300
D. Wang
BMR
Benchmark risk
BRBZ
Bromobenzene
C max
Peak plasma concentration
EPA
Environmental Protection Agency
EU
European Union
HCI
High content imaging
HZBZ
Hydrazobenzene
IVIVE
In vitro-in vivo extrapolation
KDMM
Kernel density mean of M-component
KE
Key event
KER
Key event relationship
LOAEL
Lowest-observed-adverse-effect level
MDMB
4,4
-Methylenebis (N,Ndimethyl) benzenamine
MIE
Molecular initiating event
MOA
Mode of action
MSigDB
Molecular Signature Database
NDPA
N-Nitrosodiphenylamine
NOAEL
No-observed-adverse-effect-level
POD
Point of departure
REACH
Registration, evaluation, authorization and restriction of chemical substances
RMA
Robust Multi-array Average normalization method
RPKM
Reads per kilobase per million mapped reads
TG-GATEs Toxicogenomics Project-Genomics Assisted Toxicity Evaluation System
TLR
Target learning region
TRBZ
1,2,4-Tribromobenzene
TTCP
2,3,4,6-Tetrachlorophenol
15.1 Introduction
The determination of the point of departure (POD) is an essential step for chemical
risk assessment. Currently, the gold standard in POD estimation is chronic animal
dosing studies. Rats or mice are commonly used for this purpose, though other animal
species might also be utilized. Though this approach has been essential for the current
toxicological testing regime, some shortcomings have been noted. One issue is that
high-dose animal testing often poorly predicts human toxicity. Even when it provides
meaningful results, it is difficult to obtain a mechanistic understanding of biological
pathways leading to adverse effects from the organism level toxicological response
as measured by apical endpoints. As a result, there has been a strong interest in
incorporating multiple lines of evidence relevant to human toxicology in order to
generate a more detailed understanding of toxicological properties for chemical risk
assessment. Toxicogenomics and other high-throughput assays as well as in silico
D. Wang
BMR
Benchmark risk
BRBZ
Bromobenzene
C max
Peak plasma concentration
EPA
Environmental Protection Agency
EU
European Union
HCI
High content imaging
HZBZ
Hydrazobenzene
IVIVE
In vitro-in vivo extrapolation
KDMM
Kernel density mean of M-component
KE
Key event
KER
Key event relationship
LOAEL
Lowest-observed-adverse-effect level
MDMB
4,4
-Methylenebis (N,Ndimethyl) benzenamine
MIE
Molecular initiating event
MOA
Mode of action
MSigDB
Molecular Signature Database
NDPA
N-Nitrosodiphenylamine
NOAEL
No-observed-adverse-effect-level
POD
Point of departure
REACH
Registration, evaluation, authorization and restriction of chemical substances
RMA
Robust Multi-array Average normalization method
RPKM
Reads per kilobase per million mapped reads
TG-GATEs Toxicogenomics Project-Genomics Assisted Toxicity Evaluation System
TLR
Target learning region
TRBZ
1,2,4-Tribromobenzene
TTCP
2,3,4,6-Tetrachlorophenol
15.1 Introduction
The determination of the point of departure (POD) is an essential step for chemical
risk assessment. Currently, the gold standard in POD estimation is chronic animal
dosing studies. Rats or mice are commonly used for this purpose, though other animal
species might also be utilized. Though this approach has been essential for the current
toxicological testing regime, some shortcomings have been noted. One issue is that
high-dose animal testing often poorly predicts human toxicity. Even when it provides
meaningful results, it is difficult to obtain a mechanistic understanding of biological
pathways leading to adverse effects from the organism level toxicological response
as measured by apical endpoints. As a result, there has been a strong interest in
incorporating multiple lines of evidence relevant to human toxicology in order to
generate a more detailed understanding of toxicological properties for chemical risk
assessment. Toxicogenomics and other high-throughput assays as well as in silico