Six-Pack Toxicological Studies

For the evaluation of the toxicity of the plant protection product, tests on acute toxicity, irritation and sensitization of the active substance should be reported. The relevant calculation methods used for the classification of mixtures specified in Regulation (EU) No 1272/2008 should be applied, where appropriate, in the hazard assessment of the plant protection product. There should be information on the toxic effect, toxicological structure and all other known toxicological aspects of the active substance and related substances.

Six-Pack Toxicology Tests
o Acute Oral Toxicity Test
o Acute Dermal Toxicity Test
o Acute Inhalation Toxicity Test
o Acute Eye Irritation Test
o Acute Dermal Irritation Test
o Sensitization Test

• Acute Systemic Toxicity: Studies, data and information help determine effects after a single exposure to a herbicide. It is sufficient to determine or show the toxicity of the plant protection product, its toxicity relative to the active substance, the time course of the effect and its properties. (According to Regulation EU 1272/2008)

• Acute Oral Toxicity Test; Acute oral toxicity testing will be performed unless the manufacturer can justify an alternative approach under Regulation (EC) No 1272/2008. In the latter case, the acute oral toxicity of all components must be provided or reliably estimated by a validated method. Attention should be paid to the possible effects of the ingredients on the toxic potential of the total mixture.

• Acute Dermal Toxicity Test; Signs of severe skin irritation or corrosion in a dermal study may be used instead of performing a specific irritation study.

• Acute Inhalation Toxicity Test; The study should ensure inhalation toxicity to mice of the plant protection product or the fumes it produces.

• Acute Dermal Irritation/Corrosion Test; The results of the study should provide the potential for skin irritation of the plant protection product, including the potential reversibility of the effects observed. should be done. Where insufficient data are available, they can be developed through sequential testing.

The testing strategy should follow a tiered approach: in vivo evaluation of eye irritation is recommended using an approved available in vitro testing method and when not available.

• Acute Eye Irritation/ Corrosion Test; Before undertaking in vivo studies for eye corrosion/irritation of the plant protection product, a weight-of-evidence analysis should be performed on the relevant available data. Where available data is insufficient, more data can be developed through sequential testing.

• Sensitization Test; Skin sensitization testing shall be performed unless the active substances or excipients are known to have sensitizing properties or the manufacturer cannot justify an alternative approach in accordance with Regulation (EC) No 1272/2008. In the latter case, the skin sensitizing properties of all ingredients must be provided or reliably estimated by a validated method. Attention should be paid to possible effects of components on the sensitization potential of the total mixture.

Local Lymph Node Analysis (LLNA) will be used, including a reduced variant of the assay where appropriate. If LLNA is not performed, a justification will be provided and the Guinea Pig Maximization Test will be performed. Where a guinea pig test (Maximization or Buehler) is available that meets OECD guidelines and provides a clear result, no further testing is necessary for animal welfare reasons. Potential respiratory sensitization should be considered when present or when there are indications of respiratory sensitizing effects.