Provisional text

delivered on 6 February 2025 (1)

Joined Cases C-71/23 P and C-82/23 P

French Republic

European Commission,

CWS Powder Coatings GmbH,

Billions Europe Ltd,

Cinkarna Metalurško-kemična Industrija Celje d.d. (Cinkarna Celje d.d.),

Evonik Operations GmbH,

Kronos Titan GmbH,

Precheza a.s.,

Tayca Corp.,

Tronox Pigments (Holland) BV,

Venator Germany GmbH,

Brillux GmbH & Co. KG,

Daw SE (C-71/23 P)

and

European Commission

CWS Powder Coatings GmbH,

Billions Europe Ltd,

Cinkarna Metalurško-kemična Industrija Celje d.d. (Cinkarna Celje d.d.),

Evonik Operations GmbH,

Kronos Titan GmbH,

Precheza a.s.,

Tayca Corp.,

Tronox Pigments (Holland) BV,

Venator Germany GmbH,

Brillux GmbH & Co. KG,

Daw SE (C-82/23 P)

( Appeal – Protection of human health – Regulation (EC) No 1272/2008 – Classification, labelling and packaging of substances and mixtures – Delegated Regulation (EU) 2020/217 – Classification of titanium dioxide as carcinogen category 2 by inhalation – Criteria for classifying a substance as carcinogenic – Intensity of judicial review in scientific matters – Concept of ‘intrinsic properties’ )

1. Law and science have one thing in common – more often than not, they are uncertain. (2)

2. While judges are empowered and trained to deal with legal indeterminacy, they are not scientists and are therefore not equipped to decide on the usability of contradictory or simply inconclusive scientific findings.

3. A number of EU acts, including Regulation (EC) No 1272/2008, (3) which is at issue in the present case, empower EU agencies and the European Commission to enact decisions based on scientific evaluations.

4. What should judges do when an administrative decision based on inconclusive scientific evidence becomes the matter of a legal dispute? How can judges review such a decision – which is their task in a system based on the rule of law – without encroaching, at the same time, on the power of appraisal placed on the administration to decide on scientific indeterminacy? Not for the first time do such questions arise before the EU Courts.

5. At issue in the present case is the judgment in CWS Powder Coatings and Others v Commission, (4) in which the General Court annulled the Commission’s decision to classify titanium dioxide as a suspected human carcinogen.

6. The French Government and the Commission have both appealed that judgment. At their heart, those appeals turn on two matters. First, whether the General Court overstepped the limits of permissible judicial review of a Commission decision. Second, whether the General Court erred in attributing a restrictive interpretation to the concept of ‘intrinsic properties’, as it appears in the CLP Regulation. (5)

II. Background to the proceedings

7. The CLP Regulation sets out the rules for the classification, labelling and packaging of substances and mixtures placed on the EU market. Its purpose is to ensure a high level of protection of human health and the environment as well as the free movement of substances, mixtures and articles. (6)

8. With a view to ensuring those objectives, the CLP Regulation provides that, for certain hazards, including carcinogens, the classification and labelling of substances and mixtures should be harmonised at EU level. (7) It thus lays down a procedure for the adoption of harmonised classification and labelling of such substances and mixtures (‘the classification procedure’).

9. In brief, that procedure requires that a proposal be put forward by the competent authority of a Member State or by a manufacturer, importer or downstream user of a substance. (8) The Committee for Risk Assessment (‘the RAC’) of the European Chemicals Agency (ECHA) then adopts an opinion on the proposal within 18 months of receipt, giving the parties concerned an opportunity to comment on that opinion. (9) ECHA then forwards the RAC Opinion and any related comments to the Commission for decision. Where the Commission finds that the harmonisation of the classification and labelling of the substance concerned is appropriate, it may amend the CLP Regulation ‘to adapt [it] to technical and scientific progress’. (10) That adaptation takes the form of a regulation.

10. The RAC formulates its classification proposal by examining the information identified by manufacturers, importers and downstream users on the physical, health or environmental hazard of a given substance for its adequacy, reliability and scientific validity. (11) That information is then evaluated by applying to it the criteria for classification laid down in the CLP Regulation. (12)

11. The relevant criteria to determine the carcinogenicity of a substance are contained in section 3.6 of Annex I to the CLP Regulation. (13)

12. Therein, a ‘carcinogen’ is defined as ‘a substance or a mixture of substances which induce cancer or increase its incidence. Substances which have induced benign and malignant tumours in well performed experimental studies on animals are considered also to be presumed or suspected human carcinogens unless there is strong evidence that the mechanism of tumour formation is not relevant for humans.’ (14)

13. The classification of a substance as a carcinogen involves two interrelated determinations: the evaluations of strength of evidence and consideration of all other relevant information. (15)

14. On that basis, carcinogens may be classified into one of two categories, as presented in Table 3.6.1 of Annex I to the CLP Regulation:

15. Titanium dioxide, the substance at issue in the present case, was classified as a category 2 carcinogen.

16. Classification in that category occurs if there is only a suspicion, arising from human and/or animal studies, that a substance or mixture has the potential to cause cancer in humans, but where the evidence is not sufficiently convincing to place that substance in category 1. On the contrary, classification in category 1 requires that it is either known that a substance may cause cancer, based on evidence of causality obtained from human studies between the exposure to that substance and the development of cancer (category 1A) or that it is presumed that the substance has carcinogenic potential for humans, based on animal studies with sufficient evidence of animal carcinogenicity (category 1B).

17. Whether of sufficient or only limited value, the evidence on the basis of which classification is determined must come from ‘reliable and acceptable studies’. (16) The first main point of the present appeals relates to the question of whether a study that was used for concluding on the carcinogenicity of the substance at issue – titanium dioxide – was correctly deemed ‘reliable’ in that classification exercise.

18. Apart for human and animal studies, other factors, set out in points 3.6.2.2.4. to 3.6.2.2.6. of Annex I to the CLP Regulation, need to be considered to establish the likelihood that a substance poses a carcinogenic hazard in humans. Some of the enumerated additional factors include the ‘routes of exposure’ (17) and the ‘mode of action and its relevance for humans’. (18)

19. Where the criteria for classification cannot, due to the uncertainty of the scientific information obtained, be applied directly, Article 9(3) of the CLP Regulation and point 1.1.1.3 of Annex I thereto require an evaluation based on the ‘weight of evidence’ approach. That evaluation demands an expert judgment, in which ‘all available information bearing on the determination of hazard is considered together’. (19)

20. In that process, ‘the quality and consistency of the data shall be given appropriate weight. … Both positive and negative results shall be assembled together in a single weight of evidence determination’. (20)

21. Finally, in accordance with point 3.6.2.2.1. of Annex I to the CLP Regulation, the classification of a substance as a carcinogen is intended for substances which have the ‘intrinsic properties’ to cause cancer. The second main point of dispute in the present appeals concerns the interpretation of that concept – that is, the ‘intrinsic properties’ of a substance –, which lacks any definition or further explanation in the CLP Regulation.

22. In May 2016, the Agence nationale de sécurité sanitaire de l’alimentation, de l’environnement et du travail (National Agency for Food, Environmental and Occupational Health and Safety (ANSES), France) (‘the competent French authority’) submitted to ECHA a dossier proposing the harmonised classification and labelling of titanium dioxide as a category 1B carcinogen by inhalation (Carc. 1B, H350i). (21)

23. The substance at issue in the present case, titanium dioxide, is an inorganic chemical with the molecular formula TiO2.

24. It is listed under EC number 236-675-5 (22) and occurs in different sizes, as both micro- and nanometric particles.

25. By reason of its ultraviolet ray absorption properties, titanium dioxide is used in powder form in various products, mostly as a pigment for lending whiteness and opacity.

26. Accordingly, the use of titanium dioxide includes paints, coating materials, varnishes, plastics, laminated paper, cosmetic products (including toothpaste and sunscreens), medicinal products and toys. (23)

27. The competent French authority based its classification proposal principally on four inhalation studies. Of those studies, two showed tumour development following exposure to titanium dioxide (the Lee (1985) and Heinrich (1995) studies), while the two other showed no tumour development (the Muhle (1989) and Thyssen (1978) studies). (24)

28. Following consultations, ECHA referred the matter to the RAC. On 14 September 2017, the RAC adopted a unanimous opinion on the classification of titanium dioxide as a category 2 carcinogen by inhalation (‘the RAC Opinion’).(25)

29. The conclusion thus reached is based on a weight of the evidence approach, marked by two different findings.

30. On the one hand, the RAC concluded that there is insufficient evidence based on human or animal studies supporting the classification of titanium dioxide as a category 1A or 1B carcinogen. In other words, it considered that there was insufficient evidence that titanium dioxide constitutes a ‘known’ or ‘presumed’ carcinogen.

31. On the other hand, the RAC found that there was sufficient evidence supporting classification as a category 2 carcinogen by reason, inter alia, of (1) toxicity data, including the Lee and Heinrich studies referred to in point 27 of this Opinion; (26) (2) the ‘mode of action’ in rats; (27) (3) studies regarding ‘interspecies differences’; (28) (4) evidence from studies of other poorly soluble, low toxicity particles; (29) (5) the conclusion by a working group of the International Agency for Research on Cancer that there was ‘sufficient evidence’ that titanium dioxide is carcinogenic in experimental animals; (30) and (6) human epidemiological data. (31)

32. On the basis of the RAC Opinion, the Commission drew up a draft regulation on the harmonised classification and labelling of, inter alia, titanium dioxide, which was submitted for public consultation between 11 January and 8 February 2019.

33. On 18 February 2020, Commission Delegated Regulation (EU) 2020/217 (32) (‘the contested regulation’) was published.

34. The contested regulation makes the necessary changes to the CLP Regulation to reflect the resulting classification of titanium dioxide. (33) In the table in Annex VI, under index number 022-006-00-2, it introduces the harmonised classification of titanium dioxide ‘in powder form containing 1% or more of particles with aerodynamic diameter ≤ 10 μm’ as a category 2 carcinogen, with the Hazard statement Code ‘H351 (inhalation)’. (34)

35. In its recital 5, the contested regulation explains that ‘in its scientific opinion of 14 September 2017 on the substance titanium dioxide, [the] RAC proposed to classify that substance as carcinogen category 2 by inhalation. As titanium dioxide-induced lung carcinogenicity is associated with inhalation of respirable titanium dioxide particles, retention and poor solubility of the particles in the lung, it is appropriate to define respirable titanium dioxide particles in the titanium dioxide entry. The deposited particles, but not solutes of titanium dioxide, are assumed to be responsible for the observed toxicity in the lung and subsequent tumour development. In order to avoid unjustified classification of non-hazardous forms of the substance, specific notes should be laid down for the classification and labelling of the substance and mixtures containing it. In addition, as some hazardous dust or droplets could be formed during the use of mixtures containing titanium dioxide, it is necessary to inform the users of the precautionary measures that need to be taken to minimise the hazard for human health.’

36. Among the notes that accompany the classification in the contested regulation is Note W. That note provides that:

‘it has been observed that the carcinogenic hazard of this substance arises when respirable dust is inhaled in quantities leading to significant impairment of particle clearance mechanisms in the lung. This note aims to describe the particular toxicity of the substance; it does not constitute a criterion for classification according to this Regulation.’ (35)

37. By reason of the changes brought about by the contested regulation, and pursuant to Article 4(10) of the CLP Regulation, titanium dioxide and mixtures containing titanium dioxide ‘shall not be placed on the market unless they comply with this Regulation’. That means that products containing titanium dioxide must also have affixed to them certain warning phrases and labels as well as, where necessary, an accompanying safety data sheet. (36)

38. The classification of a substance as ‘carcinogenic’ also has effects outside the framework established by the CLP Regulation.

39. As the applicants at first instance in Case T‑279/20 and in Case T‑288/20 explain, such a classification brings with it, among other effects, a prohibition to use titanium dioxide in the production of cosmetic products and toys, (37) the classification of that substance as hazardous waste and related handling obligations, (38) and the possible exclusion from the use of certain consumer information labels such as the EU Ecolabel. (39)

40. At the same time, a category 2 classification does not necessarily entail a complete prohibition on the use of a substance. For example, the Cosmetic Products Regulation and the Toy Safety Directive each provide for a procedure to declare safe for use a substance that is listed as carcinogenic, mutagenic or toxic for reproduction under the CLP Regulation. (40) These procedures were respectively used to adopt a regulation to permit the continued use of titanium dioxide in cosmetic products (41) and to confirm, by means of a report, that there is no or negligible risk to children arising from the use of titanium dioxide in toys. (42) At the time of writing, a proposal for a regulation on the safety of toys that would declare certain uses of titanium dioxide safe is under negotiation by the co-legislators. (43)

41. On 12 and 13 May 2020, CWS Powder Coatings GmbH (in Case T‑279/20), Billions Europe Ltd, Cinkarna Metalurško-kemična Industrija Celje d.d., Evonik Operations GmbH, Kronos Titan GmbH, Precheza a.s., Tayca Corp., Tronox Pigments (Holland) BV and Venator Germany GmbH (in Case T‑283/20), Brillux GmbH & Co. KG and DAW SE (in Case T‑288/20), all suppliers or downstream users of titanium dioxide on the EU market (collectively, ‘the applicants at first instance’) brought actions requesting the annulment of the contested regulation. (44)

42. On 23 November 2022, the General Court handed down the judgment under appeal, by which it annulled the contested regulation on two grounds: (1) the failure by the RAC to take account of a possible difference in particle density in one of the studies (Heinrich study) used to show tumour development following exposure to titanium dioxide; and (2) the failure to correctly interpret the concept of ‘intrinsic properties’, as used in the CLP Regulation, to conclude that titanium dioxide has an ‘intrinsic property’ to cause cancer.

1. The first reason for annulment: the particle density of titanium dioxide

43. The first reason for annulment essentially related to the failure, in the RAC Opinion, to take account of a possible difference in particle density between micro- and nano-sized particles of titanium dioxide when calculating what constitutes the inhalation of a maximal tolerated dose of titanium dioxide particles by rats. (45)

44. That element of discussion arises from the RAC’s attempt to respond to criticism of the Lee study that the experimental exposure level in that study ‘clearly exceeded’ the maximal tolerated dose. (46)

45. Exposure above the maximal tolerated dose of a chemical is important because such a dose may cause effects ‘which can lead to tumour development as a secondary consequence unrelated to the intrinsic potential of the substance itself to cause tumours at lower less toxic doses’. (47) Thus, if it can be found that a study exceeded the maximal tolerated dose, that study may not be reliable to conclude that the tested substance has the intrinsic properties of a carcinogen.

46. To assess whether the maximal tolerated dose was exceeded in the Heinrich and Lee studies, the RAC used the overload calculation proposed by ‘Morrow’ (in two studies dated 1988 and 1992) (‘the Morrow overload calculation’). (48)

47. While it is not necessary to discuss the details of that analysis, what is important is that the RAC Opinion found that the exposure doses, and therefore the lung overload of the Lee study, were excessive. (49)

48. For the Heinrich study, however, the RAC Opinion made no such conclusion.

49. The General Court’s criticism of the contested regulation, and, by extension, of the RAC Opinion, concerned the RAC’s finding that the Heinrich study was relevant.

50. First, in the judgment under appeal, the General Court determined that the Heinrich study constituted the ‘decisive study’ for the purposes of the RAC Opinion. The hazard classification at issue was therefore ‘based’ on that study, and ‘the other studies, including the Lee study, were taken into account purely on a supplementary basis’. (50)

51. Second, the General Court explained that ‘it is common ground that the Heinrich and Lee studies did not indicate the density of the particles tested’. (51) Those studies indicated only ‘certain characteristics of those particles, namely, as regards the Lee study, micro-sized particles and, as regards the Heinrich study, “P25” grade nano-sized particles’. (52)

52. The judgment under appeal then found that those ‘P25’ particles have a tendency to agglomerate, (53) which would result in a lower particle density than that assumed by the RAC: ‘the agglomeration creates void spaces which are less dense than the material.’ (54)