Dose-Response Assessment for Developmental Toxicity II. Comparison of Generic Benchmark Dose Estimates with No Observed Adverse Effect Levels

1994 ◽  
Vol 23 (4) ◽  
pp. 487-495 ◽  
Author(s):  
B Allen
Keyword(s):  
Adverse Effect ◽  
Dose Response ◽  
Developmental Toxicity ◽  
Response Assessment ◽  
Benchmark Dose

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

scholarly journals Estimation of Benchmark Dose of Cumulative Cadmium Exposure for Renal Tubular Effect

2021 ◽  
Vol 18 (10) ◽  
pp. 5177
Author(s):  
Kazuhiro Nogawa ◽  
Yasushi Suwazono ◽  
Yuuka Watanabe ◽  
Carl-Gustaf Elinder
Keyword(s):  
Adverse Effect ◽  
Least Squares ◽  
Dose Response ◽  
Cadmium Exposure ◽  
Benchmark Dose ◽  
Tubular Damage ◽  
Limit Values ◽  
Adverse Effect Level ◽  
Effect Level ◽  
Renal Tubular

Objectives: The aim of this study was to determine the no observed adverse effect level (NOAEL), the lowest observed adverse effect level (LOAEL) and the benchmark dose low (BMDL) of cadmium exposure by re-evaluation of the dose–response relationship between cumulative cadmium exposure and renal tubular damage reported previously. Methods: The participants were workers (326 men and 114 women) employed for at least three months between 1931 and 1982. Blood cadmium (Cd-B) and air cadmium (Cd-A) were collected at regular intervals with urinary β2-microglobulin as the tubular effect marker. Cumulative Cd-A and Cd-B were estimated by multiplying concentration and working period. The BMDL was calculated using Benchmark Dose Software (version 3.1.2). The benchmark response (BMR) was set at 5% or 10%. Results: By logistic regression, the NOAEL of mean cumulative Cd-B was 7122 months nmol/L. The LOAEL of cumulative Cd-A and least-squares cumulative Cd-B was 691 yrs μg/m3 and 8586 months nmol/L, respectively. Among various models for dose–response relationships, a probit model was adopted as the best fitting model. The obtained BMDLs of cumulative Cd-A were 272.3 yrs µg/m3 (BMR5%) and 707.5 yrs µg/m3 (BMR10%). The BMDLs of mean cumulative Cd-B were 3967.2 months nmol/L (BMR5%) and 7798.1 months nmol/L (BMR10%). The BMDLs of least-squares cumulative Cd-B were 3588.6 months nmol/L (BMR5%) and 8616.3 months nmol/L (BMR10%). Assuming a working period of 40 years, the BMDLs for BMR10% corresponded to 17.7 µg/m3 (Cd-A) and 1.8~2.0 µg/L (Cd-B). Discussion: This study provides new valuable information to enhance the reliability of limit values and thereby make a significant contribution to preventing the health effects of Cd in exposed workers.

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.

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