Systemic toxicity of di (2-ethylhexyl) adipate (DEHA) in rats following 28-day intravenous exposure.

Abstract

Di (2-ethylhexyl) adipate (DEHA) is a potential plasticizer alternative for di-2-ethylhexyl phthalate (DEHP). Toxicity of DEHA has been studied mostly via oral exposure but not assessed after repeated intravenous exposure. The present study shows the toxicity effects after intravenous administration for 28 consecutive days and the reversibility of the effects following a 14-day recovery period. The study was conducted under GLP conditions. Four groups of rats (15/sex/group) each received either vehicle or DEHA in vehicle (100, 200, or 450 mg/kg/day). Criteria for evaluation included clinical observations, body weight, food consumption, clinical pathology (hematology, serum chemistry, coagulation, urinalyses), gross (necropsy) evaluation, organ weight and histopathological evaluation. There were no DEHA-related changes in all the endpoints evaluated at 100 or 200 mg/kg/day. There were no test article-related changes in clinical pathology or gross necropsy observation at 450 mg/kg/day. At the high-dose, DEHA-related findings included clinical observations, decreased body weight gain and food consumption, increased liver weight in females associated with minimal hepatocellular hypertrophy, and decreased thymus weight in males and females without histopathology findings. All these findings were completely reversible within a 14-day recovery period. Therefore, the 200 mg/kg/day dose is considered to be the No-Observed-Effect Level (NOEL).

• Authors: Haiyan Xu, Barbara Musi, Zhimei Wang, Tiansheng Zhou, Qihong Huang, Juanhua Liu, Tiantian Li, Zhen Jiang, Songping Liao, Glosson Jill, Edward Koo
• Journal: Regulatory toxicology and pharmacology : RTP (Regul Toxicol Pharmacol) Vol. 104 Pg. 50-55 (Jun 2019) ISSN: 1096-0295 [Electronic] Netherlands
• PMID: 30826316 (Publication Type: Journal Article)
• Copyright: Copyright © 2019 Elsevier Inc. All rights reserved.

Chemical References

• Adipates
• dioctyl adipate

Topics

• Adipates (administration & dosage, toxicity)
• Administration, Intravenous
• Animals
• Body Weight (drug effects)
• Dose-Response Relationship, Drug
• Energy Intake (drug effects)
• Female
• Liver (drug effects)
• Male
• Rats
• Rats, Sprague-Dawley
• Thymus Gland (drug effects)