Following a request from the European Commission, the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) was asked to deliver an opinion on the safety of pyrroloquinoline quinone disodium salt (PQQ), trade name BioPQQ™, as a novel food (NF) pursuant to Regulation (EC) No 258/97. The assessment, which follows the methodology set out in Commission Recommendation 97/618/EC, is based on the data supplied in the original application, the initial assessment by the competent authority of Ireland, the concerns and objections of a scientific nature raised by the other Member States and the responses of the applicant.
PQQ is produced by fermentation using Hyphomicrobium denitrificans CK-275 and purification process. The final form of the PQQ is a reddish-brown powder with a minimum purity of 99.0%. The source organism does not have a history of use in food. Notwithstanding the limited knowledge on the bacterial strain, neither the live bacteria nor the DNA are present in the NF above the detection limits of the analytical techniques applied. H. denitrificans is included in the microbiological specifications of the NF. The Panel therefore considers that the use of H. denitrificans does not raise concerns about the safety of PQQ.
The information provided on the composition, specifications, batch-to-batch variability, stability and production process of PQQ is sufficient and does not raise safety concerns.
The applicant intends to market PQQ for use in food supplements for healthy adults, except pregnant and lactating women, at a maximum proposed level of consumption of 20 mg/day (corresponding to 0.29 mg/kg bw per day for a 70-kg person). Food supplements containing PQQ are not intended for use by children. PQQ is naturally present at low levels in various food products. The proposed level of consumption is at least 250 times higher than the estimated background intake of PQQ occurring naturally in foods.
Taking into account the composition and the intended use levels of PQQ, the Panel considers that the consumption of PQQ is not nutritionally disadvantageous.
Information on the absorption, distribution, metabolism and excretion of PQQ in animals and humans is limited.
An in vitro bacterial reverse mutation assay, three in vitro chromosomal aberration tests and one in vivo micronucleus test were conducted with PQQ. Based on these studies, the Panel concludes that there is no concern with regard to potential genotoxicity of PQQ.
Twelve clinical studies were conducted on PQQ with doses up to 100 mg/day for up to 24 weeks. These studies do not raise safety concern. The Panel notes, however, that these studies were not designed to assess renal function and are of limited value for the safety assessment.
A 14-day dose-range finding study, a 90-day repeated-dose toxicity study and a 28-day renal toxicity have been conducted in rats using BioPQQ™. A 90-day repeated-dose toxicity study was also conducted using a PQQ product from another manufacturer with 98% purity. The Panel considers the findings of crystal and protein in urine at 200 mg/kg bw in the 28-day toxicity study as the critical effect based on the fact that renal toxicity was observed at a concentration of 768 mg/kg bw in the 14-day study. Therefore, the Panel considers 100 mg/kg bw from the 90-day study on BioPQQ™, which included a thorough urinalysis, as the overall no-observed-adverse-effect-level (NOAEL).
Considering the NOAEL of 100 mg/kg bw per day and the maximum proposed level of consumption, the Panel concludes that the margin of exposure (of 344) is sufficient.
The Panel concludes that the NF, pyrroloquinoline quinone disodium salt (BioPQQ™), is safe under the intended conditions of use as specified by the applicant.