&EPA
United States
Environmental Protection
Agency
Prevention, Pesticides,
And Toxic Substances
(7505C)
EPA 738-R-97-042
July 1997
Rejection Rate Analysis for
Submissions of Product
Chemistry Data, Confidential
Statement of Formula, and
Product Label for Registration and
Reregistration
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••"•..-., .->.---.-- •
, i '--',1:'- :•:,*'•.-i,
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REJECTION RATE ANALYSIS FOR SUBMISSION OF PRODUCT CHEMISTRY
DATA, CONFIDENTIAL STATEMENT OF FORMULA, AND PRODUCT LABEL FOR
REGISTRATION AND REREGISTRATION
Product Chemistry Review Section
Registration Support Branch
Registration Division
Office of Pesticide Program
U.S. Environmental Protection Agency
April 1996
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Acknowledgement
This report was prepared with the collaboration of the
following members of the Product Chemistry Review Section (PCRS)
Amelia Acierto
Tyrone Aiken
Treva Alston
Michael Clifford (AARP)
Indira Gairola
Dr. Bipin Gandhi
Dr. Sami Malak
Dr. Shyam Mathur
Anna Skapars
Alfred Smith
Dr. Harold Podal'l, Section Head
April 1996
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GLOSSARY
AI - ACTIVE INGREDIENT - The component of a pesticide product
which kills or otherwise controls the target pest.
AGENCY - United States Environmental Protection Agency
ANSI - American National Standards Institute
AOAC - Association of Official Analytical Chemists
CAS - CHEMICAL ABSTRACTS SERVICE - A subsidiary of the American
Chemical Society whose services include the proper naming and
cataloging of chemicals, with assignment of a CAS number for each
chemical.
CFR - CODE OF FEDERAL REGULATIONS - A codification of the general
and permanent rules published in the Federal Register by the
executive departments and agencies of the Federal Government.
CSF - CONFIDENTIAL STATEMENT OF FORMULA - A company-confidential
listing which includes among other information the identities and
amount of the ingredients contained in a pesticide formulation.
The form containing this information (EPA Form 8570-4) is
submitted by the registrant or applicant at the time of
application for registration, re-registration, or change in
formulation.
2,4-D - 2,4-dichlorophenoxy acetic acid
EP - END USE PRODUCT - A pesticide product whose labeling bears
instructions for using or applying the product (as packaged and
sold, or after dilution by the user) for controlling pests or
regulating plant growth. The term excludes products with
labeling which allows the product for use in formulating other
pesticide products.
EUP - EXPERIMENTAL USE PERMIT - A permit authorized under FIFRA,
Section 5, which is granted to applicants allowing- them to
conduct testing of a new proposed pesticide product and/or use
outside of the laboratory, generally on 10 acres or more of land
or water surface. EUPs are most commonly used for larger scale
testing of efficacy and gathering crop residue chemistry data.
FFDCA - FEDERAL FOOD, DRUG, AND COSMETIC ACT - The law which
regulates, among other things, the use of drugs (human and
veterinary), chemicals in cosmetics and human and animal foods;
this includes the legal requirement of tolerances for pesticide
residues (Sections 408 and 409) in or on food and feed items.
These tolerances are established by EPA.
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FIFRA - FEDERAL INSECTICIDE, FUNGICIDE, AND RODENTICIDE ACT - The
law which sets forth the regulations of the sale, distribution,
and use of pesticides in the United States.
GC or GLC - Gas-Liquid Chromatography
GLP - GOOD LABORATORY PRACTICES - Standards established in 40 CFR
160 to assure the quality and integrity of data submitted by
registrants. Provisions of the GLP standards include record
•keeping, personnel, and laboratory equipment requirements.
GRAS - Generally recognized as safe as designated by FDA.
GRN - Guideline Reference Number - Reference to the Pesticide
Assessment Guidelines. Product chemistry consists of GRN series
61, 62, and 63 of the Pesticide Assessment Guidelines.
INERT INGREDIENT - Any substance other than the active ingredient
which in intentionally added to a pesticide formulation.
INTEGRATED FORMULATION - A formulation in which the source is not
an EPA registered product or is obtained in a manner that will
not permit its inspection by the Agency per FIFRA.
IUPAC - INTERNATIONAL UNION OF PURE AND APPLIED CHEMISTRY
MP - MANUFACTURING USE PRODUCT - Any product intended (labeled)
for formulation or repackaging into other pesticide products.
"ME-TOO" PRODUCTS - An application for registration of a
pesticide product that is substantially similar or identical in
its uses and formulation to products that are currently
registered.
MRID NO. - MASTER RECORD IDENTIFICATION NUMBER - This is an EPA
identification number assigned to data submitted in the form of
individual studies in support of an administrative action (e.g.,
an application for registration, reregistration, or experimental
use permit).
NMR - NUCLEAR MAGNETIC RESONANCE
NC - NOMINAL CONCENTRATION - The amount of an ingredient which is
expected to be present in a typical sample of a pesticide product
at the time that the product is produced, expressed as a
percentage by weight based on the pure ingredient.
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PEST - Any insect, rodent, nematode, fungus, weed, or any other
form of terrestrial or aquatic plant or animal life or virus,
bacteria, or other micro-organisms on or in living man or other
living animals that is injurious to health or the environment.
(see FIFRA Section 2 (t) and 25 (c) (1) .
PESTICIDE - Any substance or mixture of substance intended for
preventing, destroying, repelling, or mitigating any pest, and
any substance or mixture or substances intended for use as a
plant regulator, defoliant, or desiccant.
PESTICIDE ASSESSMENT GUIDELINES - Protocols referenced in 40 CFR
158 that provide registrants with guidance on how to conduct
required studies. Copies of the guidelines can be obtained from
the National Technical Information Service.
PR NOTICE - PESTICIDE REGULATION NOTICE - A written notice
generally issued by the Registration Division to pesticide
registrants that communicates important changes in regulatory
policy or procedures. Each PR Notice is assigned a two part
number beginning with the year issued and the cardinal number
issued within that year (e.g. 87-1, 87-2, 92-1, etc). The name
of the notice is derived from the Pesticide Regulation Division,
a precursor organization to the Registration Division of the
Office of Pesticide Programs.
PCRS - PRODUCT CHEMISTRY REVIEW SECTION - The section where the
review chemists for product chemistry are located. Within the
organization, it is in the Registration Support Branch of the
Registration Division.
PAI - PURE ACTIVE INGREDIENT - An active ingredient that is
purified as close to 100% as technically feasible.
REGISTRATION NUMBER - The EPA registration number is a
hyphenated, two part number assigned by the Registration Division
to identify each product registration (e.g., 1253-79); the first
number is the assigned company number and the second number is
the specific product number. The registration number is required
by FIFRA to appear on the product's label.
REGISTRATION PROCESS - The process and final agency action
authorizing the legal sale, distribution, and use of a pesticide
product. The process includes OPP's consideration of scientific
legal, and regulatory requirements of the product and results in
the agency issuing either a Notice of Registration or a denial to
the applicant.
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REREGISTRATION - Section 4 of FIFRA required EPA to reregister
all pesticides originally registered before 1984 on specified
timetable. Reregistration priority is given to chemicals with
the highest potential for exposure-high volume and food use
chemicals (List A chemicals). Through this priority process,
four lists of pesticides (Lists A,B,C, and D), were established
under FIFRA '88. The reregistration process consists of the
following: the agency identifying the studies necessary to
conduct human health and environmental risks assessments;
obtaining and reviewing these studies and determining where the
pesticide's uses do not pose unreasonable adverse risks.
SOP - STANDARD OPERATING PROCEDURE - A standard operating
procedure is a written procedure that conveys procedures for
various functions performed by Office of Pesticide Programs (OPP)
staff. SOP's address both technical and administrative matters.
TGAI - TECHNICAL GRADE ACTIVE INGREDIENT - The commercial grade
of an active ingredient prior to the addition of any additive or
solvent.
TOLERANCE - The maximum permissible residue levels for a
pesticide in raw agricultural products and processed foods.
Whenever a pesticide is registered for use on a food or a feed
crop, a tolerance (or exemption from the tolerance requirement)
are enforced by the Food and Drug Administration and Department
of Agriculture. Established tolerances and exemptions
commodities are listed in 40 CFR Section 180; tolerances for food
additives in food for human consumption are listed in 40 CFR
Section 185; and tolerances for feed additives in animal feed are
listed in 40 CFR Section 186.
USDA - UNITED STATES DEPARTMENT OF AGRICULTURE
WSP - WATER SOLUBLE PACKAGING
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Summary
A survey was made for FY94 through early FY95 of the overall
and individual rejection rates for the various product chemistry
information submitted. This pertains to the CSF, Product Label
and certain specific product chemistry information (pertaininq to
characterization of the product, its manufacture and/or
formulation, analysis/ and selected physical/chemical
properties). The vast majority of the submissions reviewed by
the Product Chemistry Review Section are end-use producta. it
was found that:
1. The overall rejection rate in FY94 for all submissions
was 33 ± 20%.
2. The rejection rate for the CSF is the highest and that
for the product chemistry data (CRN series 61, 62, 63) the
lowest.
3. The rejection rate for the Product Label submissions has
the greatest % variability in the rejection rate. This may be
due largely to differences in the degree of detail of such
reviews by a few of the chemists.
Finally, a number of courses of action are suggested here
(Section VI) to reduce the rejection rates.
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TABLE OF CONTENTS
Subject
Acknowledgement
Glossary
Summary
Page
i
ii
vi
I. Introduction 1
II. Purpose of Product Chemistry Reviews 1
III. Content and Specific Objectives of the
Product Chemistry Review -2
IV. Survey of Overall Rejection Rates 3
V. Survey of Reasons for Rejecting Different Studies
A. Number of CSFs, Product Labels, and
Product Chemistry Data Submissions
Reviewed and Rejection Rates .4
B. Reasons and Corresponding Percentages
for Rejecting the CSF, Product Label,
and Product Chemistry Data -5
C. Summary of Rejection Rates of Various
Reasons Comprising an Overall Average
Rejection Rate of 28% -8
VI. Courses of Action To Reduce Rejection Rates
Appendix -9
I. Detailed Listing of Reasons for Rejecting the
CSF, Product Label, and Product Chemistry
Information -9
II. List of Documents Relevant to Product Chemistry
Requirements 18
III. Questions from Industry and Response from
PCRS/RSB/RD Regarding this Report 21
IV. Minutes of Meeting with Industry 36
V. Questions Raised by Industry During the 2/29/96
Meeting ^
VII
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I. Introduction
A. Objective
The objective of this analysis is to delineate the most
common omissions and/or flaws in submissions of product
chemistry information, Confidential Statement of Formula
(CSF) , and Product Labels so as to reduce the need for
resubmissions, and to thereby expedite the registration
and/or reregistration process.
B. Approach
The approach taken was to survey the chemists of the
Product Chemistry Review Section for the reasons why
submissions are turned back for additional or corrected
information. It should be noted that this rejection rate
analysis applies to the current product chemistry submission
review^ process. An effort is currently underway to
streamline some of the product chemistry submission
requirements.
II. Purpose of Product Chemistry Reviews
The purpose of the product chemistry reviews is, in brief,
three-fold:
(1) determination of the completeness of the submissions to
meet the data requirements called for in 40 CFR 158, the
Standard Operation Procedure (SOP) for Technicals, the SOP
for Manufacturing-Use Products (MPs) and End-Use Products
(EPs), and in certain PR Notices (cited in the Appendix of
this report);
(2) determination of the validity of the data submitted,
i.e., the method of analysis, methods of property
measurement, validation of those methods, certification of
Good Laboratory Practice Standards (GLPs) for certain
properties, and certification of limits;
(3) determination of (a) the internal consistency of the
data submitted, i.e., is the CSF consistent with the
analytical data provided in Guideline Reference Number (CRN)
62-1 and 62-2 and (b) the reasonableness of the values,
e.g., are the values for the CRN 63 properties internally
consistent as well as consistent with the chemical identity
(ID) and structure of the active ingredient.
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III. Content and Specific Objectives of the Product Chemistry
Reviews
The information reviewed by PCRS pertains to 1) physical and
chemical characterization of the TGAI, MP and/or EP, 2) the CSF which
Is based on the above, and 3) the Label which is based on 1) and 2)
above. To characterize a product, PCRS chemists review the
information provided on the identity of the product/ its
manufacturing and/or formulation process/ its composition, and
analysis, and various physical/chemical properties; the latter of
which are relevant to identifying the product/ pointing up its
physical and chemical hazards, e.g., flammability, and its proper or
adequate storage and disposal (based on its stability/reactivity
characteristics). The "studies" reviewed then/ are actually 1)
specific descriptive information such as on the manufacturing process
or analytical method used for the product and 2) values of specific
physical/chemical properties generally determined by well known and
reproducible methods.
Specifically/ the following information is reviewed as per 40
CFR 158.150 - 158.190 depending upon what is being registered or
reregistered.
(1) the CRN 61, 62, and 63 data requirements where relevant,
including requests for waivers,
(2) the Confidential Statement of Formula (CSF), and/or
(3) the product Label for the following types of products:
(a) the technical grade active ingredient (TGAI)
(b) the manufacturing-use product (MP)
(c) the end-use product (EP)
The end-use product may consist of or be derived from any of
the following:
(1) the TGAI alone
(2) an integrated formulation process where the source is not
an EPA registered product or is obtained in a manner that will not
permit its inspection by the agency as per FIFRA.
(3) non-integrated formulation process employing a registered
TGAI, or
(4) from the MP, involving the addition of other ingredients.
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IV. Survey of Overall Rejection Rates
The survey initially made was that of the rejection rates by
each chemist of the product chemistry submissions and resubmissions
for registration and reregistration which were reviewed in FY94. The
overall results were as follows:
New submissions/regist.
Mew submissions/reregist
Resubmissions
Overall
(*by 10 Chemists)
No. of Cases
Reviewed*
1020
614
924
2558
% Relection Rate
46
25
23
33 i 20
Excluding the reviews by the chemists with the three highest
rejection rates, the overall results for the remaining seven chemists
were as follows:
Hew submission/regist.
New submission/reregist.
Resubmissions
Overall
No. of Cases
Reviewed**
833
494
788
2115**
% Rejection Rate
36
12
16
23 t 11
(**reviews of 7 chemists corresponding to 83* of all reviews by PCRS)
It is seen that the rejection rates of the submissions for
reregistration dropped by more than 1/2 (from 25 to 12%) and that for
all resubmissions dropped by about 30% (from 23 to 16%). Similarly,
our overall rejection rate for all product chemistry submissions and
resubmissions dropped by a third (from 33 to 23%).
The lower rejection rates for a given type of. submission e.g.,
new submissions/registration, are due largely to a more uniform
interpretation of the regulations regarding the product chemistry
requirements. The inconsistencies, in question, are in part being
resolved through the use of the same product chemistry review forms
by the PCRS chemists and by more selective reviews by the Section
Head/PCRS. In addition, as seen below, the rejection rate survey has
facilitated our focusing on those areas of our reviews where there
are the greatest inconsistencies.
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V.
A.
Survey of Reasons for Rejecting Different Studies
Number of CSFs, Product Labels, and Product Chemistry Data
Submissions Reviewed and Rejection Rates
To facilitate this analysis, each cheaist was requested to keep
track of the reasons why he or she rejects the CSF, Product Label or
the product chemistry elements (CRN 61, 62, or 63). It may be noted
that a particular submission may have more than one reason for its
rejection? hence, the total % rejected is necessarily greater than the
rejection rate for the submission per se. The overall total* were A*
follows:
CSF
Label
Product Chemistry*
Number
Reviewed"
709
601
638
23 i 10
14 t 10
12 1 7
% Variability*
43
71
58
m)by six chemists
*)% variability - (% deviation/% rejected) x 100
«)GRN Series 61, 62, and 63
Thus for 709 CSFs reviewed by six chemists, 23% were rejected,
with an average deviation of ± 10%; this corresponds to an average %
( 10/23 )°x 1009or£43%*he CSF* °£ l3'33*' **• P««»nt variability is
The sum of the percentages rejected for the CSF, product label,
and product chemistry is 49%, while the corresponding overall average
% rejection (see Section IV) is in the range of 23 - 33% (according
to the number of chemists involved). This corresponds to about 2
reasons on the average for the rejection of a submission.
*™- f interest to note that while the rejection rat*
for the CSFs is the highest, the variability or measure of the
inconsistencies in the reviews is the lowest, i.e., 43% vs 71% for
the product label. There are apparently a greater number of
requirements associated with the review of a CSF, although the
chemists appear here to be more consistent in their reasons for
rejecting a CSF. The higher percent variability associated with the
review of a product label may be due largely to the greater detail
which a few chemists go into in their review of the product label,
c.f., items 4d and 4e, Miscellaneous Reasons, Product Label, Section
V. B below.
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B. Reasons and Corresponding Percentages for Rejecting the CSF,
Product Label, and Product Chemistry Data
The reasons for rejecting the CSF, product label, and
product chemistry elements along with their corresponding
percentages are as follows:
Reasons for Rejecting CSF Submissions - (% rejected for
indicated reason):
1. Components of inert ingredient are:
a) not sufficiently identified, e.g., new trade names
b) are new inerts
c) are not cleared for the intended use [40 CFR 180.1001
(c) , (d) , or (e) ] or by FDA under 21 CFR 170-199 such
as indirect food additives or generally recognized as
safe (GRAS), and/or
d) Not exempted from requirement of tolerances.
_____________________—_——__———————_—————————_——_______7%
2. Technical source product for active ingredient is:
a) not registered, has been canceled, or has been
transferred to a new company.
b) not given correctly, or
c) for a "roe-too" product a different source is used or
data for same source is not provided
. 4 . 5%
3. Certified limits of active ingredients and inerts are
incorrect; should be based on the nominal concentrations
and be within those prescribed under 40 CFR 158.175; or have
another reasonable basis. Certified limits for active
ingredients in an alternate formulation should be the same
as those in the basic formulation.
A 4-
——————————————————— — —————————————————————q^
4. Nominal concentrations of ingredients are not given or
calculated correctly, i.e., not based on the pure active
ingredients, do not agree with the label declaration values.
3.5%
5. The density, pH, and/or flammability are not specified in the
CSF and/or do not agree with the corresponding values given
under CRN 63-7,-12, and -15, respectively, in the Product
Chemistry submission.
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6. Miscellaneous
a) CSF is not provided, not signed, and/or dated
b) An inert ingredient of toxicological concern (List 1)
is present
c) CAS number, sources, and/ or purpose of each component is
not specified
Total weight not given or in error
d)
» Reasons for Rejecting Product Label Submissions
Indicated Reason):
2%
Total 23%
(% Rejected for
1. Ingredient Statement: a) the chemical names of the active
ingredients are not identical to those on the CSF or are in
error, or b) the label claim does not agree with the nominal
concentrations of the ingredients as required by PR Notice
91-2 or with the lower certified limits if registered prior
to 7/1/91.
2. The storage and disposal instructions for the pesticide and
container are not in compliance with PR notice 84-1 for
household use products or PR Notice 83-3 for all other uses.
••»••»••.»••.»••_.___....__.__.. . _ __ ___ ______ ____ .«.«. _____ .«..»____ __ A Q.
— — — — 4-6
3. The appropriate physical and chemical hazard statement
regarding flammability or explosive characteristics of the
product is not provided, is incomplete, or is incorrect.
------------------------------------------------------- 3%
4. Miscellaneous:
a) Footnotes to the ingredient statement are missing where
required such as "contains petroleum distillates"; "contains
the toxic substance - - -"; or "contains methyl alcohol."
b) The label text of the alternate formulation product is
not identical to that of the basic formulation as required
in 40 CFR 152.43.
c) Net weight or measure of the contents is missing from
the label.
d) The percentages for active and inert ingredients are
not aligned according to the decimal point. The active and
inert ingredients headings are not aligned to the same
margin.
e) Percentages less than one do not have a zero preceding
the decimal point.
f) The EPA registration/establishment number is missing or
in error.
Total
-2%
14%
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e Reasons for Rejecting Product Chemistry (CRN 61,62,63) Submissions
- (% rejected for indicated Reason):
® General Reasons
1. Product chemistry data do not agree with CSF or Product
label
2. Data incorrectly referenced (MRIDs, etc.)
3. Incomplete data
4. Data not provided for unregistered source of active
ingredient:
5. Data not provided for end-use product.
- - - - 4%
® CRN 61
• Composition incomplete or does not agree with CSF
• MSDS's have not been submitted for all active ingredients and
inert ingredients.
® A description of the manufacturing/formulation process has not
been provided. Information (MSDS's) on starting materials
used in manufacturing process not provided. Quantities of
ingredients used in formulation do not agree with those in
» A discussion of the formation of impurities during
manufacture/formulation, in packaging, or during storage
has not been provided.
GRN 62
• If formed by an integrated system, five batch analyses for
active ingredients, impurities,etc., have not been reported,
• The analytical method has not been validated by conducting
recovery studies; accuracy and precision data are missing;
sample calculations and associated data (spectral, GC, or
nmr) have not been provided in support of claimed active
ingredients.
® Where required, Good Laboratory Practice statements have not
been submitted, cf., 40 CFR 160.105 and 40 CFR 160.135.
2%
3%
GRN63
• Data are incomplete, needs upgrading, or are not submitted
• Flammability (63-15) has not been determined (or requested to
be waived with reason provided) on the complete product
including the propellant; for aerosols, flame extension tests
are required; for non-aerosols, flash points should be
determined.
« Corrosion characteristics (63-20) are not determined in
conjunction with the one year storage stability test (the
latter which needs to be determined but not provided unless
specifically requested by the EPA); the corrosivity tests need
to be provided for materials which the product will coae in
contact with.
Total 12%
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C. Summary of Rejection Rates of Various Reasons Comprising an
Overall Average Rejection Rate of 28%.
The rejection rates due to the various reasons comprising an overall
average rejection rate of 28% (between the 33% for 10 chemists and 23%
for 7 chemists) are as follows:
pertaining to inert ingredients (Section VB.l) 4%
problem(s) associated with technical source (Section VB.2) 2.6%
Incorrect certified limits (Section VB.3) 2.3%
incorrect calculation of nominal concentrations) (Section VB.4) 2%
inconsistency or omission of density/pH/flammability 1.1%
value(s) (Section VB.5)
• miscellaneous reasons for rejecting CSF (Section VB.6) 1.1%
Subtotal 13%
Product Label
• incorrect ingredient statement (Section VB.l) 2.9%
* inadequate storage and disposal instruction (Section VB.2) 2.3%
• inadequate physical and chemical hazard statement (Section VB.3) 1^7%
• miscellaneous reasons for rejecting product label (Section VB.4) 1.1%
« -, ^ „,_ , ^ Subtotal 8%
Eroduct Chemistry
• general reasons for rejecting product chemistry (see Section VB) 2.3%
• incompleteness or incorrectness CRN 61 information 1.1%
(see Section VB)
* incompleteness or incorrectness of CRN 62 information 1.7%
(see Section VB)
• incompleteness or incorrectness of CRN 63 data (see Section VB) 1.7%
Subtotal 7%
Total 28%
VI. Courses of Action to Reduce Rejection Rate-
These may be summarized as follows (see Appendix v for additional
suggestions):
1. Revise CSF to make it more user-friendly, e.g., provide a
checklist for industry to complete CSF.
2. Allov/ wider certified limits for the inert ingredients than
given in 40 CFR 158.175. A reason for this should be given.
3. Streamline the data requirements for the physical chemical
properties (CRN Series 63) for manufacturing use and end-use products
(produced by a non-integrated formulation process employing registered
active ingredients) by self-certification by the registrant of many of
the data requirements.
4. The review chemists should continue to meet and agree on all of
the data requirements for technicals, manufacturing use, and end-use
products so that there is greater consistency in the reviews.
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APPENDIX
I. Detailed Listing of Reasons for Rejecting the CSF, Product
Label/ and Product Chemistry Information
• General Reasons
1. The chemical composition of a new inert ingredient is not
provided. If one or more components of the inert ingredient,
such as present in certain dyes or fragrances/ is a new inert
ingredient by itself, then its data requirements must comply with
PR Notice 87-6. The Registrant is responsible for having the
supplier provide the complete composition of an inert that is not
cleared to the EPA.
2. The specific TGAI source used is not registered or identified
by the correct EPA registration number such as when transferred
to another company. Alternatively, one or more of a multi-
technical source may have been canceled. In such cases, the
Registrant may wish to specify another registered source of the
TGAI in question. The product chemistry data for a TGAI source
which is not registered must be provided for the registration of
the corresponding MP or EP.
3. One or more pieces of the requisite product chemistry data
for CRN Series 61, 62, and/or 63 have not been submitted. In
those cases where the required data (e.g. a specific physical
chemical property) are not applicable for technical reasons this
should be stated with a brief explanation. Similarly, for the
reregistration of a pesticide, complete information on the
various TGAI sources must also be provided, i.e., Series 61, 62,
and 63 data including the CSF.
4. The registrant provides only the CSF when applying for a "ME-
TOO" registration instead of submitting also series 61, 62, and
63 data.
5. If the formulation is for a food use, all inert ingredients
must be exempted from residue tolerance requirements.
6. If the formulation contains a toxic inert ingredient it must
comply with the data requirements specified in PR Notice
87-6.
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7. For a "ME-TOO" end-use product registration, two or more EPs
on the market are cited by the Registrant. We need to know the
specific registered EP to which the "ME-TOO" is to be compared.
8. Multiple technical sources for an active ingredient which
have different AI percentages are cited in a single CSF for an
EP.
• Confidential Statement of Formula [CSF - EPA form 8570-4 (Rev.
12-90)]
A copy of the CSF form and the directions given on the
reverse side of the yellow copy are given for reference purposes.
1. The complete chemical composition of each pesticide
formulation is not provided for the registration of a pesticide;
for application for an amended registration involving a formula
change; or for reregistration of a pesticide. The CSF must be
filled out completely and according to the instructions specified
on the reverse side of the CSF.
2. If the TGAI contains several substances at a
concentration i 0.1% it is advisable to list such components as
follows in Column 10: (a) individually/ if pesticldally active/
(b) as "total other ingredients" if not pesticidally active or
not related to the active ingredient/ and/or (c) "total related
compounds", if related to the active ingredient.
3. The nominal concentration of the pure active ingredient
(AI) should be given in parenthesis in Column 13b below the
percentage by weight of the technical source product. The
nominal concentration is calculated by multiplying the percentage
by weight of the technical source product by the percent active
ingredient in the technical source product.
4. The upper and lower certified limits under Columns 14a
and 14b should be based on the nominal concentration of the AI/
in accordance with 40 CFR 158.175 and not on the percentage by
weight of the technical source product.
5. Incomplete analysis of inert ingredients (which have not
been previously cleared for use in pesticide products) . The
chemical nasa, CAS Number/ and percentage present of each
component of an inert must be provided if it has not been
previously cleared. The sum of the percentages of the components
present in the inert must equal 100%.
6. To facilitate the registration process, registrants
should see to it that suppliers provide the requisite information
if the latter is company "confidential". Material Safety Data
Sheets (MSDSs) may be supplied if they contain the requisite
-10-
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information cited above (in 5)).
7. The EPA registration number is not specified under Column
12 of the CSF. Frequently, the source product has been
transferred but the new company number has not been provided.
8. One or more of a multi-technical source has been
previously canceled.
9. When a product is a 100% repack of a registered product,
the name and supplier of the product should be specified under
Columns 10 and 11, and the number, 100%, should be specified
under Column 13b. No certified limits are required under Columns
14a and 14b. A notation should b« made on the CSF that this
product is a 100% repack of a certain registered product.
10. Must indicate in block A,."Basic" or "Alternate". If
more than one Alternate, must number "Alternate #1, Alternate #2,
etc.
11. In Column 10, the source product for the active
ingredient must be entered separately.
12. Flash point/flame extension must be given as directed.
For pressurized products or aerosols, the flame extension test
should be on the entire mixture Including the prope11ant (no
flash point is required here) .~
13. Alternate formulations must have the same certified
limits for each active ingredient as the basic formulation.
14. If the alternate formulation contains an inert
ingredient or impurity of toxicological significance, tho
formulation must have the same upper certified limit for that
substance as the basic formulation.
15. For pesticide formulations intended for use on raw
agricultural commodities after harvest, applied to growing crops
or applied to animals intended for consumption, the registrant or
applicant should ensure that the inert ingredients are exempted
from the requirement of a tolerance under 40 CFR 180.1001,
paragraph CcJ, (d) or (e).
16. Vhen an active ingredient (AI) is formed in an
integrated system, the registrant/applicant should specify the AI
and its certified limits on the CSF.
17. An upper certified limit is required for toxicologically
significant impurities such as dioxins or nltrosamines, in
accordance with 40 CFR 158.175(a)(3).
-13-
-------
18. For some compounds such as 2,4-D, the CSF should
indicate the appropriate Association of Official Analytical
Chemists (AOAC) analytical method number for each active
ingredient and the AOAC manual edition, in accordance with PR
Notice 81-4.
• Label (40CFR 156.101
1. The label claim concentration of the AI is not the same
as its nominal concentration as per PR Notice 91-2. Some
flexibility is allowed in the case of sodium hypochlorlte bleach
products which are relatively unstable and require up to 25%
over-formulation for the product to have a reasonable shelf-life
in commerce. Some leeway is therefore allowed here in the
selection of the nominal concentration and lower certified limit
for the Confidential Statement of Formula, so that the customary
label claim used for such products may still be used.
2. The headings in the ingredient statement for the active
ingredient* and inert ingredients are not the same type size, not
aligned to the same margin, or are not equally prominent.
3. Trademark or proprietary names are used for the active
Ingredient. The name used shall be the accepted common name if
there is one, followed by the chemical name. The common name may
be used alone, only if it is well known, such as the ANSI name
established by the American National Standards Institute. If no
common name has been established, the chemical name alone shall
be used.
4. Pesticidally active ingredients should be listed
separately in the ingredient statement as required in PR Notice
81-4.
5. The "STORAGE AND DISPOSAL" statement is deficient.
Industrial and agricultural products marketed in containers over
one gallon for liquids and over five pounds for dry material
should be labeled in accordance with PR Notice 83-3. Household
or domestic use products marketed in containers one gallon or
less for liquids and five pounds or less for dry material (except
for lawn fertilizer products or lawn pesticide products up to 50
pounds, aa long as directions are for domestic use) should be
labeled in accordance with PR Notice 84-1. Products containing
solid CALCIUM HYPOCHLORITE, liquid SODIUM HYPOCHLORITE or liquid
CALCIUM HYPOCHLORITE should txa labeled in accordance with the
ERRATA SHEET for PR notice 84-1 dated April 12, 1984.
6. The registration number is not cited on product.
-14-
-------
7. The net contents or measure of contents are not
specified on the label. This should usually be placed on the
bottom of the main label. If the pesticide is a liquid, the net
contents should be expressed in conventional U.S. units of fluid
ounces, pints, quarts and gallons. If the pesticide is a solid
or semisolid, viscous or pressurized, or is a mixture of liquid
and solid, the net contents shall be expressed in terms of
weight, expressed as avoirdupois pounds and ounces.
8. The ingredient statement is not in accordance with 40 CFR
156.10(g) (1) . The label should contain the name and percentage
by weight of each active ingredient, and the total percentage by
weight of the inert ingredients.
9. The ingredient statement is not placed on the front panel
of the label.
10. If the pesticide formulation contains 10% or more of
petroleum distillates or xylene-boiling range products in the
formulation, the label should contain the following statement,
with a footnote to the inert ingredients below the ingredient
statement: "Contains petroleum distillates" or "contains xylene
range aromatic solvent."
11. The statement: "This product contains the toxic
substance [name]" should be included on the label when such
substances are present, as required in PR Notice 87-6.
12. On some labels, the "PHYSICAL OR CHEMICAL HAZARDS"
statement is missing or incomplete. Warning statements on the
flammability or explosive characteristics of the pesticide are
required in accordance with 40 CFR 156.10(h)(2)(iii).
13. If the pesticide product is sprayed around electrical
outlets or electrical equipment, the following statement should
be added under th« "PHYSICAL OR CHEMICAL HAZARDS" heading: "Do
not use this product in or on electrical equipment due to the
possibility of shock hazard."
14. The solvent used in the pesticide formulation should be
included la the inert ingredients on the label claim.
15. Percentages less than one percent should have a zero
preceding the decimal point, and the decimal points of the
percentages of all the ingredients should be aligned.
16. The manufacturing-use product label should state the
following: "This product is for formulating end-use products
only".
15
-------
17. In the case of Experimental Use Permits (EUPs), the
statement Experimental Use Permit should be given on the label as
required by 40 CFR 172.6.
• Series 61, 62, 63 Data
Series 61 Data
1. The data given in the analysis does not agree in the case
of "Me-Too" products.
2. All of the starting materials including solvent and
catalysts are not properly identified.
3. No MSDSs are provided.
4. The quantities of the starting materials used par batch
(or fed per unit time, if the process is continuous) and amount
of product produced are not indicated.
5. A simplified process flow chart is not given.
6. Impurities cited in the CSF are not discussed in CRN 61-
3, i.e., the source and cause of formation, where known.
7. The registrant does not clearly identify the product
(TGAI, MP, or EP) for which the product chemistry data is
submitted.
8. The chemical identity (or identities, including molecular
formula, molecular weight, and structure, where known) and
composition of the TGAI, MP and/or EPs are not clear.
9. CSF components are not supported by the analytical data.
10. CAS numbers are not provided or are incorrect.
11. IUPAC nomenclature not followed.
12. The synthetic method and reaction conditions, including
order of addition of reactants (if batch), are not indicated.
Series 62 Data
1. The analyse* of five (5) production batches are not
provided.
2. The analytical methods used do not follow the GLP
requirements.
16
-------
3. The analysts provided do not concur with the
corresponding figures in the CSF, e.g., the lower and upper
certified limits ere not clear from the analysis.
4. Reason for upper and lower certified limits exceeding the
standards (40 CFR 158.175(b)(2)) not discussed.
3. The analytical method has not been validated by recovery
studies to assure a 100% material balance.
6. The analytical method used is not adequately described or
referenced to enable verification of the analyses if required.
7. The registrant does not submit analytical method for the
TGAZ produced in an integrated formulation system.
8. inadequate validation of the analytical method for the
AZs and/or no indication of the use of GLPs for certain data,
i.e., GRH Series 62-1, 62-3, 63-8, 63-9, 63-11, and 63-17.
9. Upper and lower certified limits are not provided.
10. Analytical data presented, e.g., XR, MS, GC, or IQCR, are
not Interpreted.
•fiat
Series 63 Data
1. Certain generic data for the AI are not provided when it
is produced as an admixture (with solvent and/or other
components) and not isolated, i.e., 61-1, 62-3, 63-3 (when neat)
and 63-8 through 63-11 data.
2. Description of method used to determine a physical
chemical property is not given, e.g., Series 63-13 pertaining to
stability is sometime described as simply "stable", without
reference to the conditions/ etc.
3. Units of measurement for a physical chemical property are
not given or are not in the most useful form, e.g., vapor
pressure should be given at 25* C in mm Hg or torrs.
4. The registrant relies solely on data for the PAX (for
other than generic data) rather than what is called for in the
Table under 40 CPU 158.190.
5. The data for GRH 63-13 (stability) is used
Interchangeably with 63-17 (storage stability).
17
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II. List of Documents Relevant to Product Chemistry
Requirements
40CFR 158.150 - 158.190
21CFR 170-199
PR Notice 81-4 dtd 9/30/81:
PR Notice 83-3 dtd 3/29/83:
PR Notice 84-1 dtd 2/17/84:
PR Notice 87-6 dtd 5/12/87
PR Notice 90-1 dtd 5/1/90:
PR Notice 91-2 dtd 5/2/91:
PR Notice 52-5 dtd 10/9/92:
PR Notice 94-8 dtd 9/7/94:
Code of Federal Regulations/
Protection of Environment
Parts 150-189, Revised July
1, 1994, pp 107-114.
Food and Drugs
Label Improvement Program:
Label Revisions to
Accommodate New AOAC Methods
of Chemical Analysis.
Label Improvement Program:
Storage and Disposal Label
Statements.
.#
Clarification of Label
Improvement Program for
Farmworker Safety and
Pesticide Storage and
Disposal Instructions.
Inert Ingredients in
Pesticide Products; Policy
Statement
Inert Ingredients in
Pesticide Products; Revised
Policy Statement
Accuracy of Stated
Percentages for Ingredient
Statements
Product Chemistry Data
Requirements for Registration
and Reregistration of End
Use Products
Water Soluble Packaging (WSP)
18
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A ,* ,.7 an <:{ ; < HZ
[ DowEIanco
308/2E
February 1, 1996
Document Processing Desk
Office of Pesticide Programs (7504Q
U. S. Environmental Protection Agency
Room 266A. Crystal MaO i
1921Jeflersoa Davis Highway
Ar lington. VA 22201
Attcaticn: Mr. HareME. Fodafl (7505W)
PRODUCT CHEMISTRY REJECTION RATE ANALYSIS MEETING • FEBRUARY 29,1996
I am certainty glad to see tfatf the aestiag ** h«v« tst!. bees woridnf toward £« several weds
now be held this ™*«fr This kner a to address deoals mociated with the mffitng tad to make
ceruic that the bass ace all covered between all parties involved. Tie specific amogesveas by my
undemanding are as foUowK
Rate Aii«hr«iB Mecttaa.'
Due: Febnuoy 29,1996
Timer 9:00 am - 3:00 pm
Locarier Oyseal Statiom Coeftfeac* Room
Representatives from several Xndostxy Orzaaszatjna, iadodisf AC?A. CSMA, CMA, aad CfDA have
beat iztvited. Ray McAllister, Director of RcgolatDcy Attain of AGFA (202 ST2-3
ibe invotvcxoent of mdosizy ua/wiuuuiB aad a wtvjtfnnmree of ACPA has as
I had previous^ flu wanted to year ofBce a draft of the qaestJcas/unintncHtf catagflai to daa that are in
response to the July 1995 Protect Chearisoy Rejeetioa Rate Acalysis dm was pccfndi by yo« office,
j^ COCv rtf tnJa^ nfM*s&nw/QQ^B]^9B^^t QDCS^DBDft IS GK3O9BBI WiOfc tlUl *6ttEf IS 8^L CQQ3fiHt COmnF vO w^QC^C OP
No changes have beea oads sines the dzaft was prepared aad shared whfc yo*
With regard to the pcoftaa fee thts»e«jaf on Febnary 29, l996,pleaMi
suggcstioeafer any additieas or ehascex an wekwa*.
Your
Merfya L. Tone*, PhJX
Repcesmring Dowgaacar
U.S. Regulatory, Toxicctofi «a*
QjD
(317) 337-4736 (FAX>
MLJ/car
Eockwura
-19-
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Mr. Harold E. Podall C1505W)
Febfuay I, 1996
PlgC 2
Prefect Ctaeiftry Xejcctta JUtt Auiy*
Reriew
Welcome 4 Meco'ng Purpose
Peter Canfleiai, USEPA or
Stevt Johuoo. USEPA
Ray McAllisBH, ACPA
Objechts of Meeting and Places* Deafl*
Review of Rejecoon Rate Anaijrns
DcatikdSuagnaryaf afl Cunclvainn/AgirBneaa Faciiitt
Oibet Needed TnfiniiLjiio»
HmUPobO, USEPA
loots, Dowdneo
-20-
21_MLJ.DOC
-------
RBJBCTXC* 1ATI IKlLYflXf—PRODUCT OQBCX8TRY
XVPUTt TO IP*'! MfiaOCDT OF PRODUCT dXKXgTRY
The Agricultural Crop Protection Association has taken the
initiative to solicit and compile comments from meab«? companies
and from other related chemical business associations on the
recently released EPA Rejection Rate-Product Chemistry Report
from the office of Harold Podall. This effort is for the purpose
of identifying any items in the report that require further
clarification, to challenge policy or practices that are deemed
inappropriate, and to suggest changes as may be helpful. This
exercise has resulted in only a limited number of comments which
suggests that most registrants have found that actions taken in
recent times have been timely, consistent and reasonable. The
Product Chemistry Review Section is to be commended for the
quality of their actions and especially in this case, their focus
on continuous improvement. At the same time, certain actions
could further improve overall registration actions. The
following is a compilation of items that we suggest should be
discussed further.
car General
Generation of the CSF is a guideline requirement,
however it is not always identified as such in a
separate report. Changes to the CST are often
submitted by cover letter without study due to EPA
Product Manager's filing requirements. Zt might be
helpful to track a CSF in the same manner as a study
amendment, noting the KRID number of the prior
submission.
A check-list for industry to complete a CSF would
further lower the rejection rate.
Clear direction should be provided to include
registered purity of the technical in a given location.
Bov are files on inert ingredients kept? If trade
names change on proprietary inerts or blends of inerts,
how are file numbers used to capture these changes and
how can registrants provide most accurate references?
-21-
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Off ipeoifio - rage S
(3) The requirement that the active ingredient(s)
certified limits comply with 40 cnt 15S.175 range of
limits is understood; however, the requirement is
applied inconsistently and should be addressed here as
a pioTiificant issue. The rang* of limits for inert
ing-radiants often need to be relatively vide in order
to produce products according to formulation
performance standards such as vettability, emulsion
characteristics, pellet friability, suspensioa
properties, etc. Further inert ingredient* can not
generally be analyzed for. Setting arbitrarily narrow
limits serves no purpose and product submissions should
not be rejected on this basis.
(4) It is very helpful to add the label claim on the
CSF for convenient and accurate reference. Some
registrants report the label claim for active
ingredients at the bottom of the CSP fora and if the
form is updated, this could be added as an item to be
completed.
(5) Is reporting of the density, pB and flammability
really needed or even appropriate on the CSF? This is
not confidential information and should not be provided
to others from this document. This should be shared
from the Product Chemistry Reports.
(6) What is the intent for signing the CSF? It
generally is not signed by a manufacturing
representative who vould realistically have control of
the process. Other documents such as the label are not
signed but accuracy of the document are understood to
be accepted by the registrant providing the documents.
(6) Eov are impurities of very low levels (ppm) best
reported? It is not realistic to include them in
column 13 where the total weight is to be reported.
(e) Bow are inert ingredients that are sometimes added
or sometimes not added to be reported in columns 13 end
14 This situation occurs in some cases when minor
inerts may or may not be needed to achieve correct
properties such as pH, color, wetting properties, etc.
or in cases such as spraying a foam control agent as
needed to control foaming during manufacturing. Some
registrants have bean advised in these cases to report
a very low level of the inert (0.001%) just to capture
it as an inert that may be used.
-22-
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»*ge « • label
Coordinating
CSF and Label
difficult to
la the ingredient veigata for the
important tout la many case® are
risibility la these eas«« i«
tag* 7 • euioelime €&
USES' s ere required for in«rt ingredients. If
alternate •eurces of inerts are used, are USD's
the MW MUTO* also
free
^k^bsV & M ^ ^> vs^ev4Hk% v VN^^^B • vfe ^
^•smT^^BBL^Li^L^B ^E^sV^H^H.^^^L^Bm^B ^^D C
of impurities during
of
formation
maaafaotttrias/fonMlatioo bay* not b««a
g«o*r*l discussion including reasonably
e&smieal reactions should suffios.
Lack of agreement with quantities of ingredients
in formulation with that reported in the CSF is
expected because batches are usually pilot scale if a
study vbereas CSF utilises typical commercial batdi
amounts for convenient mathematical conversion, i.e.
100 pounds. Are typical amounts in a batoli for the
of real importance to the Agency?
Ires use of the registered purity of an
The CSF
active ingredient, whereas production amounts typically
reflect actual assay of the technical and adjustment of
solvent or carrier are made in formulation process.
Could the CSF and directions be provided in electronic
form with built in calculations made where appropriate,
i.e., totals and calculations limits of actives,
correcting for purity?
Vage 7 • Guideline €2
Five batch analyses are und«rstood to only be required
for formulated products produced by an integrated
system •upon request". Heed for five (5) batdi
analyses would be improved with clearer directions for
integrated and non- Integra ted processes.
Data used as confirmatory to validated analytical
r^tthods (spectral, CC, or NKR) bav« generally not been
provided and we beli«v« this should not be routinely
naeded.
-23-
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tags 7 • Guideline «J
The requirement for conducting and reporting storage
stability and corrosion characteristics tests needs to
be clarified.
Kissing data cannot be addreased vithin a study, only
by a vaiver. This requires coordination of the
registration manager and scientist submitting the
study. Can reasons for not completing required data be
included in the study, while complying vith CLP
requirements)? Waivers could be included in the study
review, industry often utilises the same vaiver
response for every product submission for the same
active ingredient, vast ing reviav time and inflating
tha rejection rate.
Corrosion continues to be a required element vhen it is
tied to a conditional study (storage stability) that is
not submitted unless requested or negative in findings
are identified (PR Notice 92-5). Corrosion should be
conditional or better defined to reduce the number of
rejections and vaiver requests.
Page 10
(8 Under "General Reasons) When reporting multiple
aources of technical vith different Active ingredient
percentages, could a single CSP fora ba prepared if
agreement could be reached on the format or should an
alternate CSP be prepared in each case? One registrant
has suggested soae ideas hov this could ba
accomplished.
(2 Under "CSP) Options "b" and "c" have in several
cases been rejected previously. A consistent policy
needs to be applied here. We support use of options
"b" and "c" but using them should not result in
rejections and delaya.
(3 Under "CSP") one registrant reported that tha
nominal concentration vas identified vith a note at
tha bottom of the CSP to avoid confusion Vith the
numbers appearing in a column and being confused and
inappropriately added vith other numbers in column 13.
(10 Under "CSP") Further clarification and sharing of
ideas on hov "Alternate" or "Basic" formulation options
should be reported is proposed.
-24-
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(it Under *CSF) Tcis requirement for reporting
XOAC analytical Bethod number is nev and is not
necessarily appropriate. Isporting tbs
Bethod should bs preferred. Z& another part of
report, tbs need to follow IUPJLC noBsnclatart i*
stated. Tbese points need to bs clarified.
Other • When an active ingredient is not isolated, it is
preferred in many cases to report tbe percent active
ingredient and impurities on tbe basis of tbe
as if it vere isolated. 1
inf<
fhis rtquirts additional
request to better understand tbs statistical analysis
in tbe report vas Bade by one registrant. OB vbat
basis vere three revieverm (and some times four)
from tbe analysis and bov vas tbs overall rejection
rate of 2t% arrived at?
What vas tbe Bake-up of tbe reviewers: Were tbey all
or partially contract revievers? If contract reviovers
vere used, does tbis explain soae of the variation
noted?
What quality Btasurss ars plannsd to •nsurs
consistancy in judgamsnt on tbs part of diffsrsnt
rsviavsrs?
Will tbis analysis bs rspeatsd and prograss tovard
consistancy in rsvisv of studias bs rsportsd?
Raj set ion rats would bs rsducsd with »ors formal
eoBBunication and vrittan guidancs form Product
CbaBistry Rsvl«v Ssction, i.a. issuance of SOP for
tschnieals, B&nufacturing us« products and and
products.
Guidance iu format ion is typically subBltted in tbs form
of a study, particularly for GRV 62 and «3. Tbs
studies can only address conducted experiBents and
cannot include the absence of data as prescribed under
vaiver requests, which are subsitted under a cover
letter by the registrant.
Directions for the CSF should be consistent with those
included in reregistration docvaents, which are Bore
specific in completing physical property data, notably
density which only adressess liquids and solids.
Directions for form (§570-4) itaa 7, only addresses
requireBents for formulated products.
•25-
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Other considerations forwarded as part of this exercise
have been to explore application of tha "Self
Cartif ication" ccncapt to product chemistry packages at
laast for salaotad cases. Tba registrant* would also
like to better understand how C8F filas am saintained
in IPA and to axplora means to assura that both tha
registrant's and Agency's records are currant and
correct. There have also been challenges to the nev
requirement that two original CSP's be provided with
registration actions.
There is interest in exploring with The Agency tha
preparation of a nev CSP fora following discussion of
the above items. Lastly we believe that there may be
benefit in holding a formulation seminar with
representatives from formulation laboratories, industry
registration representatives, and the Product Chemistry
Review Section. This could provide insight and
understanding both for the reviewers and tha
registration representatives. Most of the above issues
can be resolved by improved consistency and clearer
guideline direction. Separate activities involving the
rewriting of 40 CFR 158 and the Pesticide Assessment
Guidelines will also be helpful.
After the Product Chemistry Review Section has the
opportunity to review the comments in this document,
industry representatives will make every effort to find
a date before Christmas that will allow a meeting in
the Washington, D.C. area to discuss details of the
issues in an open forum setting. We look forward to
this opportunity.
-26-
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ftespons* to
On Sejeotiea ftate Analysis
I)
Generation of the CSP U « guideline..
five C8F is often associated with
for filiaf purposes within the Agensy. Tit* €SP~is,
however, the official document which reflects the
registrant's specific product and it is treated as
A efeeefc list for industry to oomplete.
Sine* eaofe item on the CSP is
could generally serve as a
fee filled in, ai
tfef» «F
Ml itees are to
4)
and any blanks should fes readily noticed.
Clear direction should be provided to include .......
The composition of the technical is listed on the CSP.
This provides an explicit and detailed suKtary of the
composition of the CSP.
Botr are files on inert ingredients kept?
Piles on inert ingredients are generally filed
according to the manufacturer and kept in a separate
file area. Piles are generally updated when new
information is provided.
CSF
S) Tb« r*quir«a«nt that th« activ« ingredient* (•)
certified limits comply with 40 CPR 15t.l75
Xgree. This area is one which atftds to be
reevaluated.
€) It is very helpful to add the label claim....
Agree. This is generally dona.
7) Is reporting of the dansity,
Since the CSP serves as a summary of the composition of
the product, these characteristics help to further
describe the product.
8) What is the intent for signing tb« CSP?
The comments are relevant, and th« signing of th« CSP
may not be needed. Hov«v«r, the signing does
demonstrate a lev«l of responsibility with the company.
Presumably, the person signing assumes the
responsibility for correctness.
9) Bow are impurities of vary low Isvsls (ppm)....
Impurities of very low levels are reported as found.
Xf no levels are detected, then the leval reported is
usually the detection limit (Per ax&sple,
-------
10) lev ara inert ingredients that ara sometimes addad
Tha usual procedure is to identify those ingradiants
that ara actually addad to tha product. Zf other
ingradiants are available vhich oould b« us«d, than
such ingradiants ara listed as alternates. Tbo levels
listed under those actually addad ara considered to
refer also to any alternate unless otherwise Indicated.
Any inerts vhich may ba added should be 1 is tad. The
levels vhich may ba expected to be added should ba
noted.
11. Coordinating changes in tha ingredient weight* for CiF and
label ara important but in many casas ara difficult to achieve.
Flexibility in these cases is needed.
Ghangas in ingrodiant vaights ara parmittad at long as tha
parcant by vaight of pura activa ingradiant remains tha sama.
Tha vaights of inert ingradiants may ba variad as long as tha
parcant by vaight of all inart ingradiants is tha
12. USDS' s ara required for inert ingradiants. Zf alternate
sources of inarts ara used, ara MSDS's from that source also
required?
KSD6'» ara not required to be subsitted for inert ingredients
from end-use products unless the inert ingredient is a nav inert
as specified in PR Notice 91-2. MSDS may be required on case by
case basis.
13. Degree of details required in discussion on the formation of
impurities during manufacturing/formulation have not bean
consistent. A general discussion including reasonable feasible
chemical reaction should suffice.
Ansver;
For non- integrated formulations where active ingredient sources
ara EPA registered, a general discussion is adequate, unless the
impurity is toxicologically significant. For products produced
by integrated formulation in vhich case the source of active
ingredient is not EPA registered, then a complete detailed
discussion of impurities is required.
_
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14. Lac* of agroaaant with quantities of ingredient*
formulation vith that reported la the Ctr U expected
batches are usually pilot seal* ia a study, vberaas C?F utilises
typical commercial batch amounts for oonvaaiaat »ath«iiatioai
ooaversioa, i.o. 100 pounds, are typical amounts ia a batch for
tha Ctr of raal importance to tha agency?
Confidential
raflact tha typical
of Formula and tha labal claim ahoul4
praaant in tha fonailata4 pro^stf
la tha lovar and uppar eartifla€ limits.
Tba CSF roquiras uaa of ragiatarad wurity of an
actlva iagradiaat, vharaaa production amouata typiemlly rafloot
actual aaaay of tha tachnical and adjuataant of aolvai^ or
oarriar ara aada in foranlatioa procaaaaa. Could th* CSV and
Airaotiona bo providad ia alactroaic fora vita built ia
calculations aada vfcara appropriata, i.a.r totala and calculation
of liaita of aotiva, oorracting for purity?
amavar to Qw«itioa us
Probably
Q«**tiom i
-------
Questioa 17 1 Data used as confirmatory to validated analytical
methods (spectral, GC, or KXR) have generally Dot be«n provided
and we believe this should not be routinely needed.
Aaswwr to Questiom 17 1
Analytical methods for new technicals vill need to b» validated
by the XPA's laboratory in Beltsville, Maryland. Therefore,
product samples (GRH-1) , complete description of the method,
company validated data, method precision, method accuracy, staple
calculation, and sample chroma togramn are needed to be submitted
to KPA's laboratory for validation. Published methods acceptable
to the scientific community (AOAC, ACS, ASTK, company scientists,
etc.) can be referenced. Further, EPA approved enforcement
methods for technical sources, can be referenced when submittinf
for registration or reregistration of products containing these
sources.
Question Its The requirement for conducting and reporting
storage stability and corrosion characteristics needs to be
clarified.
Answer to Question its
The storage stability and corrosion characteristics studies,
requirements of GRNs 63-17 and 63-20, respectively should be
conducted for at least one year vhen the product is stored in
commercial packaging materials under ambient warehouse
conditions. Some registrants, tend to take the short cut and
conduct a short term stability study (14 to 30 days) , a
requirement of CRN 63-13 for the technical grade of active
ingredient. The chemist promptly rejects this information
requesting compliance with the guidelines. Both studies can be
conducted simultaneously and the results can be submitted in the
form of sample analysis to satisfy the storage stability and
visual observations to satisfy the corrosion characteristics.
7 -Guide line 63
19) Kissing data cannot be addressed within a study; only
by a vaiver. Reasons for not completing required data
are often included in the study. The presence of CLP
requirements does not prevent a discussion of missing
data.
20) Corrosion continues to be a required element when it is
tied to a conditional study (storage stability) ........
The test for corrosion is a separate test for the
product. The applicants often make the association
with storage stability since it is convenient.
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tl. (ft Smdar "asmaral laasoma") ifeam rsportimf
of tooaaioal vitto «if faraat aetiva iagredlamt pateaa
a simgla Car form ba prsparsd if agrtamaat soaid to®
tas format or smomld am altarmata cm? ba fnpAr«4 ia
vith 4if f«r«Bt «otiv«
siagl* OF. Za ftooordaao* vitfc 40 CF1
nay te
do mot qualify as am altarnata forsulatiea.
tt.
r*j*ct*d
fba Inatructlona eo tte C8f {Itm 10)
aboold b« lUt«d.
t*
(>
arei«
pelvam IS
vita a mot* at t** better •£
vita ta« atab«n app^agimg im a
amd iaappropriatrtj a4d«4 vita otaav
This is an aoe*pt*bl« practice. IB aooordano« vith PR-Mot ic«
91-2, th« iabal elaim must «qual th« noainal ooneantratiee.
8Lnc« thara i« no plae« on th« CSF for t2M nominal oojy>3ntr«tion,
placing it at tfca bottom and identifying it vita an astariak ia
aoeaptabla.
14. (&• o&dar "CST^) rartaar olarifieatioa amd abazim of i«aaa
om mov "mltarmata1* or "Ba»lo» formolatiea optioas
raportad ia proposad.
With tlM prosant format of the CSF, th« r^istrmnt ia to
chock tho box vhich id«ntifi«s tho formulation aa basic or
altamata. If th«r« is moro than on« altarnato, thtso should bs
distinguishod should lat«r r«f«r«nc« bscom« n«c«ssary« i.a..
altarnats 1, 2, ate.
-31-
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*•• (1 , uader «*€«?•)
, Tsis requirem
*&*lytio*l »etmo4 lumber is »ow aa4
it for reportiag tae
-. —- - ... .. _- — — *• aot aeoessarilT
appropriate, lepertimg tae emforoemeat metao4 sae«14 be
preferred. la aaotaer pert of tae report, tae aoee* to follow
nomeaolature is stated. Taese poiats aee4 to
In accordance with the Pesticide Assessment Guidelines a
description of the analytical methods must be provided. The
description should be a detailed description of each stop in the
analytical method and a statement of the precision and accuracy
of the analytical method. However, a method may be referenced
which is standard for determining the per cent of the component
involved. ^^
Since the ZUPAC provides standard rules for naming chemical
compounds, its guidelines/rules are to be used for naming
chemical compounds.
29. otaer-wasa am aotivs iagredieat is aot isolated, it is
preferred ia maa? oases to report tae pereeat active iagradiant
tad impurities em the basis of the teeaaioal as if it wars
isolated. This requires additional disoussioa.
An active ingredient is to be reported as it is or will be
used in the formulation.
27. The rejection rate analysis for new submissions for
registration, new submissions for raregistration, and
resubmissions were made before (33 ± 20%) and after (23 ± 11%)
three chemists transferred from the Section. The figures were
arrived at by simply asking each chemist to estimate his/her
rejection rate for the indicated type of submission.
For the rejection rates of the Confidential statement of
f?*!??* i?Fa)i Lab€l*' and Product chemistry information (CRN
61-63), the rejection rate analysis was conducted with the
current group of six chemists. Each chemist kept track of his or
her rejections of the CSFs, Labels, and Product Chemistry (CRN
Series 61, 62 and 63 information) and of the reasons for the
rejection of the latter, over a period of about 6 months. The
results were then tabulated, i.e., 23 t 10% for the CSPs, 14 ±
10% for the Labels and 12 ± 7% for the Product Chemistry
including a breakdown of the rejections for each reason.
28. one of the reviewers is supported under a contract with the
American Association of Retired Persons (AARP). NO other
contractor was used. The variations in the rejection rates
appear to be due largely to the differences among the chemists in
their interpretation of the data requirements and of the adecuacy
of the information provided. *
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29. (1) By continued checking of tha Product Chemistry reports
of tha chemists by tha Section Bead (or taam leader) to
facilitate consistent reviews by tha chemists and (2) by
continued maating with tha chemists as a group to review and
aoraa upon tha Coda of Federal of Regulation* (crm) for ton
product Chemistry (plus tha CSF or Confidantial statsjmejit of
Formula).
Peer review meetinga (with a chairman) similar to those
conducted by tha Industrial Chemistry Branch of OPPT for their
ptfX raviaws has been triad but were not particularly baaaficial.
gm»p meetings may ba triad again, possible with a saallar, mora
sal act group of submissions.
30. Tha rajaction rates have decreased significantly in tb* past
24 months, i.e., from about 50% to 23%, particularly in tha area
of tha product chemistry properties (CRN Series 63). Tha
rajaction rataa in general will continue to ba monitored and an
analyses of tha rejection rates repeated if necessary, e.g., if
tha rajaction rate exceeds 10% (and there is no clear reason or
solution for this).
31. SOPs for Technical, Manufacturing Use and End Use Products
vill ba updated according to the need and our resources.
32. Where required for the pure active ingredient, tha backup
data may be waived provided a relevant literature reference ia
cited. Data may also ba waived for a technical, manufacturing-
use product or end-use product if there is a sound technical
raason for not obtaining such data. We ara currently looking
into tha streamlining of specific data requirements for the CRN
Series 63 properties, relevant to our current reviews and future
naads.
33. We currently require the pH, density, and flammability,
where technically sound, for the reregistration as well as tha
registration of a technical, KP or EP (pertinent to any exposure
and/or physical/chemical hazard from the handling/use of the
product). Such information should be on the CSF and consistent
vith tha values or information in the latest product chemlatry
information. This information where relevant should also b*
provided for aerosola (for the liquid phase for pH and density,
and for the entire product for flaraability determination).
-33-
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$41 Other considerations forwarded as part of thia
exercise have been to sxplore application of tha
•felf certification* concept to product chemistry packages* tt
least Cor selected casas. Tha regiatrants would also ilka to
better understand how CSF files are maintained in IF* and to
explore »^an» to a**ur» that both th« r*gi§tr*nt'« and &g«ncy'c
raoord* ar« ourr«at and oorract. Tbaro hava also b««B ehallanga*
to tha nav r«quir«»ant that two original CSF' a b« providad vith
ra^iatration action*.
JLanrar to Quaatioa 34 1
On tha Uaua of Product Oxamiatry Salf-Cartificatioat At praaant
a coudttaa i* looking into tha faaaibility of a "Salf-
Cartification" program that vill covar product
On tha iaaua of maintaining tha CSF filaa: Bard copiaa of tha
CSF's ara circulatod to tha acianca branchac for raviav, than
filad in tha corresponding jackat* in ona brovn anvalopa attachad
to tha jackat's intarior covar. Tba antira jackat U CBI that
can ba chackod only by rogulatora claarad for handling CBI
information. All CSF' a, old and nav, ara foldad and atorad in
tha saaa anvalop*. In addition, tha Pro j act Coordination Sac t ion
of tha Ragiatration Support Br&nch/RO ia currant ly scanning tha
CSFs of all products, a program that may taka mora than two yaars
to complata. Zf and when CBI information can ba diaaaminatad
alactronically aaong OPP'a program officaa, tha chamiats vill
hava tha option of using alactronic CSFs for rafarancas instaad
of hard copias that requira borrow ing tha full jackat and mora
tima to process.
On tha iasua of requiring two original CSFa va ars not avara of
this requirement.
-34-
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Question lit There is interest im Deploring vitb tte Jtaeaoy tha
preparation of a nov CSF form folloving discussion of the abovo
items. Lastly ve boliovo that there may be benefit im holding a
Formulation Seminar vith representatives from formuUtioa
laboratories, industry registration representativea, i
Chemistry lavlev Section. This could provide iasigStt
understanding both for tho revievers and the registrar
representatives. Most of the above issues can bo resolved by
improved consistency and clearer guideline direction*. Separate
activities involving the revriting of 40 CFft IS* and f
Guidelines vill also be helpful.
om lit
OB tbo iacoo of tbo C8F vo agroo. * rovlaod C87 earn bo
frioadly and oxplioit. Sovoral isouao will noo4 to bo e£ariflo4,
inel«diag but not limltod tot CBZ and ooa-CBX information,
nominal oonooatrations, product purity, product typo
(inooetieido, barbieido, ote.) and elaoo
-------
Meeting with Industry and Association on 2/29/96 at CS-1 to Discuss
Rejection Rate Analysis
The purpose of this meeting was to discuss the responses from the
Product Chemistry Review Section (PCRS) to the questions and
suggestions by Industry on this Rejection Rate Analysis report. The
agenda of the meeting, questions and suggestions from Industry on how
to improve the product chemistry reviews and reduce the rejection
rate/ and PCRS's answers are attached. Also attached are key
comments and suggestions made at the meeting on how to improve the
product chemistry reviews. These pertained largely to the CSF
(Confidential Statement of Formula) to make it more "user friendly"
to the submitter or registrants. It was agreed that OPP would be
receptive to a specific proposal from industry involving a .revised
and improved fora for the CSF.
H. Podall
2/29/96
-36-
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ST.
HATSBP BY
*/ay««
PBRTMKTHq TO THB COKFIDgirriXl.
FOMTOTA
IC8F1 1
There is a need for an KRXD number to track the CSF.
Answers The CSF is currently bain? tracked by ona or more MRJDs in
connection vith or as part of the submit tad data. Upon reviewing
tha submitted data, raflactad on tha CSF, rafarancas ara made to
tha Reg. *o. and data on tha CSF. Therefore, additional tracking
sheets vili not ba nacassary.
Question; Is it nacassary to usa cartifiad limits for inarts?
xn«vers Cartifiad limits for inarts ara regulated by
40CFR158.155(b) , (c)«(d) . With tha axcaption of enforcing tha
nominal concantrations and limits for tha activa ingredients and
thosa of toxicological concarn, anforcamant mathods for othar
ino^adiants ara not ragulatad (40CFRI158.180) . It follovs that tha
limits for ingradiants of non toxicological concarn ara flaxibla.
formulations.
Thara is naad for flexibility in raporting
«t -
alt«mata
Xnav«r: Sinca altarnata formulations ara considared as similar
products, tha regulations of 40CFRI152.43 apply. Similar or
Substantially Similar Products rafars to products of similar
composition which (a) hava tha sama nominal concantrations of tha
activa ingradiants as thosa of tha ragistarad product (labal
claim); (b) unlika tha regulations of [40CFR§152.43(1) ], tha
cartifiad limits for aach activa ingredient should be within the
standard limits of 4OCFRf 158.175; (c) tha inert ingredients are
claarad for food/non-food uses,* (d) substitution of an inert vith
another should not affect the physical/chemical properties of the
product; (a) tha upper limits of ingredients of toxicological
concarn must not exceed those found in the registered product
[40CFRS152.43 (2) ]; (f) the upper limits of ingredients of non
toxicological concern ara flexible; (g) the labal text/precautions
of similar products must be identical [40CFRS152.43 (3) ]; (h) the
anforcamant analytical methods must b« suitable for use on similar
products (40CFR§152.43(4) ]; and (i) minor changes in labeling
and/or composition from a currently registered product should not
s'ignificantly increase the risk to man and the environment. It
should be noted that product similarity is compared against one
registered product, not two or nore. When more than one alternate
formulation under the same Reg. No. and of tha same date, it is
preferable to distinguish between the formulations by designating
them as "Alt l","Alt 2", etc.
i
Question; Tha current CSF, Fora 8570-4, is not suitable for
technicals. There is a need to develop one.
Answer; Tha industry workgroup will contribute to developing, a
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more "Friendly user Form" that may accommodate technicals and
standardize the vay the nominal concentration can be expressed on
the CSFs.
Question; References were made, during the meeting, to a recent FR
Notice pertaining to revising the product chemistry Guidelines.
Industry wanted to know the number and date of publication.
Answer: One industry member stated that he has access to published
Notices and he will provide the number and date of publications to
industry members.
Question; There is a need to standardize the nominal concentration
on the CSF.
Answer; This issue and the next (17) are part of upgrading the
current CSF cited under issues I4 above.
Question; There is a need to standardize the density units
required in box 7 of the CSF.
Answer; Depending on the nature of the product, densities can be
expressed in g/ml, g/cc, Ibs/gal or lbs/ft3-
Question; Is there a need to sign the CSF?
Answer;
person.
The purpose of signing the CSF is to provide a contact
Question; How are toxic components of end-use products documented
on the CSFs?
Answer; Ingredients designated by the Agency as toxicologically
significant as per PR Notice 90-1 should be listed on the CS~s of
pesticide products. The percentages by weight off such ingredients
should be listed in Column 13 (b) and the upper limits in Column
14 (a).
Questiop; What is the deadline for compliance with PR Notice 91-2
pertaining to enforcing the nominal concentrations on the labels of
products undergoing reregistration?
Answer: The deadline for products undergoing registration is July,
1997. The deadline for reregistration runs parallel to the
decision-making process on reregistration actions even if they are
delayed to or beyond the year 2002 as mandated by congressional
extensions.
Quest ion,; How are inerts of finite amounts listed on -the CSFs?
Answer; They may be listed in percentages or parts per million if
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so determined.
What is the situation vith electronic forms of the CSF«?
Answer; Because the CSFs are classified documents, electronic
forms are not in use at this tiae.
Question; Bov can missing data and data vaiver* b« justified?
Answer; Kissing data can be justified by stating tte«t the testing
is in progress or is not applicable as per PR notice 52-5* Data
waivers can be justified on the basis of regulatory .and/or
scientific reasons. Examples; the requirement is not applicable
because the product is solid, or liquid, do*s not contain a
combustible liquid, is not recommended for use around electrical
equipment, etc. Kissing data and data vaiver not accompanied by a
statement, are entered in the computer systea as data gaps.
Therefore, it is advisable for applicants to make the necessary
statements .
Question; The corrosion characteristics continues to be a required
element when it is tied to a conditional study (storage stability) .
The corrosion characteristics study should be conditional or better
defined to reduce the number of rejections and vaiver requests.
Answer; The corrosion characteristics and storage stability are
tvo separate properties which can be determined separately.
However, since both studies have common experimental design and
duration, both tests can be carried out simultaneously.
Question; Is there a need to report impurities from cross
contamination on the CSFs?
Answer: Carryover impurities of toxicological concern from cross
contamination should be reported to the Agency. There is no need
to report cross contaminants on the CSFs.
Question; What are the implications of the ongoing project
pertaining to Product Chemistry Self-Certification?
Answer; An OPP coaaittee has looked into the feasibility of
"Self-Certification" which would cover non- integrated
manufacturing-use and end-use pesticide products. It is planned
that a PR Notice will be published during this fiscal year, for
solicitation of public comments prior to final publication. The
program should achieve its stated objective of streamlining,
simplification and acceleration of the registration/reregistration
process for such products.
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Question; What are the reasonf of requiring duplicate copits of
the CSFS?
Answer; The Product Chemistry Review Section is not aware of such
regulations. Duplicate copies, however, My facilitate the review
process.
Question; Ingredients of pesticidal activity/ should they be
listed separately on the label and CSFs?
Answers Tes. As per PR notice 81-4, each ingredient of pesticidal
Activity at > 0.1% by weight should be listed separately on the
label and CSF as "Related Compounds". Ingredients of non-
pesticidal activity are Included with the inert ingredient* on both
the label and CSF.
Question: Should net hods of analysis be provided for toxic
Ingredients as per PR notice -81-4?
Ansver; Tes. Methods for the active ingredients, impurities, and
those of toxicological concern are required as per 40CFTIS138.HO.
Question: What comprises a trade secret?
Answer; On the basis of FIFRASlO(l) (A), (B), or (C), product
chemistry data requirements which are considered to be trade secret
or "CBI", meaning Confidential Business Information, comprises GRRs
61-2, 61-3, 62-1 and 62-2. The analytical methods for the active
Ingredients are non-CBI, whereas methods for ingredients ot
toxicological concern, If any, are CBI. The CSFs, although
containing non-CBI information, are considered CBI. Labels of all
products are non-CBI. It should be noted that the certified limits
for the active ingredients on the CSFs are non-CBI. The limits are
made available to the states for enforcement.
Question; What are the requirements of the Good Laboratory
Practices Standard (GLP)?
Answer; As per 40 CFR 160.135 all provisions of the GLP standards
described in Part 160 of 40 CFR apply to CRN 62-1 (preliminary
analysis), 62-3 (enforcement analytical method), 63-8 (solubility),
63-9 (vapor pressure), 63-11 (K^) and 63-13 (stability).
All provisions of the GLP standards, except those listed un 40
CFR 160.135(b), apply t'o the following properties; product
identity 61-1, manufacturing process 61-2, discussion of impurities
61-3, certification of ingredient limits 62-2, color 63-2*,
physical state 63-3, odor 63-4*, mj>. 63-5*, b.p. 63-6*', density
63-7, dissociation constant 63-10*, pH 63-12, oxidising/reducing
action 63-14, flammability 63-15, explodability 63-16, storage
-40-
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stability 63-17, viscosity 63-18, miscibility 63-19, corrosion
characteristics 63-20, dielectric breakdown voltage 63-21. Those
properties with asterisks are required only for technicals and not
CPs unless the EPs are produced in an integrated system.
Question: Is the Agency checking to see if they have the
fragrance data before requesting it?
Answer: Yes. A search is always performed in Agency's Chemical
Vocabulary/ where all inert ingredients including dyes
and perfumes are entered once complete chemical.
identity is received. However, for each different trade
name, complete chemical identity is required unless it
appears in Chemical Vocabulary*
Question: Seven percent of the rejections for the CSFs are due to
inert ingredient deficiencies. Would EPA be able to
identify how many of these were due to dye/fragrance
problems?
Answer: About 1%. There are many cases where registrant will
enter up to 40 alternate dyes and fragrances.
Question: How many dye/fragrances have been outright rejected
due to the lack of sufficient information in the
last 5 years?
Answer: This question mayhaveto be further clarified. If the
use of the term sufficient information is meant to
Include the necessary toxlcological, ecotoxicological,
and environmental fate data, the answer would be few,
if any rejections. If sufficient information means
compositional information only, the number would be
significantly greater. Unfortunately, many fragrances
are not accepted due to the lack of compositional
information. If a new component exceeds 0.1% in the
formulated product, it is considered a new inert
ingredient.
Question: How much time is spent (estimated) dealing with the
dye/fragrance issues?
Answer: Dyes and fragrances are considered inert ingredients.
It takes about the same time to verify a particular
dye and/or perfume in the formula as any other inert
ingredient unless it is a new dye or a new perfume
for which the complete chemical identity is required.
-41-
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Question: Why can't the Agency provide a list of all
dye/fragrances that have been accepted for certain
use products( e.g., antimicrobials)?
Answer: A listing of accepted dyes and fragrances by product
type may be construed as trade secret information that
is protected from disclosure under section 10 of FXFRA.
An alternative would be a listing of dyes and/or
fragrances, preferably by trade name and manufacturer.
Before such a list could be disseminated, EPA would
liXely need the consent of the fragrance/dye
manufacturers to list their products by trade name.
Our previous experience indicate at least some of the
manufactures may b« reluctant (if not opposed to)
providing such consent. One alternative that is
currently available to registrants is to inquire
whether we have the requisite information on a given
dye or fragrance prior to using that component in a
product.
Question: Would the Agency be willing to sit down with
formulators and dye/fragrances suppliers to develop a
system that works better than the current one?
Answer: The Agency is certainly willing to consider ways to
enhance its efficiency in the regulation of pesticides,
including suggestions for improvements in this area.
Question: Some rejections occur because the percentages for
active and inert ingredients are not aligned according
to the decimal point or the active and inert
ingredients headings are not aligned to same margin.
Are all product chemistry reviews in agreement with
this? Many household products do not seem to follow
this format.
Answer: This is a labeling issue and the final printed label
is expected to comply with what is required in
40CFRS156.10(g)(l).
Question: Is the Label Review Manual consistent with 40CFR
for the placement of Ingredient statement?
Answer: Yes. The Label Review Manual is consistent with
40CFRS156.10(6)(2)(i). For further information on
this, you may contact Mr. Jim Downing of the Labeling
group of the Registration Support branch
-42-
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Question: What is being don* in regards to possible siodifi cat ions
of the csr?
Answer: The Product Cheaistry Review Section is currently
reviewing the suggestions Bade by an Industry Workgroup
headed up by Dr. Lyn Lail of Clba-Geigy.
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