National Toxicology Program

                                 May 22, 1995


NTP UPDATE FROM  THE NTP LIAISON OFFICE
	1) NTP Board of Scientific Counselors' Technical Reports Review Subcommittee
	   June 20-21, 1995

	2) Update:  Biennial Report on Carcinogens (BRC) -- Proposed Revised
	   Criteria Available for Review

	3) NTP Board of Scientific Counselors' Meeting -- June 29, 1995

	4) NTP Workshop:  Validation and Regulatory Acceptance of Alternative 	   Test Methods Oct. 30 - Nov. 1,1995, Bethesda, MD

	5) Report of NTP Workshop: "Mechanism-Based Toxicology in Cancer Risk 	   Assessment: Implications for Research, Regulation, and Legislation" 	   January 11-13, 1995

	6) NTP Technical Reports Availability

	7) NIEHS and NTP information in electronic format world-wide


1)	PEER REVIEW OF DRAFT NTP TOXICOLOGY AND 
	CARCINOGENESIS TECHNICAL REPORTS AND SHORT-TERM 
	TOXICITY REPORTS

The NTP Board of Scientific Counselors' Technical Reports Review Subcommittee will meet June 20 and 21, 1995, in the Conference Center, Building 101, South 
Campus, National Institute of Environmental Health Sciences (NIEHS), 
111 Alexander Drive, Research Triangle Park, North Carolina. The meeting will 
begin at 8:30 a.m. on both days and is open to the public. The primary agenda 
topic is the peer review of draft Technical Reports of long-term toxicology and 
carcinogenesis studies and one short-term toxicity study from the National 
Toxicology Program.

Additionally, on June 21, a series of presentations will be made concerning 
the toxicologic fidings from collaborative prechronic inhalation studies on 
carbon disulfide. There will be a presentation titled "Update on the New Diet 
(NTP-2000) for Rats and Mice in NTP Toxicology and Carcinogenesis Studies."

Tentatively scheduled to be peer reviewed on June 20 and 21 are draft Technical 
Reports of six two-year studies , listed alphabetically, along with supporting 
information in the following table. Similar information is given for the 
short-term report on 1,4-butanediol. All studies were done using Fischer 344 
rats and B6C3F1 mice, while one two-year study also employed Sencar mice. The 
order of review is given in the far right column of the table. Copies of the 
draft Reports may be obtained, as available, from: Central Data 
Management, MD E1-02, P.O. Box 12233, Research Triangle Park, NC 27709 
(919/541-3419).

In addition to the traditional two-year study results, the studies with 
butyl benzyl phthalate, t-butylhydroquinone, salicylazosulfapyridine, and 
scopolamine hydrobromide trihydrate included groups run under mild dietary 
restrictions. A separate report will deal with the effects of dietary 
restrictions on the results of these four studies, and will draw some 
conclusions about the usefulness of this approach to performing toxicology 
and carcinogenesis studies.

Persons wanting to make a formal presentation regarding a particular Technical 
Report must notify the Executive Secretary by telephone, by FAX, or by mail 
no later than June 14, 1995, and provide a written copy of comments in advance 
of the meeting so copies can be distributed to all Subcommittee members and 
NTP staff and made available at the meeting. Written statements should 
supplement and may expand on the oral presentation.Oral presentations 
should be limited to no more than five minutes.

The program would welcome receiving toxicology and carcinogenesis information 
from completed, ongoing, or planned studies by others, as well as current 
production data, human exposure information, and use patterns for any of 
the chemicals listed in this announcement. Please contact Central Data 
Management at the address given above, and they will relay the information 
to the appropriate staff scientist.  

The Executive Secretary, Dr. Larry G. Hart, P.O. Box 12233, 
Research Triangle Park, North Carolina 27709 (telephone 919/541-3971;   
FAX 919/541-0719)  will furnish a final agenda and a roster of 
Subcommittee members prior to the meeting. Summary minutes subsequent to 
the meeting will be available upon request.

 
2)	Update: BIENNIAL REPORT ON CARCINOGENS (BRC)

Background:

The Biennial Report on Carcinogens is prepared in response to section 301 (b) 
(4) of the Public Health Service Act which stipulates that the Secretary of the 
Department of Health and Human Services shall publish a report which contains a 
list of all substances (i) which either are known to be human carcinogens or 
may reasonably be anticipated to be human carcinogens; and (ii) to which a 
significant number of persons residing in the United States are exposed. This 
responsibility has been delegated by the Secretary to Director, National 
Toxicology Program (NTP). Dr. Kenneth Olden, Director of the National 
Institute of Environmental Health Sciences (NIEHS) and the NTP, has initiated 
a review of the BRC to broaden input to its preparation, broaden the scope 
of scientific review associated with the Report, and provide review of the 
criteria used for inclusion of substances in the BRC.

An ad hoc working group of the NTP Board of Scientific Counselors was 
established to receive public comments on the existing criteria and review 
and make recommendations on the criteria for listing substances in the BRC. 
This ad hoc working group had a balance of expertise and views and represented 
Academia, Industry, Labor, State, Public and Private Organizations. The 
working group reviewed the criteria in an open, public meeting in 
Washington, D.C. on April 24 & 25, 1995.

Meeting Report Available -- Public Input Encouraged

A brief Summary of the Meeting, and the Current and Proposed Revised Criteria, 
are available upon request from: The NTP Liaison Office: P.O. Box 12233, 
MD: A3-01, Research Triangle Park, NC  27709. Phone: (919) 541-0530, 
Fax:  (919) 541-0295.
The report will be received and reviewed by the NTP Board of Scientific 
Counselors at their June 29 meeting.  Public input on the 
report is encouraged.  Please see Item #3 below, for additional information.

Copies of the report will be available in June and can be obtained by contacting 
The NTP Liaison Office: P.O. Box 12233, MD: A3-01, 
Research Triangle Park, NC  27709. Phone: (919) 541-0530, 
Fax:  (919) 541-0295.
 
3)	NTP Board of Scientific Counselors' Meeting

The (NTP) Board of Scientific Counselors, will meet in the Conference Center, 
Building 101, South Campus, National Institute of Environmental Health Sciences 
(NIEHS), 111 Alexander Drive, Research Triangle Park, North Carolina, on 
June 29 , 1995.

The primary agenda topic will be concerned with the report and recommendations 
of the ad hoc working group of the NTP Board from their review of the criteria
for 
listing substances in the Biennial Report onCarcinogens (BRC) (formerly Annual 
Report on Carcinogens) on April 24 and 25, 1995.  

Specifically, the Board will:
	(1) review the report and recommendations of the ad hoc working group;
	(2) receive public comments on the report; and
	(3) develop Board recommendations concerning the selection criteria. 


The  preliminary agenda topics with approximate times are as follows:

 8:30 a.m. - 8:45   -- Report of the Director, NTP.
 8:45 a.m. - 9:15   -- Report of the Director, 
                       Environmental Toxicology Program (ETP).
 9:15 a.m. - 9:45   -- Report of the NTP Workshop on "Mechanism-Based Toxicology 
                       in Cancer Risk Assessment: Implications for Research, 
                       Regulation, and Legislation" held January 11-13, 1995.
10:00 a.m. - 10:20  -- Report on the Meeting of the Ad Hoc Working Group 
                       to Review Criteria for Listing of Substances in the BRC.
10:20 a.m. - 11:00  -- Board Discussion of the Working Group Report.
11:00 a.m. - 12:00  -- Public Comments on the Report.
 1:15 p.m. - 2:15   -- Further Discussion and Development of Recommendations
	                   by the Board Concerning the BRC Selection Criteria.
 2:15 p.m. - 2:25   -- Report on Technical Reports Review Subcommittee
Activities.
 2:25 p.m. - 2:55   -- Chemicals Nominated and Recommended for Study by the 
                       Interagency Committee for Chemical Evaluation and 
                       Coordination (ICCEC) on December 14, 1994, will be 
                       presented for discussion and time will be allowed for 
                       public comment. Chemicals evaluated by the ICCEC were 
                       (with CAS Nos. in parentheses):  
                       (1) Arsenic Trioxide (1327-53-3); 
                       (2) Ethidium Bromide (1239-45-8); 
                       (3) 5-(Hydroxymethyl)furfural (67-47-0); 
                       (4) Isoamyl Acetate (123-92-2); and 
                       (5) MX [3-chloro-4-(dichloromethyl) 5-hydroxy-2-
                       (5H)-furanone]  (77439-76-0).  
                       One chemical previously evaluated was rereviewed:  
                       Hexamethyldisilazane (999-97-3).
 3:15 p.m. - 3:45   -- Concept Review: In Vitro and In Vivo Genetic Toxicology 
                       Testing.
 3:45 p.m. - 4:30   -- Alternative Methods - Status and Plans:
                    -- RFA for Research in "Mechanistically Based Alternative 
                	   Methods in Toxicology" .
                    -- Proposed Workshop on "Alternative Test Methods in
Toxicology: 
                       Validation and Regulatory Acceptance".
Adjournment

Public Comments Encouraged

The meeting is open to the public, and public input concerning the criteria for 
listing a substance in the Biennial Report on Carcinogens is encouraged.  
A brief summary of the ad hoc working group meeting, and the current and 
proposed revised criteria, are available on request from the NTP Liaison 
Office, P.O. Box 12233, MD A3-01, Research Triangle Park, NC 27709, 
Phone: (919) 541-0530, FAX: (919) 541-0295 (see item 2 above). This 
summary also will be published in the Federal Register in late May or early 
June. Written comments can be submitted to Dr. Larry G. Hart, NTP Board 
Executive Secretary. Formal oral comments during the meeting will be limited 
to five minutes to permit maximum participation. Written comments accompanying 
oral statements are encouraged.  To assure consideration by the Board at the 
meeting, written comments must be received by June 23, 1995.  Registration to 
attend is not required; however, to ensure adequate seating, we ask that those 
planning to attend let us know.   To register, submit written comments or 
announce intention to make oral comments ,  receive information on the agenda, 
or be put on the mailing list for summary minutes subsequent to the meeting, 
please contact: Dr. L. G. Hart, P.O. Box 12233, Research Triangle Park, 
NC 27709; telephone: (919) 541-3971; FAX:  (919) 541-0719.
 
4)   Validation and Regulatory Acceptance of Alternative Test Methods 
     Workshop

A Workshop on Validation and Regulatory Acceptance of Alternative Test Methods  
is  planned for October 30-November 1, 1995, at the NIH Natcher Conference Center

in Bethesda, MD. The purpose of the workshop is to receive comments from the 
public and a review panel on the draft report of the ad hoc Interagency 
Coordinating Committee on the Validation of Alternative Methods (ICCVAM). 
ICCVAM was established by the Director, NIEHS and NTP, in response to the 
NIH Revitalization Act of 1993 (Public Law No. 103- 43), which directed NIEHS to:

(a) establish criteria for the validation and regulatory acceptance of 
alternative testing methods; and 
(b) to recommend a process through which scientifically validated alternative 
methods can be accepted for regulatory use.  Comments and recommendations from 
the workshop will be considered by the ICCVAM in preparing a final report.  

The draft report will be available for review by the public in early October.  
In developing the draft report ICCVAM is considering information obtained from 
several sources.  These include 1) a questionnaire completed by each agency 
regarding their procedures for test methods approval; 2) public comments
submitted 
in response to a request published in the Federal Register (December 7, 1994) 
and an NTP Liaison Office - December 1994 mailing; 3) presentations from various 
government scientists; and 4) a review of pertinent published literature.

Registration information will be announced in a future mailing. To be placed on 
the mailing list to receive registration information and/or a copy of the draft 
report, please contact: The NTP Liaison Office, P.O. Box 12233, MD: A3-01, 
Research Triangle Park, NC  27709; telephone: (919) 541-0530; 
FAX: (919) 541-0295.  

If you have questions or comments about the ICCVAM, you can contact 
Dr. William Stokes at (919) 541-7997; FAX: (919) 541-0719, 
or on the internet at stokes@niehs.nih.gov.
 
5)    UPDATE: NTP WORKSHOP ON "MECHANISM-BASED 
      TOXICOLOGY IN CANCER RISK ASSESSMENT: IMPLICATIONS 
      FOR RESEARCH, REGULATION, AND LEGISLATION"   
      JANUARY 11-13, 1995

A diverse group of over 200 participated in the workshop designed to bring 
regulators, researchers, and legislators together to address the following goals:

To assess the scientific foundation for using mechanism-based 
toxicology to address critical issues in risk assessment.

To identify and propose solutions to the regulatory problems which may 
emerge by the use of mechanistic  toxicology in conducting risk 
assessments.

To determine the applicability of mechanism-based toxicology and risk 
assessment to current legislative issues.

Workgroups addressed five areas of risk assessment and how mechanism based 
toxicology can be applied in these areas:
 
Screening chemicals and priority setting, 
Hazard Identification, 
Dose-response relationships, 
Species extrapolation, 
Distribution of risk.


Workgroups defined areas of consensus, areas of debate, knowledge and information

gaps, strategies for moving forward, and input into the review of criteria for
the 
Biennial Report on Carcinogens.

The workshop report will be available from the NTP Liaison Office in early June. 

In addition, a summary of the meeting will be presented to the NTP Board of 
Scientific Counselors during their June 29 meeting (see Item #3 above).

Copies of the report will be available in June and can be obtained by contacting:
 The NTP Liaison Office, P.O. Box 12233, MD: A3-01, 
Research Triangle Park, NC  27709, Phone: (919) 541-0530,  
Fax:  (919) 541-0295.
 
6)	NTP Technical Reports Availability

Abstracts of the following most recently published NTP reports are now available 
on the Internet (GOPHER.NIEHS.NIH.GOV, defined in your Gopher setup 
configuration).  Full copies of these reports are also available free of
charge 
from Central Data Management while supplies last.  

NTP Technical Report on the Toxicity Studies of Isoprene (CAS No. 78-79-5) 
administered by inhalation to F344/N Rats and to B6C3F1 Mice.  (TOX-31)

NTP Technical Report on the Toxicology and Carcinogenesis Studies of Tricresyl 
Phosphate (CAS No. 1330-78-5) in F344/N Rats and B6C3F1 mice (Gavage and Feed 
studies).  (TR-433)

NTP Technical Report on the Toxicology and Carcinogenesis Studies of 
4,4'-Thiobis(6-t-butyl-m-cresol) (CAS No. 96-69-5) in F344/N Rats and 
B6C3F1 mice (Feed studies).  (TR-435)

NTP Technical Report on the Toxicology and Carcinogenesis Studies of Ozone 
(CAS No. 10028-15-6) and Ozone/NNK (CAS No. 10028-15-6/64091-91-4) in 
F344/N Rats and B6C3F1 mice (Inhalation studies).  (TR-440)

NTP Technical Report on the Toxicology and Carcinogenesis Studies of 
p-Nitrobenzoic Acid (CAS No. 62-23-7) in F344/N Rats and B6C3F1 mice 
(Feed studies).  (TR-442)

	To request NTP documents contact:
	Central Data Management
	National Institute of Environmental Health Sciences
	P.O. Box 12233
	Mail Drop E1-02
	Research Triangle Park, NC  27709
	FAX number:	(919) 541-3687
	Telephone number:	(919) 541-3419
	Internet Email Address	CDM@NIEHS.NIH.GOV
NIEHS AND NTP INFORMATION: IN ELECTRONIC FORMAT WORLD-WIDE

In addition to contacting the NIEHS and NTP directly, selected information in electronic
format is made available world-wide.  For example, The 1994 NTP Annual Plan,
The 7th Annual Report on Carcinogens (Summary), and The Status of All NTP Studies are all available on the Internet.
 
To view this information requires access to the Internet and internet client
software. The server is located at the National Institute of Environmental Health Sciences.
To access this server using the Gopher client the address is ntp.niehs.nih.gov and 
the URL is http://ntp.niehs.nih.gov/ntp when using one of the world wide web 
browsers e.g. Mosaic or Netscape. 

For information contact: Dr. W. Eastin, NIEHS, P.O. Box 12233, 
Research Triangle Park, NC  27709 : telephone: (919) 541-7941