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3.1.2.: Criteria for classification of substances as acutely toxic

3.1.2.1. ►M12  Substances can be allocated to one of four hazard categories based on acute toxicity by the oral, dermal or inhalation route according to the numeric criteria shown in Table 3.1.1. ◄ Acute toxicity values are expressed as (approximate) LD50 (oral, dermal) or LC50 (inhalation) values or as acute toxicity estimates (ATE). Explanatory notes are shown following Table 3.1.1.


Table 3.1.1

Acute toxicity hazard categories and acute toxicity estimates (ATE) defining the respective categories

Exposure route

Category 1

Category 2

Category 3

Category 4

Oral (mg/kg bodyweight)

ATE ≤ 5

5 < ATE ≤ 50

50 < ATE ≤ 300

300 < ATE ≤ 2 000

See:

Note (a)

Note (b)

Dermal (mg/kg bodyweight)

ATE ≤ 50

50 < ATE ≤ 200

200 < ATE ≤ 1 000

1 000 < ATE ≤ 2 000

See:

Note (a)

Note (b)

Gases (ppmV (1))

ATE ≤ 100

100 < ATE ≤ 500

500 < ATE ≤ 2 500

2 500 < ATE ≤ 20 000

see:

Note (a)

Note (b)

Note (c)

Vapours (mg/l)

ATE ≤ 0,5

0,5 < ATE ≤ 2,0

2,0 < ATE ≤ 10,0

10,0 < ATE ≤ 20,0

see:

Note (a)

Note (b)

Note (c)

Note (d)

Dusts and mists (mg/l)

ATE ≤ 0,05

0,05 < ATE ≤ 0,5

0,5 < ATE ≤ 1,0

1,0 < ATE ≤ 5,0

see:

Note (a)

Note (b)

Note (c)

(1)   Gas concentrations are expressed in parts per million per volume (ppmV).

Notes to Table 3.1.1:

(a) The acute toxicity estimate (ATE) for the classification of a substance is derived using the LD50/LC50 where available.
(b) The acute toxicity estimate (ATE) for the classification of a substance in a mixture is derived using:
the LD50/LC50 where available,
the appropriate conversion value from Table 3.1.2 that relates to the results of a range test, or
the appropriate conversion value from Table 3.1.2 that relates to a classification category.
(c) The ranges of the acute toxicity estimates (ATE) for inhalation toxicity used in the Table are based on 4-hour testing exposures. Conversion of existing inhalation toxicity data which have been generated using a 1-hour exposure can be carried out by dividing by a factor of 2 for gases and vapours and 4 for dusts and mists.
(d) For some substances the test atmosphere will not just be a vapour but will consist of a mixture of liquid and vapour phases. For other substances the test atmosphere may consist of a vapour which is near the gaseous phase. In these latter cases, classification shall be based on ppmV as follows: Category 1 (100 ppmV), Category 2 (500 ppmV), Category 3 (2 500 ppmV), Category 4 (20 000 ppmV).

The terms ‘dust’, ‘mist’ and ‘vapour’ are defined as follows:

dust: solid particles of a substance or mixture suspended in a gas (usually air),
mist: liquid droplets of a substance or mixture suspended in a gas (usually air),
vapour: the gaseous form of a substance or mixture released from its liquid or solid state.

Dust is generally formed by mechanical processes. Mist is generally formed by condensation of supersaturated vapours or by physical shearing of liquids. Dusts and mists generally have sizes ranging from less than 1 to about 100 μm.

3.1.2.2. Specific considerations for classification of substances as acutely toxic
3.1.2.2.1. The preferred test species for evaluation of acute toxicity by the oral and inhalation routes is the rat, while the rat or rabbit are preferred for evaluation of acute dermal toxicity. When experimental data for acute toxicity are available in several animal species, scientific judgement shall be used in selecting the most appropriate LD50 value from among valid, well-performed tests.
3.1.2.3. Specific considerations for classification of substances as acutely toxic by the inhalation route
3.1.2.3.1. Units for inhalation toxicity are a function of the form of the inhaled material. Values for dusts and mists are expressed in mg/l. Values for gases are expressed in ppmV. Acknowledging the difficulties in testing vapours, some of which consist of mixtures of liquid and vapour phases, the table provides values in units of mg/l. However, for those vapours which are near the gaseous phase, classification shall be based on ppmV.
3.1.2.3.2. ►M12  Of particular importance in classifying for inhalation toxicity is the use of well articulated values in the highest hazard categories for dusts and mists. ◄ Inhaled particles between 1 and 4 microns mean mass aerodynamic diameter (MMAD) will deposit in all regions of the rat respiratory tract. This particle size range corresponds to a maximum dose of about 2 mg/l. In order to achieve applicability of animal experiments to human exposure, dusts and mists would ideally be tested in this range in rats.
3.1.2.3.3. In addition to classification for inhalation toxicity, if data are available that indicates that the mechanism of toxicity was corrosivity, the substance or mixture shall also be labelled as ‘corrosive to the respiratory tract’ (see note 1 in 3.1.4.1). Corrosion of the respiratory tract is defined by destruction of the respiratory tract tissue after a single, limited period of exposure analogous to skin corrosion; this includes destruction of the mucosa. The corrosivity evaluation can be based on expert judgment using such evidence as: human and animal experience, existing (in vitro) data, pH values, information from similar substances or any other pertinent data.