Are Structural Analogues to Bisphenol A Safe Alternatives? Comparative In-vitro and In-vivo Approaches to Study Reproductive Toxicity in Male Rats

Abstract

Background: Environmental health has emerged recently from observing the low outcomes of reproductive success of wildlife, birds and fish population in relation of their exposure to industrial chemicals. The intensive use of pesticides in agriculture and exposure of toxic chemicals which directly or indirectly lead to alterations in the reproductive functions of both human and wildlife to the concept of endocrine disrupting chemicals (EDCs). In the modern day EDCs list bisphenol A (BPA) has taken a prominent place. BPA is mainly used these days in the manufacturing of plastic bottles, plastic utensils, food containers, baby toys, feeding bottles and medical equipment. Studies have also shown that apart of wide range of useful applications BPA has hazardous mode of action on many systems of the body. Due to its wide range of toxic actions BPA has been banned in many countries including the European Union (EU) in several daily use items. This ban has led to the introduction of many BPA analogues which are considered to be safer than BPA and are these days used in the production of many daily use items. Bisphenol B (BPB), bisphenol F (BPF) and bisphenol S (BPS) are among the top of the safe BPA list. These all analogues consist of two phenol groups attached with a carbon of any other chemical bridge. Since these structurally similar compounds to BPA are expected to have similar or even stronger toxicological effects on humans and wildlife. Due to the ban of BPA in some other countries the production of these BPA analogues is at rise and is expected that this production is going to increase by double in the future. On the other hand, BPA analogues have already registered their presence in many environmental compartments as well as food, beverages and drinking water which has not only increased the risk of exposure to occupational and also general population. In the recent years studies have also shown that some of these analogues have shown estrogenic activity, potentials of inducing oxidative stress and as well as anti-androgenic effects in many experimental animal studies. Although the toxicity of BPA has been studied in great detail regarding reproductive functions in both mammalian and non-mammalian species though data regarding BPA analogues is scare. This brings the need for making a comprehensive data bank on the so called safe analogues of BPA. The main purpose of the present set of studies is to assess both in-vitro and in-vivo effects of these analogues on the sperm and testicular tissues of male rats. In this regard another set of sub-chronic study was done to compare the reproductive toxicity in male rats after exposure to the BPA analogues. In the last but not the least another set of experiments was carried out to understand the potential effects of BPA and its analogues BPB, BPF and BPS on the development of male reproductive system in both prenatal and neonatal male rats.