title: The metabolite 3,4,3',4'-tetrachloroazobenzene (TCAB) exerts a higher ecotoxicity than the parent compounds 3,4-dichloroaniline (3,4-DCA) and propanil.
abstract: 3,4,3',4'-tetrachloroazobenzene (TCAB) is not commercially manufactured but formed as an unwanted by-product in the manufacturing of 3,4-dichloroaniline (3,4-DCA) or metabolized from the degradation of chloranilide herbicides, like propanil. While a considerable amount of research has been done concerning the toxicological and ecotoxicological effects of propanil and 3,4-DCA, limited information is available on TCAB. Our study examined the toxicity of TCAB in comparison to its parent compounds propanil and 3,4-DCA, using a battery of bioassays including in vitro with aryl hydrocarbon receptor (AhR) mediated activity by the 7-ethoxyresorufin-O-deethylase (EROD) assay and micro-EROD, endocrine-disrupting activity with chemically activated luciferase gene expression (CALUX) as well as in vivo with fish embryo toxicity (FET) assays with Danio rerio. Moreover, the quantitative structure activity response (QSAR) concepts were applied to simulate the binding affinity of TCAB to certain human receptors. It was shown that TCAB has a strong binding affinity to the AhR in EROD and micro-EROD induction assay, with the toxic equivalency factor (TEF) of 8.7×10(-4) and 1.2×10(-5), respectively. TCAB presented to be a weak endocrine disrupting compound with a value of estradiol equivalence factor (EEF) of 6.4×10(-9) and dihydrotestosterone equivalency factor (DEF) of 1.1×10(-10). No acute lethal effects of TCAB were discovered in FET test after 96h of exposure. Major sub-lethal effects detected were heart oedema, yolk malformation, as well as absence of blood flow and tail deformation. QSAR modelling suggested an elevated risk to environment, particularly with respect to binding to the AhR. An adverse effect potentially triggering ERβ, mineralocorticoid, glucocorticoid and progesterone receptor activities might be expected. Altogether, the results obtained suggest that TCAB exerts a higher toxicity than both propanil and 3,4-DCA. This should be considered when assessing the impact of these compounds for the environment and also for regulatory decisions.
authors.affiliation: Institute for Environmental Research, RWTH Aachen University, Worringerweg 1, 52074 Aachen, Germany. Electronic address: xiao.hongxia@bio5.rwth-aachen.de.
authors.forename: Hongxia
authors.initials: H
authors.lastname: Xiao
authors.affiliation: Institute for Environmental Research, RWTH Aachen University, Worringerweg 1, 52074 Aachen, Germany. Electronic address: jochen.kuckelkorn@bio5.rwth-aachen.de.
authors.forename: Jochen
authors.initials: J
authors.lastname: Kuckelkorn
authors.affiliation: Institute for Environmental Research, RWTH Aachen University, Worringerweg 1, 52074 Aachen, Germany. Electronic address: leonie.nuesser@rwth-aachen.de.
authors.forename: Leonie Katharina
authors.initials: LK
authors.lastname: Nüßer
authors.affiliation: Institute for Environmental Research, RWTH Aachen University, Worringerweg 1, 52074 Aachen, Germany. Electronic address: floehr@bio5.rwth-aachen.de.
authors.forename: Tilman
authors.initials: T
authors.lastname: Floehr
authors.affiliation: Institute for Environmental Research, RWTH Aachen University, Worringerweg 1, 52074 Aachen, Germany. Electronic address: michael.hennig@rwth-aachen.de.
authors.forename: Michael Patrick
authors.initials: MP
authors.lastname: Hennig
authors.affiliation: Institute for Environmental Research, RWTH Aachen University, Worringerweg 1, 52074 Aachen, Germany; College of Resources and Environmental Science, Chongqing University, Tiansheng Road Beibei 1, Chongqing 400715, People's Republic of China. Electronic address: ross@bio5.rwth-aachen.de.
authors.forename: Martina
authors.initials: M
authors.lastname: Roß-Nickoll
authors.affiliation: Institute for Environmental Research, RWTH Aachen University, Worringerweg 1, 52074 Aachen, Germany; State Key Laboratory of Pollution Control & Resource Reuse, School of the Environment, Nanjing University, Xianlin Avenue 163, Nanjing 210023, People's Republic of China; College of Resources and Environmental Science, Chongqing University, Tiansheng Road Beibei 1, Chongqing 400715, People's Republic of China. Electronic address: andreas.schaeffer@bio5.rwth-aachen.de.
authors.forename: Andreas
authors.initials: A
authors.lastname: Schäffer
authors.affiliation: Institute for Environmental Research, RWTH Aachen University, Worringerweg 1, 52074 Aachen, Germany; State Key Laboratory of Pollution Control & Resource Reuse, School of the Environment, Nanjing University, Xianlin Avenue 163, Nanjing 210023, People's Republic of China; College of Resources and Environmental Science, Chongqing University, Tiansheng Road Beibei 1, Chongqing 400715, People's Republic of China; Key Laboratory of Yangtze Water Environment, Ministry of Education, Tongji University, Siping Road 1239, Shanghai 200092, People's Republic of China. Electronic address: henner.hollert@bio5.rwth-aachen.de.
authors.forename: Henner
authors.initials: H
authors.lastname: Hollert
mesh_terms: D000814:Aniline Compounds / Q000633:toxicity*; D001391:Azo Compounds / Q000633:toxicity*; D002722:Chlorobenzenes / Q000633:toxicity*; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D054750:Ecotoxicology; D004785:Environmental Pollutants / Q000633:toxicity; D006540:Herbicides / Q000633:toxicity*; D011411:Propanil / Q000633:toxicity*; D018336:Receptors, Aryl Hydrocarbon; D018675:Toxicity Tests
chemical_list: D000814:Aniline Compounds; D001391:Azo Compounds; D002722:Chlorobenzenes; D004785:Environmental Pollutants; D006540:Herbicides; D018336:Receptors, Aryl Hydrocarbon; C013279:3,4,3',4'-tetrachloroazobenzene; C014464:3,4-dichloroaniline; D011411:Propanil; D019363:Cytochrome P-450 CYP1A1
keywords: 3,4,3ʹ,4ʹ-Tetrachloroazobenzene (TCAB); AhR-mediated activity; Endocrine disrupting; Propanil; Quantitative structure activity response model (QSAR); Zebrafish