United States
Environmental Protection
Agency
Office of
Pesticides and Toxic Substances
Washington OC 20460
July 1981
oEPA Chloramben
(3 amino 2,5-dichlorobenzoic acid)
Pesticide Registration
Standard
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Pesticide Registration Starvtord: Chlorarober
(3 amino 2,5-dichlorobenzoic acid)
May, 1961
Office of Pesticides and Toxic Substances
Environmental Protection Agency
401 M Street, S.W.
Washington, D.C. 21460
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Project Support
Denise M. Keehner
Project Manager (SPRD)
Jacob's Engineering Group Inc. Hazard Evaluation
Technical Oversight:
David Van Ormer
Bertram Litt
John Leitzke
William Rabert
Lionel Richardson
David Severn
Ram Rakshpal
Charles Trichilo
Charles Lewis
James Yowell
Tfoxicologist (HED)
Statistician (HED)
Wildlife Biologist (HED)
Wildlife Biologist (HED)
Environmental Chemist (HED)
Environmental Chemist (HED)
Environmental Chemist (HED)
Residue Chemist (HED)
Plant Scientist (BFSD)
Plant Scientist (BFSD)
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TABLE OF (TOTEM'S
Chapter One
How to Register Under a Registration Standard
Chapter Two
Agency Position on Chloramben
1. Introduction
2. Description of Chemical
3. Regulatory Position
4. Regulatory Rationale
5. Criteria for Registration Under the Standard
6. Acceptable Ranges and Limits
A. Manufacturing-use Chloramben
1. Tolerance Reassessment
B. Ehd-Use Products
Paqe Number
1-1
2-1
2-1
2-1
2-2
2-2
2-4
2-5
2-6
2-7 through 2-14
Chapter Three
Data Requirements and Data Gaps
3-1
Chapter Four
Product Chemistry of Chloramben
Introduction
A. Manufacturing-Use Chloramben
1. Product Chemistry Profile
2. Data Caps
3. Topical Discussions
B. Soluble Concentrate Chloramben
1. Data Gaps
2. Topical Discussions
C. Flowable Concentrate Chloramben
1. Data Gaps
2. Topical Discussions
D. Etaulsifiable Concentrate Chloramben
1. Data Gaps
2. Topical Discussions
E. Granular Chloramben
1. Data Gaps
2. Topical Discussions
4-1
4-1
4-1
4-1
4-2
4-4
4-7
4-8
4-10
4-10
4-10
4-12
4-12
4-12
4-14
4-14
4-15
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Chapter Five
Environmental Fate of Chloramben 5-1
Use Profile 5-1
A. Manufacturing-Use Chloramben 5-6
1. Environmental Fate Profile 5-6
2. Acute Exposure Profile 5-7
3. Data Gaps 5-7
4. Topical Discussions 5-8
B. Formulations of Chloramben 5-15
1. Exposure Analyses 5-15
Chapter Six
Residue Chemistry of Chloramben 6-1
A. Manufacturing-Use Chloramben 6-1
1. Residue Chemistry Profile 6-1
2. Data Gaps 6-2
3. Topical Discussions 6-2
B. Formulations of Chloramben 6-16
1. Data Requirements 6-16
Chapter Seven
Toxicology of Chloramben 7-1
A. Manufacturing-Use Chloramben 7-1
1. Toxicology Profile 7*-l
2. Onccqenic Risk Assessment 7-3
3. Data Gaps 7-7
4. Topical Discussions 7-10
B. Soluble Concentrate Chloramben 7-20
1. Tbxicology Profile 7-20
2. Data Gaps 7-20
3. Topical Discussions 7-22
C. Flowable Concentrate Chloramben 7-25
1. Toxicology Profile 7-25
2. Data Gaps 7-25
3. Topical Discussions 7-25
D. Emulsifiable Concentrate Chloramben 7-27
1. Toxicology Profile 7-27
2. Data Gaps 7-27
3. Tbpical Discussions 7-28
ii
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E. Granular Chlorambpn t-31
1. Toxicology Profile 7-31
2. Data Gaps 7~31
3. Ttopical Discussions 1-32
Chapter Eight
Ecological Effects of Chloramben 8-1
A. Manufacturing-Use Chloramben 8-1
1. Ecological Effects Profile 8-1
2. Data Gaps 8-2
3. Topical Discussions 8-3
B. Soluble Concentrate Chloramben 8-6
1. Ecological Effects Profile 3-6
2. Risk Assessment 8-6
3. Data Gaps 8-7
4. Ttopical Discussions 8-8
C. Flowable Concentrate Chloramben 8-10
1. Ecological Effects Profile 8-10
2. Risk Assessment 8-10
3. Data Gaps 8-11
4. Ttopical Discussions 8-12
D. Emulsifiable Concentrate Chloramben 8-13
1. Ecological Effects Profile 8-13
2. Risk Assessment 8-13
3. Data Gaps 8-14
4. Ttopical Discussions 8-14
E. Granular Chloramben 8-15
1. Ecologial Effects Profile 8-15
2. Risk Assessment 8-15
3. Data Gaps 8-15
4. Ttopical Discussions 8-15
Chapter Nine
Case Bibliography 9-1
Guide to Use of Bibliography 9-1
A. Section I 9a-l
B. Section II 9b-l
111
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CHAPTER I: HOW TO REGISTER. OTDE? A REGISTRATION STANDARD
1. Organization of Che Standard
2. Purpose of che Standard
3. Requirement co Re-register Under che Standard
4. "Product Specific" Data and "Generic" Data
5. Data Compensation Requirements under FIFRA 3(c)(l)(D)
6. Obtaining Data co Fill " Data Gaps"; FTFSA 3(c)C2)(3)
7. Amendments co che Standard
1. Organization of che Standard
This firsc chapter explains /che purpose of a Registration Standard and
summarizes che legal principles involved in registering or re-registering under
a Standard. The second chapter sets forth che requirements chat oust be net to
obtain or retain registration for products covered by this particular
Registration Standard. In che remaining chapters, the Agency reviews the
available data by scientific discipline, discusses the Agency's concerns with
the identified potential hazards, and logically develops Che conditions and
requirements chat would reduce chose hazards to acceptable levels.
2. Purpose of che Standard
Section 3 of che Federal Insecticide, Fungicide, and Rodenticide Act (TTJXA)
provides chat "no person in any State aay distribute, sell, offer for sale,
hold for sale, ship, deliver for shipment, or receive (and having so received)
deliver or offer Co deliver, Co any person any pesticide which is not
registered with che Administrator [of EPA]." To approve che registration of a
pesticide, che Administrator oust find, pursuant to Section 3(c)(5) chat:
"(A) its composition is such as to warrant che proposed claims for it; ,
(B) its labeling and other oaterial required co be submitted comply
with che requirements of chis Act;
(C) it will perform ics intended function without unreasonable adverse
effects on the environment; and
(D) when used in accordance with widespread and commonly recognized
practice it will aot generally cause unreasonable adverse effects
on che environment." *
In oaking chese findings, che Agency reviews a wide range of daca which
registrants are required Co submit, and assesses che risks and benefits
associated with the use of the proposed pesticide. But the established
approach to making these findings has been found to be defective on two councs:
Firsc, SPA and its predecessor agency, the United States Department of
Agriculture (USDA), routinely reviewed registration applitations on a "product
by product" basis, evaluating each product-specific application somewhat
independently. In che review of products containing similar components, chere
was Little opportunity for a retrospective review of che full range of
pertinent daca available in Agency files and in the public literature. Thus che
".product by product" approach vas ofcen inefficient and sometimes resulcad in
inconsistent or incomplete regulacory judgments.
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Second, over the '/ears, as a resulc of inevitable and continuing advances in
scientific knowledge, sethodology, and policy, the data base for aany
pesticides case co be considered inadequate by current scientific and
regulatory standards. Given the Long history of pesticide regulation in
several agencies, it is even likely that naterials aay have been lost froa the
data files. When EPA issued new requirements for registration in 1975 (40 CJR
162) and proposed new guidelines for hazard testing in 1978 (43 FR 29636, 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 compliance with current requirements, [See FIFRA Section 3(g)].
Facing the enormous job of re-reviewing and calling-in new data for the
approximately 35,000 current registrations, and realizing the inefficiencies of
the "product by product" approach, the Agency decided that a new, more
effective aethod 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
available to the Agency on a particular active ingredient and its current uses,
and sets forth the Agency's comprehensive position on the conditions and
requirements for registration of all existing and future products which contain
that active ingredient. These conditions and requirements, all of which oust
be aet to obtain or retain full registration or reregistration under Section
3(c)(5) of FITRA, include the submission of needed scientific data which- the
Agency does not now have, compliance with standards of toxicity, composition,
labeling, and packaging, and satisfaction of the data compensation provisions
of FURA 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 aay classify each product for
"general use" or "restricted use" [FITRA Section 3(d)j. A pesticide is
classified for "restricted use" when some special regulatory restriction is
needed to ensure against unreasonable adverse effects to man or the
environment. Many such risks of unreasonable adverse effects can be lessened
if expressly-designed label precautions are strictly followed. Thus the special
regulatory restriction for a "restricted use"^pesticide is usually a
requirement that it be applied only by, or under the supervision of, an
applicator who has been certified by the State or Federal government as being
competent to use pesticide safely, responsibly, and in accordance with label
directions. A restricted-use pesticide can have other regulatory restrictions
•40 C7R I62.11(c)(5)l instead of, or in addition to, the certified applicator
requirement. These other regulatory restrictions aay include such actions as
seasonal or regional limitations on use, or a requirement for the aonitorlng of
residue levels af-ter use. A pesticide classified for "general use," or not
classified at all, is available for use by any individual TOO is in compliance
with State or local regulations. The Registration Standard review compares
information about potential adverse effects of specific uses of the pesticide
with risk criteria listed in 40 C7R 162.11(c), and thereby determines whether a
product needs to be classified for "restricted use." If the Standard does
classify a pesticide for "restricted use," this determination is seated in the
second chapter.
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3. Requirement to Reregister TJr.dar the Standard
TITZA Section 3(g), as amended in 1-973, directs EPA to reregister all currently
registered products as expeditiously as possible. Congress also agreed that
reregistration 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, oust apply for reregistration. His application aust contain proposed
labeling that complies with this Standard.
SPA will issue a notice of intent to cancel the registration of any currently
registered product to which this Standard applies if the registrant fails to
comply with the procedures for reregistration set forth in the Guidance Package
which accompanies this Standard.
4. "Product Specific" Data and "Generic" Data
In the course of developing this Standard, EPA has determined the types of data
needed for evaluation of the properties and effects of products to which the
Standard applies, in the disciplinary areas of Product Chemistry, Environmental
Fate, Toxicology, Residue Chemistry, and Ecological Effects. These
determinations are based primarily on the data Guidelines proposed in 43 FR
29696, July 10, 1973; 43 FR 37336, August 22, 1978; and 45 FR 72948, November
3, 1980, as- applied to the use patterns of the products to which this Standard
applies. Where it appeared that data from a normally applicable Guidelines
requirement was actually unnecessary to evaluate these products, the Standard
indicates that the requirement has been waived. 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 some time and are, the Agency believes,
relatively familiar to registrants. Data which w« have found are needed to
evaluate the registrability of some products covered by the Standard aay 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 produc- categories. (See the
third chapter.) The various kinds of data normally required for registration
of a pesticide product can be divided into tvo basic groups:
A. Data that are product specific , i.e. data that relates only to the
the properties or effects of a product with- a particular
composition (or a group of products with closely similar
composition); and
3. Generic data that pertains to the properties or effects of a
particular ingredient, and thus is relevant to an evaluation of
the risks and benefits of all products containing that ingredient
(or all such products having a certain use pattern),, regardless of
any such product's unique composition.
The Agency requires certain "product specific" data for each product to
characterize the product's particular composition and physical/chemical
properties (Product Chemistry), and to characterize the product's acute
toxicity (which is a function of its total composition). The applicant for
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registration or reregistration of any product, whether it is a sanufacturing-
use or end-use product, and without regard to its intended use pattern, sust
submit or cite enough of this kind of data to allow E?A to evaluate the
product. For such purposes, "product specific" data on any product other than
the applicant's is irrelevant, unless the ocher 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 aay affect efficacy and where failure of efficacy could cause
public health problecs*
All other data needed to evaluate pesticide products concerns che properties or
effects of a particular ingredient of products (normally a pesticidally active
ingredient, but in some cases a pesticidally inactive, or "inert",
ingredient). Some data in this "generic" category are required to evaluate the
properties and effects of all products containing that ingredient [e.g., the
acute ID-50 of the active ingredient in its technical or purer grade; see
proposed 40 C7R 163.31-l(a), 43 F*. 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
C7R 163.32-1, 43 FR-37363, which requires subchronic oral testing of the active
ingredient with respect to certain use patterns only). Where a particular data
requirement is use-pattern dependent, it will apply to each end-use, product
which is to be labeled for that use pattern (except where such end-use product
is formulated from a registered manufacturing-use product permitting such
formulations) and to each manufacturing-use product with labeling that allows
it to be used to aalce end-use products with that use pattern. Thus, for
example, a subchronic oral dosing study is needed to evaluate the safety of any
aanufacturing—use product that legally could be used to make an end.-use, food-
crop pesticide. But if an end-use product's label specified it was for use
only in ways that involved no food/feed exposure and no repeated human
exposure, the subchronic oral dosing study would not be required to evaluate
the product's safety; and if a manufacturing-use product's label states that
the product is for use only in making end-use products not involving food/feed
use or repeated human exposure, that subchronic oral study would not be
relevant to the evaluation of the manufacturing—use product either.
If a registrant of a currently registered manufacturing-use or end-use product
wishes to avoid the costs of data compensation [under FIFRA Section 3(c)(l)(D)]
or data generation [under Section 3(c)(2)(3)] for "generic" data that is
required only with respect to some use patterns, he may elect to delete those
use patterns from his labeling at the tiae he reregisters his product. An
applicant for registration of a new product under this Standard nay similarly
request approval for only certain use patterns.
5. 2ata- Comoensation Requirements under FTT3A 2(c)(lHD)
Under FIFSA Section 3(c)(l)(D), an applicant for registration, reragistration,
or amended registration sust offer to pay compensation for certain existing
data the Agency has used in developing the Registration Standard. The data for
which compensation oust be offered is all data which are described by all che
following criteria:
A. "he data --ere rirst submitted to i?A (or :o its aredecessor
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agencies, UST3A or FDA), on or after January L, 1970;
3. The data, vare submitted to EPA (or USDA or FT3A) by some other
applicant or registant in support of an application for an
experimental use permit, an amendment adding a new use to a
registration, or for registration, or to support or maintain in
effect an existing registration;
C. They are the kind of data which are relevant to the Agency's
decision to register or reregister the applicant's product
under the Registration Standard, taking into account the
applicant's product's composition and intended use patrern(s);
D. The Agency has found the data to be valid and usable in reaching
regulatory conclusions; and
£. They are not data for which the applicant has been exempted by
FIFHA Section 3(c)(2)(D) from the duty to offer to pay
compensation. (This exemption applies to the "generic" data
concerning the safety of an active ingredient of the applicant's
product, not to "product specific" data. The exemption is
available only to applicants whose product is labeled for end-
uses for which the active ingredient in question is present in
the applicant's product because of his use of another registered
product containing that active ingredient which he purchases from
another producer.)
An applicant for reregistration of an already registered product under this
Standard, or for registration of a new product under this Standard, accordingly
aust determine which of the data used by EPA in developing the Standard must be
the subject of an offer to pay compensation, and must submit with his
application the appropriate statements evidencing his compliance with FTFRA
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 aost cases, data which is
specific to another firm's product will not suffice to allow EPA to evaluate
the applicant's product, chat is, will not be useful to the Agency in
determining whether the applicant's product is registrable. There aay be
cases, however, where because of close similarities between the composition of
two or aore products, another firm's data aay suffice co allow EPA co evaluate
some or all of the "product specific" aspects of the applicant's product. In
such a case, the applicant may choose to cite that data instead of submitting
data from tests on his own product, and if he chooses that option, he would
have to comply with the offer-to-pay requirements of Section 3(C)(1)(D) for
that data.
Each applicant for registration or reregistration of a manufacturing—ise
product, and aach applicant for registration or reregisfration of an end-use
product, who is not exempted by FTTSA Section 3(c)(2)(D), aust comply with the
Section 3(c)(l)(D) requirements with respect co each item of "generic'1 data
that relates Co his product's intended uses.
A detailed description of :he procaduras an applicant aust follow in applying
for rsregistration (or new registration) under this Standard is found in the
Guidance Package for chis Standard.
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5. Obtaining 3aca :o -ill "T3ata Gaps"; 7ITSLA 3(e)(2)(3)
Some of :he
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amendment to Che Standard, or aay deny Che application for registration on the
grounds chat Che proposed product would cause unreasonable adverse effects Co
the environment. In the former case, when additional data have been
satisfactorily supplied, and providing that che data do not indicate the
potential for unreasonable adverse effects, the Agency will then amend the
Standard Co cover che nev registration.
Each Registration Standard is based upon all data and information available to
che Agency's reviewers on a particular dace prior to the publication date.
This "cut-off" date is stated at the beginning of che second chapter. Any
subsequent data submissions and any approved amendments will be incorporated
into che Registration Standard by aeans of addenda, which are available for
inspection at EPA in Washington, O.C., or copies of which aay be requested froa
che Agency. When all che present "data gaps" have been filled and the
submitted data have been reviewed, che Agency will revise the Registration
Standard. Thereafter, when the Agency determines that the internally
maintained addenda have significantly altered the conditions for registration
under che Standard, the document will be updated and re-issued.
While Che Registration Standard discusses only the uses and hazards of products
containing the designated active ingredient(s), the Agency is also concerned
with the potential hazards of some inert ingredients and impurities.
Independent of the development of any one Standard, the Agency has initiated
the evaluation of some inert pesticide ingredients. Where the Agency has
identified inert ingredients of concern in a specific product to which the
Standard applies, these ingredients will be pointed out in the Guidance Package.
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CHAPTER II
AGENCY POSITICN CN CHLOPAMBEN
Introduction
This chapter describes in detail the Agency's regulatory position on pesticide
products which contain chloramben as the sole active ingredient. The
regulatory position adopted by the Agency incorporates a number of
considerations. Foremost: among these considerations is an analysis of the
registrability of chloramben based on the risk criteria found in Section
162.IK a) of Title 40 of the U.S. Code of Federal Regulations. Following the
Aaency's statement on the registrability of chloramben is the rationale for
this basic determination.
In addition to this decision, standards of product composition, acute toxicity.
labeling, and use are established. Applicants for the registration of
chloramben products must meet these standards to obtain registration. The
rationale for establishing a particular standard follows the presentation of
the standard. Regulatory actions such as reouiring protective clothing during
application are prescribed, and additional data are requested. The basis for
any regulatory action can be found by reading the rationale for the action,
which follows the chosen regulatory option.
In general, the scientific basis for any regulatory action, including
establishing data requirements, can be found in the disciplinary chapters.
References to Aoency guidelines for testing are provided when appropriate.
Description of Chemical
Chloramben is a herbicide used for the control of a variety of annual grasses
and broadleaf weeds in agricultural and ornamental crops, both in non-domestic
and domestic settings. Chloramben is the common name for 3-amino 2,5-
dichlorobenzoic acid. Currently registered manufacturing-use products are
limited to Sodium Chloramben (the sodium salt of chloramben) and Methyl
Chloramben (the methyl ester of chloramben).
Chloramben formulated products are marketed under the trade names Araiben,
Vegiben, Weedone, and Ornamental Weeder. These products represent a wide range
of product types (soluble concentrates, flowable concentrates, emulsifiable
concentrates, and granulars) and contain a variety of forms of chloramben
(sodium chloramben, methyl chloramben, ammonium chloramben and moncroethyl
ammonium chloramben).
Products containing mixtures of chloramben and other active ingredients are not
covered under this Standard.
2-1
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Regulatory Position for Chloramben
Chloramben, as described in this Standard nay be registered for sale,
distribution, reformulation and use in the United States. Considering all
information available to the Agency as of October 1, 1980, the Agency finds
that none of the risk criteria found in Section 162.11(a) of Title 40 of the
U.S. Cede of Federal Regulations were met or exceeded for Chloramben.
The Agency has determined that Chloramben does not cause an unreasonable
adverse effect with proper label directions and precautions. Chloramben
products currently registered may be reregistered subject to the conditions
imposed. New products may be registered under this Standard and are subject to
the same requirements.
Regulatory Rationale for Chloramben
Chloramben was referred for review to the Rebuttable Presumption Against *
Registration (RPAR) Program in October of 1980. The referral of this pesticide
to the RPAR Program was based on an oncogenicity study on technical Chloramben
(3-amino 2,5-dichlorobenzoic acid), conducted by Gulf South Research Institute
(GSRI) for the National Cancer Institute (NCI). This study indicates that
Chloramben administration results in hepatocellular carcinoma in female mice.
The NCI study reports statistically significant incidences of hepatocellular
carcinoma in female mice receiving 10,000 and 20,000 ppn dietary doses of
chloramben.
This study was reviewed by the Environmental Protection Agency (EPA) and was
found to contain minor flaws in protocol and study conduct. The Agency's
review indicates that although the study is flawed, the NCI results do indicate
a clear positive result at the 20,000 ppm dose in female mice, and that the,
study is adequate for risk assessment purposes.
Additional data were collected and reviewed by the Agency to complete the
assessment of the oncogenicity of chloramben. No other studies indicating
chloramben related chronic effects were identified, and an oncogenicity study,
completed in 1978 by Huntington Research Center, reported no statistically
significant increases in tumour incidence in mice receiving dietary doses of
100, 1,000, and 10,000 ppm of chloramben. In addition, a chronic feeding study
in rats completed in 1979 by Litton Bionetics reported no chloramben dose-
related chronic effects in rats at dietary doses of 100, 1,000, and 10,000
ppm. Available mutagencity testing (Anes test) utilizing technical chloramben
yielded negative results.
A major concern regarding any potential long-term exposure in humans to a
pesticide product is the risk of developing delayed toxic effects, principally
cancer. The results presented in the NCI bioassay of chloramben are utilized
in the completion of an oncogenic risk assessment. The results of this risk
assessment are factored into the decision to proceed or not to proceed with a
presumption against the registration of chloramben.
2-2
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In order to assess this risk for exposure to chloramben, a worst-case situation
based on the conclusions of the NCI bioassay of chloramben is utilized. using
die-NCI data as the 'oasis for a risk assessment, vas obtain a potency of 1.05 x
Reported Incidence of Hepatocellular Carcinoma in Female Mice
Dose (ppm)
0 10,000 20,000
2/67 (0.03) 7/48 (0.15) 10/50 (0.20)
The dose-response relationship assumed in the risk analysis is that of the
linear multi-stage model. The lifetime probability of canc§r due to ingesting
chloramben has been determined to be on the order of Ix 10"" (see chapter 7
for detailed determination).
For applicator exposure, a dietary exposure equivalent is calculated for risk
assessment. Applicator exposure data were not available on chloramben per se.
However, exposure studies involving pesticides used in a similar manner to
chloramben were available for extrapolation and use in an applicator risk
assessment.
The Agency assumed that the largest segment of die applicator population at
greatest risk dirough exposure to chloramben was applicators of
soluble/flowable concentrate products ii» soybeans. Use of chloramben in
soybeans represents 96% of chloramben usage. Both granular and
soluble/flowable concentrate products are currently registered for use in
soybeans. Of these two formulation types, die liquid formulations present die
highest potential for significant exposure. The lifetime probability of cancer
due to chloramben application in soybeans of soluble/flowable concentrate
products has been determined to be on die order of Ix 10~ (see chapters 5 and
7 for detailed determination). This represents a worst-case assessment.
_q
The Agency is 95%_confident that these risk levels (dietary: Ix 10 ; and
applicator: Ix 10 ) will not be exceeded by die dose (virtually safe dose)
as determined in chapters 5 and 7-
Section 3(c)(8) of die Federal Insecticide, Fungicide, and Rodenticide Act
(FIFRA) directs die Agency not to initiate a Rebuttable Presumption Against
Registration (REAR) action unless die action is based on a validated test or
other sigificant evidence raising prudent concerns of unreasonable adverse
effects to man or die environment. Human exposure to pesticides through any
medium or pathway is a central issue in evaluating unreasonable adverse effects
of pesticide products. It is die Agency's policy to attempt to reduce
exposure, whenever possible, to acceptable levels widiout issuing an RPAR
action.
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The Agency determined that the existing data base on chloramben does not
support a Rebuttable.Presumption Against Registration. Results from the risk
assessment completed by the Agency, combined with the weight of the data base,
indicate that issuing a Rebuttable Presumption Against the Registration of
chloramben at this time would not be prudent regulatory policy.
The Agency thus decided to reregister all pesticide products containing
chloramben as the sole active ingredient, provided the conditions are met as
described under the heading: "Criteria for Registration Under the Chloramben
Standard". These conditions include the submission of applicator exposure data
on a typical liquid formulation as a data requirement.
Criteria for Registration Under the Chloramben Standard
To be subject to this Standard, chloramben products must:
1. contain chloramben as the sole active ingredient;
2. be within acceptable standards of composition as specified;
3. be within acute toxicity limits as specified;
4. be labelled for acceptable end-uses as specified; and
5. bear required labeling as specified.
Manufacturing-use chloramben products must bear label directions for
formulation into acceptable end-uses.
Applicants for registration or reregistration of chloramben products under this
Standard must comply with all terms and conditions described in the following
sections, including commitment to fill data gaps on a time schedule specified
by the Agency and when applicable offer to pay compensation to the extent
required by 3(c)(l)(D) and 3(c)(2)(D) of the Federal Insecticide, Fungicide,
and Rcdenticide Act (FIFFA), as amended, 7 U.S.C. 136(c)(l)(D) and
136(c)(2)(D). As discussed in Chapter I, applicants for the registration of
chloramben products under this Standard must contact the Agency for specific
instructions, including updated information on data requirements and companies
whose data must be cited and to whom compensation must be offered.
2-4
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A. Manufacturing-use Chloramben
1. Acceptable Range and Limits
Summary Table
Product Conposition Acute Toxicity End-Use Patterns
Active Ingredient: Acute Oral: Outdoor
Any Percentage with appropriate Category I-IV terrestrial uses
certification of limits. (food or nonfood)
Acute Dermal:
Category I-IV
Acute Inhalation:
Category I-IV
Primary Eye:
Category I-IV
Primary Dermal:
Category I-IV
a. Product Composition Standards
Currently registered chloramben manufacturing-use products include the sodium
salt of chloramben and the methyl ester of chloramben. Manufacturing-use
chloramben products with any percentage of sodium or methyl chloramben are
acceptable under this Standard with appropriate certification of limits.
The Agency has determined that information on the physical/chemical properties
of technical chloramben (3 amino 2,5-dichlorobenzoic acid) cannot be used to
fulfill product chemistry requirements for manufacturing-use sodium chloramben
or methyl chloramben. Available data indicate that the physical/chemical
properties of sodium and methyl chloramben are different from the
physical/chemical properties of technical grade chloramben. Information on the
physical/chemical properties of both sodium and methyl chloramben are required
in addition to information on technical grade chloramben (3 amino 2,5-
dichlorobenzoic acid).
b. Acute Toxicity Limits
Manufacturing-use chloramben products with established acute toxicity category
I-IV ratings for each of the acute effects (acute oral, dermal, and inhalation
toxicity and primary eye and dermal irritation) are acceptable under this
Standard.
2-5
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c. Use Patterns
Manufacturing-use chloramben products must be labeled for formulation into end-
use herbicides intended for outdoor terrestrial uses (food or nonfood).
Chloramben is currently registered for use in a variety of food crops, and for
use in annual and perennial flowers, shrubs, and trees.
Tolerances have been established for chloramben use on the following crops:
soybeans, tomatoes, lima beans, corn, peanuts, beans (dry, edible), cantaloupe,
cucumbers, peppers, pumpkin, beans (snap) , squash, sunflower, and sweet
potatoes.
The Agency will consider additional tolerances on food or feed crops provided
that applicants for the registration of the additional crop(s) submit a
petition(s) , supply appropriate residue data, and demonstrate that the addition
of the tolerance(s) will not result in an unacceptable risk to the general
population. Applicants must also demonstrate that the. additional food-use
pattern(s) will not result in an unacceptable risk to applicators.
The Agency will accept applications for additional tolerances because available
data indicate that the currently estimated dietary intake of chloramben per day
is .09% of the ADI (see Tolerance Reassessment) .
The Agency will consider additional non-food, terrestrial outdoor uses of
chloramben provided that applicants for the registration of the additional
use(s) submit any additional data required for the registration of the use, and
demonstrate that the use pattern will not result in an unacceptable risk to
applicators.
2. Required Labeling
All manufacturing-use chloramben products must bear appropriate labeling as
specified in 40 CFR 162.10.
Registrants have the option of supplying requested rotational crop studies or
of placing the following prohibition on labels of all end-use products
containing chloramben:
"Do not rotate to other crops"
3. Tolerance Reassessment
Tolerances of 0.1 ppm have been established for residues of chloramben in all
food crops for which chloramben is registered. This level was originally
established at the limit of detectability of chloramben. The theoretical
maximum residue contribution (TMRC) of chloramben to the human diet is .013
mg/day. This figure is adjusted for the percentage of chloramben treated crops
to arrive at the maximum estimated chloramben intake figure of .00022 mgAg/day
(see Chapter 6 for full dietary exposure analysis).
The "No Observable Effect Level" (NOEL) in dogs was reported to be 25 mgAg
body weight (Hazleton Laboratories, 0028). The acceptable daily intake (ADI)
calculated from this figure is .25 mgAg/day. The maximum estimated chloramben
intake per day is .09% of the calculated ADI.
2-6
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3. Soluble Concentrate Chloramben
1. Acceptable Ranges and Limits
Summary Table
Product Composition Acute Toxicity End-Use Patterns
Active Ingredient: Acute Oral: Outdoor terrestrial
Any percentage with appropriate Category III-IV food-uses or nonfood
certification of limits.
Acute Dermal:
Inert Ingredients: Category III-IV
Inert ingredients in food-use
formulations must be cleared Acute Inhalation:
for such use under Category III-IV
40 CFR 180.1001.
Primary Eye:
Currently registered soluble Category III-IV
concentrate products containing
23.4% Ammonium Chloramben Primary Dermal:
are substantially similar. Category III-IV
a. Product Composition Standards
Currently registered chloramben soluble concentrate products include several
products containing 23.4% ammonium chloramben and one product containing 15.7%
ammonium chloramben and 47.2% monomethyl-ammonium chloramben. The Agency has
determined that existing soluble concentrate products containing the ammonium
salt of chloramben are substantially similar. The sole soluble concentrate
product containing a mixture of the ammonium and monomethyl ammonium salts has
been determined to be unique.
Soluble concentrate chloramben products with any percentage of sodium
chloramben, ammonium chloramben, monanethyl-ammonium chloramben, or methyl
chloramben are acceptable for consideration under this Standard, with
appropriate certification of limits.
Inert ingredients in food-use formulations must be cleared for such use under
40 CFR 180.1001.
b. Acute Toxicity Limits
Soluble concentrate products with established acute toxicity category III-IV
ratings for each of the acute effects (acute oral, dermal and inhalation
toxicity and primary eye and dermal irritation) are acceptable for
consideration under.this Standard.
2-7
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c. Use Patterns
Soluble concentrate chloramben products containing ammonium and/or monomethyl-
ammcnium chloramben can be registered for non domestic or domestic-use in
soybeans, dry beans , peanuts , sunflowers, corn , lima beans, squash, pumpkins,
asparagus (seedling), and sweet potatoes.
Currently registered dosage rates and application methods are acceptable (see
page 5-4) pending submission of required residue chemistry data listed in the
manufacturing-use section of chapter III.
Proposed soluble concentrate chloramben products containing sodium chloramben
or methyl chloramben can also be registered for non domestic-use or domestic-
use in soybeans, dry beans, peanuts, sunflowers, corn, lima beans, squash,
pumpkins, asparagus (seedling) , and sweet potatoes provided any additional
requested residue data reflecting the proposed use of the pesticide on the crop
is submitted and found to be acceptable.
Soluble concentrate chloramben products can be registered for use in any crop
for which a tolerance for chloramben (or exemption from a tolerance) , has been
granted.
2. Required Labeling
All soluble concentrate chloramben products must bear appropriate labeling as
specified in 40 CFR 162.10.
3. Regulatory Rationale
Product Composition Standards: The Agency finds no reason to limit soluble
concentrate formulations to the ammonium or moncmethyl ammonium salts of
chloramben as the active ingredients, provided any additional required data
reflecting the proposed use of the product on the crop is provided.
The Agency finds no reason to limit the % active ingredient in formulations as
long as the amount of active ingredient applied per acre does not exceed
acceptable levels and result in residues which exceed the tolerance.
Acute Toxicity Standards: The Agency limited acute toxicity to categories III
through IV because domestic use is acceptable under this Standard.
Use Patterns: The Agency finds no reason to limit the use of soluble
concentrate products to currently registered crops. The use of soluble
concentrate chloramben products on other crops (for which a tolerance or
exemption from a tolerance has been granted) is acceptable provided any
additional residue data are submitted on the use of the product on the crop.
2-8
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C.
Flowable Concentrate Chloramben
1. Acceptable Ranges and Limits
Product Conposition
Active Ingredient:
Any percentage with appropriate
certification of limits.
Inert Ingredients:
Inert Ingredients in food-use
formulations must be cleared
for such use under
40 CFR 180.1001.
Currently registered flowable
concentrate products containing
sodium chloramben are sub-
stantially similar.
Summary Table
Acute Toxicity
Acute Oral:
Category III- IV
Acute Dermal:
Category III-IV
Acute Inhalation:
Category III-IV
•Primary Eye:
Category III-IV
Primary Dermal:
Category III-IV
End-Use Patterns
Outdoor terrestrial
food-uses or nonfood
a. Product Composition Standards
Currently registered chloramben flowable concentrate products contain 21% and
83% sodium chloramben. The Agency has determined that existing flowable
concentrate chloramben products are substantially similar.
Flowable concentrate chloramben products with any percentage of sodium
chloramben, ammonium chloramben, monomethyl-ammonium chloramben, or methyl
chloramben are acceptable for consideration under this Standard, with
appropriate certifica'tion of limits.
Inert ingredients in food-use formulations must be cleared for such use under
40 CFR 180.1001.
b. Acute Toxicity Standards
Flowable concentrate products with established acute toxicity category III-IV
ratings for each of the acute effects (acute oral, dermal, inhalation toxicity,
and primary eye and dermal irritation) are acceptable for consideration under
this Standard.
c. Use Patterns
Flowable concentrate chloramben products containing sodium chloramben can be
registered for domestic or non domestic use in soybeans, dry beans, peanuts,
and sunflowers.
2-9
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Currently registered dosage rates and application methods are acceptable (see
page 5-4) pending submission of required residue chemistry data listed in the
manufacturing-use section of chapter III.
Proposed flowable concentrate chloramben products containing ammonium
chloramben, monomethyl ammonium chloramben, or methyl chloramben can also be
registered for non domestic or domestic use in soybeans, dry beans, peanuts/
and sunflowers provided any additional requested residue data reflecting the
use of the pesticide on the crop is submitted and found to be acceptable.
Flowable concentrate chloramben products can be registered for use in any crop
for which a tolerance for chloramben (or exemption from a tolerance) has been
granted.
2. Required Labeling
All flowable concentrate chloramben products must bear appropriate labeling as
specified in 40 CFR 162.10.
3. Regulatory Rationale
Product Composition Standards: The agency finds no reason to limit flowable
concentrate formulations to the sodium salt of chloramben as the active
ingredient provided any additional required residue data reflecting the
proposed use of the product.cn the crop(s) is provided.
The Agency finds no reason to limit the % active ingredient in formulations as
long as the amount of active ingredient applied per acre does not exceed
acceptable levels and result in residues which exceed tolerances.
Acute Tbxicity Standards: The Agency limited acute toxicity to categories III
through IV because donestic use is acceptable under this Standard.
Use Patterns: The Agency finds no reason to limit the use of flowable
concentrate products to currently registered crops. The use of flowable
concentrate products on other crops (for which a tolerance or exemption from
tolerance has been granted) is acceptable provided any additionally required
residue data are submitted on the use of the product on the crop.
2-10
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D. Smulsifiable Concentrates
1. Acceptable Ranges and Limits
Summary Table
Product Composition Acute Toxicity End-Use Patterns
Active Ingredient: Acute Oral: Outdoor terrestrial
Any percentage with appropriate Category III-IV food uses or nonfood
certification of limits
Acute Dermal:
Inert Ingredients: Category III-IV
Inert Ingredients in food-use
formulations must be cleared Acute Inhalation:
for such use under Category III-IV
40 CFR 180.1001.
Primary Eye:
The currently registered Category III-IV
emulsifiable concentrate
product contains 23.2% Primary Dermal:
methyl chloramben. Category III-IV
a. Product Composition Standards
The currently registered emulsifiable concentrate chloramben product contains
23.2% methyl chloramben.
Emulsifiable concentrate chloramben products with any percentage of sodium,
methyl, ammonium, or moncmethyl ammonium chloramben are acceptable for
consideration under this Standard, with appropriate certification of limits.
Inert Ingredients in food-use formulations must be cleared for such use under
40 CFR 180.1001.
b. Acute Toxicity Limits
Emulsifiable concentrate products with established acute toxicity category III-
IV ratings for each of the acute effects (acute oral, dermal and inhalation
toxicity and primary eye and dermal irritation) are acceptable for
consideration under this Standard.
c. Use Patterns
Emulsifiable concentrate products containing methyl chloramben can be
registered for non domestic-use in snap beans, cantaloupes, and cucumbers.
Currently registered dosage rates and application methods are acceptable (see
page 5-4) pending submission of required residue chemistry data listed in the
manufacturing-use section of chapter III.
-------
Proposed emulsifiable concentrate chloramben products containing sodium,
ammonium or monomethyl ammonium chloramben can be registered for domestic or
non-domestic use in snap beans, cantaloupes, and cucumbers provided any
additional requested residue data reflecting the proposed use of the pesticide
on the crop is provided.
Emulsifiable concentrate products can be registered for use in any crop for
which a tolerance (or exemption from a tolerance) has been granted.
2. Required Labeling
All emulsifiable concentrate chloramben products must bear appropriate labeling
as specified in 40 CFR 162.10.
3. Regulatory Rationale
Product Composition Standards: "Hie Agency finds no reason to limit
anulsifiable concentrate formulations to the methyl ester of chloramben as the
active ingredient, provided any additional residue data reflecting the proposed
use of the product on the crop is provided, and found to be acceptable.
The Agency finds no reason to limit the % active ingredient in formulations as
long as the amount of active ingredient applied per acre does not exceed
acceptable levels and result in residues above tolerance levels.
Acute Toxicity Standards: The Agency lijnited acute toxicity to categories III-
IV because emulsifiable concentrate products containing sodium, ammonium, and
monomethyl ammonium chloramben can be registered for domestic use.
*
Use Patterns: The Agency finds no reason to limit the use of emulsifiable
concentrate chloramben products to currently registered crops. The use of
flowable concentrate products on other crops (for which a tolerance or
exemption frcm a tolerance has been granted) is acceptable provided any
additionally required residue data are submitted on the use of the product on
the crop.
2-12
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E. Granular Chloramben
1. Acceptable Ranges and Limits
Summary Table
Product Comoosition
Active Ingredient:
Any percentage with appropriate
certification of limits.
Inert Ingredients:
Inert ingredients in food-use •
formulations must be cleared
for such use under
40 CFR 180.1001.
Currently registered granular
products containing ammonium
chloramben are substantially
similar.
Currently registered granular
products containing ammonium and
moncmethyl ammonium chloramben
are substantially similar.
Acute Toxicity
Acute Oral:
Category III-IV
Acute Dermal:
Category III-IV
Acute Inhalation:
Category III-IV
Primary Eye:
Category III-IV
Primary Dermal:
Category III-IV
End-Use Patterns
Outdoor
terrestrial food
(or non food) uses
a. Product Composition Standards
Currently registered granular chloramben products contain 1.3%-10.8% ammonium
chloramben, and mixtures of 2.82%-5.4% ammonium chloramben and 8.46%-17.3%
moncmethyl ammonium chloramben.
Granular chloramben products with any percentage of sodium, methyl, ammonium or
moncmethyl ammonium chloramben are acceptable for consideration under this
standard with appropriate certification of limits.
Inert Ingredients in food-use formulations must be cleared for such use under
40 CFR 180.1001.
b. Acute Tbxicity Limits
Granular chloramben products with established acute toxicity category III-IV
ratings for each of the acute effects (acute oral, dermal, and inhalation
toxicity and primary eye and dermal irritation) are acceptable for
consideration under this Standard.
2-13
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c. Use Patterns
Granular chloramben products containing ammonium and roonomethyl ammonium
chloramben can be registered for domestic or non-domestic use in soybeans, dry
beans, peanuts, sunflowers, com, sweet potatoes, transplanted tomatoes and
peppers, lima beans, pumpkins, squash, asparagus (seedling), and ornamentals.
Currently registered dosage rates and application methods are acceptable (see
page 5-4) pending submission of required residue chemistry data listed in
chapter III.
Proposed granular chloramben products .containing scdium or methyl chloramben
can be registered for domestic or non-domestic use in soybeans, dry beans,
peanuts, sunflowers, corn, sweet potatoes, transplanted tomatoes and peppers,
lima beans, pumpkins, squash, asparagus (seedling), and ornamentals, provided
any additional requested residue data reflecting the proposed use of the
product on the crop is provided and found to be acceptable.
Granular chloramben products can be registered for use in any crop for which a
tolerance (or exemption from a tolerance) has been granted.
2. Required Labeling
All oranular chloramben products must bear appropriate labeling as specified in
40 CFR 162.10.
3. Regulatory Rationale
Product Composition Standards: The Agency finds no reason to limit granular
chloramben products to the ammonium or monomethyl ammonium salts of chloramben
as the active ingredients, provided any additional residue data reflecting the
proposed use of the product on the crop is provided, and found to be acceptable,
The Agency finds no reason to limit the % active ingredient in formulations as
long as the amount of active ingredient per acre does not exceed acceptable
levels and result in residues above tolerance levels.
Acute Tbxicity Standards: The Agency limited the acute toxicity of granular
products to categories III-IV because granular products containing ammonium
chloramben, moncmethyl ammonium chloramben, scdium chloramben and methyl
chloramben can be registered for domestic use.
Use Patterns: The Agency finds no reason to limit the use of granular
chloramben to currently registered crops. The use of granular chloramben on
other crops covered by chis Standard (for which a tolerance or exemption from a
tolerance has been granted) is acceptable provided any additional residue data
are submitted and found to be acceptable.
2-14
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CHAPTER III
DATA REQUIREMENTS AND DATA GAPS
A. Manufacturing-use Chloramben
1. Generic Data Requirements;
Table 3-1, entitled: Generic Data Requirements and Data Gaps for Manufacturing-
use Products includes those data that pertain to the properties or effects of
chloramben as an active ingredient. Thus, these data are relevant to an
evaluation of the risks and benefits of all products containing chloramben.
Providing data to fill indicated gaps in the data base is the primary
responsibility of the registrant(s) of manufacturing-use chloramben.
Registrants of end-use products which are not exempted by FIFRA Section
3(c)(2)(D) are also responsible for the submission of these data. Applicants
for the registration or reregistration of manufacturing-use chloramben products
must acknowledge reliance on existing data which 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 accumulaticnare
required on both sodium chloramben and methyl chloramben. Requested data on
the fate of sodium chloramben will support the registrations of all products
containing sodium, ammonium, and monomethyl ammonium chloramben. Requested
data on methyl chloramben will support the registrations of all products
containing methyl chloramben.
In addition, the Agency is requiring the completion of an applicator exposure
study. The study should be conducted with a typical soluble or flowable
concentrate formulation, mixed and then applied by ground equipment to a
typical (160 acres) soybean field at recommended application rates. This study
is required because the decision not to presume against the registration of
chloramben was based, in part, on the results of the applicator oncogenic risk
assessment. The risk assessment used data extrapolated from exposure studies
on pesticides used in a similar manner to chloramben. The Agency is requiring
this study to verify the exposure estimates used in the oncogenic risk
assessment.
Product Chemistry Data
Certain data on the physical/chemical properties of technical chloramben (3-
amino 2,5-dichloro benzoic acid) are required for the registration of both
sodium and methyl chloramben.
3-1
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Toxicology Data
The sodium salt of chloramben has been determined to be equivalent to
chloramben for the purposes of extrapolating "generic" toxicity data.
A summary report in Agency files indicates that the methyl ester of chloramben
hydrolyzes to chloramben within days of application to the soil. Provided that
evidence is submitted documenting the breakdown of methyl chloramben to
chloramben after application, and provided an acceptable metabolism study is
submitted on methyl chloramben, all subchronic and chronic toxicology generic
data requirements may be fulfilled for the methyl ester and sodium salt by
testing with chloramben (or the sodium salt).
Ecological Effects Data
Fish and wildlife (ecological effects) safety testing must be conducted on
sodium chloramben ("for'the registration of products containing sodium
chloramben) and on the methyl ester (for the registration of products
containing methyl chloramben). Separate testing is required because data
indicate that the physical/chemical properties (ie. solubility) of methyl
chloramben and sodium chloramben differ. These differences could influence the
acute toxicity of these compounds to fish and wildlife.
Residue Chemistry Data
Data on the storage of PAC between harvest and sampling are required for the
registration of both sodium and methyl chloramben.
3-2
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2. Product Specific Data Requirements; Manufacturing-use Chloramben
Table 3-2, entitled: Product Specific Data Requirements for Manufacturing-use
Products includes those data that relate only to the properties or effects of
a product with a specific composition (or substantially similar composition) .
Thus, these data are required of each product (or substantially similar
product) to characterize the product's particular composition and
physical/chemical properties, and to characterize the product's acute toxicity.
Product composition 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
chloramben 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 manufacturing-
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 a manufacturing-use
chioramben product.
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 chloramben products, methyl and sodium chloramben,
are not substantially similar for the purposes of establishing product-specific
testing requirements.
Product Chemistry Data
Data requirements 163.61-3 through 163.61-7 (product composition data) apply to
each proposed or currently registered manufacturing-use chloramben product.
Data requirements 163.61-8(7) through 163.61-8(18) (physical/chemical
properties data) apply to manufacturing-use products which are not the same as
the technical grade of the active ingredient. These data are required on both
sodium and methyl chloramben.
Toxicology Data
Data requirements 163.81-1 and 163.81-2 (acute oral and dermal toxicity) apply
to manufacturing-use products which are not toxicolcgically equivalent to the
technical grade of the active ingredient. Sodium chloramben has been
determined to be equivalent to chloramben. Separate testing on methyl
chloramben must be supplied.
Data requirements 163.81-3 through 163.81-6 apply to each manufacturing-use
product or substantially similar product. Testing must be supplied on both
sodium and methyl chloramben. Methyl chloramben is not equivalent to
sodium chloramben for the purposes of extrapolating acute toxicity data.
3-3
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B. End-Use Chlorainben Products
Applicants for the registration of end-use products containing chloramben are
advised that if the Agency does not receive commitments, within the specified
time frame, from manufacturing-use chloramben registrants to fill data gaps
identified for the manufacturing-use product (Table 3-1) , manufacturing-use
product registrations will be suspended. Forraulators must then bear the burden
of supplying these data if continued availability of the manufacturing-use
product is desired.
1. Generic Data Requirements
Table 3-3, entitled: Generic Data Requirements and Data Gaps for End-use
Products Containing Ammonium Chloramben includes generic data which are
required for the registration of all end-use products containing ammonium or
monomethyl ammonium chloramben. Ammonium and monomethyl ammonium chloramben
end-use products are prepared by an integrated formulation system. Certain
product chemistry data are required on technical grade ammonium and technical
grade moncmethyl ammonium chloramben for tine registration of end-use products
containing these salts.
The Agency has determined that acute oral and dermal toxicity testing on
technical grade chloramben or sodium chloramben will not fulfill the
requirements for acute testing on technical grade ammonium and monomethyl
ammonium chloramben. However, chronic or long term toxicology testing on the
ammonium or moncmethyl ammonium salts is not required.
The Agency has determined that fate data on technical ammonium and monomethyl
ammonium chloramben are not required. Requested data on sodium chloramben will
suffice.
Because data on the toxicity of sodium or methyl chloramben to fish and
wildlife cannot be used to assess the toxicity of end-use products containing
ammonium or monomethyl ammonium chloramben, additional data on these salts are
required. Because there are no manufacturing-use products which contain
ammonium or monomethyl ammonium chloramben, these data must be supplied by the
producers of end-use ammonium or monomethyl ammonium chloramben products.
3-4
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2. Product Specific Data Requirements for End-Use Products
Table 3-4: Product Specific Data Requirements and Data Gaps for Soluble
Concentrate Chlorambin
Table 3-5: Product Specific Data Requirements and Data Gaps for Flowable
Concentrate Chloramben" *~~
Table 3-6: Product Specific Data Requirements and Data Gaps for Emulsifiable
Concentrate Chloramben
i
Table 3-7: Product Specific Data Requirements and Data Gaps for Granular
Chloramben
Tables 3-4 through 3-7 include those data 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 characterize the product's particular composition and
physical/chemical properties, and to characterize the products acute toxicity.
Product composition data are required for each end-use product. Providing data
to fulfill this requirement is the responsibility of each applicant for the
registration or reregistration of an end-use Chloramben 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 Chloramben product.
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.
Substantially Similar Products
Existing Soluble Concentrate Chloramben products (containing 23.4% ammonium
Chloramben) are substantially similar to each other.
Existing Soluble Concentrate Chloramben products (containii'g a mixture of
ammonium and moncmethyl ammonium salts) are substantially similar to each other.
Existing Flowable Concentrate Chloramben products (containing sodium
Chloramben) are substantially similar to each other.
Existing Granular Chloramben products (containing ammonium Chloramben) are
substantially similar to each other and to S.C. products containing ammonium
Chloramben.
Existing Granular Chloramben products (containing a mixture of ammonium and
moncmethyl ammonium Chloramben) are substantially similar to each other and to
S.C. products containing ammonium and moncmethyl ammonium Chloramben.
3-5
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Product Chemistry Data
Data requirements 163.61-6 through 163.61-7 (product composition data) apply
to each proposed or currently registered end-use chloramben product.
Ibxicology Data
Data requirements 163.81-1 through 163.81-6 apply to each end-use chloramben
product or substantially similar product.
3-6
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RFMERIC IWTA RBOUIRMHTO ANJ1 IWTA fiAPS
FOR
(luidolino
Citation
rnmo of Art? Data
TOst Required?
T\r«Rt frtos RPA Ihvo Data to
Substance Partially or Totally
Satisfy Roquirmcnt?
niblioqraphic Must Additional Data be Submitted
Citation under FIFRA 3(c)(2)(B>? rf ro,
dead] ine for nuhminnkm.
FiiviRnMMrarrAT. FAIT
!63.62-7(b)
163.62-7(c)
163.62-R(b)
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163.62-R(d)
ir,3.62-R(o)
163.62-9(b)
163.62-9(c)
163.62-9(d)
163.62-9(0)
l63.62-in(h)
163.62-lO(d)
163.62-10(0)
163.62-in(f)
163.62-10(q)
163. 62-11 (h)
163. 62-ll(r)
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Hydrolysis
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Motabnl inn
Annorol)ic Aquatic
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Volatility
Adsorp./Dnsorp.
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•Unrrontrial Fiold
Dissipation
Aquatic Fiold
Dissipation
Terrestrial/
Aquatic Plssip.
Aquntio Tnpacr
Comb. ft Tank Hixos
I/jnq Trrm Study
Rotational Crop
trriqatod Cropn
Finh AwnnilnHon
Appl Ic/itnr
rxfonuro Study
Yes
YOB
Yes
Yos
No
Mr>
Yos
No
YOB
th
Yes
tin
Nr>
fto
1JD
YOB
I*
Yos
Yon
Sodium f. Methyl Partial: SodUm
aUoramhon* No: Mothy.1
Sodiiin f. Metliyl No
ChJoramhon
Sndiim (, Methyl No
Chloramhon
Sorlim ft Methyl Ito
Chlornmhen
Soditm f. Methyl Ho
rhloramhon
Soliim K Methyl No
Chlorambon
Reprosontativo No
Formulations
Formulations
5VxUi«n ft Mothyl Yes: SmUum
Chlornrtion Hn: Mothyl
Typlonl liiqiii'l fr>
FojTmilnt.lon
Union Oirhido, 19R1, 0172 Yos: Hay, 19R3
Yos: May, 1903
Yos: Mny, 19R3
Yos: flay, 19R3
Yes: toy, I9R3
Yon: May, 19R3
Yos: Mny, 19R3
Yos: Mpy, 11IH3
fwfin, 1970, 0020 Yosi: Hay, 19R3
Yon: Hny, 10R2
* 'IV'rlinirnl qrp'lo rti|orap*ion
or porliin rMornrtx^n r.nit nrl-hyl rhlornn*v?n.
These data requirements are current as
of M»y, 198}. Ip^er t.n ruMnnoR iwcknce
for updated requirements.
-------
TWJLF-3-1 (con)
GTNRRTC IWTA IVXIIIRfiMFOTS AND IWA GAPS
FOR WNUFACnJRItn-USR dll/TRAMBFN
Guideline Name of Am Data Ttst Irtts EPA Have Data to Blblioqrviphic
Citation -msl- Required? Substance Partial ly or Totally Citation
.Satisfy Requirement?
PimKT awns™
I63.61-3(b) Identification Yos "nrch. Grade* Yos
)63.6l-3(c) Cnmrnsition Yos Ttech. Grade Ho
163.61-7 Analytical Yes TYich. Grade Partial! Heed Amchnm, 1972, 0083
Methods » Data data
161.61-8(1) Color Yon Itch. Grade Yes Amchnm Products, 1967,
Amchcm Products, 1959,
Amchnm Products, I960,
163.61-8(2) Odor Yos Itch. Grade Ho
163.6178(3) Mnltinq Point Yes TVjrh. Grade Yes
163.61-8(4) Solubility Yos Tech. Grade Yes
163.61-8(5) Stability YOB Ttech. Grade Ho
163.61-8(6) Octanol/Hnter Yos Iferh. Grade tto
Amnhen Products,
Ainchom Products ,
Amchcm Products,
Annhom Products,
Amchnm Products ,
Amchnm Products,
1967,
1959,
1960,
1%?,
1959,
1960,
Must Additional Dntn ho SitmiM-.od
under FIFRA 3(c)(2)(R)7 If no,
deadline for taitxnission.
No
Yos:
Yes:
0081
0124
0125
Yost
0081
0124
0125
0081
0124
0125
Yos:
Vest
October, 1981
October. 1981
October, 1981
October, 1981
October, 1981
Partition
Coofficimt
U.1.61-8P) Physical Stato Yos
163.61-8(R) Dnnsity or Yos
Specific Gravity
161.61-8(9) noirinq Point Mr.
163.61-8(10) Vapor Prosnuro Yos
16?. 61-8(11) r^l *""
TVx*. Grade
TVvh. GrarV;
TV?r)». Grndo
Yes
fto
Part.in)
ftnchom Products, 1967, OOB1
Amcliom Products, 1959, 0121
Amnhora Products, 1960, 0125
ftnrhom, 1967, 0081
YOSJ Ontohor, 1981
Yop: Octohrr, 1981
Yosi October, 1<»B1
* 'ly-clinical Grndo Chlornrtvn Acid
These data requlreaente are current as
of May, 1981. Defer to guidance package for
updated requirements.
-------
-i (con)
CENRRIC DATA RFCHIRFmrrR AND IOTA GAPS
f(V
Citation
•mxicnuxw
163.81-1
163.B1-2
163.B1-7
163.82-1
163.82-2
163.82-3
163.82-4
163.82-5
I63.B3-1
lfi3.R3-2
163.83-3
163.B3-4
163.B4-1-4
163.85-1
Namo of Tt»nt Aro Data
feat Rnqulrod?
Anuto Oral Yon
TVwicity
Arnte normal Yon
TYjxicity
Acute Dnlnyod No
Hnurotoxicity
Sifcchronir Oral Yon
Tnxicity
Suhohronir Yon
(21-dny) normal IViixirlty
Suhnhmnio 90- HD
day normal Tox.
Inhal. IVrx.
Suhrhmnic No
Hnuratoxicity
Chronic Foodinq Yon
Ohoononioity Yoa
Vnrti tnnon io i ty Yon
Rnproflllct ion Yon
Mutaqoniritv Yon
M^tifthoJ ism You
Tent noon RPA Ifcwc Dnta to mhlioqniphic Hunt Mditionnl Dnta ho SuNiittivi
5?i*«tanoo Partially or "totally Citation uvV>r FIFRA 3(c)(2)(n>? If m,
Satisfy Unquiromcfit? rlo.VHino for fntmisnion.
•nrsch. Ora-lo* Yon Ilijiloton, 19S9, 0022 Ms
T*x4\. GrafV: Yos Hazloton, 1959, 0023 Hr>
Tferti. ft-aite Partial: Hx-d Litton, 1979, 0171 Yon: fVrtohor, 19B1
product purity
TVrh. Orarto No Yos: May, 1983
•nrch. Grado Partial: rVxH Litton, 1979, 0171 Yoo: October. 1981
prodiK^ purity
for 0171
•frioh. Crade Partial: NtxYl I1PC, 1978, 0170 Yos: Octohor, 1981
product purity hit ton, 1979, 0171
for 0170,0171 NCT. 1977, 0019
TVoh. (VfKlo Hn Yoa: May, 1983
Trx^h. (Vndo Partial: N"od AMR, 1'156, 0029 Yon: Octohor, 1981
prryluot purity
for 0029
TYxl). (Vndo Partial Amlorpon, 1972, OS02 Yoa: May, 19R3
TVxih. Orado (. th Yon: M*y, 19R3
Hothvl
Ifil.nr.-l nrmonHc Aninnl tin
Snfofy TV^tintj
* TYvhniral Chlorartion ArW or Frrliim (lilor/imhon
•* iv>chnlnnl Oilomrtwin Arid or Bortiim Chlornrtion nrr\ Hothyl Clilor.inhon
These data requirements are current an
of May, 1981. Refer to guidance package for
updated requirements.
-------
FOR
TAnU3-3-l(non)
IWA RBOUIRfTIETrTR AND DftVA OAPS
Ruirtol Jne
Citation
NiW! of Tlnst Arc Data
Iteat Rrxiulred?
1Y>8t Docs EPA Have Pnta to niblinqraphic Must Additional natn be Ruhmittod
Substance nartially or Trjtal ly Citation under FIFKA 3(c)(2)(n>? If BO,
Rat.infy ncqiiiremnnt? deadline for submission.
ROOUXIICAL EFFECTS
163.71-1
163.71-2
163.71-3
163.71-5
163.72-1
163.72-2
163.72-3
163.72-4
163.72-5
Avian Sinqle Yps
IVec Oral USO
Avian Dietary Yos
t/:so
Mflpuw 1 ifin Acuto fk>
•nnxiniry
r.irauJ. ft Actual tin
FioW 1\Rstinq for
Maranals/Pirds
Finh Acute Yos
IC50
Acute Tbxirity Yes
to Aquatic
Invertohratos
Acute Tbxioit.y No
to Estuarine R
Marine Orqaninns
n*iryo)ntvnf> r. No
Aquatic Organ. tk)
Sodium (, . No Yes: October, 19R1
Mothyl Chloramhen
Sodium ft Yost Sodiim Wild. Intti'l, 1978, OOS9 Yes: October, 19R1
Aff. Mnd. Bras., 1973, 0036
HPthyl ChlorartXHi Partiali Methyl, Aff. Mrd. Rns., 1973, 0039
nood wild water
waterfowl study
Sodiim ft Yes: Sodium U. Carbide, 1978, 0060 YOB: October, 19R1
U. Carbide, 1978, 0061
Methyl ChJonwben tb: Methyl
Sodium ft No Yes: October, 1901
Methyl CMorantwn
ir<3.72-r>
1V>x. ft
Studies
r.inui. t. Actual
Fiold TV^Bting for
Aquatic
1- Tr>nt-.inq rrquirod on both podium find nrhhy) (*iloran*x-n.
These data requirements are current as
of May, 19&1. Refer to guidance package
for updated requirements.
-------
•BWK-3-1 (st
TVnt
RFSinUR OimiPITO
Motnholifin in Plants
Motfiholinm in Animals
Analytical Hotfmrts
FOR HAMIFACniRTTC-USE OIUWAMBFH
Am nata Tnst ft»s EPA llavo Data to Bihl ioqraphic Must ArWltional Dnl-n bo SiUTinfttoT!
nnepiirorl? .«5iihstnnoc Partially or Ibtally Citation undor FIFRA 3(c)(2)(n>? If no.
SntiBfy Rcquiromnnt?
Yon Rrp. Form.* Yos Swansson,
Amchoni,
Amrhcm,
Arochnro,
Aroohnm,
Anonorn,
Anyndn,
AmohMn,
Arocnom,
Amohcin,
AniCnOITI ,
Ancticni ,
Nnrttrm,
Arachom,
Amnhom,
Amonem,
No
You Rop. Form.* Yos mrtiem,
Atnchnm,
Amohom,
Amohom,
AnRhoni,
Ainchom,
Annhom,
doa^lino for nuhmission.
1966, 0169 Ho
1960, 0127
1063, OOOR
1965, 0076
1961, 0079
1963, 0090
1963, 0106
1961, 0159
1964, 0161
]963, 0162
1963, 0161
1964, 0164
1961, 0154
1961, 0104
1961, 0157
1978, 0101
1963, 015B Nn
1965, 0077
1964, 0107
1978, 0057
196fl, 0085
196?. 0166
1967, 0167
-------
TAPLT-3-1 (con)
CFNFPTC IWTA P.Rni>IRrTirfrrS AND DATA OATO
prm MAMUFArnxmiNTr-iiFE cnrniwnng
flnmo of 1Y>nt-.
TVT.t
Arc tat*
Rnquircil?
TY?st
PuhflbmoQ
Doos EPA llnvo Data to
Partially or TVjtnlly
Sntisfy Roquiromont?
nihl ioqraphic
Citation
Miisfc ArMlMnonl Ititn bn Puhmitto«i
unrtor F1FPA 3»r»r2)«ri? It no.
PRRIHIf! gilTUCTTO (con)
Datot RAC
PoyhoanB
YOB
. Porm.*
YOB
Pnnnutn
Yos
YOB
YOB
.' Porm.
Bnp. Porm.
• Form•
Yes
Yos
Yes
ftnrliom, 19fi5, 0071
Amchom, I960, 00fl4
Stonffor, 197!) , 0041
Amnhom, 1967, 0044
Rlnnm, 197fl, 0050
•Amchom, 197ft, 0057
Arorhom, 197B, 0101
Amchcm, 1%1, 0104
Amnhom, 1975, 0109
Amchora, 19fi7, 0120
Amrhnm, 197fi, 01 in
Amchom, 196), 0135
Amchom, 1961, 0136
Mo
, 1967, 0044
Amrhom, 1965, 0076
Amchoni, 1965, 0077
Amchon, 196R, 0004
Amrhom, 1975, 0109
Amrh?m, 1967, 0044
Amrhom, 1964, 0093
Amrbrm, 1975, 0109
Amchom, 1963, 0162
Amchom, 1964. 0008
Amchom, 1067, 0044
Amrhom. 1961, 0106
Amchom, 1975, 0109
Amohom, 1963, 0102
Mo
Ho
Mo
-------
TABLE-J-l (con)
GENERIC DATA REQUIREMENTS AND DATA GAPS
FOR MANUFACTURING-USE CHLORAMBEN
Nama of Test
Teat
Are Data Test Does EPA Have Data to Bibliographic
Required? Substance Partially or Totally Citation
Satisfy Requirement?
Must Additional Ditn be Submitted
under FIFRA J(c)(:i)(B)? it so,
deadline Cor submission.
HES1UUK CHBHlSIHlt (COn)
Hesldue uata> RAC
Lima Beans Yes
Corn Yes
Sweet Potatoes Yes
Punpkln, Squash Yes
Rep. Form.
Rep. Form.
Rep. Form.
Rep. Form.
Yes
Yes
Yes
Yes
Amchem, 1967, 0044 No
Amchem, 1963, 0098
Amchen, 1963, 0108
Amchem, 1975, 0109
Amchem, 1967, 0044 No
Amchem, 1964, 0080
Amchem, 1975, 0109
Amchem, 1969, 0110
Amchem. 1967, 0044 No
Amchem, 1964, 0078
Amchem, 1975, 0109
Amchem, 1967, 0044 No
Amchem, 1968, 0084
Amchem, 1964, 0164
-------
TAHLR-3-1 (con)
fiFNFRIC IOTA RnoniWnniTR AND IWTA RAPS
pnn MAn»FA(?nmiMn-URR
Hnpr> of "Hr-at
Tnnt
FtRSiniF! CIIFMISlTOf (con)
nnsidiio Data i RAC
IW Hoans
Snap tloaiw
Cucumbers
Unions
Sunflower
St-ornqo l*»ta
Pnsiduo Dntat
Proennsnd FondB
Arc Data
Required?
Yen
Yfifl
Yos
Yon
YOS
Yen
No
TteBt
Substance
pjpp. Frjrm.
Rnp. Fbrn.
Rnp. Form.
Pjop. Form.
Hnp. Form.
Rnp. Form.
Pona FVA llnvn Dnta to
Partially or 1*jtally
Sntiafy Rcquircmont-.?
Yon
Yes
Yen
Yon
Yos
Mo
Bibliographic
Citation
flMmti-r-m \G&'1
/wrnmi $ i "P ' »
/Virhnm, )96fl,
Amnhcm, 1964,
Amchom, 1964,
Antcncffif l9nRf
Anchoin t \ OfiR f
^ronhont f l9f Puhmlttr-H
undor FJFUA 3(p)»2)*n)? If so,
deadline for submission.
004 '. tin
OOR4
oonn
0096
0149
0149 Ho
0149 No
0149 No
0)00 No
Yoa: Mny, 1903
Fraiduw in Meat, Millr,
Poultry, and
tin
Data requirements are current as
of May, 1981. Refer to guidance package
for updated requirements.
* From application of roproRontntivo formulations.
-------
TAnLE-3-2
pRnnuor-sprciFir IWTA REquinmFwrs win OATA CAPS
FOR MAHiiFAonmiNn-iisF, oiiruwmFM pnmicrs
Huiflo] ino
Citation
Harm of Am Data
TVK?t Pjrxplinvl?
Substance
Drvs EPA llavo Data to
Partially or "totally
Satisfy Requirement?*
» nlhl ioqraphic Hunt Additional Data Po Suhmitlo-1
Citation under FIFRA 3(c)(2)(n)V If so,
doadlino for Butiiisnion.
pinrocr CHEMISTRY
163.61-3
Prod. Identity
and Plsclocuro of
Dnncription of
Yos
Yos
Each KIP**
Each MIIP
Yos: Mothyl Chlornmhon
Yos: Po-liin "
Ho
Mo
Yos:
October,
Manufaotiirim Procoss
163.61-5
163.61-6
163.61-7
163.61-0(7)
163.6l-fl smw an fho
•IVchnical Crnrto of Km AcH
-------
:--»-2 (ron)
FDR
IWTA nrcrmraiiRTrs win WTA OMB
nii/uwmw pnonicrs
Ouidoltno
Citation
irwicoi/™
I63.ni-!
Mnmo of
Tfcst
Acute Oral
Tbxicity
Am nnta
Hoquirod?
Yon
TfcBt
Suhotanco
MUP**
f>ios EPA Ibivo Data to
Partially or "mtally
Satisfy Pwniironrnt?*
Partial: Methyl
Sitfmit product purity
nib] ioqraphic
Citation
llazloton, 1959, 0022
llazleton, 1966, 0024
Must Arlditional tttta ho Sirtmlttfvl
indrr FIFKA 3(c)(2)(n)7 Tf no,
dcadlino for submlsnion.
Yos: Octohor, IWl
un.m-2
Dnrmal
Acutft InhfyJ. Yon
Trjxlcil-y
Prim. Eye Yos
Irritation****
Primary !>>rmnl Yos
Irritation
Yon
HUP**
HIP***
MUP***
HIP***
HJP***
Cor 0024
Yon: Sodium Chlorambon
Ftoj Mothyl ailoranhon
Yost
HT.S Hfthyl Chloranbon
YOB i Sort! urn "
Not Mnthyl Chloromhon
Yosi
Not Mothyl Chloramhon
YOBI Sodium "
Mo
* For Currently nrxiistorod ProrliictB.
*• RtXTiircrt for Manufacturihq-URC PtorturtB vihich are not the anno nfl the
TYx:hnlcal Ornrto of tho Artivc Inrirodiont. SaUim Chlomirhon has hccn
dotonninral to he Mm samp as Tochnlcal Chlorambon Acid. Mothyl Chlorambon
Kan boon dnterminod to bo diffomnt.
•** Kach Mannfacturinc}-uso Product or SiihRtnntial'ly Similar Product.
**** A domonntration of pi! hotwoon 1 and .1, or J2 and 14 or a domonatration
of dermal irritability will tr> sufficient to oatroorizc a product aa an
ocular irritant, and additional testing will not ho roqiiimd.
llnzlotnn, 1959, 0023 Yon: Octo»>or, 1WU
Cnc Hon., 1978, OOfiS
Food K l)n«), 1978, 0062 Yos« Octohor, 19B1
CTC HOB., 197H, 0064 Yoss October, 19RI
CfC HOB., 197fl, 0061 YOBJ Octohor, J'JPl
YOB: Octnhor, 19BI
Theoe data, requirements are current as
of May, 198l. Refer to guidance package
for updated requirements.
-------
iv\nLF:-3-3
ORIKRIC rWTA RJXUTnmmrS AMD IWA O\PS
FOR rHD-uflB ojrmwmFw PRODUCTS oowrAiNiNn AMMONIUM
Guide! ino
Citation
Root/Xi i rv\i
163.71-1
J63.71-2
163.71-3
163 .71-S
163.72-1
163.72-2
163 .72-3
lfi.1.72-4
163 .72-5
163 .72-6
Name of Thst Arc Dnta Trflt Dnos EPA llnve Data to nihlioqraphic Must Additional linta ho Fulinjtl
TVMt Required? Substance Partially or Totally Citation under FJFRA 3(c)(2)(n)7 If so.
Satisfy Requirement? deadline For submission.
. EFFRCTS
Avian SinqJo Yos Ammonium and Mono- No
noso Oral U)50 cnet.hyl nimnniun*
Avian Dietary Yes " fb
IC50
Knnn.il inn Acute Mo
•nnxicity
Simul. t, Actual No
Field TYintinq for
Hnmnals/nirds
Fish Acute Yos Annoniiin .ind Mono- No
LC5P methyl amnonlun*
Acute Tbxiclty Yes " Hr>
to Aquatic
Invertebrates
Acute Ibxicity No
to Estuarine &
Marino Orqanisms
Buhryolnrviie r. No
Life-Cycle
Aquatic Orqan. Mo
Tox. ft Residue
Studies
Simul. d Actual Mn
Field Tlnstirtq for
Aquatic Orqanisras
Yes: October, 1901
Yos: October, I9RI
Yos: October, 19R1
Yes: October, 1981
* Tr>ntinii Roquircd on TV>chnicnl Crado Amnnnliim and.Tr-chnleal Rrado MonomothyJ
Anmnniini Chloramhrn. Data on TV-rhnicnl Chloramhm Acid, Snrliim Chloran*vn
or Unthyl rhlornirtwn cnnnot he extrapolated to Ammonium Chlormrtion or
Monomothyl Aimonium Chloramhrn.
These data requirements are current as
of May 1981. Refer to guidance package
for updated requirements.
-------
TAULB-3-3 (con)
GENERIC DATA KBgUIUB-IENIS AND DATA GAPS
FOIl ENIMJSB CIIUKAMUEN PRODUCTS COOTAININQ AMMONIUM
Glide line
Citation
Niine of Are Data Test
'teat Rxjulred? Substance
Does EPA Have Duta to Bibliographic Must Additional Data be Submitted
Partially or 'totally Citation under FIFRA 3(c)(2)(B)? if 30,
Satisfy Requirement? dsadline for submission.
PROOUCr CHEMISTRY
163.
163.
163.
IJ3.
163.
IbJ.
Io3.
Io3.
163.
163.
163.
163.
163.
163.
61-3(b)
61-3(c)
61-;
61-8(1)
61-8(2)
61-8(3)
61-tl(4)
6l-d(5)
61-8(6)
61-3(7)
61-il(8)
61-3(9)
61-8(10)
61-8(11)
Identification
Composition
Analytical
Methods Si Data
Color
Odor
Meltinj Point
Solubility
Stability
Uctanol/Mater
Partition
Coefficient
Physical State
Density or
Specific Gravity
Balling Point
Vjoor Pressure
(XI
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
143
Yes
Yes
•tech.
•tech.
•tech.
•tech.
•tech.
Tech.
•tech.
Tech.
•tech.
•tech.
•tech.
Tech.
T»ch.
Grade'
Grade
Grade
Grate
Grade
Grade
Grade
Grade
Grade
Grade
Grade
Grade
Grade
(to
(to
to
No
No
No
No
(to
143
Yes
No
No
(to
Yes:
Yes:
Vest
Yasi
Yos:
Yes:
Yes,
Yes:
Yes:
Yes:
Yes:
Yes:
October,
October,
October,
October,
October,
October,
October,
October,
October,
October,
October,
October,
1931
1931
1931
1931
19iU
1931
1931
1981
1981
1931
1981
1981
Teclinic.il Grade Airooniun and Maramethyl ftmonlum Ghloranben
These data requirements are current as
of Hay, 198l. Refer to guidance package
for updated requirements.
-------
TAflLE-3-J (con)
GENERIC DATA REQUIKEMB«S AND DMA GAPS
FOR END-USE PRODUCTS COHIYUNING AMMONIUM QIUWAMBEN
Noire of 'teat API Data Tteat Dxs EPA Hava Data to Bibliographic Must Additional DUa be Subnitt-jd
Citation 'test »:^uired? Substance Partially or 1btally Citation utvter FIFRA 3(c)(2)(U(? If »a,
Satisfy Requirement? deadline Cor submission.
•lUXtOOUJUV
LbJ.Ul-1 Acute Oral Yas Ammonium & tto Yes: October, 1981
'Ibxicity nmanetliyl amnonium*
161.U1-2 Acute Dermal Yes Amuniun & Ma Yes> October, 1981
•Jbxicity ttanomethyl aumoniun*
on tectwiical grade ainnoniun and nonoraethyl annoniura chloraifcen "n>eae data requirements are current as
are retired. Acute oral and dermal toxlcity testirq on technical of Hay, 1981. Refer to guidance package
sodium cliloraraben (or chloranben) will not satisfy tills requirement. package for updated requirements.
-------
TAIU/:-3-4
PRODUCT-SPECIFIC IWTA RnouinoiFwrs AND rwm GAPS
FOR sniimtj; conrnwnvm: minwinra ptnniiCTS
Guideline
Citation
Nnroo of Are rvita
Tlnst Required?
Tlnnt fries PPA llavo Data to IHhlioqraphio Must Additional fmtn IV. Bulmifhivl
Substance Partially or Ttotally Citation under FIFRA 3(c)(2)(R)V if no.
Satisfy Requirement.?* deadline for mtfmiosion .
PRODUCT CHEMISTRY
16.1.61-6
ifcclaration
Yes
Each B.C. Product
Ho
Yes:
Octobor,
108 1
of Inqrodiont t.tmitn ' ""
163.61-7
163.61-8(1)
161.61-8(2)
Mil. 61-8(7)
161.61-8(8)
163.61-8(9)
161.61-8(10)
163.61-8(11)
163.61-8( 12)
161.61-8(13)
161.61-8(14)
163.61-8(15)
163.61-8(16)
163.61-8(17)
163.6l-8(ln)
Prorluct Analyt.
Methods and Data
Color
O:V>r
Physical State
Density or
Specific Gravity
Polling Point
Vapor Pressure
P»
Storaqe Stab.
Flaimability
Oxidizinn-or
Roducinq Action
Rxplosivonoss
Miscibility
Viscosity
Corrosion
Characteristics
Yes
Yes
Yes
Yes
Yen
Yes
Yes
Yes
Yes
Yea
YOB
Yes
Yes
Yes
Yes
Each B.C. Product
Each B.C. Product
Each B.C. Product
F.Tch B.C. Product
SC***
SC***
sc**
sc***
BC***
SC***
SC***
sc***
sc***
sc***
sr***
Partial: Nood Data
No
No
Yes
tin
No
No
tb
No
Nn
No
No
No
Nr>
No
Yos:
Yes:
Yen:
YOB:
Yes:
Yea:
Yes:
Yes:
Yen:
Yes:
Yes:
Yes:
Yes:
Yos:
Octobor,
October,
October,
Octobor ,
October ,
Octobor,
Octobor,
October,
Octobor,
Octobor,
October,
Ortohor,
Octobor,
October,
1981
1981
1981
1981
1981
19(11
1981
1981
1981
1981
19111
1981
1981
1981
* For Currently Reql stored Products
** Enrh Soluble f*r»wr>ntrflto Pmdiiot _ • .
*** Rnrh Bnli*>lo Cnncnntrc'tc Prndiict or Suhstantiallv Similar Product
These data requirements are current
as of May. 198l. Refer to guidance
package for updated requirements.
-------
(oon)
PRODUCT-SPECIFIC DATA RFQUIREHFNrS AMD tWTA CAPS
pnn sniunif ontiowiwiT: oir/xwinrri pnnnucrs
Guideline
Citation
Ttwicmxw
163.B1-1
163 .Rl -2
flrane of
Tnst
Acute Oral
Tbxioity
Acute Dermal
Toxioity
Am Data
Required?
Yes
Yes
•tost
Substance
SC"
sc*»
toes EPA llavo Pata to
Partially or Totally
Satisfy Rnquircnrnt?*
Partial t fteod product
purity for 0001, 0024
Mr>s Amnonium Chloranfcon
Partial: Aram. * Mono-
methyl amnoniim, need
product purity for 0002
Bibliographic
Citation
Dioscarch, 1969, 0001
llazleton, 1966, 0024
Biosoarch, 1969, 0002
Must Additional Dnta hr: flu) nit led
indor FIFRA 3(c)(2)(n>? If an,
deadline for submission.
Yes: October, 19B1
Yos: Ontobor, 19RI
163.RI-3
163 .Rl-4
163.ni-5
Acute Inhnl. Yna
Toxicity
nc**
Prim. Fyo
Irritation
Ynn
Prinviry Dermal Yen
Irritation
ft"
Nb
Hoi Ammnniun Chloramhcn
Partial: Ann. & Mono-
mnthyl nmnoniun, nncri
product purity for 0003
No: Amnonim Chloramhon
P«rtiii]i Amu. t Hnno-
mothyl nmnoniun, nnc<1
pmrtnrt purity for 0002
Biosparch, 1969, 0003
Yns: October, I9R1
Yosj fV;tohor, 19R1
Bioscarch, 1%9, 0002 Yon: Octohnr, l<»fll
•
**
For Currently Rrjqinterod Products
Raoh 5V5li*>lo Cnnc^ntrato Product or Substantially Similar Prorluct.
Currently Registered Products Containlnt| Ammanim Chloramhon llave Been
Dntonninnd to bn Substantially Similar, and Currently Rogisterod Produrts
Contalnint] Armnniun Chloranhcn and Honomcthylnmnnniini Chlorambm aro
Sifatnntially Similar. Rrquirrd tostinq is bn he completed on Formulations
containinn 23.4» Ammniiin rhlorambm AT1D 15.7» Ammnniim Chlor.imbro &
47.2» Monomnthyl-ammninn Chloramben riiould hn tested.
These data requirements are
current as of May, 1981.
Refer to guidance package
for updated requirements.
-------
IWTA wrnuiRFMnrrs win IWA rj\pr,
FOR FirwMiu: COHCEMTRATK otrnRAfmFii PROPHCTS
Guideline
Citation
N.imr? of
Tr-st.
Are nata
Required?
TV-si-
Substance.
Dies FPA llave Data to
Partially or "totally
Satisfy Requirement?*
nihl iorjraphic
Citation
Host Additional ITata Po fUihmittod
under FtFRA 3(c)(2)(n>? If so,
do.idlinp for suhnission.
PROUJCT QIFWJftnflf
lfil.fil-7
161.61-R(
163.61-R(2)
163.fil-R(0)
Ifi3.fil-n(10)
lfi.1.6 1-8(14)
ifi3.fit-n(is)
Ifi3.61-n(16)
lA3.61-n(17)
nrxrlarntion Yos
of Inqrrrliont r.imitn
Prodiiot Analyt. Yos
Nothota nnrl Data
Color Yos
CHor YOB
Phyoiral State Yos
rv>nnlty cr You
Specific Gravity
Pol ling Point. Yos
Vapor Prcssum Yos
pi! Yon
Storaqo Stab. Yos
FlaniiK^ility Yos
OxWizinq or Yos
Rnduninq Action
Rxplosivcncss Yos
MiRcibility yes
Visoosity Yos
Corrosion Yos
Characteristics
Each F.C. Product**
Each F.C. Product**
Ench F.C. Product.**
Fach P.C. Product**
Rich F.C. Product**
PC***
PC***
FC**
FT***
FT***
PC***
PC***
FC***
FC***
PC***
PC***
No
Partial: Nrxxl
Data
No
Nh
Yos
Ho
No
Ib
Ha
No
No
Ho
No
No
Mn
No
Yos: Octohor, 1901
Yes: October,
Yos: October, 19H1
Yes: October, 19R1
Yes: October, 19RI
Yes:
Yos:
YOB:
Yos:
Yos:
Yos:
Yos:
Yos:
Yos:
Yos:
October ,
October,
October,
October ,
October,
October,
October,
Octohor,
October,
October,
I9!U
1901
1981
19R1
|OR1
1981
19H1
*
**
For Currently Rnqintored Products
Each Flowablc Concentrato Product
*** Each FJowahlo Concentrate Product or Substantially Similar Product
These data requirements are current
aa of May 198l. Refer to guidance
package for updated requirements.
-------
TABLE-3-5 (con)
PRODUCT-SPECIFIC OYfft RBQUIRFNEWS AND DATA GAPS
FUR FUMAULE CONCENIKATE QILORAMBBN PRODUCTS
Uuidelitr:
CitJtion
IVWICOUJGY
H>3.31-1
luJ.ai-2
ll>3.ai-3
163.U1-4
16J.81-5
Nims of Arc Dit.i 'lost 0X3 EPA lUve Uita to Bibliographic
1^3 t R>quiroJ/ Substance Partially or Ibtally Citation
Sitiafy Requirement?*
Acute Oral Yes EX.1** Yes
Ibxicity
Acute D>ntul Yos FC" Yea
'Ibxicity
Acute InnjL. Ye3 PC** Yes
•Ibxicity
Prim. Eye Yea PC** Yes
Irritation
Primary lXjnn.il Yes FV:** Yea
Hizleton,
llazleton.
Cue tea.,
1959,
1959,
1978,
U022
0023
0065
Pood & Droj, 1J7U, 0062
CDC Ri3,,
CDC RJS.,
197d,
197U,
0064
0063
Must ftllitional Ulta t>? Submittod
un.ier fIFRA 3(c)(2)(U)i> IE so,
deadline Cor submission.
Mi
(to
rto
No
ito
Irritation
P.ir Currently Itegistere>1 Products
Bich Plorf.ible Oaiiointrate ProJuct or Substantially Similar Product.
Currently ItegistoreJ Prcxlucts Containiiv^ GoJiun QilorainbJn llive Been
Dit'jnnined to be Substantially Similar. 'Ibstiiig is to be completed on
Fonnul.itions containing Sodium Qilorjinto.'n or 'Itacimical ailor.nntxjn Acid.
These data requirements are current
as of May, 1981. Refer to guidance
package for updated requirements.
-------
ppnnirr-spnriFic rwm nrouiPFMFirrn wm IWA
FOR nnn.siFiAnu: cnNrornwrE an/uwmpN pnonncrs
Ouidolino
Citntion
Untno oC
TVst
Aro flnta
nrquircd?
TVst
S«ihBtnnco
Dnon BPA llavo Pnta to Bibl lonrnphic
Pnrtlnlly or Totally Citation
Satisfy Hnquiromnnt.?*
Must /VWitioool tota IV Sirtnlttorl
undor PIFRA 3(c)(2)(D)7 If ro,
deadline for submission.
PRODUCT cnmisnw
nnrlarntion Yos
of Inqrodient. Limits
Rach E.C. Product**
163.61-7
163.M-RU)
I63.61-R(2)
l63.fl-R(7)
163.61-R(fl)
163.f.l-R(9)
163.61-R(in)
163.61-R(1U
163.61-RU2)
I63.61-fl(13)
163.6l-R(14)
163.61-B(1S)
163.I>1-R(16)
163.61-fl()7»
I63.61-fl(in)
Pmduct Analyt. .
Hothods and Dntn
Color
ntor
Physical Rtnto
Dnnnity or
Spocific Oravtty
noilinr] Point
Vapor Pmssurr*
P"
Storaqo RtRb.
FlnniuihiHty
OxicHzim or
Rcduninn Action
Fxpjosiwnofis
Miscibillty
Viscosity
Corrosion
Chnractorist ics
Yos
Yos
Yos
Yos
Yos
Yos
Yes
Yos
Yos
Yos
Yos
Yos
Yos
Yos
•Yos
Rnch
Rnch
Bach
F.icb
BT**«
BC***
BC**
BC**«
BC***
BC***
BC***
BC***
BC***
BC***
BC*«*
tin
Yos
No
No
No
No
No
No
No
No
Ho
No
For Currently DrqistoroH Product.
FVirh nnulnifiablo Concont.ratc Product
Rnch Rnulslfiahlo Conrontrnto Product, or SifetantinJly Similar Product
Yesi October, 19RI
Yes: October, 19R1
Yon: Ontohor, 19R1
Yosi October, 19R1
Yos: Octohor, I9R1
Yos: Octobor,
Yos: Octohor, 19R1
Yes: Octohor, 1<»R1
Yoa: Octohor, 19R1
Yes: Octohor, 19R1
Yos: Octobor, 19W
Yos: Octohor, 19R1
Yos: Octohor, 1901
Yos: Ortobor, 19R1
Yos: October, 19R1
Ttiese data requirements are current as of
Hay, 1991. Ttefer to guidance package for
updated requirements.
-------
FOR
TAP.IE-3-6 (onn)
rwm RBTUiRmrrri'S AND DATA CVSPR
onucFMrnATE anrwwnm prmiors
Gnirlel jno
Cltntlnn
ToximinnY
lfi3.Bl-l
163.BI-2
ir>3.Ri-3
163.R1-4
ir,3.IU-5
Mctmn of Ano natn iv«»t
iv>j?t nnq\iir(y1? Siihstanro
Acute Oral Yt>s FT**
Toxicity
Aouto pprnp) Yos RC**
IVwirlty
Araito Inhal . Yoa FT**
TYixicity
Prim. Pyo Yon FT**
Irritation
Primary Rnrmnl Yrs FT**
Dnos HPA llavn Pnta hn
Partially or 1r.ta]]y
Satisfy nnqiiircmnnt?*
Partial! Need product
purity for 0024
Partial: Uncrt Pmrt»irt.
purity for 0143
Partial: Unort rrty1llc''
purity for 0144
Partial: Mood product
pirlty for 0143
No
niblionmphir; Must M>Utinnnl rr>ta tn Submit ti*l
Citation iwvlor FIFRA 3(r)(2)(r»)7 1C so,
«!
llazloton, 196n. 0143 YOB: October, 19R1
Yos: Ortcbnr, joni
Irritation
These data requirements are current ac
of May, 19R1. Refer to guidance
package to updated requirements.
* For Currently Rnqistercd Product.
** Panh Rnulnifiahlp fVinront.rflte Profluot or Substantially Slnilar Product.
-------
TAnLn-i-7
pnnraicT-PPECTFTC IV\TA RFttiiRFMEwrs win DATA CAPS
FOR GRANULAR dllPIWmEN PPOTCJCrS
Giiidol ino
Citation
llmitt of Are Dnta TY>nt toon EPA llavo Mnta to Bibliographic Must AiHitional rtit-o Do Submit! r. I
TV>st Required? Pittance Partially or -totally Citation under FIFRA 3(c)(?-(n)7 If no,
Satlnfy Requirement?* Headline for suhminnion.
PRODUCT aiEMISTRY
163.61-6
mclaration
Yoa
finch GR. Product
tto
Yes:
Ontohor,
1981
of Ingredient Limits
161.61-7
16.1.61-8(1)
163.61-8(2)
163.61-8(7)
163.61-8(8)
163.61-8(9)
161.61-8(10)
161.61-8(11)
161.61-8(12)
16.1.61-8(11)
161.61-8(M)
163.61-8(15)
163.61-8(16)
161.61-8(17)
16.1. 61-8(18)
Product Analyt.
Methods and Data
Color
O/tor
Physical State
Dnnsity or
Spool fi'c Gravity
nailing Point
Vapor Pressure
PH
Storage Stab.
Flanmablllty
Oxidizing or
Reducing Action
ExpJonivenons
Mincihillty
Vinoonity
Corrosion
Characteristics
Yea
Yon
Yen
Yen
Yen
No
Yen
Yen
Yen
Yen
Yes
Yos
Yon
Yen
Yos
Each GR. Product
Each GR. Product
Each GR. Product
Each GR. Product
GR***
GR***
GR***
GR***
GR***
GR***
GR***
GR***
GR***
GR***
No
No
No
Yos
Nn
No
No
tto
tto
No
tto
Nn
Nn
tto
Yon:
Yon:
Yon:
Yen:
Yon:
Y"s»
Yon:
Yes:
Yen:
Yens
Yon:
Yon:
Yon:
Octolx-r,
Octohor,
Octohor,
Octohor,
Octohor,
Octohor,
Octnhor,
October,
Octohor,
Octohor ,
October,
October,
October,
1981
1981
lOfll
1981
191)1
1981
1981
1981
19D1
1981
1981
1981
1981
* For Currently Rrqlstorod Productn
** Each Granular Product
*** Each Granular Product or Subst.antla.11y Similar Product.
IM « current as of
May, 1981. Refer to guidance package for
updated requirements.
-------
TARLE-1-7 (oon)
WTA imiiRmmrs AMD IOTA CAPS
FOR GRANULAR aiinwmm PRT«ICTS
Huidelino
Citation
rtmn of
Aro n.itn
Required? Subatonoo
nnos EPA Ilivc Data to
Partially or Totally
Satisfy Roqiiirpmont.?*
nihlionraphio
Citation
Must Additional rv>ta ho
under FIFRA 3(c)(?)int?
10 for submission.
TCJXICOIjOnY
K.3.R1-1
161.BI-2
161.BI-4
ifi.i.ni-s
Arutc Oral Yes
Toxicity
Acut.o
1V>xioity
YOR
Acute Inhal. Yes
Ttoxicity
Prim. Ryr>
Irritntion
Prim.
Irritntton
Yon
Yos
HR"
OR**
RR**
OR**
CR**
Partial? product
purity for nnni, 0021
No: Amnoniim
Partial: Ann. R Mono-
mf>thy) aaam., nnorl
product purity for
0002
Hi
No: Atmonlum
Partial: Ann. (, Mnno-
mothyl minon., nocd
product purity for
0001
Nn: Ammnnium
Partial: Arm. (• Mnno-
mnthy) nmnon., nnotl
product purity for
0002
Biosoarch, I960, 0001 You: October, 1
Ila7.lnton, 1966, 0024
niosoaroh, J969,0002 Yns: Octohor, 19ni
Yea: Octobor, 19RI
Rioscarch, 1969,0001 Yos: Ontohi^r, 19ni
, 1969, 0002 Yos: October, 19R1
For Currently Rcqistored Products
Eiwrh Granular Product or Substantially Similar Product.
Currontly Rcqintorod Products r/mtaininq Annonium Chloramhon llavo
Dr-torninrd to ho Substantially Similar, and Currontly nrrjlBterod Products
Contalninn Aimnnium Chloramhon anrl Mononothylamnniim Chlorambon aro
Substantially Similar. Tfcstinq in to ho onmploted on Formulations
containing 21.4» Aimnnium Chlorambon Affi 15.7% Anrmniim Chloramhon f.
47.2* Hrmomot.hyl-aniiioninii CJilorambon should ho tootod.
Itiese data requirements are current as of
tby, 1981. Refer to guidance packayo for
updated requirements.
-------
CHAPTER IV
PRODUCT CHEMISTRY
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 added ingredients,
active and inert, which are equal to or greater than 0.1 percent of the
product by weight.
To establish 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 the formation of
manufacturing impurities and other product ingredients, intentional and
unintentional. Further, to assure that the composition of the product as
marketed will not vary from the composition evaluated at the time of
registration, applicants are required to submit a statement certifying
upper and lower composition limits for the active and inert ingredients, or
upper limits only for some 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 to establish the physical and chemical properties of both the
herbicidal active ingredient and its formulations. For example, data are
needed concerning the identity and physical state of the active ingredient
(e.g., flammability, corrosiveness or storage stability). The Agency uses
these data to characterize each herbicide and to determine its
environmental and health hazards.
B. Chloramben Manufacturing-Use Products
1. Product Chemistry Profile
Technical grade chloramben is 3-amino 2,5-dichlorobenzoic acid.
Two manufacturing-use products are currently registered. These are the
sodium salt of chloramben and the methyl ester of chloramben.
Some data are available on the physical and chemical properties of
technical grade chloramben. (Amchera, 196?, 0081; Amehem, 1959, 0124;
Amchem, 1960, 0125). It is a white crystalline powder, melting at about
195°C. (The pure material melts at 201 C.) It has an aqueous
solubility of 700 ppm, and is easily soluble in ethanol (17.3 g/100 ml).
It is 50 percent ionized at a pH of 5.6.
Sodium chloramben is a crystalline powder with a bulk density about three
quarters that of water. It is very soluble in water and insoluble in
aromatic solvents. It has no known oxidizing or reducing action. (Amchem,
1974, 0054)
4-1
-------
Methyl chloramben is a crystalline solid only slightly soluble in water
(120 ppm) and soluble in organic solvents (alcohol, acetone, ether, and
aronatic solvents), (Amchem, 1966, 0037)
Methods for the determination of chloramben in the technical grade chemical
have been submitted to the Agency (Amchem, 1979, 0054; Amchem, 197?,
0083). Although these methods are old, they seem adequate for quality
control and enforcement purposes.
Analytical methods have been supplied both for the assay of manufacturing-
use and formulated products, and for the determination of isomers of
chloramben in low concentration (Amchem, 1979, 0054; Amchem, 197?, 0083).
These methods also are adequate for quality control and enforcement
purposes.
2. Data Requirements and Data Gaps
Listed below are the Product chemistry data needed to support adequately
the registration of manufacturing-use chloramben products. Preceding each
data requirement is the section of the proposed guidelines for the
registration of pesticides in the United States (43 FR 29696 July 10, 1978)
which describes the type of data required. Applicants for registration
must submit or cite the following information, which either has not yet
been submitted to the Agency, or is insufficient to satisfy the
requirements.
-------
Data Reouirement
Technical Manufacturing-
Chloramben Use Chloramben
Acid Sodium Methyl
163. 51-3 Identification of product and
disclosure of ingredients
163.61-4(a) C
imposition of starting and
X XX
163.61-4(b)
163.61-5
163.61-6(a)
163.61-6(b)
163.61-7
«
163.61-8(c)
intermediate materials in
manufacturing process
Detailed manufacturing process
Discussion on formation of
unintentional ingredients
Declaration of Limits
Certification of Limits
Analytical methods and results
(results)
Physical and Chemical properties
color
odor
stability
octanol/water partition coefficient
density
vapor pressure
pH
storage stability
flammability
oxidizing or reducing action
explosiveness
miscibility
viscosity
corrosion characteristics
X
X
X
X
X
X
X
X
X
X
X X
(results)
X
X
X
•
X
X
X
X
X
X
X
X
X
X
X
4-3
-------
3. Topical Discussions
a. Chemical Identity
The Proposed Guidelines require identifying information including chemical
names, product names, and numerical codes of all substances known or
assumed to be present in pesticide products. (163.61-3)
"Chloramben11 is the common name accepted by the American National Standards
Institute (ANSI) for the chemical 3-amino 2,5-dichlorobenzoic acid.
Chloramben is also known by the trade names Amiben, Vegiben, and Weedone.
The common name will be used throughout this Standard in lieu of other
chemical or trade names. The Chemical Abstracts number is 133-90-4, the
EPA Shaughnessy code is 029901 and the molecular formula is
CgH2Cl2(NH2)CCOH. It has the following structure:
COOH
Cl
Cl
The following structures represent respectively sodium Chloramben (Chemical
Abstracts number 1954-81-0) and methyl Chloramben (Chemical Abstracts
number 7286-84-2):
COONa
COOCH,
Cl
Cl
These are-similar to Chloramben itself except that the carboxylic acid
hydrogen has been replaced by sodium or by the methyl group.
b. Manufacturing Processes
Because the route by which a pesticide is synthesized determines the nature
and amount of potentially toxic impurities, a detailed description of the
manufacturing process is required (163.61-4).
The details of the process which have been submitted are lacking in many
details, including concentrations, equipment used, the process solvents,
the reaction conditions (including temperatures and periods of time for
elevated temperatures), purification steps, quality control measures, an
indication of whether batch or continuous process is used, and a
description of materials used for packaging. The confidential appendix to
this document contains the submitted information on the manufacturing
processes. This information is not sufficiently detailed, and does not
provide sufficient data to fulfill requirements.
4-4
-------
c. Formation of Unintentional Ingredients
Section 163.61-5 of the Proposed Guidelines requires registrants of_
technical grade, manufacturing-use, and formulated products to submit a
theoretical discussion of the formation of unintended substances in the
product.
Available data on known impurities in chloramben manufacturing-use products
are summarized in the confidential discussion appendix to this document. A
discussion of the formation of these impurities in sodium and methyl
chloramben manufacturing-use products is required.
Use of the specific nitrosamine detector in the analysis of "Amiben"
(Amchem, 1978, 0153) indicates that nitrosamines are not present in this
formulation. The level of detection was .05 ppm. Available information on
the manufacturing process does not cause suspicions of nitrosamine
formation. Additional data are not required on nitrosamines.
d. Ingredient Limits in Pesticide Products
The Guidelines require that upper and lower limits be established for each
active ingredient and each intentionally added inert in a pesticide product
(163.61-6). She two manufacturing-use chloramben products contain
approximately 90 percent of chloramben acid equivalent in both cases.
Upper and lower limits have not been established and certified for
manufacturing-use methyl chloramben.
e. Analytical Methods and Data
The Guidelines require submission of, or reference to, analytical methods
for measuring each active ingredient and each identifiable impurity in a
pesticide product (163.61-7).
Section 163.61-7 of the Proposed Guidelines also require that applications
for registration of pesticide products contain analytical data obtained by
methods supplied to the Agency.
Acceptable methods for the determination of chloramben and some impurities
in manufacturing-use chloramben are contained in the confidental discussion
appendix. Data obtained by the method are not available.
f. Physical and Chemical Properties
For every pesticide product, the Proposed Guidelines require data on
certain physical and chemical properties useful for identification purposes
or for evaluation of hazard potential (163.61-8).
A small amount of data are available on the physical and chemical
properties of chloramben acid, sodium chloramben, and methyl chloramben.
An outline of the properties of chloramben acid, sodium chlcramben, and
methyl chloramben was given in the product chemistry profile earlier in
this chacter. Sane additional details on these comcounds follows:
4-5
-------
Chloramben (Amchem, 196?, 0081; Amchem, 1959, 0124; Amchem, 1960, 0125)
Color: White
Melting Point: 200-201°C
Physical State: Crystalline solid
Stability: Stable towards oxidation and heat under conventional
conditions
Solubility: Water, .07g/100g; ethanol, 17.3g/100g
Vapor Pressure: .0007 ran Hg at 100
Sodium chloramben: (Amehem, 1979, 0054; Amehem, 1979 jacket 264-306)
Color: Conflicting data submitted
Melting Point: 271°C ,
Physical State: Crystalline solid, described as granular hollow sphere
Stability: Temperature stable at least up to the melting point.
Solubility: Very easily soluble in water, insoluble in aromatic solvents
Methyl chloramben: (Amehem, 1966, 0037)
Color: Off white
Melting Point: 63-64 C
Physical State: Crystalline solid
Stability: Temperature stable at least up to the melting point. Stable
under GC conditions.
Solubility: Water, 120 ppm; soluble in aromatic solvents (alcohol,
acetone, ether, aromatic solvents)
-------
C. Soluble Concentrate Chloramben
In this category there are two basic configurations or formulations of
chloramben. First, there is a formulation in which the ammonium salt of
chloramben is the sole active ingredient at a concentration of 23.4
percent. There is a second formulation in which ammonium chloramben (15.7
percent) and the nonomethyl ammonium salt (47.2 percent) of chloramben are
both ingredients.
These end-use products are produced by an integrated formulation system.
Product chemistry data are required on technical grade ammonium and
monomethyl ammonium chloramben, as well as on specific end-use products.
No physical or chemical properties were disclosed for ammonium or
monomethyl ammonium chloramben or any end-use formulations.
1. Data Gaps
Data needed on technical grade ammonium and moncmethyl ammonium
chloramben in soluble concentrate products:
1) Identification 163.61-3 (b)
2) Composition of material 163.61-3(c)
3) Analytical methods and data 163.61-7
4) Physical and chemical properties
a. Color (moncmethyl ammonium chloramben) 163.61-8(c)(l)
b. Cdor 163.61-8(c)(2)
c. Melting point 163.61-8(c)(3)
d. Solubility 163.61-8 (c) (4)
e. Stability 163.61-8(c) (5)
f. Octanol/Water particion coefficient 163.61-8(c)(6)
g. Physical state 163.61-8(c) (7)
h. Specific gravity or density 163.61-8(c)(8)
i. Boiling point 163.61-8(c)(9)
j. Vapor pressure 163.61-8(c) (10)
fc. pH 163.61-8(c) (11)
Data needed on soluble concentrate end-use products:
1) Declaration and certification of limits 163.61-6
2) Analytical methods and data 163.61-7
3) Physical and chemical properties
a. Color 163.61-8(c) (1)
b. Cdor 163.61-8(c) (2)
c. Density or Specific Gravity 163.61-8(c) (8)
d. Boiling Point 163.61-8(c) (9)
e. Vapor Pressure 163.61-8(c)( 10)
f. pH . 163.61-8(c) (11)
g. Storage Stability 163.61-8(c)(12)
h. Flammability 163.61-8(c)(13)
i. Oxidizing or Reducing Action 163.61-8(c)( 14)
j . Explosiveness 163.61-8(c) (15)
k. Miscibility 163.61-8(c) (16)
1. Viscosity 163.61-3 (c) (17)
m. Corrosion Characteristics 163.61-3(c) (18)
4-7
-------
2. Topical Discussions
The Agency has not received acceptable product chemistry data for any
soluble concentrate chloramben product nor for technical grade ammonium
chloramben or moncmethyl ammonium chloramben.
The following are data required of all soluble concentrate formulated
products of chloramben.
a. Chemical Identity and Disclosure of Ingredients
The proposed Guidelines require that the technical grade of each active
ingredient in a formulated product be identified by name and by statement
of formula identifying each reasonably identifiable substance in the
technical grade chemical. Each of these substances shall be listed as a
percentage or as ppm (by weight) of the technical chemical used in the
product.
Data on technical grade ammonium and technical grade moncmethyl ammonium
chloramben have not 'been submitted in sufficient detail.
In addition, the proposed Guidelines require that applications for
registration of a formulated product shall contain identifying information
on each substance known to be present in the product, and those reaction
products and degradation products known or theorized to be formed in the
pesticide product during its manufacture or during its marketable life.
Insufficient data have been submitted.
b. Active Ingredient Limits
For all pesticides, the Guidelines require that the upper and lower limits
be established for each active and inert ingredient, and upper limits for
each possible reaction product and degradation product (163.61-6). Current
registrations of soluble concentrate chloramben contain 23.4 percent
ammonium chloramben in the case where ammonium chloramben is the sole
active ingredient and 15.7 percent ammonium chloramben and 47.2 percent
moncmethyl ammonium chloramben in the case where the two salts are mixed.
For neither soluble concentrate formulation of chloramben has an upper and
lower active ingredient limit been established for possible reaction
products or degradation products.
c. Analytical Methods and Data
The Guidelines would require submission of, or reference to, analytical
methods measuring each active ingredient in a pesticide product (163.61-
7). Methods for the determination of total anionic amino compound present
and for the determination of chloramben and its iscmers have been submitted
(Arachem, 1979, 0054; Amchem, 197?, 0083). The determination is done in two
steps. First, all amino compounds are determined via diazcmetric
titration. The chloramben itself is determined by methylating the
carboxylic acid group and determining the methyl ester concentration via
gas chrcmatography. In this method the methyl 3-amino 2,5-dichlorobenzoate
-------
is separated by the gas chronatographic technique fron other related amino
compounds (most of which are related aminodichlorobenzoic esters) and
determined as a pure isoner.
Section 163.61-7 of the Proposed Guidelines requires that applicants for
registration of pesticide products submit analytical data obtained by
methods supplied to the Agency. Data obtained by the method described
above have not been submitted for soluble concentrate products.
Section 163.61-7 of the Proposed Guidelines would also require that
registrants.of the formulated products produced by the integrated
formulation system (Proposed Guidelines Section 163.61-1) submit methods
not only for the active ingredient but for each identifiable impurity
associated with manufacture of the technical chemical. Since the active
ingredients (ammonium and monomethyl ammonium chloramben) in soluble
concentrate products are not registered manufacturing-use products, the
manufacturing process for these products is an integrated formulation
system. Analytical methods, and data obtained from these methods are
required for each identifiable impurity.
Such methods and data have not been submitted for any chloramben
formulation.
d. Physical and Chemical Properties
For every pesticide product the Proposed Guidelines would require data on
certain physical and chemical properties useful for identification purposes
or for evaluation of hazard potential. (163.61-8)
There are no data available except for the off-white color of ammonium
chloramben.
4-9
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D. Flowable Concentrate Chloramben
In this category are formulations of sodium chloramben (a registered
manufacturing-use' chemical) as the sole active ingredient. The two
registered formulations contain 83 and 21 percent sodium chloramben,
respectively.
1. Data Gaps
1) [Declaration and certification of limits 163.61-6
2) Data from analytical methods 163.61-7
3) Physical and chemical properties
a. Color 163.61-8(c) (1)
b. Cdor 163.61-8(c)(2)
c. Density or Specific Gravity 163.81-8(c) (8)
d. Boiling Point 163.61-8(c) (9)
e. Vapor Pressure 163.61-8(c) (10)
f. pH 163.61-8(0)(11)
g. Storage Stability 163.61-8(c) (12)
h. Flammability 163.61-8(c) (13)
i. Oxidizing or Reducing Action 163.61-8(c) (14)
j. Explosiveness 163.61-8(c)(lS)
k. Corrosion Characteristics 163.61-8(c) (18)
2. Topical Discussions
The product chemistry of sodium chloramben per se has been dealt with under
Manufacturing-use Products.
a. Ingredient Limits in Pesticide Products
For all pesticide products, the Guidelines would require that upper and
lower limits be established for each active and inert ingredient, and upper
limits for each impurity, reaction product, and degradation product (163.61-
6).
For no flowable concentrate formulation of chloramben have limits been
established for impurities, reactions products or degradation products.
b. Analytical .Methods and Data
The Guidelines would require submission of, or reference to, analytical
methods measuring each active ingredient in a herbicide product (163.61-7).
Methods for the determination of chloramben in flowable concentrate
formulations have been submitted and are attached in the Confidential
Appendix. These methods are similar to those outlined under Section C of
this chapter for soluble concentrates of chloramben.
Section 163.61-7 of the Proposed Guidelines would require that applications
for registration of pesticide products contain analytical data obtained by
methods supplied to the Agency. Data obtained by the methods referred to
above have not been submitted.
4-10
-------
c. Physical and Chemical Properties
For every pesticide product/ the Proposed Guidelines require data on
certain physical and chemical properties useful for identification purposes
or for evaluation of hazard potential (163.61-8). None of the required
data have been submitted.
4-11
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E. Emulsifiable Concentrate Chloramben
There is one registered emulsifiable concentrate of chloramben. Methyl
chloramben is contained as the sole active ingredient at 23.2 percent:
1. Data Gaps
1) Declaration and certification of limits 163.61-6
2) Analytical methods and data 163.61-7
3) Physical and chemical properties
a. Color 163.61-8(c)(l)
b. Cdor 163.61-8(c)(2)
c. Density or Specific Gravity 163.81-8(c) (8)
d. Boiling Point 163.61-8(c) (9)
e. Vapor Pressure 163.61-8(c) (10)
f. pH 163.61-8(c)(11)
g. Storage Stability 163.61-8(c) (12)
-h. Flammability 163.61-8 (c)( 13)
i. Oxidizing or Reducing Action 163.61-8(c) (14)
j. Explosiveness 163.61-8(c) (15)
k. Corrosion Gharacteristics 163.61-8(c) (18)
2. Topical Discussions
The product chemistry of methyl chloramben per se has been described
previously/ under Manufacturing-use products.
a. Ingredient Limits in Pesticide Products
For all pesticide products, the Guidelines would require that upper and
lower limits be established for each active and inert ingredient, and upper
limits for each impurity, reaction product, and degradation product (163.61-
6).
Upper and lower limits have not been established for impurities, reaction
products or degradation products in the currently registered emulsifiable
concentrate product.
b. Analytical Methods and Data
The Guidelines would require submission of, or reference to, analytical
methods measuring each active ingredient in a herbicide product (163.61-7).
Methods for the determination of chloramben in soluble concentrate
formulations have been submittec and are attached in the confidential
appendix. These methods are not readily adaptable to the analysis of
chloramben in emulsifiable concentrate formulations, and hence the lack of
a suitable analytical method is identified as a data gap.
Section 163.61-7 of the Proposed Guidelines would require that applications
for registration of pesticide products contain analytical data obtained by
methods supplied to the Agency, No such data have been submitted.
4-12
-------
c. Physical and Chemical Properties
For every pesticide product, the Proposed Guidelines require data on
certain physical and chemical properties useful for identification purposes
or for evaluation of hazard potential (163.61-8). None of the required
data has been submitted.
4-13
-------
F. Granular Chlorainben
Granular chloramben exists in two different forms. The first is granular
chloramben where 'the sole active ingredient is ammonium chloramben. This
exists in formulations of 1.3 percent, 4.3 percent and 10.8 percent
ammonium chloramben. The second formulation is one in which ammonium
chloramben is mixed with moncmethyl ammonium chloramben. This exists in
two different concentrations. One is 5.4 percent ammonium chloramben plus
17.3 percent moncmethyl ammonium chloramben. The other is 2.82 percent
ammonium chloramben and 8.46 percent monomethyl ammonium chloramben.
Granular chloramben products, like soluble concentrate chloramben products,
are produced by integrated formulation systems. Consequently, product
chemistry data are required on the technical grade ammonium and monomethyl
ammonium chloramben in 'addition to data on specific end-use products.
1. Data Gaps
Data needed on technical grade ammonium and moncmethyl ammonium
chloramben:
1) Identification 163.61-3(b)
2) Composition of material 163.61-3(c)
3) Analytical methods and data 163.61-7
4) Physical and chemical properties
a. Color (monomethyl ammonium chloramben) 163.61-8 (c) (1)
b. Cdor 163.61-8(c)(2)
c. Melting point 163.61-8(c)(3)
d. Solubility 163.61-8(c)(4)
e. Stability 163.61-8(c) (5)
f. Octanol/Water particicn coefficient 163.61-8(c) (6)
g. Physical state 163.61-8(b) (7)
h. Specific gravity or density 163.61-8(c)(8)
i. Boiling point...., 163.61-8(c)(9)
j. Vapor pressure 163.61-8(c) (10)
Ic. pfi 163.61-8(c) (11)
Data needed on granular end-use products:
1) Declaration and certification of limits 163.61-6
2) Analytical methods and data 163.61-7
3) Physical and chemical properties
a." Color 163.61-8(c)(l)
b. Cdor 163.61-8(cM2)
c. Density or Specific Gravity 163.61-8(c)(8)
d. Boiling Point 163.61-8(c)(9)
e. Vapor Pressure 163.61-8(c) (10)
f. pfl 163.61-8(c)( 11)
g. Storage Stability 163.61-8(c) (12)
h. Flammability 163.61-8(c)( 13)
i. Oxidizing or Reducing Action 163.61-8(c) (14)
j . Explosiveness 163.61-8(c) (15)
k. Miscibility 163.61-3(c) (16)
1. Viscosity 163.61-8 (c) (17)
m. Corrosion Characteristics 163.61-3(c) (18)
4-14
-------
2. Topical Discussions
The Agency has not received acceptable product chemistry data for any
granular chloramben product. Mo data on technical grade ammonium or
rvonomethyl ammonium chloramben have been submitted.
a. Chemical Identity and Disclosure of Ingredients
The proposed Guidelines require that the technical grade of each active
ingredient in a formulated product be identified by name and by statement
of formula identifying each reasonably identifiable substance in the
technical grade chemical. Each of these substances shall be listed as a
percentage or as. ppm (by weight) of the technical chemical used in the
product.
Data on technical grade ammonium and moncmethyl ammonium chloramben have
not been submitted in sufficient detail.
In addition, the proposed Guidelines require that applications for
registration of a formulated product shall contain identifying information
on each substance known to be present in the product, and those reaction
products and degradation products known or theorized to be formed in the
pesticide product during its manufacture or during its marketable life.
Insufficient data have been submitted.
b. Active Ingredient Limits in Pesticide Produces
For all pesticide products, the Guidelines would require that upper and
lower limits be established for each active and inert ingredient, and upper
limits for each impurity, reaction product, and degradation product (163.61-
5).
For no granular formulation of chloramben has an upper and lower limit been
established.
c. Analytical Methods, and Data
The Guidelines would require submission of, or reference to, analytical
methods measuring each active ingredient in a herbicide product (163.61-
7). Methods for the determination of chloramben in soluble concentrate
formulations have been submitted, as previously discussed. It is felt that
these methods may not be suitable for the determination of chloramben in
granular formulations because the prescence of large quantities of solid
inerts, which are likely to have adsorptive properties, mate uncertain
recoveries of chloramben from granular formulations.
Section 163.61-7 of the Proposed Guidelines would require that applications
for registration of pesticide products contain analytical data obtained by
methods supplied to the Agency. Such analytical data have not been
submitted.
Section 163.61-7 of the Proposed Guidelines would also require that
registrants of formulated products produced by an integrated formulation
system (Proposed Guidelines, Section 163.61-1) submit methods not only for
4-15
-------
the active ingredient, but for each identifiable impurity associated with
manufacture of the technical chemical. Such methods have not been
submitted for any chloramben formulation. Since the active ingredients
(ammonium and monbmethyl ammonium chloramben) in granular chloramben
products are not registered inanufactur ing-use products, the manufacturing
process for these products is an integrated formulation system. Analytical
methods and data obtained through the use of these methods are required for
each identifiable impurity,
d. Physical and Chemical Properties
For every pesticide product, the Proposed Guidelines would require data on
certain physical and chemical properties useful for identification purposes
or for evaluation of hazard potential (163.61-8). None of the required
data has been submitted.
4-16
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CHAPTER V
ENVIRONMENTAL FATE OF CHLORAMBEN
A. 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 a 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.
Chloramben is available in four types of formulations: soluble
concentrates, flowable concentrates, emulsifiable concentrates, and
granulars. These formulations contain a variety of salts and esters of
chloramben including sodium chloramben, methyl chloramben, ammonium
chloramben, and moncmethyl ammonium chloramben. Sodium chloramben and
methyl chloramben are registered manufacturing-use products. The Agency
has determined that data on the fate of chloramben in the environment are
required on sodium and methyl chloramben. Data requested on sodium
chloramben will support the registrations of products containing the sodium
salt and products containing the ammonium and moncmethyl ammonium salts.
B. Use Profile
The herbicide chloramben is used for the control of seedling annual grasses
and seedling broadleaf weeds. The mechanism of action is the inhibition of
root development in weed seedlings. The use of chloramben is principally
pre-emergent, with some post-emergent use also.
Chloramben is registered for use in dry beans (white, navy, kidney, pinto,
and lima), peanuts, soybeans, sunflowers, corn, sweet potatoes, squash,
pumpkins, asparagus (seedling), transplanted tomatoes and peppers,
snapbeans, lima beans, cantaloupes, cucumbers, annual and perennial
flowers, shrubs, and trees.
Based on a preliminary quantitative usage analysis (PQJJA) of chloramben
prepared by.Economic Analysis Branch (EAB), about 96 percent of the
chloramben production is used on soybeans primarily in the north central
states. This use represents approximately 7 percent of the total U.S.
soybean acreage.
Of 24 federally registered products, Union Carbide Agricultural Products,
Inc. is the major producer with seventeen registered products. There are
four other registrants. Chloramben is registered as the ammonium salt/
diethanolamine salt, sodium salt, moncraethyl ammonium salt, and the methyl
ester. Table 5-1 presents a complete listing of the chloramben federal
registrations together with the form and concentration of the active
ingredient(s). Chloramben' is the sole active ingredient in 16
5-1
-------
registrations. These 16 registrations include soluble concentrates,
flowable concentrates, emulsifiable concentrates, and granular
formulations. Mot covered under this standard but included in Table 5-1
are eight registered mixtures of chloramben with other herbicides. Most of
the registered orcducts are designed for general agricultural use.
However, one granular formulation, *264-191 is used primarily by
homeowners. Table 5-2 gives the registered application rates of chloramben
as indicated on product labels.
5-2
-------
TABLE 5-1
Registration *
264-138
264-167
264-175
264-178
264-191
264-243
264-251
264-253
264-254
264-256
264-260
264-266
Form'
SC
G
G
SC
G
G
G
WP
WP
EC
EC
SC
Chloramben Registrations
2
264-274
264-278
264-279
264-305
264-306
449-534
635-630
T
T
PC
EC
FC
% Active Ingredient
23.4% ammonium chloramben
10.8% ammonium chloramben
10.8% ammonium chloramben
23.4% ammonium chloramben
1.3% ammonium chloramben
4.3% ammonium chloramben
5.4% ammonium chloramben plus
17.3% monanethylammonium
chloramben
27.7% sodium chloramben and
50.0% atrazine
41.7% sodium chloramben and
12.5% linuron
15.7% diethanolamine
chloramben and
30.1% diethanolamine dinoseb
23.2% methyl chloramben
15.7% ammonium chloramben and
47.2% monanethylammonium
chloramben
2.32% ammonium chloramben and
8.46% monanethylammonium
chloramben
98.8% methyl chloramben
97.2% sodium chloramben
83.0% sodium chloramben
21.0% sodium chloramben
17.5% ammonium chloramben
12.9% norea
5.4% ammonium chloramben and
4.0% norea
-------
Registration
635-631
2749-160
2749-202
43142-29
43142-30
TABLE 5-1
Chloramben Registrations - Continued
Form
FC
G
SC
FC
% Active Ingredient
17.5% ammonium chloramben and
12.9% norea
10.8% anmonium chloramben
23.4% ammonium chloramben
17.5% ammonium chloramben and
12.9% norea
5.4% ammonium chloramben and
4.0% norea
1) Source for Table 5-1 was a PRD-1 printout dated June 12, 1980.
2) SC = Soluble Concentrate, G = Granular, WP = Wettable Powder,
EC = anulsifiable Concentrate, T = Technical, FC = Flowable Concentrate,
5-4
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TABLE 5-2
REGISTERED APPLICATION RATES FOR CHLORAMBEN
Formulation Type
Soluble Concentrates
23.4%-62.9%
Site
Soybeans, dry beans,
peanuts, sunflowers
Arolication Rate
(1)
(Ib. a.i. per acre)
Flowable Concentrates
21%-83%
Corn
Lima beans, squash, pumpkin
Asparagus (seedling)
Sweet potatoes
Soybeans, dry beans,
peanuts, sunflowers
Emulsifiable Concentrate
23.2%
Granular
1.3%-22.7%
2-3
2
2-4
3
4
2-3
Lima beans, squash, pumpkin 2-4
Asparagus (seedling) 3
Sweet potatoes 4
Snap beans, cantaloupes, 2-3
cucumbers
Soybeans, dry beans, 2-3
peanuts, sunflowers
Corn 2
Sweet potatoes 4
Ornamentals 4-6
Transplanted tomatoes and 4
peppers, lima beans,
pumpkins, squash,
asparagus (seedling)
(1) Where ranges are given, the higher rates are for heavy soils.
5-5
-------
C. Manufacturing-Use Chloramben
1. Environmental Fate Profile
Sodium Chloramben
Sodium chloramben appears to be resistant to hydrolysis. This conclusion
is, however, based on retention of phytotoxicity rather than actual field
residue data. Limited studies indicate that there is no loss of
phytotoxicity when aqueous solutions of chloramben are kept in the dark.
Photodegradation of sodium chloramben aqueous solutions appears to occur
readily in sunlight. Total loss of phytotoxicity occurs in two days. Loss
of phytotoxicity on dry soil is somewhat slower, being about 30 percent in
48 hours.
Soil bacteria bring about a loss of phytotoxicity in sodium chloramben
after several weeks. It appears that this is due to a decarboxylation.
The rate of reaction appears to be independent of soil pH within the range
of 4.3 to 7.5.
Chloramben may have bactericidal properties towards Rhizobium japonicum.
No other data are available on the effects of chloramben on other bacteria,
nor on activated sludge.
The mobility of sodium chloramben is governed principally by its high
solubility in water and its apparent limited strength of adsorption to soil
particles. It appears to easily leach down in most soil types by rainfall.
This factor, together with an apparent slow rate of bacterial degradation,
indicates a potential for groundwater contamination.
Probably all plants grown in contact with sodium chloramben take up the1
compound. In some plants the subsequent movement of compound away from the
roots is very slow, whereas in others it readily spreads throughout the
plant. The fate of chloramben in plants includes decomposition, a
detoxifying conjugation which proceeds fairly rapidly, or a detoxifying
conjugation which goes slowly, if at all.
Methyl Chloramben
The methyl ester -of chloramben acid appears to have the expected properties
of a carboxylic acid ester. It is apparently not hydrolysed after a short
period in contact with water at slightly acid pH values (5 to 6). Bacteria-
mediated hydrolysis appears to be quick: approximately 50 percent of the
ester is converted to the free acid" in about one week when in contact with
wet soil. A subsequent and slower bacteria reaction, shown by a loss of
phytotoxicity, is probably a decarboxylation, as with sodium chloramben.
The leaching behavior of the methyl ester is governed 'by its aqueous
solubility, which is much lower than that of the sodium salt (120 ppm and
250,000 ppm, respectively). For a given rainfall the ester seems to leach
down about 15 percent of the distance travelled by the sodium salt.
-------
2. Exposure Profile
Exposure to persons involved in the manufacture, handling, storage or
shipment of technical or manufacturing-use grade chloramben is possible
through four pathways; accidental ocular or dermal exposure, inhalation
exposure, and repeated dermal exposure. Due to the scarcity of data on
occupational exposure of these two grades of chloramben, it is impossible
to quantitatively assess the human and wildlife exposure hazard.
There is little likelihood of oral and ocular exposure occurring unless by
accident, the low volatility of flowable and soluble concentrates
indicates that there is also little chance of inhalation exposure under
normal circumstances. The granular chloramben may present a higher
possibility of inhalation exposure to workers involved in bulk loading,
unloading, and packaging of the substance. Due to its dry and solid
physical state, the chances of it being inhaled in these work areas as an
airborne particulate are moderately high.
In addition, repeated dermal exposure to all forms of manufacturing-use and
technical grade chloramben present the highest exposure hazard. This may
occur in the manufacturing and shipping phases of its production but the
greatest repeated exposure is expected during bulk handling operations.
Should significant amounts of chloramben be spilled, drained, discharged or
disposed of in the natural environment, aquatic life in waters affected by
direct drainage or leaching are expected to receive high dosages of
herbicide.
3. Data Requirements and Data Gaps
Not all the requirements of Section 163.62 (43 FR 29696, July 10, 1978)
need to be fulfilled to support the registration of chloramben as a
manufacturing-use product and as a formulated product, because the use
pattern indicates that chloramben is unlikely to enter the environment in
particular specified ways.
To support the registration of all chloramben products, it is necessary to
submit or cite the following data tested on both sodium and methyl
chloramben.
163.62-7 Physico-Chemical Degradation
(b) Hydrolysis
(c) Phytodegradation in water *
(c) Photodegradation in soil
163.62-8 Metabolism
(b) Soil metabolism - aerobic
(c) Soil metabolism - anaerobic
163.62-9 Mobility
(b) Leaching
(d) Adsorption/desorption
163.62-10 Field Dissipation
(b) Terrestrial
163.62-11 Accumulation
(b) Rotational crops
(d) Fish accumulation
5-7
-------
In addition to the above listed requirements, a field study measuring
applicator exposure to liquid formulations of chloramben is required. The
study should be conducted with a typical soluble or flowable concentrate
formulation, which is mixed and then applied by ground equipment to a
typical (160 acres) soybean field at recommended application rates. The
Agency is requiring this study to verify the exposure estimates used in the
oncogenic risk assessment.
Data Gaps
Although some data on the environmental fate of chloramben are currently
available, none of the data requirements have been satisfied sufficiently
with the exception of fish accumulation data on sodium chloramben.
4. Topical Discussions
Corresponding to, each of the Topical Discussions listed below is the number
of the section in the "Proposed Guidelines for Registering Pesticides in
the United States" (43 FR 29696, July 10, 1978) which explains the minimum
data that the Agency requires in order to adequately assess a pesticide's
Environmental Fate.
All topics related to the Environmental Fate of chloramben as an active
ingredient are discussed under Manufacturing-Use Chloramben.
a. Physico-Chemical Degradation 163.62-7
These studies should identify decomposition rates and pesticide residues
which could adversely affect the environment. They include studies of the
degradation of chloramben in the prescence of water, and when subject to
the action of light. Studies already carried out suggest that there are
three pathways of degradation. One, the formation of free chloramben acid
by ionization of the sodium salt or the breaking of the ester bond of
methyl chloramben, results in a compound which is fully phytotoxic. A
second pathway, a loss of the carboxylic acid group, probably occurs by the
action of some bacteria, and results in an apparently non-phytotoxic
compound. A third degradation pathway occurs under the influence of
sunlight, and appears to involve the loss of a chlorine atom from the
chloramben molecule. This too, involves a loss of phytotoxicity. It
should be noted that loss of phytotoxicity is not a suitable measure of the
extent of hydrolysis or photodegradation as these processes may veil
proceed by way of degradation products which have some level of
phytotoxicity.
i. Hydrolysis
Hydrolysis data are required to support the registration of all
manufacturing-use products and end-use formulations of chloramben.
Sodium Chloramben
Chloramben free acid and its salts (sodium, ammonium, etc.) appear to be
resistant to hydrolysis, judging from data showing the retention of
phytotoxicity after several weeks of chloramben in non-sterile moist soils
(Sheets, 1968, 05107). More recent data (Union Carbide, 1980, 0172) show
that when protected from light, chloramben acid undergoes slow degradation
5-3
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in aqueous solution. Eighty-five percent or larger amounts of chloramben
initially present were recovered after one year at an acid pH and 25 C.
These studies will partially satisfy Agency requirements for hydrolysis
data on sodium chloramben. Data are needed on hydrolysis at other pH's for
sodium chloramben.
Methyl Chloramben
The methyl ester is susceptible to hydrolysis by bacterial action in soil
which contains enough moisture to support bacterial activity. An Amehem
document (Amchem, 1966, 0148) showed that the methyl ester gave no
measureable hydrolysis in 48 hours when in contact with well water at a pH
of 5 to 6; however, when soil (and therefore bacteria) was present in the
water there was a measurable hydrolysis within 48 hours, involving a
cleavage of the ester bond to yield the free chloramben acid.
The methyl ester is hydrolyzed in moist soil to the free acid; however, if
the soil is first sterilized, no breakdown of the ester occurs (Corbin,
1967, 0586; Talbert, 1970, 05111).
The presumption from these studies is that the methyl ester is relatively
unaffected by water in the absence of bacteria; however, these data are
inadequate to meet the requirements of the section. Additional testing on
methyl chloramben are required.
ii. Photodegradation
Photodegradation studies in water are required to support the registration
of all chloramben formulations for non-crop uses. Studies in soil are
required to support the registration of all chloramben formulations
intended for crop uses.
Several studies have been made of the effects of sunlight on chloramben.
All these studies are inadequate in that the products of photolysis were
not sufficiently identified or characterized. These studies do provide
insight into the Photodegradation of chloramben.
Chloramben on the surface of field-capacity soil and irradiated for 48
hours lost 38 percent of its herbicide activity, whereas the loss on dry
soil was 30 percent. There was a loss of phytotoxicity to oats in 7.5
hours after exposure to sunlight on the surface of field capacity soil
(Fickle, 1974, 0589).
An aqueous solution of the sodium salt became yellow-brown, indicating
chemical change, upon exposure to sunlight for periods of up to 14 days.
The products were not identified except for chloride ions (Crosbv, 1969,.
0587; Plimmer, 1969, 05106).
Two days exposure to sunlight was sufficient to produce total loss of
phytotoxicity of chloramben aqueous solutions to cucumbers. However,
similar solutions kept' in the dark showed no change in phytotoxicity after
2 days (Hahn, 1969, 0594).
There are no data on the extent of Photodegradation under cloudy
conditions. Available data on the photolysis of chloramben are not
5-9
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sufficient to determine the effects of light on chloramben. All data are
required on both sodium and methyl chloramben par section 163.62-7.
There are no data to indicate whether the first products of
photodegradation retain phytotoxic properties, or whether photodegradation
involves an immediate loss of herbicidal properties.
b. Metabolism 163.62-8
Data on metabolism are required to determine the nature of pesticide
residues and their availability to rotational crops, and to help in the
assessment of potential disposal and reentry hazards. Although
preliminarydata presented in the following discussions provide insight into
the metabolism of chloramben, .the data are inadequate and do not satisfy
the guideline requirements. The data gaps exist for both methyl and sodium
chloramben.
i. Soil Metabolism
Aerobic metabolism studies are required to support the registration of all
formulations. Anaerobic soil metabolism studies are required to support
the registration of all formulations intended for field and vegetable crop
uses.
Sodium Chloramben
An experiment with pure chloramben showed that phytotoxicity to Italian rye
grass (8 pern in soil) became negligible after 16 weeks in a sandy loam and
a silty clay loam. In a clay, however, after 16 weeks only about 60
percent of the control level of rye grass growth was present (Sheets, 1968,
05107). These results are probably due to the different levels of
bacterial activity in the soils; however, the Agency cannot rule out ttje
possibility that the different results were due to different leaching rates
through the soils. Another study (Amchem, 1967, 0043) snowed that after a
period of 4-6 weeks a rapid loss of chloramben occurs in soils with a high
organic content, probably due to the microbial populations reaching a
logarithmic phase in their growth cycle at this point.
A study of the effect of pH on loss of herbicide activity showed a similar
rate of loss at pfi levels of 4.3, 5.3, 6.5, and 7.5, the soil being
unchanged in respects other than pH (Corbin, 1967, 0586).
Only minimal data on the metabolism of sodium chloramben are available.
Additional data specified in Section 163.62-8(b,c) are needed to determine
metabolism of chloramben in soil.
Methyl Chloramben
Soil bacteria cause hydrolysis of chloramben methyl ester to the free acid
at a rate directly dependent on the content of water (Amchem, 1965, 1966,
0148). Chloramben methyl ester is hydrolyzed in wet soil by bacterial
action. Approximately 50 percent of the compound is converted to the free
acid in from 2 to 3 days. When the soil was partially dried the rate of
hydrolysis was less, with about 30 percent being hydrolyzed in 14 days.
If, however, the soil is first sterilized, no breakdown of the ester occurs
(Corbin, 1967, 0586; Talbert, 1970, 05111).
5-10
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Data provided are insufficient to differentiate between physico-chemical
degradation and rp.icrobial degradation. Therefore, all data are required
per section 163.62-3.
c. Mobility 163.62-9
Data on mobility are required to determine pesticide residue movement in
the environment and to assess the potential for loss of usable land and
water resources. Data summarized below provide insight into the mobility
of chloramben. These data do not satisfy Agency requirements. Mobility
data are needed on both sodium and methyl chloramben.
i. Leaching
Leaching data are required to support registration of end-use formulations
intended for terrestrial noncrop and field/vegetable crop uses.
Basic to an understanding of the leaching properties of the various forms
of chloramben are their aqueous solubilities and their ability to bind to
soils. The salts all dissolve freely in water to the extent of about
250,000 ppm; the free acid, about 700 ppm; and the methyl ester, about 120
pern (McLane, 196?, 0147; Amchem, 1965, 0115). With such solubilities all
fonns of chloramben, at the levels used in application to soil, should be
conpletely dissolved by 3-inches of rainfall and readily leach through the
soil. Therefore.,, any .failure of the herbicide to leach down with such rain
would indicate aisorption on soil particles. Available data on the
leaching characteristics of chloramben products provide preliminary
indications that a potential groundwater contamination problem could exist
as a result of chloramben uses.
Sodium Chloramben
Chloramben free acid and its salts (sodium, ammonium) are leached down
typically 8 to 12 inches by a 3-inch rainfall (Amchem, 1965, 0115; Pauser,
1963, 0131; McLane, 196?, 0147). An experiment involving 2 soils (a silty
clay loam and a sandy loam) in which water was forced upwards by
evaporation frcm the soil surface showed that chloramben (initially placed
5-6 inches below the surface) moved upwards through both soils at a rate
similar to that of other aromatic acid herbicides, and faster than the
rates of all other groups of herbicides tested (substituted ureas,
triazines, thiocarbamates, and toluidines) (Harris, 1967, 0595). Virtually
all the chloramben herbicide activity had moved into the top inch of soil.
Clearly some fraction of the chloramben had been left exposed on the soil
surface and was subject to photcdegradation. It has been noted that the
nature of the photcdegradation products of chloramben is mostly unknown.
(See Topical Discussion on Photolysis). Movement of chloramben upwards
probably occurs to some extent during any evaporation period such as that
following rainfall.
Methyl Chloramben
The solubility of the methyl ester of chloramben is about 120 ppm (Amchem,
1965, 0115; McLane, 196?, 0147). In contrast to the 8 to 12 inch leaching
of sodium chloramben by a 3 inch rainfall, the methyl ester is leached down
only about 1.5 inches (Amchem, 1965, 0115; Pauser, 1963, 0131; McLane,
5-11
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196?, 0147). After hydrolysis of the methyl ester in soil (a matter of a
few days), the free acid of chloramben leaches as quickly as the salts of
chloramben (Talbert, 1970, 05111).
These data are insufficient to evaluate the potential for sodium and methyl
chloramben to leach; all studies specified in 163.62-9 b and d are required.
ii. Adsorption/Desorption
A laboratory study using radioisotopic or nonradioisotopic analytical
techniques is required to support the registration of all chloramben
formulations intended for terrestrial uses. Data summarized below provide
insight into the adsorptive/desorptive properties of chloramben. These
data do not satisfy Agency requirements. Data are required on both sodium
and methyl chloramben.
There have been some studies of the nature of the adsorption process
between chloramben free acid and a calcium montmorlllonite clay, which
indicate that the adsorbed form has a protonated carboxylic acid group and
a protonated amine group (Berkheiser, 1976, 0541). Another study on
adsorption to a silt loam showed an increase in adsorption by decreasing
the pH of the water-soil mixture (Barter, 1969, 0596).
However, all such studies confirm that although chloramben is adsorbed by
soil colloids, the amount adsorbed and the strength of the adsorption
forces are far less than for many other herbicides. This helps to account
for the uniform adsorption and leaching behavior of chloramben in various
soil types.
These studies go only a short way to satisfying the requirements of Section
163.62-9(d). All data specified in the section are needed to determine the
adsorption/desorption behavior of chloramben.
d. Field Dissipation 163.62-10
Field dissipation studies using representative formulations under actual
use conditions are required to support the registration of all chloramben
formulations intended for terrestrial uses. The data summarized below
provide insight into the dissipation of chloramben. These data do not
satisfy flgency requirements. Data are needed on both sodium and methyl
chloramben.
No complete field dissipation study has been found in the chloramben
literature. However, it is possible to build a picture of chloramben
dissipation as a combination of bacterial breakdown in the upper levels of
oil and leaching to lower levels of soil where bacterial action is
progressively less (Anchem, 1967, 0043). Probably, chloramben finding its
way down to these levels remains intact and will travel with any movement
of liquid water, with a corresponding dilution. Some fraction of
chloramben will move upwards to the surface of soil (through
evaporation) ,where photodegradation will occur given a sufficiently high
intensity of sunlight.
However, no data exists with respect to the formulated products containing
sodium and methyl chloraraben. Therefore, additional studies as
5-12
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described in 163.62-10 b are needed in crop use areas using representative
formulations of methyl and sodium chloramben.
e. Accumulation 163.62-11
Data on accumulation are required to determine accumulation in food webs
and to assess the potential adverse effects on nontarget organisms.
i. Rotational Crops
Rotational crop studies are required to support the registration of all
chloramben formulations intended for field/vegetable crops. Data
summarized below provide insight into the accumulation of chloramben in
rotational crops. These data do not satisfy Agency requirements. Data are
needed on both sodium and methyl chloramben according to 163.62-11 b.
Registrants have the option of completing these studies or of placing the
following phrase on labels of all end-use products containing any salt or
ester of chloramben:
"Do not rotate to other crops"
Chloramben is readily taken up by soybean plant roots at a rate
proportional to its rate of application on the soil. Soybean roots cause
decomposition of the carboxylic acid group, releasing carbon dioxide, at
the rate of about 1 microgram chloramben in 8.5 hours per plant (Freed,
1960, 0128). However, movement of chloramben away from the roots and
through soybean plants is very slow, with no observed tendency to
concentrate in any particular regions (Freed, 1960, 0128). By contrast, in
barley, chloramben readily passes into the upper parts of the plant (Freed,
1960, 0128). One study has shown that chloramben added to ground soybean
seed is firmly held, and requires a prolonged extraction for recovery
(Freed, 1960, 0128). However, it should not be assumed that uptake of
chloramben by plant roots is the only, or even the preferred, path of
uptake. Green foxtail, for exammple, undergoes no control when chloramben
is located in the root zone at a soil concentration of 3 ppm, but is well
controlled when chloramben is in the shoot zone at the same concentration
(Knacke, 1967, 05100).
It is wise to assume that the plants grown on soil treated with chloramben
takeup the herbicide, unless there is evidence to the contrary. Morning
glory is resistant to chloramben. In a •comparison of it with velvetweed,
which is susceptible, it was found that both species take up approximately
equal quantities of chloramben, with the raate of uptake being faster in
morning glory. However, morning glory quickly detoxifies chloramben to N-
glucosyl chloramben, while velvetweed glucosylates chloramben at a far
slower"rate (Stroller, 1969, 05110).
ii. Fish Accumulation
A laboratory study employing radioisotopic or nonradioisotopic analytical
techniques is required to support the registration of all chlcramben
formulations intended for terrestrial noncrop and field/vegetable, crop uses.
5-13
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A flow-through fish accumulation test, acceptable in meeting registration
requirements, was performed on Bluegill Sunfish using chloramben and C-
chloramben (presumably technical acid) at 1 ppm (Iwan, 1978, 0020). Edible
and nonedible tissue maximum bioconcentration factors (BCF's) were 1.14 and
2.19, respectively, early in the exposure phase of the study. BCF's
declined gradually during exposure and declined rapidly in the depuration
phase. Little potential for significant fish accumulation is indicated by
this study. Testing is needed on methyl chloramben.
5-14
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D. Chloramben End-Use Formulations
Chloramben end-use products contain four varieties of the active
ingredient: sodium chloramben, methyl Chloramben, ammonium Chloramben, and
moncmethyl ammonium Chloramben. Requested fate data on sodium Chloramben
will satisfy Agency requirements for all products containing sodium,
ammonium, and monomethyl ammonium Chloramben. Requested data on methyl
chloramben will satisfy Agency requirements for all products containing
methyl chloramben.
1. All Formulations - Exposure Profile
Chloramben is found in low levels in plants and crops grown on chloramben-
treated soils. In some plants it is more or less uniformly distributed
throughout the plant, and in others (e.g. soybean plants) it tends to
remain in the roots.
Chloramben not taken up by plants will escape microbial attack as it is
leached downwards. Because of its apparent stability in aqueous solution
it is likely to reach depths at which microbial activity is low or absent.
This chloramben is likely to enter ground water or well water or be subject
to underground movement into streams. Monitoring studies may be required
to define adequately the potential hazard. Chloramben appears to be
persistent, and therefore poses a potential contamination problem in ground
water.
Because of the lack of data on the environmental fate of chloramben in
soils or on its presence in ground water, it is not possible to give a
quantitative assessment of human or wildlife exposure to chloramben
fronthese sources. However, a potential exists for it to reach ground
water or well water, and for its movement from soils into streams.
The non-dietary exposure to humans that may arise from the end-use of a
formulated chloramben herbicide is that associated with tank mixing,
dilution, loading, and application operations. Although there has been to
date no data reported on the non-dietary exposure of humans to chloramben
as a consequence of these activities, numerous studies have been performed
on exposures resulting from comparable activities with comparable chemical
formulations. These studies have been reviewed in order to derive numbers
that would be suitable for estimating dermal and inhalation exposure levels
resulting from mixing, loading, and application of chloramben.
Available studies indicate that dermal and respiratory exposures are the
main pathways by which pesticides are absorbed into the human body during
application. Exposure data available for three application activities were
reviewed: 1) application of liquid by ground boon, 2) mixing and loading
of a liquid for either aerial or ground application, 3) application of a
liquid by fixed-wing aircraft. Adequate information on application of a
granular substance by ground equipment and homeowner application was not
available.
Extrapolation of the existing data on other pesticides to chloramben has
been carried out on the basis that exposure is proportional to
concentration of active ingredient in the spray, other factors being
equal. The worst case dermal exposure calculated in this way for
chloramben represents a 23% soluble concentrate chloramben formulation
5-15
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mixed with water and applied to soybean fields at the rate of three pounds
active ingredient per acre. A closely similar result is obtained if a 2.7
pound a.i. per acre, application of a flowable concentrate is made to
soybean fields.
It was assumed that the average applicator would spray chloramben on 100
acres per day and on a total of 160 acres per year. A further assumption
was that dermal exposure (to liquid formulations) would result in the
absorption into the body of 10% of the active ingredient coming into
contact with the skin, and that respiratory uptake would result in 100
percent absorption.
Since these calculations are based on applicator exposure to a given
quantity of active ingredient per acre sprayed on a constant number of
acres, variations in the time spent spraying will not affect the total
exposure, nor the results of the calculations. Variations in the
percentage of active ingredient likewise will not affect the calculations,
as more dilute solution for spraying would necessitate a greater volume of
solution to be sprayed per acre in order to obtain the same rate of
application per acre.
2. Soluble and Flowable Concentrate: Exposure Profile
Ground Application
Ground application is the^ primary means by which soluble and flowable
chloramben concentrates are applied to crops as a pre-emergence herbicide.
This is usually done by the fanner himself and is typically accomplished
with a tractor or truck-mounted boon and tank. There are twenty nozzles on
the boon located approximately 18" to 20" above the ground (Lewis, 1980).
Applicators typically mix, load, and apply the material themselves;
however, in some cases mixer-loaders are employed to perform that function
separately. Application will take anywhere from six to twelve hours a day.
Miller, et al. (1980) nave developed data indicating that applicators of
arsenic acid applied in a similar manner will be exposed to concentrations
which, when adjusted for penetration and chloramben a.i. (active
ingredient) concentration convert to levels of 4.31 to 0.16 rag/day (dermal;
4.29-0.15 mg/day, respiratory: 0.016-0.007 mg/day). Staiff, et al. (1975)
have developed numbers for the same ground application activites of
paraquat dichloride which, when adjusted for % chloramben concentration and
skin absorption, convert to levels of 2.84 to 0.01 mg/day (dermal: 2.82-
0.01 mg/day, respiratory: 0.01-negligible mg/day). These numbers are not
applicable to levels of exposure received from mixing and loading.
The results of the comparative analyses arte presented in the following
text and in Table 5:3. All numbers are presented in units of milligrams
per day penetrated chemical. The numbers are also presented as worst and
best cases. The best case reflects the use of adequate protective clothing
including long-sleeved shirt, hat, and gloves. The worst case reflects the
employment of minimal protective clothing not including long-sleeved shirt,
hat, or gloves.
Minimum and maximum respiratory exposures reflect the range of field
exposure data. In all cases a cautious attitude by the applicator was
assumed and accidental spillage was assumed to be minimal.
5-16
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TABLE 5.3. RANGE OF ABSORPTION LEVELS FOR FORMULATED CHLORAMBEN
ma/day
ACTIVITY
DERMAL
Maximum Minimum
RESPIRATORY
TOTAL
Maximum Minimum Maximum Minimum
1. Ground Application
of Soluble and Flowable
Concentrate
- farmer/planter 4.29
2. Mixing-Loading
of Soluble andvFlowable
Concentrate
- mixer-loader
(farmer/planter) 16.63
3. Aerial Application
of Soluble and Flowable
Concentrate1
0.01
0.016 N
(b)
0.08
0.42
0.002
4.31 0.01
17.05
0.08
- pilot
- flagger
2.62
4.28
0.08
0.17
0.50
3.47
0.005
0.54
3.12
8.75
0.09
0.71
(a) Miller (1980), Staiff (1975)
(b) Lower than detection level.
(c) Peoples (1979), Staiff (1975)
NOTE: All values on this table have been adjusted for absorption to the body after
exposure and for chloramben concentration (a.i.) during application. This was done to
develop justifiable comparisons between available data and chloramben applications.
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Mixing and Loading
Liquid chloramben is available to field applicators in 5-gallon and 30-
gallon containers (Lewis, 1980, 05116). These containers are mixed with
water in loading tanks, mounted either on tractors, trucks, or planes. The
method of mixing also varies depending on the degree of applicator
sophistication. In some cases, commercial applicators employ enclosed
siphon systems which greatly reduce the dermal exposure observed. In other
cases, containers are simply punctured and poured directly. For enclosed
systems levels of exposure have been observed (Peoples, 1979, 05119) that,
when adjusted for chloramben concentration, indicate 17.05-0.59 mg/day
(dermal: 16.63-0.44 trig/day, respiratory: 0.42-0.15 mg/day). Miller (1980,
05117) indicates, for the same application, levels of 2.27-0.08 mg/day
(dermal: 2.27-0.08 mg/day, respiratory: 0.003-0.002 mg/day). In one
instance, when a direct transfer system was used, no gloves were worn and
the individual mixer-loader was noted as being careless, levels of 94.54-
22.63 mg/day were observed (dermal: 94.44-22.53 mg/day, respiratory: 0.1-
0.1 mg/day). Approximately 95 percent of this exposure is normally
expected to be to the hands (Wolfe, 1961, 05120).
Aerial Application
A very small percentage of the total chloramben applied is by aircraft
(Lewis, 1980, 05116). When this method of application is employed, dermal
and respiratory exposure occurs during mixing-loading, flying, and flagging
operations. Levels for combined dermal and respiratory exposure are
estimated to range from 3.12-0.09 mg/day and 9.75-0,71 mg/day for pilots
and flaggers, respectively.
Peoples (1979, 05119) has observed combined levels that, after adjustment
for chloramben concentrations, are 3.12-0.50 mg/day for pilots (dermal:
2.62-0.4 mg/day, respiratory: 0.50-0.10 mg/day). For the same operations,
Miller (1980, 05117) has observed penetration to pilots at 1.27-0.09 mg/day
(dermal: 1.26-0.08 mg/day, respiratory: 0.005 mg/day).
Annual Exposure Levels
Presently there is not a great deal of data available on overall annual non-
dietary exposure. However, since this exposure estimate is based on
information on the calculated daily non-dietary exposure and the annual
application rates of the herbicide chloramben, a range of projections can
be developed. The following assumption can be derived from the EPA
Chloramben Use Summary Report (Lewis, 1980, 05116).
The Use Summary Report indicates that for application of a liquid
formulation, a tractor-mounted applicator can treat approximately 80 acres
per ten-hour day while, for the same time period, a skid truck-mounted
applicator may be able to treat 140 acres. An average rate of 100 acres
treated per ten-hour day was assumed for annual exposure purposes.
Plots of land employed for soybean production in the United States are
assumed to range in size from 40 to 400 acres. Based on information from
University of Illinois representatives, the average soybean acreage is 160
acres.
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Chloramben is applied to soybean crops, in the liquid form, at a rate of
2.0 to 3.0 pounds a-.i. (active ingredient) per acre. A rate of 2.5 pounds
a.i. was assuned as an average.
In view of these assumptions of a 2.5 pound per acre a.i. application rate
and a 4,000,000 pound per year consumption, 1,600,000 acres are treated per
year. Assuming 160 acre soybean units, there are approximately 10,000
persons exposed to chloramben per year. These persons will be exposed to
estimated doses levels of between 27.3 and 0.016 milligrams of chloramben
per year, depending upon methods of application and acreage treated. The
estimates of annual chloramben penetration levels for the different methods
of application and acreages treated are summarized in Table 5-4.
3. Granular Formulations - Exposure Profile
The potential of granular formulations for forming dusts represents a
special human inhalation hazard, particularly during loading
operations.However, total exposure from granular applications is assumed to
be minimal in relation to liquid formulations since no mixing operations
are involved. The granular formulation for domestic use involves a shaker
canister and exposure from this application method is also assumed to be
low.
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TABLE 5-4. ANNUAL CHLQPAMBEN EXPOSURE ESTIMATES
Soluble and Flowable Concentrates
1.
2.
ACTIVITY
Ground Application
- farmer/planter
Mixing-Loading
-mixer /loader
f f a-rmtxr /r»1 am-or- \
Total: Farmer/Planter
Exposure
3. Aerial Application
- pilot
- flagger
mg/daya
Worst "Best"
Case Case
4.31
17.05
21.36
3.12
8.75
0.01
0.08
0.09
0.09
0.17
rog/person/yr
Worst "Best"
Case Case
6.9
27.3
34.2
5.0
14.0
0.016
0.13
0.146
0.14
1.14
a) Table 5-3.
b) (mg/day) x (1 day treatment/100 acres possible) x (160 acres/person/yr).
.5-20
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CHAPTER VI
RESIDUE CHEMISTRY
A. Introduction
For any pesticide which has uses that may directly result in residues on
food or feed, the Agency sets an allowable residue level, or tolerance, for
each conmodity on which it may occur. A tolerance level for a particular
chemical on a particular conmodity is a function of the chemical's
toxicity, the percentage of an average daily diet comprised by the
commodity, and the amount of residue that can be expected to occur on that
commodity at the maximum directed rate
-------
Some measurements on the uptake, distribution, and excretion of chloramben
in animals have been made. It appears that cows exrete ingested chloramben
in the urine and feces, but not in the milk. Dogs also excrete chlorainben
in the urine and feces. If dogs store any part of the ingested chloramben,
it probably is not more than about 0.2 percent of the total ingested.
The analysis of low levels of chloramben appears to present no .unusual
difficulty. The submitted gas chromatographic method is satisfactory in
itself, and is clearly capable of modification and improvement as discussed
in the Topical Discussion on analytical methods.
2. Data Requirements and Data Gaps
•
The proposed guideline? 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, however, the Agency must have sufficient data
to be assured that the residues of the parent chemical and its metabolites
have been identified.
Data Gaps
The following data are required to support the tolerances for chloramben:
1) Information on the storage of agricultural material between sampling
and residue analysis. Data on the storage conditions, and on the
stability of the residues during storage are required.
3. Topical Discussions
a. Use Patterns and Restrictions
Chloramben is applied principally as a pre-emergent herbicide used alone or
in combination with other herbicides for the control of weeds and annual
grasses in various food crops and ornamentals. The varous formulations of
chloramben are registered for use on dry beans (navy, white, kidney, pinto,
and lima) peanuts, soybeans, sunflowers, corn, sweet potatoes, squash,
pumpkin, asparagus (seedling), transplanted tomatoes and peppers, lima
beans, snap beans, cantaloupes, cucumbers, annual and perennial flowers,
shrubs, and trees.
Chloramben is available in soluble, flowable, and emulsifiable concentrates
and granular formulations containing from 1.3% to 83.0% chloramben.
Formulations are applied at time of planting or immediately following
transplanting; on tomatoes and peppers chloramben may be applied at layby.
Liquid formulations are sprayed from truck or tractor sprayers or by
aircraft; granular formulations are applied from tractor drawn planter or
broadcast applicators. Rates of application presented in Chapter 4 range
from 2 to 4 pounds active ingredient per acre for food crops and from 4 to
6 pounds per acre for ornamental uses. Formulations are applied only once
per season on agricultural crops and twice per season on ornamentals.
-------
Chloramben formulations contain the following label restrictions. Granular
and liquid formulations for use on sunflowers have label warnings
prohibiting grazing treated areas and using treated plants for feed or
forage. The use on peanuts is restricted to Oklahoma and northern Texas.
The use on com is confined to heavy soils in Illinois, Indiana, Iowa,
Kansas, Minnesota, Missouri, Nebraska, and Ohio.
With the exception of ornamentals, the uses of chloramben are for food uses
and are expected to result in residues in human food and animal feed.
b. Uptake, Distribution, and Metabolism in Plants
In addition to what may remain of an original application of the chemical,
residues may also consist of the chemical's metabolites, as formed by the
plant crop to which it was applied. The major and minor pathways of the
chemical's absorption, transformation, and distribution can be deduced
experimentally from the analysis of radiolabeled applications.
Applications by various routes, for example to the roots or leaves, will
show differences in absorption rates. The distribution of the chemical and
its metabolites can be examined by measuring the radioactivity present in
various plant fractions. Isolated metabolites can then be characterized by
cnromatography, partitioning, or electrophoresis. Metabolic
transformations often result in an increase of polarity of the foreign
chemical to facilitate elimination. Metabolites characterized as highly
polar may have undergone conjugation with naturally occurring amino acids,
sugars, or sugar acids. Further chemical analysis can help identify the
exact nature of the conjugations. Other possible major transformations can
occur by hydrolysis, oxidation/reductions, or the breaking of unstable
bonds. The absorption, distribution, and metabolic fate of the chemical
determine the potential quantity and identity of pesticide residues in
plants used for food or feed.
Chloramben movement into plants is a passive diffusion process and does not
require metabolic energy (Stoller, 1969, 0538). Chloramben that enters the
plant tissue undergoes a conversion to N-glucosyl chloramben (Swanson,
1966, 0169; Frear, 1978, 0556; Colby, 1965, 0553). Formation of N-^lucosyl
chloramben is related to the carbohydrate content of the plant. Soybeans
depleted of carbohydrate reserves absorb less chloramben and produce less N-
glucosyl chloramben than do plants under normal illumination (Swanson,
1969, 0538). N-glucosyl chloramben is not phytotoxic while chloramben is.
The "resistant" plants such as soybean or morning glory have an efficient
glycosylation system in their tissues. The "susceptible" plants (e.g.
velvet leaf) do not have an efficient glycosylation system and chloramben
accumulates to exert its phytotoxic effect (Stoller, 1969, 0538).
In addition to the glycosylation reaction, the decarboxylation type of
reactions have also been reported. Thus soybean roots when treated with
* C chloramben (with CCOH) evolve CO, (Anchem, nd, 0127).
Carrots planted in chloramben treated soil absorb,chloramben. Carrot
slices when incubated with C chloramben evolve CO- (Ashton, 1966,
0548). Attempts to find possible degradation products of chloramben, viz.,
2,5-dichloroaniline and 2,5-dichlorophenol in lima bjeans, peppers, sweet
potatoes, peanuts and soybeans (Amchem 1963, 0008; 1965, 0076; 1961, 0079;
1963, 0098; 1963, 0106; 1961, 0159; 1964, 0161; 1963, 0162; 1963, 0163;
1964, 0164) grown on cnloramben treated soil were not successful.
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Pre-emergent Treatment
The movement of chloramben in the plants shows a unique pattern. Soybeans
placed in ^ C chloramben solution take up chlorainben through their
roots. Radioautography of these plants revealed very little upward
movement of chloramben (Amchem, 1960, 0127). On the other hand, barley,
which is susceptible to chloramben, transports chloramben into the upper
parts of the plant easily (Amchem, I960, 0127). The behavior of the root
system may be important, together with glycosylation, in determining
whether a particular species is susceptible or resistant to chloramben.
14
Soybeans grown in soil treated with C chloramben accumulate
chloramben. Plants that had barely emerged fron soil contained 23 ppm and
50 ppm of chloramben for a 3 Ibs/A and 6 Ibs/A application respectively
(Amchem, 1961, 0154) .
These levels decreased markedly with time to as low as 3.5 percent of the ^
initial level after 56 days. Chloramben that had entered the plant was
stored predoninantly as. a conjugate. No detectable amount of chloramben
was found in mature seeds. Glycosylation cannot be involved in this
decrease, as radiolabel would remain. Metabolic decarboxylation does not
seemingly proceed fast enough to account for the decrease.
Post Emergent Treatment
Though chloramben is used pricipally as a herbicide in pre-emergent
applications, some studies have been made to investigate the effects of
foliar or post emergence application, mainly with a view to find out the
sites where chloramben would accumulate at maturity. Soybean plants grown
under greenhouse conditions were applied with C chloranben at a rate of
9 Ibs/A on the surface of leaves. The accumulation of C was studied in
the various parts of the plant at harvest. The seeds contained the least
amount of radioactivity (16 cpm) as compared with leaves, stems, and roots
(279, 1253, 740 cpn respectively) (Amchem, 1961, 0104; 1961, 0157). The
direction of movement was downwards from the leaves to the roots. When
chloramben was applied post emergent to soybean plants 104-132 days before
harvest at a rate of 3 lbs/Af neither soybean seeds nor hay showed
chloramben residues higher than 0.1 ppm (Anchem, 1978, 0101).
c. Metabolism in Animals
The identity of residues in animal products used for food may, as with
plants, be largely determined by the metabolic fate of the chemical in the
living organism. Livestock or poultry may ingest chemicals through treated
feed or forage. Gastrointestinal absorption, biotransformation, and. body
distribution are usually studied by the feeding of animals with the
unlabeled or radiolabeled chemical. The degree to which the parent
cattpound and its plant metabolites are absorbed or excreted can often vary
with the forage or fodder crop on which the chemical was administered, and
so actual feeding practices are usually approximated. Residues in excreta,
bleed, milk, eggs, or tissue are then measured and characterized.
The majority of crop residue data on raw agricultural commodities
(RAC)indicate that detectable residues would not occur in the feed items..
Since detectable residues are not expected to occur in feed items
metabolism data are not required.
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Studies have been submitted which provide insight into the metabolism of
chloramben in animals. In order to find out the fate of chloramben in
animals, an experiment was conducted where a cow was given chloramben (at 5
pan level) in feed (St. John Jr., 1970, 0577). Milk, urine, and feces were
analyzed for chloramben content. Eighty-eight and one-half percent of the
chloramben was excreted in the urine and 4.6 percent in the feces, and no
trace was found in the milk.
Similar experiments in dogs have yielded similar results. Two dogs kept on
a diet of 0.5 mg chloramben per kilogram body weight per day, six days per
week, for four weeks, showed no detectable levels of chloramben (less than
0.01 ppm) in any of their tissues, including fat (Amchem, 1967, 0085).
Chloramben levels in feces and urine were measured on pooled samples for
each dog for the last week of the study. These levels were consistent with
excretion of the major part of the ingested chloramben. These data
indicate that no more than 0.2 percent of total administered chloramben are
retained in canine tissues after a 28-day experiment.
The data discussed above, on residues of chloramben in animal tissues/ are
inadequate in that an inadequate number of animals were studied. There are
no data on residues of chloramben in poultry and eggs. The data available
on bovine metabolism leaves in doubt the fate of approximately seven
percent of the fed chloramben.
d. Analytical Methods
There must be available, before a tolerance may be granted, practicable
analytical methods for the detection and measurement of the residue and its
metabolites. Every commodity considered for a tolerance must have some
applicable method. Such methods are often published and widely used;
others may involve adaptions of common analytical procedures. In general,
any analytical method suggested for consideration must be characterized in
four ways: first, there should be some assurance as to the efficiency of
the extraction procedure, so that the analysis is not carried out on
partial samples; second, the method should afford a measure of the 'total
toxic residue', including toxic degradation, metabolic, or other conversion
products; third, the method must be thoroughly validated by analyses of
representative samples in comparison to blank values significantly lower
than the proposed tolerance and; fourth, the validation should conclude
with an estimate of sensitivity/ i.e./ the least concentration of pesticide
which can be detected with a reasonable degree of assurance.
At least one method must be suitable as a regulatory enforcement method, in
that it does not require the use of untreated crop samples for blanks, that
it is rapid/ that it makes use of commonly available equipment and
reagents, and that it is sufficiently specific to identify and measure a
specific pesticide in the presence of other residues likely to occur on the
same commodity.
Method of Analysis of Chloramben
Since chloramben is evidently present in a conjugated form/ alkaline
hydrolysis is necessary to free all the bound chloramben (Amchem/ 1963,
0158). Two methods have been used for chloramben determinations, one a
colorimetric method and the other involving gas liquid chromatography. The
6-5
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colorimetric method involves a diazotizaticn and coupling of chloramben to
N-(l-naphthyi)ethylene diamine dihydrochloride (Amchem, 1964, 0077; 1964,
0107) or to 1-naphthol (Amchem, 1978, 0057), after which the optical
absorbance is measured in a spectrophotcmeter. The gas chronatographic
method involves conversion of chloramben to the methyl ester form, which is
quantitated in the gas chrcmatograph (Amchem, 1978, 0057; 1968, 0085; 196?,
0166; 196?, 0167). Further details of these methods are given:
Colorimetric Method
Fifty gram portions of sample are reduced to a fine paste with methanol in
a blender. The mixture is warmed on a steam bath after adding sodium
hydroxide to hydrolyse chloramben conjugates. The mixture is filtered and
the filtrate made strongly acid, and extracted with ethyl ether. The
ethereal layer is in turn extracted into an aqueous alkaline solution,
which is then made strongly acid and again extracted into ethyl ether. The
ether layer is separated and evaporated to dryness. The residue is
refluxed with methanol and sulfuric acid to esterify all chloramben free
acid. Water and toluene are added; all ester is dissolved in the toluene
layer, which undergoes a conventional Florisil clean-up. The methyl
chloramben is eluted in the 15 percent ethyl ether-hexane fraction. After
evaporation of all the solvent the ester is diazotized (sodium nitrite-
acid, then ammonium sulfonate solution) and coupled with N-(l-naphthyl)-
ethylene diamine dihydrochloride. The color intensity is measured at the
absorption maximum (approximately 528 nm).
The method is sensitive to 0.1 ppm (three times background signal) and
gives recoveries of 70^-100 percent. It has been validated for pepper, dry
beans, punpkins, squash, sweet potatoes, corn, and peanuts.
This method is not suitable for enforcement purposes because it
necessitates the use of a "blank", i.e. carrying a sample through the
analytical procedure for comparison with the crop sample of interest.
Gas Chrcraatographic Method
Twenty-five gram portions of sample are finely ground in a blender and
refluxed with raethanolic sodium hydroxide to hydrolyse conjugated
chloramben.- The mixture is filtered (after centrifugation if necessary) ,
water is added, and the solution is evaporated. Addition of water and
evaporation is repeated until all methanol is eliminated. The pH is
brought to 1.0 and the solution is extracted with diethyl ether. The ether
is in turn extracted by an aqueous phosphate buffer (pH 5.8). The aqueous
layer is acidified to pH 1 and again the ether extraction is carried out.
Chloramben in the ether layer is esterified with diazcmethane to the methyl
ester,- and the solution of methyl chloramben is concentrated to exact low
volume (0.5 ml or 1.0 ml). This solution is used for injection into a gas
chrgnatograph, fitted with a 6 foot 3 percent Carbowax 20M column at
230 •. The recommended detector is a micrccoulometric detector used in
the halogen mode. Alternatively, an electron capture detector may be
used. Detention time is about 15 to 20 minutes (50 ml nitrogen carrier gas
per minute). If a 5 ft. x 1/8 in. 5 percent QF-1 column at 200
isothermal is used, the retention time of the methyl ester is about 5
minutes.
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The lower sensitivity (three times background) of this method is about 10
nanograms of methyl ester, which corresponds to 10 ppb chloramben in the
original sample. The method has been validated for lima beans, soybeans
and soybean forage, peanuts, corn and corn silage, and navy beans.
This method is suitable for enforcement purposes, as it has adequate
sensitivity, precision, and specificity, and does not require the use of a
"method blank". It is capable of further improvement, however, notably in
speed and efficiency of extraction of residues from plant materials.
e. Residue Data
In addition to provisions for analytical methodology, a second prerequisite
to the granting of tolerances is the generation of supporting data.
Residue experiments generally consist of:
1) Data about the stability of extracted residues under storage;
2) An examination of raw consumable commodities for residues of the
pesticide chemical after treatment corresponding to the proposed
uses.
Residue data generally disclose: the nature of the residue (i.e., parent
compound or transformation product); the level of the residue as it occurs
in the whole raw agricultural commodity, the commodity being in the form in
which it moves in interstate commerce; the distribution of the residue in
the processing of the commodity for consumption, including washing,
brushing, trimming, curing, drying, cooking, or canning. Some data may be
available comparing various methods for the intentional removal of
residues. Residue data can be obtained by field experiments, by animal
treatment studies, by soil persistence studies, or by the monitoring of
actual residues in marketed food or feed products, by which tolerances can
be enforced or reassessed.
Soybeans
The recommended application rate for soybeans is 2-3 Ibs/acre. Soybean
plants of Harosoy variety treated with chloramben at 4 and 8 Ibs/acre pre-
emergent, did not show more than 0.1 ppm of chloramben residues in the
mature beans (Amchem, 1965, 0071).
Soybeans of Clark 63 variety treated with cloramben pre-emergent at the
rate of 6 Ibs/A and harvested after an interval of 110 days showed a
residue content of less than 0.04 ppm in the mature beans. ' (Amchem, 1968,
0084)
When chlorambRn was applied (1.5-2.0 Ibs/A) as a mixture with vernam TE (2
Ibs/A) pre-emergent, the residue levels in soybeans from three locations
representing two varieties (Wbodviorth, Williams) were less than 0.02 ppm
whether bean or forage was analyzed. (Amchem, 1979, 0041)
Soybeans of the "Hill" variety were treated with a liquid formulation of
chloramben at a rate of-4 or 8 Ibs per acre. Analysis of soybeans at
maturity showed a residue content of less than 0.1 ppm for both rates of
application. (Amchem, 1967, 0044)
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Five varieties of mature soybeans (Clements, 2msoy, Wayne, Beeson,
Williams) from five field experiments were analyzed for residues of
trifluralin and chloramben, by gas field chromatography. In these tests,
trifluralin and chloramben r*ere applied as a pre-emergent tank mix
combination at 1-2 and 2.5-5.0 Ibs/A, respectively. Residues of chloramben
ranging from 0.02-0.06 ppm were measured in three samples while no
detectable residues were found in the two remaining samples. (Amchem,
1978, 0050)
Samples of soybeans and soybean plants from either locations representing
six varieties (Amsoy, Adelphia, Corsoy. Lee, Dare, Hill) were treated with
a formulated mixture of sodium salt of chloramben plus Lorax (N-3,4-
dichlorophenyl-N-1-methoxy—N-l methyl urea). Plants were treated at a rate
of 1 1/2 Ibs. of chloramben plus 1/2 Ib. of Lorax per acre and also at
twice this rate. Chloramben content was determined by gas liquid
chromatography. No residues of chloramben greater than 0.1 ppm were found
in soybeans or soybean forage. The samples taken at a very early harvest
(38 days after treatment) as well as samples treated at twice the normal
rate also showed no chloramben residues greater than 0.1 ppm. (Amchem,
1978, 0057)
Soybean and soybean hay samples from six locations were analyzed for
chloramben residues resulting from post emergence treatment with chloramben
(3 Ibs/A, 104 to 132 days prior to harvest). None of the treated or
control samples showed residues of chloramben greater than 0.1 ppm when
analyzed by a gas-liquid chromatographic method. The recovery of
chloramben from fortified samples ranged from 70 percent to 108 percent
with an average of 87 percent. (Amchem, 1978, 0101)
14
In.a greenhouse study soybean seedlings were treated with chloramben C
( C in the carboxyl group) on the leaf surface at a rate of 9 Ibs/A.
The plants were allowed to grow to maturity. The leaves were collected
upon abscission.
14
At harvest roots, stems, pods, and seeds were analyzed for C content.
The seeds showed the least amount of radioactivity, while the stems and
roots contained the bulk of radioactivity. (Amchem, 1961, 0104)
Nine sets of samples from nine locations representing eight varieties of
soybeans (Lee 68, Adelphia, XK505, Wells, Williams, Ansoy 71, Ansoy,
Chippewa 64) treated with 3 Ibs. of active ingredient of chloramben per
acre, were analyzed for chloramben and trifluralin residues. None of the
samples showed any residue of chloramben greater than 0.1 ppm nor any
residue of trifluralin greater than 0.05 ppm. (Amchem, 1975, 0109A)
In another study, four sets of samples from four locations representing
four varieties of soybeans treated with 1 1/2 to 3 Ibs. of active
ingredient of chloramben per acre in combination with another herbicide
failed to show chloramben residue greater than 0.1 ppm. (Amchem, 1975,
0109A)
Neither of two sets of samples (XK505 and Harosoy) from two locations,
treated with 1.5 Ibs. plus 1.5 Ibs. active ingredient of chloramben per
acre, nor a sample (Ansoy 71) treated with 3 Ibs. of active ingredient of
chloramben showed a residue content higher than 0.1 ppm on analysis.
(Amchem, 1975, 0109A)
6-8
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Three varieties of soybeans (Hill, Clark 63, and Amsoy) at five locations
were treated with both liquid and granular formulations containing nixed
amine salt of chloramben, at a rate of 3 and 6 Ibs. per acre. Mature
beans, immature beans and pods, immature plant or whole plant were all
analyzed for chloramben content and no residue greater than 0.1 ppm was
detected. (Mchem, 1967, 0120)
Ten varieties of soybeans (Clay, Corsoy, Clark 63, Swift, Harosoy 63,
Wayne, Amsoy 71, Teweles 304, Woodworth, Williams) in 14 locations were
treated with- chloramben as a tank mix with alochlor at rates ranging from 2-
3.3 Ibs. of chloramben per acre. None of the treated samples showed
residues of chloramben equal to or greater than 0.1 ppm. (Amchem, 1976,
0118)
The chloramben content of de-oiled soybean cake and soybean oil from mature
soybeans representing four varieties (Harosoy, Lindarin, Hill, and Lee)
treated with chloramben at 8-9 Ibs. per acre were analyzed. Except for one
instance of Lindarin soybean cake showing a chloramben content of less than
0.2 ppm, no residue was found in other samples. (Amchem, 1961, 0135)
14
Soybean plants treated pre-emergent with C labeled chloramben at 3 and
6 Ibs. per acre and grown under greenhouse conditions showed very little
chloramben in the bean pods as compared with the other parts of the plant
which contained the bulk of chloramben. At a chloramben application rate
of 3 Ibs. per acre, 0.1 ppm was present in bean pods. The upper, middle,
and lower thirds of the plant contained 0.47, 0.89, and 1.39 ppm,
respectively. When the application rate was 6 Ibs. per acre, the bean pods
showed a residue content of 0.2 ppm. The upper, middle, and lower thirds
of the plants showed a residue content of 0.87, 2.72, and 5.32 ppm,
respectively. (Amchem, 1961, 0136)
In general, residues of chloramben in soybeans are below tolerance levels.
Peanuts
Peanuts of the "Starr" variety from five locations were treated with a
liquid formulation of chloramben at a rate of 6 Ibs/acre (twice the
recommended rate) 18, 72, 95, 141, and 179 days before harvest, and the
residue content of peanuts was analyzed. All the samples that had received
treatment 72 to 179 days before harvest, showed residues less than 0.1 ppm.
The samples that were harvested 18 days after treatment with chloramben
showed a residue content of 0.43 ppm. (Smchem, 1967, 0044)
Peanut plants treated with chloramben at 6 Ibs/acre (twice the recommended
rate) were harvested and the presence of 2,5-dichloraniline, a possible
metabolite of chloramben arising through a decarboxylation reaction, was
measured in the peanut hulls and meat. The method used was sensitive to
0.1 ppm and no traces of 2,5-dichloraniline was found in the hulls or the
meat portion of peanuts. (Amchem, 1965, 0076)
Analysis of peanut hulls, foliage, and nuts collected 95-151 days after
treatment did not show-any residue of chloramben. Foliage collected 72
days after treatment had less than 0.1 ppm residue. Foliage collected 18
days after treatment showed 0.42 ppm. (Amchem, 1965 estimated, 0077)
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Peanuts of the "Starr" variety when treated at the rate of 6 Ibs/acre with
chloramben 101 days before harvest showed a residue content of less than
0.4 pern. (Arnchem", 1968, 0084)
Peanuts of "Spanhorima", "Starr", and "Spancross" varieties in three
locations were treated with chloramben at the rate of 3 Ibs/acre 138, 112,
and 162 days before harvest. The residue content of the harvested peanust
was less than 0.1 ppra. (Amchem, 1975, 0109A)
These data indicate that peanuts treated with reccnmended levels of
chloramben are not likely to contain residues above tolerance levels.
Peppers
The recommended rate of application is 4 Ibs/acre. Peppers of four
varieties (Yellow Wonderr World Beater, California Wonder, Delaware Bell)
in three locations were treated at 4-16 Ibs/acre 50 to 81 days before
harvest. In all cases the harvest peppers contained less than 0.1 ppm of
chloramben residue. (Amchem, 1967, 0044)
Chloramben treated peppers showed less than 0.1 ppm of 2,5-dichloroaniline,
a potential metabolite of chloramben arising from decarboxvlation. (Bois,
1964, 0093)
Peppers of five varieties (California Wonder, Bell, Cannoe, Keysonte
Resistant Giant, Yellow Wonder) on eight locations were treated with
chloramben at the rate of 4 Ibs/acre 36, 47, 51, 52, 59, 60, 68, and 77
days before harvest. All the peppers analyzed showed residues less than
0.1 ppm. (Amchem, 1975, 0109A)
Yellow Wonder peppers and World Beater peppers were treated with 11 and 16
Ibs/acre respectively and no traces of 2,5-dichloroaniline was found using
a method sensitive to 0.1 ppm. (Amchem, 1963, 0162) In another study'
Yellow Wonder and World Beater peppers were treated with chloramben at
rates of 8 and 16 Ibs/acre and were harvested in two batches one after 50
days of treatment and the other after 70 days of treatment. Analysis of
the peppers showed less than 0.1 ppm chloramben residues in all the cases
irrespective of dosage or the interval elapsed before harvest. (Amchem,
1964, 0008)
These data indicate that chloramben residues in peppers will not be above
the tolerance level when treated at the recommended rate.
Tomatoes
The recommended application rate is 4 Ib/acre. Five varieties of tomatoes
were treated with chloramben at rates ranging from 6 to 16 Ibs/acre. The ^
residue content of immature green, mature green, and mature red tomatoes
was not greater than 0.1 ppm in all cases (Amchem, 1967, 0044).
Chloramben residues ranged from 0.03 to 0.05 ppm in tomatoes treated at a
rate of 4 Ibs/acre. When the application rate was 8 Ibs/acre the residue
levels ranged from 0.05 to 0.14 ppm. (Amchem, 1963, 0106)
Tomatoes of "Heinz 1439", "Campbell 28", "Marglobe", and "Heinz 1327"
showed chloramben residue content of less than 0.1 ppm in the mature fruit,
6-10
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when the plants had been treated at 4 Ibs/acre. The time elapsed frcm
treatnent to harvest ranged frcm 25 to 112 days in these studies. (Amchem,
1975, 0109A)
In a laboratory radiotracer study, pure chlorainben labeled in the carboxyl
group with C was used on tomatoes grown under greenhouse conditions.
Chloramben was used at rates equivalent to 3 or 6 Ibs/acre, 63 days before
harvest. At an application rate of 3 Ibs/acre the fruits contained
residues of 0.06 ppm but at 6 Ibs/acre the residues were 0.15 ppm. Plants
that have received treatnent at layby (22 days before harvest) of 6
Ibs/acre showed a residue content of 0.52 ppm in the fruits (Amchem, 1963,
0102). Treatnent of tomatoes under actual field conditions will not, in
all probability, occur at less than 60 days before harvest.
In general, the data indicate that residue levels in tomatoes will not
exceed tolerances.
Lima Beans
The recommended rate of application is 2-4 Ibs/acre. Lima beans from five
locations that had been treated with chloramben at the rate of 6 Ibs/acre
ranging from 73-98 days before harvest, showed less than 0,1 ppm of
chloramben residues. (Amchem, 1967, 0044)
Lijna beans from two locations where chloramben was applied at twice the
recommended rate showed no residue of 2,5-dichloroaniline, a potential
metabolite that arises from decarboxylation of chloramben. (Amchem, 1963,
0098)
In a radiotracer study lima beans grown in a greenhouse were treated with
C- labeled chloramben at the rate of 3 and 6 Ibs/acre. Analysis of the
mature bean showed a residue content of 0.03 ppm when the recommended rate
of 3 Ibs/acre was employed. At the exaggerated level of 6 Ibs/acre the
residue content was 0.09 ppm. The immature beans showed a residue content
of 0.08 ppm at 3 Ibs/acre rate and 0.22 ppm at 6 Ibs/acre rate of
application. (Amchem, 1963, 0108)
Lima beans from four locations representing four varieties (Mibres,
Bridgeton, Thergreen, Fordhook Bush) treated at rates.of 3-4 Ibs/acre, 70-
94 days before harvest failed to show chloramben residues greater than 0.1
ppm. (Amchem, 1975, 0109A)
In summary, recommended application rates of chloramben on lima beans
result in residues below the tolerance limit.
6-11
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The recommended rate of application is 2 Ibs/acre. Corn plants were
treated at 3 Ibs/acre and 9 Ibs/acre. The com at tassel stage and
immature ears were harvested after 41, 66, and 101 days, respectively after
chloramben treatment and on analysis showed less than 0.1 ppm of chloramben
residues. (Amchem, 1967, 0044) ~At a dosage of 4 Ibs/acre and 16 Ibs/acre
treatment, the silage, mature corn kernels and mature corn cob (84, 119,
119 days after treatment, respectively) showed no greater than 0.1 ppm of
chloramben. (Amchem, 1967^0044) Corn treated at 2 and 6 Ibs/acre and
harvested after 139 or 190 days showed a residue content less than 0.1
ppm. (Amchem, 1967, 0044)
Mo residues were found in silage, corn kernels, or corn cobs harvested from
different locations that had been treated as high as 16 Ibs/acre (eight
times the recommended rate). (Amchem, 1965 estimated, 0080) Analysis for
the potential metabolite 2,5-dichloraniline was conducted on silage and
kernels collected from the 16 Ibs/acre treatments and no traces of this
material were found. .(Amchem, 1965 estimated, 0080)
Corns of different varieties treated with chloramben at 1.5 to 2 Ibs/acre
or in combination with atrazine, did not show residues greater than 0.1 pm
in corn (samples consist of silage, immature ears, immature whole plant and
whole plant). (Amchem, 1975, 0109A) Corn samples from four different
locations representing four varieties of corn (PAG 5X7.- Pioneer 3206 and
Agway 800, McCurdy 95) that had been treated with a formulation of
chloramben plus atrazine 1+2 Ib/A or 2+4.1b/A were analyzed and no residue
of chloramben greater than 0.1 ppm was found. The atrazine levels were
less than 0.25 ppm in the same samples. (Hazleton Labs, 1969, 0110)
These data indicate that residues below tolerances are found in corn
treated in accordance with label recommendations.
Sweet Potatoes
The recommended rate of application is 4 Ibs/acre. Sweet potatoes of
"Georgia Red" and "Tenhoma" varieties treated with a liquid formulation of
chloramben at the rate of 4 or 8 Ibs/acre 145-197 days before harvest did
not show chloramben residue content greater than 0.1 ppm (Amchem, 1967,
0044).
Use of either liquid or granular formulations of chloramben at the rate of
6 Ibs/acre 111 days before harvest did not show a chloramben residue more
than 0.1 ppm. Sweet potatoes of "Nemagold" variety were treated with
granular or liquid formulation of chloramben at rates of 8 Ibs/acre (or 9
Ibs/acre in one case) did not show residues greater than 0.1 ppm (Amchem,
1967, 0044).
Sweet potatoes of "Centennial" variety when treated with a liquid
formulation of chloramben at 6 or 32 Ibs/acre 117 days before harvest
showed no residues of chloramben greater than 0.1 ppm (Amchem, 1967, 0044).
In a rate of disappearance study sweet potatoes of the "Nemagold" and
"Yellow Sweet Potato" variety were treated with a liquid formulation of
chloramben at 16 Ibs/acre. Analysis of yellow sweet potatoes harvested at
6-12
-------
three stages very immature (56 days after treatment), immature (97 days
after treatment), and mature potatoes (124 days after treatment) showed
residues contents of 2.5 pan, 0.25 ppm, and less than 0.1 ppm,
respectively. Analysis of the "Nemagold" variety at very immature (61
days), immature (79 days) and mature (111 days) stages showed a residue
content of 0.11 ppm, less than 0.1 ppm, and less than 0.1 ppm, respectively
(Amchem, 1967, 0044).
Sweet potatoes treated at the exaggerated levels of 32 Ibs/acre did not
show any residue of 2,5-dichloroaniline, a potential metabolite of
chloramben (Amchem, 1965 estimated, 0078).
Two varieties of sweet potatoes ("Centennial" and "Yellow") from four
locations treated at 4 Ibs/acre 116-125 days before harvest did not show
more than 0.1 ppm of chloramben residues (Amchem, 1975, 0109A).
Residues of less than the tolerance level occur in sweet potatoes treated
at the recommended application rate.
Pumpkin, Squash
The recommended rate is 2-4 Ibs/acre. In a rate of disappearance study
squash of "Crcokneck" variety were treated at 8-12 Ibs/acre and the squash
vines, immature fruit, mature fruit (early harvest), and mature fruit (late
harvest) were analyzed for chloramben residue content. All the samples
showed less than 0.1 ppm residue (Amchem, 1967, 0044).
Seven squash varieties (Table Queen, Buttercup, Butter Nut, Yellowneck,
Green Hubbard, Boston Marrow, Zucchini) from seven locations were treated
at the rate of 8 Ibs/acre with a granular formulation of chloramben and
harvested after 100-144 days of treatment. In all the cases the chloramben
residue content was less than 0.1 ppm (Amchem, 1967, 0044).
Pumpkins of the type "Big Tom" and "Small Sugar", treated at the rate of 8
Ibs/acre 100-104 days before harvest did not show any chloramben residue
greater than 0.1 ppm. "Kentucky Field" pumpkins when treated with a
granular formulation of chloramben at the rate of 3 Ibs/acre 119 days
before harvest showed residues less than 0.1 ppm (Amchem, 1967, 0044).
Pumpkins of the Jack-o-Lantern variety showed less than 0.04 ppm of
chloramben .residues when treated with chloramben at 6 Ibs/acre 111 days
before harvest (Amchem, 1968, 0084).
Squash of four varieties, (Butternut, Golden Summer Crcokneck, Yellow
Crcokneck, Golden Hubbard) from six locations treated with chlcramben at a
rate of 2 to 4 Ibs/acre 53-90 days before harvest failed to show chloramben
residues greater than 0.05 ppm (Amchem, nd, 0109).
Using a method sensitive to 0.1 ppm, no trace of 2,5-dichloroaniline, free
or bound was found in Big Tom pumpkin, Acorn squash, and Zucchini treated
at twice the recommended rate of chloramben (Amchem, 1964, 0164).
These data show chloramben applied at the recommended rate gives residues
below the tolerance limit for pumpkin and squash.
6-13
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Dry Beans and Snap Beans
The recommended rate of application is 2-3 Ibs/acre. Beans of.five
varieties (Red Kidney, Pinto, Pinto U.I. Ill, Navy Beans, great Northern)
treated with a liquid formulation of chloramben at rates of 3-8 Ibs/acre
showed no chloramben residues higher than 0.1 pan (Amchem, 1967, 0044).
Navy beans of the "Gratiot" variety treated with chloramben at the rate of
3 Ibs/acre showed a chloramben residue content of less than 0.04 ppm
(Ainchem, 1968, 0084).
Chloramben treated dry beans showed less than 0.1 ppm of 2,5-
dichloroaniline, a potential metabolite of chloramben (Amchem, 1964,
0093).
"Great Northern" dry beans treated with chloramben at the rate of 4
Ibs/acre and "Pinto" dry beans treated at the rate of 8 Ibs/acre failed to
show 2,5-dichloraniline higher than 0.1 ppm using a method sensitive to 0.1
ppm (Menem, 1963, 0008).
Beans of different types treated with chloramben at different rates ("Great
"Northern" 3-4 Ibs/acre, "Red Kidney" 3 Ibs/acre, "Navy" 2 Ibs/acre,
"Pinto" 3-8 Ibs/acre) did not show a residue of chloramben higher than 0.1
ppm (Amchem, 1964, 0096).
Four varieties of snap beans (Tender Pot, Black Valentine Bush, Blue lake,
Tender Crop Gal Val 50). from four locations treated with chloramben at the
rate of 4-8 Ibs/acre 52-98 days before harvest, showed chloramben residues
less than 0.1 ppm (Amchem, 1968, 0149).
These data show that residues below tolerances result from use of
chloramben on "dry" beans and snap beans.
Cucumber
The recommended rate of application is 2-3 Ibs/A. Three varieties of
cucumbers (Crispy Formula 58, Burpee Pickler, Sunnybrcok Slicer) treated
with chloramben at the rate of 2 to 8 Ibs/acre 69-71 days before harvest
did not show chloramben residues greater than 0.1 pan in the fruit
(Anchera, 1968, 0149).
Melons
The recommended rate of application is 2-3 Ibs/A. Musk melon ("Samson
Hybrid"), watermelon ("Sugar Baby") and cantaloupe (Bale's Best Jumbo)
treated at 8, 6 and 6 Ibs/acre, respectively, showed no detectable
chloramben residues in the fruit (Amchem, 1968, 0149).
Sunflower
The recommended rate of application is 2-3 Ibs. per acre.
Sunflower plants (Peredovik, Sun Hybrid 304, and an unknown variety) were
treated with a Chloramben/trifluralin tank mix (3 Ibs/acre chloramben plus
6-14
-------
1 Ib/acre trifluralin) 122 to 135 days before harvest. The whole seeds on
analysis contained less than 0.01 ppm of chloramben and less than 0.05 pan
of trifluralin (Amchem, 1979, 0100).
Adequacy of Residue Data
Several crops which may be treated with chloramben are further processed
after harvesting, in the course of which may occur a concentration of any
residues of chloramben. These comprise tomatoes (to tomatoe pastes and
purees), soybean (to soybean oil), peanuts (to peanut oil)/ sunflowers (to
sunflower oil), and corn (to corn oil) .
Available crop residue data on tomatoes, soybeans, peanuts, and sunflowers
indicate that, in general, residues do not occur at detectable levels on
the raw agricultural commodities at harvest. Therefore, processing studies
are not required.
Residues in Meat, Milk, Poultry, and Eggs
For this Section, data should show whether residues will result in meat
(muscle, liver, kidney, fat), poultry, eggs, or milk. The toxicant fed
should correspond to the aged residues found in the item of feed, which may
or may not be the parent pesticide. The studies should be performed at
several dosage levels, including exaggerated dosages, preferably threefold
and tenfold.
The bulk of residue data on raw agricultural commodities (RAC) indicate
residues below tolerance levels. Since data indicate that residues are
present below the level of detection, feeding studies are not required.
4. Dietary Exposure
The exposure of humans to pesticide residues from registered use via the
food chain is a function of several factors:
a) The established tolerance for a commodity (in ppm)
b) The percentage of a commodity in the daily diet.
c) The percent of that commodity that is treated with the pesticide (an
adjustment factor for total population exposure).
d) The assumed amount of food consumption by an average person, 1.5 kg
per day.
e) The assumed body weight of an average person, which is 60 kg.
When these factors are substituted into a formula (i.e, (axbxcxd)
divided by e), the human exposure to those pesticide residues in a
commodity is found in terms of mg of pesticide per kg of body weight per
day.
This potential daily exposure is compared with an 'Allowable Daily Intake1 ,
which is set on the basis of toxicological 'No Observable Effect Level1 ,
plus a margin of safety factor of lOOx, to allow for a lOx greater
sensitivity of humans-over test animals, and to allow for the possibility
of an individual who is lOx more sensitive than the average person. In
order to determine the 'No Observable Effect Level' for a pesticide
chemical, the Agency must have adequate acute and chronic studies.
6-15
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The estimates of human dietary exposure to chloramben are presented in
Table 5-1 and are based on tolerance levels. The data indiate that dietary
exposures to chloramben will range from less than .0005 to 0.013 mg/day
(0.000008 to 0.00022 mgAg body weight). Annual dietary exposure is then
estimated at from less than 0.16 to 4.7 mg/person. The maximum value
reflects the possibility that a person's diet includes all chloramben-
treated crops, when in actuality this is unlikely to occur. Chloramben is
used on only seven percent of soybean crops, four percent of tomato crops,
thirteen percent of bean crops, three percent of peanut crops and less that
one percent of corn crops in the United States. The minimum values (or
adjusted values) in Table 5-1 reflect adjustments for these particular
crops.
C. Chloramben End-Use Formulations
1. Registration Requirements
There are no residue chemistry data required for the non-food use of
chloramben.
For future registration of a product for use on a food or feed crop not
covered by this Standard, the Agency must be provided with a petition for
tolerance, a full range of data including a validated method for analysis
of residues in or on the raw agricultural commodity, data on metabolism of
chloramben in plants and (when appropriate) in animals, and residue data
reflecting the proposed use of the pesticide on the crop.
6-16
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TABLE 6-1
DIETARY EXPOSURE TO CHLCRAMBEN
Tolerance
ppm
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
Food
Factor
0.92
2.87
0.19
1.00
0.36
0.31
0.52
0.73
0.12
0.11
0.98
0.11
0.03
0.40
Daily
Intake
mg/dav ma/dav
0.0014
0.0043
0.0003
0.0015
0.0005
0.0005
0.0008
0.0011
0.0002
0.0002
0.0015
0.0002
0.0001
0.0006
0.013
Adjusted
Dietary
Intake
0.0001
0.00015
0.00004
0.0000.2
0.00002
0.00006
o.oooni
0.00001
0.000002
0.000002
0.000002
0.000002
0.00001
0.00001
0.00045
Soybeans
Tomatoes
Lira Beans
Corn
Peanuts
Beans, Dry, Edible
Cantaloupe
Cucumbers
Peppers
Pumpkin
Beans, Snap
Squash
Sunflower
Sweet Potatoes
TOTAL
When data available, values based on percentage of sites treated with
chloramben. For site where percentage of treatment is unknown, one
percent is assumed.
6-17
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CHAPTER VII
TOXICOLOGY OF CHLORAMBEN PRODUCTS
A. Introduction
A wide range of chloramben products are currently registered for use.
Manufacturing-use products consist of sodium chloramben and methyl chloramben.
End-use formulations contain chloramben as the active ingredient/ present as
the sodium salt, ammonium salt, moncmethyl amuonium salt or methyl ester.
Toxicology testing is required for registration of all manufacturing-use
products and end-use formulations of chloramben. The majority of tests (acute
and chronic) are to be performed on the manufacturing-use product or the
technical grade of the active ingredient, if different. Acute toxicity testing
of all end-use formulations must also be conducted. For purposes of
extrapolating toxicology safety data, the sodium salt of chloramben has been
determined to be equivalent to chloramben (3-amino-2,5-dichlorobenzoic acid).
A summary report in Agency files indicates that the methyl ester of chloramben
hydrolyzes to chloramben acid, through microbial degradation, within days of
application to soil. Provided evidence is submitted documenting this reaction,
all data requirements associated with the food-use pattern of methyl chloramben
may be fulfilled through testing with chloramben acid or the sodium salt.
A potential RPAR (Rebuttable Presumption Against Registration) trigger study on
technical chloramben conducted by the National Cancer Institute (NCI) indicated
that chloramben administration resulted in hepatocellular carcinoma in female
mice. Three additional chronic feeding studies, employing a lower dose range j
than the NCI study do not indicate oncogenic potential. However, these studies
are of limited value for "measuring the oncogenic potential of chlpramben since
the MZD (Maximum Tolerated Dose) was not used. Available mutagenicity testing
is negative.
Toxicological data submitted to date are primarily on technical chloramben.
Some data have been submitted on sodium and methyl chloramben and end-use
formulations containing either methyl chloramben, ammonium chloramben, sodium
chloramben or an ammonium cnloramcen/moncmethyl amnonium chloramben mixture.
B. Chloramben Manufacturing-Use Products
1. Toxicology Profile
a. Sodium Chloramben
The Agency has determined that data .requirements for sodium chloramben may be
fulfilled by testing with technical chloramben (3-amino 2,5-dichloro benzoic
acid). The high acute oral LD5Q of 100% technical chloramben (5,620 mg/kg)
in male rats suggests a very low acute oral hazard to human beings. Gross *
pathologic changes included congested lungs, kidneys, and adrenals. Dermal
LD-0 values of 3,160 mg/kg and greater than 5 g/kg> respectively, for
7-1
-------
technical chloramben (100 percent purity) and sodium chloramben (85 percent
chloramben acid equivalent) administered to male and female albino rabbits
indicate a low potential for human dermal toxicity. Based on the LC5Q
determination of greater than 200 mg/1 (sodium chloramben) in male and female
rats, a low acute inhalation hazard is expected. Sodium chloramben may
irritate human eyes based on a primary eye irritation study in albino rabbits.
Mild to moderate conjunctival irritation persisting for 7 days was noted in
this study.
No subchronic dermal or feeding studies are available on either technical
chloramben or sodium chloramben. Two-year feeding of technical chloramben (97
percent purity) to male and female beagles did not result in any toxic
effects. Slight to slight-to-mcderate vacuolation of liver cells was noted in
3 of 8 dogs at the high dose level (10,000 ppm). The "No-Observed Effect
Level" (NOEL) for the study is 1,000 ppn (25 mgAg bcdy weight/day) .
A 1963 chronic feeding study in albino rats will not satisfy Agency
requirements because of insufficient test animals, a high incidence of non-
chloramben related mortality, disparity of animal weights, and limited
histopathological reporting. A 1979 chronic feeding study in rats reported
that chloramben in the diet at concentrations of 100, 1,000, and 10,000 ppm did
not cause any significant effect.
An oncogenic study on technical chloramben (90-95 percent purity) by the
National Cancer Institute concluded that chloramben was carcinogenic to female
mice, producing hepatocellular carcinoma. The Agency considers the NCI
Bioassay, although flawed, adequate for risk assessment. An eighteen month
oncogenic study of technical chloramben conducted by Huntingdon Research Center
concluded that chronic ingestion of the compound by O>1 mice did not result in
any compound-related tumors at dosages less than the maximum tolerated dose
(yfTD). Primary compound associated tissue alterations were confined to the
liver in all treated mice and were compatible with that observed in enzyme
induction. No dose-related trends in benign or malignant tumors were
identified in the 1979 chronic feeding study in rats discussed above. However,
the dosages employed in this study (100, 1,000, and 10,000 ppm) were also less
than the'MTD.
A sub-mammalian point mutation test (no metabolic activation) using technical
chloramben (90-99 percent purity) was not mutagenic to the test organisms.
Further rmtagenicity testing is required as are teratogenicity studies.
A very limited metabolic study indicated no retention of the compound in the
liver, kidney, muscle, fat, and blood of dogs fed chloramben. Residues in the
urine and feces were detected.
7-2
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b. Methyl Chlorainben
Although the acute toxicity properties of the methyl ester of chloramben are
expected to differ from those of the sodium salt, the effects of chronic
exposure as a result of food ingestion are similar based on the breakdown of
the methyl ester in soil to chloramben acid.
The methyl ester of chloramben has a higher acute toxicity than does either
technical chloramben or sodium chloramben. The acute oral LD-g value of
1,710 mg/kg following administration of the technical methyl ester to male rats
results in a Toxicity Category III designation, still indicating a generally
low acute oral toxicity hazard. Major necropsy findings include congestion of
the lungs, liver, kidney, and pancreas; pale-appearing spleen; and
gastrointestinal inflammation.
No other testing was conducted with the technical methyl ester of chloramben.
2. Human Risk Assessment Evaluation
a. Acute Exposure
The chloramben exposure profile (see Environmental Fate Chapter) reveals that
persons who handle, store or ship the manufacturing-use products sodium
chloramben and methyl chloramben will be exposed principally by the dermal
route. Without proper precautions, the compound may get in the eyes.
Based on the previous toxicological assessments, single exposure by the dermal
route will likely pose a low acute hazard. Single exposure to eyes may be
quite irritating based on primary eye irritation studies conducted with sodium
chloramben and methyl chloramben. Methyl chloramben appears to be greater
ocular irritant than sodium chloramben. Swallowing a lethal dose of sodium or
raethyl chloramben by accident seems unlikely based on the relatively high acute
oral LDe0 values resulting from administration of the two compounds to rats.
The acute inhalation toxicity hazard is also expected to be low based on the
available toxicology data.
Exposure to chloramben formulations during soil application will be principally
by the dermal route. Acute dermal testing with chloramben formulated products
to date indicates a low acute dermal hazard.
b. Chronic Exposure
A major concern regarding any potential long-term exposure in humans to a
pesticide product is the risk of developing delayed toxic effects, including
cancer. In order to assess this risk for chloramben exposure, the reported
conclusions of the National Cancer Institute (NCI) bioassasy of chloramben are
utilized. The NCI study concluded that administration of technical chloramben
resulted in hepatocellular carcinoma in female B6C3F1 mice. No other
oncogenic, mutagenic, reproductive or teratogenic effects were noted in
submitted studies.
7-3
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The only incidence data that lends itself to risk assessment through fitting a
mathematical ncdel is that of the female mice with liver hepatocellular
car cinema .
Female Mice-Liver Hepatocellular Carcinoma Incidence
Dose (ppm)
0 10,000 20,000
2/67 (0.03) 7/48 (0.15) 10/50 (0.20)
The dose-response relationship assumed in the analysis is that of the linear
multi-stage developed by Crump whereby
P(D) = l
and P is the response (incidence) and D is the dose.
The estimation of the parameter, q, by the maximum likelihood method yields the
following estimator of oncogenic risk:
qj- 1.05 x 10"5
The model utilized (Global 79) also provides the upper and lower confidence
limits for the additional risk. For a risk level of 1 x 10 °, the upper
confidence^ limit is estimated to be 1.59 x 10~ . The dose producing a risk
of 1 x 10~ and the average 95% confidence limit for this dose (the virtual
safe dose) are estimated to be .095 ppm and .060 ppm, respectively.
The estimation of the oncogenic risk parameter is tentative, however, given
that only two data points could be utilized.
i. Dietary Exposure
3y utilizing the risk parameter and determining the level of chloramben
expected in the diet, the lifetime probability of a cancer due to dietary
exposure can be calculated (P = qX) where X is the ppm in the diet. Table 7-1
gives the individual risks associated with ingestion of registered crops
treated with chloramben.
7-4
-------
As discussed in Chapter 6 (Residue Chemistry), the exposure of humans to
chloramben residues is a function of several factors:
a. the established tolerance of the crop (in ppm).
b. percentage of crop in the daily diet.
c. percent of crop treated with chloramben.
d. average consumption of crop per person per day.
e. weight of average person (60 kg).
The estimate of human dietary exposure to chloramben as presented in Table 5-1
is 0.00045 mg/day.
Lifetime average ppm in the diet is therefore .0003 ppm.
.00045 = .0003
1.5
TABLE 7-1
ONCCGENIC RISK ASSOCIATED WITH THE INGESTION OF CHLORAMBEN
Lifetime Probability or
Lifetime Average Estimator of Cancer Due to Ingesting
Product ppm in Diet Oncogenic Risk Chloramben
All chloramben
treated crops
3 x 10~4
1.05 x 10~5
3,15
x 10"9
ii. Non-Dietary Exposure
For applicator exposure, a dietary exposure equivalent is calculated for risk
assessment. Non-dietary exposure is calculated for the soluble/flowable
concentrate (refer to the discussion on non-dietary exposure in Chapter 5 -
Environmental Fate). The following assumptions from Chapter 5 are used in
deriving the occupational risk of chloramben exposure.
7-5
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1) Potential Exposure Routes and Absorption Data:
Formulation Activity
Worst Case
(ing/year)
Soluble or
Flowable
Concentrate
Mixing-Loading
(mixer-loader or
fanner/planter)
27.3
Ground Application 6.9
Best Case
(mg/year)
0.13
0.016
TOTAL:
34.2
0.146
2) A lifetime average pern exposure (as a dietary equivalent) is calculated
based on 40 years of exposure in a 70-year lifetime.
Worst Case Best Case
Soluble/Flowable Concentrate
0.052
0.0002
The following table gives the individual risks associated with application of
chloramben formulations based on a worst-case and best-case exposure level.
TABLE 7-2
CNCCGENIC RISK ASSOCIATED WITH THE CHLORAMBEN APPLICATIONS
Product
Lifetime Average
ppm Exposure
Estimator of
Oncogenic Risk
Lifetime Probability of
Cancer due to Chloramben
Application
(includes dietary)
Soluble/Flowable
Concentrate
Worst Case
Best Case
0.052
0.0002
1.05 x 1Q~1
1.05 x 10
5.46 x 10~g(5.49 x lo"Z)
2.10 x 10~*(5.15 x 10~y)
7-6
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3. Data Requirements and Data Gaps
•The following are toxicology data requirements for registration of
manufacturing-use products. Listed after each requirement is the section in
the Proposed Guidelines of August 22, 1978, (43 FR, No. 163 37336) that
describes the type of data required.
a. Food Use or Non-Food Use
All applicants, regardless of end-use, must submit or cite the following data;
Category of Test Guideline Number
Acute Oral Toxicity (rat) 163.31-1
Acute Dermal Toxicity (rabbit) 163.81-2
Acute Inhalation Toxicity (rat) 163.81-3
Primary Eye Irritation (rabbit) 163-81-4
or Demonstration of pH 1-3 or 12-14
or Demonstration of Dermal Irritation of Category I
Primary Dermal Irritation (rabbit) 163.81-5
Skin Sensitization (guinea pig) 163.81-6
Data Gaps
Sodium Chloramben
The following tests are required for the reregistration of manufacturing-use
sodium chloramben, regardless of its end-use:
Category of Test Guideline Number
Skin A skin sensitization test
Sensitization in the guinea pig is required 163.81-6
Methyl Chloramben
The following dataware required for the reregistration of manufacturing-use
methyl chloramben, regardless of its end-use:
Category of Test Guideline Number
Acute Oral The purity of the methyl
chloramben used in testing 163.81-1
male rats must be submitted.
Acute Dermal An acute dermal toxicity
Toxicity study, preferably in the
albino rabbit, is required. 163.81-2
7-7
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Acute Inhalation
Toxicity
Primary Eye
Irritation
Dermal Irritation
Sfcin
Sensitization
An acute inhalation study in
the rat is required.
A primary eye irritation test
in the albino rabbit is required
A dermal irritation test in the
albino rabbit is required.
A skin sensitization test
in the guinea pig is required.
163.81-3
163.81-4
163.81-5
163.81-6
b. Food Use (Requires a Tolerance or Exemption)
All applicants for registration or reregistration of technical chloramben
products which are formulated into end-use products intended for use on food
must submit or cite the following:
Category of Test
Subchronic Oral Toxicity
Subchronic 21-Day Dermal Toxicity.
Dermal Sensitization
Chronic Feeding
Oncogenicity
Teratology
Reproduction
Mutagenicity
Metabolism in Laboratory Animals..
Guideline Number
163.82-1
163.82-2
163.82-6
163.83-1
163.83-2
163.83-3
163.83-4
163.83-1 to 4
163.85-1
Data Gaps
Sodium Chloramben
The following tests are required for the reregistration of manufacturing-use
sodium chloramben intended for food use.
Subchronic
dermal toxicity
Chronic feeding
Onccgenicity
A 21-day dermal toxicity
study in the albino rabbit
is required. T63.82-2
The purity of chloramben used
in the 1979 chronic feeding
study must be supplied. 163.83-1
Compound purity must be
submitted for the 1979 rat
study and 1978 mouse study. 163.83-2
7-8
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Teratogenicity Teratogenicity testing in
two mammalian species is
required. 163.83-3
Reproduction Product purity is required
for the exisiting reproduction
study. 163.83-4
Mutagenicity A mammalian in vitro point
mutation test; a sensitive
sub-mammalian point mutation
test (with metabolic activa-
tion); a primary ENA damage
test; and a mammalian in vitro
cytcgenetics test are required. 163.84-1
Metabolism A general metabolism study
in'one mammalian species
is required. 163.85-1
Methyl Chloramben
Provided that evidence is submitted documenting the hydrolysis of the methyl
ester to chloramben acid after application to the soil, data requirements
associated with the food-use pattern of methyl chloramben may be fulfilled for
the most part through testing with chloramben acid or the sodium salt. The one
exception is that a general metabolism study on methyl chloramben must be
submitted. The data gaps detailed above for sodium chloramben pertaining to
food-use must be filled in order to allow reregistration of the methyl ester in
a food-use pattern.
c. Non-Food Use (Nondomestic, Outdoors)
All applicants for registration or reregistration of technical products which
are formulated into end-use products intended for non-food, nondomestic,
outdoor uses must submit or cite the following:
Data Gaps
Sodium Chloramben
Teratogenicity Teratogenicity testing
in two mammalian species
is required. 163.83-3
7-9
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Mutagenicity A mamalian in vitro point
mutation test; a sensitive
•sub-mammalian point mutation
test; a primary DMA damage test? 163.84-1
and a mammalian in vitro through
cytogenetics test are required. 163.84-4
Methyl Chloramben
Metabolism A general metabolism is required 163,85-1
if not submitted in conjunction
with the food-use requirements
4. Topical Discussions
a. Sodium Chloramben
The following topical discussions describe available toxicity data on sodium
Chloramben and state whether they are adequate for Agency regulatory purposes.
Acute Oral Toxicity
The minimum testing needed on acute oral toxicity is one test, in the
laboratory rat, on the technical chemical and on the manufacturing-use product
if different.
The acute oral LD-- of technical Chloramben (100 percent purity) was 5,620
mg/kg body weight in male rats (Hazleton Laboratories, 1959, 0022). Confidence
limits could not be calculated due to an "all or none" response. Toxic effects
included depression characterized by inactivity and ataxia , labored
respiration, sprawling of limbs, ptosis, lack of coordination and excessive
urination. Gross pathologic findings included congested lungs, kidneys and
adrenals. This is an adequate determination in males, which would place
technical Chloramben in Category 'IV, indicating a very low acute oral hazard.
An acute oral LDen determination using sodium Chloramben (85 percent
Chloramben acid equivalents) administered to male and female rats suggests a
similarly low acute toxicity hazard. The study is not considered to fulfill
Agency requirements because of problems in determining the actual LDe value.
No further testing is required given the valid LD5Q determination for
technical Chloramben.
Acute Dermal Toxicity
The minimum testing needed on acute dermal toxicity is one test, preferably in
the albino rabbit, on the technical chemical and manufacturing-use product.
7-10
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The acute dermal LD-0 value (intact skin) for male and female albino rabbits
exposed to technical chloramben (100 percent purity) was determined to be
greater than 3,160 ngAg body weight (Hazleton Laboratories, 1959, 0023).
Depression characterized by inactivity was noted at highest dose levels.
Little or no dermal absorption of the applied material was noted. Mild to
moderate erythema and mild edema were observed initially, but subsided within
two days. This study fulfills Agency requirements for testing on intact skin
and indicates a Toxicity Category III-IV designation.
A dermal LD-Q determination for manufacturing-use sodium chloramben (85
percent chloramben acid equivalent) applied to the intact and abraded skin of
rabbits indicated a value greater than 5 g/kg body weight (CDC Research, 1978,
0065). No dermal reactions, adverse reactions or mortality were noted over the
study course. A Toxicity Category IV designation is indicated. These two
studies are adequate to fulfill Agency requirements for acute dermal toxicity
testing. No further tests are required.
Acute Inhalation Toxicity
The minimum data requirement for acute inhalation toxicity is one test,
preferably in the albino rat, on the technical chemical and on each
manufacturing-use product.
No tests on technical chloramben are available.
Acute inhalation testing as conducted with sodium chloramben (82.8 percent
chloramben acid equivalent) resulted in an LC_Q determination of greater than
200 mg/1 to male and female albino rats (Food and Drug Research Laboratories,
1978, 0062). This value would place sodium chloramben in Toxicity Category IV,
indicating a very low acute inhalation hazard. The study is considered to
fulfill Agency requirements for acute inhalation testing. No further testing
is required.
Primary Eye Irritation
The minimum testing needed to evaluate eye irritation potential is one test, in
albino rabbits, on each manufacturing-use product. If the test substance has a
pH of 1-3 or 12-14, however, it will be judged corrosive, and an eye irritation
test is not needed. Also, if the test substance has been judged to be dezmally
corrosive, an eye irritation test is not needed.
The acute eye irritation study on technical chloramben (100 percent purity)
does not meet Agency requirements because of deficiencies in protocol. A
primary eye irritation study en sodium chloramben (85 percent chloramben acid
equivalent) administered to female rabbits is considered to fulfill Agency
requirements for this test (CDC Research, 1978, 0064). Mild to moderate ocular
irritation was observed at 24 hours in 6 of 6 rabbits. Irritation in all cases
7-11
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cleared within 7 days. The results indicated a slight acute eye irritation
hazard based on a Toxicity Category III designation. No further testing is
required.
Primary Dermal Irritation
The minimum testing needed to evaluate dermal irritation potential is one test,
preferably in the albino rabbit, on each manufacturing-use product.
Sodium chloramben (85 percent chloramben acid equivalent) was very slightly
irritating to intact and abraded rabbit skin at either 24 or 72 hours (CDC
Research, 1978•, 0063). The study is adequate to place sodium chloramben in
Category IV, indicating a very low potential for dermal irritation. No further
tests are required.
Skin Sensitization
The minimum requirement for assessing skin sensitization is an intradermal test
in one mammalian species, preferably the guinea pig, on each manufacturing-use
product.
No testing is available for either technical chloramben or manufacturing-use
sodium chloramben. Tests are therefore required to assess skin sensitization.
Acute Delayed Neurotoxicity
An acute delayed neurotoxicity evaluation is not required because chlorainben is
not expected to cause acetylcholinesterase depression, nor is its chemical
structure related to that of substances that induce delayed neurotoxicity.
Subchronic Oral Toxicity
The minimum testing needed to assess subchronic oral toxicity is one test in
each of two mammalian species, a rodent and a non-rodent, on the technical
chemical.
No adequate rodent subchronic (90-day) oral test of the technical product is
available. A 28-day dietary feeding study in male albino rats does not fulfill
Agency requirements for this test.
A two-year feeding study in male and female beagles on technical chloramben (97
percent purity) satisfies the requirement .for a non-rodent study. In this
study, beagle dogs received chloramben in the diet at 0, 100, 1,000 and 10,000
ppm (Hazleton Laboratories, 1963,, 0028). Both test and control groups
exhibited normal behavior and weight gain. Values for hematological,
biochemical, and urinary analyses were within normal ranges. Organ/body weight
ratios were not affected. Organs examined histologically revealed no
significant alterations. Slight to slight-to-moderate vacuolation of liver
cells was found in 3 of 8 dogs at the high dose level (10,000 ppm). The NOEL
reported in the study is 1000 ppm (25 mgAg body weight/day).
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Because chronic testing in the mouse and rat is available, additional
subchronic oral toxicity testing is not required.
Subchronic 21-Day Dermal Toxicity
The minimum requirement to assess subchronic 21-day dermal toxicity is one
study, preferably in the albino rabbit, on the technical product. This study
is required for all uses of chloramben.
No studies of subchronic dermal toxicity on technical chloramben are
available. Testing is therefore required.
Subchronic 90-Day Dermal Toxicity
A subchronic 90-day dermal toxicity test is not required because chloramben is
not purposely applied to skin, and its use will not result in human exposure
comparable to/ for example, the exposure of swimmers to swimming pool additives
or garment wearers to pesticide-impregnated fabric.
Subchronic Inhalation
A subchronic inhalation test is not required on technical chloramben since its
use would not likely result in toxic concentrations as determined from the
results of the acute inhalation LC50 value (greater than 200 mg/1) for sodium
chloramben.
Subchronic Neurotoxicity
A subchronic neurotoxicity evaluation is not required on chloramben because it
is not expected to induce neuropathy or delayed neurotoxicity, and because it
does not have a molecular structure closely related to that of a compound that
is known to induce neuropathy or delayed neurotoxicity.
Chronic Feeding
A chronic feeding study is required in one mammalian species, preferably the
laboratory rat, using the technical product.
A chronic oral toxicity study in albino rats conducted by Hazleton Laboratories
(1963; 0027, 0088, 0089) will not satisfy Agency requirements because of
deficiencies in study protocol and data reporting. A recently submitted
chronic feeding study in Sprague-Dawley rats (Litton Bionetic, 1979, 0171) will
fulfill Agency requirements following receipt of product purity information.
Results of this study indicate that administration of technical chloramben at
dose levels of 100, 1,000 and 10,000 ppm did not result in any dose-related
chronic effects. The dose levels chosen were significantly less than the
previously established MTO of approximately 32,000 ppm for rats. Body weight^
food consumption, and survival were comparable among test and control animals.
Results of clinical testing were negative.
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Oncogenicity
Oncogenicity tests using the technical material are required in two mammalian
species, normally the rat and mouse.
A National Cancer Institute (NCI) study submitted on technical chloramben (90-
95 percent purity) administered for 80 weeks to Osborne-tMendel rats and B6C3F1
mice concluded that chloramben was carcinogenic to the female mice, producing
hepatocellular carcinoma (National Cancer Institute, 1977, 0019). The liver in
female mice was the only site where the occurrence of carcinoma was reported to
be significant. The pathologic findings other than liver cell cancer do not
establish a clear trend. There was some evidence that chloramben had a
goitrogenic effect based on the observed incidence of follicular-cell
hyperplasia of the thyroid. However, insufficient number of controls were
available to draw a firm conclusion. The incidence of hemangiomas (blood
vessel tumors) in male rats was significant at the low-dose level but not the
high-dose level. This borderline positive supports the positive result seen in
female mice. The incidence of hemangiomas in female rats was not significant
at either dose level.
t
The study did contain some flaws in study protocol and study conduct. Among
the identified deficiencies were the following: a high probability of
improperly mixed feed, improperly designed exhaust vents in mixing rooms, and
improperly cleaned feed-mixing pots, and feed-mixing areas. Although the study
had definite shortcomings, the Agency was able to use this study in an
oncogenic risk assessment. The Agency therefore considers this study adequate
to fulfill requirements for oncogenic testing in both rats and mice.
The eighteen month oncogenic study of technical chloramben of unspecified
purity fed to CD-I male and female mice will supplement Agency requirements
for oncogenic testing in mice following submission of the detailed composition
of the test chemical (including minor impurities). In this study, chloramben
was fed to CD-I mice at levels of 0, 100, 1/000 and 10,000 ppm in the diet
(Hunting-ton Research Center, 1978, 0170). These doses were considerably below
a previously determined ^^^D level of greater than 30,000 ppm. Behavior,-
appearance, and survival were considered normal and comparable between control
and test animals. Differences in body weight and food consumption in treated
group animals were not considered to be compound related. All organ weight
values were considered to be within normal ranges and no trends were
established.
Palpable masses were found primarily in male mice (all groups) and were
considered to be associated with bacterial infection of the preputial gland.
Primary compound associated tissue alterations were confined to the liver in
all treated mice. The main hepatocellular reaction -was a histomorphological
alteration compatible with that observed in enzyme induction. Changes were
more oauiicn in treated mice than in controls and were generally observed in a
dose-dependent fashion. Secondary pathological changes associated with the
compound were reflected by an increased incidence and severity of amyloidosis
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in high dose mice when compared to controls. Liver and kidneys fron low and
mid-dose mice had incidence rates much lower than the controls. Other tissue
findings, including benign and malignant neoplasms, were randomly distributed
among the mice at all dose levels.
The 1979 chronic feeding study discussed above (Litton Bionetics, 1979, 0171)
will supplement Agency requirements for oncogenic testing in rats, provided
that compound purity is submitted. The study reported no significant
differences in either neoplastic or nori-neoplastic lesions between control and
test animals fed chloramben at concentrations of 100, 1,000, and 10,000 ppm
(MTD level approximately 30,000 ppm). Neoplastic lesions were predominantly
benign and occurred for the most part in the pituitary gland (chromophobe
adenoma), adrenal gland (cortical adenoma), testes (interstitial cell tumor)
and mammary gland (carcinoma and fibroadenoma). Spontaneous lesions of note
included telangiectasis in the adrenal cortex (46 percent of these animals also
exhibited cortical adenomas) , degenerative cardiomyopathy, chronic inflammation
of the kidneys, murine pneumonia and galactostasis and galactocele.
Mo further testing is required.
Teratology
The minimum requirement for evaluating a pesticide for teratogenicity is
testing in two mammalian species. It is required for both food and nonfood
uses of chloramben. No tests are available on chloramben to assess
teratogeniceffects. Therefore, tests on two mammalian species utilizing either
sodium chloramben or technical chloramben (3-amino 2,5-dichloro benzoic acid)
must be submitted.
Reproduction
The minimum requirement for measuring effects on reproduction is one test using
the technical chemical in the rat, lasting two generations. This is required
for all food uses.
Technical chloramben (unspecified purity) fed to CFE rats at doses of 500,
1,500 and 4,500 ppn resulted in a decrease in weight gain (at the 25th week)
between the FQ and F^ generations (AME Associates, 1966, 0029). Controls
did not exhibit a change in weight gain over the three filial generations. In
addition, at these dosages, there was also a dose-dependent trend in decreased
fertility index (3 generations) and lactation index (2 generations).
Provisionally, the study does not meet Agency requirements for a reproduction
test. It will be judged for adequacy when the detailed composition of the test
chemical is provided.
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Mutagenicity
The- following studies represent the minimum requirements for data on the
potential heritable effects of chloramben.
1. A mammalian in vitro 'point mutation test.
2. A sensitive sub-mammalian point nutation test (Bacteria, fungi, insect).
3. A primary ENA damage test (i.e., sister chromatid exchange or unscheduled
DMA synthesis.
4. A mannalian in vitro cytogenetics test. If this test suggests a positive
result, a dominant lethal or heritable translocation test may be required.
After results from these test systems and other toxicology disciplines have
been considered, additional testing may be required to further characterize or
quantify the potential genetic risks.
A sub-mammalian point mutation test (Anderson et al., 1972, 0502) using
technical chloramben (90-99 percent purity) does not fulfill Agency
requirements due to the absence of a metabolic activation system and is
considered supplemental.
Study results indicated that "Amiben" was not mutagenic to histidine-requiring
mutants of Salmonella typhimurium, did not result in chemically induced
mutations of the rll type in T, bacteriophage and did not result in
reversions to the wild type in AP72 and N17 rll mutants T4 bacteriophage.
A sub-mammalian point mutation test is still required, as well as tests
designed to meet requirements 1, 3 and 4 as noted above.
Metablism in Laboratory Animals
A general metabolism study on chloramben must be carried out to fulfill Agency
requirements.
A subchronic feeding study in dogs provides supplemental information on
chloramben metabolism (Hazleton Laboratories, 1967, 0086). Residues were
measured in tissues and excreta of dogs fed chloramben for 28 days as a working
mixture of 999 parts lactose and one part Amiben (0.1 percent) prepared on a
weight/weight basis. Samples of liver, kidney, muscle, fat, and blood from
control and high-dose (20 ppm) animals were analyzed by gas chrcmatography.
Residues in liver, kidney, blood, muscle, and fat were less than 0.02 ppm
chloramben for both controls and high-dose animals. Chloramben residues in the
urine and feces were 0.43 and 0.086 ppm, respectively, in the high-dose animals
as opposed to the 0.02 ppm in the controls.
This study does not adequately investigate mammalian metabolism of chloramben
and will not be considered to fulfill Agency requirements. A valid metabolism
studv must be submitted.
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Clinical Trials
No clinical studies in humans have been conducted using chloramben. None are
presently required by Agency Guidelines.
Emergency Treatment
No information is available on the prevention and treatment of chloramben
intoxication.
b. Methyl Chloramben
The following topical discussions describe available toxicity data on the
methyl ester of chloramben and state whether they are adequate for Agency
regulatory purposes. With the exception of a metabolism study, subchronic and
chronic tests required for'a food-use registration of manufacturing-use methyl
chloramben may be satisfied by testing on sodium chloramben or technical
chloramben provided that evidence is submitted documenting the breakdown of the
methyl ester to chloramben after application to the soil. Refer to Section
B.4.a for topical discussions of chronic and subchronic tests performed with
manufacturing-use sodium chloramben.
Acute Oral-Toxicity
The minimum testing needed on acute oral toxicity is one test, in the
laboratory rat, on the technical chemical and on the manufacturing-use product
if different.
The technical methyl ester of chloramben administered to male rats as a 30
percent weight/volume suspension in corn oil resulted in an LD5Q value of
1,710 mg/kg (Hazleton Laboratories, 1966, 0024). Confidence limits were 1260-
2330 mg/kg. Principal toxic effects included depression, gasping, labored
respiration, ataxia, sprawling of limbs, depressed righting and placement!
reflexes, muscular stiffness, and death (the latter at doses of 2, 150, 4, 640
and 10,000 mg/kg). Major necropsy findings included congestion of the lungs,
liver, kidneys, and pancreas; pale-appearing spleen and gastorintestinal
inflammation. These results place manufacturing-use methyl chloramben in
Toxicity Category III for acute oral toxicity.
This study will satisfy Agency requirements for an acute oral toxicity
determination in rats following receipt of product purity.
Acute Dermal Toxicity
The minimum testing needed on acute dermal toxicity is one test, preferably in
the albino rabbit, on each manufacturing-use product.
No tests on the technical methyl ester of chloramben are available. Testing on
acute dermal toxicity must be submitted.
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Primary Eye Irritation
The minimum testing needed to evaluate eye irritation potential is one test, in
albino rabbits, on each manufacturing use product. If the test substance has a
pH of 1-3 or 12-14, however, it will be judged corrosive, and an eye irritation
test is not needed. If the test substance has been judged to be dermally
corrosive, an eye irritation test is not needed.
No eye irritation testing has been performed with methyl chloramben. Such
testing must be submitted.
Primary Dermal Irritation
The minimum testing method to evaluate dermal irritation potential is one test/
preferably in the albino rabbit, on each manufacturing-use product.
No testing is available on the methyl ester of chloramben. Results of such
testing must therefore be submitted.
Skin Sensitization
The minimum requirement for assessing skin sensitization is an intradermal test
in one mammalian species, preferably the guinea pig, on each manufacturing-use
product.
No skin sensitization test is available on methyl chloramben. Testing is
therefore required.
Acute Delayed Neurotoxicity
An acute delayed neurotoxicity evaluation is not required because methyl
chloramben is not expected to cause acetylcholinesterase depresssion, nor is
its chemical structure related to that of substances that induce delayed
neurotoxicity.
Metabolism in Laboratory Animals
A general metabolism study on methyl chloramben must be carried out to fulfill
Agency requirements.
No tests are available on the metabolism of methyl chloramben. A metabolic
study of manufacturing-use methyl chloramben is required in order to determine
its fate in the body and potential metabolites. Data on plasma elimination
must be included. Such information is necessary to assess applicator exposure
risk.
Clinitoal Trials
No clinical studies in humans have been conducted using methyl chloramben.
None are currently required under Agency Guidelines.
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Emergency Treatment
No information is available on the prevention and treatment of methyl
chloramben intoxication.
5. Required Labeling
Precautionary labeling of each product must correspond to the toxicity
categories determined by five acute toxicity tests. Acceptable categories of
acute toxicity and the corresponding required labeling are discussed in the
Agency Position Chapter of this Standard.
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C. Chloramben End—Use Formulations
1. Soluble Concentrate Chloramben
a. Toxicology Profile
Existing soluble concentrate chloramben end-use products (registration numbers
264-138, 264-178, 2749-202, and 264-266) contain either ammonium chloramben
(23.4%) or a combination of ammonium chloramben (15.7%) and monomethylammonium
chloramben (47.2%).
For purposes of -chronic and subchronic toxicity testing, the Agency has
determined that ammonium chloramben and monomethylammonium chloramben are
equivalent to technical chloramben. Subchronic and chronic testing is not
required on the ammonium or monomethylammonium salts.
The Agency has determined that technical chloramben acid and sodium chloramben
are equivalent to ammonium and moncmethyl ammonium chloramben for purposes of
subchronic and chronic toxicity testing.
Available acute toxicity testing on ammonium and moncmethyl ammonium chloramben
indicate that that these salts appear to be 3 to 4 times as acutely toxic as
chloramben acid. Therefore, acute oral and dermal toxicity testing on
technical grade ammonium and moncmethyl ammonium chloramben are required.
Acute testing of end-use products is also required.
Available acutetoxicity data submitted on a soluble concentrate end-use
ammonium salt formulation indicates an acute oral LD-Q value of 7.94 ml/kg or
7,940 mg/kg (assuming a density of 1.0 g/ml) in male albino rats.
Acute toxicity testing submitted on a combination of ammonium chloramben
(10.87%) and monomethylammonium chloramben (34.5%) indicates an acute oral
LDe0 value of 3.5 ml/kg or 3,500 mg/kg (assuming a density of 1.0 g/ml) in
male albino rats.
A dermal LD-g value of 8 ml/kg or 8,000 mgAg (assuming a density of 1.0
g/ral) in male albino rabbits was reported for this same combination of ammonium
chloramben and monomethylammonium chloramben. This product resulted in slight
conjunctival involvement at 24 hrs. following a 0.1 ml aliquot administration
in male albino rabbits.
b. Data Requirements and Data Gaps
The Agency has determined that existing soluble concentrate end-use products
containing ammonium chloramben as the sole active ingredient are substantially
similar to one another for the purposes of acute toxicity testing. Data gaps
identified for acute testing of such soluble concentrate products may be
fulfilled through the submission of tests on an end-use soluble concentrate
product containing 23.4% ammonium chloramben.
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Acute toxicity tests have been submitted on a chloramben soluble concentrate
formulation containing 10.8% ammonium salt and 34.5% moncmethylammonium salt.
The percents of active ingredient as stated do not correspond with any of the
registered formulated products containing this mixture. A decision to accept
this product as representative of formulations containing these salts awaits
submission of further information regarding inerts in the test substance.
Data Gaps
Generic Data
Category of Test
Acute Oral
Acute Dermal
Data Requirements
An acute oral toxicity test
in the rat is required on
technical grade anmonium and
monomethyl ammonium chloramben
An acute dermal toxicity test
in the rat is required on
technical grade anmonium and
monomethyl ammonium chloramben
Guideline Number
163.81-1
163.81-2
Product Specific Data
Category of Test
Acute Oral
Acute Dermal
Data Requirements
Test material composition
and density most be submitted
on the anmonium salt and anmonium
(10.8%)/moncmethylammonium
(34.5%) salt soluble concentrates.
An acute dermal toxicity
study, preferably in the
albino rabbit, is required for an
end-use soluble concentrate
product containing 23.4% ammonium
chloramben. Product data on the
anrncTiiumAcnomethylaninonium
chlorambenm test substance must be
submitted.
Guideline Number
163.81-1
163.81-2
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Primary Eye
Irritation
Primary Dermal
Irritation
Acute Inhalation An acute inhalation study in 163.81-3
the rat is required for an
end-use soluble concentrate
containing 23.4% ammonium
chloramben and an end-use soluble
concentrate containing 15.7%
ammonium chloramben and 47.2%
monomethylammonium chloramben.
A primary eye irritation test 163.81-4
in the albino rabbit is required
for a representative 23.4%
ammonium chloramben product unless
it has a pH of either 1-3 or 12-14
or unless it has been judged dermally
corrosive. If so, it will be
regulated as a corrosive substance.
Product data on the amroonium/monomethyl-
ammonium chloramben test substance must
be submitted.
A primary dermal irritation 163.81-5
test, preferably in the albino
rabbit, is required for an end-use
soluble concentrate containing 23.4%
ammonium chloramben. Product data
on the ammonium/monomethylammonium
test substance must be submitted.
c. Topical Discussions: Soluble Concentrate Products
Acute Oral Toxicity
The minium testing needed on acute oral toxicity is one test in the laboratory
rat on each soluble concentrate end-use product.
The acute oral LD-- of an ammonium salt formulation of chloramben
(unspecified concentration) was determined to be 7.94 ml/kg or 7940 mgAgr
assuming a density of 1.0 g/fal (Hazleton Laboratories, 1966, 0024). Confidence
limits were 5.84 to 10.8 ml/kg. Principal toxic effects following
administration of doses up to 21.5 ml/kg in male albino rats included
depression, gasping, labored respiration, ataxia, sprawling of the limbs,
depressed righting and placement reflexes, muscular stiffness and death (the
latter at 10.0 and 21.5 ml/kg). Compound related necropsy findings included
congestion of the lungs, kidneys, adrenal, and pancreas; pale appearing spleen;
and inflammation of the diaphragm, peritoneum, and pyloric portion of the
stomach. Based on these results, the product is placed in Toxicity Category IV.
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This study will be considered an- adequate determination of oral toxicity of an
ammonium chloramben formulated product in male and female rats following
identification of the specific test product, including product density.
The acute oral LD-Q of the formulated ammonium (10.8 percent)/monomethy1-
ammonium (34.5 percent) product administered to male albino rats is 3.5 mlAg
or 3,500 ing/kg assuming a density of 1.0 g/ml (Biosearch Inc., 1969, 0001).
Confidence limits were calculated at 2.4 to 5.2 mlAg. Animal mortality
occurred at least two hours following dosing and was preceded by weaJcness and
lassitude. Data submitted separately indicate that the 3.5 mlAg value
corresponds to 1,900 mgAg of salt and 1,680 mgAg of acid. The high LDc0
value places the compound in Toxicity Category III, indicating a low acute oral
hazard. This study will be considered sufficient for testing the acute oral
toxicity of the formulation in rats if evidence is submitted showing that the
test material is representative of the registered ammonium/monomethylammonium
compound. Product density must also be submitted.
Acute Dermal Toxicity
The minimum testing needed on acute dermal toxicity is one test, preferably in
the albino rabbit, on each soluble concentrate end-use product.
No studies on the acute dermal toxicity of soluble concentrate end-use products
containing 23.4% ammonium chloramben have been submitted.
A soluble concentrate end-use product containing 10.8% ammonium chloramben and
34.5% moncmethylammonium chloramben has been tested on the intact and abraded
skin of male albino rabbits at levels up to 8 mlAg or 8,000 mgAg> assuming on
a density of 1.0 g/ml (Biosearch, Inc., 1969, 0002). There was no evidence of
skin irritation at any time. Given the very high LD5Q value a Toxicity
Category IV designation is appropriate. This study will be judged for adequacy
as an acute dermal determination for the registered ammonium chloramben/
monomethyl ammonium chloramben soluble concentrate product following submission
of composition and density of the test material.
Acute Inhalation Toxicity
An acute inhalation toxicity test is required on a soluble concentrate
formulation if it causes a respirable vapor.- or if 20% or more of the
aerodynamic equivalent is composed of particles not larger than 10 microns. No
vapor pressure data are available on chloramben products. Until data are
submitted which indicate otherwise, a test will be needed on each
representative chloramben soluble concentrate formulation.
Primary Eye Irritation
The minimum testing needed to evaluate eye irritation protential is one test,
in albino rabbits, on each soluble concentrate product. If the test substance
has a pfi of 1-3 or 12-14, however, it will be judged corrosive, and an eye
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irritation test is not needed. If the test substance has been judged dermally
corrosive, the test substance will be judged to be corrosive to the eye and an
eye irritation test is not needed.
No studies on primary eye irritation have been submitted on a soluble
concentrate product containing 23.4% ammonium chloramben. Such testing must be
submitted.
A soluble concentrate product containing 10.8% ammonium/34.5% methylammonium
chloramben was not considered to be an ocular irritant based on a 0.1 ml
aliquot adminstered in male albino rabbits (Biosearch, Inc., 1969, 0003).
Slight conjunctiva! involvement was noted at 24 hours but was negative at 48
hours. No other signs of eye irritation were noted throughout the 14-day
observation period. The study is adequate to place this formulated product in
Toxicity Category III, indicating a low eye irritation potential. In order to
satisfy Agency requirements for testing of the ammonium/monomethylammonium
chloramben soluble concentrate, product composition of the test material cited
above must be submitted.
Primary Dermal Irritation
The minimum testing needed to evaluate dermal irritation potential is one test,
preferably in the albino rabbit, on each soluble concentrate end-use product.
Testing on soluble concentrate formulations containing ammonium chloramben is
not available and must therefore be submitted.
The previously cited study of dermal toxicity of a 10.8% ammonium/34.5% methyl-
ammonium chloramben product (Biosearch Inc., 1969, 0002) will be judged for
adequacy as a dermal irritation test of the registered ammonium/monanethyl-
ammonium chloramben soluble concentrate product following submission of test
material composition. No evidence of skin irritation was noted after
application of the test material to either the intact or abraded skin of male
albino rabbits.
Skin Sensitization
A dermal sensitization study is not required because use of the formulated
product will not result in repeated human skin contact.
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2. Flowable Concentrate Chloramben
a. Toxicology Profile
Two flowable concentrate end-use products, containing 83.0% sodium chloramben
(registration number 264-305) and 21.0% sodium chloramben (registration number
264-306), respectively, are currently registered. The Agency has determined
that acute toxicity tests submitted on manufacturing-use sodium chloramben
and/or chloramben (3-amino-2,5-dichlorobenzoic acid) may be used to fulfill
acute toxicity testing requirements on these flowable concentrates. Refer to
the Toxicology Profile and Topical Discussions on manufacturing-use sodium
chloramben for a summary of existing toxicolcgical data on either sodium
chloramben or chloramben.
b. Data Requirements and Data Gaps
None identified for flowable concentrates containing sodium chloramben.
c. Topical Discussions
Acute Oral Toxicity
The minimum testing needed on acute oral toxicity is one test in the laboratory
rat on each formulated flowable concentrate product.
No tests on flowable concentrate formulations containing sodium chloramben are
available. Acute toxicity testing on technical chloramben will fulfill test
requirements on the flowable concentrate formulations. Refer to Section
B.4.a. (Topical Discussions - Sodium Chloramben).
Acute Dermal Toxicity
The minimum testing needed on acute dermal toxicity is one test, preferably in
the albino rabbit, on each formulated flowable concentrate end-use product.
No acute dermal tests are available on flowable concentrate chloramben. A
dermal LD-. test on sodium chloramben meets Agency requirements. Refer to
Section B.4.a. No further testing is required.
Acute Inhalation Toxicity
An acute inhalation toxicity test is required on a flowable concentrate
formulation if it causes a respirable vapor, or if 20% or more of the
aerodynamic equivalent is composed of particles not larger than 10 microns. No
vapor pressure information on a chloramben product is available. Until such
data are supplied, a test will be needed on flowable concentrate chloramben.
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No tests of acute inhalation toxicity are available on this formulation type.
However, available acute inhalation testing with sodium chloramben (refer to
Section B.4.a) may be used to fulfill this test requirement for flowable
concentrate end-use products.
Primary Eye Irritaiton
The minimum testing needed to evaluate eye irritation potential is one test, in
albino rabbits, on each formulated flowable concentrate end-use product.
Testing on flowable concentrate formulations containing sodium chloramben is
not available. A dermal irritation study using manufacturing-use sodium
chloramben will fulfill Agency requirements for the flowable concentrate
formulations. Refer to Section B.4.a.
Skin Sensitization
Dermal sensitization testing is not required because use of these products are
not expected to result in repeated human skin contact.
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D. Bnulsifiable Concentrate Chloramben
a. Toxicology Profile
A single end-use product, containing 23.2% methyl chloramben (registration
number 264-260), is registered in this category.
Acute toxicity tests have been conducted en a methyl chloramben emulsifiable
concentrate (unspecified composition). Based on an LD-^ determination of
5.01 ml/kg or 5,010 mg/kg (assuming a density of 1.0 g7ml) in male rats, a low
acute oral hazard is expected.
Dermal testing of the formulated methyl chloramben product in rabbits at doses
up to 3.16 ml/kg of body weight or 3,160 mg/kg (assuming a density of 1.0 g/ml)
did not result in animal mortality. Gross signs of dermal irritation included
moderate to marketed erythema at all doses on both abraded and intact skin,
slight to moderate edema, and blanching.
Exposure in male and female rats to an aerosol of a formulated methyl
chloramben product "at a concentration of 2.0 mg/1 did not cause any animal
deaths. Based on a probable Toxicity Category III designation, a low acute
inhalation hazard in human beings is expected.
Acute eye irritation was noted after a single application of the formulated
methyl chloramben end-use products. Irritation in unrinsed eyes consisted of
moderate or marked conjunctival redness, chemosis, and discharge; slight or
moderate corneal opacity, slight iritis, and corneal vaacularization and
sloughing of epithelium. Based on these findings, the methyl chloramben end-
use compound can be expected to represent an eye irritation hazard in humans.
No further tests were submitted on an emulsifiable concentrate containing
methyl chloramben.
b. Data Requirements and Data Gaps
Provided that evidence is submitted indicating that the test substance
described above is equivalent to the emulsifiable concentrate (23.2% methyl
chloramben) currently registered, existing acute toxicity tests on the compound
will be acceptable. The density of the test substance must also be
submitted. The following data gaps remain.
Data Gaps
None identified for the currently registered product.
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c. Topical Discussions
Acute Oral Toxicitv
The minimum testing needed on acute oral toxicity is one test in the laboratory
rat on the emulsifiable concentrate end-use product.
The LD5p value for the formulated methyl chloramben emulsifiable concentrate
administered to rale albino rats is 5.01 ml/kg or 5,010 mg/kg (assuming a
density of 1.0 g/taL) with confidence levels from 5.84 to 10.8 ml/mg (Hazelton
Laboratories, Inc., 1966, 0024). Toxic effects included depression, gasping,
labored respiration, ataxia, sprawling of limbs, depressed righting and
placement reflexes, muscular stiffness, bloody crust around eyes and nose,
salivation and excessive urination. The necropsy findings consisted of
congestion of the lungs, kidneys, adrenals, and pancreas; pale-appearing
spleen? and inflammation of the diaphragm, peritoneum and pyloric portion of
the stomach. This study will be considered to fulfill Agency requirements for
acute oral toxicity testing in male and female rats following characterization
of the compound.
No further testing is required.
Acute Dermal Toxicity
The minimum testing needed on acute dermal toxicity is one test, preferably in
the albino rabbit, on the emulsifiable concentrate end-use product.
Dermal .testing of the formulated methyl chloramben product in rabbits at doses
up to 3.16 ml/kg of body weight did not result in animal mortality (Hazleton
Laboratories, 1968, 0143). Principal toxic effects included slight depression
and labored respiration in the majority of animals. One animal exhibited rapid
respiration and hyperactivity. Gross signs of dermal irritation consisted of
moderate to marked erythema at all doses on both abraded and intact skin,
slight to moderate edema and blanching. Atonia and slight or moderate
desquamation developed predominantly in the highest dose group during the
course of the study and were all still present on two animals at termination.
Assuming a density of 1.0 g/ml, the LDe0 value (>3,160 mgAg) is designated
Toxicity Category III-IV. Information chacterizing the test substance
(including product density) must be submitted.
Acute Inhalation Toxicity
An acute inhalation toxicity test is required on an emulsifiable concentrate
product if it causes a respirable vapor, or if 20% or more of the aerodynamic
equivalent is composed of particles not larger than 10 microns. No vapor
pressure data are available on chloramben products. Until such data are
supplied, a test will be needed on the emulsifiable concentrate containing
mehtyl chloramben.
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Exposure in male and female rats to an aerosol of the methyl chloramben end-use
product at a concentration of 2.0 mq/1 of air did not cause any animal deaths
(Hazleton Laboratories, 1968, 0144). Toxic effects noted after initial
exposure were restlessness, inactivity, shallow breathing and puffy and glassy
eyes. Abnormalities observed upon gross necroposies included red spots, brown
spots, and clear tan spots in the lungs, massive consolidation in the lungs,
dark kidney medulla and discolored cervical glands. Red spots, clear tan
spots, and dark brown spots were noted in the lungs of control animals. The
study cannot be considered to fulfill Agency requirements for an acute
inhalation toxicity determination until the product is completely characterized.
Primary Eye Irritation
The minimum testing needed to evaluate eye irritation potential is one test, in
albino rabbits, on the emulsifiable concentrate end-use product. If the test
substance has a pH of 1-3 or, 12-14, however, it will be judged corrosive, and
an eye irritation test is not needed. If the test substance has been judged to
be dermally corrosive, it will also be considered corrosive to the eye and an
eye irritation test is not needed.
Acute eye irritation was noted in rabbits after a single application of 0.1 ml
of the formulated methyl chloramben product (Hazleton Laboratories, 1968,
0143). Principal toxic effects included blinking, preening and/or phonation
immediately following dosage. Terminal weight loss was noted in one animal.
Irritation in nonirrigated eyes consisted of moderate or marked oonjunctival
redness, chemosis and discharge; slight or moderate corneal opacity (persisting
in one case beyond 7 days); slight iritis; and corneal vascularization and
sloughing of epithelium (1 animal). Slight conjunctival irritation was
observed in a few of the rinsed eyes. Based on these data, the compound is
placed in Toxicity Category'II.
A complete characterization of the test product must be provided before this
study can be considered to fulfill Agency requirements.
Primary Dermal Irritation
The minimum testing needed to evaluate dermal irritation potential is one test,
preferably in the albino rabbit, on the formulated emulsifiable concentrate.
Dermal irritation effects were noted during the acute dermal toxicity testing
of the emulsifiable concentrate product (Hazleton Laboratories, 1968, 0143).
Gross signs of dermal irritation consisted of moderate to marked erythema at
all doses on both abraded and intact skin, slight to moderate edema and
blanching. Atonia and slight to moderate desquamation developed predominantly
in the highest dose group during the course of the study and were still present
in two animals at termination. These data indicate a slight dermal irritation
hazard based on a probable Toxicity Category III designation. No further
testing is required.
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Skin Sensitization
*
Deraal sensitization testing is not required because the use pattern indicates
that repeated human skin contact is unlikely under conditions of use.
7-30
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4. Granular
a. moxicity Profile
Seven qranular chlorarbon end-use products arp currently reaisteroH . Five
products consist of either 1.3%, 4.3%, or 10.8% ammonium chloranben
"(registration numbers 264-167, 264-175, 264-191, 264-243, and 2749-169). T\*D
products are a mix of ammonium chloramben and moncme thy 1 ammonium chloramben at
either a 5.4% and 17.3% level or 2.82% and 8.46% level, respectively,
(registration numbers 264-251 and 264-274).
For purposes of chronic and subchronic toxicity testinq, the Agency has
determined that ammonium chloramben and monanethylammonium chlorannen are
equivalent to technical chloramben acid.
Acute oral and dermal toxicity testina is reauired on technical qrade ammonium
and moncmethyl ammonium chloramben in addition to testinq on end-use products.
No tests are available to assess either the acute toxicity or possible skin or
eye effects of granular chloramben end-use formulations. However, the Agency
has determined that granular products containing the ammonium salt of
chloramben are substantially similar to soluble concentrate products containina
this salt. Likewise, granular products containing a mixture of the ammonium
and moncmethyl ammonium salts have been determined to be substantially similar
to soluble concentrate products containing these salts. Data aaps identified
for soluble concentrate products are directly applicable to granular products.
b. Data Requirements and Data Gaps
The Agency has determined that existing granular end-use products containing
ammonium chloramben are substantially similar to one another and to soluble
concentrate chloramben products containing this salt for the purposes of acute
toxicity testing . In "the same respect , granular end-use products containing a
mixture of ammonium chloramben and moncmethylammonium chloramben are considered
to be substantially similar to each other and to soluble concentrate products
containing this salt. Data gaps identified for acute toxicity testing of
soluble concentrate products apply also to granular chloramben products. See
the Soluble Concentrate portion of this chapter for details.
7-31
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c. Topical Discussions
Sere Topical Discussions for Soluble Concentrate products.
7-32
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CHAPTER VIII
ECOLOGICAL EFFECTS OF CHLORAMBEN
A. Introduction
In order to evaluate the ecological effects of chloramben, various toxicity
tests are required. Depending on the characteristics and uses of chloramben
end-use formulated products, data requirements for wildlife and aquatic
organisms can be completely or primarily satisfied with tests for chloramben
manufacturing-use products. However, for some end-use formulations which
include active ingredients different from those in the manufacturing-use
products, the technical grade of each active ingredient must be used in
toxicity testing. Additional tests with end-use formulations can be required
if testing for manufacturing-use products is insufficient to make an adequate
hazard evaluation. An evaluation of hazard to wildlife and aquatic organisms
requires the assessment of'risk to potentially affected non-target organisms,
taking into consideration the environmental chemistry and toxicological
characteristics of chloramben and its end-use formulations.
The discussion in this chapter relating to the ecological effects of chloramben
is divided into two sections. In the first section the manufacturing-use
products of chloramben are discussed with an ecological effects profile, a
review of data requirements and gaps, and a topical review of pertinent
studies. In the second section, the formulated end-use products of chloramben
are grouped into generic categories which are then also discussed with
ecological effects profiles, reviews of data requirements and gaps, and topical
reviews. An additional feature of the second section is the application of
worst-case risk assessments where adequate toxicity data permit comparisons of
toxicity levels with worst-case estimates of environmental concentration
levels. These risk assessments were incorporated into the appropriate
ecological effects "profiles.
B. Chloramben iManuf acturing-Use Products
1. Ecological Effects Profile: Sodium and Methyl Chloramben
a. Sodium Chloramben
Currently available data indicate that manufacturing-use sodium chloramben is
of low acute toxicity to most terrestrial wildlife. A test employing the
Bobwhite Quail and the Pekin Duck found dietary LCgn's to be greater than
3,160 ppm active ingredient for each species using a technical material
containing 97.2 percent sodium salts of chloramben. Another test, using the
Mallard Duck, found the dietary LC5Q to exceed 4,650 ppm active ingredient
with a technical material containing 91.6 percent sodium chloramben. No avian
acute oral toxicity testing results are available for sodium chloramben. Tests
with rats and dogs indicate a lack of acute dietary toxicity of technical
chloramben to levels of 10,000 ppm (see Chapter VII). In addition, the acute
oral LD50 for male rats was found to be 5,620 mgAg for technical chloramben.
Currently available data also indicate that manufacturing-use sodium chloramben
is of low toxicity to fish. Acute toxicity tests with Bluegill Sunfish and
Rainbow Trout demonstrate 96-hour LC5Q's exceeding 1,000 mg/1 using a
technical material containing 91.6 percent sodium chloramben. Fish
accumulation tests (see Chapter V) indicate that little potential exists for
8-1
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significant bioaccumulation of chloramben or the sodiun chloramben
T.anufacturing-use product. >fo studies are available on the acute toxicity of
sodium chloramben to' aquatic invertebrates.
b. Methyl Chloramben
Less data for toxicity to wildlife are available for the methyl chloramben
manufacturing-use product than for the sodium chloramben manufacturing-use
product. One test employing the Bobwhite Quail and the Pekin Duck found
dietary ^^'s to be greater than 3,160 ppm active ingredient for the
technical methyl chloramben test material (98.8% active ingredient). No avian
oral toxicity testing results or other dietary data are available. Only one
oral or dietary study on mammals is available. In this study the acute oral
LD_n to rats was found to be 1,710 mgAg, indicating a greater toxicity for
thi methyl ester (see Chapter VII).
No studies have been submitted detailing aquatic toxicity tests for the methyl
chloramben manufacturing-use products. However,- limited data based on a letter
and a memorandum, indicate that methyl chloramben may be moderately to highly
toxic to aquatic organisms. Reported results include a 96-hour LC.Q of 4 ppm
for a 20 percent material with Bluegill and an indicated 24-hour l£cfl of
between 2 and 16 ppm for "amiben ester" at 2 Ibs/gallon with the Fathead
Minnow. The test material for these reported results is assumed to have been
the methyl chloramben formulated product (Registration No. 264-260). No other
data is available for fish, invertebrates, or fish accumulation.
2. Data Requirements and Data Gaps: Sodium and Methyl Chloramben
The following fish and wildlife studies testing the effects of the technical
grades of sodium and methyl chloramben are required for the registration of
chloramben manufacturing-use products:
Required Test Guidelines Section
Avian Single-Cose Oral LD^ 163.71-1
Avian Dietary LC-0 (2 tests) 163.71-2
Fish Acute LC5Q ?2 tests) 163.72-1
Acute Toxicity to Aquatic Invertebrates 163.72-2
a. Sodium Chloramben
Acceptable studies have been submitted for the Avian Dietary
Acute LC-0 tests. Data gaps exist for the following required tests:
Required Test Data Gap Reason for Data Gap
Avian Single-Dose Oral LD-Q Non-submission of study.
Acute Toxicity to Aquatic Invertebrates Non-submission of study.
Submission of studies to fill the required test data is required for completion
of registration requirements for sodium chloramben manufacturing-use products.
b. Methyl Chloramben
There are no acceptable studies which have been submitted for the methyl
chloramben manufacturing-use product except for the avian dietary test with an
8-2
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upland game species. Therefore/ acceptable studies for all of the required
tests for manufacturing-use products must be submitted for registration of the
methyl chloraraben manufacturing-use products, except that the avian dietary
test need only provide data for the wild waterfowl species (preferably the
Mallard Duck).
3. Topical Discussions: Sodium and Methyl Chlorainben
a. Sodium Chloraraben
Birds
Birds may be exposed to pesticides by feeding on pesticide granules,
contaminated plants, or insects, and by dermal contact and/or inhalation when
close to outdoor sprays and dust. To assess the impact of a pesticide on
birds, the Agency requires certain avian toxicity tests to support the
registration of pesticides. For registration of every manufacturing-use
product and formulated product for outdoor application, avian acute oral LD^g
and avian dietary EC-0 tests are required. According to Proposed Guidelines
Section 163.71-2, the avian dietary test should be conducted with an upland
game bird species (preferably the Bobwhite Quail) and a wild waterfowl species
(preferably the Mallard Duck) . The avian single-dose Oral LD5Q test is to be
performed on one of the two species used in the avian dietary test (Proposed
Guidelines Section 163.71-1).
An acceptable study meeting the requirements of the guidelines has been
submitted for a test with the Mallard Duck (Wildlife Int'l, 1978, 0059). This
study found a dietary LC-0 in excess of 5,620 ppm (5,150 ppm active
ingredient) for a sodium chloramben test material containing an active
ingredient level of 91.6% sodium chloramben. No toxic symptoms or deaths are
reported at test concentration levels up to 5,620 ppm (5, 150 ppm active
ingredient). An additional acceptable study (Affiliated Medical Research,
1973, 0036) found dietary LC-0's in excess of 3,160 (3,070 ppm active
ingredient) for both the Bobwnite Quail and Pekin Duck. The test material in
this study contained the sodium salt of chloramben (97.2 percent) as the active
ingredients. No acute oral LD5Q study has been submitted for sodium
chloramben.
Freshwater Fish
The minimum data required for establishing the acute toxicity of manufacturing-
use sodium chloramben for fish are determinations of 96-hour LCen's - the
fish acute LC5Q tests (Proposed Guidelines Section 163.72-1). Tne fish acute
I£-Q test is co be performed with a coldwater species (preferably the Rainbow
Trout) and a warmwater species (preferably the Bluegiil Sunfish) .
Acceptable studies meeting guidelines requirements have been submitted for
tests with both the coldwater and warmwater fish species. The study featuring
the coldwater species (Rainbow Trout) demonstrated a 96-hour LCeQ in excess
of 1,000 mg/1 (916 mg/1 active ingredient) for the sodium chloramben test
material containing an active ingredient level of 91.6 percent sodium
chloramben (Union Carbide, 1978, 0061). No mortalities were observed at up to
the 1,000 mg/1 concentration level and the 96-hour h^-observed-effect level
(NOEL) was 100 mg/1 (91.6 mg/1 active ingredient). The study featuring the
warmwater species (Bluegiil Sunfish) demonstrated a 96-hour LC-0 also in
excess of 1,000 mg/1 (916 mg/1 active ingredient) for the same3test material
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(Union Carbide, 1978, 0060). In this test, no mortalities were observed at up
to the 1,000 mg/1 concentration level and the 96-hour NOEL was 180 mg/1 (165
mg/1 active ingredient).
Aquatic Invertebrates
A determination of the 48-hour EC50 for an aquatic invertebrate species is
required to support the registration of all manufacturing-use products and for
all formulated products intended for outdoor application (Proposed Guidelines
Section 163.72-2). Nb study on toxicity to aquatic invertebrates has been
submitted.
Other Organisms
Several other published reports on chloramben toxicity were reviewed, but
conclusions about levels of toxicity cannot be verified since the test material
was inadequately described. These reports include the following studies.
Published literature reported low levels of toxicity of chloramben and
chloramben sodium salt to honeybees—low mortality and little effect on
reproduction (Morton and Moffett, 1972, 0535; and Morton et al., 1972, 0536).
Another study reported chloramben to be non-toxic to earthworms when injected
with 100 rogAg (Chio and Sanborn, 1978, 0524). A review article (Butler, 1977,
0549) indicates that toxic effects on algae occur at concentrations of 15-3000
ppm, with chloramben and its ammonium salt less toxic than the methyl ester.
b. Methyl Chloramben
Birds
As discussed in greater detail for the sodium chloramben manufacturing-use
product, to assess the potential impact of a pesticide on birds, the Agency
requires certain avian toxicity tests to support the registration of
pesticides. The avian dietary LC_fl test should be conducted with an upland
game bird species (preferably the Bobwhite Quail) and a wild waterfowl species
(preferably the Mallard Duck). The avian single-dose oral LC5Q test is to be
performed on one of the two species used in the avian dietary test.
A study (Affiliated Medical Research/ 1973, 0039), acceptable in meeting
guidelines requirements for testing on an upland game bird, found dietary
LC-0's in excess of 3,160 ppm methyl chloramben for both the Bobwhite Quail
ana Pekin Duck. The level of active ingredient in the test material,
identified as Aniben Methyl Ester, was 98.8 percent.
Freshwater Fish
The minimum data required for establishing the acute toxicity of manufacturing-
use methyl chloramben for fish are determinations of 96-hour LC~Q'S—the fish
acute LC-0 test (Proposed Guidelines Section 163.72-1). The fish acute
LC__ test: is to be performed' with a coldwater species (preferably the Rainbow
TrSut) and a warmwater species (preferably the Bluegill Sunfish).
Amchem Products, Inc. factory correspondence (Otten, 1970, 0146a) reports
testing results on Fathead Minnows showing that after 24 hours -all test fish
were alive at 2 pern and all were dead at 16 ppm. The test material is
described as Pmiben Ester (2 Ib/gal active ingredient as methyl ester). In
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addition, a letter (Hughes, 1970, 0146b) reported a 96-hour LCc0 of 4 pan for
a test material identified as Amiben Ester (as a 20 percent material). The
test fish were Bluegill, and all fish were killed in 24 hours at 15 ppn. These
reports are unacceptable in meeting guidelines requirements because technical
materials were not used and the data are very limited.
Aquatic Invertebrates
A determination of the 48-hour EC-0 or LC5Q for an aquatic invertebrate
species is required to support the registration of all manufacturing-use
products and for all formulated products intended for outdoor application
(Proposed Guidelines Section 163.72-2). No study on toxicity to aquatic
invertebrates has been submitted.
Other Organisms
An unverified review article (Butler, 1977, 0549) reported that toxic effects
on algae occur at concentrations of 15-3000 ppm, with the methyl ester more
toxic than chloramben or amnonium chloramben.
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C. Chloramben Formulated Products (for End-Use Application)
1. Soluble Concentrates
Currently registered soluble concentrate chloramben products include the
following listed products.
Registration No. Active Ingredients
264-138 23.4% Ammonium Chloramben
264-178 23.4% Ammonium Chloramben
2749-202 23.4% Ammonium Chloramben
264-266 15.7% Ammonium Chloramben
and 47.2% Monomethyl-
ammonium Chloramben
a. Ecological Effects Profile and Risk Assessment:
Soluble Concentrates
Profile
The data previously described for the chloramben manufacturing-use products are
not directly applicable to the toxicity and hazard evaluation of soluble
concentrate products since these products contain ammonium chloramben and
moncmethyl ammonium chloramben as active ingredients. No studies have been
submitted on tests using technical grades of these two active ingredients.
However, some test data on ammonium chloramben formulations (containing 23.4
percent active ingredient) serve to indicate low toxicity to wildlife and
fish. In an avian dietary test with the Mallard Duck, an LOg of greater
than 4,650 ppm (1,090 ppm active ingredient) was found for a test material
containing 23.4 percent ammonium salts of chloramben and related
aminodichlorobenzoic acids. In an avian acute oral toxicity test with the
Bobwhite Quail, an LDc0 of 7.7 ml/kg was found for the same test material.
Very brief fish acute coxicity testing reports indicate, in one test, a 24-hour
LCSO greater than 50 ppm with the Fathead Minnow and another test a 96-hour
LC_Q greater than 250 ppm with Bluegill Sunfish.
In a preliminary report on testing with a test material containing 10.8
percentammonium chloramben and 34.5 percent moncmethyl ammonium chloramben, 96-
hour LCen's greater than 1000 ppm, 1000 ppm, and 750 ppm for Fathead Minnow,
Bluegill Sunfish, and Rainbow Trout, respectively, are reported.
Risk Assessment
Only one study on the toxicity of one of the active ingredients -in the soluble
concentrates is of sufficient quality for use in risk analysis. A dietary
LC-0 and a no-observed-effects level (NOEL) of over 1090 ppm active
ingredient in the Mallard Duck was found. Assuming a maximum broadcast
application rate of 4.0 Ib. active ingredient per acre (EPA's Use Pattern
Summary Report for Chloramben) an environmental concentration is estimated
for short rangegrass application as a hypothetical worst-case for residues on
vegetation. The following table portrays the vorst-case risk analysis which
applies to the soluble concentrates containing only ammonium chloramben as the
active ingredient:
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Environmental Worst-Case Toxicity (pan) No Effect Ratio Hazard Patio
Residue VDEL L£5r (Residue/ (Residue/
Feature/ Cone, (ppm) active ingredient NOEL) —5&1
Species
Short Range Grass 960
Mallard Duck >1090 >1090 <0.38 <0.38
Since the No-Effect Ratio and Hazard Ratio which were calculated are less than
one, the ammonium chloramben soluble concentrate does not pose a likely
significant risk of acute toxicity to waterfowl at current application rates.
b. Data Requirements and Data Gaps: Soluble Concentrates
The following fish and wildlife studies testing the effects of technical grade
ammonium chloramben and technical grade monomethyl ammonium chloramben are
required as a minimum for the registration of chloramben formulated products
containing these salts:
Required Test Guidelines Section
Avian Single-Dose Oral LD-n 163.71-1
Avian Dietary LC5Q (2 tests) 163.71-2
Fish Acute LC5Q T2 tests) 163.72-1
.Acute Toxicity to Aquatic Invertebrates 163.72-2
In addition to the above-listed minimum testing requirements, additional tests
can be required for registration of formulated products depending on the use
pattern/ mobility, persistence, toxicity, bioaccumulation, and other
characteristics of the formulated product or its active ingredients. One or
more of the following tests could be required; the criteria used for
requirement determination are listed in the designated section of the Proposed
Guidelines of July 10, 1978:
Potentially Required Test Guidelines Section
Mammalian Acute Toxicity 163.71-3
Avian Reproduction 163.71-4
Simulated and Actual Field Testing
for Mammals and Birds 163.71-5
Acute Toxicity to Estuarine and
Marine Organisms 163.72-3
Sonbryolarvae and Life-Cycle Studies of
Fish and Aquatic Invertebrates 163.72-4
Aquatic Organism Toxicity and Residue Studies 163.72-5
Simulated or Actual Field Testing for Aquatic Organisms 163.72-6
Depending on certain conditions (see Guidelines Sections 163.72-1 and 163.72-
2), the Fish Acute LC-- and the Acute Toxicity to Aquatic Invertebrates tests
could require the testing of the formulated product as well as the technical
S-7
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grade of the active chloramben ingredient for the registration of the
respective formulated product.
For soluble concentrate products containing only ammonium chloramben, data gaps
exist for every one of the six minimum required tests. For each of these
tests, the technical grade -of the ammonium chloramben active ingredient is to
be used as the test material. Submission of these required tests is required
for registration of these -products.
For soluble concentrate products containing monomethyl ammonium chloramben as
an active ingredient, additional data gaps exist for every one of the six
minimum required tests of this additional active ingredient. For each of these
additional tests, the technical grade of the mononethyl ammonium chloramben
active ingredient is to be used as the test material. Submission of these
required tests is necessary for registration of this product.
Due to insufficient product chemistry, environmental fate/ and toxicity
information, the need for any of the additional potentially required tests
which have been listed cannot be determined. Following submission of studies
covering the minimum registration requirements, the Agency will determine if
any of the potentially required tests are necessary.
c. Topical Discussions: Soluble Concentrates
Birds
As discussed in greater detail for the sodium chloramben manufacturing-use
product, to assess the potential impact of a pesticide on birds, the Agency
requires at a minimum certain avian toxicity tests to support the registration
of pesticides. The avian dietary LCeg test should be conducted with an
upland game bird species (preferably the Bobwhite Quail) and a wild waterfowl
species (preferably the Mallard Duck). The avian single-dose oral LD^Q test
is to be performed on one of the two species used in the avian dietary test.
These tests are to be performed using the technical grade of each active
ingredient.
No studies have been submitted which are acceptable in meeting these minimum
requirements for registration. However, supplemental testing data (which is,
however, unacceptable in meeting minimum registration requirements) is
available for birds. In a good avian dietary LC-- test on the Mallard Duck
with an ammonium chloramben formulation (Registration No. 264-138), an NOEL and
an LCe0 of greater than 4,650 ppm (1990 ppm active ingredient) were found
(Truslow Farms, 1974, 0049). An avian single-dose oral LD,0 study found an
LD_n of 7.1 ml/kg in testing on Bobwhite Quail with the same test material
(GaJsriel, 1969; ID Mo. 0145). The latter study is of limited value because
only five male birds were tested per level .and little test data were reported.
Freshwater Fish
Several unpublished reports on chloramben toxicity to fish were reviewed, but
conclusions about toxicity cannot be verified, because the test procedures and
test material identity were unavailable.
Amchem Products, Inc. factory correspondence (Otten, 1970, 0146a) indicates a
24-hour LC.Q exceeding 50 ppm for a soluble concentrate product (2 Ib/gal
active ingredient as chloramben ammonium salt) using Fathead Minnows. In
addition, a letter (Hughes, 1970, 0146b) indicates a 96-hour LCSO in excess
8-8
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of 250 pan for "Amiben" (composition unspecified) using Bluegill Sunfish. A
preliminary report (Bionomics, 1970, 0051) indicates 96-hour LQjnS exceeding
1,000 ppm, 1,000 ppm, and 750 ppm for the Fathead Minnow, Bluegill Sunfish, and
Rainbow Trout, respectively. The test material, "Amiben Concentrate,"
contained lO.Spercent ammonium chloramben and 34.5 percent and mononethyl
ammonium chloramben.
8-9
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2. Flowable Concentrates
Currently registered flowable concentrate chloramben products include the
following listed formulated products:
Registration No. Active Ingredients
264-305 83.0% Sodium Chloramben
264-306 21.0% Sodium Chloranben
a. Ecological Effects Profile and Risk Assessment:
Flowable Concentrates
Profile
Since the active ingredient in flowable concentrate chloraraben products is
sodium chloramben, the toxicity to wild organisms for both may be estimated
from tests for manufacturing-use sodium chloramben (see the Ecological Effects
Profile for sodium chloramben manufacturing-use product).
Risk Assessment
In the following vorst-case assessment of risk to wildlife and aquatic
organisms for both flowable concentrates, values for maximum hypothetical
environmental concentrations of the active ingredient of the flowable
concentrate products are compared with the toxicity data for various tested
species. Assuming a maximum broadcast application rate of 4.0 Ib/acre (EPA's
Use Pattern Summary Report for Chloramben), environmental concentrations are
estimated for direct application to water, for field runoff water, and for
short range grass (as hypothetical worst-case situations for residues of the
flowable concentrate products). The No Observed Effects Levels (NOEL'S) and
LC 's for various fish and wildlife are taken from valid studies described
previously for the sodium chloramben manufacturing-use product. The following
table portrays the worst-case risk analysis which applies to both the flowable
concentrate products:
3-10
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Environmental Worst-Case Toxicity (pom) No Effect Ratio Hazard Ratio
Feature/ Residue (Residue/
Species Cone, (pom) NOEL(ai) LC5Q(ai) NOEL)
Water Receiving
Direct Application*
Bluegill
Sunfish 2.94 165 >916 0.018 <0.0032
Rainbow
Trout 2.94 91.6 >916 0.032 <0.0032
Runoff Water**
Bluegill
Sunfish 1.77 165 >916 0.011 <0.0019
Rainbow
Trout 1.77 91.6 >916 0.019 <0.0019
Short Range Grass
Mallard Duck 960 >5150 >5150 <0.19 <0.19
Bobwhite
Quail 960 N.A. >3070 N.A. <0.31
N.A. = Not available.
* = Assumes ccraplete mixing in a six inch layer of standing water.
** = Assumes 10% of application in one inch of runoff water.
Since the No-Effect Ratios and Hazard Ratios which were calculated are
substantially less than one, sodium chlcramben flowable concentrates do not
pose a likely significant risk of acute toxicity to fish or birds at current
application rates of 4 pounds active ingredient per acre. Based on
toxicological testing with manuals (see Chapter VII), the hazard to mammals is
also judged to be insignificant. There are no data available to evaluate the
hazard to aquatic invertebrates. Data described in Chapter V for chloramben
(acid form) indicate little potential for significant bioaccumulation in fish.
b. Data Requirements and Data Gaps: Flowable Concentrates
The minimum required tests and potentially required tests for registration of
flowable concentrates are the same as for all formulated pesticide products and
have been discussed already for the soluble concentrates. Since flowable
concentrate products contain only sodium chloramben as active ingredient, tests
submitted and described for the sodium chloramben manufacturing-use product
also serve to fulfill the minimum testing requirements for flowable
concentrates.
Therefore, the data gaps in the minimum testing requirements for flowable
concentrates containing sodium chloramben are the same as for the sodium
chloramben manufacturing-use product:
Required Test Data Gap Reason for Data Gap
Avian Single-Dose Oral ID.Q Non-submission of study.
Acute Toxicity to Aquatic invertebrates Non-submission of study.
8-11
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Submission of tests to fill in these data gaps is required for registration of
the flowable concentrate products. IXie to insufficient product chemistry,
environmental fate,, and toxicity information, the need for any of the
additional potentially required tests cannot be determined. Following
submission of studies covering the minimum registration requirements, the
Agency will determine if any of the potentially required tests are necessary.
c. Topical Discussions: Flowable Concentrates
See the Topical Discussions section for the sodium chloramben manufacturing-use
product for topical discussions relevant to the flowable concentrate products.
No studies have been submitted for the flowable concentrate products per se.
8-12
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3. Emulsifiable Concentrate
The currently registered emulsifiable concentrate chloramben product is the
following formulated product:
Registration No. Active Ingredients
264-260 23.2% Methyl Chloramben
a. Ecological Effects Profile and Risk Assessment:
Emulsifiable Concentrates
Profile
Since the active ingredient in the chloramben emulsifiable concentrate product
is methyl chloramben, the tpxicity to wild organisms may be estimated from
tests for the manufacturing-use methyl chlorainben (see the Ecological Effects
Profile for methyl chloramben manufacturing-use product).
Risk Assessment
With the exception of the dietary data on an avian upland game species,
Bobwhite Quail, no data were available on the toxicity of methyl chloramben for
a risk assessment. In the following worst-case assessment of risk to wildlife,
for the emulsifiable concentrate, the value for maximum hypothetical
environmental concentrations of the active ingredient of the emulsifiable
concentrate product is compared with the toxicity for the avian upland game
species.
Assuming a maximum broadcast application rate of 3.0 pounds active ingredient
per acre (EPA's Use Pattern Summary Report for Chloramben ), environmental
concentrations are estimated for short range grass (as the hypothetical worst-
case situation for residues of the emulsifiable concentrate product). T^e NOEL
and LC^Qfor Bobwhite Quail are taken from the valid study described
previously for the methyl chloramben manufacturing-use product. The following
table portrays the worst-case risk analysis which applies to the emulsifiable .
concentrate product:
8-13
-------
Environmental Worst-Case
Feature/
Species
Residue
Cone* ocm
Short Range Grass 720
Bobwhite
Quail
Toxicity No Effect Ratio
NOEL LC5Q (Residue/
active ingredient NOEL)
>3120 >3120
<0.23
Hazard Ratio
(Residue/
<0.23
Since the No-Effect Ratio and Hazard Ratio which were calculated are
substantially less than one, methyl chloramben emulsifiable concentrate does
not pose a likely significant risk of acute toxicity to birds at current
application rates of 3 pounds active ingredient per acre. Based on
toxicological testing with mammals (see Chapter VII), the hazard to mammals is
also judged to be insignificant. There are no data available to evaluate the
hazard to fish or aquatic invertebrates.
b. Data Requirements and Data Gaps: Emulsifiable Concentrate
The minimum tests and potentially required tests for registration of
emulsifiable concentrates are the same as for all formulated pesticide products
and have been discussed already for the soluble concentrates. Since the
emulsifiable concentrate products contain only methyl chloramben as the active
ingredient, tests submitted for registration of the methyl chloramben
manufacturing-use product would also serve to fulfill the minimum testing
requirements for the emulsifiable concentrates.
With the exception of an acceptable avian dietary LCeQ with an upland game
bird species, no acceptable studies have been submitted for the methyl
chloramben manufacturing-use product. Therefore the data gaps in the minimum
testing requirements for the emulsifiable concentrates are the same as for the
raethyl chloramben manufacturing-use product. Submission of tests to fill in
these data gaps is required for registration of the emulsifiable concentrate
products.
Due to insufficient product chemistry, environmental fate, and toxicity
information, the need for any of the additional potentially required tests
cannot be determined. Following the submission of studies covering the minimum
registration requirements, the Agency will determine if any of the potentially
required tests are necessary.
c. Topical Discussions: Emulsifiable Concentrate
See the Topical Discussions section for the methyl chloramben manufacturing-use
product for topical discussions relevant to emulsifiable concentrate products.
8-14
-------
4. Granular Chloramben
Currently registered granular Chloramben products include the following listed
formulated products:
Registration No. Active Ingredients
264-167 10.8% Ammonium Chloramben
264-175 10.8% Ammonium Chloramben
264-191 1.3% Ammonium Chloramben
264-243 4.3% Ammonium Chloramben
2749-169 10.8% Ammonium Chloramben
264-251 5.4% Ammonium Chloramben and 17.3%
Monomethyl ammonium Chloramben
264-274 2.82% Ammonium Chloramben and 8.46%
Monomethyl ammonium Chloramben
a. Ecological Effects Profile and Risk Assessment
Granular
Profile
Since granular Chloramben products contain ammonium Chloramben or ammonium
Chloramben with monomethyl ammonium Chloramben as active ingredients (as do the
soluble concentrate formulated products), the ecological effects profile of the
soluble concentrates is directly applicable to granular products and will not
be repeated here. Granular products, however, can pose a unique hazard to
birds. Birds may selectively pick up granules as food or as grit for
incorporation into their gizzards. An evaluation of this hazard cannot be
made, however, without the required toxicity data for birds.
Risk Assessment
There are insufficient toxicity data for any sort of risk assessment for
wildlife or aquatic organisms.
b. Data Requirements and Data Gaps: Granular
The minimum data requirements for granular products are the same as those for
the soluble concentrates. Fulfillment of data gaps which have been identified
for the soluble concentrates will serve to fulfill the minimum data
requirenents for the granular products at the same time. Testing is required
on technical grade ammonium and technical grade moncmethyl ammonium Chloramben.
However, due to insufficient product chemistry, environmental fate, and
toxicity information, the need for any of the additional potentially required
tests cannot be determined. Following the submission of studies covering
minimum registration requirements, the Agency will determine if any of the
potentially required tests are necessary.
c. Topical Discussions: Granular
Refer to the Topical Discussion section for the soluble concentrates for
topical discussions relevant to the granular products.
3-15
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TD USE OF BIBLIOGRAPHY
-------
Guide Co Use of This Bibliography
Cor.cer.c of Bibliography. This bibliography concains citations of all
-he studies reviewed by EPA in arriving ac the positions and conclusions
stated elsewhere in this standard. The bibliography is divided into
3 sections: (1) citations that contributed information useful to the review
of the chemical and considered to be part of the data base supporting
registrations under the standard, (2) citations examined and judged to be
inappropriate for use in developing the standard, and (3) standard
reference aaterial . Priaary sources for studies in this bibliography have
been the body of data submitted to EPA and its predecessor agencies in
support of past regulatory decisions, and the published technical
Units of Entry. The unit of entry in this bibliography is called a
"study". In the case of published materials, this corresponds closely to
an article. In the case of unpublished materials submitted to the
agency, the Agency has sought to identify documents at a level parallel to
a published article from within the typically larger volumes in which they
were submitted. The resulting "studies" generally have a distinct title
(or at least a single subject), can stand alone for purposes of review, and
can be described with a conventional bibliographic citation. The Agency
has attempted also to unite basic documents and commentaries upon them,
treating them as a single study.
f.'l1.uS'en^ifiCa5ig!L4 Entries • The entries in this bibliography are sorted by
author, date of the document and title. Each entry bears, to the left of the
preceeded by a colon (ie. :0039). At
bibliography is an alpha-numeric identifier
H .
SSfi^ £h~ •? *?? °f *iS bibli°9raPhy is an alpha-numeric identifier (5s
a citit>oT'Me iTflnfi^oT5 ^^ to 2mplete ** identification number for
* Cltat-on ((,le- GS~0086:0039). These numbers are called "Temporary Record '
^ri'rSuSs:3'^ ^ ^ * -d at «* "-^y^
?ora of the Entry, in addition to the Temporary Becord Identifier (TRID) ,
each entry consists of a bibliographic citation containing standard
elements followed, in the-case of materials submitted to EPA, by a
description of the earliest known submission. The bibliographic
conventions used reflect the standards for the American National Standards
Institute (ANSI), expanded to provide for certain special needs. Some
explanatory notes of specific elements follow:
a. Author. Whenever the Agency could confidently identify one,
the Agency has chosen to show a personal author. When no individual
was identified, the Agency has shown an identificable laboratory or
testing facility as author. As a last resort, the Agency has shown
the first known submitter as author.
b. Document Date. When the date appears as four digits with no
question marks, the Agency took it directly from the document. When a
four-digit date is followed by a question nark, the bibliographer
-------
deduced che dace from evidence in che document. When che dace
appears as (19??), che Agency was unable co deceraine or escioace che
dace of che document.
c. Tide. This is che Chird element in che cicacion. In some cases it
has been necessary for che Agency bibliographers Co create or enhance
a document cicle. Any such edicorial insertions are contained
between square brackets.
d. Trailing Parenthesis. For studies submitted co us in che past, the
trailing parenthesis include (in addition Co any self-explanatory
cext) che following elements describing che earliest known submission.
(1) Submission Date. Immediately following the word
'received' appears che date of the earliest known
submission.
(2) Administrative Number. The next element, immediately
following the word 'under', is the registration number,
experimental permit number, petition number, or other
administrative number associated with the earliest known
submission.
(3) Submitter. The third element is the submitter, following
the phrase 'submitted by'. When authorship is defaulted Co
the submitter, this element is omitted.
(4) Volume Identification. The final element in the crailing
parenthesis identifies Che EPA accession number of the
volume in which the original submission of the study
appears. The six-digit accession number follows che symbol
'CDL', standing for "Company Data Library". This accession
number is in turn followed by an alphabetic suffix which
shows the relative position of che study within che volume.
For example, within accession number 123456, the first
study would be 123456-A; che second, 123456-B; the 26th,
123456-Z; and che 27th 123456-AA.
.-3
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OFFICE OF PESTICIDE PROGRAMS
PESTICIDE DOCUMENT MANGEMENT SYSTEM
CASE HELICGRAPHy
9.4
-------
OFFICE OF PESTICIDE PROGRAMS
PESTICIDE DOCUMENT MANAGEMENT SYSTEM
CASE BIBLIOGRAPHY
Section 1: Citations Considered to be Part of the Data Base
Supporting Registrations Under the Standard .
I .P.* Citation
GS-0086:
:0039 Affiliated Medical Research (1973) Subacute toxicity of
Amiben methyl ester in the diet of two wild fowl species -
Bobwhite Quail and Pekin Duck. (Unpublished report
received 8-17-73 under 264-138; CDL:128274)
:0036 Affiliated Medical Research (1973) Subacute toxicity of
Amiben sodium salt in the diet of two wild fowl species -
Bobwhite Quail and Pekin Duck. (Unpublished report
received 11-20-73 under 264-138; CDL:132340)
:0124 Amchem Products, Incorporated (1959) Chemical and physical
properties of amiben and dinoben. (Unpublished study
received 10-19-59 under 264-138; CDL:002082)
:0127 Amchem Products, Incorporated (1960) Amiben results on
soybeans, summary. (Unpublished report received 7-5-60
under 2.64-138; CDL:002083)
:0125 Amchem Products, Incorporated (1960) Chemical and physical
properties of chloramben. (Unpublished study received 7-
5-60 under 264-138; CDL:002083)
:0104 Amchem, Products (1961) Amiben C14 special problem.
(Unpublished report received 2-1-62 under 264-Q;
CDL:121497)
:0136 Amchem Products, Incorporated (1961) C14 Amiben pre-
emergent tracer study in soybeans. (Unpublished study
received 6-13-61 under 264-138; CDL:002088)
:0154 Amchem Products, Incorporated (1961) Metabolism of Amiben
in plants. (Unpublished study received under 264-
138; CDL: 002083)
:0159 Amchem Products Inc., (1961) Metabolite analysis 2,5
dichlorophenol in soybeans. (Unpublished study
reveiwed 4-3-67 under.7F0591; CDL: 090758)
:0135 Amchem Products, Incorporated (1961) Method of analysis
for traces of amiben in de-ciled soybean meal as developed
by Dr. V.H. Freed with minor modifications by Amchem
Residue Lab-in colloboration with Dr. Freed. (Unpublished
study received 6-2-61 under 264-138; CDL:002087)
-------
:0079 Amchem Products, Incorporated (1961) Separation and
detection of 2,5-dichlorobenzoic acid, 3-
arainobenzoic acid and 2,5-dichloro-3-aminobenzoic
acid (Amiben) by paper chromatography.
(Unpublished report received 8-4-61 under 264-138;
CDL:101235)
:0103 Amchem Products, Incorporated (1963) Addenda to residue
data on tomatoes. (Unpublished report received 3-14-63
under 264-Q; CDL:121515)
:0106 Amchem Products, Incorporated (1963) Amiben analysis in
tomatoes. (Unpublished study received 01-01-01 under 264-
Q; CDL:121500)
:0098 Amchem Products, Incorporated (1963) Analysis of Araiben
treated lima bearxs for possible traces of 2,5-
dichloroaniline. (Unpublished study received 11-1-63
under 264-X; CDL:121407)
:0158 Amchem Products, Inc. (1963) 14C-Amiben in lima beans;
extraction efficiency study, translocation study.
(Unpublished study received 4-3-67 under 7F0591;
CDL:090758)
:0102 Amchem Products (1963) Evaluation for NR use of Amiben on
tomatoes. (Unpublished review dated 3-15-63;
CDL:121516)
:0016 Amchem Products, Incorporated (1963) Factory
correspondence. Subject: combined dichloroaniline in
lima bean plants. (Unpublished memo received 12-18-63;
CDL:121521)
:0108 Amchem Products, Incorporated (1963) Lima bean residue
data and analytical method. (Unpublished study received
11-7-63 under 264-Q; CDL:121493)
:0162 Amchem Products, Incorporated (1963) Metabolite analysis
2 ,5-dichloroaniline in dry beans and peppers.
(Unpublished study received 4-3-67 under 7F0591;
CDL:090758)
:0163 Amchem Products, Incorporated (1963) Metabolite analysis
2,5-dichloroaniline in lima beans. (Unpublished
study received 4-3-67 under 7F0591; CDL: 090758)
-.0107 Amchem Products, Inc. (1964) Amiben residue analysis on
lima bean plants. (Unpublished study received 1-7-
64 under 264-Q; CDL:121505)
:0093 Amchem (1964) Amendment to previous evaluations of data
for NR registrations on dry beans and peppers.
(Unpublished review dated 3/4/64; CDL:121507)
-------
:0078 Amchem Products, Incorporated (1964) Analysis of sweet
potatoes for possible residues of Amiben. (Unpublished
report received 6-17-64 under 264-167, 264-138;
CDL:101242)
:0080 Amchem Products, Incorporated (1964) Analysis of corn for
possible residues of Amiben. (Unpublished study received
8-18-64 under 264-138, 264-167; CDL:101234)
:0008 Amchem Products, Incorporated (1964) Analysis of dry beans
and peppers treated with 3-amino-2,5-dichlorobenzoic acid
for possible traces of 2,5 dichloroaniline . (Unpublished
study received 2-28-64 under 264-175; CDL:121513)
:0097 Amchem Products, Incorporated (1964) Lima bean residues,
letter from Libby, McNeill , and Libby. (Unpublished
letter received 1-23-64; CDL:121494)
:0164 Amchem Products, Incorporated (1964) Metabolite analysis
2,5-dichloroaniline in pumpkin and squash. (Unpublished
study rceived 4-3-67 under 7F05991; CDL:090758)
:0161 Amchem Products, Inc. (1964) Metabolite analysis 2,5
dichloroaniline in sweet potatoes (improved
methodology). (Unpublished study received 4-30-67
under 7F0591; CDL: 090758)
:0096 Amchem Products, Incorporated (1964) Validation of
analysis of Amiben in dry beans. (Unpublished study
received 1-30-64 under 264-138, 264-167; CDL: 121518)
:0076 Amchem Products, Incorporated (1965) Amiben on peanuts
supplement No. 1: Analysis of Amiben treated peanuts for
possible presence of 2 ,5-dichloroaniline . (Unpublished
report reeceived 4-13-65 under 264-138, 264-167;
CDL:101240)
:0071 Amchem Products, Incorporated (1965) Improved method for
determination of residues in soybeans. (Unpublished study
received 10-26-65 under 264-138; CDL:101238)
:0115 Amchem Products, Incorporated (1965) Information sheet.
(Unpublished study received 12-1-65 under 264-Q;
CDL:106953
:0077 Amchem Products, Incorpora :ed (1965) Section 3: Residue
analysis; analysis of peanuts for possible residues of
Amiben. (Unpublished report received 2-24-65 under 264-
138, 264-167; CDL:101241)
:0010 Amchem Products, Incorporated (1966) Amiben solubilities.
(Unpublished report received 01-01-01 under 264-Q;
CDL: 1215-14)
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:0140 Amchem Products, Incorporated (1966) Chemical data sheet:
methyl ester of Amiben. (Unpublished study received 2-26-
70 under OF0957; CDL:091633)
:0148 Amchem Products, Incorporated (1966) Rate of hydrolysis of
various esters of amiben. (Unpublished report received 01-
01-01)
:0044 Amchem Products, Incorporated (1967) Analytical methods
and sample data on drybeans . (Unpublished report received
4-3-67 under 7F0591; CDL:090758)
:0045 Amchem Products, Incorporated (1967) Radiotracer and
metabolism Studies. (Unpublished report received 4-3-67
under 7F0591; CDL:090758)
:0043 Amchem Products, Incorporated (1967) Soil residues.
(Unpublished study received 4-3-67 under 7F0491;
CDL:090758)
:0085 Amchem Products, Incorporated (1968) Amiben tissue storage
study. (Unpublished study rerceived 10-15-68 under
7F0591; CDL:090759)
:0149 Amchem Products, Incorporated (1968) Analysis of cucumbers
for Possible residues of Amiben. (Unpublished study
received 01/01/01) .
:0084 Amchem Products, Incorporated (1968) Improved methodology
for the determination of Amiben residues in various
crops. (Unpublished study received 10-25-68 under 7F0591;
CDL:090759)
:0109 Amchem Products, Incorporated (1968) Residue analysis of
Amiben super 6 liquid and granular. (Unpublished study
received 5-23-75 under 264-266; CDL:101106)
:0006 Amchem Products, Incorporated (1969) Analytical methods
and data for detection of residues on soybeans.
(Unpublished study received 10-6-69 under 264-ELR,
264-ELE; CDL:101237)
:0110 Amchem Products, Incorporated (1969) Residues of Amiben
and Atrazine in corn. (Unpublished report received 10-22-
69 under 264-ELG; CDL.-101220)
:0166 Arachem Products, Incorporated (196?) Gas chromatographic
method for the analysis of lima beans for possible
residues of Amiben. (Unpublished study received 4-3-67
under 7F0591; CDL:090758)
:0167 Amchem Products, Incorporated (196?) Gas chromatographic
method 'for the analysis of tomatoes for possible residues
of Amiben. (Unpublished study received 4-3-67 under
7F0591; CDL:090758)
-------
:0120 Amchem Products, Incorporated (196-?) Residues on
soybeans. (Unpublished report received 01/01/01).
:0081 Amchem Products, Incorporated (196?) The name, chemical,
identity, composition of Amiben. (Unpublished study
received 3-31-67 under 7F0591; CDL.-090879)
:0118 Amchem Products, Incorporated (1976) Amiben/Lasso on
soybeans chloramben analyses. (Unpublished report
received 4-13-76 under 264-138; CDL:225085)
:0067 Amchem Products, Incorporated (1978) Amiben PKa values.
(Unpublished study received 6-22-78 under 264-306;
CDL:234221)
:0056 Amchem Products, Incorporated (1978) Amiben sodium
salt/corn residues. (Unpublished study received 6-22-78
under 264-306; CDL:234221)
:0057 Amchem Products, Incorporated (1978) Amiben sodium
salt/soybean residues. (Unpublished study received
6-22-78 under 264-306; CDL:234221)
:0101 Amchem Products, Incorporated (1978) Analysis of soybeans
and soybean hay (dry vines) for possible residues of
chloramben resulting from postemergence treatments with
Amiben. (Unpublished report reeceived 4-11-79 under 264-
138; CDL:238013)
:0069 Amchem Products, Incorporated (1978) Formulation
stability. (Unpublished study received 6-22-78 under 264-
306; CDL.-234221)
:0153 Amchem Products, Incorporated (1978) N-Nitrosamine
analyses/formulated products. (Unpublished study received
7-11-78 under 264-138, 264-244; CDL.-234361)
:0054 Amchem Products, Incorporated (1979) Physical/chemical
properties of technical grade sodium Chloramben.
(Unpublished study received 4-10-79 under 264-305;
CDL:238008)
:0083 Amchem Products, Incorporated (197?) Procedure for the
determination of 3-amino 2,5-dichlorobenzoic acid
(Chloramben) in Amiben formulations. (Unpublished study
received 4-10-79 under 264-306; CDL:238007)
:0029 A.iM.S. Associates (1966) Reproduction study in albino rats
with Amchem Products Inc., - Amiben (3-amino-2,5-
dichlorobenzoic acid). Project *200-064. (Unpublished
study received February 28, 1967 under 7F0591 prepared
for Amchem Products Inc., CDL:090760)
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:0502 Anderson, K . J .; Leighty/E.? Takahashi , M.T. (1972)
Evaluation of herbicides for possible mutagenic
properties. Journal of Agricultural and Food Chemistry
20(3): 649-656.
:0548 Ashton, P.M. (1966) Fate of Amiben-14C in carrots. WEEDS
14(1):55-57.
:0092 Baker, E.M. (1964) Addena to evaluation for NR use on lima
beans. (Unpublished report received 11-1-63 under 264-Q;
CDL:121504)
:0541 Berkheiser, V.E.; Ahlrichs, J.L. (1976) UV and IR
spectral characteristics of chloramben in selected
environments. Weed Science 24(1): 107-114.
:0051 Bionomics, Incorporated (1970) Acute toxicity of Amiben
concentrate (65-319) to Fathead Minnow, Bluegill, and
Rainbow Trout. (Unpublished study received 4-9-70 under
264-ELR, 264-ELE; CDL:100524)
:0002 Biosearch, Incorporated (1969) Acute dermal toxicity -
rabbits of Amchem 65-319. (Unpublished study received
October 6, 1969 under 264-ELR, 264-ELE; prepared for
Amchem Products, Inc.; CDL:100527)
:0145 Biosearch/ Incorporated (1969) Acute oral toxicity -
Bobwhite Quail. (Unpublished report received 4/70)
:0001 Biosearch, Incorporated (1969) Acute oral toxicity - rats
of Amchem 65-319. (Unpublished study received October 6,
1969 under 264-ELR, 264-ELE; prepared for Amchera
Products, Inc.; CDL:100527)
:0003 Biosearch, Incorporated (1969) Draize eye irritation -
rabbits of Amchem 65-319. (Unpublished study received
October 6, 1969 under 264-ELE, 264-ELR; prepared for
Amchera Products, Inc.; CDL:100527)
:0504 Burchfield, H.P.; Storrs, E.E.; Kraybill, H.F. (1975) The
maximum tolerated dose in pesticide carcinogenicity
studies. Environ. Qual. Saf . , Suppl. 3(Pesticides): 599-
603.
:0549 Butler, G.L. (1977) Algae and Pesticides. Pages 19-62,
Residue Reviews Residues of Pesticides and Other
Contaminants in the Total Environmental-Vol. 66. Francis
A. Gunther, Jane Davies Gunther^. Illustrated. New York,
NY: Springer-Verlag.
:0065 CDC Research Incorporated (1978) Acute dermal application
(LD50) in rabbits of sodium chloramben. (Unpublished
study received 6/22/78 under 264-305; CDL:234220)
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:0063 CDC Research, Incorporated (1978) Primary skin irritation
in rabbits of sodium chloramben. (Unpublished study
received 6/22/78 under 264-305; CDL:234220)
:0064 CDC Research Incorporated (1978) Rabbit Eye Irritation in
rabbits of sodium chloramben. (Unpublished study
received 6/22/78 under 264-305; CDL:234220)
:0524 Chio, Hang; Sanborn, J.R. (1978) The metabolism of
atrazine, chloramben, dicamba in earthworms (Lumbricus
terrestris) from treated and untreated plots. Weed Science
26(4): 331-335.
:0156 Colby, S.R. (1965) Herbicide metabolism: N-glycoside of
Amiben isolated from soybean plants. Science Vol. 150,
No. 3696, p. 619. (Study received 4-3-67 under 7F0591;
CDL:090758)
:0586 Corbin, Frederick T.; Upchurch, Robert P. (1967)
Influence of pH on detoxification of herbicides in soil.
WEEDS 15(4): 370-377.
:0587 Crosby, D.G.; Leitis, E. (1969) Photodecomposition of
chlorobenzoic acids. Journal of Agricultural and Food
Chemistry 17(5) 1033-1035.
:0007 Diablo Laboratories (1964) Analysis of dried beans for
possible amiben residues (Unpublished study received
1-31-64 under 264-167; CDL:121512)
:0033 Dow Chemical Company (1969) Analytical method for
determination of Amiben and Dinoseb in formulations.
(Unpublished study received 12-30-69 under 264-ELA;
CDL:100736)
:0050 Blanco Products, Incorporated (1978 )^ Trifluralin and
chloramben residue data on soybeans. (Unpublished report
received 2-9-78 under 1471-35; CDL:232828)
:0589 Fickle, J.S. (1974) Environmental factors affecting the
movement and persistence of chloramben in solis.
Dissertation Abstracts International 34(9): 4160.
:0062 Food and Drug Research Laboratories, Incorporated (1978)
Inhalation toxicity study of amiben sodium salt #3599 in
adult Sprague - Dawley rats. (Unpublished study
received 6/22/78 under 264-305; CDL:234220)
:0556 Frear, D.S.; Swanson, H.R.; Mansager, E.R.; Wien, R.G.
(1978) Chloramben metabolism in plants: isolation and
identification of glucose ester. Journal of Agricultural
and Food Chemistry 26(6):1340-1351.
:0128 Freed, Virgil H. (1960) Determination of amiben in soil.
(Unpublished study received 8-24-61 under 264-167;
CDL:120434)
-------
:0594 Hahn , R.R.; Burnside, O.C.; Lavy, T.L. (1969) Dissipation
and phytotoxicity and dicamba. Weed Science 17(1): 308.
:0595 Harris, Clare Irving (1967) Movement of herbicides in
soil. WEEDS 15(3): 214-216.
:0596 Harter, R.D.; Ahlrichs, J.L. (1969) Effect of acidity on
preactions of organic acids and amines with
montmorillonitic clay surfaces. Proceedings of the Soil
Science Society of America. 33(6): 859.
:0023 Hazleton Laboratories, Incorporated (1959) Acute dermal
application - rabbits of technical grade chloramben.
(Unpublished study received February 28, 1967 under
7F0591; prepared for Amchem Products Inc.; CDL:090760
:0022 Hazleton Laboratories, Incorporated (1959) Acute oral
administration - rats of technical grade chloramben.
(Unpublished study received February 28, 1967 under
7F0591; prepared for Amchem Product Inc.; CDL:090760)
:0028 Hazleton Laboratories, Incorporated (1963) Two-Year
dietary feeding-dogs of technical grade chloraraben(?) .
(Unpublished study received February 28, 1967 under
7F0591; prepared for Amchem Products Inc.; CDL:090760)
:0024 Hazleton Laboratories, Incorporated (1966) Acute oral
administration - Rats of ammonium salt, technical methyl
ester, and formulated methyl ester. (Unpublished study
received February 28, 1967 under 7F0591; prepared for
Amchem Products Inc.; CDL:090760)
:0143 Hazleton Laboratories, Incorporated (1968) Acute dermal
application - rabbits, acute eye application - rabbits of
65-81-B. (Unpublished study received 01/01/01)
:0144 Hazleton Laboratories, Incorporated (1968) Acute
inhalation exposure - rats of 65-81-B (Technical Grade
Methyl Ester). (Unpublished study received 01/01/01)
:0146 Hughes, J.S. (1970) Letter dated January 26, 1970 to John
E. Gallagher/ Amchem Products, Inc. (Unpublished;
prepared by Louisiana Wildlife and Fisheries
Commission)
:0170 Huntington Research Center (1978) Eighteen (18) month
oncogenic study following prolonged oral administration in
Crl: COBS CD-I mice of amiben acid technical/ volumes I
and II. (Unpublished study received July 9, 1980 under
7F0591; prepared for Union Carbide Agricultural Products
Division; CDL:242821)
:05100 Knake, Ellery L.; Appleby, Arnold P.; Furtick, William R.
(1967) Soil incorporation and site of uptake of
preemergence herbicides. WEEDS 15(3): 228-232.
-------
: 05116 Lewis, C. (1980) Use Pattern Summary Report for
Chloramben. U.S. Environmental Protection Agency, Plant
Sciences Branch, Benefits and Field Studies Division.
:0171 Litton Bionetics, Incorporated (1980) Two-Year
carcinogenesis study in rats of technical grade
chloramben. (Unpublished study received 1/15/80 under
7F0591; prepared for Union Carbide Agricultural Products
Divison; CDL:241603)
:0147 McLane, S.R.; Parkins, M.D. (196?) Biological and physical
attributes of several amiben derivatives. (Unpublished
study received 01/01/01)
:05117 Miller, C.S.; Hoover, W.L.; Culver (1980) Exposure of
pesticide applicators to Arsenic Acid. Arch. Environ.
Contain. Toxicol. 9: 281.
:0536 Morton, H.L.; Moffett, J.O. (1972) Toxicity of herbicides
to newly emerged honey beees. Environmental Entomology
1(1): 102-104.
:0019 National Cancer Institute (1977) Bioassay of chloramben
for possible carcinogenicity (Study received December 15,
1977; prepared by Gulf South Research Institute for NCI;
CDL:233410)
:0146a Otten, R.J. (1970) Factory Correspondence. Subject:
Amiben - fish toxicity- (Unpublished; submitted by
Amiben Products, Inc.)
:05119 Peoples, S.A.; Maddy, K.; Datta, P.R.; Johnston, L.;
Smith, C.; Conrad, D.; Copper, C. (1979) Monitoring of
potential exposures of mixer loaders, pilots and flaggers
during application of Tributyl Phosphorotrithioate (DEF)
and Tributyl Phosphorotrithioite (Foloex) to cotton
fields in the San Joaquin Valley of California in 1979.
California Department of Food and Agriculture : 45-676.
:05106 Plimmer, J.R.; Hummer, B.E. (1969) Photolysis of amiben
(3 amino-2 5-dichloro benzoic acid) and its methyl ester.
Journal of Agricultural and Food Chemistry 17(1): 83-85.
:0131 Rauser, W.E.; Switzer, C.M. (1063) Effects of leaching on
the persistence of Amiben toxicity in various soils.
(Unpublished study received 2-17-64 under 264-138;
CDL:002092)
:0570 Samosvat, L.S.; Voynova, I.V. (1975) Colorimetric method
of determination of amiben in air, water and soil.
National Technical Information Service, Dept. of Commerce.
:05107 Sheets, T.J.; Smith, J.W.; Kaufman, D.D. (1968)
Persistence of benzoic and phenyl acetic acids in soils,
Weed Science 16(2): 217-222.
-------
:05118 Staiff, D.C.; Comer, S.W.; Armstrong, J.F.; Wolfe, R.R.
(1975) Exposure to the herbicide Paraquat. Bull.
Environ. Contam. Toxicol.
:0041 Stauffer Chemical Company (1979) Summaries and analytical
reports for tank mixes containing Vernam 7E. (Unpublished
reported received 6-20-79 under 476-2155; CDL:238641)
:0577 St. John, L.E. Jr.; Lisk, D.J. (1970) Excretory pathway
of amiben in a lactating cow. Journal of Agricultural and
Food Chemistry 18(3): 482-484.
:05110 Stoller, E.W. (1969) Kinetics of amiben absorption and
metabolism as related to species sensitivity. Plant
Physiology 44(6):, 854.
:0538 Stoller, E.W. (1970) Mechanism for the differential
translocation of Amiben in plants. Plant Physiology
46(5): 732-737.
:0169 Swanson, C.R.; Kadunce, R.E.; Hodgson, R.H.; Frear, D.S.
(1966) Amiben Metabolism in Plants I. Isolation and
identification of an N-glucosyl complex. Weeds. Vol.
14, No. 4. pp. 319. (Study received 4-3-67 under 7F0591;
CDL:090758)
:05111 Talbert, R.E.; Runyan, R.L.; Baker, H.R. (1970) Behavior
of amiben and dinoben derivatives in Arkansas soils.
Weed Science 18(1): 10-15.
:0539 Torstensson, Lennart; Stade, Eva (1976) Effects of some
herbicides on soil microorganisms and on the rhizobium-
leguminosae symbiosis. Sweedish Weed Conference J
(Proceedings) 17(Weeds Weed Control): K2-K7.
:0049 Truslow Farms (1974) Mallard Duck LC50 of ammonium
chloramben - 23.4%. (Unpublished report received 7/20/74
under 264-Q; CDL:132485)
:0020 Union Carbide Environmental Services (1978) Bluegill
sunfish bioconcentration study. (Unpublished report
received 8-30-78 under 264-138; CDL:235264)
:0018 Union Carbide Environmental Services (1978) Channel
catfish bioconcentration study. (Unpublished report
received 8-30-78 under 264-138; CDL:235265)
:0060 Union Carbide Environmental Services (1978) The acute
toxicity of Amiben sodium salt to Bluegill Sunfish.
(Unpublished study received 6/22/78 under 264-306;
CDL:234221)
10
-------
:0061 Union Carbide Environmental Services (1978) The acute
toxicity of Amiben sodium salt to the Rainbow Trout.
(Unpublished study received 6/22/78 under 264-306;
CDL:234221)
:0172 Union Carbide (1981) Fate of chloramben. (Unpublished
study received 2/3/81 under 264-306; CDL: )
:0157 Warren, L.C.; Behrens , R. (1961) C14 Amiben study in
soybeans post-emergence application. (Unpublished study
received 4-3-67 under 7F0591; CDL.-090758)
:0059 Wildlife International, Limited (1978) Eight day dietary
LC50 Mallard Duck of Amiben sodium salt. (Unpublished
study received 6/23/78 under 264-305; CDL:234220)
; 05115 Wildung, Raymond Earle; Chesters, Gordon; Armstrong,
David E. (1968) Chloramben (amiben) degradation in soil.
Weed Research 8(3): 213-225.
05120 Wolfe, H.R.; Durham, W.F.; Batchelor, G.S. (1961) Health
hazards of some dinitro compounds, effects associated
with agricultural usage in Washington State.
0048 Zweig , G.; Sherma, J. (1972) Analytical Methods for
Pesticides and Plant Growth Regulators. Volume VI: Gas
Chromatographic Analysis. (Report received 01-01-01
under 3125-277; CDL:225408)
11
-------
OFFICE OF PESTICIDE PROGRAMS
PESTICIDE DOCUMENT MANAGEMENT SYSTEM
CASE BIBLIOGRAPHY
Section 2: Citations Examined and Judged to be Citations
Inappropriate for Use in Developing the Standard
Citation
:0518 Altman, J.; Campbell, C.L. (1977) Effect of herbicides on
plant diseases. Annual Review of Phytopathology Vol. 15:
pp. 499-
:0013 Amchem Products, Incorporated (1960) Call report: Factory
correspondence. Subject: soybean plant residues.
(Unpublished study received 01/01/01 under 264-Q;
CDL:121514)
:0012 Amchem Products, Incorporated (1960) Phytotoxicity of
Amiben (appendix VIII). (Unpublished study submitted
under 264-Q? CDL:121514)
:0047 Amchem Products, Incorporated (1960) Residue Program for
Soybeans. (Unpublished study received 3-15-60 under 24-
EX013; CDL:127038)
:0017 Amchem Products, Incorporated (1961) Procedure for the
determination of traces of 3-amino-2,5-dichlorobenzoic
acid in tomatoes. (Unpublished study received 3-11-61
under NR8970-4; CDL:126195)
:0152 Amchem Products, Incorporated (1964) Analysis of pumpkin
and squash for possible residues of Amiben. (Unpublished
study received 3-25-64 under 264-175, 264-178; CDL:002148)
:0138 Amchem Products, Incorporated (1965) Section 3 Residue
Analysis: Analysis of peanuts for possible residues of
amiben. (Unpublished study received 2-24-65 under 264-
138; CDL:002097)
:0038 Amchem Products, Incorporated (1966) Amiben toxicity
summary: a formulation comparison* (Unpublished study
received under c957; CDL:098715)
:0046 Amchem Products, Incorporated (1967) Methods of residue
analysis. (Unpublished study received 4-3-67 under
7F0591; CDL:090758)
:0087 Amchem Products, Incorporated (1968) Analysis of forage
samples for possible residues of amiben. (Unpublished
study received 10-25-68 under 7F0591; CDL:090759)
-------
:0031 Amchem Products, Incorporated (1968) Soybean residue
data. (Unpublished study received 5-7-73 under 7F0591;
CDL:008500)
:0099 Amchem Products, Incorporated (196?) Method for the
determination of amiben liquid or granular formulations.
(Unpublished study received 01-01-01 under 264-Q;
CDL:121347)
:0068 Amchem Products, Incorporated (1978) Physical chemistry of
sodium salt of Amifaen. (Unpublished study received 6-22-
78 under 264-306; CDL:234221)
:0100 Amchem Products, Incorporated (1979) Chloramben and
Trifluralin analyses of sunflowers treated with Amiben and
Treflan tank mix PPI . (Unpublished report received 3-7-79
under 264-138; CDL:238153)
:0519 Ashton, F.M.S; DeVilliers, O.T.; Glenn, R.K.; Duke, W.B.
(1977) Localization of metabolic sites of action of
herbicides. Pesticide Biochemistry and Physiology 7(2):
122-141.
:0072 Baker, R.S. (1960) Leaching and adsorption. (Unpublished
study received 8-24-61 under 264-167; CDL:106953)
:0112 Baron, P.O. (1968) Review of toxicology data.
(Unpublished review dated 8/8/68; CDL:106948)
:0004 Biosearch, Incorporated (1969) Acute inhalation toxicity -
rats of Amchem 65-319. (Unpublished study reeceived
October 6, 1969 under 264-ELR, 264-ELE; prepared for
Amchem Products, Inc.; CDL:100527)
:0145 Biosearch, Incorporated (1969) Acute oral toxicity -
Bobwhite Quail. (Unpublished report received 4/70)
:0001 Biosearch, Incorporated (1969) Acute oral toxicity - rats
of Amchem 65-319- (Unpublished study received October
6, 1969 under 264-ELR, 264-ELE; prepared for Amchem
Products, Inc.; CDL:100527)
:0003 Biosearch, Incorporated (1969) Draize eye irritation -
rabbits of Amchem 65-319. (Unpublished study received
October 6, 1969 under 264-ELE, 264-ELR; prepared for
Amchem Products, Inc.; CDL:100527)
:0094 Bois, H. (1964) Evaluation of data for NR registration for
Achemm Amiben Granular on soybeans and dry beans.
(Unpublished review dated 2-12-64; CDL:121510)
:0095 Bois, H. (1964) Memorandum of conference. Subject: NR
Registration for Amchem Amiben Granular on dry beans and
peppers. (Unpublished memo dated 2-13-64; CDL:121509)
-------
:0520 Burgis, D.S. (1972) Herbicide tests on pepper transplants
and seeded peppers. Proceedings of the Florida State
Horticultural Society 84: 183-186.
:0168 Burnside, O.G. (1965) Longevity of Amiben, Atrazine, and
2,3,6-TBA in incubated soils. Weeds. Vol. 13, No. 3,
page 274. (Study received 4-3-67 under 7F0591; CDL.-090758
:0584 Burnside, O.C.; Schultz, M.E. (1978) Soil persistence of
herbicides for corn, sorghum, and soybeans during
the years of application. Weed Science 26(2): 108-115.
:0550 Carey, A.E.; Wiersma , G.B.; Tai , H; Mitchell, W.G. (1973)
Organo chlorine pesticide residues in soils and crops of
the corn belt region USA 1970. Pesticide
Monitoring Journal 6(4) 369-376.
:0521 Carney, A.N.; Stephenson, G.R.; Ormrod, D.P.; Ashton,
G.C. (1973) Ozone-herbicide interactions in crop plants.
Weed Science 21(6):508-511.
:0014 Caswell, R.I. (1963) Addenda to review of residue data on
tomatoes. (Unpublished review dated 4-30-63; CDL:121525)
:0015 Caswell, R.I. (1964) Review of sweet potato residue data.
(Unpublished review dated 7/27/64; CDL:121527)
:0066 CDC Research Incorporated (1978) Acute oral LD50 in rats
of sodium chloramben. (Unpublished study received 6/22/78
under 264-305; CDL:234220)
:0522 Chang, Fa-Yan; Smith, Leon W.; Stephenson, Gerald R.
(1971) Insecticide inhibition of herbicide metabolismin^
.leaf tissues. Journal of Agricultural and Food Chemistry
19(6): 1183-1186.
:0523 Chen, M.L.; Chen, V. K-H. (1977) Electrical measurement
of membrane properties change of conductance of soy
lecithin membranes by the herbicide chloramben.
Proceedings of the American Phytopathological Society 4:
135.
:0551 Chow, Paul N.P. (1975) Absorption of herbicides by wheat
as influenced by the phenoxy compound. Journal of
Agricultural and Food Chemistry 23(4): 730-736.
:0542 Coffey, David L.; Warren, George F. (1969) Inactivation
of herbicides by activating carbon and other absorbents.
Weed Science 17(1): 16-19.
:0525 Colby, S.R. (1966) The mechanism of selectivity of
Amiben. WEEDS 14(3): 197-201.'
:0073 Colby, S.R.; Baker, R.S.; Warren, G.F. (1962) Residue of
C14 Amiben in greenhouse tomatoes. (Unpublished study
received 3-11-63 under NR-7532; CDL:120695)
-------
:0552 Colby, S.R.; et al (1964) Fate of Amiben in tomato
plants. Journal of Agricultural and Food Chemistry 12:
320-321.
:0155 Colby, S.R.; Warren, G.F.; Baker, R.S. (1964) Fate of
amiben in tomato plants. Agricultural and Food
Chemistry. Vol. 12, No. 4, p. 320. (Study received
4-3-67 under 7F0591; CDL:090758)
:0585 Cooke , A.R. (1966) Controlled studies on the interaction
of rainfall and preemergence herbicide activity.
Mededelingen van de Rijksfaculteit Landbouwwetenschappen
te Gent 31(3): 1165-1170.
:0586 Corbin, Frederick T.; Upchurch, Robert P. (1967)
Influence of pH on .detoxification of herbicides in soil .
WEEDS 15(4): 370-377.
:0505 Crouch, E.;- Wilson, R. (1979) Interspecies comparison of
carcinogenic potency. Journal of Toxicology and
Environmental Health 5(6): 1095-1118.
:0113 Dale, L.B. (1970) Review of toxicity data. (Unpublished
review dated 2/9/70; CDL:106950)
:0005 Dale, L.B. (1969) Review of acute toxicity data for Amchem
65-319. (Unpublished report completed December 1, 1969
under 264-ELE, 264-ELR; CDL:100533)
:0555 Doll, J.D.; Penner, D.; Meggit, W.F. (1970) Herbicides
and phosphorous influence on root absorption of amiben
and atrazine. Weed Science 18(3): 357-359.
:0032 Dow Chemical Company (1969) Acute toxicological prope-rties
of Premerge 21 Weed Killer. (Unpublished study received
12/30/69 under 464-GIG; prepared for Dow Chemical Company;
CDL:003598)
:0111 EPA (1967) Review of data on technical grade chloramben.
(Unpublished review dated 1/17/67; CDL.-106947)
:0583 Eshel, Yael; Warren, George, F. (1967) A simplified
method for determining phytotoxicity, leaching and
adsorption of herbicides in soil. WEEDS 15(2): 115-118.
:0526 Fabacher, D.L.; Chambers, H. (1974) Resistance to
herbicides in mosquitofish. Environmental Letters 7(1):
15-20.
:0590 Frear, D.S. (1976) The Benzoic Acid Herbicides. Pages 541-
607, In Herbicides. Chemistry, Degradation, and Mode of
Action (Vol.2). Kearney, P.C. and D.D. Kaufman.
Illustrated. New York, N.Y. Marcel Decker.
-------
:0165 Freed, V.H. (1961) Old colorimetric method for Amiben
residue analysis in soybean meal and soybean oil.
(Unpublished study received 4-3-67 under 7F0591;
CDL:090758)
:0591 Freed, V.H.; Chiou, C.T = ; Hague, R-. (1977) Chemodynamics
transport and behavior of chemicals in the environment a
problem in environmental health. Environmental Health
Perspectives 20:55-70.
:0558 Geshtout, Yi3 N.; Zharasov, Sh U. ;Bainazarova, Kh E. ;
Kostutinov, E.; Baranovskii, M.F. (1973) Herbicides in a
fallow/cereals/row crop rotation. Vestnik
Sel'skokhozyaistuennoi Nauki Kazakhstana 16(12): 30-34.
:0506 Gram, T.E.; Litterst, C.L.; Mimnaugh, E.G. (1974)
Enzymatic conjugation of foreign chemical compounds by
rabbit lung and liver. Drug Metabolism and Disposition
2(3): 254-258.
:0593 Greig, James, K.; Motes, J.E. (1966) Persistence of
preemergent herbicides in controlling weeds in sweet
potato plantings. Proceedings of the North Central Weed
Control Conference 20: 25-26.
:0597 Hailing, C.S. (1971) Pesticide mobility in soils.
Proceedings of the Soil Science Society of America. 35(5)
737.
:0528 Harrison, G.W.; Weber, J.B. (1975) Comparative
phytotoxicities of five herbicides in ten North Carolina
soils. Proceedings 28th Annual Meeting Southern Weed
Science Society: 283-291.
:0026 Hazleton Laboratories, Incorporated (1959) Acute eye
application - rabbits of technical grade chloramben.
(Unpublished study received February 28, 1967 under
7F0591; prepared for Amchem Products Inc.; CDL:090760)
:0025 Hazleton Laboratories, Incorporated (1959) Twenty-Eight
day dietary feeding-rats of technical grade chloramben.
(Unpublished study received February 28, 1967 under
7F0591; prepared for Amchem Products Inc.; CDL:090760)
:0114 Hazleton Laboratories (1961) Progress report (26-week
dietary feeding - rats; seven week dietary feeding dogs.
(Unpublished study data 6/22/61 under 7F0591; CDL:106951)
:0116 Hazleton Laboratories (1963) Summary report - two year
dietary feeding - dogs. (Unpublished study dated 5/15/63
under 7F0591; CDL:106955)
:0028 Hazleton Laboratories, Incorporated (1963) Two-Year
dietary feeding-dogs of technical grade chloramben(?) .
(Unpublished study received February 28, 1967 under
7F0591; prepared for Amchem Products Inc.; CDL:090760)
-------
:0027 Hazleton Laboratories, Incorporated (1963) Two-Year
dietary feeding-rats of technical grade chloramben(?).
(Unpublished study received February 28, 1967 under
7F0591; prepared for Amchem Products Inc.; CDL:090760)
:0088 Hazleton Laboratories, Incorporated (1967) Supplement to
final report (1963) - two year dietary feeding - rats of
technical grade chloramben(?) (Unpublished study
received 8/19/67 under 7F0591)
:0086 Hazleton Laboratories, Incorporated (1967) 28-Day oral
administration - dogs of technical grade chloramben.
(Unpublished study received 10/25/68 under 7F0591;
CDL:090759)
:0150 Hazleton Laboratories, Incorporated (1973) Analysis of
amiben and trifluraln residues in soybeans (Beans) .
(Unpublished study received 8-20-73 under 264-138;
CDL:008803)
:0598 Holloman, M.E.; Hutto, Fay Y.; Kennedy, M.V.; Swanson,
C.R. (1976) Thermal degradation of selected herbicides.
Journal of Agricultural and Food Chemistry 24(6): 1194-
1198.
:0529 Houghton, J.N. (1974) Ecological changes in weed
populations as a result of crop rotations and herbicides.
Dissertation Abstracts International 34(9): 4160-4161.
:0508 Hubbeling, N; Chaudhary, K.C. Basu (1970) Mutagenic
effect of a herbicide on Verticillium dahlia^. Meded .
Fac. Landbouwwetensch Rijksuniu Gent 35(2):' 627-635.
:0009 Hughes, R.E.; Freed, U.K. (1960) Physical/chemical
properties and analytical method for Amiben. (Unpublished
study received 01/01/01 under 264-Q; CDL:121514)
:0509 Iden, D.L.; Schroeter, A.L. (1977) Allergic contact
dermatitis to herbicides. Archives of Dermatology 113(7):
9-83.
:0599 Ivie, G.W.; Casida, J.E. (1971) Sensitized
photodecomposition and photosensitizer activity of
pesticide chemicals exposed to sunlight on silica gel
chromatoplates. Journal of Agricultural and Food Chemistry
19(3): 405-409.
:0561 Kapusta , George; Rouwenhorst, D.L. (1973) Interaction of
selected pesticides and Rhizobium jabonicum in pure
culture and under field conditions. Agronomy Journal
65(1): 112-115.
:0562 Knake, Ellery L.; Wax, Loyd M. (1968) The importance of
the shoot of giant foxtail for uptake of preremergence
herbicides. Weed Science 16(3) :~ 393-395.
-------
:05101 Kune, F. (1975) Control of pesticide persistence in soil
with special respect to microbial activity. Zbl. Bakt.
Abt. II 130(1) : 82-103 .
:0531 Lee, O.P. (1973) Studies on the mode of action of 3-amino-
2,5- dichlorobenzoic acid on tobacco callus tissue in
vitro. Dissertation Abstracts International 34(2): 483.
:0532 Linscott, J.J. (1969) Phytotoxicity and movement of
amiben derivatives in soil. Weed Science 17(2): 170-174.
:0533 McCorkle, P.M.; Chambers, J.E.; Yarbrough, J.D. (1977)
Acute toxicities of selected herbicides to Fingerling
channel catfish, Ictalurus punctatus. Bulletin of
Environmental Contamination and Toxicology 18(3): 267.
:0563 Melville, D.R.; Oakes, J.Y. (1976) Residual effects of
herbicides in cotton, corn and soybean rotations.
Louisiana Agriculture 19(3): 8-9.
:0564 Miller, J.C. Jr.; Penner, D.; Baker, L.R. (1973) Basis
for variability in the cucumber for tolerance to
chloramben methyl ester. Weed Science 21(3): 207-211.
:0565 Moody, Keith; Kust, Cyril A.; Buchholtz , Kenneth P.
(1970) Uptake of herbicides by soybean roots in culture
solutions. Weed Science 18(5): 642-647.
:0566 Moomaw, R.S.; Burnside, O.C. (1979) Corn residue
management and weed control in close-drilled soybeans.
Agronomy Journal 71(1): 78-80.
:0534 Morton, H.L.; Moffett, J.O. (1972) Effects of herbicides
on honeybees. Proceedings of the Western Society of Weed
Science 25: 15-16.
:0535 Morton, H.L.; Moffett, J.O. (1972) Ovicidal and
larvacidal effects of certain herbicides on honeybees.
Environmental Entomology 1(5): 611-614.
:0567 Olumbe, Johnes W.K.; Veatch, Collins (1969) Organic
matter-amiben interaction on nodulation and growth of
soybeans. Weed Science 17(2): 264-265.
:0082 Otten, R.J. (1969) Memo presenting isomer content of
material used in Hazleton chronic feeding study.
(Unpublished communication received 9/25/72 under 7F0591;
CDL:026765)
:0568 Phillips, R.E.; Egli, D.B.; Thompson, L.J. (1972)
Absorption of herbicides by soybean seeds and their
influence on-emergence and seedling growth. Weed Science
20(5): 506.
-------
:0545 Purkayastha, R. (1969) Direct detection of ionizable
herbicides by electrophoresis. Bulletin of Environmental
Contamination and Toxicology 4(4): 246-255.
:0569 Rieder, G.; Buchholtz, K.P.; Kust, Cyril A. (1970) Uptake
of herbicides by soybean seed. Weed Science 18(1): 101-105
:0514 Robens, J.F. (1978) Tests for possible carcinogenicity of
20 pesticides in Osborne Mendel Rats and B-6C-3F-1 Mice.
Toxicology and Applied Pharmacology 45(1) 236.
:0571 Samosvat, L.S.; Voinova, I.V. (1973) Contribution to the
determination of residues of herbicides and their
metabolites in food products by TLC. Vopros Pitaniia 32(1)
11-78.
:0573 Sarpe, N.; Pyrzhol, L.; Beliano, I. (1975) The influence
of various herbicides on the physiological and biochemical
changes in soybeans and weed plants under conditions of
irrigation. Trudy Usesoyuznogo Nauchno-Issledova tel'
skogo Instituta Zashchity Rastenii 43: 60-72.
:0574 Schrader, John W.; Doll, Jerry D.; Meggit, William F.
(1968) Injection of herbicides for soil placement and to
study site of uptake in the field. Proceedings of North
Central Weed Control Conference 23: 51-53.
:0160 Segal, H.S. (1961) Metabolite analysis 2,5-dichloroaniline
in soybeans. (Unpublished study received 4-3-67 under
7F0591; CDL:090758)
:0105 Shaughnessy, J.A. (1964) Evaluation of data for NR
registration for Amiben on corn. (Unpublished study
received 8-28-64; CDL:121499)
:0576 Sherma/ J.; Touchstone, J.C. (1975) Quantitative thin-
layer chromatography of chloramben herbicide using
densitometry. Chromatographia 8(6): 261-264.
:0130 Slife, F.W. (1964) The translocation of amiben in plants.
(Study received 2-17-64 under 264-138; CDL:002092)
:0537 Stephenson, G.R.; Phatak, S.C.; Makowski, R.I.; Bouw,
W.J. (1980) Phytotoxic interactions involving metribuzin
and other pesticides in tomatoes. Canadian Journal of
Plant Sciences 60(1): 167-175.
:0578 Stoller, E.W.; Wax, L.M. (1968) Amiben herbic metabolism
and selectivity. Weed Science 16(3): 283-288.
:0517 Stupnikov, A.A. (1977) Prophylaxis of animal poisoning
with herbicides and arboricides. Veterinariya (Moscow) 6:
89-91.
8
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:0074Sutherland, M.L. (1961) C14 Aniben ore-emerged tracer
study in soybeans. (Unpublished study received 7-26-61
under 264-138; CDL:101239)
:0129 Sutherland, M.L.; Segal, H.S. (1964) Araiben residues in
food crops. (Study received 2-17-64 under 264-138;
CDL:002092)
:0580 Swanson, C.R.; Hodgson, R.H.; Kadunce, R.E.; Swanson,
H.R. (1966) Amiben metabolism in plants II physiological
factors in N-Glucosyl amiben formation. WEEDS 14(4): 323-
327.
:0582 Taylor, T.D.; Warren, G.F. (1970) Movement of several
herbicides through excised plant tissue. Weed Science
18(1): 64-68.
:0581 Taylor, T.D.; Warren, G.F. (1970) The effect of metabolic
inhibitor.s on herbicide movement in plants. Weed Science
18(1): 68-74.
:0090 U.S. Laboratories, Incorporated (1968) Recovery of Amiben
from dry lima beans, sweet corn, sweet corn forage, sweet
potatoes and soybeans. (Unpublished report received
10/25/68 under 7F0591; CDL:090759)
:0091 U.S Laboratories, Incorporated (1968) Recovery of Amiben
from tomatoes, bell peppers, and summer squash.
(Unpublished report received 10/25/68 under 7F0591;
CDL:090759)
:0132 Warren, G.F. (1963) Adsorption of Amiben in soils.
(Unpublished study received 2-17-64 under 264-138;
CDL:002092)
:05113 Weber, J.B. Jr. (1970) Behavior of herbicides in soils.
Beltwide Cotton Production Research Conferences
(Proceedings) :35-36.
:0583 Welker, W.V. Jr.; Brogdon, J.L. (1972) Effects of
continued use of herbicides in asparagus plantings. Weed
Science 20(5): 428.
*ll S GOVERNMENT PRINTING OFFICE: 1981 341-085/4470
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