Objective: Food colorants (synthetic, inorganic and natural) represent one of the major categories of food additives. Synthetic colorants were banned due to their adverse effects on animals and human. However, syn- thetic dyes are still in use because they are cheap, and stable. Methods: In the present in vivo study conducted on female albino rats (Rattus norvegicus), the effect of sun- set yellow (SY) and sodium benzoate (NaB) combina- tions on the hematological and histological profile was assessed. Different combinations of SY plus NaB were dissolved in water and administered daily to experi- mental rat groups for 12 weeks. Group 1 (control) re- ceived only water, group 2 received 5 mg SY plus 10 mg NaB, group 3 received 5 mg SY plus 100 mg NaB, group 4 received 50 mg SY plus 100 mg NaB, group 5 received 50 mg SY plus 10 mg NaB, group 6 received 200 mg SY plus 750 mg NaB, and group 7 received 20 mg SY plus 75 mg NaB. Histopathological examina- tions were performed on liver and kidney of rats at the end of the experiment. Results: The results revealed a decrease in RBCs count, hematocrit, WBCs, MCV and Hb levels upon the administration of SY plus NaB. The results also showed no increase in MCH, MCHC and platelet count. Liver and kidney tissues showed some lesions due to the administration of the tested compounds in comparison to the control animals. Conclusion: The chemical stress caused by the SY and NaB combinations caused some degenerative changes in the liver and kidneys of rats. It could be concluded that SY and NaB combinations causes some damage in liver and kidney tissues of experimen- tal animals. Therefore, using SY and NaB combinations should be limited. Keywords: Sodium benzoate, Sunset yellow, Synthetic food additives, Food colorant, Hematology, Histology Introduction Food additives are first conceptualized in the 1958 amendment to the Food, Drug and Cosmetic Act in the USA 1 . They are substances not consumed as food by themselves or considered as food ingredients, and their addition is necessary to preserve food or enhance its fla- vor or to improve/maintain its nutritional quality 2 . The act defined the terms “food additive” (section 201 (s) of the act) and “unsafe food additive’’ (section 409 (a) of the act), “if FDA finds an additive to be safe, based ordinarily on data submitted by the producer to the agency in a food additive petition (FAP), the agency issues a regulation specifying the conditions under which the additive may be safely used” 3 . On the other hand, European Parliament and the Council published the REGULATION (EC) No. 1333/2008 on food addi- tives indicating that the toxicity of additives evaluated before January 2009 should be re-evaluated by Euro- pean Food Safety Authority 4 . Food colorings or color additives represent one of the major categories of food additives 5 . Food coloring is any substance that imparts color when it is added to drinks or foods. They found in different forms (pow- ders, liquids and gels) and used in food production as well as in domestic cooking, in addition to non-food uses including pharmaceuticals, cosmetics and medical devices 6-9 . Food colorants include synthetic, inorganic and natural colors 7,10 . Several natural colorants (i.e., caramel, lycopene and carmine) are produced due to consumer concerns about synthetic colorants. With the Mohamed Yassin Ali 1 , Abdel Moniem Sadek Hassan 1 , Zaher Ahmed Mohamed 1 & Mohamed Fawzy Ramadan 2,3 1 Biochemistry Department, Faculty of Agriculture, Fayoum University, 63514, Egypt 2 Agricultural Biochemistry Department, Faculty of Agriculture, Zagazig University, Zagazig 44519, Egypt 3 Deanship of Scientific Research, Umm Al-Qura, Makkah, Saudi Arabia Correspondence and requests for materials should be addressed to M. F. Ramadan (hassanienmohamed@yahoo.com) Received 29 January 2019 / Received in revised form 17 April 2019 Accepted 18 April 2019 DOI 10.1007/s13530-019-0400-x ©The Korean Society of Environmental Risk Assessment and Health Science and Springer 2019 pISSN : 2005-9752 / eISSN : 2233-7784 Toxicol. Environ. Health. Sci. Vol. 11(2), 155-167, 2019 Abstract Effect of Food Colorants and Additives on the Hematological and Histological Characteristics of Albino Rats