Comparison of the Short Term Toxicity of Phthalate Diesters and Monoesters in Sprague-Dawley Male Rats

Abstract

This study was carried out to investigate the short term toxicity of nine phthalate diesters including di-2 (ethylhexyl) phthalate (DEHP) , di (n-butyl) phthalate (DBP) , di-n-octyl phthalate (DnOP) , diethyl phthalate (DEP) , butylbenzyl phthalate (BBP) , dimethyl phthalate (DMP) , di-isodecyl phthalate (DIDP) , diundecyl phthalate (DUP) , and di-isononyl phthalate (DINP) and five phthalate monoesters including mono- (2-ethylhexyl) phthalate (MEHP) , monobutyl phthalate (MBuP) , monobenzyl phthalate (MBeP) , monoethyl phthalate (MEP) , monomethyl phthalate (MMP) and phthalic acid (PA) in Sprague-Dawley male rats. Animals were administered 250 mg/kg/day (monoesters and PA) or 500 mg/kg/day (diesters) of phthalate for two weeks. All animals were examined for body and organ weights, blood hematology, serum biochemistry, and urine analysis. The body weight gain was significantly lower in rats treated with BBP, DBP, DINP, MEHP, MBuP, and PA than that of control. Liver weights were significantly increased in the DEHP,DBP, DnOP, DIDP, and MEHP groups as compared to the control group. Testes weights were significantly decreased only in the DEHP-, DnOP-, and DIDP-treated groups as compared to the control. Significant differences in hematological changes were not observed in any treatment groups. Significant increases in blood glucose levels were observed in the DEHP, MEHP, and MBeP groups. Aspartate aminotransferase (AST) levels were significantly increased in the DBP, DUP, DINP, MBuP, and MBeP groups, whereas alanine aminotransferase (ALT) levels were significantly increased only in the DEHP and MEHP groups. Serum ALP levels were significantly higher in phthalate diester (500 mg/kg/day) -treated rats as compared to control. However, the total cholesterol level was significantly reduced in the DEHP- and DIDP-treated groups, whereas serum triglyceride (TG) levels were higher in the DINP-, MEHP-, and MBuP-treated groups. These results suggest that short term toxicity of phthalate monoesters produces adverse effects as similar to phthalate diesters in Sprague-Dawley rats.

Investigation of the Potential Environmental Risks of Phthalate Derivatives Designed To Be Environmentally Friendly

“…The results showed that monoester products and glucuronic acid conjugates may show reproductive toxicity and biotoxicity (fish) and exert adverse effects on organisms. This finding is consistent with the fact that some metabolites of phthalates may have toxic effects and side effects in vivo (Kwack et al 2009, 2010). Potential environmental risk assessments of metabolites generated by biological metabolic processes have become an indispensable screening step in the molecular design of environmentally friendly phthalate derivatives.…”

Endocrine disruptors in the diet of male Sparus aurata: Modulation of the endocannabinoid system at the hepatic and central level by Di-isononyl phthalate and Bisphenol A

“…Similarly, in male mice exposed to BPA at 5 or 5000 μg/kg/day during fetal development, food intake remained unaltered or decreased, respectively (Angle et al, 2013) whereas in rats (both male and female), perinatal exposure to 50 μg/kg/day did not alter the food intake (Wei et al, 2011). Regarding DiNP, its administration at higher dosages in male rats for two weeks and for two years, decreased or did not alter the food intake (Kwack et al, 2010;Lington et al, 1997). Interestingly, a recent in vitro study using pico-and nanomolar doses of DiNP reported a decrease of npy mRNA expression in human neuronal cells (Rendel et al, 2017), confirming its negative effect on appetite control.…”

Association of diethylhexyl phthalate with obesity-related markers and body mass change from birth to 3 months of age

“… 1 4 Since PI has been commonly used as a valid index for the body density of newborns due to it having dimensions similar to those of density, we tested relations between DEHP metabolites and obesity-related markers at birth, including PI, and found significant decrease of PI and increase of TG by DEHP exposure. Since decreased PI and increased TG have been considered as risk factors for obesity after birth and in adults, 25 and lipid profile including TG was changed in the DEHP-treated Sprague-Dawley rats, 26 27 we evaluated body mass change during 3 months after birth after controlling for body mass increase accompanying infant growth and confirmed a significantly relative body mass increase during the 3 months after birth by DEHP exposure, supporting the contention that DEHP exposure in early life may increase the development of obese infants resulting in higher rate of obesity-related diseases. Moreover, exposure to DEHP in our study showed a marginally significant association for reduced leptin level after adjustment for newborns’ sex (data not shown here).…”