DEDUCT | Database of Endocrine Disrupting chemicals and their Toxicity profiles

2,3',4',6-Tetrabromodiphenyl ether

Associated AOPs with Level of Relevance - 1 AOPs with at least 1 KE associated with chemical, where the KE(s) are neither MIE nor AO

AOP Identifier	AOP Title	AO Classification	OECD Status	Taxonomic applicability	Coverage Score ⓘ The fraction of KEs within the AOP, that are mapped to the chemical-associated toxicological endpoints.	KE Identifier	KE Name
AOP:8	Upregulation of Thyroid Hormone Catabolism via Activation of Hepatic Nuclear Receptors, and Subsequent Adverse Neurodevelopmental Outcomes in Mammals	Nervous system disease	Under Development	Rat	0.11	KE:281	Thyroxine (T4) in serum, Decreased
AOP:17	Binding of electrophilic chemicals to SH(thiol)-group of proteins and /or to seleno-proteins involved in protection against oxidative stress during brain development leads to impairment of learning and memory	Developmental disorder of mental health	WPHA/WNT Endorsed	Rat, Mouse, Human	0.1	KE:1392	Oxidative Stress
AOP:41	Sustained AhR Activation leading to Rodent Liver Tumours	Cancer; Gastrointestinal system disease	Under Review	Rattus sp. ABTC 42503, Mus sp. 2000082	0.2	KE:854	Alterations, Cellular proliferation / hyperplasia
AOP:42	Inhibition of Thyroperoxidase and Subsequent Adverse Neurodevelopmental Outcomes in Mammals	Cognitive disorder	WPHA/WNT Endorsed	Human, Rat, Mouse	0.12	KE:281	Thyroxine (T4) in serum, Decreased
AOP:54	Inhibition of Na+/I- symporter (NIS) leads to learning and memory impairment	Developmental disorder of mental health	WPHA/WNT Endorsed	Homo sapiens, Rattus sp.	0.1	KE:281	Thyroxine (T4) in serum, Decreased
AOP:110	Inhibition of iodide pump activity leading to follicular cell adenomas and carcinomas (in rat and mouse)	Cancer; Endocrine system disease	-	Rattus norvegicus, Mus musculus	0.29	KE:1023	Increased, Thyroid-stimulating hormone (TSH)
AOP:110		Cancer; Endocrine system disease	-	Rattus norvegicus, Mus musculus	0.29	KE:281	Thyroxine (T4) in serum, Decreased
AOP:112	Increased dopaminergic activity leading to endometrial adenocarcinomas (in Wistar rat)	Reproductive system disease; Cancer	-	Rattus norvegicus	0.17	KE:747	Decreased, Prolactin
AOP:119	Inhibition of thyroid peroxidase leading to follicular cell adenomas and carcinomas (in rat and mouse)	Cancer; Endocrine system disease	-	Rattus norvegicus, Mus musculus	0.29	KE:1023	Increased, Thyroid-stimulating hormone (TSH)
AOP:119		Cancer; Endocrine system disease	-	Rattus norvegicus, Mus musculus	0.29	KE:281	Thyroxine (T4) in serum, Decreased
AOP:128	Kidney dysfunction by decreased thyroid hormone	Urinary system disease	Under Development	Sprague-Dawley, Homo sapiens	0.09	KE:281	Thyroxine (T4) in serum, Decreased
AOP:134	Sodium Iodide Symporter (NIS) Inhibition and Subsequent Adverse Neurodevelopmental Outcomes in Mammals	Cognitive disorder	-	Rat, Homo sapiens	0.11	KE:281	Thyroxine (T4) in serum, Decreased
AOP:155	Deiodinase 2 inhibition leading to increased mortality via reduced posterior swim bladder inflation	Unclassified	WPHA/WNT Endorsed	Fathead minnow, Zebrafish	0.17	KE:1003	Decreased, Triiodothyronine (T3)
AOP:156	Deiodinase 2 inhibition leading to increased mortality via reduced anterior swim bladder inflation	Unclassified	WPHA/WNT Endorsed	Zebrafish, Fathead minnow	0.17	KE:1003	Decreased, Triiodothyronine (T3)
AOP:157	Deiodinase 1 inhibition leading to increased mortality via reduced posterior swim bladder inflation	Unclassified	WPHA/WNT Endorsed	Zebrafish, Fathead minnow	0.17	KE:1003	Decreased, Triiodothyronine (T3)
AOP:158	Deiodinase 1 inhibition leading to increased mortality via reduced anterior swim bladder inflation	Unclassified	WPHA/WNT Endorsed	Zebrafish, Fathead minnow	0.17	KE:1003	Decreased, Triiodothyronine (T3)
AOP:159	Thyroperoxidase inhibition leading to increased mortality via reduced anterior swim bladder inflation	Unclassified	WPHA/WNT Endorsed	Zebrafish, Fathead minnow	0.25	KE:1003	Decreased, Triiodothyronine (T3)
AOP:159		Unclassified	WPHA/WNT Endorsed	Zebrafish, Fathead minnow	0.25	KE:281	Thyroxine (T4) in serum, Decreased
AOP:175	Thyroperoxidase inhibition leading to altered amphibian metamorphosis	Unclassified	-	African clawed frog	0.25	KE:281	Thyroxine (T4) in serum, Decreased
AOP:176	Sodium Iodide Symporter (NIS) Inhibition leading to altered amphibian metamorphosis	Unclassified	-	African clawed frog	0.2	KE:281	Thyroxine (T4) in serum, Decreased
AOP:188	Iodotyrosine deiodinase (IYD) inhibition leading to altered amphibian metamorphosis	Unclassified	-	African clawed frog	0.2	KE:281	Thyroxine (T4) in serum, Decreased
AOP:189	Type I iodothyronine deiodinase (DIO1) inhibition leading to altered amphibian metamorphosis	Unclassified	-	African clawed frog	0.5	KE:1116	Decreased, Triiodothyronine (T3) in tissues
AOP:189		Unclassified	-	African clawed frog	0.5	KE:1003	Decreased, Triiodothyronine (T3)
AOP:190	Type II iodothyronine deiodinase (DIO2) inhibition leading to altered amphibian metamorphosis	Unclassified	-	African clawed frog	0.33	KE:1116	Decreased, Triiodothyronine (T3) in tissues
AOP:190		Unclassified	-	African clawed frog	0.33	KE:1023	Increased, Thyroid-stimulating hormone (TSH)
AOP:192	Pendrin inhibition leading to altered amphibian metamorphosis	Unclassified	-	African clawed frog	0.25	KE:281	Thyroxine (T4) in serum, Decreased
AOP:193	Dual oxidase (DUOX) inhibition leading to altered amphibian metamorphosis	Unclassified	-	African clawed frog	0.25	KE:281	Thyroxine (T4) in serum, Decreased
AOP:194	Hepatic nuclear receptor activation leading to altered amphibian metamorphosis	Unclassified	-	African clawed frog	0.17	KE:281	Thyroxine (T4) in serum, Decreased
AOP:220	Cyp2E1 Activation Leading to Liver Cancer	Cancer; Gastrointestinal system disease	WPHA/WNT Endorsed	Rodents, Homo sapiens	0.2	KE:1392	Oxidative Stress
AOP:260	CYP2E1 activation and formation of protein adducts leading to neurodegeneration	Nervous system disease	-	Human	0.14	KE:1392	Oxidative Stress
AOP:321	Reduced environmental pH leading to thinner shells in Mytilus edulis	Unclassified	-		0.09	KE:10039	Higher antioxidant enzyme activities and lipid peroxidation
AOP:363	Thyroperoxidase inhibition leading to altered visual function via altered retinal layer structure	Unclassified	Under Review	Zebrafish	0.25	KE:1003	Decreased, Triiodothyronine (T3)
AOP:363		Unclassified	Under Review	Zebrafish	0.25	KE:281	Thyroxine (T4) in serum, Decreased
AOP:364	Thyroperoxidase inhibition leading to altered visual function via decreased eye size	Unclassified	Under Development		0.25	KE:1003	Decreased, Triiodothyronine (T3)
AOP:364		Unclassified	Under Development		0.25	KE:281	Thyroxine (T4) in serum, Decreased
AOP:365	Thyroperoxidase inhibition leading to altered visual function via altered photoreceptor patterning	Unclassified	Under Development		0.25	KE:1003	Decreased, Triiodothyronine (T3)
AOP:365		Unclassified	Under Development		0.25	KE:281	Thyroxine (T4) in serum, Decreased
AOP:366	Competitive binding to thyroid hormone carrier protein transthyretin (TTR) leading to altered amphibian metamorphosis	Unclassified	-		0.14	KE:281	Thyroxine (T4) in serum, Decreased
AOP:367	Competitive binding to thyroid hormone carrier protein thyroid binding globulin (TBG) leading to altered amphibian metamorphosis	Unclassified	-		0.14	KE:281	Thyroxine (T4) in serum, Decreased
AOP:437	Inhibition of mitochondrial electron transport chain (ETC) complexes leading to kidney toxicity	Urinary system disease	Under Development		0.2	KE:1392	Oxidative Stress
AOP:438	reactive oxygen species generation leading to increased cardiovascular morbidity and mortality	Cardiovascular system disease	-		0.08	KE:1392	Oxidative Stress
AOP:439	Activation of the AhR leading to metastatic breast cancer	Thoracic disease; Cancer	Under Development	Humans, Mice	0.11	KE:1971	Increased, tumor growth
AOP:444	Ionizing radiation leads to reduced reproduction in Eisenia fetida via reduced spermatogenesis and cocoon hatchability	Unclassified	-		0.11	KE:1392	Oxidative Stress
AOP:446	PM-related Adverse outcome pathway frameworks on various systems	Respiratory system disease	-		0.05	KE:1392	Oxidative Stress
AOP:447	Kidney failure induced by inhibition of mitochondrial electron transfer chain through apoptosis, inflammation and oxidative stress pathways	Urinary system disease	-		0.08	KE:1392	Oxidative Stress
AOP:448	ROS, inflammation, and activation of nAChR lead to increased incidence of cardiovascular morbidity and mortality	Cardiovascular system disease	-		0.06	KE:1392	Oxidative Stress
AOP:450	Inhibition of AChE and activation of CYP2E1 leading to sensory axonal peripheral neuropathy and mortality	Nervous system disease	-	Rattus norvegicus, Mus musculus, Homo sapiens	0.14	KE:1392	Oxidative Stress
AOP:452	Adverse outcome pathway of PM-induced respiratory toxicity	Respiratory system disease	-		0.09	KE:1392	Oxidative Stress
AOP:453	Reactive oxygen species and subsequent oxidative stress lead to increased incidence of digestive morbidity and mortality in the general population	Gastrointestinal system disease	-		0.08	KE:1392	Oxidative Stress
AOP:457	Succinate dehydrogenase inhibition leading to increased insulin resistance through reduction in circulating thyroxine	Inherited metabolic disorder	-	Human	0.33	KE:1392	Oxidative Stress
AOP:457		Inherited metabolic disorder	-	Human	0.33	KE:281	Thyroxine (T4) in serum, Decreased
AOP:458	AhR activation in the liver leading to Subsequent Adverse Neurodevelopmental Outcomes in Mammals	Cognitive disorder	-	Rat, Mouse, Monkey, Human	0.12	KE:281	Thyroxine (T4) in serum, Decreased
AOP:459	AhR activation in the thyroid leading to Subsequent Adverse Neurodevelopmental Outcomes in Mammals	Cognitive disorder	-	Human, Mouse, Rat	0.22	KE:1392	Oxidative Stress
AOP:459		Cognitive disorder	-	Human, Mouse, Rat	0.22	KE:281	Thyroxine (T4) in serum, Decreased
AOP:463	The AOP framwork on silica nanopariticles induced hepatoxicity	Gastrointestinal system disease	-		0.09	KE:1392	Oxidative Stress
AOP:464	Calcium overload in dopaminergic neurons of the substantia nigra leading to parkinsonian motor deficits	Nervous system disease	-		0.05	KE:1392	Oxidative Stress
AOP:469	Reactive oxygen speicies overproduction leading to increased digestive morbidity and mortality in generation population	Gastrointestinal system disease	-		0.08	KE:1392	Oxidative Stress
AOP:470	Deposition of energy leads to abnormal vascular remodeling	Cardiovascular system disease	Under Review	Human, Rat, Mouse, Rabbit	0.25	KE:1392	Oxidative Stress
AOP:470	Deposition of energy leads to abnormal vascular remodeling	Cardiovascular system disease	Under Review	Human, Rat, Mouse, Rabbit	0.25	KE:2244	Altered Stress Response Signaling
AOP:478	Deposition of energy leading to occurrence of cataracts	Nervous system disease; Monogenic disease	Under Review	Human, Mouse, Rat, Rhesus monkeys, Rabbit, Guinea pig	0.1	KE:1392	Oxidative Stress
AOP:479	Mitochondrial complexes inhibition leading to left ventricular function decrease via increased myocardial oxidative stress	Cardiovascular system disease; Thoracic disease	Under Development		0.14	KE:1392	Oxidative Stress
AOP:482	Deposition of energy leading to occurrence of bone loss	Musculoskeletal system disease	Under Review	Human, Mouse, Rat, Rhesus monkeys	0.14	KE:1392	Oxidative Stress
AOP:483	Deposition of Energy Leading to Learning and Memory Impairment	Developmental disorder of mental health	Under Review	Mouse, Rat, Rabbit, Dog, Pigs, Cow, Human	0.25	KE:1392	Oxidative Stress
AOP:483		Developmental disorder of mental health	Under Review	Mouse, Rat, Rabbit, Dog, Pigs, Cow, Human	0.25	KE:2244	Altered Stress Response Signaling
AOP:488	Increased reactive oxygen species production leading to decreased cognitive function	Cognitive disorder	-	Human	0.14	KE:1392	Oxidative Stress
AOP:495	Androgen receptor activation leading to prostate cancer	Reproductive system disease; Cancer	-		0.11	KE:854	Alterations, Cellular proliferation / hyperplasia
AOP:497	ERa inactivation alters mitochondrial functions and insulin signalling in skeletal muscle and leads to insulin resistance and metabolic syndrome	Inherited metabolic disorder; Disease of metabolism	-		0.12	KE:1392	Oxidative Stress
AOP:501	Excessive iron accumulation leading to neurological disorders	Nervous system disease	-	Homo sapiens	0.25	KE:1392	Oxidative Stress
AOP:507	Nrf2 inhibition leading to vascular disrupting effects via inflammation pathway	Cardiovascular system disease	-	Mouse, Zebrafish, Human	0.17	KE:1392	Oxidative Stress
AOP:509	Nrf2 inhibition leading to vascular disrupting effects through activating apoptosis signal pathway and mitochondrial dysfunction	Cardiovascular system disease	-		0.14	KE:1392	Oxidative Stress
AOP:510	Demethylation of PPAR promotor leading to vascular disrupting effects	Cardiovascular system disease	-	Human, Mouse, Zebrafish	0.1	KE:1392	Oxidative Stress
AOP:511	The AOP framework on ROS-mediated oxidative stress induced vascular disrupting effects	Cardiovascular system disease	-	Human, Mouse, Zebrafish	0.06	KE:1392	Oxidative Stress
AOP:521	Essential element imbalance leads to reproductive failure via oxidative stress	Unclassified	-	Murinae gen. sp.	0.14	KE:1392	Oxidative Stress
AOP:535	Binding and activation of GPER leading to learning and memory impairments	Developmental disorder of mental health	-	Mouse, Human	0.11	KE:1392	Oxidative Stress
AOP:540	Oxidative Stress in the Fish Ovary Leads to Reproductive Impairment via Reduced Vitellogenin Production	Unclassified	-		0.11	KE:1392	Oxidative Stress
AOP:541	Excessive ROS generation leading to increased incidence of vascular calcification by VSMC phenotype switching	Cardiovascular system disease	-		0.08	KE:1392	Oxidative Stress

Associated AOPs with Level of Relevance - 2 AOPs with at least 1 AO associated with chemical, and no associated MIE

AOP Identifier	AOP Title	AO Classification	OECD Status	Taxonomic applicability	Coverage Score ⓘ The fraction of KEs within the AOP, that are mapped to the chemical-associated toxicological endpoints.	KE Identifier	KE Name
AOP:139	Alkylation of DNA leading to cancer 1	Cancer	-	Homo sapiens, Mus musculus	0.25	KE:885	Increase, Cancer
AOP:474	Succinate dehydrogenase inactivation leads to cancer by promoting EMT	Cancer	Under Development	Human and other cells in culture	0.2	KE:885	Increase, Cancer
AOP:505	Reactive Oxygen Species (ROS) formation leads to cancer via inflammation pathway	Cancer	-	Human, Mouse, Rat	0.4	KE:1392	Oxidative Stress
AOP:505		Cancer	-	Human, Mouse, Rat	0.4	KE:885	Increase, Cancer
AOP:513	Reactive Oxygen (ROS) formation leads to cancer via Peroxisome proliferation-activated receptor (PPAR) pathway	Cancer	-	Human, Mouse, Rat	0.2	KE:885	Increase, Cancer
AOP:534	Succinate dehydrogenase (SDH) inhibition leads to cancer through oxidative stress	Cancer	-	Vertebrates	0.33	KE:1392	Oxidative Stress
AOP:534		Cancer	-	Vertebrates	0.33	KE:885	Increase, Cancer
AOP:546	Succinate dehydrogenase inactivation leads to cancer through hypoxic-like mechanisms	Cancer	-	Human and other cells in culture	0.2	KE:885	Increase, Cancer

Associated AOPs with Level of Relevance - 3 AOPs with at least 1 MIE associated with chemical, and no associated AO

AOP Identifier	AOP Title	AO Classification	OECD Status	Taxonomic applicability	Coverage Score ⓘ The fraction of KEs within the AOP, that are mapped to the chemical-associated toxicological endpoints.	KE Identifier	KE Name
AOP:411	Oxidative stress Leading to Decreased Lung Function	Respiratory system disease	-	Homo sapiens	0.25	KE:1392	Oxidative Stress
AOP:424	Oxidative stress Leading to Decreased Lung Function via CFTR dysfunction	Respiratory system disease	-	Human	0.17	KE:1392	Oxidative Stress
AOP:425	Oxidative Stress Leading to Decreased Lung Function via Decreased FOXJ1	Respiratory system disease	-	Human	0.17	KE:1392	Oxidative Stress
AOP:472	DNA adduct formation leading to kidney failure	Urinary system disease	-		0.11	KE:1392	Oxidative Stress

No associated AOPs with Level of Relevance 5

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