Abstract
To evaluate the safety of pyrroloquinoline quinone (PQQ) disodium salt prepared by microbial fermentation using Methylophilus methylotrophus NCIB 10515(T), bacterial reverse mutation test, in vivo rat micronucleus test, and acute and subchronic oral toxicity studies in rats were conducted. Bacterial reverse mutation and in vivo rat micronucleus tests revealed that PQQ disodium salt was not mutagenic and clastogenic. The mean lethal dose (LD50) was found to be higher than 2 g/kg body weight (bw) in rats. In a 90-day oral toxicity study, Sprague-Dawley (SD) rats were fed PQQ disodium salt at daily doses of 50, 100, or 200 mg/kg bw. No treatment-related abnormalities were observed in growth, food intakes, hematology and coagulation parameters, clinical chemistry and urine analysis parameters, organ weights, and histopathological examination parameters. Thus, the no-observed-adverse-effect-level (NOAEL) was set at 200 mg/kg bw/day, the highest level tested in this study. Our data support previous studies that reported the NOAEL values ranged from 100 to 400 mg/kg bw/day for PQQ disodium salt prepared by other manufacturing methods (by chemical synthesis or by microbial fermentation using Hyphomicrobium denitrificans) and indicated that PQQ disodium salt is safe as a food ingredient.
Keywords: Pyrroloquinoline Quinone Disodium Salt; Methylophilus Methylotrophus NCIB 10515 (T), Bacterial Reverse Mutation Test; In Vivo Micronucleus Test in Rats; Acute Oral Toxicity; Subchronic Oral Toxicity in Rats
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