title: Characterizing the human equivalent dose of herbal medicines in animal toxicity studies.
abstract: BACKGROUND
  Herbal medicines have been generally believed to be safe. With the increasing use of herbal medicine worldwide, however, the safety of traditional herbal drugs frequently becomes a medical issue.
  
  
  OBJECTIVE
  This study was aimed to characterize the safe dose of herbal medicines through the systematic review for "human equivalent dose (HED)" from animal-based toxicity studies.
  
  
  METHODS
  A literature search for animal-based toxicity studies of herbal medicines in eight databases, including PubMed and Embase, was performed without language restriction. From the "no observed adverse effect level (NOAEL)" of each animal study, HED values were then calculated according to the composition (single or multiple herbs) and indication of the medicines.
  
  
  RESULTS
  Among 729 relevant articles identified in the initial screening, 112 (233 studies comprising 105 single-herb and 128 multiple-herb studies) that met our inclusion criteria were finally reviewed. The total average HED value (from mouse, rat, rabbit and dog) was 278.1±358.0 mg/kg, and the values for single- and multiple-herb studies were 322.7±488.4 mg/kg and 241.5±189.2 mg/kg, respectively. When the studies were analyzed according to herbal drug indication, drugs used for revitalization had the highest HED value (433.0±265.2 mg/kg), while those for infectious diseases had the lowest (110.6±118.6 mg/kg).
  
  
  CONCLUSIONS
  Our results provide important information regarding the safe dose of herbal medicines; thus, these data offer researchers and practitioners information critical for drug development or clinical application.
authors.affiliation: Korean Medical College of Daejeon University, 22-5 Yongwoon-dong, Dong-gu, Daejeon 301-724, Republic of Korea.
authors.forename: Ji-Won
authors.initials: JW
authors.lastname: Bae
authors.affiliation: Korean Medical College of Daejeon University, 22-5 Yongwoon-dong, Dong-gu, Daejeon 301-724, Republic of Korea.
authors.forename: Da-Hyun
authors.initials: DH
authors.lastname: Kim
authors.affiliation: Korean Medical College of Daejeon University, 22-5 Yongwoon-dong, Dong-gu, Daejeon 301-724, Republic of Korea.
authors.forename: Wha-Won
authors.initials: WW
authors.lastname: Lee
authors.affiliation: Korean Medical College of Daejeon University, 22-5 Yongwoon-dong, Dong-gu, Daejeon 301-724, Republic of Korea.
authors.forename: Hyo-Young
authors.initials: HY
authors.lastname: Kim
authors.affiliation: Liver and Immunology Research Center, Daejeon Oriental Hospital of Daejeon University, 22-5 Daeheung-dong, Jung-gu, Daejeon 301-704, Republic of Korea. Electronic address: ckson@dju.ac.kr.
authors.forename: Chang-Gue
authors.initials: CG
authors.lastname: Son
mesh_terms: D000818:Animals; D006801:Humans; D019055:No-Observed-Adverse-Effect Level; D008517:Phytotherapy / Q000009:adverse effects*; D018675:Toxicity Tests
keywords: Adverse drug reaction; HED; Herbal medicine; NOAEL safety