Effects of citrate ester plasticizers and bis (2-ethylhexyl) phthalate in the OECD 28-day repeated-dose toxicity test (OECD TG 407)

Abstract

Citrate esters are considered functional alternatives to phthalate plasticizers, but their toxicity remains poorly understood. The toxicity of citrate esters, including triethyl 2-acetylcitrate (ATEC) and trihexyl O-acetylcitrate (ATHC), were examined together with that of bis (2-ethylhexyl) phthalate (DEHP) using the Organization for Economic Co-operation and Development Test Guideline 407 (OECD TG407). Following 28-day oral administration, no significant differences in body weight or the weight of the brain, pituitary, heart, epididymis, seminal vesicles, or coagulating gland were found between the vehicle control and DEHP, ATEC or ATHC groups. In the 400 mg/kg day DEHP group, liver, adrenal, thymus, spleen, kidney, testis, and prostate weights were significantly increased. In the 400 mg/kg day ATHC group, kidney, adrenal, thymus, testis and prostate weights were significantly increased. In the 400 mg/kg day ATEC group, kidney, adrenal and testis weights were significantly increased. Hepatocyte size was significantly increased in the 400 mg/kg day DEHP group, suggestive of hepatotoxicity, but was not increased in the ATEC or ATHC groups. There were no significant differences in white blood cell, red blood cell or platelet counts, hemoglobin concentrations, hematocrit, mean corpuscular volume, fasting glucose, insulin, or testosterone concentrations between the vehicle control and DEHP, ATEC and ATHC groups. In the ATHC 400 mg/kg day group, T3 was decreased while T4 was increased, suggestive of disruption of thyroid function. The results of the OECD TG407 subacute repeated dosing toxicity test indicate ATEC is less toxic compared to ATHC or DEHP and could be recommended as an alternative to phthalate plasticizers.