Safety Assessment of Vanillic Acid: Subacute Oral Toxicity Studies in Wistar Rats

Vanillic acid (VA) is a flavoring agent, a phenolic acid, and an intermediary by-product formed during transformation of ferulic acid to vanillin. It has been investigated for diverse pharmacological actions and used in Chinese medicine for decades. However, there is no information in the literature about its mechanism of toxicity or safety with long-term use. The present study will not only supply information on its pharmacological profile but also encourage evidence-based pharmacotherapeutic use. Hence, we performed a subacute toxicity study.

According to the Organisation for Economic Co-operation and Development Test Guideline 407 (2008), 3 groups of rats were formed consisting of 12 rats (6 male and 6 female) in each group. For the subacute toxicity, the dose was chosen after a limit test was conducted. VA (1000 mg/kg/day) was orally administered for 2 weeks to the treatment group, whereas the control group received an equivalent volume of the vehicle. To assess reversibility, VA (1000 mg/kg/day, p.o.) was administered to the satellite group for 2 weeks and animals were observed for an additional 2 weeks after treatment. The adverse signs, variation in body weight, and mortality were evaluated throughout the study period. On days 15 and 29, blood was collected to evaluate essential biochemical and hematological parameters. The animals were subsequently weighed and sacrificed. The weights of internal organs were recorded; gross necroscopy and histopathological studies were performed.

The hematological parameters of the satellite group increased and the serum sodium level decreased after the treatment. Satellite groups showed no other major change in biochemical parameters when compared to the control group. In addition, relative organ weights, gross necropsy examinations and histopathological structure of the internal organs showed no major alterations.

VA showed no adverse effect on the process of leukopoiesis, erythropoiesis or on internal organs, as verified by hematological and biochemical evaluations, gross necropsy, and histopathological studies. The decrease in serum sodium is not considered as a major toxic effect.