indicates a moderate toxicity to fish, the following precautionary labeling
appears appropriate. Ebr the technical.: "Do not discharge into lakes,
streans, ponds, or public waters mless in accordance with an NPDES permit."
And for the emulsifiable concentrate: "Avoid direct application to any body of
water. Do not apply where runoff is likely to occur. Dd 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.
species
estimated
96-hour LC-50 max acceptable tox cone (NRTC)
Bluegill sunfish
Sfeinbow trout
Crucian Carp
Channel Catfish
Guppy
10.0 ppn
3.9 ppm
4.9 ppm
4.9 ppn
8.6 ppm
0.8 ppn to 1.7 ppn
0.3 ppn to 0.7 ppn
0.4 ppn to 0.8 ppn
0.4 PFm co 0.8 ppm
0.7 ppn to 1.5 ppn
101
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DISCIPLINARY REVIEW
Ecological Effects Profile
Etiological Effects Hazard 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
organians. Fish appear to be the most sensitive class tested.
A diverse selection of soil microorganians were evaluated against
three concentrations of Metolachlor: 5, 25, and 150 ppm. Cftly static, not
cidal, effects were noted (Ercegovich, Bogus, and Buly, 1978). Another
study using the same concentrations showsd no effects on nitrification at
the two lower levels, and only tsnporary inhibition at the high level
(Ercegovich, vallejo, and Bogus, 1978). Effects on wastewater treatment
microorganians 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. tfawever, in reproduction studies,
Bobwhite Quail and Mallard ducks fed 10 ppn in their diet for 17 weeks
experienced significant (p<0.001) reproductive impairment: fewer chicks
surviving to 14 days. . "Ifen 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 manmals. 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 IC-50 of 25.1 ppn.
Fish were clearly the most acutely sensitive of the organisms tested.
The cold-water fish teinbow trout had an LC-50 of 3.9 ppn, and the warm-
water SLuegill sunfish had an LC-50 of 10.0 ppn, indicating that
Mstolachlor 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 shoved comparable
LC-50's ranging between 4.9 and 11.0 ppn. 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 Metolachlor: Information on the toxicity of
the Hnulsifiable Cbncentrate to non-target wildlife organians 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 well 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 Metolachlor than with any other technical
chanical. 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 beccme 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 Qtvirormental Ekte chapter, because of the relative stability of
Metolachlor 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 Metolachlor 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 manmalian wildlife do not appear threatened by acute effects. Data are
not presently available on toxicity to non-target plants nor to soil and
surface invertebrates. Metolachlor's resistance to hydrolysis and
metabolisn, and the possibility of non-target plant uptake, suggest that
birds may be exposed to residues in non-sensitive weeds, crops, or soil
organians from the pre-amergent application of Metolachlor to soil. (If
Metolachlor is applied post-emergent or to non-tilled fields, a higher
dietary exposure would 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 Metolachlor 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 rest, the Technical in order to assess the hazard associated with
the use of the Ehiulsifiable 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 EH 163.71-2 (see the
discussion on 'Birds') .
Suggested Labeling
For "technical Matolachlor:
"Do not discharge into lakes, streams, ponds, or public waters unless in
accordance with an NPDES permit. Fbr guidance, contact your regional
office of EPA."
For anulsifiable Cbncentrate tetolachlor:
"Avoid direct application to any body of water. Ed not apply where runoff
is likely to occur. Do not contaminate water by cleaning of equipment or
disposal of wastes. Eb not apply when weather conditions favor drift fran
target area."
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BIBLIOGRAPHY
Each of the following studies contributed useful information to the
/^ency's review of the ecological effects of Metolachior, and is considered
part of the data base which supports registrations under this Standard.
Buccafusco, Robert J. (1978a). /cute "toxicity test Results of CGA-24705 to
Bluegill Sunfish (Lepomis raacrochirus). Fteport #BW-78-181. Received
July 13, 1978 under 100.597. (Unpublished study prepared by EG&G,
3ionimics; Submitted by Ciba-Geigy Cbrp.f Qreensboro, N.C.; CDL:234396)
Buccafusco, Ftabert J. (1978b). A:ute toxicity test Results of CGA-24705 to
Rainbow Trout (Salroo gairdneri) . Report #BW-78-6-186. Fteceived July
13, 1978 under 100-597. (Unpublished study prepared by 3G&G, Bioncmics;
Submitted by Ciba-Geigy Carp., Greensboro, N.C.; CEL:234396)
Dionne, E. (1978). Qironic "toxicity of CGA-24705 to the Fathead Minnow
(Pimephales promelas); received 12-13-78 under 100-587, (Prepared
by 3G&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 Metolachior, [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-OG78. Fteceived Bab 6, 1978 under 100-583. (Uhpublishe
report prepared by Ffesticide Research lab., Pennsylvania State Ihiversity
for Ciba-Geigy Gorp., Greensboro, N.C.; CDL: 232789-F)
Ercegovich, C.D.; V&llejo, R.P.; Bogus, E.R. (1978). The Effects of 5, 25, and
125 PPM of Metolachior, [2-Chloro-N- (2-ethyl-6-methylphenyl)-N-(2-methoxy-l-
methylethyl) acetamide], on Soil Nitrification. E-3/2-CG78. Received Fteb 6,
1978 under 100-583. (Ihpublished study prepared by Efesticide Research lab.,
Pennsylvania State Ihiversity for Ciba-Geigy Corp., Greensboro, N.C.?
CDL:232789-G)
Fink, R. (1974a) . Eight-Day Dietary ££-50 — Mallard Ducks technical CGA-
24705: Project Jb. 108-111. Received September 26, 1974 under 5G1553.
(Unpublished study by Ttuslow E^rm, Inc. for Ciba-Geigy Cbrp., Greensboro,
N.C.; CDL: 112840-0)
Fink, R. (1974a) . Eight-Day Dietary [£-50 — Bobwhite Quail technical CGA-
24705: Project tto. 108-111.. Received September 26, 1974 under 5G1553.
(Unpublished study by Trusiow Ekrm, Inc. for Ciba-Geigy Corp., Greensboro,
N.C.; CDL:112840-P)
Fink, R. (1976). feute Oral LD-50 - Mallard Duck: CGA-24705 technical: Pinal
Report. Fteceived November 23, 1976 under 100-587. (Unpublished study
prepared by Ttuslow to, Inc. for Ciba-Geigy Cbrp., Greensboro, N,C.;
CDL: 2269 55-D)
10 5
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Fink, R. (1978a). Che-Generation Reproduction Study - Bobwhite Quail
CGA-24750 technical Final Fteport; received 12-13-78 under 130-537,
(Lhpublished report prepared by Wildlife International Ltd. for Ciba-Gsigy
Corp., Greensboro, N.C.; CEL:236620)
Fink, R. (1978b). Che-Generation Reproduction Study - Mailard Duck
CGA-24705 technical Final Report; received 12-13-78 under 100-587,
(Ihpublished report prepared by Wildlife International Ltd. for Ciba-Cfeigy
Corp., Greensboro, N.C.; CDL:236620)
Houseworth, L.D. (1973a) Effect of CGA-24705 on Microbial Fbpulations in TVo
Soils: Report No. 2. Received Sep 26, 197 4 under 5G1553. (Unpublished study
prepared by Ihiversity of Missouri—Golunbia, Department of Plant rathology
for Ciba-Geigy Gorp., Qreensboro, N.C.; CEL:94222-F)
Sachesse, K.; Ullraan, L. (1974b). A^ute Ibxicity to Rainbow Trout, Crucian
Carp, Channel Catfish, Bluegill, and Guppy of "technical CGA-24705: Project
Nd. Siss 3516. Received September 26, 1074 inder 5G1553. (Lhpublished
study prepared by Ciba-Geigy Ltd., Basle, Switzerland, that includes a
cable fran Ciba-Geigy Cbrp., Greensboro, N.C. on fish nane change;
CEL;112840-N)
Vilkas, A.G. (1976). teute Ibxicity of CGA-24705 Technical to the 'Water Flea
Daphnia magna~ Received November 23, 1976 under 100-587. (Unpublished
study prepared by /aquatic Environmental Sciences, Lhion Carbide Cbrp. for
Ciba-Geigy Gorp., Greensboro, N.C.; CDL: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 chanical. Technical Metolachlor, at least
ninety percent the pure compoind, is an off-white, odorless liquid, soluble in
water, and miscible with several organic solvents.
The Delimitation of Risks to Hunvans
lb review our "toxicology findings, "technical Metolachlor'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. Chce an exposure
occurs, Metolachlor is rapidly metabolized and excreted. Although the
available chronic effects studies ware 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, shipnent, 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 hunan 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 Metolachlor. 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 vrorkers, acute risks higher than
those foind for "technical Metolachlor are normally acceptable,- because the
Agency expects members of such occupations to be responsive to a chanical's
accompanying label precautions, fbwever, because it is evidently possible
to manufacture a "technical Metolachlor with a mild acute toxicity, the
Agency should only register Technical Metolachlor products that fall into
'toxicity Categories" III or tv for each of the five acute tests: acute
oral toxicity, acute dermal-toxicity, acute inhalation toxicity, primary
eye irritation, and primary dermal irritation"! "technical Metolachlor
products that fall into nunerically lower 1 Tbxicity Categories' are likely
to be substantially different in either impurities or inerts from the
chanical 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 Metolachlor 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 or using
this produce". Lh^ess tne 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 \4iich 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
lb 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 gane birds. Fish ware the most
sensitive species tested, with relatively low l£-50's arid 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 Metolachlor wastes
into freshwater aquatic habitats. The organisns that may be exposed by
route of freshwater aquatic discharge are fish, aquatic invertebrates, and,
because of plant uptake, local avian or mammalian 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 Nfetolachlor can poind 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 in accordance with in NPDSS permit" is therefore necessary to
help control contamination of the aquatic 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 Metolachlor 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 decontanination. 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 reconmend at this time is to place
Technical Metolachlor in a landfill disposal site approved for pesticides.
10 8
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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 frcm measured applications to use sites, 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 Mstolachlor. Until these .risks are quantified, the Agency should
presume that as concerns Etiological Effects, a "technical Matolachlor
product will be registrable if it bears the following warnings:
Under 'hazards to wildlife': "Do not discharge into lakes, streams,
ponds, or public waters, unless in accordance with an NPDES perm it. For
guidance"!" contact your Regional UTtice ot SPA."" ThHer 1 storage and
disposal' directions: "Open dumping or~open burning.is prohibited-
Thoroughly clean containers or tanks Before re-use, or re-^seaT~and"offer
for .recycling or reconditioning. Pesticide or rinsate that cannot be
used, recycled, or chemically reprocessed, and tanks or other containers
thatcannot be refused or recycled should be disposed of. in a landfill
approved for pesticides. Consult federal, state, or locarUisposal
authorities for approved alternative procedures."
Section 162.11(a) of 40 CFR states that the Agency shall presume against
the registration of a pesticide product which meets or exceeds certain specific
risk criteria set forth therein. Because the available data 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 ragisterable for sale, distribution, and re-formulation in the
United States.
EMULSIFIABLE CONCENTRATES of METOLACHLOR
This Standard will presently only cover 'emulsifiable concentrate' 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, envirormental fate, toxicology, residue chemistry, and ecological
effects of new formulation types and their application methods >©uld be needed
to evaluate the registrability of such products.
Etaulsifiable Cbncentrate formulations containing Metolachlor alone are
appropriate for the control of weeds in non-dcmestic, outdoor, terrestrial food-
crop fields. When not 'tank mixed' with other herbicides, the Ehiulsifiable
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-etiergence
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 tolaranca for other crops in the grouping without requiring
additional data. 5br>fetolachlor, however, the presently available residue
data are only sufficient to support tolerances for, and thereby enable the use
of Snulsifiable Concentrate J^fetolachlor on: corn grown for grain (excluding
popcorn) , soybeans, (Cbncep-treated) grain sorghun, and peanuts. Presently
available residue data show that Metolachlor Enulsifiable Concentrate can be
applied pre—emergence to corn fields at a rate of up to 6 lbs. ai/acre, to
soybean fields at a ra~Ee of up to 3 IBs ~ai/acre7 ~Eo grain sorghum fields-at
rates of up to 2^172 lbs."aiTacre,-and to peanuts at up to 3 lbs.ai/acre,
without"exceeding the established tolerances"!
If the crop treated with the Ehiulsifiable Concentrate' is lost, it may be
replanted inmediately with com, soybeans, peanuts, or (Goncap-treated) grain
sorghum without a second treatment.
Ihe 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 snail grains may
be planted in the spring following treatment. Do not graze or feed forage or
loader from-cotton or small grains to livestock. 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 Ehiulsifiable 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
poinds per gallon formulation can cause serious eye irritation, including
irreversible-corneal opacity. Like the active ingredient, any Ehiulsifiable
Cbncentrate may produce skin sensitization with repeated exposures.
The Exposure 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 Ehiulsifiable Cbncentrate has a high vapor
pressure, as do most products with organic solvents, an unprotected mixer
or diluter who is handlirg an open container without adequate ventilation
may be exposed to fumes. 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. Hnovffi 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
Snulsifiable Cbncentrate formulations. The acute risks to himans caused by.
the handling of these Ehiulsifiable Cbncentrate 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 frcm mixing or loading in a poorly
ventilated area, and the danger of spray inhalation near the point of •
ground spray application. Ebccept 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 v*ould 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 there 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 toxicity
higher tHan Category HIT t
As concerns acute inhalation toxicity, although Metolachlor is an
outdoor use pesticide and is cctrmonly mixed, diluted, and loaded outdoors,
because most Bnulsifiable 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 cctrmonly occur outdoors,
because the spraying is limited to grornd spraying, and because the
accompanying warning "Do not breathe vapors" vould 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 seme protective apparatus, and without restricting
the chemical to use by trained applicators, the Agency cannot be assured
that such equipment would be consistently used. M additional limit that
will not affect efficacy can be put on the exposure to vapors by limiting
the physical/chemical property 'vapor pressure' to less than 1.0 itm Hg.
The Agency will thus find acceptable a Mstolachlor formulation with an
acute inhalation toxicity as high but no higher than a Category II, and a
vapor pressure" between 0.0"5~and 1.0 mmHIg.
With the above limitations on tEe Hermal and inhalation hazards, the
Agency does not see the need to prescibe a re-entry interval for
iMetolachlor. Nevertheless, users should be aware that the "application of
a pesticide in such a manner as to directly or through drift expose wrkers
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 sarie 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 Matolachlor 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 vorkers or
applicators, and it may be assumed that such protective equipment as
goggles are conmonly available to pesticide applicators. "Itus assurance
allows the Agency to accept a Metolachlor formulation with a primary eye
irritation as high as Category _I.
As concerns primary dermal irritation, because of the likelihood of
accidental dermal exposures, the Agency should not accept a formulation
with a dermal irritation higher than Category II. (Category II is
acceptable for dermal irritation, but not for cJermal 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 'pH' to the relatively
neutral range of pH 6 to pH 8.
ITTe Agency oonsTders~~the dermal sensitization risk to be acceptable in
the case of Bnulsifiable Concentrates of Metolachlor because t«3 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 wasn
contaminated clothing before refuse". Even though applicators and
agricultural workers vdx> may cane in contact .with the chanical might be •
untrained in the handling of pesticide chemicals, the Agency can reasonably
assurie that the simple and unencunbering 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 Hnulsifiable 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 "flaitmable" 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 Statements7" and 'Storage andTisposal'
sections of the label. Second, because it would require special training
for safe handling, no Jfetolachlor Ehiulsifiable Cbncentrate should be
explosive or shock sensitive. Third, a corrosive pesticide might, burn
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' 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 mor-e 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 ffetolachlor on an incremental risk and
benefits assessment basis. The established tolerances provide a more than
2003 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.
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The Deliroitation of Risks to Wildlife
The potential effects to wildlife due to Pfetolachlor exposures
resulting from the use of the foemulations are estimated in toxicity
studies on the "technical, lb review our Efcological Effects findings for
the Technical, the available wildlife studies suggested several potential
hazards for wildlife. Though the toxicity of Technical Nfetolachlor to
birds was shown to be low in one dietary LC-50 test, a several month
dietary exposure of 10 ppn was show 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 ppn. Aquatic invertebrates have a lesser,
though still significant, sensitivity to ffetoiachlor.
As stated in our Exposure Profile, several aspects of Matolachlor's
fate, including its tendency to leach or rinbff, 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 Metolachlor residues on to herbivores, including birds.
Thus, several concerns about wildlife risks arise frcm the suspicion
that Mstolachlor residues will migrate to and persist in aquatic habitats.
The most notable of these potential, but as yet inquantified, 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 v^ich 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 v*hen vreather conditions favor drift to
aquatic sites, the Agency does not forsee an inmanent risk to wildlife from
the routine use of Metolachlor formulations. Thus, the Agency considers
these as yet uiquantified risks to be tamporarily acceptable, at least
until a quantification becomes possible, if the labels for Metolachlor
formulations present the following statements under 'hazards to wildlife':
"Avoid direct application to any body of water. Do not apply where runoff
is likely to occur. Do not contaminate water by cleaning of equipment or
disposal oTVastes. Do not apply when weather conditions "Favor drift from
areas treaEed."
As with the Technical, disposal practices involving soil injection,
landspreadir>g, hydrolysis, incineration, open burning, or discharge into a
sevage system are not supported by the current data. Disposal should thus
be limited to landfill disposal sites approved for pesticides: "Open
dumping or open burnirg is prohibited. Do not re-use empty container^
triple rinse or equivalent. Pesticide or rinsate that cannot be used,
recyclecf, or cEemically reprocessed, aricT triple-rinsed containers witn
their rinsate, should be disposed of in a landfill approved for
pesticides. Consult federal, state, or-local disposal authorities for
approved altemative~"procedures.*
113
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Section 162.11(c) of 40 CFR states that the Agency may classify for
'general use', 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
v<*uch 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 Ehtulsifiable Concentrate fetolachlor which
was in accord with all the 'Standards' suggested in the above discussions;
and eye exposure can be effectively eliminated by the requirement to "Vfear
goggles or face shield when handling". An Ehtulsifiable 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
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CHEMICAL DATA SHEETS
Chemical Data Sheets have been prepared for the components, hydrolysis
products, and xnown metabolites of manufacturing-use Metolachlor. The Data
Sheets are divided into Components COMOOl througn COMOll, 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.
i j 117
; Preceding page blank J
-------
COMPONENT NUMBER COMOOl
01. Chemical Abstracts Chemical names;
01 Acetamide, 2-chloro-N-(2-ethyl-6-methylphenyl)-N-(2-methoxy-l-
methylethyl>-(CA9)
02 o-Acetotoluidide, 2-chioro-6'-ethyl-N-(2-methoxy-l-methylethyl)-
?CA8)
02. Other Chemical Names;
01 2-Chloro-N-(2-ethyl-6-methylphenyl)-N-(21-methoxy-11-methylethyl)-
acetamide
02 Acetanilide, 2-chloro-21-ethyl-N-(2-methoxy-l-methylethyl)-61-methyl
03 N-(2'-Methoxy-1'-methylethyl)-2-ethyl-6-methy1-chloroacetanilide
04 N- (Chloroacetyl)-6-ethyl-N-(2-methoxyisopropyl)-o-toluidine
03. Structural Formula;
04. Molecular (Empirical) Formula;
C 15H22C1N02
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
O
1 1 9
Preceding page blank
-------
Chemical Data Sheets OOM-002 through CDM-011 have been
omitted in this Sample Registration Standard because of
confidentiality claims by the manufacturer.
120
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HYDROLYTIC PRODUCT NUMBER HP001
01. Chemical Abstracts Chemical Names;
01 i-Propanol, 2-[(2-ethyl-6-methyiphenyl)amino]- (CA9)
02 1-Propanol, 2-(6-ethyl-o-toluidino)- (CAS)
02. Other Chemical Names;
01 i-Propanol, 2-(2-ethyl-6-methylanilino)-
02 2-[(2-Ethyl-6-methyl)amino]-1-propanol
03. Structural Formula;
04. Molecular (Empirical) Formula;
^12^19^
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)
-------
HYDRQLYTIC PRODUCT JiUMBER HP002
01. Chemical Abstracts Chemical Names;
01 3-Morpholinone, 4-{2-ethyl-6-methylphenyl)-2-hydroxy-5-methyl-
02 3-Morpholmone, 4-(6~ethyl-o-tolyl)-2-hydroxy-5-methyl-
02. Other Chemical Names;
01 4-(2-Ethyl-6-methylphersyl )-2-hydroxy--5-rnethyl-3-trorpholinone ,
03. Structural Formula;
05. Chemical Abstracts (C^S) Registry Ntmber;
06. Approved Condon Name; None
07. Other Carcron Names, Trade Names, or Codes;
01 CGA No. 4S751
02 MHP (morpholirione hydrolytic product)
k
04. Molecular (empirical) Formula;
c,,h1qno
14 IS 3
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, 21 -ethyl-2-hydroxy-N- {2-methoxy-l-nvethylethyl) -6' -methyl'
02 (2-Ethyl-6-me thyIpheny1)-2-hydroxy-N- (2-methoxy-l-
methylethyl)acetamide,
03. Structural Formula;
04. Molecular (Bnpiricai) Formula;
Ci5H23N03
05. Chemical Abstracts (CAS) Registry Number;
06. Approved Gormen Name; None
07. Other Common Names, Trade Names, or Codes;
01 CGA No. 40172
123
-------
METABOLITE NUMBER METOO2
01. Chemical Abstracts Chemical Names;
01 Acetamide, N- (2-e thyl-6-rnethylphenyl) -2-hydroxy- (CA9)
02 o-Acetotoluidide, 6'-ethyl-2-hydroxy-(CAS)
02. Other Chemical Names;
01 Acetanilide, 2'-ethyl-2-hydroxy-6'-methyl-
02 N- (2-Ethyl-6-methylphenyl)-2-hydroxyace tamide
Structural Formula;
C-C^OH
04. Molecular (Empirical) Formula;
C11H15N02
05. Chenical Abstracts (CAS) Registry Number;
06. Approved Camion 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-
methylethyl)- (CA9)
02 o-Acetotoluidide, 2-chloro-6'-ethyl-N-(2-hydroxy-l-methylethyl)~
TCA8)
02. Other Chemical Names;
01 Ace tan Hide, -2-chloro-2'-ethy1-N-(2-hydroxy-l-methylethyl )-6'-methyl-
0 2 2-Chloro-N-(2-e thy1-6-me thylpheny1)-N-(2-hyd roxy-1-
methylethyl)acetamide
03. Structural Formula;
04. Molecular (Bnpirical) Formula;
C14H20C1CK)2
05. Chemical Abstracts (CAS) Registry Number;
06. Approved Camion Name; None
07. Other Common Names, Trade Names, or Codes;
01 CGA No. 41638
125
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METABOLITE NUMBER METQ04
01. Chemical Abstracts Chemical Names;
01 DL-Alanine, N-(2-ethyl-6-niethylphenyl)-N-(hydroxyacetyl)- (CA9)
02 DL-Alanine, N-(6-ethyl-o-tolyl)-2-(hydroxyacetyl)- (CAB)
02. Other Chemical Names;
01 Propanoic acid, 2-[H-(2-ethyl-6-methylphenyl)-2-hydroxyacetamido]-
02 Propionic acid, 2-[U-(6-ethy 1-o-tolyl)-2-hydroxyacetamido]-
03 N- (2-Ethyl-6-roethylphenyl)-tJ-(hydroxyacetyl)alanine
03. Structural Formula?
04. Molecular (Enpirical) 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
12 6
-------
METABOLITE NUMBER MET005
01. Chemical Abstracts Chemical Names;
01 Acetamide, N-(2-ethyl-6-roethylphenyl)-N-(2-roethoxy-l-methylethyl)-
(CA9)
02 o-Acetotoluidide, 6'-ethyl-N-(2-methoxy-l-methylethyl)- (CA8)
02. Other Chemical Names;
01 Acetanilide, 2' ^thyl-N-(2-methoxy-l-methylethyl)-6'-methy1-
02 N-(2-Ethyl-6-methylphenyl) -N- (2-methoxy-l-methylethylJacetamide
03. Structural Formula;
04. Molecular (Empirical) Formula;
C15H23lX>2
05. Chemical Abstracts (CAS) Registry Number;
06. Approved Cottinon Name; None
07. Other Common Names, Trade Names, or Codes;
01 Dechloranetolachlor
02 CGA No. 41507
12 7
-------
METABOLITE NUMBER-METCOO6
01. Chemical Abstracts Chemical Names;
01 £cetamijde, N- (2-ethyl-6-methyiphenyl) -N- (2-hydroxy-l-methylethyl) -
(CA9)
02 o-Acetotoluidide, 6'-ethyl-N-(2-hydroxy-l-methylethyl)- (CAS)
02. Other Chemical Names;
01 Acetanilide, 2'-ethyl-N-(2-hydroxy-l-methylethyl)-6'-methy1-
02 N- (2-Ethyl-6-methylphenyl) -tt- (2-hydroxy-l-methylethyl Jacetamide
03. Structural Formula;
04. Molecular (Empirical) Formula;
C14H21^
05. Chemical Abstracts (CAS) Registry Number;
06. Approved Caimon Name; None
07. Other Common Names, Trade Names, or Godes;
01 CGA No. 42446
128
-------
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'-ethy1-6'-methy1-
02 N- (2-Ethyl-6-roethylphenyl)acetamide
03. Structural Formula;
04. Molecular (Bnpirical) Formula;
Ciihi5no
05. Chemical Abstracts (CAS) Registry Number;
06. Approved Conmon Name; None
07. Other Common Names, Trade Names, or Codes;
01 CGA No. 42444
129
-------
METABOLITE NUMBER MET008
01. Chemical Abstracts Chemical Names;
01 3-Morpholinone, 4-(2-ethyl-6-methylphenyl)-5-methyl- (CA9)
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;
C14H19N02
05. Chemical Abstracts (CAS) Registry Number;
06. Approved Comran Name; None
07. Other Common Names, Trade Names, or Codes;
01 CGA No. 40919
130
-------
METABOLITE NUMBER MET009
01. Chemical Abstracts Chemical Names;
01 Acetamide, 2-chloro-N-(2-ethyl-6-methylphenyl)- (CA9)
02 o-Acetotoluidide, 2-chloro-6'-ethyl- (CA8)
02. Other Chemical Names;
01 Acetanilide, 2-chloro-2'-ethyl-6 '-methyl
02 2-Chloro-N-{2-ethyl-6-methylphenyl)acetamide
03. Structural Formula;
04. Molecular (Empirical) Formula;
C, ,H, .C1N0
11 14
05. Chanical Abstracts (CAS) Registry Number;
06. Apprcr/ed Conmon Name; ttone
07. Other Gomroon Names, Trade Names, or Codes;
01 CGA Ho. 13656
131
-------
;
METABOLITE NUMBER MET010
01. Chemical Abstracts Chemical Names;
01 Benzenamine, 2-ethyl-N-(2-methoxy-l-methylethyl)-6-methyl- (CA9)
02 £-Toluidinef 6-ethyl-N-(2-methoxy-l-nethylethyl)- (CA8)
02. Other Chemical Names;
01 Aniline, 6-ethyl-N-(2-methoxy-l-methylethyl)-6-methyl-
02 2-Ethyl-N-(2-methoxy-l-methylethyl)-6-roethylbenzenamine
03. Structural Formula;
ON
04. Molecular (Empirical) Formula;
C13H2l"°
05. Chemical Abstracts (CAS) Registry Number;
06. Approved Corrrvon Name; None
07. Other Common Names, Trade Names, or Codes;
01 CGA No. 38502
132
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METABOLITE NUMBER,METQ11
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-methylethyl
S-conjugate with Glutathione
02. Other Chenical Names;
01 Acetanilide, 2'-ethyl-2-mercapto-N-(2-methoxy-l-methylethy) -6' -
methyl-,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-61 -ethyl-N-(2-methoxy-l-
methylethyl)-o-acetotoluid ide
03. Structural Formula;
04. Molecular (Empirical) Formula;
C25H38N4°8S
05. Chemical Abstracts (CAS) Registry Number;
06. Approved Comnon Name; None
07. Other Common Names, Trade Names, or Codes;
01 Metolachlor glutathione conjugate
02 CGA NO. 43826
tlOOC-CHCHjCHj
133
-------
METABOLITE NUMBER MDT012
01. Chemical Abstracts Chemical-Names ;
01 Acetamide, N-(2-ethyl-6-methylphenyl)-2-raercapto-N-(2-methoxy-l-
methylethyl)-,S-con]ugate with Glucuronic acid (CA9)
02 o-Acetotoluidide, 21-ethyl-2-mercapto-N-(2-raethoxy-l-methylethyl)-,
S-conjugate with Glucuronic acid (CAS)
02. Other Chemical Names;
01 Acetanilide, 21-ethyl-2-mercapto-N-(2-methoxy-l-methylethyl) -6' -
methyl-,S-conjugate with Glucuronic acid
02 Glucuronic acid, 1-S- [ [ [ (2-ethyl-6-roethylphenyl) (2-methoxy-l-
methylethyl)-amino]carbonyljmethyl]-1-thio-
03 Glucuronic acid, 1-S-[[[6-ethyl-o-tolyl)(2-methoxy-l-methylethyl)
carbamoy1]methy1]-1-thio-
03. Structural Formula;
CrOt-i-C
•H C-OM
COOH
04. Molecular (Qnpirical) Formula;
C21H30tW8S
05. Chemical Abstracts (CAS) Registry Number;
06. Approved Cortinon Name; None
07. Other Common Names, Trade Names, or Codes;
01 Metolachior glucuronic acid conjugate
02 Compound N
134
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METABOLITE NUMBER METO13
01. Chemical Abstracts Chemical Names;
01 Acetamide, N-(2-ethyl-6-methylphenyl)-N-(2-hydroxy-l-methylethyl)-2-
mercapto-, 0-glucoside, S-conjugate with Glucuronic acid (CA9)
02 £-Acetotoluidiae, 61 -ethyl-N-( 2-hydroxy-l-methylethyl )-2-raercapto-,
0-glucosiae, 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, l-rS-[ [(6-ethyl-o-tolyl) (2-glucosyl(l)-l-
methylethyl)carbamoyl]methyl]-1-thio-
03 Glucuronic acid, 1-S-[[[(2-ethyl-6-methylphenyl)(2-glucosyl(1)-l-
methylethyl)amino]carbonyl]methyl]-1-thio-
03. Structural Formula;
04. Molecular (Qnpirical) Formula?
C26H39N°i3S
05. Chemical Abstracts (CAS) Registry Number;
06. Approved Conroon Name; ttone
07. Other Common Names, Trade Names, or Codes;
01 Caitpound No. 0
0
HOCH
COOtt
135
-------
METABOLITE NUMBER METO14
01. Chemical Abstracts Chemical Names;
01 • Acetamide, N-(2-ethyl-6-raethylphenyl)-N-(2-hydroxy-l-methoxyethyl)-2-
raercapto-, S-conjugate-with Glucuronic acid (CA9)
02 o-Acetotoluidide, 2'-ethyl-N-(2-hydroxy-l-methylethyl )-2-mercapto-,
S-conjugate with Glucuronic acid (CA8)
02. Other Chemical Names;
01 Azetanilide, 2'-ethyl-N-(2-hydroxy-1-jnethylethyl)-2-raercapto-6'-
methyl-, S-conjugate with Glucuronic acid
02 Glucuronic acid, 1-S-[[[(2-ethyl-6-methylphenyl)(2-hydroxy-1-
methylethyl)amino]carbcnyl]methyl]-1-thio-
03 Glucuronic acid, 1-S-[[(6-ethyl-o-tolyl)(2-hydroxy-1-
methylethyl)carbamoyl]methyl]-1-thio-
03. Structural Formula;
04.
Molecular (EJnpirical) Formula;
C^H^NOgS
Chemical Abstracts (CAS) Registry Number;
Approved Conroon Name; None
Other Gcaranon Names, Trade Names, or Codes;
0i Demethyimetolachlor glucuronic acid conjugate
136
-------
METABOLITE NUMBER METG15
01. Chemical Abstracts Chemical Names; .
01 Acetamide, N- (2-ethy1-6-methylphenyl)-2-hydroxy-N- (2-raethoxy-l-
methylethyl)-, O-conjugate with Glucuronic acid (CA9)
02 o-Acetotoluidide, 2*-ethyl-2-hydroxy-N-(2-methoxy-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-
methylethyl )amino]carbony]methyl]-
03 Glucuronic acid, 1-0-[[(6-ethyl-o-tolyl)(2-methoxy-l-methylethyl)-
carbamoyl ] methyl ] -
03. Structural Formula;
04. Molecular (Empirical) Fomula;
C2ia31N09
05. Chemical Abstracts (CAS) Registry Number;
06. Approved Caimon Name; None
07. Other Common Names, Trade Names, or Codes;
01 Metolachlor glucuronic acid conjugate
137
-------
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 o-Acetotoluidide, 2'-ethyl-2-hydroxy-N-(2-hydroxy-l-rnethylethyl)-,
O-conjugate with Glucuronic acid
02. 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-nvethylphenyl)(2-hydroxy-l-
methylethyl )amino] carbonyl] methyl j -
03 Glucuronic acid, 1-0-([(6-ethyl-o-tolyl)(2-hydroxy-l-methylethyl)-
carbamoyl]methyl]- ~
03. Structural Formula;
CO OH
04. Molecular (Empirical) Formula;
C20H291C9
05. Chemical Abstracts (CAS) Registry Number;
06. Approved Conroon Name; None
07. Other Conroon Names, Trade Names, or Codes;
01 Desmethylmetolachlor glucuronic acid conjugate
138
-------
METABOLITE NUMBER MET017
01. Chemical Abstracts Chemical Names;
01 Acetamide, N- (2-ethy 1-6-methylphenyl) -2-hydroxy-if- (2-hydroxy-l-
methylethyl)-, Q-glucoside, O-conjugate with Glucuronic acid (CA9)
02 cWVcetotoluidide, 6'-ethyl-2-hydroxy-N-(2-hydroxy-l-methylethyl)-,
O-glucoside, O-conjugate with Glucuronic acid (CA8)
02. Other Chemical Names;
01 Acetanilide, 2'-ethyl-2-hydroxy-N-(2-hydroxy-l-niethylethyl)-6
methyl-,0-glucoside, O-conjugate with Glucuronic acid
02 Glucuronic acid, 1-0-[[(6-ethyl-o-tolyl)(2-glucosyl(l)-l-
me thy lethyl}-carbamoyl ] me thy 1 ]
03 Glucuronic acid, 1-0-[[[((2-ethy1-6-methylphenyl)(2-glucosyl{15-1-
raethylethyl)amino]carbonyl]methyl]-
03. Structural Formula;
» MjT « T
* OH * «
\ «
nc-cm£-o-^-
g O HG~<3M
W-6h
HC-OH
04. Molecular (Bnpirical) Formula;
C26H39IW14
05. Chemical Abstracts (CAS) Registry I&smber;
06. Approved Comton Name; None
07. Other Common ! James, Trade flames, or Codes; None
139
-------
METABOLITE NUMBER: 018
01. Chemical Abstracts Chemical Names:
01 CXiinoline, N-(2-methoxy-i-methylethyl)-8-
ethyl-3-hydroxy-2-oxo-l,2,3,4-tetrahydro-
02. Other Chemical Names:
01 8-5thy1-3-hydroxy-N-(2-methoxy-l-methylethyl)-
2-oxo-l ,2,3,4- tetrahydroquinol ine
03. Structural Formula:
CH
M- Ctf—CH,— OCH
04. Molecular (Empirical) Formula:
C15H21N03
05. Chamical Abstracts (CAS) Registry Number:
06. Approved Common Names, Trade Names, or Godes:
140
-------
METABOLITE NUMBER: 019
01. Chemical Abstracts Chemical Names:
01 Acetamide, 2-hydroxy-N-(2-methyl-6-vinylphenyl)-
N- (2-me-choxy-l-tfiethylethyl) -'
02. Other Chemical Names:
01 2-hydroxy-N-(2-mothyl-6-vinylphenyl)-N-
(2-methoxy-l-methylethyl) acetamide
03. Structural Formula:
^CH-CK^-O-CWj
a
-DL-W
04. Molecular (Efctpirical) Formula:
Ci5h2iN03
05. Chemical Abstracts (CAS) Registry Number:
&
06. Approved Cannon Names: None
07. Other Common Names, Trade Names, or Codes:
14 1
-------
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:
C14H19N02
05. Chemical Abstracts (CAS) Registry Number:
C
06. Approved Cannon 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:
C+f—C4H2— OCHs
04. Molecular (Empirical) Fornula:.
C14H191S02
05. Chemical Abstracts (CAS) Registry Number:
06. Approved Corrrncn Names: None
07. Other Caimon Names, Trade Names, or Codes:
143
-------
METABOLITE"NUMBER: 022
01. Chemical Abstracts Chemical Names: •
01 Aniline, N-(2-inethoxyT-l-methylethyl)-2-methyl-6-vinyl-
02. Other Chemical Names:
01 N-(2-methoxy-l-methylethyl)-(2-methyl-6-v inyl)
aniline
03. Structural Formula:
CH,
04. Molecular (Bnpirical) Formala:
C13H19NO
05. Chemical Abstracts (CAS) Registry Number:
06. Approved Ccmmon Names: None
07. Other Ccmmon Names, Trade Names, or Codes:
144
-------
METABOLITE NUMBER: 023
01. Chemical Abstracts Chemical Napes:
01 Indole, 2,3-dihydro-N-{2-methoxy-l-methylethyl)-7-methyl-
02. Other Chemical Names:
01 N-(2-methoxy-l-methylethyl)-7-methy1-2,3-dihydroindole
aniline
03. Structural Formula:
GH-Ctt,—OCH
04.
05.
06.
07.
Molecular (BTpirical) Formula:
C13H19NO
Chemical Abstracts (CAS) Registry Number:
Approved Common Names: None
Other Common Names, Trade Names, or Codes:
145
-------
METABOLITE NUMBER: 024
01. Chemical Abstracts Chemical Names: • , -
01 Qainoline, N-(l-hydroxyethyl)-8-methyl-2-oxo-l,2,3,4-tetrahydro-
02. Other Chemical Names: -
01 8-Methyl-N-(1-hydroxyethvl)-2-oxo-l,2,3,4-tetrahydroquinoline
03. Structural Formula:
04. Molecular (Bnpirical) Formula:
C12H15N02
05. Chemical Abstracts (CAS) Registry Number:
06. Approved Common Names: None
07. other Common Names, Trade Names, or Codes:
146
-------
BIBLIOGRAPHY
14 7
-------
GUIDE TO THE USE CF THIS BIBLIOGRAPHY
Content of the 3ibliography
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 ware: (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 vdiich were found to contribute useful information to the
Agency's review of Metolachlor 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
dociments at a level parallel to a published article frcm within the typically
larger volumes in which they ware 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 attanpted to unite basic docunents and conmentaries
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 Anerican National
Standards Institute (ANSI), explanded to provide for special needs. Seme
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
showi 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 docunent. When a four
digit date is followed by a question mark, the bibliographer deduced
the date from evidence in the docunent. When the date appears (19??) ,
we were inable to determine or estimate the date of the docunent.
Preceding page blank
-------
(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. toy such editorial insertions are contained between
square brackets.
(d) Trailing Parentheses. Fbr 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
•received' appears the date of the earliest known
submission.
(2) Administrative Number. The next element, immediately
following the wrd 'under', is the registration number,
experimental permit nuitber, petition nunber, 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
for* 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
volune in which the original submission of the study
appears. The six-digit accession nunber follows the symbol
'CDL', which stands for "Cbmpany Data Library." Ihis
accession nunber is in turn followed by an alphabetic suffix
which shows the relative posiution of the study within the
volune. Fbr example, within accession number 123456, the
first study would be 123456-A; the second, 123456-8; the
26th, 123456-Z; and the Z7th, 123456-AA.
150
-------
* Affiliated Medical Research, Incorporated (1974a) Acute Dermal LDtc 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 LD-Q 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:11284Q-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 No. 121-2255-34. (Unpublished study received
Sep 26, 1974 under 5G1553; prepared for Ciba-Geigy Corp., Greensboro, N.C.;
CDL:11284Q-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 (1974i) Primary Eye Irritation of CGA-
24705-6E in Albino Rabbits: Contract No. 121-2255-34. (Unpublished study
received Sep 26, 1974 under 5G1553; prepared for Ciba-Geigy Corp.,
Greensboro, N.C.; CDL:11284Q-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-<2)
151
\
-------
Ahrens, J.F.; Cuoanski, 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 arid Rationale for Decision Making in Ajuatic 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). Gommon name for the pest control
chemical 2-chloro-N-(2-ethyl-6-methylphenyl)-N-(2-methoxy-l-methylethyl)
acetamide "metolachlorIn 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) Saimonella/Hammalian-Microscnie Mutagenicity Test
with CGA 24705 (Test for Mutagenic Properties m 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 GG&-24705 iri 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
-------
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-247G5 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.; Boss, 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 ffhich are Converted to the
CGA-379i3 Moiety: GACC-74Q43. (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.y 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
Chanagro 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, L.G.; Herman, M.M. (1977a) Metalochlor Plus Atra2ine Plus Paraquat
Tank Mix Soil Dissipation: ABR-77068. (Unpublished study containing
studies Ortho T-4088, Ortho T-4089, AG-A 4084 I-IV, AG-A 4085 I-IV; received
Nov 8, 1977 under 1QQ-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 10Q-EUP-59 prepared by Ciba-
Geigy Corp., Greensboro, N.C.;
14
Barrows. M.E. (1974) Exposure of fi|^ 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.C.; CDL:94376-E)
Bathe, R. (1973) Acute Oral LD,-Q 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
New 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,' A. (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?]
Bianetric Testing Incorporated (1973) Metabolism 14C-CGA-24705 Corn
Biosynthesized Metabolites in a lactating Goat: A-1G04. (Unpublished
study received Sep 26, 1974 under 5G1553; prepared for Ciba-Geigy Corp.,
Greensboro, N.C.; CDL:94217-J)
Bleidner, W.E.y Baker, H.M.; Lsvitsky, M.; Dswen, W.K. (1954) Determination of
3-(p-chlorophenyl)-1, 1-dlinethy1urea 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.: CDL:94221-A)
Bohn, 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. . Onaha, 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, Dallas, Texas. Raleigh, N.C.: Glover Printing for the Southern Weed
Science Society:
-------
* Buccafusco, Robert J. (1978a) Acute Toxicity Test Results of GGA-24705 to
Bluegill Sunfish (Lepomis macrochirus): Report #8W-78-6-181.
(Unpublished study received Jul 13, 1978 under 100.597; prepared by E G &
G,Bioncmics, Submitted by Ciba-Geigy Gorp., 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.r 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 2/14. (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 Corp.,
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 Sunroary: 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)
IM
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 Sunmary: Dual 6EC -t- 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
or Lexone Tank Mix. (Unpublished study that includes
Nov 25, 1975'under 100-EUP-43; CDL:94832-C;. 94830)
15 5
SEC + Sencor 50% U.P.
reports 1-49; received
-------
Ciba-Geigy Corporation (1975e) Efficacy arid Crop Safety Summary GA-2-686 15G
Herbicide for Corn. (Unpublished study including surinary tables and
efficacy tests 1-6, 8-14L; received. Feb 9, 1976 under 100-EUP-44;
CDL:96496-B)
Ciba-Geigy Corporation (1975£) Name, Chemical Identity and Composition of CGA-
24705. (Unpublished study received Nov 25, 1975 under 1QQ-EUP-43;
CDL:94879-A)
in im
Ciba-Geigy Corporation (1975g) Results o£ Dual 6E and Cycle 80W
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; CBL: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, Cual/PRE, Dual & Lorox, III.l - III.10; received
Jan 19, 1977 under 100-583; CDL:95738-E; 95757)
(R* (R)
Ciba-Geigy Corporation (1976c) IXial ' + Sencor Pre-emergence.
(Unpublished study that includes reports 1.1 - 1.78 with a summary, II.1 -
II.62 with a summary ana III.l - III.33 with a summary, and received Jan 19,
1977 under 100-583; CDL:95738-C:95744; 95765; 95756; 95769; 95741)
Ciba-Geigy Corporation (1976d) EMal^ 6E + Lorox^ Pre-emergence.
(Unpublished study that includes reports 1.1 - 11.27 with a sunmary, and
III.l - III.28 with a summary; received Jan 19, 1977 under 100-583;
CDL:95738-D; 95740; 95760; 95759; 95758)
( D \
Ciba-Geigy Corporation (1976e) Dial1, 6E Preemergence. (Unpublished study
that includes reports 1.1 - 1.139 with a sunmary, ll.l-II.94 with a summary,
and III.l - III.33 with a surcnary; received Jan 19, 1977 under 100-583;
CDL:95733-B; 95742; 95766; 95743; 95752; 95751; 95762; 95761)
(R)
Ciba-Geigy Corporation (1976f) Dial 6E Preplant Incorporated. (Unpublished
study that includes reports 1.1 - 1.40 with a summary, II.1-II.21 with a
summary and III.1-III.19 with a summary; received Jan 19, 1977 under
100-583; CDL:95738-A; 95755; 95754; 95753)
/ R\
Ciba-Geigy Corporation (1976g) Compatibility of Dual 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, 1.1 - 1.8, III.1-III.5; Dual/PRE, 1.1 -1.4,
III.l - III.5: received Jan 19, 1977 under 100-583; CDL:95738-F; 95746)
156
-------
Ciba-Geigy Corporation (19.76i) Rotational Crops.- (Unpublished study that
includes reports Dual/PRE, I. - 1.48 with a summary; DUAL/PP*• I.l -v 1.11
with a summary; Dual + Sencor/PRE, 1.1-1.9'with a sunmary; Cual + Lorox/PRE,
I.l, - 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 sunmary; 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 suirmary; 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 sunmary;
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 (1977i) Ciba-Geigy Rating System. (Unpublished study
received Nov 1-, 1977 under 100-583; CDL:232134-C)
(R) f R)
Ciba-Geigy Corporation (19'77j) EXial 6E + AAtrex—Preemergence.
(Unpublished study that includes reports 1-35 with a summary and 1C-32C with
a surrmary; received Feb 18, 1977 under 100-583; CDL:228101-C; 228114; 228115)
(R) (R)
Ciba-Geigy Corporation (1977k) Dual ; 6E + AAtrex —Preplant , .
Incorporated. (Unpublished study that includes reports 1-96 with a sunmary,
1C-32C with a«sunmary, and 1D-10D with sunmary;'received Feb 18, 1977 under
100-583; CDL:22810l-D; 228116; 228117; 228118; 228119; 228120)
Ciba-Geigy Corporation (19771) Dual 6E Alone —Preemergence. (Unpublished
study that includes reports 1-139 with a sunmary, 1C-70C with a sunmary, and
1D-12D with sunmary; received Feb 18, 1977 under 100-583; CDL;228101-A:
22S102; 228103; 228104; 228105;. 228106; 228107; 228108)
15 7
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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
sunmary, and 1D-HD with sunmary; received Feb 18, 1977 under 100-583;
CDL:228101-3; 228109; 228110; 228118; 228111; 228112; 228113)
(R) * R)
Ciba-Geigy Corporation (1977n) Dual 8E + AAtrexv + Paraquat or
Roundup. (Unpublished study containing reports 1-22 with a summary, 1C-27C
with a sunmary; received Nov 8, 1977 under 100-EUP-59; CDL:232194-D, 232200,
232201)
(R) (R)
Ciba-Geigy Corporation (1977o) Dual 8E + AAtrex Early Post.
(Unpublished study containing reports 1-47 with a sunmary, 1C-15C with a
summary; received Nov 8, 1977 under 100-EUP-59; CDL:232194-E, 232202, 2312203)
(R)
Ciba-Geigy Corporation (1977p) IXial 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) Dual 8E Alone. -(Unpublished study that
includes reports 1-32 with a sunmary; received Nov 14, 1977 under 100-EUP-
61; CDL:96624-A; 96618)
' R)
Ciba-Geigy Corporation (1977r) Dualv /Atrazine Prepack: Chemistry Data
Section. (Unpublished study; received June 20, 1977 under 100-590;
CDL:230686-A)
{R) (R)
Ciba-Geigy Corporation (1977s) Dual 8E + Banvel^ . (Unpublished study
containing reports 1-21, with a sunmary, 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 sunmary, 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) Dial + Lorox — Soybeans Preemergence: Phyto
Summary or i/13/77 Sufcmission. (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 urrier 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 10C-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)
/ D )
Ciba-Geigy Corporation (1977ab) Dual PRE Yield Questions. (Unpublished
study; received Nov 1, 1977 under 100-583; CDL;232134-1)
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. (1977a£) Dual ^ PPI Yields. (Unpublished study;
received Nov 1, 1977 under 100-583; CDL:232134-M)
Ciba-Geigy Corporation (1977ag) Dual PPI Yield Dkata. (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:232134-0)
Ciba-Geigy Corporation (1977ai) IXial + 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 Sunroary 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 1.00-583; CDL:232134-Z) ¦
Ciba-Geigy Corporation (1977am) Dual^ + Sencor^Yields. (Unpublished
study; received Nov 1, 1977 under 100-583; CDL:232134-Y)
(R) (R)
Ciba-Geigy Corporation (1977an) Dial + Sencor Yields. (Unpublished
study; received Nov 1, 1977 under 100-583; CDL:232134-M)
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 arid 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
Sunmary 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
Sunmary of 1/13/77. (Unpublished study; received Nov 1, 1977 under 100-
583; CDL:232134-L)
Ciba-Geigy Corporation ;i977as) 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 sumnary, 1C-12C with a sunmary, and ID -16D
with a sumnary; 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 sunmary, 'and 1D-
12D with a summary; received Jun 20, 1977 under 100-590; CDL:23Q672-B,
230678, 230679, 230680, 230681)
Ciba-Geigy Corporation (1977ayj Response to EPA Comments,Concerning Marginal
Soybean. [tolerance to DaaV PPI or PRE, Dual + Lorox 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 3, 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 sumnary, 1-39 with a summary; received Feb 18,
1977 under 100-583; CDL:22S101-^; 228123; 223124)
* 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 Cbws: Methods.
(Unpublished study; received Sep 26, 1974 under 5G1553; CDL:94216-G)
16 0
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Ciba-Geigy Limited (1973?) 'CGA 24 705 Feeding Study in Milk Cows: Methods.
• (Unpublished study prepared by Ciba-Geigy Ltd.; St. Aubin, Switzerland;
received ttov 14, 1977 under 8G2019; CDL:96626-<)
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 jnder 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.
(Unpuolished study including Addendum; received Jan 13, 1978 under 7F1913;
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. (Unpublished study
including Addendum; received Jan 13, 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.j Guyot, D.; Fouillet, X.; Rouaud, J.L. (1974a) Essai de
Toxici'te de 3 Mois chez Le Chien par Voie Orale du Produit CGA 24 705.
[Three-Month Oral Toxicity Trial of CGA 24 705 in DogJ: IC-DREB-R-74Q1~9.
(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, 3.; Galland L.; Guyot, D.; Fouillet, X.; Rouaud, J.L. (1974b) Essai de
Toxicite de 3 Mois chez Le Rat par Voie Craie 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 Prcduit 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, U.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)
16 1
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* Counselinanj.C.J.; Roger, J.C. (1973) Biological Report, Goat Metabolism Study
with jzS- C-CGA-24705 ana jtr- C-CGA-17020. (Unpublished study
received Nov 25, 1975 under 6G1708; prepared by Ciba-Geigy Corp.,
Greensboro, N.C.; CDL:94984-K)
Cullen, T.; Balu, K. (1973) Determination of CGA-18762 Residues in Corn Forage,
Scover, and Grain by Microcouianetric Gas Chromatography. Method AG-249
dated Jun 20, ^.973. (Unpublished study received Nov 6, 1975 under 4G1469;
prepared by Ciba-Geigy Corp., Ardsley, N.Y.; CDL:95190-B)
Davis, T.W. (1976) Report to Ciba-Geigy Corporation: Eye Irritatioin Ttest with
CGA-24705 + Atrazine (2.5:2.0) 4.5L:IBT No. 601-08061. (Unpublished study
received Jun 20, 1977 under 100-590; prepared by Industrial Bio-Test
Laboratories, Inc. for Ciba-Geigy Corp.; Greensboro, N.C.; CDL:230687-A)
Derot, P. (1976) Desherbage du maise: L' association metetlilachlor +
atrazine.[Weed control in maize: A mixture of metetilachlor (CGA24705) and
atrazine] La Defense des Vegetaux 30(177): 39-48.
Dest, W.M.; Peters, R.A., Barrett, M. (1976) The control of crabgrass and
redroot pigweed in the silage corn. Pages 55-58, In Proceedings of the
Thirtieth Annual Meeting of the Northeastern Weed Science. Society; Jan 6-8,
1976, Boston, Massachusettes. Salisbury, Md.: University of Maryland,
Vegetable Research Farra:
Dietz, W.P.; Jennings, V.M. (1976) 1975 No-till corn herbicide results in
northeast Iowa. Pages 151-152, 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:
Diner, A.M.; Davis, D.E.; Tryelove, B. (1977) Absorption and translocation of
root and foliar-applied C-metolachlor in soybean: Abstract. Pages - ,
In Proceedings of the Thirtieth Meeting of the Southern 'Weed Science
Society; Jan 19-21, 1977, Dallas, Texas. Raleigh, N.C.: Glover Printing
for the Southern Weed Science Society.
* Dicnne, E- (1973).. Chronic Toxicity c€ CGA-24705 to the-Fathead. Minnow
(Pimephales prone las); received 12-13-78 under 100-587, (Prepared •
by EJG&G Bionomics for Ciba-Geigy- Corporationf Greensboro,-
CX: 236620)
Donald A. Willigan, Incorporated (1975) Supplementary Report to Contract No.:
120-2255-34: Histopathological Evaluation: Twenty-One day Repeated Dermal
Toxicity of CGA 24705-6E in Rabbits. (Unpublished study received Mar 26,
1975 under 5F1606; prepared by Affiliated Medical Research, Inc., Princeton,
N.J. for Ciba-Geigy Corp., Greensboro, N.C.; CDL:94377-A)
* Draize, J.H. (1959) The Appraisal of Chemicals in Food, Drugs, and Cosmetics.
Austin, Texas: Association of Food and Drug Officials of the United States.
Dreier, H. (1977) Report to,Ciba-Geigy Corporation: Acute Aerosal Inhalation
Toxicity Study with Dual 8E (FL-770350) in Albino Rats: IBT 8562-10823.
(Unpublished study received Nov. 8, 1977 under 100-EUF-059; prepared by
Industrial Bio-Test laboratories, Inc. for Ciba-Geigy Corp., Greensboro,
N.C., including Addendum C — Validation by Ciba-Geigy Corp.; CDL:232191-C)
16 2
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1 d
Dupre, G.D. (1974a) Abbreviated Anaerobic Metabolism of C-CGA-24705 in •
Slit 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)
14
Dupre, G.D. (1974b) Leaching Characteristics of C-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)
14
Dupre, G.D. (1974c) Runoff Characteristics of C-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, N.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 Estijuating
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 ReporUJProject Report 32/77: Uptake, Transfer
and Degradation of CGA 24705 (Dualv ) by Pquatic Organisms. AC 2.52.
(Unpublished study received Feb 6, 1978 under 100-583; prepared by Ciba
Geigy Ltd., Basle, Switzerland; CDL:232739-C)
Environmental Protection Agency (1977) 2-Chloro-N-(2-ethyl-6-methylphenyl)-N-(2-
methoxy-l-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 Actinanycetes, 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.; Valleno, R.P.; Bogus, E.R. (1978) The Effects of 5, 25, and
125 PFM of Metolachlor, [2-Chloro-N-(2-ethyl-6-methylphenyl)-M-(2-methoxy-l-
methylethyl) acetamide], on Soil nitrification. E-3/2-CG78. (Unpublished
study received ?eD 6, 1978 under 100-583; prepared by Pesticide Research
Lab., Pennsylvania State University for Ciba-Geigy Corp., Greensboro, H.C.;
CDL:232789-G)
16 3
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Eschiapati, D.; Eachler, C. (1976) Metetilachlor + Atrazine, a new herbicide
for corn crops. Resuroos XI Seminario Brasileiro de Herbicidas e Ervas
Daninhas, Londnna, 1976: 44-45.'
Fink, R. (1974a) Eight-Day Dietary I£5Cj—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-O)
Fink, R. (1974b) Eight-Day Dietary LC.Q—Bobwhite Quail Technical CGA-24705:
Project tto. 108-111. (UnpublishedDstudy 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)
Flnky (1978a) .. Ore-Generation: Reproduction Study - Bobwhite- Quail
CQV.-Z4750. technical Final Report; received 12-12-78 under 100-587,
(Unpublished, report, prepared, by Wildlife International Ltd- for Ciba-Geigy
Corp.,. Greensboro,. N.C.r CDL:23662Q)
Einlcr R- (1978b). cue-Generation Reproduction Study — Mallard DucJc
CGk-24705 technical Final Report? received 12.-13-78' under 100-587",
(Unpublished. ' ' prepared, by Wildlife International Ltd- for Ciba-^jeigy
Corp.^ Greensboror N.C.; COLi236620}
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,
Mimeograph Series, 240)
Fritz, H. (1976) Reproduction Study CGA 24705 Tech. Rat: Seg. II: (Test for
Teratogenic or Qnbryotaxic Effects): FH 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, ikges 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)
1 6.4
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Gfeller,.. VJ. (1974) Tolerability Trial in Milk Cows with CGA 24 705: 14, 21 and
28 day Feeding Study: AC 9.26;' T73/23. (Unpuolished 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 Chromatographic 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-
Y)
Gross, D. (1974a) Project Report Ito. 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 Ilo..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-<5eigy Ltd., Basle,' Switzerland; CDL:94378-H)
Guth, J.A. (1974) CGA 24705: Dotal' 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 Metaraitron 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: Mdendum to Project Report' 7/74:
• Metabolism of CGA 24 705 in'the Rat: AC 2.52; (Unpublished study received
Nov 25, 1975 under 6G17G8; prepared by Ciba-Geigy Ltd., Basle, Switzerland;
CDL:94984-P)
Hambock, H. (1974c) 'Project Report Ito. 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 ito. 601-07539. (Unpublished study received
Dec 29, 1975 under 1Q0-EUP-45; prepared by Industrial'Bio-Test Laboratories,
Inc., For Ciba-Geigy Corp., Greensboro, N.C.; CDL:224074-B; 231913)'
1 6 5
-------
Harvey, R.G.; Baker, C.R. (1974?) Annual Weed Control in Com 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)
Hemrichs, L. (1975) Determination of CGA-247Q5 and Procyazme in GA-2-686 15G
by Gas Chromatography: Method PA-71 T dated Oct 9, 1975. (Unpublished
study received Feb 9, 1976 under 1Q0-EUP-44; prepared by Ciba-Geigy Corp.,
Greensboro, N.C.; CDL:96496-A)
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 1QQ-EUP-61; prepared by Ciba-Geigy Corp.,
Greensboro, N.C.; CDL:96623-A)
* Helseth, J.; Cole, G. (1973) The Determination of CGA-24705 in Bnulsifiable
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, ?, (1970) Extraction of Radioactive Metabolites frcm 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:9438Q-A) ...
* Hermes, P. (1972) Biphasic Extraction of Radioactive Metabolites frcm 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;t24705 plus atrazine
yellow nutsedge control in corn. Pages 65-70, 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.
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)
16 6
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Hogenbocm, P.W. (1976) Metetilachlor - a new grass herbicide, ftesumas XI
.Semmario Brasileir de Herbicidas e Eruas Daininhas, Londrina, 1976: 127-
128.'
Hollicay, 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 3i'o-Test Laboratories, Inc., for Ciba-Geigy
Corp., Greensboro, H.C.; CDL:224074-C)
Hormann, W.D.; Guth, J.A.; Formica, G.,- Schenker, M. (1974) CGA 24705: Gas
Chromatographic Determination of Ttital 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-£)
Houseworth, L.D. (1977) Residues of Metolachlor and Atrazine in or on Corn
Grain Resulting frcm 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 sunmary ABR-77028; received Jun 20, 1977
under 100-590; prepared by Ciba-Geigy. ¦ Corp.; Greensboro, N.C.; CDL:23Q685-A)
Houseworth, L.D. (1977) Residues of Metolachlor and Dicamba in or on Corn Gram
Resulting frcm 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 fran 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.; GDL:95767-A)
Houseworth, L.D.; Rolla, H. (1977a) Residues of Metolachlor and Atrazine in or
on Com 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)
16 7
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Houseworth, L.D.; Rolla, H. (1977b) Residues 'of'Metolachlor in or on Sorghum
Resulting fran 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 8G2C19; prepared by Ciba-
Geigy Corp., Greensooro, N.C.; CDL:96625, 96626-A, 96626-B, 96626-C, 96626-D)
Iggo, G.A. (1.975} Results of screening preemergence heroic ides for sugarcane.
Pages 11-14, In 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(?L-751873) in Albino Rats: IBT.Ho. 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) Canparison of acid aralid herbicides for canning
pea .weed control. Page 30, In Proceedings of . the North' Central Weed ¦
Control Conference; December-5-11, 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 Pius 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-rl)
14
Kaiser, F. (1974) Soil Degradation Study of Ciba-Geigy C-CGA-24705.
(Unpublished study received Mar 27, 1975 under 5F1606; prepared by
Analytical Biochemistry I^boritories, Inc., Submitted by Ciba-Geigy Corp.,
Greensboro, N.C.; CDL: 94376-A)
168
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Karlhuber, B.; Ramsteiner, K. (1973) CGA 247C5: Gas Chromatographic Residue
Determination in Plant Material,. Grains and Soil.. (Provisional): AG 2.53;
REM 2/73. (Unpublished study, rece-ived 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., Greensooro, N.C.; CDL-232855-3)
* Kennedy, G.L. (1976a) Letter [dated Dec 10, 197.6, 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)j 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:95_768-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 Roiofson. (Unpublished study received Jan 19, 1977 under 7F1913;
prepared by Industrial Bio-Test Laboratories, Inc., for Ciba-Geigy Corp.,
Greensboro, N.C.; CDL:9576S-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. Qnaha, Neb.; by the
Stauffer Chemical Company for the North Central Weed Control Conference.
Lazzara, K.; Paa, H. (1975) Report to Ciba-Geigy Corporation: Acute Decimal
Toxicity Study with 1:4 Aqueous Suspension of CGA-24705 + Atrazme (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 Ccmpatabilities Test Report for CGA-24705-
6E, GA-2-621,¦with other Herbicides]: AG Request -to. 4349. (Unpublished
study received Mar 26, 1975 under 5F1606; prepared by Ciba-Geigy Corp.,
Greensboro, N.C.; CDL:94384-A)
Lorenzi, H.J. (1976j). Herbicide tests on corn crops. Resumes XI Serainario
Brasileiro de Herbicidas e Eruas Daninhas, Londrina, 1976: 38:39
Maher, J.; 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:23G686-B)
* Marco, G. (1974) Surrmary of Section D: CGA-24705-Com: 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:942i7-A; 94222)
* Marco, G. (1975) Summary 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)
Mattscn, 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-B)
* 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 Itov 8, 1977 under 100-EUP-59; prepared by Ciba-Geigy Gorp.,
Greensboro, N.C.; CDL:232193-H)
Mattson, A.M.; Xahrs, 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 Nov 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 Reside Data CGA-24705-r^trazine
Canbinations as Com Herbicides TanK Mixes-Dual ' 6EC Plus AAtrex1, SOW
or AAtrex 4L Flowable Combination Formulation-GA-2-6-622 4.5L
Preemergence and Preplant Incorporated Applications: GAAC-75081.
(Unpublished study including reports PG-A-2974; AG-A-3057; AG-A-3070; AG-A-
3288; AG-A-3298; AG-A-3325; AG-A-3326; AG-iV-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.; Holla, 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 6G17Q8; prepared
by Ciba-Geigy Corp., Greensboro, N.C. CDL:94984-A; 94878)
Mattson, A.M.; Kahrs, R.A.; Schneller, J. (1965) Use of Microcoulametric gas
chrcmatograph 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 7il-76, In Proceedings of the
Thirtieth Annual Meeting of the Northeastern Ifeed 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 seme new herbicides used alone and in combination with
atrazine or alachlor. Pages 46-47, In Proceedings of the Northeastern Weed
Science Society.
171
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MichieKa, R.W.: Iinicki, R.D.: Sanody, J. (1977). Weed control in potatoes
with prep 1 ant. Incorporated herbicides applied alone, in ccmbination, and
with follow-up preemergence herbicides. Pages 197-198 _ln Proceedings of the
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 100-533; prepared by Ciba-Geigy Corp., Greensboro, 1J.C.;
CDL:95763-B)
Miyazaki, S. Kahrs; R.A. (1974) Specificity of the Residue Determination of
CGA-24705 Metabolic Residues m 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 ccmbination 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 Dual 8E in Albino Rats: IBT No. 8530-10822.
(Unpublished study received ttov 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)
" i~
Nham, Dan; Harrison, W.A. (1977b) Report to Ciba-Geigy Corporation: Acute
Dermal Toxicity Study with Dual 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)
Noll, C.J.(1976). Chemical weed control on snap beans. Pages 202-204, In
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Norton, J.A. (1978) Letter Sent to George LaRocca data Aug 28, 1978. Dual 8E
Herbicide iRequest for Acceptance of Finished Labeling to Allow Use on Corn
Grown for Grain, Excluding Popcorn.) Received May 1978 under 100-597.
(Submitted by Ciba-Geigy Corp., Greensboro, N.C.)
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
Generic Standard] to Mr. Henry M. Jacoby, dated Feb 21, 1978. (Unpublished
172
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letter fran the files of the Office of Pesticide Programs, Technical
Services Division. Received Feb 22, 1978 under 100-583 prepared by-Ciba-
Geigy Corp., Greensboro, N.C; CDL:232898)
Norton, J.A. (1977) Letter sent to Henry Jacoby dated My 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 ooth
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 fiie in Generic Standards Branch, OPP)
Norton, J.A. (1978) Letter sent to Henry Jacooy 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 - Binctnial Nomenclature - Channel Catfish.] Received Feb 27,
1978 under 100-583. (Sucunitted 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 Binanial
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)
* Cncins Research and Breeding Center (1974) Three-Month Dietary Feeding Study in
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17 3
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14
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14
* Roger, J.C.; Cassidy, J.E. (1974a) Metabolism and Balance Study of 0- C-
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14
* Roger, J.C.; Cassidy, J.E. (1974b) Metabolism and Balance Study of 0- C-
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14
Roger, J.C. (1973?) Radioassay of C 0~ by Acid Neutralization and
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14
Roger, Counselman, C.J. (1973) Goat Metabolism Study with C-CGA-24705
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14
Roger, J.C.; Counselman, C.J. (1973) Goat Metabolism Study with C-CGA-
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Sachsse, K. (1973b) Skin Irritation in the Rabbit after Single Application of
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Sachsse, K.; Uliman, L. (1974b) Acute Toxicity to Rainrow Trout, Crucian Carp,
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17 6
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* Schenker, M. (1975a) CGA 24705: Determination of the Degradation Product CGA
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17 7
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14
Simoneaux, B. (1972b) Measurement of Total Organic C in soils by -
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1 7 8
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Sumner, D.D. (1978a) Audit Report Dated Nov 21-, 1975: 28-Day Mouse Pilot Study
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14
Sumner D.D.Cassidy, J.E. (1974a) A Comparison of £ C-CGA-24705 Corn , .
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14
Sumner, D.D.; -Cassidy, J.E. (1974c) The Uptake and Distrioution of # C-
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Sumner, D.D.; Cassidy, J.E. (1974d) The Uptaice and Distribution of jzJ-14C-
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26, 1975 under 5F1606; prepared by Ciba-Geigy Corp., Greensboro, N.C.;
CDL:94385-C) .
¦ 14
Sumner, D.D.; Cassidy, J.E. (1974e) The Uptake of 0- C-CGA-24705 and Its
Aged Soil Degradation Products in Rotation Carrots: GAAC-74112.
(Unpublished study received Mar 26, 1975 under 5F1606; prepared by Ciba-
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14
Sumner, D.D.; Cassidy, J.E. (1974f) The Uptake of C-CGA-247C5 and Its
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' 14
Sumner, D.D.; Cassidy, J.E. (1974g) The Uptake of
-------
Sumner, D.D.; Cassidy, J.E. (1974h) The Uptake of C-CGA-24705 and Its
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(Unpublished study received Mar 26, 1975 under 5F1606; prepared by Ciba-
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Sumner- D.D.; Cassidy J.E. (1974i) Uptake of Nonextractable Soil Metabolites o£
0- C-CGA-24705 by Carrots: GAAC-74057. .(Unpuolished study received
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Sumner, D.D.; Cassidy J.E. (1974]) Uptake of Nonextractable Soil Metabolites of
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Sumner. D.D.; Cassidy J.E. (1974k) Uptake of Nonextractable Soil Metabolites of
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14
Sumner, D.D.; Cassidy, J.E. (1975b) The Uptake and Distribution of 0- C-
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(Unpublished study received Nov 26, 1975 under 6G1708; prepared by Ciba-
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18 0
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Truslow Farms Incorporated (1974b) Eight-Day Dietary LC,-n—Mallard Ducks
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14
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> FSTNTINS OF?lCE: _9HC 3«J2 -085 /
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