Program - Society of Toxicology

44 th Annual Meeting
and ToxExpo
Program Description
#663 9:40 PERFORMANCE OF BCOP, IRE, ICE, AND HET-
CAM IN DETECTING SUBSTANCES THAT
INDUCE SEVERE IRRITATION AND
IRREVERSIBLE OCULAR DAMAGE. N. Y.
Choksi 1,2 , D. A. Allen 1,2 , C. Inhof 1,2 , J. Truax 1,2 , R. R.
Tice 1,2 and W. S. Stokes 2 . 1 ILS, Inc., Research Triangle
Park, NC and 2 NICEATM, NIEHS/NIH/DHHS,
Research Triangle Park, NC.
#664 10:10 THE STATE OF THE SCIENCE ON IN VITRO
TEST METHODS FOR DETECTING MILD TO
MODERATE OCULAR IRRITANTS. C. Eskes, T.
Hartung and V. Zuang. ECVAM, IHCP, European
Commission–DG JRC, Ispra, Varese, Italy. Sponsor: W.
Stokes.
#665 10:40 CHALLENGES IN THE VALIDATION OF
ALTERNATIVE TEST METHODS TO EVALUATE
OCULAR TOXICITY. T. Hartung, C. Eskes and V.
Zuang. European Centre for the Validation of
Alternative Methods, European Commission DG JRC,
Ispra, Varese, Italy. Sponsor: W. Stokes.
Tuesday Morning, March 8
8:30 AM to 11:30 AM
Room RO4
WORKSHOP SESSION: MODE OF ACTION IN RELEVANCE OF
RODENT LIVER TUMORS TO HUMAN CANCER RISK
Chairperson(s): Yvonne Dragan, National Center for Toxicological Research,
Jefferson, AR and Michael Holsapple, International Life Sciences Institute,
Washington, DC.
Endorsed by:
Carcinogenesis SS*
Regulatory and Safety Evaluation SS
Risk Assessment SS
The recent adoption of the IPCS mode of action paradigm (Sonich-Mullin et al.,
2001, Regul Toxicol Pharmacol 34:146-152) coupled with the recent ILSI
human relevance framework (Cohen et al., 2003, Crit Rev Toxicol 33:581-589)
have led to an approach for the systematic analysis of data on modes of carcinogenic
action of chemicals in experimental animals and its application to the
assessment of human cancer risk assessment. Hazard identification and risk
assessment paradigms depend on the presumption of similarity of rodents to
humans, yet species-specific responses and high dose to low dose extrapolation
plague the development of appropriate risk assessments. The first step in a mode
of action analysis is to establish the key biochemical and cellular events,
temporal occurrence, and dose response concordance relationships common to
each mode of action of a chemical. The next step is to assess the biological plausibility
and relevance to human cancer risk of the proposed mode(s) of action
taking kinetic and dynamic factors into consideration. The identification of key
events can be used to bridge species and dose differences. These discussions
will be used to generate a minimal dataset necessary to establish selected modes
of action. This mode of action framework has been previously applied to rodent
liver tumors associated with exposure to peroxisome proliferators mediated
through the alpha receptor (Klaunig et al., 2003, Crit Rev Toxicol 33:655-780).
More recently, several additional modes of action for rodent liver cancer development
have been described including cytotoxicity, P450 induction, hormone
mediated and porphyrogenicity / metal overload. An understanding of the mode
of action underlying cancer development in the liver will place rodent liver
tumors into a more appropriate perspective when human risk assessment is
performed.
#666 8:30 MODE OF ACTION IN RELEVANCE OF
RODENT LIVER TUMORS TO HUMAN CANCER
RISK. M. P. Holsapple 1 and Y. P. Dragan 2 . 1 HESI,
Washington, DC and 2 NCTR, Jefferson, AR.
#667 8:35 THE PATHOGENESIS OF RODENT
HEPATOCARCINOGENESIS: POTENTIAL
APPLICATIONS TO HUMAN CANCER RISK. H.
C. Pitot. Oncology, McArdle Lab., University of
Wisconsin, Madison, WI.
#668 9:05 FRAMEWORK FOR EVALUATING THE HUMAN
RELEVANCE OF CARCINOGENIC MODES OF
ACTION IN ANIMALS. S. M. Cohen. Pathology and
Microbiology, University of Nebraska Medical Center,
Omaha, NE.
#669 9:35 MODE OF ACTION AND HUMAN RELEVANCE
OF PHENOBARBITAL-LIKE RODENT LIVER
CARCINOGENS. A. R. Boobis 1 , B. G. Lake 2 , E.
Harpur 3 , J. M. Rice 4 and J. I. Goodman 5 . 1 Experimental
Medicine and Toxicology, Imperial College London,
London, United Kingdom, 2 BIBRA International Ltd.,
Carshalton, United Kingdom, 3 Sanofi-Synthelabo,
Malvern, PA, 4 Georgetown University, Washington, DC
and 5 Michigan State University, East Lansing, MI.
#670 9:55 MODE OF ACTION AND HUMAN RELEVANCE
OF METAL OVERLOAD AND
PORPHYRINOGENIC COMPOUNDS. J. E.
Klaunig 1 , A. Nyska 2 , J. Popp 3 , A. Smith 4 , W. Stott 5 and
G. Williams 6 . 1 Indiana University, Indianapolis, IN,
2 3 NIEHS/NTP, Research Triangle Park, NC, Purdue
Pharmacology, New York, 4 MRC Toxicology,
University of Leicester, United Kingdom, 5 The Dow
Chemical Company, Midland, MI and 6 New York
Medical College, Valhalla, NY.
#671 10:15 HORMONAL PERTURBATION AS A MODE OF
ACTION FOR RODENT LIVER TUMORS. T.
Pastoor 4 , Y. Dragan 1 , M. Cunningham 3 , I. White 7 , J.
Teeguarden 6 , H. Pitot, III 5 and C. Capen 2 . 1 NCTR,
Jefferson, AR, 2 Ohio State University, Columbus, OH,
3 NIH/National Center for Toxicogenomics, Research
Triangle Park, NC, 4 Syngenta CropScience, Greenboro,
NC, 5 University of Wisconsin, Madison, WI,
6 ENVIRON Corporation, Collegeville, PA and
7 University of Leicester, Leicester, United Kingdom.
#672 10:35 RODENT HEPATIC TUMORS: CYTOXICITY
MODE OF ACTION. V. L. Dellarco 1 , S. Cohen 2 , D.
Wolf 3 , R. Maronpot 4 and D. Jacobson-Kram 5 . 1 Office of
Pesticide Programs, U.S. EPA, Washington, DC,
2 University of Nebraska Medical Center, Omaha, NE,
3 Health and Environmental Effects Research
Laboratory, U.S. EPA, Research Triangle Park, NC,
4 NIEHS, National Toxicology Program, Research
Triangle Park, NC and 5 CDER, U.S. FDA, Rockville,
MD.
TUESDAY
up-to-date information at www.toxicology.org 101