Furthermore, in the event a priority data need is considered filled, it does not necessarily mean that the study has been completed and that ATSDR has accepted the data. It does, however, indicate that the Agency no longer considers it a priority to initiate additional studies at this time.

A priority data need remains unchanged:

Specific Criteria

Examples of specific criteria for two categories of priority data needs are described below.

In updating the SSARP, the status of the priority data needs may change as new information becomes available. Further, during the literature review, new studies may be identified suggesting other effects of concern, such as those related to endocrine disruptors and children's health, which were not included in the original list of priority data needs. In such cases, additional priority data needs may be added to the research agenda. For example, in addressing issues relating to children's health, ATSDR considers it a priority to obtain data on exposure levels in children; therefore, when such information is available, it is used to fill this additional priority data need (e.g., cadmium, chlordane, chlorinated dibenzopdioxins, DDT, lead, and pentachlorophenol, see Table 1).

In contrast, the Agency may consider a previously identified priority data need to no longer be a priority to fill at this time and thus be deleted from the list of priority data needs. However, it remains a data need for the Agency. For example, as a result of reevaluation of the database for dinbutyl phthalate, two of its previously identified priority data needs, i.e., immunotoxicity and neurotoxicity studies via oral exposure are no longer considered to be priority data needs. This is due to the fact that the immune system does not appear to be a target for dinbutyl phthalate toxicity and that additional neurotoxicity studies do not seem necessary because of the lack of effects seen in longterm neurotoxicity studies. In addition, under the Agency's Voluntary Research Program, the Halogenated Solvents Industry Alliance, Inc. (HSIA) proposed to fill a trichloroethylene priority data need (doseresponse data for intermediateduration, oral exposure) by conducting PBPK modeling to obtain the data for oral exposure using existing inhalation data. However, ATSDR is concerned that, based on the existing data for this exposure duration, it is not clear if the most sensitive end point for oral exposure is the same as that for inhalation exposure. Therefore, the Agency believes it is prudent not to consider it a priority to conduct a PBPK study to obtain the oral data at this time pending evaluation of additional information. This is reflected in Table 1 from which this priority data need has been deleted.

Update of Activities in the SSARP

An update of the activities associated with the mechanisms for implementing the ATSDR SubstanceSpecific Applied Research Program (SSARP) is discussed below.

A. TSCA/FIFRA

In developing and implementing the SSARP, ATSDR, NIEHS/NTP, and EPA have identified a subset of priority data needs for substances of mutual interest to the federal programs. These priority data needs are being addressed through a program of toxicological testing under TSCA according to established procedures and guidelines. On several occasions when ATSDR identified priority data needs for oral exposure, other agencies needed inhalation data. In response, ATSDR considers proposals to conduct inhalation studies in conjunction with physiologically based pharmacokinetic (PBPK) studies in lieu of oral studies. ATSDR expects that inhalation data derived from these studies can be used with PBPK modeling to address its oral toxicity priority data needs. Currently, an EPA/ATSDR test rule, under development, includes eight ATSDR substances, i.e., benzene, chloroethane, cyanide (hydrogen cyanide and sodium cyanide), methylene chloride, tetrachloroethylene, toluene and trichloroethylene, and addresses 13 ATSDR priority data needs (Table 2). The test rule is presently undergoing ATSDR and EPA final review and is anticipated to be available for public comment in Spring 2006.

At least seven metals included in the ATSDR's SSARP (arsenic, beryllium, chromium, manganese, mercury, nickel, and selenium, associated with 21 priority data needs) (Table 2) have been forwarded to EPA through TASARC for toxicity testing. The EPA is currently developing a risk assessment framework for metals. Once the framework has been adopted, the EPA will solicit testing proposals for these metals and pursue appropriate testing mechanisms at a later date. B. PrivateSector Voluntarism

As part of the SubstanceSpecific Applied Research Program (SSARP), ATSDR announced a set of proposed procedures for conducting voluntary research in the Federal Register (57 FR 4758) on February 7, 1992. Revisions based on public comments were published on November 16, 1992 (57 FR 54160). Privatesector organizations are encouraged to volunteer to conduct research to fill specific priority data needs at no expense to ATSDR. All study protocols and final reports are subjected to ATSDR's external peer review, and ATSDR accepts the study results based on the peer reviewers' recommendation and the industry groups' satisfactory response to the reviewers' comments.

To date, ATSDR has established memoranda of understanding with four industry groups. Through the voluntary research efforts of these organizations, at least 15 research needs (12 priority data needs and 3 data needs) for methylene chloride, tetrachloroethylene
(perchloroethylene), trichloroethylene, polychlorinated biphenyl compounds [PCBs], and vinyl chloride have been or are being filled (Table 2).

Industry groups which conducted studies under the Voluntary Research Program include:
The American Chemistry Council (ACC) [Formerly the Chemical Manufacturers Association (CMA)]

ATSDR accepted the ACC studies ``Vinyl chloride: Combined inhalation twogeneration reproduction and developmental toxicity study in CD rats.''

General Electric Company (GE)

GE conducted studies on polychlorinated biphenyls including ``An assessment of the chronic toxicity and oncogenicity of Aroclors 1016, [[Page 71509]]
1242, 1254, and 1260 administered in diet to rats,'' ``PCB congener analyses,'' and ``Metabolite detection as a tool for determining naturally occurring aerobic PCB biodegradation.'' Although these studies do not specifically address ATSDR's priority data needs for PCBs, they do address other Agency research needs for these substances. Halogenated Solvents Industry Alliance, Inc. (HSIA)

To date, ATSDR has entered into five MOUs with HSIA to conduct studies to fill priority data needs for methylene chloride, tetrachloroethylene and trichloroethylene. In addition, in 2002, HSIA signed a letter of agreement with ATSDR stating that HSIA volunteers to conduct studies to fill ATSDR's remaining priority data needs for tetrachloroethylene (perchloroethylene) and trichloroethylene. These studies are being done in conjunction with the EPA/ATSDR test rule and EPA's Voluntary Children's Chemical Evaluation Program. In some cases, HSIA first conducted a study via inhalation which was followed by route extrapolation via PBPK modeling to obtain data for oral exposure. This is because, for specific chemicals, EPA requires inhalation data while ATSDR has determined that ingestion of contaminated environmental media is the primary exposure route at hazardous waste sites.

HSIA studies accepted by ATSDR include:
``Addressing priority data needs for methylene chloride with physiologically based pharmacokinetic modeling'' which evaluates acute and subchronicduration toxicity and developmental toxicity via oral exposure.
``Methylene chloride: 28 day inhalation toxicity study in the rat to assess potential immunotoxicity.''
``Immunotoxic potential of orally administered dichloromethane from immunotoxicity studies conducted by the inhalation route.'' (PBPK modeling)
``Trichloroethylene: Inhalation developmental toxicity study in CD rats.'' HSIA will conduct PBPK modeling to obtain data for oral exposure based on the inhalation data.
``Trichloroethylene (TCE): Immunotoxicity potential in CD rats following a 4week vapor inhalation exposure.'' The final report of the study is undergoing ATSDR's external peer review. Pending ATSDR's acceptance of the inhalation study, HSIA will conduct PBPK modeling to obtain data for oral exposure based on the inhalation data. ``Perchloroethylene: Study of effects on embryofetal development in CD rats by inhalation administration.'' HSIA will conduct PBPK modeling to obtain data for oral exposure based on the inhalation data. Electric Power Research Institute, Inc. (EPRI)

In addition to the substancespecific MOUs described above, ATSDR also signed an MOU with EPRI to conduct a study ``Validation of test methods for assessing neurodevelopment in children.'' In this particular case, ATSDR and three other federal agencies (the Food and Drug Administration, EPA, and NIEHS) were also funding partners. C. CERCLAFunded 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 substancespecific investigations. A notforprofit Internal Revenue Code 501(c)(3) organization, the MHPF comprises 11 minority health professions schools at historically black colleges and universities. The MHPF mission is to research health problems that disproportionately affect poor and minority citizens. The purpose of the cooperative agreement was to address substancespecific data needs for priority hazardous substances identified by ATSDR. In addition, the agreement strengthened the environmental health research opportunities for scientists and students at MHPF member institutions and enhanced existing disciplinary capacities to conduct research in toxicology and environmental health. The MHPF published a report, ``Environmental Health and Toxicology Research Program: Meeting Environmental Health Challenges Through Research, Education, and Service,'' that describes the research findings and other successes from the first 5 years of the program.

In the first five year project period that concluded during FY 1997, nine priority data needs for 21 priority hazardous substances and 22 other research needs for these and other substances were addressed. Research initiated in the second 5year project period included studies to address 10 additional priority data needs for chlordane, dinbutyl phthalate, lead, manganese, the polycylic aromatic hydrocarbons (PAHs), zinc, and eight other research needs. To date, 14 priority data needs have been filled through this cooperative agreement (Table 1).

During 2003, ATSDR announced a new five year cooperative agreement program with the MHPF. The purpose of the program is to apply findings from the previous ten year environmental health and Toxicology Research Program and to improve public health and environmental medicine in low income and minority communities. The new program builds on earlier efforts and expands the Program's public environmental health impact on affected communities. Activities across the following four research and environmental public health focus areas were funded to initiate this new program: substancespecific toxicology research, environmental exposure assessment, communitybased environmental health education, and environmental health education for primarycare providers. No additional priority data needs are being addressed under this new program.

To date, Program research findings and other activities have resulted in the publication of more than 50 manuscripts in peer reviewed journals. The institutions which have received awards and their respective studies are listed in Table 2.

D. National Toxicology Program (NTP)

Section 104(i)(5) of CERCLA directs the administrator of ATSDR (in consultation with the administrator of EPA and agencies and programs of the Public Health Service) to assess whether adequate information on the health effects of priority hazardous substances found at NPL sites is available. Where adequate information is not available, ATSDR, in cooperation with the National Toxicology Program (NTP), is required to assure the initiation of a program of research designed to determine these health effects (and techniques for developing methods to determine such health effects).

ATSDR continues to collaborate with NTP to address priority data needs of mutual interest. Chemicals for which NTP has conducted studies (or is in the process of conducting studies) to fill ATSDR's priority data needs include carbon tetrachloride, 1,1dichloroethene, dinbutyl phthalate, disulfoton, and heptachlor (Table 2).

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.

In support of the Great Lakes Critical Programs Act of 1990, ATSDR announced in Fiscal Year 1992 the availability of $2 million for a grant
[[Page 71510]]
program to conduct research on the potential for short and longterm adverse health effects from consumption of contaminated fish from the Great Lakes basin. Research undertaken through this program is intended to build on and amplify the results of past and ongoing fish consumption research in the Great Lakes basin. The ATSDRsupported research projects focus on known highrisk populations to define further the human health consequences of exposure to persistent toxic substances (PTSs) identified in the Great Lakes basin. These atrisk populations include sport anglers; African Americans, Asians and other nonEnglish speaking populations; pregnant women; fetuses, nursing infants, and children of mothers who consume contaminated Great Lakes sport fish; the elderly, and the urban poor. To date, the research activities of the ATSDR Great Lakes Human Health Effects Research Program have resulted in 70 publications in peerreviewed journals.

Currently, 14 priority data needs for 24 priority hazardous substances (including 15 PAHs) identified in the SSARP are being addressed through this program. The institutions which have received awards and their respective studies are listed in Table 2.

F. Other ATSDR Programs

In its role as a public health agency addressing environmental health, ATSDR may collect human data to validate substancespecific exposure and toxicity findings. The need for additional information on levels of contaminants in humans has been identified, and remains as a priority data need for 59 of the 60 priority substances (Table 1). In some cases, ATSDR anticipates obtaining this information through exposure and health effects studies, and through establishing and using substancespecific subregistries of people within the Agency's National Exposure Registry who have potentially been exposed to these substances. Regarding the priority data need for exposure
subregistries, the list of the 60 priority hazardous substances in the SSARP was forwarded to ATSDR's Division of Health Studies for consideration as potential candidates for subregistries of exposed persons, based on criteria described in its 1994 document, ``National Exposure Registry: Policies and Procedures Manual (Revised),'' Agency for Toxic Substances and Disease Registry, Public Health Service, U.S. Department of Health and Human Services, Atlanta, Georgia, NTIS Publication No. PB95154571. Currently, ATSDR has established exposure subregistries for benzene, dioxin, 1,1,1trichloroethane (not included in the SSARP), trichloroethylene, and tremolite asbestos.

G. Conclusion

The results of the research conducted via the SSARP are expected to provide information necessary to improve the database used to conduct comprehensive public health assessments of populations living near hazardous waste sites. The information will enable the Agency to establish linkages between levels of contaminants in the environment and levels in human tissue and organs associated with adverse health effects, ultimately helping to determine methods for interdicting exposure and mitigating toxicity. 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 information base for addressing a broader range of data needs. The Agency plans to provide an update on the status of this research program approximately every three years or sooner, as needed.

Dated: November 17, 2005.
Kenneth Rose,
Acting Director, Office of Policy, Planning, and Evaluation, National Center for Environmental Health, Agency for Toxic Substances and Disease Registry.
Table 1.ATSDR's SubstanceSpecific Priority Data Needs for 60 Priority Hazardous Substances Status change Substances PDN ID \1\ PDN description Program \2\ \3\ Comments \4\ Aldrin/Dieldrin............... 1A.......... Doseresponse .............. Filled........ An MRL was data in animals derived in the for 2000 updated intermediate ATSDR duration oral toxicological exposure. profile. 1B.......... Bioavailability from soil.
1C.......... Exposure levels .............. .............. This priority in humans data need, living near previously hazardous waste addressed in a sites and other study in the populations, Great Lakes such as exposed Research workers. Program, is no longer investigated in that study. 1D.......... Potential ATSDR......... candidate for subregistry of exposed persons. Arsenic....................... 2A.......... Comparative EPA........... toxicokinetic studies to
determine if an appropriate
animal species can be
identified.
2B.......... Halflives in EPA........... surface water, groundwater. 2C.......... Bioavailability EPA........... from soil.
[[Page 71511]]
2D.......... Exposure levels G. Lakes...... Filled........ In addition to in humans the data from living near the Great Lakes hazardous waste Research sites and other Program, populations, background such as exposed level data are workers. available in ATSDR's 1993 toxicological profile, and at least seven ATSDR studies that evaluated urine arsenic levels and potential adverse health effects are available. Also, additional studies are available in ATSDR's 2000 updated toxicological profile. Asbestos...................... 3A.......... 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.
3B.......... Immunotoxicity studies of
individuals
occupationally exposed to
asbestos.
3C.......... Development of human and rat lung retention models to aid in
extrapolating between rat and human data.
3D.......... 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.
3E.......... 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.
3F.......... 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.
3G.......... Potential ATSDR......... Filled........ ATSDR candidate for established subregistry of registry to exposed persons. follow the health of people who were exposed to asbestos in Libby, Montana. The name of the registry is the Tremolite Asbestos Registry (TAR). Benzene....................... 4A.......... Doseresponse EPA........... .............. Reproductive data in animals toxicity study for acute and is the only intermediate component of duration oral this PDN that exposure. The is included in subchronic the EPA/ATSDR study should test rule. include an
extended
reproductive organ
histopathology. [[Page 71512]]
4B.......... Prenatal EPA........... .............. Previously developmental planned study toxicity study in the MHPF via oral Research exposure. Program to address this priority data need was canceled. 4C.......... Neurotoxicology EPA........... battery of
tests via oral exposure.
4D.......... Epidemiologic .............. Filled........ Based on an studies on the evaluation of health effects the data in of benzene ATSDR's 1997 (Special updated emphasis end toxicological points include profile. ATSDR immunotoxicity). will continue to evaluate new data as they become available to determine if additional studies are needed. 4E.......... Exposure levels .............. Filled........ Reference range in humans concentrations living near are available hazardous waste (Ashley et al. sites and other 1992, 1994; populations, Needham et al. such as exposed 1995), and at workers. least one ATSDR study that evaluated blood benzene levels and potential adverse health effects is available. ATSDR acknowledges that reference concentration data can support exposure and health assessments at waste sites, but the Agency also continues to recognize the importance of collecting additional data on uniquely exposed populations at waste sites. Benzidine..................... 5A.......... Doseresponse
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). 5B.......... Exposure levels in humans
living near
hazardous waste sites.
5C.......... Exposure levels in children. 5D.......... Potential ATSDR......... candidate for subregistry of exposed persons. Beryllium..................... 6A.......... Doseresponse EPA........... data in animals for acute and intermediate duration
inhalation
exposures. The subchronic
study should include
extended
reproductive organ
histopathology. 6B.......... Prenatal EPA........... developmental toxicity study via inhalation exposure.
6C.......... Environmental EPA........... fate in air; factors
affecting
bioavailability in air.
6D.......... Analytical .............. Filled........ Based on an methods to evaluation of determine the data in environmental ATSDR's 2000 speciation. updated toxicological profile. 6E.......... Immunotoxicology EPA........... battery of
tests following oral exposure. [[Page 71513]]
6F.......... Exposure levels .............. Filled........ Reference range in humans concentrations (adults) living in urine are near hazardous available waste sites and (Paschal et al. other 1998, CDC populations, 2005). ATSDR such as exposed acknowledges workers. that reference concentration data can support exposure and health assessments at waste sites, but the Agency also continues to recognize the importance of collecting additional data on uniquely exposed populations at waste sites. 6G.......... Exposure levels .............. Filled........ Reference range in children. concentrations in urine are available (CDC 2005). 6H.......... Potential ATSDR......... candidate for subregistry of exposed persons. Cadmium....................... 7A.......... Analytical .............. Filled........ Based on an methods for evaluation of biological the data in tissues and ATSDR's 1999 fluids and updated environmental toxicological media. profile. 7B.......... Exposure levels G. Lakes...... Filled........ In addition to in humans the data from (adults) living the Great Lakes near hazardous Research waste sites and Program, other reference range populations, concentrations such as exposed in blood and workers. urine are available (CDC 2005), and at least nine ATSDR studies that evaluated blood and urine cadmium levels and potential adverse health effects are available. 7C.......... Exposure levels .............. Filled........ Reference range in children. concentrations in blood and urine are available (CDC 2005). Carbon tetrachloride.......... 8A.......... Doseresponse
data in animals for chronic
oral exposure. The study
should include extended
reproductive organ and
nervous tissue histopathology. 8B.......... Immunotoxicology NTP........... Filled........ NTP dosefinding battery of study and one tests via oral study in exposure. ATSDR's 1994 updated toxicological profile addressed the priority data need. 8C.......... Halflife in .............. Filled........ One study in soil. ATSDR's 1994 updated toxicological profile provided information on halflife in soil. 8D.......... Exposure levels .............. Filled........ Reference range in humans concentrations living near in blood are hazardous waste available sites and other (Ashley et al. populations, 1992, 1994; such as exposed Needham et al. workers. 1995). ATSDR acknowledges that reference concentration data can support exposure and health assessments at waste sites, but the Agency also continues to recognize the importance of collecting additional data on uniquely exposed populations at waste sites. 8E.......... Potential ATSDR......... candidate for subregistry of exposed persons. Chlordane..................... 9A.......... Oral MHPF.......... Filled........ Availability of multigeneration studies in the al studies to MHPF Research evaluate Program. reproductive toxicity.
9B.......... Bioavailability studies
following
ingestion of contaminated media.
[[Page 71514]]
9C.......... Exposure levels .............. Filled........ Reference range

FOR FURTHER INFORMATION CONTACT Yee-Wan Stevens, M.S., Applied Toxicology Branch, Division of Toxicology and Environmental Medicine, ATSDR, 1600 Clifton Road, NE., Mailstop F32, Atlanta, Georgia 30333, telephone: (770) 4883325, fax: (770) 4884178.