Developmental Effects of Di-n-butyl Phthalate after a Single Administration in Rats

Disruption of Retinol (Vitamin A) Signaling by Phthalate Esters: SAR and Mechanism Studies

“…Furthermore, after long-term culture DBuP lost inhibitory activity suggesting that it was metabolized to the non-inhibitory monoester or another metabolite. The lack of pathway inhibitory activity by MBuP in this in vitro system is contrary to results from in vivo studies which conclude that the monoester is the active form responsible for the effects of DBuP [ 32 ]. This lack of inhibition by MBuP may be related to factors unique to the in vitro system and further emphasizes the importance of metabolite analysis in understanding how phthalates disrupt the RSP in vitro which also may shed light on in vivo mechanisms.…”

“…This is based on (1) the similarities in the types of malformations induced in the male reproductive system in utero by both PEs and VAD; (2) data presented here showing that PEs cause the equivalent of VAD in vitro by interfering with the synthesis of RA; (3) PEs that are the most potent inhibitors of RA synthesis in vitro are also the most effective inducers of reproductive system malformations in utero; and (4) mechanistic studies documenting the essential role that RA synthesis plays in male reproductive system development and function. This hypothesis is further supported by studies showing that in utero exposure to DBuP during critical periods in development led to malformations, suggestive of homeotic transformations, in the axial skeleton of male and female rats [ 32 ] and that a VAD diet also causes a pattern of homeotic transformations in the rat axial skeleton [ 33 , 50 ]. It should also be noted that excessive levels of RA also induce distinct patterns of homeotic transformations in the mouse axial skeleton [ 17 , 51 ].…”

Preventive Effect of Aloe fleurentiniorum Extract against DBP in pregnant female rats

“…In addition, the present study found that there was a significant redu ct ion in fetal body weight and length, morphological and skeletal abnormalities of fetuses(Fig5&6 plate 3&4) viz maxilla bone elongation, abnormal appearance of the neck, reduction of the mandible bone, syndactyly of forelimbs and hindlimb phalanges, and less ossification of the ribs, the vertebral column was compressed and the terminal caudal vertebrae were absent in pregnant female rats treated with a single dose of 2000 mg/kg of DBP. This study is in agreement with the studies of [43,12,13,14,7,8] and disagreed with the study of Xie et al [44] who found an increase in fetal body weight following t reat m en t with 100 mg/kg/day of DBP.…”

Paternal exposure to di‐n‐butyl‐phthalate induced developmental toxicity in zebrafish (Danio rerio)

“…Although there are chemicals that induce both axial skeleton and skull malformation in zebrafish (Baker, Peterson, & Heideman, 2013), we found malformations in axial skeleton only. The malformations in axial skeleton induced by DBP were comparable with that of dietary vitamin A deficiency (VAD) in rats (Ema et al, 1997; Kaiser, Merrill, Stein, Breburda, & Clagett‐Dame, 2003; See, Kaiser, White, & Clagett‐Dame, 2008). Oxidation of vitamin A to its active metabolite all‐trans‐retinoic acid (atRA) is regulated by the retinol signaling pathway (RSP) (Balmer & Blomhoff, 2002).…”