Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/12848
標題: 利用局部淋巴結分析(LLNA)偵測納乃得、谷速松及混合農藥之皮膚過敏性
Detection of skin sensitization capacity of methomyl, azinphos-methyl and mixed pesticides by local lymph node assay (LLNA)
作者: 林宜慧
Lin, Yi-Hui
關鍵字: local lymph node assay (LLNA);局部淋巴結分析(LLNA);methomyl;azinphos-methyl;mixed pesticide;dibutyl phthalate (DBP);納乃得;谷速松;混合農藥;鄰苯二甲酸二丁酯(DBP)
出版社: 獸醫學系暨研究所
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Experimental Animals. 59: 245-249, 2010. Basketter DA, Blaike L, Dearman RJ, Kimber I, Ryan CA, Gerberick GF, Harvey P, Evans P, White IR, Rycroft RJG. Use of the local lymph node assay for the estimation of relative contact allergenic potency. Contact dermatitis. 42: 344-348, 2000. Basketter DA, Lea LJ, Dickens A, Briggs D, Pate I, Dearman RJ, Kimber I. A comparison of statistical approaches to the derivation of EC3 values from local lymph node assay dose responses. Journal of Applied Toxicology. 19: 261-266, 1999. Basketter DA, Gerberick GF, Kimber I. Measurement of allergenic potency using the local lymph node assay. Pharmacological Sciences. 22: 264-265, 2001. Boverhof DR, Wiescinski CM, Botham P, Lees D, Debruyne E, Repetto-Larsay M, Ladics G, Hoban D, Gamer A , Remmele M, Wang-Fan W, Ullmann LG, Mehta J, Billington R, Woolhiser MR. Interlaboratory validation of 1% pluronic L92 surfactant as a suitable, aqueous vehicle for testing pesticide formulations using the murine local lymph node assay. Toxicology sciences. 105: 79-85, 2008. Buehler EV. Prospective testing for delayed contact hypersensitivity in guinea pigs. The Buehler method. Methods in immunotoxicology. 2: 343-356,1965. Bugelski PJ. Genetic aspects of immune-mediated adverse drug effects. Nature Reviews Drug Discovery. 4: 59-69, 2005. Cockshott A, Evans P, Ryan CA, Gerberick GF, Betts CJ, Dearman RJ, Kimber I. The local lymph node assay in practice: a current regulatory perspective. Toxicology. 25: 387-394, 2006. Cumberbatch M, Scott RC, Basketter DA, Scholes EW, Hilton J, Dearman RJ, Kimber I. Influence of sodium lauryl sulphate on 2,4-dinitrochlorobenzene-induced lymph node activation. Toxicologist. 77: 181-191, 1993. Dean JH, Twerdok LE, Tice RR, Sailstad DM. ICCVAM evaluation of the murine local lymph node assay. Regulatory Toxicology and Pharmacology. 34: 258-273, 2001. Dearman RJ, Cumberbatch M, Hilton J, Clowes HM, Fielding I, Heylings JR, Kimber I. Influence of dibutyl phthalate on dermal sensitization to fluorescein isothiocyanate. Toxicology. 33: 24-30, 1996. Federal insecticide, fungicide, and rodenticide act. As Amended Through P.L. 110–246, Effective May 22, 2008. Fukuyama T, Tajima Y, Ueda H, Hayashi K, Shutoh Y. Allergic reaction induced by dermal and/or respiratory exposure to low-dose phenoxyacetic acid, organophosphorus, and carbamate pesticides. Toxicology. 261: 152-161, 2006. Gad SC, Dunn BJ, Dobbs DW, Reilly C, Walsh RD. Development and validation of an alternative dermal sensitization test: the mouse ear swelling test (MEST). Toxicology. 84: 93-114, 1986. Gallagher E, Enzler T, Matsuzawa A, Karin M. 5-bromo-2-deoxyuridine (BrdU) and 7-amino-actinomycin (7-AAD) staining for cell proliferation assay. Protocol Exchange. 10: 1038, 2007. Gell PGH, Coombs RRA, Hachmann PJ. Classification of allergic reactions responsible for clinical hypersensitivity and diseases. Clinical Aspects of Immunology. Oxford: Blackwell Scientific Publications. 761-81, 1975. Gerberick GF, Ryan CA, Kimber I, Dearman RJ, Lea LJ, Basketter DA. Local lymph node assay: validation assessment for regulatory purposes. American journal of contact dermatitis. 11: 3-18, 2000. Harkness JE, Wagner JE. The biology and medicine of rabbits and rodents. 2nd ed. Lea & Febiger, Philadelphia, 1983. Heylings JR, Clowes HM, Cumberbatch M, Dearman RJ, Fielding I, Hilton J, Kimber I. Sensitization to 2,4-dinitrochlorobenzene: influence of vehicle on absorption and lymph node activation. Toxicologist. 109: 57-65, 1996. Hoppin JA, Umbach DM, London1 SJ, Henneberger PK, Kullman GJ, Alavanja MCR, Sandler DP. Pesticides and Atopic and Nonatopic Asthma among Farm Women in the Agricultural Health Study. American Journal of Respiratory and Critical Care Medicine. 177: 11-18, 2008. 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Chemical allergy: Translating biology into hazard characterization. Toxicological sciences. 120: S238-S268, 2011. Kimber I, Dearman RJ, Scholes EW, Basketter DA. The local lymph node assay: developments and applications. Toxicology. 93: 13-3, 1994. Kimber I, Hilton J, Dearman RJ, Gerberick GF, Ryan CA, Basketter DA, Scholes EW, Ladics GS, Loveless SE, House RV, Guy A. An international evaluation of the murine local lymph node assay and comparison of modified procedures. Toxicology. 103: 63-73, 1995. Kimber I, Pichowski JS, Basketter DA, Dearman RJ. Immune responses to contact allergens: novel approaches to hazard evaluation. Toxicology letters. 106: 237-246, 1999. Lalko J, Laol D, Api AM. Ethanol and Diethyl Phthalate: Vehicle Effects in the Local Lymph Node Assay. Toxicology. 23: 171-177, 2004. McGarry HF. The murine local lymph node assay: Regulatory and potency considerations under REACH. Toxicology. 238: 71-89, 2007. Magnusson B, Kligman AM. The identification of contact allergens by animal assay. The guinea pig maximization test. The Journal of Investigative Dermatology. 52: 268-276, 1969. Makrides C, Koukouvas M, Achillews G, Tsikkos S, Vounou E, Symeonides M, Christodoulides P, Ioannides M. Methomyl-Induced Severe Acute Pancreatitis: Possible Etiological Association. Journal of the Pancreas. 6: 166-171, 2005. Matsuda T, Maruyama T, Iizuka H, Kondo A, Tamai T, Kurohane K, Imai Y. Phthalate esters reveal skin-sensitizing activity of phenethyl isothiocyanate in mice. Food and Chemical Toxicology. 48: 1704-1708, 2010. Och FMM ven, Vandebriel RJ, Prinsen MK, De Jong WH, Slob Wm Loveren H ven. Comparison of dose–responses of contact allergens using the guinea pig maximization test and the local lymph node assay. Toxicology. 167: 207-215, 2001. Organization for Economic Cooperation and Development. 2002. OECD guideline for testing of chemicals: acute dermal irritation/corrosion. Organization for Economic Cooperation and Development. 2009. OECD guideline for testing of chemicals: Skin Sensitisation: Local Lymph Node Assay Penagos H, Ruepert C, Partanen T, Wesseling C. Pesticide Patch Test Series for the Assessment of Allergic Contact Dermatitis Among Banana Plantation Workers in Panama. Dermatitis. 15: 137-145, 2004. Roldan-Tapia L, Leyva A, Laynez F, Santed FS. Chronic Neuropsychological Sequelae of Cholinesterase Inhibitors in the Absence of Structural Brain Damage: Two Cases of Acute Poisoning. Environ Health Perspect. 113: 762–766, 2005. Takeyoshi M, Iida K, Suzuki K, Yamazaki S. Skin sensitization potency of isoeugenol and its dimers evaluated by a non-radioisotopic modification of the local lymph node assay and guinea pig maximization test. Journal of Applied Toxicology. 28: 530-534, 2008. Takeyoshi M, Noda S, Yamasaki K. Difference in responsiveness of mouse stain against p-Benzoquinone as assessed by non-radioisotopic murine local lymph node assay. 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USEPA Reregistration Eligibility Decision: Azinphos-methyl. United States Environmental Protection Agency, 1998. USEPA Reregistration Eligibility Decision: Methomyl. United States Environmental Protection Agency. 1998. Health effects test guidelines. OPPTS 870.2600 Skin sensitization. United States Environmental Protection Agency. 2003. Health effects test guidelines. OPPTS 870.2600 Skin sensitization. Vandebriel RJ, De Jong WH, Spiekstra SW. Allergic reaction induced by dermal and/or respiratory exposure to low-dose phenoxyacetic acid, organophosphorus, and carbamate pesticides. Toxicology. 162: 77-85, 2000a. Vandebriel RJ, De Jong WH, Spiekstra SW, Van Dijk M. Assessment of preferential T-helper 1 or T-helper 2 induction by low molecular weight compounds using the local lymph node assay in conjunction with RT-PCR and ELISA for interferon-γ and interleukin-4. Toxicology and applied pharmacology. 162: 77-85, 2000b. Vocanson M, Hennino A, Rozieres A, Cluzel-Taihaedat M, Poyet G, Valeyrie M, Benetiere J, Tedone R, Kaiserlian D, Nicolas JF. Skin exposure to weak and moderate contact allergens induces IFN-γ production by lymph node cells of CD4+ T-cell-depleted mice. Original article. 129: 1185-1191, 2009. Wang B, Esche C, Mamelak A, Freed I, Watanabe H, Sauder DN. Cytokine knockouts in contact hypersensitivity research. Cytokine & growth reviews. 14: 381-389, 2003. Wijk Fv, Stefan N. Assessment of drug-induced immunotoxicity in animal models. Drug Discovery Today: Technologies. 3: 103-109, 2006. Woolhiser MR, Munson AE, Meade BJ. Comparison of mouse strains using the local lymph node assay. Toxicology. 146: 221-227, 2000. Wright ZM, Basketter DA, Blaikie L, Cooper KJ, Warbrick EV, Dearman RJ, Kimber I. Vehicle effects on skin sensitizing potency of four chemicals: assessment using the local lymph node assay. International journal of cosmetic science. 23: 75-83, 2001.
摘要: 
許多類型的農藥,諸如有機磷類及胺基甲酸鹽類,具有較高的風險過度暴露足以危害到人類健康,可能導致過敏性氣喘,或者是過敏性接觸性皮膚炎。近幾年,過敏性接觸性皮膚炎已成為人類生活中一重要課題。為了檢測潛在的化學過敏物,研究人員發展出一種小鼠局部淋巴結分析 (local lymph node assay, LLNA)的方法,提供了定量且客觀的數據,適合做為劑量反應關係評估的標準。本研究中,利用LLNA檢測納乃得、谷速松以及四種混合農藥潛在皮膚過敏反應,並以2,4-dinitrochlorobenzene (DNCB)為陽性對照組,選用10% dibutyl phthalate (DBP)添加做為提升淋巴結細胞增生反應的增敏劑 (sensitizing agent)。實驗結果顯示,納乃得、谷速松及其他三種混合農藥 (包括陶斯寧、益保扶以及益達胺+第滅寧)具有較低或者陰性皮膚過敏反應。DNCB組及貝芬菲克利組之刺激指數 (stimulated index, SI值)皆大於3。然而,在添加10% DBP增敏劑後,僅造成部分組別輕微提升細胞增生活性,甚至有些組別加入DBP抑制了原有的細胞增生反應;針對貝芬菲克利混合農藥之兩單一農藥原體,在進行LLNA結果顯示SI值皆小於3。綜合本實驗結果,顯示納乃得及谷速松可能不具皮膚過敏反應;此外,DBP無法對任何過敏物質皆具良好的增敏效應,應為一種部分促進物;對於貝芬非克利混合農藥,我們發現到兩種非過敏原的農藥原體在相互調配混合後,可能影響原有的皮膚過敏特性。為了避免直接暴露於農藥過敏原之噴灑環境當中,建議農友及相關使用者應做好適當的防護措施,且建議農藥申請者在販售及註冊混合農藥時,對於皮膚過敏此一選項,應提供詳盡的實驗數據讓使用者做為參考,而非以現有之單一農藥原體本身的檢測結果做為主要依據。

Several types of pesticides, such as organophosphates and carbamate have a high risk of affecting human health, causing allergic rhinitis or allergic contact dermatitis. In recent years, allergic contact dermatitis has become an important subject in human life. In order to detect the potential chemicals allergens, the murine local lymph node assay (LLNA) has been developed and provided quantitative data suitable for dose response assessment. In this study, we designed to detect the potential skin sensitization of methomyl, azinphos-methyl technical pesticides, and 4 mixed pesticides by LLNA. The 2,4-dinitrochlorobenzene (DNCB) was used as positive control, and the 10% dibutyl phthalate (DBP) was added to increase the lymph node cells proliferative responses. The result of LLNA tests demonstrated methomyl, azinphos-methyl and other 3 mixed pesticides (include chlorpyrifos+cypermethrim, imidacloprid+carbofuran and imidacloprid+deltamethrin) with a low or negative skin sensitizing activity. DNCB and a mixed pesticide (carbendazim + hexaconazole) had a stimulated index (SI) more than 3. However, there was only a slightly increase or even reduction of the response after added 10% DBP. For the single pesticide of carbendazim and hexaconazole, the LLNA results showed that SI value were less than 3. In conclusion, methomyl and azinphos-methyl do not induce dermal sensitizing effects. In addition, not all of the skin sensitization of tested pesticides were augmented by DBP which may be regarded as partial enhances. For the mixed pesticides, we consider that the mixture of two pesticides may able to affect the skin sensitization. In order to avoid the potential hazard of pesticide allergens, appropriate protective measures should be taken for farmer and pesticide applicator, and we suggest the mixed pesticide products must provide the detailed skin sensitization information when registered.
URI: http://hdl.handle.net/11455/12848
其他識別: U0005-0808201122225600
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