• Development and Reproduction
• /
• v.21 no.2
• /
• pp.121-130
• /
• 2017

4-Nonylphenol (NP) is a surfactant that is a well-known and widespread estrogenic endocrine disrupting chemical (EDC). Although it has been known that the affinity of NP to ERs is low, it has been suggested that low-dose NP has toxicity. In the present study, the endocrine disrupting effects on reproduction, and the weight of gonads, epididymis, and uterus were evaluated with the chronic lower-dose NP exposing. This study was designed by following the OECD test guideline 443 and subjected to a complete necropsy. In male, NP had an effect on the weight of the testis and epididymis in both $F_0$ and $F_1$. In females, NP decreased the weight of ovary and uterus in $F_0$ but not in pre-pubertal $F_1$ pubs. Fertility of male and female in $F_0$ or $F_1$ was no related with NP administration. The number of caudal-epididymal sperm by body weight (BW) was not different between groups in both $F_0$ and $F_1$. Besides, the difference of the sperm number between generations was not detected. The number of ovulated oocytes was similar between groups in $F_0$, but significantly decreased in NP 50 group of $F_1$. The litter size and sex ratios of offspring in $F_1$ and $F_2$ were not different. The accumulated mating rate and gestation period were not affected by the NP administration. Those results shows that chronic lower-dose NP administration has an effect of endocrine disruptor on the weight of gonads and epididymis of $F_0$ and $F_1$ but not in reproduction. Based on the results, it is suggested that chronic lower-dose NP exposing causes endocrine disruption in the weight of gonad and epididymis but not in the reproductive ability of next generations.

• Korean Journal of Environmental Biology
• /
• v.22 no.4
• /
• pp.532-536
• /
• 2004

Due to the fourth-instar larvae of C. riparius have a sensitive to ecdysteroidal molting hormones for the life cycle developments, accordingly the emerged adult affected corresponding to larval phase's environments. The emerged female from larval phase exposure to DEHP observed a fact body and clumsy fling behavior in females. The body volume of treated female groups was clearly larger than that of control fe- males. In the 2D/E gel 1108 protein spots were identified. The visualized protein spots allowed extraction of 27 protein spots differed more than 3 fold in DEHP treated animals, which was approximately 2.4％ of the total protein spots. In this view, the body volume (or morphological characters) was well observed and detected faster than physiological detection for various EDCs. In this study, the body volume as a detecting po-int for EDCs suggested a bio-marker in individual levels.

• Toxicological Research
• /
• v.21 no.4
• /
• pp.333-338
• /
• 2005

Many of thyroid hormones disrupting chemicals induce effects via interaction with thyroid hormone and retinoic acid receptors and responsive elements intrinsic in target cells. We studied thyroid hormones disrupting effects of food additives and contaminants including BHA, BHT, ethoxyquin, propionic acid, sorbic acid, benzoic acid, CPM, aflatoxin B1, cadmium chloride, genistein, TCDD, PCBs and TDBE in recombinant HeLa cells containing plasmid construct for thyroxin responsive elements. The limit of response of the recombinant cells to T3 and T4 was $1\times10^{-12}\;M$. BHA. genistein, cadmium and TBDE were interacted with thyroid receptors with dose-responsive pattern. In addition, BHA, BHT, ethoxyquin, propionic acid, benzoic acid, sorbic acid, and TBDE showed synergism while cadmium chloride antagonism for T3-induced activity. This study elucidates that recombinant HeLa cell is sensitive and high-throughput system for the detection of chemicals that induce thyroid hormonal disruption via thyroid hormone receptors and responsive elements. Also this study raised suspect of BHA. BHT, ethoxyquin, propionic acid, benzoic acid, sorbic acid, TBDE, genisteine and cadmium chloride as thyroid hormonal system disruptors.

• Korean Journal of Environmental Biology
• /
• v.27 no.4
• /
• pp.323-333
• /
• 2009

Parabens are alkyl esters of p-hydroxybenzoic acid, which are widely used in foods, cosmetics, and pharmaceutic products as preservatives. Absorbed parabens are metabolized fastly and excreted. Actually human body is exposed to complex mixture of parabens. Safety assessment at various toxicological end points revealed parabens have a little acute, subacute and chronic toxicities. Some reports have argued that as parabens have estrogenic activity, they are associated with the incidence of breast cancer through dermal absorption by cosmetics. There is an inference that antiandrogenic activity of parabens may give rise to a lesion of male reproductive system, but also there is an contrary. At cellular level, parabens may inhibit mitochondrial function of sperms and androgen production in testis, but also there is an contrary. Parabens seem to have little or no toxicity in embryonic development. Parabens can cause hemolysis, membrane permeability change in mitochondria and apoptosis, suggesting cellular toxicity of parabens. Parabens evoked endocrine disruption in several fish species and have toxic effect on small invertebrates and microbes. Therefore, the toxicity of parabens should be considered as a potentially toxic chemical in the freshwater environment. In conclusion, though parabens may be considered as a low toxic chemical, more definite data are required concerning the endocrine disrupting effect of parabens on human body and aquatic animals according to route and term of exposure as well as the residual concentration of parabens.

• Korean Journal of Environmental Biology
• /
• v.32 no.4
• /
• pp.271-285
• /
• 2014

Aluminum flows into the river from the abandoned mine leachate, industrial wastewater, and sewage and is responsible for acute toxicity in aquatic organisms. Recently, the number of reports have indicated the increased toxicity in a variety of aquatic organisms' due to the aluminum toxicity. In this study, we reviewed the toxicity of aluminum on aquatic invertebrates, fishes and amphibians and suggested the guideline for management of aluminum residues in aquatic environment and strategies for aluminum toxicity evaluation. In aquatic animals aluminum complexes evoke gill dysfunction primarily, the cytotoxicity, genotoxicity, oxidative stress, disruption of endocrine function, reproductive success, metabolism and homeostasis. Notably, at environmentally relevant concentration, aluminum complex can alter the hormone levels in fish in acidic condition. Further, since the solubility of aluminum is higher in the acidic and basic conditions, thus it is likely that the toxic effects of aluminum may not only occur in acidic water near the abandoned mines but also in lakes and rivers, where pH is raised by algal bloom.

• Korean Journal of Ecology and Environment
• /
• v.38 no.1 s.110
• /
• pp.11-17
• /
• 2005

Egg masses of C. plumosus were collected from Jungnang Stream in Seoul and reared in an incubator chamber. The larvae of C. plumosus were treated with potential endocrine disruption chemicals (EDCs) such as Diethylhexyl phthalate (DEHP), Bisphenol A (BPA) and Tebufenozide, and the effects of morphological abnormalities were observed. The deformities of the mentum following exposure to EDCs showed the smooth/round tooth, the loss of ${\ge}$1 tooth, reduced median lateral teeth (MLT) and light brown color. The incidence rates of the mentum deformity were associated with chemicals: BPA (73.7 ${\sim}$ 90.9%)>tebufenozide (57.6 ${\sim}$ 78.9%)>DEHP (46.2 ${\sim}$ 85.7%). The deformity type of the mentum showed MIX (MLT+LT, 32 ${\sim}$ 46%)>MLT (25 ${\sim}$ 34%)>LT (lateral teeth, 3 ${\sim}$ 7%). Also, the incidence of MIX type was in the order of BPA (46%)>DEHP (33%) >tebufenozide (32%), and that of MLT type showed DEHP (34%)>tebufenozide (31%)>BPA (25%). As the concentration of Tebufenozide increased, the incidence of light brown mentum was dose dependent. While the incidences of light brown mentum following exposure to BPA and DEHP were not associated with their concentrations.

• Journal of Ginseng Research
• /
• v.47 no.3
• /
• pp.385-389
• /
• 2023

Background: Ginseng has been used as a traditional medicine for treatment of many diseases and for general health maintenance. Previously, we showed that ginseng did not demonstrate estrogenic property in ovariectomized mouse model. However, it is still possible that disruption of steroidogenesis leading to indirect hormonal activity. Methods: The hormonal activities were examined in compliance with OECD guidelines for detecting endocrine disrupting chemicals: test guideline (TG) No. 456 (an in vitro assay method for detecting steroidogenesis property) and TG No. 440 (an in vivo short-term screening method for chemicals with uterotrophic property). Results: Korean Red Ginseng (KRG) and ginsenosides Rb1, Rg1, and Rg3 did not interfere with estrogen and testosterone hormone synthesis as examined in H295 cells according to TG 456. KRG treatment to ovariectomized mice did not show a significant change in uterine weight. In addition, serum estrogen and testosterone levels were not change by KRG intake. Conclusion: These results clearly demonstrate that there is no steroidogenic activity associated with KRG and no disruption of the hypothalamic-pituitary-gonadal axis by KRG. Additional tests will be performed in pursuit of cellular molecular targets of ginseng to manifest mode of action.

• Toxicological Research
• /
• v.31 no.4
• /
• pp.331-337
• /
• 2015

Synthetic pyrethroids (SPs) are the most common pesticides which are recently used for indoor pest control. The widespread use of SPs has resulted in the increased exposure to wild animals and humans. Recently, some SPs are suspected as endocrine disrupting chemicals (EDCs) and have been assessed for their potential estrogenicity by adopting various analyzing assays. In this study, we examined the estrogenic effects of lambda-cyhalothrin (LC) and cypermethrin (CP), the most commonly used pesticides in Korea, using BG-1 ovarian cancer cells expressing estrogen receptors (ERs). To evaluate the estrogenic activities of two SPs, LC and CP, we employed MTT assay and reverse-transcription polymerase chain reaction (RT-PCR) in LC or CP treated BG-1 ovarian cancer cells. In MTT assay, LC ($10^{-6}M$) and CP ($10^{-5}M$) significantly induced the growth of BG-1 cancer cells. LC or CP-induced cell growth was antagonized by addition of ICI 182,720 ($10^{-8}M$), an ER antagonist, suggesting that this effect appears to be mediated by an ER-dependent manner. Moreover, RT-PCR results showed that transcriptional level of cyclin D1, a cell cycle-regulating gene, was significantly up-regulated by LC and CP, while these effects were reversed by co-treatment of ICI 182,780. However, p21, a cyclin D-ckd-4 inhibitor gene, was not altered by LC or CP. Moreover, $ER{\alpha}$ expression was not significantly changed by LC and CP, while down-regulated by E2. Finally, in xenografted mouse model transplanted with human BG-1 ovarian cancer cells, E2 significantly increased the tumor volume compare to a negative control, but LC did not. Taken together, these results suggest that LC and CP may possess estrogenic potentials by stimulating the growth of BG-1 ovarian cancer cells via partially ER signaling pathway associated with cell cycle as did E2, but this estrogenic effect was not found in in vivo mouse model.

• Journal of Environmental Health Sciences
• /
• v.29 no.2
• /
• pp.7-15
• /
• 2003

Di-2-ethylhexyl phthalate (DEHP), is a widely used plasticizer known to be a suspected endocrine disrupter, but its exact effects on aquatic organisms are not yet known. When Japanese medaka (Oryzias latipes) were exposed from the time of hatching to 3 months of age to an aqueous DEHP solution at nominal concentrations of 1, 10, and 50 $\mu\textrm{g}$/l, DEHP treated female fish showed distinct reproductive effect. And the midge (Chironomus riparius.). an aquatic invertebrate, was exposed to DEHP to evaluate the effects on reproductive processes via sediment toxicity. The test endpoints included emergence, sex ratio, fecundity, and the viability of F1 offspring egg ropes. The result implied that the normal developmental and/or reproductive processes in C. riparius had been disrupted when exposed to DEHP, the effect also being displayed in the next generation. In summary, DEHP hinders the development of reproductive organs in the female Japanese medaka and C. riparius.

• Journal of Microbiology and Biotechnology
• /
• v.33 no.10
• /
• pp.1351-1360
• /
• 2023

Endocrine-disrupting chemicals (EDCs) are compounds that disturb hormonal homeostasis by binding to receptors. EDCs are metabolized through hepatic enzymes, causing altered transcriptional activities of hormone receptors, and thus necessitating the exploration of the potential endocrine-disrupting activities of EDC-derived metabolites. Accordingly, we have developed an integrative workflow for evaluating the post-metabolic activity of potential hazardous compounds. The system facilitates the identification of metabolites that exert hormonal disruption through the integrative application of an MS/MS similarity network and predictive biotransformation based on known hepatic enzymatic reactions. As proof-of-concept, the transcriptional activities of 13 chemicals were evaluated by applying the in vitro metabolic module (S9 fraction). Identified among the tested chemicals were three thyroid hormone receptor (THR) agonistic compounds that showed increased transcriptional activities after phase I+II reactions (T3, 309.1 ± 17.3%; DITPA, 30.7 ± 1.8%; GC-1, 160.6 ± 8.6% to the corresponding parents). The metabolic profiles of these three compounds showed common biotransformation patterns, particularly in the phase II reactions (glucuronide conjugation, sulfation, GSH conjugation, and amino acid conjugation). Data-dependent exploration based on molecular network analysis of T3 profiles revealed that lipids and lipid-like molecules were the most enriched biotransformants. The subsequent subnetwork analysis proposed 14 additional features, including T4 in addition to 9 metabolized compounds that were annotated by prediction system based on possible hepatic enzymatic reaction. The other 10 THR agonistic negative compounds showed unique biotransformation patterns according to structural commonality, which corresponded to previous in vivo studies. Our evaluation system demonstrated highly predictive and accurate performance in determining the potential thyroid-disrupting activity of EDC-derived metabolites and for proposing novel biotransformants.