Results of ILSI/HESI International Act Study
Bold: Unexpected responses

Human carcinogens

phenacetin
cyclophosphamide
melphalan
Immunosuppressive human carcinogen
cyclosporin A
Human hormone carcinogen
diethylstilbestrol
17-!-estradiol
Nongenotoxic rodent-only carcinogenbased on Epidemiology
clofibrate
phenobarbital
reserpine
dieldrinmethapyrilene
based on mechanism
haloperidol
chloroform
chlorpromazine
metaproterenol
Wy-14643
DEHP
sulfamethoxazole
Non-genotoxic non-carcinogensulfisoxazole
mannitol
ampicillin

rasH2

p53+/-

Positive
Positive
EquivocalTg.AC

XPA-/-

XPA/p53

Neonatal

SHE

Negative
Equivocal
Equivocal

Negative

Negative

Negative
Positive

Negative
Positive
Positive

Equivocal

Positive

Positive

Positive

Negative

Positive

Negative
Negative

Positive
Positive

Positive

Positive
Positive

Negative
Positive

Positive
Positive

Negative
Negative

Positive
Positive
Positive
Positive
Positive
Positive

GavageSkin

Negative
Positive
Positive

Negative
Positive
Positive

Equivocal

Positive

Positive
Negative

Positive
Equivocal

Positive
Negative
Negative
Negative
Negative
Negative
Negative
Negative
Negative
Positive
Positive
Negative

Negative
Negative
Negative
Negative
Negative
Negative
Equivocal
Negative
Negative
Negative
Equivocal
Negative

Negative
Negative
Negative

Negative
Negative
Negative

Positive
Negative

Negative

Negative
Negative
Negative
Negative

Negative
Negative

Negative

Negative

Negative
Negative
Negative
Negative
Equivocal
Negative
Negative

Negative
Negative
Negative

Negative

Negative

Positive
Negative
Negative

Negative
Negative

Negative
Negative
Negative

Negative
Negative

Negative

Positive
Positive
Positive
Positive
Negative
Negative
Positive

1Regulatory perspectives in USA, EU,and Japan
Model

USA: FDATG.AC
Others*Japan: MHLW

Accepted
Genotoxic and non-genotoxic

rasH2
p53KO

EU: CPMP

Accepted
Clear or equivocal
genotoxic

Accepted
Genotoxic andnon-genotoxic

Accepted
Dermal applications only
Partially accepted

Accepted
Clear or equivocal
genotoxic
Not accepted
Unstable vector

Not accepted*XPA KO, XPA+p53KO, neonatal models

MacDonald et al: Toxicological Sciences 77, 188-194 (2004)

28th Annual Symposium ofSociety of Toxicologic Pathology
Session 3
Alternative Mouse Modelfor Carcinogenicity Assessment(Washington, D.C., June 23, 2009)

11.4.133

Chair-persons and Speakers
Session 3
Alternative Mouse Model for Carcinogenicity Assessment
Chairs: Daniel G. Morton (Pfizer) & James A. Swenberg (University of North Carolina)

・ An Industry Perspective on Utility of Short-term Carcinogenicity Testing inTransgenic Mice in Pharmaceutical Development (Richard .D. Storer, Merck)・ Alternative Mouse Models for Carcinogenicity Assessment: Industry Useand Issues with Pathology Interpretation (Gerald G. Long, Eli Lilly)
・ European Perspectives on Alternative Mouse Carcinogenicity Models(Bernard Leblanc, Pfizer)
・ The Ito Medium Term Carcinogenicity Model (Hiroyuki Tsuda, Nagoya City
University of Medical School)
・ Genetically Modified Mouse Models for Hazard Identification and Risk
Assessment in Toxicology and Carcinogenesis: Strength and Weaknesses(John E. French)Carcinogenicity Alternative Mouse Models
Working Group Survey
Preferred Selection of Models
・ Replacement of 2 year mouse with rasH2
・ p53 for potential genotoxicity
・ Mechanistic studies
Generally rasH2
Single responses for other models
・ CAMM acceptable for testing biologicals

Presented by Gerald G. Long of Eli Lilly & Company