11-oxahexadecan-16-olide

Endpoint summary

Description of key information

The experimental in vivo acute oral toxicity study the LD50 was 16.8 ml/kg (11.9 - 23.8 ml/kg).

The trend analysis QSAR prediction (OECD QSAR Toolbox) where the domain is made up of other "Ether, Cyclic" and Lactone rings gives a LD50 value of 5420 mg/kg which is slightly more toxic than the in vivo data.

The read-Across QSAR prediction (OECD QSAR Toolbox) where the domain is also made up mainly of other "Ether, Cyclic" and Lactone rings gives a LD50 value of 6280 mg/kg which is again slightly more toxic than the in vivo data.

However, the experimental data and the trend analysis and read-across predictions are all above the current criteria for oral acute 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:

1976

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

no

Test type:

fixed dose procedure

Limit test:

no

Specific details on test material used for the study:

Colourless solid

Species:

rat

Strain:

Wistar

Remarks:

Albino derived from Wistar

Details on test animals or test system and environmental conditions:

Males 129-240g.
Females 106-160g.
Housed in groups of 2 in screen-bottomed stainless steel cages in a well ventillated room maintained at 25@C.

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

single dose

Doses:

single doses at 1.25, 2.5, 5.0, 10.0, 20.0 or 30.0 mL/kg

No. of animals per sex per dose:

2 males and 2 females per dose group

Control animals:

no

Details on study design:

- Duration of observation period following administration: Observed for 14 days post treatment
- Necropsy of survivors performed: yes/no

Statistics:

LD50 calculated according to the method of Weil (Biometrics 8 (1952) 249-263).

Sex:

male/female

Dose descriptor:

LD0

Effect level:

1.25 mL/kg bw

Based on:

test mat.

Remarks on result:

not determinable due to absence of adverse toxic effects

Sex:

male/female

Dose descriptor:

LD0

Effect level:

2.5 mL/kg bw

Based on:

test mat.

Remarks on result:

not determinable due to absence of adverse toxic effects

Sex:

male/female

Dose descriptor:

LD0

Effect level:

5 mL/kg bw

Based on:

test mat.

Remarks on result:

not determinable due to absence of adverse toxic effects

Key result

Sex:

male/female

Effect level:

10 mL/kg bw

Based on:

test mat.

Remarks on result:

not determinable due to absence of adverse toxic effects

Key result

Sex:

male/female

Effect level:

20 mL/kg bw

Based on:

test mat.

Remarks on result:

other: See remarks

Remarks:

1/2 males died and 2/2 females died.

Sex:

male/female

Dose descriptor:

LD100

Effect level:

30 mL/kg bw

Based on:

test mat.

Remarks on result:

other: See remarks

Remarks:

2/2 males died and 2/2 females died.

Mortality:

At 20.0 ml/kg, 1 male died and 2 females died.
At 30.0 ml/kg, 2 males died and 2 females died.

Clinical signs:

other: No comments.

Gross pathology:

No comments.

Interpretation of results:

GHS criteria not met

Conclusions:

The LD50 was calculated to be 16.8 ml/kg with confidence limits of 11.9 and 23.8 ml/kg.

Executive summary:

The LD50 was calculated to be 16.8 ml/kg with confidence limits of 11.9 and 23.8 ml/kg.

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:

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: 3391-83-1
SMILES: O=C1CCCCCCCCCOCCCCCO1

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
Please see the attached OECD [Q]SAR Toolbox report.
These profiles are routinely combined for acute oral toxicity:
Toxic hazard classification by Crammer (Original and Enhanced).
Organic functional groups.
Lipinski Rule OASIS.
Structural similarity.
Chemical elements.
Additional sub-categorisation via filtering points by test conditions:
Test guideline.
Test type.
Test organisims (species).
Route of administration.
Reliability.
Substance type.
Test material equivalent to submission substance identity.

5. APPLICABILITY DOMAIN
The prediction is based on 5 values within the range 1.37 - 1.73, log(1/mol/kg)
Prediction confidence = ± 0.196, log(1/mol/kg) (95.0%)
Very high confidence in the result as indicated by the 95% confidence interval.

6. ADEQUACY OF THE RESULT
Predicted LD50 in rats is6.28E3(4E3;9.86E3) mg/kg with good confidence in the prediction.
Therefore giving good confidence to the prediction.

Interpretation of results:

GHS criteria not met

Conclusions:

The predicted value is very similar to the other "Ether, Cyclic" and Lactone rings.
Predicted LD50 in rats is6.28E3(4E3;9.86E3) mg/kg with good confidence in the prediction.

Executive summary:

Predicted LD50 in rats is 6280 mg/kg.

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:

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: 3391-83-1
SMILES: O=C1CCCCCCCCCOCCCCCO1

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
Please see the attached OECD [Q]SAR Toolbox report.
These profiles are routinely combined for acute oral toxicity:
Toxic hazard classification by Crammer (Original and Enhanced).
Organic functional groups.
Lipinski Rule OASIS.
Structural similarity.
Chemical elements.
Additional sub-categorisation via filtering points by test conditions:
Test guideline.
Test type.
Test organisims (species).
Route of administration.
Reliability.
Substance type.
Test material equivalent to submission substance identity.

5. APPLICABILITY DOMAIN
Prediction range:
1.31E+03 - 2.25E+04, mg/kg (95.0% confidence)
Statistic of the prediction model:
N = 4; count of data points
R2 = 0.717; coefficient of determination
R2adj = 0.576; adjusted coefficient of determination
Q2 = -0.977; coefficient of determination by "leave-one-out" validation
SSR = 0.0284; sum of squared residuals
s = 0.119; sample standard deviation of residuals
F = 5.07; Fisher function
Fa = 39.0; Fisher threshold for statistical significance (95.0% confidence)

6. ADEQUACY OF THE RESULT
Predicted LD50 in rats is 5.42E3(1.31E3;2.25E4) mg/kg with good R2 and R2adj values indicating high
confidence in the prediction.
The R2 value is high at 0.717 and the RE2adj is also high at 0.576.
Therefore giving good confidence to the prediction.

Interpretation of results:

GHS criteria not met

Conclusions:

Predicted LD50 in rats is 5.42E3(1.31E3;2.25E4) mg/kg with good R2 and R2adj values indicating high confidence in the prediction.

Executive summary:

Predicted LD50 in rats is 5420 mg/kg.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

11 900 mg/kg bw