인체 간세포주 HepG2 및 발광박테리아를 활용한 유기인계 난연제와 그 혼합물의 독성 스크리닝
Toxicity of Organophosphorus Flame Retardants (OPFRs) and Their Mixtures in Aliivibrio fischeri and Human Hepatocyte HepG2
0
조회
0
다운로드
2
인용
0
참고문헌
키워드
초록
Background: Organophosphorus f lame retardants (OPFRs) are a group of chemical substances used in building materials and plastic products to suppress or mitigate the combustion of materials. Although OPFRs are generally used in mixed form, information on their mixture toxicity is quite scarce. Objectives: This study aims to elucidate the toxicity and determine the types of interaction (e.g., synergistic, additive, and antagonistic effect) of OPFRs mixtures. Methods: Nine organophosphorus f lame retardants, including TEHP (tris(2-ethylhexyl) phosphate) and TDCPP (tris(1,3-dichloro-2-propyl) phosphate), were selected based on indoor dust measurement data in South Korea. Nine OPFRs were exposed to the luminescent bacteria Aliivibrio fischeri for 30 minutes and the human hepatocyte cell line HepG2 for 48 hours. Chemicals with significant toxicity were only used for mixture toxicity tests in HepG2. In addition, the observed ECx values were compared with the predicted toxicity values in the CA (concentration addition) prediction model, and the MDR (model deviation ratio) was calculated to determine the type of interaction. Results: Only four chemicals showed significant toxicity in the luminescent bacteria assays. However, EC50 values were derived for seven out of nine OPFRs in the HepG2 assays. In the HepG2 assays, the highest to lowest EC50 were in the order of the molecular weight of the target chemicals. In the further mixture tests, most binary mixtures show additive interactions except for the two combinations that have TPhP (triphenyl phosphate), i.e., TPhP and TDCPP, and TPhP and TBOEP (tris(2-butoxyethyl) phosphate). Conclusions: Our data shows OPFR mixtures usually have additivity; however, more research is needed to find out the reason for the synergistic effect of TPhP. Also, the mixture experimental dataset can be used as a training and validation set for developing the mixture toxicity prediction model as a further step.
Abstract
Background: Organophosphorus f lame retardants (OPFRs) are a group of chemical substances used in building materials and plastic products to suppress or mitigate the combustion of materials. Although OPFRs are generally used in mixed form, information on their mixture toxicity is quite scarce. Objectives: This study aims to elucidate the toxicity and determine the types of interaction (e.g., synergistic, additive, and antagonistic effect) of OPFRs mixtures. Methods: Nine organophosphorus f lame retardants, including TEHP (tris(2-ethylhexyl) phosphate) and TDCPP (tris(1,3-dichloro-2-propyl) phosphate), were selected based on indoor dust measurement data in South Korea. Nine OPFRs were exposed to the luminescent bacteria Aliivibrio fischeri for 30 minutes and the human hepatocyte cell line HepG2 for 48 hours. Chemicals with significant toxicity were only used for mixture toxicity tests in HepG2. In addition, the observed ECx values were compared with the predicted toxicity values in the CA (concentration addition) prediction model, and the MDR (model deviation ratio) was calculated to determine the type of interaction. Results: Only four chemicals showed significant toxicity in the luminescent bacteria assays. However, EC50 values were derived for seven out of nine OPFRs in the HepG2 assays. In the HepG2 assays, the highest to lowest EC50 were in the order of the molecular weight of the target chemicals. In the further mixture tests, most binary mixtures show additive interactions except for the two combinations that have TPhP (triphenyl phosphate), i.e., TPhP and TDCPP, and TPhP and TBOEP (tris(2-butoxyethyl) phosphate). Conclusions: Our data shows OPFR mixtures usually have additivity; however, more research is needed to find out the reason for the synergistic effect of TPhP. Also, the mixture experimental dataset can be used as a training and validation set for developing the mixture toxicity prediction model as a further step.
참고문헌 (26)
- Ma Y, "Human exposure to halogenated and organophosphate flame retardants through informal e-waste handling activities - a critical review", Environ Pollut, 268(Pt A), pp.115727~ (2021)
- Li W, "Organophosphate esters in indoor dust from 12countries: concentrations, composition profiles, and human exposure", Environ Int, 133(Pt A), pp.105178~ (2019)
- Gwon HR, "Occurrence, distribution, and potential exposure risk of organophosphate flame retardants in house dust in South Korea", Sci Total Environ, 770, pp.144571~ (2021)
- "Dyson global dust study"[URL]
- de la Torre A, "Organophosphate compounds, polybrominated diphenyl ethers and novel brominated flame retardants in European indoor house dust : use, evidence for replacements and assessment of human exposure", J Hazard Mater, 382, pp.121009~ (2020)
- Rosenmai AK, "Organophosphate ester flame retardants have antiandrogenic potential and affect other endocrine related endpoints in vitro and in silico", Chemosphere, 263, pp.127703~ (2021)
- "Draft screening report: an assessment of whether the use of TCEP, TCPP and TDCP in articles should be restricted"[URL]
- Dishaw LV, "Developmental exposure to organophosphate flame retardants elicits overt toxicity and alters behavior in early life stage zebrafish(Danio rerio)", Toxicol Sci, 142(2), pp.445~454 (2014)
- Oliveri AN, "Developmental exposure to an organophosphate flame retardant alters later behavioral responses to dopamine antagonism in zebrafish larvae", Neurotoxicol Teratol, 67, pp.25~30 (2018)
- Sun L, "Developmental exposure of zebrafish larvae to organophosphate flame retardants causes neurotoxicity", Neurotoxicol Teratol, 55, pp.16~22 (2016)
- Liu X, "Endocrine disruption potentials of organophosphate flame retardants and related mechanisms in H295R and MVLN cell lines and in zebrafish", Aquat Toxicol, 114-115, pp.173~181 (2012)
- Saquib Q, "Organophosphorus flame retardant TDCPP displays genotoxic and carcinogenic risks in human liver cells", Cells, 11(2), pp.195~ (2022)
- Li F, "Toxicological effects of tris(2-chloropropyl)phosphate in human hepatic cells", Chemosphere, 187, pp.88~96 (2017)
- Kim S, "Thyroid disruption by triphenyl phosphate, an organophosphate flame retardant, in zebrafish(Danio rerio)embryos", larvae, and in GH3 and FRTL-5 cell lines, 2015, pp.160, 188~196
- Kim MI, "Environmental health practice" (2023), Shinkwang
- Groten JP, "Toxicology of simple and complex mixtures", Trends Pharmacol Sci, 22(6), pp.316~322 (2001)
- De Zwart D, "Complex mixture toxicity for single and multiple species : proposed methodologies", Environ Toxicol Chem, 24, pp.2665~2676 (2005)
- George TK, "Assessment of the probabilistic ecological risk assessment-toxic equivalent combination approach for evaluating pesticide mixture toxicity to zooplankton in outdoor microcosms", Arch Environ Contam Toxicol, 45(4), pp.453~461 (2003)
- Backhaus T, "Predictive environmental risk assessment of chemical mixtures : a conceptual framework", Environ Sci Technol, 46(5), pp.2564~2573 (2012)
- Faust M, "Predicting the joint algal toxicity of multi-component s-triazine mixtures at low-effect concentrations of individual toxicants", Aquat Toxicol, 56(1), pp.13~32 (2001)
- Belden JB, "How well can we predict the tox-icity of pesticide mixtures to aquatic life?", Integr Environ Assess Manag, 3(3), pp.364~372 (2007)
- Antonopoulou M, "Genotoxic and toxic effects of the flame retardant tris(chloropropyl)phosphate(TCPP)in human lymphocytes, microalgae and bacteria", Toxics, 10(12), pp.736~ (2022)
- Zhang Y, "Impact of mixture effects between emerging organic contaminants on cytotoxicity : a systems biological understanding of synergism between tris(1, 3-dichloro-2-propyl)phosphate and triphenyl phosphate", Environ Sci Technol, 54(17), pp.10722~10734 (2020)
- Bajard L, "Prioritization of hazards of novel flame retardants using the mechanistic toxicology information from ToxCast and Adverse Outcome Pathways", Environ Sci Eur, 31, pp.14~ (2019)
- Bliss CI, "The toxicity of poisons applied jointly", Ann Appl Biol, 26(3), pp.585~615 (1939)
- Escher B, "Exploring the concepts of concentration addition and independent action using a linear low-effect mixture model", Environ Toxicol Chem, 39(12), pp.2552~2559 (2020)