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Determination of Serum Di-(2-ethylhexyl) phthalate and Bisphenol A Level in Children with Idiopathic Central Precocious Puberty

김정현|김호성|김덕희|이은별|채현욱|이우정|이선우
대한소아내분비학회 (Korean Society Of Pediatric Endocrinology)|2009.12|Annals of Pediatric Endocrinology & Metabolism|제14권 제2호|pp. 154-162

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Precocious pubertyEndocrine disruptorsBisphenol ADi-(2-ethylhexyl) phthalate
주제분류소아과학

초록

목 적:플라스틱 가소제로 흔히 사용되는 di-(2-ethylhexyl) phthalate (DEHP) 및 각종 식품 포장용기의 소재인 bisphenol A는 에스트로겐 유사 작용이 있다고 알려져 있으며, 소아에서는 성조숙증 발병과의 연관성이 보고된 바 있으나 충분한 연구가 부족한 실정이다. 본 연구는 특발성 진성 성조숙증 환아를 대상으로 내분비교란물질로 알려진 DEHP 및 bisphenol A의 혈중 농도를 측정하여 연관성 여부를 확인하고자 하였다. 방 법:외래 방문 환자 중 특발성 진성 성조숙증 환아 30명(여아 29명, 남아 1명)과 정상 대조군 30명(여아 29명, 남아 1명)을 대상으로 하였다. 신체 검진 및 골연령을 측정하였으며, 혈중 성호르몬 농도 및 성선자극호르몬방출호르몬 자극검사를 시행하여 성조숙증을 진단하였다. 혈장 DEHP 및 bisphenol A의 농도는 gas chromatography/mass spectrometry (GC/MS) 방법으로 분석하였다. 결 과:성조숙증군과 정상대조군의 평균 연령은 8.6±0.9세 대 7.8±1.1세였으며, 신장 표준편차점수는 1.3±1.0 대 -0.4 ±1.1(P˂0.005),체중 표준편차점수는 1.3±1.3 대 -0.2± 1.3(P˂0.005),체질량지수는 17.6±1.5 kg/m2 대 16.2±1.8 kg/m2 (P˂0.005),골연령은 9.5±1.1세 대 7.9±1.9세(P˂0.005)로 성조숙증군의 신체발육이 앞서 있었다. Bisphenol A 검출농도는 두 군간에 차이가 없었으나(성조숙증군 11.2±10.3 ng/mL 대 정상대조군 16.2±12.5 ng/mL) DEHP의 농도는 성조숙증군에서 의미있게 증가한 결과를 보였다(159.01±92.78 ng/mL 대 103.55±92.98 ng/mL, P˂0.05). 결 론:본 연구에서 특발성 진성 성조숙증 환자에서 증가된 혈중 DEHP의 농도는 성조숙증의 발생 원인 중의 하나로 작용할 가능성을 시사한다. 그러나 채취 과정에서 검체가 오염되는 경우를 배제할 수 없고, 질환 발병과 무관한 인체 노출 범위가 아직까지 확립되지 않았다는 문제가 있다. 향후 내분비교란물질과 성조숙증 발생 사이의 연관성에 대한 보다 광범위한 연구와 내분비교란물질의 동물 및 인체 내 작용 및 기전에 대한 연구가 필요하리라 사료된다.

Abstract

Purpose:Environmental endocrine disruptors may affect the endocrine system or sexual development in children. Several recent studies have focused on indoor and dietary pollutants such as di-(2-ethylhexyl) phthalate (DEHP), which is used as a plastic softener, and bisphenol A, which is used in food-packaging materials. Despite the accumulation of data and the substantial arguments implicatinf these pollutants in endocrinal disorders, no clear evidence has been established yet. Thus, we assessed the serum levels of DEHP and bisphenol A in patients diagnosed with idiopathic central precocious puberty (CPP) to estimate the possible environmental hazards associated with increasing number of cases of precocious puberty. Methods:The study included 30 patients (29 girls and 1 boy) with idiopathic CPP and 30 normal control children who visited the pediatric endocrinology clinic. CPP was diagnosed on the basis of clinical & hormonal tests, including the gonadotropin-releasing hormone-stimulation test. The serum DEHP and bisphenol A levels were analyzed by gas chromatography/mass spectrometry. Results:The mean chronological ages (CA) in the idiopathic CPP and control groups were similar (8.6±0.9 vs. 7.8±1.1 years). However, the overall growth stage in the CPP group was advanced. The CPP group had a significantly higher height SDS (1.3±1.0 vs. -0.4±1.1, P˂0.005) and weight SDS (1.3±1.3 vs. -0.2±1.3, P˂0.005) than the control group. Bone age was significantly more advanced in the CPP group than in the control group (BA-CA:14.6±9.4 months vs. 0.8±15.3 months, P˂0.005). While the serum bisphenol A levels were not significantly different between the groups (11.2±10.3 vs.16.2±12.5 ng/mL), the DEHP levels were significantly higher in the CPP group than in the control group (159.01±92.78 vs. 103.55±92.98 ng/mL, P˂0.05). Conclusion:This study suggests that DEHP, one of most commonly used plasticizers, may be an etiologic factor for precocious puberty.

참고문헌 (40)

  1. Patton GC, "Pubertal transitions in health", Lancet, 396, pp.1130~1139 (2007)
  2. Terasawa E, "Fernandez DL Neurobiological mechanisms of the onset of puberty in primates", Endocr Rev, 22, pp.111~151 (2001)
  3. Gorai I, "Estrogen-metabolizing gene polymorphisms, but not estrogen receptor-alpha gene polymorphisms, are associated with the onset of menarche in healthy postmenopausal Japanese women", J Clin Endocrinol Metab, 88, pp.799~803 (2003)
  4. Ojeda SR, "The Oct-2 POU domain gene in the neuroedocrine brain: a transcriptional regulator of mammalian puberty", Endocrinology, 140, pp.3774~3789 (1999)
  5. Navarro VM, "Developmental and hormonally regulated messenger ribonucleic acid expression of KiSS-1 and its putative receptor, GPR54, in rat hypothalamus and potent luteinizing hormone-releasing activity of KiSS-1 peptide", Endocrinology, 145, pp.4565~4574 (2004)
  6. Shahab M, "Increased hypothalamic GPR54 signaling: a potential mechanism for initiation of puberty in primates", Proc Natl Acad Sci USA, 102, pp.2129~2134 (2005)
  7. Parent AS, "The timing of normal puberty and the age limits of sexual precocity: variations around the world, secular trends, and changes after migration", Endocr Rev, 24, pp.668~693 (2003)
  8. Herman-Giddens ME, "Hasemeier CM. Secondary sexual characteristics and menses in young girls seen in office practice: a study from the Pediatric Research in Office Settings network", Pediatrics, 99, pp.505~512 (1997)
  9. Lee PA, "Age of puberty: data from the United States of America", APMIS, 109, pp.81~88 (2001)
  10. 박미정, "한국 청소년의 성성숙 시기 및 장기간의 초경연령 추세분석", Korean Journal of Pediatrics, 49(6), pp.610~616 (2006), 대한소아과학회
  11. Massart F, "High incidence of central precocious puberty in a bounded geographic area of northwest Tuscany: An estrogen disrupter epidemic?", Gynecol Endocrinol, 20, pp.92~98 (2005)
  12. Comas AP, "Precocious sexual development in Puerto Rico", Lancet, 1, pp.1299~1300 (1982)
  13. Colon I, "Identification of phthalate esters in the serum of young Puerto Rican girls with premature breast development", Environ Health Perspect, 108, pp.895~900 (2000)
  14. Krstevska-Konstantinova M, "Sexual precocity after immigration from developing countries to Belgium: evidence of previous exposure to organochlorine pesticids", Hum Reprod, 16, pp.1020~1026 (2001)
  15. European Commission. Communication from the Commission to the Council and the European Parliament on the implementation of the Community Strategy for Endocrine Disrupters - a range of substances suspected of interfering with hormone systems of humans and wildlife Report, "European Commission", European Commission 2001., ~, pp.No.COM (2001)262 final (2001)
  16. Guillette LJ Jr, "Contaminant-induced endocrine disruption in wildlife", Growth Horm IGF Res, 10(B), pp.45~50 (2000)
  17. Sharara FI, "Environmental toxicants and female reproduction", Fertil Steril, 70, pp.613~622 (1998)
  18. Denham M, "Akwesasne Task Force on the Environment. Relationship of lead, mercury, mirex, dichlorodiphenyldichloroethylene, hexachlorobenzene, and polychlorinated biphenyls to timing of menarche among Akwesasne Mohawk girls", Pediatrics, 115, pp.e127~e134 (2005)
  19. Tsuda H, "Carcinogenesis and Its Modification by Environmental Endocrine Disruptors: In Vivo Experimental and Epidemiological Findings", Jpn J Clin Oncol, 33, pp.259~270 (2003)
  20. Matsumoto A, "Bisphenol A levels in human urine", Environ Health Perspect, 111, pp.101~104 (2003)
  21. Markey CM, "In utero exposure to bisphenol A alters the development and tissue organization of the mouse mammary gland", Biol Reprod, 65, pp.1215~1223 (2001)
  22. Olea N, "Estrogenicity of resin-based composites and sealants used in dentistry", Environ Health Perspect, 104, pp.298~305 (1996)
  23. Peck C, "Toxic potential of the plasticizer di(2- ethylhexyl) phthalate in the context of its disposition and metabolism in primates and man", Environ Health Perspect, 45, pp.11~17 (1982)
  24. Harris CA, "The estrogenic activity of phthalate esters in vitro", Environ Health Perspect, 105, pp.802~811 (1997)
  25. Reddy MK, "Partial purification and immunoreactivity of an 80,000-molecular-weight polypeptide associated with peroxisome proliferation in rat liver", Biochem J, 188, pp.731~740 (1980)
  26. Marshall WA, "Variations in pattern of pubertal changes in girls", Arch Dis Child, 44, pp.291~303 (1969)
  27. Greulich WW, "Radiographic atlas of skeletal development of the hand and wrist. 2nd ed" (1993), Stanford University Press
  28. Suh BK, "Diagnosis and treatment of precocious puberty", J Korean Pediatr Soc, 44, pp.607~613 (2001)
  29. Den Hond E, "Endocrine disrupters and human puberty", Int J Androl, 29, pp.264~271 (2006)
  30. Mckee RH, "Phthalate exposure and early thelarche", Environ Health Perspect, 112, pp.A541~A543 (2004)
  31. Welshons WV, "Large effects from small exposures. I. Mechanisms for endocrine-disrupting chemicals with estrogenic activity", Environ Health Perspect, 111, pp.994~1006 (2003)
  32. "National Toxicology Program (NTP). U.S. Department of Health and Human Services, National Institute of Environmental Health Sciences, National Institute of Health. National Toxicology Program's Report of Endocrine Disruptors Low- Dose Peer Review (2001)/URL:/"[URL]
  33. Jobling S, "A variety of environmentally persistent chemicals, including some phthalate plasticizers are weakly estrogenic", Environ Health Perspect, 103, pp.582~587 (1995)
  34. Lovekamp-Swan T, "Mechanisms of phthalate ester toxicity in the female reproductive system", Environ Health Perspect, 111, pp.139~145 (2003)
  35. Silva MJ, "Urinary levels of seven phthalate metabolites in the U.S. population from the National Health and Nutrition Examination Survey (NHANES) 1999-2000", Environ Health Perspect, 112, pp.331~338 (2004)
  36. "Testing of component parts with respect to section 108 of the CPSIA (CPSC Docket Number: CPSC-2009-0063)"[URL]
  37. Meek ME, "Bis(2-ethylhexyl)phthalate: evaluation of risks to health from environmental exposure in Canada", J Environ Sci Health Part C, 12, pp.179~194 (1994)
  38. Koch HM, "Internal exposure of nursery-school children and their parents and teachers to di(2- ethylhexyl)phthalate (DEHP)", Int J Hyg Environ Health, 207, pp.15~22 (2004)
  39. Inoshita H, "The different effects of endocrine-disrupting chemicals on estrogen receptor- mediated transcription through interaction with coactivator TRAP220 in uterine tissue", J Mol Endocrinol, 31, pp.551~561 (2003)
  40. Takahashi O, "Disposition of orally administered 2, 2-bis(4-hydroxy phenyl)propane (bisphenol A) in pregnant rats and the placental transfer to fetuses", Environ Health Perspect, 108, pp.931~935 (2000)

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