[Code of Federal Regulations]
[Title 40, Volume 14]
[Revised as of July 1, 2003]
From the U.S. Government Printing Office via GPO Access
[CITE: 40CFR79.60]

[Page 532-541]
 
                   TITLE 40--PROTECTION OF ENVIRONMENT
 
         CHAPTER I--ENVIRONMENTAL PROTECTION AGENCY (CONTINUED)
 
PART 79--REGISTRATION OF FUELS AND FUEL ADDITIVES--Table of Contents
 
            Subpart F--Testing Requirements for Registration
 
Sec. 79.60  Good laboratory practices (GLP) standards for inhalation 
exposure health effects testing.

    (a) General Provisions--(1) Scope. (i) This section prescribes good 
laboratory practices (GLPs) for conducting inhalation exposure studies 
relating to motor vehicle emissions health effects testing under this 
part. These directions are intended to ensure the quality and integrity 
of health effects data submitted pursuant to registration regulations 
issued under sections 211(b) or 211(e) of the Clean Air Act (CAA) (42 
U.S.C. 7545).
    (ii) This section applies to any study described by paragraph 
(a)(1)(i) of this section which any person conducts, initiates, or 
supports on or after May 27, 1994.
    (iii) It is EPA's policy that all health effects data developed 
under sections 211(b) and (e) of CAA be in accordance with provisions of 
this section. If data are not developed in accordance with the 
provisions of this section, EPA may consider such data insufficient to 
evaluate the health effects of a motor vehicle's fuel or fuel additive 
emissions, unless the submitter provides additional information 
demonstrating that the data are reliable and adequate and EPA determines 
that the data are sufficient.
    (2) Definitions. As used in this section, the following terms shall 
have the meanings specified:
    Batch means a specific quantity or lot of a test fuel, additive/base 
fuel mixture, or reference substance that has been characterized 
according to Sec. 79.60(f)(1)(i).
    CAA means the Clean Air Act.
    Carrier means any material which is combined with engine/motor 
vehicle emissions or a reference substance for administration to a test 
system. ``Carrier'' includes, but is not limited to, clean, filtered 
air, water, feed, and nutrient media.
    Control atmosphere means clean, filtered air which is administered 
to the test system in the course of a study for the purpose of 
establishing a basis for comparison with the test atmosphere for 
chemical or biological measurements.
    Experimental start date means the first date the test atmosphere is 
applied to the test system.
    Experimental termination date means the last date on which data are 
collected directly from the study.
    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 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

[[Page 533]]

photographs, videotape, 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, 
analytical standard, or material other than engine/motor vehicle 
emissions and/or its carrier, that is administered to or used in 
analyzing the test system in the course of a study. A ``reference 
substance'' is used to establish a basis for comparison with the test 
atmosphere for known chemical or biological measurements, i.e., positive 
or negative control substance.
    Specimen means any material derived from a test system for 
examination or analysis.
    Sponsor means person who initiates and supports, by provision of 
financial or other resources, a study or a person who submits a study to 
EPA in response to the CAA Section 211(b) or 211(e) Fuels and Fuel 
Additives Registration Rule or 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 system is exposed to a test atmosphere under laboratory conditions 
to determine or help predict the health effects of that exposure in 
humans, other living organisms, or media.
    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.
    Study initiation date means the date the protocol is signed by the 
study director.
    Test substance means a vapor and/or aerosol mixture composed of 
engine/motor vehicle emissions and clean, filtered air which is 
administered directly, or indirectly, by the inhalation route to a test 
system in a study which develops data to meet the registration 
requirements of CAA section 211(b) or (e).
    Test system means any animal, microorganism, chemical or physical 
matrix, to which the test, control, or reference substance is 
administered or added for study. This definition 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.).
    (3) 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 section 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 
section.
    (4) Statement of compliance or non-compliance. Any person who 
submits to EPA a test in compliance with registration regulations issued 
under CAA section 211(b) or section 211(e) shall include in the 
submission a true and correct statement, signed by the sponsor and the 
study director, of one of the following types:
    (i) A statement that the study was conducted in accordance with this 
section; or
    (ii) A statement describing in detail all differences between the 
practices used in the study and those required by this section; or
    (iii) 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 section.
    (5) Inspection of a testing facility. (i) A testing facility shall 
permit an authorized employee or duly designated representative of EPA, 
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 
section 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

[[Page 534]]

these records in litigation or formal adjudicatory hearings.
    (ii) EPA will not consider reliable for purposes of showing that a 
test substance does or 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 section. 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.
    (6) Effects of non-compliance. (i) Pursuant to sections 114, 208, 
and 211(d) of the CAA, it shall be a violation of this section and a 
violation of this rule (40 CFR part 79, subpart F) if:
    (A) The test is not being or was not conducted in accordance with 
any requirement of this part; or
    (B) Data or information submitted to EPA under part 79, including 
the statement required by Sec. 79.60(a)(4), include information or data 
that are false or misleading, contain significant omissions, or 
otherwise do not fulfill the requirements of this part; or
    (C) Entry in accordance with Sec. 79.60(a)(5) for the purpose of 
auditing test data is denied.
    (ii) 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 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.
    (iii) If data submitted in compliance with registration regulations 
issued under CAA section 211(b) or section 211(e) are not developed in 
accordance with this section, EPA may determine that the sponsor has not 
fulfilled its obligations under 40 CFR part 79 and may require the 
sponsor to develop data in accordance with the requirements of this 
section in order to satisfy such obligations.
    (b) Organization and Personnel. (1) Personnel. (i) 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.
    (ii) Each testing facility shall maintain a current summary of 
training and experience and job description for each individual engaged 
in or supervising the conduct of a study.
    (iii) There shall be a sufficient number of personnel for the timely 
and proper conduct of the study according to the protocol.
    (iv) Personnel shall take necessary personal sanitation and health 
precautions designed to avoid contamination of test fuel and additive/
base fuel mixtures, test and reference substances, and test systems.
    (v) 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.
    (vi) 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, fuel and fuel/additive 
mixtures, test 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.
    (2) Testing facility management. For each study, testing facility 
management shall:
    (i) Designate a study director as described in Sec. 79.60(b)(3) 
before the study is initiated.
    (ii) Replace the study director promptly if it becomes necessary to 
do so during the conduct of a study.
    (iii) Assure that there is a quality assurance unit as described in 
Sec. 79.60(b)(4).

[[Page 535]]

    (iv) Assure that test fuels and fuel/additive mixtures and test and 
reference substances have been identified as to content, strength, 
purity, stability, and uniformity, as applicable.
    (v) Assure that personnel, resources, facilities, equipment, 
materials and methodologies are available as scheduled.
    (vi) Assure that personnel clearly understand the functions they are 
to perform.
    (vii) 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.
    (3) Study director. For each study, a scientist or other 
professional person with a doctorate degree or equivalent in toxicology 
or other appropriate discipline 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:
    (i) The protocol, including any changes, is approved as provided by 
Sec. 79.60(g)(1)(i) and is followed;
    (ii) All experimental data, including observations of unanticipated 
responses of the test system are accurately recorded and verified;
    (iii) Unforeseen circumstances that may affect the quality and 
integrity of the study are noted when they occur, and corrective action 
is taken and documented;
    (iv) Test systems are as specified in the protocol;
    (v) All applicable good laboratory practice regulations are 
followed; and
    (vi) All raw data, documentation, protocols, specimens, and final 
reports are archived properly during or at the close of the study.
    (4) Quality assurance unit. 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 section. 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.
    (i) Quality assurance unit duties. (A) Maintain a copy of a master 
schedule sheet of all studies conducted 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.
    (B) Maintain copies of all protocols pertaining to all studies for 
which the unit is responsible.
    (C) 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.
    (D) Periodically submit to management and the study director written 
status reports on each study, noting any problems and the corrective 
actions taken.
    (E) Determine that no deviations from approved protocols or standard 
operating procedures were made without proper authorization and 
documentation.
    (F) 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.
    (G) 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.
    (ii) The responsibilities and procedures applicable to the quality 
assurance unit, the records maintained by

[[Page 536]]

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 inspection to authorized employees or duly 
designated representatives of EPA.
    (iii) An authorized employee or a duly designated representative of 
EPA shall have access to the written procedures established for the 
inspection and may request test facility management to certify that 
inspections are being implemented, performed, documented, and followed 
up in accordance with this paragraph.
    (c) Facilities--(1) General. Each testing facility shall be of 
suitable size and construction to facilitate the proper conduct of 
studies. Testing facilities which are not completely located within an 
indoor controlled environment shall be of suitable location/proximity 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.
    (2) Test system care facilities. (i) 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, quarantine or 
isolation of animals or other test systems, and routine or specialized 
housing of animals or other test systems.
    (ii) 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, and reference substances known to be biohazardous, 
including volatile atmospheres and aerosols, radioactive materials, and 
infectious agents. The animal handling facility must operate under the 
supervision of a veterinarian.
    (iii) 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.
    (iv) Facilities shall have proper provisions for collection and 
disposal of contaminated air, water, 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.
    (v) Facilities shall have provisions to regulate environmental 
conditions (e.g., temperature, humidity, day length, etc.) as specified 
in the protocol.
    (3) Test system supply/operation areas. (i) There shall be storage 
areas, as needed, for feed, bedding, supplies, and equipment. Storage 
areas for feed and bedding shall be separated from areas where the test 
systems are located and shall be protected against infestation or 
contamination. Perishable supplies shall be preserved by appropriate 
means.
    (ii) Separate laboratory space and other space shall be provided, as 
needed, for the performance of the routine and specialized procedures 
required by studies.
    (4) Facilities for handling test fuels and fuel/additive mixtures 
and reference substances. (i) As necessary to prevent contamination or 
mixups, there shall be separate areas for:
    (A) Receipt and storage of the test fuels and fuel/additive mixtures 
and reference substances;
    (B) Mixing of the test fuels, fuel/additive mixtures, and reference 
substances with a carrier, i.e., liquid hydrocarbon; and
    (C) Storage of the test fuels, fuel/additive mixtures, and reference 
substance/carrier mixtures.
    (ii) Storage areas for test fuels and fuel/additive mixtures and 
reference substances and for reference mixtures shall be separate from 
areas housing the test systems and shall be adequate

[[Page 537]]

to preserve the identity, strength, purity, and stability of the 
substances and mixtures.
    (5) Specimen and data storage facilities. Space shall be secured for 
archives for the storage and retrieval of all raw data and specimens 
from completed studies.
    (d) Equipment--(1) Equipment design. Equipment used in the 
generation, measurement, or assessment of data 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.
    (2) Maintenance and calibration of equipment. (i) 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.
    (ii) The written standard operating procedures required under 
Sec. 79.60(e)(1)(ii)(K) 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.
    (iii) 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 non-
routine 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.
    (e) Testing Facilities Operation--(1) Standard operating procedures. 
(i) 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 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.
    (ii) Standard operating procedures shall be established for, but not 
limited to, the following:
    (A) Test system room preparation;
    (B) Test system care;
    (C) Receipt, identification, storage, handling, mixing, and method 
of sampling of test fuels and fuel/additive mixtures and reference 
substances;
    (D) Test system observations;
    (E) Laboratory or other tests;
    (F) Handling of test animals found moribund or dead during study;
    (G) Necropsy or postmortem examination of test animals;
    (H) Collection and identification of specimens;
    (I) Histopathology
    (J) Data handling, storage and retrieval.
    (K) Maintenance and calibration of equipment.
    (L) Transfer, proper placement, and identification of test systems.
    (iii) Each laboratory or other study area shall have immediately 
available manuals and standard operating procedures relative to the 
laboratory procedures being performed. Published literature may be used 
as a supplement to standard operating procedures.
    (iv) A historical file of standard operating procedures, and all 
revisions thereof, including the dates of such revisions, shall be 
maintained.
    (2) 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.
    (3) Animal and other test system care. (i) There shall be standard 
operating procedures for the housing, feeding, handling, and care of 
animals and other test systems.
    (ii) All newly received test systems from outside sources shall be 
isolated

[[Page 538]]

and their health status or appropriateness for the study shall be 
evaluated. This evaluation shall be in accordance with acceptable 
veterinary medical practice or scientific methods.
    (iii) 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 
shall 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.
    (iv) When laboratory procedures require test animals to be 
manipulated and observed over an extended period of time or when studies 
require test animals to be removed from and returned to their housing 
units for any reason (e.g., cage cleaning, treatment, etc.), these test 
systems shall receive appropriate identification (e.g., tattoo, color 
code, etc.). Test system identification shall conform with current 
laboratory animal handling practice. All information needed to 
specifically identify each test system within the test system-housing 
unit shall appear on the outside of that unit. Suckling animals are 
excluded from the requirement of individual identification unless 
otherwise specified in the protocol.
    (v) Except as specified in paragraph (e)(3)(v)(A) of this section, 
test animals of different species shall be housed in separate rooms when 
necessary. Test animals of the same species, but used in different 
studies, shall not ordinarily be housed in the same room when 
inadvertent exposure to the test 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.
    (A) Test systems 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.
    (B) [Reserved]
    (vi) Cages, racks, pens, enclosures, and other holding, rearing, and 
breeding areas, and accessory equipment, shall be cleaned and sanitized 
at appropriate intervals.
    (vii) Feed and water used for the test animals 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 or water are not present at greater than trace levels. 
Documentation of such analyses shall be maintained as raw data.
    (viii) 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.
    (ix) 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.
    (x) All test systems shall be acclimatized to the environmental 
conditions of the test, prior to their use in a study.
    (f) Test fuels, additive/base fuel mixtures, and reference 
substances--(1) Test fuel, fuel/additive mixture, and reference 
substance identity. (i) The product brand name/service mark, strength, 
purity, content, or other characteristics which appropriately define the 
test fuel, fuel/additive mixture, or reference substance shall be 
reported for each batch and shall be documented before its use in a 
study. Methods of synthesis, fabrication, or derivation, as appropriate, 
of the test fuel, fuel/additive mixture, or reference substance shall be 
documented by the sponsor or the testing facility, and such location of 
documentation shall be specified.
    (ii) The stability of test fuel, fuel/additive mixture, and 
reference substances under storage conditions at the test site shall be 
known for all studies.
    (2) Test fuel, additive/base fuel mixture, and reference substance 
handling. Procedures shall be established for a system for the handling 
of the test fuel, fuel/additive mixture, and reference substance(s) to 
ensure that:
    (i) There is proper storage.
    (ii) Distribution is made in a manner designed to preclude the 
possibility of

[[Page 539]]

contamination, deterioration, or damage.
    (iii) Proper identification is maintained throughout the 
distribution process.
    (iv) The receipt and distribution of each batch is documented. Such 
documentation shall include the date and quantity of each batch 
distributed or returned.
    (3) Mixtures of test emissions or reference solutions with carriers.
    (i) For test emissions or each reference substance mixed with a 
carrier, tests by appropriate analytical methods shall be conducted:
    (A) To determine the uniformity of the test substance and to 
determine, periodically, the concentration of the test emissions or 
reference substance in the mixture;
    (B) When relevant to the conduct of the experiment, to determine the 
solubility of each reference substance in the carrier mixture before the 
experimental start date; and
    (C) To determine the stability of test emissions or a reference 
solution in the test substance before the experimental start date or 
concomitantly according to written standard operating procedures, which 
provide for periodic analysis of each batch.
    (ii) Where any of the components of the 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.
    (iii) If a chemical or physical agent is used to facilitate the 
mixing of a test substance with a carrier, assurance shall be provided 
that the agent does not interfere with the integrity of the test.
    (g) Protocol for and conduct of a study--(1) Protocol. (i) Each 
study shall have a written protocol that clearly indicates the 
objectives and all methods for the conduct of the study. The protocol 
shall contain but shall not be limited to the following information:
    (A) A descriptive title and statement of the purpose of the study.
    (B) Identification of the test fuel, fuel/additive mixture, and 
reference substance by name, chemical abstracts service (CAS) number or 
code number, as applicable.
    (C) The name and address of the sponsor and the name and address of 
the testing facility at which the study is being conducted.
    (D) The proposed experimental start and termination dates.
    (E) Justification for selection of the test system, as necessary.
    (F) Where applicable, the number, body weight, sex, source of 
supply, species, strain, substrain, and age of the test system.
    (G) The procedure for identification of the test system.
    (H) A description of the experimental design, including methods for 
the control of bias.
    (I) Where applicable, a description and/or identification of the 
diet used in the study. 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.
    (J) Each concentration level, expressed in milligrams per cubic 
meter of air or other appropriate units, of the test or reference 
substance to be administered and the frequency of administration.
    (K) The type and frequency of tests, analyses, and measurements to 
be made.
    (L) The records to be maintained.
    (M) The date of approval of the protocol by the sponsor and the 
dated signature of the study director.
    (N) A statement of the proposed statistical method.
    (ii) 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.
    (2) Conduct of a study. (i) The study shall be conducted in 
accordance with the protocol.
    (ii) The test systems shall be monitored in conformity with the 
protocol.
    (iii) Specimens shall be identified by test system, study, nature, 
and date of collection. This information shall be located on the 
specimen container or

[[Page 540]]

shall accompany the specimen in a manner that precludes error in the 
recording and storage of data.
    (iv) 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.
    (v) All data generated during the conduct of a study, except those 
that are 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.
    (h) Records and Reports--(1) Reporting of study results. (i) A final 
report shall be prepared for each study and shall include, but not 
necessarily be limited to, the following:
    (A) Name and address of the facility performing the study and the 
dates on which the study was initiated and was completed, terminated, or 
discontinued.
    (B) Objectives and procedures stated in the approved protocol, 
including any changes in the original protocol.
    (C) Statistical methods employed for analyzing the data.
    (D) The test fuel, additive/base fuel mixture, and test and 
reference substances identified by name, chemical abstracts service 
(CAS) number or code number, strength, purity, content, or other 
appropriate characteristics.
    (E) Stability, and when relevant to the conduct of the study, the 
solubility of the test emissions and reference substances under the 
conditions of administration.
    (F) A description of the methods used.
    (G) 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.
    (H) A description of the concentration regimen as daily exposure 
period, i.e., number of hours, and exposure duration, i.e., number of 
days.
    (I) A description of all circumstances that may have affected the 
quality or integrity of the data.
    (J) The name of the study director, the names of other scientists or 
professionals and the names of all supervisory personnel, involved in 
the study.
    (K) 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.
    (L) 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.
    (M) The locations where all specimens, raw data, and the final 
report are to be kept or stored.
    (N) The statement, prepared and signed by the quality assurance 
unit, as described in Sec. 79.60(b)(4)(i)(G).
    (ii) The final report shall be signed and dated by the study 
director.
    (iii) 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.

[[Page 541]]

    (iv) A copy of the final report and of any amendment to it shall be 
maintained by the sponsor and the test facility.
    (2) Storage and retrieval of records and data. (i) 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, 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.
    (ii) All raw data, documentation, protocols, specimens, and interim 
and final reports shall be archived for orderly storage and expedient 
retrieval. 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.
    (iii) An individual shall be identified as responsible for the 
archiving of records.
    (iv) Access to archived material shall require authorization and 
documentation.
    (v) Archived material shall be indexed to permit expedient 
retrieval.
    (3) Retention of records. (i) Record retention requirements set 
forth in this section do not supersede the record retention requirements 
of any other regulations in this subchapter.
    (ii) Except as provided in paragraph (h)(3)(iii) of this section, 
documentation records, raw data, and specimens pertaining to a study and 
required to be retained by this part shall be archived for a period of 
at least ten years following the completion of the study.
    (iii) Wet specimens, samples of test fuel, additive/base fuel 
mixtures, 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, 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 a longer period than that set forth in 
paragraph (h)(3)(ii) of this section.
    (iv) The master schedule sheet, copies of protocols, and records of 
quality assurance inspections, as required by Sec. 79.60(b)(4)(iii) 
shall be maintained by the quality assurance unit as an easily 
accessible system of records for the period of time specified in 
paragraph (h)(3)(ii) of this section.
    (v) Summaries of training and experience and job descriptions 
required to be maintained by Sec. 79.60(b)(1)(ii) may be retained along 
with all other testing facility employment records for the length of 
time specified in paragraph (h)(3)(ii) of this section.
    (vi) Records and reports of the maintenance and calibration and 
inspection of equipment, as required by Sec. 79.60(d)(2) (ii) and (iii), 
shall be retained for the length of time specified in paragraph 
(h)(3)(ii) of this section.
    (vii) 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 sponsor 
of the study for archival.
    (viii) Records required by this section may be retained either as 
original records or as true copies such as photocopies, microfilm, 
microfiche, or other accurate reproductions of the original records.