Lack of genotoxicity in vivo for food color additive Tartrazine Maria Bastaki, Ph.D. a, * , Thomas Farrell, Ph.D. b , Sachin Bhusari, B.V.Sc & AH, Ph.D., DABT c , Kamala Pant, M.S. d , Rohan Kulkarni, M.Sc., Ph.D. e a International Association of Color Manufacturers (IACM), 110117th St, Suite 700, Washington, DC 20036, United States b Global Regulatory Affairs, Colorcon Inc., 275 Ruth Rd, Harleysville, PA 19438, United States c Global Scientific and Regulatory Affairs, The Coca-Cola Company,1 Coca Cola Plaza, NW, Atlanta, GA 30313, United States d Genetic Toxicology, BioReliance/Sigma-Aldrich Corp., 14920 Broschart Road, Rockville, MD 20850, United States e Toxicology, Study Management, BioReliance/Sigma-Aldrich Corp., 14920 Broschart Road, Rockville, MD 20850, United States article info Article history: Received 16 February 2017 Received in revised form 13 April 2017 Accepted 24 April 2017 Available online 25 April 2017 Keywords: Food color Tartrazine FD&C Yellow No. 5 E102 INS 102 Genotoxicity abstract Tartrazine is approved as a food color additive internationally with INS number 102, in the United States as food color subject to batch certification “Food, Drug, and Cosmetic” (FD&C) Yellow No. 5, and in Europe as food color additive with E number 102. In their evaluation of the color (2013), the European Food Safety Authority (EFSA) expressed concerns of potential genotoxicity, based primarily on one genotox- icity study that was not conducted according to Guidelines. The present in vivo genotoxicity study was conducted according to OECD Guidelines in response to EFSA's request for additional data. The animal species and strain, and the tissues examined were selected specifically to address the previously reported findings. The results of this study show clear absence of genotoxic activity for Tartrazine, in the bone marrow micronucleus assay and the Comet assay in the liver, stomach, and colon. These data addressed EFSA's concerns for genotoxicity. The Joint WHO/FAO Committee on Food Additives (JECFA) (2016) also reviewed these data and concluded that there is no genotoxicity concern for Tartrazine. Negative findings in parallel genotoxicity studies on Allura Red AC and Ponceau 4R (published separately) are consistent with lack of genotoxicity for azo dyes used as food colors. © 2017 Published by Elsevier Ltd. 1. Introduction Tartrazine (chemical name: trisodium salt of 4,5-dihydro-5-oxo- 1-(4-sulfophenyl)-4-[4-sulfophenyl-azo]-1H-pyrazole-3- carboxylic acid) is a color additive permitted for use in foods and beverages, dietary supplements, pharmaceuticals, and other con- sumer products worldwide. In the United States, it is approved as a “Food, Drug, and Cosmetic” (FD&C) color additive listed by the name FD&C Yellow No. 5 in the Code of Federal Regulations (21 CFR 74.705) and is subject to batch certification. In the European Union (EU), it is approved as a color additive with E number 102 (E102), and internationally it is an approved food color listed in the Codex Alimentarius with International Numbering System (INS) number 102 (INS 102). Tartrazine was most recently evaluated for its safety as a food additive by the Joint FAO/WHO Expert Committee on Food Additives (JECFA) at their 2016 meeting (JECFA, 2016). It was pre- viously evaluated by European bodies, including the EU Scientific Committee for Food (SCF) in 1975 and 1984 and by the European Food Safety Authority (EFSA) in 2009 and 2013 (EFSA, 2009; European Food Safety Authority, 2013). Until recently, JECFA and SCF had established an Acceptable Daily Intake (ADI) of 0e7 mg/kg body weight (bw)/day for Tatrazine, based on a NOAEL dose equivalent to 750 mg/kg bw/day derived from a chronic toxicity study in rats. As of its last Scientific Opinion of 2013, EFSA has maintained the previously established ADI. In the most recent safety evaluation in 2016, JECFA increased the ADI to 0e10 mg/ Abbreviations: CP, Cyclophosphamide; EFSA, European Food Safety Authority; EU, European Union; FD&C, Food, Drug, and Cosmetic; GLP, Good Laboratory Practices; INS, International Numbering System; JECFA, Joint FAO/WHO Expert Committee on Food Additives; MMS, Methyl methanesulfonate; MnPCE, micro- nucleated PCE; NCE, normochromatic erythrocytes; OECD, Organisation for Eco- nomic Co-operation and Development; PCE, polychromatic erythrocytes; SCF, Scientific Committee for Food; US FDA, United States Food and Drug Administration. * Corresponding author. E-mail addresses: mbastaki@iacmcolor.org (M. Bastaki), tfarrell@colorcon.com (T. Farrell), sbhusari@coca-cola.com (S. Bhusari), kamala.pant@sial.com (K. Pant), rohan.kulkarni@sial.com (R. Kulkarni). Contents lists available at ScienceDirect Food and Chemical Toxicology journal homepage: www.elsevier.com/locate/foodchemtox http://dx.doi.org/10.1016/j.fct.2017.04.034 0278-6915/© 2017 Published by Elsevier Ltd. Food and Chemical Toxicology 105 (2017) 278e284