In a 4 week multiple dose study (GCP) designed to evaluate in vivo the safety and tolerability of HMRlignan™ and its metabolism into enterolactone after continuous 4 weeks administration at high doses (315 or 1350 mg) in healthy male volunteers, HMRlignan™ was demonstrated to be well tolerated, with no treatment related adverse events. HMRlignan™ and enterolactone levels were both elevated over the treatment period (approximately 10 times over the normal population average). After the treatment period, the levels returned back to control level.

Additional Safety Studies (according to GLP guidelines)

Genotoxic potential
•	Ames test: negative
•	Chromosome aberration: negative
•	Rat micronucleus: negative
Short-term toxicity
•	28 day studies the rat and dog: well tolerated
•	Teratogenic potential in the rat
•	No adverse effect on reproductive performance
•	No teratogenic potential, no adverse effects
Subchronic dietary toxicity study in the rat
•	No adverse effects. Slight anti-estrogenic effect