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

Substance name: Benzene-1,2,4-tricarboxylic acid 1,2-anhydride (trimellitic anhydride)
CAS number: 552-30-7
EC number: 209-008-0

The substance is proposed to be identified as meeting the following SVHC criteria set out in Article 57 of the REACH Regulation: Equivalent level of concern having probable serious effects to human health (Article 57 f)

Disclaimer: Comments provided during public 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. RCOM has not been agreed by the Member State Committee nor has the document been modified as result of the MSC discussions.

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	
4636
2016/10/19	Company,
Germany	In chapter 9 of the Annex XV Dossier of Benzene-1,2,4-tricarboxylic acid 1,2-anhydride (TMA) are described the following uses: manufacture of polymers, esters, and epoxyresins and paints. A professional use of TMA is possible for laboratory use. Consumer uses are not expected because in principle any polymer manufactured using TMA will not contain any TMA in the finalized article.
If TMA is used for manufacture of polymers it is a use outside the scope of authorization (Titel VII) of REACH according to Article 2, (8).
In Article 3, (15) an intermediate is defined as a substance that is manufactured for and consumed in or used for chemical processing in order to be transformed into another substance. The substance TMA is transformed into another substance, the polymer, during the chemical synthesis.
If a substance is used within scientific R&D this use is exempted from authorization by Article 56, (3). Q&As 585 and 1030 provide further guidance on the scope of the exemption.

Article 2, (8):
“8. On-site isolated intermediates and transported isolated intermediates shall be exempted from:
(a) Chapter 1 of Title II, with the exception of Articles 8 and 9; and
(b) Title VII.”

Article 3, (15)
“15. intermediate: means a substance that is manufactured for and consumed in or used for chemical processing in order to be transformed into another substance (hereinafter referred to as synthesis):”

Article 6, (2)
“2. For monomers that are used as on-site isolated intermediates or transported isolated intermediates, Articles 17 and 18 shall not apply.”

Article 56, (3)
“3. Paragraphs 1 and 2 shall not apply to the use of substances in scientific research and development. Annex XIV shall specify if paragraphs 1 and 2 apply to product and process orientated research and development as well as the maximum quantity exempted.”

FAQ 585

FAQ 1030	Thank you for your comment. The justification for SVHC is based on intrinsic properties of the substance, not on use, exposure and risk. Comments regarding use, exposure, alternatives and risks may, where relevant, be considered at later stages of the risk management process of the substance.	
		-		
4637
2016/10/19	Company,
Germany	In chapter 9 of the Annex XV Dossier of Benzene-1,2,4-tricarboxylic acid 1,2-anhydride (TMA) are described the following uses: manufacture of polymers, esters, and epoxyresins and paints. A professional use of TMA is possible for laboratory use. Consumer uses are not expected because in principle any polymer manufactured using TMA will not contain any TMA in the finalized article.
If TMA is used for manufacture of polymers it is a use outside the scope of authorization (Titel VII) of REACH according to Article 2, (8).
In Article 3, (15) an intermediate is defined as a substance that is manufactured for and consumed in or used for chemical processing in order to be transformed into another substance. The substance TMA is transformed into another substance, the polymer, during the chemical synthesis.
If a substance is used within scientific R&D this use is exempted from authorization by Article 56, (3). Q&As 585 and 1030 provide further guidance on the scope of the exemption.

Article 2, (8):
“8. On-site isolated intermediates and transported isolated intermediates shall be exempted from:
(a) Chapter 1 of Title II, with the exception of Articles 8 and 9; and
(b) Title VII.”

Article 3, (15)
“15. intermediate: means a substance that is manufactured for and consumed in or used for chemical processing in order to be transformed into another substance (hereinafter referred to as synthesis):”

Article 6, (2)
“2. For monomers that are used as on-site isolated intermediates or transported isolated intermediates, Articles 17 and 18 shall not apply.”

Article 56, (3)
“3. Paragraphs 1 and 2 shall not apply to the use of substances in scientific research and development. Annex XIV shall specify if paragraphs 1 and 2 apply to product and process orientated research and development as well as the maximum quantity exempted.”

FAQ 585

FAQ 1030	Thank you for your comment. The justification for SVHC is based on intrinsic properties of the substance, not on use, exposure and risk. Comments regarding use, exposure, alternatives and risks may, where relevant, be considered at later stages of the risk management process of the substance.	
		-		
4718
2016/10/20	The European Chemical Industry Council (Cefic),
Industry or trade association,
Belgium	-	Thank you for the information. The information will be taken up in the supporting document.	
		Attachment: 4718_Cefic - SRM-PPRM Statement.pdf

4771
2016/10/21	United Kingdom,
Member State	Uncertainties in the risk estimates calculated by the Dutch Health Council
The dossier submitter suggests that an OEL of 0.04 mg/m3 may not be sufficiently protective of health based on risk estimates calculated by the Dutch Health Council. In our opinion the level of uncertainty that is associated with these risk estimates is too high to permit their use for regulatory risk management activities. In the study that was used to derive the exposure-response relationship, the exposure ranges for groups that included individuals with occupational asthma are very broad. There are considerable overlaps between the exposure ranges identified for the five exposure categories (for example the exposure values for exposure category 1 are entirely encompassed by the exposure values for exposure category 2). If the exposures leading to cases of sensitisation were at the upper end of each exposure range, a very different exposure-response relationship would be predicted. We also question whether it is appropriate to use linear extrapolation to calculate risks at low doses. It would be informative to include the confidence intervals around these risk estimates.	Thank you for your comment. The support document exactly states that: “In the case of respiratory sensitizers, it is difficult to establish what the threshold dose is for the induction and elicitation phases of response. Firstly, there are currently no accepted or validated animal tests available to test for respiratory sensitisation for classification purposes, nor do the studies conclusively determine a respiratory sensitizing effect. Hence, it is not possible to derive a dose-response relationship. Therefore, the identification of respiratory sensitizers relies on human data, mainly from epidemiological studies or case reports. The data in those studies often lack sufficiently detailed exposure information to derive a no effect level. The toxicological endpoint further makes the risk assessment difficult. The sensitizing (induction) dose may vary significantly between individuals. Although it is plausible that a threshold exists below which no allergic sensitization may be expected, in most cases the threshold level will be too low to discern using the techniques presently available. It is commonly believed that the elicitation threshold lies even lower than the sensitization threshold and may not even be identified due to technical restrictions (e.g. response already occurs at or below level of detection). Consequently, the derivation of a safe concentration is not routinely possible and any figure derived would be associated with large uncertainty.”  (page 29 of SD)

The reference values derived by the Dutch Health Council have been added to the support document to give insight on where a possible reference value may be, where the Dutch Health Council too stresses the uncertainties. It shows that the values they derived are well below the OEL (even before the linear extrapolation), indicating that the OEL may not be sufficiently protective for respiratory sensitisation. 

The BMD10% for the underlying data was rounded 18 ug/m3. The BMDL10% (95% C.I.) was 8 ug/m3. No upper limit of the BMD was provided. 	
4788
2016/10/21	Health & Environment Alliance (HEAL),
International NGO,
Belgium	HEAL supports the adoption of TMA as a substance of very high concern, particularly as there might be irreversible damage to lung functions, before it is appreciated that there is a health problem.	Thank you for your support	

Specific comments on the justification
Number / Date	Submitted by (name, submitter type, country)	Comment	Responses	
4623
2016/10/17	ANSES,
Academic institution,
France	ANSES considers that TMA gives indications of an equivalent level of concern (ELoC) according to article 57(f) of REACH.

Severity and type of possible health effects:

Available human data demonstrate that TMA is causing serious respiratory health effects.
- Workers exposed to TMA, followed for 3-years, in a prospective study showed that 11% responded positive to IgE at exposure range 2 to 130 µg/m3 ;
- In a cross-sectional study of 196 workers in manufacturing industry, around 60% of the subjects presented non-specific irritations and 15% more specific manifestations (e.g. rhinitis asthma), only 25% were asymptomatic;
- Some clinical cases of severe pulmonary disease-anaemia syndrome due to TMA were reported in the literature;
- According to an industrial survey, the prevalence of occupational asthma was 2-11% for TMA exposure (published in 1999);
- Respiratory sensitisation can occurs at low levels below French occupational exposure limit.

The respiratory sensitisation potential of TMA is further supported by available animal data.
TMA is classified in CLP regulation as: STOT SE 3: Eye Dam. 1; Resp. Sens. 1 and Skin Sens. 1.

Potency:
Regards to potency, no subcategorisation is proposed but the classification was harmonised under dir. 67/548/EEC before CLP regulation and subcategorisation criteria. Moreover, no sub-categorisation is notified in the inventory.

Two other acid anhydrides, HHPA or MHHPA, were identified SVHC according to Article 57(f). According to the report, TMA respiratory sensitisation occurs in the same range of exposure level (10-50 µg/m3) for HHPA/MHHPA and 10-40 µg/m3 for TMA suggesting is a potent respiratory sensitiser (See Table 12, pp 42).

Irreversibility and delay of health effects:
Regards to the irreversibility of the effects, although some improvement has been observed after moving sensitized workers to low-exposure jobs, no follow-up study is available to address the irreversibility or delay of the damage to lung. Nevertheless, it is generally accepted that induction phase of respiratory sensitisation is irreversible and that elicitation phase of respiratory sensitisation can lead to irreversible lung dysfunction.

Other factors
- Societal concern
Although respiratory sensitisation has been observed below occupational exposure limits, no case of respiratory health effects has been reported with TMA since 2000. The dossier submitter suggests that this may be explained by nowadays RMM and PPEs.

- Concentration-based risk assessment
From the human data available, it is not possible to derive a “safe” no effect level for sensitisation.

Quality of life affected.
They are no specific data on the affected quality of life but sensitised workers were affected to new tasks.

Conclusion
Altogether, TMA has been shown to cause serious respiratory health effects in relation to a substantial incidence of sensitized workers as well as to the severity of the effects reported in some case reports. Respiratory sensitization is considered an irreversible condition. On this basis and by analogy with previous cases with similar profile (HHPA and MHHPA), ANSES considers that it gives indications of an equivalent level of concern (ELoC) according to article 57(f) of REACH.	Thank you for your support	
		-		
4624
2016/10/17	Germany,
Member State	The German CA supports the identification of TMA as substance of very high concern.	Thank you for your support	
4692
2016/10/20	Belgium,
Member State	The following items are present in the Annex XV dossiers to substantiate that the substances fulfill the art. 57(f) criteria:
- Serious and permanent organ dysfunction is possible (can cause asthma and  allergic rhinitis/conjunctivitis).
- The health effects are irreversible.
- The consequences for society are high.
- It is difficult to perform a concentration-based risk assessment.
Therefore, Belgium supports the identification of the substance as SVHCs based on art. 57(f) of the REACH regulation.	Thank you for your support	
4715
2016/10/20	ChemSec,
International NGO,
Sweden	ChemSec supports the identification of TMA as a Substance of Very High Concern based on it being a respiratory sensitiser. The evidence presented out in the dossier points at severe and irreversible human health effects following exposure to the substance.	Thank you for your support	
4718
2016/10/20	The European Chemical Industry Council (Cefic),
Industry or trade association,
Belgium	Members of the Cefic sector groups SRM (Solvent Resin Manufacturers) and PPRM (Polyester Powder Resin Manufacturers) use the substance TMA (trimellitic anhydride – CAS number 552-30-7) in quite significant quantities for the production of polyester resins for the paint industry. TMA is being safely used on the different production sites of our members.	Thank you for the information. The information will be taken up in the supporting document.	
		See the embedded attachment in part I table: 4718_Cefic - SRM-PPRM Statement.pdf		
4753
2016/10/21	Company,
France	No comment on this part	Thank you for your information.	
				
4758
2016/10/21	Norway,
Member State	The Norwegian CA supports that benzene-1,2,4-tricarboxylic acid 1,2-anhydride fulfills the criteria in Article 57 (f) and should be identified as a SVHC. We agree to the following: The potency of benzene-1,2,4-tricarboxylic acid 1,2-anhydride is in the same range as the cyclic anhydrides HHPA and MHHPA already being identified as SVHC and included in the Candidate List. Benzene-1,2,4-tricarboxylic acid 1,2-anhydride causes serious and permanent impairment of lung function in humans, and it is not possible to derive a "safe" no effect level below which sensitization is prevented. Several case studies, case reports and epidemiological studies demonstrate that benzene-1,2,4-tricarboxylic acid 1,2-anhydride gives rise to an equivalent level of concern to those substances listed in Article 57 (a) to (e).	Thank you for your support	
4765
2016/10/21	The Polyester Monomers Consortium,
Other contributor,
United Kingdom	The polyester Monomers Consortium disagrees with the proposal to classify TMA as an SVHC.	Thank you for your information.	
4771
2016/10/21	United Kingdom,
Member State	SVHC property - Equivalent level of concern having probable serious effects to human health (Article 57 f)

Respiratory sensitisers may be identified as SVHC where it can be shown that they are of an equivalent level of concern (ELoC) to CMR substances.  It has been agreed that the ELoC assessment should be made on a case-by-case basis and it should be demonstrated that the impacts caused by these substances on both the health of affected individuals and society as a whole are comparable to the impact of CMRs.

Currently the assessment considers a number of factors to conclude on ELoC:

Type and severity of possible health effects
Irreversibility of health effects
Delay of health effects
Derivation of a safe level of exposure
Quality of life
Societal concern

As all respiratory sensitisers can be said to fulfil all of these factors, it seems that some other criteria should be applied to separate respiratory sensitisers where there is a clear need for additional action owing to ongoing cases of ill health from those which are being effectively managed. Otherwise simply being classified as a respiratory sensitiser is sufficient to be identified as SVHC which does not appear to have been the intent of the legislator. Further consideration of these factors should be made.

Initially it should be shown that there are current real concerns regarding risks and that authorisation is the most appropriate risk management measure to control the identified risks. Consideration should be given to the consequences and proportionality of such an action and whether substitution is possible and/or necessary.

As with the previous cases for ADCA, HHPA & MHHPA, we cannot currently support identification of respiratory sensitisers as SVHC.	The NL-MSCA wishes to point out that the number of factors to conclude on ELoC to CMR substances is followed for TMA specifically. Its strong potency to induce respiratory sensitisation. Case studies have given insight on the severity of TMA related effects and consequences for the workers. Moreover, it has been indicated that current OELs may not be protective for respiratory sensitisation. Therefore, we do not agree that additional criteria would be required.

In the RMOA for TMA it was concluded that identification as SVHC and authorisation would be the most appropriate risk management option. 
	
		-		
4772
2016/10/21	Sweden,
Member State	We agree with the argumentation put forward in the Annex XV dossier and consider TMA to be a substance for which there is scientific evidence of probable serious effects to human health which give rise to an equivalent level of concern to CMR substances (Category 1A or 1B). We believe that TMA should be identified as an SVHC according to REACH article 57(f), mainly based on the following reasons:
- The overall data from humans and animals indicate that TMA can cause serious lung damage. If the exposure is prolonged and no interventions take place it can be reasonably assumed that lung damage may become permanent. In addition, serious but generally reversible reactions may occur.
- Respiratory sensitisation to TMA is a permanent and adverse condition that can have a profound negative impact on a person’s quality of life due to the measures the affected individuals must take in order to eliminate all exposure, for instance not being able to continue working in their chosen profession.	Thank you for your support	
4784
2016/10/21	CHEM Trust,
National NGO,
United Kingdom	CHEM Trust supports the inclusion of TMA in the candidate list based on Article 57 f due to its capability to cause serious and permanent impairment of lung functions as a respiratory sensitiser.	Thank you for your support	
4795
2016/11/01	Finland,
Member State	The Finnish CA supports benzene-1,2,4-tricarboxylic acid 1,2-anhydride (trimellitic anhydride, TMA) to be identified as a SVHC according to  Article 57(f) of REACH Regulation based on its respiratory sensitising properties. For this hazard class, TMA has a harmonised classification Resp Sens 1; H334: “May cause allergy or asthma symptoms or breathing difficulties if inhaled”. The Finnish CA agrees with the equivalent level of concern (ELoC) assessment presented in the Annex XV report. There is scientific evidence of probable serious effects to human health which gives rise to ELoC. Furthermore, TMA has similar properties to two other cyclic anhydrides (HHPA and MHHPA) that have been identified as SVHC according to Article 57(f) of REACH Regulation and placed on the candidate list.

The Finnish CA considers that after inclusion of the substance in the candidate list (for eventual inclusion in the Annex XIV) it can still be further explored which risk management measures would be the most appropriate.
	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	
4624
2016/10/17	Germany,
Member State	p. 37, Table 10: The detailed description of exposure and risks of workers in the Annex XV dossier of the NL CA is acknowledged. However, it remains unclear if any of the reported uses will be subject to authorisation as manufacture of TMA and the use of TMA as an intermediate are exempted from such obligations.
In the Annex XV dossier no information is given about residual amounts of unreacted TMA in the manufactured polymers. In addition, the NL CA states that finalized articles will not contain any TMA. Therefore, it is not clear if the risk of respiratory sensitisation of workers will be reduced by SVHC identification of TMA and an inclusion of TMA in Annex XIV.	Thank you for your comment. If a substance is used for manufacture of a polymer does not automatically indicate that the substance is outside of scope for authorisation. 
Presented information in the registration dossier does not indicate that the uses are exempted from authorisation nor are such claims made. 	
4640
2016/10/20	Company,
United States	We have identified the use of TMA as an epoxy potting compound for reinforcing honeycomb structures.
Additional investigation will be required to determine whether alternatives exist.	Thank you for your comment. 	
4718
2016/10/20	The European Chemical Industry Council (Cefic),
Industry or trade association,
Belgium	-	Thank you for the information. The information will be taken up in the supporting document.	
		See the embedded attachment in part I table: 4718_Cefic - SRM-PPRM Statement.pdf		
4753
2016/10/21	Company,
France	IVA is one of the three Europe-based enamel producers. Enamels are only used by its direct customers: the winding wire industry. The winding wire industry supplies insulated wire for various activities like car industry (starters, alternators, electrical motors), energy, household appliances…

Total European enamel market is estimated at 40 to 45 kT / year.

TMA is one of the monomers used systematically for the manufacture of PEI PolyEster Imides and PAI PolyAmide Imides enamels. These enamels consist basically in a polymer dissolved in solvents. TMA is one of the constituent (monomer) of both PEI and PAI enamels.
PEI and PAI market share is more than 70% of the European enamel market.

For IVA, TMA annual consumption is more than 1000 T.

TMA is supplied in 1000 kg Big Bags BB.

Process is as follows:
1) Storage.
2) Sampling for quality control
3) BB opening and discharge into a cone.
4) Transfer from the discharge cone to a storage silo.
5) Transfer from the storage silo to a hopper.
6) Transfer from hopper to the reaction (synthesis of the polymer): TMA is no more present a this stage  - and then is no more present in the finished product: the enamel

2) and 3) are the only process steps where TMA exposure can occur [for 2) it is very limited].
For all the other steps TMA is transferred in closed circuits (pneumatic transfer using nitrogen), there is no exposure.

Exposure is controlled by Risk Management Measures and validated by exposure monitoring.

Risk Management Measures are the following, applying for steps 2) and 3)

- Personal Protective Equipment PPE: Full face mask including a P3 category dust protection (cartridges A2B2P3)  – disposable overall (used one shift maximum), nitrile gloves
- Procedure on PPE wearing, storing, cleaning disposing. Training on this procedure. Control by internal audits.
- Periodic workshop cleaning (where the TMA Big Bags are discharged) using a HEPA vacuum cleaner
- Local Exhaust Ventilation at the TMA Big Bag discharge cone linked to Dust filters; periodic control of Local Exhaust Ventilation efficiency
- All wastes (PPE, filters etc…) contaminated with TMA isolated, identified and sent to an external approved waste disposal company for incineration

Exposure monitoring (Occupational Exposure Limit considered: 0.04 mg/m3):

Exposure monitoring are performed by a government approved Laboratory.
- 6 exposure monitoring have been performed from 2007.
Considering the Full face mask with a protection factor at 30 (this factor is considered for the regulatory exposure measurements in France), all exposure results are under the Occupational Exposure Limit.

Conclusion:
TMA exposure risk is controlled by the applied Risk Management Measures and is safely used in IVA.
TMA, as a monomer, is no more present in the enamel, then obviously no more present in the downstream industrial sectors and in the various consumer equipments which contain insulated wires.	Thank you for the information. The information will be taken up in the confidential part of the supporting document.
	
		-		
4771
2016/10/21	United Kingdom,
Member State	Uses - Three uses are listed in section 8.1. These are use in the manufacture of polymers, in the manufacture of esters and use as a laboratory chemical. The first two of these would appear to be the manufacture of other substances and so qualify as intermediate uses. The last use may fall under the Scientific Research & Development definition [Article 3(23)].  Therefore the listed uses may not be in scope of authorisation.
Alternatives – TMA is used to make other substances and this is dependent on its structure and reactivity. Alternatives are likely to be of similar activity and hazard.
Risk – the literature clearly shows that historically there were risks associated with the use of TMA in the workplace. The Health and Occupation Research Network (THOR) collects and disseminates data on work related ill-health for the UK and there have been no cases of occupational asthma linked to TMA reported between 2005 and 2014 (chest physicians and occupational physicians) and between 2006 and 2015 (general practitioners). The dossier submitter also was unable to find any reports in the literature more recent than 2006. This would suggest that following classification of TMA as a respiratory sensitiser appropriate risk management measures have been put in place in the workplace.	Thank you for the information. The information will be taken up in the supporting document.