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Classification

Acute toxicity

According to 3.1.3.6 of Annex I to CLP calculation of Acute Toxicity classification is based on two approaches:

1) data available for all ingredients
2) data are not available for all ingredients

First approach applies when the total concentration of the relevant ingredient(s) with unknown acute toxicity is ≤ 10 %. In this case formula from 3.1.3.6.1 of Annex I to CLP is used (see below  ).

Second approach applies when the total concentration of the relevant ingredient(s) with unknown acute toxicity is > 10 %. In this case formula from 3.1.3.6.2.3 of Annex I to CLP is used (see below  ).


Relevant ingredient means ingredient present in concentration of 1 % (w/w for solids, liquids, dusts, mists and vapours and v/v for gases) or greater (unless there is a reason to suspect that an ingredient present at a concentration of less than 1 % is still relevant for classifying the mixture for acute toxicity) (CLP, Annex I, 3.1.3.3(a)).

Ingredient with known acute toxicity is an ingredient which:

has acute toxicity category, or
has LD50 (oral, dermal) / LC50 (inhalation), or
has established ATE value(s), or
is not acutely toxic (e.g., water, sugar).

If mixture contains ingredients for which you know nothing about their acute toxicity properties, they should be treated as ingredients with unknown acute toxicity.

If a mixture does not contain any ingredients with unknown acute toxicity, the first approach (data available for all ingredients) is applied. If a mixture contains substance(s) with unknown acute toxicity you should check concentrations of which is(are) ≥ 1 % and make summation of concentrations only those which are ≥ 1 %. If the sum is ≤ 10 % the first approach is applied (data available for all ingredients), otherwise the second approach is applied (data are not available for all ingredients).

Example 1
Example 2
Example 3
Example 4

1) Data available for all ingredients

The below formula is applied for mixtures, where the total concentration of the relevant ingredient(s) with unknown acute toxicity is ≤ 10 % (CLP, Annex I, 3.1.3.6.1).

100
ATE mix
=
Σ
n
C i
ATE i

where:

ATE mix Acute Toxicity Estimate of the whole mixture,
C i concentration of ingredient i (% w/w or % v/v),
i the individual ingredient from 1 to n,
n the number of ingredients,
ATE i Acute Toxicity Estimate of ingredient i.

2) Data are not available for all ingredients

If the total concentration of the relevant ingredient(s) with unknown toxicity is > 10 %, a modified additivity formula in CLP Annex I, 3.1.3.6.2.3 must be used.

100 - (Σ C unknown if > 10 %)
ATE mix
=
Σ
n
C i
ATE i

where:

ATE mix Acute Toxicity Estimate of the whole mixture,
Σ C unknown if > 10 % concentration sum of relevant ingredients with unknown toxicity (% w/w or % v/v),
C i concentration of ingredient i (% w/w or % v/v),
i the individual ingredient from 1 to n,
n, the number of ingredients
ATE i Acute Toxicity Estimate of ingredient i.

When approach (formula) is selected, below two questions should be answered for every ingredient with known acute toxicity:

what is its Acute Toxicity Estimate (ATE) value for appropriate route (oral, dermal and inhalation)?
is its concentration above the cut-off limit for appropriate category (1, 2, 3 and 4)?

Calculation of ingredient's ATE

If substance is listed in Table 3 of Annex VI to CLP, but neither acute toxicity category nor harmonised ATE are presented in the table as well as no LD50/LC50 value is available, this means it is known that such a substance does not possess acute toxicity properties. In this case, ATE of the substance equals to 0, therefore, such ingredient need not be considered in the calculation of mixture's acute toxicity.

Acute Toxicity Estimates (ATEs) are the way of expressing acute toxicity. ATE for mixture's ingredient may be based on LD50 (oral, dermal) or LC50 (inhalation) or appropriate Acute toxicity hazard category of ingredient (CLP, Annex I, 3.1.2.1).

LD means "Lethal Dose". LD50 is the amount of a chemical, given all at once, which causes the death of 50 % of test animals.
LC means "Lethal Concentration". LC50 is the concentration of a chemical in air, which causes the death of 50 % of test animals.

If substance is listed in Table 3 of Annex VI to CLP and harmonised ATE value is available for this substance in column "Specific Conc. Limits, M-factors and ATE", this value must be used. If acute toxicity category and LD50/LC50 are also known, the harmonised ATE has a priority.
If harmonised ATE is not known, but both acute toxicity category from Table 3 of Annex VI to CLP and LD50/LC50 are available, the LD50/LC50 value must be used as ATE to calculate mixture's acute toxicity.
If only acute toxicity category from Table 3 of Annex VI to CLP is known (no ATE, no LD50/LC50) you should convert the category to ATE (cATpE - converted Acute Toxicity point Estimate) based on the Table 3.1.2 of Annex I to CLP (see table below).

For example, if ingredient of a mixture is classified as 'Acute Tox. 3: H301' (H301 - oral route of exposure) based on Table 3.1.2 of Annex I to CLP the cATpE for oral route = 100.

The hazard class Acute Toxicity is differentiated into (CLP, Annex I, 3.1.1.2):

acute oral toxicity,
acute dermal toxicity,
acute inhalation toxicity.

Classification of a mixture must be calculated for each route of exposure, therefore, the above 4 steps of definition Acute Toxicity Estimate(s) should be considered for oral, dermal and inhalation.

Table 3.1.2 of Annex I to CLP

Exposure routes Classification category or
experimentally obtained acute toxicity range estimate
Converted acute toxicity point estimate
Oral 0 < Category 1 ≤ 5 0.5
(mg/kg 5 < Category 2 ≤ 50 5
bodyweight) 50 < Category 3 ≤ 300 100
300 < Category 4 ≤ 2 000 500
Dermal 0 < Category 1 ≤ 50 5
(mg/kg 50 < Category 2 ≤ 200 50
bodyweight) 200 < Category 3 ≤ 1 000 300
1 000 < Category 4 ≤ 2 000 1 100
Gases 0 < Category 1 ≤ 100 10
(ppmV) 100 < Category 2 ≤ 500 100
500 < Category 3 ≤ 2 500 700
2 500 < Category 4 ≤ 20 000 4 500
Vapours 0 < Category 1 ≤ 0.5 0.05
(mg/l) 0.5 < Category 2 ≤ 2.0 0.5
2.0 < Category 3 ≤ 10.0 3
10.0 < Category 4 ≤ 20.0 11
Dust/mist 0 < Category 1 ≤ 0.05 0.005
(mg/l) 0.05 < Category 2 ≤ 0.5 0.05
0.5 < Category 3 ≤ 1.0 0.5
1.0 < Category 4 ≤ 5.0 1.5

The terms 'dust', 'mist' and 'vapour' are defined as follows (CLP, Annex I, note (d) to Table 3.1.1):

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.


If mixture contains ingredient without established acute toxicity category, but the known LD50/LC50 value is:

above 2 000 mg/kg bodyweight for oral route,
above 2 000 mg/kg bodyweight for dermal route,
above 20 000 ppmV for inhalation (gases) route,
above 20.0 mg/l for inhalation (vapours) route,
above 5.0 mg/l for inhalation (dust/mist) route

such ingredient is treated as ingredient without acute toxicity properties and need not be considered in the calculation of mixture's classification. Mentioned above values are maximum values for appropriate route of exposure that lead to acute toxicity category 4 (CLP, Annex I, Table 3.1.1).

Example 5
Example 6
Example 7
Example 8
Example 9

Cut-off limits

Cut-off limit is a concentration limit, above which classified ingredient is taken into account for classification purposes. The generic cut-off values are listed in Table 1.1 of Annex I to CLP. In the table below cut-off limits for acute toxicity are presented.

Hazard class Generic cut-off values to be taken into account
Acute Toxicity:
 -  Category 1-3:
    Acute Tox. 1
    Acute Tox. 2
    Acute Tox. 3
0.1 %
 -  Category 4:
    Acute Tox. 4
1 %


Ingredient of a mixture classified as Acute Tox. category 1 or 2 or 3 at concentration below 0.1 % is ignored,
Ingredient of a mixture classified as Acute Tox. category 4 at concentration below 1 % is ignored.

In case if there is no information on ingredient's acute toxicity, but LD50 or LC50 or ATE is available, this value should be used to determine acute toxicity category using Table 3.1.1 of Annex I to CLP.

If LC50 is available, but without information on physical form (dust/mist or vapour) the category of acute toxicity should be determined for both dust/mist and vapour, which should be used later for calculation of inhalation acute toxicity as dust/mist and vapour. For example, LC50 = 4.0 mg/l will lead to Acute Tox. 3: H331 for vapours and to Acute Tox. 4: H332 for dusts/mists. Please take into account that there is a special case of inhalation acute toxicity calculation (see below).

Example 10
Example 11
Example 12

All ingredients have the same category

If the converted acute toxicity point estimates for all components of a mixture are within the same category, then the mixture should be classified in that category (CLP, Annex I, 3.1.3.3.(c)). Other words, if all components are classified at the same category of acute toxicity for the same route of exposure, the mixture should be classified in that category and for that route.

For example, if all ingredients are classified as Acute Tox. 2: H300 (oral) then the whole mixture is also should be classified as Acute Tox. 2: H300.

Example 13
Example 14
Example 15

Special case for acute inhalation toxicity

When calculating inhalation acute toxicity of a mixture the hazard arose from three physical forms should be assessed:

gases,
vapours,
dusts/mists.

In turn, if physical form of a mixture or knowledge on its use may exclude some route of inhalation exposure, such a route not need to be assessed. For example, for gaseous mixture inhalation acute toxicity should be calculated for a gas physical form. For liquid mixture - vapour and mist are the most appropriate. For solid mixture - dust.

If mixture contains ingredients with known inhalation acute toxicity category only (no ATE, no LC50), this category should be used to determine converted Acute Toxicity point Estimate (cATpE) for every proper physical form that should to be assessed.

If ATE or LC50 is available for e.g. mist, this value must be used in calculation of inhalation acute toxicity for mist physical form.

If mixture contains ingredient without established acute toxicity category, only ATE or LC50 is available for e.g. mist tested form, but hazard of vapour physical form should be assessed, ATE/LC50 (mist) value can not be used directly for calculation of inhalation acute toxicity for vapour physical form. This value should be used to convert it to category of acute toxicity and based on the obtained category the cATpE should be determined for vapour form. The same way the hazard for mist should assessed, when for some ingredient ATE or LC50 value for vapour is available only.

For example, if hazard for vapour should be assessed and mixture contains ingredient with known LC50 (mist) = 2.0 mg/l (no category is available), based on Table 3.1.1 of Annex I to CLP this value leads to category 4 (between 1.0 and 5.0). In turn, for vapour and category 4 converted ATE (cATpE) = 11.

If both mists and vapours may be formed during any expected use, inhalation acute toxicity categories should be calculated separately for both forms and the most severe must be selected.

Example 16
Example 17
Example 18
Example 19
Example 20
Example 21
Example 22
Example 23

Additional labelling provisions

In case if a component without any useable information for classification (unknown acute toxicity) is used in a mixture at a concentration ≥ 1 %, the label and section 2.2 of safety data sheet must contain following information: "x percent of the mixture consists of component(s) of unknown acute toxicity" (CLP, Annex I, 3.1.3.6.2.2).

Hierarchy of hazard categories

Hazard
Acute oral toxicity, category 1 (Acute Tox. 1: H300)
Acute oral toxicity, category 2 (Acute Tox. 2: H300)
Acute oral toxicity, category 3 (Acute Tox. 3: H301)
Acute oral toxicity, category 4 (Acute Tox. 4: H302)
Hazard
Acute dermal toxicity, category 1 (Acute Tox. 1: H310)
Acute dermal toxicity, category 2 (Acute Tox. 2: H310)
Acute dermal toxicity, category 3 (Acute Tox. 3: H311)
Acute dermal toxicity, category 4 (Acute Tox. 4: H312)
Hazard
Acute inhalation toxicity, category 1 (Acute Tox. 1: H330)
Acute inhalation toxicity, category 2 (Acute Tox. 2: H330)
Acute inhalation toxicity, category 3 (Acute Tox. 3: H331)
Acute inhalation toxicity, category 4 (Acute Tox. 4: H332)

A more severe classification for a mixture overrides a less severe classification. If a mixture is classified for more than one route of exposure then all relevant classifications should be communicated in section 2.2 of safety data sheet and the appropriate hazard communication elements included on the label (CLP, Annex I, 3.1.4.2.).

For example, if ingredients of a mixture lead to classification both as acute oral toxicity category 2 (Acute Tox. 2) and acute dermal toxicity category 4 (Acute Tox. 4) the category Acute Tox. 2 must be selected. The hazard statement H300 is applied to acute oral toxicity category 2 and hazard statement H312 is applied to acute dermal toxicity category 4. Both H300 and H312 belong to different routes of exposure (oral and dermal), therefore, both of them must be indicated (Acute Tox. 2: H300, H312).

To select pictogram, signal word and precautionary statements please refer to Annex I, part 3, Table 3.1.3 of Regulation (EC) no 1272/2008 (CLP).

In addition to classification for inhalation toxicity, if data are available that indicates that the mechanism of toxicity is corrosivity, mixture should also be labelled as EUH071 - 'Corrosive to the respiratory tract'. In addition to an appropriate acute toxicity pictogram, a corrosivity pictogram (GHS05) may be added (CLP, Annex I, Table 3.1.3, Note 1; Annex II, 1.2.6).

Example 24
Example 25
Example 26

See also Example 1  and Example 8  in section Examples.