Using alternative test methods to predict endocrine disruption and reproductive adverse outcomes: do we have enough knowledge?

Svingen, Terje; Schwartz, Camilla Victoria Lindgren; Rosenmai, Anna Kjerstine; Ramhøj, Louise; Johansson, Hanna Katarina Lilith; Hass, Ulla; Draskau, Monica Kam; Davidsen, Nichlas; Christiansen, Sofie; Ballegaar, Anne-Sofie Ravn; Axelstad, Marta

doi:10.1016/j.envpol.2022.119242

Cited by 19 publications

(10 citation statements)

References 47 publications

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“…Despite the growing evidence supporting a potential endocrine-disrupting the role of phthalates, parabens, and PFAS, very few chemicals are currently classified as EDCs by the EU. Svingen et al, 2022 Our results suggested the presence of inverse associations between some specific chemicals concentrations and OSI. We observed associations for phthalates, with a significant signal for DEHP metabolites among Swedish women, and parabens, with a significant signal for methylparaben among Estonian women.…”

Section: Discussionmentioning

confidence: 52%

Association between chemical mixtures and female fertility in women undergoing assisted reproduction in Sweden and Estonia

Bellavia

Zou

Björvang

et al. 2023

Environmental Research

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Section: Discussionmentioning

confidence: 52%

Association between chemical mixtures and female fertility in women undergoing assisted reproduction in Sweden and Estonia

Bellavia

Zou

Björvang

et al. 2023

Environmental Research

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“…Because of these stringent criteria, very few substances are in fact (to date) regulated based on their EDC properties ( Svingen et al, 2022 ), which leads on to a third challenge. With the emerging paradigm of relying more on NAMs for chemical risk assessment purposes, there is an obvious challenge with the “adverse effect in an intact organism” criterion.…”

Section: Endocrine Disrupting Chemicalsmentioning

confidence: 99%

“…How good the predictions have to be to reasonably safeguard human health, however, remains a debatable question and something that must be properly integrated in future risk assessment strategies. Because the fact remains, that in many instances the predictive power remains quite poor, even for well-defined endocrine disrupting modalities such as “androgenic” and male reproduction ( Svingen et al, 2022 ).…”

Section: Adverse Outcome Pathways—opportunities and Challenges For En...mentioning

confidence: 99%

“…Firstly, because the AOP framework is very well suited for addressing the current regulatory needs for identifying EDCs. Secondly, because EDC identification represents an area of chemical toxicology where predicting in vivo effect outcomes using data from new approach methodologies (NAMs) is challenging, as we recently argued ( Svingen et al, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

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Endocrine Disruptors in a New Era of Predictive Toxicology and Dealing With the “More is Different” Challenge

Svingen

2022

Front. Toxicol.

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Environmental chemicals, including endocrine disrupting chemicals (EDCs), pose a threat to human health. Actions are taken by scientists, assessors, regulators, and policymakers around the world to improve testing strategies for chemical substances, including pushing towards greater reliance on data from new approach methodologies to replace animal toxicity studies. This paradigm shift is envisioned to ultimately replace animal testing altogether for many purposes. As regards identification and regulation of EDCs, this poses certain challenges in that current guidelines—at least within the European regulatory framework—stipulate that adverse outcomes are to be demonstrated in an intact organism. The new testing paradigm is, of course, to find ways of dealing with this dilemma. However, another challenge still remains, even if the “intact organisms” definition changes or is replaced, namely the challenge of predicting apical adverse effects resulting from endocrine disruption. The adverse outcome pathway (AOP) framework provides a good platform for identifying and regulating EDCs based on both non-animal and animal (or human) data, but also here we are confronted with the same challenge: how to predict adverse effects in complex organism from simple test assays that are based on reductionist principles? In this article, the challenge of “emergent properties” in predictive toxicology is highlighted as a cautionary footnote because, although a future relying far less on animal toxicity testing is both desirable and sensible, the pace at which we transition to the new paradigm should ensure that human health, and the environment, is safeguarded from harmful chemical substances.

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“…This challenge is becoming even more pressing with modern toxicology moving towards higher dependence on alternative test methods rather than more traditional large-scale animal toxicity testing for screening and prioritizing chemical substances of concern ( Pistollato et al, 2021 ). This is not least important in hypothesis-driven testing, or predictive toxicology, where knowledge about toxicological mechanisms and measurable key events increasingly feed into causal adverse outcome pathways (AOPs) ( Ankley & Edwards, 2018 ; Audouze et al, 2021 ; Paini et al, 2022 ; Svingen et al, 2022 ). Once robust AOPs have been developed, chemicals can increasingly be assessed using alternative methods; in essence reducing the reliance on more traditional in vivo (animal) protocols.…”

mentioning

confidence: 99%

Editorial: Methods and Protocols in Developmental and Reproductive Toxicology

Hougaard

Svingen²

2022

Front. Toxicol.

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Editorial on the Research Topic Methods and Protocols in Developmental and Reproductive ToxicologyUndisturbed reproductive development is a prerequisite for life-long reproductive health. Many stages of perinatal life are vulnerable to disturbances such as exposure to environmental chemicals and drugs that can interfere with molecular and cellular processes. Of concern is the enormous number of chemicals and pharmaceuticals in existence and for which humans and wildlife can be exposed through their life cycles (Rockström et al., 2009;Svingen and Vinggaard, 2016;Hougaard, 2021).Although there are international regulations and guidelines in place for testing and assessing chemical substances for their potential toxicity, they are in many ways inadequate in dealing with the vast number of chemicals in use coupled with the myriad of potential effect they can have on complex living organisms. This challenge is becoming even more pressing with modern toxicology moving towards higher dependence on alternative test methods rather than more traditional large-scale animal toxicity testing for screening and prioritizing chemical substances of concern (Pistollato et al., 2021). This is not least important in hypothesisdriven testing, or predictive toxicology, where knowledge about toxicological mechanisms and measurable key events increasingly feed into causal adverse outcome pathways (AOPs)

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Using alternative test methods to predict endocrine disruption and reproductive adverse outcomes: do we have enough knowledge?

Cited by 19 publications

References 47 publications

Association between chemical mixtures and female fertility in women undergoing assisted reproduction in Sweden and Estonia

Association between chemical mixtures and female fertility in women undergoing assisted reproduction in Sweden and Estonia

Endocrine Disruptors in a New Era of Predictive Toxicology and Dealing With the “More is Different” Challenge

Editorial: Methods and Protocols in Developmental and Reproductive Toxicology

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