棉酚對於國人健康風險評估

Health risks assessment of gossypol in Taiwanese population

邢化萱(Hua-Hsuan Hsing)

指導教授 ： 吳焜裕

國立臺灣大學/公共衛生學院/職業醫學與工業衛生研究所/碩士(2017年)

https://doi.org/10.6342/NTU201800395

摘要

2013年，臺灣發生「棉籽油事件」，引起國內對於棉酚的關注，棉酚已被證實具有生殖毒性，會抑制男性的精子生成，導致無精子症，且毒性作用具不可逆性；對女性會導致子宮內膜萎縮和閉經症。文獻指出棉酚在動物組織中具有蓄積性，過去五年國內進口近十公噸的棉仔粕用於動物飼料中，推測相關農產品可能殘留棉酚，且國人可能因動物源性食品而暴露；鑒於目前仍未有棉酚對於國人健康影響等相關研究，因此本研究目的之一為評估棉酚對於國人的健康風險；第二是初步探討棉酚和不孕症的相關性。
健康風險評估採用世界衛生組織(WHO)的食品中化學物質之健康風險評估流程進行，而暴露評估則使用貝氏統計馬可夫鏈蒙地卡羅(BSMCMC)的抽樣方法作模擬，根據文獻中棉酚殘留的實驗數據或參數，建立模擬動物源性食品中棉酚的模型，得到合理的事後分布，並配合國家攝食資料數據估算終生平均每日暴露劑量(LADD)和危害指標(HI)。在資料有限的情況下，本研究假設兩種暴露情境，結果危害指標均大於1，顯示棉酚對於國人的健康風險需要重視，並以此結果推算飼料中游離棉酚的建議含量，建議未來應對飼料和食品中棉酚殘留進行系統性監測。
本研究初探的個案來自茂盛醫院，共招募28位不孕症患者，透過問卷收集人口學變項、生活習慣和飲食習慣等，以及受試者血液檢體，並建立人體血漿中棉酚的線上固相萃取搭配液相層析串聯質譜儀方法，分析受試者血漿中棉酚含量。本研究的分析方法具有良好的線性(r^2 > 0.995)，同日和異日的準確度與精密度皆落在15%誤差範圍內，偵測極限(LOD)為0.25 ng/ml，而定量極限(LOQ)為1 ng/ml。結果於1位受試者血漿中成功偵測到低濃度的棉酚，雖因樣本數的限制，無法更進一步探討與不孕症相關性，但仍可證實國人的棉酚暴露，未來研究需要較長時間來納入更多不孕症和控制組受試者，另外亦可針對分析方式進行改善，如增加棉酚代謝物以及精液分析，來評估棉酚與不孕症的相關性。

關鍵字

棉酚 ； 不孕症 ； 貝氏統計馬可夫鏈蒙地卡羅 ； 液相層析串聯式質譜儀

並列摘要

In 2013, a food safety incidence occurred in some manufactures had illegally mixed cottonseed oil into other forms of cooking and edible oil. This event evoked public health concern. As an anti-fertility agent, gossypol was studied mainly in relation to its inhibition of spermatogenesis; however, the result shows that the spermatogenesis suppression is irreversible. For woman, gossypol resulted in amenorrhea and atrophic endometrium.
There is a lack of study on health effect of gossypol in Taiwan. Therefore, this study aims to demonstrate a health risk assessment process for Taiwanese to assess the potential health risk of gossypol in animal revived food. Second, we conducted a pilot study of the association between the infertility disease and gossypol exposure by developing an on-line solid-phase extraction-liquid chromatography-tandem mass spectrometry (LC-MS/MS) method to analyze gossypol in human serum.
Human health risk assessment was conducted using the United States Environmental Protection Agency (U.S. EPA) risk assessment process. For exposure assessment, exposure levels given two exposure scenarios were simulated by Bayesian Statistic Markov chain Monte Carlo (BSMCMC). The information of gossypol residues was collected along with the residues model estimation as the prior distribution. The updated distribution of the estimated exposure was then used to determine the life average daily dose (LADD) and the hazard index (HI). As the result, the hazard indexes were all greater than 1, indicated the exposure of gossypol in Taiwan should be concerned. Thus, we estimated the recommended free gossypol residues in animal feedstuffs. It is important to monitor the gossypol residues in food and in animal feedstuffs systematically in the future.
With REC approval and informed consented, a total of 28 infertility diseases patients at a hospital in Middle Taiwan were recruited in this pilot study. Subjects were asked to fill in the questionnaire to understand their diet and health conditions, and then the blood of subjects were collected.
The analysis method in this study provides good accuracy, precision and linearity. Low concentration of gossypol (> LOQ) was detected in one subject. This study successfully applied an analysis method to detect low concentration of gossypol to prove intake of gossypol. We recommend recruiting more patients to further discuss the association between the infertility disease and gossypol exposure. Besides, the analysis method could be improved by detecting semen samples and additional analytes.

並列關鍵字

Gossypol ； infertility disease ； LC-MS/MS ； BSMCMC

參考文獻

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