Comparative Evaluation of Di-(2-Ethylhexyl) Phthalate and Tri-(2-Ethylhexyl) Trimellitate-Induced Alterations in Serum Albumin in Sprague-Dawley Rats

Abstract

Background: Plasticizers are widely used in polyvinyl chloride (PVC) products to enhance flexibility and durability. Di-(2-ethylhexyl) phthalate (DEHP), a commonly used phthalate plasticizer, has been associated with toxic effects involving oxidative stress, inflammation, and organ dysfunction. Tri-(2-ethylhexyl) trimellitate (TOTM) has emerged as an alternative plasticizer because of its lower migration potential and reduced systemic availability. However, comparative evidence regarding the renal effects of DEHP and TOTM remains limited.

Objective: The present study aimed to compare the effects of DEHP and TOTM exposure on serum albumin levels in Sprague-Dawley rats.

Methods: Fifty male Sprague-Dawley rats were randomly divided into five groups (n=10/group). Animals received normal saline, DEHP (300 mg/kg/day and 600 mg/kg/day), or TOTM (300 mg/kg/day and 1000 mg/kg/day) through oral gavage for 30 consecutive days. Serum albumin levels were measured at baseline, Day 15, and Day 30. Statistical analysis was performed using repeated-measures ANOVA followed by Tukey’s post hoc test.

Results: Baseline serum albumin levels were comparable among all groups. A significant reduction in serum albumin was observed in rats exposed to DEHP 600 mg/kg/day at Day 30 (3.90 ± 0.32 g/dL) compared with control animals (5.40 ± 0.01 g/dL; p<0.001). No significant alterations were observed in the DEHP 300 mg/kg/day group or either TOTM-treated group. Repeated-measures ANOVA demonstrated a significant treatment effect (F=21.26, p<0.001, η²=0.65).

Conclusion: High-dose DEHP exposure significantly reduced serum albumin levels, suggesting impaired renal protein handling and possible glomerular dysfunction. In contrast, TOTM did not significantly influence serum albumin concentrations, indicating a comparatively safer renal profile. These findings support the potential replacement of DEHP with TOTM in biomedical and consumer applications.