A Nobel Ideal
Welcome to the club.
1988 Nobel Prize winners George Hitchings (left) and Gertrude Elion (right) congratulate Martin Rodbell.
Photo credit: Arnold Greenwell
"The fundamental thing is the opportunity to be creative," said Martin Rodbell speaking about the environment necessary for scientists to arrive at new breakthroughs. Rodbell is a scientist emeritus at the NIEHS and winner of the 1994 Nobel Prize in medicine or physiology. He spoke at a reception held in his honor at the NIEHS on October 13.
Rodbell was honored for his work in discovering G-proteins, guanine nucleotide-dependent coupling entities which transmit signals within cells. G-proteins bind to GTP to regulate diverse hormonal functions involving adenylyl cyclase activation, phospholipase C, membrane ion channels, protein synthesis, and cellular growth and differentiation. More than 300 receptors are known to interact with G-proteins, and aberrations in the function of what Rodbell called these "communication devices" underlie a variety of disease states including cancer, diabetes, cholera, and alcoholism.
The impact of this discovery has been enormous because identification of the G-proteins and understanding of how they function is essential to basic biomedical research. Rodbell will share the $930,000 prize with researcher Alfred G. Gilman who, building on Rodbell's theory, characterized the chemical nature of G-proteins. Gilman is chair of the Department of Pharmacology at the University of Texas Southwestern Medical Center. Said Ruth L. Kirschstein, deputy director of the National Institutes of Health, "Drs. Rodbell and Gilman have made significant findings in understanding how cells perceive and react in a coordinated way to the thousands of messages that bombard them. This Nobel Prize underscores how important such basic studies are to understanding normal cell function and the diseases that result when cell processes go awry."
One of our own.
NIEHS Director Kenneth Olden congratulates scientist emeritus Martin Rodbell on winning the 1994 Nobel Prize in medicine.
Photo credit: Arnold Greenwell
Speaking at the reception honoring Rodbell and his 38-year career at the NIH, Phillip Gorden, director of the National Institute of Diabetes and Digestive and Kidney Diseases, said, "Marty Rodbell is about neither big science or little science. He's about what the intramural program at NIH is all about. . . . He's about creativity." Rodbell worked from 1956 to 1960 at the National Heart Institute before becoming a biochemist at the National Institute of Arthritis and Metabolic Disease where he performed the research honored by the Nobel Prize. He joined the NIEHS in 1985 and served as scientific director until 1989. Rodbell has functioned since 1989 as chief of the Laboratory of Cellular and Molecular Pharmacology and is the institute's first scientist emeritus. Said NIEHS Director Kenneth Olden, "We have every right to claim him as one of our own." Rodbell received his B.A. in biology at Johns Hopkins University and his Ph.D. in biochemistry at the University of Washington.
In 1984 Rodbell received the prestigious Gairdner International Award, considered a stepping-stone to the Nobel Prize. Rodbell has also been honored with the Richard Lounsberry Award from the National Academy of Sciences and an honorary doctorate from Montpelier University in France. He is a member of a number of distinguished scientific societies including the National Academy of Sciences and the American Academy of Arts and Sciences. Rodbell also serves on the Board of Associate Editors of
Environmental Health Perspectives.
Rodbell is highly regarded by his fellow scientists, not only for his work, which has resulted in over 100 publications in the highest quality scientific journals, but also for the training and direction he has provided to emerging scientists throughout his career. Said John A. McLachlan, scientific director of the NIEHS, "[Rodbell] stimulated and developed a real impetus for basic science at the NIEHS." It is through his leadership and tutelage that Rodbell has attempted to foster in young researchers what many regard as his most exemplary quality as a scientist: his ability to think creatively and to translate that creative thought into meaningful scientific discovery. In a good-natured jab at Rodbell's scientific ardor, Gorden said, "If you give him a piece of chalk and a blackboard, he transforms into the Jimmy Swaggart of science."
It was the opportunity to exercise this passion, however, that Rodbell credits with fostering his scientific success. "I was given the privilege to think for myself, to be an iconoclast," he said. Rodbell has lamented that in today's economic environment, opportunities such as the one he had are increasingly hard to find. "To be frank about it, the world ain't the same. Now everything is targeted. Everything is bottom-line." With characteristic humility, Rodbell gave credit to his fellow scientists, saying, "Science is a synergy of effort. It comes out of our culture. It comes from a kind of symbiosis between individuals." He went on to encourage his fellow scientists not to search for the bottom line but to reach for greater scientific understanding. "We should be able to together bring about a better world, a world that we, as humans, can be proud of."
Two New NIEHS Developmental Centers
Columbia University in New York City and the University of Louisville in Louisville, Kentucky, join Tulane University Medical Center in New Orleans as NIEHS Developmental Centers. The centers program at the NIEHS provides focused research efforts, brings together diverse scientific disciplines to solve environmental problems, and attracts and trains young investigators. Centers also answer questions from the public on environmental problems and help identify emerging problems in the environmental health field. The NIEHS Centers Program funds 15 Environmental Health Sciences Centers and 5 Marine and Freshwater Biomedical Sciences Centers at universities throughout the United States. Developmental centers have two goals: to develop promising programs that may later be able to compete for an Evironmental Health Sciences Center grant and to encourage research programs that study environmentally related health problems of economically disadvantaged and/or medically underserved populations.
The Columbia University Developmental Center will study the major environmental health problems of socioeconomically disadvantaged populations, including the neurotoxicity and treatment of lead exposure, air pollution associated with asthma and other pulmonary disease, the effects of environmental factors on reproduction, and the contributions of environmental exposures to cancer. The center director is Joseph Graziano, of the School of Public Health.
Joseph Graziano.
Photo credit: Columbia University
The University of Louisville will study biochemical, chemical, and molecular biomarkers to define exposure of human populations. The center will focus on metabolism of acrylonite and vinyl chloride in rat and human liver cells; biomarkers of exposure involving hemoglobin and DNA adducts of acrylonite; and evaluation of the p53 tumor-suppressor gene as a biomarker. The center director is Russell A. Prough of the Department of Biochemistry, School of Medicine.
Russell A. Prough.
Photo credit: University of Louisville
The Tulane University Medical Center was the first NIEHS Developmental Center to be funded and studies environmental components of disease in minority populations. The center is developing an exposure assessment tool to assess blood-lead levels in children, as well as studying hypertension and lead exposure in minority populations and air pollution associated with childhood lung disease. The center funds community-based research in the Mississippi River delta region to study health effects from environmental chemical exposures. The center director is Janet M. Hughes of the Department of Biostatistics and Epidemiology in the School of Public Health and Tropical Medicine.
Janet M. Hughes
Photo credit: Tulane Unversity
NIEHS Awards Grants on Gene Expression
The NIEHS has awarded six grants in response to its Request for Applications (RFA) "Toxic Substances Effects on Developmental Gene Expression." The goal of the grants is to stimulate research at the interface of developmental biology and developmental toxicology to generate mechanistic data on how environmental agents alter the basic processes of development and thereby contribute to developmental abnormalities in humans. Applicants were encouraged to have elements of both toxicology and molecular biology in their experimental design.
The following grants were awarded:
-
Jonathan L. Tilly, Johns Hopkins University, "Selective Ovotoxicity and Cell Death Gene Expression";
-
William F. Greenlee, Purdue Research Foundation, "TCDD-dependent Regulation of Thymus Development";
-
Jean M. Lauder, UNC-Chapel Hill, "Regulation of GABA Expression in Neurotoxins";
-
George M. Stancel, University of Texas Health Science Center-Houston, "Developmental Toxicity of Environmental Estrogens";
-
Charles J. Bieberich, American Red Cross, "Effect of Environmental Toxicants on
Hox
Gene Expression";
-
Rocky S. Tuan, Thomas Jefferson University, "Molecular Basis of Toxicant-induced Vertebral Anomalies."
NTP Accessed 38,000 Times via Gopher
In the nine months following the creation of the NIEHS Gopher Server, the NTP directory has been accessed more than 38,000 times by various organizations throughout the world. Gopher is designed to allow easy navigation of the Internet and access to information by even novice computer users. Most of these users accessing the NTP directory have used a full-text search to locate a particular chemical in the directory and then accessed the study report abstracts, Annual Report on Carcinogens, NTP Annual Plan, historical control tables, study status, or results-to-date for that chemical.
In the past, it took days or weeks (or sometimes months for those overseas) to obtain copies of technical reports and other results of NTP testing. Access via Gopher is almost instantaneous. Furthermore, users can browse through hundreds of abstracts interactively and download the ones they want to their own workstations without having to print a hard copy.
To view the NTP directory on the NIEHS Gopher server, you must have access to the Internet or an Internet client software such as Gopher, or Mosaic. The server is located at the NIEHS, and the address is GOPHER.NIEHS.NIH. GOV. Gopher client and server software is available via anonymous File Transfer Protocol from BOOMBOX.MICRO.UMN. EDU in the /PUB/GOPHER Directory. Mosaic client and server software is available in the /Web/xmosaic-source/ and in binary form in the directory/Web/xmosaic-binaries/. The Internet email address is CDM@NIEHS.NIH.GOV.
To obtain NTP information through the mail, contact Central Data Management, MD A0-01, NIEHS, PO Box 12233, Research Triangle Park, NC 27709 USA; telephone: (919) 541-3419, FAX: (919) 541-4714.
McLachlan Accepts Tulane Post
John A. McLachlan.
Photo: NIEHS
After a 21-year NIEHS career during which he progressed from research associate to scientific director, John A. McLachlan has accepted the position of director of the Tulane-Xavier Center for Bioenvironmental Research and professor of pharmacology at Tulane University in New Orleans. McLachlan leaves the NIEHS after serving as scientific director longer than any of his predecessors, having developed and implemented many new initiatives including a major reorganization of the institute's intramural research program. During his tenure, the NIEHS established a clinical program in collaboration with UNC-CH and Duke University, and established education and outreach efforts including summer internships and an annual environmental career symposium for high school students and teachers. As scientific director, McLachlan supervised a workforce of approximately 700 scientists and support personnel in 19 different laboratories and branches and oversaw a yearly budget in excess of $90 million. McLachlan's hallmark was his emphasis on basic research while facilitating the application of fundamental findings to toxicology testing and human studies.
During McLachlan's early years at the institute, not everyone would have labeled him as potential executive material, despite his high energy and incisive intellect. He has often joked about his inclination to wear sandals and other "hippie" attire. However, he amply demonstrated his abilities with his scientific successes and solid leadership as head of the developmental endocrinology and pharmacology section, in the Laboratory of Reproductive and Developmental Toxicology beginning in 1976. He later became the laboratory chief, a post he retains until his departure for Tulane.
McLachlan is internationally known for his research on diethylstilbestrol (DES) and the health effects of other environmental estrogens. He was one of the first to recognize the global health implications of environmental estrogens both in terms of research and policy. Using a mouse model, he confirmed the association between maternal use of DES and cancers and malformations of the female reproductive tract in offspring and further identified malformations in male offspring as well. His recent findings on the ontogeny of the estrogen response and the role of growth factors and related signaling pathways in estrogen action continue to provide provocative new ideas for biology and medicine. Since 1979, he has been at the center of organizing several international conferences on estrogens in the environment. McLachlan has delivered over 120 invited lectures and published more than 150 research and overview articles in the scientific literature.
In a memo to NIEHS employees announcing his decision, McLachlan said, "Like many of you, I have spent most of my adult life at the institute and regard it, and you, with utmost respect and affection. It will be hard to go, but new opportunities and challenges afforded at Tulane excite and energize me." NIEHS Director Kenneth Olden called McLachlan a leader in his field and said he plans to have him back to NIEHS as a visiting scientist. "John will continue to be a part of the institute," Olden said. The search for a new scientific director is in progress.
NTP Invites Chemical Nominations
The National Toxicology Program invites members of the public, unions, industry groups, state and local governments, environmental organizations, academia, etc., to nominate chemicals or other agents to be studied by the NTP.
Of the 70,000 substances in commerce, adequate toxicological data are available for only 10-20%. Identifying those chemicals that have the potential to produce an adverse health effect has been the primary objective of the NTP. Established in 1978, the NTP coordinates toxicology studies within the Department of Health and Human Services. NTP's member agencies are NIH's National Institute of Environmental Health Sciences, FDA's National Center for Toxicological Research, and CDC's National Institute for Occupational Safety and Health.
Including studies done under its predecessor, the NCI Cancer Bioassay Program, NTP has completed more than 400 two-year studies in rats and mice since its establishment. Technical reports have been published for each of these bioassays, and most are available as bound booklets through the NTP Data Management Group, [telephone (919) 541-3419] or through the National Technical Information Service in Springfield, Virginia. Traditional toxicity tests, such as the two-year chronic bioassay to detect carcinogens, have been the basis for most regulatory decisions regarding the safety of environmental chemicals. Testing the high priority chemicals is critical to achieving the overall NTP goal of protecting public health by preventing exposures and generating the data that can make risk assessments more reliable. Abstracts of NTP study results and other NTP data and information are also available through the Internet, a relatively recent development which has greatly expanded dissemination of NTP information (see adjoining story).
There are no restrictions on chemical nominations; they may focus on individual chemicals, classes of chemicals, or broad public health issues. Nominations may be made for studies that will 1) identify chemical hazards, 2) improve the risk assessment process, 3) test hypotheses of mechanisms of action, 4) reduce the number of animals needed for toxicity/carcinogenicity evaluations, or 5) lead to new mechanistically based short-term tests.
The more information presented in a chemical nomination, the stronger the nomination. It is essential that specific and substantive reasons why a chemical should be studied are given. If possible, the nomination should contain the Chemical Abstracts Service (CAS) number of the chemical, especially if it has more than one name. CAS numbers can be obtained from
The Merck Index,
available in the reference sections of most public and university libraries. Information on the volume of chemical manufactured or in use and information on its uses is also helpful. A bibliography of any previous research is valuable, including animal and other laboratory studies, epidemiological studies, and medical case studies.
However, even if little or none of this background information is available, nominations will still be considered. Every letter of nomination will receive a response. Letters nominating chemicals and supporting information should be sent to:
Chemical Nomination Office c/o Errol Zeiger MD A2-02, NIEHS, PO Box 12233, Research Triangle Park, NC 27709 USA.
NTP to Study 22 Chemicals
The following chemicals are being considered for short- and long-term toxicology and carcinogenesis studies. The NTP welcomes comments on these chemicals and relevant information including ongoing toxicological studies, current or future trends in production and import, use patterns, human exposure levels, environmental occurrence, and toxicological data.
Contact may be made by mail to: William Eastin, NIEHS/NTP, PO Box 12233, Research Triangle Park, NC 27709, by telephone (919) 541-7941, FAX (919) 541-4714, or E-mail at eastin@niehs.nih.gov
Riddelliine
(CAS no. 23246-96-0). Two-year studies via oral gavage in B6C3F
1
mice and F344 rats. Riddelliine is a pyrrolizidine alkaloid found in plants of the genus
Senecio
in the western United States. Riddelliine and other alkaloids in these plants can cause the death of livestock if ingested in high quantities, or may contaminate meat as a residue. Riddelliine may also contaminate commercial grains, milk, and honey, and is found in some herbal teas. In NTP 90-day studies riddelliine was found to cause hepatic toxicity in mice and rats and hepatic neoplasia in rats. Two-year carcinogenicity studies of standard design are proposed to determine the shape of the dose- response curve for carcinogenicity in rats, and further evaluate the toxic and carcinogenic potential in mice.
Urethane/ethanol mixture
(CAS no. 51-79-6/64-17-5). Two-year studies via dosed-water in B6C3F
1
mice and F344 rats. Urethane and ethanol are byproducts of fermentation and are commonly found in alcoholic beverages and in many foods. Urethane has been recognized as a rodent and nonhuman primate carcinogen, while the International Agency for Research on Cancer has determined that alcoholic beverages are human carcinogens. Two-year studies that are planned will include separate groups of male and female mice exposed to urethane (CAS no. 51-79-6), ethanol (CAS no. 64-17-5), or to several levels of urethane and ethanol in the drinking water. The studies will include an assessment of the toxicokinetics of urethane, with and without ethanol, following repeated dosing. Studies of urethane DNA adducts are planned to address the issue of the dosimetry of DNA alterations.
Dichlorodiphenyl sulfone
(CAS No. 80-07-9). Two-year studies via dosed-feed in B6C3F
1
mice and F344 rats. Dichlorodiphenyl sulfone is a component of high temperature plastics. A known inducer of cytochrome P450s, dichlorodiphenyl sulfone was shown to cause marked hepatomegaly in NTP prechronic studies. Other studies have shown facile oral absorption and a relatively simple metabolite pattern, as well as self induction of metabolism with repeated administration. Carcinogenicity studies with dichlorodiphenyl sulfone are planned with both sexes of rats and mice.
Elmiron
(CAS no. 37319-17-8). Fourteen-day studies via oral gavage in B6C3F
1
mice and F344 rats. Elmiron is a pentosan polysulfate used as an experimental drug in the United States for the treatment of interstitial cystitis and used in Europe to prevent thrombosis and hyperlipidemia. The U.S. FDA nominated elmiron to the NTP as an "orphan" drug in need of chronic toxicity and carcinogenicity evaluation. Currently, 14-day studies are being undertaken to determine if expected effects on the clotting system will be the basis on which to select doses for further evaluations. Chronic toxicity and carcinogenicity evaluations by standard designs are under consideration.
Benzophenone
(CAS no. 119-61-9). Two-year studies via dosed-feed in B6C3F
1
mice and F344 rats. Benzophenone is found in many consumer products, e.g., as a fragrance and flavor enhancer, photoinitiator, ultraviolet curing agent, a polymerization inhibitor, and in the manufacture of pesticides and various pharmaceuticals. In NTP 13-week studies, the oral administration of benzophenone was found to cause hepatocellular hypertrophy in rats and mice and evidence of cholestatic liver injury and renal damage in rats. Marked induction of hepatic CYP 450 IIB was observed in rats and mice. Chronic toxicity and carcinogenicity studies are proposed for this chemical, with a stop exposure group using a dose which produced marked liver and kidney lesions in prechronic studies. Toxicokinetic studies are also planned.
2-Hydroxy-4-methoxybenzophenone
(CAS no. 131-57-7). Two-year studies via dosed-feed in B6C3F
1
mice and F344 rats. 2-Hydroxy-4-methoxybenzophenone is a UV stabilizer used in cosmetic, pharmaceutical, and plastic products. In NTP 13-week studies by the oral and topical routes, similar sites of toxicity were seen, primarily the liver and kidney, and effects on sperm density and the length of the estrous cycle were noted. Two-year studies of standard design are planned for this chemical by the oral route of administration.
Methacrylonitrile
(CAS no. 126-98-7). Two-year studies via oral gavage in B6C3F
1
mice and F344 rats. Methacrylonitrile is an industrial chemical widely used in a variety of organic processes related to the manufacture of polymers. It is a highly reactive unsaturated aliphatic nitrile found in cigarette smoke and is known to liberate cyanide
in vivo
. Methacrylonitrile has been studied extensively by the NTP including 14-day and 90-day studies in rats and mice by gavage. In addition, absorption, disposition, toxicokinetics, cell proliferation, and developmental toxicity studies have been performed. This chemical will be the subject of modeling efforts with physiologically based pharmacokinetic modeling techniques and is also recommended for 2-year chronic toxicity and carcinogenicity studies of a standard design.
Acrylonitrile
(CAS no. 107-13-1). Two-year studies via oral gavage in B6C3F
1
mice and F344 rats. Acrylonitrile is extensively used for the manufacture of synthetic fibers, resins, elastomers, rubber and plastics. There is limited evidence for the carcinogenicity of acrylonitrile in workers and it has been shown to produce chromosome damage in the blood cells of exposed workers. Acrylonitrile has produced brain, stomach, and zymbal gland tumors in 2-year studies in rats, but has not been studied in mice. Clues to critical metabolites may be gained from comparative studies in mice. Therefore, acrylonitrile will be studied in mice by the standard NTP protocol. Toxicokinetic estimates will be derived by analysis of an acrylonitrile-glutathione conjugation product in the urine.
m-
Nitrotoluene
(CAS no. 99-08-1). Two-year studies via dosed-feed in B6C3F
1
mice and F344 rats. The nitrotoluenes are high production volume chemicals used in the synthesis of agricultural and rubber chemicals and in various dyes. There are differences in the patterns of metabolism of nitrotoluenes. The
ortho
-isomer undergoes a series of microflora-mediated reactions leading to an intermediate with high capacity to bind to hepatic DNA and induce unscheduled DNA synthesis. In extensive NTP prechronic studies an unexpected finding was the presence of chemically induced mesothelioma in male rats receiving
o-
nitrotoluene. Studies demonstrated that microflora metabolism was not necessary for the mesothelioma response. Chronic toxicity and carcinogenicity studies are planned with
o
-nitrotoluene (CAS no. 88-72-2) and
p
-nitrotoluene (CAS no. 99-99-0), as well as
m
-nitrotoluene.
m-
Cresol
(CAS no. 108-39-4). Two-year studies via dosed-feed in B6C3F
1
mice and F344 rats. The cresols are monomethyl derivatives of phenol, and are found as constituents of coal tar, in various industrial solvents and resins, and in some essential oils. There are no adequate chronic toxicity and carcinogenicity studies of the cresols. The NTP has performed comparative 13-week toxicity studies in rats and mice by the dosed feed route. The isomers were found to exhibit generally similar patterns of toxicities, with the
o-
isomer (CAS no. 95-48-7) being somewhat less toxic than
m
- or
p
-cresol (CAS no. 106-44-5). Comparative chronic toxicity and carcinogenicity studies in rats and mice are planned for the cresols.
2,4-Decadienal
(CAS no. 25152-84-5). Thirteen-week and 2-year studies via oral gavage in B6C3F
1
mice and F344 rats. 2,4-Decadienal is one of the class of dienaldehydes that occur naturally in a variety of foods as by-products of the peroxidation of polyunsaturated lipids. Ingested lipid oxidation products and oxidized fats have been reported to cause damage to the liver and kidneys, increased cellular proliferation in the gastrointestinal tract, and other nonspecific tissue injury. Several researchers have suggested a possible link between lipid peroxidation products in the diet and human cancer. 2,4-Decadienal, as well as 2,4-hexadienal (CAS no. 142-83-6), will be studied in prechronic and chronic toxicity and carcinogenicity studies in rats and mice.
Dipropylene glycol
(CAS no. 25265-71-8). Two-year studies via dosed-water in B6C3F
1
mice and F344 rats. Dipropylene glycol is a component of antifreeze, air fresheners/sanitizers and is used as a stabilizer in cosmetics, as a component in polyester, alkyd resins, plastics, as a plasticizer and as a solvent. It was found to be of low to moderate toxicity in NTP 13-week studies. Mortality, hepatocellular lesions including atypical foci and an adenoma were seen in rats at the highest dose. Findings in mice were limited to increased liver weights. Carcinogenicity studies of a standard design are proposed for dipropylene glycol.
Arsenic trioxide
(CAS no. 1327-53-3). (Study plans are being formulated.) Arsenic trioxide is a by-product of copper or lead smelting operations and is used in pesticides, in the manufacture of glass, pharmaceuticals and other industrial chemicals. Arsenic and arsenic compounds have been classified as human carcinogens by IARC, Arsenic is a common water contaminant and there is need for information on biomarkers of exposure for low dose risk estimations. Specific study designs are under development.
Tamoxifen
(CAS no. 10540-29-1). (Conjugated estrogens study plans are being formulated.) Conjugated estrogens are listed by IARC as human carcinogens causing endometrial cancer. Estrogens are prescribed for prevention of osteoporosis in post-menopausal women and are used as oral contraceptives. Tamoxifen is a mixed estrogen agonist/ antagonist known to be effective in the treatment and prevention of estrogen sensitive breast cancer. Tamoxifen also causes endometrial cancer in humans. Studies are being designed to help characterize dose-response relationships and cancer risks for estrogen agonist and antagonists.
MX
[3-Chloro-4-(dichloromethyl)-5-hydroxy-2-furanone] (CAS no. 77439-76-0). (Study plans are being formulated.) MX is a mutagenic by-product of water and wood pulp chlorination and has been determined to account for about half of the mutagenic potency of finished drinking water. The EPA has nominated MX for carcinogenicity studies with the expectation that the outcome could influence U.S. drinking water contaminant standards. Study designs are incomplete.
Nomination Principles for NTP Studies
The NTP Executive Committee operates under the principle that industry will evaluate chemicals or other agents for health and environmental effects as intended and mandated by the Congress under legislative authorities. The NTP, acting under its nomination principles, will solicit nominations for NTP studies from the following categories:
1. Chemicals found in the environment that are not closely associated with a single commercial organization;
2. Biological or physical agents that may not be adequately evaluated without federal involvement;
3. Commercial chemicals with significant exposure that were first marketed before current testing requirements or those that generate too little revenue to support further evaluations;
4. Potential substitutes for existing chemicals or drugs that might not be developed without federal involvement;
5. Substances that occur as mixtures for which evaluations cannot be required of industry;
6. Chemicals or agents that will aid our understanding of chemical toxicities, or our understanding of the use of test systems to evaluate potential toxicities;
7. Chemicals that should be evaluated to improve the scientific understanding of structure-activity relationships and thereby help limit the number of chemicals requiring extensive evaluations;
8. Emergencies or other events that warrant immediate government evaluation of a chemical or agent.
The NTP will assess the specific needs for studies, evaluate existing literature and testing data, assess ongoing evaluations in the government and private sector, and also determine how the chemical fits into an overall plan for improving the test systems before committing to specific studies. The selection of a chemical or agent by the NTP Executive Committee does not automatically commit the NTP to evaluate that chemical or agent. The priority of the chemicals and the proposed studies are assessed during the selection of contractors to conduct the studies. During any of these phases the chemical or study may be withdrawn if higher priority studies are found, or if the study proves to be impractical.
Last Update: June 24, 1998