CLP Regulation Annex I. Section 3.1.
Acute Toxicity Estimates (ATE) are numerical values used to classify substances and mixtures for acute toxicity based on oral, dermal, or inhalation exposure routes. The CLP Regulation provides guidelines for their calculation and application.
1. Definition and Purpose of ATE
- ATE represents the estimated lethal dose (LD50) or lethal concentration (LC50) for 50% of a tested population.
- It is primarily used to classify substances and mixtures in acute toxicity categories.
- Manufacturers, importers, and downstream users must determine ATE values where applicable.
2. Acute Toxicity Classification Criteria
Substances are classified into one of four acute toxicity categories based on the exposure route and ATE values:
| Exposure Route | Category 1 (Fatal) | Category 2 (Fatal) | Category 3 (Toxic) | Category 4 (Harmful) |
| Oral (mg/kg body weight) | ATE ≤ 5 | 5 < ATE ≤ 50 | 50 < ATE ≤ 300 | 300 < ATE ≤ 2000 |
| Dermal (mg/kg body weight) | ATE ≤ 50 | 50 < ATE ≤ 200 | 200 < ATE ≤ 1000 | 1000 < ATE ≤ 2000 |
| Inhalation (gas) (ppmV) | ATE ≤ 100 | 100 < ATE ≤ 500 | 500 < ATE ≤ 2500 | 2500 < ATE ≤ 5000 |
| Inhalation (vapor) (mg/L) | ATE ≤ 0.5 | 0.5 < ATE ≤ 2.0 | 2.0 < ATE ≤ 10 | 10 < ATE ≤ 20 |
| Inhalation (dust/mist) (mg/L) | ATE ≤ 0.05 | 0.05 < ATE ≤ 0.5 | 0.5 < ATE ≤ 1.0 | 1.0 < ATE ≤ 5.0 |
- ATE values are based on existing toxicological data, bridging principles, or calculation methods when experimental data is unavailable.
3. Methods for Determining ATE for Substances
- Using LD50 or LC50 Data:
- If LD50 or LC50 values are available from studies, they are directly used as ATE values.
- Bridging Principles (for Similar Substances/Mixtures):
- If a similar tested substance or mixture exists, ATE can be extrapolated using the bridging principles.
- Calculation Methods:
- If no LD50/LC50 data is available, ATE can be estimated based on constituent concentrations using summation formulas.
4. ATE for Mixtures – Calculation Method
For mixtures, ATE is calculated using the weighted sum of the ATE values of individual components:
ATEmixture=100∑(CiATEi)ATE_{\text{mixture}} = \frac{100}{\sum \left( \frac{C_i}{ATE_i} \right)}ATEmixture=∑(ATEiCi)100
where:
- CiC_iCi = concentration of component iii (in %)
- ATEiATE_iATEi = acute toxicity estimate of component iii
- Components ≥ 1% must be included in the calculation.
- Highly toxic components (< 1%) should be considered if they contribute significantly to overall toxicity.
5. Special Considerations and Exemptions
- ATE values do not apply to harmonized hazard classifications already included in Annex VI of the CLP Regulation.
- If an ATE is not provided for a substance in Annex VI, the manufacturer must determine an appropriate ATE based on available data.
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