Two‐generation reproduction study of di‐2‐ethylhexyl terephthalate in Crl:CD rats

Abstract

Increases in liver weights were found in the male and female animals exposed to 0.6% or 1.0% DEHT in the diet. Because there were no accompanying histopathologic changes, this effect was not considered adverse. Significant decreases in feed consumption in the female animals from the groups consuming 1.0% DEHT in the diet during lactation accompanied reduced postnatal pup body weights and rate of weight gain. Reductions in pup body weights later in lactation may also have been due to direct consumption of the treated feed by the pups or taste aversion to the same. Reduced relative spleen weight was found in male weanling pups from the 1.0% group in both generations and reduced relative spleen and thymus weights were found in female pups from the 1.0% group in the F(2) generation at necropsy on PND 21. Therefore, for parental and pup systemic toxicity, 0.3% DEHT in the diet (182 mg/kg/day) was considered no-observed-effect level (NOEL). The 1.0% DEHT (614 mg/kg/day) in the diet exposure concentration was considered a NOEL for F(0) and F(1) reproductive toxicity endpoints.

Non-phthalate plasticizers in German daycare centers and human biomonitoring of DINCH metabolites in children attending the centers (LUPE 3)

“…Again, no indications of genotoxicity from diverse in vitro tests have been demonstrated. In repeated dose studies, the liver was the primary target organ of DEHT, whereas in developmental studies, only decreased maternal growth was observed with no effect on the fetus or reproduction (Barber & Topping, 1995;Faber et al, 2007;Wirnitzer et al, 2011). For DEHA, repeated dose toxicity studies in animals found reduced body weight gains, but no evidence of carcinogenicity in rats.…”

Developmental toxicity and uterotrophic studies with di‐2‐ethylhexyl terephthalate

“…Prior investigations into the potential for DEHT to cause developmental toxicity include a rat two generation reproduction study conducted using dietary concentrations of 0.3, 0.6, and 1.0% DEHT (Faber et al, 2007). Consumption of diets containing up to 1.0% DEHT did not affect male or female fertility.…”

“…Parameters were measured as described above for the rat study except the laparohysterectomies were carried out on GD 18. Doses used in these studies were based on prior dietary studies (Knapp, 2005; Faber et al, 2007) or dietary levels capable of providing a maximal dose level of 1000 mg/kg/day to the test animals.…”

“…Extensive safety data for DEHT (the di‐2‐ethylhexyl ester of terephthalic acid) including acute toxicity, genotoxicity, subchronic studies, chronic toxicity, metabolism, and a rat two‐generation reproductive toxicity study have been reported previously (Barber and Topping, 1995; Faber et al, 2007) and along with the data reported in this study, have been reviewed in support of various regulatory approvals of food contact applications. Current Food and Drug Administration (FDA) approved end uses result in potential estimated daily dietary concentrations of approximately 16 ppb.…”

“…The chemical structures of DEHT and its structural isomer DEHP (the di‐2‐ethylhexyl ester of ortho ‐phthalic acid), have been depicted in an earlier report (Faber et al, 2007). Mono‐2‐ethylhexyl phthalate (MEHP), the persistent metabolite formed after DEHP exposure, is the moiety responsible for reproductive and developmental toxicity concerns that have arisen with the use of DEHP (Center for Evaluating Risks to Human Reproduction, 2005).…”