Subchronic Toxicity Assessment of Arsenic-Contaminated Rice Following Repeated Oral Administration in Wistar Rats

Arsenic is a naturally occurring metalloid with well-established toxic and carcinogenic properties, and dietary exposure through rice (Oryza sativa L.) represents a significant public health concern, particularly in populations with high rice consumption. Flooded paddy cultivation increases arsenic bioavailability, facilitating its accumulation in rice grains. While chemical monitoring and risk assessment indices are commonly used to estimate arsenic exposure, these approaches provide limited insight into the biological effects of long-term consumption. This study aimed to evaluate the subchronic toxicity of arseniccontaminated rice using a 90-day oral exposure model in Wistar rats, focusing on toxicological endpoints relevant to food safety assessment. Rice samples were selected using a conservative worst-case exposure strategy based on inductively coupled plasma–mass spectrometry (ICP-MS) arsenic profiling across several regencies in North Sumatra, Indonesia. Red, brown, and white rice samples with the highest arsenic concentrations in their respective categories were administered orally to female Wistar rats at doses of 8.1, 16.2, and 24.3 g/kg body weight per day for 90 consecutive days. A negative control group received 0.5% carboxymethyl cellulose sodium, while a positive control group received inorganic arsenic (0.3 mg/kg body weight). Clinical signs, body-weight changes, hematological parameters, serum biochemical markers of hepatic and renal function, and histopathological alterations in the liver and kidneys were evaluated. No mortality or severe clinical toxicity was observed in rice-treated groups. Bodyweight gain, relative organ weights, hematological indices, and renal biomarkers remained comparable to controls. Mild elevations in hepatic enzymes and focal hepatocellular alterations were observed only at the highest brown rice dose. In conclusion, subchronic oral exposure to arsenic-contaminated rice resulted in minimal systemic toxicity under the conditions tested, with the liver identified as the primary target organ at higher exposure levels. These findings provide biologically relevant evidence to support food safety evaluation of arsenic-contaminated rice.