National Toxicology Program

We are pleased to providethe following information to highlight and update our readerson the 1998 programs and initiatives of the National ToxicologyProgram. We invite and encourage public input and participationin all aspects of our programs.

• Request for Public Reviewand Comment on EMF Working Group Assessment of Health Effects

• NTP Center for the Evaluationof Alternative Toxicological Methods & ICCVAM

• International Workshop toEvaluate Research Needs on the use and Safety of Medicinal Herbs:September 23-24, 1998

• Review of NTP Draft TechnicalReports Scheduled for October 30, 1998

• Workshop on the ScientificIssues Relevant to the Assessment of Health Effects from Exposureto Methylmercury, November 18-20, 1998

• Report on Carcinogens

• NTP Solicits Nominations forChemicals for Toxicological Evalution

• NTP Board Meeting Report fromFebruary 5-6, 1998

• NTP Website Update

• New NTP List-Server ProvidesAnnouncements and Updates as soon as information if Available
  
  

Request for Public Review andComment on EMF Working Group Assessment of Health Effects(see enclosed flyer - click on "close button" to return to Update)

NTP Center for the Evaluationof Alternative Methods & ICCVAM

Review of Murine Local LymphNode Assay as an Alternative Test Method for Contact HypersensitivitySeptember 17, 1998 (Request for Public Comment by August14, 1998)

A meeting is planned to reviewthe murine local lymph node assay (LLNA) as an alternative toxicologicaltest method for assessing the contact hypersensitivity (allergiccontact dermatitis) potential of chemicals and products. The meetingis sponsored by the NTP Interagency Center for the Evaluationof Alternative Toxicological Methods (NTP Center) and co-sponsoredby the Interagency Coordinating Committee on the Validation ofAlternative Methods (ICCVAM). The meeting will be held from 8:30a.m. to 4:30 p.m. on September 17, 1998, at the Gaithersburg Hilton,620 Perry Parkway, Gaithersburg, Maryland, and is open to thepublic.

The LLNA was proposed to the ICCVAMfor consideration as a stand-alone test to identify chemicalsthat have a potential to cause contact hypersensitivity. An ICCVAMImmunotoxicity Working Group composed of Federal employees determinedthat there was sufficient information available to merit an independentscientific peer review of the LLNA test method. Peer review hasbeen determined to be an essential prerequisite for considerationof a method for regulatory acceptance. The peer review panel willbe charged with developing a scientific consensus on the usefulnessof the test method to generate information for various human healthrisk assessment purposes. Following evaluation at this peer reviewmeeting, the proposed test method and results of the peer reviewwill be forwarded to the NTP Center and then to ICCVAM and theFederal agencies for consideration. Federal agencies will determinethe regulatory acceptability of the method according to theirmandates.

Public Comments Requested

The NTP Center invites the submissionof written comments on the proposed LLNA test method, and otheravailable information regarding the usefulness of the LLNA, includinginformation about completed, ongoing, or planned studies. Writtencomments and additional information should be sent by mail, fax,or e-mail to the NTP Center at the address listed below by August14th. Written comments will be made available to the peerreview panel members, ICCVAM agency representatives and experts,and will be made available for attendees at the meeting.

Members of the public who wishto present oral statements at the meeting should also contactthe NTP Center as soon as possible, but no later than September11, 1998. Speakers will be assigned on a first-come, first-servebasis and will be limited to a maximum of five minutes in presentationlength. Written comments accompanying the oral statement shouldbe submitted in advance so that copies can be made and distributedto the peer review panel members.

Background Information is AvailableUpon Request

The NTP Center will furnish anagenda and a roster of peer review panel members just prior tothe meeting. Summary minutes and a final report of the LLNA peerreview meeting will be available subsequent to the meeting uponrequest to the Center. Copies of the proposed LLNA Test MethodProtocol and supporting documentation may be obtained from theNTP Center for the Evaluation of Alternative Toxicological Methods,MD EC-17, P.O. Box 12233, Research Triangle Park, NC, 27709; (919)541-3398, FAX (919) 541-0947, e-mail: ICCVAM@niehs.nih.gov.The LLNA test method documents and copies of written public commentscan also be viewed at the Documents Management Branch, Food andDrug Administration, 5630 Fishers Lane, Room 1061, Rockville,MD, 20852 on Monday through Friday from 9:00 a.m. to 4:00 p.m.

Request for Information forReview of Corrositex and the Frog Embryo Teratogenesis Assay inXenopus (FETAX) as Alternative Test Methods (Comment by September1, 1998)

The NTP Center and ICCVAM arerequesting information and data that would be helpful in evaluatingthe usefulness of two other test methods for which upcoming independentscientific peer review meetings are being planned.

The methods are: 1) Corrositex®,an in vitro alternative method for assessing the dermalcorrosivity potential of chemicals and products; and 2) the FrogEmbryo Teratogenesis Assay in Xenopus (FETAX), an alternativemethod for developmental toxicity. The FETAX is a 96 hour assaythat has been used for both human health and ecological assessments.Potential regulatory applications of FETAX to human health developmentaltoxicity assessments include screening and prioritizing compoundsfor further testing, evaluating complex mixtures in environmentalsamples, and as supplemental information in a weight-of-evidenceevaluation of human developmental toxicity hazards.

Data submitted should addressone or more of the criteria for validation and regulatory acceptanceas provided in NIH publication 97-3981, "Validation and Regulatory Acceptance of Toxicological Test Methods: A Report of the Ad HocInteragency Coordinating Committee on the Validation of Alternative Methods" Copies of the report are available by request to the NTP Center or by accessing the following internet website:Alternative Methods.

How to submit information:Information shouldbe sent by mail, fax, or e-mail to the NTP Interagency Centerfor the Evaluation of Alternative Toxicological Methods as soonas possible, but no later than September 1, 1998. The NTP Centermailing address, phone, fax, and e-mail are as follows: MD EC-17,P.O. Box 12233, Research Triangle Park, NC, 27709; Tel: (919)541-3398; (919) 541-0947 (FAX); ICCVAM@niehs.nih.gov (e-mail).

NTP Advisory Committee on AlternativeToxicological Methods meets September 25, 1998

The first meeting of the AdvisoryCommittee on Alternative Toxicological Methods (the Committee)will be held from 8:45 a.m. to 4:00 p.m. on September 25, 1998in the Conference Center, Building 101, South Campus, NIEHS, 111T.W. Alexander Drive, Research Triangle Park, North Carolina,27709. The meeting will be open to the public from 8:45 a.m. toadjournment with attendance limited only by space available.

The Committee has been establishedto provide advice on the activities and priorities of the NTPCenter and ICCVAM, and to provide advice on ways to foster partnershipactivities and productive interactions among all stakeholders.The Committee will discuss processes, priorities and recent andproposed activities of the Center and the ICCVAM. The AdvisoryCommittee is composed of knowledgeable representatives drawn fromacademia, industry, public interest organizations, other Stateand Federal Agencies, and the International community.

Background

The Committee's advisory rolewill be very important to the NTP's fulfilling specific mandatesprovided to the National Institute of Environmental Health Sciencesby Public Law 103-43, Section 1301. The NIEHS was directed to(1) develop and validate toxicological testing methods, includingalternative methods that can reduce or eliminate the use of animalsin acute or chronic toxicity testing, (2) establish criteria forthe validation and regulatory acceptance of alternative testingmethods, and (3) recommend a process through which scientificallyvalidated alternative methods can be accepted for regulatory use.Criteria and processes for validation and regulatory acceptancewere developed in conjunction with 14 other Federal agencies andprograms with broad input from the public. These are describedin the document "Validation and Regulatory Acceptance ofToxicological Test Methods: A Report of the Ad Hoc InteragencyCoordinating Committee on the Validation of Alternative Methods"NIH publication 97-3981, March 1997, which is available on theinternet at Alternative Methods, or byrequest to the Center at the address provided below.

A standing Interagency CoordinatingCommittee on the Validation of Alternative Methods (ICCVAM) wassubsequently established as a collaborative effort by NIEHS and13 other Federal regulatory and research agencies and programs.The ICCVAM facilitates cross-agency communication and coordinationon issues relating to validation, acceptance, and National/ Internationalharmonization of toxicological test methods. The ICCVAM workswith the Center to carry out the scientific review of proposedmethods of multi-agency interest, and provides recommendationsregarding their usefulness to appropriate agencies. The ICCVAMalso provides a mechanism for interagency communication with stakeholdersthroughout the process of test method development and validation.The following Federal regulatory and research agencies and organizationsare participating in this effort:

Consumer Product Safety Commission
Department of Defense
Department of Energy
Department of Health and Human Services

Agency for Toxic Substances and Disease Registry
Food and Drug Administration
National Institute for Occupational Safety and Health/CDC
National Institutes of Health
National Cancer Institute
National Institute of Environmental Health Sciences
National Library of Medicine

Department of the Interior
Department of Labor

Occupational Safety and Health Administration

Department of Transportation

Research and Special Programs Administration

Environmental Protection Agency

The Center was established toprovide operational support for the ICCVAM and to assist Federalagencies by coordinating and facilitating (1) the interagencyreview and adoption of toxicological test methods of multi-agencyinterest and (2) the participation and communication with otherstakeholders throughout the process of test method developmentand validation. The Center organizes, in collaboration with ICCVAM,independent scientific peer reviews and workshops for test methodsof interest to Federal agencies. Peer review panels are convenedto develop scientific consensus on the usefulness of test methodsto generate information for specific human health and/or ecologicalrisk assessment purposes. Expert workshops are convened to evaluatethe adequacy of current test methods for assessing specific toxicities,to identify areas in need of improved or new methods, to evaluateproposed validation studies, and to evaluate the validation statusof methods. The Center provides an opportunity for partnershipswith other agencies and organizations to facilitate the development,validation, and review of alternative testing methods. The Centerand ICCVAM seek to promote the scientific validation and regulatoryacceptance of toxicological test methods that will enhance agencies'ability to assess risks and make decisions, and that will refine,reduce, and replace animal use whenever possible. The Center Officeis located at NIEHS and can be contacted by telephone (919) 541-3398;fax (919) 541-0947, or email, iccvam@niehs.nih.gov.

For further information contactthe Committee's ExecutiveSecretary, Dr. Larry Hart, Environmental Toxicology Program, P.O. Box 12233, NIEHS, Research Triangle Park, North Carolina 27709,telephone (919) 541-3971, FAX (919) 541-0295, or the Center Director,Dr. William S. Stokes, NTP Interagency Center for the Evaluationof Alternative Toxicological Methods, Environmental ToxicologyProgram, P. O. Box 12233, NIEHS, Research Triangle Park, NorthCarolina 27709, telephone (919) 541-3398, FAX (919) 541-0947.Dr. Hart will have an agenda available with times and a rosterof Committee members prior to the meeting and summary minutessubsequent to the meeting.

International Workshop to EvaluateResearch Needs on the Use and Safety of Medicinal Herbs: September23-24, 1998

The international workshop willbe held September 23-24, 1998 at the National Institute of EnvironmentalHealth Sciences Conference Center in the Research Triangle Park,North Carolina. Herbal medicines and dietary supplementsaccount for one of the fastest growing markets in U.S. pharmaciesand constitute a multi-billion dollar industry. Given the increasinguse of some medicinal herbs and the paucity of toxicological data,the NIEHS has organized a workshop to bring together a panel ofnational and international experts to discuss the use of the medicinalherbs and dietary supplements and to establish research needsthat address public health concerns. The workshop speakers willaddress the following session topics and, in two open discussionsessions, workshop attendees will have the opportunity to make5 minute presentations of ongoing research and/or discussion ofadditional research needs:

Workshop Sessions Will Include:

• Benefits and Risks Associatedwith the Use of Medicinal Herbs
• International Research onthe Efficacy and Safety of Dietary Supplements and Medicinal HerbsWorldwide
• Research on Medicinal Herbsand Dietary Supplements in the U.S.
• Panel Discussion on ResearchNeeds to Assure Safety of Medicinal Herbs and Dietary Supplementsin the U.S.
• Open discussion of OngoingResearch or Additional Research Needs

Co-sponsors for the workshop includeNational Institutes of Health's Office of Dietary Supplements,National Institute of Environmental Health Sciences, and the Officeof Research on Women's Health; the Department of Health and HumanServices' National Toxicology Program and Office of Disease Preventionand Health Promotion; the Food and Drug Administration's Officeof Special Nutrition and the Society for the Advancement of Women'sHealth Research.

To view the preliminary programfor the workshop, visit the NTP Home Page at http://ntp.niehs.nih.gov/ntp. For those without access to the Internet, you may request acopy of the preliminary program from the NTP Liaison Office. Toregister or to receive additional information please contact (noregistration fee):

Jaime Edge at the National ToxicologyProgram Liaison Office,
P.O. Box 12233, MD: A3-01,
Research Triangle Park, North Carolina27709, USA
Tel: (919) 541-0530, Fax: (919) 541-0295, e-mail: edge@niehs.nih.gov

Review of NTP Draft TechnicalReports Scheduled for October 30, 1998

Reports will be Available on the Web

The NTP Board of Scientific Counselors'Technical Reports Review Subcommittee will meet at NIEHS on October30, 1998, to review the draft Technical Reports for the long-termtoxicology and carcinogenesis studies on the following chemicals:ethylene glycol monobutyl ether; glutaraldehyde; methyleugenol;and oxymetholone. It is expected that there will be a reconsiderationof the two-year study report on triethanolamine (TR # 449), andthat there will be further discussions on the Helicobacterissue.

Copies of the reports will beavailable on the NTP website http://ntp.niehs.nih.gov/ntp as soon as they are available, but no later than September 30.Hard copies can be obtained by contacting Central Data Management.

Public Input Encouraged

Public comment on any agenda itemis welcomed. In order to facilitate planning for the meeting,persons wanting to make a formal presentation during the publiccomment period must notify the Executive Secretary, Dr. LarryG. Hart, P.O. Box 12233, NIEHS, Research Triangle Park, NC 27709telephone (919) 541-3971; FAX (919) 541-0295; or e-mail at hart@niehs.nih.govprior to the meeting and if possible provide a written copy oftheir comments in advance of the meeting. Written statements shouldsupplement and may expand on the oral presentation, or may besubmitted in lieu of an oral presentation. Oral presentationsshould be limited to no more than five minutes.

An agenda, and/or roster of Boardmembers are available on request from the NTP Board ExecutiveSecretary, Dr. Larry Hart, P.O. Box 12233, NIEHS, Research TrianglePark, NC 27709. Summary minutes subsequent to the meeting willbe available upon request.

Workshop on the ScientificIssues Relevant to the Assessment of Health Effects from Exposureto Methylmercury: November 18-20, 1998

An interagency group working underthe auspices of the Committee on Environment & Natural Resources,OSTP, of The White House has organized a workshop in Raleigh,NC to focus on assessing and interpreting epidemiologic studiesof the human health effects associated with chronic, low-levelexposure to methylmercury. The planning committee is chaired bythe NIH/NIEHS with representatives from:

Environmental ProtectionAgency
Centers for Disease Control and Prevention
Agency for Toxic Substances Disease Registry
Food and Drug Administration
Department of Health and Human Services
National Oceanic and Atmospheric Administration
Office of Science and Technology Policy
Office of Management and Budget

The purpose of the workshop isto discuss and evaluate the major epidemiologic studies associatingmethylmercury exposure with an array of developmental measuresin children. The product of the workshop should facilitate agreementon risk assessment issues.

Workshop participants will tryto reach consensus on what we can conclude and what the uncertaintiesare for each of the studies alone and for the studies taken together.The major studies being considered are those which have examinedpopulations in Iraq, the Seychelles, the Faeroe Islands and theAmazon along with the most relevant animal studies for estimatinghuman risks.

Questions to be addressed:

1. For each study, what are the relative exposures to organicor inorganic mercury?
2. What are the sources of exposure? Is the consumption of fish,shellfish and marine mammals the dominant source? Are dental amalgams,occupational exposures or other sources significant confounders?
3. What is the specificity and sensitivity of health endpoints,e.g., behavioral, neurological, and developmental? What are themost specific and sensitive tests of these endpoints? How arethese tests impacted by cultural or behavioral practices?
4. Are the developmental tests used comparable across differentstudies? Across species?
5. What are the confounders that affect health endpoints positively(e.g., [selenium], omega-3 fatty acids) and negatively (e.g.,PCBs; alcohol use; health conditions with neurological effects,such as diabetes)? Do they influence the interpretation of thestudy.
6. What is the variability within and across populations studiedin mercury exposure and host factors (e.g., age, gender, nutritionalstatus and practices, and genetic predisposition)?
7. For each epidemiologic study of interest, which features ofits statistical design, research protocol or execution in thefield are particularly strong or weak? To what extent do thesestrengths and weaknesses affect the validity and reliability ofscientific inferences based on these studies?
8. What are the contributions of animal or experimental studiestoward interpretation of the human studies?
   

A public comment session willprovide the opportunity for additional views and comments. Writtencomments can also be submitted.

The preliminary program for theworkshop will be posted on the individual agency web pages, includingthe NIEHS at http://www.niehs.nih.gov andNTP at http://ntp.niehs. nih.gov as soon asavailable. For further information about the workshop,including registration, please e-mail: liaison@starbase.niehs.nih.govor Fax (919) 541-0295.

REPORT ON CARCINOGENS

Section 301 (b) (4) of the PublicHealth Service Act, as amended, provides that the Secretary, Departmentof Health and Human Services, shall publish a report which containsa list of all substances (1) which either are known to be humancarcinogens or may reasonably be anticipated to be human carcinogens;and (2) to which a significant number of persons residing in theUnited States are exposed. The Report on Carcinogens (RoC) isprepared by the NTP. To date eight editions have been published.

Nominations for listing/delistingin the RoC go through a multi-phase, peer review process involvingtwo Federal scientific review groups and one non-government scientificpeer review body (a subcommittee of the NTP Board of ScientificCounselors). All NTP Board meetings are open, public meetingsthat include a public comment session. All data relevant to thecriteria for inclusion or removal of candidate substances or exposurecircumstances in the Report are evaluated by the three scientificreview committees.

8th Edition

The Eighth Report on Carcinogens(RoC) was approved by the Secretary and forwarded to Congresson May 13, 1998. The Eighth RoC contains 198 entries, 14 of whichhave not appeared in earlier Reports. The Eighth Report also containsthe reclassification of one chemical. The list is divided intotwo parts: 1) Agents, Substances, Mixtures or Medical TreatmentsKnown To Be Human Carcinogens (29 entries); and 2) Agents,Substances, or Mixtures which may Reasonably Anticipated ToBe Human Carcinogens (169 entries). The new listings for the8th Report are:

• Azacitidine [reasonablyanticipated to be a human carcinogen]
• p-Chloro-o-toluidine and itsHcl salt [reasonably anticipated to be a human carcinogen]
• Chlorozotocin [reasonablyanticipated to be a human carcinogen]
• Cyclosporin [known to bea human carcinogen]
• Danthron (1,8-Dihydroxyanthraquinone)[reasonably anticipated to be a human carcinogen]
• 1,6-Dinitropyrene [reasonablyanticipated to be a human carcinogen]
• 1,8-Dinitropyrene [reasonablyanticipated to be a human carcinogen]
• Disperse Blue 1 [reasonablyanticipated to be a human carcinogen]
• Furan [reasonably anticipatedto be a human carcinogen]
• O-Nitroanisole [reasonablyanticipated to be a human carcinogen]
• 6-Nitrochrysene [reasonablyanticipated to be a human carcinogen]
• 1-Nitropyrene [reasonablyanticipated to be a human carcinogen]
• 4-Nitropyrene [reasonablyanticipated to be a human carcinogen]
• Thiotepa [reclassify asknown to be a human carcinogen]
• 1,2,3-Trichloropropane [reasonablyanticipated to be a human carcinogen]

The 8th RoC is the first Editionprepared following the expanded review procedures which now includea third level of scientific review by an external peer reviewsubcommittee of the NTP Board of Scientific Counselors meetingin public session with opportunity for public input. The 8th Reportis also the first to contain new listings based on the applicationof the revised criteria approved by the Secretary, HHS, on September13, 1996, which allow conclusions regarding carcinogenicity inhumans or experimental animals to be based on scientific judgment,with consideration given to all relevant information. This allowsfor the application of a broader scientific base by the inclusionof more biology in hazard identification and the review of alltypes and extent of data necessary to evaluate a substance andits potential to cause cancer in humans. The RoC is prepared bythe NTP with the assistance of other Federal health research andregulatory agencies and non-government institutions. The listingof a substance in the RoC is descriptive in nature and representsan initial step in hazard identification, which is generally consideredthe first step in the analytical process known as risk assessment.

The criteria used in the reviewprocess and the detailed description of the review proceduresare contained in the 8th RoC and can be accessed on-lineat: http://ehis.niehs.nih.gov.

To order a copy contact EnvironmentalHealth and Information Systems (EHIS):

e-mail: ehis@niehs.nih.gov
Fax: 919-541-0273
Phone: 919-541-3841

Questions regarding the RoC shouldbe directed to Dr. C. W. Jameson via e-mail: jameson@niehs.nih.govor by telephone: (919) 541-4096.

9th Edition

The Ninth Edition of the RoC isscheduled for publication in 1999. Nominations for listing ordelisting from the Ninth Report are currently being reviewed.In 1997, 14 substances or exposure circumstances were reviewedfor listing in or removal from the Ninth Report. This review includedthe multiphased, peer review process involving two Federal scientificreview groups and one non-government, scientific peer review body(a subcommittee of the NTP Board of Scientific Counselors) whichmet in an open, public meeting that included a public commentsession. All available data relevant to the criteria for inclusionor removal of candidate substances or exposure circumstances inthe Report were evaluated by the three scientific review committees.The nominations reviewed in 1997 for the 9th RoC were:

• Dyes metabolized to Benzidine(Benzidine dyes as a class) [known to be a human carcinogen]
• 1,3-Butadiene [known tobe a human carcinogen]
• Cadmium and Cadmium compounds[known to be a human carcinogen]
• Chloroprene [reasonablyanticipated to be a human carcinogen]
• Phenolphthalein [reasonablyanticipated to be a human carcinogen]
• Saccharin [reasonably anticipatedto be a human carcinogen] Proposed for delisting
• Smokeless Tobacco [knownto be a human carcinogen]
• Strong inorganic acid mistscontaining sulfuric acid [known to be a human carcinogen]
• Tamoxifen [known to bea human carcinogen]. There is also conclusive evidence thattamoxifen therapy reduces the risk of contralateral breast cancerin women with a previous diagnosis of breast cancer.
• Tetrachlorodibenzo-p-dioxin(TCDD) [known to be a human carcinogen]
• Tetrafluoroethylene [reasonablyanticipated to be a human carcinogen]
• Tobacco Smoking [knownto be a human carcinogen]
• Trichloroethylene [reasonablyanticipated to be a human carcinogen]
• UV [known to be a humancarcinogen]

Review of an additional 12 nominationsfor listing in or delisting from the 9th RoC (including a re-reviewof TCDD by the NTP Board Subcommittee for the RoC) will be carriedout in 1998. These nominations are:

• Alcoholic Beverages [listingas a known human carcinogen]
• Boot and Shoe Manufactureand Repair [listing as a known human carcinogen]
• Diesel Particulates (fromdiesel engine exhaust) [listing as reasonably anticipated tobe a known human carcinogen]
• Environmental Tobacco Smoke[listing as a known human carcinogen]
• Ethyl Acrylate (monomer usedto produce polymers and copolymers for use in latex paints, textiles,etc. [delisting]
• Ethylene Oxide (industrialchemical used as an intermediate in the manufacture of other chemicals;e.g., ethylene glycol and is widely used in the health care industryas a sterilant) [upgrade to known human carcinogen]
• Isoprene (is the monomericunit of natural rubber and naturally occurring terpenes and steroidsand widely used in the production of isoprene-butadiene copolymers)[listing as reasonably anticipated to be a known human carcinogen]
• Methyl-t-Butyl Ether (usedas an additive in unleaded gasoline in amounts up to 11%) [listingas reasonably anticipated to be a known human carcinogen]
• Nickel and Nickel Compounds(many industrial and commercial applications) [upgrade to knownhuman carcinogen]
• Nickel Refining [listingas a known human carcinogen]
• Silica, Crystalline (exposurefrom mining and quarrying of coal and other minerals, stone cutting,production of glass and ceramics and in occupations such as sandblasting,polishing and grinding) [upgrade to known human carcinogen]
• 2,3,7,8-Tetrachlorodibenzo-p-dioxin(TCDD) [re-review for upgrade to known to be a human carcinogen]

December 2-3 Board Review Opento the Public

The NTP Board of Scientific Counselors'Report on Carcinogens Subcommittee meeting on December 2 and 3,1998, will be held in the Conference Center, Building 101, SouthCampus, National Institute of Environmental Health Sciences (NIEHS),111 T.W. Alexander Drive, Research Triangle Park, North Carolina.

The meeting is open to the publicand will include a public comment period. Those wishing to commentshould contact the Executive Secretary, Dr. Larry Hart at:

NIEHS
P.O. Box 12233
Research Triangle Park, NC 27709
Telephone (919) 541-3971
Fax: (919) 541-0295
e-mail: hart@niehs.nih.gov

An agenda for the meeting, rosterof committee members, and additional information regarding themeeting will be distributed by Dr. Hart as it is available.

Background Documents to beavailable November 1

Background summary documents oneach of the nominations to be reviewed at the December Board meetingwill be provided to reviewers around November 1 and will be availableto the public shortly thereafter. Background documents includeall available data relevant to the criteria for inclusion or removalof candidate substances or exposure circumstances in the RoC.

Copies of draft background documentscan be obtained from:

Dr. C. W. Jameson
Report on Carcinogens
National Toxicology Program,
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

Request for Nominations forFuture Evaluation for Listing/Delisting

NTP encourages the nominationof agents, substances or mixtures for listing or delisting inthe RoC. The procedures for nomination and review, and the revisedcriteria for listing or delisting agents, substances or mixturesare available in the 8th Report and can be accessed on-lineat: http://ehis.niehs.nih.gov. Copies may also be requestedfrom Dr. C. W. Jameson at the previously listed address.

Petitions for listing or delistingan agent, substance or mixture in the RoC may be submitted byany interested party and should be sent to Dr. Jameson.

Petitions will be reviewed asexpeditiously as possible. Any questions regarding the process,procedures, or the information contained herein may also be directedto Dr. Jameson.

NTP Solicits Nominations for Chemicals

The NTP continues to solicit chemicalsand chemical classes to be tested for toxicity. This program wasestablished by the U.S. Department of Health and Human Servicesto characterize the toxicity of chemicals and coordinate chemicaltoxicity testing within the Department. The NTP is made up ofresearch and testing activities of the National Institute of EnvironmentalHealth Sciences (NIEHS), the National Institute for OccupationalSafety and Health (NIOSH), and the Food and Drug Administration(FDA). The NTP supports research and testing to increase the toxicologicinformation on selected chemicals, and to develop and validatetoxicology tests. Chemicals are selected for testing on the basisof the data and information needs of NTP member agencies and otherGovernment agencies, and in response to public concerns regardingthe safety and health effects of specific chemicals or chemicalclasses.

Chemicals are tested for any orall of the following health-related effects, including reproductiveand developmental toxicity, carcinogenicity, genetic toxicity,immunotoxicity, neurotoxicity, general toxicity, and chemicalmetabolism and disposition, as well as other effects that maybe considered relevant to human health concerns. The results ofthe NTP testing are used by other Federal and State agencies andprivate sector organizations. The results also are available tothe public, and are published in the open scientific literature.

There is no time limit for nominatingchemicals and health effects to be tested. The NTP will considereach nomination as it is received, but the available resourceswill limit the numbers of chemicals that can be tested, or thetypes of tests that can be performed. Please send all chemicalnominations and relevant information about the nominated chemicalsto: Errol Zeiger, Ph.D., J.D., Chemical Selection Office (EC-14),National Institute of Environmental Health Sciences, P.O. Box12233, Research Triangle Park, NC 27709

NTP Board of Scientific Counselors Meeting, February 5-6, 1998

The NTP Board, complemented byfour expert reviewers, met on February 5 and 6 with the primaryagenda topic being a comprehensive evaluation of the strategiesfor the use of transgenic mouse models in bioassays for carcinogenesis.The Board was asked to advise the NTP on the following issues:(1) Is the NTP approach to evaluation and validation of transgenicmodels for use in cancer bioassays sufficient and appropriate?;(2) How can existing models be best utilized? What are their limitations?;(3) What new models are needed, i.e., should the NTP seek to developorgan-specific tumor models?; and (4) Are the scientific needsof regulatory agencies being adequately addressed? Program scientistsdescribed and presented carcinogenesis findings for two mousemodels, the p53 deficient and the Tg.AC., complementary systemsthat identify trans-species carcinogens, and do not identify non-carcinogensand chemicals inducing strain-specific responses. Also, resultswere presented for collaborative studies between NIEHS and Japanon a third mouse model, the ras H2. Perspectives on regulatoryutility of transgenic models were provided by FDA and EPA representatives.

In summary, there was a 76% concordancebetween outcomes in the three transgenic lines and findings inthe long-term rodent bioassay or human experience, with all eighthuman carcinogens studied being detected. Chemicals most likelyto be missed based on the results were nongenotoxic mouse liver,kidney, and/or adrenal carcinogens, which would account for about10% of the chemicals in the NTP database, and include small halogenatedalkanes and alkenes, a number of drugs, industrial chemicals andpesticides. There was need expressed for site-specific modelssuch as for brain and prostate tumors, cancers that are increasingin the human population.

The Board reviewed and providedcomments on nine chemicals and four mixtures recommended for toxicologicalstudies by the NTP Interagency Committee for Chemical Evaluationand Coordination (ICCEC), and on six chemicals that the ICCECrecommended not be studied. The Board reviewed and approved aconcept proposal for continuing pathology support for the Program,and were briefed on recent meetings of the Report on Carcinogensand Technical Reports Review Subcommittees, as well as recentactivities of the Interagency Coordinating Committee on the Validationof Alternative Methods.

Summary minutes for the NTP Boardof Scientific Counselors meeting can be obtained from: CentralData Management, NIEHS/NTP, P.O. Box 12233, MD: E1-02, ResearchTriangle Park, NC 27709; Tel: (919) 541-3419, Fax: (919) 541-3687;e-mail: CDM@niehs.nih.gov

NTP website Update

A major goal of the NTP is toprovide more timely access to our information, draft technicalreports, background summaries for the Report on Carcinogens; testingdata, etc. Throughout this issue of the UPDATE you will note frequentreference to the web for access. Changes are underway with theNTP website, and we encourage you to continue to visit our homepagehttp://ntp.niehs.nih.gov/ntp and monitor the changes. The redesign underway is to provide easier accessto the breadth of NTP activities.

We welcome and appreciate yourfeedback. One frequent suggestion has been to return to providing the full version of the Annual Plan on the website [click in close box to return to Update] in place ofthe current "Summary Annual Plan" because of the largeamount of study and other information presented in the full version.We hope to have the current NTP Annual Plan available on the NTPwebsite by August 1, 1998.

Let us assure you however thathard copy access remains a priority for all those interested inthe program who do not have the world wide web access and theserequests will be promptly filled.

NTP E-Mail List-Server Established

A new list-server will enableus to disseminate announcements and up to the minute informationto a large number of people at one time. The information includedin the quarterly UPDATE and other announcements will be distributedto the list-server as soon as the information becomes available.We believe the list-server will enable us to reduce the numberof people receiving paper copies of the UPDATE and replace theirdistribution with electronic copies. If you have subscribed tothe list-server and do not wish to continue to receive paper copiesof the UPDATE and other Liaison Office mail-outs, please e-mailthe Liaison and Scientific Review Office at liaison@starbase.niehs.nih.gov

To subscribe to the list-serveremail to:ntpmail-request@list.niehs.nih.gov with the word "subscribe" as the body of the message.