3T3 Phototoxicity Poster Presented at the 2013 SOT Meeting
This page contains supplemental information for the poster titled “Screening of Cosmetics Ingredients for Phototoxic Potential Using the In Vitro 3T3 Neutral Red Uptake Phototoxicity Test” (Abstract Number 1479 Poster Board 536) presented at the Society of Toxicology annual meeting in the poster session “Alternative High-Throughput Models I: March 12, 2013 from 1:00 PM to 4:30 PM”. For more information on the 3T3 Phototoxicity assay, please visit the 3T3 phototoxicity assay section of our website. For more information on IIVS, the other assays that we have commercially available, and more of our activities, please explore the the website or contact us at email@example.com.
Screening of Cosmetics Ingredients for Phototoxic Potential Using the In Vitro 3T3 Neutral Red Uptake Phototoxicity Test
Authors: Labib, R(1), Gilberti, E(1), Gettings, S(1) and Raabe, H(2)
(1)Avon Products, Inc., Suffern, NY, USA
(2)Institute for In Vitro Sciences, Inc., Gaithersburg, MD, USA
Phototoxicity is an acute toxic response after exposure to a phototoxicant and either UV radiation or visible light (UV/VIS). Phototoxicity from substances applied topically typically occurs at the site of photo-irradiation. Phototoxicity is the result of direct cellular damage caused by a nonimmunulogical inflammatory response. Clinically, phototoxicity resembles an exaggerated sunburn (erythema, increased skin temperature, pruritis and edema). Phototoxicity reactions have been reported for both synthetic substances and those which occur naturally (eg., botanical extracts). Although symptoms generally subside quickly, the potential for substances used in topical products to cause phototoxicity is clearly of concern for manufacturers of cosmetics, personal care and other consumer products. Historically, the potential to cause phototoxicity from substances applied topically was evaluated by utilizing various animal models; however in 1997 the 3T3 Neutral Red Uptake Phototoxicity Test (3T3 NRU PT) was validated by ECVAM’s Scientific Advisory Committee as an in vitro method for evaluating the phototoxic potential of chemicals shown to absorb in the UV/VIS range. To illustrate the utility of the 3T3 NRU PT as a useful screening tool in the safety evaluation of potential cosmetic ingredients, the results of the evaluation of 42 botanical extracts and 25 synthetic chemicals found to absorb in the UV/VIS range are reported. Most substances evaluated were found not to be photoxic in vitro; however, 9 substances were identified as potentially/probably phototoxic in the 3T3 NRU PT and were eliminated from further consideration for use as cosmetic ingredients. Several substances found to be non-phototoxic in the 3T3 NRU PT were formulated with other ingredients in a prototype cosmetic formulation and subject to clinical testing. No manifestations of phototoxicity were observed in any of the test subjects in the prototype formulation containing any of the substances identified as non-phototoxic in vitro.
Cannon, C., Neal, P., Southee, J., Kubilus, J., Klausner, M., 1994. New epidermal model for dermal irritancy testing. Toxic. In Vitro, 8, 889-891.
Ceridono, M., Tellner, P., Bauer, D., Barroso, J., Alépée, N., Corvi, R.,, De Smedt, A., Fellows, MD., Gibbs, NK., Heisler, E., Jacobs, A., ,Jirova, D., Jones, D., Kandárová, H., Kasper, P., Akunda, JK., Krul, C., Learn, D., Liebsch, M., Lynch, AM., Muster, W., Nakamura, K., Nash, JF., Pfannenbecker, U., Phillips, G., Robles, C., Rogiers, V., Van De Water, F., Liminga, UW., Vohr, HW., Wattrelos, O., Woods, J., Zuang, V., Kreysa, J., Wilcox, P., (2012). The 3T3 neutral red uptake phototoxicity test: practical experience and implications for phototoxicity testing-the report of an ECVAM-EFPIA workshop. Regul. Toxic. and Pharma., 63, 480-488.
Chan, E.W.C., Lim, Y.Y. (2006). Antioxidant activity of Thunbergia laurifolia tea. Journal of Tropical Forest Science, 18, 130–136. Commission Directive 2000/33/EC of 25 April 2000 adapting to technical progress for the 27th time Council Directive 67/548 E on the classification, packaging, labelling of dangerous substances, Annex V, method B41 Phototoxicity – In vitro 3T3 NRU phototoxicity test, 2000. Official Journal of the European Communities, L136, 98–107.
Dijoux, N., Yannick, G., Caroline, B., Sandrine, D., Claude, F., Corinne, C., Pierre-Jacques, F., 2006. Assessment of the phototoxic hazard of some essential oils using modified 3T3 neutral red uptake assay. Toxic. In Vitro, 20, 480-489.
EMEA (European Agency for the Evaluation of Medicinal Products), CPMP (Committee for Proprietary Medicinal Products) (2002) Note for guidance on photosafety testing. CPMP/SWP/398/01, EMEA, London, http://www.emea.eu.int pg7.
Holliday, I., 1998. Australian Native Plants Society (Australia), http://anpsa.org.au/h-fla.html (visited 14, January 2013).
Jones, P.A., King, A.V., Earl, L.K., Lawrence, R.S., 2003. An assessment of the phototoxic hazard of a personal product ingredient using in vitro assays. Toxic. In Vitro, 17, 471–480.
Kaidbey, K., Mitchell, F., 1989. Photosensitizing potential of certain non-steroidal anti-inflammatory agents. Archives of Dermatology, 125:783-6.
Leistner, O.A., 2005. Seed plants of southern tropical Africa: families and genera. Southern African Botanical Diversity Network Report No. 26. SABONET, Pretoria.
Lovell, W.W, 1993. A scheme for in vitro screening of substances for photoallergenic potential. Toxic. In Vitro, 7; 95-102. Lugović L, Situm M, Ozanić-Bulić S, Sjerobabski-Masnec I., 2007. Phototoxic and photoallergic skin reactions. Collegium Antropologicum, 31, 63-7.
Mang, R., Stege, H., Krutmann, J., 2011. Mechanisms of Phototoxic and Photoallergic Reactions, in Frosch, PJ., Menne, T., Lepoittevin, J.-P., (Eds.). Contact Dermatitis (4th Edition), Springer Berlin Heidelberg, New York, pp 155-163.
Martin, MR., Tipping, PW., Sickman, JO., 2009. Invasion by an exotic tree alters above and belowground ecosystem component. Biological Invasions, 11:1883-1894.
Neumann, N.J., Blotz, A., Wasinska-Kempka, G., Rosenbruch, M., Lehmann, P., Ahr, H.J., Vohr, H.W., 2005. Evaluation of phototoxic and photoallergic potentials of 13 compounds by different in vitro and in vivo methods. Journal of Photochem. and Photobio. B: Biology, 79, 25-34.
Native Plant Database. University of Texas at Ausin. Erythrina herbacea L. http://www.wildflower.org/plants/result.php?id_plant=ERHE4 (visited 14, January, 2013).
OECD, 2004. OECD Guidelines For the Testing of Chemicals no.432 In Vitro 3T3 NRU Phototoxicity Test (original guideline adopted 13th April 2004). http://www.oecd.org/
Kaidbey, K.H., Kligman, A.M., 1978. Identification of topical Photosensitizing agents in humans. Journal of Invest. Dermat., 70, 149-151.
Kaidbey, KG., Kligman AM., 1980. Identification of contact photosensitizers by human assay. “Current concepts in cutaneous toxicity, edited by V.A. Drill and P. Lazar. Academic Press Inc., pp. 55-68, New York, NY.
Kaidbey, K.G., Kligman, A.M. (1980). Photomaximization test for identifying photoallergic contact sensitizers. Contact Dermatitis, 6, 161-169.
Kejlova, K., Jirova, D., Bendova, H., Gajdos, P., Kolarova, H., 2010. Phototoxicity of essential oils intended for cosmetic use. Toxic. In Vitro, 24, 2084-2089.
Sharma, P., Bodhankar, S.L., Thakurdesai, P.A., 2012. Protective effect of aqueous extract of Feronia elephantum correa leaves on thioacetamide induced liver necrosis in diabetic rats. Asian Pac J Trop Biomed., 2: 691-695.
Spielmann, H., Liebsch, M., Doering, B., Moldenhauer,F., (1996). First results of the EU/COLIPA validation trial “In vitro phototoxicity testing”. In vitro toxicology, 9(3); 325-338.
Spielmann, H., Balls, M., Döring, B., Holzhütter, H.G., Kalweit, S., Klecak, G., L’Eplattenier, H., Liebsch, M., Lovell, W.W., Maurer, T., Moldenhauer. F. Moore. L., Pape, W., Pfannbecker, U., Potthast, J., De Silva, O., Steiling, W., and Willshaw, A. 1994. EEC/COLIPA project on in vitro phototoxicity testing: First results obtained with a Balb/c 3T3 cell phototoxicity assay. Toxic. In Vitro, 8:, 793-796.
Spielmann, H., Balls, M., Dupuis, J., Pape, W.J.W., Pechovitch, G. De Silva, O., Holzhütter, H.G., Clothier, R., Desolle, P., Gerberick, F., Liebsch, M., Lovell, W.W., Maurer, T., Pfannenbecker, U., Potthast, J.M., Csato, M. Sladowski, D., Steiling, W., and Brantom, P. 1998. The international EU/COLIPA In vitro phototoxicity validation study: results of phase II (blind trial), part 1: the 3T3 NRU phototoxicity test. Toxic. In Vitro, 12, 305-327.
US FDA (2003) Guidance for industry - Photosafety Testing. US Dept. of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER), Rockville (USA), (http://www.fda.gov/cder/guidance/index.htm) pg. 22.
Yiming, L., Wei, H., Aihua, L., Fandian, Z., 2008. Neuroprotective effects of breviscapine against apoptosis induced by transient focal cerebral ischaemia in rats. Journal of Pharmacy and Pharmacology. 60, 349–355.