ANNEX 4 TO FINAL REPORT

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1 European Commission, Joint Research Centre Institute for Health and Consumer Protection Ispra/Italy Examination and assessment of consequences for industry, consumers, human health and the environment of possible options for changing the REACH requirements for nanomaterials REFERENCE: IHCP/2011/I/05/27/OC ANNEX 4 TO FINAL REPORT BASELINE SCENARIO AND CORRELATING COSTS CASE STUDIES 09 January 2013 BiPRO Beratungsgesellschaft für integrierte Problemlösungen in cooperation with

2 ii Content 1 Overview on content of Annex 4 and brief summary of applied cost assessment - Baseline scenario applied to nano TiO 2, nano ZnO and nano diamond Case study for nano titanium dioxide (TiO2)... 6 Option 1: Explicitly require registrants to describe the scope of the registration dossier (substance identification and physico-chemical properties)...6 Option 2: Explicitly require registrants to provide more detailed characterisation of nanomaterials/nanoforms (substance identification and physico-chemical properties)...7 Option 3: Require that nanoforms are explicitly addressed in the endpoint sections (substance identification and physico-chemical properties)...8 Option 4: Require detailed description of the test material/sample and sample preparation (substance identification and physico-chemical properties) Option 5: Require scientific justifications for grouping/read-across/qsar and other nontesting approaches for different forms (substance identification and physicochemical properties) Option 7: Require that nanoforms are explicitly addressed in the endpoint sections (human health hazards, environmental fate, environmental hazards) Option 8: Require detailed description of the test material/sample and sample preparation (human health hazards, environmental fate, environmental hazards) Option 9: Require scientific justifications for grouping/read-across/qsar and other nontesting approaches for different forms (human health hazards, environmental fate, environmental hazards) Option 10: Require considerations of most appropriate/relevant metric with preferable presentation in several metrics (human health hazards, environmental fate, environmental hazards) Option 14: Require that bioaccumulation is addressed specifically for the nanoform (environmental fate and hazards) Option 15: Specify that adsorption/desorption behaviour of nanomaterials should not be assessed based on K d values derived from K oc and K ow (environmental fate and hazards) Option 20: Require identification of uses and exposure assessment of the nanoform (exposure assessment and risk characterisation) Case study for nano zinc oxide (ZnO) Option 1: Explicitly require registrants to describe the scope of the registration dossier (substance identification and physico-chemical properties) Option 2: Explicitly require registrants to provide more detailed characterisation of nanomaterials/nanoforms (substance identification and physico-chemical properties) Option 3: Require that nanoforms are explicitly addressed in the endpoint sections (substance identification and physico-chemical properties)... 20

3 iii Option 5: Require scientific justifications for grouping/read-across/qsar and other nontesting approaches for different forms (substance identification and physicochemical properties) Option 7: Require that nanoforms are explicitly addressed in the endpoint sections (human health hazards, environmental fate, environmental hazards) Option 8: Require detailed description of the test material/sample and sample preparation (human health hazards, environmental fate, environmental hazards) Option 9: Require scientific justifications for grouping/read-across/qsar and other nontesting approaches for different forms (human health hazards, environmental fate, environmental hazards) Option 10: Require considerations of most appropriate/relevant metric with preferable presentation in several metrics (human health hazards, environmental fate, environmental hazards) Option 14: Require that bioaccumulation is addressed specifically for the nanoform (environmental fate and hazards) 27 Option 15: Specify that adsorption/desorption behaviour of nanomaterials should not be assessed based on K d values derived from K oc and K ow (environmental fate and hazards) Option 20: Require identification of uses and exposure assessment of the nanoform (exposure assessment and risk characterisation) Case study for nanodiamond Option 1: Explicitly require registrants to describe the scope of the registration dossier (substance identification and physico-chemical properties) Option 2: Explicitly require registrants to provide more detailed characterization of nanomaterials/nanoforms (substance identification and physico-chemical properties) Option 3: Require that nanoforms are explicitly addressed in the endpoint sections (substance identification and physico-chemical properties) Option 4: Require detailed description of the test material/sample and sample preparation (substance identification and physico-chemical properties) Option 5: Require scientific justifications for grouping/read-across/qsar and other nontesting approaches for different forms (substance identification and physicochemical properties) Option 7: Require that nanoforms are explicitly addressed in the endpoint sections (human health hazards, environmental fate, environmental hazards) Option 8: Require detailed description of the test material/sample and sample preparation (human health hazards, environmental fate, environmental hazards) Option 9: Require scientific justifications for grouping/read-across/qsar and other nontesting approaches for different forms Option 10: Require considerations of most appropriate /relevant metric with preferable presentation in several metrics Option 14: Require that bioaccumulation is addressed specifically for the nanoform... 37

4 iv Option 15: Specify that adsorption/desorption behaviour of nanomaterials should not be assessed based on K d values derived from K oc and K ow Option 20: Require identification of uses and exposure assessment of the nanoform Extrapolation of compliance costs to industry Impacts on Authorities... 44

5 5 1 Overview on content of Annex 4 and brief summary of applied cost assessment - Baseline scenario applied to nano TiO 2, nano ZnO and nano diamond This Annex describes presentation and discussion of costs of options included in the baseline (compliance costs) 3 case studies extrapolated compliance costs to industry impacts on Authorities. The aspect of size being considered as characteriser or identifier has a great impact on the registration obligation and consequently on the testing costs. Considering size as a characteriser would result in elaboration of an updated lead dossier, in which information on one (or several) nanoforms would be included. As already explained in the main report the information requirements for the lead dossier would be triggered by the allocated tonnages of the bulk form and the nanoform. On the contrary, considering size as an identifier would lead to elaboration of a separate lead dossier for nanomaterials. Especially with regard to surface treated nanomaterials no exact advice/guidance is available how to register these nanomaterials. This aspect has already been discussed extensively in the main report and will not be repeated at this stage. Based on these uncertainties the project team has elaborated two sub-options for each identified option by assessing the costs for an possible dossier update and costs for elaboration of a separate lead dossier for nanomaterials. The exact provisions and information requirements have already been discussed in detail in Annex 1 to this report and will therefore not be repeated again. With regard to compliance costs for Competent Authorities, it should be mentioned that these costs are to be considered separately from the baseline scenario. It has proved as not possible to assess costs for Competent Authorities after a possible implementation of specific options. Instead, possible costs have been calculated on the basis of costs which have been published prior to the implementation of the REACH Regulation

6 6 2 Case study for nano titanium dioxide (TiO2) The current lead dossier for TiO 2 includes information on various forms of this substance: the bulk form of TiO 2, nano TiO 2, silanised TiO 2 (e.g. TiO 2 805) and alumina/silica coated sub-pigmentary TiO 2. Due to reasons of simplification the project team will focus on nano TiO 2 and its silanised form for the further cost assessment. Depending on synthesis methods or manufacturing processes, nano TiO 2 can crystallize in different morphologies or shapes. Not only the shape but also the surface of nano TiO 2 can be functionalized according to the subsequent intended application, e.g. by treating the nanomaterial with a silane. As already indicated above, surface treated TiO 2 (e.g. silanised TiO 2 ) has partly been assessed in the scope of the registration process. Option 1: Explicitly require registrants to describe the scope of the registration dossier (substance identification and physico-chemical properties) Although extensive information on (eco)toxicological behaviour of nano TiO 2 and probably surface treated/functionalised nano TiO 2 has been submitted via the lead dossier, the presence/absence of nano TiO 2 has not explicitly been considered in the substance specification of the lead dossier. In the case of a subsequent consideration of nano TiO 2 and its surface treated derivative(s) in the already submitted lead dossier, an update of the lead dossier would be required in which the aspect of nano TiO 2 and its forms is considered appropriately. Against this background subsequent discussions within the SIEF would be required during which the aforementioned varieties of nano TiO 2 would be taken into account for an update/re-defining of the current Substance Identification. Within this process it would/could be decided whether any shape of nano TiO 2 could be covered by the lead dossier (as long as there is information available that shape of nano TiO 2 has no influence on testing results) or whether specific shapes should explicitly be excluded (if information is available that specific shapes, such as e.g. tubular forms, might pose additional hazards). The current lead dossier includes already information on silanised TiO 2, which the project team assumes to be a nanomaterial. This decision of the TiO 2 SIEF would be based on data from literature and indications whether discrepancies in (eco)toxicological and physico-chemical properties among the various forms of TiO 2 have been recognised. According to Article 5 of Commission Regulation EC No 340/2008 (on the fees and charges payable to the European Chemicals Agency pursuant to REACH Regulation (EC) No 1907/2006) no fees are charged by the ECHA in the case of updating dossiers which affects the change in the composition of the substance. Based on the provided information from the steering group that the TDIC held 10 meetings in order to agree on the substance identity for TiO 2 the contractor infers that another 10 meetings might be required to agree on the substance identity for nano TiO 2 and its nanoforms. These proposed 10 meetings would lead to additional costs of 9,000.

7 7 Compliance costs: 9,000 In the course of elaborating a separate lead dossier for nano TiO 2, the scope of the lead dossier would be discussed within the SIEF. Since the definition of the SID in the pre-sief is a standard procedure in the course of elaboration of a lead dossier, it can be inferred that the same costs would occur as in the abovementioned case (size as characteriser). Compliance costs: 9,000 Option 2: Explicitly require registrants to provide more detailed characterisation of nanomaterials/nanoforms (substance identification and physico-chemical properties) In the course of the preparation of the RIP-oN2 reports a broad range of methods have been identified and suggested which are suitable for determining the particle size distribution of nanomaterials. Depending on the state of the nanomaterial (powder, suspension, aerosol) the following methods have been identified and proposed for an in-depth analysis of the granulometry of nanomaterials: for powders: transmission electron microscopy (TEM), scanning electron microscopy (SEM), scanning mobility particle sizer (SMPS), Field Flow Fractionation (FFF), Laser Diffraction Particle Size Analyser, Photon Correlation Spectroscopy (PCS) dispersion of nanomaterials: Dynamic Light Scattering (DLS), PCS, nanoparticle tracking analysis (NTA), Analytical Ultracentrifuge (AUC), Hydrodynamic Fractionation (HDF), cryo- TEM aerosols of nanomaterials: differential mobility analyzer, scanning mobility particle sizer (SMPS), electrical low pressure impactor (ELPI), Optical Particle Counter (OPC), Aerosol Particle Sizer (APS), Fast Mobility Particle Sizer (FMPS) In the case of an update, the current lead dossier would have to be supplemented by additional information on particle size distributions of the two forms of TiO 2 (nano TiO 2, silanised nano TiO 2 ). Determining the particle size distribution via TEM or Laser Diffraction Particle Size Analysis would lead to testing costs between 2,000 and 4,000 (for TEM) per tested substance. The same costs would occur for the functionalised nano TiO 2 (the project team assumes that silanised nano TiO 2 is a nanomaterial which is stable at solid state and do not require solution/dispersion for stabilization). The completion of the correlating IUCLID endpoints would result in additional costs of 1,000 (equivalent to the efforts for 1 working day per tested substance). Shape and surface area are two further parameters which strongly depend on the production process of the nanomaterial. It is therefore suggested that this information is submitted individually by every joint submission member. Based on the findings of the RIP-oN2 report, the shape of nanomaterials can be determined via the transmission electron microscopy (TEM). On the other hand the Brunauer, Emmet and Teller (BET) method is the most appropriate method for conducting

8 8 the surface area of nanomaterials. Determination of the surface area would result in testing costs of 2,000 and 3,000 per tested substance and it is assumed that the completion of the correlating IUCLID endpoint (IUCLID endpoint 1.4 "Analytical information") would be associated with efforts of 1 working day (1,000 per tested substance), at the maximum. The update of the current lead dossier for TiO 2 by submitting information on the described methods would lead to additional costs between 12,000 and 18,000 for the characterisation of nano TiO 2 and silanised nano TiO 2. If the wording of the Annexes of the REACH Regulation is adapted in a way that the aforementioned information is mandatory for every joint submission member, these costs would be expected for every registrant. Supplementary information which could be submitted for further characterisation by the (individual) registrant could be crystalline structure geometry incl. aspect ratio hydrophobicity surface charge photo(catalytic) properties Submitting additional information would be decided on a case by case basis, whether the listed methods are essential for an unambiguous characterisation of the nanomaterial. Compliance costs: 12,000 18,000 The cost structure, as outlined above, would also occur in the case of elaboration of a separate lead dossier for nano TiO 2 which could also cover further nanoforms, e.g. silanised nano TiO 2. However, based on results of a questionnaire which was sent to the TDIC (Titanium Dioxide Industry Consortium; see Annex 5), no elaboration of a separate lead dossier for nano TiO 2 is envisaged. Compliance costs: 12,000 18,000 Option 3: Require that nanoforms are explicitly addressed in the endpoint sections (substance identification and physico-chemical properties) In the course of a brief screening of physico-chemical properties which are publicly available via ECHA s website for registered substances, 19 IUCLID endpoints have been identified which were submitted in order to fulfill the information requirements for this compartment. The outcome of this screening is that is not clear to which form of TiO 2 (bulk/nano/surface treated nano) analytical data were submitted. In case of implementing Option 3 in the REACH Regulation, additional endpoint study records would be required in order to fulfill the information requirements for the nanomaterial. In the context of nano TiO 2 and silanised nano TiO 2 additional 38 endpoint study

9 9 records would be required in order to supplement information for 19 endpoints by subsequently performed testing results, waiving statements, read-across approach or (Q)SAR, if applicable. Given the assumption that additional 4 physico-chemical tests would be required in order to characterise the nanomaterials adequately, 7 new IUCLID endpoint study records would be prepared and completed. Information requirements for the remaining 31 endpoint study records would be fulfilled via waiving, read-across, grouping or (Q)SAR, where scientifically justifiable. The project team assumes that the following additional tests would be required in order to characterise nano TiO 2 and silanised nano TiO 2 adequately: SEM micrograph (Scanning electron microscopy; IUCLID point 4.1 "Appearance/physical state/colour"; ; per tested substance) Density (IUCLID point 4.4 "Density"; ; per tested substance) Granulometry (IUCLID endpoint 4.5 "Particle size distribution (Granulometry)"; 2,000 4,000 ; per tested substance) Water solubility (IUCLID endpoint 4.8 "Water solubility"; 4,500 5,500 ; per tested substance) Referring to the outlined testing strategy, performing of these tests would lead to additional costs between 7,300 and 10,830 per tested substance (14,600 21,660 for nano TiO 2 and silanised nano TiO 2 ). Monitoring of tests and completion of the corresponding IUCLID endpoints would lead to additional costs of 4,000 (equivalent to the efforts of four working days per tested substance; 8,000 for tested nano TiO 2 and silanised nano TiO 2 ). Completion of the remaining 31 endpoint study records (via waiving, read-across or (Q)SAR) is estimated to lead to additional costs of 4,000 per tested substance (equivalent to the efforts of four working days) and 8,000 for two tested substances, respectively. Practical implementation of requirements of Option 3 would result in final costs of 30,600 and 37,660. Compliance costs: 30,600 37,660 In a separate lead dossier for nano TiO 2 also information on physico-chemical properties of further nanoforms, such as silanised nano TiO 2, could be included. Since the elaborated option is applicable to substances which are placed on the market in a tonnage band of more than one tone per year the calculated costs, as outlined above, would also occur in the process of the elaboration of a separate lead dossier for nano TiO 2. Compliance costs: 30,600 37,660

10 10 Option 4: Require detailed description of the test material/sample and sample preparation (substance identification and physico-chemical properties) The lead dossier contains information on physico-chemical properties which mainly relates to the bulk form of TiO 2. Physical properties of nano TiO 2, which differ from the properties of the bulk form of TiO 2 - e.g. density of surface treated TiO 2 (only applicable if there is no corresponding surface treated bulk form of TiO 2 available), water solubility (due to discussions whether insolubility in water of substances is also applicable to nanomaterials), granulometry - would have to be taken into account separately in the dossier. For instance, the current lead dossier lists testing results to 8 physico-chemical endpoints. The update of the lead dossier would require additional information of the two nanoforms of TiO 2 for the 8 IUCLID endpoints in the IUCLID section 4 "Physical and chemical properties" if it is regarded that there are differences in the properties between the various forms. Since the project team has no detailed information with respect to the physico-chemical properties of nano TiO 2 and the surface treated derivative, no suggestions can at this moment be proposed whether new tests would have to be carried out or whether the determined parameters are applicable to all forms of TiO 2. It is nevertheless regarded that the detailed description on test material and sample preparation would lead to additional efforts of 1,000 (equivalent to the efforts of 1 working day), at the maximum. Compliance costs: 1,000 In the course of the preparation of a lead dossier for nano TiO 2, a prior in-depth characterisation of the tested nanomaterials would have to be carried out by taking into account the aforementioned parameters. Since prior characterisation of the testing material/testing sample and the sample preparation is already a standard procedure during the performing of tests, it can be inferred that the required efforts would result in the same costs (1,000 - equivalent to the efforts of 1 working day) as for the case of updating the lead dossier. Compliance costs: 1,000 Option 5: Require scientific justifications for grouping/read-across/qsar and other nontesting approaches for different forms (substance identification and physico-chemical properties) With regard to physico-chemical properties of nano TiO 2 an in-depth evaluation is to be performed whether the submitted data gathered in the course of the preparation of the lead dossier are applicable to nano TiO 2 and its surface treated form. Physical properties, such as melting point, density or water solubility indicated in the lead dossier would have to be re-evaluated for their applicability to all forms (e.g. also for surface treated) and shapes of nano TiO 2 via a read-across approach.

11 11 These considerations would have to be done in both cases update of the lead dossier (in case of considering particle size as characteriser) or elaboration of new lead dossier for nano TiO 2 (in case of considering particle size as identifier). It is assumed by the project team that a (re-)evaluation of existing data and a probable literature research would lead to efforts of 2,000 (equivalent to the efforts of two working days). Compliance costs: 2,000 Option 7: Require that nanoforms are explicitly addressed in the endpoint sections (human health hazards, environmental fate, environmental hazards) Given that particle size as considered as a characteriser, the current lead dossier of TiO 2 would be subjected to an update in which the various nanoforms of TiO 2 would be addressed separately in the endpoint study records, if applicable. The current lead dossier for TiO 2 includes information on various forms of this substance: the bulk form of TiO 2, nano TiO 2, silanised TiO 2 (e.g. TiO 2 805) and alumina/silica coated sub-pigmentary TiO 2. Due to reasons of simplification the project team will focus only on nano TiO 2 and its silanised form for the further cost assessment. Based on these introduced premises every endpoint in the dossier would have to be supplemented by up to two additional entries that would cover the various nano forms of TiO 2. According to the publicly available information on the lead dossier for TiO 2, which are provided by ECHA via its website for registered substances, 40 IUCLID endpoints (inclusive 3 endpoints, covering PNEC and DN(M)EL values) have been created in which the information of at least two different nanoforms of TiO 2 is included with regard its environmental fate and pathway and (eco)toxicological properties. Following the aforementioned argumentation, the current lead dossier would have to be supplemented with up to 80 additional entries, which would include amongst others - waiving statements, testing results, read-across, grouping approaches or supporting monitoring data. Given the assumption that the current lead dossier would be supplemented by up to 77 testing results (incl. (Q)SAR) or by up to 77 waiving statements, read-across or grouping approaches, the required efforts would lead to additional efforts between 38,500 (equivalent to 38.5 working days, required for entering testing data) and 19,250 (equivalent to working days, required for completion of IUCLID endpoints with either waiving statements, data from read-across or grouping). Compliance costs: 19,250 38,500 A lead dossier for nano TiO 2 would have to be elaborated, in which separate information on environmental fate and behaviour and (eco)toxicity for nano TiO 2 and its silanised derivative could be included.the range of efforts for fulfilling information requirements of Option 7 would be defined by the tonnage bands and the resulting information requirements of the Annexes. Based on the tonnage bands a cost structure as follows can be outlined (in this context it should be noted that only tests which are listed in the Annexes VII X have been considered for the cost assessment):

12 12 In the case of elaborating a separate lead dossier for nano TiO 2 for a tonnage band between 1 10 t/y only information requirements for Annex VII would have to be fulfilled either via 9 testing results or via 9 non-testing approaches (e.g. waiving/read-across). Completion of IUCLID endpoints with 18 testing results (for nano TiO 2 and silanised nano TiO 2 ) would lead to additional costs of 9,000 (equivalent to the efforts of 9 working days), whereas completion of the corresponding IUCLID endpoints via non-testing approached (waiving/read/across) is assumed to lead to additional costs of 4,500 (equivalent to the efforts of four and half working days). If the lead dossier would be in the same tonnage band (> 1,000 t/y) as the current lead dossier for TiO 2, it is assumed that the same costs (19,250 38,500 ) would occur. Summarised it can be simplified that compliance costs would cover a broad range between 4,500 and 38,500. Compliance costs: 4,500 38,500 Option 8: Require detailed description of the test material/sample and sample preparation (human health hazards, environmental fate, environmental hazards) In the course of the preparation of the lead dossier for TiO 2, informations on various forms of TiO 2 (incl. nano materials) were gathered and submitted by the lead registrant. The nanomaterials have been assessed partly according to currently valid international testing guidelines. In fact, approximately 37 endpoint study records have been created with regard to the assessment of environmental fate and pathways and (eco)toxicological behaviour. The aspect of sample preparation of nanomaterials has recently been considered and included in the "Appendix R7-1 Recommendations for nanomaterials applicable to Chapter R7a Endpoint specific guidance". It would have to be evaluated whether the already accomplished tests have been prepared accordingly and the performing of the tests corresponded to internationally applicable standards. Furthermore, it would have to be assessed whether the sample preparation has been carried out according to the requirements laid out in the recently updated Guidance Document. If not, focus should be laid on the fact whether performing of new tests would be more suitable if no alternatives are available for an appropriate assessment of nanomaterials. The project team assumes that updating of the endpoint study records by supplementing detailed information on test sample/sample preparation would lead to additional efforts of 2.5 working days for the 37 study records (equivalent to 2,500 ). Compliance costs: 2,500 In a separate lead dossier for nano TiO 2 detailed information on test substance/sample preparation would be submitted. Prior characterisation of the testing material/testing sample and the sample preparation is already a standard procedure during the performing of tests. Nevertheless, completing the corresponding parts of the IUCLID endpoints will incur compliance costs which depend also on the tonnage band and the resulting information requirements in the lead dossier. Depending on the tonnage band which would be covered by the lead dossier additional costs between 750 (Annex VII) and 2,500 (Annex X) would occur.

13 13 Compliance costs: 750 2,500 Option 9: Require scientific justifications for grouping/read-across/qsar and other nontesting approaches for different forms (human health hazards, environmental fate, environmental hazards) The current lead dossier for TiO 2 includes information on environmental fate and pathways and (eco)toxicological behaviour for different forms of TiO 2. For instance, several robust study summaries have been created for IUCLID endpoint 7.3 "Irritation / corrosion" unfortunately the publicly available entries to this endpoint do not allow any conclusions which form of TiO 2 was subject to the assessment. It should therefore be evaluated whether information requirements for skin irritation/corrosion for silanised TiO 2 could be fulfilled by applying a read-across approach to TiO 2 and the surface treating substance (silane). Referring to this example information requirements for every IUCLID endpoint for the compartment of environmental fate and pathways and (eco)toxicity would be re-evaluated in order to decide whether read-across/qsar is applicable to each other for the various forms of TiO 2 or whether consequently new testings/testing proposals would be required. After a brief examination of submitted information on environmental fate and pathways and (eco)toxicity it has been revealed that information requirements for a broad range of IUCLID endpoints (10 IUCLID endpoints) have been fulfilled by a read-across approach. As it has already been explained in Option 5 the practical implementation of non-testing methods, such as read-across approach, reveal a quite differentiated picture: usually read-across is made for similar substances than it is usually justified. Furthermore, read-across for different forms is done implicitly by simply submitting the data of different forms in the same dossier, but without an appropriate justification. Option 7 proposes that nanoforms are explicitly addressed in the endpoint sections consequently the aforementioned 10 endpoints would have to be amended in the updating process by including information on nano TiO 2 and its silanised derivative. In a subsequent step a re-evaluation of already submitted information would be performed during which the quality of the submitted information would be assessed whether it is applicable to the at least two nanoforms of TiO 2. It is the project team s assumption that re-evaluation of already submitted information for the 10 endpoints would incur in compliance costs of approximately 2,000 (equivalent to the efforts of two working days). Compliance costs: 2,000 A separate dossier would be elaborated for nano TiO 2 which could also include information on e.g. surface treated nano TiO 2. The abovementioned approach would also be applied for nano TiO 2 and its surface treated derivative. Although this procedure can be regarded as a standard procedure in the course of the data gap analysis, it is considered that this option would nevertheless incur the same costs.

14 14 Compliance costs: 2,000 Option 10: Require considerations of most appropriate/relevant metric with preferable presentation in several metrics (human health hazards, environmental fate, environmental hazards) A large part of the testing results refer to the mass metric, such as data on effect level for acute inhalation toxicity (mg/l). The acute inhalation toxicity is a good example for extending the current testing techniques in order to measure variable parameters. Referring to the inhalation study, it could be regarded as relevant to assess the hazard of nanomaterials in relation to particle number and surface area which might especially be of high relevance with regard the presence/absence of aggregates/agglomerates. In the case of subsequently considering surface area or particle number as a relevant parameter for inhalation toxicity, tests for determining these relevant parameters would be required with the same testing sample with which inhalation toxicity testing has been carried out. In order to analytically determine adverse effects of nanomaterials in relation to mass and other parameters, such as surface area, particle number or surface charge, a prior adjusting of the analytical equipment, its implementation and validation of the appropriate testing method is considered to be required in order to carry out those tests parallel to e.g. the inhalation test. This procedure is assumed to lead to additional costs of 10,000. A parallel determination of the particle size (costs: between 2,000 and 4,000 ) and/or surface area (costs: between 2,000 and 3,000 ) would result in final costs between 14,000 and 17,000 (for one tested nanomaterial) and 18,000 and 24,000 for two tested nanomaterials. Compliance costs: 18,000 24,000 A separate lead dossier for nano TiO 2, which could also include information on further nanoforms, such as silanised nano TiO 2, would also require a prior analytical adjustment as it has been discussed above for the case of a dossier update. It can therefore be inferred that the same cost range would occur in the course of elaboration of a separate lead dossier for nano TiO 2. Compliance costs: 18,000 24,000 Option 14: Require that bioaccumulation is addressed specifically for the nanoform (environmental fate and hazards) If the current lead dossier would have to be updated, testing results of bioaccumulation of nano TiO 2 would have to be taken into account, too. Chemical properties, such as lipophilicity, play a negligible role when the bioaccumulative behaviour of nanomaterials is assessed since - due to their small

15 15 particle size - nanomaterials can still penetrate organic issues. Derivation of nanomaterials, such as surface treatment, can also influence the uptake process into the organism. In order to fulfill data requirements of Annex IX, a bioaccumulation test preferably on fish would be carried out according to OECD 305. A brief screening of the testing results/test performing revealed that several bioaccumulation tests were carried out with nano TiO 2 but not with its surface treated form, e.g. silanised nano TiO 2. A possible implementation of the proposed requirements of Option 14 in the REACH Regulation would affect information requirements of Annex IX, 9.3 and in the case of TiO 2 would result in performing the bioaccumulation test preferably on fish with the silanised nanoform of TiO 2. Performing the test (54, ,500 ), test monitoring and creation and completion of the corresponding IUCLID endpoint 5.3 and endpoint summary (1,000 ; equivalent to the efforts of 1 working day) would lead to costs between 55,000 and 113,500 for one tested nanomaterial. Compliance costs: 55, ,500 Implementation of the proposed option would affect information requirements of Annex IX, The information requirements defined therein have to be applied to substances which are manufactured or imported in quantities of 100 tonnes or more per year. In order to fulfill data requirements of Annex IX, a bioaccumulation test preferably on fish would be carried out according to OECD 305. Performing of the bioaccumulation test, test monitoring and creation and completion of the corresponding IUCLID endpoint 5.3 and endpoint summary would result in total costs between 55,000 and 113,500. Since information on bioaccumulation of nano TiO 2 has already been included in the dossier, performing of this test would only affect further nanoforms of TiO 2, e.g. the silanised nano form of TiO 2. However, the TDIC (Titanium Dioxide Industry Consortium) has already indicated in a questionnaire, forwarded to the consortium in the course of performing this project that an elaboration of a separate lead dossier for nano TiO 2 is not envisaged. Compliance costs: 55, ,500 (only if lead dossiers covers a tonnage band of more than 100 t/y) Option 15: Specify that adsorption/desorption behaviour of nanomaterials should not be assessed based on K d values derived from K oc and K ow (environmental fate and hazards) A brief examination of the submitted information on the adsorption/desorption behaviour revealed that the information requirements for this IUCLID endpoint have been fulfilled via a read-across approach. As it has been discussed in Option 9, reach-across approaches should be considered in detail in particular it should be considered whether information requirements of nano TiO 2 can be fulfilled via a read-across approach to the bulk form of titanium or a titanium-containing compound. If this strategy is not scientifically justifiable, the information requirements could be fulfilled via testing. The costs for performing the appropriate method would vary between 2,500 5,187

16 16 (Adsorption Screening Test, according to OECD 121) and 32,000 (Adsorption/ Desorption according to OECD 106; no price for the corresponding test has been calculated in the cited Fleischer List), if outcome of adsorption screening test reveals a further need for subsequent information on adsoption/desorption (according to current information requirements for Annex IX, ). Test monitoring and completion of IUCLID endpoints and summaries would lead to additional costs of 2,000 (equivalent to the efforts of 2 working days) for performing abovementioned two tests with one nanomaterial and would lead to a final cost range of 3,500 to 33,000. Appropriate assessment of the adsorption/desorption behaviour of nano TiO 2 and its silanised nano form would lead consequently to final costs between 7,000 and 66,000. Compliance costs: 7,000 66,000 A separate lead dossier for nano TiO 2 would be elaborated, in which also the silanised nano form of TiO 2 could be subjected to a Chemical Safety Assessment. The same costs would occur as for the abovementioned case of a dossier update if the lead dossier for nano TiO 2 would cover a tonnage band of more than 10 tonnes per year. Compliance costs: 7,000 66,000 (only if lead dossier covers a tonnage band of more than 10 t/y) Option 20: Require identification of uses and exposure assessment of the nanoform (exposure assessment and risk characterisation) Based on information provided in the questionnaire no nanospecific uses have been considered in the lead dossier. Instead, all uses for nano TiO 2 are indicated to be covered by uses for pigmentary TiO 2. TiO 2, of which several bulkforms and nanoforms have been assessed in the course of the elaboration of the lead dossier, is classified as not hazardous. According to the current classification for TiO 2 no exposure assessment and no correlating risk assessments would be required. Additional costs may occur in the case of a subsequent classification (e.g. hazard assessment, carried out after implementation of the abovementioned options reveals the necessity for a subsequent classification of (nano) TiO 2 ). Since the project team cannot predict possible adverse effects of nano TiO 2, no costs for nanospecific exposure assessment can be estimated. Compliance costs: not predictable In the case of elaborating a lead dossier for nano TiO 2, uses of nano TiO 2 and its surface treated derivatives will be identified and the corresponding hazard assessment, risk assessment and risk characterisation will be elaborated separately for each of the three nanomaterials of TiO 2. Since the requirements of Option 20 would have to be fulfilled for every substance which is subjected to a

17 17 registration, it can reasonably be inferred that implementation of the requirements of this option would lead to no additional costs in the course of the elaboration of a lead dossier for nano TiO 2. In this context it should be pointed out that according to Article 14 of the REACH Regulation a chemical safety assessment should be performed and a chemical safety report should be completed only for those substances which are manufactured or imported in quantities of more than 10 tonnes per year. It should be pointed out that the TDIC (Titanium Dioxide Industry Consortium) has indicated via a questionnaire that an elaboration of a separate lead dossier for nano TiO 2 is not envisaged. Compliance costs: not predictable 3 Case study for nano zinc oxide (ZnO) In the case of nano ZnO the substance can exhibit different crystallization properties which result in different nanostructures and shapes, such as nanowires (or nanorods), nanobelts (nanoribbons), comb-like nanowires array, nanoneedles arrays, and nanorings 2. Furthermore, nanomaterials can be modified on the surface in order to introduce completely new properties to the nanomaterial or to prevent undesirable effects. ZnO nanoparticles tend to agglomerate due to their large surface area and high surface energy. In order to counteract this tendency and at the same time to improve the dispersion of the nanoparticles, the ZnO surface is modified by a broad range of substance classes. Depending on the solvent (organic, aqueous) organoalkoxysilanes or polymethacrylic acids are attached on the surface of nano ZnO for improving the desired properties 3. From the information content which is publicly accessible via ECHA s website for registered substances the lead dossier for ZnO includes information on various forms of ZnO: bulk form of ZnO, nano ZnO, surface treated ZnO (triethoxycaprylylsilane-coated ZnO and dimethoxydiphenylsilane/triethoxy-caprylylsilane crosspolymer-coated ZnO). Due to reasons of simplification the project team will focus its cost assessment activities on these three various nanoforms of ZnO, irrespective of the fact whether the identified number of characterised forms in the lead dossier might be misinterpreted. Option 1: Explicitly require registrants to describe the scope of the registration dossier (substance identification and physico-chemical properties) Although information on (eco)toxicological behaviour of nano ZnO and surface treated ZnO has been submitted via the lead dossier, the presence/absence of nano ZnO has not explicitly been considered in the substance specification of the lead dossier. In the case of a subsequent consideration of nano ZnO in the already submitted lead dossier, an update of the lead dossier is required in which the aspect of the nano ZnO is considered appropriately. 2 J. Zhang; Y. Yang; B. Xu; F. Jiang; J. Li; J. Cryst. Growth 280 (2005) E. Tang; G. Cheng; X. Ma; X. Pang; Q. Zhao; Appl. Surf. Sci. 252 (2006) and literature cited therein.

18 18 Within the required details on test material, triethoxycaprylylsilane-coated ZnO has been characterised by its particle size (< 200 nm), surface area (12 24 m 2 /g) and the attached TEM images. Another surface treated substance (dimethoxy-diphenylsilane/triethoxy-caprylylsilane crosspolymer-coated ZnO) has been characterised by the same identical parameters as the latter substance. Unfortunately information is missing on prior sample preparation and therefore the project team cannot distinguish whether the tested substance is an aggregate/agglomerate of surface treated nano ZnO. Against this background the discussions with regard to the scope of the registration dossier of ZnO should consider also the abovementioned varieties of the nano ZnO within the SIEF. The SIEF would have to decide whether all of the abovementioned various shapes and forms of nano ZnO would be covered by the updated Substance Identification of ZnO or whether certain shapes and forms should explicitly be excluded. Since the dossier already contains information on surface treated substances which are assumed to be nanomaterials (due to the submitted analytical information, such as particle size of < 200 nm, surface are and TEM images) decision should be made whether further surface treated/functionalised nanomaterials should be covered by the lead dossier. This decision of the ZnO SIEF would be based on data from literature and indications whether discrepancies in (eco)toxicological and physico-chemical properties among the various forms of ZnO have been recognized. According to Article 5 of Commission Regulation EC No 340/2008 no fees are charged by the ECHA in the case of updating dossiers which affects the change in the composition of the substance. Referring to the provided information that 10 meetings were required in order to establish the boundaries of the SID for TiO 2 the project team assumes that at least the same efforts would be required in order to re-define the scope of the registration dossier for ZnO. The incurred efforts are regarded to lead to compliance costs of 9,000. Compliance costs: 9,000 In the course of elaborating a separate lead dossier for nano ZnO, the scope of the envisaged registration of the nanomaterial would be discussed. Since the definition of the SID in the pre-sief is a standard procedure in the course of elaboration of a lead dossier, it can be inferred that the same costs would occur as in the abovementioned case (size as characteriser). Compliance costs: 9,000 Option 2: Explicitly require registrants to provide more detailed characterisation of nanomaterials/nanoforms (substance identification and physico-chemical properties) As already explained in the case study for nano TiO 2, a broad range of methods have been identified and suggested in the RIP-oN2 report, which are suitable for determining particle size distribution of nanomaterials. Following methods have been taken into account:

19 19 for powders: transmission electron microscopy (TEM), scanning electron microscopy (SEM), scanning mobility particle sizer (SMPS), Field Flow Fractionation (FFF), Laser Diffraction Particle Size Analyser, Photon Correlation Spectroscopy (PCS) dispersion of nanomaterials: Dynamic Light Scattering (DLS), PCS, nanoparticle tracking analysis (NTA), Analytical Ultracentrifuge (AUC), Hydrodynamic Fractionation (HDF), cryo- TEM aerosols of nanomaterials: differential mobility analyzer, scanning mobility particle sizer (SMPS), electrical low pressure impactor (ELPI), Optical Particle Counter (OPC), Aerosol Particle Sizer (APS), Fast Mobility Particle Sizer (FMPS) In the case of an update, the current lead dossier would have to be supplemented by additional information on particle size distributions of three remaining forms of ZnO (nano ZnO, two coated forms of nano ZnO). Determining the particle size distribution via TEM or Laser Diffraction Particle Size Analysis would lead to testing costs between 2,000 and 4,000 (for TEM) per tested substance. The two surface treated ZnO substances could be characterised via the same route or via e.g. Dynamic Light Scattering (DLS) (if the substances are only available and stable in a dispersion; currently the project team has no indication in which state the surface treated particles are processed). The completion of the correlating IUCLID endpoints would result in additional costs of 1,000 per tested substance (equivalent to the efforts for 1 working day) and 3,000 for three tested nanomaterials. Information on surface functionalisation/treatment of a nanomaterial can partially have enormous impact on the registration costs especially in the case of considering the surface treatment/functionalisation as an identifier. In this case for every single surface treated/functionalised nanomaterial a separate lead dossier would have to be elaborated and submitted (in case the tonnage band of the surface treated nanomaterial exceeds the critical threshold of 1 tonne per year). If the aspect of surface functionalisation/treatment is considered as a characteriser, the appropriate information would be addressed in the corresponding IUCLID endpoint and sections (IUCLID endpoint 1.2 "Composition" and 1.4 "Analytical Information"). The update of the current lead dossier by creating additional three entries in the IUCLID endpoints 1.2 and 1.4 is not regarded to be associated with high efforts and costs and therefore additional costs can be regarded as negligible if surface functionalisation/treatment is taking into account as a characteriser. Shape and surface area are two further parameters which strongly depend on the production process of the nanomaterial. It is therefore suggested that this information is submitted individually by every joint submission member. Based on the findings of the RIP-oN2 report, the shape of nanomaterials can be determined via the transmission electron microscopy (TEM). On the other hand the Brunauer, Emmet and Teller (BET) method is the most appropriate method for conducting the surface area of nanomaterials. Determination of the surface area would result in testing costs of 2,000 and 3,000 per tested substance and it is assumed that the completion of the correlating IUCLID endpoint (IUCLID endpoint 1.4 "Analytical information") would be associated with efforts of 1 working day (1,000 ) per tested substance, at the maximum. Updating of the current lead dossier for ZnO by submitting information on the described methods would lead to additional costs between 6,000 and 9,000 per tested substance (18,000 and 27,000 for three tested nanomaterials). If the wording of the Annexes of the REACH Regulation is

20 20 adapted in a way that the aforementioned information is mandatory for every joint submission member, these costs would be expected for every registrant. Compliance costs: 18,000 27,000 The cost structure, as outlined above, would also occur in the case of the elaboration of a separate lead dossier for nano ZnO in which also characterisation of further nanoforms, e.g. surface treated nanomaterials, could be included. Compliance costs: 18,000 27,000 Option 3: Require that nanoforms are explicitly addressed in the endpoint sections (substance identification and physico-chemical properties) A brief examination of physico-chemical data via ECHA s website for registered substances revealed that within 17 IUCLID endpoints no information on nano ZnO has been submitted. In order to fulfill the information requirements which would result after a possible adaption of the REACH Regulation, additional endpoint study records would have to be created for every nanoform, if applicable. In the context of nano ZnO and its two surface treated forms a total of 51 new endpoint study records would have to be created in order to fulfill the information requirements of the 17 IUCLID endpoints for the three additional nanomaterials. Given the assumption that additional 4 physico-chemical tests would be required in order to characterise the three nanomaterials adequately, 11 IUCLID endpoint study records would be prepared and completed. Information requirements for the remaining 40 endpoint study records would be fulfilled via waiving, read-across, grouping or (Q)SAR, where scientifically justifiable. The project team assumes that following additional tests would be required in order to characterise three nanomaterials adequately: SEM micrograph (Scanning electron microscopy; IUCLID point 4.1 "Appearance/physical state/colour"; ; per tested substance) Density (IUCLID point 4.4 "Density"; ; per tested substance) Granulometry (IUCLID endpoint 4.5 "Particle size distribution (Granulometry)"; 2,000 4,000 ; per tested substance) Water solubility (IUCLID endpoint 4.8 "Water solubility"; 4,500 5,500 ; per tested substance) Referring to the outlined testing strategy, performing of these tests would lead to additional costs between 7,300 and 10,830 per tested substance (21,900 32,490 for nano ZnO and two different surface treated nanoforms of ZnO). Monitoring of tests and completion of the corresponding IUCLID endpoints would lead to additional costs of 4,000 (equivalent to the efforts of four working days per tested substance; 12,000 for nano ZnO and two surface treated nanoforms of ZnO). Completion of the remaining 40 endpoint study records (via waiving, read-across

21 21 or (Q)SAR) is estimated to lead to additional costs of 5,000 (equivalent to the efforts of five working days per tested substance) and 15,000 for three tested nanoforms of ZnO. Additional costs would arise if more than form of uncoated nano ZnO is identified, e.g. presence of various shapes of nano ZnO and if it scientifically evident that the shape has influence on physicochemical properties. Practical implementation of requirements of Option 3 would result in final costs of 48,900 and 59,490. Compliance costs: 48,900 59,490 In a separate lead dossier for nano ZnO also information on physico-chemical properties of further nanoforms, such as surface treated nanoforms, could be included. Since the elaborated option is applicable to substances which are placed on the market in a tonnage band of more than one tone per year the calculated costs, as outlined above, would also occur in the process of the elaboration of a separate lead dossier for nano ZnO. Compliance costs: 48,900 59,490 Option 4: Require detailed description of the test material/sample and sample preparation (substance identification and physico-chemical properties) The lead dossier contains information on physico-chemical properties which mainly relate to the bulk form of ZnO. Physical properties, which differ from the properties of the bulk form of ZnO (e.g. density of surface coated ZnO, water solubility) would have to be taken into account separately in the dossier. For instance, the current lead dossier lists testing results to 6 physico-chemical endpoints. The update of the lead dossier would require additional information of three nanoforms of ZnO for the 6 IUCLID endpoints in the IUCLID section 4 "Physical and chemical properties". Since the project team has no detailed information with respect to the physico-chemical properties of nano ZnO and the surface treated derivatives, no suggestions can at this moment be made whether new tests would have to be carried out or whether the determined parameters are applicable to all four forms of ZnO. It is nevertheless regarded that the detailed description on test material and sample preparation would lead to additional efforts of 1,000 (equivalent to the efforts of 1 working day), at the maximum. Compliance costs: 1,000 In the course of the preparation of a lead dossier for nano ZnO, a prior in-depth characterisation of the tested nanomaterial would have to be carried out by taking into account the aforementioned parameters. Since prior characterisation of the testing material/testing sample and the sample preparation is already a standard procedure during the performing of tests, it can be inferred that

22 22 the required efforts would result in the same costs (1,000 - equivalent to the efforts of 1 working day) as for the case of updating the lead dossier. Compliance costs: 1,000 Option 5: Require scientific justifications for grouping/read-across/qsar and other nontesting approaches for different forms (substance identification and physico-chemical properties) The current provisions of Annex XI provide the registrant with a broad range of methods in order to avoid (unnecessary) testing. Methods, such as (Q)SAR, grouping of substances or the read-across approach are non-testing methods, by which information requirements for an endpoint are fulfilled by using data of similar substance (classes) which exhibit the same properties. However, practical implementation of these provisions reveals a quite differentiated picture: usually read-across is made for similar substances than it is usually justified. Furthermore, read-across for different forms is done implicitly by simply submitting the data of different forms in the same dossier, but without an appropriate justification. With regard to the physico-chemical properties of nano ZnO an in-depth evaluation is to be performed whether the current available data of ZnO, gathered in the course of the preparation of the lead dossier, are transferable to nano ZnO and its surface treated forms. A brief literature research revealed no differences between some common physical properties, such as melting point or oxidising properties. For instance one of the conclusions of the "Specific Advice on Fulfilling Information Requirements for Nanomaterials under REACH (RIP-oN 2)" is that no update of the guidance is regarded necessary with regard to the assessment of oxidising properties of nanomaterials. This strategy could be applied to nano ZnO which would differ only in their shape and size. In contrast, nano ZnO modified via e.g. surface treatment is characterised by completely different physico-chemical properties (e.g. density). The lead dossier contains testing results of two additional surface treated substances (triethoxycaprylylsilane-coated ZnO and dimethoxy-diphenylsilane/ triethoxy-caprylylsilane crosspolymer-coated ZnO). It might be questioned whether the melting point of the surface treated substances is identical to that of the untreated nanoparticle or the bulk substance or whether the surface treated substances would decompose upon heating. These considerations would have to be done in both cases update of the lead dossier (in case of considering particle size as characteriser) or elaboration of new lead dossier for nano ZnO (in case of considering particle size as identifier). The current lead dossier contains physico-chemical data for the bulk-form of ZnO - no entry has been identified in which a grouping/read-across/q(sar) approach to (or from) a nano-form has been undertaken. Non-testing methods, such as read-across, grouping or (Q)SAR should be evaluated from the outset if such methods are applied for fulfilling information requirements. The project team assumes that a (re-)evaluation of existing data and a probable literature research would lead to efforts of 3,000 (equivalent to the efforts of three working days).

23 23 Compliance costs: 3,000 Option 7: Require that nanoforms are explicitly addressed in the endpoint sections (human health hazards, environmental fate, environmental hazards) As already pointed out above in Option 3, the project team does not intend to carry out an in-depth research on environmental and (eco)toxicological properties of nano ZnO and its surface treated derivatives. Instead the project team will rely on the already submitted lead dossier of ZnO and the carried out tests which entries can be viewed via ECHA s website for registered substances. In the course of preparation of the lead dossier for ZnO, information has been included on various forms of ZnO: bulk form of ZnO, nano ZnO and two surface treated ZnO substances which are assumed to be nanoparticles. Given that particle size is as a characteriser, the current lead dossier of ZnO would be subjected to an update in which the various nanoforms of ZnO would be addressed separately in the endpoint study records, if applicable. Consequently every endpoint in the dossier would have to be supplemented by up to three additional entries that would cover the various nanoforms of ZnO. According to the publicly available information on the lead dossier for ZnO, which are provided by ECHA via its website for registered substances, 44 IUCLID endpoints (inclusive 2 endpoints, covering PNEC and DN(M)EL values) have been created in which the information of the three different nano forms of ZnO is included with regard its environmental fate and pathway and (eco)toxicological properties. Following the aforementioned argumentation, the current lead dossier would have to be supplemented with up to 132 additional entries, which would include amongst others - waiving statements, testing results, read-across, grouping approaches or monitoring data. Given the assumption that the current lead dossier would be supplemented by up to 130 testing results (incl. (Q)SAR) or by up to 130 waiving statements, read-across or grouping approaches, the required efforts would lead to additional efforts between 65,000 (equivalent to 65 working days, required for entering testing data) and 32,500 (equivalent to 32.5 working days, required to fulfill information requirements via waiving, read-across or grouping). In contrary to the elaborated Option 3 the project team does not intend to outline a possible testing scenario, as it has been carried out in Option 3 for the physicochemical properties, since several of the affected IUCLID endpoints will be addressed in other options below. Compliance costs: 32,500 65,000 If a separate lead dossier for nano ZnO would have to be elaborated, information on environmental fate and behaviour and (eco)toxicity of three different nanoforms of ZnO could be addressed separately in the technical dossier. The range of efforts for fulfilling information requirements of Option 7 would be defined by the tonnage bands and the resulting information requirements of the Annexes. Based on the tonnage

24 24 bands a cost structure as follows can be outlined (in this context it should be noted that only tests which are listed in the Annexes VII X have been considered for the cost assessment): In the case of elaborating a separate lead dossier for nano ZnO for a tonnage band between 1 10 t/y only information requirements for Annex VII would have to be fulfilled either via 9 testing results or via 9 non-testing approaches (e.g. waiving/read-across). Completion of IUCLID endpoints with 27 testing results (for nano ZnO and two surface treated nano ZnO) would lead to additional costs of 13,500 (equivalent to the efforts of 13,5 working days), whereas completion of the corresponding IUCLID endpoints via non-testing approached (waiving/read/across) is assumed to lead to additional costs of 6,750 (equivalent to the efforts of 6,75 working days). If the lead dossier would be in the same tonnage band (> 100 1,000 t/y) as the current lead dossier for ZnO, it is assumed that the same costs (32,500 65,000 ) would occur. Summarised it can be simplified that compliance costs would cover a broad range between 6,750 and 65,000. Compliance costs: 6,750 65,000 Option 8: Require detailed description of the test material/sample and sample preparation (human health hazards, environmental fate, environmental hazards) In the course of the preparation of the lead dossier for ZnO, information on various forms of ZnO (incl. nanomaterials) have been gathered and submitted by the lead registrant. The nanomaterials have been assessed partly according to currently valid international testing guidelines. In fact, approximately 25 endpoint study records have been created with regard to the environmental fate and pathways and (eco)toxicological behaviour. The aspect of sample preparation of nanomaterials has recently been considered and included in the "Appendix R7-1 Recommendations for nanomaterials applicable to Chapter R7a Endpoint specific guidance". It would have to be evaluated whether the already accomplished tests have been prepared accordingly and the performing of the tests corresponded to internationally applicable standards. Furthermore, it would have to be assessed whether the sample preparation has been carried out according to the requirements laid out in the recently updated Guidance Document. If not, focus should be laid on the fact whether performing of new tests would be more suitable if no alternatives are available for an appropriate assessment of the nanomaterials. The project team assumes that updating of the endpoint study records by supplementing detailed information on test sample/sample preparation would lead to additional efforts of 2 working days for the 25 study records (equivalent to 2,000 ). Compliance costs: 2,000 For a new lead dossier for nano ZnO detailed information on test substance/sample preparation would be submitted. Since prior characterisation of the testing material/testing sample and the sample preparation is already a standard procedure during the performing of tests, the resulting effort would nevertheless entail costs of 2,000 (if the separate lead dossier would include same number of performed tests and would cover the same tonnage band as lead dossier for ZnO).

25 25 Compliance costs: 2,000 Option 9: Require scientific justifications for grouping/read-across/qsar and other nontesting approaches for different forms (human health hazards, environmental fate, environmental hazards) The current lead dossier for ZnO includes information on environmental fate and pathways and (eco)toxicological behaviour for different forms of ZnO. For instance, information on the acute oral toxicity is available for the bulk form and the nano form of ZnO, but not for the two surface treated substances. It should therefore be evaluated whether information requirements of the acute oral toxicity of the triethoxycaprylylsilane-coated ZnO could be fulfilled by applying a read-across approach to nano ZnO and triethoxycaprylylsilane. Referring to this example information requirements for every IUCLID endpoint for the compartment of environmental fate and pathways and (eco)toxicity would be once again evaluated in order to decide whether grouping/readacross/qsar are applicable to each other for the various forms of ZnO or whether consequently new testings/testing proposals would be required. A brief screening of submitted information on environmental fate and pathways and (eco)toxicity revealed that read-across has been carried out from one bulk-substance to another bulk-substance (e.g. read-across from ZnSO 4 to ZnO) but not from one form of ZnO to another form. Given the assumption that the current lead dossier would have to be supplemented by including information on nano ZnO and the two surface treated nanoforms of ZnO it is the project team s assumption that re-evaluation of already submitted information for the endpoints would incur in compliance costs of approximately 3,000 (equivalent to the efforts of three working days). Compliance costs: 3,000 In the case of particle size being regarded as an identifier, a separate dossier would be elaborated for nano ZnO which could also include information on surface treated nanomaterials. The abovementioned approach would also be applied for nano ZnO and the two surface treated substances. Although this procedure can be regarded as a standard procedure in the course of the data gap analysis, it is considered that this option would nevertheless incur the same costs. Compliance costs: 3,000

26 26 Option 10: Require considerations of most appropriate/relevant metric with preferable presentation in several metrics (human health hazards, environmental fate, environmental hazards) The current lead dossier for ZnO covers a broad range on results of hazard assessments carried out with various forms of ZnO: the bulk form of ZnO, nano ZnO and two surface treated substances which are assumed to be nanoparticles. A large part of the testing results refer to the mass metric, although in some rare cases (acute toxicity inhalation) surface area has been submitted as additional information for the characterisation of the testing substance. The acute inhalation toxicity performed with nano ZnO is a good example for extending the current testing techniques in order to measure variable parameters. Therefore a basis is given for indicating the hazardous effects in correlation to the surface area. In the case of subsequently considering the particle number as a relevant parameter for inhalation toxicity, a test for determining this relevant parameter would be required with the same testing sample the inhalation toxicity testing was carried out. In order to analytically determine adverse effects of nanomaterials in relation to mass and other parameters, such as surface area, particle number or surface charge, a prior adjusting of the analytical equipment, its implementation and validation of the appropriate testing method is considered to be required in order to carry out those tests parallel to e.g. the inhalation test. This procedure is assumed to lead to additional costs of 10,000. These adjusting-related costs are regarded as one-time costs and will not incur after performing of every test. A parallel determination of the particle size (costs: between 2,000 and 4,000 ) and/or surface area (costs: between 2,000 and 3,000 ) would result in final costs between 14,000 and 17,000 (for one tested nanomaterial) and 22,000 to 31,000 for three tested nanomaterials. Compliance costs: 22,000 31,000 A separate lead dossier for nano ZnO, which could also include information on further nanoforms, such as silanised nano ZnO, would also require a prior analytical adjustment as it has been discussed above for the case of a dossier update. It can therefore be inferred that the same cost range would occur in the course of elaboration of a separate lead dossier for nano ZnO.Testing of nano ZnO and two surface treated nanomaterials of ZnO, during which also particle size and/or surface area would be taken into account, would lead to costs between 22,000 and 31,000. Compliance costs: 22,000 31,000

27 27 Option 14: Require that bioaccumulation is addressed specifically for the nanoform (environmental fate and hazards) If the current lead dossier would have to be updated, testing results of bioaccumulation of nano ZnO would have to be taken into account, too. Chemical properties, such as lipophilicity, play a negligible role when the bioaccumulative behaviour of nanomaterials is assessed since - due to their small particle size - nanomaterials can still penetrate organic tissues. Derivation of nanomaterials, such as surface treatment, can also influence the uptake process into the organism. In order to fulfill data requirements of Annex IX, a bioaccumulation test preferably on fish would be carried out according to OECD 305. A brief review of the submitted information on bioaccumulation revealed that information requirements have been fulfilled via a read-across approach to the bulk form of Zinc. In the case that the performed read-across approach is not applicable to nano ZnO, subsequent testing on bioaccumulation would be required (if no other non-testing methods, such as (Q)SAR are available). Performing of the test (54, ,500 ), test monitoring and creation and completion of the corresponding IUCLID endpoint 5.3 and endpoint summary (1,000 ; equivalent to the efforts of 1 working day) would lead to additional costs between 55,000 and 113,500 per tested substance. These costs would increase if additional bioaccumulation tests would be performed on fish with different surface treated nanoforms of ZnO, for which the information requirements could not be fulfilled via other means such as read-across, grouping or (Q)SAR. The final additional costs would incur between 162,000 and 337,500 for three tested nanoforms of ZnO. Compliance costs: 165, ,500 The proposed option would affect information requirements of Annex IX, The information requirements defined therein have to be applied to substances which are manufactured or imported in quantities of 100 tonnes or more per year. In the case that the lead dossier would include information on nano ZnO and its two surface treated forms and would additionally cover information requirements of Annexes VII IX, additional costs would incur between 165,000 and 337,500. Compliance costs: 165, ,500 (only if lead dossier covers a tonnage band of more than 100 t/y) Option 15: Specify that adsorption/desorption behaviour of nanomaterials should not be assessed based on K d values derived from K oc and K ow (environmental fate and hazards) In order to predict the environmental fate of a substance, knowledge on its adsorption/desorption behaviour on/from solid surfaces is one of the key parameters. In this option the adsorption/desorption behaviour (K d ) should be assessed experimentally, instead of being estimated from the K oc and K ow values. It is regarded as necessary to deviate from the previous methods of

28 28 predicting this parameter from the distribution coefficients K oc and K ow since the argument of insolubility of particles at the nanoscale cannot be applied anymore. Table R of the "Guidance on information requirements and chemical safety assessment Chapter R.7a: Endpoint specific guidance" gives an extensive overview on applicable testing methods for the measurement of adsorption. A brief screening of the submitted information on the corresponding endpoint revealed that neither for the bulk form, nor for the nanoform of ZnO a testing was performed. The costs for performing the appropriate method would vary between 2,500 5,187 (Adsorption Screening Test, according to OECD 121) and 32,000 (Adsorption/Desorption according to OECD 106; no price for the corresponding test has been calculated in the cited Fleischer List) if outcome of adsorption screening test reveals a further need for subsequent information on adsoption/desorption (according to current information requirements for Annex IX, 9.3.3). Additional tests would have to be performed with surface treated nano ZnO which would result in a multiplication of occurring costs. Test monitoring and completion of IUCLID endpoints and summaries would lead to additional costs of 2,000 (equivalent to the efforts of 2 working days) for performing abovementioned two tests with one nanomaterial and would lead to a final cost range of 3,500 to 33,000. Possible implementation of the option s requirements would affect data needs of Annex VIII, and Annex IX, The lead registrant has fulfilled the information requirements for the IUCLID endpoint "Adsorption/desorption by a waiving approach. Consequently, either in case of an update or in case of elaboration of a separate lead dossier (if the lead dossier covers a tonnage band of at least more than 10 tonnes per year) the lead registrant would have to perform the required tests for three nanoforms. Performing of tests, test monitoring and completion of the IUCLID endpoint and the summary would lead to additional costs between 10,500 and 99,000. Compliance costs: 10,500 99,000 Option 20: Require identification of uses and exposure assessment of the nanoform (exposure assessment and risk characterisation) The current lead dossier includes a broad range on (eco)toxicological information on various forms of ZnO: bulk form, nano form and two surface treated substances which are assumed to be nanoparticles. The indicated classification (according to CLP) refers to ZnO with different degrees of purity: "ZnO standard" and "ZnO lower grade". For "ZnO standard" following classification has been assessed in the course of the elaboration of the lead dossier: Aquatic Chronic 1; H410: Very toxic to aquatic life with long lasting effects.

29 29 The corresponding classification of "ZnO lower grade" reads as follows: Acute Tox. 4; H302: Harmful if swallowed Acute Tox. 4; H332: Harmful if inhaled Repr. 1A; H360: May damage fertility or the unborn child STOT Rep. Exp. 2; H373: May cause damage to organs through prolonged or repeated exposure Aquatic Chronic 1; H410: Very toxic to aquatic life with long lasting effects Based on the assessed classification it can be argued that ZnO poses particular hazards after swallowing, inhalation, prolonged exposure and release to the environment. In the case that the uses of the three nanoforms differ from those for the bulk form separate exposure assessments and risk characterisations would have to be carried out for the three nanoforms of ZnO separately which would result in risk reduction measures and exposure scenarios. However, the Zn REACH Consortium has already indicated in the completed questionnaire that no nano-specific uses have been considered in the course of the elaboration of the dossier. Referring to the questionnaire the uses for nano ZnO are covered by the uses for its bulk counterpart. The project team is not in a position to predict possible classification of nano ZnO and its surface treated derivatives if the proposed requirements of the outlined options would be implemented in the REACH Regulation. Therefore costs for nanospecific exposure assessment cannot be predicted. Compliance costs: not predictable In the case of elaborating a lead dossier for nano ZnO, uses of nano ZnO and the two surface treated nanomaterials will be identified and the corresponding hazard assessment, risk assessment and risk characterisation will be elaborated separately for each of the three nanomaterials of ZnO. Since the requirements of Option 20 would have to be fulfilled for every substance which is subjected to a registration, it can reasonably be inferred that implementation of the requirements of this option would lead to no additional costs in the course of the elaboration of a lead dossier for nano ZnO. In this context it should be pointed out that according to Article 14 of the REACH Regulation a chemical safety assessment should be performed and a chemical safety report should be completed only for those substances which are manufactured or imported in quantities of more than 10 tonnes per year. At the time of the preparation of this report the project team has no indications for an intended elaboration of a separate lead dossier for nano ZnO and the possible tonnage band which would be covered. Compliance costs: not predictable

30 30 4 Case study for nanodiamond As already explained in the main report a lead registrant dossier for crystalline synthetic diamond in the tonnage band of 100 1,000 t/y has been submitted at ECHA. The lead dossier explicitly excluded the presence of nano diamond. In the context of further cost assessment the project team assumes that only one non-surface treated nanoform of diamond will be relevant. Option 1: Explicitly require registrants to describe the scope of the registration dossier (substance identification and physico-chemical properties) The substance definition included in the lead dossier for diamond does exclude nanomaterials. In case registrants will be required to describe the scope of the existing lead dossier in more detail and to explicitly state whether nano-forms are included or not, it would be necessary to update the substance identification of the lead dossier. In case the update concerns information which is provided by joint submission members individually, joint submission dossiers would have to be updated accordingly. According to Article 5 of Commission Regulation EC No 340/2008 the Agency does not levy a fee for updates due to a change in the composition of a substance. It is therefore assumed that an update to describe in more detail the scope of a dossier will be seen as an update of substance composition and no additional cost will arise. Communication between registrants and consulting of experts to conduct the dossier update will be necessary, which is assumed to result in costs of approximately 2,000 (equivalent to the efforts of 2 working days) for diamond. As it is assumed that in case of diamond only one nanoform exists, these will be onetime costs and a scientific discussion whether data can be shared between different nanoforms will not be required. Compliance costs: 2,000 In case a new registration dossier has to be elaborated for diamond, a detailed description of the nanomaterial can be included during elaboration of the dossier and as explained above, a scientific discussion whether data can be shared between different nanoforms is not required for diamond. Compliance costs: 2,000 Option 2: Explicitly require registrants to provide more detailed characterization of nanomaterials/nanoforms (substance identification and physico-chemical properties) Size as characterizer: In case size is seen as characteriser, there are two suboptions regarding particle size distribution. Suboption one assumes that data on particle size distribution is provided in the scope of the joint submission. Acquisition of information on endpoint related data for physical-chemical properties will result in additional costs. Although most of the physico-chemical data including primary particle size distribution should be available for nano-materials since these data should have been gathered

31 31 during development of the nanoform, data on particle size distribution during use or release of nano diamond is assumed not to be available for all uses and environmental conditions. Determination of particle size for nano-materials is assumed to result in costs of approximately 1,500. Against the background that nano diamond is used in different applications with potential release to waste water (release to solid waste is not very likely) at least additional 3 tests, resulting in total costs of 5,500 (incl. test monitoring, elaboration of IUCLID endpoint),, seem to be necessary although for most applications data on particle size distribution may be available. The additional costs for updating the lead dossier can be shared between the 5 individual registrants. In case every registrant has to submit data on particle size on his own (suboption 2), costs for elaboration of data have to be paid by every single registrant. As already indicated above, submitting information on granulometry in the individual dossier would result in an opt-out from the joint submission and to higher registration fees. Assuming 5 registrants, this would mean that the total costs for data gathering are five times higher. In this case an update of the lead dossier would not be necessary in this case as all registrants will include the relevant data in their individual registration dossiers. Compliance costs: 5,500 The same as discussed above is also valid in this case with the exemption that an update of the lead dossier would not be necessary, as a separate (joint) registration for nano diamond has to be prepared. In case a separate registration dossier has to be elaborated for nano-diamond, data on particle size, behaviour during use can either be included in the lead dossier for nano diamond (suboption 1) which means that costs for elaboration of data and inclusion in the dossier file can be shared between the assumed 5 registrants. In case of suboption 2 costs for generation of data on particle size distribution of the individual products of a registrant and preparation of the IUCLID file have to be paid by the single registrants. Compliance costs: 5,500 Option 3: Require that nanoforms are explicitly addressed in the endpoint sections (substance identification and physico-chemical properties) In the current lead dossier for synthetic diamond 19 IUCLID endpoints have been completed in order to characterise the substance appropriately. In the context of nano diamond the same number on IUCLID endpoints is assumed to be completed in the case of a dossier update. Given the assumption that additional three physico-chemical tests would be required in order to characterise the nanomaterials adequately, 3 new IUCLID endpoint study records would be prepared and completed. Information requirements for the remaining 16 endpoint study records would be fulfilled via waiving, read-across, grouping or (Q)SAR, where scientifically justifiable. The project team

32 32 assumes that following additional tests would be required in order to characterise nano diamond adequately: SEM micrograph (Scanning electron microscopy; IUCLID point 4.1 "Appearance/physical state/colour"; ; per tested substance) Granulometry (IUCLID endpoint 4.5 "Particle size distribution (Granulometry)"; 2,000 4,000 ; per tested substance) Water solubility (IUCLID endpoint 4.8 "Water solubility"; 4,500 5,500 ; per tested substance) Referring to the outlined testing strategy performing of these tests would lead to additional costs between 6,800 10,000 for nano diamond. Monitoring of tests and completion of the corresponding IUCLID endpoints and summaries would lead to additional costs of 3,000 (equivalent to the efforts of three working days). Completion of the remaining 16 endpoint study records (via waiving, read-across or (Q)SAR, if applicable) is estimated to lead to additional costs of 2,000 (equivalent to the efforts of two working days). Practical implementation of requirements of Option 3 would lead to final costs of 11,800 to 15,000. Compliance costs: 11,800 15,000 Elaborated requirements of Option 3 would affect substances that are placed on the EU market in a volume of more than one tonne per year. Therefore, elaboration of a separate lead dossier for nano diamond would lead to same compliance costs, as it has been outlined above for the case of a dossier update. Compliance costs: 11,800 15,000 Option 4: Require detailed description of the test material/sample and sample preparation (substance identification and physico-chemical properties) Size as characterizer: As the lead dossier for diamond does not refer to nano diamond, data for single endpoints have to be elaborated and included in the lead dossier for an update for those IUCLID endpoints for which properties of nano diamond differs from those of diamond. When the lead dossier for diamond has to be updated, detailed data on nano diamond will be included together with the data for the endpoints relevant for nano diamond. It is nevertheless regarded that the detailed description on test material and sample preparation would lead to additional efforts of 1,000 (equivalent to the efforts of 1 working day), at the maximum. Compliance costs: 1,000 The same is true in case of elaborating a lead dossier for nano diamond. Although prior characterisation of testing material/testing sample and sample preparation is already a standard

33 33 procedure during performing of tests, it can nevertheless be inferred that required efforts would result in costs of 1,000 (equivalent to the efforts of 1 working day). Compliance costs: 1,000 Option 5: Require scientific justifications for grouping/read-across/qsar and other nontesting approaches for different forms (substance identification and physico-chemical properties) The current provisions of Annex XI provide the registrant with a broad range of methods in order to avoid (unnecessary) testing. Methods, such as (Q)SAR, grouping of substances or the read-across approach are non-testing methods, by which information requirements for an endpoint are fulfilled by using data of similar substance (classes) which exhibit the same properties. However, practical implementation of these provisions reveal a quite differentiated picture: usually read-across is made for similar substances than it is usually justified. Furthermore, read-across for different forms is done implicitly by simply submitting the data of different forms in the same dossier, but without an appropriate justification. Against the background that the lead dossier for diamond and therefore also the joint submissions submitted to ECHA so far do not cover nano diamond, no justifications for non-testing approaches addressing nano diamond have been submitted. In any case, either in case the existing lead dossier for diamond is expanded to nano diamond or a new lead dossier is elaborated for nano diamond, fulfilling information requirements for nano diamond by performing non-testing methods such as read-across or grouping should be scientifically justified. Grouping and (Q)SAR are considered to be simply accomplished for nano diamond as it is not expected that several forms of nano diamond have to be assessed individually. Grouping of possible nanoforms if scientifically justifiable would result in cost-reduction. With regard to physico-chemical properties of nano diamond an in-depth evaluation is to be performed whether the submitted data gathered in the course of the preparation of the lead dossier are also applicable to nano diamond. These considerations would have to be done in both cases update of the lead dossier (in case of considering particle size as characteriser) or elaboration of new lead dossier for nano diamond (in case of considering particle size as identifier). It is assumed by the project team that a (re-)evaluation of existing data and a probable literature research would lead to efforts of 1,000 (equivalent to the efforts of one working day). Compliance costs: 1,000

34 34 Option 7: Require that nanoforms are explicitly addressed in the endpoint sections (human health hazards, environmental fate, environmental hazards) According to the publicly available information on the lead dossier for diamond, which are provided by ECHA via its website for registered substances, 33 IUCLID endpoints (inclusive 2 endpoints, covering PNEC and DN(M)EL values) were created in which the information of diamond is included with regard its environmental fate and pathway and (eco)toxicological properties. Referring to the postulated requirements of Option 7 every endpoint would have to be amended by information on nano diamond either with 31 testing results or 31 non-testing approaches (waiving/read-across). Completing of 31 IUCLID endpoints with testing results is assumed to lead to costs of 15,500 (equivalent to the efforts of 15,5 working days), whereas completing via nontesting approached is assumed to incur costs of 7,750 (equivalent to the efforts of 7,75 working days). Compliance costs: 7,750 15,500 It has been stated on several occasions that a lead dossier for nano diamond would cover only a tonnage band between 1-10 t/y. In the case of elaborating a separate lead dossier for nano diamond for a tonnage band between 1 10 t/y only information requirements for Annex VII would have to be fulfilled either via 9 testing results or via 9 non-testing approaches (e.g. waiving/read-across). Completion of IUCLID endpoints with 9 testing results (for nano diamond) would lead to additional costs of 4,500 (equivalent to the efforts of 4,5 working days), whereas completion of the corresponding IUCLID endpoints via nontesting approached (waiving/read/across) is assumed to lead to additional costs of 2,250 (equivalent to the efforts of 2.25 days). Compliance costs: 2,250 4,500 Option 8: Require detailed description of the test material/sample and sample preparation (human health hazards, environmental fate, environmental hazards) As the lead dossier for diamond does not refer to nano diamond, the data for single endpoints has to be included in the lead dossier update in any case. When the lead dossier for diamond will be updated, detailed data on the test material will be included together with the data for the endpoints relevant for nano diamond. Detailed description of the test material is considered to be the standard procedure in the course of performing tests and subsequently completing the IUCLID endpoints nevertheless, these efforts would lead to costs of approximately 2,000 (equivalent to the efforts of two working days) in order to comply with the requirements which are regarded to be mandatory. Compliance costs: 2,000

35 35 The same is true in case a lead registrant dossier has to be prepared for nano diamond. Detailed information on the test material used to elaborate the required tests can be included in the IUCLID file during elaboration of the single endpoint records. Detailed description of the test material is considered to be the standard procedure in the course of performing tests and subsequently completing the IUCLID. As it has been outlined on several occasions in this report the lead dossier of nano diamond would cover only a tonnage band between 1-10 t/y. Description of test material/sample preparation for tests which are mandatory according to the requirements of Annex VII are considered to lead to compliance costs of 750 (0.75 working days). Compliance costs: 750 Option 9: Require scientific justifications for grouping/read-across/qsar and other nontesting approaches for different forms The current lead dossier for synthetic diamond includes - amongst others - information on environmental fate and pathways and (eco)toxicological behaviour. Since only synthetic diamond has been subjected to an assessment for environmental fate and pathways and (eco)toxicological behaviour, information requirements for every IUCLID endpoint for the affected compartments would be re-evaluated in order to decide whether read-across/qsar is applicable also to nano diamond or whether consequently new testings/testing proposals would be required. In a subsequent step a re-evaluation of already submitted information would be performed during which the quality of the submitted information would be assessed whether it is applicable to nano diamond. It is the project team s assumption that re-evaluation of already submitted information for the endpoints would incur in compliance costs of approximately 2,000 (equivalent to the efforts of two working days). Compliance costs: 2,000 A separately elaborated lead dossier for nano diamond would cover only a tonnage band between 1-10 t/y. Although the abovementioned procedure can be regarded as a standard procedure in the course of the data gap analysis, it is considered that this option would incur costs of approximately 750 since only testing results gathered for synthetic diamond for the required tests according to Annex VII would have to be evaluated on their applicability on nano diamond. Compliance costs: 750

36 36 Option 10: Require considerations of most appropriate /relevant metric with preferable presentation in several metrics Against the background that the lead dossier for diamond and therefore also the joint submissions submitted to ECHA so far do not cover nano diamond, no data has been submitted. Therefore, no studies have to be repeated due to presentation of the results in irrelevant metrics and no literature data has to be replaced by new studies. In any case, either in case the existing lead dossier for diamond is expanded to nano diamond or a new lead dossier is elaborated for nano diamond, use of literature data would have to be justified and a discussion about the relevance of the metric used in the publication could easily be included. Some additional testing might be required to be able to provide results in different metrics (for example to be able to record chamber concentration in mg/m 3 and particles/m 3 during an inhalation study which might be interesting against the background of agglomeration). In case of nano diamond most of the literature available is related to mass metric. However, only very limited toxicological literature on nano diamond is available so that most toxicological information requirements will have to be satisfied with data from studies which will have to be performed. In order to fulfil the information needs, additional analytical methods have to be implemented and validated. Referring to the inhalation study, which is mentioned above as an example, additional analytical methods would have to be implemented with which a correlation between observed adverse effects and the metric parameter (e.g. particle number or surface area) could be analysed. In order to analytically determine adverse effects of nanomaterials in relation to mass and other parameters, such as surface area, particle number or surface charge, a prior adjusting of the analytical equipment, its implementation and validation of the appropriate testing method is considered to be required in order to carry out those tests parallel to e.g. the inhalation test. This procedure is assumed to lead to additional costs of 10,000. A parallel determination of the particle size (costs: between 2,000 and 4,000 ) and/or surface area (costs: between 2,000 and 3,000 ) would result in final costs between 14,000 and 17,000 (for one tested nanomaterial). Compliance costs: ,000 In the case of particle size being considered as an identifier, a new lead dossier would have to be elaborated for nano diamond. In order to analytically determine adverse effects of nanomaterials in relation to mass and other parameters, such as surface area, particle number or surface charge, the same prior procedure would have to be undertaken as discussed above with regard to the analytical adjustment. Testing of nano diamond, during which also particle size and/or surface area would be taken into account would lead to costs between 14,000 and 17,000 (for one tested nanomaterial). Compliance costs: 14,000 17,000

37 37 Option 14: Require that bioaccumulation is addressed specifically for the nanoform Taking into account the size as a characteriser of a substance, the lead dossier for synthetic diamond would have to be updated by adding the testing results of the performed bioaccumulation test with nano diamond. The bioaccumulation behaviour of bulk substances is mainly enhanced by the presence of lipophilic functional groups in a substance. This principle can only be applied to nonparticular substances. Since diamond is water insoluble and has no lipophilic functional groups, an uptake and accumulation across lipophilic tissues can therefore be excluded. These arguments have been the basis for the waiving of the IUCLID endpoint "Bioaccumulation: aquatic/sediment". Literature data indicate that nano diamond may exhibit water soluble/dispersible properties against this background a subsequent bioaccumulation test on fish would have to be performed in order to fulfill the information requirements. Performing of the test (54, ,500 ), test monitoring and creation and completion of the corresponding IUCLID endpoint 5.3 and endpoint summary (1,000 ; equivalent to the efforts of 1 working day) would lead to additional costs between 55,000 and 113,500 for one tested substance. Additional costs: In the preamble to this case study it has been assumed that a lead dossier for nano diamond for a tonnage band between 1-10 t/y would have to be prepared. Therefore only information requirements of Annex VII would be applied to in this dossier. Since the abovementioned testing needs would be relevant for tonnage bands above 10 t/y, this test can be regarded as not obligatory for this case. Additional costs: 0 Option 15: Specify that adsorption/desorption behaviour of nanomaterials should not be assessed based on K d values derived from K oc and K ow The current lead dossier of diamond would be subject to an update in which data to nano diamond would be submitted subsequently. In order to predict the environmental fate of a substance, knowledge on its adsorption/desorption behaviour on/from solid surfaces is one of the key parameters. In this option the adsorption/desorption behaviour (K d ) should be assessed experimentally, instead of being estimated from the K oc and K ow values. It is regarded as necessary to deviate from the previous methods of predicting this parameter from the distribution coefficients K oc and K ow since the argument of insolubility of particles cannot be applied anymore on nanoparticles. Table R of the "Guidance on information requirements and chemical safety assessment Chapter R.7a: Endpoint specific guidance" gives an extensive overview on applicable testing methods for the measurement of adsorption. The costs for performing the appropriate method would vary between 2,500 5,187 (Adsorption Screening Test, according to OECD 121) and 32,000

38 38 (Adsorption/Desorption according to OECD 106; no price for the corresponding test has been calculated in the cited Fleischer List) for one tested substance. Taking also into account that 1 working day would be required for test monitoring and for completion of the corresponding IUCLID endpoint (IUCLID "Adsorption/desorption), the resulting costs for updating this endpoint would amount to 3,500 and 33,000. Additional costs: 3,500 33,000 In the preamble to this case study it has been assumed that a lead dossier for nano diamond for a tonnage band between 1-10 t/y would have to be. Therefore only information requirements of Annex VII would be applied to this dossier. Since the abovementioned testing needs would be relevant for tonnage bands above 10 tonnes/year, these tests can be regarded as not obligatory for this case. Additional costs: 0 Option 20: Require identification of uses and exposure assessment of the nanoform The existing lead dossier for diamond does only refer to bulk diamond and the included chemical safety assessment does not address nano diamond. When the existing lead dossier for diamond will have to be updated, uses of nano diamond will have to be collected and a separate chemical safety assessment will have to be performed for nano diamond. Nano diamond is not classified as hazardous and it is currently assumed that this will be valid after the hazard assessment which means that an exposure assessment and a risk characterisation will not be required. As it is assumed that only one nanoform of diamond exists, no additional assessments of other forms have to be performed. Therefore, no additional costs besides costs for an update of the existing lead dossier are expected. Compliance costs: not predictable In case a separate lead dossier has to be elaborated for nano diamond, the relevant tonnage band would be 1-10 tpa. According to Article 14 REACH, a chemical safety assessment shall be performed and a chemical safety report completed for all substances subject to registration in quantities of 10 tonnes or more per year per registrant. This means that a CSA would not be required for nano diamond. Additional costs: not expected

39 39 Table A4-1: Overview on compliance costs for nano TiO 2, nano ZnO, nano diamond Baseline options and resulting compliance costs ( ) No. No. JRC * Nano TiO 2 Nano ZnO ** Nano diamond*** Size as characteriser Size as identifier Size as characteriser Size as identifier Size as characteriser Size as identifier ,000 9,000 9,000 9,000 1,800 1, ,000 16,000 10,000 16,000 12,000 24,000 12,000 24,000 5,500 5, ,600 27,660 20,600 27,660 29,900 40,490 29,900 40,490 10,300 13,500 10,300 13, ,000 1,000 1,000 1,000 1,000 1, ,000 2,000 3,000 3,000 1,000 1, ,250 38,500 4,500 38,500 32,500 65,000 6,750 65,000 7,750 15,500 2,250 4, , ,500 2,000 2,000 2, ,000 2,000 3,000 3,000 2, ,000 24,000 18,000 24,000 22,000 31,000 22,000 31,000 14,000 17,000 14,000 17, , ,500 55, , , , , ,500 55, , ,000 64,000 7,000 64,000 10,500 99,000 10,500 99,000 3,500 32, Not predictable Not predictable Not predictable Not predictable Not predictable Not predictable : 146, , , , , , , , , ,800 37,350 45,800 Average per nanoform 73, ,080 64, ,080 96, ,997 88, , , ,800 37,350 45,800 *: Due to reasons of simplification the project team assumed that only nano TiO 2 and surface treated nano TiO 2 would be subjected to an update process or elaboration of a new registration dossier. Resulting costs might increase with further nanoforms of TiO 2. **: Due to reasons of simplification the project team assumed that only nano ZnO and two surface treated nanoforms of ZnO would be subjected to an update process or elaboration of a new registration dossier. Resulting costs might increase with further nanoforms of ZnO. ***: Due to reasons of simplification the project team assumed that only nano diamond would be subjected to an update process or elaboration of a new registration dossier. Resulting costs might increase with further nanoforms of diamond.

40 40 5 Extrapolation of compliance costs to industry Based on the elaborated table the following overview of proposed cost range per option and per nanomaterial can be given which also serves as a basis for the subsequent extrapolation of compliance costs for industry: Table A4-2: Overview on compliance costs (in ) for baseline options Compliance costs for each option (in ) Option Annex VII Annex VIII Annex IX Annex X 1 2,000 4,500 2,000 4,500 2,000 4,500 2,000 4, ,500 6,000 9,000 6,000 9,000 6,000 9, ,800 19,830 11,800 19,830 11,800 19,830 11,800 19, ,000 1,000 1,000 1, ,000 1,000 1,000 1, ,250 4,500 10,833 21,667 10,833 21,667 10,833 21, ,000 2,000 1,000-2,000 1,000-2, ,000 2,000 1,000 2,000 1,000 2, ,000 17,000 14,000 17,000 14,000 17,000 14,000 17, , ,500 55, , ,000 66,000 7,000 66, Not predictable Not predictable Not predictable Not predictable Final costs: 39,050 54,830 48,633 77, , , , ,997 Please note that the assessed options have different impacts on costs, depending on the tonnage band. Options, which would affect information requirements for Annex VII under REACH, would also have to be fulfilled for the higher Annexes (VIII, IX and X). In contrary, options which would affect information requirements for Annexes IX and X, would have no impacts on Annex VII and VIII. In chapter 8 of the final report additional cost estimations for untreated nanomaterials have been undertaken (see Table 8.2), which correlate to lead dossiers including information on bulk and nanoform of a substance). The analogous compliance costs for the aforementioned case read as follows:

41 41 Table A4-3: Compliance costs for elaboration of registration dossiers which only include information on bulk and non-surface treated nanoform nanomaterials/-forms Tonnage band 1-10 t/y t/y 100 1,000 t/y > 1,000 t/y Percentage distribution 10 % 20 % 50 % 20 % Resulting lead dossiers Testing costs per nanoform ( ) 39,050 54,830 48,633 77, , , , ,997 Final costs ( ) 195,250 1,096, ,330 3,119,880 2,765,825 25,749,700 1,106,330 10,319,880 Overall final costs ( ) 4,5 40 mio Given that 10 % of the initially postulated 500 2,000 nanomaterials are untreated nanoforms the elaboration of lead dossiers that include information on bulk and nanoform would lead to additional costs between 4,5 mio and 40 mio (accumulated final costs, according to last row of the aforementioned table) if the majority of the updated lead dossiers (50 %) are assumed to be in the tonnage band 100 1,000 t/y. According to the introduced grouping-approach (see Figure 8.1), affected nanomaterials can be allocated in 9 formgroups. Within these formgroups it is postulated to apply the provisions of the option scenario on one representative nanomaterial (e.g. the most reactive form) and to apply extensive read-across approach on the remaining members of the same formgroup. After an examination of the information requirements of the different options the project team concludes that only required tests in options 4, 8, 10, 14, 15 (3.4, 4.2, 4.4, 4.8 and 4.9) can be used as a basis for a read-across or grouping approach. Baseline scenario, applied on elaboration of lead dossiers that include information on bulk and surface treated nanoform, results in compliance costs as follows:

42 42 Table A4-4: Compliance costs for elaboration of registration dossiers which include information on bulk and surface treated nanoform Compliance costs for 450 1,800 surface treated nanoforms Tonnage band 1-10 t/y t/y 100 1,000 t/y > 1,000 t/y Percentage distribution 0 % 20 % 50 % 30 % Resulting nanoforms Testing costs per nanoform/formgroup ( ) 39,050 54,830 48,633 77, , , , ,997 Final costs ( ) 0 4,376,970 28,078,920 Final costs after grouping: Overall final costs ( ) 0 3,096,970 21,678,920 24,892, ,747,300 9,292,425 72,147,300 14,935, ,318,380 5,575,455 43,318, mio 400 mio /18 mio mio (after grouping/read across) Compliance costs between 18 mio and 140 mio are expected for 450 1,800 surface treated nanomaterials, if a partial read-across approach as outlined above can be applied. If each nanomaterial had to be tested separately and assessed according to the information requirements of Annexes VII X, the resulting testing costs would be significantly higher (between 44 mio and 400 mio ). As it has already been explained in the main report, this approach can only be only be performed if testing of only one representative within one formgroup is considered as sufficient in order to fulfil the information requirements of the remaining members of the same formgroup and if the surface treated nanoforms cannot be registered as mixtures. If lead dossiers would be elaborated that include only information on surface treated nanoforms, analogous applying of grouping and partial read-across results in compliance costs as follows :

43 43 Table A4-5: Compliance costs for elaboration of registration dossiers which only include information on surface treated nanoform Compliance costs for 450 1,800 surface treated nanoforms Tonnage band 1-10 t/y t/y 100 1,000 t/y > 1,000 t/y Percentage distribution 5 % 53 % 40 % 2 % Resulting nanoforms Testing costs per nanoform ( ) Final costs ( ) Final costs after grouping: Overall final costs ( ) 39,050 54,830 48,633 77, , , , , ,900 4,934, ,900 3,434,700 11,817,819 74,409,138 8,361,819 57,449,138 19,913, ,397,840 7,433,940 57,717, ,697 9,287, ,697 2,887, mio 270 mio/17 mio 120 mio (after grouping/read across) Partial applying of read-across approach would reduce the compliance costs from initially 33 mio mio to 17 mio mio. The overall compliance costs would sum up to 22,5 mio mio ((4,5 mio 40 mio ) + (18 mio -140 mio )).

44 44 6 Impacts on Authorities According to the ECHA "General Report 2010 The year of registration", dossiers were submitted at ECHA and accepted for processing. The submitted number of dossiers correlated to 3,400 registered phase-in substances. The following overview has been extracted from the report cited above in order to emphasize the disparity in the number of submitted dossiers of the states within the EEA. Table A4-2 shows the distribution in percentage terms of the submitted dossiers for each Member State: Table A4-2: Dossiers submitted in all Member States of the European Economic Area for the 2010 deadline Since the number of registered substances by 2010 was far less than initially expected and since it is furthermore expected that this trend will be reflected in the forthcoming registration period in 2013 with 13,300 new dossiers (according to the presentation of ECHA s Sixth Stakeholders Day from 18 May 2011; the estimated number of substances to be registered has meanwhile been adjusted downwards from 3,500 to 2,300). It is furthermore assumed that between 500 and 2,000 nanomaterials are affected by registration obligations under REACH. Given an estimated number of between EU manufacturers/ importers it is assumed that approximately 1,500 dossiers might be submitted at the ECHA. Compared to the vast number of EU manufacturers/importers who are placing non-nanomaterials on the EU market and compared to the vast amount of substances which are listed in the EINECS, it can be inferred that incurring efforts and resulting costs for the Competent Authority, in order to implement ECHA s draft decisions on non-compliant dossiers, can be regarded as compliance costs,

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