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A Biologically‐Based Dose—Response Model for Developmental Toxicology
Author(s) -
Leroux Brian G.,
Leisenring Wendy M.,
Moolgavkar Suresh H.,
Faustman Elaine M.
Publication year - 1996
Publication title -
risk analysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.972
H-Index - 130
eISSN - 1539-6924
pISSN - 0272-4332
DOI - 10.1111/j.1539-6924.1996.tb01092.x
Subject(s) - organogenesis , developmental toxicity , biology , toxicology , computational biology , computer science , bioinformatics , genetics , gene , pregnancy , gestation
The methods currently used to evaluate the risk of developmental defects in humans from exposure to potential toxic agents do not reflect biological processes in extrapolating estimated risks to low doses and from test species to humans. We develop a mathematical model to describe aspects of the dynamic process of organogenesis, based on branching process models of cell kinetics. The biological information that can be incorporated into the model includes timing and rates of dynamic cell processes such as differentiation, migration, growth, and replication. The dose‐response models produced can explain patterns of malformation rates as a function of both dose and time of exposure, resulting in improvements in risk assessment and understanding of the underlying mechanistic processes. To illustrate the use of the model, we apply it to the prediction of the effects of methylmercury on brain development in rats.