[Federal Register Volume 61, Number 124 (Wednesday, June 26, 1996)]
[Proposed Rules]
[Pages 33178-33200]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 96-16203]




[[Page 33177]]


_______________________________________________________________________

Part II





Environmental Protection Agency





_______________________________________________________________________



40 CFR Part 799



Proposed Test Rule for Hazardous Air Pollutants; Proposed Rule

Federal Register / Vol. 61, No. 124 / Wednesday, June 26, 1996 / 
Proposed Rules

[[Page 33178]]



ENVIRONMENTAL PROTECTION AGENCY

40 CFR Part 799

[OPPTS-42187; FRL-4869-1]
RIN 2070-AC76


Proposed Test Rule for Hazardous Air Pollutants

AGENCY: Environmental Protection Agency (EPA).

ACTION: Proposed rule.

-----------------------------------------------------------------------

SUMMARY: EPA is proposing a test rule under section 4(a) of the Toxic 
Substances Control Act (TSCA) to require manufacturers and processors 
of 21 hazardous air pollutants (HAPs) (biphenyl, carbonyl sulfide, 
chlorine, chlorobenzene, chloroprene, cresols [3 isomers], 
diethanolamine, ethylbenzene, ethylene dichloride, ethylene glycol, 
hydrochloric acid, hydrogen fluoride, maleic anhydride, methyl isobutyl 
ketone, methyl methacrylate, naphthalene, phenol, phthalic anhydride, 
1,2,4-trichlorobenzene, 1,1,2-trichloroethane, and vinylidene chloride) 
to test these substances for certain health effects. EPA is also 
soliciting proposals for enforceable consent agreements (ECAs) 
regarding the performance of pharmacokinetics studies which would 
permit extrapolation from oral data to predict risk from inhalation 
exposure. EPA is also withdrawing the oncogenicity testing proposed for 
vinylidene chloride on August 12, 1986 (51 FR 28840).
DATES: Written comments on this proposed HAPs test rule must be 
received by EPA on or before December 23, 1996. Proposals for 
pharmacokinetics studies must be received by EPA on or before October 
24, 1996. EPA will hold a public meeting in Washington, DC prior to the 
close of the comment period. If any person requests an additional 
public meeting by November 25, 1996, EPA will hold a second public 
meeting in Washington, DC.

ADDRESSES: Submit three copies of written comments on this proposed 
HAPs test rule, identified by document control number (OPPTS-42187A; 
FRL-4869-1) and three copies of proposals for pharmacokinetics studies, 
identified by document control number (OPPTS-42187B; FRL-4869-1) to: 
U.S. Environmental Protection Agency, Office of Pollution Prevention 
and Toxics (OPPT), Document Control Office (7407), Rm. G-099, 401 M 
St., SW., Washington, DC, 20460.
    A public version of the rulemaking record supporting this action, 
excluding confidential business information (CBI), is available for 
inspection at the TSCA Nonconfidential Information Center, Rm. NE-B607, 
401 M St., SW., Washington, DC 20460, from 12 noon to 4 p.m., Monday 
through Friday, except on legal holidays.
    All comments which contain information claimed as CBI must be 
clearly marked as such. Three additional sanitized copies of any 
comments containing information claimed as CBI must also be submitted. 
Nonconfidential versions of comments on this proposed rule will be 
placed in the rulemaking record and will be available for public 
inspection at the TSCA Nonconfidential Information Center. Unit IX of 
this preamble contains additional information on submitting comments 
containing information claimed as CBI.
    Comments and data may also be submitted in electronic form by 
sending electronic mail (e-mail) to: <a href="/cdn-cgi/l/email-protection#305e535953705540515d51595c1e5540511e575f46"><span class="__cf_email__" data-cfemail="bcd2dfd5dffcd9ccddd1ddd5d092d9ccdd92dbd3ca">[email protected]</span></a>. Such 
comments and data must be submitted in an ASCII file avoiding the use 
of special characters and any form of encryption. Comments and data 
will also be accepted on disks in WordPerfect in 5.1 file format or 
ASCII file format. All comments and data in electronic form must be 
identified by (OPPTS-42187A) (FRL-4869-1). No information claimed as 
CBI should be submitted through e-mail. Comments in electronic form may 
be filed online at many federal depository libraries. Additional 
information on electronic submissions can be found under Unit X of this 
preamble.

FOR FURTHER INFORMATION CONTACT: Susan B. Hazen, Director, 
Environmental Assistance Division (7408), Office of Pollution 
Prevention and Toxics, U.S. Environmental Protection Agency, Room E-
543B, 401 M St., SW., Washington, DC 20460; telephone: (202) 554-1404; 
TDD: (202) 554-0551; e-mail: TSCA-H<a href="/cdn-cgi/l/email-protection#a5cad1c9cccbc0e5c0d5c4c8c4ccc98bc0d5c48bc2cad3"><span class="__cf_email__" data-cfemail="90ffe4fcf9fef5d0f5e0f1fdf1f9fcbef5e0f1bef7ffe6">[email protected]</span></a>. For specific 
information regarding this action or related activities, contact Gary 
E. Timm, Chemical Control Division, OPPT; telephone: (202) 260-1859; e-
mail: <a href="/cdn-cgi/l/email-protection#93e7fafefebdf4f2e1ead3f6e3f2fef2faffbdf6e3f2bdf4fce5"><span class="__cf_email__" data-cfemail="07736e6a6a296066757e476277666a666e6b2962776629606871">[email protected]</span></a>.

SUPPLEMENTARY INFORMATION:
    Regulated persons. Potentially regulated persons are manufacturers 
(including importers) and processors of the chemical substances 
included in this proposed test rule. Processors, small-quantity 
manufacturers, and manufacturers of small quantities of these 
substances solely for research and development purposes, while legally 
subject to the rule, would be required to comply with the rule only if 
directed to do so in a subsequent notice.

                                                                        
------------------------------------------------------------------------
                                                Examples of regulated   
                 Category                              persons          
------------------------------------------------------------------------
Manufacturers                               Persons who manufacture or  
                                             import 500 kg (1,100 lbs)  
                                             or more of a subject       
                                             chemical per year.         
                                            Persons who produce a       
                                             subject chemical as a      
                                             byproduct.                 
                                                                        
Processors                                  Persons who process one or  
                                             more subject chemicals.    
                                                                        
Small-quantity manufacturers                Persons who manufacture or  
                                             import less than 500       
                                             kg(1,100 lbs) per year of a
                                             subject chemical.          
                                                                        
Manufacturers of small quantities of these  Persons who manufacture     
 substances solely for research and          quantities of these        
 development purposes                        substances no greater than 
                                             those necessary for        
                                             purposes of scientific     
                                             experimentation or analysis
                                             for research and           
                                             development purposes.      
------------------------------------------------------------------------

    This table is not intended to be exhaustive, but, rather, provides 
a guide for readers regarding entities likely to be regulated by this 
action. This table lists the types of persons of which EPA is now aware 
that potentially could be regulated by this action. To determine 
whether you would be subject to this rule, you should examine Unit 
IV.F. of the preamble entitled ``Persons Required to Test'' and consult 
40 CFR 790.42.

I. Statutory Authority

    This notice proposes a test rule under section 4 of the Toxic 
Substances Control Act (TSCA), 15 U.S.C. 2603 et seq., that would 
require certain health effects testing for 21 chemical substances 
listed as hazardous air pollutants (HAPs) in section 112 of the Clean 
Air Act (CAA), 42 U.S.C. 7412.
    Section 2(b)(1) of TSCA, 15 U.S.C. 2601(b)(1), states that it is 
the policy of the United States that ``adequate data should be 
developed with respect to the effect of chemical substances and 
mixtures on health and the environment and that the development of such 
data should be the responsibility of those who manufacture and those 
who process such chemical substances and mixtures[.]'' To implement 
this policy, section 4(a) of TSCA authorizes EPA to require by rule 
that manufacturers and processors of chemical substances conduct 
testing if the Administrator finds that:


[[Page 33179]]


    (1)(A)(i) the manufacture, distribution in commerce, processing, 
use, or disposal of a chemical substance or mixture, or that any 
combination of such activities, may present an unreasonable risk of 
injury to health or the environment, [or]
    (1)(B)(i) a chemical substance or mixture is or will be produced 
in substantial quantities, and (I) it enters or may reasonably be 
anticipated to enter the environment in substantial quantities or 
(II) there is or may be significant or substantial human exposure to 
such substance or mixture, [and]
    (1)(A)(ii) and (1)(B)(ii) there are insufficient data and 
experience upon which the effects of the manufacture, distribution 
in commerce, processing, use, or disposal of such substance or 
mixture or of any combination of such activities on health or the 
environment can reasonably be determined or predicted, and
    (1)(A)(iii) and (1)(B)(iii) testing of such substance or mixture 
with respect to such effects is necessary to develop such data[.]

    Thus once the Administrator has made a finding under TSCA section 
4(a)(1)(A)(i) that a chemical substance may present an unreasonable 
risk of injury to health or the environment or a finding under section 
4(a)(1)(B)(i) that a chemical substance is or will be produced in 
substantial quantities and either it may enter the environment in 
substantial quantities or there may be significant substantial human 
exposure to the chemical substance, EPA may require any type of health 
effects or environmental testing necessary to address unanswered 
questions about the effects of the chemical substance. EPA need not 
limit the scope of testing required to the factual basis for the 
section 4(a)(1)(A)(i) or (B)(i) findings as long as EPA finds that data 
relevant to a determination of whether a substance does or does not 
present an unreasonable risk of injury to health or the environment are 
insufficient and that testing is necessary to develop such data. This 
concept is explained in more detail in EPA's statement of policy for 
making findings under TSCA section 4(a)(1)(B) (frequently described as 
the ``B policy'') in the Federal Register of May 14, 1993 (58 FR 
28736). Unit V of this preamble also describes the B policy. Moreover, 
EPA need not limit the scope of the requirement only to testing needed 
to support regulatory action under TSCA. For further discussion of 
findings under TSCA section 4, see Unit V of this preamble and the 
document entitled ``TSCA Section 4 Findings for 21 Hazardous Air 
Pollutants'' in the record for this rulemaking.
    In this proposed rule, EPA intends to use its TSCA section 4 
authority to obtain data necessary to implement section 112 of the CAA, 
which provides a detailed strategy for the assessment and management of 
HAPs. EPA has used this broad TSCA section 4 authority in the past to 
support regulatory programs requiring health and environmental effects 
testing data. See, e.g., final test rule for the Office of Solid Waste 
chemicals (53 FR 22300, June 15, 1988); final test rule for the Office 
of Water Chemicals (58 FR 59667, November 10, 1993). Additional users 
of information collected under this test rule would include other 
federal agencies (e.g. the Agency for Toxic Substances and Disease 
Registry (ATSDR), the National Institute for Occupational Safety and 
Health (NIOSH), the Occupational Safety and Health Administration 
(OSHA), the Consumer Product Safety Commission (CPSC), other program 
areas within EPA (such as the hazardous waste program under the 
Resource Conservation and Recovery Act (RCRA), the Toxics Release 
Inventory (TRI), the Integrated Risk Information System database 
(IRIS), and the Office of Pesticide Programs (OPP)), and state and 
local environmental authorities.
    Supporting statutory authority for this proposed rule is provided 
by section 112(b)(4) of the CAA, 42 U.S.C. 7412(b)(4), which 
specifically authorizes EPA to use any authority available to EPA to 
obtain the information needed to make determinations regarding the 
addition or deletion of substances to the statutory list of HAPs in CAA 
section 112(b)(1), 42 U.S.C. 7412(b)(1). If the data collected under 
this proposed test rule show that a chemical substance is not a concern 
to human health, this information would be helpful in making decisions 
concerning delisting the substance from the Clean Air Act HAPs list.
    This toxicity testing program is also intended to fulfill in part 
EPA's statutory obligation under section 103(d) of the CAA, 42 U.S.C. 
7403(d), to conduct a research program on the health effects of HAPs. 
This preamble, along with the supporting material in the record, 
provides information that would be used in the research program under 
CAA section 103(d) for the HAPs proposed for testing in this rule.

II. Uses for Data

    EPA will primarily use the data proposed to be collected under this 
rule to implement several provisions of section 112 of the CAA, 
including the determination of residual risk (see below), the 
estimation of the risks associated with accidental releases of 
chemicals, and determinations whether or not substances should be 
removed from the CAA section 112(b)(1) list of hazardous air pollutants 
(delisting). The acute toxicity test data and developmental toxicity 
test data will be useful in judging risks from accidental release. The 
term ``accidential release'' is used broadly in this proposal to 
include any short-term, relatively high-level chemical exposure lasting 
from several minutes to several hours. Such a release may result from 
various causes, including spills, transportation accidents, process-
upset conditions, or short bursts during charging of reaction vessels. 
All data are relevant to delisting decisions and all non-acute data 
will be used by EPA in meeting its statutory obligation under CAA 
section 112(f), 42 U.S.C. 7412(f), to assess the risk remaining (i.e. 
residual risk) after the imposition of technology-based emission 
standards (maximum achievable control technology or MACT standards) 
required by CAA section 112(d), 42 U.S.C. 7412(d). Section 112(e) of 
the CAA, 42 U.S.C. 7412(e), directs EPA to promulgate these standards 
between 1992 and 2000.
    Section 112(f)(1) of the CAA requires EPA to submit, by November 
1996, a report to Congress that will describe the methods for assessing 
the risk remaining after the application of technology-based standards 
under section 112(d) of the CAA. These methods will be used to assess 
any residual risk for persons exposed to MACT-regulated emissions. The 
assessment will include an analysis of both cancer and noncancer 
endpoints. Data generated by the proposed test rule would be used in 
the analysis to determine the nature and magnitude of any residual 
risk.
    Within eight years after the promulgation of technology-based 
standards, EPA may need to set additional standards (``post-MACT 
standards'') to protect public health with an ample margin of safety. 
Section 112(f)(2) of the CAA specifies that if MACT standards have not 
reduced lifetime cancer risk to the individual most exposed to known or 
suspected carcinogenic emissions from a source to a level of less than 
1 in a million (1 x 10<SUP>-6), health-based emission standards must be 
promulgated in order to protect public health with an ample margin of 
safety. EPA, therefore, would use data obtained under this proposed 
rule to determine whether health-based post-MACT standards are needed 
and, if they are needed, to assist in establishing the appropriate 
level of these standards.
    For noncancer health effects, EPA applies an appropriate 
mathematical model to toxicity data in order to determine the benchmark 
dose level. The benchmark dose or concentration (BMD/C) is defined as 
the statistical

[[Page 33180]]

lower confidence limit on the dose estimated to produce a predetermined 
level of change in response (the benchmark response--BMR) relative to 
controls. If the data are not amenable to modeling, a no-observed-
adverse-effect level (NOAEL) or a lowest-observed-adverse-effect level 
(LOAEL) may be obtained from an evaluation of the toxicity database. 
``Uncertainty factors'' are then applied to these levels to account for 
uncertainties in deriving a dose-response estimate for human exposure 
(reference concentration (RfC)) from experimental data. An RfC is 
defined as ``an estimate (with uncertainty perhaps spanning an order of 
magnitude) of a continuous inhalation exposure to the human population 
(including sensitive subgroups) that is likely to be without 
appreciable risk of deleterious noncancer health effects during the 
lifetime'' (Ref. 1).
    Uncertainties due to the extrapolation of effects data between 
species and for individual susceptibility within a species are 
accounted for by uncertainty factors. Because RfCs are intended to 
characterize risk for lifetime exposures, an uncertainty factor may be 
applied if the effects data are extrapolated from a subchronic study. 
An additional uncertainty factor is applied if a LOAEL is used to 
derive the RfC rather than a NOAEL. To provide an accurate 
characterization of lifetime risk, the database for a chemical should 
be comprehensive and, in principle, should address all potential 
endpoints at critical life stages. Therefore, an uncertainty factor 
also may be applied if data for appropriate endpoints are not 
available. Thus while each uncertainty factor may range up to 10, the 
composite factor used to derive an RfC for a chemical with a limited 
database may be on the order of up to 3,000 for inhalation studies and 
up to 10,000 for oral studies. Five uncertainty factors are never 
applied at the same time (i.e. no composite uncertainty factor can be 
greater than 10,000) because such derivations are considered too 
inaccurate to be used.
    Large composite uncertainty factors result in lower RfCs (higher 
risk estimates) than do smaller composite uncertainty factors. If the 
RfC is low, EPA may be required to promulgate more stringent emission 
standards. Industrial plants subject to these standards would, in turn, 
be required to meet such standards, perhaps necessitating the 
installation of more costly emission controls. Better and more complete 
health effects data, on the other hand, may permit EPA to use smaller 
composite uncertainty factors, resulting in higher RfCs and, as a 
consequence, less stringent emission standards. Thus the economic cost 
of using poor-quality health effects data to make residual risk 
determinations under CAA section 112(f) could be considerable.
    In addition, secondary--though as important--uses of the data to be 
collected under this proposed rule would be:
    (1) Helping to better inform communities and citizens of toxic 
chemical hazards in their own localities. Understanding health effects 
associated with these chemicals is integral to furthering the public's 
involvement in environmental decisionmaking, especially at the state 
and local level. To be an effective participant in this process, the 
public needs information on both the inherent toxicity (i.e., hazard) 
of a chemical and the potential sources of exposure to the chemical. 
This rule will provide valuable information on health effects related 
to the affected chemicals, and under TSCA, such health and safety data 
are available to the public. Taken together with such publicly 
available information sources such as the Toxics Release Inventory 
(TRI), which provides site-specific information on chemical releases 
into the environment, the health effects data generated under this rule 
will allow all segments of the public to better assess the risks 
associated with the releases of these chemicals. Taken as part of a 
comprehensive right-to-know program, these data will provide the basis 
for individuals, communities, governments, producers, and users to 
assess the nature and relative severity of toxicity among different 
chemicals, as well as to assess site-specific, individual chemical 
risk.
    (2) Assisting other agencies (e.g., ATSDR, NIOSH, OSHA, CPSC) in 
assessing chemical risks and in taking appropriate action within their 
programs. For example, OSHA has expressed a need for the data that will 
be acquired under the proposed rule. Fifteen of the 21 HAPS are 
candidates for OSHA's Permissible Exposure Limit (PEL) update and an 
additional 3 have no corresponding PEL. OSHA does not have authority to 
require testing, and must rely on toxicology data collected by other 
agencies for their risk assessments (Ref. 2). Establishing an ongoing 
mechanism for updating its PELs continues to be a high priority for 
OSHA. Five of the HAPs are on ATSDR's list of hazardous substances 
found at National Priorities List sites and are the subject of 
toxicological profiles. CPSC noted that 11 of the 21 substances are 
found in or are emitted by consumer products (Ref. 3).
    (3) Assisting EPA in evaluating delisting petitions received under 
the CAA and the Emergency Planning and Community Right-to-Know Act 
(EPCRA), 42 U.S.C. 1101 et seq., in making better clean-up decisions 
under the Comprehensive Environmental Response, Compensation, and 
Liability Act (CERCLA), 42 U.S.C. 9601 et seq., in assessing inert 
ingredients in pesticide products, in setting more appropriate 
standards for hazardous wastes under RCRA, and by providing support for 
chemical risk assessment activities under TSCA.
    (4) Assisting state and local permitting authorities in setting 
standards within their programs.
    (5) Supporting assessments of ``burst'' exposures (high-level 
releases of short duration), such as in the accidental release 
prevention program under section 112(r) of the CAA, 42 U.S.C. 7412(r), 
due to the inclusion of an acute testing protocol.
    Many HAPs are of broad programmatic interest, and are included in 
the Agency's Integrated Risk Assessment System (IRIS) database. Thus, a 
secondary benefit of this rule is that the health effects data 
generated by the rule may result in improvement to the data and 
increased confidence in the RfCs contained in IRIS. Improvements to the 
IRIS data can result in considerable benefits to the public since IRIS 
is publicly available and is used by a wide variety of governmental and 
non-governmental entities to assess the safety of chemicals.
    In some cases where EPA has had access to better data, the Agency 
has been able to revise standards to make them less stringent, thus 
mandating less economically costly levels of control. For example, EPA 
has revised the maximum contaminant levels (MCL) of barium (from 1 mg/L 
to 2 mg/L) and selenium (from 0.01 mg/L to 0.05 mg/L) in drinking water 
and withdrew the MCL for silver (0.05 mg/L) based on new data (Ref. 4).
    Data have also been used to remove chemical substances from lists 
of regulatory significance. Acrylic acid was removed from a list of 
``high-risk'' pollutants developed under section 112(i)(5) of the CAA, 
42 U.S.C. 7412(i)(5), for the early reductions program. The high-risk 
listing for this chemical was based on its predicted environmental 
exposure being at least 10 times larger than its RfC. Designation of 
acrylic acid as ``high risk'' had the effect of limiting the use of 
offsetting reduction of other pollutants in meeting early reduction 
goals. Recent data,

[[Page 33181]]

including those related to reproductive effects, developmental 
toxicity, and bioavailability, resulted in a decrease in the 
uncertainty factor for database deficiency by a factor of three and an 
increase in the RfC by the same amount (i.e. from 0.0003 mg/m<SUP>3 to 
0.001 mg/m<SUP>3). Consequently, acrylic acid no longer met the 
criteria for the high-risk list.
    Serious deficiencies exist in the current toxicity database for the 
189 HAPs listed in the CAA, in that no toxicity data exist for many 
HAPs regarding various endpoints of concern. This problem is expected 
to be especially serious because post-MACT residual risks will arise 
primarily from exposures to emissions that contain different 
combinations of HAPs in varying concentrations. In view of the large 
number of HAPs of concern and the much larger number of combinations of 
those HAPs found in the mixtures of emissions subject to residual risk 
evaluation, the toxicity database should provide consistent 
characterization of individual HAPs. Therefore, EPA is proposing to 
obtain an even, across-the-board database for the HAPs listed in this 
proposed rule.
    In its report regarding the risk assessment of HAPs, the National 
Academy of Sciences (NAS) states that ``[a]vailability of requisite 
data varies widely among the 189 [HAPs] chemicals'' (Ref. 5). According 
to this report, ``the toxicity data are incomplete on almost all 189 
chemicals'' (Ref. 5). For example, the level of carcinogenic risk for 
approximately 40% of the 189 HAPs cannot be classified under EPA's 
current cancer risk classification system (Ref. 6). Moreover, while 
quantitative estimates exist for 70% of the HAPs that have been 
classified for cancer risk, about 70% of these estimates are based only 
on oral data and thus may not reliably characterize the potential risk 
encountered through inhalation exposure.
    In evaluating 124 of the 189 HAPs for noncancer risk, EPA found 
that the databases for about 62% of the 124 HAPs were not adequate for 
deriving an RfC (Ref. 7). Even for those HAPs that have an RfC, the 
level of uncertainty associated with such figures is often high. EPA 
would use data from the testing proposed in this rule to identify the 
critical health risks posed by many individual HAPs and to characterize 
the adverse impact posed by exposure to mixtures of HAPs. EPA 
anticipates that the test data produced in response to this rule would 
provide the consistent database that the National Academy says is 
lacking at this time.

III. Testing Approach and Selection of Chemical Substances for This 
Proposed Rule

A. Testing Approach Chosen by EPA

    With respect to EPA's responsibilities for meeting the requirements 
under section 112 of the CAA, the central question is: How broad and 
deep a data set should EPA require on each HAP?
    Regarding specific endpoints and routes of exposure, CAA section 
112(b)(2), 42 U.S.C. 7412(b)(2), indicates that Congress intended that 
adverse effects from any endpoint by any route of exposure be taken 
into account in listing substances as HAPs. According to this 
subsection, substances added to the Clean Air Act HAPs list shall 
include:

    * * * pollutants which present, or may present, through 
inhalation or other routes of exposure, a threat of adverse human 
health effects (including, but not limited to, substances which are 
known to be, or may reasonably be anticipated to be, carcinogenic, 
mutagenic, teratogenic, neurotoxic, which cause reproductive 
dysfunction, or which are acutely or chronically toxic) * * * .

    Thus the CAA indicates that Congress was very concerned about the 
wide variety of health risks attributable to HAPs and intended that 
data necessary for characterizing both cancer and noncancer health 
risks from exposure to HAPs be developed.
    Faced with a broad range of options and little specific guidance 
from Congress, EPA decided that some provision should be made for 
evaluating the health effects endpoints listed in the CAA, including 
respiratory tract toxicity, systemic effects, reproductive toxicity, 
developmental toxicity, genotoxicity, neurotoxicity, and 
carcinogenicity. EPA's objective was to select endpoints representing 
serious health effects that could occur as a result of exposure to 
HAPs. Each endpoint represents a health effect of concern arising from 
one or more of the following exposures--local concentrations (e.g., 
hotspots and plumes), area-wide sources, or accidental releases of 
HAPs.
    EPA believes that it is critical to evaluate the respiratory tract 
thoroughly in addition to examining extra-respiratory effects (i.e., 
systemic toxicity) because inhalation is an important exposure route of 
concern. Carcinogenicity testing is significant because cancer is a 
serious health effect that may be caused by long-term, low-level 
exposure to toxic substances. Developmental toxicity addresses the 
potential of chemical substances to interfere adversely with human 
development (i.e., to cause death, structural abnormalities, growth 
alterations, and/or functional deficits in the immature organism that 
may be more sensitive than the adult to many chemical substances). 
Reproductive testing is designed to assess the effects of an 
environmental agent on male and female fertility and general 
reproductive function to humans exposed prenatally as well as 
postnatally. There is general consensus among toxicologists regarding 
the assessment of cancer and reproductive and developmental effects, 
and further explanation can be found in EPA's risk assessment 
guidelines (Guidelines for Carcinogen Risk Assessment (51 FR 33992, 
September 24, 1986); Guidelines for Developmental Toxicity Risk 
Assessment (56 FR 63798, December 5, 1991); Guidelines for Reproductive 
Toxicity Risk Assessment (Pub. No. EPA/600/AP-94/001, February 1994). 
Finally, certain aspects of the neurotoxicity and immunotoxicity 
testing required in this proposed rule warrant more explanation, which 
is provided below. EPA recently published a proposed revision of the 
1986 Guidelines for Carcinogen Risk Assessment (see ``Proposed 
Guidelines for Carcinogen Risk Assessment'' at 61 FR 17960, April 23, 
1996 (FRL-5460-3)).
    Neurotoxicity resulting from chemical exposure can affect an 
organism in many ways, causing, for example, functional and structural 
deficits as well as behavioral effects. To assess neurotoxicity, EPA is 
proposing a screening-level battery, consisting of the functional 
observational battery and motoractivity and neuropathology tests. At 
this time, EPA is not proposing to require additional, more specialized 
testing for cognitive functions such as learning, memory, and 
performance.
    The interest in the potential toxic effects of chemicals on the 
immune system arises from the critical role that the immune system 
plays in maintaining health. EPA considers the field of immunotoxicity 
a promising, scientifically sound, and important area in public health 
protection. From time to time, the Agency has considered information on 
the effects of chemicals on the immune system in risk assessments. For 
example, in its draft report reassessing the effects of dioxin 
compounds on human health (Ref. 8), EPA considered the effects of 
dioxin on the immune system to serve as an important health endpoint 
that provides useful information in developing a hypothesis about 
toxicity. In the draft reassessment report, however, EPA arrived at the 
preliminary conclusion that ``the impact of dioxin and related 
compounds on the immune system and

[[Page 33182]]

implications for characterizing risks are largely unknown at this 
time.''
    This rule calls for an immunotoxicity screening test which can be 
performed as a satellite test to either a 90-day subchronic test or a 
reproductive effects test. This immunotoxicity screen will help 
identify chemicals as potential immunotoxicants. EPA is not proposing 
more comprehensive immunotoxicity testing at present because the 
application of immunotoxicity data in risk assessment has not yet 
sufficiently matured. As EPA's science policy develops and the Agency's 
use of immunotoxicity data in risk assessment increases, EPA will 
reconsider this position. Meanwhile, EPA seeks comments on its proposed 
approach of using a minimal screen and its preliminary conclusion that 
it is premature at this time to include more comprehensive 
immunotoxicity testing in this proposed HAPs test rule.
    In developing this proposed rule, EPA considered the following 
range of options to select the information needed to characterize 
health effects of concern to implement section 112 of the CAA.
    Option 1. One-species 90-day inhalation subchronic plus follow-up 
for known or suspect toxicities. Under this option, a 90-day inhalation 
subchronic test would be required, as well as testing for endpoints 
that have already been identified as existing or potential concerns, 
including cancer, by previous test results of the HAP at issue or 
structurally similar agents. A one-species 90-day inhalation test is 
considered the minimum information for the development of an RfC. The 
inhalation RfC takes into account toxic effects both for the 
respiratory tract (portal-of-entry effects) and peripheral to the 
respiratory system (extra-respiratory effects). Well-defined and well-
conducted inhalation subchronic toxicity studies--that provide for 
histopathologic evaluation of organ toxicities, including the 
respiratory tract--are considered to be reliable predictors of certain 
kinds of chronic toxicity. But such studies do not, or do not 
adequately, account for neurological, developmental and reproductive 
toxicities. An RfC based solely on a 90-day subchronic test is, thus, 
usually given a low confidence rating because some potentially 
important toxic endpoints are not characterized.
    In addition, EPA believes that for 90-day inhalation subchronic 
testing to constitute a minimally credible option, such a test should 
at least be augmented by testing for adverse health effects that are 
suggested or indicated, but not adequately characterized, by existing 
information such as short-term test data, mechanistic information or 
structure-activity relationships (SAR). Even with this modification, 
however, Option 1 still provides no test data on those health endpoints 
of concern for which no current information exists. If such testing 
were included, these effects might become critical in evaluating dose-
response relationships or in demonstrating that a standard uncertainty 
factor is inadequate or inappropriate.
    EPA thus believes that Option 1 is insufficient to meet EPA's 
mandate under section 112 of the CAA because the endpoints listed in 
section 112(b)(2) of the CAA, in particular, reproductive, 
developmental, and neurological toxicities, would be considered for 
testing only if data already exist that indicate or suggest the 
potential for these adverse effects. Moreover, this option also does 
not adequately address health risks associated with acute or accidental 
releases.
    EPA did not select Option 1 for the reasons stated above. EPA 
believes that the TSCA section 4 program adopted for testing HAPs must 
go further toward ensuring that no serious health threat exists from 
both long- and short-term exposure for endpoints of potential concern 
for which there are no existing data.
    Option 2. Option 1 plus inhalation screening for untested toxicity 
endpoints. The second option considered by EPA would require the 
incorporation of screening level testing for certain untested 
toxicities into Option 1. Like Option 1, Option 2 would include testing 
for endpoints (including cancer) that have already been identified as 
existing or potential concerns. At a minimum Option 2 would consist 
of--a 90-day subchronic inhalation study, a screening test for 
reproductive effects (i.e., a one-generation reproductive effects 
study), a subchronic inhalation neurotoxicity screening battery 
(consisting of the functional observation battery and motor activity 
and neuropathology tests), an E. coli reverse mutation assay, gene 
mutation in somatic cells in culture detection, an in vivo cytogenetics 
test (chromosomal analysis or micronucleus assay), and an 
immunotoxicity screening test. Any toxicity suggested but not 
characterized by existing studies in the toxicological literature would 
still be followed up on through more rigorous protocols.
    Although Option 2 would conserve resources while allowing for the 
testing of a broader range of endpoints, including cancer, it has 
serious shortcomings. First, a one-generation reproductive test does 
not adequately address reproductive and developmental risk. Two-
generation tests (in which animals have been exposed prenatally as well 
as postnatally, including the prepubertal period) are generally needed 
to evaluate the effects on reproduction from most exposures to chemical 
substances (Ref. 9). Two-generation tests permit the evaluation of 
delayed or latent manifestations of some toxicities, detection of 
effects absent in the first generation, and the expression and 
detection of some effects that may have a heritable basis. Because the 
standard two-generation reproductive test would not detect internal 
malformations, however, developmental toxicity testing is also needed 
for an adequate assessment of developmental risk. The Agency's policy 
is to require developmental testing in two species to adequately 
characterize the risk because of species-specific differences.
    EPA did not select Option 2 because this level of testing would not 
provide an adequate evaluation of developmental or reproductive 
toxicity. Additional follow-up testing would be required to confirm 
suggestive results obtained in screening studies and provide data 
adequate for risk assessment under this option. Such testing would 
require an additional rulemaking cycle, costing further resources and 
incurring so much delay that data would not be available to meet the 
deadlines for setting risk-based standards. Moreover, this option does 
not adequately address health risks, such as respiratory tract effects 
and neurotoxicity, associated with acute or accidental releases.
    Option 3. Option 1 plus less than chronic testing for noncancer 
endpoints of concern. In addition to the 90-day inhalation subchronic 
testing specified in Option 1, this option would add inhalation testing 
to assess reproductive effects (i.e., two-generation reproductive test) 
and developmental effects (developmental toxicity tests in two 
mammalian species). Option 3 includes an acute toxicity testing 
guideline for histopathology of the respiratory tract, kidney, and 
liver and a bronchoalveolar lavage after four hours of exposure. EPA 
believes that it is necessary to characterize the acute effects 
associated with accidental releases of HAPs. In addition, a respiratory 
sensory irritation assay is included. Acute and subchronic inhalation 
neurotoxicity screening batteries consisting of the functional 
observation battery, and motor activity and neuropathology tests would 
also be conducted. As in Option 2, first-tier tests would be required 
for mutagenicity

[[Page 33183]]

(i.e., an E. coli reverse mutation assay, gene mutation in somatic 
cells in culture detection, an in vivo cytogenetics test (chromosomal 
analysis or micronucleus assay)), as well as immunotoxicity.
    Option 3 would follow Options 1 and 2 in requiring a cancer 
bioassay where concern for cancer is indicated by short-term data, 
general toxicity data, mechanistic information or structure-activity 
relationships (SAR). Where no cancer bioassay data exist, testing two 
species in both sexes would be required. If cancer bioassay data exist 
but are found to be too uncertain for inhalation dose-response 
assessment, a modified test, such as testing of the opposite sex in two 
species, may be required (Ref. 10).
    The Option 3 level of testing would enable EPA to better 
characterize risk associated with both acute and longer-term exposures 
by providing data to identify and evaluate all the health effects 
listed under section 112 of the CAA and by providing data for dose-
response evaluation within the general time frame for risk-based 
standards under CAA section 112(f). Accordingly, EPA has selected the 
Option 3 level as its preferred option for testing under this proposed 
rule.
    Option 4. Option 3 plus chronic testing. Under this option, in the 
absence of existing adequate data, EPA would require chronic inhalation 
bioassays (for both cancer and noncancer effects) in two different 
mammalian species for each chemical substance. The balance of the test 
program would be the same as under Option 3 (developmental studies in 
two mammalian species, a two-generation reproductive study, acute and 
subchronic neurotoxicity screening batteries, first-tier mutagenicity 
tests, an immunotoxicity screening test, and acute testing). In 
general, cancer bioassay data in two species, a two-generation 
reproductive test, and a developmental study in two species are 
required to establish a high-confidence RfC. Because the RfC is 
intended to serve as a lifetime estimate, lifetime exposure studies to 
evaluate potential health endpoints at various critical life stages 
should be considered.
    To a greater degree than under other options, the broad and deep 
database that would be produced by this comprehensive testing scheme 
could help defuse complaints that EPA frequently regulates industrial 
activities without sufficient data regarding either the need for an 
appropriate level of regulation or what such a level should be. EPA has 
decided, however, that the disadvantages of choosing this option 
outweigh its considerable benefits. The extensive chronic testing 
required under Option 4 would impose a significant cost on industry. In 
addition, as compared to Option 3, the strain that choosing this option 
would place on certain resources--such as inhalation testing facilities 
and supplies of laboratory animals--would significantly diminish the 
cost-effectiveness of compiling the data. For these reasons, EPA did 
not select this option. EPA is soliciting comments on the testing 
approach to the HAPs that it has selected in this proposal.
    It should be noted that, regardless of the test option chosen, if 
adequate toxicity data on a HAP is produced by testing using a route of 
exposure other than inhalation, route-to-route extrapolation may be 
possible (see Unit IV.D. of this preamble).

B. National Academy of Sciences Approach

    In section 112(o) of the CAA, 42 U.S.C. 7412(o), Congress directed 
EPA to arrange for the NAS to review EPA's risk assessment methodology 
relevant to HAPs subject to section 112. EPA has considered the 
recommendations of the NAS regarding the assessment of risks associated 
with HAPs. The NAS recommended that EPA ``* * * compile for each of the 
189 chemicals an inventory of the existing and relevant chemical, 
toxicologic, clinical, and epidemiologic literature'' (Ref. 5). It also 
recommended that EPA ``screen the 189 chemicals for priorities for the 
assessment of health risks, identify the data gaps, and develop 
incentives to expedite generation of the needed data by other public 
agencies (such as the National Toxicology Program, the Agency for Toxic 
Substances and Disease Registry, and state agencies) and by other 
organizations (industry, academia, etc.)'' (Ref. 5). As discussed in 
Unit III.C. of this preamble, EPA agrees and has taken this approach. 
To identify testing needs and help prioritize HAPs testing, Syracuse 
Research Corporation, an EPA contractor, has identified and summarized 
the existing health and exposure literature on the HAPs, and has 
identified testing programs currently in progress (Refs. 11, 12).
    The NAS report also discussed how a gradual, highly iterative 
testing approach to the generation of health effects data on HAPs might 
work. The report recommended that HAPs could be prioritized on the 
basis of their acute toxicity and chemical structure, and testing might 
proceed stepwise, on a case-by-case basis, from acute toxicity to 
studies of the uptake, distribution, retention, and excretion of the 
substance, to subchronic toxicity, and ultimately, if needed, to 
endpoint testing in animals. Depending on the animal toxicity data 
produced by this iterative testing scheme, according to the NAS, EPA 
might decide that further studies of human toxicity or mechanisms of 
toxicity are warranted.
    Although EPA agrees with the need to prioritize testing, it has 
taken a different approach to prioritization that is based on 
consideration of exposure potential and the rulemaking schedule of 
section 112 of the CAA. The amount and type of existing data vary 
greatly among the chemical substances that Congress designated as HAPs. 
In practice, therefore, no single uniform iterative approach based on 
toxicity factors alone would apply to all chemical substances. For 
example, one HAP might have only acute and short-term test data, while 
longer-term studies might exist for another HAP. Nevertheless, both the 
NAS and EPA approaches recognize that existing data must be considered 
if EPA is to avoid requiring duplicative testing that previously 
produced adequate data.
    An iterative testing approach based on toxicity factors alone would 
be time consuming and require multiple rulemakings. This process would 
take too long to collect useful data for making decisions needed to 
meet upcoming statutory deadlines established in the CAA. Furthermore, 
multiple iterative rulemakings to develop needed test data would be 
prohibitively costly to EPA and would not recognize limitations on EPA 
resources. For Option 3, EPA's preferred testing level, follow-up 
testing would rarely be required beyond that level proposed in this 
rule. Such testing, if necessary, would be required in a separate 
rulemaking.
    To make the multichemical decisions required under section 112 of 
the CAA regarding, for example, residual risk and delisting HAPs, EPA 
believes that it needs a consistent, even database covering HAPs across 
the same broad set of endpoints. EPA believes that Option 3 will permit 
timely gathering of a consistent database on HAPs more efficiently and 
at less cost to industry and EPA than is possible with other 
approaches.

C. Review of Data and Selection of HAPs

    In choosing candidates for this proposed test rule, EPA considered, 
consistent with TSCA section 4 requirements, the potential for a 
chemical substance to present an unreasonable risk of injury to health 
or the environment, the production

[[Page 33184]]

volume of the substance, the amount of emissions produced by the 
chemical substance entering or reasonably anticipated to enter the 
environment or become a source of exposure for humans, the sufficiency 
of the existing database, and the need for further testing to develop 
needed data. Consequently, as indicated in Unit IV of this preamble, 
and explained in a separate document in the record entitled ``TSCA 
Section 4 Findings for 21 Hazardous Air Pollutants'', each candidate 
listed for testing in this proposed rule is:
    (1) Considered to have the potential of presenting an unreasonable 
risk of injury to health or the environment (except in the case of 
ethylene glycol, for which no A finding was made--see the table in Unit 
V of this preamble);
    (2) Produced in quantities exceeding 1,000,000 pounds per year;
    (3) Emitted (i.e., released into the atmosphere) in the amount of 
50 tons (100,000 pounds) per year or more according to the 1993 Toxics 
Release Inventory (TRI);
    (4) Considered to have health effects data needs not addressed in 
other testing and research programs;
    (5) Considered to have health effects data that are insufficient 
under TSCA section 4 for determining effects of the HAP on health; and
    (6) Considered to need further testing to develop the needed data.
    The determination that data are insufficient to ascertain the 
effects of the HAPs on human health is based on several factors. First, 
EPA determined the effects of concern (toxicological endpoints) and the 
depth and quality of data which the Agency needs in order to make 
residual risk determinations. This decision and the range of options 
EPA considered are discussed in Unit III.A. of this preamble. Having 
made the decision that standard endpoint tests are appropriate, EPA 
reviewed existing studies and, for the purposes of this rule, compared 
such studies against the testing methodology used in the 1985 version 
of the EPA test guidelines for these endpoints. The 1985 test 
guidelines were the first test guidelines issued by EPA for its TSCA 
chemical testing program and represent widely accepted, peer-reviewed 
methods for characterizing chemical toxicity.
    The reasons why existing studies were judged to be inadequate are 
explained in a separate document in the record entitled ``TSCA Section 
4 Findings for 21 Hazardous Air Pollutants'', and summarized in the 
table in Unit V of this preamble. The reasons are varied but include 
the following examples--not studying the appropriate endpoint; too few 
dose levels; inappropriately high- or low-dose levels; and too few 
animals to have statistical confidence in the results. Nevertheless, in 
some cases, EPA toxicologists determined that data were adequate when 
the weight of evidence from several flawed studies, which, when 
considered individually were determined to be inadequate, gave an 
adequate characterization of the toxicity of the substance. Thus expert 
judgment must always play a role in determinations of data adequacy. 
Indeed, the determination of adequacy is so intimately connected to the 
unique characteristics of study design for each toxicological endpoint 
that EPA is unable to articulate a universal test of data adequacy that 
might be applied consistently in all situations. EPA is soliciting 
comments on its approach to determining data adequacy for the HAPs.
    To select HAPs for testing, EPA initially reviewed the production 
data and TRI data for all 189 HAPs. EPA realizes that TRI data 
represent estimates of environmental emissions of the TRI-listed 
chemicals and do not account for all chemical substances in the United 
States. Nevertheless, TRI figures offer the most complete, readily 
available emissions data, and EPA has determined that this database is 
sufficient for the purpose of helping EPA select high-emission HAPs for 
consideration as potential test candidates. While publicly available 
sources of production data are cited in the analysis supporting this 
rule, data from these sources were checked against the TSCA chemical 
inventory update production data, most of which are claimed as CBI.
    After reviewing TRI data for all HAPs, EPA decided to select a 
number of HAPs for initial consideration by focusing its attention on 
HAPs with TRI emissions of 50 tons or more per year. The 66 HAPs in 
this group constituted a reasonably sized group for further review. The 
selection of 50 tons per year or more as a cutoff is appropriate 
because this number captures high-emission HAPs and because section 112 
(a)(1) of the CAA, 42 U.S.C. 7412(a)(1), defines ``major source'' as 
emitting ``* * * 10 tons per year or more of any hazardous air 
pollutant or 25 tons per year or more of any combination of hazardous 
air pollutants * * *.''
    A survey of testing conducted by EPA under TSCA section 4, the 
Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA), and other 
testing programs supplemented a preliminary review of health findings 
from secondary source documents and the IRIS database. This initial 
survey revealed that certain HAPs having high emissions (50 tons or 
more) already have a large inhalation toxicology database or are 
subject to testing or research in existing programs. Therefore, EPA 
decided not to pursue additional testing under this rule for benzene, 
butadiene, carbon disulfide, chromium, cyanide, ethylene oxide, 
formaldehyde, lead, methanol, methyl tertiary butyl ether, methylene 
chloride, tetrachloroethylene, toluene, trichloroethylene, vinyl 
chloride, and vinyl acetate. Additional testing under TSCA for these 
chemicals may be considered at some time in the future.
    EPA decided that the remaining group of 50 HAPs could be handled 
most efficiently by promulgating more than one rule. Consequently, 21 
high-emission HAPs were scrutinized further and were selected as 
candidates for this proposed rule, and the remaining 29 HAPs were 
deferred for consideration in subsequent HAPs test rulemaking efforts. 
In the second HAPs test rule, EPA plans to focus on persistent HAPs 
that may bioaccumulate. EPA may, therefore, require ecological and 
environmental testing for these HAPs. EPA also may require testing in 
the second rule to collect data needed to implement the ``Great 
Waters'' program of section 112(m) of the CAA, 42 U.S.C. 7412(m).
    During the selection process for this proposed rule, EPA's 
contractor undertook a comprehensive search of the toxicological, 
health, and exposure literature for the 21 HAPs proposed for testing in 
the current rule (Refs. 11, 12). EPA's contractor performed the 
literature search in a stepwise manner to save both time and expense. 
The first step was to review secondary source health effects documents. 
EPA's contractor identified documents published by EPA, the 
International Agency for Research on Cancer (IARC), and ATSDR and 
extracted relevant data. EPA performed online Environmental Mutagen 
Information Center (EMIC) searches for genetic toxicity information 
(Ref. 13). In addition, an article entitled ``Genetic Activity Profiles 
of 110 Hazardous Air Pollutants Listed Under Title III of the Clean Air 
Act'' (Ref. 14) and the International Commission for Protection against 
Environmental Mutagens and Carcinogens (ICPEMC) have provided useful 
summary information.
    EPA realizes that using secondary sources of information is not 
ideal. For example, it is possible that a secondary source document 
could miss an important study or that the document could fail to 
properly interpret a study. Consequently, whenever essential

[[Page 33185]]

information appeared to be missing from the review documents or was not 
explained clearly, EPA's contractor consulted original articles.
    Through its contractor, EPA next checked several sources for 
relevant published and unpublished studies. It obtained unpublished but 
publicly available studies submitted to EPA under TSCA, searched the 
Toxic Substances Control Act Test Submissions (TSCATS) database by CAS 
Registry number, and reviewed the National Toxicology Program (NTP) 
Results Report (generated from NTP's CHEMTRACK database) to locate 
completed but unpublished NTP studies. With the contractor's 
assistance, EPA next undertook an update search of the open literature 
to locate any as yet unidentified studies published either shortly 
before or after the review documents appeared. For this purpose, EPA's 
contractor searched the National Library of Medicine (NLM) TOXLINE 
database for studies published during a period of time beginning three 
years prior to the date of the review document initially used to obtain 
toxicity information and ending on the date of the search.
    In addition, EPA's contractor consulted with representatives of 
NIOSH, OSHA, the Food and Drug Administration (FDA), the National 
Institute of Environmental Health Sciences (NIEHS), and various 
chemical companies. The purpose of these inquiries was to determine if 
these organizations had any information on completed or ongoing studies 
that might not be found in any readily available database. Through its 
contractor, EPA also contacted the Chemical Industry Institute of 
Toxicology (CIIT), as well as trade associations and allied 
organizations to determine whether these organizations were sponsoring 
or knew of any relevant studies currently in progress. Finally, EPA's 
contractor closely reviewed data sheets compiled by EPA's IRIS RfD/RfC 
Working Group to ascertain if the group had identified any additional, 
otherwise unlocated information.
    Varied levels of scrutiny were applied to different types of 
toxicity testing information throughout the literature search. Because 
the primary focus of the review of acute, subchronic, and chronic 
systemic toxicity literature was inhalation exposure, only inhalation 
studies were reviewed for these endpoints. Although oral studies can 
provide important information on target organ toxicity and should be 
considered in the design of any testing protocol, these studies usually 
provide limited information on the effects of a compound on the 
respiratory tract. In addition, the systemic dose remote to the 
respiratory tract for many compounds is affected by modulation of 
uptake at the portal of entry into the body. This modulation is not 
only from first-pass effects but from other influences of anatomy and 
physiology (Ref. 15). Because EPA's literature search did not encompass 
oral acute and subchronic toxicity studies, the preliminary findings of 
risk that EPA is making below, under TSCA section 4(a)(1)(A), are not 
based on such studies. Thus, oral acute and subchronic studies may 
provide additional evidence of potential toxicity.
    The contractor reviewed studies of carcinogenicity, neurotoxicity, 
and reproductive and developmental toxicity, regardless of the route of 
administration.
    EPA took a different approach to identify HAP candidates for 
immunotoxicity testing. EPA relied on an EPA document ``Hazardous Air 
Pollutants: Profiles of Non-Cancer Toxicity from Inhalation Exposures'' 
(Ref. 16), containing a database that was developed from EPA and ATSDR 
documents and data files, and from the Hazardous Substances Data Bank 
(HSDB) of NLM. The contractor searched recent literature (i.e., 1989 to 
present) for immunotoxicity data on the 21 HAPs in both MEDLINE and 
TOXLINE. For chemicals with ATSDR Toxicological Profiles, the profile 
was used to identify immunotoxicity data. Much of the identified 
immunotoxicity literature used rather insensitive indicators of impact 
(e.g., organ weight changes, histopathology, leukocyte counts, and 
total serum protein determinations), that were judged to constitute an 
inadequate evaluation of suppression of immune system responsiveness 
(Ref. 17). Thus, an immunotoxicity screening test is being proposed in 
this rule for many of these HAPs.
    Although EPA has made intense and thorough attempts to identify all 
relevant studies, EPA recognizes the limitations inherent in relying on 
secondary sources and realizes that its literature search may have 
failed to locate studies recently undertaken or completed. Therefore, 
EPA solicits comments bringing to its attention any valid studies not 
identified in its search efforts.

D. Previous TSCA Testing Actions Affecting These Chemical Substances

    Eight of the substances included in this proposed rule have been 
the subject of previous testing under TSCA section 4. Testing by the 
inhalation route was not generally required, however, and acute 
effects--including respiratory tract effects--were not generally a 
target endpoint. This subunit will briefly summarize previous testing 
decisions and explain the relationship between those activities and 
this proposed rule.
    1,1'-Biphenyl was recommended by the Interagency Testing Committee 
(ITC) in its 10th report for environmental effects and chemical fate 
testing (47 FR 22585, May 25, 1982). Focusing only on environmental 
testing, EPA found that 1,1'-biphenyl may present an unreasonable risk 
to the environment and issued a test rule requiring environmental 
effects and chemical fate testing of the chemical on September 12, 1985 
(50 FR 37182). This proposed rule complements the earlier action by 
requiring health effects testing of 1,1'-biphenyl, namely, acute 
toxicity, respiratory sensory irritation, subchronic toxicity, 
developmental toxicity, reproductive toxicity, neurotoxicity and 
immunotoxicity.
    Chlorobenzene was recommended to EPA for health and environmental 
effects testing in the first report of the ITC (42 FR 55026, October 
12, 1977). Subsequently, EPA found that the chemical may present an 
unreasonable risk to human health (an A finding) and issued a rule 
requiring reproductive effects testing (51 FR 24657, July 8, 1986). 
Although the preamble of the proposed rule described specific 
neurotoxicity concerns, EPA stated that neurotoxicity testing 
requirements were not being proposed because it had not issued 
neurotoxicity test guidelines at that time. Instead EPA explained its 
then-current views on neurotoxicity testing in the preamble and 
solicited public comment on those views (45 FR 48524, July 18, 1980). 
Because a neurotoxicity screening battery guideline (OPPTS 870.6200) 
has since been proposed, this rule proposes the testing of 
chlorobenzene for neurotoxicity, acute toxicity, respiratory sensory 
irritation, subchronic toxicity, and immunotoxicity.
    Cresols are members of a chemical category consisting of three 
isomers: ortho-, para-, and meta-cresol. Based on both A and B 
findings, a test rule proposed on July 11, 1983 (48 FR 31812) would 
have required testing of cresols for subchronic toxicity, mutagenicity, 
carcinogenicity, developmental toxicity, reproductive effects, 
neurotoxicity, and skin sensitization. The final rule, published on 
April 28, 1986 (51 FR 15771), which specified testing for all three 
isomers and provided a rationale for this decision, required testing 
for mutagenicity, developmental toxicity, and reproductive effects. 
Data received

[[Page 33186]]

under this test rule satisfy the HAPs data needs for these endpoints. 
Based on the results from this first tier of tests, a conditionally 
required cancer bioassay was not triggered. In addition, oral 
subchronic toxicity studies and subchronic neurotoxicity studies were 
conducted by EPA's Office of Solid Waste. In accordance with the need 
for data on respiratory tract effects, today's rule proposes acute and 
subchronic inhalation toxicity, respiratory sensory irritation, acute 
neurotoxicity, and immunotoxicity tests for all three cresol isomers 
(see Unit IV.B. of this preamble). For the purposes of this proposal, 
the three cresol isomers are counted as a single chemical.
    Methyl isobutyl ketone was the subject of a negotiated testing 
agreement between EPA and industry for mutagenicity, developmental 
toxicity, and subchronic testing (47 FR 58025, December 29, 1982, and 
48 FR 44905, September 30, 1983). Data received under the negotiated 
testing agreement satisfy the HAPs data needs for these endpoints. 
Methyl isobutyl ketone is also being tested for neurotoxicity under a 
TSCA enforceable consent agreement (ECA) with industry (announced at 60 
FR 4514, January 23, 1995 (FRL-4924-8)). This rule proposes testing for 
reproductive toxicity, acute toxicity, respiratory sensory irritation, 
and immunotoxicity to complement ongoing testing and existing data.
    Phenol is the subject of a test rule proposed on the basis of A and 
B findings on November 22, 1993 (58 FR 61654). That rule proposed 
subchronic toxicity, neurotoxicity, and reproductive and developmental 
toxicity testing and a study of phenol's pharmacokinetics. EPA has 
received a proposal for an ECA for this chemical substance that would 
cover the testing proposed in the 1993 rule. The rule proposed herein 
would add acute inhalation toxicity, respiratory sensory irritation, 
and immunotoxicity to the testing program for phenol. Under the 
procedures set forth at 40 CFR 790.22, members of the CMA Phenol Panel 
and EPA have negotiated an ECA which provides for the testing proposed 
in November 1993 as well as additional testing, including 
immunotoxicity. Such testing would meet the HAPs-related data needs for 
phenol. If the ECA is successfully concluded, EPA will drop the testing 
requirement for phenol from the final HAPs rule.
    1,2,4-Trichlorobenzene has been tested for carcinogenicity under a 
test rule (51 FR 24657, July 8, 1986) based on an A finding. Data 
received under this test rule satisfy the HAPs data needs for this 
endpoint. Although the preamble of the proposed rule described specific 
neurotoxicity concerns, EPA stated that neurotoxicity testing 
requirements were not being proposed because it had not issued 
neurotoxicity test guidelines at that time (45 FR 48545, July 18, 
1980). Because a neurotoxity screening battery guideline (OPPTS 
870.6200) has since been proposed, this rule proposes the testing of 
1,2,4-trichlorobenzene for acute toxicity, respiratory sensory 
irritation, neurotoxicity, immunotoxicity, and developmental toxicity.
    Oncogenicity testing for vinylidene chloride was called for in a 
proposed test rule based on an A finding on August 12, 1986 (51 FR 
28840). The rule proposed that distribution, metabolism, and excretion 
studies and an inhalation oncogenicity study be conducted in mice on 
behalf of EPA's Office of Air Quality Planning and Standards (OAQPS). 
EPA has not finalized the vinylidene chloride proposal and is hereby 
withdrawing it. EPA is not pursuing these studies because the Agency 
has concluded that, at this time, an oncogenicity bioassay would do 
little to add to EPA's understanding of the oncogenic potential of the 
substance. Today's rule proposes testing for acute toxicity, 
respiratory sensory irritation, and neurotoxicity.

IV. Proposed Testing

A. Testing and Reporting Requirements

    EPA is proposing specific testing and reporting requirements for 
each of the 21 HAPs as specified in table 1 in Sec. 799.5053(a)(5) of 
this proposed rule. EPA is proposing for the first time in a TSCA 
section 4 rule to require an immunotoxicity screen and an acute 
inhalation toxicity test that focuses on respiratory damage and 
sublethal systemic toxicity. These and other test guidelines are 
discussed below in Unit IV.C. of this preamble.
    EPA is proposing to require a modified inhalation carcinogenicity 
bioassay using only the male rat and female mouse when existing oral 
carcinogenicity data and supporting information for a chemical 
substance are deemed too uncertain to determine its carcinogenicity via 
inhalation (Ref. 10). The reduced protocol is less expensive than a 
traditional bioassay. However, test sponsors would also have the 
alternative of performing pharmacokinetics studies and using route-to-
route extrapolation from existing adequate oral toxicity data under 
enforceable consent agreements (EDAs) in lieu of this and other test 
requirements if the Agency decides to use this approach (see Units 
IV.D. and IV.E. of this preamble).
    A total of 21 months would be given for the submission of final 
reports for acute toxicity testing because the acute inhalation 
toxicity with histopathology guideline proposes to make certain 
histopathology studies contingent upon the results of the 90-day 
subchronic studies. The time for the submission of immunotoxicity 
studies would vary as a function of the test with which they can be 
combined (e.g., subchronic and reproductive effects).

B. Test Substance

    EPA is proposing that a substance of at least 97% purity be used as 
the test substance. EPA recognizes that exposure to HAPs will occur as 
exposure to complex mixtures and that ideally one would like data on 
the mixtures themselves. However, it is not practical to test mixtures 
due to the huge number of possible combinations. EPA will thus evaluate 
the toxicity of HAP mixtures using data on the relatively pure 
components in order to avoid the possible confounding effects of 
impurities that might be found in technical grade substances. These 
impurities, if substantial contributors to air pollution, should also 
be captured as separate entries on the CAA list of HAPs. EPA believes 
that a purity of 97% is available or readily achievable for all 
substances covered by this rule.
    For cresols, the subject of the test rule is a mixture (CAS No. 
1319-77-3) of three isomers: ortho- (CAS No. 95-48-7), para- (CAS No. 
106-44-5) and meta- (CAS No. 108-39-4). The mixture and individual 
isomers are contained in the CAA section 112(b)(1) list of hazardous 
air pollutants. Most human exposure is to the mixture. However, because 
the mixture is of variable composition, EPA believes that it would be 
very burdensome to test every possible variation of the mixture, which 
would have different proportions of isomers. Therefore EPA is proposing 
to follow the approach taken in the final test rule for cresols (51 FR 
15771, 15776, April 28, 1986) and test each isomer (see Unit III.D. of 
this preamble).
    Another critical factor in study design for HAP testing is the low 
vapor pressure of several of these substances (diethanolamine, 1,1'-
biphenyl, phthalic anhydride). This raises two questions. To which 
forms of the chemical are humans exposed--vapor, aerosol or particle? 
How does one design a valid toxicity study that can be used to assess 
human risk to such exposures? Given the reported TRI releases to the 
atmosphere for these substances, EPA has assumed that exposures are to

[[Page 33187]]

aerosols or particulates from the condensation of high temperature 
stack gases. EPA is proposing that diethanolamine, 1,1'-biphenyl and 
phthalic anhydride be tested via aerosol exposure. EPA invites 
manufacturers and processors to submit information about the forms of 
these substances that are encountered in ambient exposures and the 
forms that should be tested, and encourages the development of 
pharmacokinetics data that would permit testing by the less expensive 
oral route for HAPs with low vapor pressure.

C. Test Guidelines

    The 11 guidelines being proposed for use in testing HAPs under this 
rule are included in the recently harmonized health effects test 
guidelines proposed by EPA's Office of Prevention, Pesticides, and 
Toxic Substances (OPPTS). When final, these harmonized guidelines will 
incorporate an updated version of the test guidelines previously 
developed for use under TSCA and FIFRA into a single set. A notice of 
availability and request for comments on the proposed guidelines was 
published in the Federal Register of June 20, 1996 (61 FR 31522).
    The 11 guidelines proposed for use in testing HAPs are included in 
the public version of the record for this rulemaking at the address 
specified in the ``ADDRESSES'' section of this document. The complete 
set of proposed guidelines is available electronically from the EPA 
Public Access Gopher (gopher.epa.gov) under the heading: 
``Environmental Test Methods and Guidelines''; by internet e-mail: 
<a href="/cdn-cgi/l/email-protection#86e1f3efe2e3eaefe8e3f5c6e3f6e7ebe7efeaa8e3f6e7a8e1e9f0"><span class="__cf_email__" data-cfemail="1275677b76777e7b7c7761527762737f737b7e3c7762733c757d64">[email protected]</span></a>; by mail: Public Docket and Freedom of 
Information Section, Field Operations Division (7506C), Office of 
Pesticide Programs, U.S. Environmental Protection Agency, Washington, 
DC 20460; or in person or for courier pick-up: Room 1132, CM #2, 1921 
Jefferson Davis Highway, Arlington, VA; telephone: (703) 305-5805.
    The 11 guidelines proposed to be used for testing HAPs are as 
follows:
    (1) Acute Inhalation Toxicity with Histopathology, OPPTS 870.1350, 
EPA Pub. No. 712-C-96-291, June 1996;
    (2) Subchronic Inhalation Toxicity, OPPTS 870.3465, EPA Pub. No. 
712-C-96-204, June 1996;
    (3) Inhalation Developmental Toxicity Study, OPPTS 870-3600, EPA 
Pub. No. 712-C-96-206, June 1996;
    (4) Reproduction and Fertility Effects, OPPTS 870.3800, EPA Pub. 
No. 712-C-96-208, February 1996;
    (5) Carcinogenicity, OPPTS 870.4200, EPA Pub. No. 712-C-96-211, 
June 1996;
    (6) Escherichia coli WP2 and WP2 uvrA Reverse Mutation Assays, 
OPPTS 870.5100, EPA Pub. No. 712-C-96-247, June 1996;
    (7) Detection of Gene Mutations in Somatic Cells in Culture, OPPTS 
870.5300, EPA Pub. No. 712-C-96-221, June 1996;
    (8) In Vivo Mammalian Cytogenetics Tests: Bone Marrow Chromosomal 
Analysis, OPPTS 870.5385, EPA Pub. No. 712-C-96-225, June 1996;
    (9) In Vivo Mammalian Cytogenetics Tests: Erythrocyte Micronucleus 
Assay, OPPTS 870.5395, EPA Pub. No. 712-C-96-226, June 1996;
    (10) Neurotoxicity Screening Battery, OPPTS 870.6200, EPA Pub. No. 
712-C-96-238, June 1996; and
    (11) Immunotoxicity, OPPTS 870.7800, EPA Pub. No. 712-C-96-351, 
June 1996.
    To be considered in this rulemaking, comments on the 11 proposed 
test guidelines that are specific to HAPs testing must be submitted to 
the OPPT Document Control Office. The comments must be submitted in the 
manner specified in the ``DATES'' and ``ADDRESSES'' sections at the 
beginning of this document. Comments on the 11 proposed guidelines, 
which are not specific to the HAPs test rule must be submitted to the 
Office of Pesticide Programs by August 19, 1996, at the address 
identified in the Federal Register of June 20, 1996 (61 FR 31522).
    The process of developing OPPTS harmonized guidelines described 
above is proceeding at the same time as the development of the HAPs 
test rule. The OPPTS harmonization process may result in the revision 
of the guidelines prior to the end of the ocmment period for this 
proposed rule. If so, EPA will announce the availability of those of 
the 11 guidelines used in the HAPs rule that have been revised in order 
to allow for public comment on the applicability of the revised 
guidelines to the HAPs rule. If any of these 11 guidelines has not been 
revised by the end of the comment period for this proposed rule, EPA 
may issue the corresponding HAPs-specific guideline independent of the 
OPPTS harmonization process.
    EPA is proposing to modify the subchronic inhalation toxicity test 
guideline (OPPTS 870.3465) for the purposes of this rulemaking to 
include enhanced histopathology of the respiratory tract and an assay 
for cell damage via lung lavage. EPA is requesting comment on adding 
these parameters to the subchronic test guideline for testing HAPs.
    As part of this rulemaking, EPA proposes to use the acute 
inhalation toxicity with histopathology test guideline (OPPTS 
870.1350). As indicated in Unit III.A. of this preamble, the study of 
sublethal effects, especially effects on the respiratory system, 
associated with accidental release and acute exposures is necessary for 
the HAPs. The standard acute inhalation toxicity test guideline (OPPTS 
870.1300) focuses on gross lesions, body weight changes, and effects on 
mortality. The acute inhalation toxicity with histopathology test 
guideline assesses two endpoints: (1) histopathology of the respiratory 
tract, kidney, liver, and other target organs; and (2) cell damage via 
lung lavage. The guideline takes a stepwise approach to the evaluation 
of acute toxicity and initially requires a 4-hour exposure at three 
concentration levels. If the 4-hour study shows positive results in 
histopathology or the bronchoalveolar lavage, a 1-hour study and an 8-
hour study would be required to define better the time and 
concentration dependence of acute exposures. Histopathology is being 
proposed for the respiratory tract, liver, and kidney. Other target 
organs identified by either gross pathology in the 4-hour acute study 
or by histopathology in the 90-day study would also have to be examined 
by histopathology in the 4-hour acute study. If these results are 
positive in the 4-hour study, histopathology in the 1-hour and 8-hour 
studies would be required. The 4-hour acute testing may be combined 
with acute neurotoxicity testing.
    A respiratory sensory irritation test using American Standard Test 
Method (ASTM) E 981-84 is also being proposed to provide a quantitative 
estimate of the sensory irritant potential of an inhaled chemical. 
Irritation is detected by a characteristic change in the breathing 
pattern of mice, which results in a reduction in the breathing rate 
during exposure to a test atmosphere.
    For all testing proposed in this rule, test sponsors would have to 
conduct testing and generate data in accordance with the specified test 
guideline. Data developed under the final rule must be reported in 
accordance with TSCA Good Laboratory Practice (GLP) Standards, 40 CFR 
part 792.
    EPA is considering three alternative procedures for handling these 
test guidelines in the context of the final HAPs test rule. The first 
alternative is for the final HAPs rule to incorporate the guidelines by 
reference. Under this alternative, the text of the guideline would not 
appear in the Code of Federal Regulations. Instead the rule would 
include a reference to the guideline which would be available on the 
internet and elsewhere, as noted above.

[[Page 33188]]

A copy of the applicable guideline would also be maintained in the 
public version of the rulemaking record.
    The second alternative would be for the final HAPs rule to refer to 
the guideline, the text of which would be available on the internet and 
elsewhere, as the pre-approved protocol. However, test sponsors may use 
other protocols after such protocols have been approved by EPA 
(``previously approved equivalents''). If EPA decides on this course of 
action, the Agency may issue a supplemental notice proposing specific 
implementation procedures if they are significantly different from the 
following procedures. A test sponsor would be required to submit to EPA 
for review and approval each test protocol that such sponsor believes 
is equivalent to the corresponding OPPTS test guideline. A submission 
would have to demonstrate equivalency, include a description of the 
differences between the sponsor's protocol and the corresponding OPPTS 
guideline, and indicate the rationale for changing the guideline. The 
deadline for these submissions would be 90 days after the effective 
date of the final HAPs rule. In the case of a study where the design 
depends upon the results of an earlier test (such as carcinogenicity 
where the dose level is contingent upon the results of a subchronic 
study), the deadline is 90 days following the date of submission of the 
final report for that study.
    The third alternative is for the final HAPs rule to reference the 
guidelines currently in part 798 of title 40 of the Code of Federal 
Regulations and modify these guidelines to make them as nearly 
identical as possible to the harmonized OPPTS guidelines. The 
modifications that the Agency currently believes would be appropriate 
are set forth in a separate document in the record entitled 
``Modifications to Health Effects Test Guidelines Currently in 40 CFR 
Part 798 for Use in the HAPs Test Rule''. EPA is soliciting comment on 
these three alternative procedures.

D. Route-to-Route Extrapolation

    EPA would consider route-to-route extrapolation of toxicity data 
from routes other than inhalation when it is scientifically defensible 
to empirically derive the inhalation risk. Derivation of the inhalation 
risk is generally only reasonable when portal-of-entry effects (toxic 
effects on the respiratory tract from inhalation exposure) and/or 
first-pass effects can be ruled out or adequately characterized.
    ``First-pass'' effects refer to the metabolism that can take place 
in portal-of-entry tissue, prior to a chemical's entry into the 
systemic circulation. For example, after oral administration, many 
chemicals are delivered to the liver via the portal vein from the 
gastrointestinal (GI) tract before they enter into the systemic 
circulation. The respiratory tract can also exhibit a first-pass effect 
after inhalation due to its various cell types and metabolic enzyme 
systems. The first-pass action can alter the disposition of the parent 
and metabolites, thereby modulating the dose to remote or systemic 
target tissues in a route-dependent fashion. Therefore, unless this 
first-pass effect and dosimetry are adequately understood and taken 
into account, substantial error can be introduced in route-to-route 
extrapolation.
    In the absence of data to determine dosimetry via inhalation, 
quantitative route-to-route extrapolation is subject to substantial 
error when a chemical is thought to be susceptible to first-pass 
effects (e.g., metabolized) or when a potential for portal-of-entry 
effects is indicated (e.g., skin irritation after dermal 
administration). There are situations where oral data should not be 
used for route extrapolation to inhalation. For example, chemicals with 
a short active half-life that were administered by gavage may result in 
high short-term blood concentrations and consequently much greater 
effects than the much lower constant blood levels that occur with 
inhalation exposure. Conversely, if a chemical requires metabolic 
activation via a rate-limited reaction, bolus dosing via gavage may 
underestimate the dose. Consideration of factors such as these is 
important in judging whether the oral study of interest qualifies for 
route extrapolation.
    Regardless of the toxic endpoint considered, EPA's ability to 
perform quantitative route-to-route extrapolation is critically 
dependent on the amount and type of data available. The minimum 
information generally needed includes both the nature of the toxic 
effect and a description of the relationship between exposure and the 
toxic effect. The actual impact of exposure by different routes can 
best be estimated by taking account of factors that influence 
absorption at the portal of entry, such as:
    (1) Physicochemical characteristics of the chemical (e.g., 
disassociation state, molecular weight, partition coefficient, 
reactivity, solubility);
    (2) Exposure factors (e.g., concentration, duration, regimen); and
    (3) Physiologic parameters (e.g., barrier capacity as related to 
variability in species, blood flow, cell types and morphology, 
metabolism, pH, specialized absorption sites, storage in cells) and 
those parameters that influence dose that are remote to the portal of 
entry including metabolism, clearance, tissue binding, tissue blood 
flows, tissue:blood partition coefficients, and tissue volumes.
    Oral toxicity data are the most commonly available data as 
alternatives to inhalation data. Oral data are problematic for route-
to-route extrapolation in the following instances:
    (1) When groups of chemicals are expected to have different 
toxicities by the two routes, for example, metals, irritants, and 
sensitizers.
    (2) When a first-pass effect by the liver is expected.
    (3) When a respiratory tract effect is established but nodosimetry 
comparison can be clearly established between the two routes.
    (4) When the respiratory tract was not adequately studied in the 
oral studies.
    (5) When short-term inhalation studies, dermal irritation, or in 
vitro studies indicate potential portal-of-entry effects at the 
respiratory tract, but the studies themselves are not adequate for risk 
assessment.
    Dose-response data from other routes of exposure, such as 
intravenous, intraperitoneal, subcutaneous, dermal, and intramuscular 
routes also may be available. Intravenous data can provide reliable 
information on blood levels, but such information should be 
supplemented by knowledge of the quantitative relationship between 
exposure concentration and blood levels in order to be useful. The 
other routes usually are less useful in route-to-route extrapolation 
because the pharmacokinetics are, in general, poorly characterized.
    Methods for route-to-route extrapolation vary in accuracy and, 
therefore, in inherent uncertainty. The simplest approach is to use 
default absorption values for each exposure route dependent on the 
chemical class in question. Such values have only been developed for a 
few classes of organic chemicals. Because this approach entails 
increased uncertainty compared with those that use pharmacokinetics 
(PK) data and physiologically based pharmacokinetics (PBPK) modeling, 
use of default absorption values is generally considered highly 
uncertain for quantitative dose-response assessment.
    EPA's optimal but most complex and data intensive method for 
performing route-to-route extrapolation involves the development of a 
PBPK model that describes the disposition (deposition, absorption, 
distribution, metabolism, and elimination) of the chemical for the 
routes of interest (Ref. 15). Such models

[[Page 33189]]

account for fundamental physiological and biochemical parameters and 
processes such as blood flows, ventilatory parameters, metabolic 
capacities, and renal clearance tailored by the physicochemical (e.g., 
blood:air and tissue:blood partitions) and biochemical properties 
(e.g., binding, depletion of cofactors) of the chemical in question. 
PBPK models should be used in conjunction with toxicity and mechanistic 
studies in order to relate the effective dose associated with an 
adverse effect for the test species and conditions to other scenarios. 
Although the development of a full PBPK model can involve greater 
effort than other methods using pharmacokinetics data, the application 
of pharmacokinetics modeling to determine health risk provides a 
considerable improvement in the reliability of an extrapolation across 
routes. The use of an existing model structure, essentially a template, 
can greatly reduce the effort required for model development of 
analogous chemicals.
    More limited pharmacokinetics data such as measurement of 
bioavailability and disposition of an internal dose marker (e.g., blood 
cholinesterase activity, enzyme elevation, and amount of chemical bound 
to protein) may be used for route-to-route extrapolation in conjunction 
with a consideration of the uncertainties involved in each case. As 
above, if the portal of entry is affected by the agent, then more 
elaborate data may be required.
    EPA realizes that the use of pharmacokinetics data for route-to-
route extrapolation, as well as for the broader purpose of generally 
identifying the mechanisms by which exposure to a specific agent causes 
particular health effects, is a fast-developing and often controversial 
area of science at this time. However, under certain circumstances, as 
explained above, route-to-route extrapolation based on valid 
pharmacokinetics data can offer a useful and less expensive alternative 
to testing or retesting by another route of exposure.

E. Opportunity To Submit Proposals for Enforceable Consent Agreements 
for Pharmacokinetics Studies

    Basic pharmacokinetics parameters provide information on a 
substance's absorption, distribution, biotransformation, and excretion 
which can aid in understanding the potential for accumulation of the 
substance in various tissues or organs and the mechanism of toxicity. 
Basic PK parameters can be determined through use of the OPPTS 
harmonized test guideline for pharmacokinetics studies (870.7485). EPA 
considered but rejected the option of requiring the use of this 
guideline in this proposed rule because the Agency is interested in a 
more sophisticated level of study that could potentially support PBPK 
modeling.
    EPA believes that enforceable consent agreements (ECAs) and testing 
consent orders offer an opportunity to obtain this more in-depth 
understanding of the pharmacokinetics of HAPs. The Agency, therefore, 
is inviting manufacturers to submit proposals for pharmokinetics 
studies for HAPs to be used in the ECA process. Each study proposal 
should include the name of the chemical(s), a detailed description of 
the proposed pharmacokinetics study, and discussion of the application 
of the pharmacokinetics data in performing route-to-route 
extrapolations. Study proposals should reflect an understanding of the 
scientific reasoning presented in Unit IV.D. of this preamble, the 
existing database on the chemical and testing required under this 
proposed test rule. EPA expects to use a previously published decision 
tree (Ref. 15) as an element in the evaluation of these proposals. As 
noted in Unit IV.D., these data may be used for route-to-route 
extrapolation with a level of uncertainty in inverse proportion to 
their level of complexity and sophistication.
     Each study proposal should be labeled: ``Proposal for 
Pharmacokinetics Study of (name of chemical),'' identified by document 
control number (OPPTS-42187B, FRL-4869-1), and sent to: U.S. 
Environmental Protection Agency, Office of Pollution Prevention and 
Toxics, Document Control Office (7407), Room G-099, 401 M St., SW., 
Washington, DC 20460. Proposals for pharmacokinetics studies must be 
received by EPA no later than October 24, 1996. Enforceable consent 
agreements must be negotiated and signed no later than 12 months after 
the date of proposal of this rule in order to permit timely development 
of the final HAPs rule.
    EPA will review the submissions and will select promising 
candidates for negotiation under the procedures in 40 CFR 790.22. If 
the Agency decides to proceed with the ECA process, it will publish a 
notice in the Federal Register soliciting persons interested in 
participating in or monitoring negotiations for the development of ECAs 
for PK studies to notify the Agency in writing.
    EPA noted in Unit IV.D. that the development and use of a PBPK 
model represents the optimal approach to route-to-route extrapolation. 
The development of such models is often a complex and uncertain task 
that in most cases lies beyond the expectations of performance that 
could be embodied in an ECA. However, EPA would like to encourage 
extension of the data generated under the ECAs described above to the 
development of PBPK models. EPA envisions that PBPK models could be 
developed through voluntary cooperative arrangements and is interested 
in a dialogue with industry and others on ways to encourage and support 
PBPK model development.

F. Persons Required To Test

    Based on the findings in Unit V of this preamble, EPA is proposing 
that persons who manufacture (including import) or process, or who 
intend to manufacture or process 1,1'-biphenyl, carbonyl sulfide, 
chlorine, chlorobenzene, chloroprene, cresols (all three isomers), 
diethanolamine, ethylbenzene, ethylene dichloride, ethylene glycol, 
hydrochloric acid, hydrogen fluoride, maleic anhydride, methyl isobutyl 
ketone, methyl methacrylate, naphthalene, phenol, phthalic anhydride, 
1,2,4-trichlorobenzene, 1,1,2-trichloroethane, and vinylidene chloride, 
other than as an impurity, at any time from the effective date of the 
final test rule to the end of the reimbursement period, be subject to 
the testing requirements in this rule. Manufacturers would be required 
to submit letters of intent to conduct testing or exemption 
applications (40 CFR 790.45). However, under 40 CFR 790.42, processors, 
small-quantity manufacturers, and manufacturers of small quantities of 
these substances solely for research and development purposes would not 
be required to submit letters of intent or exemption applications 
unless directed to do so in a subsequent notice as described in 40 CFR 
790.48(b).
    EPA is proposing to exempt those manufacturers and processors that 
produce the chemical substances listed above only as an impurity, as 
defined in 40 CFR 790.3, because it would be difficult and 
prohibitively expensive for EPA, manufacturers, and processors to 
identify with complete assurance all chemical substances that contain 
the 21 substances solely as an impurity. In addition, EPA would find it 
difficult to apply both the exemption and reimbursement processes to 
those who manufacture and/or process these chemical substances solely 
as an impurity. EPA's reimbursement regulations, issued pursuant to 
TSCA section 4(c), 15 U.S.C. 2603(c), state that those persons who 
manufacture or process chemical substances as impurities are not 
subject to test

[[Page 33190]]

requirements unless a particular test rule specifically states 
otherwise (40 CFR 791.48(b)). EPA finds no basis to propose such a 
requirement in this rule.
    Persons who manufacture these substances as byproducts, as defined 
in 40 CFR 791.3(c), would be subject to the testing requirements set 
forth in this proposed rule. The total amount of imports and domestic 
production of these chemical substances, including the amount produced 
as a byproduct, would be used in determining reimbursement shares under 
the TSCA section 4 data reimbursement regulations in 40 CFR part 791. 
In a previous multichemical test rule (undertaken for EPA's Office of 
Solid Waste) for which EPA had likewise proposed that byproducts be 
subject to the rule, an industry commenter objected to this inclusion 
based on historical grounds. The commenter said, ``The historical roots 
of section 4 in the Eckart Subcommittee work on TSCA were the sharing 
of the costs of test generation in direct proportion to the economic 
benefits which producers derived from the chemicals.'' In response to 
this comment, EPA explained that,

    EPA does not agree that the intention of Congress to have 
producers share the cost of testing should be interpreted to exclude 
producers of byproducts from TSCA section 4 testing requirements. 
While economic benefit is not derived directly from the production 
of the subject chemical, the production and disposal of the 
byproduct are a result of a production process by which the company 
does derive economic benefit (an indirect benefit). (53 FR 22300, 
22305, June 15, 1988)

    Carbonyl sulfide would be the first chemical substance subject to a 
TSCA section 4 test rule that is produced almost exclusively as a 
byproduct. Although some carbonyl sulfide is reported to be used in 
chemical synthesis, its large production and release, as reported in 
the TRI, is due to its creation as a byproduct which is unwanted. 
Consistent with EPA's position on byproducts testing, as explained 
above, all persons reporting the release of carbonyl sulfide in the TRI 
would be considered to be manufacturers of carbonyl sulfide and would 
be subject to the provisions of this proposed rule.

V. Findings

    As explained in Unit I of this preamble, EPA is proposing findings 
under TSCA sections 4(a)(1)(A) and 4(a)(1)(B) for the 21 HAPs subject 
to this rule. The findings are summarized in the table below. The 
detailed discussion of the findings for each chemical substance 
included in this rule is contained in a separate document entitled 
``TSCA Section 4 Findings for 21 Hazardous Air Pollutants'' that is 
available in the rulemaking record. Requirements for sections 
4(a)(1)(A) and 4(a)(1)(B) findings appear in Unit I of this preamble.
    In articulating its policy for making findings under TSCA section 
4(a)(1)(B) (frequently described as the ``B policy'', see Unit I of 
this preamble), EPA has defined ``substantial production'' as aggregate 
annual production of 1 million pounds or more and ``substantial 
release'' as an annual release, from all sources, into the environment 
of 1 million pounds or 10% of production, whichever is lower (58 FR 
28736, 28746, May 14, 1993). These definitions apply to the terms 
``substantial production'' and ``substantial release'' as used in this 
preamble. (As explained in Unit III.C. of this preamble, all the 
chemical substances proposed for testing in this proposed rule are 
emitted into the atmosphere in the amount of 50 tons per year or more 
according to the TRI.) EPA also defined ``substantial human exposure'' 
as an annual exposure of 100,000 members of the general population, 
10,000 consumers, or 1,000 workers. Id.

                                      TSCA Section 4(a) Statutory Findings                                      
----------------------------------------------------------------------------------------------------------------
                                                                                           4(a)(1)(A)(ii)/(iii) 
          Chemical substance            4(a)(1)(A)(i) Finding    4(a)(1)(B)(i) Finding<SUP>a    and 4(a)(1)(B)(ii)/  
                                             is based on:             is based on:        (iii) Finding are for:
----------------------------------------------------------------------------------------------------------------
                                                                                                                
1,1'-Biphenyl--------------------------Reproductive toxicity----Substantial production:--Acute toxicity\6\,\9\--
(CAS No. 92-52-4)                      Respiratory toxicity      53.5 million lbs        Subchronic             
                                                                Substantial human         toxicity\5\,\9\       
                                                                 exposure: 20,351        Developmental          
                                                                 workers                  toxicity\2\           
                                                                Consumer exposure        Reproductive           
                                                                                          toxicity\1\           
                                                                                         Neurotoxicity\7\       
                                                                                         Immunotoxicity\7\      
                                                                                         Respiratory sensory    
                                                                                          irritation\7\         
----------------------------------------------------------------------------------------------------------------
Carbonyl Sulfide                       Oncogenicity             Substantial production:  Acute toxicity\6\      
(CAS No. 463-58-1)                     Neurotoxicity             production is at least  Subchronic toxicity\7\ 
                                                                 as much as              Developmental          
                                                                 environmental release    toxicity\7\           
                                                                 (produced as a          Reproductive           
                                                                 byproduct)               toxicity\5\,\6\       
                                                                Substantial              Neurotoxicity\6\,\7\   
                                                                 environmental release:  Oncogenicity\7\        
                                                                 16.7 million lbs        Immunotoxicity\7\      
                                                                                         Genetic toxicity\7\    
                                                                                         Respiratory sensory    
                                                                                          irritation\7\         
----------------------------------------------------------------------------------------------------------------
Chlorine                               Respiratory toxicity     Substantial production:  Acute toxicity\5\,\8\  
(CAS No. 7782-50-5)                                              22.3 billion lbs                               
                                                                Substantial human                               
                                                                 exposure: 170,000                              
                                                                 workers                                        
                                                                Consumer exposure                               
                                                                Substantial                                     
                                                                 environmental release:                         
                                                                 78,498 million lbs                             
----------------------------------------------------------------------------------------------------------------

[[Page 33191]]

                                                                                                                
Chlorobenzene                          Respiratory toxicity     Substantial production:  Acute toxicity\6\      
(CAS No. 108-90-7)                     Developmental toxicity    210 million lbs         Subchronic             
                                       Reproductive toxicity    Substantial human         toxicity\3\,\4\,\6\,\8
                                       Liver toxicity            exposure: 17,056         \                     
                                       Kidney toxicity           workers                 Neurotoxicity\7\       
                                       Neurotoxicity            General population       Immunotoxicity\6\,\7\  
                                                                Substantial                                     
                                                                 environmental release:                         
                                                                 2.58 million lbs                               
----------------------------------------------------------------------------------------------------------------
Chloroprene                            Respiratory toxicity     Substantial production:  Acute toxicity\3\,\6\  
(CAS No. 126-99-8)                     Reproductive toxicity     321 million lbs         Reproductive           
                                       Liver toxicity           Substantial human         toxicity\7\,\8\       
                                       Neurotoxicity             exposure: 17,749        Neurotoxicity\6\,\8\   
                                       Hematotoxicity            workers                 Immunotoxicity\7\      
                                       Developmental toxicity   General population       Respiratory sensory    
                                                                Substantial               irritation\7\         
                                                                 environmental release:                         
                                                                 1.7 million lbs                                
----------------------------------------------------------------------------------------------------------------
Cresols                                                                                                         
(CAS No. 1319-77-3)                                                                                             
mixture of 3 isomers:                                                                                           
                                                                                                                
ortho-isomer                                                                                                    
(CAS No. 95-48-7)                                                                                               
                                                                                                                
para-isomer                                                                                                     
(CAS No. 106-445)                                                                                               
                                       Respiratory toxicity     Substantial production:  Acute toxicity\8\      
meta-isomer                            Developmental toxicity    84.3 million lbs        Subchronic             
(CAS No. 108-39-4)                     Neurotoxicity            Substantial human         toxicity\5\,\8\       
                                                                 exposure: 132,742       Acute                  
                                                                 workers                  neurotoxicity\5\,\6\  
                                                                Consumer exposure        Immunotoxicity\6\,\7\  
                                                                General population       Respiratory sensory    
                                                                Substantial               irritation\7\         
                                                                 environmental release:                         
                                                                 1.5 million lbs                                
----------------------------------------------------------------------------------------------------------------
Diethanolamine                         Reproductive toxicity    Substantial production:  Acute toxicity\8\      
(CAS No. 111-42-2)                     Neurotoxicity             198 million lbs         Subchronic toxicity\5\ 
                                                                Substantial human        Developmental          
                                                                 exposure: 573,025        toxicity\6\           
                                                                 workers                 Reproductive           
                                                                Consumer exposure         toxicity\7\           
                                                                                         Neurotoxicity\5\,\6\,\7
                                                                                          \                     
                                                                                         Immunotoxicity\7\      
                                                                                         Respiratory sensory    
                                                                                          irritation\7\         
----------------------------------------------------------------------------------------------------------------
Ethylbenzene                           Developmental toxicity   Substantial production:  Acute toxicity\6\      
(CAS No. 100-41-4)                     Kidney toxicity           11.4 billion lbs        Developmental          
                                       Neurotoxicity            Substantial human         toxicity\2\           
                                                                 exposure: 80,726        Reproductive           
                                                                 workers                  toxicity\7\           
                                                                Consumer exposure        Neurotoxicity\6\,\7\   
                                                                General population       Immunotoxicity\6\,\7\  
                                                                Substantial              Respiratory sensory    
                                                                 environmental release:   irritation\7\         
                                                                 8.8 million lbs                                
----------------------------------------------------------------------------------------------------------------
Ethylene dichloride                    Oncogenicity             Substantial production:  Acute                  
(CAS No. 107-06-2)                     General systemic          14.3 billion lbs         toxicity\1\,\4\,\5\,\6
                                        toxicity                General population        \                     
                                                                Substantial human        Subchronic             
                                                                 exposure: 77,111         toxicity\4\,\5\,\8\   
                                                                 workers                 Developmental          
                                                                Consumer exposure         toxicity\2\           
                                                                Substantial              Reproductive           
                                                                 environmental release:   toxicity\9\           
                                                                 4 million lbs           Neurotoxicity\6\,\7\   
                                                                                         Respiratory sensory    
                                                                                          irritation\7\         
----------------------------------------------------------------------------------------------------------------
Ethylene glycol                                                 Substantial production:  Acute toxicity\7\      
(CAS No. 107-21-1)                                               7.2 billion lbs         Subchronic             
                                                                Substantial human         toxicity\4\,\6\       
                                                                 exposure: 1,133,792     Neurotoxicity\7\       
                                                                 workers                 Immunotoxicity\5\      
                                                                Consumer exposure        Respiratory sensory    
                                                                Substantial               irritation\7\         
                                                                 environmental release:                         
                                                                 17.5 million lbs                               
----------------------------------------------------------------------------------------------------------------
Hydrochloric acid                      Respiratory toxicity     Substantial production:  Acute toxicity\5\,\6\  
(CAS No. 7647-01-0)                                              5.75 billion lbs                               
                                                                Substantial human                               
                                                                 exposure: 1,131,879                            
                                                                 workers                                        
                                                                Consumer exposure                               
                                                                Substantial                                     
                                                                 environmental release:                         
                                                                 287.7 million lbs                              
----------------------------------------------------------------------------------------------------------------

[[Page 33192]]

                                                                                                                
Hydrogen fluoride                      Respiratory toxicity     Substantial production:  Acute                  
(CAS No. 7664-39-3)                    Liver toxicity            322 million lbs          toxicity\3\,\5\,\6\,\8
                                       Eye irritation           Substantial human         \                     
                                                                 exposure: 182,589       Subchronic             
                                                                 workers                  toxicity\8\,\10\      
                                                                Substantial              Developmental          
                                                                 environmental release:   toxicity\7\           
                                                                 9.2 million lbs         Reproductive           
                                                                                          toxicity\7\           
                                                                                         Neurotoxicity\7\       
                                                                                         Immunotoxicity\7\      
                                                                                         Respiratory sensory    
                                                                                          irritation\7\         
----------------------------------------------------------------------------------------------------------------
Maleic anhydride                       Respiratory toxicity     Substantial production:  Acute toxicity\7\      
(CAS No. 108-31-6)                     Eye irritation            382 million lbs         Developmental          
                                                                Substantial human         toxicity\2\           
                                                                 exposure: 37,897        Neurotoxicity\7\       
                                                                 workers                 Oncogenicity\5\,\6\    
                                                                                         Immunotoxicity\7\      
                                                                                         Respiratory sensory    
                                                                                          irritation\7\         
----------------------------------------------------------------------------------------------------------------
Methyl isobutyl ketone                 Developmental toxicity   Substantial production:  Acute toxicity\5\,\6\  
(CAS No. 108-10-1)                     Neurotoxicity             175 million lbs         Reproductive           
                                                                Substantial human         toxicity\7\           
                                                                 exposure: 467,763       Immunotoxicity\7\      
                                                                 workers                 Respiratory sensory    
                                                                Consumer exposure         irritation            
                                                                General population                              
                                                                Substantial                                     
                                                                 environmental release:                         
                                                                 27.7 million lbs                               
----------------------------------------------------------------------------------------------------------------
Methyl methacrylate                    Respiratory toxicity     Substantial production:  Acute                  
(CAS No. 80-62-6)                      Liver toxicity            1,200 million lbs        toxicity\1\,\3\,\4\,\6
                                       Kidney toxicity          Substantial human         \                     
                                       Neurotoxicity             exposure: 120,788       Developmental          
                                                                 workers                  toxicity\2\           
                                                                Consumer exposure        Reproductive           
                                                                Substantial               toxicity\7\           
                                                                 environmental release:  Neurotoxicity\3\,\4\,\6
                                                                 2.8 million lbs          \,\8\                 
                                                                                         Immunotoxicity\6\,\7\  
                                                                                         Respiratory sensory    
                                                                                          irritation\7\         
----------------------------------------------------------------------------------------------------------------
Naphthalene                            Respiratory toxicity     Substantial production:  Acute toxicity\5\,\6\  
(CAS No. 91-20-3)                      Neurotoxicity             235 million lbs         Reproductive           
                                                                Substantial human         toxicity\5\,\6\,\7\   
                                                                 exposure: 23,092        Immunotoxicity\6\,\7\  
                                                                 workers                 Respiratory sensory    
                                                                Consumer exposure         irritation\7\         
                                                                General population                              
                                                                Substantial                                     
                                                                 environmental release:                         
                                                                 2.8 million lbs                                
----------------------------------------------------------------------------------------------------------------
Phenol<SUP>b                                Respiratory toxicity     Substantial production:  Acute                  
(CAS No. 108-95-2)                                               3.9 billion lbs          toxicity\4\,\5\,\8\   
                                                                Substantial human        Immunotoxicity\4\,\5\,\
                                                                 exposure: 192,739        6\                    
                                                                 workers                 Respiratory sensory    
                                                                Consumer exposure         irritation            
                                                                General population                              
                                                                Substantial                                     
                                                                 environmental release:                         
                                                                 10 million lbs                                 
----------------------------------------------------------------------------------------------------------------
Phthalic anhydride                     Respiratory              Substantial production:  Acute toxicity\6\,\7\  
(CAS No. 85-44-9)                       sensitization            874 million lbs         Subchronic toxicity\7\ 
                                                                Substantial human        Developmental          
                                                                 exposure: 62,644         toxicity\5\,\8\       
                                                                 workers                 Reproductive           
                                                                                          toxicity\7\           
                                                                                         Neurotoxicity\7\       
                                                                                         Oncogenicity\5\        
                                                                                         Immunotoxicity\7\      
                                                                                         Respiratory sensory    
                                                                                          irritation\7\         
----------------------------------------------------------------------------------------------------------------
1,2,4-Trichlorobenzene                 Oncogenicity             Substantial production:  Acute                  
(CAS No. 120-82-1)                     Developmental toxicity    CBI                      toxicity\1\,\3\,\6\   
                                                                Substantial human        Developmental          
                                                                 exposure: 4,032          toxicity\1\,\5\,\6\   
                                                                 workers                 Neurotoxicity\6\       
                                                                General population       Immunotoxicity\7\      
                                                                                         Respiratory sensory    
                                                                                          irritation\7\         
----------------------------------------------------------------------------------------------------------------

[[Page 33193]]

                                                                                                                
1,1,2-Trichloroethane                  Oncogenicity             Substantial production:  Acute toxicity\7\      
(CAS No. 79-00-5)                      Liver toxicity            estimated - 210         Subchronic toxicity\7\ 
                                       Kidney toxicity           million lbs             Developmental          
                                       Neurotoxicity            Substantial human         toxicity\5\,\6\       
                                                                 exposure: 1,036         Reproductive           
                                                                 workers                  toxicity\7\           
                                                                General population       Neurotoxicity\6\,\7\   
                                                                                         Oncogenicity\5\        
                                                                                         In vivo cytogenicity\7\
                                                                                         Immunotoxicity\6\      
                                                                                         Respiratory sensory    
                                                                                          irritation\7\         
----------------------------------------------------------------------------------------------------------------
Vinylidene chloride                    Oncogenicity             Substantial production:  Acute toxicity\5\,\6\  
(CAS No. 75-35-4)                      Respiratory toxicity      230 million lbs         Neurotoxicity\7\       
                                       Developmental toxicity   Substantial human        Respiratory sensory    
                                       Liver toxicity            exposure: 2,675          irritation\7\         
                                       Kidney toxicity           workers                                        
                                                                Consumer exposure                               
----------------------------------------------------------------------------------------------------------------
\1\ Too few animals were tested.                                                                                
\2\ Only one species was adequately tested.                                                                     
\3\ Only one sex was tested.                                                                                    
\4\ Too few exposure levels were tested.                                                                        
\5\ Inadequate exposure duration, schedule, or route.                                                           
\6\ Only limited endpoints were assessed.                                                                       
\7\ No study addressing the specific endpoint was found.                                                        
\8\ Insufficient reporting of data to make the study useful.                                                    
\9\ No no-observed-adverse-effect level (NOAEL) was identified.                                                 
\10\ No lowest-observed-adverse-effect level (LOAEL) was identified.                                            


Notes to table:
    a ``B'' findings are based on Ref. (10). It should be noted that 
all HAPs meet the 50 tons of emissions per year selection criteria 
discussed in Unit III.C. of this preamble.
    b Findings made in 58 FR 61654, 61659-60, November 22, 1993.

VI. Economic Analysis of the Proposed Rule

    EPA has prepared and placed in the record for this proposed rule an 
economic analysis that evaluates the potential for significant economic 
impacts as a result of the testing proposed in this notice. The total 
cost of this proposed rule is estimated to range up to $41.4 million. 
The total cost of testing for each chemical substance has been 
annualized and compared with annual revenues (defined as the product of 
sales price and total supply) as an indication of potential economic 
impact. Annualized test costs, calculated over 15 years using a 7% 
discount rate, represent the equivalent constant costs that would have 
to be recouped each year of the payback period to finance the testing 
expenditure in the first year. Annualized test costs are then divided 
by the total supply of the chemical substance to derive the annualized 
unit test costs. The percent price impact is calculated by dividing the 
annualized unit test costs by the sales price and multiplying by 100.
    The upper-bound estimated total costs of testing (including both 
laboratory costs and administrative costs), annualized tests costs, and 
price impact for the chemicals in this proposed rule are as follows:

--------------------------------------------------------------------------------------------------------------------------------------------------------
                      Chemical Substances                            Total test cost ($)        Annualized test cost ($)          Price impact (%)      
--------------------------------------------------------------------------------------------------------------------------------------------------------
1,1'-Biphenyl                                                                      2,213,900                       243,074                          0.64
                                                                                                                                                        
Carbonyl sulfide                                                                   5,509,163                       609,876                            NA
                                                                                                                                                        
Chlorine                                                                              85,400                         9,376                        0.0003
                                                                                                                                                        
Chlorobenzene                                                                        972,900                       106,819                         0.098
                                                                                                                                                        
Chloroprene                                                                        1,603,488                       176,054                         0.076
                                                                                                                                                        
Cresols (all 3 isomers)                                                            2,139,600                       234,917                          0.39
                                                                                                                                                        
Diethanolamine                                                                     2,327,838                       255,584                          0.23
                                                                                                                                                        
Ethylbenzene                                                                       1,732,050                       190,170                         0.013
                                                                                                                                                        
Ethylene dichloride                                                                2,007,325                       220,393                        0.0071
                                                                                                                                                        
Ethylene glycol                                                                      986,638                       108,327                        0.0097
                                                                                                                                                        
Hydrochloric acid                                                                     85,400                         9,376                        0.0040
                                                                                                                                                        
Hydrogen fluoride                                                                  2,135,888                       234,509                         0.094
                                                                                                                                                        
Maleic anhydride                                                                   4,148,588                       454,834                          0.25
                                                                                                                                                        
Methyl isobutyl ketone                                                             1,228,913                       134,928                          0.16
                                                                                                                                                        
Methyl methacrylate                                                                1,732,050                       190,170                         0.023
                                                                                                                                                        
Naphthalene                                                                        1,242,650                       136,436                          0.16
                                                                                                                                                        
Phenol                                                                                85,400                         9,376                        0.0010
                                                                                                                                                        

[[Page 33194]]

                                                                                                                                                        
Phthalic anhydride                                                                 5,650,338                       620,377                          0.21
                                                                                                                                                        
1,2,4-Trichlorobenzene                                                               963,163                       105,750                           CBI
                                                                                                                                                        
1,1,2-Trichloroethane                                                              3,837,900                       421,381                          0.41
                                                                                                                                                        
Vinylidene chloride                                                                  708,700                        77,811                          0.12
--------------------------------------------------------------------------------------------------------------------------------------------------------


    Note: The table shows the maximum costs and impacts estimated by 
EPA. The full range of estimates is given in the economic analysis 
document placed in the record for this proposed rule.
    EPA believes, on the basis of these calculations, that the proposed 
testing of the HAPs presents a low potential for adverse economic 
impact. Because these chemical substances have relatively large 
production volumes, with the exception of carbonyl sulfide (to which 
this methodology does not apply) the annualized costs of testing, 
expressed as a percentage of annual revenue, are very small--ranging 
from 0.0003% to 0.64%. Costs of testing are therefore found to be 
insignificant relative to revenues for these chemical substances.

VII. Availability of Test Facilities and Personnel

    Although earlier studies indicated that test facilities and 
personnel were available to perform the testing specified in this 
proposed rule (Ref. 18), the impact of this rule combined with other 
testing requirements may exceed capacity for inhalation testing 
facilities in the short term. While EPA believes that over the longer 
term, additional inhalation facilities will become available, any 
short-term effects can be dealt with by adjusting study due dates in 
response to comments on this rule or in response to a request for 
modification of reporting deadlines.

VIII. Public Meeting

    EPA will hold a public meeting in Washington, DC prior to the close 
of the comment period. Announcemment of this meeting will be published 
in the Federal Register. If requested, EPA will hold an additional 
public meeting in Washington, DC.

IX. Comments Containing Confidential Business Information

    All comments will be placed in the public version of the rulemaking 
record unless they are clearly labeled as containing information 
claimed as CBI when they are submitted. CBI claims will be deemed to 
have been waived if they are not made at the time of submission of the 
document containing the information claimed as CBI, and such document 
may be made public with no further notice to the submitter. While a 
part of the rulemaking record, comments claimed as CBI will be treated 
in accordance with 40 CFR part 2. A sanitized version of all comments 
containing information claimed as CBI must be submitted to EPA for 
inclusion in the public version of the rulemaking record.
    It is the responsibility of the submitter to comply with 40 CFR 
part 2 so that all materials claimed as CBI may be properly protected. 
This includes, but is not limited to, clearly indicating on the face of 
the revelant section of the comment (as well as on any revelant 
associated correspondence) that information claimed as CBI is included 
and marking ``CONFIDENTIAL,'' ``TSCA CBI,'' or similar designation on 
the face of each section of any document or attachment in the comment 
that contains information claimed as CBI. Should putatively private 
information be put into the public file because of the submitter's 
failure to clearly claim and designate its confidential claim on the 
face of the comment, EPA will presume any such information that has 
been in the public file for more than 30 days to be in the public 
domain.

X. Rulemaking Record

    EPA has established a record for this rulemaking (docket number 
OPPTS-42187) (including comments and data submitted electronically). 
This record contains the basic information considered by EPA in 
developing this proposal and appropriate Federal Register notices. EPA 
will supplement this record as necessary.
    A public version of this record, including printed, paper versions 
of electronic comments, which does not include any information claimed 
as CBI is available for inspection from 12 noon to 4 p.m., Monday 
through Friday, except legal holidays. The public record is located in 
the TSCA Nonconfidential Information Center, Rm. NE-B607, 401 M St., 
SW., Washington, DC 20460.
    Comments in electronic form may be submitted directly to EPA at:
    <a href="/cdn-cgi/l/email-protection#0f616c666c4f6a7f6e626e6663216a7f6e21686079"><span class="__cf_email__" data-cfemail="610f020802210411000c00080d4f0411004f060e17">[email protected]</span></a>
    Comments in electronic form must be submitted in an ASCII file 
avoiding the use of special characters and any form of encryption.
    The official record for this rulemaking, as well as the public 
version, will be kept in paper form. Accordingly, EPA will transfer all 
comments received electronically into printed, paper form as they are 
received and will place the paper copies in the official rulemaking 
record which will also include all comments submitted directly in 
writing.
    The record includes the following information.

A. Supporting Documentation

    (1) Federal Register notices/EPA documents pertaining to this 
proposed rule consisting of:
    (a) ``TSCA Interagency Testing Committee; Initial Report to the 
Administrator, Environmental Protection Agency'' (42 FR 55026, October 
12, 1977).
    (b) ``Chloromethane and Chlorinated Benzenes Proposed Test Rule; 
Amendment to Proposed Health Effects Standards'' (45 FR 48524, July 18, 
1980).
    (c) ``Dichloromethane, Nitrobenzene and 1,1,1-Trichloroethane; 
Proposed Test Rule'' (46 FR 30300, June 5, 1981).
    (d) ``Tenth Report of the Interagency Testing Committee to the 
Administrator; Receipt of Report and Request for Comments Regarding 
Priority List of Chemicals'' (47 FR 22585, May 12, 1982).
    (e) ``Methyl Isobutyl Ketone and Methyl Ethyl Ketone; Response to 
the Interagency Testing Committee'' (47 FR 58025, December 29, 1982).
    (f) ``Toxic Substances Control Act; Data Reimbursement'' (48 FR 
31786, July 11, 1983).
    (g) ``Cresols; Proposed Test Rule'' (48 FR 31813, July 11, 1983).
    (h) ``Methyl Isobutyl Ketone and Methyl Ethyl Ketone Decision to 
Adopt Negotiated Testing Program'' (48 FR 44905, September 30, 1983).
    (i) ``Toxic Substances; Biphenyl; Test Rule'' (50 FR 37182, 
September 12, 1985).
    (j) ``Cresols; Testing Requirements'' (51 FR 15771, April 28, 
1986).
    (k) ``Chlorinated Benzenes; Final Test Rule'' (51 FR 24657, July 8, 
1986).
    (l) ``Toxic Substances, 1,1,-Dichloroethylene; Proposed Test Rule'' 
(51 FR 28840, August 12, 1986).
    (m) ``Guidelines for Carcinogen Risk Assessment'' (51 FR 33992 
(September 24, 1986).

[[Page 33195]]

    (n) ``Office of Solid Waste Chemicals; Final Test Rule'' (53 FR 
22300, June 15, 1988).
    (o) ``Toxic Substances Control Act (TSCA); Good Laboratory Practice 
Standards'' (54 FR 34034, August 17, 1989).
    (p) ``Metabolism and Pharmacokinetics Test Guideline'' (56 FR 
32537, July 17, 1991).
    (q) ``Guidelines for Developmental Toxicity Risk Assessment'' (56 
FR 63798, December 5, 1991).
    (r) ``TSCA section 4(a)(1)(B) Final Statement of Policy; Criteria 
for Evaluating Substantial Production, Substantial Release, and 
Substantial or Significant Human Exposure'' (58 FR 28736, May 14, 
1993).
    (s) ``Office of Water Chemicals; Final Test Rule'' (58 FR 59667, 
November 10, 1993).
    (t) ``Acetophenone, Phenol, N,N-Dimethylaniline, Ethyl Acetate, and 
2,6-Dimethylphenol; Proposes Test Rule, Notice of Opportunity to 
Initiate Negotiations for TSCA Section 4 Testing Consent Agreements'' 
(58 FR 61654, November 22, 1993).
    (u) ``Testing Consent Orders for Acetone, n-Amyl Acetate, n-Butyl 
Acetate, Ethyl Acetate, Isobutyl Alcohol, Methyl Isobutyl Ketone, and 
Tetrahyrofuran'' (60 FR 4514, January 23, 1995).
    (v) ``Executive Order 12866 of September 30, 1993; Regulatory 
Planning and Review'' (58 FR 51735, October 4, 1993).
    (w) ``Executive Order 12898 of February 11, 1994; Federal Actions 
to Address Environmental Justice in Minority Populations and Low-Income 
Populations'' (59 FR 7629, February 16, 1994).
    (x) ``Guidelines for Reproductive Toxicity Risk Assessment'' (Pub. 
No. EPA/600/AP-94/001, February 1994).
    (2) OPPTS test guidelines used in this proposed rule:
    (a) Acute Inhalation Toxicity with Histopathology, OPPTS 870.1350, 
EPA Pub. No. 712-C-96-291, June 1996;
    (b) Subchronic Inhalation Toxicity, OPPTS 870.3465, EPA Pub. No. 
712-C-96-204, June 1996;
    (c) Inhalation Developmental Toxicity Study, OPPTS 870-3600, EPA 
Pub. No. 712-C-96-206, June 1996;
    (d) Reproduction and Fertility Effects, OPPTS 870.3800, EPA Pub. 
No. 712-C-96-208, February 1996;
    (e) Carcinogenicity, OPPTS 870.4200, EPA Pub. No. 712-C-96-211, 
June 1996;
    (f) Escherichia coli WP2 and WP2 uvrA Reverse Mutation Assays, 
OPPTS 870.5100, EPA Pub. No. 712-C-96-247, June 1996;
    (g) Detection of Gene Mutations in Somatic Cells in Culture, OPPTS 
870.5300, EPA Pub. No. 712-C-96-221, June 1996;
    (h) In Vivo Mammalian Cytogenetics Tests: Bone Marrow Chromosomal 
Analysis, OPPTS 870.5385, EPA Pub. No. 712-C-96-225, June 1996;
    (i) In Vivo Mammalian Cytogenetics Tests: Erythrocyte Micronucleus 
Assay, OPPTS 870.5395, EPA Pub. No. 712-C-96-226, June 1996;
    (j) Neurotoxicity Screening Battery, OPPTS 870.6200, EPA Pub. No. 
712-C-96-238, June 1996; and
    (k) Immunotoxicity, OPPTS 870.7800, EPA Pub. No. 712-C-96-351, June 
1996.
    (3) Technical Support Documents consisting of:
    (a) TSCA Section 4 Findings for 21 Hazardous Air Pollutants.
    (b) Exposure Profiles for HAPs--Group 1.
    (c) Summary Tables on the Health Effects Data for Hazardous Air 
Pollutants (HAPs)--Group 1.
    (d) Economic Analysis of the Impact of the Test Rule.
    (4) Communications consisting of:
    (a) Written letters and memoranda.
    (b) Contact reports of telephone conversations.
    (c) Meeting summaries.

B. References

    (1) U.S. Environmental Protection Agency. ``Methods for derivation 
of inhalation reference concentrations and application of inhalation 
dosimetry.'' p. xxviii. Prepared by the Office of Health and 
Environmental Assessment, Washington, DC. EPA/600/8-90/066F (1994).
    (2) Letter from John F. Martonik, OSHA, to Susan B. Hazen, EPA, May 
31, 1995.
    (3) Letter from Val Schaeffer, CPSC, to Joe Carra, EPA, June 2, 
1995.
    (4) Orme-Zavaleta, J. ``OMB Question-Reply.'' Memorandum to Vicki 
Dellarco. May 9, 1996.
    (5) NAS. National Academy of Sciences, Washington DC, ``Science and 
Judgment in Risk Assessment'' pp. 154, 157, 265 (1994).
    (6) Siegel-Scott, C. ``Slope factors for hazardous air 
pollutants.'' Memorandum to Vicki Dellarco. September 7, 1994.
    (7) Shoaf, C.R. ``Clean Air Act chemicals with adequate databases 
for development of RfC's.'' Memorandum to Vicki Dellarco. September 20, 
1994.
    (8) U.S. Environmental Protection Agency. Health assessment 
document for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and related 
compounds, Vol. III of III, pp. 9-48 to 9-50. Prepared by the Office of 
Health and Environmental Assessment, Washington, DC. EPA/600/PB-92/001C 
(1994).
    (9) Francis, E.Z., and Kimmel, G.A. ``Proceedings of the workshop 
on one versus two-generation reproductive effects studies.'' Journal of 
the American College of Toxicology. 7:911-925 (1988).
    (10) Lai, D.Y., Baetcke, K.P., Vu, V.T., Cotruvo, J.A., and Eustis, 
S.L. ``Evaluation of reduced protocols for carcinogenicity testing of 
chemicals: Report of a joint EPA/NIEHS workshop.'' Regulatory 
Toxicology and Pharmacology. 19:183-201 (1994).
    (11) Syracuse Research Corporation. ``Summary tables on the health 
effects data for hazardous air pollutants (HARs)-Group 1.'' Syracuse, 
New York. (1995a).
    (12) Syracuse Research Corporation. ``Exposure profiles for HAPs-
Group 1.'' Syracuse, New York. (1995b).
    (13) Valcovic, L.R. Memorandum: ``Genetic toxicity evaluation of 
HAPs'' to Vicki Dellarco, July 14, 1994.
    (14) Waters, M.D., Stack, H.F., and Jackson, M.A. 1990. ``Genetic 
Activity Profiles of 110 Hazardous Air Pollutants Listed Under Title 
III of the Clean Air Act, as amended.'' U. S. Environmental Protection 
Agency. Internal Report. October 30, (1990).
    (15) Gerrity, T.R., and Henry, C.J. ed. Principles of Route-to-
Route Extrapolation for Risk Assessment. pp 1-12. Elsevier Science 
Publishing Co., Inc. New York, N.Y. (1990).
    (16) U.S. Environmental Protection Agency. ``Hazardous Air 
Pollutants: Profiles of Non-Cancer Toxicity from Inhalation 
Exposures.'' Washington, DC. EPA/600/R-93/142. September 1993.
    (17) Luster, M.I., Portier, C., Pait, D.G., White, K.L., Genings, 
C., Munson, A.E., and Rosenthal, G.J. ``Risk assessment in 
immunotoxicology. I. Sensitivity and predictability of immune tests.'' 
Fundamental and Applied Toxicology. 18:200-210 (1992).
    (18) U.S. Environmental Protection Agency. ``EPA census of the 
toxicological testing industry final report.'' (1990).

XI. Regulatory Assessment Requirements

A. Executive Order 12866

    Pursuant to Executive Order 12866 (58 FR 51735, October 4, 1993), 
it has been determined by OMB that this is a ``significant regulatory 
action.'' OMB was concerned that the amount of inhalation testing 
required by this rule may exceed the capacity of the testing industry, 
at least in the short run. This action was submitted to OMB for review, 
and any comments or changes made during that review have been 
documented in the public record.
    In addition, EPA has prepared an economic analysis of the impact of 
this

[[Page 33196]]

action, which is contained in a document entitled ``Test Rule Support 
for 21 Hazardous Air Pollutants.'' This document is available as a part 
of the public record at the address listed in Unit X of this preamble 
and is briefly summarized in Unit VI of this preamble.

B. Regulatory Flexibility Act

    Under the Regulatory Flexibility Act (5 U.S.C. 601 et seq.), EPA 
has determined that this test rule, if promulgated, would not have a 
significant impact on small businesses. EPA has identified the entities 
that currently manufacture or import the chemical substances required 
to be tested under this proposed rule and examined the practices that 
industry uses in carrying out chemical testing in response to EPA test 
rules. EPA believes that: (1) small businesses would not be expected to 
perform testing themselves, or to participate in the organization of 
the testing effort, because health effects testing of chemical 
substances is generally carried out by consortia of the large 
manufacturers or importers of the chemical substances; (2) small 
businesses would experience only very minor costs, if any, in securing 
exemption from testing requirements because exemption request 
requirements, described at 40 CFR 790.82, are minimal--particularly 
when, as in this proposed rule, EPA is not requiring exemption 
applicants to submit equivalence data (see Unit IV.F of this 
preamble)--and EPA does not charge a fee for filing such requests; and 
(3) small businesses are unlikely to be affected by reimbursement 
requirements because under the reimbursement rules (at 40 CFR 791.40 
through 791.52), manufacturers or importers with a significant share of 
production or importation are the entities that must share testing 
costs under the reimbursement rules, and small businesses generally do 
not manufacture or import a significant portion of high-volume chemical 
substances.

C. Paperwork Reduction Act

    OMB has approved the information collection requirements contained 
in this proposed rule under the provisions of the Paperwork Reduction 
Act, 44 U.S.C. 3501 et seq., and has assigned OMB control number 2070-
0033.
    The public reporting burden for this collection of information is 
estimated to average approximately the following number of hours per 
response for the chemicals listed below, including time for reviewing 
instructions, searching existing data sources, gathering and 
maintaining the data needed, and completing and reviewing the 
collection of information.

------------------------------------------------------------------------
                                                                Total   
                     Chemical substance                         burden  
------------------------------------------------------------------------
1,1'-Biphenyl                                                     20,620
Carbonyl sulfide                                                  47,644
Chlorine                                                             693
Chlorobenzene                                                      7,707
Chloroprene                                                       13,039
                                                                        
Cresols (all 3 isomers)                                            6,048
Diethanolamine                                                    21,826
Ethylbenzene                                                      14,400
Ethylene dichloride                                               16,707
Ethylene glycol                                                    7,816
                                                                        
Hydrochloric acid                                                    693
Hydrogen fluoride                                                 18,068
Maleic anhydride                                                  35,849
Methyl isobutyl ketone                                            10,471
Methyl methacrylate                                               14,400
                                                                        
Naphthalene                                                       10,580
Phenol                                                               693
Phthalic anhydride                                                51,032
1,2,4-Trichlorobenzene                                             8,091
1,1,2-Trichloroethane                                             33,133
Vinylidene chloride                                                5,439
------------------------------------------------------------------------

    The total public reporting burden is estimated to be 357,045 hours 
for all responses. The overall average per chemical is 15,524 hours.
    Burden means the total time, effort, or financial resources 
expended by persons to generate, maintain, retain, or disclose or 
provide information to or for a Federal agency. This includes the time 
needed to review instructions; develop, acquire, install, and utilize 
technology and systems for the purposes of collecting, validating, and 
verifying information, processing and maintaining information, and 
disclosing and providing information; adjust the existing ways to 
comply with any previously applicable instructions and requirements; 
train personnel to be able to respond to a collection of information; 
search data sources; complete and review the collection of information; 
and transmit or otherwise disclose the information.
    An Agency may not conduct or sponsor, and a person is not required 
to respond to a collection of information unless it displays a 
currently valid OMB control number. The OMB control numbers for EPA's 
regulations are listed in 40 CFR part 9 and 48 CFR chapter 15.
    Comments are requested on the Agency's need for this information, 
the accuracy of the provided burden estimates, and any suggested 
methods for minimizing respondent burden, including through the use of 
automated collection techniques. Send comments on the ICR to Sandy 
Farmer, OPPE Regulatory Information Division; U.S. Environmental 
Protection Agency (2136), 401 M St., SW., Washington, DC 20460, (202) 
260-2740, or electronically by sending an e-mail message to: 
<a href="/cdn-cgi/l/email-protection#197f786b747c6b376a78777d60597c697874787075377c6978377e766f"><span class="__cf_email__" data-cfemail="a2c4c3d0cfc7d08cd1c3ccc6dbe2c7d2c3cfc3cbce8cc7d2c38cc5cdd4">[email protected]</span></a>. Send a copy of these comments to the 
Office of Information and Regulatory Affairs, Office of Management and 
Budget, 725 17th St., NW., Washington, DC 20503, marked ``Attention: 
Desk Officer for EPA.'' Please remember to include the ICR number in 
any correspondence. The final rule will respond to any comments on the 
information collection requirements contained in this proposal.

D. Unfunded Mandates Reform Act and Executive Order 12875

    Pursuant to Title II of the Unfunded Mandates Reform Act of 1995 
(UMRA) (Pub. L. 104-4), EPA has determined that this action does not 
contain a Federal mandate that may result in expenditures of $100 
million or more for State, local, and tribal governments, in the 
aggregate, or the private sector in any one year. (The analysis of the 
costs associated with this action is referenced in Unit XI.A. of this 
preamble.) Therefore, this action is not subject to the requirements of 
sections 202 and 205 of the UMRA.

E. Executive Order 12898

    Pursuant to Executive Order 12898 (59 FR 7629, February 16, 1994), 
entitled ``Federal Actions to Address Environmental Justice in Minority 
Populations and Low-Income Populations,'' the Agency has considered 
environmental justice-related issues with regard to the potential 
impacts of this action on the environmental and health conditions in 
low-income and minority communities. Because many sources of HAP 
emissions are located near populations of lower socioeconomic status 
and with a higher proportion of minorities, the improved health 
database that will be generated by this action will help to protect 
these individuals and communities.

List of Subjects in 40 CFR Part 799

    Environmental protection, Chemicals, Hazardous substances, and 
Reporting and recordkeeping requirements.

    Dated: June 20, 1996.

Lynn R. Goldman,
Assistant Administrator for Prevention, Pesticides and Toxic 
Substances.

    Therefore, it is proposed that 40 CFR, chapter I, subchapter R, be 
amended as follows:

[[Page 33197]]

PART 799--[AMENDED]

    3. The authority citation for part 799 would continue to read as 
follows:

    Authority: 15 U.S.C. 2603, 2611, 2625.

    4. By adding Sec. 799.5053 to Subpart D of part 799 to read as 
follows:


Sec. 799.5053  Chemical testing requirements for hazardous air 
pollutants.

    (a) General testing provisions--(1) Identification of test 
substances. Table 1 in paragraph (a)(5) of this section identifies 
those chemical substances that shall be tested in accordance with this 
section. The purity of each test substance shall be 97 percent or 
greater unless otherwise specified.
    (2) Persons required to submit study plans, conduct tests, and 
submit data. All persons who manufacture (including those who import 
the substance or manufacture it as a byproduct) or intend to 
manufacture one or more of the substances listed in table 1 after the 
effective date listed in table 1 until the end of the reimbursement 
period shall submit letters of intent to conduct testing, submit study 
plans, conduct tests and submit data, or submit exemption applications, 
as specified in this section, subpart A of this part and parts 790 and 
792 of this chapter. Persons who manufacture or process these 
substances only as an impurity are not subject to these requirements. 
As explained in part 790 of this chapter, processors, small-quantity 
manufacturers, and manufacturers of small quantities of these 
substances solely for research and development purposes would become 
subject to these requirements only after notification in the Federal 
Register that no manufacturer had notified EPA of its intent to conduct 
testing.
    (3) Applicability of test guidelines. The guidelines and other test 
methods cited in table 1 in paragraph (a)(5) of this section are 
referenced here as they exist on the effective date listed in table 1 
for that specific test. Testing shall be conducted in accordance with 
the designated Series 870--Health Effects Test Guidelines and other 
test methods. This incorporation by reference was approved by the 
Director of the Federal Register in accordance with 5 U.S.C. 552(a) and 
1 CFR part 51. Copies may be obtained from the Public Docket and 
Freedom of Information Section, Field Operations Division (7506C), 
Office of Pesticide Programs, Environmental Protection Agency, 401 M 
St., SW., Washington, DC 20360. Copies may be inspected at the above 
address or at the Office of the Federal Register, 800 North Capitol 
Street, NW., suite 700, Washington, DC.
    (4) Interim reporting requirements. All testing requirements in 
this section are subject to the submission of interim progress reports 
every 6 months beginning 6 months after the effective date for any 
specific test listed in table 1 in paragraph (a)(5) of this section. 
The date for the submission of final reports is specified as the number 
of months after the effective date for the specific test listed in 
table 1.
    (5) Testing and reporting requirements. The substances identified 
by CAS Registry number and chemical name in the following table 1 shall 
be tested in accordance with the designated OPPTS Harmonized Guideline 
testing requirements and any additional requirements and limitations 
specified in the ``Specific requirements under this section'' column of 
table 1. The numbers and letters in this column refer to the specific 
requirements set forth in paragraph (b) of this section. Final reports 
shall be submitted by the deadlines indicated as the number of months 
after the effective date shown in table 1.

                                                     Table 1                                                    
----------------------------------------------------------------------------------------------------------------
                                                                            Specific                            
                                Chemical substance/  OPPTS harmonized     requirements       Final     Effective
            CAS No.              required testing       guidelines         under this       report       date   
                                                                            section                             
----------------------------------------------------------------------------------------------------------------
                                                                                                                
                                                                                                                
75-35-4-------------------------Vinylidene----------  -----------------  -----------------  ----------  --------
                                 chloride:                                                                      
                                Acute               870.1350           (b)(2)             21 mo                 
                                Neurotoxicity       870.6200           (b)(1)(ii)(A),     21 mo                 
                                                                        (b)(1)(iii)(A),                         
                                                                        (b)(1)(iii)(B)                          
                                                                                                                
----------------------------------------------------------------------------------------------------------------
79-00-5                         1,1,2-                                                                          
                                 Trichloroethane:                                                               
                                Acute               870.1350           (b)(2)             21 mo                 
                                Subchronic          870.3465           (b)(3)             18 mo                 
                                Developmental       870.3600                              12 mo                 
                                Reproductive        870.3800           (b)(1)(ii)(A),     29 mo                 
                                                                        (b)(5)                                  
                                Neurotoxicity       870.6200           (b)(1)(ii)(A),     21 mo                 
                                                                        (b)(1)(iii)(A),                         
                                                                        (b)(1)(iii)(B)                          
                                Carcinogenicity     870.4200           (b)(1)(i)(D),      60 mo                 
                                                                        (b)(1)(ii)(A)                           
                                In vivo             870.5385 or        (b)(1)(ii)(A)      14 mo                 
                                 cytogenetics        870.5395                                                   
                                Immunotoxicity      870.7800           (b)(1)(ii)(A)      18 mo                 
                                                                                                                
----------------------------------------------------------------------------------------------------------------
80-62-6                         Methyl                                                                          
                                 methacrylate:                                                                  
                                Acute               870.1350           (b)(2)             21 mo                 
                                Developmental       870.3600           (b)(1)(i)(A)       12 mo                 
                                Reproductive        870.3800           (b)(1)(ii)(A),     29 mo                 
                                                                        (b)(5)                                  
                                Neurotoxicity       870.6200           (b)(1)(ii)(A),     21 mo                 
                                                                        (b)(1)(iii)(A),                         
                                                                        (b)(1)(iii)(B)                          
                                Immunotoxicity      870.7800           (b)(1)(ii)(A)      21 mo                 
                                                                                                                
----------------------------------------------------------------------------------------------------------------
85-44-9                         Phthalic                                                                        
                                 anhydride:                                                                     
                                Acute               870.1350           (b)(2)             21 mo                 
                                Subchronic          870.3465           (b)(1)(ii)(B),     18 mo                 
                                                                        (b)(3)                                  
                                Developmental       870.3600           (b)(1)(ii)(B)      12 mo                 
                                Reproductive        870.3800           (b)(1)(ii)(B),     29 mo                 
                                                                        (b)(5)                                  
                                Neurotoxicity       870.6200           (b)(1)(ii)(B),     21 mo                 
                                                                        (b)(1)(iii)(A),                         
                                                                        (b)(1)(iii)(B)                          
                                Carcinogenicity     870.4200           (b)(1)(ii)(B)      60 mo                 

[[Page 33198]]

                                                                                                                
                                Immunotoxicity      870.7800           (b)(1)(ii)(B)      18 mo                 
                                                                                                                
----------------------------------------------------------------------------------------------------------------
91-20-3                         Naphthalene:                                                                    
                                Acute               870.1350           (b)(2)             21 mo                 
                                Reproductive        870.3800           (b)(1)(ii)(A),     29 mo                 
                                                                        (b)(5)                                  
                                Immunotoxicity      870.7800           (b)(1)(ii)(A)      21 mo                 
                                                                                                                
----------------------------------------------------------------------------------------------------------------
92-52-4                         1,1'-Biphenyl:                                                                  
                                Acute               870.1350           (b)(2)             21 mo                 
                                Subchronic          870.3465           (b)(1)(ii)(B),     18 mo                 
                                                                        (b)(3)                                  
                                Developmental       870.3600           (b)(1)(i)(A),      12 mo                 
                                                                        (b)(1)(ii)(B)                           
                                Reproductive        870.3800           (b)(1)(ii)(B),     29 mo                 
                                                                        (b)(5)                                  
                                Neurotoxicity       870.6200           (b)(1)(ii)(B),     21 mo                 
                                                                        (b)(1)(iii)(A),                         
                                                                        (b)(1)(iii)(B)                          
                                Immunotoxicity      870.7800           (b)(1)(ii)(B)      18 mo                 
                                                                                                                
----------------------------------------------------------------------------------------------------------------
95-48-7,                        Cresols:                                                                        
106-44-5, and                                                                                                   
108-39-4                                                                                                        
                                Acute               870.1350           (b)(2)             21 mo                 
                                Subchronic          870.3465           (b)(3)             18 mo                 
                                Neurotoxicity       870.6200           (b)(1)(ii)(A),     21 mo                 
                                                                        (b)(1)(iii)(A)                          
                                Immunotoxicity      870.7800           (b)(1)(ii)(A)      18 mo                 
                                                                                                                
----------------------------------------------------------------------------------------------------------------
100-41-4                        Ethylbenzene:                                                                   
                                Acute               870.1350           (b)(2)             21 mo                 
                                Developmental       870.3600           (b)(1)(i)(A)       12 mo                 
                                Reproductive        870.3800           (b)(1)(ii)(A),     29 mo                 
                                                                        (b)(5)                                  
                                Neurotoxicity       870.6200           (b)(1)(ii)(A),     21 mo                 
                                                                        (b)(1)(iii)(A),                         
                                                                        (b)(1)(iii)(B)                          
                                Immunotoxicity      870.7800           (b)(1)(ii)(A)      21 mo                 
                                                                                                                
----------------------------------------------------------------------------------------------------------------
107-06-2                        Ethylene                                                                        
                                 dichloride:                                                                    
                                Acute               870.1350           (b)(2)             21 mo                 
                                Subchronic          870.3465           (b)(3)             18 mo                 
                                Developmental       870.3600           (b)(1)(i)(C)       12 mo                 
                                Reproductive        870.3800           (b)(1)(ii)(A),     29 mo                 
                                                                        (b)(5)                                  
                                Neurotoxicity       870.6200           (b)(1)(ii)(A),     21 mo                 
                                                                        (b)(1)(iii)(A),                         
                                                                        (b)(1)(iii)(B)                          
                                                                                                                
----------------------------------------------------------------------------------------------------------------
107-21-1                        Ethylene glycol:                                                                
                                Acute               870.1350           (b)(2)             21 mo                 
                                Subchronic          870.3465           (b)(3)             18 mo                 
                                Neurotoxicity       870.6200           (b)(1)(ii)(A),     21 mo                 
                                                                        (b)(1)(iii)(A),                         
                                                                        (b)(1)(iii)(B)                          
                                Immunotoxicity      870.7800           (b)(1)(ii)(A)      18 mo                 
                                                                                                                
----------------------------------------------------------------------------------------------------------------
108-10-1                        Methyl isobutyl                                                                 
                                 ketone:                                                                        
                                Acute               870.1350           (b)(2)             21 mo                 
                                Reproductive        870.3800           (b)(1)(ii)(A),     29 mo                 
                                                                        (b)(5)                                  
                                Immunotoxicity      870.7800           (b)(1)(ii)(A)      29 mo                 
                                                                                                                
----------------------------------------------------------------------------------------------------------------
108-31-6                        Maleic anhydride:                                                               
                                Acute               870.1350           (b)(2)             21 mo                 
                                Developmental       870.3600           (b)(1)(i)(A)       12 mo                 
                                Neurotoxicity       870.6200           (b)(1)(ii)(A),     21 mo                 
                                                                        (b)(1)(iii)(A),                         
                                                                        (b)(1)(iii)(B)                          
                                Carcinogenicity     870.4200           (b)(1)(ii)(A)      60 mo                 
                                Immunotoxicity      870.7800           (b)(1)(ii)(A)      21 mo                 
                                                                                                                
----------------------------------------------------------------------------------------------------------------
108-90-7                        Chlorobenzene:                                                                  
                                Acute               870.1350                              21 mo                 
                                Subchronic          870.3465           (b)(3)             18 mo                 
                                Neurotoxicity       870.6200           (b)(1)(ii)(A),     21 mo                 
                                                                        (b)(1)(iii)(A),                         
                                                                        (b)(1)(iii)(B)                          
                                Immunotoxicity      870.7800           (b)(1)(ii)(A)      18 mo                 
                                                                                                                
----------------------------------------------------------------------------------------------------------------

[[Page 33199]]

                                                                                                                
108-95-2                        Phenol:                                                                         
                                Acute               870.1350           (b)(2)             21 mo                 
                                Immunotoxicity      870.7800           (b)(1)(ii)(A)      12 mo                 
                                                                                                                
----------------------------------------------------------------------------------------------------------------
111-42-2                        Diethanolamine:                                                                 
                                Acute               870.1350           (b)(2)             21 mo                 
                                Subchronic          870.3465           (b)(1)(ii)(B),     18 mo                 
                                                                        (b)(3)                                  
                                Developmental       870.3600           (b)(1)(ii)(B)      12 mo                 
                                Reproductive        870.3800           (b)(1)(ii)(B),     29 mo                 
                                                                        (b)(5)                                  
                                Neurotoxicity       870.6200           (b)(1)(ii)(B),     21 mo                 
                                                                        (b)(1)(iii)(A),                         
                                                                        (b)(1)(iii)(B)                          
                                Immunotoxicity      870.7800           (b)(1)(ii)(B)      18 mo                 
                                                                                                                
----------------------------------------------------------------------------------------------------------------
120-82-1                        1,2,4-                                                                          
                                 Trichlorobenzene:                                                              
                                Acute               870.1350           (b)(2)             21 mo                 
                                Developmental       870.3600                              12 mo                 
                                Neurotoxicity       870.6200           (b)(1)(ii)(A),     21 mo                 
                                                                        (b)(1)(iii)(A),                         
                                                                        (b)(1)(iii)(B)                          
                                Immunotoxicity      870.7800           (b)(1)(ii)(A)      21 mo                 
                                                                                                                
----------------------------------------------------------------------------------------------------------------
126-99-8                        Chloroprene:                                                                    
                                Acute               870.1350           (b)(2)             21 mo                 
                                Reproductive        870.3800           (b)(1)(ii)(A),     29 mo                 
                                                                        (b)(5)                                  
                                Neurotoxicity       870.6200           (b)(1)(ii)(A),     21 mo                 
                                                                        (b)(1)(iii)(A),                         
                                                                        (b)(1)(iii)(B)                          
                                Immunotoxicity      870.7800           (b)(1)(ii)(A)      21 mo                 
                                                                                                                
----------------------------------------------------------------------------------------------------------------
463-58-1                        Carbonyl sulfide:                                                               
                                Acute               870.1350           (b)(2)             21 mo                 
                                Subchronic          870.3465           (b)(3)             18 mo                 
                                Developmental       870.3600                              12 mo                 
                                Reproductive        870.3800           (b)(1)(ii)(A),     29 mo                 
                                                                        (b)(5)                                  
                                Neurotoxicity       870.6200           (b)(1)(ii)(A),     21 mo                 
                                                                        (b)(1)(iii)(A),                         
                                                                        (b)(1)(iii)(B)                          
                                Carcinogenicity     870.4200           (b)(1)(ii)(A)      60 mo                 
                                E.coli reverse      870.5100                              6 mo                  
                                 mutation                                                                       
                                Gene mutation       870.5300                              6 mo                  
                                In vivo             870.5385 or        (b)(1)(ii)(A)      14 mo                 
                                 cytogenetics        870.5395                                                   
                                Immunotoxicity      870.7800           (b)(1)(ii)(A)      18 mo                 
                                                                                                                
----------------------------------------------------------------------------------------------------------------
7647-01-0                       Hydrochloric acid:                                                              
                                Acute               870.1350           (b)(2)             21 mo                 
                                                                                                                
----------------------------------------------------------------------------------------------------------------
7664-39-3                       Hydrogen fluoride:                                                              
                                Acute               870.1350           (b)(2)             21 mo                 
                                Subchronic          870.3465           (b)(3)             18 mo                 
                                Developmental       870.3600                              12 mo                 
                                Reproductive        870.3800           (b)(1)(ii)(A),     29 mo                 
                                                                        (b)(5)                                  
                                Neurotoxicity       870.6200           (b)(1)(ii)(A),     21 mo                 
                                                                        (b)(1)(iii)(A),                         
                                                                        (b)(1)(iii)(B)                          
                                Immunotoxicity      870.7800           (b)(1)(ii)(A)      18 mo                 
                                                                                                                
----------------------------------------------------------------------------------------------------------------
7782-50-5                       Chlorine:                                                                       
                                Acute               870.1350           (b)(2)             21 mo                 
----------------------------------------------------------------------------------------------------------------



    (b) Test-specific requirements--(1) General. In addition to the 
testing requirements specified in table 1 in paragraph (a)(5) of this 
section and applicable test guideline-specific modifications listed 
therein, the following additional requirements and limitations also 
apply when specified for a particular chemical substance in table 1 
under ``Specific requirements under this section''.
    (i) Test species. The test animal shall be:
    (A) A mammalian species other than the rat.
    (B) A mammalian species other than the mouse.
    (C) A mammalian species other than the rabbit.
    (D) The male rat and the female mouse.
    (ii) Route of exposure. Animals shall be exposed:
    (A) Via vapor-phase inhalation.
    (B) Via inhalation of aerosol.
    (C) Orally in the diet.
    (iii) Duration and frequency of exposure. (A) Animals shall be 
exposed for a 4-hour period in an acute study.

[[Page 33200]]

    (B) Animals shall be exposed for 6 hours per day, 5 days per week 
for a 90-day period in a subchronic study.
    (2) Acute test modifications. In addition to the acute testing 
requirements specified in table 1 in paragraph (a)(5) of this section, 
the following additional requirements and limitations also apply when 
specified for a particular chemical substance in table 1 under 
``Specific requirements under this section''.
    (i) The appraisal of pulmonary irritation shall be evaluated during 
exposure to the substance by the use of the mouse respiratory sensory 
irritation assay method as outlined in ASTM E 981-84 (see paragraph 
(b)(2)(iii)(C) of this section). This method assesses the breathing 
patterns of test animals. This incorporation by reference was approved 
by the Director of the Federal Register in accordance with 5 U.S.C. 
552(a) and 1 CFR part 51. This material is incorporated as it exists on 
the date of approval and notice of any change in this material will be 
published in the Federal Register. Copies of the incorporated materials 
may be obtained from the TSCA Nonconfidential Information Center, Rm. 
NE-B607, 401 M St., SW., Washington, DC, 20460 or from the American 
Society for Testing and Materials (ASTM), 1916 Race Street, 
Philadelphia, PA 10103. Copies may be inspected at the above address or 
at the Office of the Federal Register, 800 North Capitol Street, NW., 
suite 700, Washington, DC. For information on this test guideline, the 
references in paragraph (b)(2)(iii) should be consulted.
    (ii) Results of respiratory sensory irritation assay. (A) Data 
shall be included in the final report and tabulated to show:
    (1) The magnitude of change in respiratory rate with exposure 
concentration and with time for each animal.
    (2) A response concentration, which indicates the concentration at 
which the respiration rate is decreased by 50% (RD<INF>50), will be 
calculated, along with the 95% confidence limits.
    (B) Time-effect curves shall be included in the final report to 
evaluate the onset and shape of the response.
    (iii) References.
    (A) Alarie, Y., and Luo, J.E. ``Sensory Irritation by Airborne 
Chemicals: A basis to establish acceptable levels of exposure.'' 
Toxicology of the Nasal Passages. Hemisphere Publishing Corporation: 
New York pp. 91-100 (1986).
    (B) Alarie, Y., and Stokinger, H.E. ``Sensory Irritation by 
Airborne Chemicals.'' CRC Critical Reviews in Toxicology. pp. 299-363 
(1973).
    (C) ASTM. ``Standard Test Method for Estimating Sensory Irritancy 
of Airborne Chemicals.'' In: 1984 Annual Book of ASTM Standards. Water 
and Environmental Technology. Section 11. Volume 11.04 Designation E 
981-84 pp. 572-584 (1984).
    (3) Subchronic test modifications. In addition to the subchronic 
testing requirements specified in table 1 in paragraph (a)(5) of this 
section, the following additional requirements and limitations also 
apply when specified for a particular chemical substance in table 1 
under ``Specific requirements under this section''.
    (i) Respiratory tract pathology. (A) Care shall be taken that the 
method used to kill the animal does not result in damage to the tissues 
of the upper or lower respiratory tract. The heart-lung, including the 
trachea, shall be removed in bloc.
    (B) Representative sections of the lungs shall be examined 
histologically. This shall include trachea, major conducting airways, 
alveolar region, terminal and respiratory bronchioles, alveolar ducts 
and sacs, and interstitial tissues.
    (C) The nasopharyngeal tissue shall be examined for histopathologic 
lesions. This shall include sections through the nasal cavity, and 
examination of the squamous, transitional, respiratory, and olfactory 
epithelia.
    (D) The larynx mucosa shall be examined for histopathologic 
changes. Sections of the larynx to be examined include the epithelium 
covering the base of the epiglottis, the ventral pouch, and the medial 
surfaces of the vocal processes of the arytenoid cartilages.
    (ii) Bronchoalveolar lavage. (A) The lungs shall be lavaged in situ 
or after sacrifice. If the study will not be compromised, one lobe of 
the lungs may be used for lung lavage while the other is fixed for 
histologic evaluation. The lungs shall be lavaged using physiological 
saline after cannulation of the trachea. The lavages shall consist of 
two washes each of which consists of approximately 80 percent (e.g., 5 
ml in rats and 1 ml in mice) of total lung volume. Additional washes 
merely tend to reduce the concentrations of the material collected. The 
lung lavage fluid shall be stored on ice at approximately 5  deg.C 
until assayed.
    (B) The following parameters shall be determined in the lavage 
fluid as indicators of cellular damage in the lungs: total protein, 
cell count and percent leukocytes. In addition, a phagocytosis assay 
using the procedure of Burleson (Burleson et al., 1987; Gilmour and 
Selgrade, 1993) shall be performed to determine macrophage activity. 
The following references may be consulted:
    (1) Burleson, G.R. et al. ``Poly (I): poly (C)-enhanced alveolar 
peritoneal macrophage phagocytosis: Quantification by a new method 
utilizing fluorescent beads.'' Proceedings of the Society for 
Experimental Biology and Medicine. 184:468-476 (1987).
    (2) Gilmour, G.I., and Selgrade, M.K. ``A Comparison of the 
Pulmonary Defenses against Streptococcal Infection in Rats and Mice 
Following O<INF>3 Exposure: Differences in Disease Susceptibility and 
Neutrophil Recruitment.'' Toxicology and Applied Pharmacology. 123:211-
218 (1993).
    (4) [Reserved]
    (5) Reproductive toxicity and fertility study test modifications. 
In addition to the reproductive toxicity and fertility testing 
requirements specified in table 1 in paragraph (a)(5) of this section, 
the following additional requirements and limitations also apply when 
specified for a particular chemical substance in table 1 under 
``Specific requirements under this section''.
    (i) Administration of the test substance. The test substance shall 
be administered by inhalation. The requirements of OPPTS 
870.3800(e)(2)(iii) do not apply.
    (ii) [Reserved]

[FR Doc. 96-16203 Filed 6-25-96; 8:45 am]
BILLING CODE 6560-50-F

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