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A Toxicological Evaluation of Methylliberine (Dynamine®).
Timothy S Murbach1, Róbert Glávits2, John R Endres1
1AIBMR Life Sciences, Inc., 2800 East Madison Street, Suite 202, Seattle, WA 98112, USA.
Journal of Toxicology
|January 9, 2020
Summary
Synthetic methylliberine showed no mutagenic or genotoxic effects in vitro and in vivo. However, male rats experienced reversible body weight effects and irreversible sexual organ changes at high doses, establishing a lower NOAEL for males than females.
Area of Science:
- Toxicology
- Food Science
- Pharmacology
Background:
- Methylliberine (CAS 51168-26-4) is a caffeine metabolite found in Coffea plants.
- Limited toxicological data exists for methylliberine in the public domain.
Purpose of the Study:
- To evaluate the potential health hazards of synthetic methylliberine as a food ingredient.
- To conduct a comprehensive toxicological investigation of methylliberine.
Main Methods:
- Bacterial reverse mutation test (Ames test).
- In vitro mammalian chromosomal aberration test.
- In vivo mammalian micronucleus test.
- 90-day repeated-dose oral toxicity study in Han:WIST rats with a 28-day recovery period.
Main Results:
- No in vitro mutagenic or clastogenic activity was observed.
- No genotoxicity was observed in the in vivo micronucleus test.
- In the 90-day study, no mortality or significant clinical effects were noted in either sex.
- Male rats showed dose-dependent, irreversible effects on body weight and sexual organs at the highest dose, and reversible body weight effects at a lower dose.
- No adverse effects were observed in female rats up to the highest dose tested.
- The No Observed Adverse Effect Level (NOAEL) was 225 mg/kg bw/day for females and 150 mg/kg bw/day for males.
Conclusions:
- Synthetic methylliberine demonstrates a lack of mutagenicity and genotoxicity.
- While generally well-tolerated, specific adverse effects were observed in male rats, necessitating a lower NOAEL compared to females.
- Further research is recommended to confirm the safety and assess the efficacy of methylliberine in human studies.
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