Yun-jung Yang

Acute Testis Toxicity of Bisphenol A Diglycidyl Ether in Sprague-Dawley Rats

OBJECTIVES Bisphenol A diglycidyl ether (BADGE) is a liquid compound obtained by condensation of two molecules of epichlorohydrin with one molecule of bisphenol A. General and reproductive toxicity with BADGE has been reported higher than 1000 mg/kg/day. This study was performed to show the effects of acute exposure to BADGE below 1000 mg/kg/day on the testis in adult male rats. METHODS BADGE was administered by gastric lavage in a single dose of 500, 750, 1000, and 2000 mg/kg/day in 8-week old male SPF Sprague-Dawley rats. The right testis was processed for light microscopic analysis. The left testis was homogenized and spermatids were counted to determine the daily sperm production and daily abnormal sperm production. The sperm count, sperm motility, and incidence of abnormal sperm were estimated in the epididymis. In testicular sections, the seminiferous tubules were observed for qualitative changes. The progression of spermatogenesis was arbitrarily classified as full-matured, maturing, and immature. The specimen slide was observed at 3 points and 10 seminiferous tubules were evaluated at each point. RESULTS The male rats exposed to single oral dose of BADGE at 750, 1000, and 2000 mg/kg/day were significantly increased the number of immature and maturing sperm on the testis. There were no significant differences with respect to sperm head count, sperm motility, and sperm abnormality in the BADGE treatment groups. CONCLUSIONS These results suggest that single oral exposure of BADGE 750 mg/kg/day can affect adult male testis development.

Assessment of Di (2-ethylhexyl) Phthalate Exposure by Urinary Metabolites as a Function of Sampling Time

OBJECTIVES In most DEHP exposure assessment studies, single spot urine sample was used. It could not compare the exposure level among studies. Therefore, we are going to represent the necessity of selection of proper sampling time of spot urine for assessing the environmental DEHP exposure, and the association urinary DEHP metabolites with steroid hormones. METHODS We collected urine and plasma from 25 men. The urine sampling times were at the end of the shift (post-shift) and the next morning before the beginning of the shift (pre-shift). Three metabolites of DEHP {mono(2-ethylhexyl) phthalate [MEHP], mono-(2-ethyl-5-hydroxyhexyl)phthalate [MEHHP], and mono(2-ethyl-5-oxohexyl)phthalate [MEOHP]} in urine were analyzed by HPLC/MS/MS. Plasma luteinzing hormone, follicle stimulating hormone, testosterone, and 17ß-estradiol were measured at pre-shift using a ELISA kit. A log-transformed creatinine-adjusted urinary MEHP, MEHHP, and MEOHP concentration were compared between the post- and pre-shift. The Pearsons correlation was calculated to assess the relationships between log-transformed urinary MEHP concentrations in pre-shift urine and hormone levels. RESULTS The three urinary metabolite concentrations at post-shift were significantly higher than the concentrations in the pre-shift (p<0.0001). The plasma hormones were not significantly correlated with log-transformed creatinine - adjusted DEHP metabolites. CONCLUSIONS To assess the environmental DEHP exposure, it is necessary to select the urine sampling time according to the study object. There were no correlation between the concentration of urinary DEHP metabolites and serum hormone levels.

Environmentally relevant levels of Bisphenol A may accelerate the development of type II diabetes mellitus in adolescent Otsuka Long Evans Tokushima Fatty rats

Environmental chemicals may contribute to the development of obesity and metabolic disorders such as diabetes. Bisphenol A (BPA) is one of the environmental chemicals that are widely used in daily life. This study was performed to investigate whether low dose BPA exposure can influence the occurrence of type II diabetes mellitus. Four weeks old Otsuka Long Evans Tokushima Fatty (OLETF) rats were randomly assigned to three groups of five animals and each group was given different concentrations of corn oil with BPA (0, 0.001, and 0.1 mg/kg/day). BPA 0.1 mg/kg/ day produced impairment of glucose tolerance, and induced higher insulin (p=0.028) and malondialdehyde levels (p=0.009) in serum than control group. Serum insulin levels in BPA 0.001 mg/kg/day treated group showed significantly higher than the control group (p=0.016). BPA tended to induce down-regulation of PPARγ mRNA and protein expression in white adipose tissue than control. In conclusion, low dose BPA exposed OLETF rats in adolescent period could accelerate the development of diabetes mellitus in younger adult period.

Reduction in semen quality after mixed exposure to bisphenol A and isobutylparaben in utero and during lactation periods.

This study was performed to determine the effect of low-level exposure to a mixture of bisphenol A (BPA) and isobutylparaben (IBP) on male reproduction. Corn oil, BPA (0.05 mg/kg/day), IBP (2.5 mg/kg/day), and a BPA/IBP mixture (BPA 0.05 mg/kg/day and IBP 2.5 mg/kg/day) were administered once daily by oral gavage to female rats for 5 weeks from gestation day 6 to lactation day 21. Male pups were killed at postnatal day 70 and examined for developmental characteristics, body weight, testis and epididymis weight, steroid hormones, epididymal sperm count and motility, and histological changes in testis and epididymis. The BPA/IBP mixture produced a significant downregulation of epididymal sperm count and motility. BPA or IBP alone also reduced epididymal sperm count and motility compared to control. These results indicate that exposure to low-level BPA/IBP mixture, which showed no notable physiological response in early life stages, can decrease semen quality in adulthood.

Combination effects of bisphenol A and isobutylparaben on the green macroalga Ulva pertusa

Endocrine related disorders have increased in human and wildlife due to the exposure of the endocrine disruptors (EDs). Estrogenic EDs can generate combination effects when they are present in a mixture at a concentration that does not individually induce observable effects. Therefore, this study was performed to characterize the reproductive toxicity of bisphenol A (BPA) and isobutylparaben (IBP) exposed to Ulva pertusa (U. pertusa), and also to determine the combined effects of BPA and IBP in U. pertusa. The median sporulation inhibition concentrations (EC50) of individual BPA and IBP exposure in U. pertusa showed 23.84 mg/L and 15.65 mg/L, respectively. The inhibition on sporulation of U. pertusa to a mixture of BPA and IBP at EC50 level was observed to be higher when compared to individual exposure. In conclusion, reproduction inhibition to a mixture of BPA and IBP exposure at EC50 levels was relatively greater than individual exposure to U. pertusa.

Expression of clusterin on rat epididymis exposed to bisphenol A diglycidyl during in utero and lactation

This study was performed to investigate the adverse effects of bisphenol A diglycidyl ether (BADGE) on rat epididymis. BADGE was administered orally to pregnant 8-week-old specific-pathogen-free (SPF) Sprague-Dawley female rats from gestational day 6 to lactation once daily at doses of 0 (control), 50, 200, or 400 mg kg−1 day−1. Five male pups in control and three treatment groups were culled and sacrificed by ether on postnatal days (PND) 21, 42, or 56. Body and epididymis changes in weight and developmental characteristics of each male pup were recorded. The pattern of expression of clusterin mRNA in the cauda epididymis was observed using real-time PCR. The level of expression of clusterin proteins was confirmed using Western blot analysis. Body weight of the treated group did not differ markedly from the control. The adjusted anogenital distance (AGD) (in mm kg−(1/3)) on PND 7 in the 50 mg kg−1 day−1 group was significantly shorter than control; however, on PND 14 in the 200 mg kg−1 day−1 group and on PND 4 and 14 in the 400 mg kg−1 day−1 group, AGD was significantly longer. The expression of clusterin mRNA was significantly decreased on PND 56 in the 200 mg kg−1 day−1 and on PND 42 and 56 in the 400 mg kg−1 day−1 groups. The trend in the level of expression of clusterin proteins was similar to expression of mRNA. Male rats treated with 50 mg kg−1 day−1 of BADGE exerted no effect on epididymis. Data suggests that down-regulation of clusterin expression may be involved in reproductive toxicity produced by BADGE on rat epididymis.

Distribution of serum bisphenol A diglycidyl ether and its metabolite in Korean adult men and its association with reproductive hormone levels

Bisphenol A diglycidyl ether (BADGE) is a widely used coating for food cans and containers and so can be ingested along with contained food; however, measurement of BADGE in biological samples has not previously been performed. This study was conducted to determine serum concentrations of BADGE um and to evaluate the relationship between serum BADGE level and reproductive hormone levels in adult Korean petrochemical factory and non-petrochemical workers (n=223). BADGE and BADGE·2H2O levels in serum were measured using high-performance liquid chromatography-mass spectrometry, and reproductive hormones were analyzed using radioimmunoassay and immunoradiometric assay. The relationships between BADGE and BADGE·2H2O and reproductive hormone levels were assessed using generalized linear models and the distributions of BADGE and BADGE ·2H2O were skewed to the right. Serum BADGE and BADGE·2H2O in non-petrochemicalworkers showed a positive association with follicle-stimulating hormone (FSH, ß=0.241; 95% CI, 0.016 to 0.466) but a negative association with estradiol (E2, ß=-0.116; 95% CI, -0.210 to -0.022). In this study, the serum BADGE and BADGE·2H2O concentrations were sufficiently high to produce hormonal alterations in adult men.

Light and transmission electron microscopic comparisons of sperms between petrochemical factory workers and public servants in a nonindustrialized area

In this study, we compared the semen characteristics on light microscopy and ultrastructural sperm morphology on transmission electron microscopy between workers in an industrialized area with petrochemical complexes and public servants in a nonindustrialized area. Occupational exposure to petrochemical compounds seems to decrease sperm motility and deteriorate the sperm ultrastructural arrangement, which may lead to this decrease in sperm motility.

An estimate of phthalate exposure among term pregnant women living in Bucheon: The pilot study

목적: 프탈레이트는 프탈산 plasticizers로 사용되는 esters의 한 종류로 국외에서는 많은 연구를 통해 프탈레이트의 노출에 대하여 기술하고 있으나, 우리나라에서는 이와 관련된 연구가 부족한 실정이다. 이에 우리는 만삭 임신부의 소변에서 프탈산의 노출을 평가하였다. 연구방법: 2009년 8월부터 2010년 4월까지 32명의 만삭 분만한 임신부를 대상으로 하였으며, 기관윤리위원회(Institutional Review Board)를 통과하였고, 환경과 식습관에 대하여 질문서와 산과력 및 과거력을 조사하였다. 프탈레이트의 노출을 평가하기 위해서 10가지 phthalate metabolites (mono-methyl phthalate [MMP], mono-ethyl phthalate [MEP], mono-n-butyl phthalate [MnBP], mono benzyl phthalate [MBzP], mono-(2-ethylhexyl) phthalate [MEHP], mono-[2-ethyl-5-hydroxyhexyl] phthalate [MEHHP], mono-(2-ethyl-5-oxohexyl) phthalate [MEOHP], mono-isobutyl phthalate [MiBP], mono-(2-ethyl-5-carboxypentyl) phthalate [5cx-MEPP], and mono-(2- carboxymethylhexyl) phthalate [2cx-MMHP])를 분만 전 24시간 내에 임신부의 소변에서 측정했다. 이들 자료는 예비 실험연구이다. 결과: 임신부들의 평균 나이는 31.1±3.2세, 평균 주수는 38.4±1.3주였다. Creatinine-corrected concentration (geometric mean; μg/g Cr)는 1.754 (MMP), 3.443 (MEP), 3.839 (MnBP), 2.721 (MBzP), 2.437 (MEHP), 4.042 (MEHHP), 3.504 (MEOHP), 2.805 (MiBP), 3.765 (5cx-MEPP), 3.775 (2cx-MMHP)를 나타내었다. 결론: 우리의 데이터는 분만 전 임신부의 소변에서 측정한 프탈레이트의 예비 연구자료로서 본 자료를 토대로 앞으로 다 기관연구 연구에 도움이 될 것으로 보인다.