Registration Dossier

Administrative data

Description of key information

After oral administration to male mice, a LD50 of 1400 mg/kg bw was derived. The acute dermal LD50 was greater than 5000 mg/kg bw.

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Dose descriptor:
LD50
1 400 mg/kg bw

Acute toxicity: via dermal route

Endpoint conclusion
Dose descriptor:
LD50
5 000 mg/kg bw

Additional information

Acute toxicity of delta-damascone by oral route was evaluated in the acute oral toxicity test in mice (LD50), performed by a protocol equivalent or similar to OECD Guideline 401, predating GLP (Food and Drug Research Laboratories, 1979). Sixty-one male and 61 female albino mice were administered the substance orally as a corn oil solution at a constant volume of 20 mL/kg bw at the following concentrations: 940, 1346, 1475, 1600, 1902, 2025, 2150, 2225, 2350, 2692 mg/kg bw. Animals were observed for 14 days following administration of the test material. Toxic effects and mortality were recorded throughout the duration of the test period. The LD50's for males, females and the two sexes combined were calculated using the Litchfield-Wilxocon method: males 1400 mg/kg bw; females 1850 mg/kg bw; combined 1625 mg/kg bw.

Acute dermal toxicity of delta-damascone was evaluated based on a study with its read-acrosscandidatealpha-iso-methylionone(EC name:3-methyl-4-(2,6,6-trimethyl-2-cyclohexen-1-yl)-3-buten-2-one)(MB Research Laboratories, Inc., 1973). Eight rabbits were dermally exposed to the limit dose level of 5000 mg/kg bw. The study was conducted according to a protocol similar to OECD Guideline 402. Animals were observed for 14 days and skin reactions (erythema and oedema) were recorded and scored according to the system of Draize. The LD50 was > 5000 mg/kg bw. Slight erythema was observed in 2 out of 8 animals, while moderate erythema was observed in 4 out of 8 animals. The study predated GLP.

With respect to acute inhalation toxicity, in Column 2 of REACH Annex VIII it is stated that “in addition to the oral route (8.5.1), for substances other than gases, the information mentioned under 8.5.2 (acute toxicity by inhalation) and 8.5.3 (acute toxicity by the dermal route) shall be provided for at least one other route. The choice for the second route will depend on the nature of the substance and the likely route of human exposure.” In the present case, inhalation exposure is not likely because delta-damascone has a low vapour pressure and the dermal exposure by far exceeds the inhalation exposure. As acute toxicity data on both the oral and the dermal routes of exposure are available, testing for acute inhalation toxicity is not necessary.

Justification for classification or non-classification

Based on the oral LD50 for male mice of 1400 mg/kg bw and in accordance with Directive 67/48/EEC, delta-damascone has to be classified for acute toxicity, Xn – R22: Harmful if swallowed.

In accordance with EU Classification, Labeling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008, the substance has to be classified for acute toxicity, Cat. 4 - H302: Harmful if swallowed.