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Skin irritation / corrosion

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Endpoint:
skin irritation: in vivo
Type of information:
other: data sharing dispute
Adequacy of study:
key study
Study period:
23 Jan - 30 Jan 2002
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP-guideline study with acceptable restrictions (no data on analytical purity; observation period only 7 days)
Justification for type of information:
Guidance on registration Reference: ECHA-16-G-06-EN Publ.date:November 2016
Practical guide 2: How to report weight of evidence - Reference: ECHA-10-B-05-EN Publ.date: 24/03/2010
"Guidance on information requirements and chemical safety assessment Chapter R.6: QSARs and grouping of chemicals" (ECHA 2008)

According to Article 13 of Regulation (EC) No. 1907/2006 "General Requirements for Generation of Information on Intrinsic Properties of substances", information on intrinsic properties of substances may be generated by means other than tests e.g. from information from structurally related substances (grouping or read-across), provided that conditions set out in Annex XI are met. Annex XI, "General rules for adaptation of this standard testing regime set out in Annexes VII to X” states that “substances whose physicochemical, toxicological and ecotoxicological properties are likely to be similar or follow a regular pattern as a result of structural similarity may be considered as a group, or ‘category’ of substances. This avoids the need to test every substance for every endpoint".Since the category concept is applied to the polyol esters, data gaps will be filled by interpolation, as part of a read across approach from a representative category member(s) to avoid unnecessary animal testing. Additionally, once the category concept is applied, substances will be classified and labelled on this basis.Therefore, based on the group concept, all available data on repeated dose toxicity do not meet the classification criteria according to Regulation.
See Category Justification Document Point enclosed at 13.2
Cross-referenceopen allclose all
Reason / purpose for cross-reference:
other: weight of evidence
Reference
Endpoint:
skin irritation / corrosion, other
Type of information:
(Q)SAR
Adequacy of study:
weight of evidence
Study period:
November 2016
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
accepted calculation method
Justification for type of information:
Guidance on registration Reference: ECHA-16-G-06-EN Publ.date:November 2016
Practical guide 2: How to report weight of evidence - Reference: ECHA-10-B-05-EN Publ.date: 24/03/2010
"Guidance on information requirements and chemical safety assessment Chapter R.6: QSARs and grouping of chemicals" (ECHA 2008)
Reason / purpose for cross-reference:
other: weight of evidence
Reason / purpose for cross-reference:
other: weight of evidence
Reason / purpose for cross-reference:
other: weight of evidence
Reason / purpose for cross-reference:
other: weight of evidence
Qualifier:
according to guideline
Guideline:
other: REACH Guidance on Qsars and grouping of chemicals R.6 year 2008
Principles of method if other than guideline:
See : Final report SC2 Ontology project, ECHA - Final report 12/11/2013 -Istituto Superiore di Sanità (ISS), Viale Regina Elena 299,Rome 00161, Italy
https://www.qsartoolbox.org/documents/21638082/21690894/Ontology_SC2_FinalReport.pdf/945697e2-c3bb-4891-b2e4-6c7e12222b25
Specific details on test material used for the study:
SMILES STRING C(CCCCCCC\C=C/CCCCCCCC)(=O)OCC(CC)(COC(CCCCCCC\C=C/CCCCCCCC)=O)COC(CCCCCCC\C=C/CCCCCCCC)=O

Irritation / corrosion parameter:
other: qualitative estimation
Remarks on result:
no indication of irritation
Irritation parameter:
other: qualitative estimation
Remarks on result:
no indication of irritation
Interpretation of results:
other: Not corrosive to skin
Conclusions:
The Substance Fatty acids C16-18 and C18 unsaturated, triesters with TMP CAS 68002-78-8 was predicted to be not irritating to skin of Humans
Reason / purpose for cross-reference:
other: weight of evidence
Reference
Endpoint:
skin irritation / corrosion, other
Type of information:
(Q)SAR
Adequacy of study:
weight of evidence
Study period:
November 2016
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
accepted calculation method
Justification for type of information:
Guidance on registration Reference: ECHA-16-G-06-EN Publ.date:November 2016
Practical guide 2: How to report weight of evidence - Reference: ECHA-10-B-05-EN Publ.date: 24/03/2010
"Guidance on information requirements and chemical safety assessment Chapter R.6: QSARs and grouping of chemicals" (ECHA 2008)
Reason / purpose for cross-reference:
other: weight of evidence
Reason / purpose for cross-reference:
other: weight of evidence
Reason / purpose for cross-reference:
other: weight of evidence
Reason / purpose for cross-reference:
other: weight of evidence
Qualifier:
according to guideline
Guideline:
other: REACH Guidance on Qsars and grouping of chemicals R.6 year 2008
Principles of method if other than guideline:
See: Final report SC2 Ontology project, ECHA - Final report 12/11/2013 -Istituto Superiore di Sanità (ISS), Viale Regina Elena 299,Rome 00161, Italy
https://www.qsartoolbox.org/documents/21638082/21690894/Ontology_SC2_FinalReport.pdf/945697e2-c3bb-4891-b2e4-6c7e12222b25
Specific details on test material used for the study:
SMILE: C(\CCCCCCCC)=C/CCCCCCCC(OCC(CC)(CO)COC(=O)CCCCCCC\C=C/CCCCCCCC)=O
Irritation / corrosion parameter:
other: qualitative estimation
Remarks on result:
no indication of irritation
Irritation parameter:
other: qualitative estimation
Remarks on result:
no indication of irritation
Interpretation of results:
other: Not corrosive to skin
Conclusions:
The Substance 9-Octadecenoic acid (Z)-, ester with 2-ethyl-2-(hydroxymethyl)-1,3-propanediol CAS 70024-57-6 was predicted to be not irritating to skin of Humans
Reason / purpose for cross-reference:
other: weight of evidence
Reference
Endpoint:
skin irritation / corrosion, other
Type of information:
(Q)SAR
Adequacy of study:
weight of evidence
Study period:
November 2016
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
accepted calculation method
Justification for type of information:
Guidance on registration Reference: ECHA-16-G-06-EN Publ.date:November 2016
Practical guide 2: How to report weight of evidence - Reference: ECHA-10-B-05-EN Publ.date: 24/03/2010
"Guidance on information requirements and chemical safety assessment Chapter R.6: QSARs and grouping of chemicals" (ECHA 2008)
Reason / purpose for cross-reference:
other: weight of evidence
Reason / purpose for cross-reference:
other: weight of evidence
Reason / purpose for cross-reference:
other: weight of evidence
Reason / purpose for cross-reference:
other: weight of evidence
Qualifier:
according to guideline
Guideline:
other: REACH Guidance on Qsars and grouping of chemicals R.6 year 2008
Principles of method if other than guideline:
See : Final report SC2 Ontology project, ECHA - Final report 12/11/2013 -Istituto Superiore di Sanità (ISS), Viale Regina Elena 299,Rome 00161, Italy
https://www.qsartoolbox.org/documents/21638082/21690894/Ontology_SC2_FinalReport.pdf/945697e2-c3bb-4891-b2e4-6c7e12222b25
Specific details on test material used for the study:
SMILES descriptor used for prediction: CCCCCCCCC=CCCCCCCCC(=O)OCC(CC)(CO)CO
Irritation / corrosion parameter:
other: qualitative estimation
Remarks on result:
no indication of irritation
Interpretation of results:
other: Not corrosive to skin
Conclusions:
The Substance Oleic acid CAS 2027-47-6 was predicted to be not irritating to skin of Humans
Reason / purpose for cross-reference:
other: weight of evidence
Reference
Endpoint:
skin irritation: in vivo
Type of information:
other: data sharing dispute
Adequacy of study:
key study
Study period:
06 June - 23 June 1989
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Guideline study with acceptable restrictions (only few details on the test substance given)
Justification for type of information:
Guidance on registration Reference: ECHA-16-G-06-EN Publ.date:November 2016
Practical guide 2: How to report weight of evidence - Reference: ECHA-10-B-05-EN Publ.date: 24/03/2010
"Guidance on information requirements and chemical safety assessment Chapter R.6: QSARs and grouping of chemicals" (ECHA 2008)

According to Article 13 of Regulation (EC) No. 1907/2006 "General Requirements for Generation of Information on Intrinsic Properties of substances", information on intrinsic properties of substances may be generated by means other than tests e.g. from information from structurally related substances (grouping or read-across), provided that conditions set out in Annex XI are met. Annex XI, "General rules for adaptation of this standard testing regime set out in Annexes VII to X” states that “substances whose physicochemical, toxicological and ecotoxicological properties are likely to be similar or follow a regular pattern as a result of structural similarity may be considered as a group, or ‘category’ of substances. This avoids the need to test every substance for every endpoint".Since the category concept is applied to the polyol esters, data gaps will be filled by interpolation, as part of a read across approach from a representative category member(s) to avoid unnecessary animal testing. Additionally, once the category concept is applied, substances will be classified and labelled on this basis.Therefore, based on the group concept, all available data on repeated dose toxicity do not meet the classification criteria according to Regulation.
See Category Justification Document Point enclosed at 13.2
Reason / purpose for cross-reference:
other: weight of evidence
Reason / purpose for cross-reference:
other: weight of evidence
Reason / purpose for cross-reference:
other: weight of evidence
Reason / purpose for cross-reference:
other: weight of evidence
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
Lack of details on test substance
Specific details on test material used for the study:
- Name of test material (as cited in study report): only trade name given
- Physical state: solid, white
- Analytical purity: not reported
Species:
rabbit
Strain:
other: Kleinrusse, Chbb:HM
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Fa. Thomae, Biberach, Germany
- Age at study initiation: 5-6 months
- Weight at study initiation: 2.4 kg (mean)
- Housing: individually in rabbit-battery
- Diet: Altromin 2023, ad libitum
- Water: tap water, ad libitum
- Acclimatisation: approx. 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-25
- Humidity (%): 45-70
- Photoperiod (hrs dark / hrs light): 12 / 12
Type of coverage:
semiocclusive
Preparation of test site:
other: clipped
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g
Duration of treatment / exposure:
4 h
Observation period:
72 h
Reading time points: 1, 24, 48, 72 h
Number of animals:
3 males
Details on study design:
TEST SITE
- Area of exposure: 6 cm²

SCORING SYSTEM: Draize scoring system
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: mean over 24, 48 and 72 h
Score:
0.7
Max. score:
4
Reversibility:
fully reversible within: 72 h
Remarks on result:
other: very slight erythema (grade 1) was seen at 24 and 72 h
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
other: mean over 24, 48 and 72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 48 h
Remarks on result:
other: very slight erythema (grade 1) was seen at 24h
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
other: mean over 24, 48 and 72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 48 h
Remarks on result:
other: very slight erythema (grade 1) was seen at 24h
Irritation parameter:
edema score
Basis:
mean
Remarks:
out of 3 animals
Time point:
other: mean over 24, 48 and 72 h
Score:
0
Max. score:
4
Reversibility:
other: reversibility not applicable
Remarks on result:
other: no edema observed
Irritant / corrosive response data:
All 3 animals displayed very slight erythema at reading time point 24 h; in one case (animal 1), erythema remained up to 48 h. The finding was fully reversible for all 3 animals with 48 to 72 h. No edema was seen.

Table 1: Erythema score

Animal Number

1 h

1 day

2 days

3 days

1

0

1

1

0

2

0

1

0

0

3

0

1

0

0

 

Table 2: Edema Score

Animal Number

1 h

1 day

2 days

3 days

1

0

0

0

0

2

0

0

0

0

3

0

0

0

0
Interpretation of results:
GHS criteria not met
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
CLP: not classified
DSD: not classified

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2002
Report date:
2002

Materials and methods

Test guidelineopen allclose all
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
adopted in 1992
Deviations:
yes
Remarks:
no data on analytical purity; observation period only 7 days
Qualifier:
equivalent or similar to guideline
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Version / remarks:
adopted in 1992
Deviations:
yes
Remarks:
no data on analytical purity; observation period only 7 days
GLP compliance:
yes
Remarks:
Department of health of the government of the United Kingdom, UK

Test material

Constituent 1
Reference substance name:
Fatty acids, C16-18 and C18-unsatd., branched and linear, esters with trimethylolpropane
Cas Number:
403507-18-6
IUPAC Name:
Fatty acids, C16-18 and C18-unsatd., branched and linear, esters with trimethylolpropane
Specific details on test material used for the study:
- Name of test material (as cited in study report): only trade name given
- Physical state: dark amber slightly viscous liquid
- Analytical purity: no data
- Storage condition of test material: room temperature in the dark

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: David Percival Ltd, Moston, Sandbach, Chesire, UK
- Age at study initiation: 12 to 16 weeks
- Weight at study initiation: 2.0-3.5 kg
- Housing: individually housed in suspended metal cages.
- Diet: certified Rabbit Diet (PMI Nutrition International, Nottingham, UK), ad libitum
- Water: ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17- 23
- Humidity (%): 30-70
- Air changes (per hr): at least 15
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Type of coverage:
semiocclusive
Preparation of test site:
other: clipped
Vehicle:
unchanged (no vehicle)
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL
Duration of treatment / exposure:
4 h
Observation period:
7 days
Reading time points: 1, 24, 48 and 72 h and 7 days
Number of animals:
3 males
Details on study design:
TEST SITE
- Area of exposure: dorsal/flank area
- Type of wrap if used: the treated skin was covered with a 2.5 cm x 2.5 cm cotton gauze, held in place with strip of surgical adhesive tape. In addition to prevent the animals interfering with the patches, the trunk of each rabbit was wrapped in an elasticated corset.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): residual test material was removed by gentle swabbing with cotton wool soaked in 74% industrial methylated spirits.
- Time after start of exposure: 4 h

SCORING SYSTEM: Draize scoring system

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: mean over 24, 48 and 72 h
Score:
1.33
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
other: mean over 24, 48 and 72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 h
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
other: mean over 24, 48 and 72 h
Score:
1.33
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: mean over 24, 48 and 72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 h
Irritation parameter:
edema score
Basis:
animal #2
Time point:
other: mean over 24, 48 and 72 h
Score:
0
Max. score:
4
Reversibility:
other: reversibility not applicable
Irritation parameter:
edema score
Basis:
animal #3
Time point:
other: mean over 24, 48 and 72 h
Score:
1.33
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritant / corrosive response data:
Very slight to well-defined erythema was noted in all animals (3/3) one hour after patch removal and at the 24 h observation. Very slight erythema noted in 2/3 animals skin at the 48 and 72 h observations.

Very slight to slight edema was noted in 2/3 animals on hour after patch removal and at 24 h observation. Very slight edema was observed in 1/3 animals at the 48 and 72 hour observation.
Other effects:
Light desquamation was noted at the two treated skin sites at the 7-day observation.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
CLP: not classified
DSD: not classified