{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T06:53:47Z","timestamp":1773298427625,"version":"3.50.1"},"reference-count":30,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2013,4,3]],"date-time":"2013-04-03T00:00:00Z","timestamp":1364947200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJERPH"],"abstract":"<jats:p>Background: Liquid crystal display (LCD) manufacturing involves three fabrication processes: array, panel and module processes, which result in different levels of volatile organic compound (VOC) exposure. The aim of this study was to assess the potential reproductive endocrine effects of occupational exposures during LCD manufacturing predictive of menstrual cycles as subclinical markers of female reproductive dysfunction effects of low-dose exposures. Methods: A total of 94 fabrication workers were followed for one complete menstrual cycle using daily urine samples: 23 were from the array,  53 from the panel, and 18 from the module work areas. The menstrual cycle characteristics of the study population were measured using a self-administered questionnaire.  Urine samples were collected during the first urination in the morning for at least one complete menstrual cycle. The urine was then analyzed to determine the urinary concentrations of follicular stimulating hormone (FSH), estrone conjugates (E1C), and pregnanediol-3-glucuronide (PdG). The results of this analysis were used to assess the potential effects of chemical exposure as determined by handheld volatile organic compound (VOC) monitors and 24 h canisters. Results: The concentration of total VOCs was much higher in the module making area (ND\u201321,000 ppb) than in panel (ND\u2013766 ppb) and array (58\u20131,472 ppb) making areas. The concentrations of ethanol and acetone were much higher in the module (1,974.9 and 2,283.2 ppb, respectively) and panel (2256.9 and 592.2 ppb, respectively) making areas. Compared to those in the array making area, we found that E1C (12.55, 95% confidence interval (CI): 8.49, 16.61 \u03bcg\/mg Cr) and PdG (0.53, 95% CI: 0.29, 0.77 \u03bcg\/mg Cr) levels in the module group were significantly higher in the early follicular phase; E1C (11.93, 95% CI: 6.21, 17.65 \u03bcg\/mg Cr) and PdG (0.53, 95% CI: 0.29,  0.77 \u03bcg\/mg Cr) levels were significantly higher in the periovulatory phase; and all the hormone levels, FSH (1.48, 95% CI: 0.81, 2.15 \u03bcg\/mg Cr), E1C (9.29, 95% CI: 4.92,  13.66 \u03bcg\/mg Cr), and PdG (1.01, 95% CI: 0.42, 1.60 \u03bcg\/mg Cr) were also significantly higher in the luteal phase. In addition, the FSH (0.89, 95% CI: 0.07, 1.71 \u03bcg\/mg Cr) level in the panel group was significantly higher but E1C (\u22124.49, 95% CI: \u22127.90, \u22121.08 \u03bcg\/mg Cr) was lower in the early follicular phase; and E1C (\u22125.16, 95% CI: \u22129.61, \u22120.71 \u03bcg\/mg Cr) level was significantly lower in the periovulatory phase. Conclusions: Our findings add to the evidence that exposure to multiple low-level chemicals is associated with modest changes in reproductive hormone urinary concentrations in healthy premenopausal women. In addition, the FSH (0.89, 95% CI: 0.07, 1.71 \u03bcg\/mg Cr) level in the panel group was significantly higher but E1C (\u22124.49, 95% CI: \u22127.90, \u22121.08 \u03bcg\/mg Cr) lower in the early follicular phase; and E1C (\u22125.16, 95% CI: \u22129.61, \u22120.71 \u03bcg\/mg Cr) level was significantly lower in the periovulatory phase.<\/jats:p>","DOI":"10.3390\/ijerph10041406","type":"journal-article","created":{"date-parts":[[2013,4,3]],"date-time":"2013-04-03T11:51:12Z","timestamp":1364989872000},"page":"1406-1417","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Exposure to Multiple Low-Level Chemicals in Relation to Reproductive Hormones in Premenopausal Women Involved  in Liquid Crystal Display Manufacture"],"prefix":"10.3390","volume":"10","author":[{"given":"Ching-Chun","family":"Lin","sequence":"first","affiliation":[{"name":"Institute of Occupational Medicine and Industrial Hygiene, National Taiwan University College of Public Health, Taipei 100, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chia-Ni","family":"Huang","sequence":"additional","affiliation":[{"name":"Institute of Occupational Medicine and Industrial Hygiene, National Taiwan University College of Public Health, Taipei 100, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jung-Der","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Occupational Medicine and Industrial Hygiene, National Taiwan University College of Public Health, Taipei 100, Taiwan"},{"name":"Department of Public Health, National Cheng Kung University College of Medicine, Tainan 701, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yaw-Huei","family":"Hwang","sequence":"additional","affiliation":[{"name":"Institute of Occupational Medicine and Industrial Hygiene, National Taiwan University College of Public Health, Taipei 100, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruei-Hao","family":"Shie","sequence":"additional","affiliation":[{"name":"Institute of Occupational Medicine and Industrial Hygiene, National Taiwan University College of Public Health, Taipei 100, Taiwan"},{"name":"Green Energy and Environment Research Laboratories, Industrial Technology Research Institute, Hsinchu County 310, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu-Yin","family":"Chang","sequence":"additional","affiliation":[{"name":"Institute of Occupational Medicine and Industrial Hygiene, National Taiwan University College of Public Health, Taipei 100, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shao-Ping","family":"Weng","sequence":"additional","affiliation":[{"name":"Institute of Occupational Medicine and Industrial Hygiene, National Taiwan University College of Public Health, Taipei 100, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pau-Chung","family":"Chen","sequence":"additional","affiliation":[{"name":"Institute of Occupational Medicine and Industrial Hygiene, National Taiwan University College of Public Health, Taipei 100, Taiwan"},{"name":"Department of Public Health, National Taiwan University College of Public Health, Taipei 100, Taiwan"},{"name":"Department of Environmental and Occupational Medicine, National Taiwan University College of Medicine and Hospital, Taipei 100, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2013,4,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1002\/ajim.4700280613","article-title":"Prospectively assessed menstrual cycle characteristics in female wafer-fabrication and nonfabrication semiconductor employees","volume":"28","author":"Gold","year":"1995","journal-title":"Am. J. Ind. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1002\/(SICI)1097-0274(199702)31:2<148::AID-AJIM3>3.0.CO;2-W","article-title":"Menstrual patterns of workers exposed to low levels of 2-ethoxyethylacetate (EGEEA)","volume":"31","author":"Chia","year":"1997","journal-title":"Am. J. Ind. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1136\/oem.2004.016014","article-title":"Prolonged menstrual cycles in female workers exposed to ethylene glycol ethers in the semiconductor manufacturing industry","volume":"62","author":"Hsieh","year":"2005","journal-title":"Occup. Environ. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1093\/toxsci\/50.2.249","article-title":"Assessment of adult and neonatal reproductive parameters in Sprague-Dawley rats exposed to propylene glycol monomethyl ether vapors for two generations","volume":"50","author":"Carney","year":"1999","journal-title":"Toxicol. Sci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1006\/faat.1996.0082","article-title":"Evaluation of the developmental toxicity of dermally applied monoethanolamine in rats and rabbits","volume":"31","author":"Liberacki","year":"1996","journal-title":"Fundam. Appl. Toxicol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1136\/oem.54.4.236","article-title":"Experimental exposure of male volunteers to N-methyl-2-pyrrolidone (NMP): Acute effects and pharmacokinetics of NMP in plasma and urine","volume":"54","author":"Akesson","year":"1997","journal-title":"Occup. Environ. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1002\/jat.2550150210","article-title":"Two-generation reproduction toxicity study with isopropanol in rats","volume":"15","author":"Bevan","year":"1995","journal-title":"J. Appl. Toxicol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1093\/occmed\/kqs172","article-title":"Shortened menstrual cycles in LCD manufacturing workers","volume":"63","author":"Lin","year":"2013","journal-title":"Occup. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1017\/S0033291700009247","article-title":"The design and development of a screening questionnaire (CHQ) for use in community studies of mental-disorders in Taiwan","volume":"16","author":"Cheng","year":"1986","journal-title":"Psychol. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1016\/S0015-0282(02)02998-9","article-title":"Urinary follicle-stimulating hormone peak as a biomarker for estimating the day of ovulation","volume":"77","author":"Li","year":"2002","journal-title":"Fertil. Steril."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1093\/oxfordjournals.epirev.a036193","article-title":"Epidemiology of menstruation and its relevance to women\u2019s health","volume":"17","author":"Harlow","year":"1995","journal-title":"Epidemiol. Rev."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1001\/jama.1968.03140060001001","article-title":"The length and variability of the human menstrual cycle","volume":"203","author":"Chiazze","year":"1968","journal-title":"JAMA"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/0890-6238(88)90018-4","article-title":"Assessment of menstrual variability in working populations","volume":"2","author":"Shortridge","year":"1988","journal-title":"Reprod. Toxicol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"838","DOI":"10.1093\/clinchem\/37.6.838","article-title":"Relationship of serum estradiol and progesterone concentrations to the excretion profiles of their major urinary metabolites as measured by enzyme-immunoassay and radioimmunoassay","volume":"37","author":"Munro","year":"1991","journal-title":"Clin. Chem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1016\/S0015-0282(97)00475-5","article-title":"Enzyme immunoassay method for total urinary follicle-stimulating hormone (FSH) beta subunit and its application for measurement of total urinary FSH","volume":"69","author":"Qiu","year":"1998","journal-title":"Fertil. Steril."},{"key":"ref_16","unstructured":"(2004). SAS\/ATAT 9.1 User\u2019s Guide, SAS Institute Inc."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1567","DOI":"10.1111\/j.1530-0277.1997.tb04491.x","article-title":"The impact of acute ethanol on reproductive hormone synthesis, processing, and secretion in female rats at proestrous","volume":"21","author":"LaPaglia","year":"1997","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_18","first-page":"152","article-title":"Urea and acetone content in milk as indicators for nutritionally caused fertility disorders of dairy cows","volume":"101","author":"Wenninger","year":"1994","journal-title":"Dtsch. Tierarztl. Wochenschr."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1006\/rtph.2000.1448","article-title":"Review of the epidemiological evidence relating toluene to reproductive outcomes","volume":"33","author":"Bukowski","year":"2001","journal-title":"Regul. Toxicol. Pharmacol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1080\/15287398209530145","article-title":"Teratogenicity of a commercial xylene mixture in the mouse","volume":"9","author":"Marks","year":"1982","journal-title":"J. Toxicol. Environ. Health"},{"key":"ref_21","first-page":"83","article-title":"Effects of exposure to low-level benzene and its analogues on reproductive hormone secretion in female workers","volume":"35","author":"Chen","year":"2001","journal-title":"Zhonghua Yu Fang Yi Xue Za Zhi"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1097\/00043764-199311000-00010","article-title":"Assessment of the health hazards of 1,3-butadiene and styrene. Meeting report","volume":"35","author":"Heseltine","year":"1993","journal-title":"J. Occup. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1016\/S0015-0282(98)00257-X","article-title":"Alcohol and caffeine consumption and decreased fertility","volume":"70","author":"Hakim","year":"1998","journal-title":"Fertil. Steril."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1093\/alcalc\/35.5.417","article-title":"The effects of moderate alcohol consumption on female hormone levels and reproductive function","volume":"35","author":"Gill","year":"2000","journal-title":"Alcohol Alcohol."},{"key":"ref_25","unstructured":"Stewart, R.D., Hake, C.L., Wu, A., Graft, S.A., and Forster, H.V. (1975). Acetone: Development of a Biologic Standard for the Industrial Worker by Breath Analysis, Medical Colleague of Wisconsin."},{"key":"ref_26","first-page":"146","article-title":"Prevalence of tobacco smoking, drinking and betel nut chewing among Taiwanese workers in 1999","volume":"7","author":"Liang","year":"2002","journal-title":"Mid-Taiwan J. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1080\/0951359042000196303","article-title":"Prediction of ovarian reserve based on day-3 serum follicle stimulating hormone concentrations during the pituitary suppression cycle using a gonadotropin releasing hormone agonist in patients undergoing in vitro fertilization-embryo transfer","volume":"18","author":"Onagawa","year":"2004","journal-title":"Gynecol. Endocrinol."},{"key":"ref_28","first-page":"1038","article-title":"Reproductive aging: Accelerated ovarian follicular development associated with a monotropic follicle-stimulating hormone rise in normal older women","volume":"81","author":"Klein","year":"1996","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_29","first-page":"200","article-title":"Initial and cyclic recruitment of ovarian follicles","volume":"21","author":"McGee","year":"2000","journal-title":"Endocr. Rev."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"5746","DOI":"10.1210\/jc.2002-020622","article-title":"Is the short follicular phase in older women secondary to advanced or accelerated dominant follicle development?","volume":"87","author":"Klein","year":"2002","journal-title":"J. Clin. Endocrinol. Metab."}],"container-title":["International Journal of Environmental Research and Public Health"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1660-4601\/10\/4\/1406\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T21:45:56Z","timestamp":1760219156000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1660-4601\/10\/4\/1406"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,4,3]]},"references-count":30,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2013,4]]}},"alternative-id":["ijerph10041406"],"URL":"https:\/\/doi.org\/10.3390\/ijerph10041406","relation":{},"ISSN":["1660-4601"],"issn-type":[{"value":"1660-4601","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,4,3]]}}}