{"id":"340d71af-3837-53c1-af3a-8ebed1b55221","stable_key":"aaa7baba-8689-56ab-ba1e-b71542bcb8e9:iodine-trans-inhibitor-additivity","predicate":"competes_additively","statement":"Mixtures of perchlorate, thiocyanate and nitrate inhibited human NIS-mediated iodide uptake consistently with an additive common competitive model, without evidence of synergism.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"e1b6dcb2-8f8f-51d5-b7b9-610daabcb761","mechanism_event_label":"These competitors combined approximately additively in the tested cell system.","subject":{"id":"ada0a331-72b2-557f-84f6-8583fab1129c","slug":"perchlorate-ion","display_name":"Perchlorate ion","entity_type_key":"ion"},"object":{"id":"759b6f24-098d-5b19-b891-a5ad49fade50","slug":"cellular-iodide-uptake","display_name":"Cellular iodide uptake","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"e1b6dcb2-8f8f-51d5-b7b9-610daabcb761","stable_key":"aaa7baba-8689-56ab-ba1e-b71542bcb8e9:iodine-trans-inhibitor-additivity-event","event_type":"biochemical_relationship","label":"These competitors combined approximately additively in the tested cell system.","description":"Mixtures of perchlorate, thiocyanate and nitrate inhibited human NIS-mediated iodide uptake consistently with an additive common competitive model, without evidence of synergism.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"0d051c22-c0d2-5c22-91ad-4ee6894dc7a0","slug":"slc5a5","display_name":"Human sodium/iodide symporter / SLC5A5","entity_type_key":"protein"},"role":"transporter","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"83b11ca6-52c7-5a1b-8c39-d9cdf89244e3","slug":"iodide","display_name":"Iodide ion","entity_type_key":"ion"},"role":"substrate","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"ada0a331-72b2-557f-84f6-8583fab1129c","slug":"perchlorate-ion","display_name":"Perchlorate ion","entity_type_key":"ion"},"role":"competitor","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"5d54e0a3-869f-5132-82c9-4c0ff47cd400","slug":"thiocyanate-ion","display_name":"Thiocyanate ion","entity_type_key":"ion"},"role":"competitor","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"9ec2c9b8-c1c2-53e5-8e72-6a88638b814e","slug":"nitrate-ion","display_name":"Nitrate ion","entity_type_key":"ion"},"role":"competitor","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""},{"entity":{"id":"759b6f24-098d-5b19-b891-a5ad49fade50","slug":"cellular-iodide-uptake","display_name":"Cellular iodide uptake","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":5,"notes":""}]},"contexts":[{"dimension":"cross_nutrient","value_text":"false","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"CHO cells stably expressing human NIS; individual and mixed anion exposures with 125I uptake","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Joint Hill-equation fit; perchlorate molar potency was 15 times thiocyanate and 240 times nitrate.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Relative potencies and lack of synergy are assay-specific; they do not predict individual human thyroid outcomes from environmental concentrations.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Iodine research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"iodine","display_name":"Iodine","entity_type_key":"nutrient_element"}},{"dimension":"organism","value_text":"Human NIS in hamster CHO cells","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"These competitors combined approximately additively in the tested cell system.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[iodine-trans-inhibitors2004] Relative potencies and additivity of perchlorate, thiocyanate, nitrate, and iodide on the inhibition of radioactive iodide uptake by the human sodium iodide symporter. (2004). https://pubmed.ncbi.nlm.nih.gov/15650353/ DOI: 10.1089/thy.2004.14.1012","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Cell plasma membrane","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"9f44bff9-7589-52d1-ac34-77c7828070ea","evidence_kind":"source_excerpt","locator":"Lines 440-451","start_line":440,"end_line":451,"excerpt":"### iodine-trans-inhibitor-additivity\nMixtures of perchlorate, thiocyanate and nitrate inhibited human NIS-mediated iodide uptake consistently with an additive common competitive model, without evidence of synergism.\nCondition category: normal\nnutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: These competitors combined approximately additively in the tested cell system.\norganism: Human NIS in hamster CHO cells\ntissue_or_cell_type: Cell plasma membrane\nexperimental_model: CHO cells stably expressing human NIS; individual and mixed anion exposures with 125I uptake\nlimitations: Relative potencies and lack of synergy are assay-specific; they do not predict individual human thyroid outcomes from environmental concentrations.\nexposure: Joint Hill-equation fit; perchlorate molar potency was 15 times thiocyanate and 240 times nitrate.\ncross_nutrient: false\n[iodine-trans-inhibitors2004] Relative potencies and additivity of perchlorate, thiocyanate, nitrate, and iodide on the inhibition of radioactive iodide uptake by the human sodium iodide symporter. (2004). https://pubmed.ncbi.nlm.nih.gov/15650353/ DOI: 10.1089/thy.2004.14.1012","model_system":"CHO cells stably expressing human NIS; individual and mixed anion exposures with 125I uptake","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [iodine-trans-inhibitors2004] Relative potencies and additivity of perchlorate, thiocyanate, nitrate, and iodide on the inhibition of radioactive iodide uptake by the human sodium iodide symporter. (2004). https://pubmed.ncbi.nlm.nih.gov/15650353/ DOI: 10.1089/thy.2004.14.1012","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"76da623d-a34a-5a5c-a942-d7571a85c486","stable_key":"import-aaa7baba-8689-56ab-ba1e-b71542bcb8e9","title":"Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17)","document_type":"imported_text","citation_label":"AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text.","file_path":"","sha256":"a4885eb6f58bad4a4514c958b63834619e57b10aa7f694aa97d0f65c7d36548f","revision_id":"ea8001a1-b576-5eda-a193-883c7ad59b73","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}