Abstract
This scientific report from Philip Morris' overseas lab in Germany (INBIFO, which stands for "Institut Fur Biologische Forschung," or Institute for Biological Research) explains what different types of toxicity tests (assays) measure, and what assays were in use at the time at INBIFO. The paper is not dated, but the last page indicates it was produced at the earliest in 1992.
Of interest in this document are the reasons it lists on how INBIFO chooses to use one type of toxicity test over another:
From Page 4 (2501403695):
"Selection Criteria for in Vitro Toxicity Assays:
1) most informative
2) best validated
3) most helpful in a legislative context."
Fields
- Notes
Many thanks to paralegal Beth York for forwarding this document to Doc-Alert.
- Quotes
Published Test Batteries and In Vitro Assays Used at Inbifo
[From Page 4 of 16, Bates No. 2501403695]:
Selection criteria for In Vitro Toxicity Assays
--most informative
--best validated
--most helpful in a legal context.
- Company
- Philip Morris
- Author
- Presumed organizational author, INBIFO
- Recipient
- Presumed corporate recipient, Philip Morris
RegionGermany
United States
Named OrganizationComm on Mutagenicity of Chemicals in Foo
*EPA ( use United States Environmental Protection Agency)
INBIFO, Intitut Fur Biologische Forschung (Philip Morris' secret biological research lab in Europe)"INBIFO" stands for Institut Fur Biologische Forschung, or Institute for Biological Research. It is located in Germany. Philip Morris acquired Inbifo on June 30, 1971. Its stated mission was "quantitative biological product evaluation" by using "comprehensive toxicological and physiological testing. Major activities are listed as: product evaluation and modifications, product ingredients and ETS-related technical knowledge and smoke components. Inhalation toxicology was a key feature of Inbifo. (Derived from Bates No. 2505235055/5088)
International Agency for Research on Cancer ("IARC") (International Agency for Research on Cancer ("IRAC"))International Agency for Research on Cancer ("IARC")
Natl Toxicology Program
World Health Organization (Concerned with global public health)International organization concered with public health worldwide
LitigationStmn/Produced
Named PersonAmes
Doolittle
Fielding
Frame
Hartman
Houk
Hunt
Lafi
Lee
Mckarns
Nakayama
Parry
Rosen
Sanchez
Shopsis
Willey
TypeSPCH, SPEECH, PRESENTATION
CHAR, CHART, GRAPH, TABLE, MAPS
Subjecttoxicology
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Published Test Batteries and
;In Vitro' Assays Used at INBIFO
Page 2: lzu29e00
IN VITRO
TOXI ClTY
ASSAYS
CYTOTOXICITY
GENOTOXICITY
ranking screening ranking
cytotoxic genotoxic genotoxic
with regard to or with regard
reference nongenotoxic to reference
Page 3: lzu29e00
3 Ieve{s of genotoxicity
gene mutation
DNA damage chromosomal
damage
activation and expression of
oncogenes
loss or inactivation of tumor
suppressor genes
~
Page 4: lzu29e00
Selection Criteria for In Vitro Toxicity Assays
most informative
best validated
most helpful in a legislative context
Page 5: lzu29e00
classes of assays
cytotoxicity genotoxicity
- cell viability. - gene mutation
- cell proliferation - DNA damage
- cell morphology - sister chromatid
exchange
- membrane damage
- chromosome aberration
- uptake or incorpora- - structural
tion of precursors - numerical
- metabolic effects - transformation
Page 6: lzu29e00
Published Cytotoxicity Assays
Reference Assay
Neutral Red Kenacid Hen's E Test Cell Inhibition
. Blue orio- antoic Protein of the Uridine
Rel ease Uptake Membrane Reduci:i on Uptake
BGA
FRAME (1986) +
(fund for the
rep1 acemeni'r of
animals in
medi ca1
experiments)
(D ® d
© +v ID
Shopsis et al.
- O
(1985)
N
UI
0
~
4N
0
+ + W
~
~
J
Page 7: lzu29e00
Cytotoxicity Assays at INBIFO
Class Assays at INBIFO
Automatic Neutral Red Dye Colony LDH Mitotic Distribution
Cel l Excl u- ~P~1 atin~ Re- Index o`f~le~as
Counting Release Uptake sion Effi- lease in RepTica_-
(a) ciency (b) tion Cycles
cell viability + + + + + - - -
ce11 + - + + + - + +
proliferation
cell morphology - - - - + -
membrane - + + + - +
damage
uptake or in- - - - - - -
N
U7
corporation 0
of precursors ~
.~
0
W
metabolic effects - - - - - - 10
M,
~a future development
b performed in previous INBIFO study
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Cytotoxicity Assays for Smoke
Assayed
Material
mainstream
cigarette smoke
condensate
11 (a)
11 (b)
sidestream
cig. smoke (b)
sidestream
cig. gas/vapor
phase (b)
Assay
Colony Dye LDH Lucifer Inhibition
Plating Exclusion Release Yellow of Metabolic
Efficiency Uptake Cooperation
+
+
+
+
+
Reference
Wille et al.
(1987)~
McKarns and
Dool i tt1 e (1991)
Hartman and
Rosen (1983)
Hunt (1986)
IF
(a) cigarette: 1R4F and TEST menthol, solvent: DMSO
(b) cigarette: 2R1
Page 9: lzu29e00
Published Test Batteries for Genotoxicity
,
Reference Ames Yeast HGPRT Mouse Sister Unscheduled Chromosome Trans-
Lymphoma Chromatid DNA Aberration forma-
L5178Y Exchange Synthesis tion
National Toxicology p
Program (NTP)
World Health Organi- ®
zation (WHO), 1985
Committee on Mutagen- ®
icity of Chemicals
in Food.Consumer
Products and the
Environment (COM)
GENE-TOX U.S. EPA ®
International Agency 0
for Research on
Cancer (IARC)
- - G + -- ® (+)
+ + ~ + + ® +
+ - ®
(+) + (9 (+) (+) ® (+) ,~,
c,
0
(D + - a -~
0
w
~
0
0
Page 10: lzu29e00
Salmonella typhimurium strains TA98
TA100
TA1535
TA1537
TA1538