In vivo and in vitro developmental toxicity in LPS-induced zinc-deficient rabbits

1997 ◽  
Vol 11 (6) ◽  
pp. 771-779 ◽  
Author(s):  
J Pitt
Keyword(s):  
Developmental Toxicity

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.

Safety assessment of the Clostridium butyricum MIYAIRI 588® probiotic strain including evaluation of antimicrobial sensitivity and presence of Clostridium toxin genes in vitro and teratogenicity in vivo

2016 ◽  
Vol 35 (8) ◽  
pp. 818-832 ◽  
Author(s):  
K Isa ◽  
K Oka ◽  
N Beauchamp ◽  
M Sato ◽  
K Wada ◽  
...  
Keyword(s):  
Developmental Toxicity ◽  
Health Benefit ◽  
Probiotic Strain ◽  
Clostridium Butyricum ◽  
Toxin Genes ◽  
Antimicrobial Sensitivity ◽  
Developmental Effects ◽  
Safety Studies

Probiotics are live microorganisms ingested for the purpose of conferring a health benefit on the host. Development of new probiotics includes the need for safety evaluations that should consider factors such as pathogenicity, infectivity, virulence factors, toxicity, and metabolic activity. Clostridium butyricum MIYAIRI 588® (CBM 588®), an anaerobic spore-forming bacterium, has been developed as a probiotic for use by humans and food animals. Safety studies of this probiotic strain have been conducted and include assessment of antimicrobial sensitivity, documentation of the lack of Clostridium toxin genes, and evaluation of CBM 588® on reproductive and developmental toxicity in a rodent model. With the exception of aminoglycosides, to which anaerobes are intrinsically resistant, CBM 588® showed sensitivity to all antibiotic classes important in human and animal therapeutics. In addition, analysis of the CBM 588® genome established the absence of genes for encoding for α, β, or ε toxins and botulin neurotoxins types A, B, E, or F. There were no deleterious reproductive and developmental effects observed in mice associated with the administration of CBM 588®. These data provide further support for the safety of CBM 588® for use as a probiotic in animals and humans.

scholarly journals 3D kidney organoids for bench-to-bedside translation

2020 ◽  
Author(s):  
Navin Gupta✉ ◽  
Emre Dilmen ◽  
Ryuji Morizane
Keyword(s):  
Collecting Duct ◽  
Developmental Toxicity ◽  
Human Kidney ◽  
Great Promise ◽  
Duct Systems ◽  
Recent Developments ◽  
Induced Pluripotent ◽  
Kidney Organoids

Abstract The kidneys are essential organs that filter the blood, removing urinary waste while maintaining fluid and electrolyte homeostasis. Current conventional research models such as static cell cultures and animal models are insufficient to grasp the complex human in vivo situation or lack translational value. To accelerate kidney research, novel research tools are required. Recent developments have allowed the directed differentiation of induced pluripotent stem cells to generate kidney organoids. Kidney organoids resemble the human kidney in vitro and can be applied in regenerative medicine and as developmental, toxicity, and disease models. Although current studies have shown great promise, challenges remain including the immaturity, limited reproducibility, and lack of perfusable vascular and collecting duct systems. This review gives an overview of our current understanding of nephrogenesis that enabled the generation of kidney organoids. Next, the potential applications of kidney organoids are discussed followed by future perspectives. This review proposes that advancement in kidney organoid research will be facilitated through our increasing knowledge on nephrogenesis and combining promising techniques such as organ-on-a-chip models.

In Vivo and in Vitro Structure-Dosimetry-Activity Relationships of Substituted Phenols in Developmental Toxicity Assays

1991 ◽  
Vol 16 (2) ◽  
pp. 225-229
Author(s):  
R. J. KAVLOCK ◽  
L. A. OGLESBY ◽  
L. L. HALL ◽  
H. L. FISHER ◽  
F. COPELAND ◽  
...  
Keyword(s):  
Developmental Toxicity ◽  
Substituted Phenols

Comparison of zebrafish in vitro and in vivo developmental toxicity assessments of perfluoroalkyl acids (PFAAs)

2020 ◽  
Vol 84 (3) ◽  
pp. 125-136
Author(s):  
Ola Wasel ◽  
Kathryn M. Thompson ◽  
Yu Gao ◽  
Amy E. Godfrey ◽  
Jiejun Gao ◽  
...  
Keyword(s):  
Developmental Toxicity ◽  
Perfluoroalkyl Acids

Endocrine disruption and the USFDA's Center for Drug Evaluation and Research

2003 ◽  
Vol 75 (11-12) ◽  
pp. 2605-2607
Author(s):  
A. Jacobs ◽  
Paul Brown ◽  
James Farrelly ◽  
J. E. Fisher ◽  
D. Morse
Keyword(s):  
Risk Management ◽  
Endocrine Disruption ◽  
Drug Evaluation ◽  
Developmental Toxicity ◽  
Clinical Decision ◽  
Weight Of Evidence ◽  
Endocrine Effects ◽  
Reproductive Effects

Drugs may have intended or unintended endocrine effects. Drug evaluation may include both in vitro and in vivo evaluations of toxicity and developmental/reproductive effects. After a signal is identified, human relevance is of utmost concern. An integration "tool" that formalizes a weight-of-evidence approach has been developed to assess concern about reproductive/ developmental toxicity to humans. This approach can be used to assess concern about an endocrine disruption signal. A signal alone does not mean a concern for humans. An effect needs to have biologic relevance, and exposure thresholds for effects may exist. Risk/benefit for a particular drug is a clinical decision and may vary by the drug indication. Risk management for an identified concern could include wording in patient communications, tracking distribution or limited distribution, and patient or pregnancy registries.

scholarly journals Integrating in vitro data and physiologically based kinetic (PBK) modelling to assess the in vivo potential developmental toxicity of a series of phenols

2016 ◽  
Vol 91 (5) ◽  
pp. 2119-2133 ◽  
Author(s):  
Marije Strikwold ◽  
Bert Spenkelink ◽  
Laura H. J. de Haan ◽  
Ruud A. Woutersen ◽  
Ans Punt ◽  
...  
Keyword(s):  
Developmental Toxicity ◽  
Physiologically Based ◽  
Vitro Data ◽  
In Vitro Data
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