• Environmental Mutagens and Carcinogens
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• v.21 no.2
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• pp.122-127
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• 2001

4-tert-octylphenol (OP) is a surfactant additive widely used in the manufacture of a variety of detergents and plastic products. Also, OP is known to have estrogenic activity by interacting with development and functions of endocrine system. This study was carried out to obtain toxicokinetic parameters of OP in male Sprague-Dawley rats. Male rats were administered OP, by either single oral (gavage) applications of 50, 100 or 200 mg/kg body weight. or a single intravenous injections of 1, 5 or 10 mg/kg body weight. Blood samples taken at several time intervals after administration were obtained from the femoral artery. Analysis of blood samples for OP was performed by gas chromatography mass spectrometry (GC/MS). The detection limit of OP was 1.9 ng/$m\ell$ at SIM (selected ion monitoring) mode of GC/MS. Calibration curve for analysis of the concentrations of OP in plasma was (OP/butylphenol peak area ratio) = 0.0294 $\times$ (plasma cone.) + 0.028 ($r^2$= 0.9991). The OP plasma concentration was 3921 ng/$m\ell$ immediately after single intravenous application, decreased rapidly within 45 min, and was detectable at low concentration up to 6 hr after application. When administered orally in rats (50, 100 and 200 mg/kg), OP was detected in the blood early after gavage administration, indicating the rapid initial uptake from gastrointestinal tract, with Tmax obtained from 0.67~0.83 hr. Using the AUC (area under the curve) of plasma concentration vs. time, low oral bioavailabilities of 1.2, 5.0 and 5.3% were calculated for the 50, 100 and 200 mg/kg groups, respectively.

• Journal of Environmental Health Sciences
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• v.30 no.2
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• pp.71-78
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• 2004

This study was performed to evaluate developmental and estrogenic activity of bisphenol A (BPA) and butyl benzyl phthalate (BBP) to the second generation of Sprague-Dawley rats ingested during gestational or lactational periods. Rats were given BPA 20$\mu\textrm{g}$/kg BBP 100mg/kg of pregnancy or lactation periods. Maternal body weight and neonatal body weight were recorded. The rats were sacrificed on day 21 after birth. Reproductive organs of dam and neonate were utilized for receptor binding assay. The plasma concentrations of BPA and MBep, one of the major metabolites of BBP were analyzed with HPLC. The co-administration of BPA and BBP induced slow weight gain compared with single administration in dams. Also, such mixture induced low neonatal body weights in next generation. The dams treated with BPA and BBP during lactational periods showed significant organ weight changes in liver and spleen. The dams exposed during lactational periods showed significant organ weight changes not only in liver and spleen but also in kidney, uterus and ovary. The F1 female rats exposed during lactation periods showed significant organ weight changes in liver, spleen, ovary. The F1 male rats showed significant organ weight changes in liver, kidney, epididymis, vesicular glands, prostate. However, no clear synergistic effects of BPA and BBP were noted. There was no significantly different ER$\alpha$ expression pattern between control and treated groups. However, ER$\alpha$ expression were increased in F1 male testis and female uterus. PI male showed distinct ER$\alpha$ expression, especially in the group of lactational combined exposure. Synergistic ER$\alpha$ expression was found by combined treatment of BPA and BBP. We could not find any evidences of synergistic effects on BPA and/or BBP combined administration on dams and their fetuses, except in ER$\alpha$ expression of F1 male.

• Applied Biological Chemistry
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• v.49 no.3
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• pp.254-258
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• 2006

Vitellogenin has been known as a potent biomarker protein for the estrogenic activity in fish exposed to endocrine disruptors. In this study, a piezoelectric immunosensor making use of an anticarp vitellogenin antibody and an AT-cut quartz crystal microbalance as the biological component and transducer was prepared, followed by its application to the analysis of carp vitellogenin as follows. Antibody immobilization was conducted by chemisorption of a thiolated antibody with a heterobifunctional thiolation cross-linker, sulfosuccinimidyl 6-[3-(2-pyridyldithio)propionamido]hexanoate. The reaction buffer for the immunosensor system was optimized as 0.1 M sodium phosphate (pH 7.4). Concentration-dependent sensor responses were obtained in the vitellogenin concentrations ranging from 0.4864 to 486.4000 nM, with a linear correlation between vitellogenin concentration and frequency shift in double-logarithmic scale. The limit of detection of the immunosensor for carp vitellogenin was presumed as 0.4864 nM.

• Journal of Food Hygiene and Safety
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• v.21 no.4
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• pp.258-262
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• 2006

To investigate additive effects of endocrine disruptors, we have histopathologically studied the exchanges of the reproductive organ to ovariectomized ICR mice. Female ICR mice were ovariectomized and then treated with endocrine disruptors after two weeks. Macroscopic exchanges, which were body weight, feed and water intake, of all groups were not seen during experiment period. Histopathological changes of uterine epithelial cells, vaginal epithelial cells, mammary glands and the diameter in uterine tubles were observed. In the results, the histopathological sensitivity to endocrine disruptors effect was more seen to the vaginal epithelial cell height than others. The additive estrogenic effects of endocrine disruptors, which were combinations of DEHP, DBP and BPA, were seen with E2 and BPA treatments. These results offers a sysmatic and mechanistically informative approach to assessing estrogenicity. It provides a useful profile of activity using a reasonable amount of resources and is compatible with the study of individual chemicals as well as the investigation of interactions among combinations of chemicals.

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

• Fisheries and Aquatic Sciences
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• v.24 no.10
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• pp.330-339
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• 2021

Oyster (Crassostrea gigas) is a marine bivalve mollusk widely distributed in coastal areas, and have been long widely used in industrial resources. Several studies demonstrated that fermented oyster (FO) extract attribute to bone health, but whether administration of FO play as an endocrine disruptor has not been studied. Therefore, in the present study, we investigated the effect of FO on the endocrine system in vitro and in vivo. As the results of the competitive estrogen receptor (ER) and androgen receptor (AR) binding affinities, FO was not combined with ER-α, ER-β, and AR. However, 17β-estradiol and testosterone, used as positive control, were interacted with ER and AR, respectively. Meanwhile, oral administration of 100 mg/kg and 200 mg/kg of FO doesn't have any harmful effect on the body weight, androgen-dependent sex accessory organs, estrogen-dependent-sex accessory organs, kidney, and liver in immature rats. In addition, FO supplementation has no effect on the serum levels of luteinizing hormone (LH), follicle stimulating hormone (FSH), testosterone, and 17β-estradiol. However, the relative weight of androgen- and estrogen-dependent organs were significantly increased by subcutaneously injection of 4.0 mg/kg of testosterone propionate (TP) and by orally administration of 1.0 ㎍ of 17α-ethynyl estradiol (EE) in immature male and female rats, respectively. Furthermore, TP and EE administration markedly decreased the serum LH and FSH levels, which are similar those of mature Sprague-Dawley (SD) rat. Furthermore, the testosterone and 17β-estradiol levels were significantly enhanced in TP and EE-treated immature rats. Taken together, our findings showed that FO does not interact with ER and AR, suggesting consequentially FO does not play as a ligand for ER and AR. Furthermore, oral administration of FO did not act as an endocrine disruptor including androgenic activity, estrogenic activity, and abnormal levels of sex hormone, indicating FO may ensure the safety on endocrine system to develop dietary supplement for bone health.

• Journal of Food Hygiene and Safety
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• v.21 no.2
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• pp.118-128
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• 2006

This study was conducted to determination of the endocrine distruptor function of 'Parabens' by dosing ethyl paraben, propyl paraben, isopropyl paraben, butyl paraben and isobutyl paraben to the immature SD rats. 18 groups were given vehicle control group, negative control group (Dibutyl phthalate), postive control group ($1'7-{\alpha}$ Ethynylestrdiol) and each paraben groups involved 3 dose level. Rats were injected with 62.5, 250 and 1,000mg/kg from postnatal day 19 till 21 once a day in subcutaneous and a total 3, times. There was no treatment related death. but, subcutaneous nodule, edema, alopecia and scrub formation on injection site was observed. These signs was become worse in high dose level. these signs was cause from physical stimulation by test substance which parabens were mix with com oil as vehicle. In the analysis of organ weights, absolute and relative weights of brain, spleen, liver, thymus, heart, kidneys, adrenals, ovaries and vagina were no difference with control group. but, wet and blotted weight of uterus was increased in every high dose parabens treat group. Especially, all dose level of isobutyl paraben was showed increment of uterus weight. uterus dilatation of parabens treated group was observed in gross anatomic pathology and these result was agree with wet and blotted weight of uterus. In the result of this study, estrogenic effect as endocrine distruptor was observed in ethyl paraben, propyl paraben, isopropyl paraben, butyl paraben and isobutyl paraben. and it was considered isobutyl paraben has highest estrogrnic effect under the condition of this study.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.33 no.4
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• pp.263-267
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• 2007

Parabens are used in nearly all types of cosmetics and toiletries because they are formulated well and have broad spectrum of activity, interness, low costs and excellent chemical stability in relation to pH. 2-phenoxyethanol and chlorphenesin are common preservatives which are usually used in combination with parabens in cosmetics. Toxicity of parabens is generally low but application of parabens to damaged or broken skin has resulted in sensitization. Moreover, the possibility of their estrogenic potential, anesthetic effects and reproductive toxicity has been reported. Consequently there are some regulations in use of parabens. And the maximum permitted concentrations of chlorphenesin and 2-phenoxyethanol in cosmetic products are authorized by the same reasons. So it is important to control and estimate the amount of parabens in products. In this article, we proposed a valid method for the simultaneous determination of 8 preservatives including parabens in a short time using ultra performance liquid $chromatography^{TM}\;(UPLC^{TM})$. Separation of eight components was achieved in less than 10 min and resolutions were reasonable (USP resolution ${\geqq}\;2$). And limit of detection and quantification were evaluated. The method was suitably validated for specificity, linearity, precision (repeatability, intermediate precision) and accuracy for assay (recovery) based on International conference on harmonisation (ICH) guideline. The method was applicable to analysis of preservatives in cosmetic products.

• The Journal of Korean Obstetrics and Gynecology
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• v.30 no.4
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• pp.18-44
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• 2017

Purpose: The object of this study was to observe the anti-climacterium activity of Gagamguibiondam-tang (GGOT) on ovariectomized (OVX) rats, a well-documented rodent models resembles with women postmenopausal climacterium symptoms, as including cardiovascular diseases, obesity, hyperlipidemia, osteoporosis, organ steatosis and mental disorders. Methods: In this study, anti-climacteric effects were evaluated separated into three categories; 1) anti-obese, 2) anti-uterine atrophy and 3) anti-osteoporotic effects. Five groups were used (8 rats in each group); sham control, OVX control, GGOT 500, 250 and 125 mg/kg administered groups. Twenty-eight days after bilateral OVX surgery, GGOT were orally administered, once a day for 84 days, and then the changes on the body weight and gain during experimental periods, serum estradiol levels, abdominal fat pad and uterus weights with histopathology of abdominal fat pads (total thickness and mean adipocyte diameters) and uterus (total, epithelial and mucosal thickness, percentages of uterine gland regions) for anti-obese and estrogenic effects. In addition, femur, tibia and fourth or fifth lumbar vertebrae (L4 or L5) wet, dry and ash weights, mineral density (BMD), bone strength (failure load), serum osteocalcin and bone specific alkaline phosphatase (bALP) contents, histological and histomorphometrical analyses - bone mass and structure with bone resorption, were monitored for anti-osteoporosis activity. Results: As a result of OVX, noticeable increases of body weight and gains, food and water consumption, weights of abdominal fat pad deposited in dorsal abdominal cavity, serum osteocalcin levels were demonstrated in this experiment with decrease of uterus, femur, tibia and L5 weights, serum bALP and estradiol levels. In addition, marked hypertrophic changes of adipocytes located in deposited abdominal fat pads, uterine disused atrophic changes, decreases of bone mass and structures of femur, tibia and L4 were also observed in OVX control rats with dramatic increases of bone resorption markers, the Ocn and OS/BS at histopathological and histomorphometrical analysis in this study as compared with sham-operated control rats, suggesting the estrogen-deficient climacterium symptoms - obese and osteoporosis were induced by OVX, respectively. However, these estrogen-deficient climacterium symptoms induced by bilateral OVX in rats were significantly inhibited by 84 days of continuous oral treatment of GGOT 500, 250 and 125 mg/kg, respectively. Especially, GGOT 500, 250 and 125 mg/kg showed clear dose-dependent inhibitory activities on the OVX-induced climacterium signs. Conclusion: The results suggest that oral administration of GGOT 500, 250 and 125 mg/kg has clear dose-dependent favorable anti-climacterium effects - estrogenic, anti-obese and anti-osteoporotic activities in OVX rats in this experiment.

• Development and Reproduction
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• v.4 no.1
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• pp.53-59
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• 2000

Endocrine disruptors (EDs) are exogenous chemicals which interfere several aspects of natural hormone properties. EDs with estrogenic activity have been recently reported to cause animal reproductive problems. This study was performed to investigate the effects of bisphenol A (BPA) on the mouse spermatogenesis in vivo. Male ICR mice were orally injected on a daily basis with low dose of BPA 20 mg/kg, high dose of BPA 200 mg/kg, or corn oil (vehicle control) for 7 days, and litter size and weights of body, testis, and cauda epididymis were measured. The level of serum testosterone and the expression of TGF- $\beta$$_1$ mRNA were also analyzed using RIA and RT-PCR, respectively. Also, morphological differences of testes after treatments were examined. Sperm concentration and level of serum testosterone showed a decreasing tendency detected as untreated >corn oil >low >high dose BPA treated mice, although there were no significant statistical differences. Interestingly, in mice treated with a high dose of BPA, partial disappearance of spermatozoa in seminiferous tubular lumen and the expression of TGF-$\beta$$_1$ mRNA were observed. Spermatogenesis was disrupted through TGF-$\beta$ system in the seminiferous tubules, resulting in no development of germ cells. Similarly, the litter size treated with a high dose of BPA was significantly different from that of untreated control group. In conclusion, these results that a high dose of BPA (200 mg/kg) acts as an endocrine disruptor during apermatogenesis in male mice md that there are BPA-specific lesions in the adult male reproductive tract might represent a permanently altered responsiveness to testosterone by BPA in the affected target tissue.