Comparative Toxicological Evaluation of Phthalate Diesters and Metabolites in Sprague-Dawley Male Rats for Risk Assessment

Abstract

In order to comparatively assess the systemic toxicity and sperm parameters, 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) were administered orally to Sprague-Dawley male rats at 250 (phthalate monoesters and PA) or 500 mg/kg body weight (bw)/d (phthalate diesters) for 4 wk. Liver weights were significantly increased in g roups treated with DEHP, DBP, BBP, DIDP, DINP, MEHP, and MBuP compared to the control. Testes weights were significantly reduced only in DEHP, DBP, and MEHP-treated groups compared to the control. Significant decreases in red blood cell (RBC) and hematocrit (Ht) levels were observed in DEHP-treated rats, whereas significant increases in mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), and platelet (PLT) levels were found in the DEHP-treated group. Hemoglobin (Hb) level was reduced only in the DMP group. Similar to effects on testis and epididymal weights, DEHP and MEHP significantly reduced sperm numbers and motility. In particular, DnOP, DBP, BBP, MEP, MBuP, DUP, DINP, and MBeP significantly lowered the sperm counts and sperm motility of epididymal sperm, detected by a change in the sperm motion parameters. The strongest to the weakest adverse effects for sperm motility were as follows: DEHP > DBP > DnOP > DUP > DIDP > BBP among diesters and MBuP > MEP > MEHP among monoesters, respectively. These results suggest that the adverse effects of phthalate esters (PEs) on sperm parameters in male rats are greater with phthalate diesters than monoesters, which may be useful for the risk assessment of phthalates.

This study was supported by a grant from National Institute of Toxicological Research, Korea Food and Drug Administration.