α,2,2,6-tetramethylcyclohexene-1-butyraldehyde

Endpoint summary

Description of key information

The experimental rat LD50 dosed via the oral route was 8340 mg/kg (Klimisch 4).

This experimental result is in strong agreement with the 2 QSAR predictions completed on the 2 components of Cetonal.

These are 2-methyl-4-(2,6,6-trimethylcyclohex-2-en-1-yl)butanal (CAS 73398-85-3) with a predicted LD50 of 5800 mg/kg.and 2-methyl-4-(2,6,6-trimethylcyclohex-1-en-1-yl)butanal (CAS 84518-22-9) with a predicted LD50 of 5040 mg/kg.

Therefore, even though the experimental data is on a Klimisch 4 study, the 2 QSARs on the 2 components confirms the low oral toxicity of Cetonal and the lack of classification.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

1966

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

documentation insufficient for assessment

Qualifier:

no guideline available

Principles of method if other than guideline:

The method of Litchfield , V. T. and Wilcoxon F. Journal of Pharmacology and Experimental Therapeutics , Vol 96 1949 was used in calculating the oral LD50.

GLP compliance:

no

Remarks:

Test conducted prior to the GLP guidelines

Limit test:

no

Specific details on test material used for the study:

Test material name (as stated in the report): Giv code 2-1630 (Cetonal)

Species:

rat

Strain:

other: CFE Rats of the Carworth strain

Sex:

male/female

Details on test animals or test system and environmental conditions:

Weight: 150 - 200 grams rats were used in this experiment

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

The test material was administered orally by rigid stomach tube.

Doses:

5 ; 6.5; 8.0 ; 10.0; 12.0 and 14.0 ml/Kg

No. of animals per sex per dose:

1 dose per animal per sex

Control animals:

no

Details on study design:

Following the single dosing of each level the animals were observed for five days for signs of toxicity as evidence by ataxia and or death. Throughout the observation period the animals were housed in raised wire mesh cages and maintained on their regular diet of Fox Blox and water ad libitium.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

8 340 mg/kg bw

Based on:

test mat.

LD50 = 9.1 ml/kg (7.0 - 11.8 ml/kg) with a test material density of 0.9165 g/cm3 at 20'C, thus LD50 = 9.1 ml x 0.9165g/cm3 = 8.34 g/kg = 8340 mg/Kg.

Interpretation of results:

GHS criteria not met

Conclusions:

The oral LD50 of Cetonal was calculated to be 9.1 mL (LD50 = 8340 mg/Kg) per kilogram of rat with a 19/20 confidence limit of 7.0 ml to 11.8 ml per kilogram of rat.

Executive summary:

According to this test conditions, the oral LD50 of Cetonal was calculated to be 9.1 mL (LD50 = 8340 mg/kg)  per kilogram of rat with a 19/20 confidence limit of 7.0 ml to 11.8 ml per kilogram of rat. Hence, Cetonal does not met the criteria for classication according the CLP Regulation (EC) No. 1272/2008.

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

(Q)SAR

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model and falling into its applicability domain, with adequate and reliable documentation / justification

Justification for type of information:

Justification for type of information
1. SOFTWARE
OECD [Q]SAR Toolbox
2. MODEL (incl. version number)
QSAR Toolbox 3.4.0.17
Database version: 3.8.8/3.1.2
3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
CAS: 73398-85-3
SMILES: CC(CCC1C(C)=CCCC1(C)C)C=O
4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
Please see the attached OECD [Q]SAR Toolbox report.
5. APPLICABILITY DOMAIN
The prediction is based on 10 values within the range 0.771 - 2.01, log(1/mol/kg)
Prediction confidence = ± 0.228, log(1/mol/kg) (95.0%)
6. ADEQUACY OF THE RESULT
The LD50 prediction (5800 mg/kg) in rats is similar to the Klimisch 4 study where the LD50 was 9.1 ml/kg (7.0 - 11.8 ml/kg): Result in mg/kg : Density = 0.9165 g/cm3 at 20'C, thus LD50 = 9.1 ml x 0.9165g/cm3 = 8.34 g/kg
= 8340 mg/Kg.

Qualifier:

equivalent or similar to guideline

Guideline:

other:

Version / remarks:

Experimental data taken from the OECD [Q]SAR Toolbox

Principles of method if other than guideline:

[Q]SAR prediction for CAS 73398-85-3

Interpretation of results:

GHS criteria not met

Conclusions:

2-methyl-4-(2,6,6-trimethylcyclohex-2-en-1-yl)butanal (CAS 73398-85-3) has a predicted LD50 of 5800 mg/kg with the OECD [Q]SAR Toolbox.

Reference 3

Endpoint:

acute toxicity: oral

Type of information:

(Q)SAR

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model and falling into its applicability domain, with adequate and reliable documentation / justification

Justification for type of information:

Justification for type of information
1. SOFTWARE
OECD [Q]SAR Toolbox
2. MODEL (incl. version number)
QSAR Toolbox 3.4.0.17
Database version: 3.8.8/3.1.2
3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
CAS: 84518-22-9
SMILES: CC(CCC1=C(C)CCCC1(C)C)C=O
4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
Please see the attached OECD [Q]SAR Toolbox report.
5. APPLICABILITY DOMAIN
The prediction is based on 11 values within the range 1.28 - 2.04, log(1/mol/kg)
Prediction confidence = ± 0.157, log(1/mol/kg) (95.0%)
6. ADEQUACY OF THE RESULT
The LD50 prediction (5040 mg/kg) in rats is similar to the Klimisch 4 study where the LD50 was 9.1 ml/kg (7.0 - 11.8 ml/kg): Result in mg/kg : Density = 0.9165 g/cm3 at 20'C, thus LD50 = 9.1 ml x 0.9165g/cm3 = 8.34 g/kg
= 8340 mg/Kg.

Qualifier:

according to guideline

Guideline:

other:

Version / remarks:

Experimental data taken from the OECD [Q]SAR Toolbox

Principles of method if other than guideline:

[Q]SAR prediction for CAS 84518-22-9

Interpretation of results:

GHS criteria not met

Conclusions:

2-methyl-4-(2,6,6-trimethylcyclohex-1-en-1-yl)butanal (CAS 84518-22-9) has a predicted LD50 of 5040 mg/kg with the OECD [Q]SAR Toolbox.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

8 340 mg/kg bw

Justification for classification or non-classification

According to the study test with the LD50 dosed via the oral route of 8340 mg/kg (Klimisch 4), confirmed by the two QSARs on 2-methyl-4-(2,6,6-trimethylcyclohex-2-en-1-yl)butanal (CAS 73398-85-3) with a predicted LD50 of 5800 mg/kg and on 2-methyl-4-(2,6,6-trimethylcyclohex-1-en-1-yl)butanal (CAS 84518-22-9) with a predicted LD50 of 5040 mg/kg, the Cetonal does not met the criteria for classication according the CLP Regulation (EC) No. 1272/2008.