• Molecular & Cellular Toxicology
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• v.2 no.2
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• pp.106-113
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• 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
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• v.48 no.5
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• pp.651-662
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• 2006

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 several aspects of reproductive function in rats especially sexual differentiation of the brain. To this end, the dams were provided with pulverized 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 postnatal day (PDN) 21, the day of weaning, and serum sex steroid hormone, gonadotropin levels and sexual behaviors after maturation were assessed. At Postnatal week (PNW) 20-21, serum levels of sex steroids and gonadotropins in both male and female rats, as well as estrous cyclicity in females, were not changed by perinatal exposure to DBP, DINP and DEHA, indicating that these chemicals did not affect sexual differentiation of the brain controlling the endocrine system of hypothalamo-pituitary-gonadal (HPG) axis. On the other hand, inhibitory influences on sexual behaviors, especially on ejaculation in males and lordosis in females, were observed by perinatal exposure to these chemicals. These results suggest that these chemicals may act directly on discrete regions of the hypothalamus regulating sexual behaviors, but not regulating gonadotropin secretion, thereby affect sexual differentiation of the brain with a resultant decrease in sex-specific behaviors in adulthood.

• Reproductive and Developmental Biology
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• v.30 no.4
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• pp.247-253
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• 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.

• Korean Journal of Veterinary Research
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• v.45 no.4
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• pp.545-552
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• 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.

• Journal of Environmental Health Sciences
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• v.46 no.5
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• pp.548-554
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• 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.

• Proceedings of the Korea Environmental Mutagen Society Conference
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• 2002.11a
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• pp.186-186
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• 2002

• Proceedings of the Korea Environmental Mutagen Society Conference
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• 2004.11a
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• pp.151-152
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• 2004

• Journal of Food Hygiene and Safety
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• v.22 no.3
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• pp.218-222
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• 2007

Di(2-ethylhexyl) phthalate (DEHP) and di-n-butyl phthalate (DBP) were screened for estrogenic activity using a recombinant yeast screening system consisted with estrogen receptors and ${\beta}-galactosidase$ as reporter gene. The chemicals showed estrogenic activity in ranges of $1{\times}10^{-10}\;to\;1{\times}10^{-7}M(DEHP)\;and\;of\;1{\times}10^{-9}M\;to\;1{\times}10^{-6}M(DBP)$ respectively. $17{\beta}-estradiol$, as a positive control of, showed maximal activity at $1{\times}10^{-9}M$. The concentration of half-maximal estrogenic activity was $1{\times}10^{-9}M$ for both chemicals. However, the concentration of maximal estrogenic activity was $1{\times}10^{-7}M$ for DEHP and $1{\times}10^{-8}M$ M for DBP. These results suggested that DBP was higher in relative potencies and more sensitive than DEHP. In conclusion, DEHP and DBP were both estrogenic, even though DBP was more reactive to estrogen receptor.

• Journal of Environmental Health Sciences
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• v.48 no.1
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• pp.52-58
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• 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.

• Proceedings of the Korean Society of Food Hygiene and Safety Conference
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• 2002.05a
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• pp.127-131
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• 2002

Migration of di-(ethylhexyl)phthalate (DEHF) from PVC food packaging materials detected plasticizer into food simulanting solvents(4% Acetic acid, 8% Ethanol, 50% Ethanol, 95% Ethanol, Heptane) were studied. For executing this study ,2 PVC food packaging materials detected DEHP were used. Analysis was by GC-FID and GC-MSD(selected ion monitoring) for DEHP, and optimized for quantification of plasticizer. The recovery of DEHP into food simulanting solvents were min. 87.4${\pm}$ 3.6 ∼ max. 109.9 ${\pm}$ 10.7% respectively. Following exposure to food simulants 95% Ethanol for 24hours at 60$^{\circ}C$ the migration results of 1020.90 ${\pm}$ 10.15$\mu\textrm{g}$/g, 563.54 ${\pm}$ 5.60$\mu\textrm{g}$/dm$^2$and 73.51 ${\pm}$ 5.09$\mu\textrm{g}$/g 149.22 ${\pm}$ 10.34$\mu\textrm{g}$/dm$^2$were detected from the container for lunch and for stock fish respectively.