Screening Chemicals for Reproductive Toxicity: The Current Alternatives

Brown, Nigel A.; Spielmann, Horst; Bechter, R.; Flint, Oliver; Freeman, Stuart J.; Jelínek, R; Koch, Elisabeth; Nau, Heinz; Newall, D.R.; Palmer, Anthony K.; Renault, Jean-Yves; Repetto, Marina F.; Vogel, Richard; Wiger, Richard

doi:10.1177/026119299502300615

Cited by 42 publications

(10 citation statements)

References 62 publications

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“…The chick embryo is very attractive for teratogen screening, because of its ease of storage during its development, the avoidance of the sacrifice of the mother, and the rapidity of its development. Brown et al (38) and Brown & Wiger (27) have also reported that no significant differences could be observed when comparing rat and chick limb bud MM responses with a range of potential teratogens. It is, however, possible that important metabolising enzymes may be different in rodent and avian species (20).…”

Section: The Suitability Of the Chick Heart Micromass System As A Devmentioning

confidence: 98%

An Evaluation of a Novel Chick Cardiomyocyte Micromass Culture Assay with Two Teratogens/Embryotoxins Associated with Heart Defects

2007

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This study was aimed at determining whether the chick cardiomyocyte micromass (MM) system could be employed to predict the teratogenicity/embryotoxicity of exogenous chemicals. Two documented teratogens/embryotoxins, sodium valproate (the sodium salt of valproic acid; VPA) and all -trans retinoic acid (tRA), were used in the initial phase of the study. White Leghorn 5-day-old embryo hearts were dissociated to produce a cardiomyocyte suspension in Dulbecco's Modified Eagle's Medium. Cultures were incubated at 37°C in 5% CO2 in air, and observations were made every 24 hours over 5 days, for the detection of beating. Culture viability was assessed by using the resazurin reduction assay for determining culture activity and the kenacid blue assay for determining cell number. It was found that tRA significantly reduced cell activity and beating, whilst not affecting total cell number. VPA up to 500μM induced no cytotoxicity in the MM cardiomyocyte cultures, whilst all the VPA concentrations tested reduced beating. The results demonstrate the potential of the chick cardiomyocyte MM culture assay to identify teratogens/embryotoxins that alter functionality, which may result in a teratogenic outcome, whilst not causing cytotoxicity (direct embryotoxicity). This could form part of a screen for developmental toxicity related to cardiac function, whilst limb cultures and brain cultures based on the same system could be relevant to teratogenic effects on those tissues.

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Section: The Suitability Of the Chick Heart Micromass System As A Devmentioning

confidence: 98%

An Evaluation of a Novel Chick Cardiomyocyte Micromass Culture Assay with Two Teratogens/Embryotoxins Associated with Heart Defects

2007

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“…These include whole embryos from whole embryo culture (WEC), Xenopus (FETAX) test, or chicken (CHEST); however, all these assays have been used rarely because their predictive valve is only 70–80%. [ 3 – 6 ]…”

Section: Embryo Toxicity and Cytotoxicity Assaysmentioning

confidence: 99%

Embryonic stem cells: An alternative approach to developmental toxicity testing

Tandon

Jyoti

2012

J Pharm Bioall Sci

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Stem cells in the body have a unique ability to renew themselves and give rise to more specialized cell types having functional commitments. Under specified growth conditions, these cell types remain unspecialized but can be triggered to become specific cell type of the body such as heart, nerve, or skin cells. This ability of embryonic stem cells for directed differentiation makes it a prominent candidate as a screening tool in revealing safer and better drugs. In addition, genetic variations and birth defects caused by mutations and teratogens affecting early human development could also be studied on this basis. Moreover, replacement of animal testing is needed because it involves ethical, legal, and cost issues. Thus, there is a strong requirement for validated and reliable, if achievable, human stem cell-based developmental assays for pharmacological and toxicological screening.

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“…." (12). The four systems referred to in the report were the frog embryo teratogenesis assay -Xenopus (FETAX), a chick embryo assay, micromass culture systems, and mammalian whole embryos.…”

Section: Workhops As Catalysts For New Validation Studiesmentioning

confidence: 99%

The ECVAM Workshops: A Critical Assessment of their Impact on the Development, Validation and Acceptance of Alternative Methods

Combes

2002

Altern Lab Anim

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ECVAM initiated its workshop programme in 1994, to enable it to become well informed about the state of the art of non-animal test development and validation, and about the possible incorporation of alternatives into regulatory requirements for safety testing. Fifty-one such workshops had been held on specific topics, up to 2002. In these workshops, the current status of in vitro tests and their potential uses were reviewed and recommendations were made as to the best ways forward to progress and enhance the use of in vitro methods. Reports for 46 of these workshops have been published in ATLA. Most of the workshops focused on in vitro replacement methods, although an increasing number have dealt with reduction and refinement. The recommendations in the ECVAM workshops have been progressed further by: a) the formation of ECVAM task forces; b) the organisation of further workshops; c) the activities of scientific committees; d) the provision of earmarked research funding; and e) the conduct of validation studies. Examples of each of these activities are discussed. Some individual workshops are covered in more detail, and several recommendations that have so far not been acted on are also considered. The workshops and their reports have had a substantial effect on the development and implementation of alternative methods, and have been a major factor in contributing to the success of the first nine years of ECVAM's existence. It is strongly recommended that ECVAM continues to organise workshops and to publish their findings, and suggestions are made for topics for future workshops.

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Screening Chemicals for Reproductive Toxicity: The Current Alternatives

Cited by 42 publications

References 62 publications

An Evaluation of a Novel Chick Cardiomyocyte Micromass Culture Assay with Two Teratogens/Embryotoxins Associated with Heart Defects

An Evaluation of a Novel Chick Cardiomyocyte Micromass Culture Assay with Two Teratogens/Embryotoxins Associated with Heart Defects

Embryonic stem cells: An alternative approach to developmental toxicity testing

The ECVAM Workshops: A Critical Assessment of their Impact on the Development, Validation and Acceptance of Alternative Methods

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