{"id":"b212da43-0928-51ef-8af2-21d23cb51cae","stable_key":"33bef151-bdc7-5892-aff6-0345ab149739:the-subchronic-rat-noael-is-the-highest-dose-tested","predicate":"does_not_change","statement":"In a 90-day oral study in Sprague-Dawley rats at 0, 100, 300 and 1,000 mg/kg body weight per day, the no-observed-adverse-effect level was 1,000 mg/kg per day, the highest dose tested.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"neutral","is_public":true,"mechanism_event_id":"a76eba7e-526c-56e2-a1d2-36f76fdd9491","mechanism_event_label":"In a 90-day oral study in Sprague-Dawley rats at 0, 100, 300 and 1,000 mg/kg body weight per day, the no-observed-adverse-effect level was 1,000 mg/kg per day, the highest dose tested.","subject":{"id":"9910223c-2a27-5d75-8003-91d72e71be9a","slug":"nsk-sd","display_name":"NSK-SD fermented soybean extract","entity_type_key":"chemical_species"},"object":{"id":"6df7dbee-8bb5-54cc-987b-e6ce86497a76","slug":"rat-subchronic-toxicity-findings","display_name":"Adverse findings in a 90-day rat oral toxicology battery","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"a76eba7e-526c-56e2-a1d2-36f76fdd9491","stable_key":"33bef151-bdc7-5892-aff6-0345ab149739:the-subchronic-rat-noael-is-the-highest-dose-tested-event","event_type":"observed_intervention","label":"In a 90-day oral study in Sprague-Dawley rats at 0, 100, 300 and 1,000 mg/kg body weight per day, the no-observed-adverse-effect level was 1,000 mg/kg per day, the highest dose tested.","description":"Subchronic oral toxicology battery","status":"provisional","compartment":null,"participants":[{"entity":{"id":"9910223c-2a27-5d75-8003-91d72e71be9a","slug":"nsk-sd","display_name":"NSK-SD fermented soybean extract","entity_type_key":"chemical_species"},"role":"acting component","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"6df7dbee-8bb5-54cc-987b-e6ce86497a76","slug":"rat-subchronic-toxicity-findings","display_name":"Adverse findings in a 90-day rat oral toxicology battery","entity_type_key":"cellular_process"},"role":"component the finding is about","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""}]},"contexts":[{"dimension":"duration","value_text":"90 days","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"evidence_access","value_text":"Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Rat (Sprague-Dawley, 12 per sex per group)","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"NSK-SD at 21,900 FU/g, up to 1,000 mg/kg body weight per day","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"A NOAEL at the highest dose tested is a floor, not a ceiling. The material was non-mutagenic and non-clastogenic in vitro, and a 4-week human tolerance study at 10 mg/kg per day reported no problems. None of this tests interaction with antithrombotic drugs or long-term disease outcomes. This study and the regulatory opinion share the same applicant dossier and are not independent of one another.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"organism","value_text":"Rat (Sprague-Dawley, 12 per sex per group)","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"In a 90-day oral study in Sprague-Dawley rats at 0, 100, 300 and 1,000 mg/kg body weight per day, the no-observed-adverse-effect level was 1,000 mg/kg per day, the highest dose tested.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Toxicological assessment of nattokinase derived from Bacillus subtilis var. natto. (2016) https://pubmed.ncbi.nlm.nih.gov/26740078/ DOI: 10.1016/j.fct.2015.12.025","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"route","value_text":"In vivo, oral gavage","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue","value_text":"Subchronic oral toxicology battery","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"ded25b9a-e8e2-5e88-a809-68f7ce3d98e9","evidence_kind":"source_excerpt","locator":"Lines 1379-1379","start_line":1379,"end_line":1379,"excerpt":"In a 90-day oral study in Sprague-Dawley rats at 0, 100, 300 and 1,000 mg/kg body weight per day, the no-observed-adverse-effect level was 1,000 mg/kg per day, the highest dose tested.","model_system":"Rat (Sprague-Dawley, 12 per sex per group)","directness":"reported_statement","verification_status":"source_derived_draft","notes":"","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"41cb127c-1c23-53aa-b7d0-5ec7f6fa3c99","stable_key":"import-33bef151-bdc7-5892-aff6-0345ab149739","title":"Nattokinase: what the purified enzyme cleaves, what survives being eaten, and the gap between the two (2026-09-23)","document_type":"imported_text","citation_label":"Original AI-assisted curation built from a supplied entity-first document of 105 entities and 129 claims. Every reference in that document was resolved against live PubMed with its abstract read and its DOI cross-checked on 2026-09-23, and the EFSA novel-food opinion was retrieved and read in full. That check corrected two PMIDs that pointed at unrelated papers, two DOIs, and two papers recorded as carrying no erratum that do carry one; it also reversed three findings the supplied document had stated backwards. Two papers carry a published correction, recorded as such and not as a retraction. Three sources are not indexed in PubMed and are cited by what they have. Laboratory lineages are recorded, so the four papers from one group, the three from another and the two readings of a single applicant dossier cannot be counted as separate lines of support. Study-specific doses, units, populations and limitations retained; activity units are never converted between systems. Not publisher full text.","file_path":"","sha256":"34fc46e0e849d06bfa13cb099a79b50679dd6fd0de8a5a0575326afdde3259c1","revision_id":"efd063e6-e982-5f6e-a4b8-6f2ffe4185ce","review_status":"unverified_draft","notes":""}}],"relations":[{"id":"f88d34fe-e243-5f38-b312-aaf35b066cf6","relation_type":"limits_scope_of","notes":"Low intrinsic toxicity in an animal battery does not address an interaction with an antiplatelet drug in a person with fragile cerebral vessels.","source_claim_id":"b212da43-0928-51ef-8af2-21d23cb51cae","source_claim_key":"33bef151-bdc7-5892-aff6-0345ab149739:the-subchronic-rat-noael-is-the-highest-dose-tested","source_statement":"In a 90-day oral study in Sprague-Dawley rats at 0, 100, 300 and 1,000 mg/kg body weight per day, the no-observed-adverse-effect level was 1,000 mg/kg per day, the highest dose tested.","target_claim_id":"5da84366-cafb-5ecc-ba2a-71270b48227f","target_claim_key":"33bef151-bdc7-5892-aff6-0345ab149739:a-hemorrhage-followed-combined-nattokinase-and-aspirin-use","target_statement":"A patient taking aspirin for secondary stroke prevention had an acute cerebellar hemorrhage after seven consecutive days of nattokinase at 400 mg daily, with multiple cerebral microbleeds on MRI."}],"conflicts":[],"corrections":[],"research":null}