Reaction Mass of (1R)-1-[(1S)-3,3-dimethylcyclohexyl]ethyl formate and (1R,2S)-2,6,6-trimethylcycloheptyl formate

Endpoint summary

Description of key information

Acute oral toxicity: LD50 > 5000 mg/kg bw based on a study in rats 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: LD50 > 5000 mg/kg bw based on a study in rabbits 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:

> 5 000 mg/kg bw

Quality of whole database:

One study is available which is sufficiently reliable to cover this endpoint sufficiently adequate.

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

Quality of whole database:

One study is available which is sufficiently reliable to cover this endpoint sufficiently adequate.

Additional information

Acute oral toxicity

An acute oral toxicity study with the substance was conducted in rats, according to a protocol similar to OECD TG 401 and in compliance with GLP. Ten male Wistar rats received a single dose of 5000 mg/kg bw by gavage. Animals were observed for 14 days and necropsied. There were no deaths. Main clinical signs were chromorhinorrhea, ptosis and chromodacryorrhea. No findings were observed at gross pathology. Based on the results of the study, the LD50 was > 5000 mg/kg bw.

Inhalation route

No data on acute inhalation toxicity of the substance are available. According to Column 2 of REACH Annex VIII, “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 expected to be lower than dermal because the substance has a low vapour pressure and dermal exposure is the more likely route of exposure. As acute toxicity data on both the oral and the dermal route of exposure is available, testing for acute inhalation toxicity is not necessary. However, the acute inhalation toxicity for the substance can be derived using data on the acute oral toxicity using the methodology presented in the next paragraph.

The oral LD50 of the substance is ≥ 5000 mg/kg bw. This 5000 mg/kg bw can be converted to 350000 mg/per person. An inhalation volume of one person during 4 h (standard exposure time in OECD TG for acute inhalation toxicity) is 5 m3 (assuming 10 m3/8h for workers). This means that the LC50 concentration in 1 m3 and 4 hours exposure is 70000 mg/m3.Taking into account that the absorption during inhalation route can be twice as high as during oral absorption the LC50 for inhalation would become 35000 mg/m3.The maximum saturated vapour pressure for this substance in mg/m3 is 1014 mg/m3 (13.4 Pa x 184280 MW (mg/Mol)) / (8.3 (R, gas constant) x 296°K).The LC50 value of 35000 mg/m3 cannot be reached because of the saturated vapour concentration of CP Formate of 1014 mg/m3.Though no correction has been done for rat versus human inhalation, the calculation clearly shows that there is no acute inhalation toxicity for the substance because the calculated LC50 = 35000 mg/m3, while the maximum saturated vapour pressure is 1014 mg/m3.

Acute dermal toxicity

An acute dermal toxicity study with the substance was conducted in rabbits, according to a protocol similar to OECD TG 402 and in compliance with GLP. An amount of 5.0 g/kg bw of the substance was applied to the clipped abdomen (ca. 10% body area) of 10 animals for 24 hours under occlusive conditions. The clipped sites of 1/2 of the animals were abraded with a bent tip needle. Six or seven abrasions ca. 2 -3 cm apart, extending the length of the exposure, were made. Abrasions were sufficiently deep to penetrate the stratum corneum, but not deep enough to produce bleeding. The plastic wrapping was removed and the test substance wiped after 24 hours and the animals were observed for 14 days and necropsied. Skin reactions were assessed at 24 hours post-dose and on days 7 and 14 using the numerical Draize scale. One animal died on day 7. The autopsy showed congested lungs and intestinal abnormalities. The main clinical signs in the survivors were alopecia and diarrhea. No pathological findings were found at necropsy in 3 out of 9 survivors; remaining animals showed signs of peritoneal cavity and intestinal abnormalities. Based on the results of the study, the LD50 was > 5000 mg/kg bw.

Justification for classification or non-classification

Based on oral and dermal LD50 > 5000 mg/kg bw in rats and rabbits, respectively, and the calculated inhalation LC50 of 35000 mg/m3, 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 and its amendments.