National Toxicology Program

NATIONAL TOXICOLOGY PROGRAM LIAISON AND SCIENTIFIC REVIEW OFFICE P.O. Box 12233 MD: A3-01 Research Triangle Park N.C. 27709-2233 (919) 541-0530 Fax: (919) 541-0295 E-mail: liaison@starbase.niehs.nih.gov NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES NATIONAL INSTITUTES OF HEALTH		We are pleased to provide the following information to update our readers on programs and initiatives on the National Toxicology Program. We invite public input and participation in all aspects of our programs. NTP Center for the Evaluation of Risks to Human Reproduction August 17-19, Review of Phthalates Request for Nominations for Future Center Reviews Report on Carcinogens (RoC) September 15 Public Meeting Status of the 9th Edition of the RoC Chemicals Under Review for the 10th Edition of the RoC Board Review of Nominations, December 16-17 NTP Interagency Center for the Evaluation of Alternative Toxicological Methods October 14 Advisory Committee Meeting Murine LLNA Report Available Corrositex Report Available Exposure Assessment Workshop, September 22-24 NIEHS Report Concludes Evidence Weak that Electric and Magnetic Fields (EMF) Causes Cancer Workshop Report on Methyl Mercury Available Comments Solicited on NTP Herbal Medicine Program DES Research Update NTP Requests Chemical Nominations Public Comments Solicited on Chemicals Nominated for NTP Studies Environmental Health Information Service (EHIS) Visit the NTP Home Page at http://ntp.niehs.nih.gov/ntp NTP Reports Available Online at http://ehis.niehs.nih.gov

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NTP Center to Review Seven Phthalate Esters – August 17-19, Alexandria, Virginia (Open Meeting)

Background

The NTP Center for the Evaluation of Risks to Human Reproduction was established to provide timely and unbiased, scientifically sound evaluations of human and experimental evidence for adverse effects on reproduction, including development, caused by agents to which humans may be exposed (see following article). The evaluations produced through the Center will be published as monographs in Environmental Health Perspectives and distributed to the appropriate regulatory and research agencies and other interested groups. Special efforts will be made to summarize the reports in terms that can be understood by those who are not scientifically trained.

Expert Panel Review of Phthalates

Seven phthalate esters will be evaluated by an expert panel under the auspices of the NTP Center. These were selected based on their high production volume, extent of human exposures, use in children's products, or published evidence of reproductive or developmental toxicity. The chemicals to be evaluated are listed below with their Chemical Abstract Service registry numbers:

butyl benzyl phthalate (85-68-7)
di(2-ethylhexyl) phthalate (117-81-7)
di-isodecyl phthalate (26761-40-0, 68515-49-1)
di-isononyl phthalate (28553-12-0, 68515-48-0)
di-n-butyl phthalate (84-74-2)
di-n-hexyl phthalate (84-75-3)
di-n-octyl phthalate (117-84-0)

The review will take place from August 17-19, 1999, at the Embassy Suites Hotel, 1900 Diagonal Road, Alexandria, VA with some workgroup sessions at Sciences International, Inc., 1800 Diagonal Road, Suite 500, Alexandria, VA (limited seating availability). The meeting will commence at 8:30 a.m. on August 17 in the Virginia Ballroom of the Embassy Suites Hotel.

Charge to Panel

To date, the following panel of 15 scientists have been selected for their expertise in various aspects of reproductive toxicology and other relevant areas to conduct the review:

Kim Boekelheide, MD, Ph.D.,
Brown University, Providence, RI
Bob Chapin, Ph.D., NIEHS, Research Triangle Park, NC
Mike Cunningham, Ph.D., NIEHS, Research Triangle Park, NC
Elaine Faustman, Ph.D., University of Washington, Seattle, WA
Paul Foster, Ph.D., Chemical Industry Institute of Toxicology, Research Triangle Park, NC
Mari Golub, Ph.D., Cal/EPA, Davis, CA
Rogene Henderson, Ph.D., ,Inhalation Toxicology Research Institute, Albuquerque, NM
Irwin Hinberg, Ph.D., Health Canada, Ottawa, Ontario, Canada
Bob Kavlock, Ph.D., EPA/ORD, Research Triangle Park, NC
Ruth Little, ScD, NIEHS, Research Triangle Park, NC
Jennifer Seed, Ph.D., EPA/OPPT, Washington, DC
Katherine Shea, M.D., North Carolina State University, Raleigh, NC
Shelly Tyl, Ph.D., Research Triangle Institute, Research Triangle Park, NC
Paige Williams, Ph.D., Harvard University, Cambridge, MA
Tim Zacharewski, Ph.D., Michigan State University, East Lansing, MI

The role of the panel is to rigorously evaluate all relevant data and reach a conclusion regarding the strength of scientific evidence that exposure to a chemical may or may not present a risk to human reproduction or development. The panel will:

1. Evaluate all reproductive and develop-mental toxicity studies - in humans and animals - for quality, completeness, and sufficiency. Determine consistency of reported effects within and among species. Briefly summarize relevant individual studies.

2. Review and summarize related studies paying particular attention to studies of general toxicity, pharmacokinetics, genetic toxicity, and mechanisms of toxicity, within and across species. Both in vivo and in vitro studies will be included.

3. Determine, to the extent possible, patterns of use (such as timing, duration) and exposure (such as dose, route) to humans.

4. Integrate this information, using a weight of evidence approach. Determine how human, animal and other data can reasonably be used to predict reproductive or developmental effects in humans under particular exposure conditions.

5. Provide judgments, including qualitative statements of the certainty of the judgments, that an agent presents a potential risk to human reproduction and/or development. Describe the major factors that contributed to these judgments. State the exposure circumstances under which such risk might be expected to exist.

6. Identify specific areas of uncertainty (such as inadequate pharmacokinetic data in a given species) that would prevent a more definitive assessment of human risk.

7. Identify research and testing needs that, if met, would significantly reduce the uncertainty inherent in the stated judgments of risk.

Meeting Open to the Public

The preliminary agenda for the panel meeting follows:

August 17 (beginning at 8:30 a.m.)

Opening remarks by Dr. Michael Shelby, NIEHS and Director of the Center; Dr. George Lucier, NIEHS, and Dr. Robert Kavlock, EPA, and Chair of the Expert Panel.

Panel members will present summaries of the literature they will have individually reviewed in advance of the meeting.

The Phthalate Esters Panel of the Chemical Manufacturers Association, Health Care Without Harm, and the American Council on Science and Health will summarize the deliberations of their recent literature reviews of the possible reproductive and developmental health risks of phthalate exposures.

Panel discussion will follow to identify areas where there is broad panel agreement as well as issues requiring further discussion by workgroups of the panel.

Time will be available to members of the public for comment.

August 17 (p.m.) 18 & 19

The remainder of the meeting will be an iterative series of workgroup discussions and plenary sessions. Significant conclusions and judgments reached by the panel workgroups will be presented, discussed, and agreed to by the expert panel in plenary sessions. Definitive judgments will be made for each of the seven phthalates.

August 19, 11:00 a.m. (tentatively)

Closing plenary session, review of panel conclusions.

The review will be open to the public with an opportunity scheduled for oral public comment. Attendance will be limited only by the availability of space. For registration information please contact: Ms. Peggy Sheren, CERHR, 1800 Diagonal Road, Suite 500, Alexandria, VA 22314-2808, Phone: (703) 838-9440.

New NTP Center Solicits Public Input

In line with the goal of the National Toxicology Program to provide toxicological evaluation on substances of public health concern, the NTP Center for Evaluation of Risks to Human Reproduction will provide scientifically-based, uniform assessments of the evidence for reproductive and developmental toxicity of man-made or naturally occurring chemicals or chemical mixtures. The first review to be conducted by the Center is the phthalate review described in the previous article.

Nominations of chemicals to be evaluated through the Center are solicited from the public and scientific communities, including industry, Federal, state, and local governments, academia, environmental groups, citizens, and workers. All nominations will be considered and prioritized based on a preliminary evaluation which will include literature searches and review by the core committee described below. A listing of exposures under consideration for evaluation will be published in the Federal Register, the NTP Newsletter, and through press advisories with the request for public review and comment. Once selected for evaluation, a request for comments and data, as well as the nomination of scientific experts for that particular review, will be solicited.

The initial capacity for conducting assessments will be limited to 2-3 per year. Chemicals selected for evaluation will be reviewed by expert panels of approximately 10-15 scientists selected for their expertise in various aspects of reproductive toxicology and other relevant areas. These panels will develop reports addressing the reproductive health risks to the human population of a specific chemical or a chemical mixture. Panel meetings will be open to the public and will include the opportunity for public comment.

The goals of the individual assessments are to 1) interpret for and provide to the general public information about the strength of scientific evidence that a given exposure or exposure circumstance poses a hazard to reproduction and the health and welfare of children; 2) provide regulatory agencies with objective and scientifically credible assessments of reproductive/developmental health effects associated with exposure to specific chemicals or classes of chemicals, including descriptions of any uncertainties associated with the assessment of risks; and 3) identify knowledge gaps to help establish research and testing priorities.

The Executive Summary and the final report of the expert panel will be published in Environmental Health Perspectives and will be announced and disseminated widely. Each assessment will appear as well at http://cerhr.niehs.nih.gov. A special effort will be made to summarize these reports in terms that can be understood by those who are not scientifically trained.

Scientists representing NTP agencies and Sciences International, Inc., the contractor who will support the Center, will constitute a core committee which will provide the initial review for nominations, select the expert panel membership and establish the meeting agenda.

External Oversight

Oversight will be provided through the NTP Board of Scientific Counselors’, a chartered peer review group of scientific experts primarily from outside the government. Center activities and priorities will be presented to the Board at least annually. All Board meetings will be held in open session and will include opportunity for public comment.

Public Input Solicited/Encouraged

The process includes opportunities for the public to 1) nominate chemicals for evaluation, 2) comment on nominations and the prioritizing and selecting of chemical nominations for evaluation, 3) comment on the evaluation of any particular chemical at the time of the expert panel meetings, and nominate scientists for the expert registry and/or a particular review. The public is encouraged in this initial phase of the Center operations and on a continuing basis to nominate chemicals or chemical mixtures for review through the Center and/or suggest scientists to be added to an Expert Registry from which reviewers will be appointed to serve on ad hoc panels that will assess the reproductive and developmental toxicity of selected agents.

Nominations of chemicals or chemical mixtures should be accompanied by the reason for the nomination and, whenever possible, appropriate background information, data, or literature citations.

Suggestions for scientists to be added to the Expert Registry should be accompanied by a description of their expertise and if possible a curriculum vitae. All chemical nominations and suggestions for scientists to be added to the Expert Registry should be forwarded to:

NTP Center for the Evaluation of Risks to Human Reproduction
1800 Diagonal Road
Suite 500
Alexandria, VA 22314
webmaster@cerhr.niehs.nih.gov
http://cerhr.niehs.nih.gov.

Report on Carcinogens (RoC)

NTP to Host Public Meeting to Receive Input on RoC Review Procedures

A public meeting will be held on September 15, beginning at 9 a.m., (Ronald Reagan Building, International Trade Center, 1300 Pennsylvania Avenue NW, Horizon Room, Washington, DC), to provide all interested parties an opportunity to express their views about the review process and/or the evaluation criteria that have been used in the reviews of both the 8^th and the 9^th RoCs. The process used for reviewing nominations for listing or delisting in the Reports involves multiple levels of scientific review and opportunities for public comment and participation. Comments have been received from individuals concerning the reviews for the 8^th and 9^th Reports and have identified several areas where possible changes should be considered. The public meeting will provide an opportunity for dialogue regarding the process and an opportunity for all persons with an interest to provide their insights as well as their comments on the views expressed by others.

Public Comment Encouraged

The meeting will begin at 9 a.m. and will conclude at 5 p.m. or at the conclusion of the public comment and discussion, if sooner.

A panel to include NTP staff and representatives of the NTP Board of Scientific Counselors and the NTP Executive Committee will receive comments and participate in the discussion. NTP staff will summarize the process and the listing criteria. Presentations from the panel will be tentatively from 9 – 10 a.m. The remainder of the time will be devoted to public comment and discussion.

Oral comments: Each speaker will be asked to identify their sponsoring organization (if any). The time allotted for each presentation will be largely dependent upon the number of individuals who register to speak at this one-day meeting. Speakers will be registered and assigned time on a first-come, first-serve basis. Registration to speak at this meeting will be accepted until the 9 a.m. start of the meeting. It is anticipated that at least 10 minutes will be available for each presenter to address the panel. When oral comments are read from printed copy, it is requested that 10 copies of the text be provided when registering at the meeting to be provided to the panel members and to supplement the record of the meeting.

Written comments are welcome and can be sent to Ms. Angie Wilson, NIEHS, Bldg. 101, P.O. Box 12233, A3-07, Research Triangle Park, NC 27709 or at wilson9@niehs.nih.gov. Written comments must include name, affiliation, mailing address, phone, fax, e-mail, and sponsoring organization (if any). Comments received by September 15 will be considered for their implications with respect to the reviews of nominations for the 10th edition of the RoC and the December 16-17, 1999, Board review of nominations.

Registration for Meeting: Attendance is limited only by the space available. Pre-registration to attend this meeting can be made by notifying Ms. Angie Wilson. Please indicate if you wish to make an oral presentation. On-site registration will be available the morning of September 15, from 8:30 to 9:00 a.m. When registering to comment, please provide your name, affiliation, mailing address, phone, fax, e-mail, and sponsoring organization (if any).

As background for the September 15 meeting, this mailing includes a separate statement in the form of "questions and answers" on the Report on Carcinogens, a copy of the current listing/delisting procedures, and the criteria for evaluating listings.

Additional background on the RoC can also be accessed on-line at: /index.cfm?objectid=03C9B512-ACF8-C1F3-ADBA53CAE848F635

9^th Edition of the RoC

The following 24 substances or exposure circumstances are in the final stages of review for listing in (or delisting from) the 9^th edition of the RoC. The recommendations from the multi-level review groups and the public comments have been received; and the NTP expects to provide recommendations regarding listings or delistings to the Secretary of Health and Human Services by the end of the summer. Submission to Congress and publication of the 9^th Report is anticipated in late 1999.

Alcoholic Beverage Consumption
Boot and Shoe Manufacture and Repair
1,3-Butadiene/106-99-0
Cadmium & Cadmium Compounds/7440-43-9
Chloroprene/126-99-8
Diesel Exhaust Particulates
Dyes Metabolized to Benzidine
(Benzidine Dyes as a class)
Environmental Tobacco Smoke
Ethyl Acrylate /140-88-5 (Delisting)
Ethylene Oxide/75-21-8
Isoprene/78-79-5
Methyl-t-Butyl Ether/1634-04-4
Nickel Compounds
Phenolphthalein/77-09-8
Saccharin/128-44-9 (Delisting)
Silica, Crystalline (Respirable Size)/7631-86-9
Smokeless Tobacco
Strong Inorganic Acid Mists Containing Sulfuric Acid
Tamoxifen/10540-29-1
2,3,7,8- Tetrachlorodibenzo-p-dioxin (TCDD)/1746-01-6
Tetrafluoroethylene/116-14-3
Tobacco Smoking
Trichloroethylene/79-01-6
Solar Radiation and Exposure to Sunlamps and Sunbeds

The primary uses or exposures to these substances and the recommendations regarding listing/delisting made by three review groups can be accessed on line at http://ntp.niehs.nih.gov/ntp/ NewHomeRoc/9thConsideration.html

Or requested from NTP

Report on Carcinogens, P.O. Box 12233, 79 Alexander Drive, Bldg. 4401, Room 3127, MD-EC-14, Research Triangle Park, NC 27709. For information contact: Dr. C. W. Jameson, phone: (919) 541-4096, fax: (919) 541-2242, email: jameson@niehs.nih.gov

10^th Edition of the RoC

The following 11 substances or exposure circumstances have been nominated for review in 1999 for the 10^th Report. A Federal Register Notice published in April 1999, requested public comment on the nominations through June 3 to allow consideration of the comments by the initial review groups. These nominations will be reviewed in public session on December 16-17, 1999, (see following article). A second group of nominations to be considered for the 10^th Report will be announced in early 2000 and will be reviewed during that year. Publication of the 10^th Report is expected in 2001.

Beryllium and Beryllium Compounds (CAS No. 7440-41-7)
Primary Uses or Exposures: Fiber Optics and cellular network communications systems, aerospace , defense and other industry applications. To be reviewed for possible updating of current listing of beryllium and certain beryllium compounds to a known human carcinogen in the 10^th Report.

2,2-bis-(bromomethyl) –1,3-propanediol /3296-90-0
Primary Uses or Exposures: Used in a fire retardant in unsaturated polyester resins, in molded products, and in rigid polyurethane foam. To be reviewed for possible listing in the 10^th Report.

2,3-Dibromo-1-Propanol /96-13-9
Used as a flame retardant, as an intermediate in the preparation of the flame retardant tris(2,3-dibromopropyl) phosphate, and as an intermediate in the manufacture of pesticides and pharmaceutical preparations. To be reviewed for possible listing in the 10^th Report.

Dyes Metabolized to Dimethoxybenzidine (Dimethoxybenzidine Dyes as a Class)
Dyes formerly widely used for leather, paper, plastics, rubber, and textile industries. To be reviewed for possible listing in the 10^th Report.

Dyes Metabolized to Dimethylbenzidine (Dimethylbenzidine Dyes as a Class)
Dyes formerly widely used for leather, paper, plastics, rubber, and textile industries. To be reviewed for possible listing in the 10^th Report.

IQ (2-Amino-3-methylimidazo[4,5-f]quinoline) /76180-96-6
Found in cooked meat and fish.

Styrene-7,8-oxide /96-09-3
Used mainly in the preparation of fragrances and in some epoxy resin formulations. To be reviewed for possible listing in the 10^th Report.

Toluene Diisocyanate /26471-62-57
Commercially produced as an approximate 80:20 mixture of the 2,4- and 2,6-isomers, it is primarily for use in the manufacture of flexible polyurethane foams. Considered for delisting from the Report on Carcinogens.

UV Radiation /separate consideration of three segments of the wavelength spectrum: UVA (315-400 nm), UVB (280-315 nm), and UVC (100-280 nm)
Solar and artificial sources of ultraviolet radiation. To be reviewed for possible listing in the 10^th Report.

Vinyl Bromide /593-60-2
Used commercially since 1968, primarily in the manufacture of flame retardant synthetic fibers. To be reviewed for possible listing in the 10^th Report.

Vinyl Fluoride /75-02-5
Used commercially since the 1960’s, in the production of polyvinylfluoride which is used for plastics. To be reviewed for possible listing in the 10^th Report.

December 16-17 NTP Board To Review Nominations for 10^th Edition of the RoC (Open Meeting)

Public review of the substances nominated for the 10^th edition (listed above) of the Report on Carcinogens will take place on December 16-17, 1999, at the Conference Center, Building 101, South Campus, National Institute of Environmental Health Sciences, 111 TW Alexander Drive, Research Triangle Park, North Carolina. This meeting of the NTP Board of Scientific Counselors Report on Carcinogens Subcommittee will be an open meeting and will include time for public comment.

Background summary documents on each of the nominations to be reviewed at the December meeting will be provided to Subcommittee reviewers and be made available to the public by November 1, 1999. These background documents include all available data relevant to the criteria for inclusion or removal of candidate substances or exposure circumstances in the RoC.

Copies of draft background documents can be obtained, as available, from:
Dr. C. W. Jameson
National Toxicology Program
79 Alexander Drive, Bldg. 4401
Room 3127, MD EC-14
P.O. Box 12233
Research Triangle Park, NC 27709
phone: (919)541-4096, fax: (919)541-2242, email: jameson@niehs.nih.gov

Registration for the Meeting: Individuals wishing to comment on any of the nominations to be discussed at this meeting should contact Ms. Angie Wilson at the address shown below. The deadline for receipt of written comments for this meeting will be December 1, 1999. An agenda for the meeting, roster of committee members, and additional information regarding the meeting will be available from Ms. Wilson by November 1. Ms. Wilson can be reached at NIEHS/PO Box 12233, Research Triangle Park, NC 27709, phone (919) 541-3971 or fax: (919) 541-0295 and by email: wilson9@niehs.nih.gov

NTP Interagency Center for the Evaluation of Alternative Toxicological Test Methods (NICEATM): Meeting of the Advisory Committee on Alternative Toxicological Methods

The next meeting of the NTP Advisory Committee on Alternative Toxicological Methods will be held from 8:45 a.m. to 4:00 p.m. on October 14, 1999 in the Conference Center, Building 101, South Campus, NIEHS, 111 Alexander Drive, Research Triangle Park, North Carolina 27709. The meeting will be open to the public.

The primary agenda topics will include presentations and discussions relating to the processes, priorities, and recent and proposed activities of the NTP Interagency Center and the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM). Specific agenda topics will include discussion of the current status of agency’s consideration of the LLNA test method, including regulatory acceptance status.

To obtain an agenda, information or to register to attend or comment at the meeting, please contact Ms. Angie Wilson,
NIEHS, Bldg. 101, P.O. Box 12233, A3-07, Research Triangle Park, NC 27709 or at wilson9@niehs.nih.gov.

Murine LLNA Report Available

The report "The Murine Local Lymph Node Assay: A Test Method for Assessing the Allergic Contact Dermatitis Potential of Chemicals/Compounds,'' describes the results of an independent peer review evaluation of the validation status of the LLNA that was conducted on September 17, 1998 (Federal Register 63 FR 37405-6, July 10, 1998). The LLNA was proposed as an alternative toxicological test method for assessing the allergic contact dermatitis (contact hypersensitivity) potential of chemicals and products. The review was coordinated by the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) and the National Toxicology Program (NTP) Interagency Center for the Evaluation of Alternative Toxicological Methods.

The report includes the evaluation and supporting documentation, the original test method submission, supporting data evaluations conducted by NICEATM, and a proposed protocol that incorporates the recommendations of the peer review panel.

To receive a copy of the report, please contact NICEATM at PO Box 12233, MD EC-17, Research Triangle Park, NC 27709 (mail), 919-541-3398 (phone), 919-541-0947 (fax). The report is also available at http://iccvam.niehs.nih.gov/llnarep.htm.

Corrositex® Report Available

The report "Corrositex®: An In Vitro Test Method for Assessing Dermal Corrosivity Potential of Chemicals", describes the results of an independent peer review evaluation of Corrositex® that was conducted on January 21, 1999 (Federal Register 63 FR 57303, October 27, 1998). Corrositex® was proposed by InVitro International, Inc., Irvine, CA, as an alternative toxicological test method for assessing the dermal corrosivity potential of chemicals and chemical mixtures. The review was coordinated by the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) and the National Toxicology Program (NTP) Interagency Center for the Evaluation of Alternative Toxicological Methods.

Corrositex® is an in vitro method used to determine the dermal corrosive potential of chemicals and chemical mixtures. Corrositex® is based on the ability of a corrosive chemical or chemical mixture to pass through, by diffusion and/or destruction/erosion, a biobarrier and to elicit a color change in the underlying liquid Chemical Detection System (CDS). The biobarrier is composed of a hydrated collagen matrix in a supporting filter membrane, while the CDS is composed of water and pH indicator dyes. Test chemicals and chemical mixtures, including solids and liquids, are applied directly to the biobarrier. The time it takes for a test chemical or chemical mixture to penetrate the biobarrier and produce a color change in the CDS is compared to a classification chart to determine corrosivity/noncorrosivity and to identify the appropriate US Department of Transportation (US DOT) packing group. Chemicals are prescreened for compatibility with the assay by directly applying the test chemical or chemical mixture to the CDS; if a color change is not induced, then the test chemical or chemical mixture does not qualify for testing with this assay. The US DOT currently accepts the use of Corrositex® to assign subcategories of corrosivity (packing groups) for specific chemical classes for labeling purposes according to United Nations (UN) Committee of Experts on the Transport of Dangerous Goods guidelines.

The peer review panel also concluded that Corrositex® offers advantages with respect to animal welfare considerations. Corrositex®, when used as a stand-alone assay for some testing applications such as transportation purposes, can replace the use of animals for corrosivity testing of qualified chemicals in some chemical classes. When used as part of a tiered testing strategy for corrosivity, there is a reduction in the number of animals required because positive results usually eliminate the need for animal testing, and when further testing in animals is determined to be necessary, only one animal is required to confirm a corrosive chemical. Corrositex® also provides for refinement in that most of the chemicals that are identified as negative by Corrositex® or nonqualifying in the detection system are unlikely to be corrosive when tested in the in vivo test for irritation potential.

The Peer Review Panel's Report was accepted by ICCVAM and has been forwarded to Federal agencies for their determination of the regulatory acceptability and applicability of the test method according to their statutory mandates.

The full report includes the results of the independent peer review evaluation and supporting documentation, including the original test method submission and supporting data evaluations conducted by NICEATM.

To receive a copy of the report, please contact NICEATM at PO Box 12233, MD EC-17, Research Triangle Park, NC 27709 (mail), 919-541-3398 (phone), 919-541-0947 (fax), or http://iccvam.niehs.nih.gov. The report will also be available on the ICCVAM/ NICEATM website at http://iccvam.niehs.nih.gov

Workshop on "The Role of Human Exposure Assessment in the Prevention of Environmental Disease" September 22-24 1999, Doubletree Hotel, Rockville, Maryland (Meeting Notice)

Knowledge of human exposures to agents of potential public health concern is critical for a successful and scientifically sound approach to the evaluation of human health risks resulting from environmental exposures. This workshop will focus on the exposure-response-disease paradigm and will describe current opportunities and challenges in exposure assessment research, provide usable information on disease-specific chemical exposures that will enhance integration of exposure assessment with epidemiology and toxicology studies, and highlight approaches for further research and the development of effective prevention and intervention strategies. The two and one-half day workshop is structured so that most of the time will be spent in organized breakout sessions on the state of the science and case studies that will gain focus from the plenary sessions.

Topics for Plenary Lectures
Populations at Increased Risk
Gene-Environment Interactions
Exposure Analysis Methodology
Exposure-Disease Relationships
Regulatory and Legislative Issues
Disease Prevention and Intervention

Breakout Sessions
Aggregate and Cumulative Exposure and Risk Assessment
Disproportionate Exposures and Disease Impact
Assessing Environmental Influence on Children’s Health
Integrating Exposure, Dose, Response, and Susceptibility
Exposure Assessment in Occupational and Environmental Epidemiology
Achieving Partnerships and Community Input

For the Complete Program and Registration information visit http://ntp.niehs.nih.gov/ntp or contact
Anna Lee Sabella
Environmental Toxicology Program
NIEHS
P.O. Box 12233
Research Triangle Park, NC 27709
Tel: (919) 541-4982 Fax: (919) 541-0295
E-mail: sabella@niehs.nih.gov

NIEHS Report Concludes Evidence Weak that EMF Causes Cancer

The National Institute of Environmental Health Sciences (NIEHS) and the Department of Energy (DOE) coordinated implementation of the Electric and Magnetic Fields Research and Public Information Dissemination Program (EMFRAPID Program). This six-year program was mandated in the 1992 Energy Policy Act (PL 102-486, section 2118) and designed to determine the potential effects on human disease from exposure to 60 Hz electric and magnetic fields (EMF). These fields are invisible lines of force that surround any wire or device that uses electricity. Additional details about the EMFRAPID Program are found in Federal Register, December 16, 1997 (Volume 62, No. 241, pp. 65814-65815) or http://www.niehs.nih.gov/emfrapid/.

Under this program, the NIEHS conducted a two-year review and analysis of the existing scientific data on EMF and prepared a report for the U.S. Congress that concluded that the evidence for a risk of cancer and other human diseases from EMF around power lines is weak. This assessment included an evaluation of the evidence by scientists both within and outside the field of EMF research as well as an opportunity for public comment through sponsorship of public meetings and solicitation of written comments. The NIEHS report is available free-of-charge to the public and other interested parties.

The report is available in both PDF and HTML formats at the EMFRAPIDProgram world wide website, http://www.niehs.nih.gov/emfrapid/home.htm. Copies of the report can also be obtained by sending a request by fax: 919-541-0144 or mail: EMF-RAPID Program, NIEHS/NIH, P.O. Box 12233 MD EC-16, Research Triangle Park, NC 27709; or by calling 919-541-7534.

Report of the Workshop on "Scientific Issues Relevant to Assessment of Health Effects from Exposure to Methyl Mercury" Available

The purpose of the workshop held on November 18-20, 1998, was to discuss and evaluate the major epidemiological studies associating methyl mercury exposure with an array of developmental measures in children.

The workshop agreed that the epidemiological studies confirmed that methyl mercury is an important developmental neurotoxin; and while the major studies to date are of high scientific quality, there are a number of differences between studies that make it difficult to evaluate the observed effects of low doses encountered by eating fish. The workshop made a number of recommendations concerning methods for assessment of exposure, choice of neurobehavioral endpoints , treatment of confounders and methods of statistical analysis that would improve the comparability of such studies.

To obtain a copy of the report, fax to (919) 541-0295 or email britton@niehs.nih.gov. To electronically review or print the report go the NTP homepage /index.cfm?objectid=03614B65-BC68-D231-4E915F93AF9A6872

Public Comment on NTP Herbal Medicine Program Encouraged

Medicinal herbs are some of our oldest medicines. Their increasing use in recent years is evidence of a public interest in having alternatives to conventional medicine. Herbal medicines currently account for one of the fastest growing markets in U.S. pharmacies and constitute a multi-billion dollar industry. Although approximately 1500 botanicals are sold as dietary supplements or ethnic traditional medicines, herbal formulations are not subject to FDA pre-market toxicity testing to assure their safety or efficacy.

Workshop on Evaluating Research Needs

In response to concerns regarding the use and efficacy of medicinal herbs and to recent nominations of these products for study by the NTP, a September 1998 workshop on herbal medicines was organized to address research needs. Its objectives were to discuss the use, safety, and possible health-related problems of medicinal herbs; identify how other countries evaluate and regulate medicinal herbs; establish the NTP’s role in determining their long-term safety; and recommend areas for research. A broader objective of the meeting was the focus and coordination of U.S./international research efforts. Recommendations from the workshop include a call for more research, identification and standardization of product ingredients by industry, and increased consumer education through package inserts. A summary of the workshop can be found in the Environmental Health Perspectives Journal, December 1998, (Vol. 106, No. 12, pages A590-A592).

NTP Studies

In follow-up to this workshop, the NTP staff is working with the NIH Office of Dietary Supplements, the FDA, the academic community, and others to further define and implement research that addresses deficiencies in our knowledge about herbal medicines and their potential toxicities. Several herbs and active or toxic ingredients found in some herbs have been nominated and selected for study by the NTP. These studies will focus primarily on characterization of potential adverse health effects including reproductive toxicity, neurotoxicity, and immunotoxicity associated with chronic exposures. NTP studies include both traditional toxicological research and molecular mechanistic considerations.

NTP staff are actively working with the NIH Office of Dietary Supplements, the USFDA, the academic community and others to further define and implement research to characterize risks associated with the use of medicinal herbs.

Public Input Welcome

Comments from the public and others regarding NTP research in this area including available data or supplementary information on any of the following herbs. Please forward any comments to Dr. William Eastin, NIEHS/NTP, P. O. Box 12233, Research Triangle Park, North Carolina 27709; by telephone at (919) 541-7941; by FAX at (919) 541-3687; or by email at eastin@niehs.nih.gov. The URL for the NTP homepage is http://ntp.niehs.nih.gov/ntp.

Herbs and Active or Toxic Ingredients Being Studied by the NTP

Herbs Under Review for Study

DES Research Update: Current Knowledge, Future Directions

NIEHS co-sponsored a workshop on the long-term effects of exposure to diethylstilbestrol (DES) in Washington, DC, on July 19-20, 1999, to discuss what is known currently about DES and what future research areas need to be addressed. DES, a synthetic estrogen-like hormone given to pregnant women from the 1940s through the 1970s to prevent miscarriage, has been associated with the development of vaginal clear cell carcinoma in young women exposed in utero. Although the incidence of cancer is thus far low, the risks for other reproductive problems has been reported to be as high as 90% in the exposed population. DES sons have also experienced numerous problems including subfertility. Since the mid-1970s, studies of several identified cohorts of DES-exposed individuals have clarified many of the long-term health effects of exposure to DES. This workshop provided an update on these epidemiology studies and also progress in basic research. The most significant new information from the workshop can be summarized around the following three major points: 1) There is no upper age incidence on vaginal carcinoma [new cases are occurring as population gets older]. 2) An increased incidence of breast and ovarian cancer in prenatally DES-exposed women has been documented. 3) Third generation impact is unknown but of great concern.

NTP Requests Chemical Nominations for Study

NTP studies include research and testing of selected chemicals and agents in order to characterize toxicity and determine possible adverse effects that may be associated with human and environmental exposure. Health-related effects addressed include chronic toxicity and carcinogenicity, as well as reproductive, developmental, genetic, immunological and neurological toxicity. Studies are also designed to address data gaps for specific chemicals such as fate and mechanisms of chemical toxicity and other effects that may be of human health concern. Data developed by NTP is critical to assessments of human health hazards associated with exposure to those chemicals and agents studied. NTP also supports an active program to develop and validate new and improved assays for chemical toxicity and assays that eliminate or minimize the use of laboratory animals.

NTP requests nominations of chemicals and agents for study from all sources including academia, industry, labor unions, Federal and state agencies and the general public. Nominations should be accompanied by a rationale for study, i.e. populations exposed, source of exposure, any known adverse health effects, etc. When possible, nominations should also be accompanied by available information describing production and use, possible adverse effects associated with exposure as well as a chemical name, structure and CAS number. The NTP will consider each nomination as it is received. Data received supporting nominations will be supplemented with an additional literature search, and each nomination will be carefully reviewed by the NTP Nomination Faculty to establish priority for study. The nominator will be informed of the status of his/her nomination as it moves through the selection and testing process. Please send all nominations and relevant information to:
Dr. Scott Masten
Nomination Faculty Coordinator (B3-10)
NIEHS
P.O. Box 12233
Research Triangle Park, NC 27709
Or visit the NTP web page:/index.cfm?objectid=26FF3BEF-ECDF-E36A-677D8E4EC610511C

The ICCEC Recommends Actions on Chemicals Nominated for NTP Studies: Public Input Solicited

Chemical nominations undergo several levels of review before toxicological studies are designed and implemented. The Interagency Committee for Chemical Evaluation and Coordination (ICCEC) serves as the first interagency level of review for NTP nominations.

Interested parties are encouraged to provide comments or supplementary information on the chemicals and the ICCEC recommendations that follow. The Program would welcome receiving toxicology and carcinogenesis information from completed, ongoing, or planned studies, as well as information on current production levels, human exposure, use patterns, or environmental occurrence for any of the chemicals listed in this announcement. To provide comments or information, please contact Dr. William Eastin at the address given below. Comments are requested by September 7, 1999.

Contact may be made by mail to: Dr. William Eastin, NIEHS/NTP, P. O. Box 12233, Research Triangle Park, North Carolina 27709; by telephone at (919) 541-7941; by FAX at (919) 541-3687; or by email at eastin@niehs.nih.gov. The URL for the Federal Register Notice is /index.cfm?objectid=06F2A0FF-0E0C-5600-FF47B97FE1C2C31A

Chemicals Recommended for Testing

Chemicals for Which No Testing is Recommended

Chemicals Deferred for Additional Information

Chemicals to be Withdrawn From Consideration