Unhad Stttw
Environmental Protactlon
Agancy.
Off ioi of
Pacticida* and Toxic Subattneai
WMMngton DC 20460
March 1982
PMtieidw
MCPA
(4-chloro-2-
methylphenoxyacetic acid)
Pesticide Registration
Standard
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MCPA and its Salts and Esters
Pesticide Registration Standard
Support Team
Denise M. Keehner Project Manaqer (SPRD)
Anthony B. Hall Project Manager (SPRD)
Paul N. Parsons Project Manager (SPRD)
Stephanie April Toxicologist (HED)
George Beusch Chemist (HED)
Ray Rent Chemist (HED)
John Jordan Microbiologist (HED)
Mike Rexrode Fishery Biologist (HED)
Steve Hopkins Plant Physiologist (HED)
Al Vaughn Entomologist (HED)
Bruce Sidwell Plant Physiologist (BFSD)
Roger Hoitorf Economist (BFSD)
Richard Mountfort Product Manager (RD)
March, 1982
Office of Pesticides and Toxic Substances
Environmental Protection Agency
401 M Street, S.W.
Washington, D.C. 21460
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TABLE OF CONTENTS
Chapter One Page Number
How to Register Under a Registration Standard 1
Organization of the Standard 1
Purpose of the Standard ' 1
Requirement to Re-register Under the Standard 3
"Product Specific" Data and "Generic" Data 3
Data Compensation Requirements under FIFRA 3(c)(l)(D) 5
Obtaining Data to Fill "Data Gaps" 6
Amendments to the Standard 7
Chapter Two
Agency Position on MCPA
Introduction 9
Description of Chemical 9
Regulatory^Position 9
Regulatory Rationale 10
Dietary Risk 11
Applicator Exposure 12
Test Substances for Required Testing 13
Potential for Nitrosomine Contamination 13
Potential for Dioxin Contamination 13
Criteria for Registration Under the Standard 14
Manufacturing-Use MCPA 14
Acceptable Ranges and limits 14
Product Composition Standard 14
Acute Toxicity Limits 14
Use Patterns IS
Required Labeling 15
End-Use Products 16
Acceptable Ranges and Limits 16
Product Composition Standard 16
Acute Toxicity Limits 16
Use Patterns and Application Methods 17
Additional Uses 17
Required Labeling 17
Chapter Three
Data Requirements and Data Gaps 19
Manufacturing-Use MCPA 19
Generic Data Requirements 19
Product Specific Data Requirements:
Manufacturing the MZPA 20
. End-Use MCPA Products 21
Product Speciic Data Requirements for
End-Use Products 21
Chapter Four
Product Chemistry of MCPA 35
Introduction
Manufacturing-Use MCPA
Product Chemistry Profile
Topical Discussions
Chemical Identify
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Manufacturing Process 3?
Discussion of the Formation of 37
Unintentional Ingredients
Declaration and Certification of 3t
Ingredient Limits
Product Analytical Methods and Data ^
Physical and Chemical Properties yg
Sunroary of Major Data Gaps *1
Labeling Requirements - 3<\
End-Use MCPA V°
Product Chemistry Profile ^°
Topical Discussions
Chemical Identiy V°
Active Ingredients in Pesticide Products H°
Product Analytical Methods and Data V(
Physical and Chemical Properties f
Labeling Requirements *||'
' *
Chapter Five
Environmental Fate of M2PA
Introduction VJ
Use Profile V*
Environmental Fate Profile VI
Exposure Profile &
Topical Discussions
Physico-Chemical Degradation *°
Metabolism '°
Mobility 5A
Groundwater Contamination SA
Dissipation *>}
Label Restrictions $1
Chapter Six
Toxicology of MCPA
Introduction 5y
Manufacturing-Use MCPA J'f
Toxicology Profile 5^
Acute Toxicity 54
Acute Delayed Neurotoxicity 5H
Subchronic Testing 5M
Teratogenicity and Mutagenicty Testing 5f
Reproduction Tf
Metabolism '&
Topical Discussions 55"
Acuate Oral Toxicity &
Acute Dermal Toxicity 5V
Acute Inhalation Toxicity "&
Primary Eye Irritation ST.
Primary Dermal Irritation Sk
Dermal Sensitization *>!»
Acute Delayed Neurotoxicity &
Subchronic Inhalation Toxicity S^
Subchronic Neurotoxicity fco
Chronic Feeding (*>o
Oncogenicity to
Teratogenicity t|
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Reproduction W
Mutagenicity ^
Metabolism (6
Human Exposure
Butyl and Isopropyl Ester Mixtures &
Chapter Seven ^
Residue Chemistry of MCPA
Residue Chemistry Profile TO
Data Requirements and Data Gaps 7o
Topical Discussion 7<
Uptake, Distribution, and Metabolism
in Plants 71
Metabolism in food-Producing Animals 7^
Analytical Methods 7^
Residues in Plants 13
Residues in Food-Producing Animals 7?
Other Sites
Effects on Estuarine and Marine Organisms 11
Effects on Freshwater Aquatic Invertebrates 11
Effects on Beneficial Insects I"6
Chapter Nine
Case Bibliography . .
Guide to Use of Bibliography m
Section I
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Chapter I
HOW TO REGISTER
UNDER A REGISTRAT1CN STANDARD
Organization of the Standard
Purpose of tne Standard
Requirement to Re-register Under tne Standard
"Product Specific" Data and "Generic" Data
Delta Compensation Requirements under FIFRA 3(c)(l)(D)
Obtaining Data to FiU "Data Gaps;" FIFRA 3(c)(2)(B)
Amendments to the Standard
Organization of the Standard
Tnis first cnapter 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 tne
available data by scientific discipline, discusses the Agency's concerns with
tne 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 Federal Insecticide, Fungicide, 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 tne Administrator [of EPA)." To approve tne registration
of a pesticide, the Administrator must find, pursuant to Section 3(c)(5) tnat:
"(A) its composition is such as to warrant the proposed claims for
it;
(B) its labeling and other material required to be submitted comply
with the requirements of this Act;
(C) it will perform its intended function without unreasonable
adverse effects on the environment; and
(D) wnen 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 tne risks and benefits
cissociated with the use of the proposed pesticide. But the established
approacn to making these findings has been found to be defective on two counts:
First, EPA and its predecessor agency, the United States Department of
Agriculture (USDA), routinely reviewed registration applications on a 'product-
by-product1 basis, evaluating each product-specific application somewhat
independently. In the review of products containing similar components, there
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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' approacn was often inefficient and sometimes resulted
in inconsistent or incomplete regulatory judgements.
Second, over the years, as a result of inevitable and continuing advances in
scientific knowledge, methodology, and policy, the data base for nany
pesticides came to be considered inadequate- by current scientific and
regulatory standards. Given the long history of pesticide regulation in
several agencies, it is even likely that materials may have been lost from the
data files. When EPA issued new requirements for registration in 1975 (40 CFR
162) and proposed new guidelines for hazard testing in 1978 (43 FR 29686, July
10, 1978 and 43 FR 37336, August 2, 1978), many products that had already been
registered for years were being sold and used without the same assurances of
human and environmental safety as was being required for new products. Because
of this inconsistency, Congress directed EPA to re-register all previously
registered products, so as to bring their registrations and their data bases
into conpliance with current requirements [See FIFRA Section 3(g)].
• *
Facing the enormous job of re-reviewing and oalling-in new data for the
approximately 35,000 current registrations, and realizing the inefficiencies
of the 'product-by-product' approach, the Agency decided that a new, more
effective method of review was needed.
A new review procedure has been developed. Under it, EPA publishes documents
called Registration Standards, each of which discusses a particular pesticide
active ingredient. Each Registration Standard summarizes all the data avail-
able to the Agency on a particular active ingredient and its current uses, and
sets forth the Agency's comprehensive position on the conditions and require-
ments for registration of all existing and future products which contain that
active ingredient. These conditions and requirements, all of which must be
met to obtain or retain full registration or re-registration under Section
3(c)(5) of FIFRA, include tne submission of needed scientific data which the
Agency does not now have, compliance with standards of toxicity, composition,
labeling, and packaging, and satisfaction of the data compensation provisions
of FIFRA Section 3(c)(l)(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)J. A pesticide is
classified for "restricted use" when seme special regulatory restriction is
needed to ensure against unreasonable adverse effects to man or the
environment. Many such risks of unreasonable adverse effects can be lessened
if expressly-designed label precautions are strictly followed. Thus the
special regulatory restriction for a "restricted use" pesticide is usually a
requirement that it be applied only by, or under the supervision of, an
applicator who has been certified by the State or Federal government as being
competent to use pesticides safely, responsibly, and in accordance with label
directions. A restricted-use pesticide can have other regulatory restrictions
[40 CFR 162.11(c)(5)] instead of, or in addition to, the certified
applicator requirement. These other regulatory restrictions may include such
actions as seasonal or regional limitations on use, or a requirement for the
monitoring of residue levels after use. A pesticide classified for "general
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use," or not classified at all, is available for use by any individual who is
in compliance with Stste or local regulations. The Registration Standard
review cmpares information about potential adverse effects of specific uses
oi: tne pesticides witn risk criteria listed in 40 CFR 162.11(c), and tnereby
determines vnether a product needs to he classified for "restricted use." If
tne Standard does classify a pesticide for "restricted use," this
determination is stated in the second chapter.
Requirement ^o Re-register Under tne 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 tnat 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-registration. His application must contain
proposed labeling that complies with this Standard.
EPA will issue a notice of intent to cancel the registration of any currently
registered product to which this Standard applies if the registrant
fails to comply with tne procedures for re-registration set forth in the
Guidance Package which accompanies this Standard.
"Product Specific" Data andj"Generic" Data
In the course of developing th is"Standard yEPA"has~rteterm it ial lhe--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,
Ehvironmental Fate, Ibxicology, Residue Chemistry, and Ecological Effects.
These determinations are based primarily on the data Guidelines proposed in
1978 (43 FR 29686, July 10,, 1978, and 43 FR 37336, August 2, 1978), as applied
to the use patterns of the products to which this Standard applies. Where it
appeared that data from a normally applicable Guidelines requirement was
actually unnecessary to evaluate these products, the Standard indicates that
tne requirement has been waived. On the other hand, in some cases studies not
required by the Guidelines may be needed because of the particular composition
or use pattern of products the Standard covers; if so, the Standard explains
the Agency's reasoning. Data guidelines have not yet been proposed for the
Residue Chemistry discipline but the requirements for such data have been in
effect for seme tine and are, the Agency believes, relatively familiar to
registrants. Data which we;have found are needed to evaluate tne registra-
bility of sere 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 tne second
chapter.) The various kinds of data normally required for registration of a
pesticide product can be divided into two basic groups:
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(A) data that is "product specific," i.e., data tnat relates only to tne
properties or effects of a product with a particular ccmposition (or
a group of products with closely similar composition); and
(B) "generic" data that pertains to the properties or effects of a
particular ingredient, and thus is'relevant to an evaluation of 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 (wnich is a function of its total composition). The applicant for
registration or re-registraton of any product, whether it is a manufacturing-
use or end-use product, and without regard to its intended use pattern, must
submit or cite enough'JctL 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. j
All other data needed to evaluate pesticide products coneerns-^tne-properties
or effects of a particular ingredient of products (normally a pesticidally
active ingredient, but in seme cases a pesticidally inactive, "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 ID-50 of the active ingredient in its technical or purer grade; see
proposed 40 CFR 163.81-1(a); 43 FR 37355].
Other "generic" data are required to evaluate all products which both contain
a particular ingredient and are intended for certain uses (see, e.g., proposed
40 CFR 163.82-1, 43 FR 37363, which requires subchronic oral testing of the
active ingredient with respect to certain use patterns only). Where a par-
ticular data requirement is use-pattern dependent, it win apply to each end-
use product which is to be labeled for that use pattern (except where such
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 per-
mitting such formulations) and to each manufacturing-use product with labeling
that allows it to be used to make end-use products with that use pattern.
Thus, for example, a subchronic oral dosing study is needed to evaluate the
safety of any manufacturing-use product that legally could be used to make an
end-use, food-crop pesticide. But if an end-use product's label specified it
was for use only in ways that involved no food/feed exposure and no repeated
human exposure, the subchronic oral dosing study would not be required to
evaluate the product's safety; and if a manufacturing-use product's label
states that the product is for use only in making end-use products not
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involving food/feed use or repeated human exposure, the subchronic oral study
would not be reievcint to tne evaluation of tne manufacturing-use product
either.
If .-». registrant of a currently registered manufacturing-use or end-use product
wisr.es to avoid the costs of data compensation [under FIFRA Section
3(c)(l)(D)] or data generation [under Section 3(c)(2)(B)] for "generic" data
that is required only with respect to seme use patterns, he may elect to
Delete those use patterns from his labeling at the time he re-registers his
product. An applicant for registration of a new product under this Standard
may similarly request approval of only certain use patterns.
p£ta_ Compensation Requirements under FIFRA 3(c) (I) (ID)
Under FIFRA Section 3(c)(l)(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) tne data were first submitted to EPA (or to its predecessor agencies,
USDA or FDA), on or after January 1, 1970;
(2) the data were submitted to EPA (or USDA or FDA) by some other
applicant or registrant in support of an application for an
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 tne 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) frcm the duty to offer to pay compensation.
(This exemption applies to the "generic" data concerning the safety
of an active ingredient of the applicant's product, not to "product
specific" data. The exemption is available only to applicants whose
product is labeled for end-uses for which the active ingredient in
question is present in the applicant's product because of his use of
another registered product containing that active ingredient which he
purcnases from anotner producer.)
An applicant for re-registration of an already registered product under this
Standard, or for registration of a new product under this Standard, accord-
ingly must determine wnich of the data used by EPA in developing the Standard
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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)(l)(D).
An applicant would never be required to offer to pay for "product-specific"
data submitted by another firm. In many, if not in most cases, data which are
specific to another firm's product will not suffice to allow EPA to evaluate
the applicant's product, that is, will not be useful to the Agency in
determining whether the applicant's product is registrable. There may be
cases, however, where because of close similarities between the composition of
two or more products, another firm's data may suffice to allow EPA to evaluate
scne 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 frcm tests en his own product, and if he chooses that option, he would
have to comply with the offer-to-pay requirements of Section 3(c)(l)(D) for
that data.
Each applicant for registration or re-registration of a manufacturing-use
product, and each applicant for registration or re-registration of an end-use
product, who is not exempted by FIFRA Section 3(c)(2){D), must comply with the
Section 3(c)(l)(D) requirements with respect to each item of "generic" data
that relates to his product's intended uses.
A detailed description of the procedures an applicant must follow in applying
for re-registration (or new registration) under this Standard is found in the
Guidance Package for this Standard.
Obtaining Data to Fill "Data 'Gaps^rFIFRA- 3(c)T2) (B)
Some of the kinds of data EPA needs for its evaluation of the properties and
effects of products to which this Standard applies have never been submitted
to the Agency (or, if submitted, have been found to have deficiencies
rendering them inadequate for making registrability decisions) and have not
been located in the published literature search that EPA conducted as part of
preparing this Standard. Such instances of missing but required data are
referred to in the Standard as "data gaps."
FIFRA Section 3(c)(2)(B), added to FIFRA by the Congress in 1978, authorizes
EPA to require registrants to whom a data requirement applies to generate (or
otnerwise produce) data to fill such "gaps" and submit those data to EPA. EPA
must 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 whereby
two or more "registrants may agree to share in the costs of producing data for
wnich tney are both responsible.
The Standard lists, in its summary second chapter, the "generic" data gaps and
notes the classes of products to which these data gaps pertain. The Standard
also points out that to be registrable under the Standard, a product must be
supported by certain required "product specific" data. In seme cases, the
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Agency nay possess sufficient "product specific" data en one currently
r
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Unile 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 sore inert ingredients and impurities.
Independent of the development of any one Standard, the flgeney has initiated
the evaluation of sate inert ingredients of concern in a specific product to
which the Standard applies, these ingredients will be pointed out in the
Guidance Package.
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C; j-.PTER II
TiGH'C"-' ^SITIOI' Gi '1CPA
Introduction
This chapter describes in detail the Agency's regulatory position on products
that contain MCPA as the sole active ingredient. The regulatory position
adopted by the Agency incorporates a number of considerations. Forenost anong
these considerations is an analysis of the registrability of products
containing MCPA based on tne risk criteria found in Section 162.11(a) of Title
40 of the U.S. Code of Federal Regulations. The Agency's determination and
tne rationale for its determination are presented below.
In addition to tnis decision, standards of product composition, acute
toxicity, and use are established. The rationale for establishing a
particular standard follows the presentation of the standard. Regulatory
actions such as requiring protective clothing during application are
prescribed, and any additional data to support the registrations are
requested. Tne basis for any regulatory action can be found by first reading
the rationale for the action, which follovs the chosen option. Further
information, on tne scientific basis for an action, can be found by reading
tr>e various chapters that surmrize available scientific data on the safety of
MCPA.
Description o£ Chcrical
MCPA is tne common nane for t1"1? rrv^rucsl 4-cnloro-2-methylnnenoxyacetic acid.
MCPA is a pnenoxy herbicide registered for use in a variety of crop and
ncncrop sites to control a vide spectrun of broadleaf weeds. It is
principally used in wheat, rice, and other small grains. The Chemical
Abstracts Registry (CAS) number for MCPA is 94-74-6, and the EPA Shaugnnessy
Code is 030501.
Currently registered manufacturing-use products include MCPA acid, the
dimethylamine salt of MCPA, the butoxyethyl ester, the butyl ester, the
isooctyl ester, and a mixture product containing the isobutyl, isopropyl, and
butyl esters.
P
MCPA formulated products are marketed under the trade names Mephanac ,
Nethoxone , Agroxone , MCF , and VJeedar , to name a few. These
products are available as soluble concentrates and emulsifiable concentrates,
and they contain nany different forms of MCPA (tne sodium salt, the
dietnanolamine salt, the dimethylamine salt, the isooctyl ester, the
butoxyetnyl ester, and a mixture of butyl and isopropyl esters).
Regulatory Position
MCPA (4-cnloro-2-methylphenoxyacetic acid), MCPA sodium salt, tne
dimethylamine salt of MCPA, the diethanolamine salt of MCPA, the isooctyl
ester of MCPA, the butoxyetnyl ester of MCPA, the butyl ester of MCPA, tne
mixture of butyl and isopropyl esters of MCPA, and the mixture of isobutyl,
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isopropyl, and butyl esters of MCPA as described in this Standard, nay be
registered for sale, distribution, reformulation, and use in trie United
States. In preparing this Standard, the Agency has considered the scientific
daCo obtained from tne open literature through April 1981 and data submitted
by tne registrant up to the date of publication of the Standard. Based on a
.review of these data, the Agency finds that MCPA has neither net nor exceeded
any of the risk criteria found in section 162.11(a) of Title 40 of the U.S.
Code of Federal Regulations. Gaps in the data base preclude the completion of
the Agency's risk assessment. The Agency has determined that MCPA does not
cause unreasonable adverse effects to either man or the environment when used
in accordance with prescribed label directions and precautions.
Currently registered products containing MCPA as the sole active ingredient
may be reregistered under this Standard. New products may be registered under
this Standard, provided the proposed products meet acceptable standards of
product composition, use and toxicity as described below.
Regulatory Rationale -
MCPA (4-chloro-2-methylphenoxyacetic acid) and its salts and esters are
pnenoxy herbicides with chemical structures very similar to 2,4-D. The
najority of flCPA is applied postemergence by farmers or professional
applicators. MCPA is currently registered for outdoor, nondcnestic food crop
and nonfood crop uses. From 85 to 95% of MCPA usage is on wheat, rice, barley,
oats, and rye. Other uses include applications to rangelands and turf.
The Agency has completed a thorough review of available data on tne safety of
tCPA, and has identified several studies that indicate MCPA may be
teratogenic, fetotoxic, and may affect spermatogenesis. In addition, data
were available that indicated MCPA may be a weak nutagen. Scne of the data
indicating adverse effects do not meet Agency standards for testing. Flaws in
protocol and study design reduce Agency confidence in reported results (see
Chapter 6 for details). Also, additional data were available that indicated
MCPA did not induce teratogenic, fetotoxic, reproductive, or mutagenic
effects. In tne face of conflicting and inconclusive data, the Agency does not
consider it prudent regulatory policy to proceed with a presumption against
the registration of MCPA at this time.
However, the Agency is concerned whenever positive effects are reported in
submitted data. Because of its concern, the Agency has completed a
preliminary dietary risk assessment using the No Observable Effect Level
(NOEL) of 4 mg/kg (the lowest NOEL reported). A suimary of available positive
effects data follows, and the dietary risk assessment follows this summary.
Chapter 6 includes full discussions of all reviewed data.
Available data on tne teratogenic potential of MCPA include studies indicating
that dietary administration of MCPA induced dose-related minor skeletal
defects and decreased fetal weights. The NOEL based on the incidence of minor
skeletal defects and decreased fetal weights was 25 mg/kg in rats (see Chapter
10
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6 for details). In a separate study, f-CPA was annunii^-red to rats in dietary
doses of. 2, 30, 60, and' 1:10 mg/]cg. At 60 nnc; inp rr;/'-.-;, trio nnlfor^otior. r?.tc-
vas significantly increased, and fetal weights werr ~i~ni£icantly decreased.-
Tne i>*JEL for fetotoxicity was 30 mg/kg (see Cnapter n ror details).
Available data on potential effects of MCPA administration on spematogenesis
includes a study tnat indicates dietary administration of nCPA may induce
dcse-related curtailment of spematogenic activity, tubular atrophy, and
prostatic alterations. The NOEL based on tne effects described above is 4
mgAg in beagle dogs. In a separate study, deened inadequate by Agency
standards, MCPA was administered to young male Sprague-Dawley rats at doses of
100, 500, 1,000, 2,000 and 3,000 ppm. Rats receiving inn ppm (3 mgAg/day)
had slight degeneration of tne seminiferous tubules. Those receiving doses of
500 ppn (61 mgAg/day) and 1,000 ppm (112 ngAg/day) had mild degeneration of
trie seminiferous tubules with loss of speraatids. The use of less than 10
rats per dose, the short duration of the study, and discrepancies in the
recording of seme data were the major deficiencies noted in the Agency's
rcview of tnis study.•,
Available data on potential mutagenic effects of ?1CPA include studies
suggesting MCPA is a weak mutagen in Saccharomyces cerevisiao and a weak
mutagen in Drosopnila. In addition, one study indicates that MCPA may cause
inhibition of testicular DNA synthesis in male mice.
The Agency is requiring additional testing of fICPA for reproductive effects
because available data are inconclusive (?ce Chapter 6). However, because
adverse reproductive effects were reported in several studies, the Agency has
completed a preliminary dietary risk assessment, usinn tr»e conclusions of
tne subcnronic feeding study which reported effects on spermatogenesis and a
NOEL of 4 ngAg.
Dietary Risk
In order to assess the risk for dietary exposure to MCPA, a worst case dietary
risk assessment based on the conclusions of the subchronic feeding study in
beagle dogs is used (Holsing, 1970, 000004757). The NOEL reported in this
study is tne lowest level reported that indicated adverse effects. This study
reported adverse effects on spermatogenesis and a 130EL of 4 ngA<3« (see
Table 2-1)
TABLE 2-1
Reported Incidence of Spematogenic Effects
Cose (ngAg) 0 4 8 16
Incidence 1/4 1/4 2/4 3/4
11
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The TMRC (Theoretical Maximum Residue Contribution) of MCPA to the human diet
is .77 ng/day (sec Chapter 7). The theoretical dietary exposure of an average
man equals tne TMRC divided by the weignt of the average man (60 kg): .013
mgAa/day. The oral NOEL from the study discussed above is 4 mgAg* The PADI
(Provisional Acceptable Daily Intake), using a 2,000-fold safety factor,
is .002 mgAg/day. (The ADI is termed provisional because chronic feeding
studies are not available to confirm the reported NOEL in subchronic testing.
Likewise, a 2,000-fold safety factor is used because the NOEL is from a
subchronic study.) The theoretical dietary exposure of an average man to
residues of MCPA in food exceeds tne (provisional) acceptable daily intake by
a factor of approximately 6. Thus, there is a safety factor of approximately
333 rather tnan 2,000.
The ADI is provisional and was calculated using a 2,000-fold safety factor.
Chronic testing of MCPA is required as one of the conditions for continued
registration under this Standard. Calculations of an ADI using the customary
100-fold safety factor (when long-term testing is available) and the sane ^DEL
as reported above, give an ADI of .04 mgAg. The theoretical dietary exposure
figure of .013 mgAg/day would be acceptable because it is less than the ADI.
Because the ADI is only provisional, the Agency is not taking any action to
revoke existing tolerances even though theoretical dietary exposure exceeds
tne maximum permissible intake. However, the Agency will not consider any
additional tolerances for the use of MCPA in or on food or feed until
acceptable chronic feeding data have been provided.
Applicator Exposure
The vast majority of .'1CPA is applied postemergence by farmers and professional
applicators. Product concentrations of MCPA acid equivalent range from 1 to 4
pounds active equivalent per gallon of product, with 4 pounds being tne most
ccmon. Most is broadcast by fixed-boon ground rig sprayers in about 10-30
gallons of water carrier per acre. An appreciable amount is also broadcast
aerially, especially in rice. Aerial applications use 2 to 10 gallons of
v/ater per acre. Crop sites are normally sprayed only once per season at an
average application rate of 0.5 pounds active ingredient per acre.
MCPA may induce adverse reproductive effects at concentrations as low as 4
mgAg body weight. Therefore, the Agency is concerned about applicator
exposure during tne mixing and application of spray formulations. Because the
Agency is awaiting the results of further reproductive testing, quantitative
applicator exposure and risk assessments are not being completed at this time.
The Agency will ccnplete a full applicator exposure and risk assessment if the
results of required toxicological testing confirm the Agency's preliminary
determination that MCPA may induce adverse effects on spermatogenesis.
12
-------
Test Substances for Required Testing
As a typical weak acid (pK^ = 3.1), MCPA exists in solution in tv;o fcrr .c ,
depending on the pH. Below pll 3.1, tne un-ionized, protonated torn (MCPA acid)
prodcnin^tes, and above this pH, 'TTPA anion (salt form) prec!cnin?tes. Pocnijse
of tne interconvertability of *CPA acid and salt forms, MCPA and its salts nay
be considered as one entity for most categories of testing.
For esters of MCPA, tne situation is different. The fgency has no data on tne
rates of hydrolysis of MCPA esters in living or nonliving systems, and
therefore nas no basis for saying that MCPA acid and its esters are equivalent
for testing purposes. Registrants of products containing esters of MCPA *cid
have tne option of providing all categories of data on each ester fom, or of
citing data showing that a particular ester would be equivalent to MCPA acid
under test conditions. The Agency will consider such a rationale based on
registrant-supplied data on analogous chemicals (for instance, 2,4-D).
Potential for Mitrosatnine Contamination
Amine and alkanolamine salts of phenoxyacetic acids may contain nitrosamines
as a result of (1) nitrosamine contamination of the amine or alkanolamine used
to produce tne salts, or (2) addition of nitrite to tne product to innibit
corrosion during storage. Samples of an oir.ine salt fcrnulticn of .MCPA
obtained "off-tne-shelf" contained up to .7 ppm N-nitrosodimethylanine.
Because 80% of all N-nitrosamines have been shown to be carcinogens, the
Agency is requiring analyses of products that are most likely to be
contaminated with N-nitrosamines. - -Each registrant of a nanufacturing^use --------
product containing an amine or alkanolamine salt of MCPA is required to
analyze tne product for nitrosamines immediately after manufacture, and either
certify that nitrites are not added to the formulated products, or analyze the
formulated products after storage.
Following tne submission of data and the submission of required risk
assessments where necessary in accordance witn 45 FR 42854, the Agency will
reevaluate the registrability of MCPA.
Potential for Dioxin Contamination
Some published procedures for the manufacture of MCPA use chlorocresols as
starting or intermediate materials. Chlorinated phenols are dioxin
precursors under certain conditions. The Agency is requiring the analysis
of MCPA technical acid (manufactured with chlorocresols) for chlorinated
dioxins. In addition, end-use products developed under an integrated
formulation system (for which there is no registered MCPA technical product)
must also be analyzed for cnlorinated dioxins. Alternatively,
registrants nave the option of supplying detailed discussions of why dioxins
are not likely to be found in the product.
13
-------
Criteria for Registration Under the Standard
1b be subject to tnis Standard, MCPA products nust:
- contain MCPA as tne sole active ingredient;
- be within any established standards of product canposition;
- be within acceptable acute toxicity limits;
- be labeled for acceptable end-uses; and
- bear required labeling.
The applicant for registration or reregistration of products under this
Standard must ccnply with all terms and conditions described in this Standard,
including a commitment to fill any data gaps in accordance with the time
schedule specified by the Agency, and, when applicable, offer to pay
compensation to the extent required under Section 3(c)(l)(D) of FIFRA, as
amended, 7 U.S.C. 136(c)(1)(D). As discussed in Chapter I, applicants for
registration under this Standard must contact the Agency for specific
instructions, including updated information on data and compensation
requirements.
A. Manufacturing-use MCPA
1. Acceptable Ranges and Limits
a. Product Composition Standard
MCPA manufacturing-use products are available in a variety of forms: MCPA
acid, the dimethylamine salt of MCPA, the isooctyl ester of MCPA, the butyl
ester, the butoxyetnyl ester of MCPA, and a mixture of the iscbutyl,
isopropyl, and butyl esters of MCPA. Manufacturing-use MCPA products with any
percentage of the above listed acids, salts, or esters are acceptable under
tnis Standard with appropriate certification of limits.
Manufacturing-use products containing amine and alkanolamine salts of MCPA
must be analyzed for the presence of N-nitrosamines immediately following
manufacture and after storage (see pp. 13 for option of certifying that
nitrites are not added). Registrants of products containing nitrosamines in
excess of 1 part per million must provide the Agency with a risk analysis (45
FR 42R54).
Manufacturing-use MCPA products manufactured with chlorocresols must be
analyzed for the presence of cnlorinated dioxins, or, alternatively,
registrants may provide the Agency with detailed explanations of why tne
formation of chlorinated dioxins is unlikely to occur in their product(s).
b. Acute Toxicity Limits
The Agency will consider registration of proposed manufacturing-use MCPA
products that nave established acute toxicity I-IV ratings for each of tne
following effects:
14
-------
Acute Oral Toxicity
Acute Dermal Toxicity
Acute Innalation Toxicity
Primary' Eye Irritation
Primary Dermal Irritation
c. Use Patterns
To be covered under this Standard, manufacturing-use MCPA products must be
labeled for formulation into end-use products that are intended for outdoor,
nondomestic (general) or domestic (restricted), terrestrial or aquatic, food
crop or nonfood crop applications.
Under section 130.339 of the Code of Federal Regulations Title 40, tolerances
have been established for the use of MCPA in or on barley, flax, flaxseed,
grasses, oats, pea vines, rice, rye, sorghum, vegetables (seed and pod),
wheat, cattle, goats,-: hogs, horses, milk, and sheep (see Chapter 7 for full
tables of existing tolerances).
Because the Provisional Acceptable Daily Intake (PADI) of ?CPA pas been
exceeded by the tneoretical dietary exposure figure, additional tolerances
will not be considered under this Standard (sec Tolerar.ee FfeasE'iG
Additional nonfood use patterns of MCPA are acceptable under this standard,
provided registrants demonstrate tnat the new use will not result in
unreasonable adverse effects to applicators or the environment. Products
intended for domes tic- -use -will -be -restricted-use -pesticides —
t
2. Required Labeling
Ml proposed manufacturing-use products must bear appropriate labeling as
specified in 40 CFR 162.10.,
3. Tolerance Reassessment
See the Residue Chemistry Chapter of this Standard for full discussions of
existing U.S. tolerances and Codex tolerances.
Tolerances for residues of MCPA and of its metabolite 2-methyl-4-chlorophenol
nave been established for a number of food and feed commodities (see Chapter
7). Certain esters of MCPA are not listed as included in the regulation
establishing tolerances for ; MCPA. 40 CFR 1G0.339 should be amended to add
those esters not now included, i.e., the butyl ester, and the isobutyl and
isopropyl esters.
Based on these tolerances, the theoretical maximum residue contribution (T-IRC)
of MCPA and its metabolite to the human diet is calculated to be ca 0.77 mg/day
(assuming a 1.5 kg diet), or .013 mgAg. The PADI of MCPA in the human diet
equals the no-observable-effect-level (NOEL) (4 mgAg) divided by a 2,000-fold
15
-------
safety factor. The PADI is .002 ngAg« The provisional maximum permissible
intake (P:!PI) is the ADI multiplied by 60 kg (the average weight of a human).
Tr.e PMPI is .12 ng/clay.
Tne tneoretical dietary exposure to MCPA is approximately 6 times the maximum
permissible intake. A 2,000-fold safety factor is used for the purpose of
calculating the P.ADI and PMPI because the NOEL was established in a subchronic
feeding study. It is Agency policy to utilize a 2,000-fold safety factor when
NOEL's are based on subchronic data and chronic feeding studies are
unavailable.
When the Agency uses the customary safety factor of 100 instead of 2,000, tne
theoretical dietary exposure level does not exceed the maxiraum permissible
intake.
Because tne ADI (based on existing subchronic .data) is provisional, pending
the receipt of chronic feeding data, the Agency will not take action at this
tine to revoke any existing tolerances. However, the Agency will also not
consider any additional tolerances under this Standard.
B. End-Use MCPA
1. Acceptable Ranges and Limits
a. Product Conposition Standard
j
MCPA end-use products are available in soluble and emulsifiable concentrate
formulations. nMCPA end-use products contain -*he- sodium-s^l-t-of--l4CPAT—tine-
die tnanolamine salt of MCPA, the dimethylamine salt of MCPA,-the isooctyl
ester, the butoxyethyl ester, and a mixture of the butyl and isopropyl
esters. End-use MCPA products with any percentage of the above-listed salts
or esters are acceptable under this Standard with appropriate certification of
limits.
End-use products containing amine and alkanolanine salts of flCPA must be
analyzed for the presence of N-nitrosamines intnediately following manufacture
and after storage (see pp. 13 for option of certifying that nitrites are not
added). Registrants of products containing nitrosamines in excess of 1 part
per million must provide the Agency with a risk analysis (45 FR 42854).
b. Acute Toxicity Limits
The Agency will consider the registration of MCPA end-use products for general
nondonestic use or restricted domestic use witn established acute toxicity
ratings of:
Acute oral toxicity
Acute dermal toxicity
Acute inhalation toxicity
Primary eye irritation
Primary dermal irritation
I
Yes
Amendment*
Anendment*
Yes
Yes
II
Yes
Yes
Yes
Yes
Yes
III
Yes
Yes
Yes
Yes
Yos
IV
Yes
Yes
Yes
Yes
Yes
16
-------
* An amendment is required; for the registration of products in category I _
for acute dermal toxicity and acute inhalation toxicity, because dermal
and innalational routes represent the routes with the highest potentials
for significant exposure during the rr.ixirrj nr.d application of liquid
formulations.
c. Use Patterns and Application Methods
*sfvCPA end-use products nay be used nondomestically and dcnestically as
•" lerbicides in barley, flax, flaxseed, grasses (including turf), oats,
>ea vines, rice, rye, sorghum, alfalfa, clover, vegetables (seed and pod), and
i/neat, or in noncrop areas.
,-2. Additional Uses
Because the Provisional Maximum Permissible Intake (PMPI) of MCPA has been
'exceeded by the Theoretical Maximum Residue Contribution (TMRC), additional
tolerances will not be considered under this Standard (see Tolerance
Reassessment).
ilditional nonfood use patterns are acceptable under this standard, provider
^registrants demonstrate that tne new use will net pose an unreasonable risk tc
applicators or to tne environment.
3. Required Labeling
General
IA11 end-use products must bear appropriate labeling as specified in 40 CFR
•162.10.
Product Chemistry
,i
'For some emulsifiable concentrate products, tne flash points are between 30°
,and 150°F. These products must bear the following precautionary statement:
1 "Eb not use or store near heat or open flame."
I
Environmental Fate
To decrease the likelihood of spray drift, all end-use products must bear tne
following restriction:
"Avoid use of small-diameter spray nozzles."
' •
Restrictions (see Residue Chemistry Chapter for details)
The following use restrictions are required to provide assurance that the
tolerances for meat, fat, meat byproducts, and for milk will not be exceeded:
17
-------
Snail grains, flax, and sorghum:
"Do not fornne or graze meat animals on treated areas
witnin seven days of slaughter."
Additional restrictions:
Products for use on aquatic sites (such as drainage ditch banks) must bear
restrictions against use of the product on potable water, water used for
irrigating crops, and water containing edible fish or shellfish. Treated water
should not be drained into a flowing stream that contains edible fish or
shellfish or is a potential source of potable water or irrigation water. In
lieu of labeling restrictions, appropriate tolerances for potable water, fish,
shellfish, or irrigated crops, may be necessary. Other labeling restrictions
nay be imposed as tne required environmental fate data gaps arc filled.
A restriction against the practice of growing crayfish or catfish in treated
rice fields is requirjed to preclude the possibility of residues in crayfish or
catfish:
"Do not grow crayfish or catfish in treated rice fields."
For nonfood uses, when the application rate exceeds 2 Ibs. a.e./acre (rights
of way and fallow lands), the following labeling is suggested:
"Do not forage or graze livestock on treated areas
within seven days of treatment."
18
-------
CHAPTER III
DATA PEOUinnriErTTS and DATA GAPS
A. Manufacturing-Use MCPA
1. Generic Data Requirepents;
Table A, entitled: Generic Data Requirements and Data Gaps for Manufacturing-
Use Products includes tnose data that pertain to the properties or effects of
MCPA as an active ingredient. Tnus, these data are relevant to an evaluation
of tne risks and benefits of all products containing MCPA. Providing data to
fill indicated gaps in tne data base is the primary responsibility of trie
registrant(s) of manufacturing-use MCPA. Registrants of end-use products wnich
are not exempted by FIFRA Section 3(c)(2)(D) are also responsible for the
submission of these data. To preclude unnecessary studies from being
conducted, registrants are strongly urged to consult with appropriate Agency
scientists (i.e., Hazard Evaluation Division, Office of Pesticide Program)
before initiating studies. For useful background information, consult the
Agency's Guidelines. Applicants for the registration or reregistration of
manufacturing-use MCPA products must acknowledge reliance on existing data
wnich fill indicated data requirements under FIFRA Section 3(c)(l)(D). These
data are listed under the column entitled Bibliographic Citation in this
table.
Environmental Fate Data
Data on physico-chemical degradation, mobility, metabolism, and accumulation
are required on MCPA acid AND on each salt and ester of MCPA. Because of tne
interconvertability between MCPA acid and salt forms, MCPA and its salts can be
considered one entity for Environmental Fate testing. This is not the case for
MCPA esters. The Agency has no basis for saying that MCPA and its esters are
equivalent for testing purposes. Therefore data on the fate of each ester are
required. Alternatively, registrants have the option of citing data from
analogous chemicals which indicate that a particular ester would be equivalent
to MCPA acid under test conditions.
Product Chemistry Data
Certain data on the physical/chemical properties of technical fCPA acid are
required for the registration of all salts and esters of MCPA. Additional data
specific to particular salts and esters are also required.
Toxicology Data
A full battery of toxicologies! testing is required on MCPA acid, each salt and
each estor. Alternatively, registrants may submit evidence which substantiates
that a particular salt or ester will be toxicologically equivalent to MCPA
acid.
19
-------
Ecological Effects D?.ta
Fish and wildlife (ecological effects) safety testing most be conducted on HCPA
acid (for the registration of products containing MCPA acid) and on a number of
different salts ana esters (for tne registration of products containing the
salts and esters). Separate testing is required because data indicate that the
physical/chemical properties (ie. solubility) of the salts and esters differ.
These differences could influence the acute toxicity of these compounds to fish
and wildlife.
2. Product Specific Data Requirements: Manufacturing-Use MCPA
Table B, entitled: Product Specific Data Requirements for Manufacturing-Use
Products includes tnose data that relate only to the properties or effects of a
product with a specific ccmposition (or substantially similar composition).
Thus, these data are required of each product (or substantially similar
product) to characterize the products's particular conpositicn and
physical/chemical properties, and to characterize the products's acute toxicity.
Product ccnpositicn data are required for each manufacturing-use product.
Providing data to fulfill these requirements is the responsibility of each
applicant for the registration or reregistration of a manufacturing-use fCPA
product. If the Agency has data which fulfills this requirement for a
particular product (s) then this is indicated in the chart and in the guidance
package accompanying tnis Standard.
Data on the pnysical/chemical properties and acute toxicity of manufacturing-
use products are required for eacn product or substantially similar product.
Providing data to fulfill these requirements is the responsibility of each
applicant for tne registration or reregistration of a manufacturing-use MCPA
Product specific data need not be acknowledged under FIFRA Section 3(c)(l)(D)
unless the Agency or a registrant has established that one product is
substantially similar to another product for which the Agency has received
acceptable data.
Existing manufacturing-use fICPA products are substantially similar in
ccnpositicn for the purposes of establishing product-specific testing
requirements.
Product Chemistry Data
Data requirements 163.61-3 through 163.61-7 apply to each proposed or currently
registered manufacturing-use MCPA product.
20
-------
Toxicology Date
Data requirements 163.81-1 and 163.81-2 (acute oral and dermal toxicity) apply
to manufacturing-use products wnich are not toxicolcgirr>lly equivalent to tne
tecnnical grade of tne active ingredient. Testing is required of each
manufacturing-use product. Alternatively, registrants nay choose to sutmit
references to existing data on analogous cnemicals which substantiate that a
particular salt or ester is toxicolcgically equivalent to 'CPA acid.
Data requirements 163.81-3 through 163.81-6 apply to each nanufacturing-usc
product or substantially similar product. Testing nust be supplier) on fCPA
acid and on each manufacturing-use product, unless registrants argue for
toxicological equivalence to MCPA acid by citing data on analogous chemicals.
B. End-Use MCPA Products
Applicants for the registration of end-use products containing MCPA are advised
that if the Agency does not receive commitments, within the specified time,fran
manufacturing-use MCPA registrants to fill data gaps identified for the
manufacturing-use product, manufacturing-use product registrations will bo
suspended. Fomulators nust tnen bear tne burden of supplying tnese data if
continue:', availability of the nanufacturing-use product is desired.
1. Product Specific Data Requirements for End-Use Products
Tnblo C: Product Specific Data Requirements and Data Gaps for End-Use MCPA
includes tr.cse rirrta that relate only to the properties or effects of products
with a specific composition (or substantially similar composition). Thus,
these data are required of each product (or substantially similar product) to
cnaracterize tne product's particular composition and pnysical/chemical
properties, and to characterize the products acute toxcicity.
Product composition data are required for each end-use product. Providing data
to fulfill tnis requirement is tne responsibility of each applicant for tne
registration or reregistration of an end-use MCPA product. If the Agency has
data which fulfills this requirement for a particular product(s) then this is
indicated in the chart and in the guidance package accompanying this Standard.
Data on the physical/chemical properties and acute toxicity of end-use products
are required for each product or substantially similar product. Providing data
to fulfill these requirements is the responsibility of each applicant for the
registration or reregistration of an end-use MCPA product.
Product-specific data need not be acknowledged under FIFTA Section 3(c)(l)(D)
unless tne Agency or a registrant has established tnat one product is
substantially similar to anotner product for which tne Agency has received
acceptable data.
21
-------
Substantially Similar Products
•testing of representative products containing each type of registered salt and
ester of !CPA is required.
Product Chemistry Data
Data requirements 163.61-3 through 163.61-3 apply to each proposed or currently
registered end-use MCPA product.
Toxicology Data
Data requirements 163.31-1 through 163.81-6 apply to representative products
containing each type of MCPA salt and ester.
22
-------
nrrcmc twm
cwrn
Guideline Hanc of Are Dnta Test hies rpA llavn Data to
Citation Test i Required? Substance Partially or Totally
Satisfy RcqiilrcBmts?
Product Chjenlstry
Ul.ei-lTnt Product Tes Tech Rrmto* . Tes
Identify
163.61-Kc) Product Tea Tcrh Rrade* Ho
Ccnroaltlcn
161.61-7 Analytical Tea Terh Grade* Partla.lt tlped
• nVjthtyhi t data on each
Data ' product
161.61-nlcM It Color Tea Tech Grade* . Partial1
I61.6l-R|cll2| Odw Tea Tech Grade* Partial
IC1.61-Rlc|l1t Heltlni Point Tes Tech Grad"** Partial2
I61.61-B(c)t4l Solubility Tes Tech Cra** Partial2
I61.6l-ifc)(5) Stability Tes Tech Grad-* No
I61.6l-H(cll6l Octanol/Hnter Tea Pure Font Ho
', Partition of A.l«"
Coefficient
I61.6l-8(c)|7) Physical Tea Toch Gradp* Tea
Statd
IK1.6l-Blc)|R| tensity or Tes Tech Gra.b* Partial1
. Specific
riravlty
l61.6l-fl(cH9| Dolllnq Point Tes Tech Grade Rstoro tb
161.61-ftlcHIOI Vapor Tes Pure For* tb
of A.I.'"
niblloqrnphlc Hint Mlltlonal l\ita to Rub-
rltntlm ultted Onrter FIFWX I|r)|2)|ni7
If So. f>>idllne for Sttmlsnlnn
No
Vest
Harwell. I97R, 00021977 Vest
Akzo 7out. Chomlc. 1971. OO004710
Chlpunn, 1971, 0002191 7
ATKJ 7«it Ch-mle, 197.1. OOO04735
KenilBk V*.rli Koqe, 1972, OOOO4S76
Collier. 1974, 05001559
Stevens, 1979. 05012650 ,\
Mallna, IO7I, 050O14SO
nt. John, 1965, 0000499% Yrsi
CSFl 11616-2
rSFi 11636-3
CSFi 1 1616-1
CSFl 11636-2 Yesi
C!Fi II616-J
OJF: II61R-I
St. Jdtn, 1965, OOO010OS Yesi
tr.F: 11616-2
St. John. 1965. OOOO499S Yest
r.:r: II61K-2
Yes,
Yes,
St. John, 19^5. OO0044<>S No
TSF'B of Prmlurts
St. John. 1961, 00004995 Yrsi
CSF! IK.16-2
CSFi 11616-3
rr.r: II61R-I
Yrsi
Yon*
6 mnnths
6 imnths
6 months
6 mnnths
6 ™t,,fl
6 imnths
Rmmtns
6 mmths
6 mrwittin
6 nrmths
M1.«l-aiel(lll|«l. Yes Terf.Or.vi,. No Vps, * „„,,„
*
D^ta ff^ilrnnnnts are ciirrwrt IM of rirtnly*r I*WI. Bw quiatnoc r**+»Virtn cnntalnhvj tlv nrxlliira s-iH,
dlnrthylamlnc 8.1 It and dletMnolnmln<> svilts of NCPA.
•* Data arc required on technical qr.-vle HTT(\ arid only.
••• frtta are required on the annlyt -ally pure form of >TPA acid and each ester.
I data are available on MTPA acid, the Inmctyl ester, and the mixed esters.
2 Rita arc available on NCPA acid.
-------
TAW*
Guideline
Citation
DivIroroEntal
l«3.*2-7(bt
I63.fi2-7(cl
If3.62-9(b( •
163.62-IMel
163.62-Btd)
!63.62-8(f)
l63.62-B(q)
)63.62-9(b)
163.62-9IC)
t
161.fi2-rch GradE Tes
Hon-Rndlo- No
labeled
Matorlnl
Tech firadr-' No
Rrp- Form7 Mo
l»rp. Form" Mo
Rrp. Form11 Pnrt.lnl"
Anily^cal No
CrjirV?
llrp. Fomi" Mo
Tech firnde' Ho
n^jmwvpfs
Dlblloriraphlr Mint nrUltlcml l«t.i be Sub-
Cltntlon Bitted Mntter Finw Hrl(2l(n|?
If So, fxr-adlln^ for ftiintlsftlon
Sodcriulst. 1974. 0000444R Teal
f-orV-rTulst. 1975. nsmi«45
Sod^rqulst, 1974, 00004MB Teat
Rodnnrilnt. 19^5. O'flOIMS
Tost
Test
t
«v Test
f
llclllnq. 1971. OSOI6652 Ho
Itelllnq. I9AB. 05004203
llcrzcl. 1979. IS0212K
Teat
YPJII
Yp«t
Test
Frnnlt, 1179. OSOI0951 Tost
Ycsi
Yes:
Yont
12 months
12 nrmthn
|O tmnthn
10 imntha
12 mnntha
10 mnnthiv
10 imnthq
in itontht
12 months
14 ninth*
2« nontlis
14 months
24 mnnths
IntIon
163.62-13 Disposal Reserved
and fitoraq"
flata reqiilrcnents current as of Ortcter I9BI. Ri?fer to qulrtanre parkao/? for iinhtp.1
-------
1 Radio-labeled an.ilyMo.il nractp preferred or non-r.idlo-liiheled t>x-hnlr.il qradp MTPA acid and each estor. ivyilnt-r-inf-.s tvivo tl«o
option of tostinq fl at one oononntration undnr natural or Blmiln^vl (>2no nm)
sunllqht
4 TV; requirement for Uio ttutmlsaior of tlioso data IB currently nelnq reserved pendinq the couplet ion of Armey ter.tinq
protocols.
5 For terrestrial noncron wva, orrMrd crop uson, field or vr»«r»»-nhle crop uses, and forestry uses, the mobility of t-.ho tost
siinstanoe and its ilnnrndatr'S In Kill rtvill hr» asscnapd either ly soil thin layer chromatoqraphy. soil noluim. or h.itr!h
equilibrium (.-vteorptlon/itrRorptlor ) procedures. >N
7 For domestic outdoor uses, qrcenhtMw uses, aquatic usoa, and aquatic inpact uses, the nobility of the test Bubst.ince and its
dcgradates in soil shall he asses(.!d only by tho hat.ch equilibrium (adsorption/desorptian) procedure.
8 Testing required on representative formulation types.
9 Field and vegetables crops, pastutrs land, domestic outdoor parku and omnmentaiAurf use, and rights of way.
10 Aquatic food crops.
0 \ •
^ 11 Additional data needed on MCPA huloxyethyl ester.
12 Rndlolabeled analytical grade preferredj if residue found, field testing using representative fomulations
13 Flew through only.
14 This data requirement ia currently reserved pending completion of applicable Agency guidelines.
-------
TA1UK A (continued)
CTNKIUC DATA RHCNMRFII^^HVID (WTA CAPS
pon fwiupAcninifii^B^ npcAa
Qii'toline
Citation
Ihx loo logy
161.81-1
163.81-2
163.81-7
163.82-1
163.82-2
163.82-3
163.82-4
163.82-5
163.83-1
163.83-2
161.83-3
161.83-4
163.04-1-4
163.85-1
163.. 86-1
Him* of Are liata
Tcr.t norpiirtxl?
Aruto Oral Yea
ToxIcUy
Acutn Hernnl Yes
Toxlclty
Acutn Hr>2
Dclayort
Ncurotoxiclty
- . Sttochronlc Yes
Oral
Toxlclty
S«*«*ronlc No1
(21 oViy)
Deriml Ten.
Subchronlc ' tlo1
(90-rlay)
Dcrnnl Tox.
Suhchronic No1
Inh.nl. Tox.
Subchronlc No1
Ncurotoxiclty
Chronic Yos
Onoocrntclty Yos
Terato- Yos
qenicity
Reprorluction Yos
Mutanonlclty Yos
Hetahollsm Yns
Pnitr'stic Ho
Animil
Rafoty
TVst lloos RPA llav-» nnta to nihllographlc Hunt Mrlltlonal r*nta N! Ruh-
Sijhstano; Partially or Totally Citation mlttoH Unrfcr FIFIJA l(c)(21(n)?
Satisfy Rerpilromnnts? If f5o, Dr>a<1Uno for r.u*tnlsslnn
1>:<?rti r.rar*?* Yoa llolsinq S Kunrlxin, ,1<>70, OOOO4776 Mn
HolRlnq ft KuivV.ln, l«>6n, 00004775
llolnlm, 1970, 00004756
llolsinq, 1970, 00004757
Ttech Rra«lo* Mo Yoss
T?rh Ormln* Ho Yos:
Torh nrar*!* Mo Palmer ft r^unll, 19'?, 00004441 No
Yasurfe ft Mflerti, 1«»72, 05003566
trvlne, 1900, OOOO4I617
T«rh Crar*!* Partial Rloft Parvlnen, 1976, 05004101 Yos:
Torn firacb* Partial Bottorlmrti, l«»79, 05004970 Yos:
7.cttcrt«rq, l"79, 05001571
H--»qnusson ot al, I9"'7, 05016919
Pmpplnq oh al. 1"71, 05009217
nun>»lmnior oh al, li"1?, 0501655
Tsrh f!ra/>5 Mo
n^rV.e, 197 Ib, 00004626
Elo, 1976, 05001256
Ollhert. ft Hopkins, 1978, 00041614
6 n^h.
18 months
48 months
12 months
24 months
-------
a These data are •required for the nxilstr.it Ion of technical chemic.ilft, and for the registration of other products whoneworthe
source of the active ingredient In :ho product In not registered.
* . The Agency la requiring n full battery of toxioologlcal testing on technical grade MCW\ acid to support the* food i«os of thin
active Ingredient. The Aqr»ncy has midr> a preliminary determlnnHon that acute, suhchronic and chronic toxtmloqlnl tontlnq
of MCPA acid Will provlds 'sufflcicut Information to stipport tho rrrjulremcnts for testing of the technical qrvub CR^ors of MCPA
and each mnnufacturlnq-usc MCPA snlt. Rnqistrants have the option of supplying the full hattery of acute, suhchronic. nnd
dironlc toxlcolcqiciil testing on each technical gr.ifte ester or of citing data which show th.it a particular ester or salt will
be equivalent to NCPA acid under test oondtlons.
1 Testing is available on MTPA acid.
2 Testing of the structurally similar compound, 2,4-0 is currently underway. If results are postlve, testing of MCPA is
required.
.3 May he required when acute testing Is completed.
-------
TNVF. A (continued)
DATA nmuinrjtnnr; AND DATA
rrm rvNNiiFWTiuniMn-iBE HPTA
Gulcfellne
Citation
Nanc of Arc Kit.-TesT
.Tsst RequlrrV. t Rut-stano;
n>A II* vc hnta to
Partially or Totally
Rntlafy Rrqiilrcnrnts?
Hlbllnr|rar*ilc
Citation
Hint MHtlonal ivita h? SoB-
•Ittod Unrtor FIFDA l(rl(2)(n|?
?f So, rtwllln1' for
Residue Chemistry. ..
nctahollaa Tea C-MCPA or
In Plants Tccn i
Pnrtlal
Metahollsa Tea
In Animals
Analytical Tea
C-HCPA or
i GratV
IVdinlcal or
Pun'r
Partial
Residue Tea Rep Form*
Data i RAC
Partial
Ram*.
l . OV11SS95
No
tobcrteon ct al, I1K7, OSOIS04A
Abcrq ct fll . l<)78, 0^019071 •
Klrkunol et al. 1972. 0500427}
Klrkvra>l rt al, llf.9, OSO|ll>>r, 1976. OS02I715
Fyskc. 1975. nVI44%
HnntTiorrY. 1970, onoOSVJS
toos, 1971, OSOIfilOO
FysVe, 1976. 0501)377
Ueafe. !"«, OS005791;
Collins et it], 1971. 0500172S
Bache ct al. 1961, 00004701
Lrtv} ct al. 1971. nnn04fi22
Hntllh et al, 1971. 05015451
Dnrhc ct nl. I9M, 00004702
Polrnoowa. I97B. 05017929
Conk In, I951. OOOOS552 Tcs
Tip anrl riry. |9Mi, CS 0017-109
Guarrflnll, 1170, 000047KR
Illqhim, 1975, 00004631
IliTh.in, 1974, OO004«i}2
St. J7|. Ofl004«<27
o ct al, 1971. 00004fi25
"t al. 1971, OOn01K2R
Jonson. 197J, 00004419
llrrmnn ct a), 1970, 00004492
nterkc ct al. 1972. 05001259
Mlllor ct al, 1971. 0000441B
Illqhan, 1975. 00005567
lllqlnn. 1975, 00004KI1
Illqliam ot al. 1975, 00004611
Am. CyJimniM, 1971, 00004"'4I
Am. Cyammlrl, |974. on0046O<)
tk>
-------
• Flax
Grasses,
Pastureland
and Rangeland
Oats
Rice
Rye
Sorghum
Reed i fni
Vegptahles
tea
Yes
Tea
Yes
Yes
Yes
Yes
Residue In Yea
Processed
Foods
Storage Yes
Stability
Rep Form*
Rrp Form*
l«rp Form*
Hep Form*
Kep Form*
Hep Form*
Rep Form*
Wheat Yes F«p Form*
Residues In Yes ftp Form*
Food Pro-
ducing Animals
Rpp Form*
Frp Form*
Yes
Yes
PartInl
Yes
Partial
Yea
Yes
Yes
Yea
Partial
Ho
Hnmanto, 1959. 00004473 No
CVinnMqll. 1970. OOO047M.
Ruirdlnll. 1071. 00004449 No
Rydrych et al, 1071, OO0216fl7 Ho
Irvine. 1070, 00004764 Ho
U?ng et al. 1070, 000047R5
WrrlU, |07|, 00004594
et nl. |O7S. OS001445
No
Dnta frno oth»r snnll qralm
to ry»«.
IntcrrctlorMl, 1974, 00004491 No
Ctnkln, I95S, 00005SS2 • No
Chow et al. 196S, 05001765
Winter!In et al. 1974, OOO044S1
Hendlncn, 1974, 00004454
ttunrdlqll, 1974. 000047RM
Yip and N»y. 19AA. CS 0017-109 Ho
Hontfiowry. IOTO, OOO05575
Rydrydi et al, 1971. 0002JR87
tllqhani et «l, 1974. 00005570
et al,
Jensen et al.
BJnrko ct al,
nacho et nl,
Herman et al,
njorkc et aa.
Mrrnnn et al,
IXiqrpn et al.
ct al,
1971, 00004625
1971. 00004419
1971. 0000462'!
1964. 00004701
1970, 00004491
1972. 00003259
1971. 00004624
1967, 00025154
1964. 00004702
00004766
00004765
No
Hr>
Ho
from applications of representative formi I/it Inns.
There bolnq little, If any t«*ldue4 In those raw agricultural commdltlmi f mm whlrti processed ranimdltlen imy he dcrlvrd, the
need for further data on realties In thn Intter Is
There being little. If any re*ldur> In grains, a staple of poultry rntlons. MK> nn«yt for dntn on rcnldu»a In poultry and
Is waived.
Information obtained from Individual studies Indicates that thn analysis of mnptes w.-n qrn»rnlly prrfoniRd within n frw
nnnths. and generally not later than 6 moths after nnnpllng. lln^jr the rlrrunBtnnc»?s, the nood for residue storage data In
waived.
-------
0
Gulitellno
Citation
Ecological
163.71-1
163.71-2
163.72-1
163.72-2
163.72-3
Nairn of Arc IVit.i
Test Required?
Effects
Avian Single Yes
l>3so Oral Ulgo
Avian ' Yes
Dietary ir^
Fish Acute Yes
UVn
Acute Tnx. Yes
to Aquatic
Invertebrates
Acute Tox . Yes
to Entiiarine
t Marine
TARtj: A uflBtlnued)
OFJIERIC DATA WI.AJT WrM-i FTR JMHHATA CAPS?
FOR MWIUFACniRlHG-IKn MPCA
Test Does EPA Have Data to nlhlloqraphic Must Additional aita tn r.ub-
Subst.inne Partially or Totally Citation mltt"d (hvler FIFRA i(f-W2)(n)?
Satisfy Requirements? If Roj Head 1 In" for Siitmlsalon
I
Tech Grade Ho Yes: 6 months*
Tech Grade2 Yea nrWltt. OS nnn-ini Ho
Tech Orade Partial IKTPA, OS 0017-inn Yes: fi mnni-hs
and I end-use
product ' » ^
Tech Oradn Partial4 USTPA. OS Oni7-infl Yess 'finnnihn
and 1 ei*1-»isc
product
Tech Orade Ho YPSJ f< moiiMin
nnrl 1 ep'I-use
ptwluct
Organ isim
Data requirencnta current as of nrtobor I'Hl. See quldano? package for uprbted requirements.
* 24 months after promulgatlm of Subnart .1
a These data are required for the registration of technical chemicals, and for the registration of other products whenever tho
source of the active Ingredient In the product Is not- registered.
1 Testing required In one avion specter (preferably mil lard duck or hohwhlte quail) using technical grade MCPA acid and isooctyl
and butoxyethyl esters, and the manu :acturlng-tise products containing the sodium and dlmethylamlne salts.
2 Testinq In required on one species of waterfowl (preferably mnlla'rd duck) and one species of upland game bird (preferably
hobvwhlte quail or ring-necked pheasant) using technical butoxyothyl and isooctyl esters, and ttie manufacturing-iigr-
products containing the sodium and dltmthylamtne salts.
3 Testing In btucglll sunflsh and rainbow trout In required with technical MCPA acid,'the butoxyethyl ester, and the iscortyl
ester and the manufacturing-use products containing tfw dlmetlyl;»inlne salt. Testing of the 16.7» butoxyethyl ester end-use
formulation Is also required because of Its use In rice.
4 Available data fulfill requirements for MCPA acid.
5 Testing Is required In Daphnla mngna for the B6.71 butoxyethyl ester end-use product. Aquatic Invertebrate testing is also
required on MCPA acid.
6 Testing Is required on technical MCPA acid, the butoxyethyl enter, and the Isooctylopter, and th» imnufacturlng-os" products
containing the dlncthyiamin>» salt. Testing In shrimp and fish, and .either oyster larvae testing"™: mollusc shell deposition
testing with the 66.71 butoxyethyl ester formulation la required.
-------
? n
T-ecinc wrr* raooiRfmrra Mm nrnw
FOR MwuFjeromtR-iKf: MPO\
Guideline Na*o of Are Dati Teat Orca KPA Have Data to nlnHogrnpMe Huat Additional Datn be nub-
Cl tat Ion Teat Required? nuhnt.inrr* Partially or Totnlly Cltntlon mlH~1 Under FIFIW l|r)(?Hn|?
, . Satlafy Requirements? If So, Deadline for SUhmt union
Product Cnealatry .
163.61-3 Product Yc« facti NIP" partial1
Identify
and Disclosure
of Inqrcdlenta
161.61-4 Description Yea tach NIP** No
of Mf(J PpnC£Bfl
163.61-5 Olec. of Yea Mch NIP"
Format of
Unlnt. Innre-
dlenta
163.61-6 Declaration Ye* f*ch NIP**
of Ingredient
Umlta
161.61-7 Product Yea Bach HUP** Partial1
Analyt. Pat*
I63.6l-R(cll7) Phyalcal Yea Pach NIP** Yea
State
163.61-8(cH8) Denalty or Yea f.n* NIP** Partial1
Specific
Gravity
I63.61-8ICMUI P" Yea Fach NIP** Ho
163.6MMc>M2) Storaqe Yea F,irh NIP" Ho
Stab.
I63.6l-8|e)(13l riamm- Yea Fndi NIP" Partial1
blllty
!61.6l-8lcH14) Oxldlsln) Yea fach NIP** No
Rnduclnq
Action
I63.6l-8lc)(15) explosive- Yea Rnrh NIP** No
ness
I61.6l-8(c)ll6| MlBclhlllty Yea Fnrh NIP" Ho
I63.6l-8(cl(l7| Vlamslty Yea Txch HIP** No
161.6|-3(clllR| Corrosion Yes Rmti NIP** Ho
CRF'a2
St. John. 1965, 00004915
CSFt 11636-2
CSFi 11636-3
CT-Ft 1 1616-1
St. John. 1965, 00004995
CSFi 11616-1
CSFt 11636-2
CSFi 11616-3
CSF 11636-1 thru 3
(T.Ft 1 1616-2
C?Ft M616-1
Yes i 6 mnths
Vest 6 montha
Yest 6 rnrmths
Yeat 6 mnnths
Yeat 6 months
no
Yesi 6 months
Yest 6 mrmtha
Yesi 6 mrmths
Vest 6 month*
Vest 6 months
Yesi 6 mrmths
Yesi 6 months
Yrsi 6 months
Vest 6 mnntlis
Data arc required for the reqlatratlan of each imnufarturlnq-use product.
• For currently registered producta.
for eart> nmiufacturl lift-use proluct.
I ftita are available on HTPA acid, the laonctyl enter, and ths mixed mtem.
2 llprVitprl statenrnta an- required for all mmufacturlnq-uae products.
3 Satisfactory methnda are avall.ihlo ISee Table M hut data are re, on each nanuforrurlni-une product.
-------
TABU! n (continued)
JJ
PRODUCT-SPECIFIC DATA RflQUT KWKN1T! AND DWTA (TAPS
FOR HMUFACTURIHMBT: MPOA*
Guideline
Citation
Toxicology
163.B1-1
163.81-2
163.81-3
163.81-4
163.81-5
163.81-6
Name of Are Data nest
Test Required? Substance
Acute Oral
Toxicity
Acute Dertml
Acute Inhal
Toxicity
Yes
Yes
Yes
Prim Rye Yes
Irritation****
Prim Demnl
Irritation
Dermal
Yes
Yes
NJP**
HUP**
HUP***
HUP***
HUP***
. HUP***
Docs EPA Have Data to Bibliographic Must Addition:*) nnta be Suh-
Partially or Totally Citation mitted Under FIFRA 3(r)(2)(R)?
Satisfy Requirements? • If So, Deadline for Sirt-rolssion
Yes1 Raltech, 1977, 000021972 Ho
No • Yeni 1 months
i \
No Vest 6 months
Yes2 Raltech 19??, 00021974 No
No ' Vest 6 months
No i Test 6 months
Sensitlzation
* For currently registered products.
** Required for manufacturing-use products which are not the sane as the technical grade of the active ingredient. The Agency
has mads a preliminary determination that testing on technical HCPA acid will support this requirement for tenting of the
technical grades of the esters antl manufacturing-use salts (see Table A). Acute toxicity testing of each iwinufnrturlng-
use product (or substantially similar product) which is not equivalent to the technical grades of the active
ingredients is required.
*** Required for ea<.'i manufacturing-une product or substantially similar product.
**** A demonstration of pll between 1 and 3, or 12 ami 14_or_dr-nonst-ratlon of dermal irritation will he sufficient to cateqnrlz? a
product as an ocular irritant, and additional testing will not he required.
1 . Available testing is on technical grade HCPA acid.
2 Available testing is on a sodium italt end-use formulation. This testing indicates that this product is a Category I eye
irritant. Registrants have the option of accepting this clnsolfIcntlon for their productfs) or of providing actual testing
of each product (or substantially similar product).
-------
DKTA imnnREmns »m nm-A CAPS
FOR mNHFAcnnrnK-ire: MIT*"
Guideline Nanc of Are Data . Test toca EPA Have Data to Mbllogrophlc Must Additional Data be Sub-
Citation Test Required? Substance Partially or Totally Cltatlm Bitted Undrjr FIFRA Mc)(2)ini?
Satlafy Requirements? If So, tlmdlln" for Suhmlsnlnn
Product Chemistry
163.AI-3 Product Tea
Identity t
Disclosure of
Ingredients
163.61-6 Declaration Tea
of Ingredient
Units
163.61-7 Product Tea
Analyt Methods
t Data
163.61-8lc)Ul Color Tea
163.61-8(c)(2| Odor Tea
163.61-8(c){7) Physical Tea
State
163.61-8(0)1111 pit Tea
163.6l-8lcH12) Storage Tea
Stab.
I63.6l-B(cl(13l Plasm Ten
163.61-B(cH 14) Oxidizing Tea
or Reducing
Action
161.61-fllclilS) Explosive- Tes
ness
163.6l-8(c)(l6) Nlsclblllty Tes
163.61-8(cl(17) Viscosity Tes
I63.6l-R(cl(18) Corrosion Tes
Characteristics
Each E.U.
Product"
Each E.U.
Product**
Each E.U.
Product **
Each E.U.
Product"
Each E.U.
Each E.U.
Each E.U.
Prodcut"
Each E.U.
Product"
Each E.U.
Product"
lach E.U.
:»roduct"
Each E.U.
Product"
Each E.U.
Product"
>ch E.U.
E.-»ch E.U.
Product**
Partial1
No
Partial2
Ho
No
Tea
Partial*
Partial'
Partial"
No
Mo
rio
Mo
Partial5
CSF's Test fi months
Test 6 mnnths
Test 6 mnnths
•N Test 6 months
Test •> mnnths
CSF's and tahcls Test K months
Test 6 months
Hlrth ft M.ISOD. !•»??, 00005577 Test 6 mnnths
Test 6 months
Test fi months
Trst 6 mnnths
Test R mnnths
Tes: fi mnnths
Wlrth ft W.TSOO. 19??, 0000«i577 Tent « mnnths
• These data are required for the roqlstratlnn of rnd-use HTPS products.
• For currently registered prodict
•• Each end-use ncPA Product
1 Uprtated statencnta are required for earh product.
2 Satisfactory methods nre avalliihlo (sen T.ible Al hut d>ita arc required on each rnd-usr product..
3 Reel "Product Chpmlatryi End-Use Fornilatlons* for listing of avall.-ihlr* rlitn on thh d?nsltles of rurrently
proKicta
4 Seet •Product Chemistryi End-Use Formulations* for llst.lng of avallahlp d,ita on th» r"'" of currmtly rpqlstcrod products.
5 Data are avallnhle on a dlmpthyl.-imlnc amlnp salt formulation (4«i4-1<>4|.
6 Sect 'ProAjrt Chemistry! End-4l»! Formilatlons* for listing of available dnta on the flarnm blllty of currently rrglstorM
producta.
-------
. r (continued)
o DATA
s »m rwm
ro.ffirummir^mW'
Guideline
Citation
Toxicology
163.81-1
Maim of
Test
•
Acute Oral
Toxicity
Are tlata
Required?
Yea
Test
Substance
E.U.
Product
Hoes EPA Have Data »o
Partially or Totally
Satisfy Requirements?
Partial2
niblioqraphlc
Citation
Curd. 1964,
Ourd et nl,
riust
mltt'vl
If So,
00022569
1964, 0002256B
A-V1ition.il Po»-a bo Sub-
llnfV^r FIFTIA l(r)(2M«)?
iv-adlinr- for Siihmlsr.lon
Yes: 6
mnnthn
163.81-2
163.81-3
163.81-4
Acute Dermal
Toxicity
Acute Inh.il.
Toxicity
Prim. Eye
Irritation
Yea
Yea
Yes
iro.Bi-s
Prim. Derml Yea
Irritation
R.O.
Product
E.ll. .
Product
E.ll.
Product1
,
E.ll.
Product
.
Partial
Partial"
Partial
Partial
1
Raltoch, 19??. 00021973
Raltech, 19??, 00021974
tobriel, 1971, 00004513
Raltech, 19?? 0002197fi
Yes« fi nrmths
niespndar f. »\nc|cvlne, 1979, Yens fi mnnths
00021975
Vest 6 months
Y«?st fi months
For currently roqlatored products.
Teatinq required of earh end-use product or substantially aim! lar product. The Arpncy has iitw*? a preliminary 'V»»-ormln.itlon
thati soluble conmntratos containlnq the sodium, salt are substantially similar! that soluble concentrate prtylurts rontalninq
the dlnethyJamine salt arc suhntantially almllarj that soluble concentrate products containing the diethanolamlne RiJt are
substantially nltnl Inn that emulsif table concentrate products contalnlnq the butoxyctnyl ester are similar! that cmulslfiable
concentrates containing thr« laooctyl ester are similar! and that emilnifinble concentrates contninlnq mixtures of tho butyl
and isopropyl cstera are similar.
Available data ont 2
dlethanolnmlne salt.
. soluble concentrate containing the sollum salt and a soluble concentrate contalnlnq th>»
Available data on a 2 Ih/qal. soluble concentrate contalnlnq the sorlium salt.
Available dnta on the 2 Ib/qal. sodium salt fornulation indicate that this product Is a severe irritant. Ifrviistmntn have the
option of acceptinq this classification for their product (n), or of provldinq specific tcstinq. Dnta were nlnn a«niab1e on an
emilaifiahlc concentrate nrmtalninq the butoxyet-hyl ester.
-------
CHAPTER IV
MCPA ProiXJCT CIDilSTRY
A. Introduction
FIFRA 3(c)(2)(A) requires the Agency to establish guidelines for registering
pesticides in the United States. The Proposed Guidelines require registrants
to provide quantitative data on all active and added inert ingredients, and on
impurities that are equal to or greater than 0.1 percent of the product by
weight.
To evaluate the composition of products proposed for registration, the Agency
requires data and information not only on the manufacturing and formulation
processes, but also a discussion on tne formation of manufacturing impurities
and other product ingredients, intentional and unintentional. Further, to
assure that the composition of the product as marketed will not vary from the
composition evaluated-at the time of registration, applicants are required to
submit a statement certifying upper and lower composition limits for the
active and inert ingredients, and upper limits only for seme unintentional
ingredients. Subpart D of the Proposed Guidelines (40 FR 29696, July 10,
1978) suggests specific precision limits for ingredients based on the
percentage of ingredients and the standard deviation of the analytical method.
In addition to the data on product composition, the Agency guidelines also
require data on the physical and chemical properties of both the herbioirial
active ingredient and its formulations. For example, data are needed
concerning the identity and physical-state-of-tne acti'7e-ingre^ient,--s'..'rr> as
melting point and boiling point data, ambient vapor pressure, and solubility.
Data are also required on the properties of tne formulated product to
establish labeling precautionary statements (e.g., flammability, corrosiveness,
or storage stability). The Agency uses these data to characterize the
herbicide and to determine its environmental and health hazards.
Product Chemistry; Manufacturing-Use MCPA
Product Chemistry Profile
HCPA is the common name for 4-chloro-2-nethylphenoxyacetic acid.
Manufacturing-use and end-use products are marketed under the trade names
Mephanac, Methoxone, Agroxone , MCF\ and Vfeedar . MCPA
maijfccturing-use products are available in a variety of forms, including the
technical acid, the dimethylamine salt, the isooctyl ester, the butyl oster,
tne butoxyethyl ester, and a mixture of the isopropyl, iscbutyl, and N-butyl
esters. In this Standard, MCPA refers to the undissociated acid. Esters and
salts of MCPA are identified as such.
Manufacturing-use MCPA acid contains a minimum of 35% 4-chloro-2-metnyl-
phenoxyacetic acid. The dimethylamine manufacturing-use product contains a
minimum of 64% active ingredient. The isooctyl ester manufacturing-use
products contain a minimum of 96% active ingredient. The butoxyethyl
manufacturing-use products contain a minimum of 97% active ingredient, the
-------
butyl ester contains a minimum of 97% active ingredient, and the
nancr-r-tu ring-use product, containing a mixture of esters, contains 47.5%
isopi.Tr.-yl ester, 2B.5% isobutyl ester, and 19% N-butyl ester.
Pure [1C PA is a wnite, crystalline powrter with a melting point of lift -119°C
and a bulk density of 0.7768 gm/cc. MCPA is only slightly soluble in water,
but very soluble in etnanol and ethyl ether. • Manufacturing-use MCPA salts are
highly water-soluble, and manufacturing-use MCPA esters tend to be insoluble
in water. The MCPA salts are less volatile than the esters.
Detailed manufacturing processes have not been submitted for currently
registered manufacturing-use products. Some published procedures for the
manufacture of MCPA use chlorocresols as starting or intermediate materials.
Because chlorinated phenols are dioxin precursors under certain conditions,
the Agency is requiring registrants of technical fCPA acid and integrated
end-use products manufactured with chlorocresols to analyze the product(s) for
chlorinated dioxins or, alternatively, to explain in detail why chlorinated
dioxins are unlikely to: be found in the product(s).
Amine and alkanolamine salts of phenoxyacetic acids may contain nitrosamines
as a result of (1) nitrosame contamination of the amines or alkanolamines used
to produce the salts, or (2) addition of nitrite to the product to inhibit
corrosion during storage. Each registrant of a product containing an amine or
alJcanolamine salt of MCPA is required to analyze the product immediately after
manufacture and after storage. In lieu of analyses on stored products,
registrants may certify that nitrosating agents are not added to the product
after manufacture.
For many products, Confidential Statements of Formula have not been submitted
or are outdated, incomplete, or contain errors. Although satisfactory methods
for the product analysis of MCPA and associated impurities are available,
analytical data have not been submitted by any registrant.
Topical Discussions
Chemical Identity
MCPA (Figure 1) is the common name for tne chemical 4-chloro-2-inethylphenoxy-
acetic acid. Alternative chemical names for MCPA include 2-methyl-4-chloro-
pnenoxyacetic acid and l(4-chloro-c-tolyl)oxy] acetic acid. KCPA is also known
by many trade names including Mepnanac , Methoxone , Agroxone , MCF\
and tfeedar . The Chemical Abstracts Registry (CAS) number for MCPA is
94-74-6, and the EPA Shaughnessy Number is 030501. The common name will be
used throughout tnis standard in lieu of other chemical or trade names.
-------
The cneraical formula is CgHn,Cl(Kf and tne molecular weight is 200.62.
The structural formula is:
0 CH,—C OH
2-Methyl-4-chlorophenoxyacetic acid
Figure 1
In this standard, "MCPA" refers only to the undissociated acid. Salts and
esters are identified, as such.
Manufacturing Process
Process descriptions submitted by registrants are considered Confidential
Business Information and are discussed in the Confidential Appendix.
Processes for the manufacture of technical MCPA have been submitted to the
Agency by two producers, neither of the process descriptions is sufficiently
detailed to satisfy Guidelines requirements.
Discussion of the Formation,of Uhihte~ritiohal "Ingredients
No registrant of a product containing MCPA or an MCPA derivative has submitted
a discussion of the formation of unintentional ingredients in the product as
required by the Guidelines <163.61-5).
Some published procedures for the manufacture of MCPA use cnlorocresols as
starting or intermediate materials (Synerholin and Zimmerman, 1945, 05003614;
Talbot, 1949, 05020338; Talbot, 1952, 05020337). Because chlorinated phenols
are dioxin precursors under certain conditions, the Agency requests that each
registrant of technical MCPA manufactured with chlorocresols analyze the
product for chlorinated dioxins or, alternatively, explain in detail why
chlorinated dioxins are unlikely to be found in the product.
Mine and alkanolamine salts of pnenoxyacetic acid nay contain nitrosamines as
a result of (1) nitrosamine 'contamination of the amines or alkanolamines used
to produce the salts or (2) addition of nitrite to the product to inhibit
corrosion during storage. Samples of an amine salt formulation of MCPA
obtained "off-the-shelf" contained up to 0.7 ppm N-nitrosodirtethylamine (Concn
et^'al^., 1978, 0506328). Each registrant of a product containing an amine
or alkanolamine salt of MCPA is requested to analyze the product for
nitrosamines immediately after manufacture and after storage. In lieu of
analyses of the stored product, a registrant may certify that nitrosating
agents are not added to the product after manufacture.
37
-------
Sane data or. nitrosanir.es in ar.ine salts of !O>A nave been sub?.ittr:l by
Fallck-Lenkro (Song, 1977, 00021962; Paudlcr, 1979, 00021979 - see Confidential
Appendix). However, specific data are needed on each product.
Declaration and Certification of Ingredient.Limits
For no product containing MCPA or an MCPA derivative has the registrant of the
product established upper and lower limits for the active ingredient and each
intentionally added inert ingredient, and upper limits for each identifiable
impurity as required by tne Guidelines (163.61-6).
Product Analytical Methods and Data
Fallek-Lankro (Harwell, 1978, 00021977), Akzo Zout Chemie (1971, 00004730), and
Chipman (1973, 00021917) have submitted GLC methods by which MCPA and
phenoxyacetic acid imparities in technical MCPA and in formulations are
determined as their methyl esters. A spectrophotometric method for the
determination of chloropnenol in MCPA-containing products has been submitted
(Akzo Zout Chemie, 1973, 0004735). The method will determine cnloropnenols
down to 0.02% of tne product weight. Kemisk Vaerk Koge (1972, onorv.iy?*,) nas
sutmitted a combined titrimetric-GLC method for the analysis of products
containing MCPA esters.
Various product analytical methods for MCPA and associated impurities nave
been described in the literature, including GLC (Gardner and Cvortcn, I960,
05004565; Zweig and Snerma,,1972, 05005846; Collier and Grimes, 19"M,
05003559), nigh-pressure - liquid -chrorm:orjr?.pny - tStevens-and-€ror-«4-, —.UP-a,-
05012650), and infrared spectrophotometry (Malina 1971, 05003450).
Although satisfactory methods for the product analysis of MCPA and associated
impurities are available, analytical data required by section 163.61-7 of tne
Guidelines have not been submitted by any registrant of an MCPA-containing
product.
Physical and Chemical Properties
St. John (1965, C0004995) reports the physical and cnemical properties of
purified fCPA as:
Color white
Melting point ; 118°-119°C
Solubility ethanol 153
(gm/100 gm solvent ; ethyl etner 77
at 25°C • toluene 6.0
/ xylene 5.0
N-heptane 0.5
water 0.15
Physical state: crystalline powder or flakes
Bulk density: 0.7768 gn/cc
38
-------
The pKa of MCPA has been variously reporter? as 3.09, by potcnticnetric
titration (Nelson and Faust, 1969, 05002356); 3.11, by a conductimetric inethod
(Matell and Lindenfors, 1957, 05004185); and 3.13, by a spectrophotonetric
method (Cessna and Grover, 1978, 05004R44).
Sane physical and chemical properties of technical f-CPA and ICPA esters have
been submitted by registrants. The data were submitted in conjunction with
Confidential Statements of Formula.
MCPA (acid) Iscoctyl ester Mixed esters
(Reg. fto. 11636-2) (Reg. No. 11636-3) (Reg. No. 11636-1)
Color:
Odor:
Melting Point:
Solubility
in VJater:
Physical State:
Density or
Specific Gravity:
Bulk Density:
Flamnability:
light brown
phenolic
115°C
1825 ppm at 15°C
snail flakes
0.6 gm/cc
37.4 lbs./ftj
not flammable
clear brownish
pleasant, fresh
insoluble
liquid
1.0 at 20°C
100°C
clear brownish
pleasant, fresh
insoluble
liquid
1.0 at 20°C
70°C
Summary of Major Data Gaps
No registrant of a product containing MCPA or an MCPA derivative has submitted
a detailed manufacturing process, a discussion of the formation of
unintentional substances in the product, a declaration and certification of
ingredient limits, or analytical data en the product. For many products,
Confidential Statements of Formula (EPA Form 8570-4) nave not been submitted,
are outdated, are incomplete, or contain errors. Scne inert ingredients in
food-use formulations have not been cleared for sucn use under 40 CFR
180.1001. Data on numerous physical and chemical properties have not been
submitted.
Labeling Requirements
Ingredient Statement. The ingredient statement for manufacturing-use MCPA
will list the active ingredient as:
2-metnyl-4-chlorophenoxyacetic acid N% (run.)
The ingredient statement for manufacturing-use containing MCPA derivatives
will list the active ingredient and the equivalent percentage of MCPA, for
example:
2-methyl-4-chlorophenoxyacetic acid, sodium salt N% (min.)
(Equivalent to M% of 2-methyl-4-cnloropnenoxyacetic acid)
-------
Product Chemistry; End-Use Formulations
Product Chemistry Profile
End-use MCPA products are available in emulsifiable and soluble concentrate
femulations. End-use products contain a variety of foms of MCPA, including
the sodium salt of MCPA, the diethanolamine salt of f-CPA, the dinethylamine
salt of MCPA, the isooctyl ester of MCPA, the butoxyethyl ester of MCPA and a
mixture of the butyl and isopropyl esters of MCPA.
Few data were available on the physical/chemical properties of any end-use
product. Sere data on the pH, density, and flaimability of particular end-use
products are available (see topical discussions). Because tne flash points of
several enulsifiable concentrates (the esters) range between 30° and 150°F,
special labeling is required for these products.
Mine and alkanolamine" salts of phenoxyacetic acids may contain nitrosamines
as a result of (1) nitrosomine contamination of the amines or alkanolamines
used to produce the salts or (2) addition of nitrite to the product to inhibit
corrosion during storage. Each registrant of a product containing an amine or
alkanolamine salt of F1CPA is required to analyze the product immediately after
manufacture and after storage. In lieu of analyses on stored products,
registrants nay certify that nitrosating agents are not intentionally added to
the product after manufacture.
For nany products, Confidential Statements of Formula have not boon submitted
or are outdated, incomplete, or contain errors. Although satisfactory methods
for the product analysis of 71CPA and associated impurities are available; -~ '
analytical data have not been submitted by any registrant.
Topical Discussions
Chemical Identity
End-use products formulated as soluble concentrates contain the sodium salt of
MCPA, the diethanolamine salt of MCPA, or the dimethylanine salt of f'CPA.
End-use products formulated as emulsifiable concentrates contain the
dimethylamine salt of MCPA, the isooctyl ester of MCPA, the butoxyethyl ester
of MCPA, or a mixture of butyl and isopropyl esters. The dimethylanine salt
formulations are the most frequently used products.
Active Ingredients in Pesticide Products
Product concentrations of fCPA acid equivalent range from 1 to 4 pounds acid
equivalent per gallon of product, with tne 4-pounds-per-gallon measure being
tne most common.
For no product containing an MCPA derivative has the registrant of the product
established upper and lower limits for the active ingredient and each
intentionally added inert ingredient, and upper limits for each identifiable
impurity as required by the Guidelines (163.61-6).
So
-------
Product Analytical Methods and Data
See discussion in Manufacturing-use section for details on acceptable
analytical methods. Analytical data have not been submitted by any registrant.
Physical and Chemical Properties
EPA Registration number Density
Dimethylamine Salts
148-1120 9.38
228-143 9.39
264-47 9.403
359-365 9.38
464-394 9.4
524-80 9.358
554-60 9.37
677-298 •'•'•> 9.47
802-138 8.79
1386-587 9.4
1685-61 8.58
39335-7 9.55
39511-65 9.4
Sodium Salts
264-55 9.212
359-170 9.35
802-374 9.19
39335-6 9.413
Diethanolamine Salts
554-123 9.898
Iscoctyl Esters
359-554 8.3
554-125 3.5056
39511-76 8.51
Butoxyetnyl Esters
264-240 8.971
7.5
7.5-8.0
9.0-9.5
7.4
8.0-9.0
6.8-7.2
7.5
8.0-8.5
8.0
8.0-8.6
Flanmability
190°F TOC
>200°F TCC
168°F
133°F TOC
125°F
Mixed Esters
554-91
8.308
Labeling Requirements
129°F TOC
The ingredient statement for end-use products containing MCPA derivatives will
list the active ingredient and the equivalent percentage of T-CPA, for example:
2-nethyl-4-cnlorophenoxyacetic acid, sodium salt M% (min.)
(Equivalent to H% of 2-methyl-4-chlorophenoxyacetic acid)
H\
-------
Pnysical Hazard Precautionary Labeling
The fl~:sn points of scne emulsifiahle concentrates of MCPA esters are between
80° and 150°F and labels on tnese produces are tnerefore required to bear
try? following flarmability warning (40 CFR 162.1fl(nM2)(iii)(13)l:
"Co not use or store near neat or open flame."
-------
CHAPTER V
E^VUOMEtfTAL FATE OF MCPA
Introduction
Data on the fate of a pesticide once it enters the environment are required to
predict and estimate any potentially harmful effects on man and the
environment. The fate of pesticide depends on its formulation type,
application methods or use patterns and its chemical, physical, and biological
behavior in the environment.
Environmental studies from which data are required include physical and
chemical degradation, metabolism, field dissipation, and accumulation.
MCPA is available in soluble and emulsifiable concentrate formulations. These
formulations contain a variety of salts and esters of MCPA including the
sodium salt of MCPA, the dimethylamine salt of MCPA, the diethanolamine salt
of MCPA, the isooctyl ester of MCPA, and the butoxyethyl ester of MCPA. MCPA
acid, tne dimethylamine salt of MCPA, the isooctyl ester, the butyl ester, tne
butoxyethyl ester, and a mixture of the isobutyl, isopropyl, and butyl esters
are registered manufacturing-use products. The Agency requires data on the
fate of MCPA acid in the environment, and data on the fate of each salt and
ester found in end-use products.
Because of the interconvertability of MCPA acid and salt forms, MCPA acid and
its salts may be considered as one entity for Environmental Fate testing
requirements.
For MCPA esters, the situation is different. The Agency has no data on the
rates of hydrolysis of MCPA esters in living or nonliving systems. The Agency
has no basis for assuming tnat MCPA esters are equivalent to MCPA acid for
testing purposes. Therefore, registrants of manufacturing-use MCPA esters and
registrants of integrated end-use products containing unregistered technical
esters, must provide testing on each ester, or, cite available data showing
that a particular ester would be equivalent to MCPA acid under test
conditions. Data on analogous chemicals (e.g. 2,4-D) would be acceptable.
Use Profile
MCPA is a phenoxy herbicide used on a variety of crop and non-crop sites to
control a wide spectrum of broadleaf weeds. MCPA is formulated as 1-4
pound(s) per gallon emulsifiable concentrates and soluble concentrates. There
are 62 products containing MCPA as the sole active ingredient (SAI) registered
with EPA. The forms of fCPA available as SAI are MCPA acid} sodium salt,
diethanolamine salt, dimethylamine salt, isoocytl ester, butyl ester, and
butoxyethyl ester. The dimetnylamine salt is the most frequently used
formulation. The salts are highly water soluble \/hile tne esters are not water
soluble but are readily mixed. Table 5-1 presents the forms, formulations and
number of products containing MCPA that are registered with EPA.
43
-------
Table 5.1 MCPA Formulations and Products
Form
MCPA (acid)
Salium Salt
Diethanolamine salt
Dietnylamine salt
H n
n ii
Isooctylester
Butylester
Butoxyethyl ester
(Mixture) Butyl and
Formulations
SC*
SC
SC
SC
SC or EC*
• <*•
EC or SC*
EC
EC
EC
Pounds acid
equivalent
per gallon
2
4
1
5
4
4
4
4
'total
Huinber
of Pro-
ducts
8
8
2
1
1
21
• 8
1
3
1
Manufacturing
Products
8
0
0
1
4
1
2
2
Isopropyl esters
(Mixture) Iscbutyl,
Isopropyl, and Butyl esters
* SC = soluble concentrate
EC = emulsifiable concentrate
Based on tne preliminary quantitative usage analysis prepared by EPA
economists, tne net domestic supply of MCPA for 1979 was estimated at 3.25 to
3.70 million pounds. The majority of MCPA produced in the U.S. (55 to 65%) is
used on wheat grown in tne Plains States. The second largest use (12 to 14%)
is on rice in California. These two sites, in addition to the other small
grains (barley, oats, rye), comprise 85 to 95% of MCPA annual usaqe. Other
sites for wnicn WCPA use is registered are: alfalfa, clover, flax, grasses
(grown for seed), non-crop areas, pastures, peas, rangeland, grain sorghum, and
turf. MCPA is used domestically on hcme lawns. Table 5-2 presents use
information.
Most MCPA is applied postemergencc by farmers or professional applicators.
Application Is usually made by fixed-bocm ground rig sprayers in 10 to 3C
gallons of water per acre. MCPA is also applied aerially in 2 to 10 gallons of
water per acre, primarily on rice. Application of MCPA is subject to tho same
kinds of state restrictions as other pnenoxy herbicides. These restrictions
are designed to reduce drift and off-target movement by
-------
Table 5-2. PestlcldaJ Uses of HCPA
BJP
Use Sites Formula-
tions
Small grains - Ml
oats, barley,
rye, wheat
Small grains Sodium
with legumes and amine
(clover or salts
alfalfa)
Season or Crop
Growth Stage
Apply after crop 1' as
reached 3 or 4 leaf
stage up to boot
stage.
Apply after cereal is
well-tillered and
before boot stage.
Application
Type Equipment
Postenergent Aerial or
broadcast ground rig
sprayers
Postenergent Aerial or
broadcast ground rig
sprayers
0.125 to 1.5
Ibs. active
Ingredient
per Acre
0.125 to 0.5
Ibs. ai/A
Hunter of
> Treatments/
Intervals
1 per crop
1 per crop
Cannon Tank
Mixes
Hith dicamba,
brcmoxynil,
plcloram
None
Notes and
Limitations
Application rate
depends on nature
of weeds; average
rate is about
0.5 Ibs.
Legune should be
protected from
herbicide by
grain or weed
cover. Apply
in not more than
5 to 10 gal. of
water per acre.
Rice
Sodium
and amine
salts.
butoxy-
etnanol
esters
Apply at nidseaaon
35 to 65 days after
seeding.
Postenergent Aerial
broadcast
0.75 to 1.5
Ibs. ai/A
1 per crop
None
Field should be
flooded with
2 to 3" of water.
Mr tempera-
ture should be
below 90 F.
-------
•table 5-2. Pesticidal Uses of HCPA
Use Sites
Flax
Clover and
Alfalfa
V
Grasslands
and Seed
Grasses
HIP
Formula-
tions
All
Sodium
and arolne
salts
All
Season or Crop
Growth Stage
Apply when flax has at
least 3 or 4 leaves tnd
before it cores intc
bud.
Apply in fall after
frost when legumes nee
fully dormant.
Apply when weeds an;
actively growing;
before grass boot stage.
Type
Postenergent
broadcast
Postenergent
broadcast
Postenergent
broadcast
Application
Brjuiprtnnt
Aerial or
ground rig
sprayers
Ground rig
sprayers
Aerial or
ground rig
sprayers
Number of Cannon Tank
Rate Treatments/ Mixes
Intervals
0.125 to 0.75 1 per crop With TCA,
Jbs. al/A da la pan
0.125 to 0.5 1 per crop None
Ibs. ai/A
0.5 to 1.5 tepeat as
Ibs. ai/A needed
Notes and
Limitations
Treatment air
benperature
' should be above
above 40
degrees P.
Grass for seed
is treated at
lower applica-
tion rates and
treated before
boot stage to
avoid seed blast.
PeasTfleTd" Sodium or Appljf no later than"
or green) amine 3 nodes before first
salta pea flowering (spring).
Postenergent Ground rig oTliS to tfTTfS T per crop"
broadcast sprayers, sane Ibs. ai/A
sane aerial
None
Do not spray peas
stressed tram lack
of moisture.
-------
Table 5-2. Pesticlda] Uses of NCPA
GUP
Use Sites Formula-
tions
Sorghum Sodium
salt
Turf Sodium
or amine
salt
Noncrop such All
as:
fallowland,
farm premises,
fenoerows,
commercial/
industrial
site, parks,
forest
chaparral,
shelter belts,
tlmberlanda,
roadsides and
rights-of-way
Season or Crop
Growth Stage
Apply when crop la
6 to 12" but be fort;
boot stage « Heeds
should be less than
5- tall.
Apply when weeds are
actively growing
(best In spring or
fall).
Apply when weeds are
actively growing.
Application Nunfcer of Cannon Tank
Type Equipment Rate "Treatments/ Mixes
Intervals
r
Postemergent Aerial or 0.75 Ibs. 1 per crop None
broadcast ground rig a I/A
sprayers
Postenergent Ground rig 0.5 to 2.0 Repeat as
broadcast sprayers and Ibs. ai/A necessary
knapsack
sprayers
Postemergent Mostly fixed 0.125 to 3.0 Repeat as With picloram
broadcast or ground rig Ibs. ai/A necessary
directed spray sprayers or (depends
hand-directed on weed)
sprayers,
sane aerial
Notes and
Lint tat ions
Sorghum hybrids
vary in their
tolerance to
ttPA. Use of a
surfactant may
increase chance
of crop injury.
Do not mow
within 2 days
before or after
application.
For control of
whitebcush add
1 gallon diesel
oil to ML'PA in
8 gallon water
per acre.
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Table 5.2 Manufacturing Product Labels for MCPA
Label^ Number Active Ingredient %A. I.
264-228
359-588
6305-12
7173-127
7969-34
8203-18
9618-11
39335-4
359-628
Product Name
Manufacturers
359-669
534-131
9618-12
39511-44
39511-43
11687-76
39511-45
9618-10
MCP Acid
MCP Acid
MCP Acid
MCP Acid
MCP Acid
MCP Acid
MCP Acid
MCP Acid
95%
98.5%
94%
95%
85%
94%
95%
94%
MCP Dimethylamine Salt 64.1%
MCP Isooctyl Ester 96%
MCP Isooctyl Ester 99.0%
MCP Isooctyl Ester 99.9%
ICP Isooctyl Ester 97%
MCP Butyl Ester 97%
ICP Butoxyethyl Ester 97.0%
ICP Butoxyethyl Ester 97%
MCP Isopropyl Ester 47.5%
ICP Isobutyl Ester 28.5%
ICP N-Butyl Ester 19.0%
ICPA
Rhodia MCPA Acid
ICPA (Technical Grade)
Chempar MCPA Technical Acid
O-46 MCP
*\
MCPA Acid
ICPA Acid
MCPA Acid
Rhodia MCPA Amine
(5 Ib. Concentrate)
Rhodia MCPA Isooctyl Ester
Technical MCP Ester
Technical I 0 Ester
Transvaal MCPA Isooctyl
Transvaal MCPA Butylester
MCPA Low Volatile Oxy Ester
Transvaal MCPA Low Volatile
Oxy Ester
Mixed Technical MCP
MCP Ester
Amchem Products, Inc.
Rhodia, Inc.
Robeco Chemicals, Inc.
Chempar Chemical Co., Inc.
BASF Wyandotte Corporation
Chipman Chemicals, Ltd.
Trans Chemic Industries, Inc.
Pallek-Lankro Corp.
Rhodia, Inc.
Rhodia, Inc.
AGSCO, Inc.
Trans Chemic Industries, Inc.
\fertac, Inc.
\fertac, Inc.
Transvaal, Inc.
\fertac, Inc.
Trans Chemic Industries, Inc.
-------
volatilization (particularly esters). Typical restrictions include limits on
certain formulations (usually esters), wind speed, temperature and application
method. Scne states (California and Oregon) require special permits for the.
use of pnenoxy nerbicides.
Environmental Fate Profile
Data on pnysico-cnemical degradation, mobility, and accumulation are requried
for MCPA acid, salts, and esters of MCPA. However, the Agency has determined
that because of the interconvertability of MCPA acid and salts, MCPA and salts
may be considered as one entity for testing purposes. For esters the situation
is different. The Agency has no data on the rates of hydrolysis of MCPA esters
in living and non-living systems, and, therefore, there is no reason to believe
that MCPA acid and esters are equivalent for testing purposes. Registrants of
products containing esters of MCPA acid have the option of providing all
categories of data on each ester form, or of citing data showing that a
particular ester would be equivalent to MCPA acid under test conditions. The
Agency will accept references to valid data on analyogous chemicals (i.e.,
2,4-D).
Preliminary data indicate that MCPA may not hydrolyze at pH 7, because MCPA
was not lost following heating at temperatures of 34 to 35°C for 13 days.
MCPA appears to pnotolyze, and has a photolytic half-life of 20 to 24 days in
sunlight at pH 8.3. When exposed to fluorescent light, three major photolysis
products (4-chloro-2-methyl-pnenol, 4-chloro-2-formylpnenol, and o-cresol)
are formed within 71 hours at pH 9.8.
'i
Because MCPA adsorbs to organic matter, it is degraded more rapidly in soils
containing less than .10% organic .natter .than _in .soils ogn^ining higher levels
of organic matter. The half-life of MCPA at pH 5.5 to 8.5 is 5 to 6 days. /At...
pH's of 5 and below, the half-life increases and ranges from 13 to greater than
50 days.
MCPA is degraded by aquatic organisms within 13 days of application. Soil
bacteria, fungi, and algae are capable of metabolizing MCPA, with MCPA being
utilized as a source of carbon in many species. In general, growth and other
biological functions of microorganisms are not inhibited by MCPA. However,
there are data available which indicate that MCPA may inhibit nitrogen
fixation in Phizobium spp. and in blue-green algae.
MCPA can be expected to leach in most soil types, with the degree of leaching
being inversely related to the amount of organic matter in the soil. Mobility
increases as the amount of organic natter decreases, probably duo to the
adsorption of MCPA to soil organic natter. Because of its ability to readily
leach in certain soil types, MCPA may contaminate groundwater. This would be
especially true of fCPA salts, which are highly water soluble. Sampling and
monitoring data frcm wells in Ontario, Canada indicated MCPA residues (1.1-
1,000 ppb) in 2 of the 237 wells sampled.
Since MCPA is degraded less rapidly and leaches more slowly in soils high in
organic matter, MCPA can be expected to dissipate at a much slower rate in
these soil types. The field dissipation of MCPA may require up to 20 weeks
HI
-------
following initial application. In the aquatic environment, however,
dissipation occurs much more rapidly, typically within 32 days of application.
A cannon netabolite of MCPA, 5-cnloro-o-cresol, is formed at low levels
within 1 day of application to water. Although data indicate that hCPA does
not seem to persist in water, it may indeed persist in sediments. MCPA also
seems to persist in leaf litter and the upper 3 on of soil in the forest
ecosystem.
Exposure Profile
The high volatility of most MCPA ester formulations increases the potential of
respiratory exposure, whereas the MCPA salt formulations are essentially
nonvolatile. Spray drift, primarily from aerial spraying
operations using ester formulations, may lead to exposure of humans,
livestock, wildlife, and crops outside of the application site. It is
anticipated that the most significant direct exposure will be to workers
during mixing and loading operations. Dermal and ocular exposure from
splashing of the concentrates can occur during mixing of the SC/L and EC
formulations. Respiratory exposure to highly volatile ester formulations may
also occur. However, no data are available to assess such exposures. Dermal
and ocular exposures could be minimized by the use of gloves, goggles, and
otner protective clothing while MCPA is being handled. Respiratory exposure
during mixing could be minimized by working in well ventilated areas or
wearing an appropriate respirator.
More data are necessary to fully estimate potential exposure to MCPA. These
data include: bioaccumulaticn data and the octanol/water partition
coefficient; da.ta to quantify human exposure during handling and application
operations; data showing dissipation of dislodgeable residues on plant
surfaces; and volatility data which would indicate potential inhalation
exposure.
Topical Discussions
Physico-Chemical Degradation
One preliminary study indicated that MCPA is resistant to hydrolysis at pH 7,
because MCPA \ras heated to 34 to 35°C for 13 days at pH 7 without any
noticeable loss (Soderquist and Crosby, 00004448 and 05003445). MCPA in 1%
tlaHCO-j aqueous solution (pH 8.3) has a photolytic half-life of 20 to 24 days
in sunlight (Soderquist and Crosby, 00004448 and 05003445). When exposed to
fluorescent light (>290 urn), MCPA in aqueous solution (pH 9.3) produces three
minor «10%) photolysis products: 4-chloro-2-methyl-phenol, 4-chloro-2-formyl-
phenol and o-cresol in 71 hours.
Metabolism •
MCPA is degraded more rapidly in soils containing less than 10% organic matter
tnan in soils containing higher levels of organic matter. In soils containing
less than 10% organic matter, MCPA was degraded within 1 day. In soils
containing higher percentages of organic matter, degradation was slowed to
between 3 and 9 days (Torstensson, 1975, 05008552). This may be due to
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adsorption to the soil organic natter. MCPA, when applied a second time to
soil, is degraded almost twice as fast (5 to 12 days) as it is after one
application (15 to 28 clays). The nalf-.life of MCPA, in a soil-inoculated salt
solution, is 5 to 6 days at pH 5.5 to 8.5 but increases to 13 to >50 days at
pH's of 5 and below. Preliminary evidence indicates t-.nni: oersistence is not
.influenced greatly by soil type (Loos et al., 050121941.
Unlabeled MCPA in rice paddy water under dark conditioas is almost totally
degraded (over 99%) by aquatic microorganisms in 13 days (Soderquist and
Crosby, 00004443 and 05003445).
Several bacteria are capable of metabolizing MCPA, and degradation is rare
rapid if bacteria become adapted to (CPA. The proposed MCPA degradation
patnway for Pseudonpnas (NCIB 9340) (Ganar and Gaunt, 05005451; Gaunt and
Evans, 05003416) is as follows: side-chain loss (5-chloro-o-crcsol),
hydroxylation (5-chloro-3-methylcatecnol), ring fission (/-chloro- c<- -
-methylnuconic acid), denalogenation and lactone fomation (/-carboxynethy-
lene-o(-inetnylct-£butenolide), and lactone splitting (jj-hydroxy c* -
metnyLnuconic acid). Other products isolated from culture fluids indicate the
possiblity of minor metabolic pathways.
Arthrobacter sp. and Flavobacterium peregrinum also cleave tne acetate side
cnain, yielding 5-chloro-g -cresol (Bollag ot al., 05004641). The above
bacteria, as well as Acnronobacter sp., are capable of oxidizing 5-chloro-
o-cresol and/or 4-chlorocatecnol, a potential fICPA degradation product
(Boll^g et a_l., 05004641; Loos et a.L., 05001910; Steonson and tlalker,
05004430 and 05013551). Pseudononas (NCIB 93'!0) and Arthrobacter sp.,
adapted to MCPA, ccnplete ring fission arr? dehalogenation of MCPA at'very~nlnrv
concentrations (1,000 and 2,000 ppm, respectively) within 120 hours (Bollag et
al. , 05004641; Gaunt and Evans, C5CC3-U6). Alcaligenes poradoxus JMP116 and
a"Corynebacteriun-like" bacterium also oxidize riCPA and, as with some of
the above bacteria, nay utilize MCPA as the sole carbon source (Fisheret al.
, 05003428; Jensen and Peterson, 05003757 and 05004434; Steenson and WaTJcer,
05015452). A transferrable plasmid, pJPl, allows A. paradoxus to utilize MCPA
as a carbon source (Fisher et a_l., 05003423).
Several fungi (Aspergillus niger, Fusariun culmorum, Gloeosporun kaki, G.
olivarum, Mucor sp., Penicillium sp., Scnizophyllum connune, Verticilliun
spp., and Zygorhynchus moelleri) metabolize MCPA (Faulkner and Vfoodcock,
05003766; tfel^j ima et a_l., 05005543; Tbrstensson et al., 05P04649). Two
fungal metabolites are 4-chloro-5-hydroxy-2-metnyIphenoxyacetato and
2- (2-nethyl-4-cnlorophenoxy )etnano.l.
Microorganisms, in general, are not inhibited by MCPA at recommended
application rates (0.1 to 1.5 ppn). While not inhibiting growth of Rhizobiun
spp. or blue'-green algae, MCPA at 0.1 ppn inhibits nitrogen fixation by
Rhizobium spp.; and at 20 ppn, nitrogen fixation by blue-green algae (Abou
Elfadl and Fahmy, 0500C511; Balezina, 05012661; DaSilva et al., 05005265 and
05009423; Fletcher and Raymond, 050057C8; Gillberg, OSOO^SB; Hutber et al.,
05020356; Noll and Bauer, 05020^66; Torstensson, 05004429; Vintikova et aT.,
05C03543). Soil microbial functions other than nitrogen fixation are generally
not affected by >VCPA at recommended rates of application, although nitrifi
S\
-------
cation nay be temporarily inhibited (De and Mukhopadhyay, 05004661; Grossbard,
05015630; Jensen and Sorensen, 05004656; Sooner, 050204C4; Torstcnssen,
0500418S; Verona, 05019175). The growth of bacteria, fungi, and algae
similarly is not inhibited by MCPA (Balezina, 05012661; Da Silva et al.,
05009865; Efe and Muknopaenygy, 05004661; Kulinska, 05019112; Kunert ,"0*5008678;
Metting and Rayburn, 05019047; Nakajima et-al., 05005548; Steenson and
Walker, 05015452; Torstensson, 05004188; Toure and Stenz, 05016148; Verona,
05019175; Wehr and Klein, 05015407; Wilkinson and Lucas, 05006526; Zauner et
al., 05021608).
Mobility
MCPA would be expected to leach in most soils. Phytotoxic levels of MCPA
leached 30 cm in a sandy soil column eluted with 50 cm of water (Herzel and
Schmidt, 05021236). Using soil thin-layer chromatographic techniques, MCPA
was mobile (Rr-0.6-1.0) in calcium montmorillonite clay (Helling, 05016652)
and in sandy loan and silty clay loam soils (Helling and Turner, 05004203).
Mobility increases as" the organic matter content decreases, possiblity due to
the adsorption of MCPA to this soil component.
Significant volatilization of MCPA is unlikely in the environment since no
MCPA volatilizes from an aqueous solution (pH 7.0) heated at 34 to 35°C for
13 days (Soderquist and Crosby, 00004448 and 05003445).
Adsorption of MCPA to soil requires further study. MCPA adsorbs to goethite
(nyclrated iron oxide) only at pH's below the point of zero charge «pH 8)
and adsorption increases with decreasing pH (Kavanagh et al., 05005526). The
role of such positively charged clay minerals in tne absorption of MCPA to
natural soils in unknown.
Groundwater Contamination
Because MCPA leaches in most soils, there is a potential for contamination of
groundwater (Herzcl and Schmidt, 05021236; Helling, 05016652; and Helling and
Turner, 05004203). MCPA residues were detected in 2 of 237 wells sampled in
Ontario, Canada, between 1969 and 1978 (Frank et jd., 05019954). One
positive sample had MCPA residue levels in the 1.1 to 10 ppb range and the
other positive sample had MCPA residue levels in the 101 to 1,000 ppb range.
An accidental spill of 1,000 liters of a 40% MCPA solution on soil in
Czechoslovakia contaminated wells within 150 m of the spill site. The wells
contained MCPA at 0.1 to 6.4 ppm for 8 to 11 months after the spill before the
concentrations decreased below detectable levels (Syneket al., 05009727).
Although ICPA is nobile in soils and has been detected in isolated well water
samples, degradation of MCPA in soil and water may reduce the potential for
groundwater contamination (Bollag et al^., 05004641; Faulkner and Woodcock,
05003766; Fisher, Appleton, and Pemberton, 05003428; Gamar and Gaunt, 05005451;
Gaunt and Evans, 05C03416; Jensen, 05003757; Jensen and Petersen, 05004434;
Loos et al^., 05003910; Nakajima, et a_l., 05005548; Steenson and Walker,
05015452, 05004430, 05013551; Soderquist and Crosby, 00004448; Soderquist and
Crosby, 050024-15, ; Torstenssen et al., 05004649).
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Dissipation
Using bioassays, MCPA appears to dissipate within 3 to 7 weeks from soil
treated witn 0.75 to 1.5 ppm for 6 to IS previous years (Doltose, 05011006;
Fryer and Kirkland, 05006578; Tbrstensen et al., 05004649). An initial
application of MCPA may require up to 20 weeks for complete dissipation.
In the forest ecosystem, MCPA remains in soil (0 to 3 cm) and leaf litter at
0.7 and 32 ppm, respectively, 10 months after application at 2.5 kg ae/ha
(Eronen et a_l. , 0500R355). MCPA residues in noss decline to 7% of tne
initial level within 40 days. Residues in soil (3 to 15 en deep) arc- not
detectable after 40 days.
MCPA dissipates from soil at similar rates whether applied alone or in
combination witn dicamba and bronoxynil (Suzuki, 00004563). The time required
for MCPA to dissipate to nondetectable levels from sandy and silt loam soils,
alone or in combination* is 30 to 60 days.
In the aquatic environment, MCPA dissipates rapidly (14 to 32 days) in water,
but residue levels in the flooded soil remain unchanged (Soderquist and Crosby,
00004443 and 05003445; Sokolcv et al., 05010497 and 05012269). A cannon
metabolite, 5-chloro-o-cresol, is Tomed at low levels (1.3% or less)
within 1 day of treatement. Frank et al., (05019954) detected MCPA residues
(1.1 to 1,000 ppb) in two of 237 weTTs sampled in Ontario, Canada, between 1969
and 1978.
Label Restrictions
Current label restrictions prohibit the use of MCPA-butoxyethyl ester in
greenhouses, on heavy clay soils, or wnere crcps './ill be planted in a rough,
cloddy seed bed. rCPA-diethanolamine salt or :CPA-isooctyl ester should not
be apnlied by air in the vicinity of sugar beets. .MCPA-isooctyl ester should
not •' l used around homes, recreation sites, or similar areas. MCPA-sodium
salt should not be applied with nozzles tnat produce a fine spray.
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CHAPTER VI
TOXICOLOGY OF HCPA
Introduction
A wide range of MCPA products are currently'registered for use.
Manufacturing-use products containing MCPA acid, the dimethylamine salt of
MCPA, the isooctyl ester, the butyl ester, the butoxyethyl ester, or a mixture
of the isobutyl, isopropyl, and butyl esters are currently available. End-use
products containing the sodium salt of MCPA, tne diethanolamine salt of MCPA,
the dimetnylamine salt of MCPA, the isooctyl ester of MCPA, the butoxyethyl
ester, or a mixture of tne butyl and isopropyl esters are also available.
The Agency is requiring a full battery of toxicological testing on technical
grade MCPA acid to support tne food uses of this active ingredient. The
Agency nas made a preliminary determination that acute, subchronic, and
cnronic toxicological itesting of MCPA acid will provide sufficient information
to support the requirements for testing of the technical grade esters of MCPA
and each manufacturing-use MCPA salt. Registrants have the option of
supplying the full battery of acute, subchronic, and chronic toxicological
testing on each technical grade ester and eacn manufacturing-use MCPA salt or
of citing data which show that a particular ester or salt will be equivalent
to MCPA acid under test conditions.
Manufacturing-Use MCPA
Toxicology Profile
Acute Toxicity
Single-dose oral toxicity testing of MCPA indicates that MCPA acid has a
relatively moderate acute oral toxicity in rats, with an LD^Q value of 1.33
g/kg in nale rats and .765 gAg in female rats. Ib data were available with
respect to the acute dermal toxicity, acute inhalation toxicity, primary
dermal irritation potential or dermal sensitization potential of MCPA.
Primary eye irritation testing of an end-use formulation indicates that MCPA
may be a severe irritant.
Acute Delayed iteurotoxicity
Because MCPA is structurally similar to a suspected neurotoxin, 2,4-D, testing
of MCPA may be required. The Agency is reserving its decision to require this
testing on MCPA until testing of 2,4-D has been completed. Testing of 2,4-C
is currently underway.
Subchronic Testing
Sufficient data were available to set = no-observed effect level (NOEL) for
MCPA of 3 mgAg in rats. Testing in beagle dogs indicates that MCPA may
5H
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induce dose-related curtailment of spermatogenic activity, tubular atrophy,
flnci prostntic cnangcs, including iimature and atropnio ^ppearancr?. Tne KCEL
for these effects was set at 4 mg/kg«
The Provisional Acceptable Daily Intake (PADI) of riCPA in the human diet is
.002 mgAgAfay or MPI .12 mg/day based on the NOEL reported in the subcnronic
dog study.
Teratogenicity and Mutagenicity Testing
In teratology testing of MCPA, reported results indicated that !£PA nf»y be
teratogenic and fetotoxic. The incidence of minor skeletal variants and
decreased fetal weights in mice was significantly greater at ICO r.ig/};g dietary
levels of fCPA. Tne NOEL for this effect was set at 25 mg/kg« In a separate
study at dietary levels of 60 and 100 mg/kg» the major nalformation rate was
significantly increased and fetal weights were significantly decreased. The
NOEL for fetotoxicity was set at 30 mgAg-
in mutagencity testing of ?1CPA, data were available wnicn indicated that MCPA
nay be a weak mutagen in certain study systems. MCPA was observed to induce
mutations in Saccnaroryces cerevisiae and in Drosopnila. liCPA nas also been
reported to cause inhibition of testicular DNA synthesis in male mice.
Other mutagenicity testing indicates tnat MCPA does not induce mutations.
Thus, data are inconclusive, and additional testing is required.
Reproduction
A valid reproduction study was not available for review. However, a
supplementary spematogenesis study showed that male rats receiving as low as
13 mgAg/day MCPA in drinking water had slight degeneration of the semini-
ferous tubules with loss of spermatids. It should ho noted that those effects
were erratic, but nonetheless similar events were demonstrated in the
subchronic feeding study using dogs.
M,
letabolisra
Metabolism data indicate tnat the major route of excretion is urinary
elimination in rats within 192 hours of dosing. The data did not indicate
MCPA bioaccumulation.
No other valid data on the toxicity of ?£PA acid were available for review.
Chronic feeding studies, additional reproduction studies, and oncogenicity
testing are required.
Topical Discussions
Acute Oral Toxicity
Adequate acute oral toxicity testing in rats (Raltecn, 19??, 00021972) is
available for technical grade MCPA acid. In this study, MCPA was administered
•35-
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in water by means of a feeding needle to 8 male and 3 female Sprague-Dawley
albino'rats. Tnc estimated oral LD^Q in tne male rat was found to be 1.383^
gAg body wsight v/ith 95% confidence limits of 1.124 to 1.71fi g./kg, and in tnp
female rat was determined to be 0.765 g/kg body weignt with 95% confidence
limits of 0.598 to 1.025 gAg« Gross autopsy revealed no significant specific
toxicity. Data are sufficient to satisfy Agency requirements.
No data were available on any manufacturing-use salt or ester of MCPA.
Testing is required unless registrants provide suitable evidence to
substantiate tnat particular salts and esters will be similar in toxicity to
MCPA acid.
Acute Dermal Toxicity
Mo data were available; testing of MCPA acid is required. Testing of each
manufacturing-use salt and ester of MCPA is also required unless registrants
provide suitable evidence to substantiate that particular salts and esters
will be similar in toxicity to MCPA acid.
Acute Inhalation Toxicity
Partial data are available for the sodium salt of MCPA that indicate that this
salt is in Toxicity Category IV. Testing of all other manufacturing-use salts
and esters of MCPA is also required unless registrants provide suitable
evidence to substantiate that particular salts and esters will be similar in
toxicity to MCPA acid.
Primary Eye Irritation
Available data on a soluble concentrate formulation containing the sodium salt
of :r""A indicates that this formulation is a severe irritant to the eye. This
testing places MCPA in Category I for primary eye irritation. See the topical
discussion under end-use MCPA for details on this study. Registrants have the
option of accepting this determination and classification for T1CPA acid and
each of its salts and esters, or of supplying data specific to technical grade
MCPA acid and each of its salts and esters.
Primary Dermal Irritation
No data were available; testing of MCPA acid is required. Testing of each
manufacturing-use salt and ester of MCPA is also required unless registrants
provide suitable evidence to substantiate that particular salts and esters
will be similar in toxicity to MCPA acid.
Dermal Sensitization
No data were available; testing of MCPA acid is required. Testing of eacn
manufacturing-use salt and ester of MCPA is also required unless registrants
provide suitable evidence to substantiate that particular salts and esters
will be similar in toxicity to MCPA acid.
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Acute Delayed Heurotoxicity
/
Although MCPA is not expected to cause cholinesterase depression, it is
structurally related to 2,4-D wnicn is suspected of causing neuropathy.
lasting of 2,4-D is currently underway. The Agency is reserving tnis
requirement for testing of MCPA until the results from 2,4-D testing have been
subnitted and evaluated.
Subcnronic Oral Toxicity
The minimum data requirement for subcnronic oral toxicity is one test of iiCPA
acid in two mammalian species, preferably the rat and dog. Testing of eacn
manufacturing-use salt and ester of MCPA is also required unless registrants
provide suitable evidence to substantiate that particular salts and esters
will benave similarly under test conditions.
A subcnronic oral toxicity test is required for FCPA because its uses
(application to food crops) require a tolerance.
An adequate study was conducted on Charles River rats (10 animals/sex/dose) fed
0, 4, 8 and 16 mgAg/day technical MCPA acid for 90 days (Holsing and Kundzin,
1«70, 00004776).
Tne mean body weights, weight ranges, food consumption, and survival data of
the test animals were comparable to the control values. Ito mortality was
noted.
The hematocrit and hemonlobin dot^r^.ir.ritions, erythrocyte counts, tots! *nd
differential leukocyte counts, fasting blood sugar, BUII, total serum protein,
total serum bilirubin, SGCT, serum alkaline pnosphatase, and scrum
electrophoresis, recorded at 1 and 3 months from 5 rats of eacn sex fron tne
control and each test group, revealed no significant differences from tne
control values. The serum albumin, serum sodium, serum potassium, serum
chloride, carbon dioxide, serum calcium, and SOOT determinations, mede at 3
months only from 5 animals of each sex frcm the control and each test group,
revealed no significant differences between tne test and control values. The
urine analysis conducted at 1 and 3 months revealed no abnormalities.
Organ weignts of tne heart, liver, spleen, kidneys, testes with epididynis,
thyroid, and adrenals revealed signficiant increases in the male kidney weight
and organ to-body-weight ratio for tne males at 16 mg/kg/day. Hale kidney
weignts at the 4.0 and 8.n mgAg/day levels shoved a moderate increase in
weight.
The microscopic examination of the pituitary, thyroid, heart, liver, spleen,
kidney, adre'nal, stcnacn, pancreas, small intestine, large intestine,
mesenteric lymph node, urinary bladder, testis, ovary, and bone marrow from
five male and five females fron the control and 16 mgAg level, plus the
liver, kidney and unusual lesions from five of eacn sex of tne remaining test
groups, revealed no histopathological alterations which could be considered as
compound-related. The no-effect level for rats is
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An adequate study was conducted en Beagle dogs (4 animals/sex/dose) fed (0, 4,
8 and 16 mgAg/day) technical MCPA for 13 weeks (Holsing and Kundzin, 1970;
00004757).
The appearance, behavior, and appetite, of the test animals was considered
normal. The hematology data showed normal variations. Ib compound-related
alterations were evident. The blood chemistry data revealed no significant
alterations. Within these normal observations two trends were noted, one
being the slight increase in BUM value at 13 weeks for males and the other an
increase in the bronsulphalein retention at 13 weeks in males.
The 16 ngAg males showed decreased testis weights and weight ratios. Other
organ weights were not remarkable. Microscopic examination of tissues
revealed 3 of the 4 high level dogs to exhibit curtailment of spermatogenic
activity and varying degrees of tubular atrophy. Prostatic changes associated
with the testicular abnormalities were immature or atrophic appearance. A
similar prostatic alteration was noted in 2 of 4 animals at the 320 ppn level
and 1 of 4 animals at'the 160 ppm and in 1 control dog. These data show that
the no-effect level for dogs is 4 mgAg.
A supplementary study (Holsing, 1968, 00004756) was conducted on Beagle
dogs (3 animals/sex/dose) fed technical MCPA for 13 weeks at the following
dose levels: control, 25 mgAg* 50 mgAg» 100 mgAg* There was body weight
loss noted at all dosage levels.
The hematolcgical data for low level (25 ngAg) revealed only 1 female with
gradual decrease in the hemogran at 1 month. The middle level (50 mgAg)
animals also showed lowered nemograms in addition to marked increase in hand—
cells and slignt increases in metamyelccytes. All dogs of the high dose (100
mgAg) level showed a decrease in hemograms at the 1 month interval.
The biochemical studies snowed a variety of abnormal findings throughout the
test and control animals. The abnormal findings which appear compound related
were elevated BUN at all dosage levels, elevated SCOT at all dosage levels and
a decrease in the serum postassitrn. The data resulting from the 13 week dog
feeding study indicate that the no-effect level is less than 25 mgAg.
A supplementary study (Holsing and Kundzin 1968; 00004775) was conducted on
Charles River rats (10 animals/sex/ dose) fed 0, 25, 50 and 100 mgAg/day
technical MCPA for 90 days Body weight gain inhibition was noted for both
sexes at the 100 mgAg level. Food consumption for this level showed a
decrease as compared to the control values. The doses selected were too high
to ascertain the no-effect level.
The clinical laboratory studies conducted on 5 animals of each sex from the
control and test groups, at 1 and 3 months consisting of hematocrit and
hemoglobin determinations, erythrocyte counts, total and differential
leukocyte counts, fasting blood sugar, BUN, total serum protein, total serum
bilirubin, SGPT, serum alkaline phosphatase, serum electropnoresis, plus the
serum albumin, serum sodium, serum potassium, serum chlorides, carbon dioxide,
serum calcium and SCOT revealed no significant differences between the test
and control values.
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Urino analysis conducted at 1 and 3 months and consisting of specific gravity,
pH, glucose, ketones, total protein, bilirubin, and microscopic examinationvof
trc sediment stowed no significant compound related differences between the
test and control animals. Organ weights of tne heart, liver, spleon, kidneys,
thyroid, adrenals, and testis witn epididymis. revealed a significant decrease.
Of tnese findings only the decreased liver weight appears to be conpound-
related.
The microscopic examination of the pituitary, thyroid, adrenal, heart, spleen,
kidney, liver, stomach, pancreas, snail intestines, large intestines,
mesenteric lympn node, urinary bladder, testes, ovary and bone marrow revealed
dose related cytopathologic changes in the kidney and liver. The data
indicate that tne no effect level in rats is less tnan 25 mg/kg/day.
Available data satisfy Agency requirements for testing of MCPA acid.
• s
Otner inadequate subchfonic oral toxicity tests were conducted in rats and are
briefly discussed below:
In an inadequate subchronic oral toxicity study (Hattula et al., 1077,
05003795), male Sprague-Dawley rats (10 or 20/dose) were given analytical
grade MCPA acid in drinking water at concentrations of 100, 500, 1,000, 2,nno
and 3,000 mg/liter for 9 weeks. The deficiencies in this study included
observations on less tnan 10 rats per dosage, use- of only one sex, incomplete
pathological data, lack of clinical observations, and inadequate reporting of
group findings. These deficiencies preclude tne uso of this study.
In another inadequate oral study, the toxic effects of analytical grade I-'CPA
on spematogencsis in young rats were investigate (Elo and Parvinen, 197 G,
C50C41G1). Tne use of less than 10 rats per dose, the short duration of
the study, and discrepancies in recording some of the data preclude the uso of
this study.
Subchronic Inhalation Toxicity
The minimum data requirement for subchronic inhalation toxicity is one test on
technical MCPA acid and each salt and ester, preferably using the laboratory
rat. Testing of each salt and ester is required unless registrants submit
evidence substantiating that the particular salt or ester will be similar in
toxicity to MCPA acid.
A subcnronic inhalation toxicity test is required if pesticidal use will
result in repeated inhalation exposure at a concentration which is likely to
bo toxic as determined from tne results of tne acute inhalation testing and
other testing. This test could be required pending the results of the acuto
innalation toxicity tests of the technical chemicals. The acute inhalation
testing with the acid and sodium salt 2 Ib/gallon soluble concentrate/liquid
places that in Toxicity Category IV indicating very mild toxic effects.
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Subcnronic Ileurotoxicity
V
The minimum data requirement for sutxnronic neurotoxicity testing is one test
on technical MCPA acid, using a marmalian species.
A subchronic neurotoxicity test may be required if the pesticide snows
positive results in the acute delayed neurotoxicity test or induced
irreversible neurological toxicity in a mammalian species. Testing of each
salt and ester of !CPA may also be required.
A subcnronic neurotoxicity test may be required if the neurotoxicity test is
positive for 2,4-D (and !CPA, if tested).
Chronic Feeding
The minimum data requirement for chronic feeding is one test on technical MCPA
acid, preferably using the laboratory rat. Testing of each salt and ester of
MCPA is also required'unless registrants provide evidence substantiating that
a particular salt or ester will be toxicologically equivalent to TCPA acid.
A chronic feeding study is required if pesticidal use requires a tolerance or
an exemption frcn a tolerance, requires the issuance of a food additive
regulation, or is likely to result in repeated human exposure over a
significant portion of the life span.
A cnronic test is required for 'JCPA because its uses (application to food
crops) require a tolerance. »•
No data were available to assess tne cnronic feeding of MCPA. Testing' in a
mammalian species is required, and since the dog is the more sensitive
species, a 1-year dog study is necessary with nistopatnology of the gonads.
Oncogenicity ;-
The minimum data requirement for oncogenicity is testing in two mammalian
species, preferably the rat and mouse, using technical MCPA acid. Testing of
each salt and ester is also required unless registrants provide evidence
substantiating that a particular salt or ester will be toxicologically
equivalent to MCPA acid.
An oncogenicity test is required if the active ingredient, or any of its
metabolites, degradation products, or impurities is structurally related to a
recognized carcinogen or causes a mutagenic effect; requires a tolerance or an
exemption frm a tolerance; requires the issuance of a food additive
regulation; or is likely to^result in repeated human exposure over a
significant portion of the life span.
Oncogenicity testing is required for MCPA because its uses (application to
food crops) require a tolerance.
Ilo data wore available to assess tne oncogenicity of MCPA acid or its salts or
esters. Testing in two mammalian series is required.
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To ITS tcocn ic i ty
The minimum data requirement for teratogenicity is testing in two mammalian
species, using technical i-CPA acid. Testing of each salt and ester of MCPA is
also required unless registrants subnit evidence substantiating that a
particular salt or ester will be toxicologically equivalent to MZPA acid.
Teratogenicity testing is required if pesticidal use requires a tolerance or
an exemption fron tolerance, requires the issuance of a food additive
regulation, or is likely to result in significant exposure to females.
Teratogenicity testing is required for MCPA because certain uses (application
to food crops) require a tolerance.
A supplementary study has been submitted in two parts on tne teratology of
technical grade MCPA in the rabbit (Tucker, M. L., 1978; 000041635) and
Irvine, L. F. H., 1980;^ 000041637). The Tucker study is a range finding
attempt which used an extended duration of treatment frcn day 1 to day 27
gestation. This study on two dose levels (100 mgAg and 25 mg/kg) resulted in
no live foetuses at the nigh dose and no teratology at the lower dose. In
tnis experiment there was maternal death and toxicity from lung congestion due
to improper gavage techniques in the control group as well as at both levels
of MCPA.
Based on tnis range-finding study, Irvine dosed rabbits (15/or) at 5, 12, 30
and 75 mg/kg technical !-CPA by gavage. This protocol was appropriate to core
minimal guidelines with dosing -from day 6-to -day-IB..- -Thf3j-«?_uas-aasia-3:itn.cnal
lung congestion from inappropriate gavage dosing techniques which appeared to
be dose related to >CPA. The dans affected had otner thoracid pathology sucn
as fibrous adhesions to the thorax. The litters affected by tciratogenicity
were not correlated with tne maternal pulmonary affects. The protocol
indicated that eacn group would be randomly selected to have similar mean
weight and weight distribution which was not done. The animal room
temperature was to be 17°C; 'however, tnere were sharp changes in temperature
wnicn elicited sufficient animal stress (to induce changes in weignt in
maternal animals) at time of mating. This stress was sufficient to correlate
with teratogenicity in the litters. Thus the maternal loss is not dose
related nor was the number of corporal lutea, number of implantations, total
of early plus late fetal deaths as the percentage of implantations and the
litter weight. These parameters can, however, be stress-related.
In an adequate teratogenicity test, the cormercial formulation llorotcx 750
containing 75* w/w MCPA (2-methyl-4-cnloropnenoxyacetic acid) 75% purity, was
given daily by gastric intubation to pregnant mice, 20 per group, frcn day 6
to 15 of gestation at daily doses of 5, 25, and 100 ng/kg (Palmer and Lovell,
197-1, OC04447). Litter weights and mean fetal weights were significantly
reduced at 100 mg/kg. The incidence of minor skeletal variants was
significantly greater at 100 mgAg tnan in the controls, llo overt signs of
maternal toxicity except decreased weight gain at 100 mgAg compared to tr»e
control group. The no-effect level, based on the incidence of minor skeletal
defects and fetal weignts, was 25 ngAg.
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In an adequate teratogenicity test, the technical grade fCPEE (4-cnloro-2-
metnylphenoxyacetic acid etnylester), 94.12% purity, was mixed with food at'
levels of 2, 30, 60 and 100 ngAg and given to pregnant rats, 10 to 16 per
group, from day R to day 15 gestation (Yasurla and Msecte, 1972; 05003566).
Daily intake of MCPEE, based on food consumption, was calculated to he 2.7,
30, 60, and 100 mgAg.
The no-effect level for the fetuses was 30 mgAg. At 60 and 100 mgAg» tne
malformation rate was significantly increased and fetal weights were
significantly decreased. Cleft palate, ventricular septal defect, and kidney
anomalies were the major malformations. There was no maternal toxicity except
a dose related lower rate of weight gain in comparison to the controls group.
The major malformations were not significantly different fron controls.
Another adequate study completed in Sprague-Dawley rats (Irvine,
L.F.H.,1980;000041637) using MCPA tecnnical grade 20, 50, and 125 ngAg
resulted in minimal maternal toxicity at all doses, no effect on pregnancy
incidence, no difference in maternal weight gain and no difference fron
controls for tne mean number of corpora lutea, preimplantation losses and
implantations. There was also no significant MCPA associated early or total
intrauterine deaths, and no change in number of fetuses per dam. The litter
weights in all MCPA treated groups were significantly different from control
while the sex ratios for all MCPA groups were comparable to controls.
Minor external/visceral defects of fetuses were present in all MCPA-treated
groups but the incidence of these wero not significantly different from
controls. These include skeletal and muscular anomalies, dilated ureters,
increased renal pelvic cavitation and subcutaneous haemormagic areas and
skeletal defects.
There were no major skeletal defects in any of the flCPA-treated groups or the
negative control group.
The major visceral defects included encephalocele, craniorachischisis with
anopntnalmia, open eye, onphaloc, arthrogryposia, and disphragmatic hernia;
but these did not occur in significant numbers.
In conclusion, the Yasuda study differs fron the Irvine study in the extent of
teratology occurring with MCPA in the rat but in neither study was it
considered to be significant. The one mouse study by Palmer and Lovell (1971)
indicates that MCPA is not a significant teratogen.
The minimum data requirement for testing in two mammalian six-cies using MCPA
acid has beeh satisfied by Yasuda and Maeda (1972) in the rat and by Palmer
and Lovell (1971) in the mouse.
Reproduction •
The minimum data requirement for reproduction is testing In one mammalian
species, preferably the laboratory rat, using JCPA acid, and lasting for two
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generations. Testing of eacn salt and ester of MCPA is also required unless
registrants proviJe evidence substantiating tnat a particular salt or ester
will IDG toxicologically equivalent to MCPA acid.
Reproduction testing is required if nesticirlal use requires a tolerance or an
exception fion a tolerance, requires the issuance of n food additive
regulation, or is likely to result in repeated human exposure over a
significant portion of the lifespan.
In an inadequate study of the toxic effects on spermatogenesis, analytical
grade MCPA was given to young nale Sprague-Dawley rats in tne drinking water
at concentrations of 100, 500, 1,000, 2,000 and 3,000 ppn (Elo and Parvinen,
1976, 050041E1). Rats receiving 100 ppm (3 ragAg/day) nad slignt degeneration
of tne seminiferous tubules; those receiving 500 ppn (61 mgAg/day) and 1,000
ppm (112 mgAg/3ay) had mild degeneration with loss of spermatids; and the
rats receiving 2,000 ppn (190 mgAg/day) and 3,000 ppn (246 mgAg/day) had
moderate degeneration with occasional loss of sperraatids and spernatccytes.
The effect was erratic and some rats receiving 3,000 ppn had almost normal
spematogenesis. The study does not indicate what possible effects, if any,
MCPA could have on fertility, births, or survival. The use of less than 10
rats per dose, the short duration discrepancies in recording of seme data, and
failure to use females precludes the use of this study.
The above data is not sufficient to satisfy the requirement for reproduction
testing of MCPA acid. It should be emphasized that subchronic oral testing
revealed reduced spermatogenesis and tubular atrophy in testcs in both rsts
and dogs.
Testing is required.
Mutagenicity
The minimal data requirements for mutagenicity testing v/ill be finalized
pending formulation of Agency Guidelines.
Mutagenicity testing is required for MCPA because certnin uses (application to
food crops) require a tolerance.
One study was done to evaluate the ability of f£PA to induce histidine
reversion in Salmonella typninurium (Zetterbcrcj, 1979, C5004970). Although the
study was not sufficient to satisfy the data requirement because of incomplete
protocols (i.e., use of an incomplete set of tester strains, use of a single S-
9 concentration for microscnal activation, and lack of confirmatory testing),
the data suggest tnat MCPA, and 5-cnlorosalicylic acid (hydroxnethyl derivative
of ICPA), 3-chloro-o-crcsol, 4-cnloro-cresol, and 5- chloro-3-methyl-catecnol
were not rnutagenic under tne conditions of tne test system.
An adequate study was done to evaluate fCPA in tne above mentioned system by
Lassner et ad., (1977, 05003531) \;no reports negative results using 99% pure
MCPA on a set of four AMES tester strains of SeIrenelie typnimurium wnicn wore
pretested for genetic marks in addition to testing one of these strains
against four concentrations of S-9.
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Adequate studies to evaluate the toxic and mutagenic (histidine reversion)
effects of '1CPA and its methyl ester in tne Saccharonyces corevisiac? haploid
strain rad-18 were done by Zetterberg (1979, 05004970) MCPA was observed to
induce nutations, but only at amounts (3-6x10 -5 M of undissorriated 2cid) that
caused 95 to 99% lethality. The results were highly variable and were affected
by changes in temperature and pH. The data suggest that MCPA is a weak
nutagen in this study system. Also, a relationship was reported between pH,
temperature, and number of reversions. The degree of acidity of tne p!I and
elevation of the temperature drive the activity of MCPA to induce reversion of
tne histidiene (i.e., mutagenicity).
Zetterberg states that tne increase in hydrogen ions inside the cells to an
overwhelming amount causes this mutagenicity. Zetterberg theorized that
mutagenicity (histidiene reversion) in rad-18 cells only occurs in the
presence of overwhelming increased hydrogen ion overproduction fron the MCPA
being in an acid medium. This should be considered if other in vitro
mutagenicity tests are performed. MCPA methyl ester was about 100-fold less
active tnan MCPA. Zetterberg failed to disclose the purity of the test material
he used.
An inadequate study was done to determine tne percentage of X-cnronosomal
recessive lethals in meiotic and postmeiotic male germ cells of Drosophila
that were fed MCPA (unspecified portion) at concentrations of 5 and 10 mil
(Vogel and Chandler, 1974, 05003752). An increase in the percentage of
sex-linked of recessive lethals over that of controls was observed, but tne
difference was barely significant (p = 0.015) at pH = 8. The results suggest
tr.at MCPA is a weak nutagen in Drosoprsila, but tnis conclusion is derived from
combined data at "doses" of 5 and 10 mfl. There was no dose response data in
addition to other inadequacies. IJone of tne other chemically-related
herbicides tested (i.e., 2,4-D, 2,4,5-T; fCPB) caused any significant
increases in lethals. MCPA was not tested at acidic ptt's (5.8 or below).
An adequate study by Magnusson et al., (1977, 05016939) in which Drosophila
were continuously fed MCPA (94% pure) throughout their larval stages at "doses"
of 250 and 500 ppm, reported no increased sex-chromosome non-disjunction, loss
or exchange, but in contrast indicate an increase in number of recessive
lethals for both 2,4-D and 2,4,5-T when coapared to their own controls at a
significance level (P ,0.01) when the total F^ and ?2 data wcre combined.
In a review Propping et al., (1973; 05009237) mentioned negative results
reported by Buselmaier et al., 1972, 0501655 who tested MCPA in tne host
mediated assay in mice given 1000 mgAg subcutaneously against the Salmonella
typnimurium G-46 his- and Serratia marcescens A-21 leu; these studies further
support the notion that these "hormonal" herbicides present minor hazard in
systems involving namalian metabolism at pH's of 7.2 to 7.4.
MCPA has been reported to cause inhibition of testicular DMA synthesis
following intraperitoneal injection of tne chemical to male mice at a dose of
200 mg/kg (Seiler, 1979; 05003508). The study is inadequate because of
failure to report the purity of tne MCPA sample used.
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Tne above infomation is not sufficient to satisfy the criterion of multi-test
evidence required for mutagenicity. Only insufficient dat? nas been presented
in these minimal studies and additional testing is required especially in
species as recorranenotrd above.
Metabolism
Tne minimum data requirement for metabolism is a single dose using tne
analytical pure grade of the active ingredient in the radioactively labeled
form.
A metabolism study is required for MCPA because certain of its uses
(widespread application as an herbicide on food crops) requires a chronic
feeding study and oncogenicity testing.
Unlabeled ICPA, stated to be pure, was administered for a single day in the
diet of a steer (5 ppm) and in the diet of two cows (2.5 snf 5 ppn). Ttie
unchanged MCPA could be detected, but was not adequately quantified, in the
urine of these animals (Bacne et_ a_l. , 1964, 05006168).
Unlabeled t-CPA was administered for 28 days in the diet for beef calves so
that the amount consumed was 7 or 14 mgAg/day. One day after removal from
either diet, levels of MCPA were 1.4 to 23.3 ppm in kidney tissues, 0.06 to
0.09 ppm in liver tissue, and ,0.05 ppm in muscle and fat. Calves removed from
the high-dose diet for 6 days had 0.07 to 0.34 ppm in the kidney and 0.05
ppm,muscle, liver and fat. A possible metabolite, 2-Metnyl-4-cnloropnenol , was
found occasionally in kidney tissue in trace amounts (0.05 ppm) (Bjerke and
Herman, 1971a, 00004625).
Unlabeled MCPA (98.2% pure) was administered for 23 d?ys in the diet to
yearling sheep so that tne amount consumed was 15 ngAg/d^y. One day after
remo^l from the diet, levels of MCPA were 0.31 to 1.7 ppm in kidney tissue,
0.05 .0 0.12 ppm in liver tissue, and 0.05 in fat and muscle. 2-Methyl-4-
chloropnenol was found in trace amounts (0.05 ppm) in kidney tissue (Bjerke
and Herman, 1971b, 00004626).
1/1
"C-acetic acid-MCPA, of unstated purity, was administered by gastric
injection to Sprague-E&wley rats in a dose of 3 mg. In 24 hours, 92.3% of the
radioactivity was excreted in the urine and 6.8% in the feces. Between 2 and
.°. hours after injection, the highest concentrations of radioactivity were
present in the blood, kidney, lung, heart, suprarenal gland, liver, thyroid,
and bone marrow. Radioactivity disappeared from adipose tissue more slowly
than from other tissues (Elo, 1976; 050003256).
In an adequate study (Gilbert and Hopkins, 1978, 000041634) rats rapidly
absorbed and- excreted (C O-MCPA. Urinary excretion represented tne major
route of elimination accounting for 94.9 and 36.1 percent of the administered
radioactivity in male and female animals, respectively, in 192 hours. Fecal
elimination of radioactivity accounted for only 6% of the administered
radioactivity in animals of eitner sex during tne same period. 1*»e majority of
tne eliminated radioactivity (78.19%) was excreted by animals of eitner sex
during the first 48 hours.
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3.7% of tnc administered radioactivity was detected in the 24 hour bile from 3
bil« duct cannulated rats administered 100 rag/kg. P.O. (C )-MCPA, the
levels in the urine and feces of these aninals (20.3 and 10.5% of the
administered dose). Tissue concentrations of radioactivity in tne 3 male bile-
cannulated rats were markedly higher than the levels of tissue radioactivity
in^the non-cannulated animals 24 hours after a single oral administration of
(i'¥C)-MCPA.
Altnougn the author attributes these differences to relatively poor recoveries
of the radioactivity in the bile-cannulated rats (34.5%) and or relatively
poor medical conditions of the bile-cannulated rats, no evidence is presented
to support this hypothesis.
Three other fractions having R^ values of 0,0.8 and 0.15, (each accounting
for less tnan 5% of tne sample radioactivity) were not identified in the
study. The distribution of chronatographed radioactivity was not altered by
incubating tne urine samples with Beta-glucuronidasc compared with tne levels
detected in the 0-24 hours without incubation.
The tissue radioactivity levels in rats receiving multiple administrations of
the herbicide (mgAl3/d» P.O. x!4 d) show that bioacummulations did not occur.
Female rats receiving the multiple administration of the herbicide had
sligntly higher tissue radioactivity levels than did the male animals.
The results of tne latter experiments indicated the absorptions,
distributions, and eliminations of tne radioactivity were not affected by
repeated adminstrations of the herbicide.
Thin layer chromatography of urine sample indicated the presence of 5
radioactive fractions. The major fractions (accounting for 7.89% of the
sample radioactivity) behave in a chranatograpnically similar manner to MCPA
(Rf=0.412). A second fractions (Rj=0.40), accounting for 13.8% of tne
sample radioactivity was not identified in the study.
Tissue levels of radioactivity followed a similar time course as the plasma
radioactivity levels. Tissue radioactivity was seen 3 hours after the
administration of 100 mg/kg/day, P.O. C=MCPA). The level of radioactivity
in most tissue (the fat, skin, and ovaries are exceptions) were very low 192
hours after dosing.
14
Body autography of male and female animals, 6, 24, and 48 hours after ( C)-
ttPA administration, yielded results that were similar.
The major route of excretion is urinary elimination (94.9% male and R6.1%
female) in the rat in 192 hours and much smaller percentages by the bile and
feees.
The lack of an indication of tissue bicaccumulation of tne labelled MCPA or
metabolites is preliminary evidence that toxic events presumably would not
occur within the first few days of exposure; therefore further testing is not
required.
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Hunan Exposure
Three cases reports of hunsn poisoning by riCPA were available (Popr.an and
Davies, 1964, 05003770; Johnson and Koumides, .1965, 05004100; Jones et al.,
1967, 005008955). A 32-year old nan died as , result of drinking water which
contained about 85 nl of the herbicide "Verdone" comprised of 25% MCPA. The
letnal dose was approximately 440 mg/kg of MCPA (Popham and Davies, 1964).
Deatn occurred 20 hours after admission for treatment. The blood level of
MCPA was 23 mg/100 ml. In the second fatal case, (Johnson and Koumides,
1965), 65-year old man died after drinking an unverified 57 nl of "VercJone."
The letnal dose of MCPA was estimated to be 250 ng/kg- Deatn occured 20.5
hours after tne patient was found unconscious. The blood level of MCPA was 13
mg/100 ml. Stonacn washings contained 250 mg/100 ml of MCPA. The third
patient survived oosumption of tne herbicide "Phenoxyler.e Triple," which
contained 33% tCPA, 3.5% cresols, and other impurities.
Clinical signs of toxicity were similar in the three reports and included loss
of consciousness, constricted pupils, involuntary skeletal muscle twitching,
low blood pressure, excessive oral secretions and deep sighing respiration
with coarse rales. Clinical laboratory tests in Jones .et al. (1967)
suggested that kidney damage, liver damage and gastrointestinal bleeding
occurred after MCPA ingestion.
MCPA End-Use Products
1. Soluble Concentrates
Acute toxicity testing of each end-use product or substantially similnr
product is required for the registration of these products. A determination
of substantial similarity takes into consideration both the form of the active
ingredient found in a particular product as well as the types and nature of
inert ingredients. For purposes of acute toxicity testing or end-use soluble
concentrate products, acute tests are required on representative products
containing each different type of salt and ester. Alternatively, registrants
nay submit evidence substantiating that the toxcity of their end-use product
will be equivalent to MCPA acid.
Toxicology Profile
Soluble Concentrates Containing the Sodium Salt
Sufficient data were available to show tnat the 2 Ib/gal SC/L MCPA sodium salt
had a relatively high acute oral LDcn in mice (560 ngAg) (Cure!, 1964,
00022569) Cat. Ill; a high acute dermal LD™ in rabbits (2.0 mgAg)
(Raltech, 19??, 00021973) Cat. IV; and a very high acute inhalation LC50 in
rats (21.4 mg/liter) (Biesemiar and Angevine', 1977, 00021975) Cat. IV.
Sufficient data were available to show tnat tne 2 Ib/gal SC/L MCPA sodium salt
is a severe eye irritant (Raltech 1977, 00021974) Cat. I and is a mild skin
irritant (Raltc-cn, 1977, 00021976) Cat. IV.
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Soluble Concentrates Containing Dime tny lamina Salt
No valid data v.'pre svai.l^hl^ to gs?r>sc
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Bnulsifiaole Concentrates Containing Mixture of Dutyl and Isopropyl Esters
No data vjere available to assess t^e acute oral, ncut*? riomal, acute
inhalation, prinisry eye or^ priiuary denral irritation toxicity. Testing is
required or suitable rationale Trust be subrdtted to substantiate that tne
toxicity of tnis mixture will be similar to MPCA acid.
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CHAPTER VII
.RESIDUE CHeilSTRY OF NCPA
rCPA is a selective post-emergence herbicide used for the control of
broad-leafed weeds in small gain crops, especially wheat and rice. A wide
diversity of sites comprises the remaining uses and includes both croplands
and non-crop areas.
MCPA is registered for use in the form of its sodium, diethanolamine, and
dimethylamine salts, its iscoctyl and butoxyetnyl esters, and in a mixture of
its butyl and isopropyl ester. Table 5-2 lists the individual sites registered
for MCPA use.
MCPA is not registered for use in the form of its ethanolamine, triethanola-
mine, isopropanolamine, diisopropanolamine and triisopropanolamine salts,
although these forms are sanctioned in 40 CFR 180.339 (a).
The uses of MCPA on crops are food uses, and are expected to result in residues
in human food and in feed of food-producing animals.
The uses on ornamentals, rights-of-way; agricultural, ccmercial and industrial
premises; and aquatic, forest, chaparral, nonagricultural and wasteland sites
nave generally been regarded as non-food (N.F.) uses; but sane of these are
now viewed as food (or feed) uses with a potential for contaminating food.
Residue Chemistry Profile
MCPA is readily absorbed and translocated by plants, both through the roots
and leaves. It is concentrated primarily in the metabolically active portions
of the plant. MCPA is extensively metabolized in plants to 2-methyl-4-cnloro-
phenol and subsequently to breakdown products. It is likely that 2-raethyl-4-
chloropnenol and MCPA are readily conjugated with glucose and amino acids.
Available evidence indicates that in animals MCPA binds readily to the albunin
fraction of animal serum protein and is transported to the kidneys for the
renal excretion. MCPA does not appear to accumulate in muscle or fat tissue
nor in the liver or in milk.
The first determinations of MCPA were made using spectrophotometric methods.
Currently, most assays use sore form of gas chrcmatography.
Data Requirements and Data Gaps
The proposed Guidelines for residue chemistry have not been published.
Consequently there are no citations for guidelines corresponding to the types
of-residue chemistry data required to support individual registrations. In
general, nowever, the Agency must have sufficient data to be assured that the
residues of the parent material and its metabolites have been identified.
Available residue studies on small grains are weak in two respects. They are
sparse, and it is not always possible to relate the residues to an adequately
•20
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d and validated method. It is not always clear whether or not total
rc-sri'/iu'js are in f^ct being determined. Additional cUita en grains are
required, with a revaluation of the tolerance when these are received. In
e meantime, n&nitoring of trie grains is roconnnended.
For tnc riitcn ban); use of MCPA, tolerances or labeling restrictions are needed,
to be consistent with the policy established for 2,4-D.
Topical Discussions
Uptake, Distribution, and Metabolism in Plants
wnen applied in water, it is believed tnat MCPA is liberated from its salts or
esters, by dissociation or hydrolysis, in the spray, on the plant surface or
even within" the plant. The rates of dissociation and of hydrolysis are
believed to be rapid, although there seems to have been no direct evidence for
this for tne MCPA esters. There is a question as to v.-hether or not the MCPA
esters do in fact hydrblyze as rapidly as believer]. The residue nay consist
of some intact ester. Here the Agency asks the registrant to resolve this
question by developing a rationale, with references to data or analogous
pnenoxyalkanoic acids (2,4-D for example). Tne residual inorganic sodium
salt, amine or alcohol fron these processes nay linger for a time on the plant
before dissipating. More importance has been given to the fate of IICPA, which
like the other structurally-related pnenoxy herbicides, is readily absorbed
and translocated by bie plant (Robertson fit a_l_. , l'X>7, H5C15046).
MCPA is readily absorbed via tne roots. When hydroponically grown Acrostenna
gitnago plants were exposed to carhoxv-labelerl MCPA, the radioactivitv was
readily absorbed by the roots and translocated to the upper portions of the
plant (Sanad, 1971, 05015695).
A study conducted in Dickursby, Finland, shows that residues of MCPA in soil
will be absorbed by seme species and not by others. For example, Marrow stem
kale was found to contain MCPA at levels up to 0.7 ppn at 37 and 100 days
after applications of 1.5 kg/ha and 7.5 kg/ha at planting time. Under these
seine conditions, no residues (>0.no9 ppm) could be detected in barley and
clover (Lallukka, 1974, 05021559).
In some species, MCPA accumulates in seeds of treated plants in sufficient
quantities to disturb tne growth of subsequently produced seedlings (£berg et
£l., 1978, 05019071).
Badiotracer studies snowed that MCPA readily penetrates tne plant cuticle. As
the age of the leaf increased, the amount of F-'CPA bound in the cuticle wax
increased (Kirkwood et ai . , 1972, 05004272). Addition of a surfactant
increased tnd movement of the MCPA into a plant cell. When young bean leaves,
Vicia faba were treated, the MCPA was readily translocated throughout the
plant but primarily to the shoot apex and other rapidly growing portions of
the plant (Xirkwood et al., 19f>9, 05015041; Mueller, 1976, C5021735).
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14
When leaves of Sonchus arvensis were treated with C-labeled MCPA, the
direction and extent of translocation of radioactivity varied with plant age
and stage of development. When plants were very snail (largest 3 cm),
translocation was primarily directed to other leaves of the developing
rosette. When leaves of a large rosotto were treated, (loaves 5 to 15 cm)
translocation was directed primarily to the.roots. There was greater
accumulation in secondary than in primary roots. After the shoot started to
develop, (15 to 20 cm tall) radioactivity from C-labeled MCPA applied to
rosette leaves moved both acropetally and basipetally, with the major portion
moving to tne roots. At this stage, movement was similar whether a rosette
leaf or a leaf.near the inflorescence was treated. It is reasonable to
conclude that C-labeled MCPA tends to be translocated in the direction of
the metabolic sink at the time of application (Fykse, 1975, 050144%).
Some data on tne metabolism of MCPA are available. Most of the studies
presented employ C-MCPA where the radioactivity is in the carbonyl carbon.
As a result, little information is available on the breakdown of the phenoxy
ring. ";
In one metabolism study (Montgomery, 1970, 00005575) 14C-MCPA, as the
triethanolamine salt, was applied to the foliage of wheat plants. Thirteen
days later tne plants were harvested. The plants were extracted witn 80%
ethanol and the extracts subjected to thin-layer chromatograpny. Most of the
Kf band C was in a very low R^ band, indicating that the ccmponents
or tne residue containing "C were conjugated with plant constituents. A
portion of the alcohol extract was evaporated to dryness and hydrolyzcd with
1 M hydrochloric acid on a s^team bath for one hour. After acidification, the
hydrolysate was extracted with ether and-again subjected—to-tftin=layer-
chromatography. Two radioactive components were found in tne hydrolysed -
chronatograpny. Two radioactive ccmponents were found in the hyrolyzed
extracts. One was MCPA while tne other was of lower Rj, suggesting tne
presence of a more polar ccnpound.
Analysis of field samples treated at the boot stage, for the MCPA metabolite,
assuming it to be an hydroxy-MCPA compound, indicates that seme of it may
persist in the plant up to the time of harvest. However, as with MCPA, no
detectable amount of the metabolite was translocated to the grain. GLC-Mass
spectrograpnic analysis indicates that the metabolite of flCPA in wheat is a
conjugated hydroxy-MCPA which undergoes seme rearrangement upon hydrolysis
from plant constituents.
MCPA is degraded in plants by oxidative degradation of the acetic acid side
chain witn the production of a phenol metabolite (Aberg, 1978, 05019071).
The acid chain may be removed at the ether linkage, resulting in
2-methy1-4-cnlorophenol.
This occurs in red currants and is similar to metabolism of other pnenoxy
compounds. The methyl group at the two position is replaced in an -CH
substitution to fora 2-chlorocatecnol with subsequent ring cleavage of the
latter compound. MCPA can also be expected to be conjugated with glucose or
anino acids which could be a detoxification nechanism (Loos, 1979, 05016100;
Fykse, 1976, 05013377; Leafe, 1962, 05005795; Collins et al., 1971,
73.
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L'5003725). The metabolism of the pnenoxy herbicides in plants has been
extensively studioc ever tne years. Ilov;ever, data clocumenting the metabolism
of ''CPA in flax, pe-js, rice, pasture grasses, and clover were not submitted."
flCPA is readily ttsk^p. iio ?r.d tr?r.r located throughout the plant, concentrating
primarily in the met-aboiically active portions of the plant. MCPA is exten-
sively metabolized in plants to 2-metnyl-4-chlorcphenol and subsequently to
breakcb\;n products. It is likely that the 2-metnyl-4-chlorophenol and MCPA
are readily conjugated with glucose and amino acids. Available data satisfy
Agency requirements for plant metabolism data.
i-'etr.bolism in Food-Producing Animals
When use of a pesticide on agricultural crops may result in residues in animal
feeds, the Agency requires data on the fate of the pesticide in food animals.
Data on metabolism of MCPA in food animals consists of four feeding trials.
In 1%4, a one-cow feeding trial was conducted, in which a Jersey cow was fed a
complete ration containing 50 ppm MCPA for 4 days. ?3o f^CPA residues were
detected in the milk of this cow. Since this was a study done using early
analytical methods, the phenolic metabolite or tne presence of conjugated
residues was not determined (Bacne, et al., 1%4,
When beef cattle, sheep, and dairy cattle were fed !CPA at increasing levels
ranging frorn 10 to 20no pin in the total diet for two woc-k intervals (Lcnq, ejt
el., 1979, COOH4&22), significant residues of MC?.'. «0.^r nrO or its
phenolic metabolite «0.05 ppn) v;ere not detected in r.usclc, fst, liver, or
nil!'. SiJTv^l^r \jntil a ~ciicto>*v lev^l of—?H(vT>Tm~'?rT''—•~m^>e>^-i—(^Mr^t^a-aij^tMe—
ingcstion of 1000 ppm MCPA in the total diet of dairy rows is required to cause
tne consistent appearance of residues in excess of C.05 ppm MCPA or tne
pnenolic metabolite in milk or cream. The data also show that in general
residues of the pnenoxy herbicides and their phenolic metabolites do not occur
in conjugated form in milk../ The residues dissipate within one to three days
after withdrawal of the cows from a diet containing 1000 ppn of the pnenoxy
acids. Residues of phenolic metabolite are not greater than residues of the
parent compounds in each tissue. Residues of <0.05 ppm 2-methyl-4-chlorophenol
were found only in kidney of one calf and three sheep given 500 ppm MCPA in the
total diet for 2R days and slaughtered the next day. To detectable residues
were found in any other tissues of cattle and sheep fed 250 or 500 ppm MCPA for
28 days and slaughtered the next day or a 7 days after withdravral.
JCPA readily binds to the albumin fraction of animal serum protein and is
readily transported to the kidneys for renal excretion (Matlib j5t al., 1971,
05015451). \vnen MCPB and MCPA are fed to dairy animals at low levels (5 ppm),
the MCPB is partially converted to MCPA and that MCPA is quantitatively
recovered in the urine (Bacne, et al., 19G4, 00004702). In Holencova "(1973,
05017929), seme European workers found that the formulation and materials in
tne formulation affected tne metabolism of MCPA in guinea pigs.
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Analytical Methods
Because residue data were generated ever a period of many years, different •
methods were used to determine residues. The earliest determinations were
mad*? using spectrophotoraetric methods which may or nay not have detected MCPA
present in conjugated form. (The latter would not have been detected unless
the method included a hydrolytic step to liberate the MCPA from its
conjugate).Analyses have since been nade by methods utilizing seme form of gas
chromatography. In these methods, steps were taken to liberate the MCPA and
to include it in the analysis.
Residue data were generated with one or more of the following methods:
"Procedures for determining residues of MCPA (2 methyl-4-chlorophenoxy-acetic
acid) in treated crop" by Conkin (Monsanto Chemical Company, 000005552) in
1956.
"Analysis of 2,4-D residues in milk and forage" by Yip and Ney, (1966, GS-0017-
109). (It was adapted to the determination of MCPA and modified with an
alkaline hydrolysis step).
Tne procedure described by St. John in "Plant Growth Regulators and Food
Additives", Vol. V., G. Zweig, editor, (Academic Press, New York) 1967;
000004724. (A version of this method later appeared as Rhodia Analytical
Method No. 104 and modified as Rhodia Analytical Method No. 122, described by
Guar-Jigli. (00004766 and 00021920).)
The procedure of St. John has been validated and found to givo good recoveries
of the MCPA and 2-methyl-4-chloropnenol on grass crops. Fresh crop material
is extracted with an acidified solution of acetone. An aliquot is taken for
analysis and the organic interfering medium is partitioned into diethyl ether
from a dilute solution of strong base. Then the aqueous solution is acidi-
fied, the MCPA is removed with diethyl ether, the solvent is evaporated, and
the residue is nitrated in a hot phosphoric acid solution. The methyl ester
is formed by subjecting the reside to BF^ methanol solution and partitioning
the ester into hexane for subsequent injection into a gas partitioning the
ester into hexane for subsequent injection into a gas chrcmatographic column.
This method has been validated for barley straw and grain.
MCPA recoveries were 82.6% and 72.4% at the fortification levels of 0.05 and
0.50 ppm in barley grain and 78.3% and 69.6% at the fortification levels of
0.2 to 1.00 ppm in barley straw (Higham, 1975, 00004633). MCPA recoveries
ranged from 77.1% to 76.6% and 85.7% at fortification levels of 0.10 to 0.50
ppn in wheat straw (Higham, 1974, 00004632). The method is applicable to
grasses, with spike recoveries ranging from 72 to 100% (average, 87%) and a
sensitivity-of 0.1 ppn (St. John, 1967, 00004724).
Tne procedure has been modified and expanded to determine both the free and
conjugated forms of HCPA and 2-methyl-4-chlorophenol (Montogomery, M.L., 1970,
00005575). The need for hydrolysis, in order to recover total residues, is
-------
demonstrated by comparison of the do.-Bribed netnod with a previously published
method \-nich does not include nydrclysis Ocv, P.N., 1974, n?G027r.5).
Recovery of i-CPA spikes frcn wheat grain are greater than 89% at C.05 pm.
These- ilCPA extraction procedures including a base hydrolysis step ancl slightly
modified or varied clean-up procedures nave been used to determine total MCPA,
2-methyl-4-chlorophenol residues in flax (Guyton, 1977, 00004R22), range and
pasture grasses (Guardigli, iy73, 000021920)'and peas (00004287). In flax, tne
rigorous extraction and clean-up procedures along with the determinative steps
employed should confer adequate specificity for detection of 'CPA in flax
foliage, straw, aid seed. Hydrolysis of conjugates by cold alkali treatment
probably liberate all conjugates, but this has not been demonstrated (Guyton,
C.C., 1977, 00004822).
Guardigli (1973, 00021920), subjected grasses to acid or alkaline hydrolysis
and exhaustive solvent extraction. Additional residues were not recovered
after exhaustive Soxhlet extraction. After clean-up on acid alumina, MCPA is
nitrated and methylated before determination by gas chrcroatography using
electron capture detection. The 2-nethyl-4-chlorophcnol is estimated after
thin-layer chrcmatograpny via color development of spots. A detection limit
of 0.05 ppn is found for J1CPA and tne metabolite is detected down to 0.1 ppn.
Recoveries for both compound are greater than 80%. VJhen pea vines wore
subjected to alkaline hydrolysis prior to organic solvent extraction,
detection limits of about 0.04 ppn an 0.1 were obtained for ICPA (Cuardigli,
1974, 00004737).
A method for the determination of residues in animal tissues is described by
Herman (1971; 00004627). "Trio"MCPA and "2-methyl-4-chloro3hcnol arc "extracted
from the tissues (muscle, liver,kidney and fat) with anmoniacr-i mctr.snol. The
extract is concentrated, diluted with v;ater, acidified with phosphoric acid
and partitioned into diethyl ether. Tnc two components arc separated by
liquid chromatography. on an acidic alumina column. The phenol is determined
as free phenol and tne MCPA as its methyl ester by gas chromatography, using a
microcoulcmetric detector. When muscle and liver were fortified
-------
hexane followed by dietnyl etner. The cream extracts are partitioned with
sodiirti hydroxide arid the basic solutions acidified with phosphoric acid
followed by extraction with dietnyl ether. Cleanup of the samples is
accomplished by liquid cnronatograpny en an acidic alumina column. Tne etner
eluate, containing the 2-methyl-4-chlorophenol is chrcnatographed directly.
MCPA is cluted from the column with bicarbonate solution, acidified, extracted
into ether, esterified with diazcmethane, and determined as the methyl ester
by gas chrcmatography.
When milk and cream samples were fortified with MCPA and 2-metnyl-4-chloro-
phenol over tne range of 0.05 to 1.0 ppm, recoveries of MCPA and 2-methyl-4-
chloropnenol from milk averaged 103 + 23% and 85 + 17% respectively; while
recoveries fron cream averaged 89 + 23% and 83 + 20%, respectively, within 95%
confidence limits for individual determinations. This procedure was
roverified by Bjerke e± al., (1972; 05003259) in a study where dairy cattle
were fed MCPA and residue levels in the milk and cream were determined. The
method will detect MCPA and 2-metnyl-4-chlorophenol at levels as low as 0.05
ppm.
Modificfttion of tne above milk method (See Herman et al., 1970, 00004492) to
include alkaline hydrolysis (determination of free plus conjugated residues of
MCPA plus metabolite) is outlined by Miller et al_., (1975; 00004438). The
method is sensitive to 0.02 ppm of both conpounds with average recoveries
ranging from 62 to 98% for MCPA and 60 to 92% for 2-nethyl-4-chlorophenol.
VJhen milk samples frcn covs fed JCPA at a level of 1000 ppn were examined,
(Miller et al., 1973, 00004433) tne levels of MCPA and its phenolic
metabolite were found to be the same with the alkaline hydrolysis method as
those found using an acid hydrolysis.
The general methods for cnloropnenoxy acids (including MCPA) in both fatty and
non-fatty foods, described in the Pesticide Analytical Manual, \folume 1,
Section 221, 222, 421, and 422 are recommended for enforcement purposes (See
citation under "2-roethyl-4-chlorophenoxy acetic acid in Pesticide Analytical
Manual, \folume II), provided these are modified with an alkaline hydrolysis
step to ensure recovery and measurement of conjugated residues. These methods
v/ill not determine the metabolite, 2-metnyl-4-chlorophenol. If necessary, Dow
methods ACR 70.17 (for milk and cream) and 71.10/71.10S (for animal tissues)
may be used. The latter was tested and validated in the Agency's laboratories
at 0.05 and 0.10 ppm MCPA and metabolite, but not without modifications.
Owing to the necessity for modifications, there is some question of the
validity of the residue data. Monitoring of residues in meat and milk is
therefore reconnended.
Residues in Plants
No-data are available on the presence or absence of residual inorganic salt,
amine, alcohol or intact esters on plants following the application of MPA in
the form of its sodium or amine salts or of its esters. Their clearance will
require data en the amount present or must continue to rest solely on tneir
toxicology. Uith respect to the intact ester, tne Agency requests the
registrant to estimate its amount if present (with references to data)
-------
involving analogous cncmicals, and the ability of the- anclyticnl methodology
to account for MCPA ester (if preront). In tnis connoction it should be noted
that according to the EPA Index, fCPA is registered for use in the form of its
souiuTi, diothanolaniinc and dimethylanine salts arvJ iu3 isooctyl and
butoxyethyl esters. According to -1C CFR 18C..399 (a), the use of J-CPA in the
form of its ethanolamine, diisopropanolamine and triisoprorx»nolamine salts is
sanctioned. In addition, the Product Chemistry Chapter for this Standard
indicated tnat tne isopropyl, isobutyl and butyl esters are also being
used—based upon available confidential statements of formula. It should
therefore be expected that MCPA is being used in all of these forris.
The question of nitrosamine contamination is raised in tne Product Chemistry
Chapter of this Standard. Before tne Agency can assess tne presence of absence
of residues of nitrosamine on plants the Agency will need data on the amounts
of nitrosamine contamination in those formulations containing MCPA in tne form
of its amine salts, in particular for the secondary and tertiary
alkanolanines. '
The residue data evaluated in tne following sections pertain to MCPA, its
metabolite, 2-methyl-4-cnlorophenol and their conjugates, obtained primarily
througn tne use of tne sodium and dimetnylamine salts and the isooctyl ester.
Barley:
Grab samples from Colorado, Minnesota, Montana, ar.d the Canadian provinces of
Alberta and Ontario indicate that an application of T'CPA, dinotnylamine sr,lt
(when known) at rates of 0.25 to 0.75 ib. a.e./acre in combination with Avenge
and bronoxynil results in no detectable residues «0.05 ppn) in grain, and
«0.20 ppn) in straw of wnat must be presumed to be free .MCPA. The
intervals fron treatment to harvest were ('./hen available) fi9 to 81 days. A
method of the ftncrican Cyanomid Company utilizing GLC, poorly described, or
not
-------
in the "flax", but blank values, wnicn are usually 0.2 ppm. arc nigner tnan
expected for the level of residues being measured. The reported net residues
of 0.1 ppm cannot be relied upon. The study, there for*-:, is of questionable •
value for tolerance reassessment.
In tne second study, the dimctnylamine salt of MCPA was applied at a rate of 1
Ib a.e./acre, when the flax was 3 to 4 and 5 inches high (i.e. 90 or 73 days
before harvest). Flaxseed and "meat/oil" from plots treated in accordance
with the recommended use but at an exaggerated application rate (of 1.3X) were
found to contain no detectable residues «0.04 ppm) in seed and «0.1 ppm) in
extracted (seed) meat/oil. These determinations were made by Analytical
Metnod No. 104 of Rhodia, Inc. (previously described under Analytical
methods) which does not liberate bound MCPA. Therefore bound MCPA would have
escaped detection.
The data in these 'two studies do not adequately support the contention that the
use of MCPA will not result in detectable residues in flax, ibwever, the
evidence accumulated ifc tne Standard indicates that MCPA is not translocated to
the seeds of crops, and that there is no reasonable expectation of residues of
MCPA in any form in flaxseed.
There are no data for the flax straw which may be fed to livestock. In this
case, it is reasonable to expect that residues in flax straw will resemble
tnose in the straws of tne small grains.
Grasses, Pasture and Rangf;land
A variety of range grasses growing in locations representing a cross-section
of the country were treated with a single application of the sodium salt of
MCPA at a rate of 1.5 Ib. a.e./A.
The method described by Guardigli ct a_l., (1973; 00004449) was used to
determine total residues of MCPA and 2-roethyl-4-chlorophenol as separate
entities.
Forage samples were collected at various periods after treatment and the
residues determined (Table 7-1). The maximum for residues of MCPA was 206.4
ppra at 1 day after treatment, with an average value of about 75 ppm. An
initial deposit of 220 ppm on forage grasses is estimated. The residue
remaining on pasture and range grass after 7 days (the specified waiting
period for dairy cattle) is 23.7 ppm. Samples of grass hay (fresh/green and
dried) were taken for analysis at 21 to 22 days after treatment. Maxima for
residues of MCPA were 7.90 ppm in the fresh and 13.10 ppm in the dried hay.
Inasmuch as the rate for application is somewhat higher (i.e. 2 Ibs a.e./A)
for tne dimetnylamine salt, an adjustment for the difference indicates maxima
of -2.0 x 22C = 292 ppm on day zero and 2.0 x 23.7 = 3C cpn at 7 days in
1.5 375"
pasture and range grass, and 2.n x 13.1 = 13 ppm in grass fay at the higher
TTB"
rote.
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TABLE 7-1. SllftlAW TARtJ? OF RTOtnUFR IN/TN PASTURR MID WKTXJtm GRASSES
SAI.T OF MTPA, RATF.t 1.5 Ihn a.l./Acn?)
(00004449)
Past Treatment Period (rays)
Grass Species
•lohnsonqrass
Bermuda
Sudan Grass
Bermuda
RliKqrass Fescue
Rah la Crass
Rlueqrass
Remuda
Actual
days
(1)
(3)
(1)
(2)
(0)
(2)
(1)
(0)
(1)
(1)
(3)
0-3
Phenol MCPA Actual
ppm ppm days
Forage
<0.1 93
-0.8 39
"0.4 111
-0.4 163
~0.1 103
-vl.6 59
<0.l 42
<0.1 110
-'1 .0 52
7
4
<0.1 42
-"0.8 24
.10
.16
.84 (7)
.44 (9)
.44
.55 (9)
.00 (7)
.40
.65
.60 (7)
.05
.00
.24
6-9
Phenol MCPA Actual
ppm ppm days
Foraqe
(14)
-1.6 28.68 (14)
-1.2 34.34 (14)
-1.6 18.60 (14)
~0,2 18.66 (14)
(14)
3.24 (15)
(14)
13-16
Phenol
ppm
Foraqe
-0.6
-0.8
~0.8
-2.0
-
-0.9
-
-0.4
MCPA
ppm
14.64
12.54
4.97
5.59
1.49
28.95
0.45
9.72
21-22
Actual Phenol
Hays : ppm
* \
Green/Fresh
(21) -0.4
(21) ~0.4
(21) <0.1
(21) -0.3
(21) -vO.4
(21) ~0.2
(21)
(21) -0.2
MCPA
ppm
Hay
7.14
6.53
0.12
6.82
2.82
1.28
0.15
1.84
Actual
days
(21)
(21)
(21)
(21)
(21)
(21)
(21)
21-22
Phenol
Ppm
Dried (lay
-0.4
<0.1
-0.1
-0.2 .
-0.2
MCPA
PPm
12.06
11.37
0.18
13.10
2.61
4.00
Rlueqrass, Fox- (1) <0.1 19.60 (7) - 8.76 (14) ~0.4 5.80 (21) - 4.09 (21) <0.1 O.22
tail Fescue
Timothy Crass (1) -0.2 95.40 (6) ~0.fl 38.16 (13) —0.8 6.48 (21) ~0.2 . 3.55 (21) -0.4 4.78
Rye, Foxtail (1) -0.4 49.68 (6) -2.0 14.28 (11) -1.2 6.12 (21) - 2.76 (21) "2.0 1.10
Chest, Rromeqrasa
Blueqrass, Fescue (1) <0.1 206.40
Bentqrass (3) -0.4 14.28 (7) -1.2 4.08 (14) - 0.95 (22) ~0.6 0.10 (22) - 0.12
Fescue (0) - 71.40
(3) - 34.60 (7) - 28.12 (21) - 7.90 (21) - 12.24
Orcfvird Crass (0) <0.1 73.20
nentqrass (.1) —0.4 21.84 (7) —0.9 19.68 (21) -0.1 1.57 (21) "0.4 1.17
.lohnsnnqrass (1) -^0.2 55. >O (1) "1.0 - (16) ^/0.15 1.10
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Tne metabolite, 2-netnyl-4-cnlorophenol was detectable even up to harvest in
drietf nay at 21 days after treatment. A maximum of about 2.0 ppn <.:as observed
in forage at 6 days after tne high residi*? levels in the grasses.
Trie levels of residues are consistent with those of the established tolerances.
Oats;
A single grab sample of oats from Minnesota indicates that an application at
0.25 Ib/acre of MCPA (used in combination with dicamba) will not result in
detectable residues «O.C5 ppm) of what must be presumed to be free MCPA in
oat grain and straw. The interval frcn treatment to harvest was 02 days. A
method of tne Velsicol Chemical Corporation utilizing GLC, not otherwise
described, but having adequate recovery with grain, was used (Rydrych et al.,
1971, 000236S7).
These few data and the absence of a decription of the analytical method
provide poor support -for the established tolerance. However, conclusions
drawn from residue data on tne grain, forage and straw of other small grains
are considered applicable to oats.
Rice
Results of field tests conducted from 1069 to 1971 aro summarized by Devine,
1970, 00004764; Lsng et al.., 1970, 00004765; and Rhodic . Incorporated, 1971,
00004594).
In a 1969 study (Leng et al^., 1970, 00004765), rice was treated at two stages
of growtn witn an unspecified formulation of MCPA at rates of 1 to 3 Ib a.e.
MCPA per aero in California. No residues of MCPA were detected «O.C2 ppn)
in any samples of the grain, rice mill (by-product), hulls, 'rice polish1 and
bran from treatments made 106, 103 and 73 days previously. No residues were
dett_lable «0.05 ppm) in rice straw at 106 days, but up to 0.75 ppm were
found at 78 days. The method is presumed to be tnat described and used by
Winterlin for wheat. No attempt was made to measure the conjugated i'CPA.
Rice bran and rice straw treated two times during the 1970 growing season with
MCPA at a rate of 1.5 Ibs a.e./acre in Arkansas, Texas and Louisiana were
found to contain no free MCPA residues «0.05 ppm) or MCPA which could be
liberated witft acid hydrolysis, using the method of Yip and Ney (196f3; GS 0017-
109).
Residues of TiCPA \rcre were found in straw harvested in California at levels
ranging from <0.05 ppm to 0.14 ppm (Devine, 1970, 00004764).
When MCPA was aerially applied, at a rate of 0.5 Ib a.i./A to growing
stubble rioe, no residue of MCPA was found on rice grain ans straw at narvest
time (Rnodia, Incorporated, 1C-71; 00004594). Since no analytical details were
given, it is assumed that tne free MCPA alone was determined.
-------
Tne dissipation of *CPA in a California rice field treated at a rate of 0.4 oz
ci.i./acre was investigated by Soderquist, et ad., (1975, 05003445). Samples*
orwacer, rioe plants and mud were collected at intervals for 20 days and
analyzed from MCPA by establisned methods for plants, mud an^ water. Water
residues declined to less than 0.01 ppm of MCPA within 14 days after
application; plant residues declined from 20" ppm to 1 ppm within 20 days; mud
residues remained constant at about 0.1 ppm. Photolysis of dilute aqueous
MCPA solutions with either sunlight or an indoor photoreactor yields 2-methyl-4-
chloropnenol as the major product; o-cresol and 4-chloro-2-formylphenol
also were identified. While photosensitization was observed in water taken
from the rice field, all environmental compartments except air contained
measurable amounts «0.01 ppm) at some time, but water contained the bulk of
tne applied MCPA whose eventual disappearance was shown to be due to biological
and chemical degradation and not dilution.
The one limitation in this study is the use of a relatively insensitive flame
ionization detector irf the GLC analysis (with a method sensitivity of 10
ppb). Many plant species (i.e., tobacco, tcmatoes, cotton, etc.) are
sensitive to pnenoxy herbicides in irrigation water at levels as low as 0.1
ppb. Thus the discharge to the relatively water soluble MCPA into the
irrigation canal may result in crop injury by reuse of irrigation water.
Based on grab sample data (1969-1971) from numerous locations, the use of MCPA
in normal rice production does not result in detectable residues of MCPA in
edible rough rice grain. low levels «0.70 ppm) of MCPA nay be found in
straw which nay be used for livestock feed.
The levels of residues are consistent with those of the established tolerances.
Rye:
Residue data are not available for rye grain, forage and straw. However the
conclusions drawn frcn residue data on the grain, forage and straw of other
small grains are considered to be applicable to rye. This same correlation
was possible for the grain and forage of barley, oats, rye, and wheat, though
not necessarily at the same level of tolerance, for 2,4-D in 40 CFR 130.142?.
Sorghum; ,
In studies reported by tne Interregional Research Project No. 4, (1974;
00004493) a single posteracrgence application was made to sorghum in the
preboot stage. The test locations were in tfebraska and Texas, which are
important producers of sorghum.
MCPA was applied in tne form of its sodium and dimetnylamine salts at rates of
0.5 and 2.0 Ib a.e./A; and in the form of its isooctyl ester at rates of 0.75
and 1.5 Ib a.e./A. The sodium salt alone is registered for use on sorgnum.
Rhodia Analytical Method £122 was used to determine total residues of '1CPA and
2-metnyl-4-chlorophenol as separate entities.
-------
Samples Harvested at 57 days after application of the sodiun salt at 0.5 and
2.0 Ibs a.e./A snow total residues of tICPA ranging from O..H to 0.83 ppn and
from 1.16 to 4.07 ppm in fodder. None (i.e. <0.04 ppn) was found in grain
at the- higher rate.
Residues of 2-nethyl-4-cnloropnenol (i.e. <0.1 ppn) were found in neither
fodder nor grain at the higher rate.
Residues of total MCPA, adjusted for tne difference in rates (2.0/0.75 =
2.67x) would not exceed about 1.5 ppm in the fodder.
The data remaining from the trials on the dimethylanine salt and trie isooctyl
ester support these findings.
There are no residue data on the forage. However, data on the grain forages
can be utilized for this purpose and snow residue values of up to 16 ppn after
7 days, from tne application of 2 Ibs a.e./A made up to the boot stage.
Adjusting as before for the difference in rates, residues of total MCPA would
not exceed about 6 ppm.
Levels of residues are consistent with tnose of the existing tolerances.
Sec-d and Pod Vegetables
The existing tolerance for residues in seed and pod vegetables is an extension
of a negligible residue tolerance previously established for poas alone.
The data submitted reflect tests conducted during tne period fron 1?% to
1974. The earliest residue determinations were made using colorimetric
methods described by Marquer-lt and Luce (in J. Agr. Food Chen. 3, 51; 1955)
and by Conkin (1956, 00005552). The first method is considered too
insensitive to yield reliable results at the 0.1 ppm level of the tolerance
(cf: blanks ranging fron <0.1 ppm to 0.6 ppm); and data from the DP! Monte
trials 1, 2 and 3 (described in Del Monte, 196G; 00044403) were eliminated for
this reason.
After 1965, determinations were made by means of GLC, with greater
sensitivities of the order of 0.01 to 0.02 ppm. One of these methods (that of
Chow et al., (1965, 05003765) utilizes alkali to liberate the conjugated MCPA
and tnus determines the total residues of fCPA (See Del Monte, 1973, 00004444).
Tne data of the Summary Table (7-2) indicate tnat even under exaggerated rates
(up to Z<) and timing (up to 14 days before harvest), there are no residues of
MCPA in excess of 0.1 ppm, and probably much less than this level, in peas.
Winterlin £t'al., (1574, 00004453) and Bendixen (1974, 00004454) reported the
results of postemergence shielded spray applications made in 1974 to beans
grown in California. MCPA was applied in tne fcm of its dimotnylamine salt et
from 1 to 2 Ibs a.e./acre, at 110 days before harvest.
The metnod of Chow et el., (1965, 005003765) with modifications was used to
determine total residues of f-CPA in dried lina beans, small white beans and
-------
garbanzos. Ito fCPA (i.e. <0.01 ppm to <0.02 ppm) was detected in any of
those sanples.
Supportive data from Minnesota furnished by Guardigli (1974, 000004788) from
applications to peas of MCPA in the form of its sodium salt at 1 Ib a.e./acre,
not later than the three-nodes stage before, pea flowering, indicate no residues
«0.04 ppn of MCPB, and <0/04 ppm of fCPA, and <0.01 ppm of the netabolite2-
metny1-4-chlorophenol. The method of application, aerial versus ground
application, did not affect the residue levels.
The levels of residues in peas and beans (i.e., seed and pod vegetables) and
in peavines as well, are consistent with those of the established tolerances.
Wheat
Wheat from test plots in North Dakota and two separate plots in Oregon which
has been treated with^fCPA, isooctyl ester (one is the boot stage and the
other in the tiller stage) at rates of 0.5, and 2 Ibs a.e. per acre were
analyzed for total fCPA residues.
The method used was based on that of Yip and lley (1966; GS 0017-109) and
indicates an alkaline hydrolysis as described in the section on analytical
methods.
Residues could not be detected by tnis method in samples of wheat grain
sampled at harvest. J
Montgomery T-1.L. (1970,""000005575") "reporter^ "Fi^rii^icant~T»sir)ues"1.Ti" wrv5a"t~stravr
especially following treatments at the tiller stage. Following applications
at this stage, residues at zero-day were 36 ppn, 121 ppn and -icn.6 ppn for the
three rates. At harvest (56th day) residues of f'CPA could no longer be
detected «0.05 ppm) after corrections for recovery and baciirjround.
Grab samples of spring and winter wheat frcm locations in Minnesota, Oregon,
South Dakota and Washington'indicate tnat an application of 0.25 Ib/acre of
f-CPA (used in combination with dicamba, 5-CH dicamba and bromoxynil) will not
result in detectable residues of wnat is presumed to be free MCPA «n.05
ppm) in green wheat, grain or straw. The shortest interval from treatment to
harvest was 31 days for green winter wheat. A method of the Velsicol Chemical
Corporation utilizing GLC (not otherwise described) was used with a recovery
of 80% at 0.1 ppn added MCPA (Rydrych et a_l., 1971, 0000236C7).
Field samples from Oregon indicate that an application of 0.5 Ib/acre of MCPA
(used in combination with Avenge , bromoxynil and 2,4-D at various rates up
to 0.75 Ib/acre) will not result in detectable residues «0.05 ppn) of what
is presumed to be free MCPA'in wheat grain. The application \ias nade when tne
wheat was 6 to 3 inches high and after it had tillered; the interval being 117
days to harvest. Residues were determined by the American Cyanamid Company,
with a method (see Company report C-575) utilizing a gr»s chrcnatograpf
equipped with a Coulson electrolytic conductivity detector operating in the
halogen mode. The methcn was validated for residues in wheat grain; the
sensitivity is 0.05 ppm (Hignam £t a^., 1974, OOGOP5570).
tj?
-------
Table 7-2. SUMMARY TABLE Of, MCPA ANALYSES CONDUCTED ON PEA SAMPLES
1
Pile No CROP
Monsanto
Company
00004773 Peas
and
00004441 Peas
Peas
Del Monte
Corporation
00004442 Peas
and
00004443
YEAR LOCATION MCPA TREATMENT RATE MCPA RESIDUES
1956 Idaho 0.25 lb a. e. /acre peas <0.1 ppm
»\
1956 Wisconsin 0.25 lb a. e. /acre peas <0.1 ppm
1956 Wisconsin 0.50 lb a To. /acre peas <0.1 ppm
1968 Utah 0.33 lb a. e. /acre peas (shelled)
<0.01 ppm vines
<0.01 ppm @ 37 days
MCPA FORM
Not identified
r.
Sodium Salt
00004443
Del Monte
Corporation
00004444
Peas
Peas
1972 Utah
1972 Utah
0.25 lb a.e./acre
0.50 lb a.e./acre
Peas
Peas
1973
Jtah
0.38 jib a.e./acre
peas (shelled) <0.02
ppm (30 days) vines
<0.02 ppm (16 days)
peas (shelled) <0.02 ppm
(30 days) vines <0.02 ppm
(16 days)
peas 0.010-0.013 ppm
vines 0.014-0.020 ppm
1973 Utah
0.75
lb a.e./acre
when {peas are 6-
inches tall
Sodium Salt
Sodium Salt
peas 0.013-0.020 ppm
vines 0.016-0.028 ppm
relative to checks of
0.011-0.015 ppm (peas) and 0.015-0.022 ppm
(vines)
-------
These and other studies are listed in the Summary Table of Residues in/on VJneat
(Table 7-3).
The residue levels aire consistent with tfic levels of the established
tolerances.
Grain fractions;
Because little, if any residue has been shown to be present in the grain
portion (apart from tne forage and straw) of the snail grains, there is little
or no expectation of residues in grain fractions, and therefore, no need to
establish food additive tolerances for residues in grain fractions of barley,
oats, rice, rye and wheat. The data on rice grain fractions (byproducts)
confirms this.
Small grain ^ legume mixture
MCPA has been registered for use on barley - legume mixtures, oat - legume
mixtures, rye-legune mixtures, wheat - legune mixtures, snail grain - legume
mixtures and flax - legune mixtures, but tnere is as yet no tolerance for
residues which result in the legumes from tnis use. Such a tolerance has been
proposed in Pesticide Petition No. 6E 1356, which is still pending.
Residues in Food-Producing Animals
VJhen use of a pesticide on agricultural crops results in residues in animal
feed, the Agency requires data on whether or not residues are transferred to
meat, milk, poultry and eggs.
In a beef calf feeding study (Bjerke et £l., 1971, 00004625) tv;elve yearling
calves were subdivided into four groups of three calves each and fed a diet
containing 0,250, 500 and 500 ppn of FCPA for 29 days. Average feed consump-
tion during the feeding period ranged from 194 to 291 kg per animal with no
apparent relationship to the presence of 'VCPA in the diet. Ingestion rates
for MCPA averaged 7.1 mgAg/day for the groups on the 250 ppm diet, and
14.4 to 14.5 mgAg/day for the two groups on tnc 500 ppn diet. Feeding
resulted in residues of M3PA which varied among samples of each of four tissues
at tne two feeding levels. Some variation is due to the fact tnat at the
higher feeding level one group was sacrificed 6 days after the last feeding,
during wnicn time, residues will have diminished. Residues of tCPA and 2-
nethyl-4-chloropnenol were determined in the four tissues, muscle, liver,
kidney and fat by a validated analytical method (Dow ACR 71-10), with a claimed
lover limit for sensitivity of O.C5 ppm for both components of the residue.
Significant residues were found in liver and especially in kidney at both
feeding ratess. Vvithdrawal for 6 days resulted in a substantial reduction of
residues in tnese tissues (see Summary Table of Residues in Tissues of
Calves (Table 7-4)).
In a supplement to tnis study, Jensen et al^., 1973 (00004439), incorporated
an alkaline hydrolysis step in the analytical procedure, but could not liberate
any additional residues of MCPA and cf tne metabolite, 2-mcthyl-4-chloro-
-------
•nrtr. vi
Mtwv iMU rr mitnin mAM mmr
.
nw TFAII tnrATifn nnMitcim Apvuni AT IWIWIHT mm ppsiinifs
«l«e tnmttut*
of Aqrl. OM..
rlnl«nl 09)1*114 Hnt I*H rlnlunt KHk W.15 kf •.!./*•!• <».01 m IC»» Mil l*« nwlt In
rymnlnr* dlocnl««n»mt detectable cymiailna nr
•* •!.
.m »CH» («.» th •.»./M> rt^M na
10. M INi/AI lTri.tr> t Mmiil
.o. it •!.
on. mi
IRfi<< m«tl*l l»m*l IB. II IKi/KI
li.D. it It.
BOB21U1 MhMt l"0 nrr
ill IB. If im/MI '
1*14
Kmt 1474 Mntmt ICM (H.1I Ib* •.«.>!> <•.•! n« qtaln IM qlon
IIB.Tt tta/ltl .«.yHI* <0.01 H> q»ln <«.B» n» »«w»»r Mn«nl"n
II.B lt./»l 41.11 n«MTJW
ft ml.
Mhrat nn Htmnrt* HTM |t.f !>• •.•./HI* .« Ita •.r./
Mtilool Onioil
00004M4 W>m I*TI I« O.M nv<|r»ln OI.BJ
Dlcnta IB. in IIM/KI O.n fpn Mrw tO.OI
|CD| CtOTtlnl
Cocporat lot • '
OOOOtMl Mm. lt?4 fln IWinla fCHk W.n Ib* «.•./»!« lrm*>i 10. Ji
ICM 10.11 Ita «.«./»(. <0.0f rt_ qr»lr
I
tnc<1 WYV «*H4«te<1 tMlnrf HCVA fortified •MV>|»«. II ««n* not pnHilhle to 4etrnMln
rlrt^/tta«tpr rrvlm* pnt*.m If A tv»nr> hytlrolyillN v^fl MM Inrlmi^. •nv^ipfrw. fivitt* r)*«iM N* tjAf^i In Inrllrntr
ICFA KM.
-------
Table 7.4 Summary Table of Residues in Tissues of Calves
Residues in Tissues (ppm)*
Daily
Feeding
Rate ' Calf
(ppm MCPA) Number
25Ql/ 1765
1649
1761
500l/ 1644
1645
1646
500i/ 1767
3 1764
1647
Muscle
MCPA
<0.05
<0.05
<0.05
<0.05
<0.05
<0.05
<0.05
<0.05
<0.05
Met
<0.05
<0.05
<0.05
<0.05
<0.05
<0.05
<0.05
<0.05
<0.05
Liver
MCPA
<0.05
0.10
<0.05
0.08
0.15
0.14
<0.05
<0.05
<0.05
Met
0.05
<0.05
<0.05
<0.05
<0.05
<0.05
<0.05
<0.05
<0.05
Kidney
MCPA Met
1.2
2.5y
0.58
2.0
2.2
2.7
0.34
0.07
0.05
<0.05
<0.05
<0.05
^0.05
<0.05
<0.05
<0.05
<0.05
<0.05
Fat
MCPA
<0.05
0.05
<0.05
0.06
<0.05
<0.05
<0.05
<0.05
Met
<0.05
<0.05
<0.05
<0.0b
<0.05
<0.05
<0.05
<0.05
*A11 values corrected for recoveries
I/ Fed at 250 or 500 ppm for 28 days, slaughtered on day following last feeding.
2/ Fed at 500 ppm for 28 days, slaughtered on 7th day following last feeding.
Met = Metabolite, 2-methyl-4-ch).orophenol.
-------
pnenol. Therefore it is concluded that there are no conjugated residues of
MCPA or 2-r.ctnyl-4-chlorophenol in tneso tissues.
In a sheep feeding study (Bjerke et el., 1971, 0004626), nine sheep were
subdivided into three groups of throe each and fed a diet containing 0, 250
and 500 ppm MCPA for 28 Hays. Average feed consumption duri...J the feeding
period ranged from 25 to 31 kg per animal, with no apparent relationship to
tne presence of MCPA in the diet. Ingestion rates for MCPA averaged 14.9 and
14.6 mgAg/day for the two groups on the 500 ppm diet. Residues of HCPA and
2-methyl-4-cnlorophenol were determined in the four tissues, muscle, liver,
kidney and fat, as in the calf study, using the same analytical nethcd (Dow
ACR 71.10). Significant residues were again found in liver and kidney.
Withdrawal for six days resulted in a substantial reduction of residue in
these tissues (see Summary of Residues in Tissues of Sheep (Table 7-5).
Results of an early cow feeding study (Bache et a_l., 1964, 00004701),
indicate that dietary;MCPA data a level of 50 ppm for 4 days did not result in
detectable residues of the MCPA in the milk. The level of the phenolic
metabolite was not determined.
In a subsequent study (Herman et al., 1970, 00004491; Bjerke et al., 1972,
00003259; and Herman, J.L. et al., 1971, 00004624) three lactating Itolstein
cove were fed a complete ratTon containing MCPA at six levels in sequence frcn
10 to 1000 ppm for 2 or 3 weeks at eacn level. Three cows were maintained as
controls. Six milk samples were collected during eacn 2-v/eek period (at
levels of 10, 30, 100 and 300 ppn), nine samples during tne 3-week oeriod, (at
1,000 ppm) and four samples during the 1-week withdrawal period. Cream
collected from morning milk only was obtained by compositing the milk from tne
three test COVE and separating to mediun heavy cream.
Residues of MCPA greater than 0.05 ppm and up to 0.07 ppn wore found in only
six ,^~Tiples of milk fron covs fed at the 1000 ppm level. Small residues of
O.OS ^iprn and 0.17 ppm of 2-methyl-4-chlorophenol were found in milk at tne 300
and 1000 ppm feeding levels. Residues of both are lower in cream at the 1000
pprn feeding level. Withdrawal resulted in rapid disappearance of residues
from the milk, the residues dropped below 0.05 ppm on the first to third ciay
after withdrawal.
The experimental design for the cattle feeding study leaves something to be
desired. The dairy covs were given increasing doses of riCPA; that is, tnoy
were fed 10 ppm for 2 weeks, 30 ppm for the next 2 weeks, 100 ppm for the next
2 weeks, 300 ppm for the next 2 weeks, and 1000 for the last 2 weeks.
This gives the animal's metabolism a cnance to acclimate and adapt to the
herbicide and possibly develop an increased ability to exrrrete (or secrete)
the herbicide. If untreated cows were given the higher levels without
pretreatment", higher residue levels may have resulted in milk. This is
important since early results of tne FEA survey of rcady-to-eat foods indicate
the occasional occurrence of fCPA residues in dairy products (Duggan e_t si.,
1967, 0025154). Bache et al. (1964, 00004702) have shown that the animal
-------
Table 7.5 Summary Table of Residues in Tissues of Sheep
Residues In Tissues (ppm)*
Daily
Feeding
Rate
(ppm MCPA)
500^
500^
•
Sheep
Number
2546
2547
2553
2548
2549
2554
Muscle
MCPA
<0.05
<0.05
<0.05
<0.05
<0.05
<0.05
Met
<0.05
<0.05
<0.05
<0.05
<0.05
<0.05
Liver
MCPA
<0.05
<0.05
0.12
<0.05
<0.05
<0.05
Met
<0.05
<0.05
<0.05
<0.05
<0.05
<0.05
MCPA
>N 0.31
1.7
0.45
<0.05
<0.05
3/
Kidney
Met
<0.05
<0.05
<0.05
<0.05
<0.05
<0.05
MCPA
<0.05
<0.05
<0.05
<0.05
<0.05
<0.05
Pat
Met
<0.05
• <0.05
<0.05
<0.05
<0.05
<0.05
*A11 values corrected for recoveries
If Fed at 500 ppm for 28 days, slaughtered on day following last feeding.
2J Fed at 500 ppm for 28 days, slaughtered on 7th day following last feeding.
_3/ Sample lost during analysis.
Met - Metabolite, 2-methyl-4-chlorophenol.
-------
eliminates "CPA at a high rate in urine. Were it not for tnis nigh rate of
excretion, tne criticism of tnis study night well bo valid. It is not expected
that I-CPA will be preferentially secreted in nilk under these circumstances'.
There are no residue data for poultry and eggs.
With the realization tnat residues cannot be maintained long at their highest
level of 300 ppm (as in pasture and rangeland grasses) owing to inevitable
decline of these residues, it is expected that carryover of residues into meat,
fat and meat by-products will be less tnan tnose observed in tne foregoing
feeding studies. Therefore the existing tolerances for meat, fat and meat by-
products are considered adequate. The one week preslaughter interval gives
added assurance of this.
Because tnere is little, if any, residue in tne small grains, a staple of
poultry rations, there is no expectancy of residues in poultry and eggs, and
no need for a tolerance.
• •
Other Sites
Applications of fICPA to other sites, e.g., ornamentals, rights-of-way,
agricultural, commercial and industrial premises; and aquatic, forest,
cnappatvd , non-agricultural and wasteland areas were formally regarded as
non-food uses. It is now recognized that such is not always the case.
The application of fCPA to drainage ditcn banks m?y contaminate water, the
fisn and snellfisn inhabiting it, and eventually potable water. If the
contaminated water is used for irrigation tnere may be contamination of crops.
Therefore, tnis use should be the subject of a tolerance or the subject of
labeling restrictions to preclude sucn contamination.
r concern is tne foraging or grazing by livestock of gr.iss growing on
tneiv- sites (for example, sheep are allowed to graze on golf courses). If the
rates of application are higher (and they are in sane instances) tnan the rate
of 2 Ibs a. o. /acre permitted on pasture grass, then an appropriate restriction
e.g., "Do not spray areas likely to be foraged or grazed by livestock" shouldbe
imposed. Such is tne case for rights-of-way and fallow land.
Current Tolerance Information
Under section 130.339 of CFR 40, tolerances are established for residues of
"•CPA frcn application of the herbicide in its acid form or in the form of its
sodium, ethanolamine , dietnanolame, triethanolamine , diisopropanolamine,
triisopropanolamine or dimethylamine salts or its isooctyl or butoxyetnyl
esters in or on raw agricultural commodities as follows:
-------
CaTriodity P?rt-.s per million
Darlcy, forage 20
Barley, grain 0.1 (II)
Barley, straw 2
Flax, straw .' 2
Flaxseed 0.1 (N)
Grasses, pasture 300
Grasses, rangeland 300
Grass, hay 20
Oats, forage 20
Oats, grain 0.1 (il)
Oats, straw 2
Peavines 0.1 (N)
Peavines, hay 0.1 (H)
Rioe, grain.., 0.1 (N)
Rice, straw.. .* 2
Rye, forage 20
Rye, grain 0.1 (N)
Rye, straw 2
Sorghum, fodder 20
Sorghum, forage 20
Sorghum, grain 0.1
Vegetables seed and pod 0.1
Wheat, grain 0.1 (N)
Vineat straw 2
Uneat, forage 20
Tolerances are also established for combined negligible residues (U) of MCPA
and its metabolite 2-rnethyl-4-chloropnenol in or on the following rav;
agricultural commodities:
Commodity Parts per million
Cattle, fat 0.1 (N)
Cattle, mbyp 0.1 (N)
Cattle, meat 0.1 (N)
Goats, fat 0.1 (11)
Goats, nbyp 0.1 (N)
Goats, neat 0.1 (N)
Hogs, fat 0.1 (N)
Hogs, mbyp 0.1 (13)
Hogs, meat 0.1 (N)
Horses, fat 0.1 (N)
Horses, mbyp 0.1 (11)
Horses, meat 0.1 (N)
Milk 0.1 (N)
Sheep, fat 0.1 (N)
Sheep, mbyp 0.1 (N)
Sneep, meat... 0.1 (11)
-------
Tolerance Reassessment
Theoretical :-laxinum Residue Contribution
Tolerances for residues of fCPA, and of its metabolite 2-methyl-4-chlorptK!nol
nave been established for a number of food and feed earnedities (see previous
section). Based on these tolerances, the theoretical maximum residues contri-
bution (TMRC) and KIPA and its metabolite to the human diet is calcuLafH to
be ca 0.77 mg/cfey (assuming a 1.5 kg diet). For a comparison of the TTIRC with
tnc maximum permissible daily intake (see the Regulatory Chapter of this
Standard—Chapter 2).
International Tolerances;
Codex maximum residue limits (MRLs) have not been recommended for MCPA.
Tolerances have not been established in Canada or Mexico for residues of J1CPA
in any food or feed comnodities.
• /•
Enforcement/Monitoring Actions
Tnere is no record of any enforcement action involving !CPA. Its residues are
not usually monitored in FEA or USDA surveillance programs. Owing to
weaknesses in tne residue data on the grains, and reservations over tne
methodology for neat and milk, monitoring of the grains, meat and milk is
recommended.
Labeling Requirements
Tne limitations against foraqing and grazing should be consistently
maintained. Tnere are, for example, different foraging and grazing
limitations for barley for different salts. Unless there is sane compelling
reason for these differences, they should be removed in the interest of
consistency. The following should provide assurance that tne tolerances for
meat, fat and meat by-products and for milk will not be exceeded:
"ED not forage or graze meat animals on treated areas within 7 days of
slaugnter."
"Do not forage or graze dairy animals on treated areas within 7 days after
treatment."
Until a tolerance for residues of 'CPA in potable water, fish and shellfish is
established, the use of ICPA on drainage ditch banks snould not be permitted
witnout labeling restrictions to prevent contamination of potable water, fish,
or shellfisn. If there is a probability that the ditch water is used for
irrigation, -tnen some accomodation should be made for residues in irrigated
crops.
A restriction against tne practice of growing crayfish or catfish in treated
rice fields is recommended to preclude the possibility of residues in crayfisn
or catfish.
-------
For otner so-called non-food uses, v/nen the application rate exceeds 2 lb?
a.e./acre, an appropriate restriction, e.g., "Do not spray areas likely to be
foraged or grazed by livestock" stould be imposed. Such is the case for
rights-of-way and fallow land.
-------
CHAPTER VIII
ECOLOGICAL EFFECTS OF MCPA
Introduction
In order to evaluate potential fish and \/ildlife effects resulting from the
use of ;-CPA, the Agency' requires certain toxicity testing. Depending on the
characteristics and uses of ?CPA end-use formulated products, data
requirements for wildlife and aquatic organisms can be completely or partially
fulfilled with tests on tne manufacturing-use products. However, for sane
end-use formulations whicn contain salts and esters of MCPA which are not
registered MUP's, tne technical grade of the ester or the manufacturing-use
salt in the product must be tested. Additional testing on specific end-use
products can also be required if a particular inert ingredient is determined
to significantly alter the toxicity of the active ingredient.
• t
A full battery of fish" and wildlife testing is required on MCPA acid. This
includes acute oral avian testing, fisn acute LC5Q testing, acute tcxicity
testing on aquatic invertebrates, and acute estuarine and marine invertebrate
toxicity testing. In addition, avian dietary LC^Q testing in one species
(bobwnite quail), fisn acute LC^g testing in two species, and acute
estuarine and merino invertebrate toxicity testing is required on the
following salts and esters: sodium salt, dirvcthylamine salt, butoxyethyl
ester, and isooctyl ester.
Because MCPA nan an aquatic >-uso, involving direct application to water (uso in
rice), tho Agency is" "required t6~consider~tho~ne"ea~for~a^^il:ionril~t(3Stirif] on"
end-use formulations. "Jne only end-use formulation that requires additional
testing is tne emulsifiable concentrate formulated with the butoxyotnyl ester
of MCPA. Fish acute LCcQ testing in two species, acute toxicity testing on
aquatic invertebrates, and acute estuarine and marine invertebrate toxicity
testing is required on this>formulation.
Ecological Effects Profile
Results frcm the acute aquatic studies on technical fCPA acid suggest that
MCPA is slightly toxic to freshwater fish. The calculated LCcn values for
rainbow trout and bluegills were 89 to 91 ppm and 97 ppm (USEPA, 1076, GS 0017-
108) respectively. The 48-hour Daphnia magna toxicity test produced an LC5n
>180 ppm (USEPA,1976, GS 0017-108), which suggested that MCPA acid is
practically nontoxic to freshwater invertebrates. There were no ccologic
effects data concerning aquatic organisms available on any manufacturing-use
t'CPA salts or esters. Two formulations of MCPA also appeared to be practically
nontoxic to freshwater fish. The 96-hour LCcQ for freshwater fish ranged
from 1GO to 1000 ppn (LE002G927) for MCPA sodium salt formulations. The ?6-
nour LCcp for freshwater fish was greater than 180 ppm for MCPA dinetnylamino
salt formulation (USEPA, 1972, GS 0017-104).
-------
Results frcn acute dietary studies on technical TCPA acid suggest tnat JVCPA is
practically nontoxic to birds. The calculated LC5Q values for mallard duck,
bobwrdte quail, and ring-necked pheasant were greater tnan 2000 ppm (D3witt,
1S62, GS 0017-101).
MCPA was relatively nontoxic to honey bees.
Data Requirements and Data Gaps
1. Manufacturing-use MCPA (acid, salts, esters)
The following acute wildlife and aquatic organism tests were needed on
technical MCPA (acid) in order to perform a hazard evaluation:
a) Estuarine and marine organism toxicity study (preferably 96-hour
LC™ on shrimp and fish, and either a 43-hour I£c0 oyster
emBryolarvae" or a 96-hour ECen shell deposition tor molluscs).
163.72-3. 3
b) Avian single-dose oral LDe0 testing performed on one avian species
(preferably mallard duck or bobwhite quail). 163.71-1
The following acute wildlife and aquatic organism tests are needed on
tecnnical MCPA butoxyethyl ester and isooctyl ester, and the manufacturing-use
products containing the MCPA sodium salt and dimethylamine salt:
a) - Acute 96-hour fish studies on coldwater species (preferably rainbow
trout) and a wam;atcr species (preferably blucgill sunfish).
163.72-1
b) Acute 48-nour toxicity studies on a freshwater invertebrate
(preferably Daphnia magna). 163.72-2
;
c) Acute estuarine and marine organism toxicity studies (preferably
96-hour LCjjQ for shrimp and fish, and either a 48-nour LCeo
oyster embryolarvae testing or a 96-hour EC50 mollusk shell
deposition testing). 163.72-3
d) Avian acute dietary IT^ testing performed on one species of
. waterfowl (preferably mallard duck) and one species of upland game
bird (preferably bcbwhite quail or ring-necked pheasant). 163.71-2
e) Avian single-dose oral LD^ testing performed on one avian species
(preferably mallard duck or bobwhite quail). 163.71-1
Additional chronic fish and wildlife testing may be required after review of
tne acute toxicity studies on tne technical (acid and esters) or manufacturing-
use (salts) material.
-------
2. Formulated Prcduct(s)
The direct application of !'CPA to v;ater (rice use} triggers a potential hazard
co dquatic oryaiusnis. Tue following acute toxicity studies will be required
on tne butoxyethyl ester fomulation of MCPA:
a) Acute 96-nour fisn studies on one coldwater species (preferably
rainbow trout) =>nd one warmwater species (preferably bluegill
sunfisn).
b) Acute 4G-nour toxicity study on a freshwater invertebrate (preferably
Daphnia magna).
c) Acute estuarine and narine toxicity studies (preferably 96-nour
on snrimp and fish, and either a 48-hour LCc0 oyster
ryolarvae or a 96-hour LCcQ shell deposition for molluscs).
•'•'- Topical Discussions
Effects on Freshwater Fisn
Sixteen studies (contained in twelve references) were received and evaluated
under this topic. These sixteen studies were acceptable for use in a hazard
assessment.
Author ID
Hat tula 050nf!234
USEPA GS 0017-108
Sleight C0022f>9C
Bentley OC004512
Pitcher 00026927
Tooby 05020144
McCann 00026928
Buchanan GS 0017-002
USEPA GS 0017-107
USEPA GS 0017-104
USEPA GS 0017-105
USEPA GS 0017-106
In order to establish the acute toxicity of MCPA to fish, two 96-hour acute
aquatic studies are required on tne technical material. These studies should
be performed on one coldwater species (preferably rainbow trout) and one
warmwater species (preferably bluegill). Since there are aquatic uses
involved, formulated product testing is also required.
•
'•iCPA Acid
Two acute aquatic studies (USEPA, 1976, GS 0017-108) were conducted by tne
USEPA laboratory at Beltsville on technical grade ?CPA (94% a.i.). The studies
were performed on rainbow trout end bluegill sunfish, and wore acceptable for
fulfilling the Guideline requirements for MCPA acid. Tne toxicity values were
-------
calculated as follows: rainbow trout 96-hour LC^p = 09-91 ppn; blucgill
sunfish 96-hour I£CQ = 97 ppm. These values suggest tn?.t '1CPA acid is
slightly toxic to fish.
Salts and Esters
Five studies on the 24% sodium salt formulation were submitted (3entleyf
1974,000004512; Picner, 1973, 000026927; USEPA, 1973, GS 0017-105; USEPA, 1973,
GS 0017-106). All were acceptable for fulfilling the Guideline requirements on
this formulation. The calculated !£JQ values ranged from 180 ppn to greater
than 1000 ppm, suggesting the MCPA sodium salt is practically nontoxic to fish.
Five studies were evaluated on the 52% dimethylamine salt formulation (USEPA,
1973, GS 0017-107; McCann, 1972, 000026923; USEPA, 1972, GS 0017-104). All
were acceptable in fulfilling the Guideline requirements on this formulation.
The calculated I£eg values were greater than 180 ppm for bluegill and trout.
These findings suggest that the dimethylamine salt of MCPA is practically
nontoxic to fish. ..-,
No studies were submitted on the technicals of the butoxyetnyl ester, the
butyl ester, the iscoctyl ester, the mixture of butyl/isopropyl esters, the
mixture of isobutyl, isopropyl, and butyl esters, or the manufacturing-use
products containing the sodium salt, the dimethylamine salt, or the
dietnanolamine salt.
Studies were not submitted on the butoxyetnyl ester formulation of f£PA.
Since this formulation (emulsifiable concentrate) is used on rice, 96-hour
acute fish studies on trout and bluegill are required on each of the
formulated products in order to assess the potential hazard to fish.
One study (Hattula, 1977, 05003234) was submitted on residue uptake on tne
primary metabolite and contaminant of MCPA, 4-chloro-o-cresol. This stuciy
appears scientifically sound; however, there are no Guideline requirements
regarding residue analysis. Information from this study suggests that the
primary metabolite and contaminant of MCPA, 4-chloro-o-cresol, will
bioaocumulate only moderately and cause damage to gills and kidneys in fish.
Mixtures of MCPA with Other Active Ingredients
Four studies were submitted on MCPA mixtures. (Sleight, 1973, 0022698;
Bucnanan, 1980, GS 0017-002; Tooby, 1975, 05020144; Bentley, 1974,
00004512).All were acceptable for fulfilling possible Guideline requirements.
f'ondak TP658 (dicamba + MCPA) was tested on rainbow trout and bluegill,
producing toxicity values greater than 1000 mg/1 for the 96-nour acute toxicity
to fisnPresco S (mecoprop + MCPA + 2,3,-6 Trichlorobenzion acid) was tested on
harlequin fisn and produced an LC5q = 5600 mg/1. This mixture appeared to be
practically nontoxic to fish. Weeaar 64A/MCPA (2,4-D + MCPA) was tested on
rainbow trout and bluegill, producing an LC^Q >1030 ng/1 and >75 <1000
mg/1, respectively. These findings suggested that this' mixture was
practically nontoxic to fish.
Effects Cn Estuarine and Marine Organism
-------
r?..<^ st'j:>i_-s (contained in one r-^irnrence) were receive and evaluated under
this tonic. These studies are scientifically sound and were acceptable for
use in 6 Hazard asscssaent.
Author H) .
Union Carbide 00022673
Estuarire and marine organism toxicity tests on technical and formulated
pesticides are required to support registration if tnere is an intended direct
application to an estuarine or marine environment, or if the pesticide may be
expected to enter these environments in significant concentration because of
use or mobility pattern. These studies include acute LD^Q testing on
shrimp, oysters, and estuarine fish.
The use pattern for MCPA includes rice. Costal rice acreage in Louisiana and
Texas accounts for about 792,000 acres. The proximity of this large acreage
to estuarine or marine environments justifies the need for estuarine and
marine organisms toxicity studies on the technical, as well as the formulated
product.
MCPA Acid
Ito studies were submitted on MCPA acid. The Guideline requirements for an
acute L£5Q on estuarine and marine organisms on tecnnical (acid) MCPA have
not been satisfied. Depending upon tne results of those studies, additional
cnronic tests on mysid shrijrp and/or sheepshead minnow nay be required.
Salts and Esters
Ito studies \/ere submitted on tne technicals of tne butyl ester, the
butoxyethyl ester, the mixture of the butyl and isopropyl esters, or the
manufacturing-use products containing the sodium or dimethylamine salts.
Acute testing on estuarine and marine organisms is required in order to
establish the toxicity of the technicals.
Acute estuarine and marine studios on the butoxyethyl ester formulation is
required because of the use of MCPA on rice. However, acute studies on the
formulations of the sodium salt, the dimethylamine salt, and the mixture of
the butyl and isopropyl esters are not required, since tne inert ingredients
(other than water) account for less than 4% of the total formulation.
Mixtures of flCPA with Other Active Ingredients
Two studies on the mixture Mondak 5P43 (dicamba + FCPA) were submitted, but
only one study (Union Carbide, 1975; 000022673) was acceptable for fulfilling
possible Guideline requirements on a mixture. The results of this acute
marine invertebrate test (LCcQ = 44.8 mg/1) suggest that this mixture is
slightly toxic to grass shrimp.
-------
Effects on Freshwater Aquatic Invertebrates
Two studies were received and evaluated under tnis topic. Doth studies
appearol scientifically sound and were acceptable for use in a hazard
assessment.
Author ID
USEPA GS 0017-108
Union Carbide 00022504
In order to establish the acute toxicity of MCPA to aquatic freshwater
invertebrates, a 48-hour acute aquatic study is required on the technical
material. Test organisms should be first instar Daphnia magna or early instar
ampnipods, stoneflies, or nayflies. Since aquatic uses are involved,
formulated product testing is also required.
' f
fOA Acid
One acute aquatic study (USEPA, 1976, GS 0017-108) was conducted by the USEPA
laboratory at Beltsville on technical grade MZPA acid (94% a.i.). Tnis dapnnid
study was acceptable for fulfilling Guideline requirements. The calculated 43-
hour LCtjQ value was greater than 180 ppm. This finding suggest? that TKTPA
technical (acid) is practically nontoxic to aquatic freshwater invertebrates.
Salts and Esters
Ito studies wore submitted on the technicals of the butyl ester, tne
butoxyethyl ester, the mixture of butyl and isopropyl esters, or the
manufacturing-use products containing the sodium or dimethylanino salts.
Acute aquatic DC™ testing on dapnnids will be required to establish tr.e
toxic '•y for the technicals.
Studies were not submitted on MCPA formulations (salt and esters). Guideline
requirements for acute I£cp testing on freshwater aquatic invertebrates
using these formulations nave not been satisfied. The direct application of
JCPA to water (rice use) triggers a potential hazard to aquatic organisms. In
order to assess the extent of this danger, acute aquatic freshwater
invertebrate testing, using the butoxyethyl ester formulation, will be
required. However, acute studies on tne formulations of the sodium salt, tne
dimethylamine salt, and the mixture of the butoxy and isopropyl esters is not
required, since the inert ingredients (other than water) account for less tnan
4% of each total formulation.
Mixtures of MCPA with Other Active Ingredients
One" study (Union Carbide, 1976, 00022504) on the mixture Mondak 5P4R (dicamba +
MCPA) appeared to bo acceptable for fulfilling possible Guideline requirements
on e mixture. The calculated 48-hour aquatic freshwater invertebrate LCeC
value was greater tnan 670 mg/1. This suggests that Mondak 5P43 is practically
nontoxic to dapnnids.
n
-------
Hiifr'Cts on Riir^r
Ei^i.L scuJies were- received and evaluate under this topic. Six studies were
ni:o.utable for determining MCPA toxicity tc birds.
Author ID
Fink 0002R293
Fink 00004544
Fink 00004545
Parke 00004H05
DeWitt GS 0017-101
MCPA Acid
In order to establish^the acute toxicity of MCPA to birds, the following test
is required using MCPA acid: one avian single-dose oral study on one avian
species (preferable mallard duck or bobwhite quail).
Results frcm acute dietary studies (DeWitt, 1962, GS 0017-101) on nallard
ducks, bobwnite quail, and ring-neck pheasant suggest that MCPA acid is
practically nontoxic. The calculated dietary !£CQ values were greater than
2COO ppn for each species tested.
Pr- .1 ts and Enters
Ito studies wer« submitt«YV on tne technicals of the butoxyethyl ester, tho
isooctyl ester, tne butyl ester, the mixture of butyl and isopropyl esters,
the mixture of tno isobutyl, isopropyl, and butyl esters, or tne mar.uf^cturing-
use products containing the sodium dinethylamine or diethanolenine salts.
Since these compounds are used on crops where birds nay be affected, one acute
dietary study (bobwhite quail) will be required on each technical compound to
assess the potential hazard to avian species.
Mixtures of MCPA with Other Active Ingredients
Three studies on mixtures were reviewed (Fink, 1973, 00028293; Fink, 1973,
00004544; Fin);, 1973, 00004545). All were acceptable for fulfilling possible
Guideline requirements on a mixture. Mondak TP658 (dicamba + *CPA) was tested
on bobwnite quail and mallard duck in two eight-day dietary studies. The acute
LCcQ values were 1155 ppn and 4640 ppn, respectively. These findings suggest
that this mixture is slightly toxic to avian species. Banvel 4S + Dronoxyr.il-
MCPA was tested on mallard duck in an acute dietary study. The LCcQ v/as
greater than 4640 ppn, suggesting slight toxicity to avians.
•
Effects on Beneficial Insects
Nine studies were received and evaluated under this topic. Seven studies were
not acceptable for use in a hazard assessment. The following two studios were
acceptable.
-------
Author ID
Stevenson 05001991
Glynne Jones and Cornell 05C15G32
Table 8-1; Toxicity Studies on Beneficial Insects with HCPA
Fulfills
Guideline
Species Fornulation Results Author Date IDft Requirements
Honey bee Technical Contact LD^ Stevenson 1978 05001991 HA
(Apis 100 micrograms/
mellifera) bee. Oral LDjQ
>10 micrograms/bee.
(Relatively non-
toxic.)
Honeybee Technical' Relatively non- Glynne 1954 05015632 HA
toxic thrdugh Jones &
oral exposure Connell
There is sufficient information to characterize MCPA as low in toxicity to
honeybees. There are curently no Guidelines requirements for evaluating
toxicity to nontarget insects.
-------
A. G'j!•.':: "•; Use of This Biblioiirapny
I. Content of Bibliography
This bibliography nas two sections: 1] citations tnat contributed information
useful to the review of the chemical and considered to be part of the data base
supporting registrations under tr>e standard; 2] citations examined and judged
to be inappropriate for use in developing the standard. The second section of
tne bibliography is on file witn tne Agency, and is available for review.
Primary sources for studies in tnis bibliogrpny have been the body of data
submitted to EPA and its predecessor agencies in support of past reulatory
decisions, and tne published technical literature.
2. Units of Bitry
The unit of entry in tnis bibliography is called a "study". In the case of
published materials, this corresponds closely to an article. In the case of
unpublisned materials submitted to tne agency, the Agency has sought to
identify documents at a level parallel to a published article from within the
larger volumes in wnicn they were submitted. The resulting "studies" generally
navo 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. The Agency has attempted also to unite basic documents and
commentaries upon tnem, .treating thorn as a single study.
3. Identification of Entries
The entries in tnis bibliography are sorted by autnor, date of the document,
and title. Each entry bears, to the left of the citation proper, a nine-digit
identifier. This number is unique to tne citations, and should be used at any
time specific reference is required. This number is called the "Master Record
Idef fier", or "MRID". It is not related to tne six-digit "Accession number"
wnich nas been used to identify volumes of submitted data; see paragraph
4(d)(4) below for a further explanation.
4. Form of the Entry
In addition to the Master Record Identifier (MRID), each entry consists of a
bibliograpnic citation containing standard elements followed, in the case of
materials submitted to EPA, by a description of the earliest ];nown submission.
The bibliographic conventions used reflect the standards for tne Meric?n
national Standards Insitute (ANSI), expanded to provide for certain special
needs. Seme explanatory notes of specific elements follow:
a. . Author
Whenever tne Agency could confidently identify one, the Agency has chosen to
snow a personal author, bhen no individual was indentified, the Agency has
shown an identificable laboratory or testing facility as autnor. As a lest
resort, the Agency has shown the first knov<-n submitter as author.
-------
b. Document Date
When trie date appears as four digits with no question marks, the Agency took it
directly fron the document. When a four-digit date is followed by a question
nark, tne bibiographer deduced the date from evidence in the document. When
the date appears as (19??), the Agency was unable to determine or estimate the
date of the document.
c. Title
This is the third element in the citation. In some cases it has been necessary
for the Agency bibliographers to create or enhance a document title. tr\y such
editorial insertions are contained between square brackets.
d. Trailing Parenthesis
• •
For studies submitted"to us in the past, the trailing parenthesis 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 tne work 'under', is the registration number, experimental permit
number, petition number, or other administrative number associated with the
earliest known submission.
3) Submitter. The third element is tne submitter, following
the phrase 'submitted by1, When authorship is defaulted to
the submitter, this element is emitter].
4) Volume Identification. The final element in the trailing
parenthesis identifies the EPA accession number of the
volume in which the original submission cf the study
appears. The six-digit accession number follows the symbol
'CDL', standing for "Company Data Library". This accession
number is in turn followed by an alphabetic suffix which
shows the relative position of the study within the volume.
For example, within accession number 123456, the first study
would be 123456-A; the second, 123456-B; tne 26th, 123456-Z;
and the 27th 123456-M.
-------
OFFICE OF PESTICIDE PROGRAMS
^.^ITPOTITM 55T.R*TT'B.RD RIDLTOGPAPHY
Citations Considered to be Part of the Data Rase Supporting
MRID #
005019071
005008511
000004735
000004730
005004650
005015044
000004493
000004741
registrations
Ur.der the Standard
CITATION
Aberg, B. : Eliasson, L. (1978) The herbicidal effects of chenoxy
compounds. Pages 86-100, In Chlorinated Phenoxy Acids and
Their Dioxins: Mode of Action, Health Risks and Environmental
Effects, Report from a Conference; 1977, Stockholm, Sweden.
Edited by C. Ramel. Stockholm, Sweden: Swedish Natural
Science Research Council. (Ecological bulletins (Stockholm),
no. 27)
Abou Elfadl, M.M. ; Fahmy, M. (1958) Effect of sodium 2,4-D and
M.C.P.A. on root nodulation of legumes and soil microorganisms.
Agricultural Research Review 36:333-338.
Akzo Zout Chemie Nederland B.V. .(1973) Spectrophotometric Determi-
nation of Chlorophenol in Phenoxy Acetic Acid or Phenoxy Propi-
onic Acid and Their Salts with 4-Mino Antipyrine. Method Mr.
259.3 dated Feb 12, 1973. (Unpublished study received Feb 20,
1973 under 6305-10; submitted by Robeco Chemicals, Inc., New
York, N.Y.; CDL:02238R-F)
Akzo Zout Chemie nv (1971) Gas Chromatographic Determination of
.(Methyl) -(chloro)phenoxyace tic acids and (Methyl) .(chloro)- ___
phenoxypropionic acids and Their Salts. Method nr. 247.1 dated
Apr 20, 1971. (Unpublished study received Feb 20, 1973 under
6305-10; submitted by Robeco Chemicals, Inc., New York, N.Y.;
CDL:022388-A)
Allard, R.W. ; DeRose, H.R. ; Swanson, C.P. (1946) Some effects of
plant growth-regulators on seed germination and seedling
development. Botanical Gazette 107: 575-583.
Allen, F.C. (1966) Tolerance of barley to MCPA and dicamba. Paqes
25-27 , J[n Proceedings of the New Zealand Weed and Pest Control
Conference. Vol. 19. Hamilton, New Zealand: New Zealand Weed
and Pest Control Conference.
Amchem Products, Incorporated (1968) Summary of Performance Data:
Brominal Plus. Summary of studies 002199-B through 002199-P.
(Unpublished study received Oct 30, 1968 under 264—239;
submitted by Union Carbide Agricultural Products Co., Aribler,
Pa.;(CDL: 002199-A)
American Cyanamid Company (1973) General Summary. (Unpublished
study received Sep 19, 1975 under 241-EX-64; CDL:094696-C)
-------
OFFICE OF PESTICIDE PROGRAMS
REGISTRATION STANDARD BIBLIOGRAPHY
Citations Considered to be Part of the Data Base Supporting
Registrations Under the Standard
000004609 American Cyanamid Company (1974) General Sumnary. Stannary of
studies 224170-R through 224170-V. (Unpublished study received
Jan 8, 1975 under 241-EX-64; CDL:224170-Q)
000004701 Bache, C.A.; Hardee, D.D.; Holland, R.F.; Lisk, D.J. (1964) Absence
of Phenoxyacid herbicide residues in the milk of dairy cows at
high feeding levels. Journal of Dairy Science XLVII(3):29B-299.
(Also ^n unpublished submission received Sep 12, 1968 under
8F0676; submitted by Dow Chemical U.S.A., Midland, Mich.; CDL:
092980-0)
000004702 Bache, C.A.; Lisk, D.J.; Wagner, D.G.; Wagner, R.G. (1964) Elimina-
tion of 2-Methyl-4-chlorophenoxyacetic acid and 4-(2-Methyl-4-
chlorophenoxybutyric) acid in the urine from cows. Journal of
Dairy Science XLVII(l):93-95. (Also In unpublished submission
received Sep 12, 1968 under 8F0676; submitted by Dow Chemical
U.S.A., Midland, Mich.; CDL:092980-P)
005006168 Bache, C.A.; Lisk, D.J.; Wagner, D.G.; Warner, R.G. (1964)
Elimination of 2-methyl-4-chlorophenoxyacetic acid and
4-(2-methyl-4-chlorophenoxybutyric) acid in the urine from
cows. Journal of Dairy Science 47(l):93-95.
005012661 Balezina, L.S. (1967) Vliyanie nekotorykh gerbitsidov na razvitie
pochvennykh vodoroslei. [Effect of some herbicides on the
development of soil algae.] Mikrobiolcgiya. [Microbiology.]
XXXVI(1):163-167.
000004570 Ball, R.W.E.; Soundy, M. (1958) 2,4-DB and MCPB in Lucerne:
Part I. The Effect of 2,4-DB and MCPB on the Development of the
Lucerne Plant. (Preprint, British Weed Control Conference,
November, 1958; unpublished study received Dec 5, 1960 under
359^400; prepared by May & Baker, Ltd., Agricultural and Horti-
cultural Research Station, Eng., submitted by Rhone-Poulenc,
Inc., Monmouth Junction, N.J.; CDL:023310-C)
000004454 Bendixen, W.E. (1974) Report of Planned Work Accomplished: Bean
Weed Control—Shield Spraying MCPA and 2,4-D: Project No. 19.
(Unpublished study received Feb 10, 1976 under 6E1746; prepared
by Univ. of California, Agricultural Extension Service in copo-
eration with California, Dept. of Food and Agriculture, Chemis-
try Laboratory Services, submitted by Interregional Research
Project No. 4, New Brunswick, N.J.; CDL:095368-D)
I or
-------
MRID I
000004512
000021975
000004625
OFFICE OF PESTICIDE PROGRAMS
REGISTRATION ST7'-T1.\'r PIBLIOGRArTY
Citations Considered to be P*rt of the nata Base Supporting
Registrations Under the Standard
CITATION
Bentley, R.E. (1974) Bioassay Report Submitted to Afichem Products,
Inc., Ambler, Pennsylvania: Acute Toxicity of Three Amchem Com-
pounds to Bluegill (Lepomis macrochirus) and Rainbow Trout
(Salmo gairdneri). (Unpublished study received Sep 13, 1974
under 264-55; prepared by Bionomics, EG&G, Inc., submitted by
Union Carbide Agricultural Products Co., Ambler, Pa.; CDL:
131084-B)
Biesemeier, J.A.; Argevine, D.M. (1979) Inhalation—EPA. (Unpub-
lished study received Jul 23, 1979 under 39335-1; prepared by
Raltech Scientific Services, Inc., submitted by Fallek-Lankro
Corp., Tuscalcosa, Ala.; CDL:233870-E)
Bjerke, E.L.; Herman, J.L. (1971) Residues of 2-Methyl-4-chloro-
phenoxyacetic acid and 2-Methyl-4-chlorophenol in Tissues of
Beef Calves Fed MCPA. (Unpublished study received Oct 11, Wl
under 9F0761; prepared by Dow Chemical Co., submitted by Nation-
al Agricultural Chemicals Association, industry Task Force on
Phenoxy Herbicide Tolerances, Washington, D.C.; CDL:091311-F)
- 000004626
Bjerke,-E.L.; Herman-, -J.t.—fl^T}) ltesix3ues-of-2=Methyl-4-chloro- —
phenoxyacetic acid and 2-Methyl-4-chlorophenol in Tissues of
Sheep Fed MCPA. (Unpublished study received Oct 11, 1971 under
9F0761; prepared by Dow Chemical Co., submitted by National
Agricultural Chemicals Association, Industry Task Force on
Phenoxy Herbicide Tolerances, Washington, D.C.; CDL:091311-G)
005003259 Bjerke, E.L.; 'Herman, J.L.; Miller, P.W.; Wetters, J.H. (1972)
Residue study of phenoxy herbicides in milk and cream. Journal
of Agricultural and Food Chemistry 20(5):963-967.
005004641 Bollag, J.M.; Helling, C.S.; Alexander, M. (1967) Metabolism of
4-chloro-2-methylphenoxyacetic acid by soil bacteria. Applied
Microbiology 15(6):1393-1398.
GS 0017-002 Buchanan, S., Pell, I.E., Woodhouse, R.N. (1979) Acute Toxicity of
MCPA to Mirror Carp and Rainbow Trout. (Unpublished study
received Nov 19,1980; submitted by Diamond-Shamrock Corp.)
005015003 Bueno, A.J.; Cabanilla, H.C. (1971) Study on the reaction of
recommended rice varieties to early-post and pre-emergence
herbicides. Down to Earth 27(3):8-ll.
-------
MRID #
005016555
005003491
005004844
005014225
000021917
000004782
OFFICE OF PESTICIDE PROGRAMS
REGISTRATION STANDARD BIBLIOGRAPHY
Citations Considered to be Part of the Data Base Supporting
Registrations Under the Standard
CITATION
/
Buselmaier, W.; Rcehrborn, G.; Propping, P. (1972)
Mutagenitaets-Untersuchungen mit Pestiziden im Host-mediated
assay und mit dem Dominanten Letaltest an der Maus.
Byford, W.J.; Prince, J. (1976) Experiments on the effect of
hormone weedkillers on sugar beet. Journal of Agricultural
Science 86(1):135-139.
Cessna, A.J.; Grover, R. (1978) Spectre-photometric determination
of dissociation constants of selected acidic herbicides.
Journal of Agricultural and Food Chemistry 26(1):289-292.
Chang, W.L. (1969) Performance of granular herbicides for
transplanted rice. Nung Yen Yen Chiu. [Agricultural
Research.] 18(4):11-18.
Chipman, Incorporated (1973) M.C.P. Acid. Includes undated method.
(Unpublished study received Jun 20, 1973 under 8203-18; CDL:
005990-A) 3
Chipman Chemical Company, Inc. (1967) Effectiveness and Crop Safety
Data:-SR3/67. -^Unpublished -study-including summary tables and
005003765
005006328
005003559
efficacy reports Port 64.12, Port 65.4, Port 65.21, Port 65.22,
Port 65.28, Port 66.58, Port 66.60, BB.65.100, BB.65.102,
BB.65.151, BB.66.7, BB.66.87, C.65.9, C.65.11, C.65.21, C.65.24,
C.65.40, C.65.42, C.65.57, C.66.13, C.66.16, C.66.18, C.66.45,
C.66.47, C66.49, C.66.50, PA.64.8, PA.65.2 and weed control
summary 1966, received Mar 10, 1967 under 359-601; submitted by
Rhone-Poulenc, Inc., Monmouth Junction, N.J.; CDL:023320-B)
Chow, C.; Montgomery, M.L.; Yu, T.C. (1971) Methodology and
analysis for residues of MCP and 2,4,5-T in wheat. Bulletin of
Environmental Contamination and Toxicology 6(6):576-580.
Cohen, S.Z.; Zweig, G.; law, M.; Wright, D.; Bontoyan, W.R. (1978)
Analytical determination of N -nitroso compounds in pesticides
by the United States Environmental Protection Agency—a
preliminary study. Pages 333-342, Jn Environmental Aspects
of N -Nitroso Compounds. Washington, D.C.: Environmental
Protection Agency. (IARC scientific publications, vol. 19)
Collier, R.H.; Grimes, G.S. (1974) Determination of chlorophenoxy
acids in formulations by gas-liquid chromatography of their
trimethylsilyl derivatives. Journal of the Association of
Official Analytical Chemists 57(4):781-784.
101
-------
OFFICE OF PESTICIDE PROGRAMS
REGISTRATION STANDARD BIBLIOGR^P^'
Citations Considered to be Part of the Data Rase S'Jiooortina
Registrations Under the Standard
MRID t CITATION
005003725 Collins, D.J.; Gaunt, J.K. (1970) The tnetabolic fate of
4-chloro-2-methylphenoxyacetic acid in peas. Biochemical
Journal 118(3):54.
000005552 Conkin, R.A. (1956) Procedures for Determining Residues of MCP
(2-Methyl-4-chlorophenoxyacetic acid) in Treated Crops. Method
dated Oct 29, 1956. (Unpublished study received Dec IB, 1967
under 9F0676; prepared by Monsanto Chemical Co., submitted by
National Agricultural Chemicals Association, Industry Task Force
on Phenoxy Herbicide Tolerances, Washington, D.C.; CDL:0929R1-A)
• s
005004651 Crosby,*D.G.; Bowers, J.B. (1966) Determination of 2,4-D residues
in animal products. Bulletin of Environmental Contamination
and Toxicology 1(3):104-107.
005009423 DaSilva, E.J.; Henriksson, L.E.; Henriksson, E. (1974) Effect of
pesticides on nitrogen fixation by blue-green algae. Revista
de Microbiologia 5(4):73-74.
005005265 DaSilva, E.J.; Henriksson, L.E.; Henriksson, E. (1975) Effect of
pesticides on blue-green algae and nitrcaen-fixation. Archives
of Environmental Contamination and Toxicology 3(2):193-204.
005009865 DaSilva, E.J.; Henriksson, L.E.; Udris, M. (1977) Growth responses
of mycorrhizal Boletus and Rhizopogon species to pesticides.
Transactions of the British Mycological Society 68(3):434-437.
005004661 De, B.K.; Mukhopadhyay, S. (1971) Effect of MCPA and Stam F-34 on
the occurrence of seme nutritional groups of bacteria in the
rice fields of West Bengal. International Rice Ccrmission
Newsletter 20(3):35-40.
000004442 Del Monte Corporation (1968) MCPA Rer.idues on Peas and Pea Vines:
Del Monte Code No. 19708. (Unpublished study received on un-
known date under 9F0761; submitted by Dow Chemical U.S.A., Mid-
land, Mich.; CDL:092000-H)
000004443 Del Monte Corporation (1968) MCPA Residues on Peas and Pea Vines:
Del Monte Code Mo. 19708. (Unpublished study received on un-
known date under 9F0761; submitted by Dow Chemical U.S.A., Mid-
land, Mich.; CDL:092000-H)
000004444 Del Monte Corporation (19??) Trails with the sodium salt of MCPA
for weed control inpeas. (Unpublished study conducted by Donald
W. Davis, Utah State University, togan, Utah; PCC 73-E-21).
-------
MRID f
OFFICE OF PESTICIDE PROGRAMS
REGISTRATION STANDARD BIBLIOGRAPHY
Citations Considered to be Part of the Data Base Supporting
Registrations Under the Standard
CITATION
005011096 DeRose, H.R. (1946) Persistence of some plant growth-regulators
when applied to the soil in herbicidal treatments. Botanical
Gazette 107:583-589.
000004764 Devine, J.M. (1970) Report on MZPA Residues in Rough Rice & Rice
Straw. Includes two undated methods. (Unpublished study re-
ceived Jan 22, 1971 under 9F0761; prepared by Syracuse Univ. Re-
search Corp., submitted by National Agricultural Chemicals Asso-
ciation, Industry Task Force on Phenoxy Herbicide Tolerances,
Washington, D.C.; CDL:091308-L)
GS 0017-101 DeWitt, J.B. et al., Effects of Pesticides on Fish and Wildlife,
USDI, FS.W Circ. 143 pp 4,5,33,45, 1962
005012898 Domingo, I.S.; Palis, G.T. (1966) Chemical weed control experiment
in upland rice at the La Granja Experiment Station. Philippine
Journal of Plant Industry 31(3):145-156.
005004273 Dorschner, K.P.; Buchholtz, K.P. (1956) Wetting ability of aqueous
herbicidal sprays as a factor influencing stands of alfalfa
seedlings. Agronomy Journal 48(2):59-63.
000025154 Duggan, R.E.; Barry, H.C.; Johnson, L.Y. (1967) Residues in food
and feed: Pesticide residues in total diet samples (II). Pesti-
cides Monitoring Journal 1(2):2-12. (Also In unpublished sub-
mission received Nov 5, 1970 under 1F1060; submitted by Wlsicol
Chemical Corp., Chicago, 111.; CDL:099195-U)
005006190 Edmond, D.B. (1956) The effect of MCPB (sodium
2-methyl-4-chlorophenoxybutyrate) on young red clover
(Trifolium pratense) and weeds. New Zealand Journal of
Science and Technology, Section A 38(4):397-402.
-------
OFFICE OF PESTICIDE PROGRAMS
REGISTRATION STANDARD BIBLIOGRAPHY
Citations Considered to be Part of the Data Base Supportinq
Registrations Under the Standard
MRID # CITATION
000004659 Elenewski, C.A. ; Wang, T. (1975) AvengeR (CL 84,777): Determi-
nation of CL 84,777 (l,2-Dimethyl-3,5-diphenyl-lH-pyrazoliun
methyl sulfate), Bromoxynil (3,5-Dibromo-4-hydroxylbenzonitrile)
and MCPA ( 2-Methyl-4-chlorophenoxyacetic acid) Residues in Wheat
Grain and Straw Following Ground Application of Avenqe Alone and
in combination with MCPA or Bromoxynil, (Oregon): Report No. C-
820. (Unpublished study received Nov 14, 1975 under 6F1703;
prepared in cooperation with Biodynamics , Inc., submitted by
American Cyanamid Co., Princeton, N.J.; CDL:094738-AH)
• s
000004655 Elenewski, C.A. ; Wang, T. (1975) AvengeR (CL 84,777): Determi-
nation of CL 84,777 (l,2-Dimethyl-3,5-diphenyl-lH-pyrazolium
methyl sulfate), Bromoxynil (3,5-Dibrorro-4-hydroxylbenzonitrile)
and MCPA (2-Methyl-4-chlorophenoxyacetic acid) Residues in Durum
Wheat Grain and Straw Following Aerial Application of Avenge
Alone and in Combination with MCPA or Brcmoxynil, (Minnesota):
Report No. C-823. (Unpublished study received Nov 14, 1975 un-
der 6F1703; prepared in cooperation with Biodynamics, Inc., sub-
mitted by American Cyanamid Co., Princeton, N.J.; CDL:094733-^D)
005006302 Elliott, B.R.; Lumb, J.M.; Reeves, T.G.; Telford, T.E. (1975)
Yield losses in weed- free wheat and barley due to
post-emergence herbicides. Weed Research 15 (2): 107-111.
005003256 Elo, H. (1976) Distribution and elimination of
2-methyl-4-chlorophenoxyacetic acid (MCPA) in male rats. Acta
Pharmacologica et Toxicologica 39(1): 58-64.
005004181 Elo, H.; Parvinen, M. (1976) Effect of sodium
2-methyl-4-chlorophenoxyacetate on spermatogenesis in the rat.
Journal of Reproduction and Fertility 48:243-244.
005006041 Erdelska, 0. (1966) The effect of 2-methyl-4-chlorophenoxyacetic
acid on the development of Hprdeum distichum L. Ovule.
Biologia Plantarum 8 (2): 117-121.
005008355 " Eronen, L. ; Julkunen, R. ; Saarelainen, A. (1979) MCPA residues in
developing forest ecosystem after aerial spraying. Bulletin of
Environmental Contamination and Toxicology 21(6):791-798.
-------
MRID f
005003766
OFFICE OF PESTICIDE PROGRAMS
REGISTRATION STANDARD BIBLIOGRAPHY
Citations Considered to be Part of the Data Base Supporting
Registrations Under the Standard
err AT ION
Faulkner, J.K.; Woodcock, D. (1%5) Fungal detoxication. Part
VII. Metabolism of 2,4-dichlorophenoxyacetic and
4-chloro-2-methylpnenoxyacetic acids by Aspergillus niger .
Journal of the Chemical Society :1187-1191.
000028293 Fink, R.; Broughton, W.S., Jr. (1973) Final Report: Eight-Day Die-
tary LCgQ—Mallard Ducks: Project No. 686-136. (Unpublished
study received Feb 18, 1976 under 876-25; prepared by Hazleton
Laboratories, Inc., submitted by Velsicol Chemical Corp., Chi-
cago, 111.; CDL:225100-K)
' f
000004544 Fink, R.; Broughton, W.S., Jr. (1973) Final Report: Eight-Day Die-
tary LC^—Bobwhite Quail: Project No. 686-137. (Unpub-
lished study received Dec 11, 1974 under 876-45; prepared by
Hazelton Laboratories, Inc., submitted by \felsicol Chemical
Corp., Chicago, 111.; CDL:003548-E)
000004545 Fink, R.; Broughton, W.S., Jr. (1973) Final Report: Eight-Day Die-
tary LCcQ—^Mallard Ducks: Project No. 6R6-13S. (Unpublished
study received Dec 11, 1974 under 876-45; prepared by Hazelton
Laboratories, Inc., submitted by \felsicol Chemical Corp.,
Chicago, 111.; CDL:003548-F)
005003428 Fisher, P.R.; Appleton, J.; Pemberton, J.M. (1978) Isolation and
characterization of the pesticide-degrading plasmid pJPl
from Alcaligenes paradoxus . Journal of Bacteriology
135(3):798-804.
005005788 Fletcher, W.W.; Raymond, J.C. (1956) Toxicity and breakdown of
"hormoneM herbicides. Nature 178(4525):151-152.
005005860 Flinchum, W.T.; Stansel, J.W. (1972) Effects of applications of
phenoxy herbicides on Bluebelle rice yields and dayflower
control. Pages 21-24, Jjn Texas Agricultural Experiment Station
Progress Report. College Station, Tex.: Agricultural
Experiment Station.
005005531 Flinchum, W.T.; Westfall, D.G.; Stansel, J.W. (1973) Effects of
phenoxy herbicides on yield of first and second crop rice.
Pages 1-3, Jto Texas Agricultural Experiment Station Progress
Report No. PR-3177. College Station, Tex.: Texas Agricultural
Experiment Station, TexasA & M University.
m
-------
MRID *
OFFICE OF PESTICIDE PROGRAMS
REGISTRATION STANDARD BIBLIOGRAPHY
Citations Considered to be Part of the Data Base Supporting
Registrations Under the Standard
CITATION
005019954 Frank, R.; Sirons, G.J.; Ripley, B.D. (1979) Herbicide
contamination and decontamination of well waters in Ontario,
Canada, 1969-78. Pesticides Monitoring Journal 13(3):120-127.
000004473 Frost, K.R., Jr. (1966) Weed Control Headlines 1965-1966. (Unpub-
lished study received Nov 6, 1967 under 464-398; prepared by
South Dakota State Univ., submitted by Dow Chemical U.S.A.,
Midland, Mich.; CDL:003622-R)
005006578 Fryer, 3.D.; Kirkland, K. (1970) Field experiments to investiqate
long-term effects of repeated applications of ?CPA, tri-allate,
simazine and linuron: report after 6 years. Weed Research
10(2):133-158.
005014496 Fykse, H. (1975) Untersuchungen ueber Sonchus arvensis L.: II.
Translokation von 14C-MCPA unter verschiedenen Bedinqunqen.
005013377 Fykse, H. (1976) Untersuchungen ueber Sonchus arvensis L.; III.
Metabolismus von MCPA. [Investigations with Sonchus arvensis
L: III. Metabolism of MCPA. Weed Reserach 16(5):309-316.
000004513 Gabriel, K.L. (1971) Draize Eye Irritation—Rabbits. (Unpublished
study received Nov 16, 1971 under 264-36; prepared by Biosearch,
Inc., for Amchem Products, Inc., submitted by Union Carbide
Agricultural Products Co., Ambler, Pa.; CDL:100823-A)
005005451 Gamar, Y.; Gaunt, J.K. (1971) Bacterial metabolism of
4-chloro-2-methylphenoxyacetate: formation of glyoxylate by
side-chain cleavage. Biochemical Journal 122(4):527-531.
005004565 Gardner, K.; Overton, K.C. (1960) Analysis of MCPA/TBA herbicide
formulations: II. A gas-liquid chromatograDhic method for the
determination of 4-chloro-2-methyl phenoxyacetic acid.
Analytica Chimica Acta 23:337-345.
005003416 Gaunt, J.K.; Evans, W.C. (1971) Metabolism of
4-chloro-2-methylphenoxyacetate by a soil pseudomonad:
preliminary evidence for the metabolic pathway. Biochemical
Journal 122(4):519-526.
-------
OFFICE OF PESTICIDE PROGRAMS
REGISTRATION STANDARD BIBLIOGRAPHY
Citations Considered to be Part of the Data Base Supporting
Registrations Under the Standard
MRID # CITATION
000041634 Gilbert, C.M., Hopkins, R.; MacDonald, C.M.; et al. (1978) The Met-
abolic Fate of (14O-MPCA (4-Chloro-l-methyl(Ring-U-14C) phenox-
yacetic acid) in the Rat: Report No., 1334R3-277/1.
(Unpublished study including submitter surmary, received Sep 4,
1980 under 2217-EX-2; prepared by Hazleton Laboratories Europe,
Ltd. and Boots Co., Ltd., cubmitted by PBI-Cordon Corpt., Kanasa
City, Kans.; CDL:243193-A)
005005888 Gillberg, B.O. (1971) On the effects of some pesticides
on Rhizobium and isolation of pesticide-resistant mutants.
Archives of Microbiology 75(3):203-208.
005015632 Glynne Jones, G.D.; Cornell, J.U. (1954) Studies of the toxicity
to worker honey-bees ( Apis mellifera L.) of certain chemicals
used in plant protection. Annals of Applied Biology
41(2):271-279.
000020121 Grogan, B.; Banner, J.; Hayner, J.; et al. (1970) Diuron plus
Bromoxynil—Winter Wheat. (Unpublished study including letter
dated Jun 1, 1970 from A.A. Baber to file, received Jan 26, 1971
under 352-247; submitted by E.I. du Pont de Nemours & Co.,
Wilmington, Del.; CDL:002858-A)
005015630 Grossbard, E. (1971) The effect of repeated field applications of
four herbicides on the evolution of carbon dioxide and
mineralization of nitrogen in soil. Weed Research
11(4):263-275.
000004766 Guardigli, A. (1970) MCPA Residues in Flax Seed: Field Test Project
No. STP 69-26; 69-27. Includes method no. 104 dated Nov 25,
1969. (Unpublished study received Jan 22, 1971 under 9F0761;
prepared by Rhodia, Inc. in cooperation with Univ. of Minnesota
and North Dakota State Univ. of Agriculture and Applied
Science, submitted by National Agricultural Chemicals Associa-
tion , Industry Task Force on Phenoxy Herbicide Tolerances, Wash-
ington, D.C.; CDL:091308-O)
000021920 Guardigli, A. (1973) Rhodia Analytical Method No. 122: Electron
Capture GLC Residue Measurement of Total 2-Methyl-4-chlorophen-
oxyacetic acid, MCPA, after Formation of Its Nitro Derivatives
and Esterification to Its Methyl Ester, and TLC Residue Determi-
nation of Total Chlorophenols. Method dated Oct 1973. (Unpub-
lished study received Oct 3, 1975 under 6E1681; submitted by
Rhone-Poulenc Chemical Co., Monmouth Junction, N.J.; CDL:
097351-B)
-------
MRID #
OFFICE OF PESTICIDE PROGRAMS
REGISTRATION STANDARD BIBLIOGRAPHY
Citations Considered to be Part of the Data Base Supporting
Registrations Under the Standard
CITATION
000004787 Guardigli, A. (1974) Rhodia Analytical Method No. 123. Includes
two methods dated March 1974. (Unpublished study received Jan
30, 1976 under 359-534; prepared by Rhodia, Inc., submitted by
Rhone-Poulenc, Inc., Monmouth Junction, N.J.; CDL:222737-A)
000004788 Guardigli, A. (1974) MCPB Sodium Salt in Peas: Aerial Applications.
(Unpublished study received Jan 30. 1976 under 359-534; prepared
by Rhodia, Inc., submitted by Rhone-Poulenc, Inc., Monmouth
Junction, N.J.; CDL:222737-B)
000004449 Guardigli, A.; Henckler, P.M. (1973) Final Summary: MCPA and Phenol
Metabolite in Pasture and/or Range Grasses. (Unpublished study
received on unknown date under 9F0761; prepared by Rhodia, Inc.,
submitted by Dow Chemical U.S.A., Midland, Mich.; CDL:0920ni-F)
000022569 Gurd, M.R.; Harmer, G.L.M.; Lessel, B. (1964) The Toxicity of Meco-
prop and MCPA to Rats: Report No. 1254. (Unpublished study re-
ceived Jan 21, 1965 under unknown admin, no.; prepared by Roots
Pure Drug Co., Ltd., submitted by ; CDL:102704-A)
000004822 Guyton, C.L. (1977) Procedures for the Measurement of Asulam, MCPA,
Sulfanilamide and Acetylasulam in/on Flax: Forages, Straw, Seed
and Mill-Processed Flax Seed Fractions. Method no. 143 dated
Jul 1977. (Unpublished study received Apr 13, 1979 under 359-
662; prepared by Rhodia, Inc., submitted by Rhone-Poulenc, Inc.,
Monmouth Junction, N.J.; CDL:238025-B)
000021977 Harwell, C. (1978) A Gas Chromatography Method for Determination of
2 Methyl 4 Chlorophenoxyacetic acid and Impurities in Technical
MCPA. Method no. lA/1/2 dated Jan, 1978. (Unpublished study
received Jul 23, 1979 under 39335-1; submitted by Fallek-Lankro
Corp., Tuscalcosa, Ala.; CDL:238B71-A)
005003795 Hattula, M.L.; Elo, H.; Reunanen, H.; Arstila, A.U.; Sorvari, T.E.
(1977) Acute and subchronic toxicity of
2-methyl-4-chlorophenoxyacetic acid (MCPA) in male rat. I.
Light microscopy and tissue concentrations of MCPA. Bulletin
of Environmental Contamination and Toxicology 18(2):152-15B.
005016652 Helling, C.S. (1971) Pesticide mobility in soils: II.
Applications of soil thin-layer chromatography. Proceedings of
the Soil Science Society of America 35(5):737-743.
-------
OFFICE OF PESTICIDE PROGRAMS
REGISTRATION STANDARD BIBLIOGRAPHY
Citations Considered to be Part of the Data Base Supporting
Registrations Under the Standard
MRID « CITATION
005004203 Helling, C.S.; Turner, B.C.'(1968) Pesticide mobility:
determination by soil thin-layer chromatography. Science
162(3853):562-563.
000004492 Herman, J.L.; Bjerke, E.L. (1970) Determination of MCPA and 2-Meth-
yl-4-chlorophenol in Milk and Cream by Gas Chromatography.
Method no. fCR 70.17 dated Dec 2, 1970. (Unpublished study re-
ceived Jan 11, 1971 under 9F0761; prepared by Dow Chemical Co.,
submitted by National Agricultural Chemicals Association, Indus-
try Task Force on Phenoxy Herbicide Tolerances, Washington,
D.C.i; CDL:091313-J)
000004627 Herman, J.L.; Bjerke, E.L. (1971) Determination of MCPA and 2-
Methyl-4-chlorophenol in Cattle and Sheep Tissues by Gas Chrcma-
tography. Method ACR 71.10 dated Jun 24, 1971. (Unpublished
study received Oct 11, 1971 under 9F0761; prepared by Dow Chem-
ical Co., submitted by National Agricultural Chemicals Associa-
tion, Industry Task Force on Phenoxy Herbicide Tolerances,
Washington, D.C.; CDL:091311-H)
000004491 Herman, J.L.; Bjerke, E.L.; Getzendaner, M.E. (1970) Residue of
2-Methyl-4-chlorophenoxyacetic acid and 2-Methyl-4-chlorophenol
in Milk and Cream from Cows Fed MCPA. (Unpublished study re-
ceived Jan 11, 1971 under 9F0761; prepared by Dow Chemical Co.,
submitted by National Agricultural Chemicals Association, Indus-
try Task Force on Phenoxy Herbicide Tolerances, Washington,
D.C.; CDL:091313-1)
000004624 Herman, J.L.; Bjerke, E.L.; Getzendaner, M.E. (1971) Residues of
2-Methyl-4-chlorophenoxyacetic acid and 2-Methyl-4-chlorophenol
in Milk and Cream from Cows Fed MCPA. (Unpublished study re-
ceived Oct 11, 1971 under 9F0761; prepared by Dow Chemical Co.,
submitted by National Agricultural Chemicals Association, Indus-
try Task Force on Phenoxy Herbicide Tolerances, Washington,
D.C.; CDL:091311-E)
005021236 Herzel, F.; Schmidt, G. (1979) (Testing the leaching behavior of
herbicides on lysimeters and small columns.] WaBoLu-Berichte
IV5"
-------
OFFICE OF PESTICIDE PROGRAMS
REGISTRATION STANDARD BIBLIOGRAPHY
Citations Considered to be Part of the Data Base Supporting
Registrations Under the Standard
MRID * CITATION
000004632 Higham, J.W. (1974) The Gas Chromatographic Determination of MCPA
(2-Methyl-4-chlorophenoxyacetic acid) and Bronoxynil (3,5-Dibro-
no-4-hydroxybenzonitrile) in Fortified Wheat Grain and .Straw:
Report No. C-575. (Unpublished study received Nov 14, 1975
under 6F1703; prepared in cooperation with State Univ. of New
York~0swego, Lake Ontario Environmental Laboratory, submitted
by Anerican Cyanamid Co., Princeton, N.J.; CDL:094738-D)
000004633 Higham, J.W. (1975) The Gas Chromatographic Determination of MCPA
(2-Methyl-4-chlorophenoxyacetic acid) and Bronoxynil (3,5-Dibro-
mo-4-*hydroxybenzonitrile) in Fortified Wheat Grain and Straw:
Report No. C-804. (Unpublished study received Nov 14, 1975
under 6F1703; prepared in cooperation with Biodynamics, Inc. and
State Univ. of New York—Oswego, Lake Ontario Environmental
Laboratory, submitted by American Cyanamid Co., Princeton, N.J.;
CDL:094738-G)
000005570 Higham, J.W.; Feeny, R.W. (1974) AvengeR (CL 84,777): Determi-
nation of Bromoxynil (3,5-Dibromo-4-hydrcxylen7onitrile) and
MCPA (2-Methyl-4-chlorophenoxyacetic acid) Residues in \Jheat
Grain Following Ground^ Postemergence Application Where Each.Was
Applied in Combination with Avenge (l,2-Dimethyl-3,5-diphenyl
pyrazolium methyl sulfate), (Oregon): Report No. C-578. (Unpub-
lished study received Nov 14, 1975 under 6F1703; prepared in
cooperation with State Univ. of New York—Oswego, Lake Ontario
Environmental Laboratories, submitted by American Cyanamid Co.,
Princeton, N.J.; CDL:094738-Z)
000004650 Higham, J.W.; Feeny, R.W. (1974) AvengeR (CL 84,777): Determi-
nation of MCPA (2-Methyl-4-chlorophenoxyacetic acid) Residues in
Wheat Grain and Straw Following Ground, Postemergence Applica-
tion in Combination with Avenge (1,2-Dimethyl 3,5-diphenyl
•pyrazolium methyl sulfate), (Montana): Report No. C-577. (Un-
published study received Nov 14, 1975 under 6F1703; prepared in
cooperation with State Univ. of New York—Oswego, Lake Ontario
Environmental Laboratories, submitted by American Cyanamid Co.,
Princeton, N.J.; CDL:094738-X)
lit
-------
OFFICE OF PESTICIDE PROGRAMS
REGISTRATION STANDARD BIBLIOGRAPHY
Citations Considered to be Part of the Data Base Supporting
Registrations Uncter the Standard
MRID * CITATION
000005567 Higham, J.W.; Feeny, R.W.; Cheston, K.G.; Snyder, E.H.; Wingfield,
C.B. (1975) AvengeR (AC 84,777): Determination of CL 84,
777 (l,2-Dimethyl-3,5-diphenyl pyrazolium methyl sulfate), Bro-
moxynil (3,5-Dibromo-4-hydroxylbenzonitrile) and MCPA (2-Methyl-
4-chlorophenoxyacetic acid) Residues in Barley Grain and Straw
Following Ground Application (Colorado): Report No. C-594. (Un-
published study received Jan 8, 1975 under 241-EX-64; prepared
in cooperation with Lake Ontario Environmental Laboratory, sub-
mitted by American Cyanamid Co., Princeton, N.J.; CDL:224170-T)
000004611
000004613
005014853
Higham, J.W.; Feeny, R.W.; Snyder, E.H; KUshnak, G.; O'Hare, T.R.
(1975) AvengeR (CL 84,777): Determination of CL 84,777 (1,
2-Dimethyl-3,5-diphenyl pyrazolium methyl sulfate), Brcnoxynil
(3,5-Dibromo-4-hydroxylbenzonitrile) and MCPA (2-Methyl-4-
chlorophenoxyacetic acid) Residues in Barley Grain and Straw
Following Ground Application of Avenge Alone and in Combination
with MCPA, Bronoxynil, 2,4-D and Bromoxynil plus MCPA: Montana:
Report No. C-593. (Unpublished study received Jan 8, 1975 under
241-EX-64; prepared in cooperation with Montana State Univ. and
Lake Ontario Environmental Laboratory, submitted by American
Cyanamid Co., Princeton, N.J.; CDL:224170-S)
Higham, J.W.; Feeny, R.W; Cheston. K.G.; Snyder, E.H.; Nowatski,
R.; O'Hare, T.R. (1975) AvengeR (CL 84,777): Determination
of CL 84,777 (l,2-Dimethyl-3,5-diphenyl pyrazolium methyl sul-
fate), Brcnoxynil (3,5-Dibromo-4-hydroxylbenzonitrile) and MCPA
(2-Methyl-4-chlorophenoxyacetic acid) Residues in Barley Grain
and Straw Following Ground Application of Avenge Alone and in
Combination with MCPA, Bromoxynil or 2,4-D (North Dakota): Re-
port No. C-596. (Unpublished study received Jan 8, 1975 under
241-EX-64; prepared in cooperation with Lake Ontario Environ-
mental Laboratory, submitted by American Cyanamid Co., Prince-
ton, N.J.; CDL: 224170-V)
Holroyd, J. (1957) The breakdown of MCPA, 2,4-D and CIPC in soil.
Pages 793-801, In Proceedings of the 3rd British Weed Control
Conference; 1956, Blackpool, England. Vol. 2. Droitwich,
England: British Weed Control Conference.
in
-------
MRID #
000004756
000004757
000004775
000004776
005015747
005020356
000004993
000041637
OFFICE OF PESTICIDE PROGRAMS
REGISTRATION STANDARD BIBLIOGRAPHY
Citations Considered to be Part of the Data Base Supporting
Registrations Under the Standard
CITATION
Holsing, G.C. (1968) Final Report: 13-Week Dietary/Oral Administra-
tion — Dogs: Project No. 517-101. (Unpublished study received
Jan 22, 1971 under 9F0761; prepared by Hazleton Laboratories,
Inc., submitted by National Agricultural Chemicals Association,
Industry Task Force on Phenoxy Herbicide Tolerances, Washington ,
D.C.; CDL-.091309-A)
Holsing, G.C. (1970) Final Report: 13-Week Dietary Administration —
Dogs: Project No. 517-107. (Unpublished study received Jan 22,
1971 Bunder 9F0761; prepared by Hazleton Laboratories, Inc., sub-
mitted by National Agricultural Chemicals Association, Industry
Task Force on Phenoxy Herbicide Tolerances, Washington, D.C. ;
CDL:091309-B)
Holsing, G.C. ; Kundzin, M. (1963) Final Report: Three-Month Dietary
Administration — Rats: Project No. 517-100. (Unpublished study
received Dec 18, 1970 under 9F0761; prepared by Hazleton Lab-
oratories, Inc., submitted by Dow Chemical U.S.A., Midland,
Mich.; CDL:>094531-B)
- Hols ing, -G.C. ; Kundzin ,"M.— ( 1970 ) -Final -Report : ^tree-Month -Pietary-
Administration — Rats: Project No. 517-106. ~ (Unpublished study
received Dec 18, 1970 under 9F0761; prepared by Hazleton Lab-
oratories, Inc., submitted by Dow Chemical U.S.A., Midland,
Mich.; CDL:094531-C)
Hopkins, R. ; Rain, J.M. (1971) The effect of marine pollutants on
Laminarea hyperboria. Marine Pollution Bulletin 2(5):75-77.
Hutber, G.N.; Rogers, L.J.; Smith, A.J. (1979)
pesticides on the growth of cyanobacteria .
Allgemeine Mikrobiologie 19 (6): 397-402.
Influence of
Zeitschrift fur
IR-4 Project at Rutgers, the State University (1974) MCPA—Sorghum
Residue Studies. (Unpublished study received Oct 3, 1975 under
6E1681; CDL:097351-A)
Irvine, L.F.H.; Whittaker, D. ; Hunter, J.; et al. (1980) M.C.P.A.
Oral Teratogenicity Study in the Dutch Belted Rabbit: Report
No. 1737R-277/5. (Unpublished study including submitter
summary, received Aug 28, 1980 under 2217-EX-2; prepared by
Hazleton Laboratories Europe , Ltd . , submitted by PBI-Gordon
Corp., Kansas City, Kans.; CDL:243170-A)
-------
MRID f
000004439
005004434
005003757
005004656
005008955
005004190"
005015461
005005526
000004576
005005091
005015041
OFFICE OF PESTICIDE PROGRAMS
REGISTRATION STANDARD BIBLIOGRAPHY
Citations Considered to be Part of the Data Base Supporting
Registrations Under the Standard
CITATION
Jensen, D.J.; Miller, P.W.; Berhenke, L.F. (1973) Total Residues of
MCPA and 2-Methyl-4-chlorophenol in Tissues of Animals Fed MCPA:
Report No. GH-C-689. (Unpublished study received on unknown
date under 9F0761; submitted by Dow Chemical U.S.A., Midland,
Mich.; CDL:092000-D)
Jensen, H.L.; Petersen, H.I. (1952) Decomposition of hormone
herbicides by bacteria. Acta Agriculturae Scandinavica
2:215-231.
Jensen, H.L.; Petersen, H.I. (1952) Detoxication of hormone
herbicides by soil bacteria. Nature (London) 170(4314):39-40.
Jensen, H.L.; Sorensen, H. (1952) The influence of some organic
sulfur compounds and enzyme inhibitors on Nitrosomonas europaea.
Acta Agricultural Scandinavica 2:295-304.
Jones, D.I.R.; Knight, A.G.; Smith, A.J. (1967) Attempted suicide
with herbicide containing HCPA. Archives of Environmental
Health 14(2"): 363-366.
Johnson, "H.R'.M.; Kbumides," 0." (1965) A further case of'M.C.P.A.
poisoning. British Medical Journal 2(5462):629-630.
Kaufman, P.B.; Crafts, A.S. (1956) Responses of the rice plant to
different formulations and methods of application of 2,4-D,
MCP, and 2/4,5-T. Hilgardia 24(15):411-453.
Kavanagh, B.V.; Posner, A.M.; Quirk, J.P. (1977) The adsorption of
phenoxyacetic acid herbicides on goethite. Journal of Colloid
and Interface Science 61(3):545-553.
Kemish Vaerk Koge A/S (1972) Determination of MCPA in MCPA-Isopro-
pylester. Method dated Feb 18, 1972. (Unpublished study
received Mar 6, 1972 under 961R-10; submitted by Trans Chemic
Industries, Inc., New York, N.Y.; CDL:123581-A)
Kingham, H.G.; Fletcher, J.T. (1963) The effects of MCPA and
2,3,6-TBA on glasshouse cucumbers. Weed Research 3(3):242-245.
Kirkwcod, R.C.'; Dalziel, J.; Matlib, A.; Somerville, L. (1969)
Seme factors influencing the activity of foliage applied MCPA
and MCPB in Vicia faba . Pages 650-658, In Proceedings of the
9th British Weed Control Conference; 1968. Vol. 2. Droitwich,
England: British VJeed Control Conference.
-------
MRID *
OFFICE OF PESTICIDE PROGRAMS
REGISTRATION STANDARD BIBLIOGRAPHY
Citations Considered to be Part of the Data Base Supporting
Registrations Under the Standard
CITATION
005004272 Kirkwood, R.C.; Dalziel, J.; Matlib, A.; Somerville, L. (1972) The
role of translocation in selectivity of herbicides with
reference to MCPA and MCPB. Pesticide Science 3(3):307-321."
005019112 Kulinska, D. (1967) Wjplyw herbicydow na pobieranie tlenu przez
glebe. [Effect of herbicides on oxygen uptake by soil.]
Roczniki Nauk Rolniczych, Seria A. [Annals of Agricultural
Sciences, Series A.] 93(1):125-130.
• s
005003678 Kunert, G. (1959) Der Einfluss einiger Herbicide auf die
Lipaseaktivitaet von Aspergillus niger . [Effect of some
herbicides on the lipase activity of Aspergillus niger .]
Naturwissenschaften 46(21):603.
005021559 Lallukka, R. (1974) Rester av TCA, linuron, dicamba och MCPA i
skordeprcdukter efter odling i behandlad jord—resultat fran
finska undersokningar. [Residues of TCA, linuron, dicaTiba and
MCPA in crops grown in treated soil—results of Finnish
research.] Pages 114-115, _In Herbicider i Jord—\terkan pa
Kulturvaxter. [Herbicides in the Soil—Effects on Crop
Plants.] Uppsala, Sweden: Agricultural College of Sweden,
Department of Plant Husbandry.
005004440 Large, E.G.; Dillon Vfeston, W.A.R. (1951) Ear distortion in barley
and other cereals caused by spraying with MCPA and 2,4-D.
Journal of Agricultural Science 41(4):338-349.
005005848 Lavake, D.E.; Chenault, E.W.; Wiese, A.F.; Vandiver, C.W. (1971)
Tolerance of sorghum hybrids to postemergence herbicides.
Pages 74-105, Jn Texas Agricultural Experiment Station Progress
Report. College Station, Tex.: Texas Agricultural Experiment
Station.
005005795 Leafe, E.L. (1962) Metabolism and selectivity of plant-growth
regulator herbicides. Nature 193(4814):485-486.
005006390 . Lee, S.A. (1972) Effects of six post-emergence herbicides on young
pineapple. Malaysian Pineapple 2:47-52.
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MRID #
000004765
000004622
005016100
OFFICE OF PESTICIDE PROGRAMS
REGISTRATION STANDARD BIBLIOGRAPHY
Citations Considered to be Part of the Data Base Supporting
Registrations Under the Standard
CITATION
Leng, M.L., ccmp. (1970) Summary of Residue Data for MCPA on Rice
and Rice Byproducts. (Unpublished study received Jan 22, 1971
under 9F0761; prepared by Dow Chemical Co. in cooperation with
Univ. of California—Davis, Dept. of Environmental Toxicology,
Agricultural Toxicology Laboratory, submitted by National Agri-
cultural Chemicals Association, Industry Task Force on Phenoxy
Herbicide Tolerances, Washington, D.C.; CDL:091308-M)
Leng, M.L., comp. (1971) Summary of Residue Data for 2,4-D; 2,4,5-
T; Silvex and MCPA in Milk, Meat and Meat Byproducts. (Unpub-
lished study received Oct 11, 1971 under 9F0761; prepared bv
Dow Chemical Co., submitted by National Agricultural Chemicals
Association, Industry Task Force on Phenoxy Herbicide Toler-
ances, Washington, D.C.; CDL:091311-C)
Loos, M.A. (1971) Metabolism of phenoxy herbicides by plants and
soil micro-organisms. Pages 291-304, Bi Pesticide Terminal
Residues: Invited Papers from the International Symposium on
Pesticide Terminal Residues; Feb 17-19, 1971, Tel Aviv, Israel.
Edited by A.S. Tahori. London: Butterworths.
005003910
005012194
005016319
005016939
005003450
Loos, M.A.; Bollag, J.M.; Alexander, M. (1967) Phenoxyacetate
herbicide detoxication by bacterial enzymes. Journal of
Agricultural and Food Chemistry 15(5):858-860.
Loos, M.A.; Schlosser, I.F.; Mapham, W.R. (1979) Phenoxy herbicide
degradation in soils: quantitative studies of 2,4-D- and
MCPA-degrading microbial populations. Soil Biology and
Biochemistry 11 (4)-.377-385.
Luckwill, L.C.; Campbell, A.I. (1957) The tolerance of fruit crops
to certain selective and pre-emergence herbicides. Pages
539-542, In Proceedings of the 3rd British Weed Control
Conference; 1956, Blackpool, England. Droitwich, England:
British Weed Control Conference.
Magnusson, J.; Ramel, C.; Eriksson, A. (1977) Mutagenic effects of
chlorinated phenoxyacetic acids in Drosophila nelanogaster.
Hereditas 87:121-123.
Malina, M. (1971) Collaborative study of infrared analysis of
dicamba-2-methyl-4-chlorophenoxyacetic acid and
dicaraba-2,4-dichlorophenoxyacetic acid formulations. Journal
of the Association of Official Analytical Chemists
54(3):706-710.
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MRID *
OFFICE OF PESTICIDE FHDGRWE
REGISTRY ION STANDARD BIBLIOGRAPHY
Citations Considered to be Part of the Data Base Supporting
Registrations Under the Standard
CITATION
GS 0017-110 Marquardt and Luoe (1955) Jour. Agr. Food Chem. 3:51
005004185 Matell, M.; Lindenfors, S. (1957) Thermodynamic dissociation
constants of 2,4-dichlorophenoxyacetic acid (2,4-D) and some
related plant growth regulators. Acta Chemica Scandinavica
11(2):324-328.
005015451 Matlib, M.A.; Kirkwood, R.C.; Patterson, J.D.E. (1971) Binding of
certain substituted phenoxy-acids by bovine serum albumin.
Weed'Research 11(2/3):190-192.
000026928 McCann, J.A.; Pitcher, F. (1972) [MCP Weed Killer: Toxicity to
Bluegill]: Test No. 512. (U.S. Agricultural Research Service,
Pesticides Regulation Div., Animal Biology Laboratory, unpub-
lished report.)
005019347 Metting, B.; Rayburn, W. (1979) The effects of the pre-emerqence
herbicide di-allate and the post-er^nergence herbicide MCPA on
the growth of some soil algae. Phycologia 18(3):269-272.
05013388
005013713
000004438
Meadly, G.R.W.; Pearce, G.A. (1957) The tolerance of subterranean
clover (Trifolium subterraneum L) to chlorinated
phenboxyacetic derivatives. Journal of the Department of
Agricultural, Western Australia 6:357-361, 364-368, 371-374,
380.
377-
000003472
Miller, J.H.; Kempen, H.M.; Wilkerson, J.A.; Foy, C.L. (1963)
Response of Cotton to 2,4-D and Related Phenoxy Herbicides.
Washington, D.C.: U.S. Department of Agriculture, Agricultural
Research Service. (USDA technical bulletin no. 1289)
Miller, P.W.; Jensen, D.J. (1973) Study of Alkaline Hydrolysis for
Determination of Residues of MCPA and 2-Methyl-4-chloroohenol in
Milk: Report No. GH-C 628. Method dated Feb 13, 1973. (Un-
published study received on unknown date under 9F0761; submitted
by Dow Chemical U.S.A., Midland, Mich.; CDL:092000-C)
Mobil Chemical Company (1973) Experiment: Wheat Herbicide
Screening. (Unpublished study received May 7, 1974 under
4G1505; CDL:093987-AR)
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OFFICE OF PESTICIDE PROGRAMS
REGISTRATION STANDARD BIBLIOGRAPHY
Citations Considered to be Part of the Data Base Supporting
Registrations Under the Standard
MRID # CITATION
000004773 Monsanto Company (1956) [MCP Residue in and Recovery of MCP from
Garden Peas, Flax, Rice and Oatsl. (Unpublished study received
Oct 19, 1971 under 8F0676; submitted by National Agricultural
Chemicals Association, Industry Task Force on Phenoxy Herbicide
Tolerances, Washinton, D.C.; CDL:091183-O)
000004441 Monsanto Company (19??) Petition for the establishment of
tolerances for the pesticide chemical 2-methyl-4-
chlororophenoxyacetic acid (MCPA) on raw agricultural
conmodities, Section D: The results of tests on the amount of
residues remaining, including a description of the analytical
method used. (Submitted by the National Agricultural Chemicals
Association Industry Task Force on Phenoxy Herbicide
Tolerances. December 12, 1967).
00005552 Monsanto Company (1956) Procedures for determining residues of MCP
(2-methyl-4-chlorophenoxyacetic acid/in treated crops.
000005575 Montgomery, M.L. (1970) MCPA Residue in Wheat: Oregon State Univer-
sity Report. Includes methods dated Jun 17, 1970 and Apr 1,
1970. (Unpublished study including summary report and letters
dated Apr 2, 1970 from M.L. Montgomery to Don T. Lillie and J.A.
Ignatoski, received Jan 22, 1971 under 9F0761; prepared by Ore-
gon State Univ., Dspt. of Agricultural Chemistry, submitted by
National Agricultural Chemicals Association, Industry Task Force
on Phenoxy Herbicide Tolerances, Washington, D.C.; CDL:09130S-T)
005004849 Moore, R.M. (1950) Differential effects of certain phenoxyacetic
acid compounds and phenylcarbamates on plant species: II.
Effects of foliage applications with special reference to
yields of wheat. Australian Journal of Agricultural Research
44:401-412.
005021735 Mueller, F. (1976) Summary. Pages 141-144, In Translokation von
14C-markiertem MCPA in verschiedenen EntwTcklungsstadien
mehrjaehriger Unkraeuter. fTranslocation of 14C-Labelled MCPA
at Different Stages of Development of Perennial Weeds. 1
Berlin, Germany: \ferlag Paul Parey. (Acta phytomedica, vol. 4)
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OFFICE OF PESTICIDE PROGRAMS
REGISTRATION STANDARD BIBLIOGRAPHY
Citations Considered to be Part of the Data Base Supportinq
Registrations Under the Standard
MRID * CITATION
005005548 Nakajima, S.; Naito, N.; Tani, T. (1973) Microbial transformation
of 2,4-D and its analogues. Chemical and Pharmaceutical
Bulletin 21(3):671-673.
005002356 Nelson, N.H.; Faust, S.D. (1969) Acidic dissociation constants of
selected aquatic herbicides. Environmental Science and
Technology 3(11):1186-1188.
005020766 Noll, M.; Bauer, U. (1974) Phormidium autumnale als
Indikatororganismus fuer algizide Substanzen im wasser.
• t
000004447 Palmer, A.K.; Lovell, M.R. (19??) Effect of MCPA on Pregnancy of
the Mouse. (Unpublished study received on unknown date under
9F0761; prepared by Huntingdon Research Centre, England, sub-
mitted by Dow Chemical U.S.A., Midland, Mich.; CDL:092001-C)
005015694 Parascan, D. (1966) Cercetari privind actiunea ierbicidelor asupra
semintelor de molid in timpul germinatiei lor. [Herbicide
action on the spruce seed during germination.1 Revista
Padurilor. [Forestry Review.] 81(10):543-547.
000004805 Parke, G.St.E.; Terrell, Y. (1974) Report: Eight Day Dietary LC50
Study of Anchem Weedar Sodium MCPA in Bobwhite Ouail and Mallard
Ducks. (Unpublished study received Jul 15, 1975 under 264-55;
prepared by Cannon Laboratories, Inc. for Amchem Products, Inc.,
submitted by Union Carbide Agricultural Products Co., Ambler,
Pa.; CDL:132039-A)
000021979 Paudler, W.W. (1979) Analyses of N-Nitroso Compounds. (Unpublished
study received Jul 23, 1979 under 39135-1; prepared by Univ. of
Alabama, Dept. of Chemistry, Mass Spectroscopy Laboratory, sub-
mitted by Fallek-Lankro Corp., Tuscalcosa, Ala.; CDL:238R73-A)
000026927 Pitcher, F.G. (1973) [Spot Treat: Toxicity to Bluegilll: Test
No. 609. (U.S. Environmental Protection Agency, Pesticides Reg-
ulation Div., Agricultural Research Center, Animal Biology Lab-
oratory, unpublished report.)
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OFFICE OF PESTICIDE PROGRAMS
.REGISTRAT ION STANDARD BIBLIOGRAPHY
Citations Considered to be Part of the Data Base Supporting
Registrations Under the Standard
MRID * CITATION
005003770 Popham, R.D.; Davies, D.M. (1964) A case of M.C.P.A. poisoning.
British Medical Journal 1(5384):677-678.
005009237 Propping, P.; Buselmaier, W.; Poehrborn, G. (1973) Kritiscne
Betrachtung ueber die intra-animale Kultur von Mikrcorganismen,
eine Methode zum Nachweis chemisch induzierter Mutationen.
00021973
00021976
00021974
Raltech Scientific Services, Inc. (19??) MCPA dermal
New Zaland white strain rabbits.
study in
Raltech Scientific Services, Inc. (19??) MCPA primary dermal
irritation study in New Zealand white strain rabbits.
Raltech Scientific Services, Inc. (19??) MCPA primary dermal eye
irritation study in New Zealand white strain rabbits.
00021972 Raltech Scientific Services, Inc. (19??) MCPA Oral defined LD,
005013116
005004197
000004594
005015046
study in Sprague-Dawley albino rats.
'50
Reynolds, J.D.; Proctor, J.M.; Hind, R.A. (1957) Studies with
phenoxybutyric herbicides in peas, 1955-56. Pages
499-513, In Proceedings of the 3rd British Weed Control
Conference; 1956, Blackpool, England. Droitwich, England:
British Weed Control Conference.
Rhodes, A.; Templeman, W.G. (1947) Effect of 4-chloro-2-methyl
phenoxyacetic acid on the mineral content and growth of plants
letter. Nature 160(4076):825-826.
Rhodia, Incorporated (1971) Phenoxy Herbicides on Stubble Crop
Rice. (Unpublished study received Nov 21, 1973 under 359-170;
submitted by Rhone-Poulenc, Inc., Monmouth Junction, N.J.; CDL:
230485-B)
Robertson, M.M.; Kirkwood, R.C. (1967) Differential uptake and
movement as a factor influencing selective toxicity of MCPA and
MCPB. Pages 269-277, ^n Proceedings of the 8th British Weed
Control Conference; 1966. Vol. 1. Droitwich, England:
British Weed Control Conference.
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MRID #
OFFICE OF PESTICIDE PROGRAMS
REGISTRATION STWDARD BIBLIOGRM^Y
Citations Considered to be Part of the Data Base Supporting
Registrations Under the Standard
CITATION
005006391 Rojas-Garciduenas, M. ; Ruiz, M.A. ; Carrillo, J. (1962) Effects of
2,4-D and MCPA on germination and early growth. Weeds
005017929
000023687
005015695
005005247
00fn03508
005013749
000022698
Rolencova, H. (1978) Stanoveni nekterych pesticidnich latek v
biologickem materialu. [Determination of sere pesticides in
biological material.] \feterinarstvi. [Veterinary Medicine. 1
29(4):177-179.
Rydrych, D. ; Behrens, R. ; Wallace, K. ; et al. (1972) [Residues from
Varidus Chemicals on Grains! . (Unpublished study received Jan
3, 1973 under unknown admin, no.; prepared in cooperation with
Univ. of Minnesota and others, submitted by Velsicol Chemical
Corp., Chicago, 111.; CDL:120182-A)
Sanad, A.J. (1971) Untersuchungen ueber Aufnahme und Translokation
von 14C-markierten Herbiziden in Agrostemna githago L.
und Tussilago farfara L. [Studies of the uptake and
translocation of 14C-labelled herbicides in Agrostemma
Sattar, M.A.; Paasivirta, J. (1979) Effects of MCPA on the
germination and root system of cereal crops. Chemosuhere
8(4): 201-203.
Seiler, J.P. (1979) Phenoxyacids as inhibitors of testicular m\
synthesis in male mice. Bulletin of Environmental
Contamination and Toxicology 21 (1/2): 89-92.
Sen, K.M. (1960) Studies on the Influence of Some Auxin Herbicides
on Grass-seed Crops. Wageningen, Netherlands: Centrum vcor
Landbouwpublikaties en Landbouwdocumentatie . (Verslagen van
Landbouwkundige Onderzoekingen no. 66.11)
Sleight, B.H., III (1973) Acute Toxicity of Mondak to Rluegill
(Lepomis.macrochirus) and Rainbow Trout (Salmo.gaird neri)
Report No. 040280. (Unpublished study received May 2T, 19"? 3
under unknown admin, no.; prepared by Bionomics, Inc., submitted
by Velsicol Chemical Corp., Chicago, 111.; CD:128293-A)
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OFFICE OF PESTICIDE PROGRAMS
REGISTRATION STANDARD BIBLIOGRAPHY
Citations Considered to be Part of the Data Base Suooortinq
Registrations Under the Standard
MRID # CITATION
000004448 Soderquist, C.J.j Crosby, D.G. (1974) The Dissipation of 4-Chlo-
ro-2-methylphenoxyacetic acid (MCPA) in a Rice Field. Includes
four methods dated Apr 15, 1974. (Unpublished study received
on unknown date under 9F0761; prepared by Univ. of California—
Davis, Dept. of Environmental Toxicology, submitted by Dow Chem-
ical U.S.A., Midland, Mich.; CDL:092001-E)
005003445 Soderquist, C.J.; Crosby, D.G. (1975) Dissipation of
4-chloro-2-methylphenoxyacetic acid (MCPA) in a rice field.
Pesticide Science 6(1):17-33.
' *
005012269 Sokolov, M.S.; Knyr, L.L.; Strekozov, B.P.; Agarkov, V.D. (1975)
Osobennosti povedeniya propanida, yalana, 2M-4Kh i 2,4-D v
risovykh orositel'nykh sistemakh Kubani. [Behavior of
propanide, yalan, MCPA and 2,4-D in rice irrigation systems of
the Kuban River.] Khimiya v Sel'skom Khozyaistve. [Chemistry
in Agriculture.] 13(3):224-234.
005010497 Sokolov, M.S.; Riyr, L.L.; Strekozov, B.P.; Agarkov, V.D.;
Chubenko, A.P.; Kryzhko, B.A. (1974) Povedenie nekotorykh
gerbitsidov v usloviyakh risovoi orositel'noi sistemy. [The
behavior of some herbicides under the conditions of a rice
irrigation system.] Agrokhimiya. [Agricultural Chemistry.1
(3):95-106.
005020404 Scrmer, K. (1970) Beeinflussung der Nitrifikation und des
Stickstoffhaushaltes in Bceden durch verschiedene
Pflanzenschutzmittel. [Effect of various pesticides on
nitrification and nitrogen transformations in soils.]
Landwirtschaftliche Forschung, Sonderheft 25:22-30.
000021962 Song, L. (1977) Formal Report of Analysis: Contract No. 000563.
Undated method. (Unpublished study received Jul 12, 197R under
39335-7; prepared by Thermo Electron Corp., submitted by Fallek-
Lankro Corp., Tuscalcosa, Ala.; CDL:236544-A)
000004995 St. John, L.E., Jr. (1965?) MCPA. Pages 439-454, In By N.P
(Also In unpublished submission received Jan 18, 1975 under
241-EX-64; submitted by American Cyanamid Co., Princeton,
N.J.; CDL:224170-Z)
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OFFICE OF PESTICIDE PROGRAMS
REGISTRATION STANDARD BIBLIOGRAPHY
Citations Considered to be Part of the Data Base Supportinq
Registrations Under the Standard
MRID * CITATION
000004724 St. John, L.E., Jr. (1967) MCPA. Paqes 445-454, ^n Analytical
Methods for Pesticides, Growth Regulators and Food Additives:
\folume 5. Edited by G. Zweig. Hew York: Academic Press. (Al-
so In unpublished submission received Sep 12, 1968 under RF0676;
submitted by Dow Chemical U.S.A., Midland, Mich.; CDL:092980-\P)
005019284 State Institute of Agricultural Chemistry, Finaldn (1977) Residue
Analysis of the Official Testing of Pesticides, 1976. Helsinki,
Finland: State Institute of Agricultural Chemistry. (State
Institute of Agricultural Chemistry publication No. 12)
• s
005015452 Steenson, T.I.; Walker, N. (1956) Observations on the bacterial
oxidation of chlorophenoxyacetic acids. Plant and Soil
VIII(1):17-32.
005004430 Steenson, T.I.; Walker, N. (1957) The pathway of breakdown of
2:4-dichloro- and 4-chloro-2-methyl-phenoxyacetic acid by
bacteria. Journal of General Microbiology 16(1):146-155.
005013551 Steenson, T.I.; Walker, N. (1958) Adaptive patterns in the
bacterial oxidation of 2:4-dichloro- and -
4-chloro-2-methyl-phenoxyacetic acid. Journal of General
Microbiology 18(3):692-697.
005012650 Stevens, T.; Grorud, R.B. (1979) High pressure liquid
chrcmatography of ester and salt formulations of
2-methyl-4-chlorophenoxyacetic acid. Journal of the
Association of Official Analytical Chemists 62(4):738-741.
005001991 Stevenson, J.H. (1978) The acute toxicity of unformulated
pesticides to worker honey bees (Apis mellifera L.). Plant
Pathology 27(1):38-40.
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OFFICE OF PESTICIDE PROGRAMS
REGISTRATION STANDARD BIBLIOGRAPHY
Citations Considered to be Part of the Data Base Supporting
Registrations Under the Standard
MRJD * CITATION
000004568 Suzuki, H.K. (1977) Dissipation of Banvel, Bromoxynil or MCPA or
Combination Thereof in Two Soil Types: Report No. 181. (Unpub-
lished study received Nov 2, 1977 under 876-25; prepared in co-
operation with International Research and Development Corp.;
submitted by Velsicol Chemical Corp., Chicago, 111.; CDL:
232171-B)
005009727 Synek, M.; Tibenska, M.; Vteresikova, M. (1973) Znehodnotenie
pcdzemnych vod dikotexon (Na-sol'ou kyseliny
2-methyl-4-chlorfenoxycctovej). [Contamination of ground
waters with dikotex (Na-salt 2-methyl-4-chlorophenoxyacetic
acid:] Bratislavske Lekarske Listy. [Bratislava Medical
News.] 59(2):203-207.
005003614 Synerholm, M.E.; Zimmerman, P.W. (1945) The preparation of some
substituted phenoxy alkyl carboxylic acids and their properties
as growth substances. Contributions from Boyce Thompson
Institute 14:91-103.
005020337 Talbot, F.; Foster, R.T., inventors; Imperial Chemical Industries,
assignee (1952) Improvements in or relating to the production
of soluble salts of methylchloropnenoxyacetic acids. British
patent specification 664,069. Jan 2. 7 p.
005020338 Talbot, F.f inventor; Imperial Chemical Industries, assignee
(1949) Improvements in or relating to
2-methyl-4-chloro-phenoxyacetic acid. British patent
specification 623,217. May 13. 4 p.
000004443 Thornburg, W. (1973) MCPA Residues in Peas: A Summary of Residue
Data. (Unpublished study received on unknown date under 9F0761;
prepared by Del Monte Corp., submitted by Dow Chemical U.S.A.,
Midland, Mich.; CDL:092000-1)
005003431 Tin, U.; Baruah, P.; Baruah, H.K. (1949) Biological effects of
methoxone on water hyacinth. Science and Culture 15(3):106-109.
005020144 Tooby, T.E.; Hursey, P.A.; Alabaster, J.S. (1975) The acute
toxicity of 102 pesticides and miscellaneous substances to
fish. Chemistry and Industry (London) (12):523-526.
005004188 Torstensson, L. (1974) Effects of MCPA, 2,4,5-T, linuron and
simazine on some functional groups of soil microorganisms.
Swedish Journal of Agricultural Research 4(3):151-160.
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OFFICE OF PESTICIDE PROGRAMS
REGISTRATION STANDARD BIBLIOGRAPHY
Citations Considered to be Part of the Data Base Supporting
Registrations Under the Standard
MRID # CITATION
005004429 Torstensson, L. (1975) Effects of bentazon and dinoseb on soil
microorganisms and on the Rhizobium-Leguminosae symbiosis.
Swedish Journal of Agricultural Research 5(4):177-l«3.
005008552 Torstensson, N.T.L. (1975) Degradation of 2,4-D and MCPA in soils
of low pH. Pages 262-265, Jjn Pesticides: IUPAC Third
International Congress; Jul 3-9, 1974, Helsinki, Finland.
Edited by F. Coulston and F. Korte. Stuttgart, West Germany:
George Thieme. (Environmental Quality and Safety, Supplement,
vol., 3)
005004649 Torstensson, N.T.L.; Stark, J.; Goransson, B. (1975) The effect of
repeated applications of 2,4-D and MCPA on their breakdown in
soil. Weed Research 15(3):159-164.
005004846 Tottman, D.R.; Davies, E.L.P. (1978) The effect of herbicides on
the root system of wheat plants. Annals of Applied Biology
90(1):93-99.
j
005016148 Toure, I.M.y Stenz, E. (1977) Der Einfluss ausgewaehlter Herbizide
auf Bakteriophagen urid EscherichTa"c61T ;(Tne~acttbn~of
selected herbicides on bacteriophages and Escherichia coli ~.1
Zentralblatt fuer Bakteriologie, Parasitenkunde,
Infektionskrankheiten und Hygieine, Abteilung II 132:163-177.
000041635 Tucker, M.L.r Irvine, L.F.H. (1978) MCPA Oral Teratogenicity Dose
Ranging Study in Rabbits: Report No. 684R-277/4. (Unpublished
study including submitter summary, received Sep 4, 1980 under
2217-EX-2; prepared by Hazleton Laboratories Europe, Ltd., sub-
mitted by PBI-Gordon Corp., Kansas City, Kans.; CDL:243196-A)
000022673 Union Carbine Corporation (1975?) Acute Toxicity of Mondak 5P48 to
Grass Shrimp, Palaemonetes Vulgaris and Fiddler Crabs, Una
Pugilator. (Unpublished study received Feb 28, 1979 under 876-
45? submitted by Velsicol Chemical Corp., Chicago, 111.;
CDL:237738-A)
000022504 _ Union Carbide Corporation (1976) Acute Toxicity of Mondak 5P48 to
the V7ater Flea Daphnia magna Straus. (Unpublished study
received Aug 31, 1976 under 876-45; submitted by Velsicol
Chemical Corp., Chicago, 111.; CDL:225539-A)
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OFFICE OF PESTICIDE PROGRAMS
REGISTRATION STANDARD BIBLIOGRAPHY
Citations Considered to be Part of the Data Base Supporting
Registrations Under the Standard
MRID * CIT«riCN
GS 0017-104U.S. EPA 1972. Report on the toxicity of MCPA dimethylamine salt
52.2% a.i. (Midlnd MCP Weed Killer) to bluegill and rainbow
trout. (U.S. EPA, Chemical and Biological Investigation Branch,
Beltsville, Md.; Static Jar Test Nos. 512, 11/72; 525, 12/72;
unpublished report).
GS 0017-105 U.S. EPA 9173. Report en the toxicity of MCPA, sodium salt 24%
a.i. (Spot Treat) to bluegill. (U.S. EPA, Chemical and
Biological Investigation Branch, Beltsville, Md.; Static Jar
Test No. 628, 9/73; unpublished report).
GS 0017-106 U.S. EPA 1973. Report on the toxicity of MCPA, sodium salt 24%,
a.i. (Weedar sodium MCPA) to bluegills (U.S. EPA, Chemical and
Biological Investigation Branch Beltsville, Md.; Static Jar Test
No. 693, 10/73; unpublished report.
GS 0017-107 U.S. EPA 1973. Report on the toxicity of MCPA, dimethylamine salt
52.1% a.i. (Dow MCP Amine Weed) to rainbow trout and bluegills
(U.S. EPA, Chemical and Biologist Investigation Branch,
Beltsville, Md.; Static Jar Test Nos. 553; 3/73 and 580, 5/73;
unpublished report).-
GS 0017-108 U.S. EPA 1976. Report on the Toxicity of MCPA 94% active ingredient
(technical grade) to rainbow trout, Daphnia magna and bluegill.
(U.S. EPA, Chemical and Biological Investigation Branch,
Beltsville, Md.; Static Jar Test No. 927, 1/19/76; Test No. 936,
2/2/76; Test No. 942, 2/9/76; and Test No. 972, 4/21/76;
unpublished report).
000004549 \felsicol Chemical Corporation (1965) Flax. (Unpublished study re-
ceived Jan 28, 1966 under 876-25; prepared in cooperation with
North Dakota State Univ. of Agriculture and Applied Science,
Dept. of Agronomy and Univ. of Minnesota; CDL:022209-A)
000005569 Velsicol Chemical Corporation (1972) Summary: [Tank Mixtures of
Dicamba + Bromoxynil and Dicamba + Bromoxynil + MCPA for Weed
Control]. (Unpublished study received Jan 3, 1973 under 876-25;
CDL:005050-A)
000004566 \felsicol Chemical Corporation (1972) Wheat (Fall Seeded): Report
No. 123. (Unpublished study received May 21, 1973 under 876-45;
prepared in cooperation with Northwestern Agricultural Research
Center; CDL:021027-A)
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OFFICE OF PESTICIDE PROGRAMS
REGISTRATION STANDARD BIBLIOGRAPHY
Citations Considered to be Part of the Data Base Supporting
Registrations Under the Standard
MRJD # CITATION
000004541 Velsicol Chemical Corporation (1974) Summary of Mondak Residue
Studies—Winter Wheat. (Unpublished study including Velsicol
Report #147 and 1150, received Dec 11, 1974 under 876-45; CDL:
003548-A)
005019175 Verona, 0. (1948) Effetti di alcuni erbicidi selettivi sulla
microflora, in particolare, del terreno. [Effect of sone
selective herbicides on microflora, particularly of the soil.1
Annali della Facolta di Agraria, Universita di Pisa, fAnnals
of the Faculty of Agriculture of the University of Pisa.l
9:189^199.
005003548 Vintikova, H.; Skrdleta, V.; Srogl, M. (1965) The sensitivity of
nodule bacteria to several herbicides. Pages 264-263, _In Plant
Microbes Relationships: Proceedings of a Symposium on
Relationships Between Soil Microorganisms and Plant Roots; Sen
24-28, 1963, Prague. Edited by J. Macuira and V. Vancura.
Prague, Czechoslovakia: Academia.
005003752 Vogel, E.; Chandler, J.L.R. (1974) Mutacenicity testinq of
cyclamate and some pesticides in Drosophila melanogaster.
Experientia 30(6):621-623.
005004390 Vyas, L.N.; Garg, R.K. (1974) Reversal of the effect of growth
inhibitors by gibberellic acid and indole acetic acid.
Bicchemie and Physiologic der Pflanzen 166(5/6):549-554.
005015458 Way, J.M. (1962) The effects of sub-lethal doses of MCPA on the
morphology and yield of vegetable crops: I. Lettuce. Weed
Research 2(4):233-246.
005015457 Way, J.M. (1963) The effects of sub-lethal doses of MCPA on the
morphology and yield of vegetable crops: II. Cabbage,
cauliflower and Brussels sprouts. Weed Research 3(1):11-25.
005015459 Way, J.M. (1963) The effects of sub-lethal doses of MCPA on the
morphology and yield of vegetable crops: III. Carrots and
parsnips. Weed Research 3(2):9R-108.
005015456 Way, J.M. (1963) The effects of sub-lethal doses of MCPA on the
morphology and yield of vegetable crops: IV. French and broad
beans. Weed Research 3(4):312-321.
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OFFICE OF PESTICIDE PROGRAMS
REGISTRATION STANDARD BIBLIOGRAPHY
Citations Considered to be Part of the Data Base Supporting
Registrations Under the Standard
MRID # CITATION
005019963 Way, J.M. (1964) The effects of sub-lethal doses of MCPA on the
morphology and yield of vegetable crops: V. Beet, spinach,
turnip and onion. Weed Research 4(1):12-23.
005015754 Way, J.M. (1964) The effects of sub-lethal doses of MCPA on the
morphology and yield of vegetable crops: VI. Comparison with
2,4-D, 2,4,5-T, mecoprop and 2,3,6-TBA. Weed Research
4(4):319-337.
005015407 Wehr, N.B.; Klein, D.A. (1971) Herbicide effects on Bdellovibrio
bacteriovorus parasitism of a soil pseudomonad. Soil Biology
and Biochemistry 3(2):143-149.
000004589 Welch, J. (1974) Final Report: District Project No. 244274-004.
(Unpublished study received Mar 24, 1976 under 359-170; prepared
by Rhodia, Inc., submitted by Rhone-Poulenc, Inc., Monnouth
Junction, N.J.; CDL:223772-N)
000005558 Welch, J. (1974) Product Development Department: Final Renort:
District Project No. 244274-003. (Unpublished study received
Mar 24, 1976 under 359-170; prepared by Rhodia, !nc*> submitted
by Rhone-Poulenc, Inc., Monnouth Junction, N.J.; CDL:223772-L)
005006301 Wiedman, S.J.; Appleby, A.P. (1972) Plant growth stimulation by
sublethal concentrations of herbicides. Weed Research
12(l):65-74.
005006526 Wilkinson, V.; Lucas, R.L. (1969) Effects of herbicides on the
growth of soil fungi. New Phytology 68(3):709-719.
000004453 Winterlin, M.; Radosivich, S.R. (1974) Report of Analysis: Environ-
mental Toxicology Report No. 3445. Includes undated method.
(Unpublished study received Feb 10, 1976 under 6E1746; prepared
by Univ. of California—Davis, Dept. of Environmental Toxicol-
ogy, submitted by Interregional Research Project No. 4, New
Brunswick, N.J.; CDL:095368-C)
000005577 Wirth, M.; Wasco, J.L. (19??) MCP-/amine Weed Killer: Evaluation of
Formulation M-3539. Includes undated method. (Unpublished
study received Jul 17, 1970 under 464-147; submitted by Dow
Chemical U.S.A., Midland, Mich.; CDL:003427-A)
005003566 Yasuda, M.; Maeda, H. (1972) Teratogenic effects of 4-chloro-2-
methylphenoxyacetic acid ethylester (MCPEE) in rats.
Toxicology and Applied Pharmacology 23(2):326-333.
IV5
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MRID #
OFFICE OF PESTICIDE PROGRAMS
REGISTRATION STANDARD BIBLIOGRAPHY
Citations Considered to be Part of the Data Ease Supporting
Registrations Under the Standard
CITATION
GS 0017-109 Yip and Ney (1966) Analysis of 2,4-D residues in milk and forage.
Weeds 14:167.
005021603 Zauner, E.; Bronn, W.K.; Dellveg, H.; Tressl, R. (1979)
Hemmwirkung von Nebenkanponenten der Ruebennelasse und von
Pflanzenschutzmitteln auf die Atmung und Gaerung von Hefe
( Saccharcnyces oerevisiae). [Inhibitor activity of
impurities of beet molasses and plant protectants on the
respiration and fermentation of yeast ( Saccharomyces )
. ^ «HMMMVW^M«^^^^^^^^^^^^
005004970 Zetterberg, G. (1979) Mechanism of the lethal and mutagenic
effects of phenoxyacetic acids in Saccharonyces oerevisiae .
Mutation Research 60(3): 291-300.
005005846 Zweig, G. ; Snerma, J. (1972) 2,4-Dichlorophenoxyacetic acid.
Pages 630-635, In Analytical Methods for Pesticides and Plant
Growth Regulators. Vol. VI: Gas Chromatographic Analysis. Mew
York: Academic Press.
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