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: S-(tricyclo[5.2.1.0'2,6]deca-3-en-8(or 9)-yl) O-(isopropyl or isobutyl or 2-ethylhexyl) O-(isopropyl or isobutyl or 2-ethylhexyl) phosphorodithioate
CAS number: 255881-94-8
EC number: 401-850-9

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

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	
5560
2021/10/08	Company,
Belgium		
See our response in the section specific comments below.	
		Attachment: 5560_Comments to ECHA on Annex XV Report for EC 401-850-9.docx

Specific comments on the justification
Number / Date	Submitted by (name, submitter type, country)	Comment	Responses	
5559
2021/10/07	Sweden,
Member State	The Swedish CA thank Belgium for this proposal and agrees that EC 401-850-9 meets the criteria according to Article 57(d) in REACH and is thus eligible for identification as a substance of very high concern.	The Belgian CA thanks the Swedish CA for their support to identify EC 401-850-9 as a PBT substance.	
				
5560
2021/10/08	Company,
Belgium	The Lead Registrant has reviewed the Annex XV report and found a few numerical inaccuracies in the data presented.  On page 18 of the report, the following data is provided (apparently extracted from the OECD 309 study report {Table 15, page 39}
“Unfortunately, the sterile controls were only sampled on day 31 and 91 and so only the results from these sampling points can be used. The percentages residual test item were as follows (cf. study report table 15, p. 39) :

- @ 10 μg/L viable experiment: 31 d = 29%, 91 d = 14%
- @ 10 μg/L sterile experiment: 31 d = 32%, 91 d = 10%
- @ 50 μg/L viable experiment: 31 d = 35%, 91 d = 5%
- @ 50 μg/L sterile experiment: 31 d = 31%, 91 d = 6%”
However, this doesn’t match the data from Noack’s report (see Table 15 attachment).

If we take the mean values for the two loading rates (viable and sterile), we get the following values and not what is in the report:
• 10 μg/L viable:  31d: 36%;  91d: 17%
• 10 μg/L sterile:  31d: 52%;  91d: 17%
• 50 μg/L viable:  31d: 37%;  91d: 5%
• 50 μg/L sterile:  31d: 31%;  91d: 6%

The Lead Registrant recommends that corrections are made to the report accordingly.
Thank you.
	It is indeed correct that the values in the annex XV report are extracted from table 15 of the OECD 309 study report. The reason why our values differ lies in the fact that we took into account that at the start of the experiment, the measured concentrations of applied test item are not exactly 10 and 50 µg/L, but mostly a bit higher: 

- @ “10 µg/L”, viable experiment  12.5 µg/L
- @ “10 µg/L”, sterile experiment  16.3 µg/L
- @ “50 µg/L”; viable experiment  53.5 µg/L
- @ “50 µg/L”; sterile experiment  50.0 µg/L

In order to perform the calculation in the correct way, it is necessary to compare the results from the sterile and viable experiment on a relative and not on an absolute basis. 

So, we think this represents the appropriate mathematical approach and consequently we do not alter the values.

It should be noted that in table 16, page 40, the remaining concentrations are also expressed on a relative basis.	
		See the corresponding embedded attachment in table 1 of Part I: 5560_Comments to ECHA on Annex XV Report for EC 401-850-9.docx		
5562
2021/10/13	Health and Environment Alliance (HEAL),
International NGO,
Belgium	The Health and Environment Alliance (HEAL) thanks Belgium for its proposal to identify S-(tricyclo[5.2.1.0'2,6]deca-3-en-8(or 9)-yl) O-(isopropyl or isobutyl or 2-ethylhexyl) O-(isopropyl or isobutyl or 2-ethylhexyl) phosphorodithioate  as SVHC under REACH article 57(d) due to its persistent, bioaccumulative and toxic properties, and we fully support this proposal.	The Belgian CA notes that the Health and Environment Alliance (HEAL) supports the initiative to identify EC 401-850-9 as a PBT substance.	
				
5565
2021/10/14	Norway,
Member State	The Norwegian CA supports that S-(tricyclo[5.2.1.0'2,6]deca-3-en-8(or 9)-yl) O-(isopropyl or isobutyl or 2-ethylhexyl) O-(isopropyl or isobutyl or 2-ethylhexyl) phosphorodithioate should be identified as a substance of very high concern and should be included in the Candidate List.	The Belgian CA thanks the Norwegian CA for their support to identify EC 401-850-9 as a PBT substance.	
				
5568
2021/10/15	Finland,
Member State	We thank Belgium for this proposal. We consider that S-(tricyclo[5.2.1.02,6]deca-3-en-8(or 9)-yl) O-(isopropyl or isobutyl or 2-ethylhexyl) O-(isopropyl or isobutyl or 2-ethylhexyl) phosphorodithioate fulfills the PBT criteria due to the presence of isopropyl-isopropyl (ip-ip) constituents in a concentration exceeding 0.1% (w/w). We have the following comments regarding the Annex XV report (divided as non-editorial and editorial comments):

NON-EDITORIAL COMMENTS:

page 14: “…hydrolytically stable as the substance does not present functional groups that result in hydrolysis”.
Comment: Consider modifying the sentence to e.g., “…hydrolytically stable as the substance does not present functional groups that results in significant hydrolysis”.
Reasoning: The functional group phosphorodithioate can be hydrolysed.

page 15: Comment: We would recommend to briefly specify the reasons for the reliability score of 3 for M.S.I. Report N° 6B061G.

page 18: “…As mentioned in the above paragraph, the inoculum in a simulation test is considered to be sufficiently active if the mineralization half-life of the reference substance is 0.9 days (at 10 µg/L). This means that on average viable microbial communities in a simulation test mineralize the reference substance at an initial rate of ca. 7.7 µg/L/d. In the main study, 8% CO2 formation is measured after 21 days and 59% after 89 days (without solvent). Based on the value found after 21 days, one can calculate that on average the mineralization rate is 69 µg/L/d (18000 µg/L * 0.08/21 d). Based on the CO2 formation after 89 days, the mineralization rate becomes 119 µg/L/d (18000 µg/L * 0.59/89 d). It is correct that the influence of the growth of the microbial population is difficult to take into account, but the fact that the absolute mineralization rates found in this test are substantially higher than the rates found in studies performed with standard reference substance levels indicates that the inoculum in this study actually was viable. “

Comment: As this calculation is a very important part of the assessment (due to reference substance concentration which deviated from the test guideline), we would recommend to explain in more detail how the initial rate of 7.7 µg/L/d is derived.

We also recommend to indicate the following:
-the calculated mineralisation rates are based on the assumption of linear (i.e., zero-order) kinetics, which can occur under certain conditions (e.g. Alexander, 1999) whereas from the data presented the kinetics cannot be estimated.
-In addition, the high concentration of the reference substance has probably led to a higher growth of the microbial population than would occur with the standard concentration, which also may have affected the degradation kinetics
-if non-linear kinetics occurred and the maximum degradation was actually reached earlier than 89 days, the average degradation rate during the degradation period must have been higher than the calculated values.

Based on the data presented we consider that the validity criterion regarding reference substance degradation is fulfilled (even if a non-standard approach was necessary to check this, due to the too high concentration of the reference substance).
Reference cited: Alexander, M. 1999. Biodegradation and bioremediation. Second edition. Academic Press.

page 18: Comment: We propose to change the reliability score of the “Aerobic Mineralization in Surface Water Study (Maischak H.)” to “reliable with restrictions”.
Reasoning: The reference substance degradation is needed for confirming the validity of the test and in this case this was not studied in accordance with the test guideline as a significantly higher concentration was used. Therefore, the studied parameter (CO2 production as percentage of applied amount) is not comparable to the criterion in the guideline (although a conclusion on this viability of the microbial community can still be done using another approach, as explained in the report). In addition, as mass balance was not determined, it is not possible to assess whether the target range defined in the test guideline was fulfilled.

For example the following part of the guidance R.4 is relevant:
“The R.4 includes for “1 = reliable without restrictions”: “studies or data [...] generated according to generally valid and/or internationally accepted testing guidelines (preferably performed according to GLP) or in which the test parameters documented are based on a specific (national) testing guideline [...] or in which all parameters described are closely related/comparable to a guideline method.
2 = reliable with restrictions: “studies or data [...] (mostly not performed according to GLP), in which the test parameters documented do not totally comply with the specific testing guideline, but are sufficient to accept the data or in which investigations are described which cannot be subsumed under a testing guideline, but which are nevertheless well documented and scientifically acceptable.”

EDITORIAL COMMENTS:

page 15: “Sodium benzoate was degraded by 66% in the absence of test material and 63% in its presence, confirming that the test item was inhibitory to bacteria under the conditions of the test”
Comment: The word “not” seems to be missing from the sentence (i.e. “confirming that the test item was not inhibitory to bacteria…”).

Page 15: “The applied enhancements included the use of silicone oil as a solvent and Synperonic PE 105 as a surfactant. The modifications further included increasing the test volume and extending the test duration up to 63 days.”
Comment: The use of a solvent and a surfactant could rather be considered “modifications” and the test volume and test duration as “enhancements”, in accordance with REACH guidance R.7b and R.11.

page 17: “If biodegradation would occur, one should detect degradation products as biodegradation takes place in many intermediate steps and therefore cannot occur instantaneously.”
Comment: We propose to modify to: “If biodegradation would occur, one should detect the degradation products. This would apply even in case of ultimate degradation, as biodegradation takes place in many intermediate steps and therefore ultimate degradation (to CO2 and biomass) cannot occur instantaneously.”
Reasoning: The proposed change is to take into account both primary and ultimate degradation. In principle, sometimes there could be fast primary degradation by one reaction, e.g. if fast hydrolysis takes place. But if the metabolites do not degrade further, they would certainly be detectable. On the other hand, if ultimate degradation occurs, there would likely be several metabolites.

page 18: Please specify that the values refer to the non-sterile test, e.g., by adding “in non-sterile test“ at the end of each row, as follows:
“-  @ 10 µg/L,  31 d :  3% extra disappearance in non-sterile test
- @ 10 µg/L,  91 d :  -4%, no extra disappearance in non-sterile test
- @ 50 µg/L,  31 d :  -4%, no extra disappearance in non-sterile test
- @ 50 µg/L,  91 d :  1% extra disappearance in non-sterile test”

page 18: We propose to use “primary biodegradation” instead of “biodegradation”, at least in the following paragraph (and elsewhere in the document, if appropriate):
“Looking at the data point with the highest extra disappearance of 3% in the viable test (i.e. experiment at 10 µg/L and 31 days) and assuming that dissipation of the substance is happening at the very start of the test so that only 32% of the substance is really bioavailable in the test (which represents a less conservative scenario), a biodegradation of 9.38% (=3/32) at 31 days can be estimated. Considering 9.38% of biodegradation of ip-ip constituents at day 31 and using a first-order kinetic model, a rate constant k of 0.00318 d-1 is derived leading to a biodegradation half-life of 218 days. It should be noted that using the other data points would only lead to still greater half-life estimations.

page 20: “It is also important to note that in the complementary test, in contrast to the main test, the viability of the microorganisms is not an issue at all. The reference item is degraded for 50% after 5 days incubation, showing that the microorganisms in this study are without doubt sufficiently active. In that respect the complementary test is even more indicative than the main test.”
Comment: We propose to change to: “It is also important to note that in the complementary test, in contrast to the main test, a higher degradation of the reference substance was obtained already in the beginning of the study (50% of the initial amount after 5 days incubation), showing that the microorganisms in this study are sufficiently active, even based on the percentage degradation. Due to the apparent higher microbial activity, the complementary test is even more indicative than the main test (however, it should be noted that also the main test had a sufficient microbial activity, as indicated above).”
Reasoning: As the issue with the main test has been resolved in preceding text, we suggest to change the wordings suggesting insufficient viability of the microbes in the main text.

page 20: ”In the main test the viability of the microorganisms could be questioned, but it should be noted that the results of both tests are very much in line with each other. Therefore, it is concluded that the absence of biodegradation in the main study is not triggered by the inactiveness of the microbes but by the inherent persistence of the test item. “
Comment: We propose to modify to: “It should be noted that the results of both tests are very much in line with each other. Therefore, the results of the complementary test (similar degradation of test item but higher degradation of reference substance) are in line with the conclusion that the absence of biodegradation in the main study is not triggered by the inactiveness of the microbes but by the inherent persistence of the test item.
Reasoning: The issues of viability in the main study is already addressed in preceding text (without using the data from the complementary study). Therefore, mentioning the question of viability of the main test in this part would be in contradiction to what is said before.

page 20: “Although this simulation test shows some shortcomings such as the lack of a mass balance and some uncertainty on the microbial activity of the inoculum, it allows to come to a reliable estimation of the half-life of the ip-ip constituents in fresh water”
Comment: We propose to change to: “Although this simulation test shows some shortcomings such as the lack of a mass balance and a too high concentration of the reference substance, it allows to come to a reliable estimation of the half-life of the ip-ip constituents in fresh water.”, as we consider that there is no uncertainty with the microbial activity.

page 21: “The hydrolysis study that was performed at various pH values demonstrates that the half-lives at 12°C are in the order of magnitude of 1 year.”
Comment: Consider changing the sentence to e.g. “The hydrolysis study that was performed at various pH values (4, 7 and 9) and temperatures (50-70°C) indicate that the expected half-lives in 12°C are in the order of magnitude of 1 year”
Reasoning: No test was conducted at 12°C and the lowest test temperature was 50°C, so we think that the word “indicates” rather than “demonstrates” would be more suitable here.	The Belgian CA wants to thank the Finnish CA for their extensive review of the annex XV document for EC 401-850-9 and for their support to identify the substance as a PBT substance.

This is indeed a relevant observation and the text will be adapted. Although hydrolysis of phosphorodithioates is generally very slow, in theory it can take place to some extent.

The registrant proposed reliability 3 in his registration dossier. After further consideration, the BE CA proposes to attribute reliability 2 to the study as in general the guideline instructions have been followed.
In this study the test item concentration is 100 mg/L and no methods are applied to increase the solubility of the test item in the system. This nominal concentration is circa 1000 times higher than the water solubility of the test item and for this reason we think it is appropriate to attribute a reliability score of 2. 

We realize now that our approach to determine the “usual” (initial) degradation rate of the reference substance was unnecessary complicated. We came to a rate of ca. 7.7 µg/L/d based on the assumption that the half-life of the reference substance is 0.9 days.
In fact the estimation of the initial degradation rate becomes easier to understand if one assumes that the degradation rate constant is 0.8 d-1 (cf. § 51 of the Guideline).
Degradation rate at the start equals initial concentration*rate constant (10 µg/L*0.8/d) = 8 µg/L/d.
The fact that our first value differs a bit has to do with rounding off. Assuming that k = 0.8/d, exact half-life becomes 0.866 d.

We’ll adapt the text in the Support Document in that sense.

As explained above we’ll change the “usually” expected mineralization rate in studies that are considered valid from 7.7 to 8 µg/L/d.

This observation will be mentioned in the revised text.

This observation will be mentioned in the revised text.

This observation will be mentioned in the revised text.

We note that the FI CA supports our conclusion on the validity of the study. Thank you for the suggestions to improve the wording.

The reliability score will be changed from 1 to 2 and the following clarification will be added :

…. because the reference substance degradation was not studied in accordance with the test guideline, but a conclusion on the viability of the microbial community could still be drawn, using another approach. In addition, as the mass balance was not determined, it is not possible to assess whether the target range defined in the test guideline is fulfilled. Therefore, the data documenting the test parameters do not totally comply with the specific testing guideline, but are nevertheless sufficiently documented and scientifically acceptable.

The following sentence will be added:
Therefore, the data documenting the test parameters do not totally comply with the specific testing guideline, but are nevertheless sufficiently documented and scientifically acceptable.

Indeed

Suggestion is accepted

Suggestion is accepted

We’ll change in: This would apply even in case ultimate degradation occurs as biodegradation always takes place in many intermediate steps and therefore ultimate degradation to CO2 and biomass cannot occur instantaneously.

Ok

Ok, our calculation indeed only considers biodegradation of the parent compound

Text in the Support Document will be changed as suggested

Text will be adapted as follows:

It should be noted that the results of both tests are very much in line with each other. Therefore, the results of the complementary test (similar degradation of test item but faster degradation of reference substance) support the conclusion that the absence of biodegradation in the main study is not caused by the inactiveness of the microbes but by the inherent persistence of the test item.

Text will be adapted as suggested

Text will be adapted as suggested	
				
5570
2021/10/15	Germany,
Member State	The German CA supports the identification of EC 401-850-9 as substance of very high concern according to Article 57(d) of REACH.	The Belgian CA thanks the German CA for their support to identify EC 401-850-9 as a PBT substance.	
				
5574
2021/10/16	CHEM Trust Europe,
International NGO,
Germany	CHEM Trust supports the inclusion of S-(tricyclo[5.2.1.02,6]deca-3-en-8(or 9)-yl) O-(isopropyl or isobutyl or 2-ethylhexyl) O-(isopropyl or isobutyl or 2-ethylhexyl) phosphorodithioate in the REACH candidate list due to its PBT properties based on article 57 (d). The dossier presents a convincing weight-of-evidence determination according to the provisions of Annex XIII of REACH.	The Belgian CA notes that CHEM Trust supports the initiative to identify EC 401-850-9 as a PBT substance.	
				
5583
2021/10/18	Netherlands,
Member State	NL supports the identification of EC 401-850-9 as PBT and has some minor comments for improvement of the Annex XV report.

Phototransformation in air
Comment:
The reported QSAR-derived half-life time of the ip-ip constituents in air (0.544 hours) is calculated with an inappropriate preference value for the OH radicals/cm3. As described in the REACH Guidance R.16, the default OH-radicals concentration in atmosphere is an average of 5·105 molec./cm³ over 24 hour, and not 15·105 molec./cm³ per 12-h of daylight. The half-life for the ip-ip constituents in air should therefore be 0.816 hours.

Bioaccumulation in aquatic organisms
Comment:
Regarding your comments on the bioconcentration study (M.S.I. Report N° 6B062G, reliability score of 2), please be aware that growth-correction is only possible for kinetic BCF values (BCFK). As the BCF-values are derived at steady state (BCFss), the argumentation that the BCF values represent a less conservative scenario as a possible growth dilution was not accounted, is not valid. Only when a BCFK is available, this reasoning is possible.
As already discussed in the RCOM, growth-correction is only possible for kinetic BCF values. Therefore it is suggested to change the sentence on page 24:
“Furthermore, it is important to note that these lipid normalised BCF values represent a less conservative scenario as a possible growth dilution was not accounted for in the BCF calculations.”
“Furthermore, it is important to note that these lipid normalised BCF values represent a less conservative scenario as a possible growth dilution cannot be accounted for in steady state BCF calculations.”

Algae and aquatic plants
Comment:
Please also mention the NOEC/EC10 value and that the results are based on the growth rate.
	The Belgian CA wants to thank the Dutch CA for their support to identify EC 401-850-9 as a PBT substance and for the specific comments that can help to improve the argumentation in the annex XV dossier for the substance.

That remark is correct.
The estimated half-life for reaction with OH radicals will be changed from 0.544 hours to 0.816 hours.

This remark regarding growth correction of BCFs is correct.
The text will be adapted as suggested.

In the text will be added that quantitative results are based on measurement of growth rate and that the NOEC = 0.23 mg/L.	
				
5588
2021/10/18	ChemSec,
International NGO,
Sweden	ChemSec supports the SVHC identification based on the thorough evidence laid out in the dossier, proving that this is a PBT substance.	The Belgian CA notes that ChemSec supports the initiative to identify EC 401-850-9 as a PBT substance.	
				
5589
2021/10/18	ANSES,
National Authority,
France	ANSES have some reservations at this stage in the identification of the substance EC 401-850-9 as SVHC according to 57f, based on the PBT properties of isopropyl-isopropyl (ip-ip) constituents, which is present above 0.1% (w/w) on the constitution of EC 401-850-9.

Our reservation is mainly based on the conclusion of P assessment. The evaluation of persistence properties of isopropyl-isopropyl (ip-ip) constituents is based on screening information (QSAR and experimental data) and an aerobic mineralization study in surface water (OECD 309). From this last study, a high dissipation of the substance is observed, which seems to be associated to other process (adsorption, volatilization, formation of NER may be?) and not by a (bio) degradation process. Comparing the results with the abiotic control, very low degradation of the substance is observed. An estimation of half-life is presented in the proposition, this is higher than the P/vP criteria for water (half- life above 60 days). Further clarification of the P assessment is welcome before a final conclusion can be reached.

Regarding to B properties, the conclusion is mainly based on a bioaccumulation study with fish (OECD 305C, version 1981) conducted with a mixture of 3 constituents of EC 401-850-9 (ip-ip, ib-ib, eh-eh).  Despite the methodology followed in this study deviate from the current OECD 305, the study can be considered as valid. The BCF calculated at steady state (and after lipid normalisation) are higher than 2000, thus these constituents meet the B criteria.

Ecotoxicity studies with EC 401-850-9 are available for fish, daphnia and algae. The long-term study with daphnia presents the highest toxic effects between the organisms.  The LOEC and NOEC calculated are less than 0.01 mg/L. Therefore, the substance EC 401-850-9 and ip-ip constituents (constituents likely predominant in the media) meet the toxicity criterion (T) (NOEC below 0.01 mg/L) in accordance with Annex XIII.
	See our response to the comment #5599.	
				
5595
2021/10/18	European Environmental Bureau (EEB),
International NGO,
Belgium	The EEB supports the proposal by Belgium to identify S-(tricyclo[5.2.1.02,6]deca-3-en-8(or 9)-yl) O-(isopropyl or isobutyl or 2-ethylhexyl) O-(isopropyl or isobutyl or 2-ethylhexyl) phosphorodithioate as a Substance of Very High Concern due to its PBT properties (REACH article 57(d)).
The substance should be included in the Candidate List and further risk management measures should be implemented to avoid further emissions into the environment.
	The Belgian CA notes that the EEB supports the initiative to identify EC 401-850-9 as a PBT substance.	
				
5599
2021/10/25	ANSES,
National Authority,
France	This comment replaces the one submitted by France on 18 October 2021 (comment #5589).

ANSES  would welcome a further strengthening on the P assessment in the context of the identification of the substance EC 401-850-9 as SVHC according to 57f, based on the PBT properties of isopropyl-isopropyl (ip-ip) constituents, which is present above 0.1% (w/w) on the constitution of EC 401-850-9.

The request relates to missing information that could help to understand what happened during the simulation test (OECD 309) and the reasoning of the conclusion for P. 

In the section corresponding to the simulation test OECD 309, we agree with the analysis that the dissipation is more relevant that bio(degradation) process.

The information from chromatograms is crucial, because it put in evidence that the biodegradation has hardly taken place and the abiotic degradation seems to be negligible. 

However, in the argumentation, there is limited information regarding the factors that probably contribute to the dissipation (volatilisation, NER formation..), especially considering that in DT50 calculation it is assumed that the dissipation happens at the beginning of the test and only 32% of the substance will be bioavailable. 

We suggest to add in the page 17 in the second paragraph further information about the evolution of the dissipation during the whole test, the document only shows  the results of the last two points of measurements (31 and 91 days). It is important to emphasizes that even there were considerable dissipation, there is a bioavailable fraction of the substance that remains in the test and the bio(degradation) was not extent (according to chromatograms and the comparison with the information from control sterile). A paragraph can be added in this sense at the end of the section corresponding to the simulation test on page 19.

Regarding B properties, the conclusion is mainly based on a bioaccumulation study with fish (OECD 305C, version 1981) conducted with a mixture of 3 constituents of EC 401-850-9 (ip-ip, ib-ib, eh-eh).  Despite the methodology followed in this study deviate from the current OECD 305, the study can be considered as valid. The BCF calculated at steady state (and after lipid normalisation) are higher than 2000, thus these constituents meet the B criteria.

Ecotoxicity studies with EC 401-850-9 are available for fish, daphnia and algae. The long-term study with daphnia presents the highest toxic effects between the organisms.  The LOEC and NOEC calculated are less than 0.01 mg/L. Therefore, the substance EC 401-850-9 and ip-ip constituents (constituents likely predominant in the media) meet the toxicity criterion (T) (NOEC below 0.01 mg/L) in accordance with Annex XIII.

Other minor comments:

Page 19: We agree that the study can be considered in the assessment of persistence, however some aspects of the methodology did not follow the methodology of OECD 309. We suggest to change the phrase or remove the phrase without restriction.

Page 18: please add some precisions on the determination of k and the DT50 (values used and the equation of SFO model)

Page 20: It is not clear why you did consider the parent +metabolite in the calculation of half-life. Could you clarify this?

Page 6: As the half-life calculated was not estimated in a direct manner it would be more accurate to change the conclusion as follows:  … exhibiting a half-life of more than 60 days instead of 200 days.
	This responds also to the comment submitted by France on 18 October 2021 (comment #5589)

The Belgian CA wants to thank the French CA for their support to identify EC 401-850-9 as a PBT substance and for the specific comments that can help to improve the argumentation in the annex XV dossier for the substance.

BE CA proposes to identify EC 401-850-9 as an SVHC based on art. 57(d), not 57(f).

We can only repeat that the comparison of the results from the viable and the sterile experiments clearly demonstrate that the disappearance of the test item is hardly caused by biodegradation but nearly completely by dissipation. Unfortunately, we see no elements to decide which specific processes (adsorption to glassware, volatilisation, NER formation …) are the (main) driver for this dissipation. We also see no added value in examining these dissipation processes any further in the framework of the assessment of the persistence of the test item.

In order to be able to calculate a half-life we indeed assumed that dissipation quickly takes place in the beginning of the experiment and that only 32% of the test item is actually bioavailable from the start of the experiment. We did so for the following reason. Based on this assumption we come to a half-life value that is less conservative but is still meeting the vP criterion. If we assume a gradually declining test item concentration (e.g. following a first order kinetic model) the calculated half-life will always be greater. So this approach is in our view a robust method to prove that the test item meets the vP criterion, irrespective how the measured data are interpreted. Further, if one considers figure 4 on page 45 of the report, one can see that dissipation is already substantial in the first few days of the experiments.

Regarding the chromatograms we note that in the report only a part of the chromatograms is represented, i.e. the part covering acquisition time 7 to 8 minutes. In these chromatograms the pattern of the test item resembles quite well the pattern of the internal standard and no indications are seen that degradation products are formed.

As mentioned above figure 4 indicates that dissipation is substantial from the beginning on. This observation could suggest that dissipation is mainly caused by a relatively fast process. (adsorption to glassware, NER formation ?)
See further our reply above.

The distinction between dissipation and degradation can only be made when information on the sterile experiments is available, i.e. only @ days 31 and 91.
We see no other relevant way to describe dissipation.

We can add a sentence stressing again that even after 91 days parent compound is still bioavailable and that total absence of degradation products is thus not caused by non-availability of the test item.

That is also our conclusion.

That is also our conclusion.

That is a correct assessment.
We’ll change without  with

9.38% degradation corresponds with 90.62% of the parent compound remaining after 31 days. Applying the SFO formula At = Ao.e-k.t and resolving for k (k = ln Ao - ln At / t) leads to k = 0.00318 d-1.

Because molecular weights of parent compound and metabolite differ, one must express concentrations in mol/L. Assuming that parent compound and metabolite dissipate at the same rate, one can calculate a half-life based on the ratio of the concentration of the parent that remains after 36 days (9.29 nmol/L) and the concentration that was in theory present at the start (9.29 + 1.22 = 10.51 nmol/L (and not 10.55). This approach is allowed as no other metabolites are detected.

We still think our argumentation is sufficiently solid to claim that the half-life is greater than 200 days.	

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	
5560
2021/10/08	Company,
Belgium		
See part I for our response.	
		See the corresponding embedded attachment in table 1 of Part I: 5560_Comments to ECHA on Annex XV Report for EC 401-850-9.docx