DEDUCT | Database of Endocrine Disrupting chemicals and their Toxicity profiles

3,4,5,3',4',5'-Hexachlorobiphenyl

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:77	Nicotinic acetylcholine receptor activation contributes to abnormal foraging and leads to colony death/failure 1	Unclassified	-	Honey bee	0.14	KE:341	Impairment, Learning and memory
AOP:78	Nicotinic acetylcholine receptor activation contributes to abnormal role change within the worker bee caste leading to colony death failure 1	Unclassified	-	Honey bee	0.12	KE:341	Impairment, Learning and memory
AOP:87	Nicotinic acetylcholine receptor activation contributes to abnormal foraging and leads to colony loss/failure	Unclassified	-	Honey bee	0.12	KE:341	Impairment, Learning and memory
AOP:88	Nicotinic acetylcholine receptor activation contributes to abnormal foraging and leads to colony loss/failure via abnormal role change within caste	Unclassified	-	Honey bee	0.14	KE:341	Impairment, Learning and memory
AOP:89	Nicotinic acetylcholine receptor activation followed by desensitization contributes to abnormal foraging and directly leads to colony loss/failure	Unclassified	-	Honey bee	0.12	KE:341	Impairment, Learning and memory
AOP:90	Nicotinic acetylcholine receptor activation contributes to abnormal roll change within the worker bee caste leading to colony loss/failure 2	Unclassified	-	Honey bee	0.12	KE:341	Impairment, Learning and memory
AOP:99	Histamine (H2) receptor antagonism leading to reduced survival	Unclassified	-	Zebrafish	0.14	KE:341	Impairment, Learning and memory
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	0.14	KE:281	Thyroxine (T4) in serum, Decreased
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	0.14	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:159	Thyroperoxidase inhibition leading to increased mortality via reduced anterior swim bladder inflation	Unclassified	WPHA/WNT Endorsed	Zebrafish, Fathead minnow	0.12	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: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:363	Thyroperoxidase inhibition leading to altered visual function via altered retinal layer structure	Unclassified	Under Review	Zebrafish	0.12	KE:281	Thyroxine (T4) in serum, Decreased
AOP:364	Thyroperoxidase inhibition leading to altered visual function via decreased eye size	Unclassified	Under Development		0.12	KE:281	Thyroxine (T4) in serum, Decreased
AOP:365	Thyroperoxidase inhibition leading to altered visual function via altered photoreceptor patterning	Unclassified	Under Development		0.12	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:374	Binding of Sars-CoV-2 spike protein to ACE 2 receptors expressed on brain cells (neuronal and non-neuronal) leads to neuroinflammation resulting in encephalitis	Nervous system disease	Under Development	Human	0.25	KE:352	N/A, Neurodegeneration
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:352	N/A, Neurodegeneration
AOP:457	Succinate dehydrogenase inhibition leading to increased insulin resistance through reduction in circulating thyroxine	Inherited metabolic disorder	-	Human	0.17	KE:281	Thyroxine (T4) in serum, Decreased

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:12	Chronic binding of antagonist to N-methyl-D-aspartate receptors (NMDARs) during brain development leads to neurodegeneration with impairment in learning and memory in aging	Nervous system disease; Developmental disorder of mental health	WPHA/WNT Endorsed	Monkey, Rat, Human, Mouse, Zebrafish	0.25	KE:352	N/A, Neurodegeneration
AOP:12			WPHA/WNT Endorsed	Monkey, Rat, Human, Mouse, Zebrafish	0.25	KE:341	Impairment, Learning and memory
AOP:13	Chronic binding of antagonist to N-methyl-D-aspartate receptors (NMDARs) during brain development induces impairment of learning and memory abilities	Developmental disorder of mental health	WPHA/WNT Endorsed	Human, Mouse, Monkey sp., Rat	0.1	KE:341	Impairment, Learning and memory
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:341	Impairment, Learning and memory
AOP:42	Inhibition of Thyroperoxidase and Subsequent Adverse Neurodevelopmental Outcomes in Mammals	Cognitive disorder	WPHA/WNT Endorsed	Human, Rat, Mouse	0.25	KE:402	Cognitive function, decreased
AOP:42		Cognitive disorder	WPHA/WNT Endorsed	Human, Rat, Mouse	0.25	KE:281	Thyroxine (T4) in serum, Decreased
AOP:48	Binding of agonists to ionotropic glutamate receptors in adult brain causes excitotoxicity that mediates neuronal cell death, contributing to learning and memory impairment.	Developmental disorder of mental health	WPHA/WNT Endorsed	Human, Mouse, Rat	0.22	KE:352	N/A, Neurodegeneration
AOP:48		Developmental disorder of mental health	WPHA/WNT Endorsed	Human, Mouse, Rat	0.22	KE:341	Impairment, Learning and memory
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.	0.2	KE:281	Thyroxine (T4) in serum, Decreased
AOP:54		Developmental disorder of mental health	WPHA/WNT Endorsed	Homo sapiens, Rattus sp.	0.2	KE:341	Impairment, Learning and memory
AOP:134	Sodium Iodide Symporter (NIS) Inhibition and Subsequent Adverse Neurodevelopmental Outcomes in Mammals	Cognitive disorder	-	Rat, Homo sapiens	0.22	KE:402	Cognitive function, decreased
AOP:134		Cognitive disorder	-	Rat, Homo sapiens	0.22	KE:281	Thyroxine (T4) in serum, Decreased
AOP:260	CYP2E1 activation and formation of protein adducts leading to neurodegeneration	Nervous system disease	-	Human	0.14	KE:1514	Neurodegeneration
AOP:281	Acetylcholinesterase Inhibition Leading to Neurodegeneration	Nervous system disease	-		0.1	KE:352	N/A, Neurodegeneration
AOP:300	Thyroid Receptor Antagonism and Subsequent Adverse Neurodevelopmental Outcomes in Mammals	Cognitive disorder	Under Development	Human, Mouse	0.2	KE:402	Cognitive function, decreased
AOP:405	Organo-Phosphate Chemicals induced inhibition of AChE leading to impaired cognitive function	Cognitive disorder	-	Rattus norvegicus, Mus musculus, Homo sapiens	0.2	KE:402	Cognitive function, decreased
AOP:442	Binding to voltage gate sodium channels during development leads to cognitive impairment	Cognitive disorder	Under Review	Rattus norvegicus, Mouse, Humans	0.14	KE:402	Cognitive function, decreased
AOP:458	AhR activation in the liver leading to Subsequent Adverse Neurodevelopmental Outcomes in Mammals	Cognitive disorder	-	Rat, Mouse, Monkey, Human	0.25	KE:402	Cognitive function, decreased
AOP:458		Cognitive disorder	-	Rat, Mouse, Monkey, Human	0.25	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:402	Cognitive function, decreased
AOP:459		Cognitive disorder	-	Human, Mouse, Rat	0.22	KE:281	Thyroxine (T4) in serum, Decreased
AOP:475	Binding of chemicals to ionotropic glutamate receptors leads to impairment of learning and memory via loss of drebrin from dendritic spines of neurons	Developmental disorder of mental health	Under Development	Mouse, Rat, Human, Caenorhabditis elegans	0.12	KE:341	Impairment, Learning and memory
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	0.12	KE:341	Impairment, Learning and memory
AOP:485	Thyroid hormone antagonism leading to impaired oligodendrocyte maturation during development and subsequent decreased cognition	Cognitive disorder	-	Human	0.14	KE:402	Cognitive function, decreased
AOP:486	Binding to the extracellular protein laminin leading to decreased cognitive function	Cognitive disorder	-	Human	0.14	KE:402	Cognitive function, decreased
AOP:488	Increased reactive oxygen species production leading to decreased cognitive function	Cognitive disorder	-	Human	0.14	KE:402	Cognitive function, decreased
AOP:490	Co-activation of IP3R and RyR leads to reduced IQ through non-cholinergic mechanisms	Developmental disorder of mental health	-		0.18	KE:2121	decreased, Intellectual Quotient
AOP:490		Developmental disorder of mental health	-		0.18	KE:341	Impairment, Learning and memory
AOP:499	Activation of MEK-ERK1/2 leads to deficits in learning and cognition via disrupted neurotransmitter release	Developmental disorder of mental health	-	Rattus norvegicus, Mus musculus, Homo sapiens	0.25	KE:341	Impairment, Learning and memory
AOP:500	Activation of MEK-ERK1/2 leads to deficits in learning and cognition via ROS and apoptosis	Developmental disorder of mental health	-	Rattus norvegicus, Mus musculus, Homo sapiens	0.29	KE:352	N/A, Neurodegeneration
AOP:500		Developmental disorder of mental health	-	Rattus norvegicus, Mus musculus, Homo sapiens	0.29	KE:341	Impairment, Learning and memory
AOP:520	Retinoic acid receptor agonism during neurodevelopment leading to impaired learning and memory	Developmental disorder of mental health	-	Mouse, Rat, Human	0.2	KE:341	Impairment, Learning and memory
AOP:525	Reduced oligodendrocyte differentiation during neurodevelopment leading to impaired learning and memory	Developmental disorder of mental health	-		0.08	KE:341	Impairment, Learning and memory
AOP:533	Retinoic acid receptor antagonism during neurodevelopment leading to impaired learning and memory	Developmental disorder of mental health	-		0.17	KE:341	Impairment, Learning and memory
AOP:535	Binding and activation of GPER leading to learning and memory impairments	Developmental disorder of mental health	-	Mouse, Human	0.11	KE:341	Impairment, Learning and memory
AOP:569	Decreased DNA methylation of FAM50B/PTCHD3 leading to IQ loss of children via PI3K-Akt pathway	Developmental disorder of mental health	-		0.17	KE:2121	decreased, Intellectual Quotient

No associated AOPs with Level of Relevance 3

No associated AOPs with Level of Relevance 5

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We have built a comprehensive resource which compiles potential endocrine disrupting chemicals (EDCs) based on the observed adverse effects or endocrine-mediated endpoints in published experiments on humans or rodents to support basic research. We are not responsible for any errors or omissions in the published research articles or supporting literature on potential EDCs compiled in this resource. Users are advised to exercise their own judgement on the weight of evidence for potential EDCs compiled in this resource. Importantly, our sole goal to build this resource on potential EDCs is to enable future basic research towards better understanding of the systems-level perturbations upon chemical exposure rather than influencing regulatory advice on chemical use.