United States Prevention, Pesticides EPA 712-C-98-310
Environmental Protection and Toxic Substances March 1998
Agency (7101)
4»EPA Product Properties
Test Guidelines
OPPTS 830.1000
Background for Product
Properties Test
Guidelines
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INTRODUCTION
This guideline is one of a series of test guidelines that have been
developed by the Office of Prevention, Pesticides and Toxic Substances,
United States Environmental Protection Agency for use in the testing of
pesticides and toxic substances, and the development of test data that must
be submitted to the Agency for review under Federal regulations.
The Office of Prevention, Pesticides and Toxic Substances (OPPTS)
has developed this guideline through a process of harmonization that
blended the testing guidance and requirements that existed in the Office
of Pollution Prevention and Toxics (OPPT) and appeared in Title 40,
Chapter I, Subchapter R of the Code of Federal Regulations (CFR), the
Office of Pesticide Programs (OPP) which appeared in publications of the
National Technical Information Service (NTIS) and the guidelines pub-
lished by the Organization for Economic Cooperation and Development
(OECD).
The purpose of harmonizing these guidelines into a single set of
OPPTS guidelines is to minimize variations among the testing procedures
that must be performed to meet the data requirements of the U. S. Environ-
mental Protection Agency under the Toxic Substances Control Act (15
U.S.C. 2601) and the Federal Insecticide, Fungicide and Rodenticide Act
(7U.S.C. I36,etseq.).
Final Guideline Release: This document is available from the U.S.
Government Printing Office, Washington, DC 20402 on The Federal Bul-
letin Board. By modem dial 202-512-1387, telnet and ftp:
fedbbs.access.gpo.gov (IP 162.140.64.19), internet: http://
fedbbs.access.gpo.gov, or call 202-512-0132 for disks or paper copies.
This guideline is available in ASCII and PDF (portable document format)
from the EPA 's World Wide Web site (http://www.epa.gov/epahome/re-
search.htm) under the heading "Researchers and Scientists/Test Methods
and Guidelines/OPPTS Harmonized Test Guidelines."
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OPPTS 830.1000 Background for product properties test guidelines.
(a) Scope—(1) Applicability. This guideline is intended to meet test-
ing requirements of both the Federal Insecticide, Fungicide, and
Rodenticide Act (FIFRA) (7 U.S.C. 136, et seq.} and the Toxic Substances
Control Act (15 U.S.C. 2601).
(2) Background, (i) The source materials used in developing this har-
monized OPPTS document are the OPP test guidelines Series 60 through
Series 64 (Pesticide Assessment Guidelines, Subdivision D, Product
Chemistry, EPA report 540/9-82-018, October 1982).
(ii) This guideline presents an overview of the 830 Product Properties
series of test guidelines and provides general guidance on testing proce-
dures and data submission.
(b) Purposes of product chemistry guidelines. (1) This series of
test guidelines describes protocols which may be used to perform product
chemistry testing to support the registration and reregistration of pesticides
under the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA).
It is a nonregulatory companion to 40 CFR Part 158, Data Requirements
for Registration. Circumstances when testing is required are encoded ex-
plicitly in part 158 and the user should use that regulation along with
the test guidelines in the 830 series.
(2) These guidelines supersede the earlier product chemistry guide-
lines published as Subdivision D of the Pesticide Assessment Guidelines
and provide harmonization, where possible, with similar guidelines pub-
lished by the Organization for Economic Cooperation and Development
(OECD). The earlier guidelines, Subdivision D, had four sections: Series
60—General Information, Series 61—Product Identity and Composition,
Series 62—Analysis and Certification of Product Ingredients, Series 63—
Physical and Chemical Characteristics, and Series 64—Other Product
Chemistry Requirements. In the revised guidelines, Series 60 is replaced
by this guideline, OPPTS 830.1000. Series 61 and 62 are combined in
one group titled "Group A—Product Identity, Composition, and Analy-
sis." Physical and chemical characteristics remains a separate section, ti-
tled "Group B—Physical/Chemical Properties," in the new guidelines.
The single Series 64 guideline, 64-1 Submittal of Samples, has been
placed in Group A as OPPTS 830.1900. Table 1 provides a listing of the
OPPTS test guidelines and shows the correlation between the guideline
numbers from Subdivision D and the new guideline numbers. It should
be noted that one new test guideline (OPPTS 830.7050 UV/visible absorp-
tion) has been added to the Physical/Chemical Properties group.
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Table 1.—Listing of OPPTS Test Guidelines and Correlation with Subdivision D Test Guidelines
Guideline title
Group A — Product Identity, Composition, and Analysis
Product Identity and composition
Description of materials used to produce the product
Description of production process
Description of formulation process
Discussion of formation of Impurities
Preliminary analysis
Certified limits
Enforcement analytical method
Submittal of samples
Group B — Physical/Chemical Properties
Color
Physical state
Odor
Melting point/melting range
Boiling point/boiling range
Density/relative density/bulk density
Water solubility: Column elution method; shake flask method
Water solubility, generator column method
Vapor pressure
Dissociation constant
Petition coefficient (n-octanol/water), shake flask method
Petition coefficient (n-octanol/water), generator column method
Petition coefficient (n-octanol/water), estimation by liquid chromatography
pH
Stability to normal and elevated temperatures, metals and metal ions
Oxidation/reduction: chemical incompatibility
Flammability
Explodability
Storage stability
Viscosity
Miscibility
Corrosion characteristics
Dielectric breakdown voltage
UV/visible absorption
Old guideline number
158.155
158.160
158.162
158.165
158.167
158.170
158.176
158.180
64-1
63-2
63-3
63-4
63-5
63-6
63-7
63-8
63-8
63-9
63-10
63-11
63-11
63-11
63-12
63-13
63-14
63-15
63-16
63-17
63-18
63-19
63-20
63-21
None
New guideline number
830.1550
830.1600
830.1620
830.1650
830.1670
830.1700
830.1750
830.1800
830.1900
830.6302
830.6303
830.6304
830.7200
830.7220
830.7300
830.7840
830.7860
830.7950
830.7370
830.7550
830.7560
830.7570
830.7000
830.6313
830.6314
830.6315
830.6316
830.6317
830.7100
830.6319
830.6320
830.6321
830.7050
(3) The Agency intends that the guidelines provide meaningful infor-
mation to applicants, registrants, and the general public regarding the prod-
uct chemistry data requirements for registration of a pesticide. Such guide-
lines should enable the members of the pesticide industry to use test meth-
ods acceptable to the Agency and to anticipate the costs as well as the
time involved in preparation of an application for registration. Toward
these ends, these guidelines specify the standards for acceptable testing
and the information required in a test report. The guidelines also suggest
circumstances under which an applicant should consult with the Agency
before initiating a test. In addition, the guidelines provide acceptable proto-
cols for conducting the required testing.
(4) The Agency believes that adherence to these guidelines will result
in reliable data to support applications for registration, and will accelerate
and upgrade the Agency's review and evaluation of registration applica-
tions.
(c) Useful terms. The Administrator is authorized by FIFRA to regu-
late pesticide products distributed in commerce. The term "pesticide prod-
uct" is defined in 40 CFR 152.3(s) as a pesticide in the particular form
(including composition, packaging, and labeling) in which the pesticide
is, or is intended to be, distributed or sold. The term includes any physical
apparatus used to deliver or apply the pesticide if distributed or sold with
the pesticide. All pesticide products can be classified into three categories:
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"Technical grade of the active ingredient (TGAI)," "manufacturing-use
products (MP)," and "end-use products (EP)." "Technical grade of the
active ingredient,'" which is used interchangeably with "technical chemi-
cal,'" means a material containing an active ingredient which contains no
ingredient, other than one used for manufacture or purification of the ac-
tive ingredient and which is produced on a commercial or pilot-plant pro-
duction scale (whether or not it is ever held for sale). A "manufacturing-
use product" is any pesticide product other than an end-use product. A
manufacturing-use product may consist of the technical grade of the tech-
nical grade of the active ingredient only, or may contain inert ingredients,
such as stabilizers or solvents. Manufacturing-use products are, as the term
implies, used in the production of end-use products, primarily through re-
formulation, i.e., mixing the manufacturing-use product with different
chemical substances such as solvents or diluents. An "end-use product"
is defined as a pesticide product whose labeling includes directions for
use of the product (as distributed or sold, or after combination by the user
with other substances) for controlling pests or defoliating, desiccating or
regulating of plants and does not state that the product may be used to
manufacture or formulate other pesticide products.
Formulation means the process of mixing, blending, or dilution of
one or more active ingredients with one or more other active or inert ingre-
dients, without an intended chemical reaction, to obtain a manufacturing-
use product or an end-use product. All pesticides are composed of one
or more substances. For regulatory purposes the substances are classified
either as active ingredients, intentionally-added inert ingredients, or impu-
rities. The term "active ingredient" means any substance (or group of
structurally similar substances, if specified by the Agency) that will pre-
vent, destroy, repel or mitigate any pest, or that functions as a plant regu-
lator, desiccant, or defoliant, within the meaning of FIFRA section 2(a).
In short, the active ingredients in pesticides are the substances which di-
rectly produce the intended pesticidal effect.
Pesticides contain "impurities," which are defined as any substance
(or group of structurally similar substances if specified by the Agency)
in a pesticide product other than an active ingredient or an inert ingredient,
including unreacted starting materials, side reaction products, contami-
nants, and degradation products and pesticide active ingredients other than
those intended for that product.
The Agency has become increasingly concerned about impurities in
pesticides, particularly impurities associated with an active ingredient. The
term "impurity associated with an active ingredient" means:
(1) Any impurity present in the technical grade of the active ingredi-
ent (e.g., a substance carried over from a beginning material, or from an
intermediate, and impurities formed through side reactions or by degrada-
tion of the active ingredient).
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(2) Any impurity which forms in a pesticide product through reactions
between the active ingredient and any other component of the product or
packaging of the product.
"Inert ingredient" means any substance (or group of structurally
similar substances if designated by the Agency), other than an active ingre-
dient, which is intentionally included in a pesticide product. Intentionally-
added inert ingredients include wetting agents, emulsifiers, surfactants, aer-
osol propellents, diluents, solvents, stabilizers, and the like.
The term "integrated system" (formerly called "integrated formula-
tion system") means a process for producing a pesticide that:
(1) Contains any active ingredient derived from a source that is not
an EPA-registered product; or
(2) Is a result of a reaction between an EPA-registered product and
other chemicals to form a new active ingredient; or
(3) Contains any active ingredient that was produced or acquired in
a manner that does not permit its inspection by the Agency under FIFRA
section 9(a) prior to its use in the process.
In other words, the term "integrated system" includes, but is not limited
to, any process for producing a pesticide product that would contain an
active ingredient which is not present as the result of using a registered
pesticide product. End-use products not produced by an integrated system
are unlikely to contain any impurities associated with an active ingredient
other than those impurities already identified in connection with registra-
tion of a product used to make such an end-use product. The purpose,
then, of including this definition is to distinguish between the two types
of end-products (those produced by an integrated system and those which
are not), and to impose less stringent requirements on products which are
not produced by such a system.
"Nominal concentration" means the amount of an ingredient which
is expected to be present in a typical sample of a pesticide product at
the time the product is produced, expressed as a percentage by weight.
The term "starting material" (formerly called "beginning material")
means a substance used to synthesize or purify an active ingredient (or
the practical equivalent of the technical grade ingredient if the active ingre-
dient cannot be isolated).
(d) General considerations. Data submitted to meet the requirements
for product chemistry fall into two major categories: Information on prod-
uct identity, composition, and analysis and information on specific physical
and chemical characteristics of pesticide chemicals and products.
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(1) Product identity, composition, and analysis, (i) These data in-
clude information about the product identity and composition (OPPTS
830.1550); description of materials used to produce the product (OPPTS
830.1600); description of production process (OPPTS 830.1620); descrip-
tion of the formulation process (OPPTS 830.1650); the discussion on for-
mation of impurities (830.1670), the results of preliminary analysis of
product samples (OPPTS 830.1700); the explanation of how the certified
limits were determined (OPPTS 830.1750); the description of the enforce-
ment analytical method (830.1800); and instructions on submittal of sam-
ples to the Agency (OPPTS 830.1900) These data support the conclusions
expressed in the Confidential Statement of Formula (CSF). Virtually all
of the information submitted for this section will be trade secret and con-
fidential business information (CBI).
(ii) Product composition data are used in several ways. First, the
Agency reviews the composition of a product to determine whether the
product contains any ingredient in an amount which may cause unreason-
able adverse effects on the environment. This review is based on informa-
tion available to the Agency from the public literature and its own files
about the toxicity and environmental effects of ingredients. This is the
primary use of product composition data.
(iii) The Agency also uses product composition data when reviewing
applications for conditional registration. FIFRA section 3(c)(7)(A) author-
izes the conditional registration of products which are "identical or sub-
stantially similar to any currently registered pesticide * * * or differ only
in ways that would not significantly increase the risk of unreasonable ad-
verse effects on the environment * * * ". In nearly every case, this deter-
mination involves an examination of an application and a comparison with
the composition of currently-registered products.
(iv) Finally, the Agency compares data on product composition with
information on the composition of materials used in toxicity tests and other
kinds of studies. This comparison indicates which ingredients in a pesticide
product have been evaluated by a particular study, and might lead to a
conclusion that another study is needed.
(v) Based on its conclusions concerning the environmental character-
istics and toxic properties of the pesticide, the Agency can impose appro-
priate use restrictions, labeling requirements, special packaging require-
ments, or other needed requirements.
(2) Physical and chemical characteristics, (i) Data on the physical
and chemical characteristics of pesticide chemicals and products are pre-
sented in OPPTS guidelines 830.6302 through 830.7950. Some characteris-
tics confirm or provide supportive information on the identity of ingredi-
ents and products. This is particularly true for such properties as color,
odor, physical state, melting and boiling points, density, solubility, vapor
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pressure, and pH. In addition, such data provide information which is use-
ful in reviewing the manufacturing or formulating process used to produce
the chemical or product. Marked raising or lowering of pH, melting or
boiling points, vapor pressure, density, or solubility, for example, may pro-
vide evidence of significant changes in manufacture or formulation, and
could indicate the need to investigate product composition further.
(ii) Such information as color, odor, physical state, pH, and viscosity
is also needed by the Agency to respond to emergency requests for identi-
fication of unlabeled pesticides involved in accidents or spills. Physicians,
hospitals, and poison control centers also request such information from
time to time when apparently-poisoned victims (or their families or ac-
quaintances) cannot identify specific pesticide products to which the vic-
tims have been exposed. This has often been the case when pesticides
are removed from their original containers.
(iii) Physical and chemical characteristics data are used directly in
hazard assessment. These include pH, stability, oxidizing and reducing ac-
tion, flammability, explodability, storage stability, corrosion characteris-
tics, and dielectric breakdown voltage. EPA requires a study of the corro-
sion characteristics of a pesticide to evaluate the effect of the product for-
mulation on the container; if the pesticide is highly corrosive, then lids,
liners, seams, or container sides may be damaged causing the contents
to leak during storage, transportation, handling, or use. The storage stabil-
ity study provides data on change (or lack of change) in product composi-
tion over time; if certain ingredients decompose, obviously other new
chemicals are formed whose toxicity and other characteristics need to be
considered. This situation is also true, to some extent, for data needed
on stability of technical chemicals. Depending on the results of those tests,
EPA may impose requirements for precautionary label statements.
(iv) Also, certain data in this series are needed as basic or supportive
evidence in initiating or evaluating studies required by other disciplines.
For example, the octanol/water partition coefficient is used as a criterion
in determining whether certain fish and wildlife toxicity studies (in OPPTS
guideline series 850) must be conducted. Data on vapor pressure are used
directly in determination of reentry intervals for products that may be used
in situations where residues in air pose a potential hazard (OPPTS guide-
line series 835). Data on viscosity and miscibility provide supportive infor-
mation on tank mix products (examined more extensively in OPPTS guide-
line series 835) and spray application instructions (of special concern in
guideline series 810). Determination of the UV/visible absorption spectrum
of a pesticide provides some indication of the wavelengths at which the
compound may be susceptible to photochemical degradation. Since photo-
chemical degradation is likely to occur in both the atmosphere and aquatic
environment, spectra appropriate to these media will provide information
concerning the need for further persistence testing .
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(e) Discussion of the guidelines—(1) Product identity, composi-
tion, and analysis test guidelines—(i) OPPTS 830.1550 Product iden-
tity and composition. (A) The most important requirements in the product
chemistry guidelines are contained in OPPTS 830.1550, Product identity
and composition. This guideline discusses the submission procedures for
the statement of formula identifying each active ingredient, each inten-
tionally-added inert ingredient, and, in certain cases, impurities that may
be present in the product while it is being distributed in commerce. The
purposes of the requirements in this guideline are to obtain a comprehen-
sive listing of the ingredients that may be present in a product and the
amounts of such ingredients and to assemble in one section of an applica-
tion all of the major types of identifying information on a product and
its ingredients. The composition information will be used primarily in sub-
sequent evaluations of the safety of the product. The identifying informa-
tion will be used as an aid in locating data in the public literature concern-
ing the human health and environmental properties of the product and/
or its ingredients. Identification of an ingredient calls for a variety of infor-
mation: For all ingredients, the chemical name and Chemical Abstracts
Service (CAS) number for active and intentionally-added inert ingredients,
the purpose or function of the ingredient and for active ingredients, the
molecular, structural, and empirical formula, the molecular weight (or
range), as well as other means of identification.
(B) In addition to identifying the ingredients in the product, the appli-
cant must also provide certified limits for the ingredients listed in the state-
ment of formula. Upper and lower certified limits must be established for
each active ingredient and each intentionally-added inert ingredient. In ad-
dition, for some types of products, an upper certified limit must be estab-
lished for certain impurities. The upper certified limit is the maximum
(and the lower certified limit is the minimum) amount of the ingredient
that will be present in the product at any time while it is in commerce.
(C) This guideline requests an applicant to identify the product by
the product name and trade name(s) (if different) and the company code
number assigned to the product. The Statement of Formula is required
as a means of identifying the ingredients in products. Submission of a
Confidential Statement of Formula (CSF) is insufficient. For end-use prod-
ucts, this information should be more detailed than what is required on
the CSF, in that various chemical names, and structural formulas and mo-
lecular weights for ingredients should be given. For technical materials,
impurities identified during development should be identified and
quantitated and the methods used to do so should be explained. The quan-
titative information may need to be revised after the preliminary analysis
(see OPPTS 830.1750).
(ii) OPPTS 830.1600 Description of materials used to produce the
product. (A) Most of the other product chemistry guidelines are intended
to produce data to support the information contained in the statement of
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formula. The first of these data requirements are contained in OPPTS
830.1600, concerning descriptions of beginning materials and the manufac-
turing process.
(B) The most basic pieces of information needed to determine the
composition of a pesticide product are the identity and the composition
of the materials used to produce the product. An applicant is required to
identify each beginning material used to produce his product and to supply
certain information on the beginning material. Specifically, the applicant
is required to submit a copy of available technical specifications by which
the supplier of a beginning material describes its composition, properties,
and/or toxicity as well as any other information available to the applicant
concerning the composition and properties of the beginning material. If
a beginning material is a registered pesticide product it is sufficient simply
to identify the product by its registration number. An applicant is required
to submit only the information (of the types specified) which is available
to the applicant. An applicant is not required to perform periodic chemical
analyses of his beginning materials.
(C) The description of the manufacturing process should be submitted
in detail. If a registrant is uncertain about what level of detail to include,
the Agency suggests that more specific is better. Equipment descriptions
are needed as well as process flow diagrams, reaction conditions and de-
tails of the chemical reactions intended to occur. While registrants or appli-
cants are not required to analyze starting materials, any available informa-
tion on purity of starting materials should be submitted. A schematic dia-
gram/brief description of the production process will suffice if the pesticide
is still in pilot scale production and an experimental use permit is being
sought.
(D) The level of detail for end-use products is generally less than
for the technical grade of the active ingredient and manufacturing-use
products, since impurities and side reactions rarely occur as a result of
the formulation (mixing) process, except for N-nitroso contamination (see
OPPTS 830.1670). Copies of Material Safety Data Sheets for all starting
materials should be submitted. End-use products, except for those with
potential N-nitroso contamination, may warrant a paragraph, while
technicals typically require multiple pages.
(E) A description of quality control processes, as well as quality con-
trol data, should be submitted. If several different groups oversee quality
control, a description of each and the data from each should be provided.
(iii) OPPTS 830.1620 Description of production process. (A)
OPPTS 830.1620 specifies the kind of information which should be con-
tained in this description of the production process used to make the prod-
uct. Among other things, the description should include: A statement of
the order in which beginning materials are added and their amounts; a
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description of the conditions controlled during the production process; a
description of any purification procedures; and a description of any quality
control measures. In addition, the applicant must provide a flow chart
showing the intended chemical reactions occurring during each step of the
process. A schematic diagram/brief description of the production process
will suffice if the pesticide is still in pilot scale production and an experi-
mental use permit is being sought.
(B) Based on EPA experience reviewing N-nitrosamine analyses of
many products, especially dimethylamine salts, the Agency no longer re-
quires analysis for N-nitroso contaminants in products containing:
(7) Secondary and tertiary alkylamines or alkanolamines.
(2) Representative quaternary ammonium compounds (as defined by
agreement between EPA and the International Sanitary Supply Associa-
tion) provided that:
(/) Nitrosation or nitration does not occur in an early step in synthesis.
(if) Nitrites, nitrates, or other nitrosating agents are not added to the
product or packaging.
The Agency will continue to require analysis for N-nitroso contaminants
in products containing dinitroanilines. Two representative batches of each
product are to be sampled. A total of two samples from each batch are
to be analyzed. One of these samples should be taken and analyzed as
close after the time of production as is practical and determinable. Three
months following the initial analyses, one additional sample must be taken
and analyzed from the same batch of product stored at normal storage
temperature and conditions. The maximum nitrosamine contamination al-
lowed is <1 ppm based on the limit of quantitation (LOQ) of the analytical
method.
(iv) OPPTS 830.1650 Description of formulation process. (A) If
the product is the result of a formulation process, the applicant should
provide (unless the product consists solely of a technical grade of the ac-
tive ingredient) the following information: A general description of the
process; identification of the ingredients used in the formulation; a descrip-
tion of the process equipment and process conditions; and a description
of any quality control measures. A schematic diagram/brief description of
the production process will suffice if the pesticide is still in pilot scale
production and an experimental use permit is being sought.
(B) Together, the descriptions of the materials used to produce the
product and the production/formulation process identify the major factorss
affecting the composition of a pesticide product. Agency chemists can re-
view this data along with information contained in other guidelines to de-
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termine whether the applicant's product will contain the ingredients and
conform to the certified limits listed in the statement of formula.
(v) OPPTS 830.1670 Discussion of the formation of impurities.
(A) OPPTS 830.1670 addresses the applicant's submission of a discussion
based on chemical theory of the impurities that may be present in his
pesticide products and to explain how such impurities may be formed.
Applicants are required to address impurities which either have been de-
tected by analysis of samples of the product or are expected to be present
in quantities equal to or greater than 0.1 percent of the product or at lower
concentrations in the case of impurities of toxicological concerns.
(B) EPA expects this discussion to serve several functions. The Agen-
cy will learn what kinds of impurities the applicant expects will be present
in his product as it is distributed in commerce. EPA can independently
evaluate this information to determine whether other impurities might be
present in the product. In addition, the thoroughness of the theoretical dis-
cussion can be an indication of completeness of the sample analysis re-
quirements contained in 40 CFR 158.170.
(C) This guideline states expressly that the discussion is to be based
on the information concerning beginning materials and the production/for-
mulation process described in OPPTS guidelines 830.1620 and 830.1650.
It also specifies the particular kinds of chemical reactions which must be
considered and discussed. Different requirements in this latter respect are
established for end-use products not produced by an integrated system and
all other products (end-use products produced by an integrated system and
manufacturing-use products). Applicants seeking to register end-use prod-
ucts not produced by an integrated system are subject to less stringent
requirements since the impurities associated with an active ingredient in
such a product will almost always be the impurities present in the pesticide
active ingredient used to formulate their products. Thus, for these appli-
cants, the theoretical discussion should focus on possible reactions between
the active ingredient and other ingredients in the pesticide when such infor-
mation is known. Applicants seeking to register other kinds of products
must discuss the possibility of chemical reactions involving other sub-
stances, e.g., reactions between intentionally-added inert ingredients and
packaging. If the pesticide is still in pilot-scale production and an experi-
mental use permit is sought, a discussion of impurities will be submitted
to the extent this information is available.
(vi) OPPTS 830.1700 Preliminary analysis. (A) OPPTS 830.1700
is intended to allow an applicant to confirm the conclusions reached in
the theoretical discussion. This guideline requests applicants to report the
results of analyses of five or more production batches of the product. The
analyses must be designed to measure the amount of active ingredient
present in the product and to identify and quantify (if present) any impurity
associated with an active ingredient which is expected (based an the theo-
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retical discussion) to constitute 0.1 percent or more of the product. On
a case-by-case basis, EPA may require applicants to analyze product sam-
ples for other ingredients or to provide identifying spectral data.
(B) The requirements for analysis of product batches apply to manu-
facturing-use products (including those containing solely the TGAI) and
end-use products produced by an integrated system. Data on other end-
use products will be required on a case-by-case basis. For pesticides in
the development stage, a rudimentary product analytical method and data
will suffice to support an experimental use permit. Once again, end-use
products not produced by an integrated system are subject to less stringent
requirements. Applicants seeking to register such products will be required
to provide the results of sample analysis only on a case-by-case basis.
Applicants may use any analytical method they consider appropriate. The
analytical methods used to satisfy the requirements of this guideline will
not be evaluated by the more rigorous standards concerning reproducibil-
ity, accuracy, and precision applicable to the verification methods shown
in OPPTS 830.1800. Applicants should describe each method in detail and
to state its precision and accuracy.
(C) Preliminary analysis of product samples may be completed prior
to registration using pilot plant samples or, upon request from the reg-
istrant, may be delayed until after full scale production begins, in which
case the analysis of the pilot samples for impurities should not be included
with the data. All impurities present at greater than 0.1 percent and if
of toxicological significance at levels of less than 0.1% should be deter-
mined for all samples.
(D) As stated in 53 FR 15952, May 4, 1988 (see paragraph (g)(5)
of this guideline), the Agency has identified in two ways that impurities
for which it believes that certified limits are necessary.
(7) The first is a list of specific substances or classes of substances
of known toxicological concern. In some cases, the listed substances are
currently or have been the subject of regulatory action against pesticide
products because of the risks posed by their presence as impurities in the
product. In other cases, they are identified because, historically they are
known to contribute significantly to the toxic profile of an active ingredi-
ent. For example, the oxygen analogs of organophosphate pesticides may
be more toxic than the parent compound and must be considered in setting
tolerances for the toxicologically active components of the pesticide.
(2) The second is a set of criteria for substances which are potentially
of toxicological significance; in this latter list, no specific substances are
named. While substances meeting the criteria of this second list are not
necessarily hazardous, nor have risks associated with their presence been
quantified in any specific instance, they are typical of the types of impuri-
ties that the Agency has found to be of significance in the past.
11
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(3) Impurities and classes of impurities of toxicological concern in-
clude but are not limited to:
(/) Hexachlorobenzene (HCB)
(if) Ethylene thiourea (ETU)
(///) Dichloro diphenyl trichloroethane (DDT) and other chlorinated
diphenyl ethanes and ethylenes, such as analogs and isomers of DDT,
ODD, DDE and Cl-DDT ("extrachloro DDT")
(fv) Sulfotep (tetraethyl thiodiphosphate)
(v) Halogenated dibenzodioxins
(vi) Halogenated dibenzofurans
(v//) Nitrosamines
(viif) Anilines and substituted anilines
(DC) Hydrazines
(x) Oxygen analogs of organophosphates
(xi) Sulfoxides and sulfones of organophosphates and carbamates
(4) Impurities having characteristics of potential toxicological signifi-
cance:
(/) Any impurity that is structurally related to a parent compound of
toxicological significance.
(//) Any impurity that is also an active ingredient.
(Hi) Any impurity that is identified in standard toxicology data bases
such as Toxline as being oncogenic, neurotoxic, or a developmental toxi-
cant.
(5) This list is not exhaustive and may be expanded as new informa-
tion on impurities becomes available. The Agency has reserved the right
to require certified limits for other impurities on a case-by-case basis. Reg-
istrants should contact the Agency if there is a question about the status
of any individual impurity not listed.
(6) These analyses, when required, should be to the lowest attainable
limit of detection (this varies according to sample and chemical), but must
certainly be lower than 0.1 per cent.
(vii) OPPTS 830.1750 Certified limits. (A) OPPTS 830.1750 re-
quests applicants to explain how they determined the certified limits for
the ingredients in their products. In addition, this section describes certain
12
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requirements concerning certified limits and explains that certified limits
are used in two ways. First, EPA reviews the composition of pesticide
products to determine whether the product will cause unreasonable adverse
effects on the environment. This review will involve, among other things,
an evaluation of the upper bound of the toxicity of a product, that is,
the toxicity of a product if the most hazardous ingredients were present
in the product at the upper certified limits set for such ingredients. Second,
certified limits will become the basis for future enforcement actions.
FIFRA section 12(a)(l)(C) states that it is unlawful to sell or distribute:
* * *any registered pesticide the composition of which differs at the time
of its distribution or sale from its composition as described in the statement
required in connection with its registration under section 3.
(B) The "statement required in connection with its registration" is
the statement of formula described in OPPTS 830.1550. Once a statement
of formula containing certified limits has been submitted for a product,
each quantity of the pesticide in commerce must conform to the composi-
tion described in the statement of formula (i.e., the amount of each ingredi-
ent must fall within the certified limits) or the product will be considered
in violation of FIFRA section 12(a)(l)(C).
(C) The certified limits required for each active ingredient are in-
tended to encompass good manufacturing practice variations (40 CFR
158.175(c)(3)). The upper and lower certified limits, which must be sub-
mitted for registration, represent the amounts of an ingredient that may
legally be present (40 CFR 158.175). The lower certified limit is used
as the enforceable lower limit for the product composition, while the nomi-
nal concentration appearing on the label would be the amount typically
found in the product.
(D) The Agency has compliance mechanisms, such as sampling and
analysis of products found in the marketplace, that are aimed at assuring
that products contain amounts of active ingredients which are within the
upper and lower certified limits accepted as part of the registration of those
products.
(E) The guideline states that a certified limit is valid as long as the
product is in commerce or until a specific expiration date stated on the
label. Thus, an applicant needs to predict how long the product is likely
to remain in commerce and what storage conditions may occur during that
period. Based on this information and his knowledge of the chemistry of
the product, the applicant then needs to establish certified limits that take
into account possible degradation of the product's ingredients. If an appli-
cant expects the product to contain one or more ingredients that degrade
rapidly, the applicant can place a specific expiration date on the label of
the product and a statement that the product should not be used after that
date.
13
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(F) Applicants are requested to set, for intentionally-added ingredients
and impurities, limits based on a consideration of product variability. The
limits stated should not greatly exceed those actually occurring in the prod-
uct when normal quality assurance procedures are used in the production
process. At the same time, the stated ranges should define product com-
position sufficiently for the Agency to determine its suitability for registra-
tion.
(G) Also, this guideline specifies the ingredients for which certified
limits are needed. For manufacturing-use products and those end-use prod-
ucts produced by an integrated system, the applicant must report upper
and lower certified limits for active ingredients and intentionally-added
inert ingredients and upper certified limits for impurities associated with
an active ingredient which were found or theorized to be present in quan-
tities equal to or greater than 0.1 percent of the product. Once again, for
reasons discussed earlier, end-use products not produced by an integrated
system are subject to less stringent requirements. For those products, appli-
cants are only required to provide upper and lower certified limits for ac-
tive and intentionally-added inert ingredients; upper certified limits for the
impurities in those products are not routinely required. Of course, on a
case-by-case basis EPA may require additional certified limits.
(H) These regulatory and enforcement efforts will continue to be used
to ensure that pesticide products contain what is declared on the label.
(viii) OPPTS 830.1800 Enforcement analytical methods. (A) Under
OPPTS 830.1800, applicants are requested to submit an analytical method
for detecting and measuring the quantity of each active ingredient (and
certain impurities) in their products, i.e., the TGAI, MP, or EP, depending
on the product in question. The requirements for analysis of product
batches apply to manufacturing-use products (including those containing
solely the TGAI) and end-use products produced by an integrated system.
Data on other end-use products will be required on a case-by-case basis.
For pesticides in the development stage, a rudimentary product analytical
method and data will suffice to support an experimental use permit.These
methods must be capable of determining whether the ingredient falls with-
in its certified limits and also must be suitable for use in state and federal
enforcement programs. Therefore, the applicants must submit data to estab-
lish the precision and accuracy of these methods.
(B) Analytical methods are needed for all active ingredients and all
impurities present at greater than 0.1 percent, and for toxicologically sig-
nificant impurities, but not for inerts at the present time. Validation data
for both accuracy and precision should be submitted for all methods. As
with other requirements, the Agency may require, on a case-by-case basis,
methods for additional ingredients (e.g., low level impurities or inten-
tionally-added inerts). Analytical methods for the active ingredient may
be validated by EPA laboratories at the time the product chemistry data
14
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are reviewed. Methods should not be claimed confidential, should use
commonly available equipment, and should be written to include all steps
performed even when the analyst believes that certain steps are "nor-
mally" performed in all laboratories.
(ix) OPPTS 830.1900 Submittal of samples. (A) OPPTS 830.1900
requests that a sample of an analytically-pure grade of each active ingredi-
ent and the technical grade of each active ingredient in a product be sub-
mitted to EPA. It is usually sufficient for only one applicant to submit
the analytical grade sample, and for all other applicants seeking to register
a pesticide product containing that active ingredient to rely on the first
applicant's submission. However, the same approach does not work with
regard to submission of technical gradechemicals. Each and every producer
of a technical grade of an active ingredient (TGAI) is required to submit
a sample and each applicant must specify which TGAI is used to formulate
his product.
(B) The purpose of the requirement to submit samples is for EPA
to have a small quantity of a known substance which EPA can then use
in validating its enforcement results and in making comparisons between
similar products manufactured by different producers.
(2) Physical/chemical properties test guidelines, (i) OPPTS guide-
lines 830.6302 through 830.7950 contain methods for submission of data
on the physical and chemical characteristics of a pesticide product and
its ingredients, particularly the active ingredient. These data requirements
are subject to the formulators' exemption contained in FIFRA section
3(c)(2)(D). These requirements have a variety of purposes. Some charac-
teristics, such as explosiveness and flammability, are directly related to
hazards to humans. EPA requires data on other characteristics, e.g., solu-
bility and viscosity, to assess the behavior of the product when it is used.
Still other properties like color, density, and odor are used to identify the
pesticide in emergency situations. Some characteristics, such as melting
and boiling points, are relevant to the review and evaluation of the manu-
facturing process.
(ii) The Agency requires applicants to add warning statements to their
product labels on the basis of these physical and chemical characteristics.
EPA may also require changes in use directions based on physical and
chemical characteristics of the products.
(iii) For the most part, the physical and chemical characteristics cov-
ered by these guidelines are determined routinely for all pesticide products.
Moreover, these characteristics are usually determined with testing tech-
niques which were standardized years ago and are now widely used. Each
of these guidelines contains a reference paragraph which cites standardized
testing techniques, including those published by the Organization for Eco-
nomic Cooperation and Development (OECD), the American Society for
15
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Testing and Materials (ASTM), or the Collaborative International Pesticide
Analytical Council, Limited (CIPAC). While EPA recommends that these
protocols be used where appropriate, the Agency will accept determina-
tions made using other techniques, so long as the techniques are validated
and the specific test standards in the appropriate guidelines are satisfied.
It is recommended that the applicant contact the Agency to discuss alter-
native methods prior to their use.
(iv) Certain specific considerations apply to the development of phys-
ical/chemical data for pesticides. These are summarized in the following
paragraphs.
(v) Good Laboratory Practice (GLP) Requirements. (A) All provisions
of the GLP standards, including those listed in 40 CFR 160.135 (a) and
(b) apply to the following studies:
Old guideline number
62-1
63-8*
63-9*
63-11*
63-13*
63-17
New guideline number
830.1700
830.7840
830.7860
830.7950
830.7550
830.7560
830.7570
830.6313
830.6317
Title
Preliminary Analysis
Water Solubility
Vapor Pressure
Octanol/water Partition Coefficient
Stability to Normal and Elevated Temperatures, Metals, and Metal Ions
Storage Stability
* For items marked with an asterisk, certification for GLP standards is required only for technical products (TGAI), not for end-use products (EP)
unless these end-use products are produced by an integrated system.
(B) The provisions of the GLP standards also apply to the studies
listed below. However, for the listed studies, not all GLP provisions are
applicable. The standards which do not apply are specified in 40 CFR
160.135 and registrants and laboratories conducting the studies should con-
sult 40 CFR part 160 for further details.
Old guideline number
63-2
63-3
63-4
63-5*
63-6*
63-7
63-10*
63-12
63-14
63-15
63-16
63-18
63-19
63-20
63-21
None
New guideline number
830.6302
830.6303
830.6304
830.7200
830.7220
830.7300
830.7370
830.7000
830.6314
830.6315
830.6316
830.7100
830.6319
830.6320
830.6321
830.7050
Title
Color
Physical State
Odor
Melting Point
Boiling Point
Density/Relative Density/Bulk Density
Dissociation Constant
pH
Oxidizing or Reducing Action: Chemical Incompatibility
Flammability
Explodability
Viscosity
Miscibility
Corrosion Characteristics
Dielectric Breakdown Voltage
UV/Visible absorption
* For items marked with an asterisk, certification for GLP standards is required only for technical products (TGAI), not for end-use products (EP)
unless these end-use products are produced by an integrated system.
(C) Registrants are also reminded that the GLP certification statement
required by Pesticide Regulation Notice PR 86-5 (see paragraph (g)(2)
of this guideline) must be signed by both the sponsor and the study direc-
tor.
16
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(vi) OPPTS 830.6302 (Color) and 830.6304 (Odor). (TGAI, MP).
Under 40 CFR 158.190, data on color and odor are required for TGAI
and MP forms of the pesticide. In Pesticide Regulation Notice PR 92-
5 (see paragraph (g)(4) of this guideline), the Agency waived the require-
ment that data for color and odor be generated or submitted for EP prod-
ucts because EPA has approved alternate formulations containing sub-
stitute colorants and odorants. This waiver does not apply when color and/
or odor are expected to affect product performance (efficacy). In those
cases, the Agency reserves the right to request the submission of such
data from applicants or registrants in order to make required statutory find-
ings. The Agency reserves the right to require the generation and submis-
sion of color and odor data any time it determines that such data are need-
ed to make required statutory findings.
(vii) OPPTS 830.6315 Flammability. (MP, EP). The flash point de-
termination should be conducted on the entire formulated product, not on
the active ingredient per se. For aerosols, the flame extension test method
should be conducted.
(viii) OPPTS 830.6317 Storage stability. (MP, EP). Data on storage
stability is required for the MP form of the pesticide. The requirement
for data on the EP applies only when: The product use pattern is one
for which performance (efficacy) data are required (40 CFR 158.640); the
results of the storage stability study indicate that the concentration of any
active ingredient is not within the certified limits or degradates of toxi-
cological significance are detected in the study; or product instability is
suspected or incidents of instability are reported. Previously, under Pes-
ticide Regulation Notice PR 92-5 (see paragraph (g)(4) of this guideline),
this requirement for EP data submittal was waived until the Agency could
develop alternative test methodologies which would permit the evaluation
of pesticide product composition for lengths of time in excess of one year.
The newly developed guideline permits extension of testing for longer than
one year if the product is expected to be on the market for longer than
one year or expected to be efficacious for longer than one year.
(ix) OPPTS 830.6320 Corrosion characteristics. (MP, EP). Data not
required if explanation of lack of corrosivity is reasonable (e.g., lack of
extreme pH, lack of reaction with container material).
(x) OPPTS 830.7840 and 830.7860 Solubility. (TGAI). In addition
to the water solubility data requirements of OPPTS 830.7840 and
830.7860, solvents should include n-octanol and representative polar and
non-polar solvents (e.g., methanol and hexane) commonly used for pes-
ticides. Several commonly accepted test methods for organic solubility are
available and registrants should discuss the choice of methods with the
Registration Division prior to conducting the test.
17
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(xi) General. (A) Several test methods call for the use of distilled
water. Although double distilled water is preferred, deionized water with
a resistivity above 10 megohms/cm and a total organic content below 0.01
per cent can also be used. Therefore, any water purification system can
be used provided that these required quality criteria are met.
(B) The following Table 2 summarizes the substance to be tested in
each guideline study. Circumstances when the test is required are encoded
in 40 CFR part 158.
Table 2.—Summary of Substances to be Tested in Each 830 Series Guideline
New guideline
830.1550
830.1600
830.1620
830.1650
830.1670
830.1700
830.1750
830.1800
830.1900
830.6302
830.6303
830.6304
830.6313
830.6314
830.6315
830.6316
830.6317
830.6319
830.6320
830.6321
830.7000
830.7050
830.7100
830.7200
830.7220
830.7300
830.7370
830.7550
830.7560
830.7570
830.7840
830.7860
830.7950
1982 guide-
line
158.155
158.160
158.162
158.165
158.167
158.170
158.175
158.180
64-1
63-2
63-3
63-4
63-13
63-14
63-15
63-16
63-17
63-19
63-20
63-21
63-12
None
63-18
63-5
63-6
63-7
63-10
63-11
63-11
63-11
63-8
63-8
63-9
Title
Product identity and composition
Description of Materials used to produce the product
Description of production process
Description of formulation process
Discussion of formation of impurities
Preliminary analysis
Certified limits
Enforcement analytical method
Submittal of samples
Color
Physical state
Odor
Stability to normal and elevated temperatures, metals, and
metal ions
Oxidation/reduction: chemical incompatibility
Flammability
Explodability
Storage stability
Miscibility
Corrosion characteristics
Dielectric breakdown voltage
pH
UV/visible absorption
Viscosity
Melting point/melting range
Boiling point/boiling range
Density/relative density/bulk density
Dissociation constant
Petition coefficient (n-octanol/water), shake flask method
Petition coefficient (n-octanol/water), generator column
method
Petition coefficient (n-octanol/water), estimation by liquid
chromatography
Water solubility: Column elution method; shake flask method
Water solubility, generator column method
Vapor pressure
Test substance
Technical grade of
active ingredients
Yes1
Yes1
Yes1
Yes1
Yes1
Yes1
Yes1
Yes1
Yes
Yes
Yes
Yes
Yes
No
No
No
No
No
No
No
Yes
Yes (PAI)
No
Yes (solids— PAI)
Yes (liquids— PAI)
Yes
Case-by-case
(PAI)
Yes (for non-polar
organics — PAI)
Yes (for non-polar
organics — PAI)
Yes (for non-polar
organics — PAI)
Yes (PAI)
Yes (PAI)
Yes (PAI)
Manufactur-
ing-use
product
Yes1
Yes1
Yes1
Yes1
Yes1
Yes1
Yes1
Yes1
Case-by-
case
Yes
Yes
Yes
No
Yes
Yes
Yes
Yes
Yes
Yes
No
Yes
No
Yes
No
No
Yes
No
No
No
No
No
No
No
End-use
product
Yes1
Yes1
Yes1
Yes1
Yes1
Yes1
Yes1
Yes1
Case-by-
case
No
Yes
No
No
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
No
Yes
No
No
Yes
No
No
No
No
No
No
No
1 Requirements pertaining to Product Identity, Composition, and Analysis are detailed further in the respective Test Guidelines OPPTS 830.1550
through 830.1800.
(f) Data reporting—(1) Data reporting guidance. Data submitters
are encouraged to produce complete reports for efficient review by the
Agency. This section pertains to organizing and presenting the substance
of the data report. Pesticide Regulation Notice PR 86-5 (see paragraph
(g)(2) of this guideline) pertains to physical formatting of reports (which
are referred to as "studies") and submittal packages.
(2) Data reporting format. The following paragraphs describe the
general order and format for submittal of data requirements for product
18
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chemistry. (Additional data requirements may be required as specified in
the individual test guidelines.)
(i) Title/cover page. Title page and additional documentation require-
ments (i.e., requirements for data submission and statements of data con-
fidentiality claims), if relevant to the study report, should precede the con-
tent of the study formatted below. These requirements are described in
PR Notice 86-5 (see paragraph (g)(2) of this guideline).
(ii) Table of contents.
(A) Introduction and summary. (7) Scope — procedure/tests used (in-
cluding sources).
(2) Principles of the procedure/test used including any references
which may be applicable.
(B) Materials and methods. (7) Equipment — (list and describe).
(2) Reagents and standards (if applicable) — list and describe source
and preparation.
Procedures — detailed stepwise description of procedure employed
in test.
(4) Instrumentation — detailed description of equipment employed in
test.
(5) Methods of calculation (if applicable).
(6) Other — any and all additional information that the registrant con-
siders appropriate and relevant.
(C) Conclusions. Discussion of the adequacy of procedures or tests
as well as whether the results provide acceptable accuracy and precision.
Discuss any other points which may have a bearing on the information/
data provided.
(D) Certification. Certification of authenticity by the sponsor and the
study director (including signature, typed name, title, affiliations, address,
telephone number, and date).
(E) Tables and figures (where appropriate).
(F) References.
(G) Appendices. Include: Representative chromatorgrams, etc., or any
other relevant material not fitting in any of the other sections of the report.
(3) Submittal package organization. As specified in PR notice 86-
5 (see paragraph (g)(2) of this guideline), submittal packages should be
19
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organized in the following manner. (Additional details are provided in PR
Notice 86-5).
(i) All product chemistry data within a submittal package submitted
in support of an end-use product produced from registered manufacturing-
use products should be bound as a single study under a single title page.
(ii) Product chemistry data submitted in support of a technical
productr, other manufacturing-use product, an experimental use permit, an
import tolerance petition, or an end-use product produced from unregis-
tered source ingredients, should be bound as a single study for each guide-
line group: Group A—Product identity, composition, and analysis
(830.1550 through 830.1800) and Group B—Physical/ chemical properties
(830.6302 through 830.7950).
(4) The formulators' exemption, (i) FIFRA section 3(c)(2)(D) pro-
vides that:
* * * No applicant for registration of a pesticide who proposes to purchase
a registered pesticide from another producer in order to formulate such purchased
pesticide into an end-use product shall be required to
(i) submit or cite data pertaining to the safety of such purchased product;
or
(ii) offer to pay reasonable compensation otherwise required by FIFRA sec-
tion 3(c)(l)(D) for the use of any such data.
(ii) This section, commonly called the "formulators' exemption" or
the "horizontal line provision," relieves formulators of end-use products
from the obligation to provide data concerning the safety of ingredients
in registered pesticide products they purchase.
(iii) The formulators' exemption applies primarily to the physical and
chemical characteristics portion of the product chemistry guidelines
(OPPTS 830.6302 through 830.7950). Certain sections of that portion of
the guidelines require data on the technical chemical to support the reg-
istration of both end-use products and manufacturing-use products. If an
end-use product is manufactured by using a purchased, registered manufac-
tured-use product, the end-use product registrant is exempted by FIFRA
section 3(c)(2)(D) from submitting physical and chemical property data
on the active ingredient(s) in the manufacturing-use products. Similarly,
if an applicant uses a purchased, registered end-use product to produce
his own end-use product, and the label of the applicant's product contains
only uses which appear on the label of the purchased product, the applicant
is covered by the formulators' exemption. The primary result of the formu-
lators' exemption is to lessen the data requirements for companies that
simply use a registered pesticide to make their end-use products.
(g) References. The following references should be consulted for ad-
ditional background material on this test guideline.
20
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(1) Environmental Protection Agency, Pesticide Assessment Guide-
lines, Subdivision D: Product Chemistry, Series 61-4, Addendum 1 on
Data Reporting, 1988, EPA Report 540/09-88-048.
(2) Environmental Protection Agency, Pesticide Registration Notice
PR 86-5, Standard Format for Data Submitted under FIFRA and Certain
Provisions of the FFDCA, July 29, 1986.
(3) Environmental Protection Agency, Office of Pesticide Programs,
Registration Division, Memorandum titled "Roadmap for Guidance to
Product Chemistry Guidelines," dated November 20, 1989.
(4) Environmental Protection Agency, Pesticide Regulation Notice PR
92-5, "Product Chemistry Data Requirements for Registration and Rereg-
istration of End-Use Products," October 9, 1992.
(5) FEDERAL REGISTER 53:15952, May 4, 1988, Final Rule, Pes-
ticide Registration Procedures; Pesticide Data Requirements.
21
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