[Federal Register: April 29, 2003 (Volume 68, Number 82)]
[Notices]               
[Page 22704-22709]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr29ap03-89]                         

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Agency for Toxic Substances and Disease Registry

[ATSDR-192]

 
Announcement of Final Priority Data Needs for 10 Priority 
Hazardous Substances

AGENCY: Agency for Toxic Substances and Disease Registry (ATSDR), U.S. 
Department of Health and Human Services (HHS).

ACTION: Notice.

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SUMMARY: This Notice announces the final priority data needs for 10 
priority hazardous substances (see attached Table 1) as part of the 
continuing development and implementation of the ATSDR Substance-
Specific Applied Research Program (SSARP). The Notice also serves as a 
continuous call for voluntary research proposals. The SSARP is 
authorized by the Comprehensive Environmental Response, Compensation, 
and Liability Act of 1980 (Superfund) or CERCLA, and amended by the 
Superfund Amendments and Reauthorization Act of 1986 (SARA) [42 U.S.C. 
9604(i)].
    At the time the SSARP was initiated on October 17, 1991, a list of 
priority data needs for 38 priority hazardous substances was announced 
in the Federal Register (56 FR 52178). The list was subsequently 
revised based on public comments and published in final form on 
November 16, 1992 (57 FR 54150). In 1997, ATSDR finalized the priority 
data needs for a second list of 12 substances that was subsequently 
announced in the Federal Register (62 FR 40820).

[[Page 22705]]

    Ten substances constitute the third list of hazardous substances 
for which priority data needs have been identified by ATSDR. The 10 
substances, which are included in the ATSDR Priority List of Hazardous 
Substances established by ATSDR and the U.S. Environmental Protection 
Agency (EPA) (66 FR 54014, October 25, 2001), are:

    [sbull] asbestos
    [sbull] benzidine
    [sbull] chlorinated dibenzo-p-dioxins
    [sbull] 1,2-dibromoethane
    [sbull] 1,2-dichloroethane
    [sbull] 1,1-dichloroethene
    [sbull] ethylbenzene
    [sbull] pentachlorophenol
    [sbull] 1,1,2,2-tetrachloroethane
    [sbull] total xylenes

    In developing this list, ATSDR solicited input from EPA and the 
National Institute of Environmental Health Sciences (NIEHS), both of 
which also reviewed the draft priority data needs before they were made 
available for public comment. The priority data needs were initially 
announced by ATSDR in the Federal Register on August 14, 2001 (66 FR 
42660). The public was invited to comment on them during a 90-day 
period. ATSDR received comments from four industry groups and a 
nonprofit private organization concerning programmatic and substance-
specific issues pertaining to the implementation of the research 
program. ATSDR has identified several generic issues resulting from the 
public comments. These issues and ATSDR's responses are presented 
below. ATSDR has finalized the priority data needs for these 10 
substances. Both the priority data needs documents (that provide 
ATSDR's rationale for assigning priority to a data need) and the 
response to public comments documents are available by requesting them 
in writing from ATSDR (see ADDRESSES section of this Notice).
    This Notice also serves as a continuous call for voluntary research 
proposals. Private-sector organizations may volunteer to conduct 
research to address specific priority data needs in this Notice by 
indicating their interest through submission of a letter of intent to 
ATSDR (see ADDRESSES section of this Notice). The letter should include 
a brief statement that addresses the priority data need(s) to be filled 
and the methods to be used. A Tri-Agency Superfund Applied Research 
Committee (TASARC) comprised of scientists from ATSDR, the National 
Toxicology Program (NTP), and EPA will review all submissions.

DATES: The ATSDR voluntary research program is a continuous program, 
and private-sector organizations can volunteer to fill identified data 
needs from now until that time when ATSDR announces that other research 
has been initiated for a specific data need.

ADDRESSES: Private-sector organizations interested in volunteering to 
conduct research to fill identified priority data needs should write to 
Dr. William Cibulas, Chief, Research Implementation Branch, Division of 
Toxicology, ATSDR, 1600 Clifton Road, NE., Mailstop E-29, Atlanta, 
Georgia 30333, or e-mail Dr. Cibulas at wcibulas@cdc.gov. Requests for 
the priority data needs documents and response to public comments 
documents should be addressed similarly.

FOR FURTHER INFORMATION CONTACT: Dr. William Cibulas, Chief, Research 
Implementation Branch, Division of Toxicology, ATSDR, 1600 Clifton 
Road, NE., Mailstop E-29, Atlanta, Georgia 30333, telephone (404) 498-
0140.

SUPPLEMENTARY INFORMATION: 

Background

    The Comprehensive Environmental Response, Compensation, and 
Liability Act of 1980 (Superfund) or CERCLA, as amended by the 
Superfund Amendments and Reauthorization Act of 1986 (SARA) [42 U.S.C. 
9604(i)], requires that ATSDR (1) develop jointly with EPA a list of 
hazardous substances found at National Priorities List (NPL) sites (in 
order of priority), (2) prepare toxicological profiles of these 
substances, and (3) assure the initiation of a research program to 
address identified priority data needs associated with the substances.
    The primary purpose of this research program is to provide the 
public and scientific communities with answers to some of the key 
questions regarding health effects and exposure to these substances. 
For ATSDR, this research program supplies necessary information to 
improve the database to conduct public health assessments. This link 
between research and public health assessments, and the process for 
distilling priority data needs for ranked hazardous substances from 
data needs identified in associated ATSDR toxicological profiles, are 
described in the ATSDR ``Decision Guide for Identifying Substance-
Specific Data Needs Related to Toxicological Profiles'' (54 FR 37618, 
September 11, 1989).
    At the time the Substance-Specific Applied Research Program (SSARP) 
was initiated on October 17, 1991, a list of priority data needs for 38 
priority hazardous substances was announced in the Federal Register (56 
FR 52178). The list was subsequently revised based on public comments 
and published in final form on November 16, 1992 (57 FR 54150). In 
1997, ATSDR finalized the priority data needs for a second list of 12 
substances (62 FR 40820). Currently, a total of 190 priority data needs 
have been identified for these 50 substances as described in ``Update 
on the Status of the Superfund Substance-Specific Applied Research 
Program'' (67 FR 4836, January 31, 2002).
    In 2001, ATSDR identified the priority data needs for 10 additional 
hazardous substances and announced them in draft form on August 14, 
2001 (66 FR 42660). The public was invited to comment on the draft 
priority data needs during a 90-day period. The agency responded to all 
the comments and revised the priority data needs, as needed.

ATSDR's Response to Public Comments

    As mentioned in the SUMMARY section of this Notice, ATSDR has 
identified several generic public comments on the priority data needs 
for the 10 hazardous substances. These comments and ATSDR's responses 
are presented below.
    Comment: Request for ATSDR to clarify if and how any further 
testing requests or regulatory requirements for testing will be subject 
to public scrutiny.
    Response: ATSDR published the draft priority data needs (PDNs) in 
the August 14, 2001, Federal Register Notice with a public comment 
period of 90 days. A final list of PDNs will be published following 
completion of deliberations on the comments received. In the event that 
a study is to be conducted via the mechanisms described in the Federal 
Register Notice--e.g., industry-sponsored voluntary research, or 
university-based research supported by the Comprehensive Environmental 
Response, Compensation, and Liability Act (CERCLA) funds--the study 
protocol and final report will be reviewed by ATSDR's external peer 
reviewers, and all documents related to the project will be made 
available for public inspection at ATSDR. Also, any testing that 
results from coordination with the U.S. Environmental Protection Agency 
(EPA) and development of a Toxic Substances Control Act (TSCA) test 
rule will be subjected to a public comment period consistent with EPA 
guidelines. ATSDR publishes an update of its Substance-Specific Applied 
Research Program in the Federal Register every three years.
    Comment: Concern that the Federal Register Notice makes no mention 
of the use of in vitro methodologies.

[[Page 22706]]

    Response: ATSDR agrees with the commenter and will more explicitly 
state its support of innovative methodologies, including non-animal 
testing, in future notices about the agency's Substance-Specific 
Applied Research Program. In a recently published Federal Register 
Notice updating the status of this research program (67 FR 4836, 
January 31, 2002), the agency stated that ``ATSDR encourages the use of 
in vitro assessment methods and other innovative tools for filling 
priority data needs. For example, the agency believes that 
physiologically based pharmacokinetic (PBPK) modeling could serve as a 
valuable tool in predicting across route similarities (or differences) 
in toxicological responses to hazardous substances. Therefore, on a 
case-by-case basis, a priority data need can be filled using existing 
data and modeling.'' In fact, in the ATSDR voluntary research program 
(a component of ATSDR's Substance-Specific Applied Research Program), 
the Halogenated Solvents Industry Alliance, Inc. (HSIA) has conducted 
studies to fill ATSDR's priority data needs for volatile organic 
compounds using PBPK modeling.
    Also, ATSDR is a member of the National Toxicology Program's (NTP) 
Interagency Coordinating Committee on the Validation of Alternative 
Methods (ICCVAM) and supports development, validation, and acceptance 
of alternative toxicological test methods that reduce, refine, and 
replace the use of animals, as appropriate. Through its participation 
on ICCVAM, ATSDR keeps informed of reliable and valid alternative test 
methods.
    Comment: Request for ATSDR to withdraw the endocrine disruption and 
developmental neurotoxicity priority data needs because there are no 
validated animal tests for these end points.
    Response: ATSDR has identified a priority data need to assess the 
potential for pentachlorophenol to affect endocrine functions and for 
reproductive studies with ethylbenzene. As a result of the agency's 
evaluation of the comments received from the Pentachlorophenol Task 
Force, the priority data need for in vivo endocrine disruptor studies 
via oral exposure to pentachlorophenol has been changed. This change 
resulted because the Pentachlorophenol Task Force submitted a recently 
completed two-generation reproduction study that was subsequently 
published in a peer-reviewed journal. ATSDR accepted the data and no 
longer assigned priority to this research need. With regard to 
ethylbenzene, no new information has been available to ATSDR, and the 
priority data need for ethylbenzene remains unchanged. For the same 
reason, ATSDR will not withdraw the priority data need for 
developmental neurotoxicity testing for xylenes.
    ATSDR is a nonregulatory, science-based agency. The agency is 
mandated (in consultation with EPA and agencies and programs of the 
Public Health Service) to assess whether adequate information on the 
health effects of hazardous substances is available. Where adequate 
information is not available, ATSDR, in cooperation with NTP, is 
required to assure the initiation of a research program to determine 
these health effects. Toward this end, ATSDR established the Tri-Agency 
Superfund Applied Research Committee (TASARC) consisting of scientists 
from ATSDR, EPA, and NTP to collaborate on mutual research needs and to 
discuss issues relevant to the proposed studies, such as the validation 
status and regulatory acceptance of proposed test methods. It should be 
noted that ATSDR does not develop testing guidelines or methodologies 
for toxicological research.
    Consistent with the CERCLA mandate, on August 14, 2001, ATSDR 
published a Federal Register Notice announcing the identification of 
key research needs for 10 additional hazardous substances, and provided 
a rationale for these determinations in support documents (i.e., 
priority data needs documents are available for all 10 substances). 
However, the agency did not identify, propose, or discuss specific test 
methods to be used to fill the data needs (66 FR 42660). There are no 
universally agreed upon and validated animal tests to fill the priority 
data needs for endocrine disruption and developmental neurotoxicity, 
similar to a lack of such tests to fill the priority data needs for 
biomarker and mechanistic studies. Consequently, these studies require 
basic research or other mechanisms to satisfy the information need. 
Therefore, in filling these research needs, ATSDR does not specify or 
require that certain (animal) tests be performed. Instead, ATSDR 
remains open to receiving scientific information to fill these research 
needs from a variety of sources, including organizations that may 
propose innovative methodologies involving non-animal tests. In such 
cases, the agency generally consults with programmatic experts at the 
National Institute of Environmental Health Sciences (NIEHS) and EPA, 
and outside scientists to advise the agency on the appropriateness and 
validation status of the proposed methods for filling its research 
needs. Also, ATSDR is working closely with organizations such as NTP's 
Interagency Coordinating Committee on the Validation of Alternative 
Methods (ICCVAM) to stay abreast of testing validation issues. In fact, 
ATSDR is participating fully in this committee's effort to validate a 
battery of in vivo and in vitro tests to assess endocrine disruption.
    Comment: Concern about ATSDR calling for more lethal poisoning 
tests on animals and request that ATSDR withdraw its proposal to 
conduct more acute toxicity tests on animals for these 10 substances.
    Response: The ATSDR Substance-Specific Applied Research Program is 
designed to address the most important public health research needs for 
citizens exposed to hazardous environmental substances. ATSDR has not 
required, and will not require, LD50 or other lethality data 
as an adjunct to the process. However, ATSDR often requests short-term 
(acute) toxicity data on non-lethal end points in order to determine 
the agency's health guidance values (minimal risk levels [MRLs]) for 
citizens who are possibly exposed to chemicals for durations of 14 days 
or less.
    If the agency considers the existing acute duration (14 days or 
less) database to be inadequate for fully characterizing the short-term 
toxicity of a particular hazardous substance, it will identify the need 
to conduct additional [inhalation and/or oral] studies for determining 
critical targets and establishing dose-response relationships.
    Comment: Concern that ATSDR's requests for more information ignore 
sophisticated analyses that can be conducted using, for example, 
structure-activity relationships (SAR).
    Response: In evaluating the need for additional data on a 
particular end point and assigning priority to data needs for the 10 
substances, ATSDR first reviewed the available chemical-specific data 
for a given end point. In addition, ATSDR conducted SAR analyses on 
these substances and used the information in a strength-of-evidence 
approach to determine the need to assign priority for the missing 
information.
    Comment: Request that ATSDR defer final assessment of its priority 
data needs until the industry groups have completed their work under 
EPA's voluntary children's chemical evaluation program (VCCEP), the 
hazardous air pollutants (HAPs) test rule, and an enforceable consent 
agreement (for 1,2-dichloroethane) among others.

[[Page 22707]]

    Response: ATSDR has developed a process for assigning priority to 
data needs identified in the agency's toxicological profiles for 
hazardous substances. Specifically, the process for prioritizing the 
data needs is based on a logical scientific approach as described in 
ATSDR's Decision Guide (54 FR 37618, September 11, 1989). The 
identified priority data needs (PDNs) are then subjected to public and 
peer review. Currently, ATSDR considers these PDNs to be the most 
critical research needs for these hazardous substances. However, the 
agency will continue to evaluate new data for these substances obtained 
through additional testings, e.g., industry groups' participation in 
other federal agencies' programs. Specifically, ATSDR is working 
closely with EPA on these activities where we have identified 
overlapping research priorities. Therefore, the status of these PDNs 
may change in the future. In this current Federal Register Notice 
announcing the final list of PDNs, ATSDR states that these PDNs remain 
on the agency's list but that they may potentially be filled by 
individual industry groups working under specific EPA programs (see 
Table 1).
    In summary, as a result of the agency's evaluation of all the 
public comments received for the 10 hazardous substances, two priority 
data needs were changed. Specifically, in vivo endocrine disruptor 
studies via oral exposure and multigeneration reproduction study 
involving multiple matings and examining male and female fertility via 
oral exposure were initially identified as priority data needs for 
pentachlorophenol. During the public comment period, ATSDR received 
from the Pentachlorophenol Task Force a recently completed two-
generation reproduction study that was subsequently published in a 
peer-reviewed journal. ATSDR accepted the data and no longer assigned 
priority to these research needs. No changes were made to the priority 
data needs for the other nine substances as a result of the public 
comments.

Implementation of Substance-Specific Applied Research Program

    Regarding the implementation of the SSARP, in section 104(i)(5)(D), 
CERCLA states that it is the sense of Congress that the costs for 
conducting this research program be borne by the manufacturers and 
processors of the hazardous substances under the Toxic Substances 
Control Act of 1976 (TSCA) and by registrants under the Federal 
Insecticide, Fungicide, and Rodenticide Act of 1972 (FIFRA), or by cost 
recovery from responsible parties under CERCLA. To execute this 
statutory intent, ATSDR developed a plan whereby parts of the SSARP are 
being conducted via regulatory mechanisms (TSCA/FIFRA), private-sector 
voluntarism, and through the direct use of CERCLA funds. CERCLA also 
requires that ATSDR consider recommendations of the Interagency Testing 
Committee (ITC), established under Section 4(e) of TSCA, on the types 
of research to be done. ATSDR actively participates on this committee; 
however, none of the proposed 10 substances are now on the ITC priority 
testing list.
    The priority data needs identified in this Notice reflect the 
opinion of the agency, in consultation with other federal programs, of 
the research needed pursuant to ATSDR's authority under CERCLA. They do 
not represent the priority data needs for any other program. Consistent 
with section 104(i)(12) of CERCLA as amended (42 U.S.C. 9604(i)(12)), 
nothing in this research program shall be construed to delay or 
otherwise affect or impair the authority of the President, the 
Administrator of ATSDR, or the Administrator of EPA to exercise any 
authority regarding any other provision of law, including the Toxic 
Substances Control Act of 1976 (TSCA) and the Federal Insecticide, 
Fungicide, and Rodenticide Act of 1972 (FIFRA), or the response and 
abatement authorities of CERCLA. In developing this research program, 
ATSDR has worked with other federal programs to determine common 
substance-specific data needs, as well as mechanisms to implement 
research that may include authorities under TSCA and FIFRA, private-
sector voluntarism, or the direct use of CERCLA funds.
    When deciding the type of research that should be done, ATSDR 
considers the recommendations of the Interagency Testing Committee 
established under section 4(e) of TSCA. Federally funded projects that 
collect information from 10 or more respondents and that are funded by 
cooperative agreements are subject to review by the Office of 
Management and Budget (OMB) under the Paperwork Reduction Act. If the 
proposed project involves research on human subjects, the applicants 
must comply with Department of Health and Human Services regulations 
(45 CFR part 46) regarding the protection of human subjects. Assurance 
must be provided that the project will be subject to initial and 
continuing review by the appropriate institutional review committees. 
Overall, data generated from this research program will lend support to 
others conducting human health assessments involving these 10 
substances by providing additional scientific information for the risk 
assessment process.

Substance-Specific Priority Data Needs

    The final priority data needs are identified in Table 1. Unique 
identification numbers (37A through 46G) are assigned to the priority 
data needs for this list of 10 priority hazardous substances; the 
priority data needs for the first 50 substances were assigned 
identification numbers 1A through 36E (67 FR 4836). Parts of the 
proposed research are unique to CERCLA and may be most appropriately 
addressed by ATSDR programs as follows.
    ATSDR's responsibility as a public health agency addressing 
environmental health issues is, when appropriate, to collect human data 
to validate substance-specific exposure and toxicity assumptions. ATSDR 
will obtain this information by conducting exposure and health effects 
studies, and by establishing and using substance-specific subregistries 
of people enrolled in the agency's National Exposure Registry who are 
potentially exposed to these substances. When a subregistry or a human 
exposure study is identified as a priority data need, the responsible 
ATSDR program will determine its feasibility, which depends on 
identifying appropriate populations and funding.
    In addition, the need to collect, evaluate, and interpret 
environmental data from contaminated media around hazardous waste sites 
remains a priority data need for all 10 priority hazardous substances 
ATSDR has identified for this third set.
    However, some of this information has already been collected 
through individual state programs and the EPA's CERCLA activities; 
therefore, ATSDR will evaluate the extant information from these 
programs to better characterize the need for additional site-specific 
information.
    ATSDR acknowledges that the conduct of human studies to determine 
possible links between exposure to hazardous substances and human 
health effects may be accomplished through mechanisms other than agency 
programs. We encourage private-sector organizations and other 
governmental programs to use ATSDR's priority data needs to plan their 
research activities, including identifying appropriate

[[Page 22708]]

populations and conducting studies to answer specific human health 
questions.

    Dated: April 10, 2003.
Georgi Jones,
Director, Office of Policy and External Affairs, Agency for Toxic 
Substances and Disease Registry.

Table 1.--Final Substance--Specific Priority Data Needs (PDNs) for Third
                 Set of 10 Priority Hazardous Substances
------------------------------------------------------------------------
             Substance               PDN ID       Priority data needs
------------------------------------------------------------------------
Asbestos..........................       37A  Epidemiologic studies of
                                               individuals
                                               occupationally exposed to
                                               asbestos levels lower
                                               than those experienced
                                               before the institution of
                                               current occupational
                                               standards governing the
                                               use of asbestos, but
                                               higher than current
                                               levels in the general
                                               population. These studies
                                               should be performed in
                                               conjunction with the
                                               immunotoxicity studies.
                                         37B  Immunotoxicity studies of
                                               individuals
                                               occupationally exposed to
                                               asbestos.
                                         37C  Development of human and
                                               rat lung retention models
                                               to aid in extrapolating
                                               between rat and human
                                               data.
                                         37D  Improved analytical
                                               methods for screening
                                               samples and determining
                                               the chemical structure of
                                               asbestos fibers. Also,
                                               techniques are needed to
                                               normalize studies in
                                               which different
                                               analytical methods were
                                               employed.
                                         37E  Exposure levels, fiber
                                               size distribution, and
                                               asbestos fiber type in
                                               areas with natural
                                               geologic deposits of
                                               friable asbestos and at
                                               hazardous waste sites.
                                               Also, techniques for
                                               estimating air levels of
                                               asbestos from soil
                                               concentrations and
                                               activity scenarios.
                                         37F  Exposure levels in humans
                                               living near hazardous
                                               waste sites and in other
                                               populations, such as
                                               humans living in areas
                                               with naturally high
                                               levels of friable
                                               asbestos.
                                         37G  Potential candidate for
                                               subregistry of exposed
                                               persons.
Benzidine.........................       38A  Dose-response data for
                                               acute- and intermediate-
                                               duration exposure via the
                                               oral route (the study of
                                               intermediate-duration
                                               exposure should include
                                               evaluation of
                                               reproductive and
                                               endocrine organ
                                               histopathology, lymphoid
                                               tissues histopathology as
                                               well as examination of
                                               relevant blood
                                               components, and nervous
                                               system histopathology).
                                         38B  Exposure levels in humans
                                               living near hazardous
                                               waste sites.
                                         38C  Exposure levels in
                                               children.
                                         38D  Potential candidate for
                                               subregistry of exposed
                                               persons.
Chlorinated dibenzo-p-dioxins            39A  Studies via oral exposure
 (CDDs).                                       designed to assess
                                               childhood susceptibility.
                                         39B  Comparative toxicokinetic
                                               studies examining the
                                               relative absorption of
                                               CDDs across exposure
                                               routes and the relative
                                               contribution of each
                                               exposure route to total
                                               body burdens.
                                         39C  Exposure levels in humans
                                               living near hazardous
                                               waste sites.
                                         39D  Exposure levels in
                                               children.
1,2-Dibromoethane.................       40A  Dose-response data in
                                               animals for acute- and
                                               intermediate-duration
                                               exposure by the oral
                                               route (the study of
                                               intermediate-duration
                                               exposure should include
                                               evaluation of
                                               neuropathology and
                                               observation for overt
                                               signs of neurotoxicity).
                                         40B  Multigeneration
                                               reproductive toxicity
                                               studies via oral
                                               exposure.
                                         40C  Developmental toxicity
                                               studies via oral
                                               exposure.
                                         40D  Immunotoxicity battery
                                               studies via oral
                                               exposure.
                                         40E  Exposure levels in humans
                                               living near hazardous
                                               waste sites and in other
                                               populations, such as
                                               workers exposed to 1,2-
                                               dibromoethane.
                                         40F  Exposure levels in
                                               children.
                                         40G  Potential candidate for
                                               subregistry of exposed
                                               persons.
1,2-Dichloroethane[hairsp]*.......       41A  Dose-response data in
                                               animals for acute-
                                               duration (14-day)
                                               exposure by the
                                               inhalation route,
                                               including a comparison of
                                               young and adult animals.
                                         41B  Dose-response data in
                                               animals for acute-
                                               duration (14-day)
                                               exposure by the oral
                                               route, including a
                                               comparison of young and
                                               adult animals.
                                         41C  Dose-response data in
                                               animals for intermediate-
                                               duration exposure by the
                                               inhalation route (the
                                               study should be performed
                                               in conjunction with the
                                               neurotoxicology battery
                                               of tests).
                                         41D  Neurotoxicology battery of
                                               tests following
                                               inhalation exposure.
                                         41E  Neurotoxicology battery of
                                               tests following oral
                                               exposure.
                                         41F  Dose-response data in
                                               animals for chronic-
                                               duration exposure by the
                                               oral route.
                                         41G  Developmental toxicity
                                               data for inhalation
                                               exposure (assessment of
                                               developmental
                                               cardiotoxicity and
                                               neurotoxicity).
                                         41H  Developmental toxicity
                                               data for oral exposure
                                               (assessment of
                                               developmental
                                               cardiotoxicity and
                                               neurotoxicity).
                                         41I  Additional analyses and
                                               studies for comparative
                                               toxicokinetics across
                                               species, ages, routes,
                                               and durations.
                                         41J  Children's susceptibility.
                                         41K  Exposure levels in humans
                                               living near hazardous
                                               waste sites.
                                         41L  Exposure levels in
                                               children.
                                         41M  Potential candidate for
                                               subregistry of exposed
                                               persons.
1,1-Dichloroethene[hairsp]*.......       42A  Dose-response data in
                                               animals for acute-
                                               duration exposure by the
                                               inhalation route.
                                         42B  Dose-response data in
                                               animals for chronic-
                                               duration exposure by the
                                               inhalation route.
                                         42C  Dose-response data in
                                               animals for acute- and
                                               intermediate-duration
                                               exposure by the oral
                                               route.
                                         42D  Carcinogenicity studies in
                                               two species following
                                               inhalation exposure.

[[Page 22709]]


                                         42E  Reproductive toxicity
                                               studies assessing male
                                               and female end points
                                               following inhalation
                                               exposure.
                                         42F  Developmental toxicity
                                               studies following oral
                                               exposure.
                                         42G  Immunotoxicology battery
                                               of tests following oral
                                               exposure.
                                         42H  Battery of neurobehavioral
                                               tests following
                                               inhalation exposure.
                                         42I  Children's susceptibility.
                                         42J  Exposure levels in humans
                                               living near hazardous
                                               waste sites.
                                         42K  Exposure levels in
                                               children.
                                         42L  Potential candidate for
                                               subregistry of exposed
                                               persons.
Ethylbenzene[hairsp]*.............       43A  Dose-response data for
                                               acute-duration exposure
                                               by the inhalation route.
                                         43B  Dose-response data for
                                               chronic-duration exposure
                                               by the inhalation route.
                                         43C  Dose-response data for
                                               acute- and intermediate-
                                               duration exposure by the
                                               oral route; the study of
                                               intermediate-duration
                                               exposure should include
                                               an evaluation of clinical
                                               signs of neurotoxicity
                                               and histopathology of
                                               reproductive organs,
                                               endocrine glands, and
                                               nervous system.
                                         43D  Multigeneration toxicity
                                               study examining
                                               reproductive end points
                                               and indicators of
                                               endocrine disruption
                                               following inhalation
                                               exposure.
                                         43E  Two-species developmental
                                               study with continued
                                               assessment of offspring
                                               during postnatal
                                               development following
                                               oral exposure.
                                         43F  Studies for comparative
                                               toxicokinetics.
                                         43G  Exposure levels in humans
                                               living near hazardous
                                               waste sites.
                                         43H  Exposure levels in
                                               children.
                                         43I  Potential candidate for
                                               subregistry of exposed
                                               persons.
Pentachlorophenol.................       44A  Comparative toxicokinetic
                                               studies.
                                         44B  Exposure levels in humans
                                               living near hazardous
                                               waste sites.
                                         44C  Exposure levels in
                                               children through play
                                               activities near
                                               contaminated
                                               environmental media.
                                         44D  Potential candidate for
                                               subregistry of exposed
                                               persons.
1,1,2,2-Tetrachloroethane.........       45A  Two-species developmental
                                               toxicity study by the
                                               oral route.
                                         45B  Immunotoxicity battery
                                               following oral exposure.
                                         45C  Mammalian in vivo
                                               genotoxicity assays.
                                         45D  Exposure levels in humans
                                               living near hazardous
                                               waste sites.
                                         45E  Exposure levels in
                                               children.
                                         45F  Potential candidate for
                                               subregistry of exposed
                                               persons.
Total xylenes.....................       46A  Dose-response data for
                                               chronic-duration exposure
                                               by the oral route. This
                                               study should be done in
                                               conjunction with the
                                               neurotoxicology battery
                                               of tests.
                                         46B  Neurotoxicology battery of
                                               tests following oral
                                               exposure.
                                         46C  Two-generation
                                               reproductive study
                                               following oral exposure.
                                         46D  Developmental toxicity
                                               study that includes
                                               neurodevelopmental end
                                               points following oral
                                               exposure.
                                         46E  Exposure levels in humans
                                               living near hazardous
                                               waste sites.
                                         46F  Exposure levels in
                                               children.
                                         46G  Potential candidate for
                                               subregistry of exposed
                                               persons.
------------------------------------------------------------------------
* Some of the toxicity priority data needs may potentially be filled by
  individual industry groups working under specific EPA programs.

[FR Doc. 03-9300 Filed 4-28-03; 8:45 am]

BILLING CODE 4163-70-P