The Toxicity And Toxicology Of Bisphenol A And Its Analogues On Folsomia Candida

As an additive raw material for plastic products,Bisphenol A(BPA)is widely used in packaging of food and daily necessities due to its strength and elasticity.Given the environmental health and ecological hazards of BPA,the use of BPA has been regulated and restricted in some countries and regions.Therefore,BPA structural analogues such as BPS,BPF and BPAF have been widely used as substitutes.With the detection of BPA structural analogs in various environmental and biological media(e.g.natural water,sediment,soil,aquatic animals,human blood and urine samples,etc.),their toxic hazards have received widespread attention.Recently,an increasing number of researchers have found that BPA substitutes have similar toxic effects as BPA.Compared to other environmental media,various structural analogues of BPA have been detected in rural and urban soils with longer half-lives.To the best of our knowledge,however,there are no studies on the ecotoxicity of BPA structural analogs to soil non-target animals.In conclusion,a systematically comparison of the acute toxicity(7 d survival test and 48 h avoidance test)of BPA and nine representative analogues of BPs(BPS,BPF,BPAF,BPB,BPZ,BPP,BPM,BPAP,and BPE)was conducted by using BPA as the control compound and the soil model invertebrate Folsomia Candida as experimental animals.Based on the results of acute toxicity studies,the reproductive toxicity of 10 bisphenol compounds in Folsomia Candida was studied after chronic exposure for 28 days.In addition,by comparing the data of chronic reproduction experiments of these 10 bisphenol compounds,four BPA analogs(BPS,BPF,BPP and BPM)and the control compound BPA were screened for transcriptome sequencing and bioinformatics analysis to explore the potential toxicity targets of BPs.Finally,the effects of BPs on antioxidant system(ROS,SOD,CAT,MDA,CYP450,GST,HSP70,HSP90)and endocrine(E2,ER,VTG)biomarkers of Folsomia Candida were compared.The main research contents and results include:(1)In the 7 d acute survival test,the LC50-7d values of Folsomia Candida were all greater than 1000 mg/kg,and the mortality rate was significantly higher only in the BPS and BPM treatment groups at the highest concentration of 1000 mg/kg,with a lethality rate of 5% and 20%,respectively.These results indicated that BPA and its nine analogues were less toxic to Folsomia Candida for 7-d acute survival.(2)In the 48 h acute avoidance test,Folsomia Candida exhibited significant avoidance behaviors in the BPF,BPAF and BPB treatment groups at 100 mg/kg and500 mg/kg,and in the BPAP and BPE treatment groups at 500 mg/kg.However,no significant avoidance behavior was observed in the concentration range set for the remaining five BPs.The EC50-48 h values of BPF and BPAF were 137.88 mg/kg and336.38 mg/kg,respectively,and the EC50-48 h values of the other 8 BPs were higher than the highest concentration set in this study,500 mg/kg.The EC50-48 h values of BPF and BPAF were 137.88 mg/kg and 336.38 mg/kg,respectively,while the remaining eight BPs were higher than the maximum concentration of 500 mg/kg set in this study.(3)In the 28 d reproduction experiment,all the 10 BPs involved in this study had reproductive toxicity to the Folsomia Candida,among which BPS,BPB and BPZ had the strongest reproductive toxicity,with reproduction inhibition rates of more than 20%(22.94%-39.31%)in the 4 mg/kg treatment group.The LOEC-28 d values of reproductive toxicity for the remaining seven BPs were in the following order:BPF=BPP=BPM=BPE≤20 mg/kg<BPA=BPAF≤100 mg/kg<BPAP≤500 mg/kg.(4)Based on the results of 28 d reproduction experiments and environmental distribution,this study performed transcriptome sequencing and bioinformatics analysis of the F0 generation Folsomia Candida in the BPA,BPS,BPF,BPP and BPM treatment groups at 500 mg/kg.The results showed that these five BPs mainly affected signaling pathways related to oxidative stress,substance metabolism and endocrine,suggesting that the induced reproductive toxicity may be related to these pathways.(5)Based on the results of transcriptome analysis,the antioxidant system and endocrine-related biomarkers of The F0 generation of Folsomia Candida were detected after exposure to BPA,BPS,BPF,BPP and BPM for 28 days.The results showed that the levels of ROS and MDA and the activities of SOD,CAT,CYP450 and GST in BPA,BPS and BPF exposed groups were significantly increased.In addition,the activity of HSP70 and HSP90 was also affected.These findings suggest that BPA,BPS and BPF as exogenous compounds activated the detoxification and antioxidant defense systems of Folsomia Candida and caused oxidative damage.In addition,the levels of E2,ER and VTG were significantly increased after BPA,BPS and BPF exposure,indicating that these three BPs have estrogenic effects and induce endocrine disrupting toxicity.In contrast,the E2,ER and VTG contents of white runner jumpers were significantly lower after BPP and BPM exposure,indicating that BPP and BPM can interfere with the secretion of Folsomia Candida hormones and VTG synthesis,which potentially related to their induced reproductive toxicity.In summary,acute and chronic results showed that BPA and its nine analogs exerted different degrees of effects on survival,avoidance and reproduction of Folsomia Candida,with the greatest effect on reproduction at 28 d.Combined with transcriptome screening and biomarker assays,this study reveals that oxidative damage and endocrine disruption are potential pathways of action for the reproductive toxicity of BPA,BPS,BPF,BPP and BPM induced by chronic exposure to Folsomia Candida.The ecotoxicity and toxicological data obtained from this study on BPs to non-target organisms in soil will provide a basis for further studies on the toxicity mechanisms of bisphenols to typical soil model organisms,Folsomia Candida,and also provide data support for ecological risk assessment and management of soil bisphenols.