title: Human consumption of methyleugenol and its elimination from serum.
abstract: Under a mandate from the U.S. Congress, the National Toxicology Program (NTP) of the U.S. Department of Health and Human Services conducts animal bioassays for carcinogenicity of potentially toxic chemicals to which the U.S. population might be exposed. Methyleugenol, a natural as well as synthesized substance, was nominated for study because it is structurally similar to safrole, a known animal carcinogen. Methyleugenol was found to be a very potent multisite carcinogen in male and female F344/N rats and B6C3F1 mice at all doses tested in 2-year NTP bioassays using gavage dosing. For this reason, human toxicokinetic studies were added to the traditional NTP protocol. A commercial brand of gingersnaps was found by chemists at the Centers for Disease Control and Prevention to contain a relatively high concentration of methyleugenol. After thorough scientific and clinical review, and approval by a National Institutes of Health institutional review board for the protection of human subjects, a study was conducted with nine healthy adult male and female human volunteers. The volunteers were given 12 gingersnaps for breakfast. Blood was drawn immediately before the meal and at 15, 30, 60, and 120 min afterward. The mean +/- SD fasting level of methyleugenol in serum was 16.2 +/- 4.0 pg/g wet weight. Peak blood levels were found at 15 min (mean +/- SD, 53.9 +/- 7.3 pg/g wet weight), followed by a rapid decline; the half-life of elimination was about 90 min. The peak levels were within the range of methyleugenol blood levels in the U.S. population, as measured concurrently in a subset of nonfasting participants in the Third National Health and Nutrition Examination Survey (NHANES III).
authors.affiliation: University of Texas School of Public Health, Regional Campus at Dallas, 75390, USA. arnold.schecter@utsouthwestern.edu
authors.forename: Arnold
authors.initials: A
authors.lastname: Schecter
authors.forename: George W
authors.initials: GW
authors.lastname: Lucier
authors.forename: Michael L
authors.initials: ML
authors.lastname: Cunningham
authors.forename: Kamal M
authors.initials: KM
authors.lastname: Abdo
authors.forename: Greg
authors.initials: G
authors.lastname: Blumenthal
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Silver
authors.forename: Ron
authors.initials: R
authors.lastname: Melnick
authors.forename: Christopher
authors.initials: C
authors.lastname: Portier
authors.forename: Dana B
authors.initials: DB
authors.lastname: Barr
authors.forename: John R
authors.initials: JR
authors.lastname: Barr
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Stanfill
authors.forename: Donald G
authors.initials: DG
authors.lastname: Patterson
authors.forename: Larry L
authors.initials: LL
authors.lastname: Needham
authors.forename: Woodhall
authors.initials: W
authors.lastname: Stopford
authors.forename: Scott
authors.initials: S
authors.lastname: Masten
authors.forename: Jill
authors.initials: J
authors.lastname: Mignogna
authors.forename: Kuang Chi
authors.initials: KC
authors.lastname: Tung
mesh_terms: D000284:Administration, Oral; D000328:Adult; D002273:Carcinogens / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004032:Diet; D005054:Eugenol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D005506:Food Contamination; D006801:Humans; D008297:Male; D008875:Middle Aged
chemical_list: D002273:Carcinogens; C005223:methyleugenol; D005054:Eugenol