Registration Dossier

Administrative data

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

Referenceopen allclose all

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:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals 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.

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

Referenceopen allclose all

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.
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.
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.
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.
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:
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. certificate)
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)

Additional information

Justification for classification or non-classification