Reaction mass of 3,5,6,6-tetramethyl-4-methyleneheptan-2-one and (E)-3,4,5,6,6-pentamethylhept-3-en-2-one

Endpoint summary

Description of key information

Acute oral toxicity: LD50 was found to be 6.10 g/kg bw for males and 2.35 g/kg for females, tested using a method similar to OECD TG 401

Acute inhalation toxicity: LC50 value of >35000 mg/m³ has been calculated using route to route extrapolation.

Acute dermal toxicity: The dermal LD50 value of the substance was found to be greater than 5.0 g/kg bw day in both sexes tested using a method similar to OECD TG 402

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 350 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Quality of whole database:

The acute inhalation toxicity is derived using route to route extrapolation from the acute toxicity results using 100% absorption. This assessment is considered to be sufficiently adequate to cover this endpoint.

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

> 5 000 mg/kg bw

Additional information

Acute oral toxicity study

The acute oral toxicity of the substance was evaluated in male and female Sprague-Dawley derived albino rats (10 animals per sex per dose). The animals were treated with the following dosages: 0.59, 1.00, 1.69, 2.88, and 5.0 g/kg bw by gavage. Gross signs of systemic toxicity, mortality, bodyweight was determined. Gross necropsy was performed after the 14- day observation period. Deaths occurred within six days after treatment. Central nervous system depression was present in all groups after treatment. All animals which survived the observation period gained weight. Necropsies of animals which died revealed staining around the mouth, gas in the intestinal tract and changes in the kidneys and livers in most animals while necropsies of animals at the end of the observation period were generally uneventful. The acute oral LD50 was found to be 6.10 g/kg bw for male Sprague-Dawley derived albino rats with a 95% confidence limit of 3.51 - 10.6 g/kg. The slope was found to be 2.45 for the males. The LD50 for female Sprague-Dawley derived albino rats was found to be 2.35 g/kg bw with a 95% confidence limit of 1.31 - 4.21 g/kg. The slope was found to be 4.45 for the females.

 

Inhalation route:

The acute oral toxicity does not indicate a hazard classification for the inhalation route because the LD50 is > 5000 mg/kg bw corresponding to the cut off value for vapours LC50 > 20000 mg/m³ (EU-CLP, 2009). This also indicates that the substance does not need to be classified for acute inhalation because the bioavailability via all routes will be similar. As a worst case approach the bioavailability via the inhalation route may be twice as high. For excluding the need to C&L for acute inhalation we quantified the substance concentration in the air. An oral LD50 of 5000 mg/kg bw can be roughly converted into 350000 mg/per person by multiplying it with a person’s weight (70 kg: 5000 x 70=350000). An inhalation volume for one person during 4 h (standard exposure time in the OECD TG for acute inhalation) is 5 m³ (assuming 10 m³/8h for workers). This means that an LC50 concentration in 1m³air and 4 hours exposure is 70000 mg/m³ (350000 mg/5m³). Taking into account that the absorption for the inhalation route can be twice as high as that for the oral route (based on default absorption values mentioned in REACH guidance R.8.4.2), the LC50 for inhalation would become (70000/2=) 35000 mg/m³. The maximum saturated vapour pressure for the substance is 7361 mg/m³ (calculated as: 100 Pa [vapour pressure] x 182.07 [MW, g/mole] x 1000 [conversion from g to mg] / 8.3 [R, gas constant] x 298 K [temperature pertaining to the vapour pressure]). This means that the substance cannot reach a concentration higher than 7361 mg/m³. Therefore, the calculated LC50 for inhalation (35000 mg/m³) cannot be reached and no classification and labelling is needed for the acute inhalation route.

 

Acute dermal toxicity

The dermal LD50 determination in male and female Sprague-Dawley derived albino rats of the substance was performed. Groups of ten male and ten female Sprague-Dawley rats received a single dermal dosage of the substance dissolved in a diluent. Dosages were 0.59, 1.0, 1.69, 2.88 and 5.0 g/kg bw day. All animals were observed for mortality and signs of toxicity. At the end of the 14-day observation period, the rats were weighed and sacrificed. Results showed that there was no mortality, no clinical signs observed during the 14- day observation period. At termination, gas in the intestines was observed in most of the males and a few females. No gross pathology was noted. All rats gained weight during the observation period. The dermal LD50 value of the substance was found to be greater than 5.0 g/kg bw day in both sexes.

Justification for classification or non-classification

Based on the oral LD50 of 2350 mg/kg bw and the dermal LD50 >5000 mg/kg bw, the substance does not need to be classified according to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.