Assessing the toxic dose of the potent antioxidant 3,5-dihydroxy-4-methoxybenzyl alcohol in rats.

3,5-dihydroxy-4-methoxybenzyl alcohol (DHMBA), identified from the Pacific oyster Crassostrea gigas, has dual properties to block oxidative stress as a radical scavenger and a potential cell function regulator. DHMBA has been shown to suppress adipogenesis, inflammatory activated macrophages, osteoclastogenesis, osteoblastic bone formation, and anti-cancer activity in vitro, suggesting its role in preventing and treating several diseases. The toxicological effects of DHMBA may be important for the development of its pharmacological application. However, the toxicity of DHMBA has not been determined. To evaluate the no-observed-adverse-effect level of synthetic DHMBA, this study was conducted in male and female rats at a single oral dose of DHMBA 500, 1000, or 2000 mg/kg body weight, for 14 days at 30, 100, 300, and 1000 mg/kg/day, and for 91 days at the DHMBA 1, 5, and 25 mg/kg/day dose in male and female rats. The toxicological effects of DHMBA were evaluated by analyzing the changes in general condition, including body weight, behavior, body temperature, abnormal gait, decreased mobility, decreased alternate, slowed approach response, slowed touch response, slowed auditory response, abnormal righting reflex in air, and decreased abdominal muscle tone, blood biochemistry test, macroscopic pathological examination, organ weight, histopathological examination, inflammatory changes, or obvious abnormalities in the hematopoietic system. As a result, this study demonstrated that the no-observed-adverse-effect level of synthetic DHMBA in male and female rats was 25 mg/kg/day when administered for 91 days. This result may provide important toxicological information in the use of the DHMBA as a pharmacological tool.