Chia-Fang Wu

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.

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.

Relationship of Urinary Phthalate Metabolites with Serum Thyroid Hormones in Pregnant Women and Their Newborns: A Prospective Birth Cohort in Taiwan

Background The purpose of this study was to examine the relationship of phthalates exposure with thyroid function in pregnant women and their newborns. Methods One hundred and forty-eight Taiwanese maternal and infant pairs were recruited from E-Da hospital in southern Taiwan between 2009 and 2010 for analysis. One-spot urine samples and blood samples in the third trimester of pregnant women and their cord blood samples at delivery were collected. Nine phthalate metabolites in urine were determined by triple quadrupole liquid chromatography tandem mass spectrometry, whereas serum from pregnant women and their cord blood were used to measure thyroid profiles (thyroid-stimulating hormone [TSH], thyroxine, free thyroxine, and triiodothyronine) by radioimmunoassay. Results Median levels of urinary mono-n-butyl phthalate, mono-ethyl phthalate, and mono-(2-ethyl-5-oxohexyl) phthalate (μg/g creatinine) were the three highest phthalate metabolites, which were 37.81, 34.51, and 21.73, respectively. Using Bonferroni correction at a significance of < 0.006, we found that urinary mono-benzyl phthalate (MBzP) levels were significantly and negatively associated with serum TSH in cord blood (β = -2.644, p = 0.003). Conclusions Maternal urinary MBzP, of which the parental compound is butylbenzyl phthalate, may affect TSH activity in newborns. The alteration of thyroid homeostasis by certain phthalates in the early life, a critical period for neurodevelopment, is an urgent concern.

Melamine induces human renal proximal tubular cell injury via transforming growth factor-β and oxidative stress.

Although several reports have failed to observe adverse subchronic renal effects following relatively high melamine exposure, the safety of low and continuous melamine exposure is still debatable. Recent studies suggest that long-term, low-dose melamine exposure is associated with an increased risk of urolithiasis, which has been linked to chronic kidney disease (CKD). CKD is a consequence of nephron loss and is associated with the interaction of inflammation, oxidative stress, and transforming growth factor-β (TGF-β), which increases extracellular matrix genes and cell apoptosis with progression to fibrosis and end-stage renal disease. Thus far, information is still lacking regarding the influence of melamine at the gene and protein levels, which are activated at a much earlier phase than the occurrence of the renal morphological change. In this study, we stimulated human renal proximal tubular HK-2 cells with melamine (0, 125, 250, 500, or 1000 µg/ml) for different time intervals and observed its effects on several well-documented molecular mechanisms of CKD. Here, we demonstrate that melamine can activate mitogen-activated protein kinases, NFκB, and reactive oxygen species, which results in the upregulation of interleukin-6, monocyte chemoattractant protein-1, vascular cell adhesion molecule-1, and TGF-β1 in HK-2 cells. The melamine-stimulated overexpression of TGF-β1 not only promotes fibronectin production but also leads to decreased antiapoptotic (bcl-2, bcl-xl)/proapoptotic (bad, bax) protein ratio, increased caspase-3 and caspase-9 activities, and eventually HK-2 cell apoptosis. Our study suggests that melamine exposure may be a risk factor for the chronic loss of tubular cells and may ultimately lead to tubulointerstitial damage.

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.

Second-hand smoke and chronic bronchitis in Taiwanese women: a health-care based study.

BackgroundCigarette smoking cannot fully explain the epidemiologic characteristics of chronic obstructive pulmonary disease (COPD) in women, particularly for those who rarely smoke, but COPD risk is not less than men. The aim of our study is to investigate the relationship between second-hand smoke (SHS) exposure and chronic bronchitis in Taiwanese women.MethodsWe used Taiwans National Health Insurance Bureau claims data in 1999, and cross-checked using criteria set by the American Thoracic Society; there were 33 women with chronic bronchitis, 182 with probable chronic bronchitis, and 205 with no chronic bronchitis during our interview time between 2000 and 2005. We measured second-hand smoke (SHS) exposure by self-reported measures (household users and duration of exposure), and validated this by measuring urinary cotinine levels of a subset subjects. Classification of chronic bronchitis was also based on spirometry defined according to the GOLD guidelines to get the severity of COPD.ResultsWomen who smoked and women who had been exposed to a lifetime of SHS were 24.81-fold (95% CI: 5.78-106.38) and 3.65-fold (95% CI: 1.19-11.26) more likely to have chronic bronchitis, respectively, than those who had not been exposed to SHS. In addition, there was a significant increasing trend between the severity of COPD and exposure years of SHS (p < 0.01). The population attributable risk percentages of chronic bronchitis for smokers and those exposed to SHS were 23.2 and 47.3% respectively.ConclusionsThese findings indicate that, besides cigarette smoking, exposure to SHS is a major risk factor for chronic bronchitis in Taiwanese women.

Nonlinear absorption of light: two-photon absorption and optical saturation in metalloporphyrin-doped boric acid glass

Abstract The nonlinear absorption of five metal TMPPs (TMPP: tetrakis-(3,4,5-trimethoxyphenyl)porphyrin) doped in boric acid glass are measured with the linear polarized nanosecond laser pulses at different wavelengths by Z-scan; the two-photon absorption (TPA) is dominant in the near infrared, while the characteristic of saturation absorption (SA) is observed close to the Q(0,0) band of porphyrin. The symmetry allowed two-photon π*←π transitions are suggested to be 1 B 1 g * ← S 0 and 1 B 2 g * ← S 0 , with the cross-sections δ ranging from 25×10−50 to 114×10 −50 cm 4 s / photon . We analyze the property of SA with a four-level system, and find that the magnitudes of excited-state absorptivity and saturation intensity are not affected by changing the central metal ion in these experiments.

A Crossover Study of Noodle Soup Consumption in Melamine Bowls and Total Melamine Excretion in Urine

Background Melamine exposure remains common even after the 2008 melamine-tainted baby formula incident. Another source of melamine exposure is melamine tableware. Aims To investigate if consumption...