Dose—Response Assessment for Developmental Toxicity

1994 ◽  
Vol 23 (4) ◽  
pp. 487-495 ◽  
Author(s):  
BRUCE C. ALLEN ◽  
ROBERT J. KAVLOCK ◽  
CAROLE A. KIMMEL ◽  
ELAINE M. FAUSTMAN
Keyword(s):  
Dose Response ◽  
Developmental Toxicity ◽  
Response Assessment

Dose-Response Assessment for Developmental Toxicity

1994 ◽  
Vol 23 (4) ◽  
pp. 478-486 ◽  
Author(s):  
ELAINE M. FAUSTMAN ◽  
BRUCE C. ALLEN ◽  
ROBERT J. KAVLOCK ◽  
CAROLE A. KIMMEL
Keyword(s):  
Dose Response ◽  
Developmental Toxicity ◽  
Response Assessment

Dose—Response Assessment for Developmental Toxicity

1994 ◽  
Vol 23 (4) ◽  
pp. 496-509 ◽  
Author(s):  
BRUCE C. ALLEN ◽  
ROBERT J. KAVLOCK ◽  
CAROLE A. KIMMEL ◽  
ELAINE M. FAUSTMAN
Keyword(s):  
Dose Response ◽  
Developmental Toxicity ◽  
Response Assessment

scholarly journals Predicting the in vivo developmental toxicity of benzo[a]pyrene (BaP) in rats by an in vitro–in silico approach

2021 ◽  
Author(s):  
Danlei Wang ◽  
Maartje H. Rietdijk ◽  
Lenny Kamelia ◽  
Peter J. Boogaard ◽  
Ivonne M. C. M. Rietjens
Keyword(s):  
Dose Response ◽  
In Silico ◽  
Response Curve ◽  
Developmental Toxicity ◽  
Toxicity Testing ◽  
Maximal Effect ◽  
Blood Concentrations ◽  
Reverse Dosimetry

AbstractDevelopmental toxicity testing is an animal-intensive endpoints in toxicity testing and calls for animal-free alternatives. Previous studies showed the applicability of an in vitro–in silico approach for predicting developmental toxicity of a range of compounds, based on data from the mouse embryonic stem cell test (EST) combined with physiologically based kinetic (PBK) modelling facilitated reverse dosimetry. In the current study, the use of this approach for predicting developmental toxicity of polycyclic aromatic hydrocarbons (PAHs) was evaluated, using benzo[a]pyrene (BaP) as a model compound. A rat PBK model of BaP was developed to simulate the kinetics of its main metabolite 3-hydroxybenzo[a]pyrene (3-OHBaP), shown previously to be responsible for the developmental toxicity of BaP. Comparison to in vivo kinetic data showed that the model adequately predicted BaP and 3-OHBaP blood concentrations in the rat. Using this PBK model and reverse dosimetry, a concentration–response curve for 3-OHBaP obtained in the EST was translated into an in vivo dose–response curve for developmental toxicity of BaP in rats upon single or repeated dose exposure. The predicted half maximal effect doses (ED50) amounted to 67 and 45 mg/kg bw being comparable to the ED50 derived from the in vivo dose–response data reported for BaP in the literature, of 29 mg/kg bw. The present study provides a proof of principle of applying this in vitro–in silico approach for evaluating developmental toxicity of BaP and may provide a promising strategy for predicting the developmental toxicity of related PAHs, without the need for extensive animal testing.

The developmental toxicity of inhaled methanol in the CD-1 mouse, with quantitative dose—response modeling for estimation of benchmark doses

Teratology ◽  
1993 ◽  
Vol 47 (3) ◽  
pp. 175-188 ◽  
Author(s):  
John M. Rogers ◽  
M. Leonard Mole ◽  
Neil Chernoff ◽  
Brenda D. Barbee ◽  
Christine I. Turner ◽  
...  
Keyword(s):  
Dose Response ◽  
Developmental Toxicity ◽  
Benchmark Doses ◽  
Response Modeling
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