The Agency for Toxic Substances and Disease Registry’s (ATSDR) congressionally mandated Substance-Specific Applied Research Program (SSARP) currently consists of a research agenda for 60 top hazardous substances that is being accomplished through successful partnerships with other federal agencies, universities, and industry groups.

The Comprehensive Environmental Response, Compensation, and Liability Act of 1980 (CERCLA, or “Superfund” legislation) requires ATSDR to carry out the following activities:

• Develop, jointly with the U.S. Environmental Protection Agency (EPA), a priority list of hazardous substances found at waste sites on EPA’s National Priorities List (NPL).
• Prepare toxicological profiles for hazardous substances found at NPL sites.
• Assure, in cooperation with the National Toxicology Program (NTP), the initiation of a research program to address identified data needs associated with the toxic substances, i.e., SSARP.

• Address the substance-specific information needs of the public and scientific community.
• Supply information necessary to improve the database used to conduct comprehensive public health assessments of populations living near hazardous waste sites.
• Establish linkages between levels of contaminants in the environment and levels in human tissues and organs that are associated with adverse health effects.

• Developed a “Decision Guide” in 1989 for determining research priorities for hazardous substances found at waste sites and in the environment.
• Established the Tri-agency Superfund Applied Research Committee (TASARC) in 1991 to:
• Advise ATSDR on assigning priorities for mechanisms to address research needs.
• Coordinate knowledge of research activities to avoid duplication of research in other programs and under other authorities.
• Advise ATSDR on issues of science related to substance-specific research needs.
• Maintain a scheduled forum that provides an overall review of SSARP.
• Established a research agenda in 1991 for an initial 38 hazardous substances - aldrin/dieldrin, arsenic, benzene, beryllium, cadmium, carbon tetrachloride, chloroethane, chloroform, chromium, cyanide, p,pðÀ-DDT, DDE, DDD, di(2-ethylhexyl) phthalate, lead, mercury, methylene chloride, nickel, polychlorinated biphenyl compounds (PCBs), polycyclic aromatic hydrocarbons (PAHs), which include 15 substances, selenium, tetrachloroethylene, toluene, trichloroethylene, vinyl chloride, and zinc. Comments from the public were invited.
• Expanded the SSARP in 1997 by identifying research needs for 12 additional substances (chlordane, 1,2-dibromo-3-chloropropane, di-n-butyl phthalate, disulfoton, endrin, endosulfan, heptachlor, hexachlorobutadiene, hexachlorocyclohexane, manganese, methoxychlor, and toxaphene).
• Announced research needs in 2003 for 10 additional substances (asbestos, benzidine, chlorinated dibenzo-p-dioxins, 1,2-dibromoethane, 1,2-dichloroethane, 1,1-dichloroethene, ethylbenzene, pentachlorophenol, 1,1,2,2,-tetrachloroethane, and total xylenes).
• Identified key mechanisms, with the oversight of TASARC, for filling research needs, including industry testing as a result of EPA rule-making, voluntary industry testing (studies conducted by industry groups at no expense to ATSDR), NTP testing, and direct ATSDR-supported testing, including university-based research through a cooperative agreement with the Minority Health Professions Foundation (MHPF).
• To date, of 263 research needs identified for 60 substances, 62 research needs have been filled, and an additional 68 are currently being addressed through various mechanisms.

• Lower chlorinated Aroclors (commercial polychlorinated biphenyl [PCB] mixtures) (e.g., Aroclor 1016 and Aroclor 1242), previously thought to be less toxic, are capable of producing tumors in rats. Subsequently, EPA used the data from this study to revise its cancer slope factor for PCBs.
• Exposure to benzo(a)pyrene (BaP) may adversely affect reproductive health. BaP and its break-down products accumulate in the testes and ovaries of animals exposed to BaP by ingestion or inhalation. Pathological changes were observed in the testes of male animals exposed to BaP, as well as a dose-dependent decrease in the number of active sperm.
• Developed a new ATSDR health guidance value (Minimal Risk Level) of 0.2 mg/kg/day for methylene chloride for short-term exposure via the oral route.
• Consumption of water containing large amounts of methylene chloride (approximately 600-6000 mg of methylene chloride per liter of water) may result in adverse health effects on the central nervous system, liver, and the development of newborns.
• Infants may be at risk for neurobehavioral effects from exposure to maternal blood lead levels that are less than 10 µg/dL. These results among African American subjects corroborate findings in other populations on the effects of low-level, prenatal lead exposures.
• Lead accumulated preferentially in the brain of young animals exposed to blood lead levels that are less than 5 µg/dL. This provides biological evidence that even low levels of lead can reach the brain and may cause adverse health effects during early developmental stages.
• Hydroxylated metabolites of PCBs, which are considered to be strong indicators of naturally occurring aerobic biodegradation, were detected in sediment samples collected from PCB-contaminated sites in the upper Hudson River.

Through the SSARP, ATSDR plans to broaden efforts to fill research needs through outreach to a wider range of potential federal and private-sector partners, including international organizations.

Agency for Toxic Substances and Disease Registry. Decision guide for identifying substance-specific data needs related to toxicological profiles; Notice. 1989. Fed Regist 54: 37618-37634.

Agency for Toxic Substances and Disease Registry. Announcement of final priority data needs for 38 hazardous substances. 1992. Fed Regist 57: 54150-54159.

Agency for Toxic Substances and Disease Registry. Announcement of final priority data needs for 12 priority hazardous substances and call for voluntary research proposals. 1997. Fed Regist 62: 40820-40828.

Agency for Toxic Substances and Disease Registry. Update on the status of the Superfund Substance-Specific Applied Research Program. 2002. Fed Regist 67: 4836-4854.

Agency for Toxic Substances and Disease Registry. Announcement of final priority data needs for 10 priority hazardous substances. 2003. Fed Regist 68: 22704-22709.

Archibong AE, Inyang F, Ramesh A, et al. 2002. Alteration of pregnancy related hormones and fetal survival in F-344 rats exposed by inhalation to benzo(a)pyrene. Reprod Toxicol 16(6):801-808.

Areola OO, Williams-Johnson M, Jadhav, AL. 1999. Relationship between lead accumulation in blood and soft tissues of rats subchronically exposed to low levels of lead. Toxic Subst Mech 18:1-13.

Emory E, Pattillo R, Archibold E, et al. 1999. Neurobehavioral effects of low level lead exposure in human neonates. Am J Obstet Gynecol: 181(1):S2-11.

Emory E, Ansari Z, Pattillo R, et al. 2003. Maternal blood lead effects on infant intelligence at age 7 months. Am J Obstet Gynecol: 188(4):S26-32.

General Electric Company. An assessment of the chronic toxicity and oncogenicity of Aroclors 1016, 1242, 1254, and 1260 administered in diet to rats. Final report (February 1997). Available by contacting the Division of Toxicology, ATSDR.

General Electric Company. Metabolite detection as a tool for the determination of naturally occurring aerobic PCB biodegradation. Final report (May 14, 1999). Available by contacting the Division of Toxicology, ATSDR.

Halogenated Solvents Industry Alliance, Inc. Addressing priority data needs for methylene chloride with physiologically based pharmacokinetic modeling. Final report (February 4, 1997). Available by contacting the Division of Toxicology, ATSDR.

Inyang F, Ramesh A, Kopsombut P, et al. 2003. Disruption of testicular steroidogenesis and epdidymal function by inhaled benzo(a)pyrene. Reprod Toxicol 17(5):527-537.

Jadhav AL and Areola OO. 1997. Alteration in acquisition and pattern of responding in rats subchronically exposed to low levels of lead. Res Commun Biol Psychol Psych 22(1&2):11-24.

Ramesh A, Hood DB, Inyang F, et al. 2002. Comparative metabolism, bioavailability and toxicokinetics of benzo(a)pyrene in rats after acute oral, inhalation, and intravenous administration. PAC 22:969-980.

Ramesh A, Inyang F, Hood DB, et al. 2001. Metabolism, bioavailability, and toxicokinetics of benzo(a)pyrene in F-344 rats following oral administration. Exp Toxicol Pathol 53:275-290.

Stevens, Y-W, Williams-Johnson, MM, De Rosa, CT, et al. 2002. Findings and accomplishments of ATSDR’s Superfund-mandated substance-specific applied research program. Int J Hyg Environ Health 205: 29-39.

For more information about the Computational Toxicology Laboratory, contact

Agency for Toxic Substances and Disease Registry
Division of Toxicology
1600 Clifton Road NE, Mailstop F-32
Atlanta, GA 30333
Phone: 1-888-42-ATSDR (1-888-422-8737)
FAX:   (770)-488-4178
Email: ATSDRIC@cdc.gov