How dangerous are phthalate plasticizers? Integrated approach to toxicity based on metabolism, electron transfer, reactive oxygen species and cell signaling.

Phthalate plasticizers are the most abundant man-made pollutants that have recently received wide-spread attention. There is uncertainty concerning the toxicity to humans. During the debate, scant attention has been paid to adverse effects at the molecular level which is the focus of this article. Most metabolic reports are concerned only with ester hydrolysis. In addition to that aspect, an important study deals with formation of catechol carboxylic acids which have the potential to redox cycle with the o-quinone counterparts. This electron transfer (ET) process is capable of generating reactive oxygen species (ROS) which are well known toxic agents at elevated levels. Substantial numbers of investigations find the presence of ROS leading to oxidative stress (OS) in living systems containing phthalates. Insults occur to various organs, including the reproductive system, pulmonary, central nervous system, immune system and liver. Toxic reactions are also reported involving inflammation, mitochondria and carcinogenicity. Generally, OS evidently plays a role. Of relevance are prior reviews which document extensive evidence for association of ET-ROS-OS with organ toxicity, and other deleterious reactions. In addition, cell signaling has been related to the physiological effects of phthalates. Various signaling processes participate together with involvement of ROS and association with biological effects. Suggestions for future work are offered.