LegalizeS.I. No. 393/2000 - European Communities (Classification, Packaging, Labelling and Notification of Dangerous Substances) Regulations, 2000
This is the act as published. Later amendments are not folded into the text below: each one is a separate act in this repository and an entry in this law's history.
1 amending act · 2003-03-27, S.I. No. 116/2003 - European Communities (Classification, Packaging, Labelling and Notifi…
| Note: | The letters E, O, F, F+, T, T+, C, Xn, Xi and N do not form part of the symbol. | The letters E, O, F, F+, T, T+, C, Xn, Xi and N do not form part of the symbol. | The letters E, O, F, F+, T, T+, C, Xn, Xi and N do not form part of the symbol. |
| E | O | ||
| [image omitted] | Explosive | [image omitted] | Oxidizing |
| F | F+ | ||
| [image omitted] | Highly flammable | [image omitted] | Extremely flammable |
| T | T+ | ||
| [image omitted] | Toxic | [image omitted] | Very Toxic |
| C | Xn | ||
| [image omitted] | Corrosive | [image omitted] | Harmful |
| Xi | N | ||
| [image omitted] | Irritant | [image omitted] | Dangerous for the environment |
SCHEDULE 2 ANNEX III
NATURE OF SPECIAL RISKS ATTRIBUTED TO DANGEROUS SUBSTANCES AND PREPARATIONS
R1
Explosive when dry
R2
Risk of explosion by shock, fire or other sources of ignition
R3
Extreme risk of explosion by shock, friction, fire or other sources of ignition
R4
Forms very sensitive explosive metallic compounds
R5
Heating may cause an explosion
R6
Explosive with or without contact with air
R7
May cause fire
R8
Contact with combustible material may cause fire
R9
Explosive when mixed with combustible materials
R10
Flammable
R11
Highly flammable
R12
Extremely flammable
R14
Reacts violently with water
R15
Contact with water liberates highly flammable gases
R16
Explosive when mixed with oxidizing substances
R17
Spontaneously flammable in air
R18
In use, may form flammable/explosive vapour-air mixture
R19
May form explosive peroxides
R20
Harmful by inhalation
R21
Harmful in contact with skin
R22
Harmful if swallowed
R23
Toxic by inhalation
R24
Toxic in contact with skin
R25
Toxic if swallowed
R26
Very toxic by inhalation
R27
Very toxic in contact with skin
R28
Very toxic if swallowed
R29
Contact with water liberates toxic gas
R30
Can become highly flammable in use
R31
Contact with acids liberates toxic gas
R32
Contact with acids liberates very toxic gas
R33
Danger of cumulative effects
R34
Causes burns
R35
Causes severe burns
R36
Irritating to eyes
R37
Irritating to respiratory system
R38
Irritating to skin.
R39
Danger of very serious irreversible effects
R40
Possible risk of irreversible effects
R41
Risk of serious damage to eyes
R42
May cause sensitisation by inhalation
R43
May cause sensitisation by skin contact
R44
Risk of explosion if heated under confinement
R45
May cause cancer
R46
May cause heritable genetic damage
R48
Danger of serious damage to health by prolonged exposure
R49
May cause cancer by inhalation
R50
Very toxic to aquatic organisms
R51
Toxic to aquatic organisms
R52
Harmful to aquatic organisms
R53
May cause long-term adverse effects in the aquatic environment
R54
Toxic to flora
R55
Toxic to fauna
R56
Toxic to soil organisms
R57
Toxic to bees
R58
May cause long-term adverse effects in the environment
R59
Dangerous for the ozone layer
R60
May impair fertility
R61
May cause harm to the unborn child
R62
Possible risk of impaired fertility
R63
Possible risk of harm to the unborn child
R64
May cause harm to breastfed babies
R65
Harmful: May cause lung damage if swallowed
R66
Repeated exposure may cause skin dryness or cracking
R67
Vapours may cause drowsiness and dizziness
COMBINATION OF R-PHRASES
R14/15
Reacts violently with water, liberating highly flammable gases
R15/29
Contact with water liberates toxic, highly flammable gas
R20/21
Harmful by inhalation and in contact with skin
R20/22
Harmful by inhalation and if swallowed
R20/21/22
Harmful by inhalation, in contact with skin and if swallowed
R21/22
Harmful in contact with skin and if swallowed
R23/24
Toxic by inhalation and in contact with skin
R23/25
Toxic by inhalation and if swallowed
R23/24/25
Toxic by inhalation, in contact with skin and if swallowed
R24/25
Toxic in contact with skin and if swallowed
R26/27
Very toxic by inhalation and in contact with skin
R26/28
Very toxic by inhalation and if swallowed
R26/27/28
Very toxic by inhalation and in contact with skin and if swallowed
R27/28
Very toxic in contact with skin and if swallowed
R36/37
Irritating to eyes and respiratory system
R36/38
Irritating to eyes and skin
R36/37/38
Irritating to eyes, respiratory system and skin
R37/38
Irritating to respiratory system and skin
R39/23
Toxic: danger of very serious irreversible effects through inhalation
R39/24
Toxic: danger of very serious irreversible effects in contact with skin
R39/25
Toxic: danger of very serious irreversible effects if swallowed
R39/23/24
Toxic: danger of very serious irreversible effects through inhalation and in contact with skin
R39/23/25
Toxic: danger of very serious irreversible effects through inhalation and if swallowed
R39/24/25
Toxic: danger of very serious irreversible effects in contact with skin and if swallowed
R39/23/24/25
Toxic: danger of very serious irreversible effects through inhalation, in contact with skin and if swallowed
R39/26
Very toxic: danger of very serious irreversible effects through inhalation
R39/27
Very toxic: danger of very serious irreversible effects in contact with skin
R39/28
Very toxic: danger of very serious irreversible effects if swallowed
R39/26/27
Very toxic: danger of very serious irreversible effects through inhalation and in contact with skin
R39/26/28
Very toxic: danger of very serious irreversible effects through inhalation and if swallowed
R39/27/28
Very toxic: danger of very serious irreversible effects in contact with skin and if swallowed
R39/26/27/28
Very toxic: danger of very serious irreversible effects through inhalation, in contact with skin and if swallowed
R40/20
Harmful: possible risk of irreversible effects through inhalation
R40/21
Harmful: possible risk of irreversible effects in contact with skin
R40/22
Harmful: possible risk of irreversible effects if swallowed
R40/20/21
Harmful: possible risk of irreversible effects through inhalation and in contact with skin
R40/20/22
Harmful: possible risk of irreversible effects through inhalation and if swallowed
R40/21/22
Harmful: possible risk of irreversible effects in contact with skin and if swallowed
R40/20/21/22
Harmful: possible risk of irreversible effects through inhalation, in contact with skin and if swallowed
R42/43
May cause sensitisation by inhalation and skin contact
R48/20
Harmful: danger of serious damage to health by prolonged exposure through inhalation
R48/21
Harmful: danger of serious damage to health by prolonged exposure in contact with skin
R48/22
Harmful: danger of serious damage to health by prolonged exposure if swallowed
R48/20/21
Harmful: danger of serious damage to health by prolonged exposure through inhalation and in contact with skin
R48/20/22
Harmful: danger of serious damage to health by prolonged exposure through inhalation and if swallowed
R48/21/22
Harmful: danger of serious damage to health by prolonged exposure in contact with skin and if swallowed
R48/20/21/22
Harmful: danger of serious damage to health by prolonged exposure through inhalation, in contact with skin and if swallowed
R48/23
Toxic: danger of serious damage to health by prolonged exposure through inhalation
R48/24
Toxic: danger of serious damage to health by prolonged exposure in contact with skin
R48/25
Toxic: danger of serious damage to health by prolonged exposure if swallowed
R48/23/24
Toxic: danger of serious damage to health by prolonged exposure through inhalation and in contact with skin
R48/23/25
Toxic: danger of serious damage to health by prolonged exposure through inhalation and if swallowed
R48/24/25
Toxic: danger of serious damage to health by prolonged exposure in contact with skin and if swallowed
R48/23/24/25
Toxic: danger of serious damage to health by prolonged exposure through inhalation, in contact with skin and if swallowed
R50/53
Very toxic to aquatic organisms, may cause long-term adverse effects in the aquatic environment
R51/53
Toxic to aquatic organisms, may cause long-term adverse effects in the aquatic environment
R52/53
Harmful to aquatic organisms, may cause long-term adverse effects in the aquatic environment
SCHEDULE 3 ANNEX IV
SAFETY ADVICE CONCERNING DANGEROUS SUBSTANCES AND PREPARATIONS
S 1
Keep locked up.
S 2
Keep out of the reach of children.
S 3
Keep in a cool place.
S 4
Keep away from living quarters.
S 5
Keep contents under … (appropriate liquid to be specified by the manufacturer).
S 6
Keep under … (inert gas to be specified by the manufacturer).
S 7
Keep container tightly closed.
S 8
Keep container dry.
S 9
Keep container in a well-ventilated place.
S 12
Do not keep the container sealed.
S 13
Keep away from food, drink and animal feeding stuffs.
S 14
Keep away from … (incompatible materials to be indicated by the manufacturer).
S 15
Keep away from heat.
S 16
Keep away from sources of ignition - No smoking.
S 17
Keep away from combustible material.
S 18
Handle and open container with care.
S 20
When using do not eat or drink.
S 21
When using do not smoke.
S 22
Do not breathe dust.
S 23
Do not breathe gas/fumes/vapour/spray (appropriate wording to be specified by the manufacturer).
S 24
Avoid contact with skin.
S 25
Avoid contact with eyes.
S 26
In case of contact with eyes, rinse immediately with plenty of water and seek medical advice.
S 27
Take off immediately all contaminated clothing.
S 28
After contact with skin, wash immediately with plenty of … (to be specified by the manufacturer).
S 29
Do not empty into drains.
S 30
Never add water to this product.
S 33
Take precautionary measures against static discharges.
S 35
This material and its container must be disposed of in a safe way.
S 36
Wear suitable protective clothing.
S 37
Wear suitable gloves.
S 38
In case of insufficient ventilation, wear suitable respiratory equipment.
S 39
Wear eye/face protection.
S 40
To clean the floor and all objects contaminated by this material, use … (to be specified by the manufacturer).
S 41
In case of fire and/or explosion do not breathe fumes.
S 42
During fumigation/spraying wear suitable respiratory equipment (appropriate wording to be specified by the manufacturer).
S 43
In case of fire, use … (indicate in the space the precise type of fire-fighting equipment. If water increases risk, add - ‘Never use water’).
S 45
In case of accident or if you feel unwell, seek medical advice immediately (show the label where possible).
S 46
If swallowed, seek medical advice immediately and show this container or label.
S 47
Keep at temperature not exceeding … °C (to be specified by the manufacturer).
S 48
Keep wetted with … (appropriate material to be specified by the manufacturer).
S 49
Keep only in the original container.
S 50
Do not mix with … (to be specified by the manufacturer).
S 51
Use only in well-ventilated areas.
S 52
Not recommended for interior use on large surface areas.
S 53
Avoid exposure - obtain special instructions before use.
S 56
Dispose of this material and its container at hazardous or special waste collection point.
S 57
Use appropriate containment to avoid environmental contamination.
S 59
Refer to manufacturer/supplier for information on recovery/recycling.
S 60
This material and its container must be disposed of as hazardous waste.
S 61
Avoid release to the environment. Refer to special instructions/Safety data sheets.
S 62
If swallowed, do not induce vomiting: seek medical advice immediately and show this container or label.
S 63
In case of accident by inhalation: remove casualty to fresh air and keep at rest.
S 64
If swallowed, rinse mouth with water (only if the person is conscious).
Combination of S-phrases
S 1/2
Keep locked up and out of reach of children.
S 3/7
Keep container tightly closed in a cool place.
S 3/9/14
Keep in a cool, well-ventilated place away from … (incompatible materials to be indicated by the manufacturer).
S 3/9/14/49
Keep only in the original container in a cool, well-ventilated place away from … (incompatible materials to be indicated by the manufacturer).
S 3/9/49
Keep only in the original container in a cool, well-ventilated place.
S 3/14
Keep in a cool place away from … (incompatible materials to be indicated by the manufacturer).
S 7/8
Keep container tightly closed and dry.
S 7/9
Keep container tightly closed and in a well-ventilated place.
S 7/47
Keep container tightly closed and at a temperature not exceeding … °C (to be specified by the manufacturer).
S 20/21
When using do not eat, drink or smoke.
S 24/25
Avoid contact with skin and eyes.
S 27/28
After contact with skin, take off immediately all contaminated clothing and wash immediately with plenty of... (to be specified by the manufacturer).
S 29/35
Do not empty into drains; dispose of this material and its container in a safe way.
S 29/56
Do not empty into drains, dispose of this material and its container to hazardous or special waste collection point.
S 36/37
Wear suitable protective clothing and gloves.
S 36/37/39
Wear suitable protective clothing, gloves and eye/face protection.
S 36/39
Wear suitable protective clothing and eye/face protection.
S 37/39
Wear suitable gloves and eye/face protection.
S 47/49
Keep only in the original container at a temperature not exceeding … °C (to be specified by the manufacturer).
SCHEDULE 4 ANNEX VI
CLASSIFICATION AND LABELLING REQUIREMENTS FOR DANGEROUS SUBSTANCES AND PREPARATIONS
CONTENTS
1. GENERAL INTRODUCTION
1.1 The object of classification is to identify all the toxicological, physico-chemical and ecotoxicological properties of substances and toxicological and physiochemical properties of preparations which may constitute a risk during normal handling or use. Having identified any hazardous properties the substance or preparation must then be labelled to indicate the hazard(s) in order to protect the user, the general public and the environment.
1.2 This Annex sets out the general principles governing the classification and labelling of substances and preparations referred to in Article 4 of Directive 67/548/EEC38 and in Article 3 of Directive 88/379/EEC and other relevant Directives on dangerous preparations.
It is addressed to all those concerned (manufacturers, importers, national authorities) with methods of classifying and labelling dangerous substances and preparations.
1.3 The requirements of Directive 67/548/EEC and of Directive 88/379/EEC are intended to provide a primary means by which the general public and persons at work are given essential information about dangerous substances and preparations. The label draws the attention of persons handling or using substances and preparations to the inherent danger of certain such materials.
The label may also serve to draw attention to more comprehensive product information on safety and use available in other forms.
1.4 The label takes account of all potential hazards which are likely to be faced in the normal handling and use of dangerous substances and preparations when in the form in which they are placed on the market, but not necessarily in any different form in which they may finally be used, e.g. diluted. The most severe hazards are highlighted by symbols, such hazards and those arising from other dangerous properties are specified in standard risk phrases, and safety phrases give advice on necessary precautions.
In the case of substances, the information is completed by the name of the substance under an internationally recognised chemical nomenclature, the preferred name being the one used in the European Inventory of Existing Commercial Chemical Substances (EINECS), the European List of Notified Chemical Substances (ELINCS), the EC number and the name, address and telephone number of the person established in the Community who is responsible for placing the substance on the market.
In the case of preparations, the information is completed by the indication of the designation or the trade name of the preparation, the indication of the chemical name of the substances present in the preparation in accordance with Article 7(1)(c) of Directive 88/379/EEC and the indication of the name, address and telephone number of the person established in the Community who is responsible for placing the preparation on the market.
1.5 Article 6 of Directive 67/54/EEC39 requires that manufacturers, distributors and importers of dangerous substances which appear in the EINECS but which have not yet been introduced into Annex I shall be obliged to carry out an investigation to make themselves aware of the relevant and accessible data which exist concerning the properties of such substances. On the basis of this information, they shall package and provisionally label these substances according to the rules laid down in Articles 22 to 25 40 and the criteria in this Annex.
1.6 For substances the data required for classification and labelling may be obtained:
- (a) as regards substances for which the information specified in Annex VII is required, which for convenience of reference is set out in Schedule 5, most of the necessary data for classification and labelling appear in the ‘base set’. This classification and labelling must be reviewed, if necessary, when further information is available (Annex VIII);
- (b) as regards other substances (e.g. those referred to in section 1.5 above), the data required for classification and labelling may, if necessary, be obtained from a number of different sources, for example the results of previous tests, information required by international rules on the transport of dangerous substances, information taken from reference works and the literature or information derived from practical experience. The results of validated structure-activity relationships and expert judgement may also be taken into account where appropriate.
For preparations, the data required for classification and labelling may be obtained:
- (a) if it concerns physico-chemical data, by the application of the methods specified in Annex V. For gaseous preparations a calculation method may be used for flammable and oxidising properties (see Chapter 9 of this Schedule).
- (b) if it concerns data on health effects:
- by the application of the methods specified in Annex V and/or by the application of the conventional method referred to in Article 3(5)(a) to (i) of Directive 88/379/EEC, or, in the case of R65, by the application of the rules under 3.2.3,
- however, if it concerns the evaluation of the carcinogenic, mutagenic and reproductive properties, by the application of the conventional method referred to in Article 3(5)(j) to (q) of Directive 88/379/EEC
Note concerning the performance of animal tests
The performance of animal tests to establish experimental data is subject to the provisions of Directive 86/609/EEC regarding the protection of animals used for experimental purposes.
1.7 Application of the guide criteria
Classification must cover the toxicological and physico-chemical and ecotoxicological properties of substances and preparations.
Classification of substances and preparations is made on the basis of the criteria in Chapters 2 to 4 and additionally for substances Chapter 5 of this Annex. All types of hazard must be considered. For instance, classification under 3.2.1 does not imply that the sections such as 3.2.2 or 3.2.4 can be ignored.
The choice of symbol (s) and risk phrase (s) is made on the basis of the classification in order to ensure that the specific nature of the potential dangers identified in classification is expressed on the label.
Notwithstanding the criteria given under 2.2.3, 2.2.4 and 2.2.5, substances and preparations in the form of aerosols shall be subject to the flammability criteria set out in 1.8 and 2.2 (c) of the Annex to Directive 75/324/EEC.
1.7.1. Definitions
‘Substances’ means chemical elements and their compounds in the natural state or obtained by any production process, including any additive necessary to preserve the stability of the product, and any impurity deriving from the production process used, but excluding any solvent which may be separated without affecting the stability of the substance or changing its composition.
A substance may be chemically very well defined (e.g. acetone) or a complex mixture of constituents of variable composition (e.g. aromatic distillates). For certain complex substances, some individual constituents have been identified.
‘Preparations’ means mixtures or solutions composed of two or more substances.
1.7.2 Application of the guide criteria for substances
The guidance criteria set out in this Schedule are directly applicable when the data in question have been obtained from test methods comparable with those described in Annex V. In other cases, the available data must be evaluated by comparing the test methods employed with those indicated in Annex V and the rules specified in this Schedule for determining the appropriate classification and labelling.
In some cases there may be doubt over the application of the relevant criteria, especially where these require the use of expert judgement. In such cases the manufacturer, distributor or importer should provisionally classify and label the substance on the basis of an assessment of the evidence by a competent person.
Without prejudice to Article 6, where the above procedure has been followed and there is concern over possible inconsistencies then a proposal may be submitted for the entry of the provisional classification into Annex I. The proposal should be made to one of the Member States and should be accompanied by appropriate scientific data (see also section 4.1).
A similar procedure may be followed when information is identified which gives cause for concern over the accuracy of an existing entry in Annex I.
1.7.2.1 Classification of substances containing impurities, additives or individual constituents
Where impurities, additives or individual constituents of substances have been identified, they shall be taken into account if their concentration is greater than or equal to the limits specified
- 0.1 % for substances classified as very toxic, toxic, carcinogenic (category 1 or 2), mutagenic (category 1 or 2) or toxic to reproduction (category 1 or 2)
- 1% for substances classified as harmful, corrosive, irritant sensitising, carcinogenic (category 3), mutagenic (category 3), or toxic to reproduction (category 3) 9
unless lower values have been specified in Annex I to Directive 67/548/EEC.
With the exception of substances listed specifically in Annex I, classification for physico-chemical properties and for health hazards should be carried out according to the requirements of Articles 3 and labelled according the requirements of Article 7 of Council Directive 88/379/EEC.
Classification for physico-chemical properties is carried out according to the criteria in Chapter 2, and for effects dangerous for the environment is carried out according to the criteria in Chapter 5 of this Schedule.
In the case of asbestos (650-013-00-6) this general rule does not apply until a concentration limit has been fixed in Annex I. Substances in which asbestos is present must be classified and labelled according to the principles laid down in Article 6 of Directive 67/548/EEC.
1.7.3. Application of the guide criteria for preparations
The guidance criteria set out in this Annex are directly applicable when the data in question have been obtained from test methods comparable with those described in Annex V with the exception of the criteria of Chapter 4 for which only the conventional method is applicable. In other cases, the available data must be evaluated by comparing the test methods employed with those indicated in Annex V and the rules specified in this Schedule for determining the appropriate classification and labelling.
If the health hazards are assessed by applying the conventional method referred to in Articles 3(5) of Directive 88/379/EEC, the individual concentration limits to be used are those set out either:
- in Annex I to Directive 67/548/EEC, or
- in Annex I to Directive 88/379/EEC where the substance or substances do not appear in Annex I to Directive 67/548/EEC or appear in it without concentration limits.
In the case of preparations containing mixtures of gases, classification with respect to health effects will be established by the calculation method on the basis of the individual concentration limits from Annex I to Directive 67/548/EEC or, when these limits are not in Annex I on the basis of the criteria of Annex I to Directive 88/379/EEC, as amended by Directive 90/492/EEC.
1.7.3.1 Preparations or substances described in Section 1.7.2.1 used as constituents of another preparation
The labelling of such preparations must be in conformity with the provisions of Article 7 according to the conditions foreseen in Article 3 of Directive 88/379/EEC. However, in certain cases, the information on the label of the preparation or substance described in Section 1.7.2.1 is insufficient to enable other manufacturers who wish to use it as a constituent of their own preparation(s) to carry out the classification and labelling of their preparation(s) correctly.
In these cases, the person established within the Community responsible for placing the original preparation or substance described in Section 1.7.2.1 on the market, whether it be the manufacturer, the importer or the distributor shall supply upon justified request and as soon as possible all necessary data concerning the dangerous substances present to enable correct classification and labelling of the new preparation. This data is also necessary to enable the person responsible for placing the new preparation on the market to comply with other requirements of Directive 88/379/EEC.
2 CLASSIFICATION ON THE BASIS OF PHYSICO-CHEMICAL PROPERTIES
2.1. Introduction
The test methods relating to explosive, oxidizing and flammable properties included in Annex V of Directive 67/548/EEC serve to give specific meaning to the general definitions given in Articles 2(a) to (e) 41 Criteria follow directly from the test methods in Annex V as far as they are mentioned.
If adequate information is available to demonstrate in practice that the physico-chemical properties of substances and preparations (apart from organic peroxides) are different from those revealed by the test methods given in Annex V, then such substances and preparations should be classified according to the hazard they present, if any, to those handling the substances and preparations or to other persons.
2.2 Criteria for classification, choice of symbols, indication of danger and choice of risk phrases
In the case of preparations, the criteria referred to in Article 3 (2) of Directive 88/379/EEC need to be taken into consideration.
2.2.1 Explosive
Substances and preparations shall be classified as explosive and assigned the symbol ‘E’ and the indication of danger ‘explosive’ in accordance with the results of the tests given in Annex V and in so far as the substances and preparations are explosive as placed on the market. One risk phrase is obligatory, it is to be specified on the basis of the following:
R2 Risk of explosion by shock, friction, fire or other sources of ignition
- substances and preparations except those set out below.
R3 Extreme risk of explosion by shock, friction, fire or other source of ignition
- substances and preparations which are particularly sensitive such as picric acid salts or PETN.
2.2.2 Oxidizing
Substances and preparations shall be classified as oxidizing and assigned the symbol ‘O’ and the indication of danger ‘oxidizing’ in accordance with the results of the tests given in Annex V. One risk phrase is obligatory, it is to be specified on the basis of the test results but subject to the following:
R7 May cause fire
- organic peroxides which have flammable properties even when not in contact with other combustible material.
R8 Contact with combustible material may cause fire
- other oxidizing substances and preparations, including inorganic peroxides, which may cause fire or enhance the risk of fire when in contact with combustible material.
R9 Explosive when mixed with combustible material
- other substances and preparations, including inorganic peroxides, which become explosive when mixed with combustible materials, e.g. certain chlorates.
2.2.2.1 Remarks concerning peroxides
For the explosive properties, an organic peroxide or preparation thereof in the form in which it is placed on the market is classified according to the criteria in section 2.2.1 on the basis of tests carried out in accordance with the methods given in Annex V.
For the oxidising properties the existing methods in Annex V cannot be applied to organic peroxides.
For substances, organic peroxides not already classified as explosive are classified as dangerous on the basis of their structure (e.g. R-O-O-H; R1-O-O-R2).
Preparations not already classified as explosive shall be classified using the calculation method based on the percentage of active oxygen shown in Section 9.5.
Any organic peroxide or preparation thereof not already classified as explosive is classified as oxidising, if the peroxide or its formulation contains:
- more than 5% of organic peroxides or,
- more than 0.5% available oxygen from the organic peroxides, and more than 5 % hydrogen peroxide.
2.2.3 Extremely flammable
Substances and preparations shall be classified as extremely flammable and assigned the symbol ‘F+’ and the indication of danger ‘extremely flammable’ in accordance with the results of the tests given in Annex V. The risk phrase shall be assigned in accordance with the following criteria:
R12 Extremely flammable
- Liquid substances and preparations which have a flash point lower than 0 °C and a boiling point (or in case of a boiling range the initial boiling point) lower than or equal to 35 °C.
- Gaseous substances and preparations which are flammable in contact with air at ambient temperature and pressure.
2.2.4. Highly flammable
Substances and preparations shall be classified as highly flammable and assigned the symbol ‘F’ and the indication of danger ‘highly flammable’ in accordance with the results of the tests given in Annex V. Risk phrases shall be assigned in accordance with the following criteria:
R11 Highly flammable
- Solid substances and preparations which may readily catch fire after brief contact with a source of ignition and which continue to burn or to be consumed after removal of the source of ignition.
- Liquid substances and preparations having a flash point below 21°C but which are not extremely flammable.
R15 Contact with water liberates extremely flammable gases
- Substances and preparations which, in contact with water or damp air, evolve extremely flammable gases in dangerous quantities, at a minimum rate of one litre per kilogram per hour.
R17 Spontaneously flammable in air
- Substances and preparations which may become hot and finally catch fire in contact with air at ambient temperature without any input of energy.
2.2.5. Flammable
Substances and preparations shall be classified as flammable in accordance with the results of the tests given in Annex V. The risk phrase shall be assigned in accordance with the criteria mentioned below.
R10 Flammable
- Liquid substances and preparations having a flash point equal to or greater than 21 °C, and less than or equal to 55 °C.
However, in practice it has been shown that a preparation having a flash point equal to or greater than 21 °C and less than or equal to 55 °C need not be classified as flammable if the preparation could not in any way support combustion and only so long as there is no reason to fear risks to those handling these preparations or to other persons.
2.2.6. Other physico-chemical properties
Additional risk phrases shall be assigned to substances and preparations which have been classified by virtue of Sections 2.2.1 to 2.2.5 above or by Chapters 3, 4 and 5 below, in accordance with the following criteria (based on experience obtained during compilation of Annex I):
R1 Explosive when dry
For explosive substances and preparations put on the market in solution or in a wetted form; e.g. nitrocellulose with more than 12.6% nitrogen.
R4 Forms very sensitive explosive metallic compounds
For substances and preparations which may form sensitive explosive metallic derivatives, e.g. picric acid, styphnic acid.
R5 Heating may cause an explosion
For thermally unstable substances and preparations not classified as explosive, e.g. perchloric acid > 50 %.
R6 Explosive with or without contact with air
For substances and preparations which are unstable at ambient temperatures, e.g. acetylene.
R7 May cause fire
For reactive substances and preparations : e.g. fluorine, sodium hydrosulphite.
R14 Reacts violently with water
For substances and preparations which react violently with water, e.g. acetyl chloride, alkali metals, titanium tetrachloride.
R16 Explosive when mixed with oxidizing substances
For substances and preparations which react explosively with an oxidizing agent, e.g. red phosphorus.
R18 In use, may form flammable/explosive vapour-air mixture
For preparations not in themselves classified as flammable, which contain volatile components which are flammable in air.
R19 May form explosive peroxides
For substances and preparations which may form explosive peroxides during storage, e.g. diethyl ether, 1,4-dioxan.
R30 Can become highly flammable in use
For preparations not in themselves classified as flammable, which may become flammable due to the loss of non-flammable volatile components.
R44 Risk of explosion if heated under confinement
For substances and preparations not in themselves classified as explosive in accordance with Section 2.2.1 above but which may nevertheless display explosive properties in practice if heated under sufficient confinement. For example, certain substances which would decompose explosively if heated in a steel drum do not show this effect if heated in less-strong containers.
For other additional risk phrases see Section 3.2.7.
3. CLASSIFICATION ON THE BASIS OF TOXICOLOGICAL PROPERTIES
3.1. Introduction
3.1.1. Classification is concerned with both the acute and long-term effects of substances and preparations, whether resulting from a single instance of exposure or repeated or prolonged exposure.
If adequate evidence is available to demonstrate in practice that the toxic effect of substances and preparations on man is, or is likely to be, different from that suggested by the experimental results obtained in animal tests or by the application of the conventional method referred to in Article 3 (5) of Directive 88/379/EEC then such substances and preparations should be classified according to their toxicity in man. However, tests on man should be discouraged and should not normally be used to negate positive animal data.
3.1.2. The classification of substances must be made on the basis of the experimental data available in accordance with the following criteria which take into account the magnitude of these effects:
- (a) for acute toxicity (lethal and irreversible effects after a single exposure), the criteria under Sections 3.2.1 to 3.2.3 are to be used,
- (b) for subacute, subchronic or chronic toxicity the criteria under Sections 3.2.2 to 3.2.4 are to be used.
- (c) for corrosive and irritant effects the criteria under Sections 3.2.5 and 3.2.6 are to be used,
- (d) for sensitising effects the criteria under Sections 3.2.7 are to be used,
- (e) for specific effects on health (carcinogenicity, mutagenicity and reproductive toxicity, the criteria in Chapter 4 are to be used.
3.1.3. For preparations, the classification relating to dangerous for health is carried out:
- (a) on the basis of the conventional method referred to in Article 3 (5) of Directive 88/379/EEC in the absence of experimental data. In this case, the classification is based on the individual concentration limits:
- either taken from Annex I to Directive 67/548/EEC,
- or from Annex I of Directive 88/379/EEC where the substance or substances do not appear in Annex I of Directive 67/548/EEC or appear in it without concentration limits.
- (b) or when experimental data are available, according to the criteria described under Sections 3.1.2 excluding the carcinogenic, mutagenic and toxic to reproduction properties referred to under 3.1.2 (e) which must be evaluated by the conventional method referred to in Article 3 (5) (j) to (q) of Directive 88/379/EEC.
Whichever method is used for the evaluation of the danger of a preparation, all the dangerous effects on health as defined in Annex I of Directive 88/379/EEC must be taken into consideration.
3.1.4. When the classification is to be established from experimental results obtained in animal tests the results should have validity for man in that the tests reflect, in an appropriate way, the risks to man.
3.1.5. The acute oral toxicity of substances or preparations placed on the market may be established either by a method permitting assessment of the LD50 value, or by determining the discriminating dose (the fixed dose procedure).
The discriminating dose is the dose which causes evident toxicity but not mortality and must be one of the four dosage levels specified in Annex V (5, 50, 500 or 2 000 mg per kg body weight).
The concept ‘evident toxicity’ is used to designate toxic effects, after exposure to the substance tested, which are so severe that exposure to the next highest fixed dose would probably lead to mortality.
The results of testing at a particular dose following the fixed dose method may be either:
- less than 100% survival,
- 100% survival, but evident toxicity,
- 100% survival, but no evident toxicity.
The test method requires in some cases testing at higher or lower doses, if not already tested at the relevant dose level. Refer also to the evaluation table in test method B.1 bis of Annex V.
In the criteria in sections 3.2.1, 3.2.2 and 3.2.3 only the final test result is shown. The 2 000 mg/kg dose should be used primarily to obtain information on the toxic effects of substances which are of low acute toxicity and which are not classified on the basis of acute toxicity.
3.2. Criteria for classification, choice of symbols, indication of danger, choice of risk phrases
3.2.1. Very toxic
Substances and preparations shall be classified as very toxic, and assigned the symbol ‘T +’ and indication of danger ‘very toxic’ in accordance with the criteria specified below.
Risk phrases shall be assigned in accordance with the following criteria:
R28 Very toxic if swallowed
Acute toxicity results:
- LD50 oral, rat ≤ 25 mg/kg,
- less than 100% survival at 5 mg/kg oral, rat by the fixed dose procedure.
R27 Very toxic in contact with skin
Acute toxicity results:
- LD50 dermal, rat or rabbit: ≤ 50 mg/kg.
R26 Very toxic by inhalation
Acute toxicity results:
- LC50 inhalation, rat, for aerosols or particulates: ≤ 0.25 mg/litre/4hr.
- LC50 inhalation, rat, for gases and vapours: ≤ 0.5 mg/litre/4hr.
R39 Danger of very serious irreversible effects
- Strong evidence that irreversible damage other than the effects referred to in Chapter 4 is likely to be caused by a single exposure by an appropriate route, generally in the above mentioned dose range.
In order to indicate the route of administration/exposure one of the following combinations shall be used: R39/26, R39/27, R39/28, R39/26/27, R39/26/28, R39/27/28, R39/26/27/28.
3.2.2. Toxic
Substances and preparations shall be classified as toxic and assigned the symbol ‘T’ and the indication of danger ‘toxic’ in accordance with the criteria specified below. Risk phrases shall be assigned in accordance with the following criteria.
R25 Toxic if swallowed
Acute toxicity results:
- LD50 oral, rat: 25 < LD50 ≤ 200 mg/kg,
- Discriminating dose, oral, rat, 5 mg/kg: 100% survival but evident toxicity,
R24 Toxic in contact with skin
Acute toxicity results:
- LD50 dermal, rat or rabbit: 50 < LD50 ≤ 400 mg/kg.
R23 Toxic by inhalation
Acute toxicity results:
- LC50 inhalation, rat, for aerosols or particulates: 0,25 < LC50 ≤ 1 mg/litre/4hr
- LC50 inhalation, rat, for gases and vapours: 0,5 < LC50 ≤ 2 mg/litre/4hr.
R39 Danger of very serious irreversible effects
- strong evidence that irreversible damage other than the effects referred to in section 4 is likely to be caused by a single exposure by an appropriate route, generally in the abovementioned dose range.
In order to indicate the route of administration/exposure one of the following combinations shall be used: R39/23, R39/24, R39/25, R39/23/24, R39/23/25, R39/24/25, R39/23/24/25.
R48 Danger of serious damage to health by prolonged exposure
- serious damage (clear functional disturbance or morphological change which have toxicological significance) is likely to be caused by repeated or prolonged exposure by an appropriate route.
Substances and preparations are classified at least as Toxic when these effects are observed at levels of one order of magnitude lower (i.e. 10- fold) than those set out for R48 in Section 3.2.3.
In order to indicate the route of administration/exposure one of the following combinations shall be used: R48/23, R48/24, R48/25, R48/23/24, R48/23/25, R48/24/25, R48/23/24/25.
3.2.3. Harmful
Substances and preparations shall be classified as harmful and assigned the symbol ‘Xn’ and the indication of danger ‘harmful’ in accordance with the criteria specified below. Risk phrases shall be assigned in accordance with the following criteria:
R22 Harmful if swallowed
Acute toxicity results:
- LD50 per oral, rat: 200 < LD50 ≤ 2000 mg/kg,
- discriminating dose, oral, rat, 50 mg/kg: 100% survival but evident toxicity,
- less than 100% survival at 500 mg/kg, rat oral by the fixed dose procedure. Refer to the evaluation table in the test method B1 (a) of Annex V.
R21 Harmful in contact with skin
Acute toxicity results:
- LD50 dermal, rat or rabbit: 400 < LD50 ≤ 2 000 mg/kg
R20 Harmful by inhalation
Acute toxicity results:
- LC50 inhalation, rat, for aerosols or particulates: 1 < LC50 ≤ 5 mg/litre/4hr,
- LC50 inhalation, rat, for gases or vapours: 2 < LC50 ≤ 20 mg/litre/4hr.
R65 Harmful: may cause lung damage if swallowed
Liquid substances and preparations presenting an aspiration hazard in humans because of their low viscosity:
- (a) For substances and preparations containing aliphatic, alicyclic and aromatic hydrocarbons in a total concentration equal to or greater than 10% and having either
- a flow time of less than 30 sec. in a 3 mm ISO cup according to ISO 2431, or
- a kinematic viscosity measured by a calibrated glass capillary viscometer in accordance with ISO 3104/3105 of less than 7 x 10^-6 m2/sec at 40° C
- a kinematic viscosity derived from measurements of rotational viscometry in accordance with ISO 3219 of less than 7 x 10^-6 m2/sec at 40° C
Note that substances and preparations meeting these criteria need not be classified if they have a mean surface tension greater than 33mN/m at 25° C as measured by the du Nouy tensiometer or by the test methods shown in Annex V Part A.5.
- (b) For substances and preparations, based on practical experience in humans.
R40 Possible risk of irreversible effects
- strong evidence that irreversible damage other than the effects referred to in Chapter 4 is likely to be caused by a single exposure by an appropriate route, generally in the above-mentioned dose range.
In order to indicate route of administration/exposure one of the following combinations shall be used: R40/20, R40/21, R40/22, R40/20/21, R40/20/22, R40/21/22, R40/20/21/22.
R48 Danger of serious damage to health by prolonged exposure
- serious damage (clear functional disturbance or morphological change which has toxicological significance) is likely to be caused by repeated or prolonged exposure by an appropriate route.
Substances and preparations are classified at least as harmful when these effects are observed at levels of the order of:
- oral, rat ≤ 50 mg/kg (bodyweight)/day,
- dermal, rat or rabbit ≤ 100 mg/kg (bodyweight)/day,
- inhalation, rat ≤ 0,25 mg/1, 6h/day.
These guide values can apply directly when severe lesions have been observed in a subchronic (90 days) toxicity test. When interpreting the results of a sub-acute (28 days) toxicity test these figures should be increased approximately three fold. If a chronic (two years) toxicity test is available it should be evaluated on a case-by-case basis. If results of studies of more than one duration are available, then those from the study of the longest duration should normally be used.
In order to indicate route of administration/exposure one of the following combinations shall be used: R48/20, R48/21, R48/22, R48/20/21, R48/20/22, R48/21/22, R48/20/21/22.
3.2.3.1 Comments regarding volatile substances
For certain substances with a high saturated vapour concentration evidence may be available to indicate effects that give cause for concern. Such substances may not be classified under the criteria for health effects in this guide (3.2.3) or not covered by section 3.2.8. However, where there is appropriate evidence that such substances may present a risk in normal handling and use then classification on a case-by-case basis in Annex I may be necessary.
3.2.4 Comments regarding the use of R48
Use of this risk phrase refers to the specific range of biological effects within the terms described below. For application of this risk phrase serious damage to health is to be considered to include death, clear functional disturbance or morphological changes which are toxicologically significant. It is particularly important when these changes are irreversible. It is also important to consider not only specific severe changes in a single organ or biological system but also generalized changes of a less severe nature involving several organs, or severe changes in general health status.
When assessing whether there is evidence for these types of effects reference should be made to the following guidelines:
Evidence indicating that R48 should be applied:
- (a) substance-related deaths
- (b) (i) major functional changes in the central or peripheral nervous systems, including sight, hearing and the sense of smell, assessed by clinical observations or other appropriate methods (e.g. electrophysiology)
- (ii) major functional changes in other organ systems (for example the lung).
- (c) Any consistent changes in clinical biochemistry, haematology or urinalysis parameters which indicate severe organ dysfunction. Haematological disturbances are considered to be particularly important if the evidence suggests that they are due to decreased bone marrow production of blood cells;
- (d) severe organ damage noted on microscopic examination following autopsy;
- (i) widespread or severe necrosis, fibrosis or granuloma formation in vital organs with regenerative capacity (e.g. liver).
- (ii) severe morphological changes that are potentially reversible but are clear evidence of marked organ dysfunction (e.g. severe fatty change in the liver, severe acute tubular nephrosis in the kidney, ulcerative gastritis).
- (iii) evidence of appreciable cell death in vital organs incapable of regeneration (e.g. fibrosis of the myocardium or dying back of a nerve) or in stem cell populations (e.g. aplasia or hypoplasia of the bone marrow).
The above evidence will most usually be obtained from animal experiments. When considering data derived from practical experience special attention should be given to exposure levels.
Evidence indicating that R48 should not be applied.
The use of this risk phrase is restricted to ‘serious damage to health by prolonged exposure’. A number of substance-related effects may be observed in both humans and animals that would not justify the use of R48. These effects are relevant when attempting to determine a no-effect level for a chemical substance. Examples of well documented changes which would not normally justify classification with R48, irrespective of their statistical significance, include:
- (a) clinical observations or changes in bodyweight gain, food consumption or water intake, which may have some toxicological importance but which do not, by themselves, indicate ‘serious damage’;
- (b) small changes in clinical biochemistry, haematology or urinalysis parameters which are of doubtful or minimal toxicological importance;
- (c) changes in organ weights with no evidence of organ dysfunction;
- (d) adaptative responses (e.g. macrophage migration in the lung, liver hypertrophy and enzyme induction, hyperplastic responses to irritants). Local effects on the skin produced by repeated dermal application of a substance which are more appropriately classified with R38 ‘irritating to skin’;
- (e) where a species-specific mechanism of toxicity (e.g. specific metabolic pathways) has been demonstrated.
3.2.5. Corrosive
A substance or a preparation is considered to be corrosive if, when it is applied to healthy intact animal skin, it produces full thickness destruction of skin tissue on at least one animal during the test for skin irritation cited in Annex V or during an equivalent method or if the results can be predicted, for example from strongly acid or alkaline reactions (demonstrated pH of 2 or less or 11,5 or greater. Alkaline or acidic reserve should also be taken into account).
Classification can be based on the results of validated in vitro tests.
The substance or preparation shall be classified as corrosive and assigned the symbol ‘C’ and the indication of danger ‘corrosive’. Risk phrases shall be assigned in accordance with the following criteria:
R35 Causes severe burns
- if, when applied to healthy intact animal skin, full thickness destruction of skin tissue occurs as a result of up to three minutes exposure, or if this result can be predicted.
R34 Causes burns
- if, when applied to healthy intact animal skin, full thickness destruction of skin tissue occurs as a result of up to four hours exposure, or if this result can be predicted.
- organic hydroperoxides, except where evidence to the contrary is available.
3.2.6. Irritant
Substances and preparations shall be classified as irritant and assigned the symbol ‘Xi’ and the indication of danger ‘irritant’ in accordance with the criteria given below.
3.2.6.1 Inflammation of the skin
The following risk phrase shall be assigned in accordance with the criteria given:
R38 Irritating to skin
- Substances and preparations which cause significant inflammation of the skin which persists for at least 24 hours after an exposure period of up to four hours determined on the rabbit according to the cutaneous irritation test method cited in Annex V.
Inflammation of the skin is significant if:
- (a) the mean value of the scores for either erythema and eschar formation or oedema formation, calculated over all the animals tested, is 2 or more,
- (b) or, in the case where the Annex V test has been completed using three animals, either erythema and eschar formation or oedema formation equivalent to a mean value of 2 or more calculated for each animal separately has been observed in two or more animals.
In both cases all scores at each of the reading times (24, 48 and 72 hr) for an effect should be used in calculating respective mean values.
Inflammation of the skin is also significant if it persists in at least two animals at the end of the observation time. Particular effects e.g. hyperplasia, scaling, discoloration, fissures, scabs and alopecia should be taken into account.
Relevant data may also be available from non-acute animal studies (see comments on R48, section 2.d). These are considered significant if the effects seen are comparable to those described above.
- Substances and preparations which cause significant inflammation of the skin, based on practical observations in humans on immediate, prolonged or repeated contact.
- Organic peroxides, except where evidence to the contrary is available.
Paresthesia:
Paresthesia caused in humans by skin contact with pyrethroid pesticides is not regarded as an irritant effect justifying classification as Xi; R38. The S-phrase S24 should however be applied for substances seen to cause this effect.
3.2.6.2. Ocular lesions
The following risk phrases shall also be assigned in accordance with the criteria given:
R36 Irritating to eyes
- Substances and preparations which, when applied to the eye of the animal, cause significant ocular lesions which occur within 72 hours after exposure and which persist for at least 24 hours.
Ocular lesions are significant if the means scores of the eye irritation test cited in Annex V have any of the following values:
- cornea opacity equal to or greater than 2 but less than 3,
- iris lesion equal to or greater than 1 but not greater than 1,5,
- redness of the conjunctivae equal to or greater than 2,5,
- oedema of the conjunctivae (chemosis) equal to or greater than 2,
or, in the case where the Annex V test has been completed using three animals if the lesions, on two or more animals, are equivalent to any of the above values except that for iris lesion the value should be equal to or greater than 1 but less than 2 and for redness of the conjunctivae the value should be equal to or greater than 2,5.
In both cases all scores at each of the reading times (24, 48 and 72 hours) for an effect should be used in calculating the respective mean values.
- Substances or preparations which cause significant ocular lesions, based on practical experience in humans.
- Organic peroxides except where evidence to the contrary is available.
R41 Risk of serious damage to eyes
- Substances and preparations which, when applied to the eye of the animal cause severe ocular lesions which occur within 72 hours after exposure and which persist for at least 24 hours.
Ocular lesions are severe if the means of the scores of the eye irritation test in Annex V have any of the values:
- cornea opacity equal to or greater than 3,
- iris lesion greater than 1,5.
The same shall be the case where the test has been completed using three animals if these lesions, on two or more animals, have any of the values:
- cornea opacity equal to or greater than 3,
- iris lesion equal to 2.
In both cases all scores at each of the reading times (24, 48 and 72 hours) for an effect should be used in calculating the respective mean values.
Ocular lesions are also severe when they are still present at the end of the observation time.
Ocular lesions are also severe if the substance or preparation causes irreversible colouration of the eyes.
- Substances and preparations which cause severe ocular lesions, based on practical experience in humans.
Note:
When a substance or preparation is classified as corrosive and assigned R34 or R35, the risk of severe damage to eyes is considered implicit and R41 is not included in the label. However, in the case of preparations, when calculating the sum of quotients by the formulae in 3.5(f)(ii) and 3.5(h)(ii) of Directive 88/379/EEC substances classified as corrosive shall be considered as if R41 had been assigned.
3.2.6.3. Respiratory system irritation
The following risk phrase shall be assigned in accordance with the criteria given:
R37 Irritating to respiratory system
- Substances and preparations which cause serious irritation to the respiratory system based on:
- practical observation in humans.
- Positive results from appropriate animal tests
Comments regarding the use of R37
In interpreting practical observations in humans, care should be taken to distinguish between effects which lead to classification with R48 (see section 3.2.4) from those leading to classification with R37. Conditions normally leading to classification with R37 are reversible and usually limited to the upper airways.
Positive results from appropriate animal tests may include data obtained in a general toxicity test, including histopathological data from the respiratory system. Data from the measurement of experimental bradypnea may also be used to assess airway irritation.
3.2.7 Sensitisation
3.2.7.1 Sensitisation by inhalation
Substances and preparations shall be classified as sensitising and assigned the symbol Xn, the indication of danger ‘Harmful’ and the risk phrase R42 in accordance with the criteria given below.
R42 May cause sensitisation by inhalation
- If there is evidence that the substance or preparation can induce specific respiratory hypersensitivity
- where there are positive results from appropriate animal tests
- If the substance is an isocyanate, unless there is evidence that the substance does not cause respiratory hypersensitivity
Comments regarding the use of R42
Human evidence
Evidence that the substance can induce specific respiratory hypersensitivity will normally be based on human experience. In this contact hypersensitivity is normally seen as asthma, but other hypersensitivity reactions such as rhinitis and alveolitis are also considered. The condition will have the clinical character of an allergic reaction. However, immunological mechanisms do not have to be demonstrated.
When considering the evidence from human exposure, it is necessary for a decision on classification to take into account in addition to the evidence from the cases:
- the size of the population exposed
- the extent of exposure
The evidence referred to above could be
- clinical history and data from appropriate lung function tests related to exposure to the substance, confirmed by other supportive evidence which may include:
- a chemical structure related to substances known to cause respiratory hypersensitivity
- in vivo immunological test (e.g. skin prick test)
- in vitro immunological test (e.g. serological analysis)
- studies that may indicate other specific, but non-immunological mechanisms of action, e.g. repeated low level irritation, pharmacologically mediated effects
- data from a positive bronchial challenge test with the substance conducted according to accepted guidelines for the determination of a specific hypersensitivity reaction
Clinical history should include both medical and occupational history to determine a relationship between exposure to a specific substance and development of respiratory sensitivity. Relevant information includes aggravating factors both in the home and workplace, the onset and progress of the disease, family history and medical history of the patient in question. The medical history should also include a note of other allergic or airway disorders from childhood, and smoking history.
The results of positive bronchial challenge tests are considered to provide sufficient evidence for classification their own. It is however recognized that in practice many of the examinations listed above will already have been carried out.
Substances that elicit symptoms of asthma by irritation only in people with bronchial hyper reactivity should not be assigned R42.
Animal Studies
Data from tests which may be indicative of the potential of a substance to cause sensitisation by inhalation in humans may include:
- lgE measurements (e.g. in mice)
- Specific pulmonary responses in guinea pigs
3.2.7.2. Sensitisation by skin contact
Substances and preparations shall be classified as and sensitising and assigned the symbol ‘Xi’, the indication of danger ‘Irritant’ and the risk phrase R43 in accordance with the criteria given below:
R43 May cause sensitisation by skin contact
- If practical experience shows the substance or preparation to be capable of inducing a sensitisation by skin contact in a substantial number of persons,
- where there are positive results from an appropriate animal test
Comments regarding the use of R43
Human evidence
The following evidence (practical experience) is sufficient to classify a substance or preparation with R43:
- Positive data from appropriate patch testing, normally in more than one dermatological clinic, or
- Epidemiological studies showing allergic contact dermatitis caused by the substance. Situations in which a high proportion of those exposed exhibit characteristic symptoms are to be looked at with special concern, even if the number of cases is small, or
- Positive data from experimental studies in man (see also 3.1.1)
The following is sufficient to classify a substance with R43 when there is supportive evidence:
- Isolated episodes of allergic contact dermatitis, or
- Epidemiological studies where chance, bias or confounders have not been ruled out fully with reasonable confidence.
Supportive evidence may include:
- data from animal tests performed according to existing guidelines, with a result that does not meet the criteria given in the section on animal studies but is sufficiently close to the limit to be considered significant, or
- data from non-standard methods, or
- appropriate structure-activity relationships.
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