[Federal Register Volume 66, Number 148 (Wednesday, August 1, 2001)]
[Notices]
[Pages 39767-39771]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 01-18890]


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ENVIRONMENTAL PROTECTION AGENCY

[OPP-00723; FRL-6787-4]


Combined Chronic Toxicity/Carcinogenicity Testing of Respirable 
Fibrous Particle Final Test Guideline; Notice of Availability

AGENCY: Environmental Protection Agency (EPA).

ACTION: Notice of availability.

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SUMMARY: EPA has established a unified library for test guidelines 
issued by the Office of Prevention, Pesticides and Toxic Substances 
(OPPTS) for use in testing chemical substances to develop data for 
submission to EPA under the Toxic Substances Control Act (TSCA), the 
Federal Food, Drug, and Cosmetic Act (FFDCA), or the Federal 
Insecticide, Fungicide, and Rodenticide Act (FIFRA). These test 
guidelines represent an Agency effort that began in 1991 to harmonize 
the test guidelines within OPPTS, as well as to harmonize the OPPTS 
test guidelines with those of the Organization for Economic Cooperation 
and Development (OECD). The process for developing and amending these 
test guidelines includes public participation and the extensive 
involvement of the scientific community, including peer review by the 
Scientific Advisory Panel (SAP) and the Scientific Advisory Board (SAB) 
and other expert scientific organizations. With this notice, EPA is 
announcing the availability of the final test guideline for OPPTS 
870.8355 Combined Chronic Toxicity/Carcinogenicity Testing of 
Respirable Fibrous Particles.

FOR FURTHER INFORMATION CONTACT: Barbara Cunningham, Director, Office 
of Program Management and Evaluation, Office of Pollution Prevention 
and Toxics (7401), Environmental Protection Agency, 1200 Pennsylvania 
Ave., NW., Washington, DC 20460; telephone number: (202) 554-1404; e-
mail address: [email protected].

SUPPLEMENTARY INFORMATION:

I. Does this Action Apply to Me?

    This action is directed to the public in general. Although this 
action may be of particular interest to those persons who are or may be 
required to conduct testing of chemical substances under TSCA, FFDCA, 
or FIFRA, the Agency has not attempted to describe all the specific 
entities that may be affected by this action. If you have any questions 
regarding the applicability of this action to a particular entity, 
consult the person under FOR FURTHER INFORMATION CONTACT.

II. How Can I Get Additional Information, Including Copies of this 
Document or Other Related Documents?

    1. Electronically. You may obtain electronic copies of this 
document, and certain other related documents that might be available 
electronically, from the EPA Internet Home Page at http://www.epa.gov/. 
To access this document, on the Home Page select ``Laws and 
Regulations,'' ``Regulations and Proposed Rules,'' and then look up the 
entry for this document under the ``Federal Register--Environmental 
Documents.'' You can also go directly to the Federal Register listings 
at http://www.epa.gov/fedrgstr/. You may also obtain copies of test 
guidelines from the EPA Internet Home Page at http://www.epa.gov/opptsfrs/home/guidelin.htm.
    2. In person. The Agency has established an official record for 
this final guideline under docket control number OPP-00723. The 
official record consists of the documents specifically referenced in 
this action, any public comments received during an applicable comment 
period, and other information related to this action, including any 
information claimed as confidential business information (CBI). This 
official record includes the documents that are physically located in 
the docket, as well as the documents that are referenced in those 
documents. The public version of the official record does not include 
any information claimed as CBI. The public version of the official 
record, which includes printed, paper versions of any electronic 
comments submitted during an applicable comment period, is available 
for inspection in the Public Information and Records Integrity Branch 
(PIRIB), Rm.119, Crystal Mall #2, 1921 Jefferson Davis Hwy., Arlington, 
VA, from 8:30 a.m. to 4 p.m., Monday through Friday, excluding legal 
holidays. The PIRIB telephone number is (703) 305-5805.

III. What Action is EPA Taking?

    EPA is announcing the availability of the final test guideline for 
OPPTS 870.8355 Combined Chronic Toxicity/Carcinogenicity Testing of 
Respirable Fibrous Particles.
    EPA recognizes that the current health effects test guidelines for 
chronic inhalation toxicity and/or carcinogenicity studies on chemicals 
are not specific enough for the testing of fibrous substances. These 
guidelines have to be modified to take into account testing issues 
which are unique to fibrous particles. Although a number of test 
systems and/or protocols have been utilized by the scientific community 
for evaluating the fibrogenic and carcinogenic potential of fibrous 
particles, there has been considerable debate about the scientific 
validity and utility of available test methods. Thus, there is a need 
for EPA to develop a standardized health effects test guideline for 
fibrous substances that can be used by EPA in future rulemaking, 
negotiated enforceable consent agreements, or voluntary action to 
obtain the necessary toxicologic information for risk assessment 
purposes.
    The objective of this combined chronic toxicity/carcinogenicity 
testing of respirable fibrous particles is to determine the effects of 
a fibrous substance identified to be of potential health concern in at 
least a rodent species following prolonged and repeated inhalation 
exposure. The application of this guideline should generate data which 
identify the majority of chronic toxic and carcinogenic effects and 
determine dose-response relationships.
    EPA recognizes concerns have been expressed about data development 
using animal models. While no comments were received from the animal 
advocacy

[[Page 39768]]

community, it is important to note that EPA is committed to avoiding 
unnecessary or duplicative animal testing. As part of this commitment, 
the Agency plays an important role in the Federal Interagency 
Coordinating Committee on the Validation of Alternative Methods 
(ICCVAM) (http://iccvam.niehs.nih.gov/ home.htm) whose goals are: (1) 
To encourage the reduction of the number of animals used in testing; 
(2) to seek opportunities to replace test methods requiring animals 
with alternative test methods when acceptable alternative methods are 
available; and (3) to refine existing test methods to optimize animal 
use when there is no substitute for animal testing. Further, where 
testing is needed to develop scientifically adequate data, the Agency 
is committed to reducing the number of animals used for testing, 
including, whenever possible, by incorporating in vitro (non-animal) 
test methods or other alternative approaches that have been 
scientifically validated and have received regulatory acceptance. EPA 
considers these goals and commitments to be important considerations in 
developing health effects data; however, they must be balanced with the 
essential need to conduct scientifically sound chemical hazard/risk 
assessments in support of the Agency's mission to protect human health 
and the environment studies.

IV. Response to Public Comments

    In the notice of availability for the proposed test guideline 
published in the Federal Register of July 28, 1999 (64 FR 40871) (FRL-
6078-6), EPA requested comments from the public on the proposed test 
guideline which was developed using the current EPA/OPPTS health 
effects test guideline for combined chronic toxicity and 
carcinogenicity (Ref. 1) as a template and based on the comments and 
recommendations made by a 1995 Workshop Panel on a number of scientific 
issues specific for fiber testing (Refs. 2 and 4). A number of comments 
on various issues related to the test substance and the study design 
were received from three U.S. fiber manufacturer associations, a 
European fiber industry association, a U.S. Government agency, a U.S. 
consultant, and a European scientist. All public comments were 
evaluated and a revised draft guideline with some of the public 
comments incorporated was prepared. At an EPA FIFRA SAP meeting on 
September 26, 2000, the draft guideline as well as a number of issues 
raised by the public commenters were reviewed and evaluated by the SAP. 
In addition to providing EPA with comments on the draft guideline, the 
SAP provided EPA an opinion on a number of issues raised by the public 
commenters (Ref. 3). Following are the major public comments received 
and EPA's responses to these comments.
    Comment 1. A number of commenters expressed that with the recent 
development of short-term in vitro and in vivo assay systems for 
predicting the biopersistence and toxicity of fibers, it is frequently 
possible to make informed statements about the likely hazard and risk 
posed by a fiber. Therefore, EPA should make use of these new 
developments and consider a tiered testing approach; the circumstances 
under which long-term rodent inhalation studies of a fiber are required 
should be specified in the guideline.
    Response. In the 1995 Workshop, the panel had identified a number 
of in vitro and in vivo short-term screening tests that could be used 
to develop a minimum data set for making decisions about the potential 
health hazards of fibers and for prioritizing the need for further 
testing in a chronic inhalation study. EPA is aware of the recent 
development of short-term in vitro and in vivo assay systems for 
predicting the biopersistence and toxicity of fibers and has initiated 
a plan to develop a tiered testing approach for identifying potential 
hazardous fibers for long-term inhalation studies. In response to this 
comment, the following statement indicating the use of short-term tests 
to identify potential hazardous fibers for long-term inhalation studies 
has been added in the ``Purpose'' paragraph of the guideline: ``The 
fibrous substances to be tested under this guideline will be selected 
based on data from appropriate short-term screening tests indicative of 
potential health hazard and risk concern.''
    Comment 2. A commenter indicated that there are no verified reports 
showing evidence of serious adverse health effects caused by organic 
fibers in either occupational or consumer settings and suggested that 
EPA should expressly exclude organic fibers from the guideline.
    Response. As indicated in the response to comment 1, a fibrous 
substance will be tested for chronic toxicity/carcinogenicity under 
this guideline only if it is identified to be of potential human health 
concern. The SAP believed that the guideline will have application to 
testing of some organic fibers. Since the guideline was derived 
primarily from experience with inorganic fibers and there are 
differences between organic and inorganic fibers, the following 
statement has been added to the test guideline as recommended by the 
SAP: ``While the guideline will have application to testing of organic 
fibers, additional considerations may be necessary for study of organic 
fibers.''
    Comment 3. A couple of commenters expressed that it would be very 
inefficient for the industry to have to conduct more than one study in 
order to satisfy regulatory guidelines in both Europe and the United 
States and suggested that EPA should work closely with the Organization 
for Economic Cooperation and Development (OECD) to develop a harmonized 
testing guideline for the chronic toxicity and carcinogenicity of 
fibers.
    Response. The EPA fiber testing guideline was developed based 
largely on the recommendations made by a panel of international 
experts. There are fundamental differences in the purpose and objective 
of long-term toxicity tests in Europe and the United States. In Europe, 
the primary purpose of the tests is to collect data for hazard 
identification while the United States requires the data for both 
hazard identification and dose-response assessment. Nonetheless, in the 
development of the EPA fiber testing guideline, attempts have been made 
to harmonize with available OECD guidelines to the extent possible.
    Comment 4. This comment deals with the definition and criteria of 
test materials suitable for rat inhalation studies. The guideline 
specifies that for rat inhalation studies, the fiber samples used 
should be rat-respirable. A rat-respirable fiber is defined as a fiber 
with an aspect ratio of at least 3:1 and an aerodynamic diameter of 
less than 3 m. A comment suggested that the definition of a 
``rat-respirable fiber'' should be modified to be ``a fiber with a 
geometric mean diameter (GMD) 0.8 m'' since actual 
measurement of the aerodynamic diameter of fibrous materials by 
traditional sampling techniques is not always reliable.
    Response. The definition of fibers is adopted from the 
recommendation of a Workshop Panel and is widely accepted in the field. 
The Workshop Panel recommended that respirability should be defined on 
the basis of experimental data, rather than calculated data. For many 
types of fibers, what reaches the rat lung has been well characterized; 
an upper limit of 3 m aerodynamic diameter is deemed effective 
in capturing rat-respirable fibers. The guideline defines a ``rat-
respirable fiber'' using the aerodynamic diameter rather than the 
geometric diameter because the aerodynamic diameter (and not the 
geometric diameter) is the major determinant for the respirability of

[[Page 39769]]

fibrous particles. The SAP also concluded that a definition of ``rat-
respirable fiber'' as having an aerodynamic diameter of 3 m 
would be preferable to a definition of GMD of  0.8 
m.
    Comment 5. In the definition section of the guideline, the 
``concentration'' of fibrous particles was expressed as the absolute 
number of fibers/cc. A comment suggested that ``Aerosol concentration 
should also be expressed as the total number of WHO f/cc.'' A WHO 
(World Health Organization) fiber is a fiber with a diameter < 3 
m and a length > 5 m.
    Response. On this issue, the SAP concluded that the definition of 
concentration of fibrous particles should start with the absolute 
number of fibers/cc. However, it emphasized that exposure 
concentrations should also be expressed as WHO fibers/cc as well as 
fibers greater than 20 m/cc and smaller size categories. 
Accordingly, the following statement has been added into this final 
test guideline: ``Exposure concentrations should also be expressed by 
fiber length, e.g., WHO fibers (greater than 5 m in length)/
cc, fibers with length greater than 10, 15 and 20 m/cc.
    Comment 6. There are a couple of comments on the selection of 
animal species for fiber testings. A commenter expressed that the rat 
inhalation model is not sensitive enough to reliably predict the cancer 
risk of fibers for human. The basis of the argument is that to cause 
similar risks from asbestos by chronic inhalation experiments with 
rats, the fiber concentration per milliliter (mL) measured with the 
same method as in the workplace atmosphere has to be about 100 times 
higher. Another commenter felt that although the hamster is capable of 
maximizing the number of mesotheliomas that may be induced by a fiber, 
the cost of such information outweighs its usefulness, and that the use 
of the model is controversial because hamsters are unusually sensitive 
to the development of mesothelioma.
    Response. The rat bioassay model has proven to be a fairly good 
predictor of carcinogenic potential of fibers in humans. Both the 
Workshop Panel and the SAP concluded that for identifying the 
carcinogenic potential of fibers via the inhalation route, the rat is 
clearly the species of choice because of its susceptibility to fiber-
induced pulmonary fibrosis, lung neoplasms and mesothelioma. While the 
rat model is quite effective at identifying the carcinogenic potential 
of fibers, as the commenter pointed out, it is of less value as a 
measure of carcinogenic potency. EPA uses testing not only for 
qualitative determination of carcinogenic potential, but also for 
quantitative risk assessment, and has historically required the use of 
two species. Although only the rat model has a sufficient database to 
be recommended for inhalation exposure studies with fibers, both the 
Workshop Panel and the SAP expressed that the hamster could be used if 
mesothelioma was the endpoint of interest because the hamster is more 
sensitive than the rat for this endpoint. However, the panels commented 
that the use of the hamster should not be a mandatory requirement 
because the hamster does not seem to develop lung tumors and lifetime 
hamster studies are fraught with technical problems. Hence, regarding 
animal species selection, the final test guideline recommends the rat 
to be the first species used and since the hamster is more sensitive 
than the rat with respect of fiber-induced mesothelioma, the hamster 
should be considered as a second species when results of the rat study 
show pleural toxicity or neoplasms and dose response data are needed 
for risk assessment purposes.
    Comment 7. A number of commenters expressed opinions that: ``The 
use of both sexes of rats does not appear warranted, either in expense 
or the use of additional animals; male and female rats do not appear to 
differ in their response to the pathogenic effects of fibers.''
    Response. It is true that presently, there is no evidence of a sex 
difference in response to inhaled fibers, in contrast to non-fibrous 
particles where female rats appear to be more sensitive (thus a single 
sex is adequate). As a commenter of the previous comment (comment 6) 
pointed out, the rat appears to be less sensitive than the human (with 
regard to tumorigenesis of asbestos), and this provides another reason 
for using both sexes since the use of both sexes would increase the 
total number of animals (typically from 50 to 100) and thus the 
sensitivity of the chronic bioassay. On this issue, the Workshop Panel 
concluded that testing in both sexes should be encouraged. Most of the 
SAP members also felt that both sexes of rats should be required for 
the chronic toxicity and carcinogenicity testing of fibers. Therefore, 
the final guideline maintains that ``Equal numbers of animals of each 
sex should be used at each dose level.''
    Comment 8. There are a few comments on the characterization of the 
exposure aerosol. For instance, one commenter suggested that: ``The 
system used to generate fibrous aerosols must not cause significant 
breakage and contamination of the test substance.'' Another commenter 
suggested to change the sizes of fibers required to be enriched in the 
exposure aerosol fibers to maximize the sensitivity of animal 
inhalation exposure studies: ``An exposure aerosol should be enriched 
with the following fiber size fractions: rat respirable fibers with an 
aspect ratio of at least 3:1 and an aerodynamic diameter less than 2.4 
m, and include an appropriate number of fibers with lengths of 
at least 15 m.''
    Response. The final test guideline has adopted the suggestion from 
the commenter that ``The system used to generate fibrous aerosols must 
not cause significant breakage and contamination of the test 
substance.'' Further, it specifies that: ``During the development of 
the generating system, fiber/particle size analysis should be performed 
to establish the stability of aerosol concentrations with respect to 
fiber size.'' With regard to the fibers to be enriched in the exposure 
aerosol to maximize the sensitivity of animal inhalation exposure 
studies, the guideline first specifies that the aerosol should be 
characterized in terms of fiber and non-fiber/particle size and number; 
the number of fiber should be expressed by fiber length, e.g., WHO 
fibers (greater than 5 m in length), fibers greater than 10, 
15 and 20 m in length. It is realized that different fiber 
types may have different size characteristics and it may not always be 
feasible to generate long, thin fibers (e.g., longer that 20 
m, thinner than 1 m) as was specified in the draft 
guideline. Therefore, the final test guideline no longer specifies the 
fiber size requirement and simply states that: ``The test material 
should consist of rat-respirable fibers which should be enriched with 
the most potent fraction of long, thin fibers or fibers with high 
aspect ratios. ..... If enriching the test aerosol with long, thin 
fibers is not feasible, the reasons should be clearly stated and 
justified, and the enrichment should be for the longest fibers or 
fibers with the highest aspect ratios available.''
    Comment 9. This comment relates to the selection of the highest 
fiber concentration level, known as the Maximal Aerosol Concentration 
or MAC, to be tested in a chronic inhalation exposure study. A 
commenter expressed concern that while the use of an insufficient 
number of long fibers would produce false negative results, using too 
large a mass exposure would cause pulmonary overload and produce false 
positive results. Therefore, it would be more useful operationally if 
the word ``appropriate'' is defined in the guideline: ``An appropriate 
lung burden

[[Page 39770]]

of critical fibers (long and thin) should be achieved'' (for setting 
the MAC). Another commenter felt that the definition of MAC should be 
expanded to include the following statement: ``The MAC is the highest 
concentration of test substance that will not cause a significant 
impairment (retardation) of particle clearance based on assessment of 
clearance in a 90-day subchronic inhalation study.''
    Response. The final guideline has specified that the MAC, the 
highest fiber concentration to be tested in a chronic study, should be 
set at a level at which some degree of impaired clearance and toxicity 
(as determined by parameters observed during lung burden analysis and 
bronchoalveolar lavage fluid (BALF) analysis in a 90-day subchronic 
inhalation study) are observed. The SAP concluded that there is no 
universal level of long fibers that would serve as an appropriate lung 
burden for all types of fibers. Important differences in the 
biopersistence and other key physicochemical properties account for the 
difficulty in setting a single appropriate burden. Present information 
is insufficient to set levels for what constitutes ``significant 
impairment'' of particle clearance. Both the Workshop Panel and the SAP 
concluded that a weight-of-evidence approach, based on all data of the 
90-day subchronic inhalation studies, should be used for establishing 
whether a given exposure meets or exceeds the MAC.
    Comment 10. On fiber concentration level selection, a commenter 
suggested that ``The lower exposures should be defined as some 
fractions of the highest exposure.'' Another commenter expressed that: 
``A single exposure level would suffice if it is anticipated that the 
MAC will not show carcinogenic activity.''
    Response. The guideline does not attempt to provide specific 
fractions/numbers to define the lower exposure levels. The lower levels 
should be appropriately spaced to produce a gradation of toxic effects. 
A rationale for the concentrations selected must be provided. The 
objective of a combined chronic toxicity/carcinogenicity study is to 
determine the effects of a fibrous substance identified to be of 
potential health concern. If a fibrous material is not anticipated to 
have any health hazard concern, a chronic inhalation study need not be 
performed. When a fibrous substance is to be tested, for dose-response 
analysis, at least three concentrations levels should be used.
    Comment 11. A commenter expressed that ``recovery'' animals for 
satellite dose groups in lung burden analysis and BALF analysis can 
provide important information on the interpretation of the test results 
and suggested to remove a minimal of 5 animals from each dose group at 
3, 6, 12, and 18 months of exposure and then hold until 24 months at 
which they will be evaluated for the kinetics of fiber buildup/removal 
from the lungs and progression/regression of lesions.
    Response. The final guideline has adopted the suggestions of this 
comment which is endorsed by the SAP.
    Comment 12. A couple of commenters expressed that BALF analysis 
data are useful in the 90-day studies and are not of any value in the 
lifetime studies.
    Response. Most members of the SAP felt that BALF analysis at 
interim time points (3, 6, 12, 18 and 24 months) are very useful for an 
overall evaluation of the fiber toxicity and proper interpretation of 
the study results. However, it was also felt that a decision to include 
all time points should be left to the individual study design, and some 
of the interim time points (e.g., 3, 6 and 18 months) could be omitted. 
On the basis of this, the final guideline requires BALF analysis be 
conducted only at the 12 and 24 month sacrifices and makes other time 
points optional.
    Comment 13. On clinical pathology (hematology and serum chemistry) 
and ophthalmology evaluation, there were comments that these 
determinations provide little toxicological value in the assessment of 
fiber hazard/risk and should be omitted.
    Response. The final guideline has adopted the suggestions of these 
comments which are endorsed by the SAP. However, evaluation of these 
parameters is required when clinical changes are seen in subchronic 
studies.
    Comment 14. On histopathology, a commenter suggested that: ``The 
histology slides from the scheduled sacrifices should also be stained 
with Masson-Goldner's trichrome stain that identifies collagen 
(fibrosis),'' and that: ``The scheduled sacrifices should be recorded 
according to the Wagner scoring method.''
    Response. In response to this comment, the following statement has 
been added into the final test guideline: ``The histology slides from 
the scheduled sacrifices should, in addition to standard hematoxylin 
and eosin, be stained with a method that identifies collagen 
(fibrosis).'' The SAP commented that there are many stains for collagen 
and no single stain should be specified. The Wagner scoring system has 
proved useful for providing a consistent and systemic reference for 
parenchymal disease. It also can be of value when attempting to compare 
the pathogenic effects of one fiber to another. However, use of the 
Wagner scoring system to evaluate progression of fibrosis has the 
disadvantage of being purely qualitative. The SAP suggested to take a 
consistent approach to record and grade the findings of airway disease 
and to use ``image analysis'' to assess severity of lesions. The 
recommendations of the SAP were incorporated into the final guideline.

V. How Was this Test Guideline Developed?

    On May 8-10, 1995, a Workshop on chronic inhalation toxicity and 
carcinogenicity testing of respirable fibrous particles was held in 
Chapel Hill, North Carolina. The Workshop was sponsored by the Office 
of Pollution Prevention and Toxics, Environmental Protection Agency, in 
collaboration with the National Institute of Environmental Health 
Sciences (NIEHS), the National Institute for Occupational Safety and 
Health (NIOSH), and the Occupational Safety and Health Administration 
(OSHA). The goal of the Workshop was to obtain input from the 
scientific community on a number of issues related to fiber testing. 
The Workshop Panel, which was composed of 19 international expert 
scientists in inhalation toxicology, reviewed, evaluated, and commented 
on the scientific issues of the Workshop. After extensive discussion 
and debate of the Workshop issues, the Workshop Panel provided a number 
of recommendations specific for the design and conduct of chronic 
inhalation studies of fibers (Refs. 2 and 4).
    Using the current EPA/OPPTS health effects test guideline for 
combined chronic toxicity and carcinogenicity (Ref. 1) as a template 
and based on the comments and recommendations made by the Workshop 
Panel on a number of scientific issues specific for fiber testing, EPA/
OPPT developed a proposed guideline for combined chronic toxicity and 
carcinogenicity testing of fibrous particles. In July 1999, the 
proposed guideline was announced in the Federal Register for public 
comments (64 FR 40871, July 28, 1999). A number of comments on various 
issues related to the test substance and study design were received. 
All public comments were evaluated and a revised draft guideline with 
some of the public comments incorporated was prepared.
    On September 26, 2000, the EPA FIFRA SAP held a meeting to review 
the EPA draft guideline, advise on a number of issues raised by the 
public commenters on the study protocol, and provide EPA with an 
opinion about the scientific validity of the test guideline. The final 
test guideline for OPPTS

[[Page 39771]]

870.8355 Combined Chronic Toxicity/ Carcinogenicity Testing of 
Respirable Fibrous Particles has incorporated many of the comments and 
recommendations made by the SAP (Ref. 3).

VI. Are there Any Applicable Voluntary Consensus Standards that EPA 
Should Consider?

    This notice of availability does not involve a proposed regulatory 
action that would require the Agency to consider voluntary consensus 
standards pursuant to section 12(d) of the National Technology Transfer 
and Advancement Act of 1995 (NTTAA), Public Law 104-113, section 12(d) 
(15 U.S.C. 272 note). Section 12(d) directs EPA to use voluntary 
consensus standards in its regulatory activities unless to do so would 
be inconsistent with applicable law or otherwise impractical. Voluntary 
consensus standards are technical standards (e.g., materials 
specifications, test methods, sampling procedures, and business 
practices) that are developed or adopted by voluntary consensus 
standards bodies. The NTTAA requires EPA to provide an explanation to 
Congress, through Office of Management and Budget (OMB), when the 
Agency decides not to use available and applicable voluntary consensus 
standards when the NTTAA directs the Agency to do so.
    In the notice of availability for the proposed test guideline 
published in the Federal Register of July 28, 1999 (64 FR 40871), EPA 
specifically sought comment on the availability of any applicable 
voluntary consensus standards that should be considered during the 
development of the final test guideline or any future regulatory action 
that EPA may take under TSCA. No response to this request was received.

VII. References

    The following references are cited in this document by the number 
indicated:
    1. United States Environmental Protection Agency. Health Effects 
Test Guidelines: Combined Chronic Toxicity/Oncogenicity. 40 CFR 
798.3320. pp. 165-172.
    2. United States Environmental Protection Agency. Office of 
Pollution Prevention and Toxics. Workshop on Chronic Inhalation 
Toxicity and Carcinogenicity Testing of Respirable Fibrous Partcles. 
EPA-748-R-96-001, January 1996.
    3. United States Environmental Protection Agency. FIFRA Scientific 
Advisory Panel Meeting on Test Guidelines for Chronic Inhalation 
Toxicity and Carcinogenicity of Fibrous Partcles, September 26, 2000. 
SAP Report No. 2000-0X, 01/05/2001.
    4. Vu, V., Barrett, J.C., Roycroft, J., Schuman, L., Dankovic, D., 
Baron, P., Martonen, T., Pepelko, W. and Lai, D. Workshop Report: 
Chronic Inhalation Toxicity and Carcinogenicity Testing of Respirable 
Fibrous Particles. Regulatory Toxicology and Pharmacology 24:202-212 
(1996).

List of Subjects

    Environmental protection, Chemical testing, Test guideline.


    Dated: July 17, 2001.
Stephen L. Johnson,
Assistant Administrator for Prevention, Pesticides and Toxic 
Substances.

[FR Doc. 01-18890 Filed 7-31-01; 8:45 am]
BILLING CODE 6560-50-S