Aspects of the testicular toxicity of phthalate esters.

Abstract

Di(2-ethylhexyl) phthalate (DEHP) produced seminiferous tubular atrophy and reductions in seminal vesicle and prostate weight in 4-week-old, but not in 15-week-old rats. Di-n-pentyl phthalate (DPP) did produce atrophy in the older rats but this developed more slowly than in young animals. Coadministration of testosterone or gonadotrophins did not protect against phthalate-induced testicular toxicity but did partly reverse the depression of seminal vesicle and prostate weight. Secretion of seminiferous tubule fluid and androgen binding protein by the Sertoli cells was markedly suppressed within 1 hr of a dose of DPP or mono-2-ethylhexyl phthalate (MEHP) in immature rats. This occurred less rapidly in mature rats.[14C]Mono-npentyl phthalate and [14C]MEHP penetrated the blood testis barrier only to a very limited extent. These findings and the early morphological changes in the Sertoli cells produced by DPP suggest that phthalate esters may act initially to cause Sertoli cell injury, the subsequent loss of germ cells occurring as a consequence of this.Some features of the testicular lesion could be reproduced in primary cocultures of rat Sertoli and germ cells. Structure activity studies with a range of phthalate monoesters showed good agreement between the induction of germ cell detachment in culture and testicular toxicity in vivo. Three metabolites of MEHP (metabolites V, VI, and IX) were much less toxic in culture than MEHP itself, suggesting that the latter may be the active testicular toxin from DEHP.

Health risks posed by use of Di-2-ethylhexyl phthalate (DEHP) in PVC medical devices: A critical review

“…[1985a,1985b]; Plonait et al [1993] Intestinal absorption occurs more readily in rodents than in primates, presumably because of higher concentrations of lipases [Rhodes et al, 1986]. Young rodents absorb DEHP/MEHP to a greater degree than adults [Gray and Gangolli, 1986]. Once absorbed, DEHP is widely distributed throughout the body, with fat, the lungs, absorptive organs (gastrointestinal tract), and excretory organs (liver, kidneys) being the major initial repositories.…”

Low-dose exposure to di-(2-ethylhexyl) phthalate (DEHP) increases susceptibility to testicular autoimmunity in mice

“…It was reported that exposure to DEHP causes testicular atrophy with spermatogenic disturbance (SD) in mice and rats [9][10][11][12][13][14]. Others have shown that DEHP is rapidly metabolized into mono-2-ethylhexyl phthalate (MEHP), and that MEHP induces spermatogenetic disturbance mainly via oxidative stress [9][10][11][12][13][14].…”

Phthalate, adipate and sebacate residues by HRGC-MS in olive oils from Sicily and Molise (Italy)

“…Studies on rodents involving large amounts of phthalates have shown damage to the liver and testes and birth defects (Gray, Butterworth, Gaunt, Grasso, & Gangolli, 1977). Mono-(2-ethylhexyl) phthalate (MEHP), a metabolite of DEHP, ultimately may be the active testicular toxicant and may increase the liver weight in rats (Gray & Beamand, 1984;Gray & Gangolli, 1986). In addition, a recent study showed that the di-butyl phthalate (DBP) or its metabolite mono-butyl phthalate (MBP) suppresses steroidogenesis by fetal-type Leydig cells in primates as in rodents (Ema, Murai, Itami, & Kawasaki, 1990;Hallmark et al, 2007;Parks et al, 2000).…”