Annex II: Lymph node assay (LLNA) data on 59 fragrance substances, based on a summary report submitted by the Research Institute for Fragrance

Transcription

1 Annex II: Lymph node assay (LLNA) data on 59 fragrance s, based on a summary report submitted by Research Institute for Fragrance Materials, Inc. (RIFM, 2009) 1

2 INCI name (or name) Allyl phenoxyacetate Amyl cinnamal Amyl cinnamal Amyl cinnamal Amyl cinnamal Amylcinnamyl alcohol :3 EtOH:DEP :3 EtOH:DEP 5.0, , Elahi gives ref to Basketter et al 1999, but no data on is found. It is not known if Elahi, Aptula and Roberts quote same experiment :1 AOO Aptula gives ref to Kimber et al 2003, but no LLNA data on is found. It is not known if Elahi, Aptula and Roberts quote same experiment; original reference is not given Original ref not given :3 EtOH:DEP 10.0, > 25 >6250 >1.22 > 25 concentrations 59 Anise alcohol :3 EtOH:DEP 25.0,

3 INCI name (or name) Benzaldehyde Benzaldehyde Benzyl alcohol Benzyl benzoate No data in ref No data in ref (poster abstract) :3 EtOH:DEP :3 EtOH:DEP 25.0, > 50 >12500 >4.62 > , > 50 >12500 >2.36 > 50 concentrations 75 concentrations 76 Benzyl cinnamate Benzyl salicylate :3 EtOH:DEP :3 EtOH:DEP p-tert-butyldihydrocinnamaldehyde :3 EtOH:DEP 25.0, , , Butylphenyl methylpropional (BMHCA) EtOH 30.0, Butylphenyl methylpropional (BMHCA) DEP 30.0, Butylphenyl methylpropional (BMHCA) :3 EtOH:DEP 0.3, 1.0, 3.0, 10.0,

4 INCI name (or name) Butylphenyl methylpropional (BMHCA) :3 DEP:EtOH 0.3, 1.0, 3.0, 10.0, Butylphenyl methylpropional (BMHCA) :1 AOO 10.0, Butylphenyl methylpropional (BMHCA) :1 AOO Camellia sinensis leaf Tea Leaf Absolute DMF 1, 2.5, 10, 25, , > 5.0 >1250 N/a > 5.0 concentrations 86 Cananga odorata leaf / flower oil Ylang Ylang Extra Carvone Carvone Carvone :3 EtOH:DEP 5.0, N/a :3 EtOH:DEP 25.0, :3 EtOH:DEP 25.0, :1 AOO 6.0, 12, :1 EtOH:DEP 0.1% α-tocopherol in 2 3:1 EtOH:DEP 2.0% α-tocopherol in 2 3:1 EtOH:DEP 0.1, 0.3, 1.0, 3.0, , 0.3, 1.0, 3.0, , 0.3, 1.0, 3.0,

5 INCI name (or name) 0.3% antioxidant mix (equal parts BHT, tocopherol and eugenol) in 3:1 2 EtOH:DEP 0.1% Trolox C in 3:1 2 EtOH:DEP 2.0% α-tocopherol in 2 3:1 EtOH:DEP 2 3:1 EtOH:DEP 0.1% α-tocopherol in 2 3:1 EtOH:DEP 0.3% antioxidant mix (equal parts BHT, tocopherol and eugenol) in 3:1 0.1, 0.3, 1.0, 3.0, , 0.3, 1.0, 3.0, , 0.3, 1.0, 3.0, , 0.3, 1.0, 3.0, , 0.3, 1.0, 3.0, , 0.3, 1.0, 2 EtOH:DEP 3.0, % Trolox C in 3:1 0.1, 0.3, 1.0, 2 EtOH:DEP 3.0, No data in ref (poster abstract) 5 0.5, 1, 2.5, 5, 2 4:1 AOO :1 AOO Too few concentrations tested; few details 2 4:1 AOO 1, given in ref :1 AOO 10.0, MEK

6 INCI name (or name) Cinnamyl alcohol Cinnamyl nitrile , DMF 2 propylene glycol 2 DMSO 2 90:10 EtOH:water 2 50:50 EtOH:water 0.1, 0.25, 0.5, 10.0, , , 0.25, 0.5, 10.0, , , :3 EtOH:DEP :3 EtOH:DEP % α-tocopherol in :1 EtOH:DEP 0.3% antioxidant mix (equal parts BHT, tocopherol and eugenol) in 3: EtOH:DEP % Trolox C in 3: EtOH:DEP 25.0, > 10 >2500 >0.77 > 10 No data in ref (poster abstract) 5 Report: systemic toxicity at 25% and 50%. Should have been concentrations , 2.0, 4.0, 8.0, , 1.0, 3.0, 10.0, , 1.0, 3.0, 10.0, , 1.0, 3.0, 10.0,

7 INCI name (or name) Citronellol :1 EtOH:DEP 0.3% antioxidant mix (equal parts BHT, tocopherol and eugenol) in 3: EtOH:DEP :1 EtOH:DEP % Trolox C in 3: EtOH:DEP 0.3, 1.0, 3.0, 10.0, , 1.0, 3.0, 10.0, , 1.0, 3.0, 10.0, , 1.0, 3.0, 10.0, :3 EtOH:DEP 25.0, % α-tocopherol in 0.3, 1.0, 3.0, :1 EtOH:DEP 10.0, No data in ref (poster abstract) :3 EtOH:DEP 25.0, Coumarin DMF 10, 25, 50 4 >50 >12500 >3.42 >50 Dibenzyl er :3 EtOH:DEP concentrations , Eugenol :1 EtOH:DEP Eugenol :3 EtOH:DEP 30.0, ,

8 INCI name (or name) Eugenol EtOH Eugenol DEP 30.0, , Eugenol :1 AOO 25.0, Eugenol No data in ref (poster abstract) 3 Evernia furfuracea extract Treemoss absolute :3 EtOH:DEP 5.0, 10.0, 20 4 > 20 >5000 N/a > 20 concentrations 69 Evernia furfuracea extract Treemoss absolute :3 EtOH:DEP 10.0, > 25 >6250 N/a Too few concentrations tested 62 Evernia prunastri extract Oakmoss Farnesol Farnesol :3 EtOH:DEP 25.0, N/a :1 AOO 5.0, 10.0, :1 AOO 5.0, 10.0, Should also have been tested at lower concentrations 62 Should also have been tested at lower concentrations 62 Geraniol Geraniol EtOH :1 EtOH:DEP 30.0, ,

9 INCI name (or name) Geraniol Geraniol Geraniol Geraniol trans-2-hexenal trans-2-hexenal Hexyl cinnamal DEP :3 EtOH:DEP 30.0, , :1 EtOH:DEP 30.0, :3 EtOH:DEP 5, generally 4:1 AOO -O "numerous accounts in literature" 2-Hexylidene cyclopentanone Hexyl salicylate Hydroxycitronellal Hydroxycitronellal Hydroxycitronellal :3 EtOH:DEP :3 EtOH:DEP :3 EtOH:DEP DEP :1 EtOH:DEP 0.1, 0.5, 1.0, 2.5, , 0.25, 0.5, 1.0, , , ,

10 INCI name (or name) Hydroxycitronellal Hydroxycitronellal Hydroxycitronellal Hydroxycitronellal Hydroxycitronellal Hydroxycitronellal EtOH 30.0, AOO 25, 50, EC3 value not given , 5, 10, 25, 5 4:1 AOO No data in ref (poster abstract) Too few concentrations tested; few details 5 4:1 AOO 10, given in ref 104 Hydroxyisohexyl 3- cyclohexene carboxaldehyde p-isobutyl-α-methyl hydrocinnamaldehdye :1 AOO % EtOH 1.0, 2.5, 5, 10, 25, , 25.0, 50.0, Should also have been tested at lower concentrations 34 Isocyclocitral Isocyclogeraniol :3 EtOH:DEP :3 EtOH:DEP 0.5, 1.0, 2.5, 5.0, , 10.0, 25.0, > 25 >6250 >1.62 > 25 Isoeugenol :1 AOO 0.5, concentrations 81 Too few concentrations tested 30 Isoeugenol :1 AOO 0.5, 1.0,

11 INCI name (or name) Isoeugenol :1 AOO 0.5, 1.0, Isoeugenol :1 AOO 0.5, 1.0, Isoeugenol :1 AOO 0.5, 1.0, Isoeugenol :1 AOO 0.5, 1.0, , 0.5, 1.0, Isoeugenol :1 AOO 2.5, Isoeugenol :1 AOO 0.5, 1.0, Isoeugenol :1 AOO 0.25, 0.5, 1.0, 2.5, Isoeugenol No data in ref (poster abstract) 5 Isoeugenol :1 AOO 0.25, 0.5, 1.0, 2.5, or Isoeugenol :1 AOO 0.25, 0.5, 1.0, 2.5, or Isoeugenol :1 AOO 0.25, 0.5, 1.0, 2.5, or Isoeugenol :1 AOO 0.25, 0.5, 1.0, 2.5, or Isoeugenol :1 AOO 0.25, 0.5, 1.0, 2.5, or Isoeugenol AOO 5.0, Isoeugenol MEK 5.0, Isoeugenol DMF 5.0, Isoeugenol propylene glycol 5.0, Isoeugenol DMSO 5.0,

12 INCI name (or name) Isoeugenol :10 EtOH:water Isoeugenol :50 EtOH:water 5.0, , Jasmine absolute (Grandiflorum) :3 EtOH:DEP 10.0, N/a Jasminum Sambac Flower CERA / Extract / Water d-limonene** d-limonene** d-limonene** d-limonene** d-limonene** :3 EtOH:DEP EtOH :1 EtOH:DEP :3 EtOH:DEP 10.0, 25.0, 50.0, 75.0, N/a , 20.0, 50.0, 75.0, < 10 < 250 <0.73 < , 20.0, 50.0, 75.0, Should also have been tested at lower concentrations , 20.0, 50.0, 75.0, , 20.0, 50.0, 75.0, DEP :1 AOO 25, 50, Linalool** Menthadiene-7-methyl formate :3 EtOH:DEP 5.0, > 10 > 2500 >0.51 > 10 No data in ref (poster abstract) 5 concentrations

13 INCI name (or name) 4-Methoxy-α-methyl benzenpropanal :3 EtOH:DEP 5.0, α-methyl cinnamic aldehyde Methylenedioxyphenyl methylpropanal 6-Methyl-3,5-heptadien-2- one α-iso-methylionone :3 EtOH:DEP :3 EtOH:DEP :3 EtOH:DEP 25.0, , > 5 > 1250 >0.40 > 5 concentrations , 25.0, 50.0, 75.0, Methyl octine carbonate Methyl 2-octynoate :3 EtOH:DEP 0.5, 1.0, 2.0, 5.0, < 0.5 < 125 <0.032 < 0.5 Should also have been tested at lower concentrations 84 2-Methoxy-4-methylphenol Octen-3-yl acetate :3 EtOH:DEP 7.5, 15.0, > 30 > 7500 >1.76 > 30 concentrations 65 Perillaldehyde p-mentha-1,8- dien-7-al :3 EtOH:DEP 5.0,

14 INCI name (or name) Perillaldehyde p-mentha-1,8- dien-7-al Balsam oil, Peru (Myroxylon pereirae Klotzsch) :3 EtOH:DEP 25.0, N/a Peru balsam absolute Peru balsam absolute Phenylacetaldehyde Phenylacetaldehyde 3-Propylidenephthalide Tetramethyl acetyloctahydronaphthalenes (OTNE) Trimethylbenzenepropanol Majantol Vanillin :3 EtOH:DEP 25.0, N/a :3 EtOH:DEP 0.5, 1.0, >2.5 >625 N/a :1 AOO 2.5, 5, 10, 25, No data in ref (poster abstract) :1 AOO 5, 10, 20 4 or :3 EtOH:DEP Should also have been tested at lower concentrations , :1 AOO 3.0, 10.0, ~30 ~7500 ~ :1 AOO concentrations , 5, 10, 25, 50 4 >50.0 >1250 >3.3 > * source of EC3 value value: % given in RIFM report or references; µg/cm2 given in RIFM report and RIFM poster; M calculated by SCCS working **material with low levels of oxidation according to RIFM,

15 INCI name (or name) - = no data given; A216 15

16 s to Annex II 1. Aptula, N., Roberts, D.W., Schultz, T.W., Pease, C., Reactivity assays for non-animal based prediction of skin sensitisation potential. Toxicology, 231(2-3), Ashby J, Basketter D.A., Patton, D., Kimber I Structure activity relationships in skin sensitization using murine local lymph node assay. Toxicology 103: Basketter, D.A., Gilmour, N., Dearman, R.J., Kimber, I., Ryan, C.A., Gerberick, F., Classification of skin sensitisation potency using Local Lymph Node Assay. The Toxicologist, 72(S-1), Basketter, D. A., Lea, L. J., Dickens, A., Briggs, D., Pate, I., Dearman, R. J., Kimber, I., A comparison of statistical approaches to derivation of EC3 values from local lymph node assay dose responses. Journal of Applied Toxicology, 19(4), Basketter, D.A., Wright, Z., Gilmour, N.J., Ryan, C.A., Gerberick, G.F., Robinson, M.K., Dearman, R.J., Kimber, I., Prediction of human sensitization potency using local lymph node assay EC3 values. The Toxicologist, 66(1-S), Basketter, D. A., Wright, Z. M., Warbrick, E. V., Dearman, R. J., Kimber, I., Ryan, C. A., Gerberick, G. F., White, I. R., Human potency predictions for aldehydes using local lymph node assay. Contact Dermatitis, 45(2), Elahi, E.N., Wright, Z., Hinselwood, D., Hotchkiss, S.A.M., Basketter, D.A., Smith Pease, C.K., Protein binding and metabolism influence relative skin sensitization potential of cinnamic compounds. Chemical Research in Toxicology, 17(3), Estrada, E., Patlewicz, G., Chamberlain, M., Basketter, D., Larbey, S., Computer aided Knowledge Generation for Understanding Skin Sensitization Mechanisms: The TOPS-MODE Approach. Chem. Res. Toxicol., 16, Gerberick, G.F., Ryan, C.A,. Kern, P.S., Dearman, R.J., Kimber, I., Patlewicz, G.Y., Basketter, D.A A chemical dataset for evaluation of alternative approaches to skin-sensitization testing. Contact Dermatitis 50, Loveless, S. E., Ladics, G. S., Gerberick, G. F., Ryan, C. A., Basketter, D. A., Scholes, E. W., House, R. V., Hilton, J., Dearman, R. J., Kimber, I., Furr evaluation of local lymph node assay in final phase of an international collaborative trial. Toxicology, 108(1-2), Nilsson, A.-M., Bergstrom, M.A., Luthman, K., Nilsson, J.L.G., Karlberg, A.-T., An alpha,beta-unsaturated oxime identified as a strong contact allergen. Indications of antigen formation via several pathways. Food and Chemical Toxicology, 43(11), RIFM, 2001a. Local Lymph Node Assay on p-t-butyl-α-methyl-hydrocinnamic aldehyde in EtOH. RIFM report number RIFM, 2001b. Local Lymph Node Assay on p-t-butyl-α-methyl-hydrocinnamic aldehyde in DEP. RIFM report number RIFM, 2001c. Local Lymph Node Assay on p-t-butyl-α-methyl-hydrocinnamic aldehyde in 1:3 EtOH:DEP. RIFM report number (RIFM, Woodcliff Lake, NJ, USA) 16

17 15. RIFM, 2001d. Local Lymph Node Assay on p-t-butyl-α-methyl-hydrocinnamic aldehyde in 1:3 DEP:EtOH. RIFM report number (RIFM, Woodcliff Lake, NJ, USA) 16. RIFM, 2001e. Local Lymph Node Assay on p-t-butyl-α-methyl-hydrocinnamic aldehyde in 4:1 acetone:olive oil. RIFM report number (RIFM, Woodcliff Lake, NJ, USA) 17. RIFM, 2001f. Local Lymph Node Assay on eugenol. RIFM report number RIFM, 2001g. Local Lymph Node Assay on eugenol. RIFM report number RIFM, 2001h. Local Lymph Node Assay on eugenol. RIFM report number RIFM, 2001i. Local Lymph Node Assay on eugenol. RIFM report number RIFM, 2001j. Local Lymph Node Assay on geraniol in ethanol. RIFM report number RIFM, 2001k. Local Lymph Node Assay on geraniol in DEP. RIFM report number RIFM, 2001l. Local Lymph Node Assay on geraniol in 1:3 EtOH:DEP. RIFM report number RIFM, 2001m. Local Lymph Node Assay on geraniol in 3:1 EtOH:DEP. RIFM report number RIFM, 2001n. Local Lymph Node Assay on hydroxycitronellal in 1:3 EtOH:DEP. RIFM report number RIFM, 2001o. Local Lymph Node Assay on hydroxycitronellal in DEP. RIFM report number RIFM, 2001p. Local Lymph Node Assay on hydroxycitronellal in 3:1 EtOH:DEP. RIFM report number RIFM, 2001q. Local Lymph Node Assay on hydroxycitronellal in EtOH. RIFM report number RIFM, 2001r. Local Lymph Node Assay on p-t-butyl-α-methyl-hydrocinnamic aldehyde in 4:1 acetone:olive oil. RIFM report number Unpublished report from Unilever. 30. RIFM, 2001s. Local Lymph Node Assay on isoeugenol in 4:1 acetone:olive oil. RIFM report number Unpublished report from Firmenich. (RIFM, Woodcliff Lake, NJ, USA) 31. RIFM, 2001t. Local Lymph Node Assay on isoeugenol in 4:1 acetone:olive oil. RIFM report number Unpublished report from Firmenich. (RIFM, Woodcliff Lake, NJ, USA) 32. RIFM, 2001u. Local Lymph Node Assay on isoeugenol in 4:1 acetone:olive oil. RIFM report number Unpublished report from Firmenich. (RIFM, Woodcliff Lake, NJ, USA) 33. RIFM, 2001v. Local Lymph Node Assay on isoeugenol in 4:1 acetone:olive oil. RIFM report number Unpublished report from Firmenich. (RIFM, Woodcliff Lake, NJ, USA) 34. RIFM, 2001w. Local Lymph Node Assay on p-isobutyl-α-methyl hydrocinnamaldehdye in 70% Ethanol. RIFM report number Unpublished report from Givaudan. 17

18 35. RIFM, 2002a. Local Lymph Node Assay on isoeugenol in 4:1 acetone:olive oil. RIFM report number Unpublished report from Firmenich. (RIFM, Woodcliff Lake, NJ, USA) 36. RIFM, 2002b. Local Lymph Node Assay on isoeugenol in 4:1 acetone:olive oil. RIFM report number Unpublished report from Firmenich. (RIFM, Woodcliff Lake, NJ, USA) 37. RIFM, 2002c. Local Lymph Node Assay on isoeugenol in 4:1 acetone:olive oil. RIFM report number Unpublished report from Firmenich. (RIFM, Woodcliff Lake, NJ, USA) 38. RIFM, 2002d. Local Lymph Node Assay on majantol in 4:1 acetone:olive oil. RIFM report number Unpublished report from Symrise. (RIFM, Woodcliff Lake, NJ, USA) 39. RIFM, 2003a. Local Lymph Node Assay on cinnamic aldehyde in 3:1 EtOH:DEP. RIFM report number RIFM, 2003b. Local Lymph Node Assay on cinnamic aldehyde in 3:1 EtOH:DEP with 0.1% tocopherol. RIFM report number RIFM, 2003c. Local Lymph Node Assay on cinnamic aldehyde in 3:1 EtOH:DEP with 2.0% tocopherol. RIFM report number RIFM, 2003d. Local Lymph Node Assay on cinnamic aldehyde in 3:1 EtOH:DEP with antioxidant mix. RIFM report number RIFM, 2003e. Local Lymph Node Assay on cinnamic aldehyde in 3:1 EtOH:DEP with 0.1% Trolox C. RIFM report number RIFM, 2003f. Local Lymph Node Assay on cinnamic aldehyde in 3:1 EtOH:DEP with 2.0% tocopherol. RIFM report number RIFM, 2003g. Local Lymph Node Assay on cinnamic aldehyde in 3:1 EtOH:DEP. RIFM report number RIFM, 2003h. Local Lymph Node Assay on cinnamic aldehyde in 3:1 EtOH:DEP with 0.1% tocopherol. RIFM report number RIFM, 2003i. Local Lymph Node Assay on cinnamic aldehyde in 3:1 EtOH:DEP with antioxidant mix. RIFM report number RIFM, 2003j. Local Lymph Node Assay on cinnamic aldehyde in 3:1 EtOH:DEP with 0.1% Trolox C. RIFM report number RIFM, 2003k. Local Lymph Node Assay on citral in 3:1 EtOH:DEP with 0.1% tocopherol. RIFM report number RIFM, 2003l. Local Lymph Node Assay on citral in 3:1 EtOH:DEP with antioxidant mix. RIFM report number RIFM, 2003m. Local Lymph Node Assay on citral in 3:1 EtOH:DEP with antioxidant mix. RIFM report number RIFM, 2003n. Local Lymph Node Assay on citral in 3:1 EtOH:DEP. RIFM report number RIFM, 2003o. Local Lymph Node Assay on citral in 3:1 EtOH:DEP with antioxidant mix. RIFM report number RIFM, 2003p. Local Lymph Node Assay on citral in 3:1 EtOH:DEP with antioxidant mix. RIFM report number RIFM, 2003q. Local Lymph Node Assay on citral in 3:1 EtOH:DEP with 0.1% Trolox C. RIFM report number

19 56. RIFM, 2003r. Local Lymph Node Assay on citral. RIFM report number (RIFM, Woodcliff Lake, NJ, USA) 57. RIFM, 2003s. Local Lymph Node Assay on citral. RIFM report number (RIFM, Woodcliff Lake, NJ, USA) 58. RIFM, 2003t. Local Lymph Node Assay on geraniol in 3:1 EtOH:DEP. RIFM report number RIFM, 2004a. Local Lymph Node Assay on α-amylcinnamyl alcohol. RIFM report number RIFM, 2004b. Local Lymph Node Assay on. RIFM report number (RIFM, Woodcliff Lake, NJ, USA) 61. RIFM, 2004c. Local Lymph Node Assay on d,l-citronellol. RIFM report number RIFM, 2004d. Local Lymph Node Assay on farnesol RIFM report number Unpublished report from Symrise 63. RIFM, 2004e. Local Lymph Node Assay on isoeugenol RIFM report number Unpublished report from Firmenich 64. RIFM, 2004f. Local Lymph Node Assay on 4-methoxy-α-methyl benzenpropanal. RIFM report number Unpublished report from IFF (RIFM, Woodcliff Lake, NJ, USA) 65. RIFM, 2004g. Local Lymph Node Assay on 1-Octen-3-yl acetate. RIFM report number Unpublished report from IFF 66. RIFM, 2004h. Local Lymph Node Assay on Peru Balsam Oil. RIFM report number RIFM, 2004i. Local Lymph Node Assay on Peru Balsam Absolute. RIFM report number RIFM, 2004j. Oakmoss absolute: Local lymph node assay. RIFM report number RIFM, 2004k. Treemoss absolute: Local lymph node assay. RIFM report number RIFM, 2004l. d-limonene: Local lymph node assay. RIFM report number RIFM, 2004m. d-limonene: Local lymph node assay. RIFM report number RIFM, 2004n. d-limonene: Local lymph node assay. RIFM report number RIFM, 2004o. d-limonene: Local lymph node assay. RIFM report number RIFM, 2005a. Local Lymph Node Assay on anisyl alcohol. RIFM report number RIFM, 2005b. Local Lymph Node Assay on benzyl alcohol. RIFM report number RIFM, 2005c. Local Lymph Node Assay on benzyl benzoate. RIFM report number RIFM, 2005d. Local Lymph Node Assay on benzyl cinnamate. RIFM report number

20 78. RIFM, 2005e. Local Lymph Node Assay on benzyl salicylate. RIFM report number RIFM, 2005f. Local Lymph Node Assay on cinnamyl nitrile. RIFM report number RIFM, 2005g. Local Lymph Node Assay on trans-2-hexenal in 1:3 EtOH:DEP. RIFM report number RIFM, 2005h. Local Lymph Node Assay on isocyclogeraniol in 1:3 EtOH:DEP. RIFM report number RIFM, 2005i. Local Lymph Node Assay on α-methyl-1,3-benzodioxole- 5- propionaldehyde in 1:3 EtOH:DEP. RIFM report number (RIFM, Woodcliff Lake, NJ, USA) 83. RIFM, 2005j. Local Lymph Node Assay on α-iso-methylionone in 1:3 EtOH:DEP. RIFM report number RIFM, 2005k. Local Lymph Node Assay on Methyl 2-octynoate in 1:3 EtOH:DEP. RIFM report number RIFM, 2005l. Local Lymph Node Assay on OTNE in 1:3 EtOH:DEP. RIFM report number RIFM, 2005m. Local Lymph Node Assay on tea leaf absolute. RIFM report number Unpublished report from Robertet 87. RIFM, 2006a. Local Lymph Node Assay on α-amylcinnamaldehyde. RIFM report number RIFM, 2006b. Local Lymph Node Assay on hexyl salicylate. RIFM report number RIFM, 2006c. Local Lymph Node Assay on isocyclocitral. RIFM report number RIFM, 2006d. Local Lymph Node Assay on Jasmine Absolute (Grandiflorum). RIFM report number RIFM, 2006e. Local Lymph Node Assay on Jasmine Absolute (Sambac). RIFM report number RIFM 2007a. Local Lymph Node Assay on allyl phenoxyacetate. RIFM report number RIFM, 2007b. Local Lymph Node Assay on p-t-butyl-dihydrocinnamaldehyde. RIFM report number RIFM, 2007c. Local Lymph Node Assay on carvone. RIFM report number RIFM, 2007d. Local Lymph Node Assay on carvone. RIFM report number RIFM, 2007e. Local Lymph Node Assay on dibenzyl er. RIFM report number RIFM, 2007f. Local Lymph Node Assay on Ylang Ylang Extra. RIFM report number RIFM, 2008a. Local Lymph Node Assay on 2-hexylidene cyclopentanone. RIFM report number RIFM, 2008b. Local Lymph Node Assay on p-mentha-1,8-dien-7-al. RIFM report number

21 100. RIFM, 2008c. Local Lymph Node Assay on menthadiene-7-methyl formate. RIFM report number RIFM, 2008d. Local Lymph Node Assay on 6-methyl-3,5-heptadien-2-one. RIFM report number RIFM Research Institute for Fragrance Materials, Inc. Local lymph node assay (LLNA) protocol summaries: Data presented at 46th Congress of European Societies of Toxicology 103. Roberts, D.W., Patlewicz, G., Kern, P.S., Gerberick, F., Kimber, I., Dearman, R.J., Ryan, C.A., Basketter, D.A., Aptula, A.O., Mechanistic applicability domain classification of a local lymph node assay dataset for skin sensitization. Chemical Research in Toxicology, 20(7), Smith, C.K., Hotchkiss, S.A.M., Allergic Contact Dermatitis. Taylor & Francis, New York 105. Vocanson, M., Goujon, C., Chabeau, G., Castelain, M., Valeyrie, M., Floch, F, Maliverney, C., Gard A., Nicolas, J.F The skin allergenic properties of chemicals may depend on contaminants - evidence from studies on coumarin. International Archives of Allergy and Immunology, 140, Warbrick, E.V.R., Dearman J., Ashby J., Schmezer P. and Kimber I Preliminary assessment of skin sensitizing activity of selected rodent carcinogens using local lymph node assay. Toxicology, 163(1), Wright, Z. M., Basketter, D. A., Blaikie, L., Cooper, K. J., Warbrick, E. V., Dearman, R. J., Kimber, I., Vehicle effects on skin sensitization potency of four chemicals assessment using local lymph node assay. International Journal of Cosmetic Science, 23(2),