Safety assessment of a novel, dietary pyrroloquinoline quinone disodium salt (mnemoPQQ®).

Pyrroloquinoline quinone (PQQ), a potent coenzyme antioxidant naturally occurring in foods, has been demonstrated to protect brain cells by enhancing the expression of nerve growth factors (NGF) and NGF receptors, and suppressing the fibril formation and aggression of amyloid ß. We developed mnemoPQQ®, a novel PQQ disodium salt and assessed its safety in GLP compliant toxicity studies. Acute toxicity studies of mnemoPQQ® in Wistar rats revealed that its LD50 was 1825- and 1410 mg/kg body weight (bw) in male and female rats, respectively, whereas its acute dermal LD50 was >2000 mg/kg bw. mnemoPQQ® was found to be nonirritant to the skin of rabbit in an acute dermal irritation/corrosion study, and classified mnemoPQQ® as a nonirritant to the eye of rabbit in an acute eye irritation/corrosion study. Ames bacterial reverse mutation assay and in vitro Mammalian cell gene mutation test exhibited its non-mutagenic potential. In mammalian in vivo erythrocyte micronucleus test, mnemoPQQ® was classified as non-clastogenic and non-mutagenic. A 90-day sub-chronic toxicity study, conducted at and up to the highest daily dose of 600 mg/kg body weight, revealed no evidence of systemic toxicity. All rats survived the treatment without any significant abnormal clinical signs and alterations in hematology, clinical chemistry, neurological evaluation, thyroid functions, reproductive hormone levels, sperm evaluations, vaginal cytology, endocrine functions, organ weight and gross and microscopic pathology findings. No observed adverse effect level (NOAEL) of mnemoPQQ® was found to be greater than 600 mg/kg body weight. These studies affirm that mnemoPQQ® has broad spectrum safety for human consumption.

Assessment of toxicity and tolerability of a combination vehicle; 5% Pharmasolve, 45% Propylene glycol and 50% Polyethylene glycol 400 in rats following repeated intravenous administration.

The selection of a suitable vehicle for administration of NCEs in non-clinical studies is always a challenge for poorly soluble compounds. Challenge is increased if the dose formulation is intended for intravenous (i.v.) administration where isotonic, biologically compatible pH and solution form is an absolute requirement. Vehicle toxicity and tolerability data are not readily available for a number of combination vehicles therefore, an i.v. tolerability studies was planned in rats with 5% v/v Pharmasolve (NMP), 45% v/v Propylene glycol (PG) and 50% v/v Polyethylene glycol (PEG) 400 combination, at dose volume of 0.5, 1, 2 and 5 mL/kg body weight for 28 days. The vehicle combination was administered via lateral tail vein and effects on clinical signs, body weights, feed consumption, clinical pathology and histopathology were evaluated. Clinical signs of toxicity like tremors, convulsions and death were noticed at 5 mL/kg during the course of the study. At 2 mL/kg, injection site injury without systemic toxicity was noticed. In conclusion, 1 mL/kg of a combination vehicle of 5% NMP, 45% PG and 55% PEG 400 can be administered intravenously once-a-day up to 28 days without any discomfort or injury to rats.