Bai-Hsiun Chen

The public health threat of phthalate-tainted foodstuffs in Taiwan: the policies the government implemented and the lessons we learned.

A major incident of phthalate-contaminated foodstuffs happened in Taiwan between April and July, 2011. Phthalates were deliberately added to foodstuffs as a substitute of emulsifier. We describe the course of this incident, government response and management of the crisis, and its future implications. Five major food categories, including sports drinks, fruit beverages, tea drinks, fruit jam or jelly, and health food or supplements in tablet or powder form, were contaminated with Di-(2-ethylhexyl)phthalate and/or Di-isononyl phthalate. At least 900 different food products were affected. Like the scandal of melamine-tainted infant formula, this event represents another large deliberate food contamination incident. It is important to be reminded that many governments in developing countries make rapid economic growth as their first priority, often compromising environmental safety and public health. The administration leaders need to find a balance between economic expansion and health and environmental safety.

Intake of Phthalate-Tainted Foods Alters Thyroid Functions in Taiwanese Children

Background On April-May, 2011, two Taiwan chemical companies were found to have intentionally added phthalates, Di-(2-ethylhexyl) phthalate (DEHP) and/or Di-isononyl phthalate, as a substitute of emulsifier to many foodstuffs. This study aimed to investigate whether exposure to these foods altered endocrine functions in children aged ≤10 years and, if so, whether those changes could be reversed by stopping exposure. Methods One Phthalates Clinic for Children was established in southern Taiwan between May 31 and June 17, 2011. All eligible children had their exposure information, blood and/or urine specimens collected. Endocrine functions were assessed in serum. The exposure groups were categorized into three (High, >500 ppm, Low, 1–500 ppm, and No, <1 ppm of DEHP). After six months, some children were followed up for the selected endocrine hormones. Results Sixty children were eligible in this study; all were Tanner stage 1 with no pubic hair. Compared to non-exposed group, both high and low exposure groups had significantly lower serum thyroid-stimulating hormone (TSH) levels (P = 0.001 and 0.024). At six months follow-up, serum triiodothyronine (T3) levels was significantly changed (P = 0.034) in high exposure group (n = 13). For serum estradiol (E2), the detectable rate (≥8 pg/mL) decreased from 76.9% (10/13) to 30.8% (4/13) (P = 0.070). Conclusions This study shows that serum TSH levels can be altered when children were exposed to high concentrations of phthalate-tainted foodstuffs. Serum E2 and T3 may be partially recovered after stopping exposure.

The neoplastic impact of tobacco-free betel-quid on the histological type and the anatomical site of aerodigestive tract cancers

Little is known about any consequences of swallowing tobacco‐free betel‐quid (TF‐BQ) juice/remnants following chewing and its carcinogenic impact on the upper aerodigestive tract (UADT) to gastrointestinal tract (GIT). We investigated the neoplastic impact of TF‐BQ on different anatomical locations along UADT and GIT, and differences according to their histological categories. We conducted a multicenter case–control study examining patients with 2,163 pathology‐proven UADT and GIT cancers, comparing them with 2,250 control subjects. Generalized additive models, piecewise regression and polytomous logistic models were applied to identify possible dose‐dependent structures and cancer risks. Contrary to nonsignificant GIT‐adenocarcinoma risk (aOR = 0.9), TF‐BQ users experienced a 1.7‐ to 16.2‐fold higher risk of UADT‐squamous cell carcinomas than nonusers, with the peak risk discovered in oral neoplasms. We separately observed a curvilinear and linear TF‐BQ dose‐risk relationship in oral/pharyngeal/esophageal and laryngeal cancers. Chewers of betel inflorescence were generally at a greater UADT cancer risk. A higher first‐piecewise increased risk of esophageal cancer was recognized among areca‐fluid swallowers than among nonswallowers (continuous aOR = 1.12 vs. 1.03). TF‐BQ use accounted for 66.1–78.7% and 17.8–33.2% of the cases of oral/pharyngeal and esophageal/laryngeal cancers, respectively. However, a reduction from heavy TF‐BQ consumption to low‐to‐moderate consumption only reduced 11.3–34.6% of etiologic fraction of oral/pharyngeal cancers. Alcohol supra‐additively modified the risk of TF‐BQ in determining the development of oral, pharyngeal and esophageal cancers. In conclusion, the interplay of TF‐BQ and alcohol/tobacco use, combined with how chewing habit is practiced, influences carcinogenic consequences on anatomically diverse sites of UADT and GIT cancers, and histologically different types.

High melamine migration in daily-use melamine-made tableware

Melamine is commonly used to manufacture tableware, and this could be one of the important exposure sources in humans. The study aims to measure melamine migrated from different material-made tableware by the most sensitive technique of liquid chromatography-tandem mass spectrometry (LC-MS/MS). The test samples were filled with pre-warmed designated-temperature (from room temperature (∼20 °C), 30 °C, 40 °C, 50 °C, 60 °C, 70 °C, 80 °C, to 90 °C) simulant (either distilled water or 3% acetic acid) up to 20 ml and immersed in a water bath at that designated temperature for 15 or 30 minutes (min). High melamine migration levels, ranging from 6.97 to 19.03 μg/ml, can be measured from all melamine-made samples containing 20 ml 3% acetic acid in water bath of 90 °C for 30 min, whereas melamine cannot be detectable in all other material-made samples in the same condition. In addition, the cheaper the melamine-made tableware samples, the higher the melamine migration levels. The migration of melamine amount is dependent on different temperatures, contact times, simulant, and prices of tableware. Since tableware is used in daily life, it is prudent to cautiously select materials that contain foodstuffs.

Low exposure to melamine increases the risk of urolithiasis in adults

Melamine, a widely used chemical found in many products in daily use, became a public health concern due to melamine-associated urinary stone formation in children. In adults, it is still unknown whether low-dose melamine exposure may also cause urolithiasis. To address this question, we studied 211 Taiwanese patients diagnosed with calcium urolithiasis and 211 age- and gender-matched controls. All patients completed a detailed questionnaire and provided blood and urine samples for biochemical analysis. Urinary melamine concentrations were measured by triple-quadrupole liquid chromatography tandem mass spectrometry. Compared with those whose urinary melamine levels were below the detection limit of the method, patients with urinary melamine levels of up to 3.11  ng/ml and those with levels of ≥3.12  ng/ml had 3.01- and 7.64-fold increased risk, respectively, of calcium urolithiasis after adjusting for educational level, fluid intake, cigarette smoking, betel quid chewing, alcohol drinking, urinary uric acid, calcium, creatinine, and estimated creatinine clearance rate. The population attributable risk of calcium urolithiasis averaged 50% when melamine was detected in the urine, after considering other covariates. MALDI-TOF mass spectrometry detected melamine in the stones of nine representative patients who had measurable urinary melamine levels. Thus, low-dose melamine exposure can play an important role in calcium urolithiasis in Taiwanese adults.

Urinary melamine and adult urolithiasis in Taiwan

BACKGROUND This study aims to investigate the association between urinary melamine concentration and the risk of urolithiasis in adult. METHODS From 2003 to 2007, 11 and 22 patients diagnosed with upper urinary tract uric acid urolithiasis and calcium urolithiasis, respectively, were recruited from Kaohsiung Medical University Hospital. For comparison, we randomly collected 22 sex- and age-matched subjects who come to the same hospital for regular health check-up at the same period of time. Urinary melamine concentration was measured by the method of triple-quadrupole liquid chromatography tandem mass spectrometry (LC-MS/MS). Wilcoxon rank sum test was used to compare the urinary melamine concentrations in uric acid urolithiasis patients with controls as well as in calcium urolithiasis patients with controls. FDR (false discovery rate) was used to correct the p-values for two comparisons. RESULTS Subjects with uric acid urolithiasis (median: 0.50 vs 0.06microg/mmol creatinine, Wilcoxon test: FDR_p=0.024) and with calcium urolithiasis (median: 0.14 vs 0.06, FDR_p=0.024) had significantly higher urinary melamine concentration than controls. Based on the ROC curves, subjects whose melamine levels were over 0.262 and 0.037microg/mmol creatinine, respectively, might have significant risks to have uric acid and calcium urolithiasis. CONCLUSION This preliminary study suggests that exposure to even low-dose melamine-related products still have the potential to develop both uric acid and calcium urolithiasis in adults.

Temporal changes of urinary oxidative metabolites of di(2-ethylhexyl)phthalate after the 2011 phthalate incident in Taiwanese children: findings of a six month follow-up.

A major incident involving phthalates-contaminated foodstuffs occurred in Taiwan in May 2011, leading to the quick removal of tainted food items from store shelves. We investigated changes in urinary oxidative di(2-ethylhexyl)phthalate (DEHP) metabolites, our proxy for exposure to DEHP-tainted foodstuffs in children ≤10 years, during the six months following withdrawal of the tainted food. Our hospital screened 60 possibly exposed children between May and June 2011. The childrens food intake information was collected, and they were administered one-spot urine samples at baseline and at the two and six month follow-ups. All three samples were measured for four oxidative DEHP metabolites, mono-(2-ethyl-5-hydroxyhexyl) phthalate (5OH-MEHP), mono-(2-ethyl-5-oxohexyl) phthalate (5oxo-MEHP), mono-(2-ethyl-5-carboxypentyl) phthalate (5cx-MEPP), and mono-(2-carboxymethylhexyl) phthalate (2cx-MMHP) by triple quadrupole liquid chromatography tandem mass spectrometry. Fifty-two children had been exposed. After excluding those without a full set of urine samples or adequate food intake information, 23 exposed children were studied. We found significantly positive correlations between DEHP daily intake and urinary 5OH-MEHP, 5oxo-MEHP, and 5cx-MEPP (p < 0.05). At the six month follow-up, all four metabolite concentrations had significantly decreased compared to the baseline. In conclusion, urinary DEHP metabolites decreased progressively in children after tainted food withdrawal, indicating that the main sources of phthalate contamination for children had been successfully controlled.

Rubella Seroepidemiology and Catch-up Immunization among Pregnant Women in Taiwan: Comparison between Women Born in Taiwan and Immigrants from Six Countries in Asia

Rubella vaccination in Taiwan started in 1986; mass vaccination was introduced into the national immunization program in 1992. In recent years, 17-31% of all marriages in Taiwan have been between Taiwanese men and foreign women. The aim of this study was to analyze rubella seroepidemiology and the rate of catch-up immunization in women. We recruited 10,089 pregnant women, including 1,920 immigrants, who had received prenatal examinations during 1999-2006. The rates of seronegativity among global, Taiwan-born, and non-Taiwan-born pregnant women were 14.0%, 11.9%, and 23.1%, respectively. The seronegativity of rubella antibodies decreased from 28.2% for Taiwan-born women born before September 1971 to 8.0% for those born thereafter. The rates of rubella catch-up immunization among global, Taiwan-born, and non-Taiwan-born pregnant women were 28.6%, 20.5%, and 42.2%, respectively. Our results suggest that substantial numbers of older Taiwan-born women and immigrant women remain susceptible to rubella infection.

The use of tobacco-free betel-quid in conjunction with alcohol/tobacco impacts early-onset age and carcinoma distribution for upper aerodigestive tract cancer

BACKGROUND  Recognition of how risk factors affect the age when cancers are first diagnosed may help to establish more appropriate cancer screening and preventive strategies. METHODS  To investigate the independent and synergistic effects of alcohol, tobacco-free betel-quid (TF-BQ), and cigarette use on diagnosis age and dissemination of upper aerodigestive tract squamous cell carcinoma (UADT-SCC), we recruited pathology-proven 1522 patients with UADT-SCC for study. RESULTS  A 49-, 53-, 57-, and 62-year-old stepwise older median age at carcinoma diagnosis was, respectively, found among patients with oral, pharyngeal, esophageal, and laryngeal cancer. Oral cavity (53.2%) and larynx (11.6%) were separately the dominant and recessive sites where the UADT-SCC occurred. Although alcohol and tobacco bestowed increased risks of earlier tumor occurrence only for oral/pharyngeal and oral cancers, respectively, TF-BQ was consistently observed to confer elevated age-associated risks for each UADT-SCC [adjusted hazard ratio (aHR) = 1.6-2.3]. Alcohol and TF-BQ joint consumers experienced a stepwise increased cumulative risk (CR) of contracting carcinomas of the larynx (46.2%), esophagus (47.5%), pharynx (53.5%), and oral cavity (60.5-71.0%), with >68% of CRs found among drinkers who started chewing before age 20. Alcohol + Betel + Cigarette and Alcohol + Betel users exhibited earlier diagnosis ages than non-users: 10 years ahead for oral cancer, 7, 17, and 12 years earlier for pharyngeal, esophageal, and laryngeal cancers. Noticeably, higher cumulative cancer risks regarding earlier tumor occurrence were correspondingly identified for these users aged 43, 49, 43, and 44 upward. CONCLUSIONS  Tobacco-free betel-quid, in conjunction with alcohol and/or tobacco consumption, impacts early cancer occurrence for specific UADT-SCC and influences tumor site incidence pattern of these neoplasms.

Rubella seroepidemiology and estimations of the catch‐up immunisation rate and persistence of antibody titers in pregnant women in Taiwan

Please cite this paper as: Lin C, Yang C, Shih Y, Hsu H, Yang T, Cheng Y, Chang C, Hsieh L, Chen B, Lee C, Huang Y. Rubella seroepidemiology and estimations of the catch‐up immunisation rate and persistence of antibody titers in pregnant women in Taiwan. BJOG 2011;118:706–712.