Investigations on learning and memory function in extended one-generation reproductive toxicity studies – when considered needed and based on what?

Arts, J.H.E.; Faulhammer, Frank; Schneider, Steffen; Salverda, Joanne G. W.

doi:10.1080/10408444.2023.2236134

Cited by 2 publications

(2 citation statements)

References 22 publications

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“…An expert panel evaluated epidemiological and toxicological evidence contributing to IQ loss, intellectual disability, ASD, and ADHD. PBDE exposure was associated with a 70-100% probability of 873,000 lost IQ points and 3,290 intellectual disability cases, costing Landrigan, 2006, 2014;Aschner et al, 2017 opment and the need for a variety of test methods to address different aspects of DNT (Makris et al, 2009;Arts et al, 2023).…”

Section: Scientific Advancementmentioning

confidence: 99%

Revolutionizing developmental neurotoxicity testing – a journey from animal models to advanced in vitro systems

2024

ALTEX

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Developmental neurotoxicity (DNT) testing has seen enormous progress over the last two decades. Preceding even the publication of the animal-based OECD test guideline for DNT testing in 2007, a series of non-animal technology workshops and conferences that started in 2005 has shaped a community that has delivered a comprehensive battery of in vitro test methods (DNT IVB). Its data interpretation is now covered by a very recent OECD guidance (No. 377). Here, we overview the progress in the field, focusing on the evolution of testing strategies, the role of emerging technologies, and the impact of OECD test guidelines on DNT testing. In particular, this is an example of the targeted development of an animal-free testing approach for one of the most complex hazards of chemicals to human health. These developments started literally from a blank slate, with no proposed alternative methods available. Over two decades, cutting-edge science enabled the design of a testing approach that spares animals and enables throughput to address this challenging hazard. While it is evident that the field needs guidance and regulation, the massive economic impact of decreased human cognitive capacity caused by chemical exposure should be prioritized more highly. Beyond this, the claim to fame of DNT in vitro testing is the enormous scientific progress it has brought for understanding the human brain, its development, and how it can be perturbed.

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Section: Scientific Advancementmentioning

confidence: 99%

Revolutionizing developmental neurotoxicity testing – a journey from animal models to advanced in vitro systems

2024

ALTEX

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“…Also, as indicated in our earlier example, pups may be more sensitive than adult animals requiring the introduction of asymmetric dosing, whereby adult animals and pups are exposed to different doses. But even more, it should be questioned whether the neurodevelopmental cohorts (as well as the immuno-developmental cohorts) should be dosed at all; not only to be in line with the OECD test guideline to investigate neurodevelopmental toxicity (OECD TG 426) but also to be able to distinguish between developmental neurotoxicity potentially developed during gestation and/or lactation or neurotoxicity caused by direct exposure of the pups after weaning at PND 21, see also our recent paper [12]. Also, other agencies may not accept the high dose levels used because of nonlinear kinetics that could occur at high (irrelevant) maternally toxic doses, and could request for additional studies.…”

Section: Focus On Fertility In An Eogrt Study By Echa Impairs Investi...mentioning

confidence: 99%

‘It is the Dose That Makes the Poison’ – A Critical View on Dose Level Setting in Extended-One Generation Reproductive Toxicity (EOGRT) Studies

Salverda,

Arts

2024

Journal of the Netherlands Society of Toxicology

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Adequate dose level setting is essential for the evaluation of the toxicity of a substance, meaning that the dose level should not be too low to miss the potential of a substance to exert any toxic effects; it should also not be too high to induce various effects related to systemic toxicity that would hamper a proper evaluation of specific toxicity endpoints such as reproduction and fetal development. This discussion paper is meant to highlight the challenges faced by industry as a result of ECHA’s advice to select high dose levels when conducting EOGRT studies. In our view, in its concern for finding all possible hazards, ECHA is focused on testing at dose levels that may be too high for repeat dose toxicity studies. Such high dose levels may lead to an unethical increase in animal use and animal suffering, an inability to correctly interpret results and unacceptable requests for the repetition of studies leading to an even higher demand for experimental animals.

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Investigations on learning and memory function in extended one-generation reproductive toxicity studies – when considered needed and based on what?

Cited by 2 publications

References 22 publications

Revolutionizing developmental neurotoxicity testing – a journey from animal models to advanced in vitro systems

Revolutionizing developmental neurotoxicity testing – a journey from animal models to advanced in vitro systems

‘It is the Dose That Makes the Poison’ – A Critical View on Dose Level Setting in Extended-One Generation Reproductive Toxicity (EOGRT) Studies

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