Reaction mass of 3-(4-hydroxy-4-methylpentyl)cyclohex-3-ene-1-carbaldehyde and 4-(4-hydroxy-4-methylpentyl)cyclohex-3-ene-1-carbaldehyde

Endpoint summary

Description of key information

Acute oral toxicity study: LD50 > 4971 mg/kg bw in a similar to OECD TG 401 test in rats.

Acute dermal toxicity study: LD50 > 5000 mg/kg bw in a similar to OECD TG 402 test in rabbits.

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

4 971 mg/kg bw

Quality of whole database:

The quality is sufficiently high because the selected study has been performed in a method similar to OECD TG 401, but acceptable for assessment with a Klimisch score of 1.

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

Dose descriptor:

LD50

Value:

5 000 mg/kg bw

Quality of whole database:

The quality of the study is sufficiently high. The study available pre-dates GLP and is similar to OECD TG 402, but acceptable for assessment with a Klimisch score of 2.

Additional information

Acute oral toxicity

In the oral study, performed according to a protocol similar to OECD guideline 401 and without GLP, LD50 values of >3976 mg/kg bw and >4971 mg/kg bw were obtained for female and male Sprague-Dawley rats, respectively. The combined LD50 value for both sexes was >4971 mg/kg bw. The observed clinical signs included ptosis, prostration, decreased activity, flaccid body tone and abnormal stance. Necropsy of the animals dying during the study revealed distended, fluid-filled intestines and bladder, bright red lungs and blanched adrenals. Terminal necropsy of the remaining animals revealed no visible lesions at any dose level.

Acute dermal toxicity

In the acute dermal toxicity similar to OECD 402 study with rabbits (strain unspecified) that predated GLP, a single application of 5000 mg/kg bw of test substance resulted in 2 out of 10 rabbits dying on days 7 and 13 of the observation period. No data on the type of coverage and exposure duration were provided. One rabbit which died on day 7 appeared emaciated, lethargic and ptotic and had discharge from nose and eyes on the day prior to death. Necropsy signs of the rabbit which died on day 7 included dried fecal material in the anogenital region, nose and mouth exudate, small spleen, mottled kidneys and red portions of large intestine. The other one rabbit showed also mottled kidneys and, in addition, blotchy liver and yellowish nodules on liver. Skin irritation signs were observed in all animals: slight erythema was noted in five, moderate in four and severe in one rabbit. Slight oedema was observed in two and moderate oedema was observed in eight rabbits.

Acute inhalation toxicity

No data on acute inhalation toxicity of the test 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 not likely because the test substance has a very 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 test substance can be derived using data on the acute oral toxicity using the following methodology:

The LD50 is > 3976 mg/kg bw, the highest dose tested. This value is rounded off to 4000 mg/kg bw for the calculation. The 4000 mg/kg bw can be converted to 280000 mg/per person (assuming a body weight of 70 kg). An inhalation volume of one person during 4 h (standard exposure time in OECD TG for acute inhalation toxicity) is 5 m3 (assuming 10m3/8h for workers). This means that the LC50 concentration in 1 m3 and 4 hours exposure is 56000 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 28000 mg/m3. The maximum saturated vapour pressure for this substance in mg/m3 is (0.0055 Pa x 210000 MW (mg/Mol)) /(8.3 (R, gas constant) x 293 °K) = 0.47 mg/m3. The LC50 value of > 28000 mg/m3 cannot be reached because of the saturated vapour concentration of the test substance of 0.47 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 test substance because the LC50 > 28000 mg/m3, while the saturated vapour pressure is 0.47 mg/m3. In addition, in the FFHPVC, 2008, an acute inhalation toxicity study with rats on the test substance is presented (Union Carbide, 1987). The test substance did not cause acute inhalation toxicity at 400 ppm (which is ca. 4000 mg/m3 after conversion (using the formula: 1 ppm=MW/24 mg/m3). This 400 ppm value seems to be far above the saturated vapour pressure of the test substance. It also indicates that no acute inhalation toxicity is expected.

Justification for classification or non-classification

The test substance does not need to be classified for acute oral, dermal and inhalation toxicity according to EU CLP (EC No. 1272/2008 and its amendments).