[1α(E),2β]-1-(2,6,6-trimethylcyclohex-3-en-1-yl)but-2-en-1-one

Endpoint summary

Description of key information

Acute oral toxicity in mice: LD50 is 1400 mg/kg bw in an OECD 401

Acute dermal toxicity: LD50 => 1400 mg/kg bw based on the acute oral LD50. The dermal availability is not expected to exceed the oral availability. Therefore the LD50 via the dermal route can be estimated to be lower than the oral LD50, because we assume 10% absorption via the dermal route and 50% absorption via the oral route.

Acute inhalation toxicity: LC50 value of 14000 mg/m³ was calculated for acute inhalation toxicity exceeding the saturated vapour concentration of 215 mg/m³.

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

1 400 mg/kg bw

Quality of whole database:

The available information is adequate for the dossier.

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Additional information

Acute oral toxicity:

The oral acute toxicity of the test substance was evaluated in mice, performed similar to OECD Guideline 401, predating GLP. Five albino mice per sex per dose 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. Clinical signs included: decrease of activity, ataxia, salivation, urinary incontinence, tremors. Mortality was observed at all dose levels (except at 1346 mg/kg bw). Macroscopic changes were evident in the lungs, spleen, kidneys, G.I. tract and stomach. The LD50's for males, females and the two sexes combined were calculated using the Litchfield-Wilcoxon method: males 1400 mg/kg bw; females 1850 mg/kg bw; combined 1625 mg/kg bw.

Acute inhalation toxicity

An acute inhalation toxicity study is not needed for substances for which acute oral and dermal toxicity values are available. Using route to route extrapolation the inhalation toxicity can be derived as follows: Incorporated dose = concentration x respiratory volume x exposure time: 1 mg/kg bw = 0.0052 mg/L/4h.Using a respiratory volume for a 250 g rat of 0.20 L/min and 100 % absorption and postulating 1 100% deposition and absorption (Guidance on IR/CSA, Chapter R7C, Table R.7.12-10). The LD50 was 1400 mg/kg bw for mice and therefore the LC50 is circa 14000 mg/m³ (using similar parameters for rat and mice). The maximum saturated vapour concentration for the substance is (2.72 x 192297 MW (mg/mol)) / (8.3 (R, gas constant) x 293 (°K)) = 215 mg/m³. This means that delta-damascone cannot reach a concentration higher than 215 mg/m³. Therefore the calculated LC50 for inhalation (14000 m³) cannot be reached and no classification and labelling is needed for the acute inhalation route.

Acute dermal toxicity based on acute oral LD50

The study is scientifically unjustified because the acute dermal toxicity can be derived from the acute oral toxicity using route to route extrapolation. Based on the toxico-kinetic information (see IUCLID section 7.1) the dermal availability is not expected to exceed the oral availability. Therefore we can make a worst case assumption that the LD50 via the dermal route can be estimated to be similar as or higher than the oral LD50. We assume 10% absorption via the dermal route and 50% absorption via the oral route. Based on this information it can be concluded that the performance of an acute dermal toxicity study will not add useful information on the hazard, the classification and labelling and the risk characterisation of the substance for workers and consumers. The information is thought to be sufficient to show that testing on vertebrate animals for acute dermal toxicity can be omitted, in accordance with Annex XI (1.2)

Justification for classification or non-classification

Based on an oral LD50 in mice of 1400 mg/kg bw, Delta-damascone has to be classified for Acute toxicity Cat 4:H302: Harmful if swallowed according to EU Classification, Labeling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.

Based on an oral LD50 in mice of 1400 mg/kg bw, and the estimated dermal absorption of 10% compared to 50% absorption via the oral route, delta-Damascone does not need to be classified for acute oral toxicity according to EU Classification, Labeling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.

The calculated inhalation LC50 of 14000 mg/m3 cannot be reached because the maximum saturated vapour pressure is 215 mg/m³, classification for acute inhalation is not warranted in accordance with EU Classification, Labeling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.