Food‐grade titanium dioxide decreases hematocrit and hemoglobin and increases compulsive‐like behavior in male mice

Food‐grade titanium dioxide (E171) is widely used as a food additive, and it is known that after oral consumption, E171 is translocated into the bloodstream reaching the highest titanium level at 6 h. E171 is accumulated in some organs triggering toxicity, but the effects on the blood parameters after oral consumption have been less studied. Recently, evidence shows that oral exposure to E171 induces behavioral signs of anxiety and depression. The relation between blood alterations and psychiatric disorders has been previously demonstrated. However, the oral exposure to E171 effects on alterations in blood parameters and effects linked to alterations in animal behavior has not been explored. In this short communication, we aimed to investigate the effects of E171 on specific blood parameters (hematocrit, hemoglobin, number of erythrocytes, and leukocytes) and anxiety and compulsive‐like behavior in males and females orally exposed to ~5 mg/kg for 4 weeks. The results showed that E171 decreased hematocrit and hemoglobin in male but not in female mice while leukocyte and erythrocyte count remained unaltered. Oral consumption of E171 decreased the levels of anxiety‐like behavior in females but not in male mice, while compulsive‐like behavior was increased in both male and female mice.

[1]  S. Aksit,et al.  Maternal and Cord Blood Vitamin B12, Folate and Homocysteine Levels , 2022, The Journal of Pediatric Research.

[2]  J. Chung,et al.  Titanium dioxide nanoparticles enhance thrombosis through triggering the phosphatidylserine exposure and procoagulant activation of red blood cells , 2021, Particle and Fibre Toxicology.

[3]  M. Carrière,et al.  Titanium dioxide particles from the diet: involvement in the genesis of inflammatory bowel diseases and colorectal cancer , 2021, Particle and fibre toxicology.

[4]  B. Bearzatto,et al.  Dietary nanoparticles alter the composition and function of the gut microbiota in mice at dose levels relevant for human exposure. , 2021, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[5]  R. Woutersen,et al.  Safety and efficacy of a feed additive consisting of titanium dioxide for all animal species (Titanium Dioxide Manufacturers Association) , 2021, EFSA journal. European Food Safety Authority.

[6]  Hongxing Zhang,et al.  Behaviors Related to Psychiatric Disorders and Pain Perception in C57BL/6J Mice During Different Phases of Estrous Cycle , 2021, Frontiers in Neuroscience.

[7]  J. Meijerink The Intestinal Fatty Acid-Enteroendocrine Interplay, Emerging Roles for Olfactory Signaling and Serotonin Conjugates , 2021, Molecules.

[8]  J. Pedraza-Chaverri,et al.  Food-grade titanium dioxide (E171) induces anxiety, adenomas in colon and goblet cells hyperplasia in a regular diet model and microvesicular steatosis in a high fat diet model. , 2020, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[9]  Zhuge Xi,et al.  Toxic effects of the food additives titanium dioxide and silica on the murine intestinal tract: Mechanisms related to intestinal barrier dysfunction involved by gut microbiota. , 2020, Environmental toxicology and pharmacology.

[10]  K. Gokulan,et al.  Human Intestinal Tissue Explant Exposure to Silver Nanoparticles Reveals Sex Dependent Alterations in Inflammatory Responses and Epithelial Cell Permeability , 2020, International journal of molecular sciences.

[11]  J. Fawcett,et al.  Women Are at Greater Risk of OCD Than Men: A Meta-Analytic Review of OCD Prevalence Worldwide. , 2020, The Journal of clinical psychiatry.

[12]  Dong‐Wan Kim,et al.  Toxicity of orally administered food‐grade titanium dioxide nanoparticles , 2020, Journal of applied toxicology : JAT.

[13]  A. Katelnikovas,et al.  Effect of Cationic Brush-Type Copolymers on the Colloidal Stability of GdPO4 Particles with Different Morphologies in Biological Aqueous Media , 2020, Langmuir : the ACS journal of surfaces and colloids.

[14]  D. Krewski,et al.  Derivation of whole blood biomonitoring equivalents for titanium for the interpretation of biomonitoring data. , 2020, Regulatory toxicology and pharmacology : RTP.

[15]  Mazyar Fathi,et al.  Effect of titanium dioxide nanoparticles administered during pregnancy on depression-like behavior in forced swimming and tail suspension tests in offspring mice , 2020, Toxicology and industrial health.

[16]  B. Harvey,et al.  Natural compulsive‐like behaviour in the deer mouse (Peromyscus maniculatus bairdii) is associated with altered gut microbiota composition , 2020, The European journal of neuroscience.

[17]  E. Anklam,et al.  Characterisation of food grade titania with respect to nanoparticle content in pristine additives and in their related food products , 2020, Food additives & contaminants. Part A, Chemistry, analysis, control, exposure & risk assessment.

[18]  H. van Loveren,et al.  Transcriptome changes in undifferentiated Caco-2 cells exposed to food-grade titanium dioxide (E171): contribution of the nano- and micro- sized particles , 2019, Scientific Reports.

[19]  Samuel M. Cohen,et al.  Evaluation of immunologic and intestinal effects in rats administered an E 171-containing diet, a food grade titanium dioxide (TiO2). , 2019, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[20]  A. Raggi,et al.  Repeated administration of the food additive E171 to mice results in accumulation in intestine and liver and promotes an inflammatory status , 2019, Nanotoxicology.

[21]  O. Adaramoye,et al.  Evaluation of cytogenotoxicity and oxidative stress parameters in male Swiss mice co-exposed to titanium dioxide and zinc oxide nanoparticles. , 2019, Environmental toxicology and pharmacology.

[22]  Robert J. Moore,et al.  Impact of the Food Additive Titanium Dioxide (E171) on Gut Microbiota-Host Interaction , 2019, Front. Nutr..

[23]  B. Chassaing,et al.  Dietary emulsifiers consumption alters anxiety-like and social-related behaviors in mice in a sex-dependent manner , 2019, Scientific Reports.

[24]  Lin Jia,et al.  Behavioral gastroenterology: An emerging system and new frontier of action , 2017, World journal of gastroenterology.

[25]  J. O. Flores-Flores,et al.  Food-grade titanium dioxide exposure exacerbates tumor formation in colitis associated cancer model. , 2016, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[26]  M. Cuénod,et al.  Decreased Brain Levels of Vitamin B12 in Aging, Autism and Schizophrenia , 2016, PloS one.

[27]  M. Atmaca,et al.  Frequency of anemia in chronic psychiatry patients , 2015, Neuropsychiatric disease and treatment.

[28]  J. Powell,et al.  Pharmaceutical/food grade titanium dioxide particles are absorbed into the bloodstream of human volunteers , 2015, Particle and Fibre Toxicology.

[29]  P. Alonso,et al.  Animal models of obsessive–compulsive disorder: utility and limitations , 2015, Neuropsychiatric disease and treatment.

[30]  L. Mir,et al.  Subacute toxicity of titanium dioxide (TiO2) nanoparticles in male rats: emotional behavior and pathophysiological examination , 2015, Environmental Science and Pollution Research.

[31]  H. Bouwmeester,et al.  Characterization of titanium dioxide nanoparticles in food products: analytical methods to define nanoparticles. , 2014, Journal of agricultural and food chemistry.

[32]  P. Herckes,et al.  Characterization of food-grade titanium dioxide: the presence of nanosized particles. , 2014, Environmental science & technology.

[33]  I. S. Silva,et al.  Hematology of Swiss mice (Mus musculus) of both genders and different ages. , 2014, Acta cirurgica brasileira.

[34]  B. Penninx,et al.  Hemoglobin levels in persons with depressive and/or anxiety disorders. , 2014, Journal of psychosomatic research.

[35]  Jonathon Rees Obsessive-compulsive disorder and gut microbiota dysregulation. , 2014, Medical hypotheses.

[36]  M. Kane,et al.  Marble burying and nestlet shredding as tests of repetitive, compulsive-like behaviors in mice. , 2013, Journal of visualized experiments : JoVE.

[37]  M. Ghosh,et al.  Cytotoxic, genotoxic and the hemolytic effect of titanium dioxide (TiO2) nanoparticles on human erythrocyte and lymphocyte cells in vitro , 2013, Journal of applied toxicology : JAT.

[38]  P. Westerhoff,et al.  Titanium dioxide nanoparticles in food and personal care products. , 2012, Environmental science & technology.

[39]  M. Atmaca,et al.  Neutrophils Are Decreased in Obsessive-Compulsive Disorder: Preliminary Investigation , 2011, Psychiatry investigation.

[40]  R. Paylor,et al.  Marble burying reflects a repetitive and perseverative behavior more than novelty-induced anxiety , 2009, Psychopharmacology.

[41]  Hagit Cohen,et al.  Early Post-Stressor Intervention with High-Dose Corticosterone Attenuates Posttraumatic Stress Response in an Animal Model of Posttraumatic Stress Disorder , 2008, Biological Psychiatry.

[42]  H. Meziane,et al.  Estrous cycle effects on behavior of C57BL/6J and BALB/cByJ female mice: implications for phenotyping strategies , 2007, Genes, brain, and behavior.

[43]  P. Palanza Animal models of anxiety and depression: how are females different? , 2001, Neuroscience & Biobehavioral Reviews.

[44]  S. Handley,et al.  Evaluation of marble-burying behavior as a model of anxiety , 1991, Pharmacology Biochemistry and Behavior.

[45]  Ying Yang,et al.  Strain and sex differences in anxiety-like and social behaviors in C57BL/6J and BALB/cJ mice. , 2011, Experimental animals.