Federal Register: September 21, 2000 (Volume 65, Number 184)
DOCID: FR Doc 00-24244
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Public Health Service
NOTICE: NOTICES
ACTION: Meetings:
SUBJECT CATEGORY:
National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health (NIH), National Toxicology Program (NTP); Notice of an International Workshop on In Vitro Methods for Assessing Acute Systemic Toxicity, co-sponsored by NIEHS, NTP and the U.S. Environmental Protection Agency (EPA): Workshop Agenda and Registration Information
DOCUMENT SUMMARY:
Pursuant to Public Law 103-43, notice is hereby given of a public meeting sponsored by NIEHS, the NTP, and the EPA, and coordinated by the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) and the NTP Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM). The agenda topic is a scientific workshop to assess the current status of in vitro test methods for evaluating the acute systemic toxicity potential of chemicals and to develop recommendations for future research, development, and validation studies. The workshop will take place on October 1720, 2000, at the Hyatt Regency Crystal City Hotel, 2799 Jefferson Davis Highway, Arlington, VA, 22202. The meeting will be open to the public.
In a previous Federal Register notice (Vol. 65, No. 115, pp. 37400
37403), ICCVAM requested information and data that should be considered
at the Workshop and nominations of expert scientists to participate in
the Workshop. A preliminary list of relevant studies to be considered
for the Workshop was also provided. As a result of this request, an
ICCVAM interagency Workshop Organizing Committee has selected an
international group of scientific experts to participate in this
Workshop. NICEATM, in collaboration with ICCVAM, has developed a
background summary of data and performance characteristics for
available in vitro methods. This summary will be made available to
invited expert scientists and the public before the Workshop. Requests
for the summary can be made to the address given below. This notice
provides an agenda, registration information, and updated details about the Workshop.
Workshop Background and Scope
A. Background
Acute toxicity testing is conducted to determine the hazards of various chemicals and products. This information is used to properly classify and label materials as to their lethality in accordance with an internationally harmonized system (OECD, 1998). Nonlethal endpoints may also be evaluated to identify potential target organ toxicity, toxicokinetic parameters, and doseresponse relationships. While animals are currently used to evaluate acute toxicity, recent studies suggest that in vitro methods may also be helpful in predicting acute toxicity.
Studies by Spielmann et al. (1999) suggest that in vitro cytotoxicity methods may be useful in predicting a starting dose for in vivo studies, and thus may potentially reduce the number of animals necessary for such determinations. Other studies (e.g., Ekwall et al., 2000) have indicated an association between chemical concentrations leading to in vitro cytotoxicity and human lethal blood concentrations. A program to assess toxicokinetics and target organ toxicity utilizing in vitro methods has been proposed that may provide enhanced predictions of toxicity and potentially reduce or replace animal use for some tests (Ekwall et al., 1999). However, many of the necessary in vitro methods for this program have not yet been developed. Other methods have not been evaluated in validation studies to determine their usefulness and limitations for generating information to meet regulatory requirements for acute toxicity testing. Development and validation of in vitro methods which can establish accurate dose response relationships will be necessary before such methods can be considered for the reduction or replacement of animal use for acute toxicity determinations.
This workshop will examine the status of available in vitro methods
for assessing acute toxicity. This includes screening methods for acute
toxicity, such as methods that may be used to predict the starting dose
for in vivo animal studies, and methods for generating information on
toxicokinetics, target organ toxicity, and mechanisms of toxicity. The
workshop will develop recommendations for validation efforts necessary
to characterize the usefulness and limitations of these methods.
Recommendations will also be developed for future mechanismbased
research and development efforts that might further improve in vitro
assessments of acute systemic lethal and nonlethal toxicity. B. Objectives of the Workshop
Four major topics will be addressed:
The objectives of the meeting are to:
1. Review the status of in vitro methods for assessing acute systemic toxicity:
a. Review the validation status of available in vitro screening methods for their usefulness in estimating in vivo acute toxicity,
b. Review in vitro methods for predicting toxicokinetic parameters important to acute toxicity (i.e., absorption, distribution, metabolism, elimination), and
c. Review in vitro methods for predicting specific target organ toxicity;
2. Recommend candidate methods for further evaluation in prevalidation and validation studies;
3. Recommend validation study designs that can be used to characterize adequately the usefulness and limitations of proposed in vitro methods;
4. Identify reference chemicals that can be used for development and validation of in vitro methods for assessing in vivo acute toxicity; and
5. Identify priority research efforts necessary to support the
development of mechanismbased in vitro methods to assess acute
systemic toxicity. Such efforts might include incorporation and
evaluation of new technologies, such as gene microarrays, and
development of methods necessary to generate dose response information. Workshop Information
A. Workshop Agenda
Tuesday, October 17, 2000
8:30 a.m.Opening Plenary Session
10:30 a.m.In Vitro Approaches to Estimate the Acute Toxicity Potential of Chemicals
Public Comment
Breakout Groups' Charges
12:30 p.m.Lunch Break
1:45 p.m.Breakout Groups: Identifying What Is Needed from In Vitro Methods
5:30 p.m.Adjourn for the Day
Wednesday, October 18, 2000
8:00 a.m.Plenary SessionStatus Reports by Breakout Group Co Chairs
9:00 a.m.Breakout Groups: Current Status of In Vitro Methods for Acute Toxicity
12:00 p.m.Lunch Break
1:30 p.m.Breakout Groups: Current Status of In Vitro Methods for Acute Toxicity (Cont'd)
5:30 p.m.Adjourn for the Day
Thursday, October 19, 2000
8:00 a.m.Plenary SessionStatus Reports by Breakout Group Co Chairs
9:00 a.m.Breakout Groups: Future Directions for In Vitro Methods for Acute Toxicity
12:00 p.m.Lunch Break
1:30 p.m.Breakout Groups: Future Directions for In Vitro Methods for Acute Toxicity (Cont'd)
5:30 p.m.Adjourn for the Day
Friday, October 20, 2000
8:00 a.m.Closing Plenary SessionReports by Breakout Group Co Chairs
Public Comment
Closing Comments
12:15 p.m.Adjourn
B. Workshop Registration
The Workshop meeting will be open to the public, limited only by the space available. Due to space limitations, advance registration is requested by October 13, 2000. Registration forms can be obtained by contacting NICEATM at the address given below or by accessing the on line registration form at: http://iccvam.niehs.nih.gov/invi_reg.htm. Other relevant Workshop information (i.e., accommodations, transportation, etc.) is also provided at this website.
C. Public Comment
The Public is invited to attend the Workshop and the number of
observers will be limited only by the space available. Two formal
public comment sessions on Tuesday, October 17th and Friday, October
20th will provide an opportunity for interested persons or groups to
present their views and comments to the Workshop participants (please
limit to one speaker per group). Additionally, time will be allotted
during each of the Breakout Group sessions for general discussion and
comments from observers and other participants. The Public is invited
to present oral comments or to submit comments in writing for
distribution to the Breakout Groups to NICEATM at the address given
below by October 13, 2000. Oral presentations will be limited to seven
minutes per speaker to allow for a maximum number of presentations.
Individuals presenting oral comments are asked to provide a hard copy
of their statement at registration. For planning purposes, persons
wishing to give oral comments are asked to check the box provided on
the Registration Form, although requests for oral presentations will
also be accepted onsite (subject to availability of time). Persons
registering for oral comments or submitting written remarks are asked
to include their contact information (name, address, affiliation, telephone, fax, and email).
Guidelines for Requesting Registration Form and Submission of Public Comment
Requests for registration information and submission of public
comments should be directed to the NTP Interagency Center for the
Evaluation of Alternative Toxicological Methods, Environmental
Toxicology Program, NIEHS/NTP, MD EC17, PO Box 12233, Research
Triangle Park, NC 27709; 9195413398 (phone); 9195410947 (fax);
iccvam@niehs.nih.gov (email). Public comments should be accompanied by
complete contact information including name, (affiliation, if applicable), address, telephone number, and email address.
References
[[Page 57205]]
acute oral toxicity (LD50) testing in the up and down procedure (UDP) from cytotoxicity data. ATLA, 27(6), 957966.
Dated: September 12, 2000.
Samuel H. Wilson,
Deputy Director, National Institute of Environmental Health Sciences.
[FR Doc. 0024244 Filed 92000; 8:45 am]
BILLING CODE 414001P
SUMMARY:
National Institute of Environmental Health Sciences et al. in vitro methods for assessing acute systemic toxicity; international workshop,