Registration Dossier

Administrative data

Description of key information

For this endpoint, there is no data on the isomer mixture.

The delayed contact hypersensivity of the meta isomer was evaluated in Guinea pigs in a Buehler test performed according to OECD N°406 guideline (Wang, 2011). On day 0, 7 and 14, the test and positive control group animals were given induction exposure; the negative control animals were not treated. On day 28, all the three groups were given challenge exposure on the opposite intact skin. Skin reactions were scored at 24 and 48 hours after completion of the challenge application. Positive reactions were not observed in the test group animals at the 24-hour and 48-hour examination; the sensitization rate was 0%. Erythema occurred in 10 animals in the positive control group; the sensitization rate was 66.7%. There were no positive skin responses in the negative control group; the sensitization rate was 0%. There was no mortality, and there were no remarkable clinical observations in any group.

The skin sensitization potential of the meta and para isomers was evaluated in chemico using the Danish QSAR data base and Toxtree. None of the model identified a skin sensitization alert or a skin sensitisation reactivity domain.

In conclusion, m/p-DIOL can be considered as non-sensitizing.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
21 June 2011 - 22 July 2011
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The study has some deviations and the information in the report is limited.
Qualifier:
according to
Guideline:
other: The Guidelines for the Testing of Chemicals (State Environmental Protection Administration of China, 2004.5, 406, Skin Sensitization Test)
Deviations:
no
GLP compliance:
no
Remarks:
The laboratory has no GLP accreditation (nevertheless the project plan and the report were audited by the Quality Assurance Unit)
Type of study:
Buehler test
Justification for non-LLNA method:
This study was performed for the Chinese regulatory authorities
Species:
guinea pig
Strain:
not specified
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source:
- Age at study initiation:
- Weight at study initiation:
- Housing:
- Diet and water: ad libitum except during exposure
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-23
- Humidity (%): 40-70
- Air changes (per hr): 12
- Photoperiod (hrs dark / hrs light): 12
Route:
epicutaneous, semiocclusive
Vehicle:
water
Concentration / amount:
0.2g / 100%
Day(s)/duration:
Days 0, 7 and 14
Adequacy of induction:
highest technically applicable concentration used
Route:
epicutaneous, semiocclusive
Vehicle:
water
Concentration / amount:
0.1 g /100%
Day(s)/duration:
Day 28
Adequacy of challenge:
highest non-irritant concentration
Concentration / amount:
100% (0.2g)
No. of animals per dose:
15
Details on study design:
The test substance was pre-moistened with distilled water.
Positive control substance(s):
yes
Remarks:
dinitrochlorobenzene
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
100% (0.1g)
No. with + reactions:
0
Total no. in group:
15
Clinical observations:
none
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
100% (0.1g)
No. with + reactions:
0
Total no. in group:
15
Clinical observations:
none
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
100% (0.1g)
No. with + reactions:
0
Total no. in group:
15
Clinical observations:
none
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
100% (0.1g)
No. with + reactions:
0
Total no. in group:
15
Clinical observations:
none
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
2,4-dinitrochlorobenzene mixed in vaselinum was 1.25 mg/g (the amount was 0.2 g).
No. with + reactions:
10
Total no. in group:
15
Clinical observations:
none
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
2,4-dinitrochlorobenzene mixed in vaselinum ( the amount was 0.2 g)
No. with + reactions:
10
Total no. in group:
15
Clinical observations:
none

All animals appeared active and healthy. There were no signs of gross toxicity, adverse pharmacology effects or abnormal behavior. No gross pathological changes were observed at necropsy.

Interpretation of results:
GHS criteria not met
Conclusions:
No skin reactions were observed in the test group. Based on the results of this study the substance would not be regarded as a skin sensitizer.
Executive summary:

The delayed contact hypersensivity of the meta-diols was evaluated in Guinea pigs according to OECD N°406 guideline (Buehler test).

On day 0, 7 and 14, the test and positive control group animals were given induction exposure; the negative control animals were not treated. On day 28, all the three groups were given challenge exposure on the opposite intact skin. Skin reactions were scored at 24 and 48 hours after completion of the challenge application.

Positive reactions were not observed in the test group animals at the 24-hour and 48-hour examination; the sensitization rate was 0%. Erythema occurred in 10 animals in the positive control group; the sensitization rate was 66.7%. There were no positive skin responses in the negative control group; the sensitization rate was 0%. There was no mortality, and there were no remarkable clinical observations in any group.

In conclusion, under these experimental conditions, meta-diols was considered as non-sensitizing in the Buehler test.

Endpoint:
skin sensitisation: in chemico
Type of information:
(Q)SAR
Adequacy of study:
weight of evidence
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
Guideline:
other: Chapter R.6: QSARs and grouping of chemicals
Principles of method if other than guideline:
MultiCASE CASE Ultra commercial model A33 for allergic contact dermatitis (ACD) in guinea pig and human (MultiCASE CASE Ultra 1.4.6.6 64-bit)
Leadscope Enterprise version of commercial CASE Ultra model A33 for allergic contact dermatitis (ACD) in guinea pig and human (Leadscope Predictive Data Miner, a component of Leadscope Enterprise version 3.1.1-10.)
SciMatics SciQSAR version of commercial CASE Ultra model A33 for allergic contact dermatitis (ACD) in guinea pig and human (SciQSAR version 3.1.00.)
Specific details on test material used for the study:
Smiles: C(C)(C)(O)c1cc(C(C)(C)O)ccc1
Parameter:
other: Battery of QSAR models
Remarks on result:
no indication of skin sensitisation
Remarks:
inside applicability domain
Parameter:
other: Leadscope
Remarks on result:
no indication of skin sensitisation
Remarks:
inside applicability domain
Parameter:
other: SciQSAR
Remarks on result:
no indication of skin sensitisation
Remarks:
inside applicability domain
Parameter:
other: CASE Ultra
Remarks on result:
positive indication of skin sensitisation
Remarks:
outside applicability domain
Interpretation of results:
GHS criteria not met
Endpoint:
skin sensitisation: in chemico
Type of information:
(Q)SAR
Adequacy of study:
weight of evidence
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
Guideline:
other: Chapter R.6: QSARs and grouping of chemicals
Principles of method if other than guideline:
MultiCASE CASE Ultra commercial model A33 for allergic contact dermatitis (ACD) in guinea pig and human (MultiCASE CASE Ultra 1.4.6.6 64-bit)
Leadscope Enterprise version of commercial CASE Ultra model A33 for allergic contact dermatitis (ACD) in guinea pig and human (Leadscope Predictive Data Miner, a component of Leadscope Enterprise version 3.1.1-10.)
SciMatics SciQSAR version of commercial CASE Ultra model A33 for allergic contact dermatitis (ACD) in guinea pig and human (SciQSAR version 3.1.00.)
Specific details on test material used for the study:
Smiles: C(C)(C)(O)c1ccc(C(C)(C)O)cc1 (para-DIOL)
Parameter:
other: Battery of QSAR models
Remarks on result:
no indication of skin sensitisation
Remarks:
inside applicability domain
Parameter:
other: Leadscope
Remarks on result:
no indication of skin sensitisation
Remarks:
inside applicability domain
Parameter:
other: SciQSAR
Remarks on result:
no indication of skin sensitisation
Remarks:
inside applicability domain
Parameter:
other: CASE Ultra
Remarks on result:
no indication of skin sensitisation
Remarks:
inside applicability domain
Interpretation of results:
GHS criteria not met
Endpoint:
skin sensitisation: in chemico
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
Toxtree (Estimation of Toxic Hazard - A Decision Tree Approach)

2. MODEL (incl. version number)
Version 2.6.13

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
1999-85-5: OC(c1cccc(C(O)(C)C)c1)(C)C
2948-46-1: C(C)(C)(O)c1ccc(C(C)(C)O)cc1

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
- Defined endpoint: Skinsensitisation
- Unambiguous algorithm: see attached rules
- Defined domain of applicability: rules were developed for the identification of mechanisms of toxic action for skin sensitisation using a SMARTS pattern based approach
- Appropriate measures of goodness-of-fit and robustness and predictivity: not relevant
- Mechanistic interpretation: according to the rules and decision tree of the specific end-point

5. APPLICABILITY DOMAIN
- Descriptor domain: Defined by the rules
- Structural and mechanistic domains: Defined by the rules
- Similarity with analogues in the training set: not relevant

6. ADEQUACY OF THE RESULT
The estimation is coherent with the available in vivo data
Qualifier:
according to
Guideline:
other: REACH guidance. Chapter R.6: QSARs and grouping of chemicals
Version / remarks:
May 2008
Principles of method if other than guideline:
Toxtree (Estimation of Toxic Hazard - A Decision Tree Approach) (Version 2.6.13)
Specific details on test material used for the study:
SMILES:
1999-85-5: OC(c1cccc(C(O)(C)C)c1)(C)C
2948-46-1: C(C)(C)(O)c1ccc(C(C)(C)O)cc1
Details on study design:
Identification of mechanisms of toxic action for skin sensitisation using a SMARTS pattern based approach.
Available since ToxTree 2.1.0 (under name "Skin sensitisation alerts" and "Skin sensitisation alerts (M.Cronin)"). The name is changed to "Skin sensitisation reactivity domain" by P&G team suggestion in order to reflect the fact the alerts provide grouping into reactivity mode of action and do not predict skin sensitisation potential.
Parameter:
other: Toxtree
Remarks on result:
no indication of skin sensitisation
Other effects / acceptance of results:
CAS 1999-85-5:
QSNAR.SNAr-Nucleophilic Aromatic Substitution No   OC(c1cccc(C(O)(C)C)c1)(C)C  
QSB.Schiff Base Formation No   OC(c1cccc(C(O)(C)C)c1)(C)C  
QMA.Michael Acceptor No   OC(c1cccc(C(O)(C)C)c1)(C)C  
Qacyl.Acyl Transfer Agents No   OC(c1cccc(C(O)(C)C)c1)(C)C  
QSN2.SN2-Nucleophilic Aliphatic Substitution No   OC(c1cccc(C(O)(C)C)c1)(C)C  
Q6.At least one alert for skin sensitisation? No Class No skin sensitisation reactivity domains alerts identified. OC(c1cccc(C(O)(C)C)c1)(C)C

CAS 2948-46-1:
QSNAR.SNAr-Nucleophilic Aromatic Substitution No   C(C)(C)(O)c1ccc(C(C)(C)O)cc1  
QSB.Schiff Base Formation No   C(C)(C)(O)c1ccc(C(C)(C)O)cc1  
QMA.Michael Acceptor No   C(C)(C)(O)c1ccc(C(C)(C)O)cc1  
Qacyl.Acyl Transfer Agents No   C(C)(C)(O)c1ccc(C(C)(C)O)cc1  
QSN2.SN2-Nucleophilic Aliphatic Substitution No   C(C)(C)(O)c1ccc(C(C)(C)O)cc1  
Q6.At least one alert for skin sensitisation? No Class No skin sensitisation reactivity domains alerts identified. C(C)(C)(O)c1ccc(C(C)(C)O)cc1
Interpretation of results:
GHS criteria not met
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

According to EU Regulation (EC) N0. 1272/2008 (CLP), the test item is not classified for sensitisation.