Details:

Alternative Title:
Risk Anal
Publisher's site:
http://dx.doi.org/10.1111/risa.13547
Personal Author:
Park, Robert M. ;
Description:
Uncertainty in model predictions of exposure response at low exposures is a problem for risk assessment. A particular interest is the internal concentration of an agent in biological systems as a function of external exposure concentrations. Physiologically based pharmacokinetic (PBPK) models permit estimation of internal exposure concentrations in target tissues but most assume that model parameters are either fixed or instantaneously dose-dependent. Taking into account response times for biological regulatory mechanisms introduces new dynamic behaviors that have implications for low-dose exposure response in chronic exposure. A simple one-compartment simulation model is described in which internal concentrations summed over time exhibit significant nonlinearity and nonmonotonicity in relation to external concentrations due to delayed up- or downregulation of a metabolic pathway. These behaviors could be the mechanistic basis for homeostasis and for some apparent hormetic effects.
Subject:
[+]
Animals
Article
Dose Response
Homeostasis
Hormesis
Humans
Inactivation, Metabolic
Models, Biological
Nonlinear Dynamics
PBPK
Simulation
Toxicokinetics
Uncertainty
Upregulation
Homeostasis
Hormesis

Source:
Risk Anal. 40(12):2561-2571 ;
Pubmed ID:
32632964
Pubmed Central ID:
PMC7748990
Document Type:
Journal Article ;
Funding:
CC999999/Intramural CDC HHSUnited States/ ;
Collection(s):
CDC Public Access
Main Document Checksum:
[+]
urn:sha256:afdf986f8f9a5ccf628458db9152054a4836b0e2807406b48e3b2d322ee7f1e2
File Type:

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