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pdf§ 791.85
40 CFR Ch. I (7–1–11 Edition)
Subpart D—Equipment
necesary, the Administrator may order
the transcription of the stenographic
record of the hearing, written briefs,
oral arguments or any other reasonable
aids to making an equitable decision.
(c) The final Agency order may be reviewed in federal court as provided by
26 U.S.C. 2603(c).
792.61 Equipment design.
792.63 Maintenance and calibration of equipment.
Subpart E—Testing Facilities Operation
792.81
792.83
792.90
Subpart E—Final Order
§ 791.85 Availablity
order.
of
final
Subpart F—Test, Control, and Reference
Substances
Agency
792.105 Test, control, and reference substance characterization.
792.107 Test, control, and reference substance handling.
792.113 Mixtures of substances with carriers.
The final Agency order shall be available to the public for inspection and
copying pursuant to 5 U.S.C. 552(a)(2),
subject to necessary confidentiality restrictions.
Subpart G—Protocol for and Conduct of A
Study
Subpart F—Prohibited Acts
§ 791.105
Standard operating procedures.
Reagents and solutions.
Animal and other test system care.
792.120 Protocol.
792.130 Conduct of a study.
792.135 Physical and chemical characterization studies.
Prohibited acts.
Failure to provide information required by the Agency or to pay the
amounts awarded under this rule within time alloted in the final order shall
constitute a violation of 15 U.S.C.
2614(1) or 2614(3).
Subparts H–I [Reserved]
Subpart J—Records and Reports
792.185 Reporting of study results.
792.190 Storage and retrieval of records and
data.
792.195 Retention of records.
PART 792—GOOD LABORATORY
PRACTICE STANDARDS
AUTHORITY: 15 U.S.C. 2603.
Subpart A—General Provisions
SOURCE: 54 FR 34043, Aug. 17, 1989, unless
otherwise noted.
Sec.
792.1 Scope.
792.3 Definitions.
792.10 Applicability to studies performed
under grants and contracts.
792.12 Statement of compliance or non-compliance.
792.15 Inspection of a testing facility.
792.17 Effects of non-compliance.
Subpart A—General Provisions
§ 792.1 Scope.
(a) This part prescribes good laboratory practices for conducting studies
relating to health effects, environmental effects, and chemical fate testing. This part is intended to ensure the
quality and integrity of data submitted
pursuant to testing consent agreements and test rules issued under section 4 of the Toxic Substances Control
Act (TSCA) (Pub. L. 94–469, 90 Stat.
2006, 15 U.S.C. 2603 et seq.).
(b) This part applies to any study described by paragraph (a) of this section
which any person conducts, initiates,
or supports on or after September 18,
1989.
(c) It is EPA’s policy that all data developed under section 5 of TSCA be in
accordance with provisions of this part.
Subpart B—Organization and Personnel
792.29
792.31
792.33
792.35
Personnel.
Testing facility management.
Study director.
Quality assurance unit.
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Subpart C—Facilities
792.41 General.
792.43 Test system care facilities.
792.45 Test system supply facilities.
792.47 Facilities for handling test, control,
and reference substances.
792.49 Laboratory operation areas.
792.51 Specimen and data storage facilities.
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Environmental Protection Agency
§ 792.3
been prepared (e.g., tapes which have
been transcribed verbatim, dated, and
verified accurate by signature), the
exact copy or exact transcript may be
substituted for the original source as
raw data. ‘‘Raw data’’ may include
photographs, microfilm or microfiche
copies, computer printouts, magnetic
media, including dictated observations,
and recorded data from automated instruments.
Reference substance means any chemical substance or mixture, or analytical standard, or material other than a
test substance, feed, or water, that is
administered to or used in analyzing
the test system in the course of a study
for the purposes of establishing a basis
for comparison with the test substance
for known chemical or biological measurements.
Specimen means any material derived
from a test system for examination or
analysis.
Sponsor means:
(1) A person who initiates and supports, by provision of financial or other
resources, a study;
(2) A person who submits a study to
the EPA in response to a TSCA section
4(a) test rule and/or a person who submits a study under a TSCA section 4
testing consent agreement or a TSCA
section 5 rule or order to the extent the
agreement, rule or order references
this part; or
(3) A testing facility, if it both initiates and actually conducts the study.
Study means any experiment at one
or more test sites, in which a test substance is studied in a test system under
laboratory conditions or in the environment to determine or help predict
its effects, metabolism, environmental
and chemical fate, persistence, or other
characteristics in humans, other living
organisms, or media. The term ‘‘study’’
does not include basic exploratory
studies carried out to determine
whether a test substance or a test
method has any potential utility.
Study completion date means the date
the final report is signed by the study
director.
Study director means the individual
responsible for the overall conduct of a
study.
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If data are not developed in accordance
with the provisions of this part, EPA
will consider such data insufficient to
evaluate the health and environmental
effects of the chemical substances unless the submitter provides additional
information demonstrating that the
data are reliable and adequate.
§ 792.3 Definitions.
As used in this part the following
terms shall have the meanings specified:
Batch means a specific quantity or
lot of a test, control, or reference substance that has been characterized according to § 792.105(a).
Carrier means any material, including but not limited to, feed, water, soil,
and nutrient media, with which the
test substance is combined for administration to a test system.
Control substance means any chemical
substance or mixture, or any other material other than a test substance, feed,
or water, that is administered to the
test system in the course of a study for
the purpose of establishing a basis for
comparison with the test substance for
chemical or biologicaI measurements.
EPA means the U.S. Environmental
Protection Agency.
Experimental start date means the first
date the test substance is applied to
the test system.
Experimental termination date means
the last date on which data are collected directly from the study.
FDA means the U.S. Food and Drug
Administration.
Person includes an individual, partnership, corporation, association, scientific or academic establishment, government agency, or organizational unit
thereof, and any other legal entity.
Quality assurance unit means any person or organizational element, except
the study director, designated by testing facility management to perform
the duties relating to quality assurance of the studies.
Raw data means any laboratory
worksheets,
records,
memoranda,
notes, or exact copies thereof, that are
the result of original observations and
activities of a study and are necessary
for the reconstruction and evaluation
of the report of that study. In the event
that exact transcripts of raw data have
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§ 792.10
40 CFR Ch. I (7–1–11 Edition)
Study initiation date means the date
the protocol is signed by the study director.
Test substance means a substance or
mixture administered or added to a
test system in a study, which substance or mixture is used to develop
data to meet the requirements of a
TSCA section 4(a) test rule and/or is
developed under a TSCA section 4 testing consent agreement or section 5 rule
or order to the extent the agreement,
rule or order references this part.
Test system means any animal, plant,
microorganism, chemical or physical
matrix, including but not limited to,
soil or water, or components thereof,
to which the test, control, or reference
substance is administered or added for
study. ‘‘Test system’’ also includes appropriate groups or components of the
system not treated with the test, control, or reference substance.
Testing facility means a person who
actually conducts a study, i.e., actually uses the test substance in a test
system. ‘‘Testing facility’’ encompasses only those operational units
that are being or have been used to
conduct studies.
TSCA means the Toxic Substances
Control Act (15 U.S.C, 2601 et seq.)
Vehicle means any agent which facilitates the mixture, dispersion, or
solubilization of a test substance with
a carrier.
study director, of one of the following
types:
(a) A statement that the study was
conducted in accordance with this part;
or
(b) A statement describing in detail
all differences between the practices
used in the study and those required by
this part; or
(c) A statement that the person was
not a sponsor of the study, did not conduct the study, and does not know
whether the study was conducted in accordance with this part.
§ 792.15 Inspection of a testing facility.
(a) A testing facility shall permit an
authorized employee or duly designated representative of EPA or FDA,
at reasonable times and in a reasonable
manner, to inspect the facility and to
inspect (and in the case of records also
to copy) all records and specimens required to be maintained regarding
studies to which this part applies. The
records inspection and copying requirements shall not apply to quality assurance unit records of findings and problems, or to actions recommended and
taken, except the EPA may seek production of these records in litigation or
formal adjudicatory hearings.
(b) EPA will not consider reliable for
purposes of showing that a chemical
substance or mixture does not present
a risk of injury to health or the environment any data developed by a testing facility or sponsor that refuses to
permit inspection in accordance with
this part. The determination that a
study will not be considered reliable
does not, however, relieve the sponsor
of a required test of any obligation
under any applicable statute or regulation to submit the results of the study
to EPA.
(c) Since a testing facility is a place
where chemicals are stored or held, it
is subject to inspection under section
11 of TSCA.
§ 792.10 Applicability to studies performed under grants and contracts.
When a sponsor or other person utilizes the services of a consulting laboratory, contractor, or grantee to perform all or a part of a study to which
this part applies, it shall notify the
consulting laboratory, contractor, or
grantee that the service is, or is part
of, a study that must be conducted in
compliance with the provisions of this
part.
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§ 792.12 Statement of compliance or
non-compliance.
§ 792.17 Effects of non-compliance.
(a) The sponsor or any other person
who is conducting or has conducted a
test to fulfill the requirements of a
testing consent agreement or a test
rule issued under section 4 of TSCA
will be in violation of section 15 of
TSCA if:
Any person who submits to EPA a
test required by a testing consent
agreement or a test rule issued under
section 4 of TSCA shall include in the
submission a true and correct statement, signed by the sponsor and the
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Environmental Protection Agency
§ 792.31
experience and job description for each
individual engaged in or supervising
the conduct of a study.
(c) There shall be a sufficient number
of personnel for the timely and proper
conduct of the study according to the
protocol.
(d) Personnel shall take necessary
personal sanitation and health precautions designed to avoid contamination of test, control, and reference substances and test systems.
(e) Personnel engaged in a study
shall wear clothing appropriate for the
duties they perform. Such clothing
shall be changed as often as necessary
to prevent microbiological, radiological, or chemical contamination of
test systems and test, control, and reference substances.
(f) Any individual found at any time
to have an illness that may adversely
affect the quality and integrity of the
study shall be excluded from direct
contact with test systems, test, control, and reference substances and any
other operation or function that may
adversely affect the study until the
condition is corrected. All personnel
shall be instructed to report to their
immediate supervisors any health or
medical conditions that may reasonably be considered to have an adverse
effect on a study.
(1) The test is not being or was not
conducted in accordance with any requirement of this part;
(2) Data or information submitted to
EPA under this part (including the
statement required by § 792.12) include
information or data that are false or
misleading, contain significant omissions, or otherwise do not fulfill the requirements of this part; or
(3) Entry in accordance with § 792.15
for the purpose of auditing test data or
inspecting test facilities is denied. Persons who violate the provisions of this
part may be subject to civil or criminal
penalties under section 16 of TSCA,
legal action in United States district
court under section 17 of TSCA, or
criminal prosecution under 18 U.S.C. 2
or 1001.
(b) EPA, at its discretion, may not
consider reliable for purposes of showing that a chemical substance or mixture does not present a risk of injury
to health or the environment any
study which was not conducted in accordance with this part. EPA, at its
discretion, may rely upon such studies
for purposes of showing adverse effects.
The determination that a study will
not be considered reliable does not,
however, relieve the sponsor of a required test of the obligation under any
applicable statute or regulation to submit the results of the study to EPA.
(c) If data submitted to fulfill a requirement of a testing consent agreement or a test rule issued under section 4 of TSCA are not developed in accordance with this part, EPA may determine that the sponsor has not fulfilled its obligations under section 4 of
TSCA and may require the sponsor to
develop data in accordance with the requirements of this part in order to satisfy such obligations.
§ 792.31
Subpart B—Organization and
Personnel
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Testing facility management.
For each study, testing facility management shall:
(a) Designate a study director as described in § 792.33 before the study is
initiated.
(b) Replace the study director
promptly if it becomes necessary to do
so during the conduct of a study.
(c) Assure that there is a quality assurance unit as described in § 792.35.
(d) Assure that test, control, and reference substances or mixtures have
been appropriately tested for identity,
strength, purity, stability, and uniformity, as applicable.
(e) Assure that personnel, resources,
facilities, equipment, materials and
methodologies are available as scheduled.
(f) Assure that personnel clearly understand the functions they are to perform.
§ 792.29 Personnel.
(a) Each individual engaged in the
conduct of or responsible for the supervision of a study shall have education,
training, and experience, or combination thereof, to enable that individual
to perform the assigned functions.
(b) Each testing facility shall maintain a current summary of training and
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§ 792.33
40 CFR Ch. I (7–1–11 Edition)
(g) Assure that any deviations from
these regulations reported by the quality assurance unit are communicated
to the study director and corrective actions are taken and documented.
at the testing facility indexed by test
substance and containing the test system, nature of study, date study was
initiated, current status of each study,
identity of the sponsor, and name of
the study director.
(2) Maintain copies of all protocols
pertaining to all studies for which the
unit is responsible.
(3) Inspect each study at intervals
adequate to ensure the integrity of the
study and maintain written and properly signed records of each periodic inspection showing the date of the inspection, the study inspected, the
phase or segment of the study inspected, the person performing the inspection, findings and problems, action
recommended and taken to resolve existing problems, and any scheduled
date for re-inspection. Any problems
which are likely to affect study integrity found during the course of an inspection shall be brought to the attention of the study director and management immediately.
(4) Periodically submit to management and the study director written
status reports on each study, noting
any problems and the corrective actions taken.
(5) Determine that no deviations
from approved protocols or standard
operating procedures were made without proper authorization and documentation.
(6) Review the final study report to
assure that such report accurately describes the methods and standard operating procedures, and that the reported
results accurately reflect the raw data
of the study.
(7) Prepare and sign a statement to
be included with the final study report
which shall specify the dates inspections were made and findings reported
to management and to the study director.
(c) The responsibilities and procedures applicable to the quality assurance unit, the records maintained by
the quality assurance unit, and the
method of indexing such records shall
be in writing and shall be maintained.
These items including inspection dates,
the study inspected, the phase or segment of the study inspected, and the
name of the individual performing the
inspection shall be made available for
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§ 792.33 Study director.
For each study, a scientist or other
professional of appropriate education,
training, and experience, or combination thereof, shall be identified as the
study director. The study director has
overall responsibility for the technical
conduct of the study, as well as for the
interpretation, analysis, documentation, and reporting of results, and represents the single point of study control. The study director shall assure
that:
(a) The protocol, including any
change, is approved as provided by
§ 792.120 and is followed.
(b) All experimental data, including
observations of unanticipated responses of the test system are accurately recorded and verified.
(c) Unforeseen circumstances that
may affect the quality and integrity of
the study are noted when they occur,
and corrective action is taken and documented.
(d) Test systems are as specified in
the protocol.
(e) All applicable good laboratory
practice regulations are followed.
(f) All raw data, documentation, protocols, specimens, and final reports are
transferred to the archives during or at
the close of the study.
§ 792.35 Quality assurance unit.
(a) A testing facility shall have a
quality assurance unit which shall be
responsible for monitoring each study
to assure management that the facilities, equipment, personnel, methods,
practices, records, and controls are in
conformance with the regulations in
this part. For any given study, the
quality assurance unit shall be entirely
separate from and independent of the
personnel engaged in the direction and
conduct of that study. The quality assurance unit shall conduct inspections
and maintain records appropriate to
the study.
(b) The quality assurance unit shall:
(1) Maintain a copy of a master
schedule sheet of all studies conducted
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Environmental Protection Agency
§ 792.45
inspection to authorized employees or
duly designated representatives of EPA
or FDA.
(d) An authorized employee or a duly
designated representative of EPA or
FDA shall have access to the written
procedures established for the inspection and may request testing facility
management to certify that inspections are being implemented, performed, documented, and followed up
in accordance with this paragraph.
and reference substances known to be
biohazardous, including volatile substances, aerosols, radioactive materials, and infectious agents.
(c) Separate areas shall be provided,
as appropriate, for the diagnosis, treatment, and control of laboratory test
system diseases. These areas shall provide effective isolation for the housing
of test systems either known or suspected of being diseased, or of being
carriers of disease, from other test systems.
(d) Facilities shall have proper provisions for collection and disposal of contaminated water, soil, or other spent
materials. When animals are housed,
facilities shall exist for the collection
and disposal of all animal waste and
refuse or for safe sanitary storage of
waste before removal from the testing
facility. Disposal facilities shall be so
provided and operated as to minimize
vermin infestation, odors, disease hazards, and environmental contamination.
(e) Facilities shall have provisions to
regulate
environmental
conditions
(e.g.,
temperature,
humidity,
photoperiod) as specified in the protocol.
(f) For marine test organisms, an
adequate supply of clean sea water or
artificial sea water (prepared from deionized or distilled water and sea salt
mixture) shall be available. The ranges
of composition shall be as specified in
the protocol.
(g) For freshwater organisms, an adequate supply of clean water of the appropriate hardness, pH, and temperature, and which is free of contaminants
capable of interfering with the study
shall be available as specified in the
protocol.
(h) For plants, an adequate supply of
soil of the appropriate composition, as
specified in the protocol, shall be available as needed.
Subpart C—Facilities
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§ 792.41 General.
Each testing facility shall be of suitable size and construction to facilitate
the proper conduct of studies. Testing
facilities which are not located within
an indoor controlled environment shall
be of suitable location to facilitate the
proper conduct of studies. Testing facilities shall be designed so that there
is a degree of separation that will prevent any function or activity from having an adverse effect on the study.
§ 792.43 Test system care facilities.
(a) A testing facility shall have a sufficient number of animal rooms or
other test system areas, as needed, to
ensure: proper separation of species or
test systems, isolation of individual
projects, quarantine or isolation of animals or other test systems, and routine
or specialized housing of animals or
other test systems.
(1) In tests with plants or aquatic
animals, proper separation of species
can be accomplished within a room or
area by housing them separately in different chambers or aquaria. Separation
of species is unnecessary where the
protocol specifies the simultaneous exposure of two or more species in the
same chamber, aquarium, or housing
unit.
(2) Aquatic toxicity tests for individual projects shall be isolated to the
extent necessary to prevent cross-contamination of different chemicals used
in different tests.
(b) A testing facility shall have a
number of animal rooms or other test
system areas separate from those described in paragraph (a) of this section
to ensure isolation of studies being
done with test systems or test, control,
§ 792.45 Test system supply facilities.
(a) There shall be storage areas, as
needed, for feed, nutrients, soils, bedding, supplies, and equipment. Storage
areas for feed, nutrients, soils, and bedding shall be separated from areas
where the test systems are located and
shall be protected against infestation
or contamination. Perishable supplies
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§ 792.47
40 CFR Ch. I (7–1–11 Edition)
shall be preserved by appropriate
means.
(b) When appropriate, plant supply
facilities shall be provided. These include:
(1) Facilities, as specified in the protocol, for holding, culturing, and maintaining algae and aquatic plants.
(2) Facilities, as specified in the protocol, for plant growth, including but
not limited to, greenhouses, growth
chambers, light banks, and fields.
(c) When appropriate, facilities for
aquatic animal tests shall be provided.
These include but are not limited to
aquaria, holding tanks, ponds, and ancillary equipment, as specified in the
protocol.
and equipment used for facility environmental control shall be of appropriate design and adequate capacity to
function according to the protocol and
shall be suitably located for operation,
inspection, cleaning, and maintenance.
§ 792.63 Maintenance and calibration
of equipment.
(a) Equipment shall be adequately inspected, cleaned, and maintained.
Equipment used for the generation,
measurement, or assessment of data
shall be adequately tested, calibrated,
and/or standardized.
(b) The written standard operating
procedures required under § 792.81(b)(11)
shall set forth in sufficient detail the
methods, materials, and schedules to
be used in the routine inspection,
cleaning, maintenance, testing, calibration, and/or standardization of
equipment, and shall specify, when appropriate, remedial action to be taken
in the event of failure or malfunction
of equipment. The written standard operating procedures shall designate the
person responsible for the performance
of each operation.
(c) Written records shall be maintained of all inspection, maintenance,
testing, calibrating, and/or standardizing operations. These records, containing the date of the operation, shall
describe whether the maintenance operations were routine and followed the
written standard operating procedures.
Written records shall be kept of nonroutine repairs performed on equipment as a result of failure and malfunction. Such records shall document
the nature of the defect, how and when
the defect was discovered, and any remedial action taken in response to the
defect.
§ 792.47 Facilities for handling test,
control, and reference substances.
(a) As necessary to prevent contamination or mixups, there shall be separate areas for:
(1) Receipt and storage of the test,
control, and reference substances.
(2) Mixing of the test, control, and
reference substances with a carrier,
e.g., feed.
(3) Storage of the test, control, and
reference substance mixtures.
(b) Storage areas for test, control,
and/or reference substance and for test,
control, and/or reference mixtures shall
be separate from areas housing the test
systems and shall be adequate to preserve the identity, strength, purity,
and stability of the substances and
mixtures.
§ 792.49 Laboratory operation areas.
Separate laboratory space and other
space shall be provided, as needed, for
the performance of the routine and specialized procedures required by studies.
§ 792.51 Specimen and data storage facilities.
Space shall be provided for archives,
limited to access by authorized personnel only, for the storage and retrieval of all raw data and specimens
from completed studies.
Subpart E—Testing Facilities
Operation
§ 792.81 Standard
operating
procedures.
(a) A testing facility shall have
standard operating procedures in writing, setting forth study methods that
management is satisfied are adequate
to insure the quality and integrity of
the data generated in the course of a
study. All deviations in a study from
standard operating procedures shall be
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Subpart D—Equipment
§ 792.61 Equipment design.
Equipment used in the generation,
measurement, or assessment of data
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Environmental Protection Agency
§ 792.90
authorized by the study director and
shall be documented in the raw data.
Significant changes in established
standard operating procedures shall be
properly authorized in writing by management.
(b) Standard operating procedures
shall be established for, but not limited
to, the following:
(1) Test system room preparation.
(2) Test system care.
(3) Receipt, identification, storage,
handling, mixing, and method of sampling of the test, control, and reference
substances.
(4) Test system observations.
(5) Laboratory or other tests.
(6) Handling of test systems found
moribund or dead during study.
(7) Necropsy of test systems or postmortem examination of test systems.
(8) Collection and identification of
specimens.
(9) Histopathology.
(10) Data handling, storage and retrieval.
(11) Maintenance and calibration of
equipment.
(12) Transfer, proper placement, and
identification of test systems.
(c) Each laboratory or other study
area shall have immediately available
manuals and standard operating procedures relative to the laboratory or field
procedures being performed. Published
literature may be used as a supplement
to standard operating procedures.
(d) A historical file of standard operating procedures, and all revisions
thereof, including the dates of such revisions, shall be maintained.
ness for the study shall be evaluated.
This evaluation shall be in accordance
with acceptable veterinary medical
practice or scientific methods.
(c) At the initiation of a study, test
systems shall be free of any disease or
condition that might interfere with the
purpose or conduct of the study. If during the course of the study, the test
systems contract such a disease or condition, the diseased test systems
should be isolated, if necessary. These
test systems may be treated for disease
or signs of disease provided that such
treatment does not interfere with the
study. The diagnosis, authorization of
treatment, description of treatment,
and each date of treatment shall be
documented and shall be retained.
(d) Warm-blooded animals, adult reptiles, and adult terrestrial amphibians
used in laboratory procedures that require manipulations and observations
over an extended period of time, or in
studies that require these test systems
to be removed from and returned to
their test system-housing units for any
reason (e.g., cage cleaning, treatment,
etc.), shall receive appropriate identification (e.g., tattoo, color code, ear
tag, ear punch, etc.). All information
needed to specifically identify each
test system within the test systemhousing unit shall appear on the outside of that unit. Suckling mammals
and juvenile birds are excluded from
the requirement of individual identification unless otherwise specified in
the protocol.
(e) Except as specified in paragraph
(e)(1) of this section, test systems of
different species shall be housed in separate rooms when necessary. Test systems of the same species, but used in
different studies, should not ordinarily
be housed in the same room when inadvertent exposure to test, control, or
reference substances or test system
mixup could affect the outcome of either study. If such mixed housing is
necessary, adequate differentiation by
space and identification shall be made.
(1) Plants, invertebrate animals,
aquatic vertebrate animals, and organisms that may be used in multispecies
tests need not be housed in separate
rooms, provided that they are adequately segregated to avoid mixup and
cross contamination.
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§ 792.83 Reagents and solutions.
All reagents and solutions in the laboratory areas shall be labeled to indicate identity, titer or concentration,
storage requirements, and expiration
date. Deteriorated or outdated reagents and solutions shall not be used.
§ 792.90 Animal and other test system
care.
(a) There shall be standard operating
procedures for the housing, feeding,
handling, and care of animals and
other test systems.
(b) All newly received test systems
from outside sources shall be isolated
and their health status or appropriate-
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§ 792.105
40 CFR Ch. I (7–1–11 Edition)
(2) [Reserved]
(f) Cages, racks, pens, enclosures,
aquaria, holding tanks, ponds, growth
chambers, and other holding, rearing,
and breeding areas, and accessory
equipment, shall be cleaned and sanitized at appropriate intervals.
(g) Feed, soil, and water used for the
test systems shall be analyzed periodically to ensure that contaminants
known to be capable of interfering with
the study and reasonably expected to
be present in such feed, soil, or water
are not present at levels above those
specified in the protocol. Documentation of such analyses shall be maintained as raw data.
(h) Bedding used in animal cages or
pens shall not interfere with the purpose or conduct of the study and shall
be changed as often as necessary to
keep the animals dry and clean.
(i) If any pest control materials are
used, the use shall be documented.
Cleaning and pest control materials
that interfere with the study shall not
be used.
(j) All plant and animal test systems
shall be acclimatized to the environmental conditions of the test, prior to
their use in a study.
dures, which provide for periodic analysis of each batch.
(c) Each storage container for a test,
control, or reference substance shall be
labeled by name, chemical abstracts
service number (CAS) or code number,
batch number, expiration date, if any,
and, where appropriate, storage conditions necessary to maintain the identity, strength, purity, and composition
of the test, control, or reference substance. Storage containers shall be assigned to a particular test substance
for the duration of the study.
(d) For studies of more than 4 weeks
experimental duration, reserve samples
from each batch of test, control, and
reference substances shall be retained
for the period of time provided by
§ 792.195.
(e) The stability of test, control, and
reference substances under storage
conditions at the test site shall be
known for all studies.
§ 792.107 Test, control, and reference
substance handling.
Procedures shall be established for a
system for the handling of the test,
control, and reference substances to
ensure that:
(a) There is proper storage.
(b) Distribution is made in a manner
designed to preclude the possibility of
contamination, deterioration, or damage.
(c) Proper identification is maintained throughout the distribution
process.
(d) The receipt and distribution of
each batch is documented. Such documentation shall include the date and
quantity of each batch distributed or
returned.
erowe on DSK5CLS3C1PROD with CFR
Subpart F—Test, Control, and
Reference Substances
§ 792.105 Test, control, and reference
substance characterization.
(a) The identity, strength, purity,
and composition, or other characteristics which will appropriately define the
test, control, or reference substance
shall be determined for each batch and
shall be documented before its use in a
study. Methods of synthesis, fabrication, or derivation of the test, control,
or reference substance shall be documented by the sponsor or the testing
facility, and such location of documentation shall be specified.
(b) When relevant to the conduct of
the study the solubility of each test,
control, or reference substance shall be
determined by the testing facility or
the sponsor before the experimental
start date. The stability of the test,
control or reference substance shall be
determined before the experimental
start date or concomitantly according
to written standard operating proce-
§ 792.113 Mixtures of substances with
carriers.
(a) For each test, control, or reference substance that is mixed with a
carrier, tests by appropriate analytical
methods shall be conducted:
(1) To determine the uniformity of
the mixture and to determine, periodically, the concentration of the test,
control, or reference substance in the
mixture.
(2) When relevant to the conduct of
the experiment, to determine the solubility of each test, control, or reference
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Environmental Protection Agency
§ 792.130
substance in the mixture by the testing
facility or the sponsor before the experimental start date.
(3) To determine the stability of the
test, control or reference substance in
the mixture before the experimental
start date or concomitantly according
to written standard operating procedures, which provide for periodic analysis of each batch.
(b) Where any of the components of
the test, control, or reference substance carrier mixture has an expiration date, that date shall be clearly
shown on the container. If more than
one component has an expiration date,
the earliest date shall be shown.
(c) If a vehicle is used to facilitate
the mixing of a test substance with a
carrier, assurance shall be provided
that the vehicle does not interfere with
the integrity of the test.
the study as well as solvents, emulsifiers and/or other materials used to
solubilize or suspend the test, control,
or reference substances before mixing
with the carrier. The description shall
include specifications for acceptable
levels of contaminants that are reasonably expected to be present in the dietary materials and are known to be capable of interfering with the purpose or
conduct of the study if present at levels greater than established by the
specifications.
(10) The route of administration and
the reason for its choice.
(11) Each dosage level, expressed in
milligrams per kilogram of body or
test system weight or other appropriate units, of the test, control, or reference substance to be administered
and the method and frequency of administration.
(12) The type and frequency of tests,
analyses, and measurements to be
made.
(13) The records to be maintained.
(14) The date of approval of the protocol by the sponsor and the dated signature of the study director.
(15) A statement of the proposed statistical method.
(b) All changes in or revisions of an
approved protocol and the reasons
therefor shall be documented, signed
by the study director, dated, and maintained with the protocol.
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Subpart G—Protocol for and
Conduct of A Study
§ 792.120 Protocol.
(a) Each study shall have an approved written protocol that clearly indicates the objectives and all methods
for the conduct of the study. The protocol shall contain but shall not necessarily be limited to the following information:
(1) A descriptive title and statement
of the purpose of the study.
(2) Identification of the test, control,
and reference substance by name,
chemical abstracts service (CAS) number or code number.
(3) The name and address of the sponsor and the name and address of the
testing facility at which the study is
being conducted.
(4) The proposed experimental start
and termination dates.
(5) Justification for selection of the
test system.
(6) Where applicable, the number,
body weight, sex, source of supply, species, strain, substrain, and age of the
test system.
(7) The procedure for identification of
the test system.
(8) A description of the experimental
design, including methods for the control of bias.
(9) Where applicable, a description
and/or identification of the diet used in
§ 792.130
Conduct of a study.
(a) The study shall be conducted in
accordance with the protocol.
(b) The test systems shall be monitored in conformity with the protocol.
(c) Specimens shall be identified by
test system, study, nature, and date of
collection. This information shall be
located on the specimen container or
shall accompany the specimen in a
manner that precludes error in the recording and storage of data.
(d)
In
animal
studies
where
histopathology is required, records of
gross findings for a specimen from
postmortem observations shall be
available to a pathologist when examining
that
specimen
histopathologically.
(e) All data generated during the conduct of a study, except those that are
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§ 792.135
40 CFR Ch. I (7–1–11 Edition)
generated by automated data collection systems, shall be recorded directly, promptly, and legibly in ink.
All data entries shall be dated on the
day of entry and signed or initialed by
the person entering the data. Any
change in entries shall be made so as
not to obscure the original entry, shall
indicate the reason for such change,
and shall be dated and signed or identified at the time of the change. In automated data collection systems, the individual responsible for direct data
input shall be identified at the time of
data input. Any change in automated
data entries shall be made so as not to
obscure the original entry, shall indicate the reason for change, shall be
dated, and the responsible individual
shall be identified.
not necessarily be limited to, the following:
(1) Name and address of the facility
performing the study and the dates on
which the study was initiated and was
completed, terminated, or discontinued.
(2) Objectives and procedures stated
in the approved protocol, including any
changes in the original protocol.
(3) Statistical methods employed for
analyzing the data.
(4) The test, control, and reference
substances identified by name, chemical abstracts service (CAS) number or
code number, strength, purity, and
composition, or other appropriate characteristics.
(5) Stability, and when relevant to
the conduct of the study, the solubility
of the test, control, and reference substances under the conditions of administration.
(6) A description of the methods used.
(7) A description of the test system
used. Where applicable, the final report
shall include the number of animals or
other test organisms used, sex, body
weight range, source of supply, species,
strain and substrain, age, and procedure used for identification.
(8) A description of the dosage, dosage regimen, route of administration,
and duration.
(9) A description of all circumstances
that may have affected the quality or
integrity of the data.
(10) The name of the study director,
the names of other scientists or professionals and the names of all supervisory personnel, involved in the study.
(11) A description of the transformations, calculations, or operations
performed on the data, a summary and
analysis of the data, and a statement
of the conclusions drawn from the
analysis.
(12) The signed and dated reports of
each of the individual scientists or
other professionals involved in the
study, including each person who, at
the request or direction of the testing
facility or sponsor, conducted an analysis or evaluation of data or specimens
from the study after data generation
was completed.
(13) The locations where all specimens, raw data, and the final report
are to be stored.
§ 792.135 Physical and chemical characterization studies.
(a) All provisions of the GLPs shall
apply to physical and chemical characterization studies designed to determine stability, solubility, octanol
water partition coefficient, volatility,
and persistence (such as biodegradation, photodegradation, and chemical
degradation studies).
(b) The following GLP standards
shall not apply to studies designed to
determine physical and chemical characteristics of a test, control, or reference substance:
Section 792.31 (c), (d), and (g)
Section 792.35 (b) and (c)
Section 792.43
Section 792.45
Section 792.47
Section 792.49
Section 792.81(b) (1), (2), (6) through (9), and
(12)
Section 792.90
Section 792.105 (a) through (d)
Section 792.113
Section 792.120(a) (5) through (12), and (15)
Section 792.185(a) (5) through (8), (10), (12),
and (14)
Section 792.195 (c) and (d)
Subparts H–I [Reserved]
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Subpart J—Records and Reports
§ 792.185
Reporting of study results.
(a) A final report shall be prepared
for each study and shall include, but
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Environmental Protection Agency
§ 792.195
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(14) The statement prepared and
signed by the quality assurance unit as
described in § 792.35(b)(7).
(b) The final report shall be signed
and dated by the study director.
(c) Corrections or additions to a final
report shall be in the form of an
amendment by the study director. The
amendment shall clearly identify that
part of the final report that is being
added to or corrected and the reasons
for the correction or addition, and
shall be signed and dated by the person
responsible. Modification of a final report to comply with the submission requirements of EPA does not constitute
a correction, addition, or amendment
to a final report.
(d) A copy of the final report and of
any amendment to it shall be maintained by the sponsor and the test facility.
(e) Material retained or referred to in
the archives shall be indexed to permit
expedient retrieval.
§ 792.195 Retention of records.
(a) Record retention requirements set
forth in this section do not supersede
the record retention requirements of
any other regulations in this subchapter.
(b)(1) Except as provided in paragraph (c) of this section, documentation records, raw data, and specimens
pertaining to a study and required to
be retained by this part shall be retained in the archive(s) for a period of
at least ten years following the effective date of the applicable final test
rule.
(2) In the case of negotiated testing
agreements, each agreement will contain a provision that, except as provided in paragraph (c) of this section,
documentation records, raw data, and
specimens pertaining to a study and required to be retained by this part shall
be retained in the archive(s) for a period of at least ten years following the
publication date of the acceptance of a
negotiated test agreement.
(3) In the case of testing submitted
under section 5, except for those items
listed in paragraph (c) of this section,
documentation records, raw data, and
specimens pertaining to a study and required to be retained by this part shall
be retained in the archive(s) for a period of at least five years following the
date on which the results of the study
are submitted to the agency.
(c) Wet specimens, samples of test,
control, or reference substances, and
specially prepared material which are
relatively fragile and differ markedly
in stability and quality during storage,
shall be retained only as long as the
quality of the preparation affords evaluation. Specimens obtained from mutagenicity tests, specimens of soil,
water, and plants, and wet specimens
of blood, urine, feces, biological fluids,
do not need to be retained after quality
assurance verification. In no case shall
retention be required for longer periods
than those set forth in paragraph (b) of
this section.
(d) The master schedule sheet, copies
of protocols, and records of quality assurance inspections, as required by
§ 792.190 Storage and retrieval of
records and data.
(a) All raw data, documentation,
records, protocols, specimens, and final
reports generated as a result of a study
shall be retained. Specimens obtained
from mutagenicity tests, specimens of
soil, water, and plants, and wet specimens of blood, urine, feces, and biological fluids, do not need to be retained
after quality assurance verification.
Correspondence and other documents
relating to interpretation and evaluation of data, other than those documents contained in the final report,
also shall be retained.
(b) There shall be archives for orderly
storage and expedient retrieval of all
raw data, documentation, protocols,
specimens, and interim and final reports. Conditions of storage shall minimize deterioration of the documents or
specimens in accordance with the requirements for the time period of their
retention and the nature of the documents of specimens. A testing facility
may contract with commercial archives to provide a repository for all
material to be retained. Raw data and
specimens may be retained elsewhere
provided that the archives have specific reference to those other locations.
(c) An individual shall be identified
as responsible for the archives.
(d) Only authorized personnel shall
enter the archives.
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Pt. 795
40 CFR Ch. I (7–1–11 Edition)
Subpart C—Provisional Environmental
Effects Guidelines
§ 792.35(c) shall be maintained by the
quality assurance unit as an easily accessible system of records for the period of time specified in paragraph (b)
of this section.
(e) Summaries of training and experience and job descriptions required to be
maintained by § 792.29(b) may be retained along with all other testing facility employment records for the
length of time specified in paragraph
(b) of this section.
(f) Records and reports of the maintenance and calibration and inspection of
equipment, as required by § 792.63 (b)
and (c), shall be retained for the length
of time specified in paragraph (b) of
this section.
(g) If a facility conducting testing or
an archive contracting facility goes
out of business, all raw data, documentation, and other material specified in this section shall be transferred
to the archives of the sponsor of the
study. The EPA shall be notified in
writing of such a transfer.
(h) Specimens, samples, or other nondocumentary materials need not be retained after EPA has notified in writing the sponsor or testing facility holding the materials that retention is no
longer required by EPA. Such notification normally will be furnished upon
request after EPA or FDA has completed an audit of the particular study
to which the materials relate and EPA
has concluded that the study was conducted in accordance with this part.
(i) Records required by this part may
be retained either as original records
or as true copies such as photocopies,
microfilm, microfiche, or other accurate reproductions of the original
records.
795.120
Gammarid acute toxicity test.
Subpart D—Provisional Health Effects
Guidelines
795.225 Dermal pharmacokinetics of DGBE
and DGBA.
795.228 Oral/dermal pharmacokinetics.
795.231 Pharmacokinetics of isopropanal.
795.232 Inhalation and dermal pharmacokinetics of commercial hexane.
795.250 Developmental neurotoxicity screen.
AUTHORITY: 15 U.S.C. 2603.
Subpart A [Reserved]
Subpart B—Provisional Chemical
Fate Guidelines
§ 795.70 Indirect photolysis screening
test: Sunlight photolysis in waters
containing dissolved humic substances.
(a) Introduction. (1) Chemicals dissolved in natural waters are subject to
two types of photoreaction. In the first
case, the chemical of interest absorbs
sunlight directly and is transformed to
products when unstable excited states
of the molecule decompose. In the second case, reaction of dissolved chemical is the result of chemical or electronic excitation transfer from lightabsorbing humic species in the natural
water. In contrast to direct photolysis,
this photoreaction is governed initially
by the spectroscopic properties of the
natural water.
(2) In general, both indirect and direct processes can proceed simultaneously. Under favorable conditions
the measurement of a photoreaction
rate constant in sunlight (KpE) in a natural water body will yield a net value
that is the sum of two first-order reaction rate constants for the direct (kDE)
and indirect (kIE) pathways which can
be expressed by the relationship
PART 795—PROVISIONAL TEST
GUIDELINES
Subpart A [Reserved]
Equation 1
kpE=kDE+kIE.
erowe on DSK5CLS3C1PROD with CFR
Subpart B—Provisional Chemical Fate
Guidelines
This relationship is obtained when the
reaction volume is optically thin so
that a negligible fraction of the incident light is absorbed and is sufficiently dilute in test chemical; thus
Sec.
795.70 Indirect photolysis screening test:
Sunlight photolysis in waters containing
dissolved humic substances.
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| File Type | application/pdf |
| File Modified | 0000-00-00 |
| File Created | 0000-00-00 |