Journal of Environmental Health Sciences (한국환경보건학회지)

Korean Society of Environmental Health (한국환경보건학회)
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Toxicity of Organophosphorus Flame Retardants (OPFRs) and Their Mixtures in Aliivibrio fischeri and Human Hepatocyte HepG2

인체 간세포주 HepG2 및 발광박테리아를 활용한 유기인계 난연제와 그 혼합물의 독성 스크리닝

  • Sunmi Kim (Chemical Safety Research Center, Korea Research Institute of Chemical Technology (KRICT)) ;
  • Kyounghee Kang (Chemical Safety Research Center, Korea Research Institute of Chemical Technology (KRICT)) ;
  • Jiyun Kim (Chemical Safety Research Center, Korea Research Institute of Chemical Technology (KRICT)) ;
  • Minju Na (Chemical Safety Research Center, Korea Research Institute of Chemical Technology (KRICT)) ;
  • Jiwon Choi (Chemical Safety Research Center, Korea Research Institute of Chemical Technology (KRICT))
  • 김선미 (한국화학연구원 화학안전연구센터) ;
  • 강경희 (한국화학연구원 화학안전연구센터) ;
  • 김지윤 (한국화학연구원 화학안전연구센터) ;
  • 나민주 (한국화학연구원 화학안전연구센터) ;
  • 최지원 (한국화학연구원 화학안전연구센터)
  • Received : 2023.04.07
  • Accepted : 2023.04.21
  • Published : 2023.04.30
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Abstract

Background: Organophosphorus flame 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 flame 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.

Keywords

Acknowledgement

본 연구는 화학물질·제품 안전설계 기술구축(과제번호 KK2352-10) 및 화학소재 빅데이터 플랫폼 구축(과제번호 KK2351-10) 과제의 일환으로 수행되었으며 이에 감사드립니다. 초기 시험법 구축 시 HepG2 세포주 배양에 도움 주신 한국화학연구원 조희영 책임연구원님, 김현영 선임연구원님, 상가 작용 모델을 활용한 예측값 도출에 도움 주신 서명원 선임연구원님께 감사드립니다.

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