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Eye irritation

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Endpoint:
eye irritation: in vivo
Type of information:
other: data sharing dispute
Adequacy of study:
key study
Study period:
31 Jan - 07 Feb 2002
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP-guideline study with acceptable restrictions (no data on analytical purity; no eye washing performed after treatment)
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:
eye irritation, 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
Guideline:
other: REACH Guidance on Qsars and grouping of chemicals R.6 year 2008
Principles of method if other than guideline:
Estimates eye irritation and corrosion potential by physicochemical property ranges and structural rules.
Gerner, I., Liebsch, M., Spielmann, H. (2005). Assessment of the eye irritating properties of chemicals by applying alternatives to the Draize rabbit eye test: the use of QSARs and in vitro tests for the classification of eye irritation. Alternatives to Laboratory Animals 33, 215-237.

GLP compliance:
no
Specific details on test material used for the study:
SMILES: C(CCCCCCC\C=C/CCCCCCCC)(=O)OCC(CC)(COC(CCCCCCC\C=C/CCCCCCCC)=O)COC(CCCCCCC\C=C/CCCCCCCC)=O
Irritation parameter:
other: qualitative estimation
Remarks on result:
no indication of irritation
Irritation parameter:
other: qualitative estimation
Remarks on result:
no indication of irritation

   Q1.Melting Point[℃] > 200 No   C(CCCCCCC\C=C/CCCCCCCC)(=O)OCC(CC)(COC(CCCCCCC\C=C/CCCCCCCC)=O)COC(CCCCCCC\C=C/CCCCCCCC)=O  

Q2.LogP>9.0 Yes Class NOT lesions R34, R35, R36 or R41 C(CCCCCCC\C=C/CCCCCCCC)(=O)OCC(CC)(COC(CCCCCCC\C=C/CCCCCCCC)=O)COC(CCCCCCC\C=C/CCCCCCCC)=O

Interpretation of results:
other: Not irritant to eyes
Reason / purpose for cross-reference:
other: weight of evidence
Reference
Endpoint:
eye irritation, other
Remarks:
Draize test - in vitro
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
Guideline:
other: REACH Guidance on Qsars and grouping of chemicals R.6 year 2008
Principles of method if other than guideline:
Estimates eye irritation and corrosion potential by physicochemical property ranges and structural rules.
Gerner, I., Liebsch, M., Spielmann, H. (2005). Assessment of the eye irritating properties of chemicals by applying alternatives to the Draize rabbit eye test: the use of QSARs and in vitro tests for the classification of eye irritation. Alternatives to Laboratory Animals 33, 215-237.
GLP compliance:
no
Specific details on test material used for the study:
SMILES STRING C(\CCCCCCCC)=C/CCCCCCCC(OCC(CC)(CO)COC(=O)CCCCCCC\C=C/CCCCCCCC)=O
Irritation 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 irritant to eyes
Reason / purpose for cross-reference:
other: weight of evidence
Reference
Endpoint:
eye irritation, other
Remarks:
Draize test - in vitro
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
Guideline:
other: REACH Guidance on Qsars and grouping of chemicals R.6 year 2008
Principles of method if other than guideline:
Estimates eye irritation and corrosion potential by physicochemical property ranges and structural rules.
Gerner, I., Liebsch, M., Spielmann, H. (2005). Assessment of the eye irritating properties of chemicals by applying alternatives to the Draize rabbit eye test: the use of QSARs and in vitro tests for the classification of eye irritation. Alternatives to Laboratory Animals 33, 215-237.
GLP compliance:
no
Specific details on test material used for the study:
SMILES descriptor used for prediction: CCCCCCCCC=CCCCCCCCC(=O)OCC(CC)(CO)CO
Irritation 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 irritant to eyes
Reason / purpose for cross-reference:
other: weight of evidence
Reference
Endpoint:
eye irritation: in vivo
Type of information:
other: data sharing dispute
Adequacy of study:
key study
Study period:
10 July - 13 July 1989
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Guideline study with acceptable restrictions (only few data on 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 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
only few details on study substance
GLP compliance:
yes
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
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Thomae, Biberach, Germany
- Age at study initiation: 6 months
- Weight at study initiation: 2.6 kg
- Housing: individually in rabbit-battery
- Diet: Altromin 2023 ad libitum
- Water: tap water, ad libitum
- Acclimation period: 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-25
- Humidity (%): 45-70
- Photoperiod (hrs dark / hrs light): 12 / 12
Vehicle:
unchanged (no vehicle)
Controls:
other: the untreated eye served as control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL (slightly warmed)
Duration of treatment / exposure:
24 H
Observation period (in vivo):
72 h
Reading time points: 1, 24, 48, 72 h
Number of animals or in vitro replicates:
3 MALES
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): Yes, rinsed with water
- Time after start of exposure: 24 h

SCORING SYSTEM: Draize scoring system

TOOL USED TO ASSESS SCORE: fluorescein
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
OF ALL THREE ANIMALS
Time point:
other: mean over 24, 48 and 72 h
Score:
0
Max. score:
4
Reversibility:
other: reversibility not applicable
Irritation parameter:
iris score
Basis:
mean
Remarks:
of all three animals
Time point:
other: mean over 24, 48 and 72 h
Score:
0
Max. score:
2
Reversibility:
not specified
Remarks:
reversibility not applicable
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
of all three animals
Time point:
other: mean over 24, 48 and 72 h
Score:
0
Max. score:
3
Reversibility:
other: reversibility not applicable
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
of all three animals
Time point:
other: mean over 24, 48 and 72 h
Score:
0
Max. score:
4
Reversibility:
other: reversibility not applicable
Irritant / corrosive response data:
Redness of the conjuctivae of grade 1 was seen in all 3 animals at reading time point 1 h only. In 2 cases this was accompanied by exudation. These effects disappeared within 24 h.

Table 1: Eye irritation scores 

Animal

Hours after application

1

24

48

72

A

B

C

D

E

A

B

C

D

E

A

B

C

D

E

A

B

C

D

E

1

0

0

1

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

2

0

0

1

0

1

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

3

0

0

1

0

1

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

A = Corneal Score

B = Iris Score

C = Erythema Score

D = Chemosis Score

E = Exsudation Score

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 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
adopted in 1987
Deviations:
yes
Remarks:
no data on analytical purity; no eye washing performed after treatment
Qualifier:
equivalent or similar to guideline
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Version / remarks:
adopted in 1992
Deviations:
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 / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues 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

Vehicle:
unchanged (no vehicle)
Controls:
other: the untreated eye served as control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL
Duration of treatment / exposure:
single application without washing
Observation period (in vivo):
3 days
Reading time points: 1, 24, 48 and 72 h
Number of animals or in vitro replicates:
1 female and 2 males
Details on study design:
SCORING SYSTEM: Draize scoring system

TOOL USED TO ASSESS SCORE: light source from a standard ophthalmoscope

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
out of all 3 animals
Time point:
other: mean over 24, 48 and 72 h
Score:
0
Max. score:
4
Reversibility:
other: reversibility not applicable
Irritation parameter:
iris score
Basis:
mean
Remarks:
out of all 3 animals
Time point:
other: mean over 24, 48 and 72 h
Score:
0
Max. score:
2
Reversibility:
other: reversibility not applicable
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
other: mean over 24, 48 and 72 h
Score:
0.33
Max. score:
3
Reversibility:
fully reversible within: 48 h
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
other: mean over 24, 48 and 72 h
Score:
0
Max. score:
3
Reversibility:
other: reversibility not applicable
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
other: mean over 24, 48 and 72 h
Score:
0.33
Max. score:
3
Reversibility:
fully reversible within: 48 h
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
out of all 3 animals
Time point:
other: mean over 24, 48 and 72 h
Score:
0
Max. score:
4
Reversibility:
other: reversibility not applicable
Irritant / corrosive response data:
No corneal or iris effects occurred during the study.

Moderate conjuctival irritation was observed in all treated eyes (3/3) one hour after treatment.
Minimal conjuctival irritation was noted in two treated eyes (2/3) at 24 h observation time.

Applicant's summary and conclusion

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