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Review
. 2024 Jun 23;25(13):6887.
doi: 10.3390/ijms25136887.

Regrettable Substitutes and the Brain: What Animal Models and Human Studies Tell Us about the Neurodevelopmental Effects of Bisphenol, Per- and Polyfluoroalkyl Substances, and Phthalate Replacements

Elena Morales-Grahl  1 , Emily N Hilz  1 , Andrea C Gore  1
Affiliations
Review

Regrettable Substitutes and the Brain: What Animal Models and Human Studies Tell Us about the Neurodevelopmental Effects of Bisphenol, Per- and Polyfluoroalkyl Substances, and Phthalate Replacements

Elena Morales-Grahl et al. Int J Mol Sci. .

Abstract

In recent decades, emerging evidence has identified endocrine and neurologic health concerns related to exposure to endocrine-disrupting chemicals (EDCs), including bisphenol A (BPA), certain per- and polyfluoroalkyl compounds (PFASs), and phthalates. This has resulted in consumer pressure to remove these chemicals from the market, especially in food-contact materials and personal care products, driving their replacement with structurally or functionally similar substitutes. However, these "new-generation" chemicals may be just as or more harmful than their predecessors and some have not received adequate testing. This review discusses the research on early-life exposures to new-generation bisphenols, PFASs, and phthalates and their links to neurodevelopmental and behavioral alterations in zebrafish, rodents, and humans. As a whole, the evidence suggests that BPA alternatives, especially BPAF, and newer PFASs, such as GenX, can have significant effects on neurodevelopment. The need for further research, especially regarding phthalate replacements and bio-based alternatives, is briefly discussed.

Keywords: BPA; PFAS; bio-based plastic; bisphenol; endocrine-disrupting chemical (EDC); human; neurodevelopment; phthalate; rodent; zebrafish.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Example chemical structures of (a) bisphenol, (b) per- and polyfluoroalkyl substance, and (c) phthalate legacy and new-generation endocrine disruptors (created with BioRender.com (accessed on 20 June 2024)).
Figure 2
Figure 2
(a) Zebrafish, (b) rat, and (c) human models of neurodevelopmental exposure to EDCs. In a and b, EDC exposures are controlled and typically given through prenatal and/or postnatal exposure. In rats, this typically ends at or before weaning at P21. Note that the procedures in mice and rats are similar. In humans, exposures will vary across individual subjects. hpf = hours post-fertilization; dpf = days post-fertilization; GD = gestational days; P = postnatal days; YO = years old (created with BioRender.com (accessed on 5 April 2024)).
Figure 3
Figure 3
Neurodevelopmental effects of legacy and new-generation endocrine disruptors (created with BioRender.com (accessed on 13 June 2024)).
See this image and copyright information in PMC

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