Risk assessmentcited by the Tayebat archivefull text checked A-UPF-21 in-depth review
EFSA: titanium dioxide no longer safe
Safety assessment of titanium dioxide (E171) as a food additive.
Overview
EFSA FAF Panel et al.. EFSA J 2021 · PMID 33976718 · DOI 10.2903/j.efsa.2021.6585
EFSA could not rule out DNA damage and concluded E171 is no longer safe; the EU then banned it.
Does the study support the specific claim? Yes · Methodological quality: high
Plain-language summary
Study explained simply
- What did the researchers want to find out?
Is E171 safe as a food additive?
- How was the study done?
Regulatory scientific opinion (risk assessment).
- How many people, animals or samples were studied?
Not applicable; Not applicable
- What was actually found?
Low absorption but possible accumulation; no general/organ toxicity up to 1,000 mg/kg bw/day (E171); potential immunotoxicity, inflammation, neurotoxicity, aberrant crypt foci; genotoxicity concern (DNA strand breaks, chromosomal damage) could not be ruled out; E171 no longer considered safe.
- How large was the observed effect?
Not applicable
- What do the results mean in everyday life?
One additive withdrawn after re-evaluation.
- What are the study's limitations?
Based on animal and laboratory studies; the decision was precautionary because a risk of DNA damage could not be ruled out, not because harm in people was shown; applies to one colouring (E 171) only.
- What does it say about Elawady's specific claim?
Supports C-UPF-09; limits C-UPF-11 (additives not uniformly harmless).
- Do the results apply to Germany and Europe?
High.
- What can explicitly not be concluded from this study?
That all additives are harmful.
Scientific in-depth review
1. Full reference
- Authors
- EFSA Panel on Food Additives and Flavourings (FAF), Younes M, Aquilina G, Castle L, Engel KH, Fowler P, Frutos Fernandez MJ, Fürst P, Gundert-Remy U, Gürtler R, Husøy T, Manco M, Mennes W, Moldeus P, Passamonti S, Shah R, Waalkens-Berendsen I, Wölfle D, Corsini E, Cubadda F, De Groot D, FitzGerald R, Gunnare S, Gutleb AC, Mast J, Mortensen A, Oomen A, Piersma A, Plichta V, Ulbrich B, Van Loveren H, Benford D, Bignami M, Bolognesi C, Crebelli R, Dusinska M, Marcon F, Nielsen E, Schlatter J, Vleminckx C, Barmaz S, Carfí M, Civitella C, Giarola A, Rincon AM, Serafimova R, Smeraldi C, Tarazona J, Tard A, Wright M
- Journal
- EFSA J
- Year
- 2021
- Identifier
- PMID 33976718 DOI 10.2903/j.efsa.2021.6585 · PMC8101360
- Verification
- verified – PubMed E-utilities efetch, 2026-10-25
- Retracted
- no
- Corrections
- none
- Extent checked
- full text
- Conflicts of interest and funding
EFSA scientific opinion; declarations of interest of experts published on the EFSA website (not reproduced in the full text). The EOGRT study was commissioned by interested business operators.
2. Research question
Is E171 safe as a food additive?
3. Study design and population
- Study design
- Risk assessment – EFSA FAF Panel scientific opinion (regulatory risk assessment) requested by the European Commission (EFSA-Q-2020-00262): updated safety assessment of E 171 following the 2018 EFSA nanotechnology guidance, including a new industry-commissioned extended one-generation reproductive toxicity (EOGRT) study and published literature; adopted 25 March 2021.
- Population
Not applicable
- Country
EU
- Period
Data since the 2016 re-evaluation up to adoption on 25 March 2021
- Sample size
Not applicable
- Inclusion and exclusion criteria
New relevant studies judged reliable and in line with EFSA 2018 nanotechnology guidance; studies with TiO2 nanoparticles <30 nm considered of limited relevance (<=1% of E 171 particles by number).
4. Methods and endpoints
- Exposure / intervention
E 171 (titanium dioxide food colour; <50% of constituent particles <100 nm by number) and TiO2 nanoparticles
- Comparator
Not applicable
- Endpoints
Toxicokinetics, general and organ toxicity, reproductive/developmental toxicity, neurotoxicity, immunotoxicity/inflammation, aberrant crypt foci (ACF), genotoxicity, carcinogenicity; dietary exposure
- Statistical methods
Weight-of-evidence assessment of reliability and relevance; uncertainty analysis; exposure scenarios
5. Actual results
- Results
Oral systemic availability low (E 171 probably <=0.5% in mice), but particles may accumulate (half-lives 200-450 days). No general/organ toxicity up to 1,000 mg/kg bw/day (E 171) or 100 mg/kg bw/day (TiO2 NPs >30 nm); no reproductive or developmental effects up to 1,000 mg/kg bw/day in the EOGRT study. Possible immunotoxicity/inflammation (inconsistent with E 171) and neurotoxicity (TiO2 NPs); E 171 may induce ACF in male rats at 10 mg/kg bw/day when pre-dispersed (not replicated in EOGRT up to 1,000 mg/kg bw/day). TiO2 particles can induce DNA strand breaks and chromosomal damage but not gene mutations; no threshold or particle-size cut-off could be established; no adequate carcinogenicity study of TiO2 NPs. Conclusion: genotoxicity concern cannot be ruled out; E 171 can no longer be considered safe as a food additive; no ADI established. Estimated exposure: mean up to 12.8 mg/kg bw/day and 95th percentile up to 31.4 mg/kg bw/day (toddlers, maximum-level scenario).
- Absolute risks
not applicable (no health-based guidance value could be set; no human outcome data)
- Authors' conclusion
On the basis of all available evidence and uncertainties, in particular that a concern for genotoxicity could not be ruled out, E 171 can no longer be considered as safe when used as a food additive.
6. Strengths
- Comprehensive, transparent regulatory weight-of-evidence assessment with explicit uncertainty analysis
- Includes a new guideline EOGRT study and nanoparticle-specific data
- Directly applicable to EU regulation
7. Weaknesses
- Precautionary conclusion driven by an unresolved genotoxicity concern, not by demonstrated harm in humans
- No human outcome data; no adequate carcinogenicity study of TiO2 nanoparticles
- Key ACF finding not replicated in the EOGRT study; uncertainty about internal nanoparticle exposure
- Applies to one colour additive (E 171); does not speak to other additive classes such as preservatives
8. Risk of bias
- Orienting tool
- none applicable (regulatory risk assessment; structured judgement)
- Type of assessment
- structured assessment based on the full text by a single reviewer (no formal double review)
- Full formal assessment
- no
- Overall risk of bias
- low
- Rationale
Low concern about bias of the opinion as a regulatory assessment; it is a hazard/uncertainty-based conclusion, not evidence of human harm. Structured single-reviewer judgement; a complete formal assessment requires two independent reviewers.
| Domain | Judgement | Rationale |
|---|---|---|
| Scope and evidence identification | low | All new data since 2016 plus literature, assessed for reliability and relevance against EFSA guidance. |
| Evidence appraisal | low | Study-by-study reliability assessment; reasons given for relevance decisions (e.g. NPs <30 nm). |
| Integration and uncertainty | some concerns | Conclusion rests on inability to exclude genotoxicity (precautionary); several lines of evidence inconsistent or not replicated. |
| Conflicts of interest | low | EFSA declarations of interest system; industry-funded EOGRT study evaluated independently. |
| Applicability to human risk | some concerns | Experimental data only; no human outcome evidence. |
Full-text review (25 October 2026): Conclusion confirmed. Added: requestor and adoption date, EOGRT study (industry-commissioned, no reproductive/developmental effects up to 1,000 mg/kg bw/day), ACF at 10 mg/kg bw/day (not replicated), half-lives 200-450 days, no threshold or size cut-off for genotoxicity, no ADI, exposure estimates (P95 up to 31.4 mg/kg bw/day toddlers), EFSA declarations-of-interest system. Structured judgement; bias overall changed from not_assessable to low.
9. Assessment of the statistical interpretation
Not applicable (qualitative weight-of-evidence). The 'not safe' conclusion reflects that safety could not be demonstrated (genotoxicity concern without threshold), not a quantified risk.
10. Relevance to the specific claim
Supports C-UPF-09; limits C-UPF-11 (additives not uniformly harmless).
11. Independent contrary findings
None.
12. Transferability to Germany and Europe
High.
13. Overall methodological judgement
Authoritative EU opinion showing that the additive safety system can withdraw approval when safety can no longer be confirmed; it supports the narrow claim that E 171 was found no longer safe, not that additives in general are harmful.
| Multidimensional assessment | |
|---|---|
| Authenticity of the source | verified |
| Methodological quality | high |
| Risk of bias | low |
| Precision of results | not applicable |
| Directness | direct |
| Reproducibility | not replicated |
| Consistency with the overall evidence | unknown |
| Regional transferability | high |
| Adequacy of the interpretation (by the archive) | correctly reported |
14. Open questions
Human outcomes.
15. Linked fact checks
- Some food additives are unsafe; titanium dioxide (E171) was found no longer safe as a food additive. – Studies supporting the claim
- Elawady: preservatives in industrial products are of little health concern (sodium benzoate is present in trivial amounts; preservatives are preferable to pesticide residues; 'returning to nature' is a trap). – Studies contradicting or limiting the claim
Use by the Tayebat archive
Note: according to the archive, the studies were compiled by the archive operators. Whether Dr. Elawady himself cited this study is not established.
- What the archive says about the study
Listed in the archive bibliography only (no archive interpretation card).
- A. What was actually studied?
E171 safety.
- B. What did the authors find?
Not safe due to genotoxicity concern.
- C. What conclusions do the authors themselves draw?
As above.
- D. What does the archive derive from it?
Supports additive concern.
- E. Is this derivation scientifically justified?
Correct. The conclusion is precautionary (genotoxicity concern could not be ruled out), and it concerns one colour additive; it also illustrates that EU re-evaluation works.
- Adequacy of the interpretation (by the archive)
- correctly reported