[Federal Register Volume 61, Number 63 (Monday, April 1, 1996)]
[Notices]
[Pages 14420-14427]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 96-7852]
[[Page 14419]]
_______________________________________________________________________
Part VII
Department of Health and Human Services
_______________________________________________________________________
Agency for Toxic Substances and Disease Registry
_______________________________________________________________________
Update on the Status of the Superfund Substance-Specific Applied
Research Program; Notice
Federal Register / Vol. 61, No. 63 / Monday, April 1, 1996 /
Notices
[[Page 14420]]
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Agency For Toxic Substances and Disease Registry
[ATSDR-106]
Update on the Status of the Superfund Substance-Specific Applied
Research Program
AGENCY: Agency for Toxic Substances and Disease Registry (ATSDR),
Department of Health and Human Services (HHS).
ACTION: Notice.
-----------------------------------------------------------------------
SUMMARY: This Notice is an update on the status of ATSDR's continuing
effort to implement the Substance-Specific Applied Research Program
(SSARP). Authorized by 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)), this research program was initiated on
October 17, 1991. At that time, 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).
The 38 substances, each of which is found on ATSDR's List of
Priority Hazardous Substances, are aldrin/dieldrin, arsenic, benzene,
beryllium, cadmium, carbon tetrachloride, chloroethane, chloroform,
chromium, cyanide, p,p'-DDT,DDE,DDD, di(2- ethylhexyl) phthalate, lead,
mercury, methylene chloride, nickel, polychlorinated biphenyl compounds
(PCBs), polycyclic aromatic hydrocarbons (PAHs--includes 15
substances), selenium, tetrachloroethylene, toluene, trichloroethylene,
vinyl chloride, and zinc (56 FR 52166, October 17, 1991).
Priority data needs for 12 additional priority hazardous substances
were recently identified and are also being announced in a Federal
Register Notice. The 12 substances, each of which is included in
ATSDR's List of Priority Hazardous Substances, are chlordane, 1,2-
dibromo- 3-chloropropane, di-n-butyl phthalate, disulfoton, endrin
(includes endrin aldehyde), endosulfan (alpha-, beta-, and endosulfan
sulfate), heptachlor (includes heptachlor epoxide),
hexachlorobutadiene, hexachlorocyclohexane (alpha-, beta-, delta- and
gamma-), manganese, methoxychlor, and toxaphene.
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 by indicating their
interest through submission of a research proposal to ATSDR (see
ADDRESSES section of this Notice). A Tri-Agency Superfund Applied
Research Committee (TASARC) comprised of scientists from ATSDR, the
National Toxicology Program (NTP), and the Environmental Protection
Agency (EPA) will review all proposed voluntary research efforts.
DATES: ATSDR considers the voluntary research effort to be important to
the continuing development of the SSARP. Therefore, the agency strongly
encourages private-sector organizations to volunteer at any time to
conduct research to address identified data needs unless ATSDR
announces that research has already been initiated for that specific
data need.
ADDRESSES: Private-sector organizations interested in volunteering to
conduct research may write to Dr. William Cibulas, Chief, Research
Implementation Branch, Division of Toxicology, ATSDR, 1600 Clifton
Road, N.E., Mailstop E-29, Atlanta, Georgia 30333.
FOR FURTHER INFORMATION CONTACT: Dr. William Cibulas, Chief, Research
Implementation Branch, Division of Toxicology, ATSDR, 1600 Clifton
Road, N.E., Mailstop E-29, Atlanta, Georgia 30333, telephone 404-639-
6306.
SUPPLEMENTARY INFORMATION:
Background
CERCLA as amended by SARA (42 U.S.C. 9604(i)) requires that ATSDR
(1) jointly with the EPA, develop and prioritize a list of hazardous
substances found at National Priorities List (NPL) sites, (2) prepare
toxicological profiles for these substances, and (3) assure the
initiation of a research program to address identified data needs
associated with the substances. Before starting such a program, ATSDR
will consider recommendations of the Interagency Testing Committee on
the type of research that should be done. This committee was
established under section 4(e) of the Toxic Substances Control Act of
1976 (TSCA).
On October 17, 1991, ATSDR announced the identification of the
priority data needs for 38 priority hazardous substances (56 FR 52178),
requested public comments, and invited private- sector organizations to
volunteer to conduct research to address specific priority data needs.
On November 16, 1992, the agency published a revised list of 117
priority data needs for these priority hazardous substances (57 FR
54150).
The major goals of the ATSDR SSARP are (1) to address the
substance-specific information needs of the public and scientific
community, and (2) to supply necessary information to improve the
database to conduct comprehensive public health assessments of
populations living near hazardous waste sites. This program will also
provide data that can be generalized to other substances or areas of
science, including risk assessment of chemicals, thus creating a
scientific base for addressing a broader range of data needs.
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
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.
The TASARC, comprised of scientists from ATSDR, NTP, and the EPA
has been set up:
(1) To advise on the assignment of priorities on mechanisms for
addressing data needs;
(2) To coordinate knowledge of research activities to avoid
duplication of research in other programs and under other authorities;
(3) To advise on issues of science related to substance-specific
data needs; and
(4) To maintain a scheduled forum that provides an overall review
of the ATSDR SSARP.
The TASARC has met six times since the SSARP began. This Notice is
an update on the status of ATSDR's efforts to implement the SSARP,
focusing on ongoing activities relevant to test-rule development under
TSCA/FIFRA, private-sector voluntarism, and the direct use of CERCLA
funds.
Additional data needs are being addressed through an interagency
agreement with NTP, by ATSDR's Great Lakes Human Health Effects
Research Program, and other agency programs. To date, a total of 63
research needs associated with 38 ATSDR priority hazardous substances
(including 15 polycyclic aromatic hydrocarbons) are being addressed via
these mechanisms (Table 1).
[[Page 14421]]
ATSDR believes that these priority data needs will remain on the
agency's list until ongoing studies to address them have been
completed, peer-reviewed, and accepted by ATSDR. However, priority data
needs could be deleted from the list (Table 1) if upon re-evaluation of
the existing database, the agency determines that additional studies
are no longer needed. Three recent examples follow. ATSDR, in
consultation with the TASARC, re-evaluated the database for acute
inhalation toxicity for vinyl chloride and determined no additional
data are needed at this time (Table 1). With regard to the priority
data need for oral developmental toxicity studies for
tetrachloroethylene (PERC), ATSDR recently re-evaluated the database
during the update of the toxicological profile for this substance.
ATSDR concluded that the database was sufficient to derive a minimal
risk level (MRL) for acute oral exposure based on a developmental
toxicity study. Although ATSDR believes that additional developmental
data would be useful to more fully characterize the effects and
increase the confidence level of the MRL, the agency now believes that
this data is more appropriately classified as a data need rather than a
priority data need. Therefore, this priority data need has also been
deleted from the list (Table 1). Similarly, the priority data need for
additional acute oral studies for trichloroethylene has been
reclassified as a data need and thus deleted from the list (Table 1)
because an MRL was derived during the updating of the toxicological
profile. Conversely, additional priority data needs could be included
in the ATSDR list based on assessment by agency programs (See Section
F, ``Other ATSDR Programs,'' which discusses exposure subregistries).
A. TSCA/FIFRA
In developing and implementing the Substance-Specific Applied
Research Program, ATSDR, NTP, and EPA have established procedures to
identify priority data needs of mutual interest to Federal programs.
These data needs are being addressed through a program of toxicologic
testing under TSCA. This research will be conducted according to
established TSCA procedures and guidelines. Generally, this testing
will address more than one Federal program's need. Following review and
endorsement by the TASARC oversight committee during fiscal year (FY)
1993, of the 117 priority data needs for 38 substances, approximately
60 priority data needs were referred to the EPA under TSCA/FIFRA
authorities.
During 1994, EPA added 11 ATSDR substances (and associated 26
priority data needs) to its master testing list, the first step in
test-rule development under TSCA, Section 4 (59 FR 11434, March 10,
1994). On September 30, 1994, EPA published a Federal Register Notice
soliciting testing proposals from industry to address the priority data
needs identified for ATSDR's priority hazardous substances (59 FR
49934). Although no manufacturers or processors of these substances
came forward with testing proposals, several industry groups responded
by submitting proposals to address some of the data needs via ATSDR's
voluntary research program described in detail in Section B, ``Private-
Sector Voluntarism.'' The priority data needs currently being addressed
by TSCA/FIFRA are listed in Table 2.
ATSDR shared its priority data needs for these substances with
other Federal agencies and programs. On several occasions when ATSDR
identified priority data needs for oral exposure, other agencies needed
inhalation data. In response, ATSDR is considering proposals to conduct
inhalation studies in conjunction with physiologically based
pharmacokinetic (PBPK) studies in lieu of oral bioassays. ATSDR expects
that inhalation data derived from these studies can be used with PBPK
modeling to address its oral toxicity data needs.
Table 2 includes the priority data needs for three metals, i.e.,
beryllium, chromium and mercury. However, the specific forms of the
metals to be tested are yet to be determined. The TASARC has
established a workgroup to address this issue. The workgroup will also
consider the needs of other Federal agencies and EPA programs. The EPA
will solicit testing proposals for these three metals at a later date.
B. Private-Sector Voluntarism
As part of the SSARP, on February 7, 1992, ATSDR initially
announced a set of proposed procedures for conducting voluntary
research (56 FR 4758). Revisions based on public comments were
published on November 16, 1992 (57 FR 54160). Private-sector
organizations were encouraged to volunteer to conduct research to
address these specific priority data needs.
ATSDR has been pursuing voluntary research interests with three
private-sector organizations: the General Electric Company (GE), the
Halogenated Solvents Industry Alliance (HSIA), and the Chemical
Manufacturers Association (CMA). Preliminary discussions are being held
with a fourth organization, the Shell Oil Company. Through the
voluntary research efforts of these organizations, data needs for two
classes of substances (PCB compounds and volatile organic compounds)
are being addressed (Table 2). To date, two memoranda of understanding
(MOU) have been signed by ATSDR and the interested parties. A third MOU
is under development.
General Electric Company (GE)
On February 8, 1995, ATSDR entered into an MOU with GE. This was
the first time a private-sector organization volunteered to conduct
research to address ATSDR's data needs identified in its SSARP. The MOU
with GE covers the following three studies on PCBs:
* Project 1, ``An assessment of the chronic toxicity and
oncogenicity of Aroclor-1016, Aroclor-1242, Aroclor-1254, and Aroclor-
1260 administered in diet to rats,'' was initiated on February 8, 1993.
* Project 2, ``Metabolite detection as a tool for the determination
of naturally occurring aerobic PCB biodegradation,'' was initiated on
January 2, 1995.
* Project 3, ``PCB congener analyses,'' was initiated on February
8, 1993.
While the above studies do not address ATSDR's priority data needs
for PCBs, the three projects will address some of the agency's data
needs for these substances. Specifically, although ATSDR has identified
bioassays via the inhalation and dermal routes as data needs for PCBs,
agency scientists believe information gained via GE's oral bioassay
(Project 1) is pertinent to understanding the toxicity of PCBs.
Furthermore, first-pass metabolism does not appear to play a key role
for these substances. Therefore, toxicity information to be obtained
from the GE oral bioassay is expected to be relevant to the inhalation
and dermal routes.
ATSDR has identified PCB degradation in sediment as a data need.
Additional environmental fate information is needed to estimate
exposure to PCBs under various conditions of environmental release in
order to plan and conduct follow-up exposure and health studies.
Therefore, Project 2 will address ATSDR's data need for the
environmental fate of PCBs.
Although ATSDR has not identified PCB congener analyses (Project 3)
as a data need, agency scientists believe that the toxicokinetics data
(using selected tissues from Project 1) may provide important knowledge
about the correlation of health effects with relevant PCB congeners.
[[Page 14422]]
Halogenated Solvents Industry Alliance (HSIA)
On April 4, 1995, ATSDR entered into an MOU with HSIA covering
studies to address three ATSDR priority toxicity data needs for
methylene chloride. The studies consist of acute- and subchronic-
duration, and developmental toxicity via oral exposure. The data will
be obtained by using PBPK modeling. These studies were initiated on May
23, 1995.
HSIA has also proposed to conduct a 28-day immunopathology
assessment for methylene chloride via oral exposure, a priority data
need identified by ATSDR. The agency expects to receive a study
protocol from HSIA for peer review in the near future.
Currently, HSIA and ATSDR continue to discuss voluntary research
efforts for trichloroethylene (TCE) and tetrachloroethylene (PERC).
With regard to TCE, ATSDR has recently reclassified the priority
data need for acute oral data to a data need, (see Background section
of this Notice). The agency is continuing its discussion with HSIA to
assess the possibility of conducting a study or utilizing benchmark
dose modeling to address this data need. As for immunopathology data,
HSIA proposed to first review the existing data for TCE. If the data
are inadequate and the methylene chloride immunopathology study
mentioned above has provided meaningful information, HSIA would then
conduct a similar study for TCE.
Regarding the priority data needs for PERC, HSIA plans to obtain
the oral neurotoxicity data called for by the agency by PBPK modeling.
The database to be used for modeling will include the HSIA-sponsored
inhalation neurotoxicity study recently approved by EPA. EPA and ATSDR
scientists recently reviewed and accepted the HSIA-sponsored
reproductive toxicity study of PERC via inhalation. HSIA proposed to
address ATSDR's priority data need for oral reproductive data using
PBPK modeling. As for ATSDR's priority data need for immunopathology
data, HSIA would follow the same procedures as for TCE (described
above).
Finally, with regard to ATSDR's data need for oral developmental
toxicity studies for PERC (see Background section of this Notice),
ATSDR is continuing its discussion with HSIA to obtain this data via
PBPK modeling once the EPA-required inhalation developmental toxicity
study has been completed.
Chemical Manufacturers Association (CMA)
During FY 1995, the CMA submitted a study protocol addressing two
ATSDR priority data needs for vinyl chloride, specifically, inhalation
reproductive and developmental toxicity studies in rats.
ATSDR accepted the study protocol as a candidate for voluntary
research based on ATSDR peer reviews and CMA's satisfactory response to
the peer reviewers' comments. ATSDR expects to finalize an MOU with CMA
covering this study in the near future.
EPA no longer requires inhalation neurological data for vinyl
chloride as originally stated in its solicitation Notice (59 FR 49934,
September 30, 1994). Its decision is based on a recent reevaluation of
the database.
C. CERCLA-Funded Research (Minority Health Professions Foundation
Research Program)
During FY 1992, ATSDR announced a $4 million cooperative agreement
program with the Minority Health Professions Foundation (MHPF) to
support substance-specific investigations. This cooperative venture is
supported by the direct use of CERCLA funds. About $4 million was
allocated annually for FYs 1993 to 1995 to continue this research
program that ends in September 1997.
Currently, 9 priority data needs for 21 priority hazardous
substances (including 15 PAHs) in the SSARP are being addressed by the
MHPF institutions through this program. Also, the MHPF research program
will address 13 other substance-specific data needs identified in the
ATSDR toxicological profiles concerning exposures and related health
effects. To date, more than 20 abstracts have been presented at
scientific meetings, 4 manuscripts have been published in peer-reviewed
journals, and 7 manuscripts are in preparation. The institutions
receiving awards and their respective research projects are listed in
Table 2.
A not-for-profit 501(c)(3) organization, the MHPF comprises 11
minority health professions schools. Its primary mission is to research
the health problems that disproportionately affect poor and minority
citizens. The purposes of the ATSDR-MHPF cooperative agreement are (1)
to initiate research to address ATSDR-identified data needs for
priority hazardous substances, and (2) to enhance existing disciplinary
capacities to conduct research in environmental health at MHPF member
institutions.
The areas of research at MHPF institutions include those related to
broad areas of toxicology and environmental health science. Some MHPF
members are conducting health studies of minority groups exposed to
ATSDR's priority hazardous substances.
D. National Toxicology Program (NTP)
ATSDR maintains an interagency agreement (IAG) with NTP to conduct
toxicologic testing of substances identified at NPL sites. The studies
determine levels of exposure that present a significant risk to humans
of acute, subchronic, and chronic health effects. Often these studies
include an assessment of the substance's ability to cause cancer,
reproductive toxicity, and birth defects. The results of these studies
are used by regulatory agencies such as the Food and Drug
Administration and EPA, various environmental and industrial groups,
and ATSDR to improve the ability to conduct public health assessments
at NPL sites.
Under this agreement, one toxicity priority data need identified in
the SSARP (immunotoxicology study of carbon tetrachloride) is being
addressed.
An area of ongoing research by the NTP is to study the
bioavailability of PCBs in soil, a priority data need for ATSDR.
Therefore, NTP research may also potentially address this ATSDR
priority data need.
During FY 1993, the existing IAG was modified to include toxicity
studies of ATSDR's priority hazardous substances via application of
structure-activity relationship (SAR) techniques and PBPK modeling. NTP
indicated future plans for SAR modeling for reproductive and
immunologic endpoints. ATSDR is continuing to work closely with NTP as
the agency has identified many reproductive and immunologic data needs
for the 38 priority hazardous substances. As discussed in Section A,
``TSCA/FIFRA,'' ATSDR will consider using PBPK modeling to address data
needs when models are well developed and validated. Therefore, ATSDR
will continue to work closely with NTP in its efforts to refine the
models.
E. Great Lakes Human Health Effects Research Program
Some of the priority data needs identified in the SSARP have been
independently identified as research needs through the ATSDR Great
Lakes Human Health Effects Research Program, a separate research
program. To date, 12 priority data needs for 19 priority hazardous
substances (including 15 PAHs) identified in the SSARP are being
addressed through this program. The institutions receiving
[[Page 14423]]
awards and their respective studies are listed in Table 2.
The Great Lakes Critical Programs Act of 1990 mandated that EPA, in
consultation with ATSDR, prepare a report that assesses the adverse
effects of pollutants in the Great Lakes system on the health of
individuals in the Great Lakes states. This report was recently
transmitted to the Congress by the EPA Administrator.
In support of this directive, ATSDR received funds to carry out
research. The ATSDR-supported research projects focus on at-risk
populations to further define the human health consequences of exposure
to persistently toxic substances in the Great Lakes basin. The research
activities include but are not limited to the following:
(1) Characterizing exposure and determining the profiles and levels
of Great Lakes contaminants in biologic tissues and fluids in at-risk
populations;
(2) Identifying sensitive and specific human reproductive/
developmental endpoints and correlating them to exposure to Great Lakes
contaminants;
(3) Determining the short- and long-term risk(s) of adverse health
effects in progeny whose parents were exposed to Great Lakes
contaminants;
(4) Investigating the feasibility of establishing registries and
surveillance cohorts in the Great Lakes region; and
(5) Establishing a chemical mixtures database with emphasis on
tissue and blood levels in order to identify new cohorts, conduct
surveillance and health effects studies, and establish registries and
surveillance cohorts.
During FY 1992, ATSDR announced a $2 million grant program to
conduct research on the impact on people's health from eating
contaminated fish from the Great Lakes region. On September 30, 1992,
ATSDR announced 9 awards under this program.
In FY 1993, about $3 million was allocated to support the
continuation of the research projects conducted at the 9 institutions
originally funded during FY 1992. In addition, ATSDR awarded one new
grant to the Michigan Department of Public Health to design, establish,
and operate a professionally creditable, interlaboratory quality
assurance/quality control program for the ATSDR Great Lakes Human
Health Effects Research Program. Additional funding of $3 million and
$4 million for FYs 1994 and 1995, respectively, was allocated to
continue support of the 10 research projects.
During FY 1994, ATSDR held a Great Lakes Research Symposium in
Detroit, Michigan. The proceedings of the symposium will be published
in the Journal of Toxicology and Industrial Health in the near future.
Other ATSDR Programs
In its role as a public health agency addressing environmental
health, when appropriate, ATSDR may collect human data to validate
substance-specific exposure and toxicity findings. Information on
levels of contaminants in humans has been identified and remains as a
priority data need for 37 of the 38 priority substances (Table 1).
ATSDR will obtain this information through exposure and health effects
studies, and through establishing and using substance-specific
subregistries of people within the agency's National Exposure Registry
who have potentially been exposed to these substances.
The list of 38 priority hazardous substances in the SSARP was
forwarded to ATSDR's Exposure and Disease Registry Branch (EDRB),
Division of Health Studies, for consideration as potential candidates
for subregistries of exposed persons, based on criteria described in
its 1988 document, ``Policies and Procedures for Establishing a
National Registry of Persons Exposed to Hazardous Substances.''
To date, ATSDR has selected benzene, chromium, and
trichloroethylene as primary contaminants to establish subregistries in
the National Exposure Registry. However, aldrin/dieldrin, carbon
tetrachloride, chloroethane, chloroform, cyanide, p,p'- DDT, DDE, DDD,
di(2-ethylhexyl)phthalate, mercury, methylene chloride, PAHs, selenium,
tetrachloroethylene, and vinyl chloride remain in the candidate pool.
They will be considered for selection as primary contaminants during
each selection process (Table 1).
Since the publication of the ATSDR March 10, 1994, Federal Register
Notice (59 FR 11434), EDRB has re-evaluated the databases and included
nickel, PCBs, toluene, and zinc in the candidate pool for consideration
during each selection process (Table 1). However, arsenic, beryllium,
cadmium, and lead are not considered to be in the pool of candidate
substances for an exposure registry at this time. This decision will be
re-evaluated as more information on the chemicals and exposure sites
become available.
Finally, the need to collect, evaluate, and interpret environmental
data from contaminated media around hazardous waste sites remains a
priority data need for all 38 priority hazardous substances by ATSDR.
However, agency scientists realize that a substantial amount 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 characterize
better the need for additional site-specific information.
The results of the research conducted via the SSARP will be used
for public health assessments and to reassess ATSDR's substance-
specific priority data needs. The agency expects to re-evaluate the
priority data needs for priority hazardous substances every three
years.
Dated: March 26, 1996.
Claire V. Broome,
Deputy Administrator, Agency for Toxic Substances and Disease Registry
.
Table 1.--Substance-Specific Priority Data Needs (PDN) Currently Being
Addressed Under ATSDR's Applied Research Programs
------------------------------------------------------------------------
Substance PDN ID PDN description Programs (1)
------------------------------------------------------------------------
Lead................ 1A Mechanistic studies M
on the neurotoxic
effects of lead.
1B Analytical methods
for tissue levels.
1C Exposure levels in M, G
humans living near
hazardous waste
sites and other
populations, such
as exposed workers.
Arsenic............. 2A Comparative .............
toxicokinetic
studies to
determine if an
appropriate animal
species can be
identified.
2B Half-lives in
surface water,
groundwater.
2C Bioavailability from
soil.
2D Exposure levels in
humans living near
hazardous waste
sites and other
populations, such
as exposed workers
Mercury............. 3A Multigeneration M, G
reproductive
toxicity study via
oral exposure.
3B Dose-response data E
in animals for
chronic-duration
oral exposure.
[[Page 14424]]
3C Immunotoxicology E
battery of tests
via oral exposure.
3D Exposure levels in G
humans living near
hazardous waste
sites and other
populations, such
as exposed workers.
3E Potential candidate A, G
for subregistry of
exposed persons.
Vinyl Chloride...... 4A Dose-response data O (2)
in animals for
acute-duration
inhalation exposure.
4B Multigeneration V (7)
reproductive
toxicity study via
inhalation.
4C Dose-response data
in animals for
chronic-duration
inhalation
exposure.
4D Mitigation of vinyl
chloride-induced
toxicity.
4E 2-species V (7)
developmental
toxicity study via
inhalation.
4F Exposure levels in
humans living near
hazardous waste
sites and other
populations, such
as exposed workers
4G Potential candidate A
for subregistry of
exposed persons.
Benzene............. 5A Dose-response data E
in animals for
acute- and
intermediate-
duration oral
exposure. The
subchronic study
should include an
extended
reproductive organ
histopathology.
5B 2-species M
developmental
toxicity study via
oral exposure.
5C Neurotoxicology E
battery of tests
via oral exposure.
5D Epidemiologic
studies on the
health effects of
benzene (Special
emphasis endpoints
include
immunotoxicity).
5E Exposure levels in
humans living near
hazardous waste
sites and other
populations, such
as exposed workers.
Cadmium............. 6A Analytical methods
for biological
tissues and fluids
and environmental
media.
6B Exposure levels in
humans living near
hazardous waste
sites and other
populations, such
as exposed workers.
PCBs................ 7A Dose-response data G
in animals for
acute- and
intermediate-
duration oral
exposures.
7B Biodegradation of
PCBs in water;
bioavailability of
PCBs in air, water
and soil
7C Dose-response data
in animals for
acute- and
intermediate-
duration inhalation
exposures. The
subchronic study
should include
extended
reproductive organ
histopathology
7D Epidemiologic G
studies on the
health effects of
PCBs (Special
emphasis endpoints
include
immunotoxicity,
gastrointestinal
toxicity, liver,
kidney, thyroid
toxicity,
reproductive/
developmental
toxicity).
7E Exposure levels in G
humans living near
hazardous waste
sites and other
populations, such
as exposed workers.
7F Potential candidate A (3)
for subregistry of
exposed persons.
7G (8) Chronic toxicity and V
oncogenicity via
oral exposure.
7H (8) Aerobic PCB V
biodegradation in
sediment.
7I (8) PCB congener V
analysis.
Chloroform.......... 8A Dose-response data
in animals for
intermediate-
duration oral
exposure.
8B Epidemiologic
studies on the
health effects of
chloroform (Special
emphasis endpoints
include cancer,
neurotoxicity,
reproductive and
developmental
toxicity,
hepatotoxicity, and
renal toxicity)
8C Exposure levels in
humans living near
hazardous waste
sites and other
populations, such
as exposed workers
8D Potential candidate A
for subregistry of
exposed persons.
PAHs.............. 9A Dose-response data M
in animals for
intermediate
duration oral
exposures. The
subchronic study
should include
extended
reproductive organ
histopathology and
immunopathology.
9B 2-Species
developmental
toxicity study via
inhalation or oral
exposure
9C Mechanistic studies
on PAHs, on how
mixtures of PAHs
can influence the
ultimate activation
of PAHs, and on how
PAHs affect rapidly
proliferating
tissues
9D Dose-response data M
in animals for
acute- and
intermediate-
duration inhalation
exposures. The
subchronic study
should include
extended
reproductive organ
histopathology and
immunopathology.
9E Epidemiologic G
studies on the
health effects of
PAHs (Special
emphasis endpoints
include cancer,
dermal,
hemolymphatic, and
hepatic).
9F Exposure levels in G
humans living near
hazardous waste
sites and other
populations, such
as exposed workers.
9G Potential candidate A
for subregistry of
exposed persons.
Trichloro-ethylene.. 10A Dose-response data O (2)
in animals for
acute- duration
oral exposure..
10B Neurotoxicology M
battery of tests
via the oral route.
10C Immunotoxicology V (4)
battery of tests
via the oral route.
10D Epidemiologic
studies on the
health effects of
trichloroethylene
(Special emphasis
endpoints include
cancer,
hepatotoxicity,
renal toxicity,
developmental
toxicity, and
neurotoxicity).
10E Exposure levels in
humans living near
hazardous waste
sites and other
populations, such
as exposed workers.
DDT................. 11A Dose-response data
in animals for
chronic-duration
oral exposure.
11B Comparative
toxicokinetic study
(across routes/
species).
11C Bioavailability and
bioaccumulation
from soil.
11D Epidemiologic G
studies on the
health effects of
DDT, DDD and DDE
(Special emphasis
endpoints include
immunotoxicity,
reproductive and
developmental
toxicity).
11E Exposure levels in G
humans living near
hazardous waste
sites and other
populations, such
as exposed workers.
[[Page 14425]]
11F Potential candidate A, G
for subregistry of
exposed persons.
Chromium............ 12A Dose-response data E
in animals for
acute-duration
exposure to
chromium (VI) and
(III) via oral
exposure and for
intermediate-
duration exposure
to chromium (VI)
via oral exposure.
12B Multigeneration E
reproductive
toxicity study via
oral exposure to
chromium (III) and
(VI).
12C Immunotoxicology E
battery of tests
following oral
exposure to
chromium (III) and
(VI).
12D 2-Species
developmental
toxicity study via
oral exposure to
chromium (III) and
(VI)
12E Exposure levels in
humans living near
hazardous waste
sites and other
populations, such
as exposed workers.
Tetrachloro- 13A Dose-response data V(4, 5)
ethylene. in animals for
acute-duration oral
exposure, including
neuropathology and
demeanor, and
immunopathology.
13B Multigeneration V(4, 5)
reproductive
toxicity study via
oral exposure.
13C Dose-response data
in animals for
chronic-duration
oral exposure,
including
neuropathology and
demeanor, and
immunopathology
13D 2-Species O (2)
developmental
toxicity study via
oral exposure.
13E Exposure levels in
humans living near
hazardous waste
sites and other
populations, such
as exposed workers.
13F Potential candidate A
for subregistry of
exposed persons
Aldrin/Dieldrin..... 14A Dose-response data
in animals for
intermediate-
duration oral
exposure.
14B Bioavailability from
soil.
14C Exposure levels in
humans living near
hazardous waste
sites and other
populations, such
as exposed workers.
14D Potential candidate A
for subregistry of
exposed persons.
Cyanide............. 15A Dose-response data E
in animals for
acute- and
intermediate-
duration exposures
via inhalation. The
subchronic study
should include
extended
reproductive organ
histopathology and
evaluation of
neurobehavioral and
neuropathological
endpoints.
15B 2-Species E
developmental
toxicity study via
oral exposure.
15C Evaluation of the E
environmental fate
of cyanide in soil.
15D Exposure levels in
humans living near
hazardous waste
sites and other
populations, such
as exposed workers.
15E Potential candidate A
for subregistry of
exposed persons.
Carbon Tetrachloride 16A Dose-response data
in animals for
chronic oral
exposure. The study
should include
extended
reproductive organ
and nervous tissue
(and demeanor)
histopathology.
16B Immunotoxicology NTP
battery of tests
via oral exposure.
16C Half-life in soil.
16D Exposure levels in
humans living near
hazardous waste
sites and other
populations, such
as exposed workers.
16E Potential candidate A
for subregistry of
exposed persons.
Beryllium........... 17A Dose-response data E
in animals for
acute- and
intermediate-
duration inhalation
exposures. The
subchronic study
should include
extended
reproductive organ
histopathology.
17B 2-Species E
developmental
toxicity study via
inhalation exposure.
17C Environmental fate E
in air; factors
affecting
bioavialability in
air.
17D Analytical methods
to determine
environmental
speciation.
17E Immunotoxicology E
battery of tests
following oral
exposure.
17F Exposure levels in
humans living near
hazardous waste
sites and other
populations, such
as exposed workers.
Toluene............. 18A Dose-response data E
in animals for
acute- and
intermediate-
duration oral
exposures. The
subchronic study
should include an
extended
histopathologic
evaluation of the
immune system.
18B Comparative E
toxicokinetic
studies
(Characterization
of absorption,
distribution, and
excretion via oral
exposure).
18C Neurotoxicology M
battery of tests
via oral exposure..
18D Mechanism of toluene-
induced
neurotoxicity.
18E Exposure levels in
humans living near
hazardous waste
sites and other
populations, such
as exposed workers.
18F Potential candidate A (3)
for subregistry of
exposed persons.
Nickel.............. 19A Epidemiologic
studies on the
health effects of
nickel (Special
emphasis endpoints
include
reproductive
toxicity).
19B 2-Species
developmental
toxicity study via
the oral route.
19C Dose-response data
in animals for
acute- and
intermediate-
duration oral
exposures.
19D Neurotoxicology
battery of tests
via oral exposure.
19E Bioavailability of
nickel from soil.
19F Exposure levels in
humans living near
hazardous waste
sites and other
populations, such
as exposed workers.
19G Potential candidate A (3)
for subregistry of
exposed persons.
Methylene Chloride.. 20A Dose-response data V (5,6)
in animals for
acute- and
intermediate-
duration oral
exposure. The sub-
chronic study
should include
extended
reproductive organ
histopathology,
neuropathology and
demeanor, and
immunopathology.
20B 2-Species V (5)
developmental
toxicity study via
the oral route.
20C Exposure levels in
humans living near
hazardous waste
sites and other
populations, such
as exposed workers.
20D Potential candidate A
for subregistry of
exposed persons.
[[Page 14426]]
Zinc................ 21A Dose-response data M
in animals for
acute- and
intermediate-
duration oral
exposures. The sub-
chronic study
should include an
extended
histopathologic
evaluation of the
immunologic and
neurologic systems.
21B Multigeneration
reproductive
toxicity study via
oral exposure.
21C Carcinogenicity
testing (2-year
bioassay) via oral
exposure.
21D Exposure levels in
humans living near
hazardous waste
sites and other
populations, such
as exposed workers.
21E Potential candidate A (3)
for subregistry of
exposed persons.
DEHP................ 22A Epidemiologic
studies on the
health effects of
DEHP (Special
emphasis endpoints
include cancer).
22B Dose-response data
in animals for
acute- and
intermediate-
duration oral
exposures. The
subchronic study
should include an
extended
histopathologic
evaluation of the
immunologic and
neurologic systems.
22C Multigeneration
reproductive
toxicity study via
oral exposure.
22D Comparative E
toxicokinetic
studies (Studies
designed to examine
how primates
metabolize and
distribute DEHP as
compared to rodents
via oral exposure).
22E Exposure levels in
humans living near
hazardous waste
sites and other
populations, such
as exposed workers.
22F Potential candidate A
for subregistry of
exposed persons.
Selenium............ 23A Dose-response data
in animals for
acute-duration oral
exposure.
23B Immunotoxicology
battery of tests
via oral exposure.
23C Epidemiologic
studies on the
health effects of
selenium (Special
emphasis endpoints
include cancer,
reproductive and
developmental
toxicity,
hepatotoxicity and
adverse skin
effects).
23D Exposure levels in
humans living near
hazardous waste
sites and other
populations, such
as exposed workers.
23E Potential candidate A
for subregistry of
exposed persons.
Chloroethane........ 24A Dose-response data E
in animals for
acute- and
intermediate-
duration oral
exposures. The
subchronic study
should include an
evaluation of
immune and nervous
system tissues, and
extended
reproductive organ
histopathology.
24B Dose-response data
in animals for
chronic inhalation
exposures. The
study should
include an
evaluation of
nervous system
tissues.
24C Potential candidate A
for subregistry of
exposed persons.
------------------------------------------------------------------------
\1\ ATSDR programs for addressing data needs. A=ATSDR Division of Health
Studies; E=Environmental Protection Agency-TSCA/FIFRA testing; G=Great
Lakes Human Health Research Program; M=Minority Health Professions
Foundation Schools; NTP=National Toxicology Program; V=Voluntary
research; O=Other.
\2\ No longer considered a priority data need based on recent evaluation
of the database by ATSDR.
\3\ These substances have been included in the pool of candidate
substances for subregistry development since the publication of the
Federal Register notice on March 10, 1994 (59 FR 11434).
\4\ Potentially to be addressed by ATSDR's Voluntary Research Program.
\5\ Data to be obtained by PBPK modeling.
\6\ Initiation of immunopathology study pending submission and peer
review of study protocol.
\7\ Data to be obtained from a combined 2-generation reproduction and
developmental toxicity study in rats.
\8\ Not a priority data need.
Table 2.--Groups Addressing ATSDR Priority Data Needs (PDN)
----------------------------------------------------------------------------------------------------------------
Firm, institution, agency,
ATSDR Program or Consortium Substance PDN ID
----------------------------------------------------------------------------------------------------------------
Voluntarism....................... Chemical Manufacturers Vinyl Chloride...... 4B, 4E
Association.
General Electric Company.. PCBs................ 7G, 7H, 7I
Halogenated Solvents Trichloroethylene... 10C
Industry Alliance.
Tetrachloroethylene. 13A, 13B
Methylene chloride.. 20A, 20B
Minority Health Professions Florida A & M University.. Lead................ 1A
Foundation Schools.
The King/Drew Medical Lead................ 1C
Center of the Charles R.
Drew University of
Medicine and Science.
Meharry Medical College... PAHs................ 9A, 9D
Morehouse School of Lead................ 1C
Medicine.
Texas Southern University. Lead................ 1A
Trichloroethylene... 10B
Toluene............. 18C
Tuskegee University....... Mercury............. 3A
Zinc................ 21A
Xavier University......... Benzene............. 5B
Zinc................ 21A
Great Lakes Human Health Research Michigan State University. Lead................ 1C
Program.
Mercury............. 3D
PCBs................ 7F
[[Page 14427]]
DDT................. 11D, 11E
New York State Health Lead................ 1C
Department.
Mercury............. 3D
PCBs................ 7F
State University of New Lead................ 1C
York at Buffalo.
Mercury............. 3D
PCBs................ 7E, 7F
DDT................. 11D, 11E
State University of New Lead................ 1C
York at Oswego.
Mercury............. 3A, 3D
PCBs................ 7E, 7F
DDT................. 11D, 11E
University of Illinois at Lead................ 1C
Chicago.
Mercury............. 3A, 3D
PCBs................ 7E, 7F
DDT................. 11D, 11E
University of Illinois at Lead................ 1C
Urbana-Champaign.
Mercury............. 3D
PCBs................ 7E, 7F
University of Wisconsin-- Lead................ 1C
Superior.
Mercury............. 3D
PCBs................ 7A, 7E, 7F
Wisconsin Department of Lead................ 1C
Health and Social
Services.
Mercury............. 3D, 3E
PCBs................ 7F
PAHs................ 9E, 9F
.......................... DDT................. 11D, 11E, 11F
TSCA/FIFRA........................ Environmental Protection Mercury............. 3B
Agency.
Mercury............. 3C
Benzene............. 5A
Benzene............. 5C
Chromium............ 12A
Chromium............ 12B
Chromium............ 12C
Cyanide............. 15A
Cyanide............. 15B
Cyanide............. 15C
Beryllium........... 17A
Beryllium........... 17B
Beryllium........... 17C
Beryllium........... 17E
Toluene............. 18A
Toluene............. 18B
DEHP................ 22D
Chloroethane........ 24A
National Toxicology Program....... National Institute of Carbon Tetrachloride 16B
Environmental Health
Sciences.
----------------------------------------------------------------------------------------------------------------
[FR Doc. 96-7852 Filed 3-29-96; 8:45 am]
BILLING CODE 4163-70-P
