Human risk associated with exposure to mixtures of antiandrogenic chemicals evaluated using in vitro hazard and human biomonitoring data

Ma, Yanying; Taxvig, Camilla; Rodríguez-Carrillo, Andrea; Mustieles, Vicente; Reiber, Lena; Kiesow, Anja; Löbl, Nathalie Michelle; Fernández, Mariana F.; Hansen, Tina Vicky Alstrup; Valente, Maria João; Kolossa-Gehring, Marike; David, Madlen; Vinggaard, Anne Marie

doi:10.1016/j.envint.2023.107815

Cited by 4 publications

(2 citation statements)

References 76 publications

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“…Numerous additional studies addressed the relevance of co-exposures using different mixtures including in vivo readouts ( e.g. Elcombe et al 2022 ; Heise et al 2018 ; Houtman et al 2014 ; Ma et al 2023 ; Perez-Carreon et al 2009 ; Rieke et al 2017 ; Sams and Jones 2011 ; Schmidt et al 2016 ). Some studies used combinations of substances at the NOAEL of their respective assays.…”

Section: Concepts Of How Several Substances In Mixtures Can Interact ...mentioning

confidence: 99%

“…The conduction of similar experiments in vitro should account for relevant kinetic processes, e.g. by conducting PBTK modelling (Ma et al 2023 ). Alternatively, testing complex “real-life” mixtures can be done using a whole-mixture-based in vitro strategy, as currently explored within the Green Deal project PANORAMIX (Escher et al 2022 ).…”

Section: Concepts Of How Several Substances In Mixtures Can Interact ...mentioning

confidence: 99%

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Basic concepts of mixture toxicity and relevance for risk evaluation and regulation

Bloch,

Diel,

Epe

et al. 2023

Arch Toxicol

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Exposure to multiple substances is a challenge for risk evaluation. Currently, there is an ongoing debate if generic “mixture assessment/allocation factors” (MAF) should be introduced to increase public health protection. Here, we explore concepts of mixture toxicity and the potential influence of mixture regulation concepts for human health protection. Based on this analysis, we provide recommendations for research and risk assessment. One of the concepts of mixture toxicity is additivity. Substances may act additively by affecting the same molecular mechanism within a common target cell, for example, dioxin-like substances. In a second concept, an “enhancer substance” may act by increasing the target site concentration and aggravating the adverse effect of a “driver substance”. For both concepts, adequate risk management of individual substances can reliably prevent adverse effects to humans. Furthermore, we discuss the hypothesis that the large number of substances to which humans are exposed at very low and individually safe doses may interact to cause adverse effects. This commentary identifies knowledge gaps, such as the lack of a comprehensive overview of substances regulated under different silos, including food, environmentally and occupationally relevant substances, the absence of reliable human exposure data and the missing accessibility of ratios of current human exposure to threshold values, which are considered safe for individual substances. Moreover, a comprehensive overview of the molecular mechanisms and most susceptible target cells is required. We conclude that, currently, there is no scientific evidence supporting the need for a generic MAF. Rather, we recommend taking more specific measures, which focus on compounds with relatively small ratios between human exposure and doses, at which adverse effects can be expected.

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Section: Concepts Of How Several Substances In Mixtures Can Interact ...mentioning

confidence: 99%

Section: Concepts Of How Several Substances In Mixtures Can Interact ...mentioning

confidence: 99%

Basic concepts of mixture toxicity and relevance for risk evaluation and regulation

Bloch,

Diel,

Epe

et al. 2023

Arch Toxicol

View full text Add to dashboard Cite

show abstract

Toxicology and Risk Assessment of Combined Chemicals and Nonchemical Stressors

Rider

2024

Reference Module in Biomedical Sciences

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Maternal exposure to dibutyl phthalate (DBP) impairs angiogenesis and AR signalling pathway through suppression of TGFB1I1 in hypospadias offspring

Wu,

Shi,

Zhang

et al. 2024

Ecotoxicology and Environmental Safety

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Human risk associated with exposure to mixtures of antiandrogenic chemicals evaluated using in vitro hazard and human biomonitoring data

Cited by 4 publications

References 76 publications

Basic concepts of mixture toxicity and relevance for risk evaluation and regulation

Basic concepts of mixture toxicity and relevance for risk evaluation and regulation

Toxicology and Risk Assessment of Combined Chemicals and Nonchemical Stressors

Maternal exposure to dibutyl phthalate (DBP) impairs angiogenesis and AR signalling pathway through suppression of TGFB1I1 in hypospadias offspring

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