2008 35 4 249 [19 ] WHITTLE E,BASKETTER D, YORK M,et al. Findings of an interlaboratory trial of the enucleated eye method as an alternative eye irritation test[j ]. Toxicol Methods,1992,2 : 30241. [20 ] MOLDENHAUER F. Using in vitro prediction models instead of the rabbit eye irritation test to classify and label new chemicals : a post hoc data analysis of the international ECΠHO validation study [J ]. Altern Lab Anim, 2003, 31 (1) : 31246. [21 ] PRINSEN M K. The Draize eye test and in vitro alternatives : a left2handed marriage? [ J ]. Toxicol In Vitro,2006,20 : 78281. [22 ] DEBBASCH C, EBENHAHN C, DAMI N, et al. Eye irritation of low2irritant cosmetic formulations : correlation of in vitro results with clinical data and product composition [J ]. Food Chem Toxicol,2005,43(1) : 1552165. [23 ] PRINSEN M K, KOT. TER H B. Justification of the enucleated eye test with eyes of slaughterhouse animals as an alternative to the Draize eye irritation test with rabbits[j ]. Food Chem Toxicol,1993,31 : 69271. [24 ] JONES P,BAGLEY D, FALLER C, et al. An overview of the COLIPA eye irritation research programme[j ]. ALTEX, 2006,23(Suppl) : 3242325. [25 ] MERRILL J, HAMERNIK K, SCHECHTMAN L M, et al. ICCVAM progress in evaluating in vitro test methods for identifying severe ocular irritantsπcorrosives [ J ]. ALTEX, 2006,23 (Suppl) : 2462249. [26 ] PRINSEN M K. The chicken enucleated eye test (CEET) : a practical (pre) screen for the assessment of eye irritationπ corrosion potential of test materials[j ]. Food Chem Toxicol, 1996,34 : 2912296. [27 ]. [M]. :,2006 : 4512477. [28 ] MAURER J K, PARKER R D, J ESTER J V. Extent of initial corneal injury as the mechanistic basis for ocular irritation: key findings and recommendations for the development of alternative assays [ J ]. Regul Toxicol Pharmacol,2002,36 : 1062117. [29 ],,. [J ].,2004,4 : 5152517. [30 ] PERROT S, DUTERTRE2CATELLA H, MARTIN C. Resazurin metabolism assay is a new sensitive alternative test in isolated pig corneal[j ]. Toxicol Sci,2003,72 : 1222129. [31 ] STITZEL K A. Tiered testing strategies acute local toxicity [J ]. ILAR,2002,43 (Suppl) : S212S26. [32 ] DESILVA O M,COTTIN M,DAMI N,et al. Evaluation of eye irritation potential : statistical analysis and tier testing [J ]. Food Chem Toxicol,1997,35 : 1592164. [33 ],. [J ].,2007,1 : 27231. 056 (, 100083) :,, :; ;; : R392233 ; R99 : A : 100121226 (2008) 0420249206 :2008202205 ; :2008204210 :(2006BAK02A02) ; (7082054) :,,, : :,,, : [1 ],
250 2008 35 4 [2 ],, 90 %, [3 ], ;, [4 ],,, [5 ] 2, [6 ],,, [1 ], replacement refinement),, 4,3 1, 4 [10 ] [1 ] 2 2,42,,,, ;,,, [5 ] 1 [7 ],: (1),, T [8 ] T (2),T [9 ] 3,, 1 2 11 (guinea pig maximisation test) 311 (occluded patch test of Buehler),,, 20,, 10,25,, 31111 16 3R ( reduction
2008 35 4 251, [11 ], T, 1992 Enk Katz [12 ] CD80 CD86 CD40,CD54 IL21 [13 ] IL21, IL21mRNA 1995 ( European Centre for the Validation of Alternative Methods, ECVAM), IL21 : (1 %3 %) [6 ], [8 ] 31112, IL24 Π ( GM2CSF),TGF2, IL23 ( TGF2 ) [11 ] 1997 Aiba [14 ] 2,42,24 48 CD54 CD86 HLA2DR, 1997 Rutter [15 ] 5 ( 2,42 ) 1 () IL21 mrna5 IL21mRNA, 2,4 2, 50 % IL21mRNA,,,, IL21mRNA [16 ] [8 ] 31113, U937 THP21 MUTZ23 [17 ], THP21 CD86 CD54 MCH2 [18 ], CD40 CD83 TNF2 IL28, 3, [19 ] ;MUTZ23 HLA2DR CD54 CD86 ;U937 CD86 IL21 IL28 mrna [20 ] U937 THP21 MUTZ23 3 2,42, HLA2DR CD54 CD86 MUTZ23 THP21 CD86 MUTZ23, CD86 MUTZ23 [7 ] 312,Jerchow [21 ] 2001, Π Π 3,,, ( 2 ) 31211
252 2008 35 4, : Hel230 4 2,42,,, HaCaT Hel230 [22 ] 31212,,, Π 8, [16 ], CD54 MHC2 CD11c 2,42, IL21 IL26 IL212 IL218 mrna T, [16 ] 313 Π :,, [6 ] 21, [22 ] 1996 Kubilus [23 ],, IL21 E2,, [15 ],,,, 1999 Coquette [24 ] Hel230 HaCaT IL21 IL28 IL21mRNA,Kubilus,, IL21mRNA,, Hel230 IL21, mrna, IL28 [8 ] IL21 IL218 HaCaT,, 4 IL28 IL21 IL21mRNA [25 ],,2,42 MTT,,, 4 Π,,,,, ;,,,,,3R,; Π,,, ECVAM 3R,
2008 35 4 253 T,,, 5 25,,10,,,,,3R ;,,, : [ 1 ] KIMBER I,BASKETTER D A, GERBERICK G F, et al. Allergic contact dermatitis [ J ]. Inter Immunopharmacol, 2002,2 :2012211. [ 2 ] KIMBER I,PICHOWSKI J S,BETTS C J,et al. Alternative approaches to the identification and characterization of chemical allergens[j ]. Toxicol In Vitro,2001,15 :3072312. [ 3 ]. [M]. :,2006 :4162417. [ 4 ] STAQUET M J, SPORTOUCH M, JACQUET C, et al. Moderate skin sensitizers can induce phenotypic changes on in vitro generated dendritic cells [ J ]. Toxicol In Vitro, 2004,18 :4932500. [ 5 ] BOS J D, MEINARDI. The 500dalton rule for skin penetration of chemical compounds and drugs [ J ]. Dermatol,2000,9 :1652169. Exp [ 6 ] HIROTA M,MORO O. MIP21, a novel biomarker for in vitro sensitization test using human monocytic cell line [J ]. Toxicol In Vitro,2006,13(20) :7362742. [ 7 ] PHILIPPE A,J EAN2LUC P,DELPHINE C. The cytokine2 dependent MUTZ23 cell line as an in vitro model for the screening of contact sensitization [ J ]. Toxicol Appl Pharmacol,2006,(212) :14223. [ 8 ] RYAN C A,HULETTEB C, GERBERICK G F. Appoaches for the development of cell2based in vitro methods for contact sensitization[j ]. Toxicol In Vitro,2001,15 :43255. [ 9 ] KIMBERA I,BASKETTERB D A, BUTLERC M. et al. Classification of contact allergens according to potency : proposals[j ]. Food Chem Toxicol, 2003, 9 ( 41) : 17992 1809. [10 ] GERBERICK G F, RYAN C A, DEARMAN R J, et al. Local lymph node assay(llna) for detection of sensitization capacity of chemicals[j ]. Methods,2007,41 :54260. [11 ] CLUZEL2TAILHARDA M, BONNET2DUQUENNOY M, de QUERAL D P. Chemicals with weak skin sensitizing properties can be identified using low2density microarrays on immature dendritic cells [J ]. Toxicol Lett, 2007, 174 : 982 109. [12 ] ENK A H, KATZ S I. Early molecular events in the induction phase of contact [J ]. Proc Nat Acad Sci USA, 1992,89 :139821402. [13 ] TUSCHL H, KOVAC R. Langerhans cells and immature dendritic cells as model systems for screening of skin sensitizers[j ]. Toxicol In Vitro,2001,15 :3272331. [14 ] AIBA S,MANOME H,YOSHINO Y,et al. In vitro treatment of human transforming growth factor2betal treatment derived dentritic cells with happens can induce the phenotypic and functional changes similar to epidermal Langerhans cells in the initiation phase of allergic contact sensitivity reaction [J ]. Immunol,1997,101 :68275. [15 ] RUTTER K,JAGER D,DEGWERT J,et al. In vitro model for contact sensitization, induction of IL21mRNA in human blood2derived dentritic cells by contact sensitizers [J ]. Toxicol In Vitro,1997,11 :6192626. [16 ] KIMBER I, CUMBERBATCH M, BETTS C J, et al. Dendritic cells and skin sensitisation hazard assessment[j ]. Toxicol In Vitro,2004,18 :1952202. [17 ] PEIFFER J L, LEON F, TISSIER M H. Comparison of MUTZ23,THP21 and U2937 cell lines as in vitro predictive models for contact sensitization[j ]. Toxicol Lett,2007,172 : 89290. [18 ] ASHIKAGAA T, HOYAA M, ITAGAKIA H, et al. Evaluation of CD86 expression and MHC class molecule internalization in THP21 human monocyte cells as predictive endpoints for contact sensitizers[j ]. Toxicol In Vitro,2002, 16 :7112716. [19 ] MIYAZAWA M,ITO Y,YOSHIDA Y. Phenotypic alterations and cytokine production in THP21 cellsin response to allergens[j ]. Toxicol In Vitro,2007,21 :4282437. [20 ] PYTHON F,GOEBEL C,AEBY P. Assessment of the U937
254 2008 35 4 cell line for the detection of contact allergens [J ]. Toxicol Appl Pharmacol,2007,(220) :1132124. [21 ] J ERCHOW T,WILTROUT R H, YOUNG H A. IL218 is a co2inducer of IL213 in NK and T cells ;a new potential role for IL218 in modulating the immune response[j ]. Immunol, 2001,162 :507025077. [22 ] van OCH F M M,van LOVEREN H, et al. Assessment of potency of allergenic activity of low molecular weight compounds based on IL21 and IL218 production by a murine and human keratinocyte cell line [J ]. Toxicol,2005,210 : 952109. [23 ] KUBILUS J,CANNON C,NEAL P,et al. Response of the epiderm skin model to topically applied irritants and allergens[j ]. Toxicol In Vitro,1996,9 :1572166. [24 ] COQUTTE A, BERNA N, VANENBOSCH A, et al. Differential expression and release of cytokines by an in vitro reconstructed human epidermis following exposure to skin irritant and sensitizing chemicals[j ]. Toxicol In Vitro,1999, 13 :8672877. [25 ] COQUTTE A,BERNA N,VANENBOSCH A,et al. Analysis of interleukin21a ( IL21a ) and interleukin28 ( IL28 ) expression and release in vitro reconstructed human epidermis for the prediction of in vivo skin irritation andπor sensitization[j ]. Toxicol In Vitro,2003,17 :3112321. 057 (, 100021),,,,, 1,, [1 ],, [25 ] 20 60,Amona [6,7 ],,, [8 ] [9 ],,,,, [10 ] 56 105,16 19,, ; ;;,,,, Rodrigue [11 ], 41mgΠkg Jung [12 ], 015211mgΠkg [13 ] : 01422mgΠkg, 01160mgΠkg,01123mgΠkg, 01334mgΠkg,01245mgΠkg,01460mgΠkg, 01278mgΠkg, 01836mgΠkg, 01153mgΠkg, 01794mgΠkg,11227mgΠkg,