COMMENTS ON AN ANNEX XV DOSSIER FOR IDENTIFCATION OF A SUBSTANCE AS SVHC AND RESPONSES TO THESE COMMENTS

Disclaimer: Comments provided during the consultation are made available as submitted by the commenting parties. It was in the commenting parties own responsibility to ensure that their comments do not contain confidential information. The Response to Comments table has been prepared by the competent authority of the Member State preparing the proposal for identification of a substance of very high concern. 

Substance name: 2,4,6-tri-tert-butylphenol
CAS number: 732-26-3
EC number: 211-989-5

The substance is proposed to be identified as meeting the following SVHC criteria set out in Article 57 of the REACH Regulation: Toxic for reproduction (Article 57c);PBT (Article 57d)

PART I: Comments and responses to comments on the SVHC proposal and its justification

General comments on the SVHC proposal
Number / Date	Submitted by (name, submitter type, country)	Comment	Responses	
5785
2023/10/16	Netherlands,
Member State		Thank you for these additional data further supporting the persistency of 2,4,6-TTBP. The information has been added to section 3.1.2.1.2 and the conclusion part of the support document.	
		Attachment: 5785_info_biodeg_246-tri-tert-butyl phenol.zip
		
5806
2023/10/16	ANSES,
National Authority,
France	p14 : The 2,4,6-TTBP is a difficult substance (low solubility, high Koc). According to the OECD 302C guideline, if the test material is not soluble at the test concentration, special measures, such as use of ultrasound dispersion, may have to be employed to achieve a good dispersion. In the inherent Biodegradability : Modified MITI Test (II), no information is available about special measures employed to achieve a good dispersion of the test material. There is no indication on the presence of testing vessel without activated sludge to test any loss of the substance by adsorption. This information could be mentioned in the SVHC report. Please note that according to R11, in the case of substance with reduced availability, the interpretation of such test is more difficult. We agree that the QSAR strengthen the conclusion that the substance is P. However we wonder if there are enough evidence to conclude that the substance is vP.

p25: In 6.6.2 Summary and overall conclusions on the PBT and vPvB properties, the assessment of the persistence with Catalogic should be presented.

	Unfortunately, additional data on special measures to achieve good dispersion or presence of testing vessel without activated sludge are not available in the study report and can therefore not be added to the support document.

Thank you for this suggestion, indeed the outcome of the Catalogic assessment has been added to section 6.2.2 of the support document.	

Specific comments on the justification
Number / Date	Submitted by (name, submitter type, country)	Comment	Responses	
5755
2023/09/27	Norway,
Member State	The Norwegian CA supports that 2,4,6-tri-tert-butylphenol should be identified as a substance of very high concern and should be included in the Candidate List.

We would also like to mention some further monitoring data that may be relevant as supporting information:
- Screening Programme 2020, Part 1 and 2: Plastic Additives and REACH Compounds: https://www.miljodirektoratet.no/sharepoint/downloaditem/?id=01FM3LD2UCFOEZF4ANLNGKBLJMHB5CDOGO
	Thank you for the support. 

Thank you for this supporting information, indeed a sentence has been added to section 3.2.4 of the support document on the presence of 2,4,6-TTBP in a maximum concentration of 6 ng/g dw in samples of sediment from leisure boat marinas.	
				
5772
2023/10/11	Health and Environment Alliance (HEAL),
International NGO,
Belgium	The Health and Environment Alliance thanks the Belgian competent authorities for their proposal to identify 2,4,6-tri-tert-butylphenol (2,4,6-TTB) as substance of very high concern (SVHC).

As per human health endpoints, due to the existing harmonised classification as reprotoxicant 1B of the substance under Regulation 1272/2008, we consider that the identification as a SVHC under REACH article 57(c) is unequivocal. We therefore strongly support it.
	Thank you for your support.	
				
5778
2023/10/13	Sweden,
Member State	The Swedish CA thanks Belgium for this proposal and agrees with the weight-of-evidence determination that 2,4,6-tri-tert-butylphenol meets the criteria according to Article 57(c), Article 57(d) and Article 57(e) in REACH, and is thus eligible for identification as a substance of very high concern.	Thank you for your support.	
				
5785
2023/10/16	Netherlands,
Member State	NL supports the proposal to include 2,4,6-tri-tert-butylphenol in the candidate list of SVHC in accordance with Article 57 (c, d and e) of Regulation (EC) No 1907/2006 (REACH).

We do however have the following the comments:

The WoE on persistency could be strengthened by including the available Japanese MITI I test. In this study not only BOD, but also parent compound was followed by HPLC. It appeared that after 28 d, BOD was 0% but also disappearance of the parent compound, measured with HPLC, was only 5% (i.e. negligible). Enclosed you the original report and the English summary of the test.

On page 21 in the B assessment it is mentioned that “The BCF values ranged from 4,320 after 1 week to 23,200 L/kg after 4 weeks (at 0.001 ppm w/v or 1 μg/L) and ranged from 4,830 after 2 weeks to 16,000 L/kg after 6 weeks (at 0.01 ppm w/v or 10 μg/L).”  This is correct, but why are the values measured after 8 weeks not included. We would like to propose to include a table in which all the values are presented.

With respect to the study of Tadokoro it is mentioned (on the same page) that “It is recognised that in this BCF determination, lipid normalisation is applied twice, which could lead to some uncertainty on the value.” The meaning of this statement is not clear to us. Could you please provide some further explanation what is meant here.

	Thank you for your support.

Indeed, the Japanese MITI I test has been added to section 3.1.2.1.2 and the conclusion part of the support document as well as to the applied weight-of-evidence approach.

Thank you for your suggestion. A table presenting all the values has been added to section 3.4.1 of the support document.

In their study on the influence of the lipid content of test fish on measured BCFs, Tadokoro et al. used 24 fish whose lipid content varied from 1.59% (lowest) to 9% (highest). Based on the measured values the authors claimed a BCF for fish with 1% lipid content of 2524 (for 2,4,6-TTBP). The authors applied least square linear regression to estimate this BCF. So, the first lipid normalization was applied by the authors of the study.
In our argumentation we applied a second lipid normalization (from 1% to 5%) as REACH guidance indicates that BCFs should be referred to 5% lipid content.
Although lipid normalization is applied twice (by the study authors and by us), the claim that BCF >5000 cannot be disputed as the measured values in the Tadokoro study for fish with ca 5% lipid content are all above 10,000.
	
		See the corresponding embedded attachment in table 1 of Part I: 5785_info_biodeg_246-tri-tert-butyl phenol.zip		
5793
2023/10/16	Germany,
Member State	The SVHC proposal is supported.

The German CA agrees, although not formally required, to use results from a toxicokinetics study performed in rats to investigate the bioaccumulative properties of the substance.	Thank you for your support.	
				
5794
2023/10/16	ChemSec,
International NGO,
Sweden	ChemSec supports the identification of this substance as an SVHC based on it having been officially identified as being toxic to reproduction, and also because of its PBT and vBvB properties, which are well presented in the dossier. We added this substance to the SIN List in 2014, for being a PBT substance.	Thank you for your support.	
				
5806
2023/10/16	ANSES,
National Authority,
France	ANSES supports the proposal of identification of 2,4,6-tri-tert-butylphenol as SVHC according to article 57c. The harmonised classification Toxic for reproduction category 1B (H360D: May damage the unborn child) of Substance fulfils the criteria to identify the substance as SVHC under article 57(c).

ANSES supports the proposal of identification of 2,4,6-tri-tert-butylphenol as SVHC according to article 57d.  We agree that the Substance can be identified as PBT.

ANSES  would welcome a further strengthening on the vP assessment in the context of the identification of the substance as SVHC according to 57e. Based on the WoE approach, we agree that 2,4,6-TTBP can be identified P. Further discussion is needed regarding vP conclusion
	Thank you for your support.

The dossier submitter removed the identification as SVHC according to article 57(e) of REACH from the support document as no additional data are available to strengthen the vP assessment.	
				
5808
2023/10/16	CHEM Trust Europe,
International NGO,
Germany	CHEM Trust supports the inclusion of 2,4,6-tri-tert-butylphenol (2,4,6-TTBP)
in the REACH candidate list based on its harmful properties fulfilling REACH article 57 c), d) and e). The dossier submitters compiled convincing evidence that the substance has very persistent and very bioaccumulative properties meeting the criteria of Annex XIII of the REACH Regulation. In addition, 2,4,6-TTBP  is classified as a  reprotoxic chemical 1B.

It will be important to follow up the SVHC identification with swift risk management options, given that the  OSPAR Commission already identified 2,4,6-TTBP in 2003 as a substance for priority action.
	Thank you for your support.	
				
5816
2023/10/16	Finland,
Member State	We thank Belgium for this proposal. We have the following comments on the Annex XV report:

page 6:”The OECD TG 302C study provides strong indications that 2,4,6-TTBP can be concluded as persistent and very persistent.”
Comment: We propose to modify: “The OECD TG 302C study provides strong indications that 2,4,6-TTBP can be concluded as persistent”.
Reason: We are not convinced that there is additional specific information supporting vP.
page 6: Due to reasons explained in comments below, we propose to delete or modify the sentence “In accordance with REACH Annex XIII Section 3.2.1. (d), supporting information from a laboratory study using natural seawater (Klimisch score 4) indicates that the half-life of 2,4,6-TTBP in seawater at relevant EU-temperature (9 °C) is 92 days and thus support the conclusion that the substance is very persistent.”
Regarding the Lofthus et al. (2016) article:
The studied seawater is a relevant medium for PBT assessment of the marine water compartment. However, we do not agree with the proposed approach to use the results described by Lofthus et al. for this assessment, particularly regarding the non-standard simulation study where a half-life was reported. The reasons are related to the use of an adsorbent, the representativeness of test conditions to the conditions at the sampling site, and the temperature correction of the resultsand uncertainties regarding the sample treatment.

1. The use of an adsorbent:

The test substance was administered in immobilized form in fabrics, and a significant part of the test substance may have remained in the adsorbent during the study (27-34% of the studied alkylphenols were desorbed into the water phase after 5h). The biodegradation curve reflects the sum of degradation of adsorbed and dissolved test substance and it is stated that biodegradation curve (% of sterilized controls) based on measurements from adsorbent only was similar to that based on the sum of adsorbent and water phase. We consider that this observation may suggest that the biodegradation rate may have been determined by the rate of desorption and the ability of microorganisms to utilise the adsorbed substance. The rate of desorption may be different between the sterile controls and the non-sterile test, as removal of the test substance by biodegradation affects the equilibrium of sorbed chemical vs. chemical in solution (e.g., Figure 8.5 in Alexander 1999). It is not discussed in the article whether this affects the kinetics observed. The study was conducted without agitation. Only one test concentration was used whereas, according to OECD TG 309, at least two different concentrations of test substance should be used in order to determine the degradation kinetics. The samples for the sterile controls were filtered, which may have decreased the amount of suspended matter. Filtration is mentioned only for sterile controls and not for the samples in the non-sterile test. Therefore, has a part of the difference between the sterile control and the non-sterile test been due to partitioning of the test substance to suspended matter in the non-sterile test?

2. Representativeness of the test conditions

The OECD TG 306 test guideline requires the reporting of test conditions, e.g. characteristics of the sample (date of sampling, depth, appearance, temperature, salinity, DOC (optional), delay between collection and use in the test). The same information is relevant also for the assessment of the non-standard study but this information is not completely available. It is not reported how long time it took for the sample to be transported to the laboratory. It is stated that oxygen (DO) of the seawater was approximately 8 mg/L when reaching the laboratory. Information on oxygen levels at the sampling site is missing.

The temperature of the seawater was 6-8oC when reaching the laboratory. Temperature at the sampling depth is not reported. The sampling was below the thermocline. Temperature below the thermocline is expected to be relatively stable. Based on the results by Grieger (2021) the temperature in 7 fjord basins along the Norwegian Sognefjorden is constantly below 10oC at the depth of 80 m. Trondheimsfjord, where the seawater was sampled for the study (Lofthus et al. 2016), is located in Norway at a higher latitude than Sognefjorden. Information on seawater temperature from Trondheimsfjord as well air temperatures could potentially be useful for the assessment. However, it seems likely that the temperature at the sampling depth has been constantly below 10oC. That would mean that that microorganisms were most likely adapted to that temperature. The sample was transferred to the laboratory and the experiments (OECD TG 306 and the non-standard simulation study) were conducted at 20oC. In this particular case, a question should be asked whether a test temperature of 20oC is a relevant test condition for the microbial community present in the seawater sample. The temperature optimum for the growth of psychrophiles is below 20oC (Atlas and Bartha 1997).

3. Temperature correction.

For the half-lives determined from the simulation study, temperature conversion has been conducted to 9oC using the Arrhenius equation and the default activation energy in the guidance R.7b. Regarding the temperature correction, we note that the ECHA guidance R.11 states “Consequently, for persistence assessments where the B and T criterion have been met, and simulation data exist for degradation at 20C, consideration should be given whether temperature correction should be applied. This will be particularly important where the measured half-life is close to the persistence criteria. This correction, if applied, should be based on the Arrhenius equation and extrapolate from 20C to the temperature of the environmental media at the point of sampling34.”. Thus, there is a recommendation to consider the use of the temperature correction, but no recommendation to always conduct such a correction. In addition, it should be noted that REACH Annex XIII states that the information used for the purposes of assessment of the PBT/vPvB properties shall be based on data obtained under relevant conditions. Thus the possibility that the temperature optimum for biodegradation could be below 20oC in this case should be taken into account. In that case the temperature correction according to the guidance R.7b would lead to an underestimation of the primary degradation rate. Information on the temperature dependence of microorganisms typically present in the sampling site, if available, or in similar marine habitats, could be useful to assess whether a temperature correction is justified. Even if the temperature conversion would be considered not justified, we note that the half-life at the reference temperature of 9oC remains unknown (and therefore the half-life at 20oC, which is below the cut-off for P/vP, cannot be used to exclude P/vP concern).

Considering the reasons described in points 1-3 above, the suitability of the study for the purpose of persistence assessment under REACH should be reconsidered. The text in 3.1.2.1.3.1 should be modified based on these considerations.

References:

Alexander M (1999) Biodegradation and bioremediation. Second Edition. Academic Press.

Atlas RM and Bartha R (1998). Microbial Ecology - Fundamentals and Applications in Biotechnology. Benjamin/Cummings Science Publishing.

Grieger J (2021) Hydrographical History of 7 Fjord Basins Along the Norwegian Sognefjorden with Emphasis on Oxygen Conditions. https://hdl.handle.net/11250/2771971. Bachelor thesis.

Thank you for this suggestion. 
The dossier submitter removed the identification as SVHC according to article 57(e) of REACH from the support document as no additional data are available to strengthen the vP assessment. 

Regarding the Lofthus et al. (2016) article a general paragraph was added to the support document recognising the uncertainties raised regarding the use of an adsorbent. The study can still be used as supportive information for the persistency of the substance.	
				
5817
2023/10/16	European Environmental Bureau,
International NGO,
Belgium	The EEB supports the proposal by Belgium to identify 2,4,6-tri-tert-butylphenol (2,4,6-TTBP) as a Substance of Very High Concern due to its toxicity for reproduction, as well as its PBT and vPvB properties. 2,4,6-TTBP meets the criteria for reprotoxicity due to its harmonised classification under the CLP regulation as toxic for reproduction, category 1B (H360D: May damage the unborn child). The P and vP criteria are met based on the weight of evidence assessment of all available information, including an inherent degradation test confirming lack of degradation and a test with seawater indicating a half life exceeding 90 days.  2,4,6-TTBP also fulfills the criteria for B and vB in REACH Annex XIII based on available  evidence including experimental BCFs in the range of 4300 to over 23000 L/kg. It meets the toxicity criteria for PBT substances owing to its harmonised classification as reprotox 1B and STOT RE 2.  Therefore based on the weight of evidence assessment, the substance meets the criteria for PBT and vPvB substances. The EEB recommends to consider the inclusion of multi-constituent substances and mixtures containing 2,4,6-TTBP in the candidate list.	Thank you for your support.	

PART II: Comments and responses to comments on uses, exposures, alternatives and risks

Specific comments on use, exposure, alternatives and risks
Number / Date	Submitted by (name, submitter type, country)	Comment	Responses	
5764
2023/10/10	Food Packaging Forum Foundation,
International NGO,
Switzerland	The Food Packaging Forum (FPF) is a charitable, science-based organization at the science policy interface dedicated to raising awareness for hazardous chemicals in, and environmental impacts caused by, all types of food contact materials and articles (FCMs). As our expertise is mainly on chemicals in food packaging, we focus our remarks on this aspect to provide context for any follow-up to the listing of 2,4,6-tri-tert-butylphenol as an SVHC Candidate.
2,4,6-tri-tert-butylphenol has been measured in food contact materials.
We found evidence from six studies demonstrating the presence of 2,4,6-tri-tert-butylphenol in migrates from FCMs or that have been directly extracted from food packaging or other food contact articles (Geueke et al., 2022). These six studies measured 2,4,6-tri-tert-butylphenol in polyethylene (PE), polypropylene (PP), polyethylene terephthalate (PET), recycled PET, and polyamide (PA) plastics.
The studies in question were published between 1993 and 2022 demonstrating long term continuous consumer exposure to this chemical that the authorities in Belgium have concluded is toxic for reproduction, PBT, and vPvB.
Concerns for EU FCM safety
2,4,6-tri-tert-butylphenol is not included in Annex 1 of EU 10/2011 on plastic materials and articles intended to come into contact with food. Yet, as mentioned above, it is still found in plastic food packaging.
REACH demands the substitution of SVHCs by safer alternatives in industrial products, processes, and in consumer articles solely based on their intrinsic hazard properties, not based on their risk (where both hazard properties and exposure levels would be taken into account). Authorization under REACH can be granted for specific uses and time periods in case the applicant demonstrates that the risk from using the substance is adequately controlled. Alternatively, the applicant can show that socio-economic benefits of using the substance outweigh the risks and that there are no suitable alternative substances or technologies. However, the human health effects of FCMs are excluded from the REACH authorization process.
A stricter ban of SVHCs from all possible areas of use, including FCMs, would further reduce the overall burden of these chemicals, facilitate compliance with Article 3 of the FCM Framework Regulation and help to improve public health.
Thank you for the chance to provide input into the consideration of candidate SVHCs.

Best regards,
FPF staff

Studies detecting 2,4,6-tri-tert-butylphenol in FCMs
Bourges, F., Bureau, G., & Pascat, B. (1993). Effects of electron beam irradiation on the migration of antioxidants and their degradation products from commercial polypropylene into food simulating liquids. Food Additives and Contaminants, 10(4) 443-452. https://doi.org/10.1080/02652039309374167
Li, H.K., Wu, X.F., Wu, S.L., Chen, L.C., Kou, X.X., Zeng, Y., Li, D., Lin, Q.B., Zhong, H.N., Hao, T.Y., Dong, B., Chen, S., & Zheng, J.G. (2022). Machine learning directed discrimination of virgin and recycled poly (ethylene terephthalate) based on non-targeted analysis of volatile organic compounds. Journal of Hazardous Materials, 436, 129116. https://doi.org/10.1016/j.jhazmat.2022.129116
Barkby, C.T. (1995). Migration from non-ovenable food contact materials at elevated temperatures (Doctoral dissertation, De Montfort University). Retrieved from https://dora.dmu.ac.uk/xmlui/bitstream/handle/2086/10704/Migration_from_non_ovenable_food_contact_materials_at_elevated_temperatures.pdf?isAllowed=y&sequence=2
Liang, R., Hu, Y., & Li, G. (2020). Monodisperse pillar5arene-based polymeric sub-microsphere for on-line extraction coupling with high-performance liquid chromatography to determine antioxidants in the migration of food contact materials. Journal of Chromatography A, 1625, 461276. https://doi.org/10.1016/j.chroma.2020.461276
Hu, Y.J., Du, Z.X., Sun, X.C., Ma, X., Song, J.D., Sui, H.X., & Debrah, A.A. (2021). Non-targeted analysis and risk assessment of non-volatile compounds in polyamide food contact materials. Food Chemistry, 345, 128625. https://doi.org/10.1016/j.foodchem.2020.128625
Rothenbacher, T., & Schwack, W. (2009). Nontargeted multicomponent analytical screening of plastic food contact materials using fast interpretation of deliverables via expert structure-activity relationship software. Journal of AOAC International, 92(3), 941-50. https://pubmed.ncbi.nlm.nih.gov/19610389/

Other resources
Geueke B, Groh KJ, Maffini MV, Martin OV, Boucher JM, Chiang Y-T, Gwosdz F, Jieh P, Kassotis CD, Łańska P, Myers JP, Odermatt A, Parkinson LV, Schreier VN, Srebny V, Zimmermann L, Scheringer M and Muncke J (2022) Systematic evidence on migrating and extractable food contact chemicals: Most chemicals detected in food contact materials are not listed for use. Critical Reviews in Food Science and Nutrition, 1-11. https://doi.org/10.1080/10408398.2022.2067828.
Geueke, B., Wagner, C., and Muncke, J. (2014) Food contact substances and chemicals of concern: a comparison of inventories, Food Additives & Contaminants: Part A, 31:8, 1438-1450, DOI: 10.1080/19440049.2014.931600
Geueke, B., and Muncke, J. (2018) Substances of Very High Concern in Food Contact Materials: Migration and Regulatory Background. Packag. Technol. Sci., 31: 757–769. https://doi.org/10.1002/pts.2288.
	Thank you for this additional information. The information and studies provided can potentially be taken into account during follow-up RMMs as indicated in your comments.

Indeed, the identification of a substance as SVHC by itself is not automatically a ban of the substance.

5785
2023/10/16	Netherlands,
Member State		See response to comment 5785 in part I of this RCOM	
		See the corresponding embedded attachment in table 1 of Part I: 5785_info_biodeg_246-tri-tert-butyl phenol.zip		
5794
2023/10/16	ChemSec,
International NGO,
Sweden	We have a number of alternatives to the substance published on the ChemSec Marketplace: https://marketplace.chemsec.org/alternatives/chemical/732-26-3
	Thank you for this information that can potentially be taken into account during follow-up risk management measures.