A comparison of Haber's rule at different ages using a physiologically based pharmacokinetic (PBPK) model for chloroform in rats.
Toxicology
; 176(1-2): 11-23, 2002 Jul 01.
Article
em En
| MEDLINE
| ID: mdl-12062926
ABSTRACT
Haber's rule as commonly interpreted in inhalation toxicology, can be stated as exposure concentration times duration equals a constant biological effect, or C x t=k. In other words, identical products of concentration and duration lead to the same effect. The goals of this paper are to develop a biological and pharmacokinetic modeling approach for chloroform, and to evaluate Haber's rule for different ages by taking into account the physiological changes due to growth and aging in rats. Three-dimensional dose-response surfaces for liver toxicity were generated for each age group of interest adolescent, adult, and senescent rats. The three-dimensional surfaces were then characterized with a generalized description of Haber's rule for each age group. The simulations suggest that adolescent rats need higher exposure levels in order to achieve similar levels of liver damage compared to adults or senescent rats, if the comparison is made using the same exposure length. In summary, a pharmacokinetic modeling approach with a biological framework including the chemical's mode of action, was used to relate concentration, exposure duration and effect. Major advantages of this approach include the potential ability to extrapolate to humans, the inclusion of aging in the simulations, and the ability to summarize the results using a generalized form of Haber's rule.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Envelhecimento
/
Clorofórmio
/
Exposição por Inalação
Limite:
Animals
Idioma:
En
Revista:
Toxicology
Ano de publicação:
2002
Tipo de documento:
Article
País de afiliação:
Estados Unidos