Bisphenol A (BPA), known as a typical endocrine disruptor, has been used commercially and widely for plastics and epoxy resins. BPA-based plastic is used extensively for the production of water bottles, food containers, CDs, DVDs, and panels that can be applied in construction. Epoxy resins containing BPA are used for coatings on the insides of water pipes, food cans, and thermal papers that are used in sales receipts. As its estrogenic effects and other adverse health effects have published, BPA has been regulated in many countries, and there have been efforts made to replace BPA. Other bisphenols substitutes such as bisphenol S (BPS) and bisphenol F (BPF) have been used. Currently, BPS- and BPF-based products labeled BPA-free products have been widely consumed. Because of structural similarities with BPA, however, these alternatives also show endocrine disruption effects like BPA, and many studies on adverse health effects of these alternatives are being reported. In this review, we describe the adverse health effects of bisphenols and the current status of regulation.

Nonylphenol is one of endocrine disruptors, as structurally stable, hydrophobic compounds exhibit high condensability and long-lasting in the natural environment. The purpose of this study was to determine the toxic effects of nonylphenol on Daphnia magna. In acute toxicity test, D. magna was exposed for 48 h at concentrations of 0, 10, 18, 32, 56 and 100 μg L-1 nonylphenol. In chronic toxicity test, D. magna were exposed through water for 21 days at concentrations of 0, 1.0, 1.8, 3.2, 5.6 and 10 μg L-1 nonylphenol. Acute toxicity was assessed on the basis of immobility, while chronic toxicity was assessed on the basis of fecundity. The acute toxicity test on nonylphenol was showed that the values of 24 h and 48 h EC50 were 25.0 μg L-1 and 13.7 μg L-1, respectively. In chronic test, fecundity was reduced significantly at 5.6 μg L-1 of nonylphenol. These results indicated that nonylphenol have some hazard for acute or chronic toxicity to freshwater invertebrate organism.

Endocirne disruptors (EDs) can cause fertility decrease, developmental disorder, and even cancer in animals. Until 90’s, EDs were used in various synthetic products including paints, coatings, detergents, plastics, and plasticizers. Currently, in several countries, the production, trade and use of EDs or EDs-suspected chemicals have been regulated while activity to screen the alternatives for EDs including bisphenol-A, phthalate and nonylphenol is active. Although various toxicity test method was developed and applied for screening of alternatives, however, the safety of alternatives has been not fully demonstrated. Some alternatives have high structural similarity with existing EDs, raising the possible risk of endocrine disruption by alternatives. In an effort to develop the safe alternatives, we reviewed the effects of EDs such as bisphenol-A, phthalates, nonylphenol and their substituents. In addition, in-silico analysis for endocrine disrupting activities of some alternatives was presented.

Worldwide there is concern about the continuing release of a broad range of environmental endocrine disrupting chemicals, including polychlorinated biphenyls, dioxins, phthalates, polybrominated diphenyl ethers (PBDEs), and other halogenated organochlorines persistent organic pollutants (POPs) into the environment. They are condemned for health adverse effects such as cancer, reproductive defects, neurobehavioral abnormalities, endocrine and immunological toxicity. These effects can be elicited via a number of mechanisms among others include disruption of endocrine system, oxidation stress and epigenetic. However, most of the mechanisms are not clear, thus several number of studies are ongoing trying to elucidate them in order to protect the public by reducing these adverse effects. In this review, we briefly limited review the process, the impacts, and the potential mechanisms of dioxin/dioxin like compound, particularly, their possible roles in adverse developmental and reproductive processes, diseases, and gene expression and associated molecular pathways in cells.

In mammals, the meiosis division in testes produces equal numbers of two different types of gametes: X chromosome-bearing sperm (X-spermatozoa) and Y chromosomebearing sperm (Y-spermatozoa), which have equal potential to fertilize the oocytes. Therefore, the expected 1: 1 sex ratio is observed. However, under some conditions like endocrine disruptors (EDs) exposure the sex ratio is deviated than the expected with more males or more females. And recently many hypotheses have been postulated to explain the mechanism of sex ratio deviation; however none of them introduced a proven experimental explanation. To solve this enigma, we hypothesized that the differences between X- and Y-spermatozoa survivability under specific conditions due to differences in their chromosome contents are the key leading to the sex ratio alteration. To examine our hypothesis, we combined two techniques; first, hypo-osmotic swelling (HOS) test that was applied to test viability of spermatozoa and second, fluorescence in situ hybridization that was applied on HOS-treated spermatozoa to define sex chromosome composition. In the present study, human spermatozoa were incubated with a group of EDs represent a widespread chemicals in the environment bisphenol A (BPA, 100 μM), nonylphenol (NP, 10 μg/ml), 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD, 2.5 μg/ml), genistein (Gen, 100 μM), and the following pesticides, dibromochloropropane (DBCP, 10 μg/ml), atrazine (Atraz, 500 μM), and diazinone (Diaz, 500 μM) for 6 hr at 37℃ in 5% CO2. Then, the viability of spermatozoa and their sex chromosome contents were evaluated simultaneously. Among seven chemicals studied only four chemicals (Atraz, DBCP, TCDD, and Diaz) significantly decreased Y-sperm viability when compared to those of X-spermatozoa in the same treatment group and viability of Y-spermatozoa when compared to those in the negative and positive (DMSO) control groups (p<0.05). Also, in these four treatment groups the sex ratio of live sperm population was significantly lowered compared to the control groups (p<0.05). Otherwise, Gen, BPA, and NP did not show any significant effect on viability of Yspermatozoa or decreasing sex ratio in live sperm population as compared to the control groups. It has been proven that TCDD, DBCP, and the pesticides decrease the sex ratio, but the same effect was not observed in case of Gen, BPA, and NP. From the present findings, there is no doubt that the EDs may alter sex ratio via decreasing Y-spermatozoa viability.

In the last few decades with the industrial revolution many environmental contaminants have estrogenic activity (endocrine disruptors, EDs) are released into the environment affecting the male reproductive system and male fertility. Sperm motility is one of the initial tests performed to assess sperm function; only motile sperm can achieve fertilization in vivo. The present study aimed to investigate the possible effects of a group of EDs that represent a widespread chemicals in the environment genistein (Gen), is a naturally occurring isoflavone (100 μM), bisphenol A (BPA), that is used in the manufacture of plastics and other products and released largely into the environment (100 μM), nonylphenol (NP) is an important environmental toxicant and potential endocrine disrupting chemical (10 μg/ml), TCDD, that is formed as an unwanted by-product in the manufacture of chlorinated hydrocarbons (2.5 μg/ml), atrazine (Atraz) is a herbicides (500 μM), dibromochloropropane (DBCP) is a pesticide (10 μg/ml), and diazinone (Diaz) is a insecticide (500 μM) on human sperm motility and kinematic characteristics. Human spermatozoa were incubated in Ham's F10 media with/without the tested chemicals or DMSO as positive control for 6 hr at 37℃ in 5% CO2. Then, sperm motility was assessed using computer assisted semen analyzer. Interestingly, all the chemicals tested significantly decreased sperm motility as compared to the control groups. However, only Diaz significantly decreased sperm kinematic characteristics namely, VCL, VSL, STR, VAP, and ALH. We suggest that the environmental chemicals may have an effect on male fertility via decreasing sperm motility.

This study was carried out to investigate the current status of suspected endocrine disrupting pesticides among the agricultural products in northern area of Seoul in 2007. 3,026 samples was analyzed by multiresidue method. Detected Pesticide in 11 cases were procymidone, endosulfan, chlorothalonil, chlorpyrifos, cyermethrin, fenvalerate, hexaconazole, carbendazim, pendimethalin, permethrin, parathion and exceeded 7 cases of endosulfan, procymidone, carbendazim, chlorothalonil, chlorpyrifos, cypermethrin, fenvalerate in the maximum residue limits(MRLs). Procymidone, endosulfan, chlorothalonil and chlorpyrifos comprised up to 80.5% in detected pesticides. Among the 321 cases of detected agricultural products, 287 cases(89.4%) were vegetables, 25 cases (7.8%) were fruits, Others were 9 cases(2.8%).

Although many studies have focused on the biological and toxicological effects of phenol products, in particular, in reproductive tracts, the data about their effects in this estrogenic responsive tissue are much less clear. In addition, the in vitro and in vivo data concerning ED-adverse impacts in other endocrine organs, i.e. pituitary gland, are not understood well either. Thus, a further study is needed for providing a new insight into possible impacts of estrogenic EDs including phenol products in humans and wildlife. A combination of in vitro and in vivo system for examining EDs may bring better understanding into the regulatory mechanisms underlying EDs-induced events. In addition, this information may support for developing optimal screening methods of estrogenic EDs, in particular, phenol products.

Nonylphenol (NP) is known to be an endocrine disruptor with estrogen-like activity. In this study, we tested low dose of NP and its alternative candidate Octyl-β-D-glucopyranoside (OG) on F1 female mice (n=10) from parents (P) generation to postnatal days(PND) 56. Animals [Control (tap water), NP-50 (50ug/L, drinking water), OG-50(50ug/L, drinking water)] were fed with normal chow and drinking water. ad libitum. Body weights and tissue weights were measured after sacrifice, and sera were measured using creatinine assay (n=8) and blood urea nitrogen (BUN) ELISA kit (n=8). Histopathology of kidney was used Hematoxylin & Eosin staining method and Periodic Acid-Schiff(PAS) staining method. NP treatment significantly increased body weight and kidney weight of F1 female(p<0.05). The serum levels of creatinine in NP-50 and OG-50 significantly decreased(p<0.001 and p<0.01, respectively) compared to the control group. In histopathological study, renal tubules spaces were increased and severe glomerular anomalies were found in NP-50 and OG-50. In NP-50, the thickened basal membrane was observed. The present study demonstrated that NP and OG has renal toxicity, and this toxicity due to long-term low dose treatment seems to be occurred in the next generation and female-specific.

Endocrine disruptors are exogenous chemicals that their endocrine disrupting effects mediated by androgenic signaling plays crucial roles in the control of development and several androgen-related diseases. However, there are no authorized in vitro screening and testing methods to evaluation of (anti-)androgenic activity. To find out a better in vitro cell line model, we have previously reported that 22Rv1 cells, a human prostate cancer cells contained functional Androgen Receptor (AR), might be an appropriate model for the evaluation of (anti-)androgenic endocrine disruptors. Based on this result, we developed a stable 22Rv1/mouse mammary tumor virus (MMTV) cell line to test AR-mediated transcriptional activation (TA). Using 22Rv1/MMTV cells, we established the test protocol and optimized the testing condition for AR-TA assay. In this study, we performed the inter-validation assay by four different laboratories to evaluate the 20 coded chemicals which were selected from the ICCVAM list (ICCVAM, 2003) or academic articles that exhibited exact (anti-) androgenic activity. The statistical analysis of the results of the inter-laboratory validation study revealed that there was reproducibility between the four participating laboratories. In conclusion, 22Rv1/MMTV AR-TA assay might be a quick and relatively inexpensive method, which can be used to screen large numbers of chemicals for their potential to activate or inhibit AR-mediated gene transcription. Furthermore, it will provide mechanistic data relevant to understanding adverse reactions observed in intact organisms.

Diethyl phthalate (DEP) and nonylphenol (NP) are widely spread in the natural environment as an endocrine disruption chemicals (EDs). Therefore, in this study, ultrasound (US) and ultraviolet (UVC), including TiO2, as advanced oxidation processes (AOPs) were applied to a DEP and NP contaminated solution. When only the application of US, the optimum frequency for significant DEP degradation and a high rate of hydrogen peroxide (H2O2) formation was 283 kHz. We know that the main mechanism of DEP degradation is radical reaction and, NP can be affected by both of radical reaction and pyrolysis through only US (sonolysis) process and combined US+UVC (sonophotolysis) process. At combined AOPs (sonophotolysis/sonophotocatalysis) such as US+UVC and US+UVC+TiO2, significant degradation of DEP and NP were observed. Enhancement effect of sonophotolysis and sonophotocatalysis system of DEP and NP were 1.68/1.38 and 0.99/1.17, respectively. From these results, combined sonophotocatalytic process could be more efficient system to obtain a significant DEP and NP degradation.

일부 식물성 에스트로겐(phytoestrogen)의 경우, 긍정적인 효과를 갖는 것으로 보이지만, 대부분의 내분비계 장애 물질(endocrine disruptor 또는 endocrine disrupting compound, EDC)은 노출된 개체의 내분비계를 교란시켜 인간이나 야생 동물의 건강에 해로운 것으로 알려져 있다. 선행 연구에서 본 연구자들은 사춘기 전에 단기간으로 식물성 에스트로겐인 genistein(GS)을 투여했을 때 암컷 흰쥐의 생식계가

내분비계 장애물질은 다양한 동물의 생식과 배아의 발생에 위해한 영향을 미친다고 보고되었다. 이러한 초기 배아의 비정상 발생 중 대표적인 것이 할구파편이다. 본 연구에서는 착상 전 생쥐 초기 배아를 PCB, BPA, DDT에 체내, 체외에서 각각 노출시켰다. 내분비계 장애 물질에 노출시켰던 배아는 할구파편, 불규칙한 할구와 깨짐, 일부 파괴된 투명대 배아 등의 다양한 형태학적 비정상 양상을 보였다. 착상 전 생쥐 초기배아의 세포괴사에 관여하는 유전자를 조