• Molecular & Cellular Toxicology
• /
• 제2권2호
• /
• pp.106-113
• /
• 2006

Phthalate analogues are a plasticizer and solvent used in industry. Phthalates were classified in the category of "suspected" endocrine disruptors. The purpose of our study was to screen and elucidate the endocrine disrupting activity of seven phthalate analogues. E-screen assay was performed in MCF-7 human breast cancer cells with seven phthalate analogues. In this cell proliferation assay, benzyl butyl phthalate (BBP) and dibutyl phthalate (DBP) showed high estrogenic activity. Their relative proliferation efficiencies (RPE) were 109 and 106%, respectively. In vitro estrogen receptor (ER) binding assay, BBP, di-n-octyl phthalate (DOP) and dinonyl phthalate (DNP) showed weak relative binding affinity (RBA: 0.02%) compared to $17{\beta}-estradiol\;(E2)$ (RBA: 100%). In uterotrophic assay, E2 produced a significant increase, whereas four tested phthalate analogues had potential estrogenic effects in vitro did not increased in uterus weight in immature rats. From these results, we demonstrated that phthalate analogues exhibit weak estrogenic activity in vitro assays at high concentrations. Although phthalates induced an increase in MCF-7 cell proliferation by an estrogenic effect, they could not induce a uterus weight increase in vivo. From these, we may suggest that these phthalate analogues are easily metabolized to inactive forms in vivo. Further investigation in other in vitro and in vivo experimental systems might be required.

• Journal of Animal Science and Technology
• /
• 제48권5호
• /
• pp.651-662
• /
• 2006

프탈레이트 에스테르는 플라스틱 가소제로서 이용되며 또한 유제품과 같은 음식에서 미량으로 발견되고, 종종 내분비 교란물질로 의심되고 있다. 본 연구의 목적은 DBP, DINP 또는 DEHA의 주산기 노출이 랫트에 있어 성 성숙 후, 번식기능 특히 뇌의 성분화에 어떤 영향을 끼치는 지에 대해 조사하였다. 이를 수행하기 위해서, 어미에게 식물성 에스트로겐의 함유가 낮은 분말 사료에 다음과 같은 단계적 농도의 DBP (20, 200, 2000, 10000 ppm), DINP (40, 400, 4000, 20000 ppm), DEHA (480, 2400, 12000 ppm)를 혼합한 후, 임신 15일째부터 출생 후, 21일째 (이유기)까지 섭취 시켰고, 성 성숙 후, 혈청 성호르몬 및 성선자극호르몬의 레벨과 교배행동 및 성주기 회귀를 분석하였다. 그 결과, DBP, DINP 또는 DEHA의 주산기 노출에 의한 생후 20~21주째의 암수 랫트에 있어, 성호르몬 및 성선자극호르몬의 레벨뿐만 아니라 암컷의 성주기의 회귀에 대해 어떠한 영향을 주지 않았다. 이것은 시상하부－하수체－성선축의 내분비계를 제어하는 뇌의 성분화에는 이들 화학물질이 영향을 주지 않았다는 사실을 시사한다. 하지만, 수컷의 성행동 특히, 사정 (ejaculation)과 암컷의 로도시스 반응이 억제되는 것이 관찰되었다. 이러한 결과로부터 DBP, DINP 또는 DEHA의 주산기 노출은 성선자극 호르몬의 분비에는 영향을 주지 않지만, 성행동을 제어하는 시상하부의 어떤 영역에 직접적으로 작용할 가능성 즉, 뇌의 성분화에 영향을 끼쳐 성 성숙 후, 성 특이적 행동을 억제시킬 가능성을 시사한다.

• Reproductive and Developmental Biology
• /
• 제30권4호
• /
• pp.247-253
• /
• 2006

Our previous research has identified granulin (grn) and p130 genes as sex steroid-inducible genes in the rat hypothalamus, which might be involved in sexual differentiation of the brain. Phthalate esters that are used as plasticizers and also found at low levels in foods such as dairy products are often mentioned as suspected endocrine disrupters. The purpose of the present study is to elucidate whether perinatal exposure to di-n-butyl phthalate (DBP), diisononyl phthalate (DINP) and di-2-ethylhexyl adipate (DEHA) affects hypothalamic sex steroid-inducible genes. The present study assessed the effects of perinatal exposure to DBP, DINP and DEHA on sex steroid hormones levels and hypothalamic gm and p130 mRNA expressions at postnatal day (PND) 3 and 7. Pregnant rats were fed a soy-free diet containing 20, 200, 2,000 and 10,000 ppm of DBP, 40, 400, 4,000 and 20,000 ppm of DINP, or 480, 2,400 and 12,000 ppm of DEHA from gestational day (GD) 15 to GD 3 or 7. At PND 3 and 7, perinatal exposure to these chemicals did not substantially affect serum concentrations of testosterone and estradiol. At PND 3, the expression of grn mRNA levels in males was decreased by DEHA, and that of p130 was decreased by DBP, DINP and DEHA, though the effects were not dose-dependent. At PND 7, the expression of gm gene in female pups was increased by higher doses of DBP and all the doses, except for 4,000 ppm, of DINP, while that in male pups decreased by 480 and 12,000 ppm of DEHA. Hypothalamic expression of p130 mRNA in males was increased by lower doses of DBP and all the doses of DINP, whereas that of females was decreased by 480 and 2,400 ppm of DEHA. These results suggest that these chemicals may affect the expression of gm and p130 genes by directly acting on the hypothalamus, thus leading to inappropriate expression of these genes.

• 대한수의학회지
• /
• 제45권4호
• /
• pp.545-552
• /
• 2005

The major protocol features of the rodent uterotrophic assay have been evaluated using a range of reference chemicals. The protocol variables considered include the selection of the test species and route of chemical administration, the age of the test animals, the maintenance diet used, and the specificity of the assay for estrogens. The rodents were ovariectomized under general anesthesia via bilateral flank incisions and randomly assigned to groups of 5 animals. Chemicals were DEHP, DBP, BPA and NP, were injected sc once daily with combinations of chemicals treatments for 3 days. In the results, the reported estrogenic chemicals DEHP and DBP were both negative in the single dose treatments. But, in the combinations of chemicals treatments, DEHP and DBP increased in bud number of mammary gland. Treatment of ovariectomized mice with combinations of other chemicals resulted in uterine and vaginal hyperplasia. The additive estrogenic effects were seen with the combinations of $17{\beta}$-Bestradiol and DBP treatment. the competitive estrogenic effects were seen with the combinations of $17{\beta}$-Bestradiol and nonylphenol, $17{\beta}$-Bestradiol and bisphenol-A 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. The results described illustrate the intrinsic complexity of evaluating chemicals for estrogenic activities and conform the need for rigorous attention to experimental design and criteria for assessing estrogenic activity.

• 한국환경보건학회지
• /
• 제46권5호
• /
• pp.548-554
• /
• 2020

Objectives: This study is to examine the polyvinyl chloride (PVC) materials in elementary school classrooms and libraries in Seoul, and to investigate phthalate contamination in indoor dust. Methods: PVC material was identified for building materials and furniture using portable x-ray fluorescence (XRF). Phthalates in dust samples (n=19) were extracted by ultrasonic extraction using cyclohexane and analyzed by GC-MS. Results: Diethyl phthalate (DEP), di-n-butyl phthalate (DBP), and Bis (2-ethylhexyl) phthalate (DEHP) were found in all collected dust samples (n=19), and diisonyl phthalate (DINP) was detected in all except for one sample (n=18). The concentration of DEHP (median: 2190 mg/kg) and DINP (2960 mg/kg) were higher than other compounds, suggesting that there are many products in the school that used these compounds. When comparing the phthalate concentration in the classroom (n=11) and library dust (n=8), the total concentration in the classroom (median: 10000 mg/kg) was higher than that in the library (8030 mg/kg). DEHP was the dominant compound in the library. The library is relatively more equipped with PVC furniture (n=83) and most floors are also identified as PVC material, suggesting that floors and furniture made of PVC materials are main sources of DEHP contamination. Conclusions: This study is a pilot survey for investigating phthalate contamination in elementary schools. As a result of the survey, phthalate contamination in elementary school was confirmed. However, further study requires risk assessment of children through analysis of phthalate metabolites in children based on sufficient number of samples and information about the site.

• 한국환경성돌연변이발암원학회:학술대회논문집
• /
• 한국환경성돌연변이발암원학회 2002년도 Molecular and Cellular Response to Toxic Substances
• /
• pp.186-186
• /
• 2002

• 한국환경성돌연변이발암원학회:학술대회논문집
• /
• 한국환경성돌연변이발암원학회 2004년도 KSOT/KEMS Fall Annual Meeting
• /
• pp.151-152
• /
• 2004

• 한국식품위생안전성학회지
• /
• 제22권3호
• /
• pp.218-222
• /
• 2007

에스트로젠 수용체와 리포터 유전자인 ${\beta}-galactosidase$가 도입된 효모재조합검색시험법을 이용하여 DEHP와 DBP의 내분비계 장애작용을 검색하였다. 양성대조 시험물질로 $17{\beta}-estradiol$을 설정하여 DEHP와 DBP의 에스트로젠 활성을 비교분석 하였을 때, $17{\beta}-estradiol$의 경우 $10^{-9}M$에서 가장 활성이 높게 관찰되었다. DEHP의 경우 $10^{-10}M$에서 $10^{-7}M$까지 시험하였을 때 농도의존적으로 에스트로젠활성이 증가하였으며, $10^{-7}M$의 경우 가장 강력한 에스트로젠활성을 보였다. DBP의 경우 $10^{-9}M$에서 $10^{-6}M$까지 에스트로젠활성이 관찰되었다. DEHP와 DBP의 경우 최대활성화 대비 50% 이상의 활성도를 보이기 시작하는 농도가 $10^{-9}M$로 나타나서 비슷한 농도에서 에스트로젠 활성화가 이루어지는 것으로 추측할 수 있었다. 그러나, 에스트로젠 최대활성화 시의 농도를 비교해 보면 DBP가 DEHP보다 10배 낮은 농도에서 최대활성치가 관찰되었기 때문에 DBP가 DEHP보다 에스트로젠 작용에 더 민감하게 반응하는 것으로 판단할 수 있었다. 결과적으로 본 실험에 사용되어진 시험물질인 DEHP와 DBP는 효모재조합시험법에 있어서 에스트로젠 활성을 유도하는 것으로 판단되어지며 감수성에 있어서는 DBP가 DEHP보다 높은 것으로 여겨진다.

• 한국환경보건학회지
• /
• 제48권1호
• /
• pp.52-58
• /
• 2022

Background: Few studies have evaluated the exposure to phthalates via inhalation of floor dust in children's living areas. Objectives: This study evaluated the concentration and exposure level of phthalates emitted from indoor floor dust in children's living areas. Methods: This study utilized the results of a survey conducted by the Ministry of Environment in 2019. Indoor dust was collected from 150 households with children aged 3~7 and 67 daycare centers or local children's centers by using vacuum cleaners. It was analyzed by gas chromatography mass spectrometry. Six types of phthalates were analyzed: Bis (2-ethylhexyl) phthalate (DEHP), Dibutyl phthalate (DBP), Benzyl butyl phthalate (BBP), Di-N-octyl phthalate (DNOP), Diisononyl phthalate (DINP), Di -isodecyl phthalate (DIDP). Results: The medians of DEHP concentrations were 1,028 and 1,937 mg/kg in homes and daycare centers, respectively. The median and maximum values of daily intake were calculated by applying the median and 95th percentile values (the upper 5% of the total concentration) in dust measured in the homes. The DEHP median value was 1.6 ㎍/kg/bw/day, and a maximum A value of 7.8 ㎍/kg/bw/day was calculated. When the childcare center values were applied, the median daily intake of DEHP was 3.1 ㎍/kg/bw/day and the maximum value was 29.2 ㎍/kg/bw/day. As a result of calculating the daily intake by integrating the values of home and childcare facilities, the median and maximum values of daily intake were 1.9 and 10.9 ㎍/kg/bw/day, respectively. Conclusions: This study derives phthalate concentrations among the floor dust in homes and childcare facilities where children mainly spend time, and suggests their intake of phthalates through this. In particular, it was newly suggested that the phthalate concentrations in homes and childcare facilities are different, resulting in differences in intake.

• 한국식품위생안전성학회:학술대회논문집
• /
• 한국식품위생안전성학회 2002년도 춘계학술발표대회 및 심포지움
• /
• pp.127-131
• /
• 2002

가소제가 검출된 PCV용기를 다른 식품유사침출용매(4%초산, 8%알코올, 50%알코올, 95%알코올, Heptane로 용출 실험한 결과, GC-FID와 GC-MSD(SIM Mode)에서 dimethyl phthalate(DMP), diethyl phthalate(DEP), 야-n-butyl phthalate(DBP), butyl benzyl phthalate(BBF), di(2-etylhexyl)phthalate (DEHP)의 분석한 결과 우수한 분리능력과 직선상을 보여주었다. 식품유사침출용매에 따른 전과정에 대한 각 프탈레이트 의 회수율을 시험한 결과. DEHP의 회수율은 4%초산에서 84.4 3.6%, 95%알코올에서 109.9$\pm$ 10.7%의 양호한 결과를 얻었으며, DEPH가 검출된 두 종류의 식품용기에서 식품유사침출용매에 따른 용출정도를 보기위해, 온도(2$0^{\circ}C$,6$0^{\circ}C$)와 시간(6시간,12시간,24시간,5일,10일)의 변화에 주어 실험한 결과, 도시락용기(1.10$\pm$0.18g,80$\mu\textrm{m}$ thickness)및 건어물용기(4.06$\pm$0.23g,240$\mu\textrm{m}$ thickness)모두 6$0^{\circ}C$ 95%알코올, 24시간에서 각각 1020.90 $\pm$ 10.15$\mu\textrm{g}$/g, 563.54 $\pm$ 5.60$\mu\textrm{g}$/dm$^2$, 73.51 $\pm$ 5.09$\mu\textrm{g}$/g 149.22$\pm$10.34$\mu\textrm{g}$/dm$^2$로 높았고, 시간경과에 따라 계속적인 증가 추세를 보였다.