Specific target organ toxicity - repeated exposure (STOT RE)
Non-additivity approach
The additivity approach is not applicable for calculation of STOT RE.
If a single ingredient with classification STOT RE is present in the mixture above the generic or specific concentration limit the mixture must be classified for that hazard. Other hand, if the mixture contains two or more ingredients each below the generic or specific concentration limit, even if the sum of their concentrations is above generic concentration limit, the mixture will not be classified.
The mixture is classified as a specific target organ toxicant (specific organ specified), following repeated exposure when at least one ingredient is classified as a Category 1 or Category 2 specific target organ toxicant (repeated exposure) and is present at or above the appropriate generic concentration limit as laid out in Table 3.9.4 of Annex I to CLP for Category 1 and 2 respectively.
| Component classified as |
Generic concentration limits triggering classification of a mixture as |
| Component classified as |
STOT RE 1 |
STOT RE 2 |
| STOT RE 1 |
≥ 10 % |
1.0 % ≤ C < 10 % |
| STOT RE 2 |
|
≥ 10 % (note 1) |
Note.
If a Category 2 specific target organ toxicant is present in the mixture as an ingredient at a concentration ≥ 1.0 % a safety data sheet shall be available for the mixture upon request.
Hierarchy of hazard categories
Hazard
➔
| − |
Specific target organ toxicity - repeated exposure, category 1 (STOT RE 1: H372) |
| − |
Specific target organ toxicity - repeated exposure, category 2 (STOT RE 2: H373) |
A more severe classification for a mixture overrides a less severe classification. For example, if ingredients of a mixture lead to classification both as specific target organ toxicity - repeated exposure category 1 (STOT RE 1) and specific target organ toxicity - repeated exposure category 2 (STOT RE 2) the category 'STOT RE 1' must be selected.
According to Table 1.1 of Annex III to CLP:
| − |
H372 sounds: "Causes damage to organs <or state all organs affected, if known> through prolonged or repeated exposure <state route of exposure if it is conclusively proven that no other routes of exposure cause the hazard>". |
| − |
H373 sounds: "May cause damage to organs <or state all organs affected, if known> through prolonged or repeated exposure <state route of exposure if it is conclusively proven that no other routes of exposure cause the hazard>". |
When a mixture is classified for 'STOT RE 1' or 'STOT RE 2' on the basis of ingredients the hazard statement H372 (category 1) or H373 (category 2) may be used without specifying the target organs and without specifying the routes of exposure.
To select pictogram, signal word and precautionary statements please refer to Annex I, part 3, Table 3.9.5 of Regulation (EC) no 1272/2008 (CLP).
Mixtures are classified for either or both STOT SE (single exposure) and STOT RE (repeated exposure) independently.
There is a mixture:
| Ingredient |
Conc. % (w/w) |
Classification |
| Substance A |
12 |
STOT RE 1: H372 |
| Substance B |
3 |
STOT RE 1: H372 |
| Substance C |
8 |
STOT RE 2: H373 |
| Water |
77 |
− |
Cut-off limits
| − |
There is no generic cut-off limit for STOT RE (CLP, Annex I, Table 1.1), therefore, any concentration of an ingredient with such classification is taken into account. |
Specific and Generic concentration limits
| − |
Because no specific concentration limits are applied for any ingredient, concentrations of mixture's ingredients must be compared to generic concentration limits. |
Calculation of 'STOT RE 1'
| − |
Concentration of substance A is above the generic concentration limit 10 %. This leads to classification STOT RE 1 . |
| − |
Concentration of substance B is below the generic concentration limit 10 %. This does not lead to classification 'STOT RE 1'. |
Calculation of 'STOT RE 2'
| − |
Concentration of substance A is above the generic concentration limit 10 %. This does not lead to classification 'STOT RE 2'. |
| − |
Concentration of substance B is between 1 % and 10 % of the generic concentration limit. This leads to classification STOT RE 2 . |
| − |
Concentration of substance C is below the generic concentration limit 10 %. This does not lead to classification 'STOT RE 2'. |
Selection of hazard category
| − |
Classification category 'STOT RE 1' is more severe than 'STOT RE 2', therefore, mixture is classified as 'STOT RE 1'. |
Selection of hazard statements
| − |
H372 corresponds to 'STOT RE 1'. |
Selection of pictogram and signal word
| − |
Pictogram GHS08 and signal word 'Danger' correspond to 'STOT RE 1'. |
Selection of precautionary statements
| − |
For H372 following precautionary statements are applied: P260, P264, P270, P314, P501. |
Classification and labelling of the mixture
| Classification: |
STOT RE 1 |
| Hazard statements: |
H372 |
| Pictogram: |
 |
|
GHS08 |
| Signal word: |
Danger |
| Precautionary statements: |
P260, P264, P270, P314, P501 |
There is a mixture:
| Ingredient |
Conc. % (w/w) |
Classification |
| Substance A |
8 |
STOT RE 1: H372 (lung) |
| Substance B |
8 |
STOT RE 1: H372 |
| Substance C |
8 |
STOT RE 2: H373 |
| Water |
76 |
− |
Cut-off limits
| − |
There is no generic cut-off limit for STOT RE (CLP, Annex I, Table 1.1), therefore, any concentration of an ingredient with such classification is taken into account. |
Specific and Generic concentration limits
| − |
Because no specific concentration limits are applied for any ingredient, concentrations of mixture's ingredients must be compared to generic concentration limits. |
Calculation of 'STOT RE 1'
| − |
Concentration of substance A is below the generic concentration limit 10 %. This does not lead to classification 'STOT RE 1'. |
| − |
Concentration of substance B is below the generic concentration limit 10 %. This does not lead to classification 'STOT RE 1'. |
Calculation of 'STOT RE 2'
| − |
Concentration of substance A is between 1 % and 10 % of the generic concentration limit. This leads to classification STOT RE 2 . |
| − |
Concentration of substance B is between 1 % and 10 % of the generic concentration limit. This leads to classification STOT RE 2 . |
| − |
Concentration of substance C is below the generic concentration limit 10 %. This does not lead to classification 'STOT RE 2'. |
Selection of hazard category
| − |
The mixture is classified as 'STOT RE 2'. |
Selection of hazard statements
| − |
H373 corresponds to 'STOT RE 2'. |
| − |
For mixtures there is no need to identify the target organs and routes of exposure on the label. |
Selection of pictogram and signal word
| − |
Pictogram GHS08 and signal word 'Warning' correspond to 'STOT RE 2'. |
Selection of precautionary statements
| − |
For H373 following precautionary statements are applied: P260, P314, P501. |
Classification and labelling of the mixture
| Classification: |
STOT RE 2 |
| Hazard statements: |
H373 |
| Pictogram: |
|
|
GHS08 |
| Signal word: |
Warning |
| Precautionary statements: |
P260, P314, P501 |
There is a mixture:
| Ingredient |
Conc. % (w/w) |
Classification |
Specific Conc. Limits |
| Substance D |
0.3 |
STOT RE 1: H372 |
STOT RE 1: H372: C ≥ 0.1 %
STOT RE 2: H373: 0.01 % ≤ C < 0.1 % |
| Substance E |
0.3 |
STOT RE 1: H372 |
STOT RE 1: H372: C ≥ 1 %
STOT RE 2: H373: 0.2 % ≤ C < 1 % |
| Water |
99.4 |
− |
− |
Cut-off limits
| − |
There is no generic cut-off limit for STOT RE (CLP, Annex I, Table 1.1), therefore, any concentration of an ingredient with such classification is taken into account. |
Specific and Generic concentration limits
| − |
Substances D and E have specific concentration limits (SCLs). Because SCL has a precedence over generic concentration limit, concentration of D and E must be compared to their SCLs. |
Calculation of 'STOT RE 1'
| − |
Concentration of substance D is above the specific concentration limit of 0.1 %. This leads to classification STOT RE 1 . |
| − |
Concentration of substance E is below the specific concentration limit of 1 %. This does not lead to classification 'STOT RE 1'. |
Calculation of 'STOT RE 2'
| − |
Concentration of substance D is above the upper border of specific concentration limit 0.1 %. This does not lead to classification 'STOT RE 2'. |
| − |
Concentration of substance E is inside the specific concentration limit range (0.2 ≤ C < 1 %). This leads to classification STOT RE 2 . |
Selection of hazard category
| − |
Classification category 'STOT RE 1' is more severe than 'STOT RE 2', therefore, mixture is classified as 'STOT RE 1'. |
Selection of hazard statements
| − |
H372 corresponds to 'STOT RE 1'. |
Selection of pictogram and signal word
| − |
Pictogram GHS08 and signal word 'Danger' correspond to 'STOT RE 1'. |
Selection of precautionary statements
| − |
For H372 following precautionary statements are applied: P260, P264, P270, P314, P501. |
Classification and labelling of the mixture
| Classification: |
STOT RE 1 |
| Hazard statements: |
H372 |
| Pictogram: |
|
|
GHS08 |
| Signal word: |
Danger |
| Precautionary statements: |
P260, P264, P270, P314, P501 |
See also Example 9 in section Examples.