title: A 90-Day Oral Toxicological Evaluation of the Methylurate Purine Alkaloid Theacrine.
abstract: A 90-day repeated-dose oral toxicological evaluation was conducted according to GLP and OECD guidelines on the methylurate purine alkaloid theacrine, which is found naturally in certain plants. Four groups of Hsd.Brl.Han Wistar rats (ten/sex/group) were administered theacrine by gavage doses of 0 (vehicle only), 180, 300, and 375 mg/kg bw/day. Two females and one male in the 300 and 375 mg/kg bw/day groups, respectively, died during the study. Histological examination revealed centrilobular hepatocellular necrosis as the probable cause of death. In 375 mg/kg bw/day males, slight reductions in body weight development, food consumption, and feed efficiency, decreased weight of the testes and epididymides and decreased intensity of spermatogenesis in the testes, lack or decreased amount of mature spermatozoa in the epididymides, and decreased amount of prostatic secretions were detected at the end of the three months. At 300 mg/kg bw/day, slight decreases in the weights of the testes and epididymides, along with decreased intensity of spermatogenesis in the testes, and lack or decreased amount of mature spermatozoa in the epididymides were detected in male animals. The NOAEL was considered to be 180 mg/kg bw/day, as at this dose there were no toxicologically relevant treatment-related findings in male or female animals.
authors.affiliation: AIBMR Life Sciences, Inc., 2800 East Madison Street, Suite 202, Seattle, WA 98112, USA.
authors.forename: Amy
authors.identifier: 0000-0002-9044-673X
authors.initials: A
authors.lastname: Clewell
authors.affiliation: Toxi-Coop Zrt., Magyar Jakobinusok tere 4/B, Budapest 1122, Hungary.
authors.forename: Gábor
authors.initials: G
authors.lastname: Hirka
authors.affiliation: Toxi-Coop Zrt., Magyar Jakobinusok tere 4/B, Budapest 1122, Hungary.
authors.forename: Róbert
authors.initials: R
authors.lastname: Glávits
authors.affiliation: AIBMR Life Sciences, Inc., 2800 East Madison Street, Suite 202, Seattle, WA 98112, USA.
authors.forename: Philip A
authors.initials: PA
authors.lastname: Palmer
authors.affiliation: AIBMR Life Sciences, Inc., 2800 East Madison Street, Suite 202, Seattle, WA 98112, USA.
authors.forename: John R
authors.initials: JR
authors.lastname: Endres
authors.affiliation: AIBMR Life Sciences, Inc., 2800 East Madison Street, Suite 202, Seattle, WA 98112, USA.
authors.forename: Timothy S
authors.identifier: 0000-0002-7658-858X
authors.initials: TS
authors.lastname: Murbach
authors.affiliation: AIBMR Life Sciences, Inc., 2800 East Madison Street, Suite 202, Seattle, WA 98112, USA.
authors.forename: Tennille
authors.identifier: 0000-0002-5323-8982
authors.initials: T
authors.lastname: Marx
authors.affiliation: Toxi-Coop Zrt., Magyar Jakobinusok tere 4/B, Budapest 1122, Hungary.
authors.forename: Ilona
authors.initials: I
authors.lastname: Pasics Szakonyiné