v>EPA
United States
Environmental Protection
Agency
Off ice of
Pesticides and Toxic Substances
Washington DC 20460
Polyoxyethylene ethanol
monoesters of 5- (and 6-)
carboxy-4-hexyl-2-cyclohexene-
1-octanoic acid -Iodine Complex
Pesticide Registration
Standard
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Polyoxyethylene cthanol monoesters of 5- (and
6-)carboxy-4-hexyl-2-cyc2ohexene-l-octanoic
acid - Iodine Conp.lex
Pesticide Registration Standard
Michael F. Branagan Project Manager (SPRD)
Linda Garczynski Writer Editor (SPRD)
A. E. Castillo Project Support Team (RD)
September 17, 1981
Office of Pesticides and Toxic Substances
Environmental Protection Agency
401 M Street, SW
VJashington, D.C. 20460
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- TABLE OF CONTENTS -
page
Chaptor I How to Register under a Registration Standard 1
Chapter II Regulatory Position and Rationale 9
Chapter III Summary of Data Requirements and Data Gaps 15
Chapter IV Product Chemistry 20
Chapter V Environmental Fate 21
Chapter VI Toxicology 24
Chapter VII Residue Chemistry 26
Chapter VIII Ecological Effects 27
Chapter IX Efficacy 28
Bibliography 29
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CHAPTER I: HOW TO REGISTER UNDER A REGISTRATION STANDARD
A. Organization of the Standard
B. Purpose of the Standard
C. Requirement to Reregister Under the Standard
D. "Product Specific" Data and "Generic" Data
E. Data Compensation Requirements under FIFRA 3(c)(l)(D)
F. Obtaining Data to Fill'" Data Gaps"; FIFRA 3(c)(2)(B)
G. -Amendments to the Standard
A. Organization of the Standard
This first chapter explains the purpose of a Registration Standard and
summarizes the legal principles involved in registering or reregistering under
a Standard. The second chapter sets forth the requirements that must be met to
obtain or retain registration for products covered by this particular
Registration Standard. In the remaining chapters, the Agency reviews the
available data by scientific discipline, discusses the Agency's concerns with
the identified potential hazards, and logically develops the conditions and
requirements that would reduce those hazards to acceptable levels.
B. Purpose of the Standard
Section 3 of the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA)
provides that "no person in any State may distribute, sell, offer for sale,
hold for sale, ship, deliver for shipment, or receive (and having so received)
deliver or offer to deliver, to any person any pesticide which is not
registered with the Administrator [of EPA]." To approve the registration of a
pesticide, the Administrator must find, pursuant to Section 3(c)(5) that:
"(A) its composition is such as to warrant the proposed claims for it;
(B) its labeling and other material required to be submitted comply
with the requirements of this Act;
(C) it will perform its intended function without unreasonable adverse
effects on the environment; and
(D) when used in accordance with widespread and commonly recognized
practice it will not generally cause unreasonable adverse effects
on the environment."
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In making these findings, the Agency reviews a wide range of data which
registrants are required to submit, and assesses the risks and benefits
associated with the use of the proposed pesticide. But the established
approach to making these findings has been found to he defective on two counts:
First, EPA and its predecessor agency, the United States Department of
Agriculture (USDA), routinely reviewed registration applications on a "product
by product" basis, evaluating each product-specific application somewhat
independently. In the review of products containing similar components, there
was little opportunity for a retrospective review of the full range of
pertinent data available in Agency files and in the public literature. Thus the
"product by product" approach was often inefficient and sometimes resulted in
inconsistent or incomplete regulatory judgments.
Second, over the years, as a result of inevitable and continuing advances in
scientific knowledge, methodology, and policy, the data base for many
pesticides came to be considered inadequate by current scientific and
regulatory standards. Given the long history of pesticide regulation in
several agencies, it is even likely that materials may have been lost from the
data files. When EPA issued new requirements for registration in 1975 (40 CFR
162) and proposed new guidelines for hazard testing in 1978 (43 FR 29686, July
10, 1978 and 43 FR 37336, August 22, 1978), many products that had already been
registered for years were being sold and used without the same assurances of
human and environmental safety as was being required for new products. Because
of this inconsistency, 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 rereviewing 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 method of review was needed.
A new review procedure has been developed. Under it, EPA publishes documents
called Registration Standards, each of which discusses a particular pesticide
active ingredient. Each Registration Standard summarizes all the data
available to the Agency on a particular active ingredient and its current uses,
and sets forth the Agency's comprehensive position on the conditions and
requirements for registration of all existing and future products which contain
that active ingredient. These conditions and requirements, all of which must
be met to obtain or retain full registration or reregistration under Section
3(c)(5) of FIFRA, include the submission of needed scientific data which the
Agency does not now have, compliance with standards of toxicity, composition,
labeling, and packaging, and satisfaction of the data compensation provisions
of FIFRA Section 3(c)(l)(D).
The Standard will also serve as a tool for product classification. As part of
the registration of a pesticide product, EPA may classify each product, for
"general use" or "restricted use" [FIFRA Section 3(d)]. A pesticide is
classified for "restricted use" when some special regulatory restriction is
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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 CFR 162.11(c)(5)l instead of, or in addition to, the certified applicator
requirement. These other regulatory restrictions may include such actions as
seasonal or regional limitations on use, or a requirement for the monitoring of
residue levels after use. A pesticide classified for "general use," or not
classified at all, is available for use by any individual who is in compliance
with State or local regulations. The Registration Standard review compares
information about .potential adverse effects of specific uses of the pesticide
with risk criteria listed in 40 CFR 162.11{c), and thereby determines whether a
product needs to be classified for "restricted use." If the Standard does
classify a pesticide for "restricted use," this determination is stated in the
second chapter.
C. Requirement to Reregister Under the Standard
FIFRA Section 3(g), as amended in 1978, directs EPA to reregister alJ 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, must apply for reregistration. His application must contain proposed
labeling that complies with this Standard.
EPA will issue a notice of intent to cancel the registration of any currently
registered product to which this Standard applies if the registrant fails to
corrply with the procedures for reregistration set forth in the Guidance Package
which accompanies this Standard.
D. "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, 1978; 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,
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the Standard explains the Aqency's reasoning. Data guidelines have not yet
been proposed for the Residue Chemistry discipline, but the requirements for
such data have been in effect for some time and are, the Agency believes,
relatively familiar to registrants. Data which we have found are needed to
evaluate the registrability of some products covered by the Standard may not be
needed for the evaluation of other products, depending upon the composition,
formulation type/ and intended uses of the product in question. The Standard
states which data requirements apply to which product categories. (See the
third chapter.) The various kinds of data normally required for registration
of a pesticide product can be divided into two basic groups:
1. 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
2. Generic data that pertain to the properties or effects of a
particular ingredient, and thus is relevant to an evaluation of
the risks and benefits of all products containing that ingredient
(or all such products having a certain use pattern), regardless of
any such product's unique composition.
The Agency requires certain "product specific" data for each product to
characterize the product's particular composition and physical/chemical
properties (Product Chemistry), and to characterize the product's acute
toxicity (which is a function of its total composition). The applicant for
registration or reregistration of any product, whether it is a manufacturing-
use or end-use product, and without regard to its intended use pattern, must
submit or cite enough of this kind of data to allow EPA to evaluate the
product. For such purposes, "product specific" data on any product other than
the applicant's is irrelevant, unless the other product is closely similar in
composition to the applicant's. (Where it has been found practicable to group
similar products for purposes of evaluating, with a single set of tests, all
products in the group, the Standard so indicates.) "Product specific" data on
the efficacy of particular end-use products is also required where the exact
formulation may affect efficacy and where failure of efficacy could cause
public health problems.
All other data needed to evaluate pesticide products concerns the properties or
effects of a particular ingredient of products (normally a pesticidally active
ingredient, but in some cases a pesticidally inactive, or "inert",
ingredient). Some data in this "generic" category are required to evaluate the
properties anekeffects of all products containing that ingredient [e.g., the
acute LD-50 of the active ingredient in its technical or purer grade; see
proposed 40 CFR 163.81-l(a), 43 FR 37355].
Other "generic" data are required to evaluate all products which both contain a
particular ingredient and are inl ^nded for certain uses (see, e.g., proposed 40
CFR 163.82-1, 43 FR 37363, which requires subchronic oral testing of the active
ingredient with respect to certain use patterns only). Where a particular data
requirement is use-pattern dependent, it will apply to each end-use product
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which is to be labeled for that use pattern (except where surf1, end-use product
is formulated from a registered manufacturing-use product permitting such
formulations) and to each manufacturing-use product with labeling that allows
it to be used to make end-use products with that use pattern. Thus, for
example, a subnhronic oral dosing study is needed to evaluate the safety of any
manufacturing-use product that legally could be used to make an end-use, food-
crop pesticide. But if an end-use product's label specified it was for use
only in ways that involved no food/feed exposure and no repeated human
exposure, the subchronic oral dosing study would not be required to evaluate
the product's safety; and if a manufacturing-use product's label states that
the product is for use only in making end-use products not involving food/feed
use or repeated 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)(B)l 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 tirae he reregisters his product. An
applicant for registration of a new product under this Standard may similarly
request approval for only certain use patterns.
E. Data Compensation Requirements under FIFRA 3(c)(l)(D)
Under FIFRA Section 3(cHD(D), an applicant for registration, reregistration,
or amended registration must offer to pay compensation for certain existing
data the Agency has used in developing the Registration Standard. The data for
which compensation ?nust be offered is all data which are described by all the
following criteria:
1. The data were first submitted to EPA (or to its predecessor
agencies, U.S. Department of Agriculture (USDA) or Food and Drug
Administration (FDA), on or after January 1, 1970;
2. The data were submitted to EPA (or USDA or FDA) 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;
3. 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 pattern(s);
4. The Agency has found the data to be valid and usable in reaching
regulatory conclusions; and
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5. They are not data for which the applicant has been exempted by
FIFRA Section 3(c){2)(D) from the duty to offer to pay
compensation. (This exemption applies to the "generic" data
concerning the safety of an active ingredient of the applicant's
product, not to "product specific" data. The exemption is
available only to applicants whose product is labeled for end-
uses for which the active ingredient in question is present in
the applicant's product because of his use of another registered
product containing that active ingredient which he purchases from
another producer.)
An applicant for reregistration of an already registered product under this
Standard, or for registration of a new product under this Standard, accordingly
must determine which of the data used by EPA in developing the Standard must be
the subject of an offer to pay compensation, and must submit with his
application the appropriate statements' evidencing his compliance with FIFRA
Section 3(c)(l)(D).
An applicant would never be required to offer to pay for "product specific"
data submitted by another firm. In many, if not in most cases, data which is
specific to another firm's product will not suffice to allow EPA to evaluate
the applicant's product, that is, will not be useful to the Agency in
determining whether the applicant's product is registrable. There may be
cases, however, where because of close similarities between the composition of
two or more products, another firm's data may suffice to allow EPA to evaluate
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-use
product, and each applicant for registration or reregistration of an end-use
product, who is not exempted by FIFRA Section 3{c)(2)(D), must comply with the
Section 3(c)(l)(D) requirements with respect to each item of "generic" data
that relates to his product's intended uses.
A detailed description of the procedures an applicant must follow in applying
for reregistration (or new registration) under this Standard is found in the
Guidance Package for this Standard.
F. Obtaining Data to Fill "Data Gaps"; FIFRA 3(c?(2)(B)
Some of the kinds of data EPA needs for its evaluation of the properties and
effects of products to which this Standard applies have never been submitted to
the Agency (or, if submitted, have been found to have deficiencies rendering
them inadequate for making registrability decisions) and have not been located
in the published literature search that EPA conducted as part of preparing this
Standard. Such instances of missing but required data are referred to in the
Standard as "data gaps".
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FIFRA Section 3(c)(2)(B), added to FIFRA by the Conqress in 1978, authorizes
EPA to require registrants to whom a data requirement applies to generate (or
otherwise produce?) data to fill such "gaps" and submit those data to FPA. EPA
must allow a reasonably sufficient period for this to be accomplished. If a
registrant fails to take appropriate and timely steps to fill the data gaps
identified by a section 3(c)(2)(B) order, his product's registration may be
suspended until the data is submitted. A mechanism is provided whereby two or
more registrants may agree to share in the costs of producing data for which
they are both responsible.
The Standard lists, in the third chapter, the "generic" data gaps and notes the
classes of products to which these data gaps pertain. The Standard also points
out that to be registrable under the Standard, a product must be supported by
certain required "product specific" data. In some cases, the Agency may
possess sufficient "product specific" data on one currently registered product,
but may lack such data on another. Only those Standards which apply to a very
small number of currently registered products will attempt to state
definitively the " product specific" data gaps on a "product by product"
basis. (Although the Standard will in some cases note which data that FPA does
possess would suffice to satisfy certain "product specific" data requirements
for a category of products with closely similar composition characteristics.)
As part of the process of reregistering currently registered products, EPA will
issue Section 3(c)(2)(B) directives requiring the registrants to take
appropriate steps to fill all identified data gaps — whether the data in
question are "product specific" or "generic" — in accordance with a schedule.
Persons who wish to obtain registrations for new products under this Standard
will be required to submit (or cite) sufficient "product specific" data before
their applications are approved. Upon registration, they will be required
under Section 3(c)(2)(B) to take appropriate steps to submit data needed to
fill "generic" data gaps. (We expect they will respond to this requirement by
entering into cost-sharing agreements with other registrants who previously
have been told they must furnish the data.) The Guidance Package for this
Standard details the steps that must be taken by registrants to comply with
Section 3(c)(2)(B).
Registrants are reminded that Section 6(a)(2) of FIFRA requires you at any
time to submit factual information raising concerns of possible unreasonable
adverse effects of a pesticide. You should notify the Agency of interim results
of studies in progress if those results show possible adverse effects.
G. Amendments to the Standard
Applications for registration which propose uses or formulations that are not
presently covered by the Standard, or which present product compositions,
product chemistry data, hazard data, toxicity levels, or labeling that do not
meet the requirements of the Standard, will automatically be considered by the
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Agency to be requests for amendments to the Standard. In response to such
applications, the Agency may request additional data to support the proposed
amendment to the Standard, or may deny the application for registration on the
grounds that the proposed product would cause unreasonable adverse effects to
the environment. In the former case, when additional data have been
satisfactorily supplied, and providing that the data do not indicate the
potential for unreasonable adverse effects, the Agency will then amend the
Standard to cover the new registration.
Each Registration Standard is based upon all data and information available to
the Agency's reviewers on a particular date prior to the publication date.
This "cut-off" date is stated at the beginning of the second chapter. Any
subsequent data submissions and any approved amendments will be incorporated
into the Registration Standard by means of addenda, which are available for
inspection at EPA in Washington, D.C., or copies of which may be requested from
the Agency. VJhen all the present "data gaps" have been filled and the
submitted data have been reviewed, the Agency will revise the Registration
Standard. Thereafter, when the Agency determines that the internally
maintained addenda have significantly altered the conditions for registration
under the Standard, the document will be updated and re-issued.
While the Registration Standard discusses only the uses and hazards of products
containing the designated active ingredient(s)f 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: REGULATORS POSITION AND RATIONALE
A. Introduction
B. Description of Chemical
C. Classification under Minor Use
D. Regulatory Position
E. Regulatory Rationale
F. Criteria for Registration Under the Standard
G. Acceptable Ranges and Limits
H. Required Labeling
I . Tolerance Reassessment
A. Introduction
This chapter presents the Agency's regulatory position and rationale based on
an evaluation of all registered products containing polyoxyethylene ethanol
monoesters of 5- (and 6-) carboxy-4-hexyl-2-cyclohexene-l-octanoic acid - iodine
complex as the sole active ingredient. After briefly describing the chemical,
this chapter presents the regulatory position and rationale, the criteria for
registration of products containing this chemical, labeling considerations and
a tolerance reassessment . A summary of data requirements is contained in
chapter III. A discussion of the data upon which this regulatory position is
based is presented in each of the disciplinary chapters, IV through VIII.
B. Description of Chemical
Polyoxyethylene ethanol monoesters of 5- (and 6-)carboxy-4-hexyl-2-cyclohexene-J-
octanoic acid - iodine complex is the active ingredient, found at
concentrationof 4.3 percent, in a low foaming iodophor industrial sanitizer of
food contact surfaces (eg. food processing equipment), dishes, glasses and
utensils.
The structural formulas for this active ingredient are:
C==C
/ \
),-C C-(CH7)7-C=0 I
=> \ / * ' | |
C— C 0-(C2H40)6-(C2H40)7-C2H4-OH
HO-CO
Polyoxyethylene ethanol nonoesters of 5-carboxy-4-hexyl-2-cyclohexene-l-
octanoic acid - iodine complex
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12
» •
C==C
/ \
H-.C-(CH9),-C C-(CH9)7-C=0 I
J i 5 N / i I , ,
c—c o-(c2H4o)6-(c2H4o)7-c2H4-ai
HO-CO
Polyoxyethylene ethanol monoesters of 6-carboxy-4-hexyl-2-cyclohexene-l-
octanoic acid - iodine complex
Prior to application, the 4.3 percent active ingredient in the formulated
product is'diluted in water at a rate of 1:657 to yield 25 ppm of the
bactericidal iodine. The diluted product is applied to pre-cleaned food contact
surfaces by either spraying or swabbing and to pre-cleaned dishes and utensils
by dipping, swabbing or spraying. The diluted product must remain on the
treated surface to maintain efficacy and to prevent recontamination of the
treated surface.
This product is not currently marketed as a manufacturing-use product. Only one
registrant (Pennwalt Corporation) exists for the sole registered end-use
product containing this chemical.
C. Classification Under Minor Use
End-use products (usually those with less than 25,000 pounds of active
ingredient per year) from which exposure is expected to be minimal, based on
use rates and patterns, may be classified by the Agency to be minor use
chemicals.
After extensive inquiries, the Agency has concluded that this product has never
been marketed. Accordingly, this is a minor use chemical at this time. Both
because of the minor use classification of the end-use product and because no
technical chemical is currently marketed, the environmental fate data
requirements have been reserved in this Standard. The Agency has concluded that
reservation of the requirement for environmental fate testing is justified
because the use patterns of the end-use product containing this chemical are
likely to result in a minimal potential exposure to humans and wildlife.
D< Regulatory Position
Based on a review of the available scientific data and other relevant
information on polyoxyethylene ethanol monoesters of 5-(and 6-)carboxy-4-hexyl-
2-cyclohexene-l-octanoic acid - iodine complex, the Agency has made the
following determinations:
1. Pesticide products containing this active ingredient may be registered,
subject to the terms and conditions specified in this Standard.
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2. None of the risk criteria found in section 162.11(a) of Title 40 U.S. Cork?
of Federal Regulations has been met or exceeded for this active
ingredient.
3. Mo unreasonable adverse effects have been identified for this active
ingredient when used in accordance with label directions and limitations.
4. Because residues on food contact surfaces may result in dietary exposure
to this chemical, a food additive regulation for this chemical roust be
obtained from the Food and Drug Administration (FDA) as a condition of
reregistration. The present registration of this chemical will be
cancelled if a food additive regulation cannot be obtained for this
chemical.
5. Additional data, specified in chapter III, must be developed or agreed to
be developed to maintain the existing registration or to permit new
registrations.
E. Regulatory Rationale
Based on the available product chemistry, acute toxicology and efficacy data,
the Agency has determined that hazards associated with the uses of this
chemical are very small.
Exposure to this chemical, cccuring via consumption of residues remaining on
the food contact surface, via worker exposure to the formulated product, or in
diluting the formulated product, will be very small.
Section 409 of the Federal Food, Drug and Cosmetic Act requires that a food
additive regulation be obtained for all chemicals whose use may result in
residues on food contact surfaces. In a memorandum of agreement between the
Agency and the Department of Health, Education and Welfare (36 FR 24234), both
agencies agreed that the Food and Drug Administration (FDA) will have the
responsibilty for reviewing " petitions for food additive regulations to permit
the use of sanitizers on food contact surfaces." FDA's role, therefore, is to
review the safety of residues which may occur from the use of anti-microbials
on food contact surfaces, while EPA's role is to review the information related
to the pesticidal uses of sanitizers on these surfaces.
B ued on the uses of this chemical, the Agency has concluded that the dietary
exposure lies within the purview of section 409 of the Federal Food, Drug and
Cosmetic Act. The Agency, therefore, defers the dietary risk assessment to
FDA. The Agency will limit its assessment to applicator or user risk.
Current FDA policy only permits the use of sanitizers of food contact surfaces
which have received a food additive regulation. In the past, EPA, charged with
regulating pesticides used on food contact surfaces, registered food contact
surface sanitizers which did not have a food additive regulation. Past Agency
policy required that food contact surfaces treated with uncleared sanitizers
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receive a potable water rinse to rerrove residues. FDA, by contrast, does not
permit the use of a potable water rinse after sanitization and requires that
the sanitizers themselves be the terminal or last rinse of the food contact
surface. FDA contends that the use of a final rinse to rerrove residues of the
sanitizer will counteract the antimicrobial effect of the sanitizer and may
also lead to recontamination of the treated surface.
EPA concurs with FDA's policy and is currently in the process of coordinating
its scientific review process with that agency. As with this chemical, EPA will
require all future applicants for registration of food contact surface
sanitizers to obtain a food additive regulation prior to registration. The
Agency has also decided that all presently registered food contact surface
sanitizers must be cleared by a food additive regulation. Registrants of
sanitizers which aro not cleared for use on food contact surfaces will be
required to obtain a food additive regulation at the time of reregistration. At
the time of reregistration, all chemicals not cleared for use on food contact
surfaces must remove any labeling which recommends their use as a terminal
sanitizing rinse. In addition, at the time of reregistration, all chemicals
which are cleared for use on food contact surfaces previously recommending the
use of a terminal potable water rinse must remove that recommendation.
The Agency has concluded that the limited toxicity and exposure information
available is sufficient to evaluate the applicator risks associated with the
uses of this chemical. This decision is based on two factors: (1) that
available acute toxicity data are sufficient to assess the risks from acute
exposure and (2) that the likelihood of significant chronic exposure is so low
that chronic toxicity data are not necessary to make a regulatory determination
of acceptable risk.
Based on the review of the end-use product acute toxicity data, the Agency has
concluded that proper labeling is sufficient to adequately mitigate any acute
toxicity risks.
The determination that expected chronic exposure is low is based on the
combination of low concentration of the active ingredient, in the formulated
product, the high dilution in the use solution, the staining and irritating
properties of the formulated product, and the required use of goggles and
gloves when using both the concentrated and diluted solution of this chemical.
Based on this low expected chronic exposure, the Agency has concluded that
chronic toxicity data are not required for this chemical and that the risk of a
chronic toxic effect is very low.
Since the indoor uses preclude significant environemtal exposure, except as a
diluted, spent solution which drains into the sanitary sewer, the Agency has
determined that (1) no ecological effects studies are necessary and (2)
activated sludge and hydrolysis tests are sufficient to evaluate the
environmental fate of this chemical. Because of the minor use status of this
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chemical, the Agency has further decided to reserve? its request for
environmental fate data until the total production of this active inqredientin
this and future products containing this chemical roaches 25,000 pounds per
year.
In iioht. of the determination of acceptable risk, the Agency has concluded that
it should continue the registration for this chemical, provided that a food
additive regulation is obtained for this chemical. The present registration of
this chemical will be cancelled if a food additive regulation cannot be
obtained for this chemical.
The Agency has also concluded that it will consider the registration of other
formulations of this chemical, provided that, prior to registration, (1) a
determination is made by FDA as to whether an additional food additive
regulation is required for their specific formulation and (2), if required,
that they also obtain a food additive regulation.
F. Criteria for Registration Under the Standard
To be subject to this Standard, products must meet the following conditions:
- contain polyoxyethylene ethanol monoesters of 5- (and 6-)
carboxy-4-hexyl-2-cyolohexene-l-octanoic acid - iodine complex
as the sole acive ingredient; and
- bear required labeling; and
- conform to the acute toxicity limits, product composition and use
pattern requirements stated in section 5 below.
The applicant for registration or reregistration of products subject to this
Standard must comply with all terms and conditions described in this Standard
including a commitment to fill data gaps on a time schedule specified by the
Agency and, when applicable, offering to pay compensation to the extent
required by 3(c)(l)(D) of the Federal Insecticide, Fungicide and Rodenticide
Act (FIFRA), as amended, 7 U.S.C. 136a(c)(l)(D). As discussed in chapter I,
applicants for registration under this Standard must contact the Registration
Division for specific instructions, including updated information contained in
the guidance package on data requirements and the company whose data must be
cited and to whom compensation must be offered,
G. Acceptable Ranges and Limits
1. Manufacturing-Use Products
No manufacturing-use products are currently registered. Because the active
ingredient is made during the formulation of the end-use product, the Agency
has determined that the production of the currently registered end-use product
13
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falls within the definition of an integrated formulation system. A
manufacturing-use product of any concentration of this chemical is registrable
when labeled in accordance with the results of the appropriate product
chemistry and toxicity testing.
2. End-Use Products
a. Product Composition Standard
Currently the Agency has no information on acceptable ranges and limits for the
product composition of end-use products containing this chemical. To be covered
under this Standard, end-use products containing this chemical must propose
acceptable ranges and limits for both active and inert ingredients.
b. Acute Toxicity Limits
The Agency will consider registration of end-use products containing this
chemical under a general-use classification, regardless of their toxicity
category, provided that they bear appropriate precautionary labeling.
Products whose acute toxicity potentially places them in a restricted-use
classification may be classified for general-use if these pestcides bear
labeling which will reduce the acute hazard of that product to one which is
appropriate for the general-use classification.
c. Use Patterns and Application Methods
To be registered under this standard, end-use products containing this chemical
must be labeled as a food contact surface sanitizer.
H. Required Labeling
To be considered under this Standard, end-use products must bear directions for
use as an industrial, indoor sanitizer to be used on food contact surfaces,
dishes, glasses and utensils without a terminal rinse. Spent use-dilutions of
this chemical should be disposed through the sanitary sewer. In addition, end-
use products must bear precautionary labeling which requires the use of goggles
(face shield) and gloves. All other specific labeling is presented in the
guidance package for this chemical.
I. Tolerance Reassessment
While no tolerance is required for this chemical, provisions of the Federal
Food Drug and Cosmetic Act r^uire the establishment of a food additive
regulation for the use of this chemical on food contact surfaces, dishes,
glasses and utensils. (See 21 CFR section 178.1010) A food additive regulation
must be obtained for this chemical for the registration to remain in effect.
14
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CHAPTER III: SUMMARY OF DATA REQUIREMENTS AND DATA CAPS
A. Introduction
B. Group A Charts: Generic Data Requirements
C. Group B Charts: Manufacturing-Use Data Requirements
D. Group C Charts: End-Use Product-Specific Data Requirements
A. Introduction
Applicants for registration of end-use polyoxyethylene ethanol monoesters of 5-
(and 6-)carboxy-4-hexyl-2-cyclohexene-l-octanoic acid - iodine complex products
must cite or submit the following information on the physical/chemical
properties, composition, fate and toxicity of the proposed product. Data in
this Standard that satisfy registration requirements may be cited, if the
applicant establishes that the proposed product is substantially similar to
another product for which the Agency has received acceptable acute toxicity
tests. Data may be cited provided compensation has been offered to the
submitters of these studies. The Agency will consider both active and inert
ingredients in the determination of substantially similar products. (See
chapter I for discussion of substantially similar products). Before each
requirement is listed the section of the Proposed Guidelines which describes
the type of data and when it is required [43 FR, 29696 of July 10, 1978; and 43
FR, No. 163, 37336 of August 22, 19781. Justification for the test requirement
is provided in the Guidelines. Areas where this Standard differs from the
Guidelines are discussed in the Regulatory Rationale section of chapter II.
Applicants for the reregistration of end-use polyoxyethylene ethanol monoesters
of 5- (and 6-)carboxy-4-hexyl-2-cyclohexene-l-octanoic acid -iodine complex
must submit all information identified as data gaps (see charts). A discussion
of why data additional to that already submitted are necessary, or why data
normally required are not necessary for this chemical, are explained in
footnotes to the charts. The footnotes to the charts offer an explanation of
additional data requirements or data waivers outside of the guidelines. The
data requirements specified are the minimum that will be required.
15
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DATA REQUIREMENTS CHART A
Polyoxyethylene Ethanol Manoesters of 5- (and 6-) Carboxy- 'i-llexyl-2-Cyclohexene-l-Octanoic Acid - Iodine Complex
Generic Data Requirements: ENVIRONMENTAL FATE
Guidelines
Citation
Name of Test
Com position
Does EPA have data
to partially or
totally satisfy
this requirement?
Bibliographic
Citation
Must additional data
be submitted under
FIFRA 3(c)(2KIM?
If so, due when?
163.62-7 (W
Hydrolysis
Technical Grade of
Active Ingredient
Technical Grade of
Active Ingredient
l63.62-8(g) Activated Sludge
These data requirements are current as of September, 1981. Refer to the guidance package for updated requirements.
Reserved 1/
Reserved 1/2/
1. Currently there is no manufacturing-use product for this chemical. Submission of tests normally required of a registered manufacturing-use
chemical will not be requested until such a time as the Agency receives an application for registration of a manufacturing-use chemical and
its production reaches or exceeds 25,000 pounds of A.I. per year. The Agency will monitor production of products containing this chemical
under the authority oF section 7 FIFRA. All protocols should be submitted and reviewed by the Agency prior to initiation of this test.
2. This study will be required pending development of an acceptable protocol.
September, 19S1
DATA REQUIREMENTS CHART A
Polyoxyethylene Ethanol Mjnoesters of 5- (and 6-) Carboxy- 1-Hexyl-2-Cyclohexene-1-Octanoic Acid - Iodine Complex
Generic Data Requirements: TOXICOLOGY
Guidelines
Citation
163.81-1
163.81-2
163.81-3
163.81-1
163.81-5
163.81-6
Name of Test
Acute Oral Toxicity
Acute Dermal Toxicity
Acute Inhalation Toxicity
Primary Eye Irritation
Primary Skin Irritation
Dermal Sensitizatlon
Composition Does EPA have data Bibliographic Must additional data
to partially or Citation be submitted under
totally satisfy FFRA 3?
this requirement? If so, due when?
Technical Grade of no
Active Ingredient
Tech. Grade of A.I. no
Tech. Grade of A. I. no
Tech. Grade of A. I. no
Tech. Grade of A.I. no
Tech. Grade of A. I. no
Reserved
Reserved
Reserved
Reserved
Reserved
Reserved
\J
\J
M
I/
\_l
1/
These data requirements are current as of September, 1981. Refer to the guidance package for updated requirements.
1. Currently there is no manufacturing-use product for this chemical. Submission of tests normally required of a registered manufacturing-use
chemical will not be requested until such time as the Agency receives an application for registration of a oianufactur ing-use chemical.
September,
DATA REQUIREMENTS CHART A
Polyoxyethylene Ethanol Honoesters of 5- (and 6-) Carboxy- ')-Hexyl-2-Cyclohexene-1-Octanoic Acid - Icdine Complex
Generic Data Requirements: RESIDUE CHEMISTRY
Guidelines Name of Test
Citation
Sanitizers containing this chemical must
These data requirements are current as of
Composition Does EPA have data Bibliographic
to partially or Citation
totally satisfy
this requirement?
obtain a food additive regulation for this chemical.
September, 1981. Refer to the guidance package for updated requirements.
Must additional data
be submitted under
FIFRA 3(cM2)(R)?
If so, due when?
September, 1981
16
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DATA REQUIREMENTS CHART 8
Polyoxyethylene Fthanol l-bnoesters of 5- (and 6-) Carboxy- 'l-Hexyl-2-Cyclohexene-l-Octanoic Actd - Iodine Ctfliplex
Manufacturing-Use Data Requirements: PRODUCT CHEMISTRY
Guidelines
Citation
163.61-3
163.61-W
163.61-5
163.61-6
163.61-7
163. W
Name of Test Composition Does EPA have data Bibliographic Must additional data
to partially or Citation be submitted under
totally satisfy FIFRA 3
-------
DATA REQUIREMENTS CHART C
Polyoxyethylene Ethanol htnoesters of 5- (and fi-) Csrboxy- 'i-Hexyl-2-Cycloh»xene-1-Octanoic Acid - Iodine Complex
End-Use Product-Specific Data Requirements: PRODUCT CHEMISTRY
Guidelines
Citation
163.61-3
163.61-n
163.61-5
163.61-6
163.61-7
163.61-2
163.61-3
163.6M-U
163.61-6
163.61-7
163.61-8
163.61-9
163.6U-11
163.64-12
163.61-13
163. 6H-1 M
163.61-15
163.61-16
163.61-17
163.61-18
163.61-19
163.61-20
Name of Test
Product Identitiy i
Disclosure of Ingredients
Description of
Manufacturing Process
Discussion on Formulation
of Unintentional Ingredients
Declaration !t Certification
of Ingredients Limits
Product Analytical Methods
4 Data
Color
Physical State
Odor
Roiling Point
Density or Specific Gravity
Solubility
Vapor Pressure
Octanol/Vfeter Partition
Coefficient
PH
Stability
Oxidizing/ Reducing Action
Flammability
Explosiveness
Storage Stability
Visccsity
Miscibtlity
Corroslveness
Composition
Each Product
Each Product
Each Product
Each Product
Each Product
Each Product
Each Product
Each Product
Each Product
Each Product
Each Product
Each Product
Each Product
Each Product
Each Product
Each Product
Each Product
Each Product
Each Product
Each Product
Each Product
Each Product
Does EPA have data Bibliographic
to partially or Citation
totally satisfy
this requirement?
yes
yes GS-0071-001
no
no
no
yes
no
no
no
yes
no
no
no
yes
no
no
no
no
no
no
no
no
Must additional data
be submitted under
FIFRA ?(c)(2)(B)?
If so, due when?
no y y I/
no 2/ y I/
yes/6 months £/ y 'I/
yes/6 months ?/ y I/
yes/6 months 2/ y
no 1/ I/
yes/6 months 3/ I/
yes/6 nx'nths 2/ y «/
yes/6 months 2/ y «/
no y 3/ i/
yes/6 months 2/ y «_/
yes/6 months 2/ y «_/
yes/6 months 2/ y I/
no y y M_/
yes/6 months 2/ V |^/
yes/6 months 2/ y I/
yes/6 maiths 2/ y «/
yes/6 months 2/ y M/
yes/6 months ?./ y «/
yes/6 months 2/ y i|/
yes/6 months 2/ y «/
yes/6 months 2/ 3/ «/
1. The Agency possess Information on this subject for the one and only currently r-gistered end-use product. While the Agency has information on
on this end-use product, future applications for registration of end-use products containing this chemical must supply these required data.
2. Because the only registered product is produced via an Integrated formulation system, the product chemistry data normally required for
manufacturing-use products will also be required of this end-use product.
3. Must be supplied on all future end-use products containing this chemical.
U. These requirements must be fulfilled by each applicant. Data from other applicants may not be cited. Therefore, even If the requirement has
been partially or completely fulfilled for seme products, no references are given. Except for the above Product Analytical Methods A Data
requirement (163.61-7), these requirements must be fulfilled when an application for a manufacturing-use product is received by the Agency.
18
September, 1911
-------
DATA REQUIREMENTS CHART C
Polyoxyethylene Ethanol Ktnoesters of 5- (and 6-> Carboxy- 'l-Hexyl-2-Cyclohexene-i-Octanoic Acid - Iodine Complex
End-Use Product-Specific Data Requirements: TOXICOLOCT
Guidelines
Citation
Name of Test
Composition
Does EPA have data
to partially or
totally satisfy
this requirement?
Bibliographic
Citation
Must additional data
be submitted under
FIFRA 3(c)(2MB>?
If so, due when?
163.R1-1 Acute Oral Toxicity
163.81-U Primary Eye Irritation
163.81-5 Primary 3
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CHAPTER IV: PRODUCT CHEMISTO
A. Product Chemistry - Manufacturinq-Use Product
B. Product Chemistry - End-Use Product
C. Physical and Chemical Properties
The active inqredient consists of a long chain carrier molecule which controls
the release of the loosely bound iodine. Since Chemical Abstract Registry (CAS)
numbers are assigned to relatively stable molecules and because the iodine
associated with the active ingredient readly dissociates from the long nhain
carrier molecule, no CAS number exists for this compound. The FPA Shaughnessy
number is 046924.
A. Product Chemistry - Manufacturing-Use Product
The process(es) by which a technical grade of the active ingredient of
polyoxyethylene ethanol monoesters of 5-(and 6-) carboxy-4-hexyl-2-cyclohexene-
1-octanoic acid - iodine complex can be synthesized are not available at this
time. Polyoxyethylene ethanol monoesters of 5-(and 6-) carboxy-4-hexyl-2-
cyclohexene-1-octanoic acid - iodine complex is not made separately as a
technical chemical, but only during the production of the formulated product.
B. Product Chemistry - End-Use Product
The central portion of the active ingredient, polyoxyethylene ethanol
monoesters of 5-(and 6-) carboxy-4-hexyl-2-cyclohexene-l-octanoic acid, acts as
a vehicle for the controlled storage and release of the bactericidal iodine.
According to U.S. patent number 3,917,822 (Turney, MRID ns-0074-004), the
formulated product may bo produced by the combination of polyethylene glycol
monoester of C-21 dicarboxylic acid with iodine, octyl phenol polyethylene
oxide condensate and water. The end-use product contains 4.3 percent active
ingredient.
C. Physical and Chemical Properties
1. Manufacturing-Use Products
Because no technical product is currently produced, no data are available on
the physical and chemical properties of technical polyoxyethylene ethanol
monoesters of 5- (and 6-) carboxy-4-hexyl-2-cyclohexene-l-octanoic acid -
iodine complex.
2. End-Use Product
A minimum amount of data are available on the physical and chemical properties
of the end-use product containing polyoxyethylene ethanol monoesters of 5- (and
6-) carboxy-4-hexyl-2-cyclohexene-l-octanoic acid - iodine complex. The only
non-confidential physical and chemical properties for the end-use product is
that the available iodine for the end-use product is 1.6%.
20
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CHAPTER V: EHVIRCfrMENTAL FATE
A. Use Profile
B. Environitental Fate Profile
C. Exposure Profile - End-Use Products
A. Use Profile
This chemical is a sanitizer registered for the control of bacteria on food
contact surfaces. A bactericidal concentration of 25 ppm titratable iodine is
produced by diluting the 4.3 percent formulated product in water, either
manually or in automatic dispensing equipment. Precleaned and wetted food
processing equipment is sanitized by either sprayinq, swabbing or dipping into
a solution of 25 ppm titratable iodine. Precleaned and wotted dishes, glasses
and utensils are sanitized in automated dishwashing equipment where the
formulated product is metered into water that provides a sanitizing rinse of 25
ppm titratable iodine within the dishwasher.
The sanitizing solution is to be prepared fresh each time or discarded, via
sanitary sewer, if the titratable iodine residual falls below 12.5 ppm, as
determined by a suitable test kit.
Registered Application Rates
Formulation
4.3%
(A.I.)
4.3%
(A.I.)
Site
Food Processing
Equipment
Dishes, Glasses
& Utensils
Type of
Application
Spray or
Swab
Spray,
Dip or Swab
Rate of
Application
25 ppm
Titratable Iodine
25 ppm
Titratable Iodine
B. Environmental Fate Profile
Because the indoor uses of this chemical precluded significant environmental
exposure, except as a diluted, spent rinsate which drains into the sanitary
sewer, the Agency has decided that activated sludge and hydrolysis studies are
sufficient to determine the effects of this compound on the environment. No
further environmental fate or ecological effects testing is required for the
present uses of this chemical. Because of the low production volume, the Agency
has further decided to reserve its request for the above environmental fate
data until the total production of active ingredient in this and future
products containing this chemical reaches 25,000 pounds per year.
21
-------
C. Exposure Profile End-Use Products
1. Dietary Exposure
As discussed in the Regulatory Rationale section of chapter II of this
Standard, the Agency defers the evaluation of risk from dietary exposure to the
FDA, as per the December 22, 1971 division of authority cited in 36 FR 24234.
2. Worker Exposure
a. Dermal Exposure
i. Formulated Product Mixing
Several factors contribute to the Agency's conclusion that dermal exposure to
the active ingredient in the formulated product will be very low. First, the
concentration of the formulated product is small, only 4.3%. Second, to reduce
applicator exposure, labeling will require the use of gloves when diluting the
formulated product. Third, the staining and irritating nature of the formulated
product will encourage careful handling of the product because the formulated
product irritates and stains the skin. Spills will be apparent and immediately
washed off the skin after future exposures. Fourth, mixing of the use-dilution
involves the pouring of a measured amount of the formulated product into water,
a process which can normally be done with minimal spillage.
ii. Use-Dilution Product Mixing/Handling
The 4.3% product is diluted 1:697 to make a 25 ppm solution of the iodine
complex. This material is then applied to food processing equipment by
spraying, swabbing or dipping. The requirement to use gloves while handling the
end-use product and its use-dilution will significantly lower exposure during
use of this material. Any actual exposure will be very small because of the
extremely low concentration of the active .'.ngredient in solution.
b. Ocular Exposure
The Agency has determined that the use of goggles will significantly reduce or
eliminate exposure to the formulated product as well as to the diluted product.
c. Inhalation Exposure
i. Formulated Product Mixing
Since the formulated product is an aqueous solution which (1) contains no
active or inert ingredient that is volatile and (2) is mixed either in a bucket
or dispensed by automated dishwashing equipment, the Agency has determined that
very little to no inhalation exposure may be expected to result from mixing of
the end-use product in water.
22
-------
ii. Use DiJution Product Mixing/Handling
Because the vapor pressure of the long chain polymeric carrier either as
individual droplets by themselves or contained within water droplets is
expected to be extremely low and exposure to a volatilized carrier is unlikely,
inhalation of the use dilution is unlikely.
23
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CHAPTER VI: TOXICOLOGY
A. Toxicology Profile
B. Hunan and Domestic Animal Hazard Assessment
A. Toxicology Profile
1. Manufacturing-Use Product
Because no manufacturing-use product is currently registered or produced, no
toxicology data will be requested at this time. Rather, the Agency has decided
to reserve the request for acute toxicity, primary irritation and dermal
sensitization studies until a manufacturing-use product is produced and/or an
application for registration is received.
2. End-Use Product
The toxicity data available for the formulated product are six acute studies:
two acute oral LD^Q's, two eye irritation studies and two dermal irritation
studies.
The acute oral LD in CF-1 mice of a 1% and 4.3% A.I. formulated product is
24 gm/Kg and 11 gin/Kg, respectively. The low order of acute toxicity in the
mouse places the formulated product in toxicity category IV (Latven, MRID GS-
0074-002; Latven, MRID GS-0074-003).
Instillation of a 4.3% A.I. formulated product into the eye of albino rabbits
produces immediate opacification of the cornea which persists for three days,
with inflamnation of the conjunctiva persisting in excess of seven days.
Instillation of a 1% A.I. formulated product in the eye of albino rabbits
produces inflammation and chemosis of the conjunctiva which persists for three
days without affecting the cornea or iris. The eye irritation produced in
rabbits place the eye irritation potential of both the 1% and 4.3% A.I.
formulated product into toxicity category III (Latven, MRID GS-0074-002;
Latven, MRID GS-0074-003).
The application of the undiluted 4.3% A.I. formulated product under occlusive
covering results in slight edema and deep staining of the skin of albino
rabbits, with the stain persisting for more than five days. The application of
the undiluted 1% A.I. formulated product under occlusive covering rosults in no
irritation, but slight staining of the skin. The results of the dermal
irritation test place both formulations of this chemical in toxicity category
IV (Latven, MRID GS-0074-002; Latven, MRID GS-0074-003).
While these studies do not meet the current guidelines requirements for
toxicity testing, they are considered sufficient to characterize the 4.3
percent formulated product as having a low order of acute toxicity and a low to
moderate irritation potential. The high use dilution is expected to essentially
24
-------
eliminate any acute toxicity and irritation potential for the use dilution. The
Agency has determined that toxicity data on other iodine-based sanitizers is
not relevant to the toxicological evaluation of this chemical.
B. Human and Domestic Animal Hazard Assessment
The exposure profile indicates that exposure to the formulated product may
occur by the dermal, ocular and dietary routes.
1. Dietary Exposure
The Agency has determined that the dietary exposure to this chemical lies
within the purview of section 409 of the Federal Food, Drug and Cosmetic Act
because the current uses of this product may result in residues in or on food
coming into contact with treated surfaces. A food additive regulation must be
obtained for this chemical. This clearance must be obtained: (A) for the use of
this chemical as either the sole active ingredient or in combination with other
components of a formulation, (B) for use as a sanitizer on industrial food
contact surfaces, dishes and utensils, and (C) at levels which are considered
to be safe. The Agency, therefore, defers the dietary risk assessment to FDA.
2. Worker Exposure
a. Acute Hazard
The currently registered 4.3% end-use product possesses a low order of oral
toxicity, with moderate eye and slight dermal irritating properties, under the
conditions of test. No precautionary labeling relative to the oral toxicity is
necessary, but this-product must bear labeling indicating that it is a slight
skin irritant and a moderate eye irritant as well as first aid statements
designed to significantly reduce these two hazards. The use of goggles and
gloves will reduce the risks from the formulated product. Additionaly, because
the active ingredient is very dilute, no acute toxicity or irritation hazard is
expected from the use dilution of the formulated product. No further acute
testing is required.
b. Chronic Hazard
Because the use of goggles and gloves will significantly reduce exposure to the
formulated product and virtually eliminate exposure to the active ingredient in
the use dilution of the formulated product, the Agency has determined that the
risk will be too low to justify chronic testing.
25
-------
CHAPTER VII: RESIDUE CHEMISTKf
The Agency has determined that the dietary exposure to this chemical lies
within the purview of section 409 of the Federal Food, Drug and Cosmetic Act
because the current uses of this product may result in residues in or on food
coming into contact with treated surfaces. A food additive regulation
(clearance) must be obtained for this chemical. This clearance must he
obtained: (A) for the use of this chemical as either the sole active ingredient
or in combination with other components of a formulation, (B) for use as a
sanitizer on industrial food contact surfaces, dishes and utensils, and (C) at
levels which are considered to be safe. The Agency, therefore, defers the
dietary risk assessment and necessity for residue data in this risk assessment
to FDA.
26
-------
CHAPTER VIII: ECOLOGICAL EFFECTS
A. Manufacturing-Use Products
B. End-Use Products
A. Manufactureing-Use Products
Because there is currently no registered manufacturing-use product and because
end-use products are labeled for indoor use on.ly, no fish and wildJife data are
required.
B. End-Use Products
No fish and wildlife data are required to support this end-use product. The
formulated product is used indoors, contains only 4.5 percent active ingredient
and, when used according to label directions, is diluted at a ratio of 1:657.
Therfore, the Agency has concluded that the quantities of active ingredient
released into the environment, by sewer systems, will be extremely small and
result in no discernible adverse ecological effects.
27
-------
CHAPTER IX: EFFICACY
The current registered use patterns for polyoxyethylene ethanol imnoesters of 5-
(and 6-)carboxy-4-hexyl-2-cyclohexene-l-octanoic acid - iodine complex for use
as an interior, industrial sanitizer have been found to fal] within the public
health criteria established under the Agency's efficacy waiver policy, which
may be found in a May 11, 1979 Federal Register Notice. (44 FR 27939) Pursuant
to this policy the Agency has determined that data requirements shall exist for
such instances where "...the continued presence of the target pest organisms
may pose a threat to human health, either through direct action or through
transmittal of disease." In the case of sanitizers "...all antimicrobial
products intended to control microorganisms infectious to man in any area
(inanimate surface)" will require efficacy data.
Because the efficacy of sanitizers is frequently affected by the manufacturing
process and the confidential inerts of the product, the Agency has concluded
that product-by-product review of efficacy is required for sanitizers.
Historically, the Agency has required and reviewed product-by-product efficacy
data for sanitizers. The Agency recognizes, though, that data on a registered
product is also applicable to a repackaged product. The Agency has decided
that, in the limited situation where a registrant only repackages another
registrant's product, the repackager may substantiate the efficacy of the
second product by resubmitting the efficacy data on the first product rather
than performing that study again.
The Agency has decided that, except for repackaged products, the efficacy data
are product specific and not compensable or interchangable. Antimicrobial
efficacy data are not interchangable because the formulation process affects
the efficacy of antimicrobial chemicals, the efficacy data for antimicrobials
have been reviewed by the Agency for each end-use product. Because efficacy
data are product specific, and therefore cannot be routinely cited by other
applicants, this Standard will not cite or discuss the existing data for this
chemical. Rather, the Standard will specify the tests and acceptance criteria
necessary for registration.
A. Test Requirements
Efficacy of sanitizing rinses formulated with iodophors, mixed halides, and
chlorine-bearing chemicals must be substantiated with data derived from the
AOAC Available Chlorine Germicidal Equivalent Concentration Method (Horowitz,
MRID GS-0074-001) Data from one test on each of 3 samples, representing 3
different batches, one of which is at least 60 days old, against Salmonella
typhi are required.
B. Performance Standard
Test results must show product concentrations equivalent in activity to 50,
100, and 200 ppm, of available chlorine. (The reference standard is sodium
hypochlorite).
28
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CASE BIBLIOGRAPHY
Ouide to Use of This Bibliography
1. Content of Bibliography. This bibliography contains citations of all the
studies reviewed by EPA in arriving at the positions and conclusions stated
elsewhere in this standard. The bibliography alphabetically lists all
documents reviewed by the Agency. Primary 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 literature.
2. 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.
3. Identification of_ Entries. The entries in this bibliography are sorted
by author, date of the document, and title. Each entry bears, to the left
of the citation proper, a nine-digit numeric identifier. This number is
unique to the citations and should be used at any time specific reference
is required. This number is called the "Master Record Identifier" or
"MRID". It is not related to the six-digit "Accession Number", which has
been used to identify volumes of submitted data; see paragraph 4(d)(4)
below for a further explanation. In a few cases, entries added to the
bibliography late in the review may be preceded by a nine-character
temporary identifier. This is also to be used whenever a specific
reference is needed.
4. Form of the Entry. In addition to the Master Record Identifier (MRID),
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 of 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 identifiable laboratory or testing
facility as author. As a last resort, the Agency has shown the first
known submitter as author.
29
-------
b. Document Date. When the date appears as four diqits with no
question marks, the Agency took it directly from the document. When a
four-digit date is followed by a question mark, the bibliographer
deduced the date from evidence in the document. When the date appears
as (19??), the Agency was unable to determine or estimate the date of
the document.
c. Title. This is the third element in the citation. In some cases it
has been necessary for Agency bibliographers to create or enhance a
document title. Any such editorial insertions are contained between
square brackets.
d. Trailing Parentheses. For studies submitted to us in the past, the
trailing parentheses include (in addition to any self-explanatory
text) the following elements describing the earliest known
submissions:
(1) Submission Date. Immediately following the word 'received1
appears the date of the earliest known submission, at the time
that particular document was processed into the Pesticide
Document Management System.
(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, at the time that
particular document was processed into the Pesticide Document
Management System.
(3) Submitter. The third element is the submitter, following the
phrase 'submitted by1. When authorship is defaulted to the
submitter, this element is omitted.
(4) Volume Identification. The final element in the trailing
parenthesis identifies the EPA accession number of the volume in
which the original submission of the study appears. The six-
digit accession number follows the symbol 'CDL', standing for
"Company Data Library". This accession number is in turn
followed by an alphabetic suffix which shows the relative
position of the study within the volume. For example, within
accession number 123456, the first study would be 123456-A; the
second, 123456-B; the 26th, 123456-Z; and the 27th,123456-AA.
30
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OFFICE OF PESTICIDE PROGRAMS
REGISTRATION STANDARD ALPHABETICAL BIBLIOGRAPHY
Listing of All Documents Identified in the Literature
CASE GS0074
MIRD
GS-0074-001
GS-0074-002
GS-0074-003
GS-0074-004
CITATION
Horowitz, William, ed. (1980) Disinfectants. Available Chlorine
Germicidal Concentration Official Final Action, p. 59-60
In Offical Methods of Analysis of the Association of Offical
Analytical Chemists, 13th ed. Washington, D.C. Association of
Offical Analytical Chemists
Latven, A.R. (1974) Toxicology Report for Pennwalt Corporation.
[Unpublished acute toxicity studies on 4.3% formulated product
conducted by Pharmacology Research, Inc., dated Oct 1, 19741
(Submitted by Pennwalt Corporation on Nov 27, 1974 under EPA
Reg. # 335-216; CDL: 239003)
Latven, A.R. (1974) Toxicology Report for Pennwalt Corporation.
[Unpublished acute toxicity studies on 1% formulated product
conducted by Pharmacology Research, Inc., dated Oct 1, 19741
(Submitted by Pennwalt Corporation on Nov 27, 1974 under FPA
Reg. # 335-216; CDL: 239003)
Turney, G.H. inventor (1975); Pennwalt Corporation, assignee.
Iodine-containing Anionic Sanitizers. U.S. Patent No. 3,917,822.
Nov 4. 9 pgs.
31
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