EUROPEAN COMMISSION

DIRECTORATE-GENERAL
ENVIRONMENT Directorate D - Water, Chemicals & Cohesion
ENV.D.1 – Chemicals

EUROPEAN COMMISSION

DIRECTORATE-GENERAL
ENTERPRISE AND INDUSTRY Directorate G – Chemicals, Metals , Forest-based and Textile Industries
ENTR.G.1 - REACH

C RITERIA FOR INCLUSION OF SUBSTANCES IN ANNEX IV OF

R EGULATION ( EC ) NO

. 1907/2006

CONCERNING THE R EGISTRATION , E VALUATION , A UTHORISATION AND R ESTRICTION

OF C HEMICALS (REACH)These criteria were endorsed by the REACH Competent Author ities on 19 October 2007. They constitute the first step in the review of Annex IV of the REACH Regulation to be carried out by the Commission (Ar ticle 138(4)). It should be not ed that the final decision
on the inclusion on to or dele tion of substances from Anne x IV will be taken through Comitology (regulatory pro cedure with scrutiny).

The draft document was prepared by DHI , Protection Through Knowledge (PTK) Ltd.,
and Milieu on the basis of comments to th e former draft version 2007.08.27 received from the Commission on 11, 14 and 21 September 2007, the meeting of the CA SubGroup(Annexes) on 1 October, 2007 and subseq uent comments from CAs and industry (received from the Commi ssion on 12 October 2007).

### 1 INTRODUCTION

One of the main purposes of Regula tion (EC) No 1907/2006 of the European
Parliament and the Council of 18 Decembe r 2006 (REACH) is to ensure a high level of protection of human health a nd the environment. REACH is based on the principle that manufacturers, importe rs and downstream us ers shall ensure that the manufacture, placing on the mark et and use of substances shall not adversely affect human health or the e nvironment. As part of the registration procedure, the registrant is required to document that s ubstances can be used in a safe manner, with regard to hum an health and the environment.

Annex IV of REACH identifies substa nces that are exempted from the registration, evaluation and downstr eam user provisions of REACH on the basis that sufficient informati on is known about these subst ances so that they are considered to cause minimum risk because of their intrinsic properties (Article 2(7)(a)).

The current Annex IV of REACH essentia lly reproduces the list of substances excepted from the obligation to register under the present Existing Substances Regulation (Regulation (EEC ) No 793/93). This list has not been revised since then, except with the addition of one substance, Cellulose Pulp, during the progress of the Regulation thr ough the regulatory process.

According to REACH (Article 138(4)), th e Commission is to carry out a review of Annex IV by 1 June 2008, in order to consider whether additional substances
should be added to the Annex and whethe r substances currently in the Annex
meet the basic criterion that “sufficient information is known about these substances so that they are considered to cause minimum risk because of their intrinsic properties”.

This review requires defi nition of the core requi rements of “sufficient information” and “minimum risk” and the development of additional criteria for
the evaluation of this information and th e potential risk of substances to be included, or already incl uded, in the Annex. Once the Commission, together with an advisory group of Member States and other stakeholders, have agreed on these criteria, the minimum data-set required and a form at for adding or removing substances from Annex IV, the in tent is to review each current entry and proposed new entry to see if it meets the criteria for inclusion in Annex IV, documenting the conclusion for the entry, and proposing addition to, or deletion from, the list as appropriate.

This document provides a proposal for th e assessment of whether substances should be included in Annex IV (section 2), the information and documentation requirements when making a submission re questing the addition of an additionalsubstance to the current Annex IV (sections 3 and 4), and the subsequent review process (section 5).

For the purposes of this review,

 “Sufficient information” means: the information specified in section 3 which is considered to be necessary to confirm the “minimum risk because of intrinsic properties” posed by a substance.

 “Minimum risk because of intrinsic properties” means: that negligible risk can be assumed on the basis of the intrinsic properties of the
substance.

It is important to note th at the principle of “minimum risk because of intrinsic properties” is clearly different from th e approach applied in registration under REACH. The proposed criteria for mini mum risk should apply at all tonnage levels and need to be independent of th e specific uses of the substance and the resulting exposure of humans and the en vironment as all future uses cannot possibly be predicted. Consequently, the rules described in Annex XI section 3 do not apply as they are based on an e xposure assessment of a known use of the substance. Likewise, the tonna ge of substances is not considered as the future level of manufacture and import of a substance cannot be predicted. The information requirements and associated criteria are therefore the same regardless of the tonnage currently manu factured in, or imported into, the EU.

In developing the document, the fo llowing principles were followed:

• A concrete description of what cons titutes a “minimum risk because of intrinsic properties” needed to be developed.

• Based on the description of “minimum risk because of intrinsic properties” information re quirements were defined.



### 2 CRITERIA FOR DETERMIN ING MINIMUM RISK
BECAUSE OF INTRINSIC PROPERTIES

As following Article 2.7(a) minimum risk in this exercise is based on intrinsic properties; use and exposure information will not be included. Using only information on intrinsic properties of th e substance leads to a more uncertain determination of the magnitude of risk. Du e to this inherent uncertainty and the need to include only substances which pos e a minimum risk, strict hazard-based criteria needed to be developed. Such criteria are proposed below. Minimum risk because of intrinsic properties can onl y be concluded if all criteria for physicochemical properties, toxicologi cal properties and ecotoxicological properties mentioned in sections 2.1 to 2.3 are met.

### 2.1 Physicochemical properties

All the following criteria must be met:

1. The data specified in section 3 on Information requirements must be provided.

2. The substance does not meet the criteri a for classification as dangerous in
accordance with Directive 67/548/EEC.

3. The substance does not meet any of the criteria laid out in Appendix IA of this document for the following endpoints (a. to n.):

a. Explosive , in Divisions 1.1, 1.2, 1.3, 1.4 and 1.5;

b. Flammable gas , Category 1 or Category 2;

c. Flammable liquid , Category 1, Category 2, Category 3 or Category 4;

d. Flammable solid, Category 1 or Category 2;

e. Oxidising gas , Category 1;

f. Oxidising liquid , Category 1, Category 2 or Category 3;

g. Oxidising solid, Category 1, Category 2 or Category 3;

h. Corrosive to metals, Category 1;

i. Self-reactive substance , Types A to F;

j. Pyrophoric liquid, Category 1;

k. Pyrophoric solid, Category 1;

l. Self-heating substance , Category 1 or Category 2;

m. Substance which in contact with water emits flammable gas

, Category 1, Category 2 or category 3;

n. Organic peroxide, of Type A to F.

### 2.2 Toxicological properties

All the following criteria must be met:

1. The data specified in section 3 on Information Requirements must be provided.

2. The substance does not meet the criteri a for classification as dangerous in
accordance with Directive 67/548/EEC.

3. The substance does not meet the criteria for a substance of very high concern (SVHC) in accordance with Article 57 of REACH.

4. The intrinsic properties of the substance are well below the criteria for classification as dangerous in accord ance with Directive 67/548/EEC (using all available data for all relevant toxicological endpoints). This is demonstrated by an absence of ‘ significant toxicological effects ’ in the relevant toxicological studies.

5. Absence of “ significant toxicological effects” means:

a. Acute oral toxicity: no evident toxicity 1 at dose levels ≤ 2000 mg/kg. Additionally the LD 0 must be > 5000 mg/kg where the substance has been tested at this level;

b. Acute dermal toxicity: no evident toxicity 2 at dose levels ≤ 2000 mg/kg. Additionally the LD 0 must be > 5000 mg/kg where the substance has been tested at this level;

c. Acute inhalational toxicity: no evident toxicity 2 at an exposure level
of ≤ 20 mg/litre/4h for gases or vapours and ≤ 5 mg/litre/4h for aerosols or particulates. Additionally the LD 0 must be > 50 mg/litre/4h for gases or vapours and > 12.5 mg/litre/4h for aerosols or particulates where the substan ce has been tested at this level;

d. Skin irritation: the substance does not meet the criteria for (a) assignation of the Risk Phrase R66 in Annex VI of Directive 67/548/EEC or (b) mild skin irritation according to the criteria laid down in Annex 1B of this document;

e. Eye irritation: the substance does not meet the criteria for “mildly irritating to eyes” according to the cr iteria laid down in Annex 1B of this document;

1 Comprising: an absence of clinical signs of toxicity during the post-dosing observation period, no treatment-related body weight changes, no macroscopic findings at autopsy and no microscopic findings in cases where histopathological investigations have been undertaken.f. Sensitisation: no evidence of sensiti sation potential from structural alerts, in animal tests (no eviden ce of a positive response in any animal tested) and no human evidence of sensitisation potential (no human cases of sensitisation reported);

g. Repeated dose toxicity by the oral route: no evident toxicity 2 at ≤ 500 mg/kg/day (NOAEL) in the case of a 90-day study 3 . Results from longer-term (e.g. 2-year) studies shou ld be evaluated by the applicant on a case-by-case basis using this criterion as a guide. For the purpose of reviewing current Annex IV entries, if only results from short-term studies (e.g. 28 day) are available, then these data should be evaluated on a case-by-case basi s using this criterion as a guide;

h. Repeated dose toxicity by the de rmal route: no evident toxicity 3 at
≤ 1000 mg/kg/day (NOAEL) in the case of a 90-day study 4 . Results from longer-term studies should be evaluated by the applicant on a case-by-case basis using this criter ion as a guide. For the purpose of reviewing current Annex IV entries, if only results from short-term studies (e.g. 28 day) are availabl e, then these data should be evaluated on a case-by-case basis us ing this criterion as a guide;

i. Repeated dose toxicity by the i nhalation route: no evident toxicity 3 at
≤ 2.5 mg/litre/6h/day (NOAEL) in the case of a 90-day study. 4 Results from longer-term studies s hould be evaluated by the applicant on a case-by-case basis using this criterion as a guide. For the purpose of reviewing current Annex IV entries, if only results from short-term studies (e.g. 28 day) are available, then these data should be evaluated on a case-by-case basi s using this criterion as a guide;

j. Carcinogenicity: no evid ence of carcinogen ic potential based on available data and application of relevant (Q)SAR models or other structural alerts;

k. Mutagenicity: no evidence of mutageni c potential in vitro or in vivo nor from the application of rele vant (Q)SAR models or other structural alerts;

l. Reproductive toxicity: no evidence of reproductive toxicity at

≤ 1000 mg/kg/day by the oral route, at ≤ 2000 mg/kg/day by the
dermal route or at ≤ 20 mg/litre/6h/day for gases or vapours or

≤ 5 mg/litre/6h/day for aerosols or particulates (limit tests) by the

2 Comprising: an absence of clinical signs of toxicity during the period of the study, e.g., including behavioural changes, no treatment-related body weight or food consumption changes, no macroscopic findings at autopsy, no treatment-related effects on organ weights, clinical ch emical or haematological parameters or urinalysis, no treatment-related microscopic findings.

3 The data set for application for an exemption from registration will normally include a 90-day studyinhalation route 4 , nor from the application of relevant (Q)SAR models or other structural alerts;

m. Harm to breastfed babies: the subs tance should not interfere or be suspected to be able to interfer e with lactation, nor should it be a substance which may be present in breast milk or be suspected to be able to pass over to breast milk;

n. Narcotic effects: the substance sh ould not cause any signs of CNS depression even after prolonged or repeated exposure;

o. Danger of cumulative effects: the substance should not have been
shown to accumulate in the human body or be suspected to have properties leading to such accumulation.

6. The substance must not meet any of th e screening criteria for PBT or vPvB
set out in the TGD for the CSA/CSR 5 nor must it be on the PBT working group list.

7. The substance shall not be identified or suspected to have endocrine activity from in vivo or in vitro tests, nor fr om the application of relevant (Q)SAR models or other structural alerts, wh ich may raise any concern for endocrinedisrupting properties (DG Envi ronment, ENV.D4./ETU/2005/0028r; http:/ec.europa.eu/envi ronment/endocrine/documen ts/final_report_2007.pdf)

8. The substance shall not be listed in Annex II or Annex III of the Cosmetic
Directive 76/768/EEC.



### 2.3 Ecotoxicological properties

All the following criteria must be met:

1. The data specified in section 3 on Information requirements must be provided.

2. The substance does not meet the criteri a for classification as dangerous in
accordance with Directive 67/548/EEC.

3. The substance does not meet the criteria for a substance of very high concern
in accordance with Article 57 of REACH.

4. The intrinsic properties of the substance are well below the criteria for classification as dangerous in accord ance with Directive 67/548/EEC (using all available data), i.e.:

4 There is currently limited scientific basis for the in dicated figures for the dermal and inhalation routes.

5 The TGD for the CSA/CSR is not yet finalised and, thus, the best available draft TGD will be used.a. The substance shall have a very low potential to bi oaccumulate in aquatic species, e.g. fish, i.e. experimentally determined
bioconcentration factor is < 10. For organic substances an alternative criteria of log Pow < 2.0 can be applied.

b. The substance shall be readily bi odegradable (excluding inorganic substances)

c. The aquatic toxicity shall fulfil both of the following criteria:

i. Acute, short-term EC/LC50 > 1000 mg/L, or > water solubility, or no significant adverse effects recorded at 100 mg/l in acute, short-term aquatic toxicity tests and validated QSAR data showing acute e ffects (EC/LC50) > 1000 mg/l.

ii. Chronic long-term NOEC > 10 mg/L

5. The substance must not have advers e effects on terrestrial organisms, meaning that no adverse effects are reported in any of the tests required under Annex IX of the REACH Regulation at the maximum test concentrations prescribed by the respective OECD guidelines.

6. The substance must not meet any of th e screening criteria for PBT or vPvB
set out in the TGD for the CSA/CSR 6 nor must it be on the PBT working group list.

7. The substance shall not be identified or suspected to have endocrine activity from in vivo or in vitro tests, nor fr om the application of relevant (Q)SAR models or other structural alerts, wh ich may raise any concern for endocrinedisrupting properties (DG Envi ronment, ENV.D4./ETU/2005/0028r; http:/ec.europa.eu/envi ronment/endocrine/documen ts/final_report_2007.pdf)

8. The substance shall not present a risk to the ozone layer, i.e. the substance
shall not be included in Annex I to EC 2037/2000.



### 3 INFORMATION REQUIREMENTS

The information required in a submissi on requesting the addition of a substance
to Annex IV shall be sufficient for an evaluation of the fulfillment of the criteria for determining minimum risk because of intrinsic properties. The information
shall consist of:

1. The information needed for identifica tion of the substanc e (as defined in REACH Annex VI, section 2).

6 The TGD for the CSA/CSR is not yet finalised and, thus, the best available draft TGD will be used.2. The standard information correspo nding to the endpoints set out in Annex VII, Annex VIII, Annex IX a nd Annex X, subject to the following
clarifications:

 The specific rules for adaptation provided in column 2 of the Annexes apply, in rela tion to exceptions from the standard information requirements listed above except when these are
based on exposure or risk considerations ;

 Information is required on all the physicochemical properties of the substance according to the re quirements in Annexes VII and
IX with the clarification that in formation is not required for the endpoints 7.2 Melting/freezing point, 7.4 Relative density, 7.6 Surface tension, 7.15 Stability in organic solvents and identity of relevant degradation products, and 7.16 Dissociation constant;

 Toxicological information is required sufficient to demonstrate
that the criteria set out in section 2 of this document have been met and referring to requireme nts in Annexes VII-X, as appropriate (information according to Annex X is only required when such studies are available);

 Ecotoxicological information suffi cient to demonstrate that the
criteria set out in section 2 of this document have been met and referring to requirements in Anne xes VII-X, as appropriate, with
the clarification that a minimum of one long-term toxicity study as described in endpoint 9.1 (Annex IX) for the most sensitive organism (crustacean or fish) is always required (information according to Annex X is only required when such studies are available).

3. All available test data and non-test data on the substance and its known
metabolites. This includes the information in literature and databases and, when applicable, information obtained from (Q)SARs, grouping of
substances or read-acro ss approach, in vivo and in vitro testing, and epidemiological studies, cf. Annex XI section 1. If such information is used, in accordance with Annex XI, this must be fully justified and documented. In this context, available information from risk and hazard assessments performed under intern ational, national and Community programmes or legislation as well as voluntary initiatives may be used to provide reliable information on intrinsic properties.

4. Robust study summaries, in accordan ce with the IUCLID 5 manual and the OECD HPV Chemicals Programme Manual shall be provided for a minimum of one key study per endpoint for physicochemical, toxicological and ecotoxi cological properties. If the key study for any toxicological or ecotoxicological endpoi nt is not the study giving rise tothe highest concern, the use of the particular key study must be fully justified and robust study summaries shall be provided for the study or studies showing a higher effect that the key study. Full study reports need not be submitted but the applicant s hould be in legitimate possession of, or have permission to refer to, the fu ll study report and be able to submit it to the European Commission or the contractor upon request. Evidence of such rights must be available on request (e.g. ownership, letter of access).

5. When the results submitted are not in accordance with publicly available sources (i.e. ESIS, IUCLID,...), the a pplicant must present scientific judgement which justifies that the key studies in the submission are superior to the publicly available studi es showing different results; as a minimum the applicant is requested to review the information in the
IUCLID database.

6. The information submitted shall be sufficient to enable a conclusion to be reached on the intrinsic hazard of the substance, for each relevant endpoint. The information shall be presented clearly and succinctly.

7. If the general rules for adaptation of the standard testing regime as described in Annex XI, sections 1 and 2, have been applied, their use must be fully justified. As previous ly indicated the rules described in Annex XI section 3 do not apply as they are based on an exposure assessment and, thus, a known use of the substance; consequently exposure resulting from unknown future uses cannot be addressed.

8. Commonly known substances, where ther e is clear scient ific evidence that prolonged daily and continuous human and environmental exposure
does not lead to more than minimum risk may be evaluated case-by-case as the information required in Anne xes VII to X would not add useful data to the already available information. This approach could be warranted for substances such as sugar which can be considered to
constitute a minimum risk even though a full dataset may not be available. Waiving of standard information requirements for such substances may refer to Annex XI, particularly sections 1.1 (Use of existing data) and 1.2 (Weight of ev idence). Minimum risk can, however,
not be concluded based alone on a Community risk assessment not resulting in risk management measures being recommended.

9. If grouping of substances and the r ead-across approach are applied, in accordance with Annex XI section 1.5, th is must be fully justified and documented. This means that unambiguous identification of the substances included in the grouping and information on the endpoints where the approach is applied must be clearly provided.10. Information need not be provided if testing is not technically possible due to the intrinsic physicochemical properties of a substance, cf. Annex XI section 2. If waiving of the requ irement for information is applied for this reason in accordance with Annex XI, it must be fully justified and
documented.

### 4 DOCUMENTATION REQUIREMENTS

The following documentation requirements must be met:

1. Submissions to be considered for th e inclusion of an additional substance
in Annex IV shall consist of a dossier including:

 An overall conclusion from the applicant on whether the
substance meets the criteria laid down in this document, with justification;

 A conclusion (descriptive and numerical) per endpoint based on consideration of the information required; and

 The information specified in section 3 on ‘Information requirements’ and a completed format in accordance with the instructions in Appendix 2.

2. The information in the dossier must be clearly presented in accordance
with these instructions and the info rmation requirements. The information in the dossier should be in English. Any submission with an incomplete or unclear dossier will be rejected without further consideration.

3. If there is publicly available information on the substance or known metabolites of the substance, not addr essed in the submission, which leads to any doubt on the potential risk of the substance, then the submission will be rejected without fu rther consideration.

4. If robust study summaries or other relevant information, e.g. (Q)SAR
results with clear justification, are no t presented in a clear manner for all key studies, then the submission will be rejected without further
consideration.

5. Submissions to be considered for de letion of a substance in the existing
Annex IV shall include a dossier containing a conclusion that the
substance does meet the criteria laid down in this document. Documentation and justification sha ll be provided by completion of the relevant sections of the format (Appendix 2).

### 5. PROCESS

5.1 Submissions seeking the addition to or deletion of a substance from the existing Annex IV

Submissions seeking the addition or deletion of an entry to Annex IV shall be submitted by 30 November 2007 to the national competen t authority of the country in which the applicant is based or to one of the follo wing industry associati ons (CEFIC, CONCAWE, REACH Alliance), with a copy to the Commission. 7

Only one proposal for each substance should be submitted to the Member States and industry associations (see above). Due to limited resources and the short timescales
involved in the review Member States and stak eholders should co-ordinate their efforts to achieve this end. Multiple proposals for a subs tance will be assessed separately rather than jointly due to resource constr aints (also see point 4.3 above).

The Member State or industry association to whom the submission was made will screen the proposals against the agreed criteria and, if satisfied that the criteria and information requirements are fulfilled, forward the subm ission to the contractor and the Commission 8

. If a submission does not meet the information re quirements or criteria it may be rejected by the Member State or industry association. Su ch rejection shall be communicated to the applicant and the Commission 9 with a brief justification for such rejection following a standard format to be developed by the cont ractor. If an incomplete submission is not rejected by the Member State or industry as sociation then an explanation of why the
submission does not meet the criteria s hould be forwarded by the MS or industry
association concerned to the Commission.

If one of the criteria is not met the submissi on to be considered for the inclusion of an
additional substance in Annex IV will be re jected by the contractor without further
consideration of other criteria.

The contractor will evaluate the proposals submitted to it by Member States and the industry associations and forward a summary and conclusion on either addition to, or deletion from, Annex IV to the Commission.

The strict deadline for the Member States or industry associations to forward submissions satisfying the requirements set out in this document to the contract or and the Commission shall be 10 January 2008.

7 ENV-reach-review-annex-IV@ec.europa.eu and ENTR-AnnexIV-review@ec.europa.eu

, mentioning in the subject line: “Submission of prop osal for inclusion in/deletion from Annex IV”

8 AnnexIV@dhigroup.com mentioning in the subject line: “Proposal for inclusion in/deletion from
Annex IV” as well as to ENV-reach-review-annex-IV@ec.europa.eu and ENTR-AnnexIVreview@ec.europa.eu

9 ENV-reach-review-annex-IV@ec.europa.eu and ENTR-AnnexIV-review@ec.europa.eu, mentioning in the subject line: “Rejected propo sal for inclusion in/deletion from Annex IV”

### 5.2 Evaluations of substances already in Annex IV

The existing entries of Annex IV will be revi ewed to see if they meet the developed criteria. The following appr oach will be applied:

 The contractor will collect data according to the in formation requirements for inclusion in Annex IV (see above) from easily accessible data sources, i.e. ECOTOX, GESAMP, IUCLID and HSDB. Th e developed format for submissions will be used as far as possible.

 The contractor will group substances in Annex IV, where possible, so that readacross principles can be used for all s ubstances belonging to the same group. The following grouping could be applied:

1. Sugars (e.g. glucose, L-sorbose)

2. Saturated aliphatic monocarboxylic acids (e.g. lauric acid, palmitic acid, stearic acid)

3. Fatty acids (e.g. C6-12, C12-14, C 12-18, C16-18 saturated fatty acids and/or unsaturated fatty acids)

4. Vegetable oils (e.g. sunflower oil, soybean oil, stafflower oil, linseed oil, corn oil)

5. Glycerides (e.g. C10-18, C12-14, C16- 18 and C18 unsaturated, C16-18 and mono and di-C18 unsaturated)

6. Unsaturated aliphatic acids and their salts (e.g. oleic acid and potassium oleate, stearic acid and sodium stearate, calcium distearate)

7. Esters (e.g. D-glucitol monostearate from D-glucitol and stearic acid).

 The contractor will check whether the entries fulfil the data requirements and the criteria above. Bearing in mind the histor ical evidence on substa nces in Annex IV,
the burden of proof is directed at identi fying evidence of human health or
environmental effects according to the above criteri a. This is as opposed to proposals for additions to Annex IV, wher e the burden of proof is directed at demonstrating compliance with the cr iteria and information requirements
described in section 2 of this document.

 Should the contractor find indications in the information assessed leading to the
conclusion that a substance does not fulf il the criteria the relevant industry association(s) shall be informed. They will be given the opportunity to dispute this by sending information showing that the substance in question does fulfil the
criteria for inclusion in Annex IV.

 The contractor will prepare summaries of the review of the existing entries of

Annex IV.APPENDIX IA

Criteria 10 for identification of hazardous physicochemical properties

1. Explosive. A substance shall not meet the criteria for any one of the divisions 1.1, 1.2, 1.3, 1.4 and 1.5, based on Test Series 2 to 8 in part I of the UN Recommendations on the Transport of Dangerous Goods, Manual of Tests and Criteria according to the following description and the results of the tests laid
down in Table 1 below:

(a) Division 1.1 Substances, mixtures and articles which have a mass explosion hazard (a mass explosion is one which affects almost the entire quantity present virtua lly instantaneously);

(b) Division 1.2 Substances, mixtures and articles which have a projection hazard but not a mass explosion hazard;

(c) Division 1.3 Substances, mixtures an d articles which have a fire hazard
and either a minor blast hazard or a minor projection hazard or both, but not a mass explosion hazard:

(i) combustion of which gives rise to considerable radiant heat; or

(ii) which burn one after another, producing minor blast or projection effects or both;

(d) Division 1.4 Substances, mixtur es and articles which present no significant hazard:

– Substances, mixtures and articles which present only a small hazard in the event of ignition or initiation. The effect s are largely confined to the package and no projection of fragments of appreciable size or range is to be expected. An extern al fire shall not cause virtually instantaneous explosion of almost th e entire contents of the package;

(e) Division 1.5 Very insensitive substa nces or mixtures which have a mass explosion hazard:

10 These criteria are established via the ADR, “ European Agreement Concerning the International Carriage of Da ngerous Goods by Road’ 2007 , which is the legislation applicable to transport of dangerous goods in the European Community and in internationally in all countries that are signatories to the ADR. The ADR is enacted under the auspices of the United Nations Economic Commission for Europe http://www.unece.org/trans/da nger/publi/adr/adr_e.html . Further information on the criteria and on the test methods to be applied can be obtained from the ADR and/or the UN Recommendations on the Transport of Dangerous Goods, Manual of Tests and Criteria UN Recommendations on the Transport of Dangerous Goods, Manual of Tests and Criteria– Substances and mixtures which have a mass explosion hazard but are so insensitive that there is very l ittle probability of initiation or of transition from burning to detonation under normal conditions.

Table 1 Tests necessary to apply the criteria for explosives

Category Criteria

Unstable explosives or explosives of
Division 1.1 to
1.6 For explosives of Divisions 1.1 to 1.5, the following are the core set of tests that need to be performed: Explosibility: according to UN Test Series 2 (section 12 of the UN Recommendations on the Transport of Dangerous Goods, Manual of Tests
and Criteria ). Intentional explosives 11 shall not be subject to UN Test
Series 2. Sensitiveness: according to UN Test Series 3 (section 13 of the UN Recommendations on the Transport of Dangerous Goods, Manual of Tests
and Criteria ). Thermostability: according to UN Test 3(c) (Sub-section 13.6.1 of the UN Recommendations on the Transport of Dangerous Goods, Manual of Tests
and Criteria ). Further tests are necessary to allocate the correct Division.

2. Flammable gas . A substance shall not meet the criteria fo r classification as a flammable gas, Category 1 or Category 2, laid out in Table 2 below,

Table 2 Criteria for flammable gases

Category Criteria

1 Gases, which at 20°C and a st andard pressure of 101.3 kPa: (a) are ignitable when in a mixture of 13% or less by volume in air;

or (b) have a flammable range with ai r of at least 12 percentage points regardless of the lower flammable limit.

2 Gases, other than those of Category 1, which, at 20°C and a standard pressure of 101.3 kPa, have a flammable range while mixed in air.

Note 1: Ammonia and methyl bromide are regarded as flammable gases (special cases).

3. Flammable liquid . A substance shall not meet the criteria for a flammable liquid, Category 1, Category 2, Category 3 or Category 4, laid out in Table 3
below.

11 This comprises substances, mixtures and articles which are manufactured with a view to producing a practical, explosive or pyrotechnic effect.Table 3 Criteria for flammable liquids

Category Criteria

1 Flash point < 23°C and initial boiling point ≤ 35°C

2 Flash point < 23°C and initi al boiling point > 35°C

3 Flash point ≥ 23°C and ≤ 60°C 12

4 Flash point > 60 °C and ≤ 93 °C

4. Flammable solid. A substance shall not meet the criteria for a Category 1 or Category 2 flammable solid, laid out in Table 4 below.

Table 4
Criteria for flammable solids

Category Criteria

1 Burning rate test Substances other than metal powders: (a) wetted zone does not stop fire and (b) burning time < 45 seconds or burning rate > 2.2 mm/s Metal powders burning time ≤ 5 minutes

2 Burning rate test Substances other than metal powders: (a) wetted zone stops the fire for at least 4 minutes and (b) burning time < 45 seconds or burning rate > 2.2 mm/s Metal powders burning time > 5 minutes and ≤ 10 minutes

5. Oxidising gas. A substance shall not meet the criteria for a Category 1 oxidising gas, laid out in Table 5 below.

Table 5 Criteria for oxidising gases

Category Criteria

1 Any gas which may, generally by prov iding oxygen, cause or contribute
to the combustion of other material more than air does.

12 Gas oils, diesel and light heating oils in the flash point range of 55°C to 75°C may be regarded as Category 3 for transport.6. Oxidising liquid. A substance shall not meet the criteria for a Category 1, Category 2 or Category 3 oxidising liquid, laid out in Table 6 below.

Table 6 Criteria for oxidising liquids

Category Criteria

1 Any substance or mixture which, in the 1:1 mixture, by mass, of substance and cellulose tested, spon taneously ignites; or the mean pressure rise time of a 1:1 mixture, by mass, of substan ce and cellulose is less than that of a 1:1 mixture, by mass, of 50% perchloric acid and
cellulose

2 Any substance or mixture which, in the 1:1 mixture, by mass, of substance and cellulose tested, exhibi ts a mean pressure rise time less than or equal to the mean pressure ri se time of a 1:1 mixture, by mass, of 40% aqueous sodium chlorate solution and cellulose; and the criteria for Category 1 are not met

3 Any substance or mixture which, in the 1:1 mixture, by mass, of substance and cellulose tested, exhibi ts a mean pressure rise time less than or equal to the mean pressure ri se time of a 1:1 mixture, by mass, of 65% aqueous nitric acid and cellulose ; and the criteria for Category 1 and

2 are not met

7. Oxidising solid. A substance shall not meet the criteria for a Category 1, Category 2 or Category 3 oxidising solid, laid out in Table 7 below.

Table 7 Criteria for oxidising solids

Category Criteria

1 Any substance or mixture which, in the 4:1 or 1:1 sample-to-cellulose ratio (by mass) tested, exhibits a me an burning time less than the mean burning time of a 3:2 mixture, by mass, of potassium bromate and
cellulose.

2 Any substance or mixture which, in the 4:1 or 1:1 sample-to-cellulose ratio (by mass) tested, exhibits a mean burning time equal to or less than the mean burning time of a 2:3 mixture (by mass) of potassium
bromate and cellulose and the crite ria for Category 1 are not met.

3 Any substance or mixture which, in the 4:1 or 1:1 sample-to-cellulose ratio (by mass) tested, exhibits a mean burning time equal to or less than the mean burning time of a 3:7 mixture (by mass) of potassium
bromate and cellulose and the crite ria for Categories 1 and 2 are not

met.8. Corrosive to metals. A substance shall not meet the criteria for corrosive to metals, Category 1, laid out in Table 8 below.

Table 8
Criteria for substances corrosive to metals

Category Criteria

1 Corrosion rate on steel or aluminium surfaces exceeding 6.25 mm per year at a test temperature of 55 °C.

9. Self-reactive substance. A substance shall not meet the criteria for a self-reactive substance, Types A to F, according to the criteria laid out in Table 9.

Table 9
Criteria for self-reactive substances

(a) Any self-reactive substance which can detonate or deflagrate rapidly, as packaged, shall
be defined as self-reactive substance TYPE A ;

(b) Any self-reactive substance possessing expl osive properties and which, as packaged, neither detonates nor deflagrates rapidly, but is liable to undergo a thermal explosion in that package shall be defined as self-reactive substance TYPE B ;

(c) Any self-reactive substance possessing expl osive properties when the substance or mixture as packaged cannot detonate or defl agrate rapidly or under go a thermal explosion
shall be defined as self-reactive substance TYPE C ;

(d) Any self-reactive substance wh ich in laboratory testing:

(i) detonates partially, does not deflagrate rapidly and shows no violent effect when heated under confinement; or

(ii) does not detonate at all, deflagrates sl owly and shows no violent effect when heated under confinement; or

(iii) does not detonate or deflagrate at all and shows a medium effect when heated under confinement;

shall be defined as self-reactive substance TYPE D ;

(e) Any self-reactive substance which, in laborator y testing, neither detonates nor deflagrates
at all and shows low or no effect when heated under confinement shall be defined as selfreactive substance TYPE E ;

(f) Any self-reactive substance which, in laborator y testing, neither detonates in the cavitated state nor deflagrates at all and shows only a low or no effect when heated under confinement as well as low or no explosive power shall be defined as self-reactive

substance TYPE F ;10. Pyrophoric liquid. A substance shall not meet the criteria for pyrophoric liquid, Category 1, laid out in Table 10 below.

Table 10 Criteria for pyrophoric liquids

Category Criteria

1 The liquid ignites within 5 min when added to an inert carrier and exposed to air, or it ignites or ch ars a filter paper on contact with air
within 5 min.

11. Pyrophoric solid, A substance shall not meet the criteria for pyrophoric solid, Category 1, laid out in Table 11 below.

Table 11 Criteria for pyrophoric solids

Category Criteria

1 The solid ignites within 5 minutes of coming into contact with air.

12. Self-heating substance . A substance shall not meet the criteria for a self-heating substance, Category 1 or Category 2, laid out in Table 12 below.

Table 2.11.1 Criteria for self-heating substances and mixtures

Category Criteria

1 A positive result is obtained in a test using a 25 mm sample cube at 140°C

2 (a) It does not meet the criteria for Category 1; and a positive result is obtained in a test using a 100 mm sample cube at 140°C; Exemptions from (a) for classification in Category 2 (i) a negative result is obtained in a te st using a 100 mm cube sample at 100°C
and
the unit volume of the substa nce is 450 litres or less; (ii) a negative result is obtained in a test using a 100 mm cube sample at 120°C
and
the unit volume of the substance is 3 m 3 or less; (b) It does not meet the criteria for Category 1; and a positive result is obtained in a test using a 100 mm sample cube at 140°C; and it is not a substances exempted under (a), that gives a positive result in a test using a 100 mm cube sample at 100°C;

13. Substance which in contact with water emits flammable gas . A substance shall not meet the criteria for a substance which in contact with water emits flammable gas, Category 1 Category 2 or Category 3, laid out in Table 13 below.Table 13
Criteria for substances or mixtures whic h in contact with water emit flammable

gases

Category Criteria

1 Any substance or mixture which reacts vigorously with water at ambient temperatures and demonstr ates generally a tendency for the gas produced to ignite spontaneousl y, or which reacts readily with water at ambient temperatures such that the rate of evolution of flammable gas is equal to or greate r than 10 litres per kilogram of substance over any one minute.

2 Any substance or mixture which react s readily with water at ambient temperatures such that the maximu m rate of evolution of flammable gas is equal to or greater than 20 l itres per kilogram of substance per hour, and which does not meet the criteria for Category 1.

3 Any substance or mixture which reacts slowly with water at ambient temperatures such that the maximu m rate of evolution of flammable gas is equal to or greater than 1 litre per kilogram of substance per hour, and which does not meet the criteria for Categories 1 and 2.

14. Organic peroxide. A substance shall not meet the criteria for an organic peroxide of Types A to F, laid out in Table 14 below.

Table 14 Criteria for organic peroxides

(a) Any organic peroxide which, as p ackaged, can detonate or deflagrate rapidly shall be defined as organic peroxide TYPE A ;

(b) Any organic peroxide possessing explosive properties and which, as packaged, neither detonates nor deflagrates rapidly, but is liable to undergo a thermal explosion in that package shall be defined as organic peroxide

TYPE B ;

(c) Any organic peroxide possessing explosive properti es when the substance or mixture as packaged cannot detonate or deflagrate rapidly or undergo a thermal explosion shall be defined as organic peroxide TYPE C ;(d) Any organic peroxide wh ich in laboratory testing:

(i) Detonates partially, does not defl agrate rapidly and shows no violent effect when heated under confinement; or

(ii) Does not detonate at all, de flagrates slowly a nd shows no violent effect when heated under confinement; or

(iii) Does not detonate or deflagrate at all and shows a medium effect when heated under confinement;

shall be defined as organic peroxide TYPE D ;

(e) Any organic peroxide which, in labo ratory testing, neither detonates nor deflagrates at all and shows low or no effect when heated under
confinement shall be defined as organic peroxide TYPE E ;

(f) Any organic peroxide which, in labora tory testing, neither detonates in the cavitated state nor deflagrates at all and shows only a low or no effect
when heated under confinement as well as low or no explosive power shall
be defined as organic peroxide TYPE F ;APPENDIX IB

Criteria 13 for identification of mild skin and ey e irritants, based on the results of in vivo testing

Mild skin irritant: A mean value of ≥ 1.5 - < 2.3 has been obtained for erythema/eschar or for oedema from gradings in at least 2 of 3 tested animals from grades at 24, 48 and 72 hours or , if reactions are delayed, from grades on 3 consecutive days after the onset of skin reactions, and the substance ha s not been classified as a skin
irritant based on the criteria laid down in Annex VI of Directive
67/548/EEC.

Mild eye irritant: the substance meets the criteri a laid down in Annex VI of
Directive 67/548/EEC for classifica tion as an eye irritant, namely produces at least in 2 of 3 test ed animals a positive response of: corneal opacity > 1 and/or
iritis > 1, and/or conjunctival redness > 2, and/or conjunctival oedema (chemosis) > 2
- calculated as the mean sc ores following grading at 24, 48
and 72 hours after installation of the test material,

BUT - which fully reverses within an observation period of 7 days

13 These criteria reflect the criteria established for mild skin irritants (category 3) Globally Harmonised System of Classificati on and Labelling of Chemicals (GHS) ( http://www.unece.org/tran s/danger/publi/ghs/ghs _rev00/00files_e.html)

### APPENDIX 2

Format of Dossier

The dossier shall be completed by the appli cant seeking the additi on of a substance to Annex IV, or by applicants advocating for a deletion of a substance from the existing

Annex IV.

Table 1 shall contain a clear iden tification of the applicant and substance in accordance
with the substance identifiers desc ribed in Annex VI, section 1 and 2.

Table 2 shall contain the applicant’s conclu sions (descriptive and numerical) on minimum risk based on the intrinsic propert ies of the substance, which shall be summarised for the main end-points.

Table 3 shall contain a clear identifi cation of substances for which data have been used in accordance with the rules for grouping or read-across approach (set out in Annex XI, section 1.5).

Table 4 shall contain an overview of the information submitted by the applicant, including a confirmation that the informati on requirements in section 3 of the criteria document have been met, confirmation of comp liance with the endpoint-specific criteria, values for each endpoint, and indications of adaptations accordi ng to column 2 of
Annexes VII-X and Annex XI sect ion 1 and 2, if appropriate.

More detailed information shall be provided in Annexes A-C of the submission (see below).

The dossier shall include robust study su mmaries in Annex A of the submission.

A description and justification shall be in cluded in Annex B of the submission, if the specific rules for adaptation of the standa rd information requirements (column 2 in Annexes VII-X) have been applied.

A description and justification shall be in cluded in Annex C of the submission, if the general rules for adaptation of the standard testing regime set out in Annexes VII-X have been applied (in accordance with Annex XI, sections 1 and 2).

Table 1 Identification of applicant and substance (according to Annex VI, section 1 and 2)

1.1 Applicant

1.1.1 Name, address, telephone number, fax
number and e-mail address1.1.2. Contact person

2.1. Name or other identifier of each substance 2.1.1. Name(s) in the IUPAC nomenclature or other international chemical name(s) 2.1.2. Other names (usual name, trade name, abbreviation) 2.1.3. EINECS or ELINCS number (if available and appropriate) 2.1.4. CAS name and CAS number (if available) 2.1.5. Other identity code (if available)

2.2. Information related to molecular a nd structural formula of each substance

2.2.1. Molecular and structural formula (including SMILES notation, if available) 2.2.2 Information on optical activity (if applicable and appropriate) 2.2.3. Molecular weight or molecular weight

range

2.3. Composition of each substance 2.3.1. Degree of purity (%) 2.3.2. Nature of impurities, including isomers and by-products 2.3.3. Percentage of (significant) main impurities 2.3.4. Nature and order of magnitude (......ppm, ......%) of any additives (e.g. stabilising agents or inhibitors) 2.3.5. Spectral data (ultra-violet, infra-red, nuclear magnetic resonance or mass spectrum) 2.3.6. High-pressure liquid chromatogram, gas chromatogram 2.3.7. Description of the analytical methods or the appropriate bibliographical references for the identification of the substance and, where appropriate, for the identification of impurities and additives. This information
shall be sufficient to allow the methods to be reproduced.Conclusion on minimum risk:

The table shall be completed by the applican t. For each of the endpoints listed below,
conclusions on minimum risk based on the intr insic properties of the substance shall be provided (descriptive text relati ng the appropriate data to th e criterion for the endpoints). The results of relevant robust study summari es attached at Annex A shall also be
summarised.



### Table 2 Conclusion on minimum risk

Ref.

No. Properties Summary

Physicochemical properties Explosive properties

Flammability

Oxidising properties

Corrosive to

metals

Self-reactive

substance

Pyrophoric properties;

Self-heating

substance

Substance which
in contact with
water emits flammable gas Organic peroxides

Toxicological information8.1 Skin irritation

8.2 Eye irritation

8.3 Skin sensitisation

8.4 Mutagenicity

8.5 Acute toxicity

8.6 Repeated dose toxicity

8.7 Reproductive toxicity

8.8 Carcinogenicity

8.9 Toxicokinetics

Ecotoxicological information 9.1 Aquatic toxicity

9.2 Degradation

9.3 Fate and behaviour in
the environment

Please also complete the following:

YES NO Is the substance, due to its intrinsic properties, fulfilling the criteria for PBT and/or vPvB, or is it listed in the PBT working group list? Is the substance identified or suspected to haveendocrine disrupting properties?

Is the substance listed in Annex II or Annex III of the
Cosmetic Directive 76/768/EEC?

Is the substance listed in Annex I of EC 2037/2000?Grouping of substances or read-across approach

It shall be stated if grouping of substances or read-across approach has been applied. The identity of the substances or group of substa nces used in the groupi ng or read-across shall be stated below. Identification of the substance for which data have been used according to the rules for grouping of substances or read-across approach shall be given by substance name, CAS number and EINECS or ELINCS number. The reference numbers
from Annexes VII-X should be used to indi cate the endpoints for which grouping or readacross has been applied.

Justification for the grouping or read-across shall be given at Annex C of this dossier; this documentation shall be clearly marked with the substance identity and relevant annex
number.

Table 3 Identification of substances for which grouping or read-across approach has been applied

Identity of substance or group of substances given as IUPAC name, CAS No. and EINECS or

ELINCS Endpoints for which grouping or read-across has been applied (Use reference numbers from Annexes VII-X)Table of information:This table shall be completed by the applicant.Table 4 Overview of information in the submissionAnnex Ref End Points Informationas requiredin section 3of thecriteriadocumenthave beensubmittedCompliancewith criteriaconfirmedValue ofendpointsAdaptationaccording tocolumn 2 ofAnnexes VII-XappliedAdaptationaccording toAnnex XIsections 1 and 2appliedYes/No orNAaccordingto column 2Annex VIIX or AnnexXIYes/No/NA** notappropriateUnit has tobe given foreachindividualendpointYes/NoJustification isto be annexed asseparatedocumentationYes/NoJustification isto be annexed asseparatedocumentationPhysicochemical propertiesVII 7.1 State of the substanceVII 7.3 Boiling pointVII 7.5 Vapour pressureVII 7.7 Water solubilityVII 7.8 Partition coefficient noctanol/waterVII 7.9 Flash pointVII 7.10 FlammabilityVII 7.11 Explosive propertiesAnnex Ref End Points Informationas requiredin section 3of thecriteriadocumenthave beensubmittedCompliancewith criteriaconfirmedValue ofendpointsAdaptationaccording tocolumn 2 ofAnnexes VII-XappliedAdaptationaccording toAnnex XIsections 1 and 2appliedVII 7.12 Self-ignition temperatureVII 7.13 Oxidising propertiesVII 7.14 GranulometryIX 7.17 ViscosityToxicological informationVII 8.1 Skin irritationVIII 8.1.1 In vivo skin irritationVII 8.2 Eye irritationVIII 8.2.1 In vivo eye irritationVII 8.3 Skin sensitisationVII 8.4 MutagenicityVII 8.4.1 In vitro gene mutation in bacteriaVIII 8.4.2 In vitro cytogenicity study inmammalian cells or in vitromicronucleus studyVIII 8.4.3 In vitro gene mutation study inmammalian cellsVII 8.5 Acute toxicityVII 8.5.1 By oral routeVIII 8.5.2 By inhalationVIII 8.5.3 By dermal routeVIII 8.6 Repeated dose toxicityVIII 8.6.1 Short-term repeated dose toxicitystudy (28 days)IX 8.6.2 Sub-chronic toxicity study (90Annex Ref End Points Informationas requiredin section 3of thecriteriadocumenthave beensubmittedCompliancewith criteriaconfirmedValue ofendpointsAdaptationaccording tocolumn 2 ofAnnexes VII-XappliedAdaptationaccording toAnnex XIsections 1 and 2appliedday)VIII 8.7 Reproductive toxicityVIII 8.7.1 Screening forreproductive/developmentaltoxicityIX 8.7.2 Pre-natal development toxicitystudyIX 8.7.3 Two-generation reproductivetoxicity studyX 8.7.2 Developmental toxicity study (ifavailable)X 8.7.3 Two-generation reproductivetoxicity study (if available)X 8.9.1 Carcinogenicity study (ifavailable)VIII 8.8 ToxicokineticsVIII 8.8.1 Assessment of the toxicokineticbehaviour of the substance to theextent that can be derived fromrelevant available informationEcotoxicological informationVII 9.1 Aquatic toxicityVII 9.1.1 Short term toxicity testing oninvertebrates (Daphnia)Annex Ref End Points Informationas requiredin section 3of thecriteriadocumenthave beensubmittedCompliancewith criteriaconfirmedValue ofendpointsAdaptationaccording tocolumn 2 ofAnnexes VII-XappliedAdaptationaccording toAnnex XIsections 1 and 2appliedVII 9.1.2 Growth inhibition study aquaticplants (algae)VIII 9.1.3 Short term toxicity testing on fishVIII 9.1.4 Activated sludge respirationinhibition testIX 9.1.5 Long term toxicity testing oninvertebrates (Daphnia)IX 9.1.6 Long term toxicity testing on fishIX 9.1.6.1 Fish early-life stage (FELS)toxicity testIX 9.1.6.2 Fish short-term toxicity test onembryo and sac-fry stagesIX 9.1.6.3 Fish, juvenile growth testVII 9.2 DegradationVII 9.2.1 BioticVII 9.2.1.1 Ready biodegradabilityIX 9.2.1.2 Simulation testing on ultimatedegradation in surface waterIX 9.2.1.3 Soil simulation testingIX 9.2.1.4 Sediment simulation testingVIII 9.2.2 AbioticVIII 9.2.2.1 Hydrolysis as a function of pHIX 9.2.3 Identification of degradationproductsVIII 9.3 Fate and behaviour in theAnnex Ref End Points Informationas requiredin section 3of thecriteriadocumenthave beensubmittedCompliancewith criteriaconfirmedValue ofendpointsAdaptationaccording tocolumn 2 ofAnnexes VII-XappliedAdaptationaccording toAnnex XIsections 1 and 2appliedenvironmentVIII 9.3.1 Adsorption/desorption screeningIX 9.3.2 Bioaccumalation in aquaticspecies, preferable fishIX 9.3.3 Further information onadsorption/desorptionX 9.3.4 Further information on theenvironmental fate and behaviourof the substance and/or thedegradation products (ifavailable)IX 9.4 Effects on terrestrial organismsIX 9.4.1 Short-term toxicity ininvertebratesIX 9.4.2 Effects on soil micro-organismsIX 9.4.3 Short-term toxicity to plantsX 9.4.4 Long-term toxicity testing oninvertebrates (if available)X 9.4.6 Long-term toxicity testing onplants (if available)X 9.5.1 Long-term toxicity to sedimentorganisms (if available)X 9.6.1 Long-term or reproductivetoxicity to birds (if available)36 Annex A Robust study summaries

Robust study summaries shall be included in Annex A and shall be clearly marked with
the substance name and the reference number of the relevant section in Annexes VII-X.37 Annex B Adaptation according to column 2 of Annex VII-X

A description and justification shall be included in Annex B, if the specific rules for adaptation of the standard information requirements (column 2 in Annexes VII-X) have been applied. The description sh all clearly indicate the substance name and the reference number(s) for the information requirements in Annexes VII-X, where adaptations have been applied.38 Annex C Adaptation according to Annex XI Section 1 or 2

A description and justification shall be incl uded in Annex C, if the general rules for adaptation of the standard testing regime set out in Annexes VII-X have been applied (in accordance with Annex XI, sections 1 and 2). The description shall clearly indicate the substance name and the reference number(s) for the information requirements in Annexes VII-X, where adaptations have been applied.