Subchronic Oral Toxicity Evaluation of Sodium Dehydroacetate: A 90-day Repeated Dose Study in Rats.

ABSTRACT

Objective: The present study was undertaken to evaluate the subchronic oral toxicity of sodium dehydroacetate (DHA-Na) and to determine the point of departure (POD), which is a critical factor in the establishment of an acceptable dietary intake. Methods: DHA-Na was administered once daily by gavage to Sprague-Dawley rats at dose levels of 0.0, 31.0, 62.0, and 124.0 mg/kg BW per day for 90 days, followed by a recovery period of 4 weeks in the control and 124.0 mg/kg BW per day groups. The outcome parameters were mortality, clinical observations, body weights, food consumption, hematology and clinical biochemistry, endocrine hormone levels, and ophthalmic, urinary, and histopathologic indicators. The benchmark dose (BMD) approach was applied to estimate the POD. Results: Significant decreases were found in the 62.0 and 124.0 mg/kg BW groups in terms of the body weight and food utilization rate, whereas a significant increase was found in the thyroid stimulating hormone levels of the 124.0 mg/kg BW group. Importantly, the 95% lower confidence limit on the BMD of 51.7 mg/kg BW was modeled for a reduction in body weight. Conclusion: The repeated-dose study indicated the slight systemic toxicity of DHA-Na at certain levels (62.0 and 124.0 mg/kg BW) after a 90-day oral exposure.