1,6-Octadien-3-ol, 3,7-dimethyl-, acid-isomerized

Endpoint summary

Description of key information

EYE Irritation:

The BCOP IVIS is 7.45 which is just outside the acceptance for a negative result. However, the QSARs performed on the 4 major components are all negative for eye irritation.

Therefore, no classification is required for eye irritation.

Skin Irritation:

In the in vivo OECD 404 study there is slight irritation observed over 9 days. However, this result alonside the supporting skin irritation observed in the OET test concludes that after a single application Lime Oxide is not irritating to skin and no classification is required.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1995

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

Six days acclimatation.
Unique identification.
Aluminium cages with grid floors.
Environmental max was 21'C and min 20'C and relative humidity was 54%.
A 12h ligh dark cyle.
Standard rabbit diet.

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

not specified

Amount / concentration applied:

0.5 mL

Duration of treatment / exposure:

4 hours

Observation period:

1, 24, 48, 72 hours and 14 days.

Number of animals:

3 male rabbits

Details on study design:

0.5 mL of test material was applied to the intact skin on each rabbit under 2.5 cm x 2.5 cm patches of gauze. The patches were then covered with micopore tape and the trunk was loosly bound with Elastoplast Elastic Bandage with remiained in position for 4 hours. At the end of this period the patches were removed and the skin wiped to remove surplus test material without altering the existing response or the integrity of the epidermis.

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: NA

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 12 days

Remarks on result:

probability of weak irritation

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of the study, Lime Oxide Hydrogenated is slightly irritant to rabbit skin.

Executive summary:

Slighy skin irritation observed, insufficient signs for classification.

Reference 2

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

1982

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Qualifier:

no guideline available

Version / remarks:

Valid method by Klecak,G., Geleick, H., Frey,J.R.

Principles of method if other than guideline:

One day before starting induuction procedure, a single application of 0.025 mL of each test concentration (3, 10, 30 and 100%) is simultaneously performed on one of the areas measuring 2 cm of the flank previously clipped and marked with a circular stamp.

GLP compliance:

no

Species:

guinea pig

Strain:

not specified

Type of coverage:

open

Preparation of test site:

clipped

Vehicle:

not specified

Amount / concentration applied:

0.025 mL of each test concentration (3, 10, 30 and 100%)

Duration of treatment / exposure:

24 hour

Observation period:

24 hour

Number of animals:

6-8 animals

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

24 h

Score:

1

Max. score:

4

Reversibility:

not specified

Remarks on result:

probability of weak irritation

Interpretation of results:

GHS criteria not met

Conclusions:

Mild irritation noted at 100% after a single application at 24 hours.

Executive summary:

Mild irritation noted at 100% after a single application at 24 hours.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Reference 1

Endpoint:

eye irritation: in vivo

Type of information:

(Q)SAR

Adequacy of study:

supporting study

Study period:

2017

Reliability:

1 (reliable without restriction)

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: 56058-69-6
SMILES: CC=C(C)C1CCC(C)(C)O1
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 4 neighbours' values, 3 of them equal to prediction.
Prediction confidence is measured by the p-value = 3.82E-08 (very strong confidence)
6. ADEQUACY OF THE RESULT
Very high confidence in the result as indicated by the p-value.
The single positive result is for Naphtha (petroleum), light catalytic reformed, arom.-free, therefore
considering this substance is a UVCB, this could be impurities or unknown components.
Additionally, the in vivo REACH data for this substance is confirmed as negative and considers data
from 45 studies in the eye irritation summary.
Negative for eye irritation in rabbits.

Reference 2

Endpoint:

eye irritation: in vivo

Type of information:

(Q)SAR

Adequacy of study:

supporting study

Study period:

2017

Reliability:

1 (reliable without restriction)

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: 586-62-9
SMILES: CC(C)=C1CCC(C)=CC1
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 5 neighbours' values, 3 of them equal to prediction.
Prediction confidence is measured by the p-value = 9.54E-08 (very strong confidence)
6. ADEQUACY OF THE RESULT
Very high confidence in the result as indicated by the p-value.
Additional:
Negative experimental data on p-mentha-1,4(8)-diene (CAS 586-62-9) has been submitted in the REACH dossier.
Negative for eye irritation in rabbits using predictive QSAR and experimental data.

Reference 3

Endpoint:

eye irritation: in vivo

Type of information:

(Q)SAR

Adequacy of study:

supporting study

Study period:

2017

Reliability:

1 (reliable without restriction)

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: 99-85-4
SMILES: CC(C)C1CC=C(C)CC=1
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 13 neighbours' values, 6 of them equal to prediction.
Prediction confidence is measured by the p-value = 1.55E-13 (very strong confidence)
6. ADEQUACY OF THE RESULT
Very high confidence in the result as indicated by the p-value.
The single positive result is for Naphtha (petroleum), light catalytic reformed, arom.-free, therefore
considering this substance is a UVCB, this could be impurities or unknown components.
Additionally, the in vivo REACH data for this substance is confirmed as negative and considers data
from 45 studies in the eye irritation summary.
Negative for eye irritation in rabbits.

Reference 4

Endpoint:

eye irritation: in vivo

Type of information:

(Q)SAR

Adequacy of study:

supporting study

Study period:

2017

Reliability:

1 (reliable without restriction)

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: 99-86-5
SMILES: CC(C)C1CCC(C)=CC=1
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 12 neighbours' values, 5 of them equal to prediction.
Prediction confidence is measured by the p-value = 3.37E-11 (very strong confidence)
6. ADEQUACY OF THE RESULT
Very high confidence in the result as indicated by the p-value.
The single positive result is for Naphtha (petroleum), light catalytic reformed, arom.-free, therefore
considering this substance is a UVCB, this could be impurities or unknown components.
Additionally, the in vivo REACH data for this substance is confirmed as negative and considers data
from 45 studies in the eye irritation summary.
Negative for eye irritation in rabbits.

Reference 5

Endpoint:

eye irritation: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 437 (Bovine Corneal Opacity and Permeability Test Method for Identifying i) Chemicals Inducing Serious Eye Damage and ii) Chemicals Not Requiring Classification for Eye Irritation or Serious Eye Damage)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Specific details on test material used for the study:

The test article, a colourless to pale yellow liquid, was identified as Lime Oxide.
A certificate of analysis for the test article was provided.
The test article was administered without dilution.

Species:

cattle

Strain:

not specified

Details on test animals or tissues and environmental conditions:

Corneas were obtained from bovine eyes supplied by a local abattoir. The eyes were
removed after slaughter, completely immersed in Hanks’ Balanced Salt Solution
(containing penicillin at 100 IU/mL and streptomycin at 100 μg/mL) in a suitably
sized container and transported on the same day to the testing facility.
On arrival at the test facility the eyes were carefully examined for defects including
increased opacity, scratches and neovascularisation. Only corneas free from such
defects were used.
Fresh corneas, mounted onto specifically designed holders were treated topically with
the test material. Eye corrosion / severe irritation potential was based on the combined
effect of the test article on the opacity of the cornea following the treatment and the
cornea’s ability to resist penetration of a fluorescent dye through the tissue.

Vehicle:

unchanged (no vehicle)

Amount / concentration applied:

750 μL

Duration of treatment / exposure:

10 minute incubation at 32°C ± 1°C.

Observation period (in vivo):

NA

Duration of post- treatment incubation (in vitro):

NA

Number of animals or in vitro replicates:

three corneas

Details on study design:

A volume of 750 μL of the test article was applied to each of three corneas followed
by a ten minute incubation at 32°C. After this incubation, each cornea was washed
with media containing phenol red (as a pH indicator) until this indicator showed no
pH effect occurring (and demonstrating that the test article had been removed
successfully). The corneas were then washed once in media without phenol red. The
corneas were incubated (horizontally) for 2 hours ± 10 minutes after which corneal
opacity was measured.
For the permeability endpoint, the media in the anterior chamber was replaced with
1 mL of sodium fluorescein (4 mg/mL solution), while the posterior chamber was
filled with fresh MEM. The corneas were incubated in the vertical position for
90 minutes. Following this period, the media in the posterior chamber was removed
and held in a labelled tube. Three 350 μL aliquots of this media (per cornea) were
analysed for optical density at 490 nanometers (OD490) using a spectrophotometer.
A volume of 750 μL of the negative or positive control was similarly applied to
further groups of three corneas. These groups were subject to the procedures detailed
above.

Irritation parameter:

cornea opacity score

Run / experiment:

1

Value:

4.7

Vehicle controls validity:

valid

Negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

not determinable

Other effects / acceptance of results:

Corneal Opacity:
The mean corrected opacity reading for the test article was 4.7.
The mean corrected opacity reading for the negative control was 0.0.
The mean corrected opacity reading for the positive control was 39.3.
The corneas treated with the positive control were noted to be cloudy following treatment.

Corneal Permeability:
The mean group corrected optical density for the test article was 0.185.
The mean group corrected optical density for the negative control was 0.0.
The mean group corrected optical density for the positive control was 0.203.

Interpretation of results:

study cannot be used for classification

Conclusions:

The test article, Lime Oxide, produced an IVIS score of 7.45. No prediction can be made in respect of its potential to cause eye irritation.
The assay was considered valid as the assay acceptance criteria were met.

Executive summary:

The test article, Lime Oxide, produced an IVIS score of 7.45.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)