Several studies have reported on pleiotropic toxic effects of BP-A in aquatic vertebrates and invertebrates at environmental doses (Canesi and Fabbri 2015; Crain et al. 2007; Kang et al. 2007). BP-A-induced embryotoxicity was noted previously in sea urchins (Cakal Arslan and Parlak, 2008), in zebrafish (Tse et al. 2013), in Xenopus (Gibert et al. 2011), and rodents (Chen et al. 2013). It has been reported that BP-A can alter echinoderm physiology, reproduction, and development at environmental concentrations (Bošnjak et al. 2014; Roepke et al. 2005), which can reach 17.2 µg/L (Crain et al. 2007). BP-A can induce aberrant division of the cell nucleus, leading to defective embryo development through the first cell division and retardation, along with general errors in cytoskeletal functioning in mitosis (Bošnjak et al. 2014).
The present report confirms BP-A-induced developmental and cytogenetic toxicity, while the replacement chemical (BP-S) fails to alter A. lixula early life stages, except for a moderate change in mitotic activity (metaphase/anaphase ratio, Fig. 5a). BP-A is more potent than BP-S in particular, at 10, 25, and 100 µM (~5 fold), indicating the sensitivity of A. lixula embryos to these specific bisphenols during a critical developmental period. Similar effects were also noted within Daphnia magna and in Zebrafish embryos and larvae (Liu et al. 2021). The present data suggest that BP-S raises lesser toxicity than BP-A, and confined to developmental and mitotoxic effects, however below the analogous effects obeserved for BP-A.
The toxicity order for different bisphenols reflects that they may operate via distinct mechanisms. Before 2013, BP-S had been detected in freshwater and sewage sludge, but rarely found in marine surface sediment. However, recent literature showed that BP-S concentration in aquatic environments started to increase progressively (Wu et al. 2018). This observation may indicate that BP-S compounds begin to be extensively used all over the world at different degrees with countries (Liu et al. 2021). BP-S is less biodegradable than BP-A in aquatic environments, which may lead to its accumulation in biota, and thus might be a persistent micropollutant affecting ecosystems (Danzl et al. 2009); Herrero et al. (2018) reported detrimental effects of BP-S on the transcriptional rate of genes in the model species Chironomus riparius.
In accordance with our data, several studies have reported that BP-A can induce DNA damage as well as structural and numerical chromosomal aberrations in vitro (Santovito et al. 2018; Xin et al. 2015) and in vivo (Izzotti et al. 2009). A recent study describes no cytogenetic effects for both BP-A and BP-S in human HepG2 cells (Hercog et al. 2020). Also, it has been reported that BP-S, compared to BPA, has a lower acute toxicity, similar or less endocrine disruption, similar neurotoxicity and immunotoxicity, and lower reproductive and developmental toxicity (Qiu et al. 2018).