Comments from the Developmental Neurotoxicology Committee of the Japanese Teratology Society on the OECD Guideline for the Testing of Chemicals, Proposal for a New Guideline 426, Developmental Neurotoxicity Study, Draft Document (October 2006 version), and on the Draft Document of the Retrospective Performance Assessment of the Draft Test Guideline 426 on Developmental Neurotoxicity

Ema, Makoto; Fukui, Yoshihiro; Aoyama, Hiroaki; Fujiwara, Michio; Fuji, Jun-ichiro; Inouye, Minoru; Iwase, Takayuki; Kihara, Takahide; Oi, Akihide; Otani, Hiroki; Shinomiya, Mitsuhiro; Sugioka, Kozo; Yamano, Tsunekazu; Yamashita, Keisuke; Tanimura, Takashi

doi:10.1111/j.1741-4520.2007.00148.x

Cited by 6 publications

(6 citation statements)

References 5 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For example, autism spectrum disorders (ASDs) that affect 1.1% of children in US 12 lead to morbidity and functional limitations that account for direct care and indirect costs of $126 billion per year. 14 However, we have limited knowledge about the genetic basis, environmental threats, and/or gene/environment interactions that increases the risk to develop these disorders. 15,16 The same holds true for adult neurological disorders such as, e.g., Parkinson’s, Alzheimer, and Schizophrenia.…”

Section: Introductionmentioning

confidence: 99%

Biological and medical applications of a brain-on-a-chip

Pamies

Hartung

Högberg

2014

Exp Biol Med (Maywood)

103

View full text Add to dashboard Cite

The desire to develop and evaluate drugs as potential countermeasures for biological and chemical threats requires test systems that can also substitute for the clinical trials normally crucial for drug development. Current animal models have limited predictivity for drug efficacy in humans as the large majority of drugs fails in clinical trials. We have limited understanding of the function of the central nervous system and the complexity of the brain, especially during development and neuronal plasticity. Simple in vitro systems do not represent physiology and function of the brain. Moreover, the difficulty of studying interactions between human genetics and environmental factors leads to lack of knowledge about the events that induce neurological diseases. Microphysiological systems (MPS) promise to generate more complex in vitro human models that better simulate the organ’s biology and function. MPS combine different cell types in a specific three-dimensional (3D) configuration to simulate organs with a concrete function. The final aim of these MPS is to combine different “organoids” to generate a human-on-a-chip, an approach that would allow studies of complex physiological organ interactions. The recent discovery of induced pluripotent stem cells (iPSCs) gives a range of possibilities allowing cellular studies of individuals with different genetic backgrounds (e.g., human disease models). Application of iPSCs from different donors in MPS gives the opportunity to better understand mechanisms of the disease and can be a novel tool in drug development, toxicology, and medicine. In order to generate a brain-on-a-chip, we have established a 3D model from human iPSCs based on our experience with a 3D rat primary aggregating brain model. After four weeks of differentiation, human 3D aggregates stain positive for different neuronal markers and show higher gene expression of various neuronal differentiation markers compared to 2D cultures. Here we present the applications and challenges of this emerging technology.

show abstract

Section: Introductionmentioning

confidence: 99%

Biological and medical applications of a brain-on-a-chip

Pamies

Hartung

Högberg

2014

Exp Biol Med (Maywood)

103

View full text Add to dashboard Cite

show abstract

“…The DNT Committee contributed to revise the draft TG 426 guideline by sending official comments on behalf of the Japanese Teratology Society (Fukui et al. 2004; Ema et al. 2007).…”

Section: Developmental Neurotoxicity (Dnt) Study Guidelinesmentioning

confidence: 99%

“…OECD guideline, TG 426, was developed to harmonize with previously released OPPTS 870.6300 from US EPA, although minor differences remain between the two. The DNT Committee contributed to revise the draft TG 426 guideline by sending official comments on behalf of the Japanese Teratology Society (Fukui et al 2004;Ema et al 2007). No corresponding guideline has been provided by the Japanese regulatory agencies.…”

Section: Developmental Neurotoxicity (Dnt) Study Guidelinesmentioning

confidence: 99%

Developmental neurotoxicity testing: Scientific approaches towards the next generation to protect the developing nervous system of children. An overview of the Developmental Neurotoxicity Symposium in 2011

Aoyama¹

2012

Congenital Anomalies

Self Cite

View full text Add to dashboard Cite

The Developmental Neurotoxicology (DNT) Committee has been working to promote developmental neurotoxicology and related scientific areas of interest to integrate academic and regulatory sciences in this field since the Behavioral Teratology Meeting was established by the Japanese Teratology Society in 1982. The committee has led several large-scale collaborative studies to standardize existing methodologies and held symposiums and workshops periodically at the society's annual meetings. This overview provides a history of the DNT Committee, as well as a brief summary of the DNT Symposium in 2011.

show abstract

“…2003). They have conducted collaborative studies, and also proposed a core battery of tests to detect postnatal developmental disorders, including behavioral dysfunction, in the rat (Ema et al. 2007; Makris et al.…”

Section: Introductionmentioning

confidence: 99%

“…Mizutani 1985;Tanimura 1986;Tachibana et al 1996;Okazaki et al 2003). They have conducted collaborative studies, and also proposed a core battery of tests to detect postnatal developmental disorders, including behavioral dysfunction, in the rat (Ema et al 2007;Makris et al 2009). These achievements and efforts have provided immense contributions to the development of this field.…”

Section: Introductionmentioning

confidence: 99%

Developmental neurotoxicity guideline study: Issues with methodology, evaluation and regulation*

Tsuji

Crofton

2012

Congenital Anomalies

View full text Add to dashboard Cite

Recently social concerns have been increasing about the effects of environmental factors on children's health, especially on their nervous systems. The U.S. Environmental Protection Agency (EPA) and the Organisation for Economic Co-operation and Development (OECD) have published testing guidelines for developmental neurotoxicity (DNT). Approximately 110 guideline studies have been conducted to date. Importantly, information from these studies has provided data critical for regulatory decisions for a number of chemicals. However, the DNT guidelines do not always satisfy all stakeholders because of some uncertainties in their methodology, evaluation, and regulation. Methodological issues include incomplete harmonization between EPA and OECD guidelines, criticisms of the methodology for learning and memory testing, and unspecified positive control substances. Potential artifacts in morphometric neuropathological measures, criteria for observation measures, uncertainty of postnatal offspring exposure, especially in feeding studies, and extrapolation of data from rats to humans are major evaluation issues. In addition, there is some uncertainty in the use of an additional safety factor for susceptibility of infants and children. Moreover, the DNT guidelines have extensive time and cost requirements, use large numbers of animals, and there is a limited set of laboratories that can conduct the study. This paper reviews some of these issues and summarizes discussions from the symposium 'Developmental neurotoxicity testing: Scientific approaches towards the next generation to protecting the developing nervous system of children' held at the 2011 annual meeting of the Japanese Teratology Society.

show abstract

Cited by 6 publications

References 5 publications

Biological and medical applications of a brain-on-a-chip

Biological and medical applications of a brain-on-a-chip

Developmental neurotoxicity testing: Scientific approaches towards the next generation to protect the developing nervous system of children. An overview of the Developmental Neurotoxicity Symposium in 2011

Developmental neurotoxicity guideline study: Issues with methodology, evaluation and regulation*

Contact Info

Product

Resources

About