Review of Annex IV of Reg. 1907/2006 (REACH)

Project group

DHI

Milieu Ltd.

Protection Through Knowledge (PTK) Ltd.

Content of presentation

• Introduction (section 1)• Criteria for determining minimum risk because of intrinsic

properties (section 2)– Physicochemical properties– Toxicological properties– Ecotoxicological properties

• Information requirements (section 3)• Documentation requirements (section 4)

• Process (section 5)– Submission of proposals (including format)– Evaluation of substances already in Annex IV

Introduction to criteria

• Basis for inclusion of substances in Annex IV– “sufficient information is known about these substances so that

they are considered to cause minimum risk because of their intrinsic properties”

• “Sufficient information” means the information considered necessary to confirm minimum risk

• “Minimum risk because of intrinsic properties” means that negligible risk following any known or future use of a substance can be assumed on the basis of the intrinsic properties of the substance

• Consequence: The proposed criteria do not consider specific uses of the substance and the resulting exposure as all future uses cannot be addressed

Criteria for physicochemical properties

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

• Annexes VII and IX - minus melting/freezing point, density, surface tension, granulometry, stability in organic solvents, identity of degradation products, dissociation constant

2. The substance does not meet the criteria for classification as

dangerous in accordance with Dir. 67/548/EEC

3. The substance does not meet criteria for classification under draft Reg. on C & L implementing GHS

• Broad scope (transport), dangerous and non dangerous

Criteria for physicochemical properties

Criterion 3: The substance does not meet any of the criteria for

classification in relation to:

• Explosive

• Flammable gas/liquid/solid

• Oxidising gas/liquid/solid

• Self-reactive/self heating

• Pyrophoric liquid/solid

1. in contact with water emits flammable gas

2. Organic peroxide

3. Corrosive to metals

Criteria for toxicological properties

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

• Annexes VII, VIII and IX

2. The substance does not meet the criteria for classification as dangerous in accordance with Dir. 67/548/EEC

3. Intrinsic properties of the substance are well below the criteria for classification

• Absence of ‘significant toxicological effects’ in relevant toxicological studies

Absence of ‘significant toxicological effects’

• Acute oral/dermal/inhalational toxicity• No evident toxicity at 2000mg/kg or 20/5 mg/litre/4h• LD0 > 5000 mg/kg or 50/12.5 mg/litre/4h

• Irritation • Not R66, nor a mild skin irritant (cat 3) nor mildly irritating to eyes

under GHS

• Sensitisation• No evidence of sensitisation potential from structural alerts, in

animal tests and no human evidence

Absence of ‘significant toxicological effects’

• Repeat dose oral toxicity• No evident toxicity at 500mg/kg/d in 90 day study or 1500 mg/kg in

28 day study• Similar scaled criteria for dermal and inhalation

• Carcinogenicity/mutagenicity• No evidence of C/M potential based on available data, relevant

(Q)SAR models or other structural alerts

• Reproductive toxicity• No evidence at 1000 mg/kg/d orally, scaled for dermal & inhalation• No evidence based on relevant (Q)SAR models or other structural

alerts

Criteria for ecotoxicological properties

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

• Annexes VII, VIII, IX. Data acc. to Annex X, if available

2. The substance does not meet the criteria for classification as dangerous in accordance with Dir. 67/548/EEC

3. Intrinsic properties of the substance are well below the criteria for classification

Well below the criteria for classification

• Very low potential for bioaccumulation• Log Pow < 2.0 unless BCF < 10

• Readily biodegradable

• Aquatic toxicity• Acute, short term EC/LC50 > 1000 mg/L, or• Chronic, long term NOEC > 10 mg/L

Information requirements

• Information for identification of the substance• Standard information related to the endpoints in Annexes

VII-X (with clarifications)• Robust study summaries for one key study per endpoint

– Full study reports need not be submitted, but shall be made available upon request

• General rules for adaptation of the standard testing regime (Annex XI, sections 1 and 2)– Testing does not appear scientifically necessary (use of existing

data, (Q)SAR, grouping/read-across)– Testing is not technically possible– Annex XI, section 3, does not apply as it is based on exposure

assessment

Documentation requirements

• Dossier for submissions to be considered for inclusion of an additional substance in Annex IV– Overall conclusion of compliance with the criteria– A conclusion per endpoint based on the information required– The information required and completed format

• Dossier for submissions to be considered for deletion of a substance in Annex IV– Conclusion that the substance does not meet the criteria– Documentation shall be provided by completion of relevant sections in

the format

• Strict requirements to present complete and clear dossiers• Strict rules for evaluation – e.g., if one of the criteria is not met, the

submission will be rejected without further consideration of other criteria

Format for submission

• Substance identification (according to Annex VI section 2)

• Conclusion on minimum risk – descriptive and numerical• Physicochemical properties, summary

• Toxicological information, summary of each endpoint 8.1-8.8

• Ecotoxicological information, summary of each endpoint 9.1-9.3

• Identification of substances for which read across or grouping has been applied

• Overview of information in the submission

• Annexes containing:• Robust study summaries

• Adaptation according to column 2 of Annexes VII-X

• Adaptation according to Annex XI Section 1 or 2

Annex Ref End Points Adequate Information submitted

Compliance with criteria confirmed

Value of endpoints

Adaptation according to column 2 of Annexes VII-X applied

Adaptation according to Annex XI sections 1 and 2 applied

Yes/No or NA according to column 2 Annex VII-X or Annex XI

Yes/No Unit has to be given for each individual endpoint

Yes/No Justification is to be annexed as separate documentation

Yes/No Justification is to be annexed as separate documentation

Physicochemical properties

VII 7.1 State of the substance

VII 7.3 Boiling point VII 7.5 Vapour pressure VII 7.7 Water solubility VII 7.8 Partition coefficient n-

octanol/water

… … … … … …

Format for submission - Overview of information

Proces

• Submissions seeking the addition to or deletion of a substance from the existing Annex IV– Shall be submitted by 15 Nov 2007 to the national CA

or to either CEFIC, CONCAWE or REACH Alliance– MS and industry associations screen the proposals

against the criteria – and forward submissions they find comply with the criteria and information requirements to COM and the contractor (before 30 Nov 2007)

– Contractor evaluates the proposals and forwards a summary and conclusion to COM

Proces

• Approach for evaluation of substances already in Annex IV– Grouping of entries– Data search in GESAMP, HSDB, IUCLID and

ECETOX (US-EPA)– “Bearing in mind the historical evidence on

substances in Annex IV, the burden of proof is directed at evidence of significant toxicological and environmental effects”

• Data gaps can be accepted, if the available data confirm minimum risk (compliance with criteria)

Evaluation of existing entries

• Grouping of entries– Sugars and syrups– Polymers of sugars– Oils– Fatty acids– Esters of fatty acids– Salts of fatty acids– Glycerides– Amino acids* – Minerals*– Vitamins*

* Each substance to be evaluated separately

Results of initial data search in GESAMP, HSDB, IUCLID and ECETOX (US-EPA)

Name/group Data available

GESAMP HSDB IUCLID US-EPA

Eco Human Eco Human Eco Human Eco Human

Sugars and syrups + + + +

Polymers of sugars

Oils + + + + + +

Fatty acids, + + + + +

Esters of fatty acids + + +

Salts of fatty acids + + + +

Glycerides

Amino acids + + + +

Vitamins + +

Minerals + + + + + + +

Evaluation of ecotoxicological properties

Name/group Log Pow BCF Readily Biodeg.

EC/LC 50 mg/l

NOEC mg/l

Sugars < 0 [Glucose, sucrose, mannitol, sorbitol]

1 [Mannitol, sorbitol]

Yes [Glucose] > 1000 [Glucose]

OiIs > 6 [Tallow] Yes [Safflower, linseed, corn, castor, tallow]

> 10 ≤100[Linseed, corn, castor, tallow, rapeoil] > 100 ≤1000 [Rapeoil] > 1000 [Safflower]

> 1 ≤10 EC10 (algae 96 hours) [Tallow]

Fatty acids 4.2 [C12] 7.17 [C16] 8.23 [C18] 7.73 [C18]

166 [C16] 44 [C18] ≥500<4000 [C18]

Yes [C12] Yes [C18]

> 0.1 ≤1 [C12] > 100 ≤1000 [C12, C16, C18]

250 (rotifer48 hours) [C12]

Esters of fatty acids

Yes [Coco-Me] Yes [Tallow- Me]

> 1000 [Coco-Me, tallow- Me]

Salts of fatty acids

≥3<4 [C18]

≥100<500 [C18]

Yes [C18] > 0.1 ≤1 [C18] > 1 ≤10 [C18] > 100 ≤1000 [C18]

Ecotoxicological properties - Initial pass/fail evaluation

Name/group Log Pow BCF Readily Biodeg.

EC/LC 50 mg/l

NOEC mg/l

Sugars < 0 [Glucose, sucrose, mannitol, sorbitol]

1 [Mannitol, sorbitol]

Yes [Glucose] > 1000 [Glucose]

OiIs > 6 [Tallow] Yes [Safflower, linseed, corn, castor, tallow]

> 10 ≤100[Linseed, corn, castor, tallow, rapeoil] > 100 ≤1000 [Rapeoil] > 1000 [Safflower]

> 1 ≤10 EC10 (algae 96 hours) [Tallow]

Fatty acids 4.2 [C12] 7.17 [C16] 8.23 [C18] 7.73 [C18]

166 [C16] 44 [C18] ≥500<4000 [C18]

Yes [C12] Yes [C18]

> 0.1 ≤1 [C12] > 100 ≤1000 [C12, C16, C18]

250 (rotifer48 hours) [C12]

Esters of fatty acids

Yes [Coco-Me] Yes [Tallow- Me]

> 1000 [Coco-Me, tallow- Me]

Salts of fatty acids

≥3<4 [C18]

≥100<500 [C18]

Yes [C18] > 0.1 ≤1 [C18] > 1 ≤10 [C18] > 100 ≤1000 [C18]

PASS

FAIL

FAIL

???? ?

FAIL

Discussion issues

• General proposed requirements to ‘minimum risk’ well below the criteria for classification

• Proposal of a ‘milder’ evaluation of existing Annex IV entries (available information, use of read-across, (Q)SAR)

• Time window for submissions