農藥之急性參考劑量科學評估與制定

Scientific Assessment and Setting on Acute Reference Dose for Pesticides

廖俊麟(Chun-Lin Liao) ； 李懿庭(Yi-Ting Li) ； 蔡韙任(Wei-Ren Tsai)

《臺灣農藥科學》 7期 (2019/12) Pp. 1-25

https://doi.org/10.6671/TPS.201912_(7).01

摘要

急性參考劑量（acute reference dose, ARfD）的定義，是指消費者在24小時或更短的時間內攝入食品和／或飲用水中殘留物質估算的參考劑量，該數值不會對消費者 造成短期的健康危害風險。制定農藥的急性參考劑量概念與每日可接受攝食量（acceptable daily intake, ADI）類似，需要評估藥劑之理化特性、作用機制（mode of action, MOA）、毒理動力學、動物毒理試驗或人體暴露研究等資料，並且分析不同資料的證據權重（weight of evidence），綜合評估最適合引用之推估起點劑量（point of departure, POD）與不確定因子（uncertain factors, Ufs）。本文將介紹ARfD的評估流程，包括ARfD制定基本原則及判定農藥是否需制定ARfD評估要件，並針對包括血液毒性 （haematotoxicity）、免疫毒性（immunotoxicity）、神經毒性（neurotoxicity）、肝腎毒性（liver and kidney toxicity）、內分泌干擾（endocrine disrupting effects）、發育毒性（developmental effects）、腸胃道影響（effects on gastrointestinal tract）及其他一般性症狀等不同毒性指標與評估ARfD之適用性差異進行說明。針對不確定因子設定上國際已導入採用特定化學物調節因子（chemical-specific adjustment factors, CSAFs）來精緻化相關係數，並說明調整不確定因子須考量的判定基準。一般會建議制定一個能保護所有族群的ARfD數值，但仍需特別考量對敏感性較高的特定族群（subpopulation）之危害風險。統計國際已制定農藥的ARfD資料中，最常被使用的試驗為出生前發育毒性及神經毒性試驗。本研究參考目前國際的ARfD評估指引文件及相關研究報告，闡述ARfD的制定流程，提供符合國際指引的評估基準，作為我國相關學者在評估農藥之ARfD時之參考依據，以精進短期取食風險評估及應用於殘留污染事件發生的風險評估及風險管理。

關鍵字

農藥 ； 急性參考劑量 ； 評估指標 ； 推估起點劑量 ； 不確定因子

並列摘要

Acute reference dose (ARfD) is defined as ＂Estimate the amount of a substance in food and/or drinking water, that can be ingested in a period of 24 h or less without appreciable health risk to the consumer＂. For pesticides, the process involved in setting ARfD values is similar to that used in setting acceptable daily intake (ADI) values. Both processes involve assessing the scientific studies include physical and chemical properties, mode of action, toxicokinetics, toxicological studies of animals and investigations of human exposures. After analyzing the weight of evidence from different sources, the most appropriate point of departure (POD) and uncertainty factors (Ufs) are derived. This article introduces the stepwise process to set ARfD, such as the basic concepts of ARfD and the principles to determine whether it is necessary to set an ARfD value. In this study, we also explain the relevance of setting ARfD values for various endpoints, including haematotoxicity, immunotoxicity, neurotoxicity, liver and kidney toxicity, endocrine disrupting effects, developmental effects, effects on the gastrointestinal tract and other non-specific findings. We further discuss the derivation of UFs and explain the criteria used in adjusting UFs. (Note that, in calculating UFs, the international has introduced the use of chemical-specific adjustment factors (CSAFs) to refine coefficient settings.) It is generally recommended to set one ARfD value which is capable of protecting all populations. However, it is also necessary to specially consider hazards which affect specific subpopulations. In this study, we also reviewed statistics results of pesticide's ARfDs established by a number of countries. In so doing, we found that the developmental toxicity test and the neurotoxicity test are the most commonly used endpoints of toxicological studies. In summary, the current work was primarily based on current international ARfD assessment guidelines and research reports. It provides a detailed description of the derivation process of ARfD and a practical evaluation process that is consistent with international trends. Our process can be applied in future studies which assess pesticide ARfDs and can also be used to refine short-term dietary risk assessments, conduct risk assessments, and manage cases involving incidental pesticide residues.

並列關鍵字

pesticide ； acute reference dose ； endpoints ； point of departure ； uncertainty factors