2WuXi AppTec (Suzhou) Co., Ltd., People’s Republic of China
3Zhejiang Medicine Co., Ltd., Xinchang, People’s Republic of China
Abstract
The objective of this study was to evaluate whether Pyrroloquinoline Quinone (PQQ) disodium salt prepared by fermentation using Methylobacterium Methylophilus methylotrophus NCIB 10515 has teratogenic effects on rats when administered orally from Gestation Day 6 (GD6) to GD20 and to characterize the dose response relationship with toxicity. One hundred mated female rats were randomly assigned to 1 of 4 groups (n = 25/group). The control group received vehicle (purified water) by oral gavage once per day, and the test groups received PQQ diluted in purified water by gavage at doses of 50, 100, or 200 mg/kg bw/day daily from GD 6 to GD 20. The rats were observed daily for mortality and clinical signs. Body weight was assessed on GD 0, and every 3rd day after through GD21. Food consumption was assessed on GDs 1-2, 6-7, 9-10, 12-13, 15-16, and 19-20. On GD 21, all animals were necropsied and examined macroscopically. Ovaries and uteri were examined for litter data-those without visible implantation were placed in ammonium sulfide solution to assess whether early resorptions had occurred. Live fetuses were weighed and examined for external abnormalities. Then sex was determined and crown-rump length was measured. About half of each litter’s live fetuses were fixed with modified Davidson’s fixative for soft tissue examination and the remaining fetuses in were stained with Alizarin red solution for skeletal examination. There were no treatment-related changes on clinical or macroscopic observations, litter data, sex ratio, fetal weights, crown-rump length, or fetal structure. No mortality was observed. Based on the results of this study, the No Observed Adverse Effect Level (NOAEL) of PQQ disodium salt was considered to be 200 mg/kg bw/day, the highest dose tested, for maternal toxicity and embryo-fetal developmental toxicity.
Keywords: Pyrroloquinoline Quinone; PQQ Disodium Salt; Methylophilus methylotrophus NCIB 10515, Teratogenicity; Prenatal Development Toxicity
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