Systemic toxicity of di-2-ethylhexyl terephthalate (DEHT) in rodents following four weeks of intravenous exposure

► Clinically relevant route of exposure in preclinical testing (continuous infusion). ► DEHT - a structural isomer of DEHP. ► No indication of liver, kidney or reprotoxicity of DEHT in a 4 week rat study (continuous infusion). ► Preclinical safety testing of plastizicer used in medical devices. Di-2-ethylhexyl-terephtalate (DEHT) is a general purpose plasticizer and a structural isomer to di-2-ethylhexyl phthalate (DEHP) being known for its toxicity. Despite the fact that DEHT is used in quite a number of synthetics for medical device production including equipment for intravenous administration, toxicity of DEHT has not been assessed after/during intravenous exposure. Hence we report here the results of a toxicity study in male and female rats with continuous intravenous infusion of DEHT over 4 weeks. The study was done according to OECD guidelines under GLP conditions. The dose was infused per day to male and female rats over a period of 4 weeks with saline (control), middle chain triglycerides (vehicle) as well as with 38.2, 114.5 or 381.6 mg DEHT/kg. Each group ( n = 6) was closely monitored regarding survival, body weight development, food and water consumption. Moreover blood and urine samples were taken and a standardized necropsy as wall as a histological analysis was performed after the investigation period. DEHT had no effect on survival, body weight development, food and water consumption in the whole dose range investigated. There were no indications as to hematotoxicity or immunotoxicity. Clinical chemistry and histopathology indicated no exposure related effect on hepatic, thyroidal and reproductive functions or organs. DEHT administered via intravenous infusion was tolerated systemically and locally without adverse effects up to and including 381.6 mg/kg/day (NOAEL = 381.6 mg/kg × day). In particular, there were no effects on reproductive tissues/organs, kidneys, liver hepatocytes and peroxisomes, which are known targets of DEHP-toxicity.