338
Z. Fu and J. Chen
Abbreviations
ADMET
Absorption, distribution, metabolism, excretion and toxicity
AOPs
Adverse outcome pathways
ArNH 2
Primary aromatic amines
BDEs
Bond dissociation energies
Compound I The active species of P450 enzymes
CYPs
Cytochrome P450 enzymes
DFT
Density functional theory
HAT
Hydrogen atom transfer
HO·
Hydroxyl radical
(HO–)PBDEs (Hydroxylated) polybrominated diphenyl ethers
IP
Ionization potential
KIEs
Kinetic isotope effects
MD
Molecular dynamics
MIEs
Molecular initiating events
NADPH
Nicotinamide adenine dinucleotide phosphate
NIH shift
National Institute of Health shift
OAR
Oxygen addition rearrangement
PAHs
Polycyclic aromatic hydrocarbons
PBDDs
Polybrominated dibenzo-p-dioxins
PCDD/Fs
Polychlorodibenzo-p-dioxins/furans
PCM
Polarizable continuum model
PFOS
Perfluorooctane sulfonate
QM/MM
Quantum mechanics/molecular mechanics
SET
Single electron transfer
SOM
Site of metabolism
SPCs
Substituted phenolic compounds
SSR
Spin-selective reactivity
TSR
Two-state reactivity
E ST (ππ*) Singlet–triplet excitation energy
E
Activation barriers
17.1 Introduction
17.1.1 Significance of Xenobiotic Metabolism in Chemicals
Risk Assessment
Organisms are increasingly exposed to numerous xenobiotic chemicals (e.g., environmental contaminants, drugs) via food intake, inhalation, and dermal contacts. It is
now generally recognized that these xenobiotics have the potential to disrupt physiological homeostasis, thus threatening human health. Within an organism, xenobiotic
Z. Fu and J. Chen
Abbreviations
ADMET
Absorption, distribution, metabolism, excretion and toxicity
AOPs
Adverse outcome pathways
ArNH 2
Primary aromatic amines
BDEs
Bond dissociation energies
Compound I The active species of P450 enzymes
CYPs
Cytochrome P450 enzymes
DFT
Density functional theory
HAT
Hydrogen atom transfer
HO·
Hydroxyl radical
(HO–)PBDEs (Hydroxylated) polybrominated diphenyl ethers
IP
Ionization potential
KIEs
Kinetic isotope effects
MD
Molecular dynamics
MIEs
Molecular initiating events
NADPH
Nicotinamide adenine dinucleotide phosphate
NIH shift
National Institute of Health shift
OAR
Oxygen addition rearrangement
PAHs
Polycyclic aromatic hydrocarbons
PBDDs
Polybrominated dibenzo-p-dioxins
PCDD/Fs
Polychlorodibenzo-p-dioxins/furans
PCM
Polarizable continuum model
PFOS
Perfluorooctane sulfonate
QM/MM
Quantum mechanics/molecular mechanics
SET
Single electron transfer
SOM
Site of metabolism
SPCs
Substituted phenolic compounds
SSR
Spin-selective reactivity
TSR
Two-state reactivity
E ST (ππ*) Singlet–triplet excitation energy
E
Activation barriers
17.1 Introduction
17.1.1 Significance of Xenobiotic Metabolism in Chemicals
Risk Assessment
Organisms are increasingly exposed to numerous xenobiotic chemicals (e.g., environmental contaminants, drugs) via food intake, inhalation, and dermal contacts. It is
now generally recognized that these xenobiotics have the potential to disrupt physiological homeostasis, thus threatening human health. Within an organism, xenobiotic