Opinion on the safety of titanium dioxide in toys

Table of Contents

• 1. SUMMARY 8
• 2. MANDATE FROM THE EU COMMISSION SERVICES 11
• 2.1 Background 11
• 2.2 Terms of Reference 12
• 3. SCIENTIFIC OPINION 13
• 4. MINORITY OPINIONS 20
• 5. DATA AND METHODOLOGIES 20
• 5.1 Data/Evidence 20
• 5.2 Methodologies 21
• 6. ASSESSMENT 23
• 6.1 Introduction 23
• 6.2 Chemical and physical specification 24
• 6.2.1 Chemical identity 24
• 6.2.2 Physical form 24
• 6.2.3 Molecular weight 24
• 6.2.4 Purity, composition and substance codes 24
• 6.2.5 Impurities / accompanying contaminants 24
• 6.2.6 Solubility 24
• 6.2.7 Partition coefficient (Log Pow) 25
• 6.2.8 Additional physical and chemical specifications 25
• 6.2.9 Particle shape, particle size and distribution 25
• 6.2.10 Homogeneity and Stability 27
• 6.2.11 Conclusions 27
• 6.3. Application of TiO2 in toys 28
• 6.3.1 Function and uses of TiO2 in toys 28
• 6.3.2 Titanium content in toy materials 29
• 6.3.3 Migration/ release of TiO2 from toy materials 30
• 6.3.4 Conclusions 30
• 6.4 Exposure assessment 30
• 6.4.1 General introduction to TiO2 exposure assessment from toys 30
• 6.4.2 Exposure assessment for TiO2 present in toys 32
• 6.4.2.1 Introduction 32
• 6.4.2.2 Migration/ release of TiO2 from toy materials 33
• 6.4.2.3 Exposure scenarios – inhalation 33
• 6.4.2.4 Exposure modelling – inhalation 35
• 6.4.2.5 Conclusions on potential release of TiO2 into the air 38
• 6.4.2.6 Exposure scenarios –oral 39
• 6.4.2.7 Exposure modelling- oral 41
• 6.4.2.8 Conclusion on oral exposure 43
• 6.5 Toxicokinetics 44
• 6.5.1. Inhalation exposure 44
• 6.5.1.1. Introduction 44
• 6.5.1.2 Inhalation exposure 45
• 6.5.1.3 Modelling 46
• 6.5.2. Oral exposure 46
• 6.5.2.1. Introduction 46
• 6.5.2.2. ADME 46
• 6.5.3. PBPK Modelling 47
• 6.5.4 Conclusions 47
• 6.6 Toxicological evaluation 48
• 6.6.1. Introduction on TiO2 toxicity 48
• 6.6.2. Inhalation hazard of pigmentary TiO2 48
• 6.6.3 Oral hazard of TiO2 pigment 51
• 6.6.3.1 Introduction 51
• 6.6.3.2 EFSA 2021 evaluation E171 51
• 6.6.3.3 TiO2 pigment after oral exposure 52
• 6.6.3.4 Other aspects of oral TiO2 exposure 52
• 6.6.4 Conclusions on TiO2 toxicity 53
• 6.6.5 Carcinogenicity 53
• 6.6.5.1 Inhalation exposure 53
• 6.6.5.2 Oral exposure 54
• 6.6.5.3 Dermal exposure 55
• 6.6.5.4 In vitro studies 55
• 6.6.5.5 Conclusions on carcinogenicity 56
• 6.6.6 Mutagenicity / genotoxicity 56
• 6.6.6.1 Potential genotoxic hazard of ultrafine TiO2 particles after inhalation exposure 56
• 6.6.6.2 Potential genotoxic hazard of ultrafine TiO2 particles after oral exposure 56
• 6.6.6.3 Effect of coating of TiO2 nanoparticles on genotoxicity 57
• 6.6.6.4 Modes of action for genotoxicity of ultrafine TiO2 particles 58
• 6.6.6.5 Potential genotoxic hazard of TiO2 non-ultrafine forms 59
• 6.6.6.6 Conclusions on genotoxicity 60
• 6.7 Risk assessment 62
• 6.7.1 Introduction 62
• 6.7.2. Previous risk assessments of TiO2 62
• 6.7.3 Exposure assessment 66
• 6.7.4 Toxicological Point of Departure 67
• 6.7.4.1 Introduction 67
• 6.7.4.2 PoD for inhalation 67
• 6.7.4.3 PoD for oral exposure 68
• 6.7.5 Human Equivalent Concentrations (HEC) 68
• 6.7.6 Risk characterisation 69
• 6.7.6.1 TiO2 as colouring agent for polymers 69
• 6.7.6.1 Inhalation 70
• 6.7.6.2 Oral exposure 72
• 6.7.6.3 Aggregated exposure to TiO2 in different toys 72
• 6.7.6.4 Weight of evidence 72
• 6.7.7 Final Conclusions 75
• 7. RECOMMENDATIONS FOR FUTURE WORK 77
• 8. CONSIDERATION OF THE RESPONSES RECEIVED DURING THE PUBLIC CONSULTATION 78
• 9. REFERENCES 79
• 10. GLOSSARY OF TERMS 94
• 11. LIST OF ABBREVIATIONS 94
• ANNEXES 96
• Annex I: Toys Industry data on release and content 96
• Annex II: Calculation of scenario air concentrations 103
• Annex III: Calculation of the air concentrations of TiO2 for four selected use scenarios 104
• Annex IV: Genotoxicity tables 105
• Annex V: Calculation of the Human Equivalent Concentration (HEC) 116