title: Acute and subchronic toxicity studies of pyrroloquinoline quinone (PQQ) disodium salt (BioPQQ™) in rats.
abstract: The potential use of pyrroloquinoline quinone disodium salt (BioPQQ™), as a supplemental food ingredient, was evaluated in a range of oral toxicity studies in rats including an acute study, a 14-day preliminary and a 28-day repeated-dose study, and a 13-week subchronic study. The median lethal dose of BioPQQ™ was shown to be 1000-2000mg/kg body weight (bw) in male and 500-1000mg/kgbw in female rats. In the 14-day study, high doses of BioPQQ™ resulted in increases in relative kidney weights with associated histopathology in female rats only, while a follow-up 28-day study in female animals resulted in increases in urinary protein and crystals. These findings were reversible, and resolved during the recovery period. In the 13-week study, a number of clinical chemistry findings and histopathological changes were noted, which were deemed to be of no toxicological significance, as the levels were within the historical control range, were not dose-dependent, occurred at a similar frequency in control groups, or only occurred in the control group. Based on these findings, a no-observed-adverse-effect level of 100mg/kgbw/day was determined for BioPQQ™ in rats, the highest dose tested in the 13-week study.
authors.affiliation: NC Planning & Development Division, Mitsubishi Gas Chemical Co., Inc., 5-2, Marunouchi 2-chome, Chiyoda-ku, Tokyo, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Nakano
authors.affiliation: Central Laboratories, New Drug Research Center, Inc., 452-1, Toiso, Eniwa-shi, Hokkaido, Japan.
authors.forename: Hisaaki
authors.initials: H
authors.lastname: Takahashi
authors.affiliation: Central Laboratories, New Drug Research Center, Inc., 452-1, Toiso, Eniwa-shi, Hokkaido, Japan.
authors.forename: Seiko
authors.initials: S
authors.lastname: Koura
authors.affiliation: Intertek Scientific & Regulatory Consultancy, 2233 Argentia Rd., Suite 308, Mississauga, Ontario L5N 2X7, Canada.
authors.forename: Catherine
authors.initials: C
authors.lastname: Chung
authors.affiliation: Intertek Scientific & Regulatory Consultancy, 2233 Argentia Rd., Suite 308, Mississauga, Ontario L5N 2X7, Canada. Electronic address: shahrzad.tafazoli@intertek.com.
authors.forename: Shahrzad
authors.initials: S
authors.lastname: Tafazoli
authors.affiliation: Intertek Scientific & Regulatory Consultancy, 2233 Argentia Rd., Suite 308, Mississauga, Ontario L5N 2X7, Canada.
authors.forename: Ashley
authors.initials: A
authors.lastname: Roberts
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D007928:Lethal Dose 50; D008297:Male; D019055:No-Observed-Adverse-Effect Level; D009929:Organ Size / Q000187:drug effects; D045542:PQQ Cofactor / Q000008:administration & dosage / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D023382:Toxicity Tests, Acute / Q000379:methods*; D059550:Toxicity Tests, Subchronic / Q000379:methods*
chemical_list: D045542:PQQ Cofactor
keywords: Acute; BioPQQ™; PQQ; Pyrroloquinoline quinone disodium salt; Renal toxicity; Subchronic