Registration Dossier

Administrative data

Description of key information

Skin irritation (weight of evidence): irritating to the skin, 2018

1. Skin Irritation (Read-Across: undec-9-enal): irritating to the skin at 5000 mg/kg bw, eq. or similar to OECD TG 402, 1977

2. Skin Irritation (Read-Across: undec-9-enal): not irritating to the skin at 0.5% in SDA 39 C vehicle, eq. or similar to OECD TG 404, 1972

 

Eye irritation (weight of evidence): irritating to the eye, 2018

1. Eye Irritation (Read-Across: undec-9-enal): irritating to the eye, eq. or sim. to OECD 405, 1963

2. Eye Irritation (Read-Across: undec-9-enal): not irritating to the eye at 0.5% in SDA 39 C vehicle, eq. or similar to OECD TG 405, 1972

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin irritation / corrosion, other
Remarks:
Available Acute Dermal Toxicity study (equivalent or similar to guideline: OECD TG 402), indicating potential local toxicity (skin irritation) at levels equal or exceeding 2000 mg/kg bw; study used in weight of evidence approach
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Study period:
1977
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Pre-GLP study following a method equivalent to a recognised guideline at a limit dose, with some deviations not expected to affect the reliability of the study. The source and target substances must have an aldehyde group at the 1-carbon position and either a terminal (10-position) or an internal alkene (9-position or 8-position; with the terminal alkyl group no larger than an ethyl group and/or should not multiply substituted). The substance alkyl chain length of the substance should be more than 6 carbons in length and less than 14 carbons in length and fulfil the mono-alkene definition. The substance should not have any branched akyl groups or side chains. The target and source share common structural elements in the same relative positions. The source and target have very similar physico-chemical properties and thus have similar expected toxicokinetic behaviour. The substances have similar in silico chemical reactivity predictions. This is observed within available in vivo toxicology testing where low level local and systemic toxicity is demonstrated and comparable between target and source. The substances therefore demonstrate chemical similarity.
Justification for type of information:
REPORTING FORMAT FOR THE ANALOGUE APPROACH
Further information is included in attachment to IUCLID section 13.

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
The read-across is based on the hypothesis that the source and target substances have common structural features in the same relative positions. The source and target have similar physico-chemical, toxicological properties and because of common metabolism they share common or have similar breakdown products and therefore potential mechanisms of action. Further information is included in attachment to IUCLID section 13.

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
The source and target chemicals have comparable chemical similarity. Further information is included in attachment to IUCLID section 13

3. ANALOGUE APPROACH JUSTIFICATION
The source substance is a chemically similar substance with common metabolism and common or similar degradants of the target substance. Further information is included in attachment to IUCLID section 13

4. DATA MATRIX
Further information is included in attachment to IUCLID section 13.
Reason / purpose:
read-across source
Reason / purpose:
read-across: supporting information
Reason / purpose:
reference to same study
Qualifier:
equivalent or similar to
Guideline:
other: Acute Toxicity Dermal - OECD 402
Deviations:
yes
Remarks:
Limit dose of 5000mg/kg bw applied single dose; gross pathology completed.
Principles of method if other than guideline:
The principles of the method were in accordance with the US 16 CFR 1500.3 definitions.
GLP compliance:
no
Species:
rabbit
Strain:
not specified
Type of coverage:
not specified
Preparation of test site:
not specified
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST SITE
- Type of wrap if used: Not reported.

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 5000 mg/kg
Duration of treatment / exposure:
24h
Observation period:
14 days (see 'Details on Study Design').
Number of animals:
10 per dose level ; sex not specified.
Details on study design:
- Duration of observation period following administration: 14 days- Frequency of observations and weighing: Dermal reactions appear to be scored at 24 hours by the Draize scoring system. The rabbits were observed daily for 14 days for signs of toxicity, pharmacological effects and mortality. Body weights were recorded pretest and in survivors at 14 days.
- Necropsy of survivors performed: Yes.
Irritation / corrosion parameter:
other: erythema score
Value:
2.4
Remarks on result:
other:
Remarks:
Basis: mean. Time point: 24h. Max. score: 4.0. Reversibility: no data. (migrated information)
Irritation / corrosion parameter:
other: edema score
Value:
3
Remarks on result:
other:
Remarks:
Basis: mean. Time point: 24h. Max. score: 4.0. Reversibility: no data. (migrated information)
Irritant / corrosive response data:
Redness: 2/10 rabbits = mild redness (Score = 1) ; 6/10 rabbits = moderate skin irritation (score = 3) ; 1/10 rabbits severe (score = 4)
Edema: 10/10 rabbits = moderate (score = 3)
Interpretation of results:
Category 2 (irritant) based on GHS criteria
Remarks:
Criteria used for interpretation of results: EU and implementing expert judgment
Conclusions:
The target substance: is expected to produce positive local irritation responses at 5000 mg/kg bw.
Executive summary:

The pre-GLP study was performed on a source substance following a method similar to OECD TG 402 to assess the dermal toxicity of the test material to the rabbit. The test substance was evaluated in 10 rabbits. A dose of 5000 mg/kg test substance (undiluted), was applied for 24 hours. Skin observations were made 24 hours after patch removal and then daily for 14 days for signs of toxicity, pharmacological effects and mortality. No mortalities were observed. Very slight to well defined erythema and moderate edema were noted at 24 hours in all animals. Under the conditions of this study, the LD50 is considered to be greater than 5000 mg/kg.

The target substance: is expected to produce positive local irritation responses at 5000 mg/kg bw. Based on expert judgement and applying the precautionary principle, irritation can be expected to occur at 2000 mg/kg bw and therefore classification under Regulation (EC) 1272/2008: skin irritation category 2, is applied.

Endpoint:
skin irritation / corrosion, other
Remarks:
Available Acute Dermal Toxicity study (equivalent or similar to guideline: OECD TG 402), indicating potential local toxicity (skin irritation) at levels equal or exceeding 2000 mg/kg bw; study used in weight of evidence approach
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
1977
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Pre-GLP study following a method equivalent to a recognised guideline at a limit dose, with some deviations not expected to affect the reliability of the study. The source and target substances must have an aldehyde group at the 1-carbon position and either a terminal (10-position) or an internal alkene (9-position or 8-position; with the terminal alkyl group no larger than an ethyl group and/or should not multiply substituted). The substance alkyl chain length of the substance should be more than 6 carbons in length and less than 14 carbons in length and fulfil the mono-alkene definition. The substance should not have any branched akyl groups or side chains. The target and source share common structural elements in the same relative positions. The source and target have very similar physico-chemical properties and thus have similar expected toxicokinetic behaviour. The substances have similar in silico chemical reactivity predictions. This is observed within available in vivo toxicology testing where low level local and systemic toxicity is demonstrated and comparable between target and source. The substances therefore demonstrate chemical similarity.
Reason / purpose:
read-across: supporting information
Reason / purpose:
reference to same study
Qualifier:
equivalent or similar to
Guideline:
other: Acute Toxicity Dermal - OECD 402
Deviations:
yes
Remarks:
Limit dose of 5000mg/kg bw applied single dose; gross pathology completed.
Principles of method if other than guideline:
The principles of the method were in accordance with the US 16 CFR 1500.3 definitions.
GLP compliance:
no
Species:
rabbit
Strain:
not specified
Type of coverage:
not specified
Preparation of test site:
not specified
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST SITE
- Type of wrap if used: Not reported.

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 5000 mg/kg
Duration of treatment / exposure:
24h
Observation period:
14 days (see 'Details on Study Design').
Number of animals:
10 per dose level ; sex not specified.
Details on study design:
- Duration of observation period following administration: 14 days- Frequency of observations and weighing: Dermal reactions appear to be scored at 24 hours by the Draize scoring system. The rabbits were observed daily for 14 days for signs of toxicity, pharmacological effects and mortality. Body weights were recorded pretest and in survivors at 14 days.
- Necropsy of survivors performed: Yes.
Irritation / corrosion parameter:
other: erythema score
Value:
2.4
Remarks on result:
other:
Remarks:
Basis: mean. Time point: 24h. Max. score: 4.0. Reversibility: no data. (migrated information)
Irritation / corrosion parameter:
other: edema score
Value:
3
Remarks on result:
other:
Remarks:
Basis: mean. Time point: 24h. Max. score: 4.0. Reversibility: no data. (migrated information)
Irritant / corrosive response data:
Redness: 2/10 rabbits = mild redness (Score = 1) ; 6/10 rabbits = moderate skin irritation (score = 3) ; 1/10 rabbits severe (score = 4)
Edema: 10/10 rabbits = moderate (score = 3)
Interpretation of results:
Category 2 (irritant) based on GHS criteria
Remarks:
Criteria used for interpretation of results: EU and implementing expert judgment
Conclusions:
Under the conditions of this study, the test item produced positive local irritation responses at 5000 mg/kg bw.
Executive summary:

The pre-GLP study was performed following a method similar to OECD TG 402 to assess the dermal toxicity of the test material to the rabbit. The test substance was evaluated in 10 rabbits. A dose of 5000 mg/kg test substance (undiluted), was applied for 24 hours. Skin observations were made 24 hours after patch removal and then daily for 14 days for signs of toxicity, pharmacological effects and mortality. No mortalities were observed. Very slight to well defined erythema and moderate edema were noted at 24 hours in all animals. Under the conditions of this study, the LD50 is considered to be greater than 5000 mg/kg.

Endpoint:
skin irritation: in vivo
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Study period:
1972
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Pre-GLP study following a method similar to that of a recognised guideline. The source and target substances must have an aldehyde group at the 1-carbon position and either a terminal (10-position) or an internal alkene (9-position or 8-position; with the terminal alkyl group no larger than an ethyl group and/or should not multiply substituted). The substance alkyl chain length of the substance should be more than 6 carbons in length and less than 14 carbons in length and fulfil the mono-alkene definition. The substance should not have any branched alkyl groups or side chains. The target and source share common structural elements in the same relative positions. The source and target have very similar physico-chemical properties and thus have similar expected toxicokinetic behaviour. The substances have similar in silico chemical reactivity predictions. This is observed within available in vivo toxicology testing where low level local and systemic toxicity is demonstrated and comparable between target and source. The substances therefore demonstrate chemical similarity.
Justification for type of information:
REPORTING FORMAT FOR THE ANALOGUE APPROACH
Further information is included in attachment to IUCLID section 13.

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
The read-across is based on the hypothesis that the source and target substances have common structural features in the same relative positions. The source and target have similar physico-chemical, toxicological properties and because of common metabolism they share common or have similar breakdown products and therefore potential mechanisms of action. Further information is included in attachment to IUCLID section 13.

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
The source and target chemicals have comparable chemical similarity. Further information is included in attachment to IUCLID section 13

3. ANALOGUE APPROACH JUSTIFICATION
The source substance is a chemically similar substance with common metabolism and common or similar degradants of the target substance. Further information is included in attachment to IUCLID section 13

4. DATA MATRIX
Further information is included in attachment to IUCLID section 13.
Reason / purpose:
read-across source
Reason / purpose:
read-across: supporting information
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Principles of method if other than guideline:
Equivalent or similar to USA Federal Hazardous Substances Act tests to 16 CFR 1500.3 - application for 24 hours and then observations at 24 and 72 hours.
GLP compliance:
no
Species:
rabbit
Strain:
other: albino
Type of coverage:
occlusive
Preparation of test site:
clipped
Vehicle:
other: SDA 39 C
Controls:
not specified
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5mL (net test item and vehicle)
- Concentration (if solution): 0.5%

VEHICLE
- Concentration (if solution): 99.5%
Duration of treatment / exposure:
24h
Observation period:
48h up to 72h
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: 2 x 2 cm
- % coverage: Not reported. On the day prior to the experiment 10% of the total body area of the rabbits was carefully clipped free of all hair. Small animal clippers were used since these left the skin undisturbed. On the posterior of the clipped area several minor abrasions were made so as to penetrate the stratum corneum but not disturb the derma. This is to prevent bleeding.
- Type of wrap if used: Webril patches / Occlusive dressing

REMOVAL OF TEST SUBSTANCE
- Washing (if done): None.

SCORING SYSTEM: Draize Scoring system.
Irritation parameter:
erythema score
Basis:
mean
Remarks:
n = 3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Remarks:
USA Federal Hazardous Substances Act tests to 16 CFR 1500.3 terminate observations at 72hours. Time points 24 and 72hours are used in intact skin
Irritation parameter:
edema score
Basis:
mean
Remarks:
n = 3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Remarks:
USA Federal Hazardous Substances Act tests to 16 CFR 1500.3 terminate observations at 72hours. Time points 24 and 72hours are used in intact skin
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Remarks:
n = 3
Time point:
72 h
Score:
0
Max. score:
8
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
No reponses to intact skin (or abraded skin) were observed.
Interpretation of results:
GHS criteria not met
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
For the target substance: it is not considered to be irritating to the skin of albino rabbits (within 0.5% SDA 39 C vehicle).
Executive summary:

The non-GLP study was completed on a source substance under a guideline similar to OECD 404, to assess the irritancy potential of the test material to the skin of the albino rabbit. The test substance was evaluated in 3 rabbits. A dose of 0.5 ml test substance (0.5% test item in SDA 39 C vehicle was applied to intact and abraded clipped dorsal skin site under a occlusive dressing for 24 hours. Skin observations were made 24 and 72 hours after patch removal. No erythema and edema responses were noted at 24 or 72 hours in both intact and abraded skin. Under the conditions of the study the test material produced a mean primary irritation index (PII) of 0 and is considered to be non-irritating to skin.

The target substance: is not expected to produce positive local irritation responses. Based on expert judgement when applied to the skin at 0.5% within SDA 39 C vehicle.

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
1972
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Pre-GLP study following a method similar to that of a recognised guideline. The source and target substances must have an aldehyde group at the 1-carbon position and either a terminal (10-position) or an internal alkene (9-position or 8-position; with the terminal alkyl group no larger than an ethyl group and/or should not multiply substituted). The substance alkyl chain length of the substance should be more than 6 carbons in length and less than 14 carbons in length and fulfil the mono-alkene definition. The substance should not have any branched alkyl groups or side chains. The target and source share common structural elements in the same relative positions. The source and target have very similar physico-chemical properties and thus have similar expected toxicokinetic behaviour. The substances have similar in silico chemical reactivity predictions. This is observed within available in vivo toxicology testing where low level local and systemic toxicity is demonstrated and comparable between target and source. The substances therefore demonstrate chemical similarity.
Reason / purpose:
read-across: supporting information
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Principles of method if other than guideline:
Equivalent or similar to USA Federal Hazardous Substances Act tests to 16 CFR 1500.3 - application for 24 hours and then observations at 24 and 72 hours.
GLP compliance:
no
Species:
rabbit
Strain:
other: albino
Type of coverage:
occlusive
Preparation of test site:
clipped
Vehicle:
other: SDA 39 C
Controls:
not specified
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5mL (net test item and vehicle)
- Concentration (if solution): 0.5%

VEHICLE
- Concentration (if solution): 99.5%
Duration of treatment / exposure:
24h
Observation period:
48h up to 72h
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: 2 x 2 cm
- % coverage: Not reported. On the day prior to the experiment 10% of the total body area of the rabbits was carefully clipped free of all hair. Small animal clippers were used since these left the skin undisturbed. On the posterior of the clipped area several minor abrasions were made so as to penetrate the stratum corneum but not disturb the derma. This is to prevent bleeding.
- Type of wrap if used: Webril patches / Occlusive dressing

REMOVAL OF TEST SUBSTANCE
- Washing (if done): None.

SCORING SYSTEM: Draize Scoring system.
Irritation parameter:
erythema score
Basis:
mean
Remarks:
n = 3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Remarks:
USA Federal Hazardous Substances Act tests to 16 CFR 1500.3 terminate observations at 72hours. Time points 24 and 72hours are used in intact skin
Irritation parameter:
edema score
Basis:
mean
Remarks:
n = 3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Remarks:
USA Federal Hazardous Substances Act tests to 16 CFR 1500.3 terminate observations at 72hours. Time points 24 and 72hours are used in intact skin
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Remarks:
n = 3
Time point:
72 h
Score:
0
Max. score:
8
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
No reponses to intact skin (or abraded skin) were observed.
Interpretation of results:
GHS criteria not met
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of this study the test item is not considered to be irritating to the skin of albino rabbits (within 0.5% SDA 39 C vehicle).
Executive summary:

The non-GLP study was completed under a guideline similar to OECD 404, to assess the irritancy potential of the test material to the skin of the albino rabbit. The test substance was evaluated in 3 rabbits. A dose of 0.5 ml test substance (0.5% test item in SDA 39 C vehicle was applied to intact and abraded clipped dorsal skin site under a occlusive dressing for 24 hours. Skin observations were made 24 and 72 hours after patch removal. No erythema and edema responses were noted at 24 or 72 hours in both intact and abraded skin. Under the conditions of the study the test material produced a mean primary irritation index (PII) of 0 and is considered to be non-irritating to skin.

Endpoint:
skin irritation: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro skin irritation study does not need to be conducted because adequate data from an in vivo skin irritation study are available
other:
Justification for type of information:
JUSTIFICATION FOR DATA WAIVING
In accordance with REACH Regulation (EC) 1907/2006 as amended: Annex VII, section 8..1: the skin corrosion/irritation: in vitro / ex vivo study does not need to be conducted based REACH Regulation (EC) 1907/2006: Annex XI section 1.2 (weight of evidence) and section 1.5 (grouping of substances and read-across approach). This is based on existing data through read-across to structural analogue(s) and/or constituents of the substance sufficient for classification and labelling being already available. According to ECHA Guidance on Information Requirements and Chemical Safety Assessment (Chapter R.7a: Endpoint Specific Guidance, R.7.2, July 2017) the study does not need to be conducted.
Reason / purpose:
data waiving: supporting information
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Eye irritation

Link to relevant study records

Referenceopen allclose all

Endpoint:
eye irritation: in vivo
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Study period:
1963
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Pre-GLP study following a method similar to a recognised OECD guideline. The source and target substances must have an aldehyde group at the 1-carbon position and either a terminal (10-position) or an internal alkene (9-position or 8-position; with the terminal alkyl group no larger than an ethyl group and/or should not multiply substituted). The substance alkyl chain length of the substance should be more than 6 carbons in length and less than 14 carbons in length and fulfil the mono-alkene definition. The substance should not have any branched akyl groups or side chains. The target and source share common structural elements in the same relative positions. The source and target have very similar physico-chemical properties and thus have similar expected toxicokinetic behaviour. The substances have similar in silico chemical reactivity predictions. This is observed within available in vivo toxicology testing where low level local and systemic toxicity is demonstrated and comparable between target and source. The substances therefore demonstrate chemical similarity.
Justification for type of information:
REPORTING FORMAT FOR THE ANALOGUE APPROACH
Further information is included in attachment to IUCLID section 13.

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
The read-across is based on the hypothesis that the source and target substances have common structural features in the same relative positions. The source and target have similar physico-chemical, toxicological properties and because of common metabolism they share common or have similar breakdown products and therefore potential mechanisms of action. Further information is included in attachment to IUCLID section 13.

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
The source and target chemicals have comparable chemical similarity. Further information is included in attachment to IUCLID section 13

3. ANALOGUE APPROACH JUSTIFICATION
The source substance is a chemically similar substance with common metabolism and common or similar degradants of the target substance. Further information is included in attachment to IUCLID section 13

4. DATA MATRIX
Further information is included in attachment to IUCLID section 13.
Reason / purpose:
read-across source
Reason / purpose:
read-across: supporting information
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
no
Species:
rabbit
Strain:
other: albino rabbits
Details on test animals or tissues and environmental conditions:
not reported
Vehicle:
not specified
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL
- Concentration (if solution): not reported
Duration of treatment / exposure:
Each animal had 0.1 ml of the test sample instilled into the right eye with no further treatment. The untreated left eye of each animal served as itsown control.
Observation period (in vivo):
Both the treated and control eyes were examined every twenty-four hours for four days and then again on the seventh day.
Number of animals or in vitro replicates:
3
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): no

SCORING SYSTEM: The scorings recorded were made according to the Draize scale for scoring ocular lesions.

TOOL USED TO ASSESS SCORE: not reported
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
n = 3
Time point:
24/48/72 h
Score:
0
Max. score:
12
Remarks on result:
no indication of irritation
Remarks:
maximum category score =4
Irritation parameter:
iris score
Basis:
mean
Remarks:
n = 3
Time point:
24/48/72 h
Score:
0
Max. score:
8
Remarks on result:
no indication of irritation
Remarks:
maximum category score = 2
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
n = 3
Time point:
24/48/72 h
Score:
2.33
Max. score:
9
Reversibility:
fully reversible within: 7 days
Remarks on result:
positive indication of irritation
Remarks:
maximum category score = 3
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
n = 3
Time point:
24/48/72 h
Score:
1.22
Max. score:
12
Reversibility:
fully reversible within: 7 days
Remarks on result:
other:
Remarks:
maximum category score = 4
Irritant / corrosive response data:
No corneal opacity or iris congestion was observed. A diffuse redness of the vessels of the palpebral conjunctivae did occur. This injection was accompanied by a partial eversion of the lids and some discharge. On the 7th day observation of the conjuncitvae was normal.

Applicant recalcluated the scoring to the EU/GHS scoring criteria. Individual scoring was presented within the study report.

Interpretation of results:
Category 2 (irritating to eyes) based on GHS criteria
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
The target substance: is expected to irritating the eyes of albino rabbits.
Executive summary:

The study was performed on a source substance to assess the irritancy potential of the test material to the eye following a single application in albino white rabbits. The pre-GLP study was completed under a method similar to OECD 405. A volume of 0.1 ml of the test material was placed into one eye of 3 animals. The other eye remained untreated and was used for control purposes. Assessment of ocular damage/irritation was made every 24 hour for 4 days and again on day 7 using scoring based on the Draize scale for scoring occular lesions. Instillation of the test material did not produce any corneal opacity or iris congestion. A diffuse redness of the vessels of the palpebral conjunctivae did occur. This injection was accompanied by a partial eversion of the lids and some discharge. On the seventh day of observation the conjunctivae were normal in all test animals. Under the conditions of this study, the test material is considered to be irritating the eyes of albino rabbits.

The target substance: is expected to produce positive local irritation responses based on expert judgement and applying the precautionary principle, therefore classification under Regulation (EC) 1272/2008: eye irritation category 2, is applied.

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
1963
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Pre-GLP study following a method similar to a recognised OECD guideline. The source and target substances must have an aldehyde group at the 1-carbon position and either a terminal (10-position) or an internal alkene (9-position or 8-position; with the terminal alkyl group no larger than an ethyl group and/or should not multiply substituted). The substance alkyl chain length of the substance should be more than 6 carbons in length and less than 14 carbons in length and fulfil the mono-alkene definition. The substance should not have any branched akyl groups or side chains. The target and source share common structural elements in the same relative positions. The source and target have very similar physico-chemical properties and thus have similar expected toxicokinetic behaviour. The substances have similar in silico chemical reactivity predictions. This is observed within available in vivo toxicology testing where low level local and systemic toxicity is demonstrated and comparable between target and source. The substances therefore demonstrate chemical similarity.
Reason / purpose:
read-across: supporting information
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
no
Species:
rabbit
Strain:
other: albino rabbits
Details on test animals or tissues and environmental conditions:
not reported
Vehicle:
not specified
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL
- Concentration (if solution): not reported
Duration of treatment / exposure:
Each animal had 0.1 ml of the test sample instilled into the right eye with no further treatment. The untreated left eye of each animal served as itsown control.
Observation period (in vivo):
Both the treated and control eyes were examined every twenty-four hours for four days and then again on the seventh day.
Number of animals or in vitro replicates:
3
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): no

SCORING SYSTEM: The scorings recorded were made according to the Draize scale for scoring ocular lesions.

TOOL USED TO ASSESS SCORE: not reported
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
12
Remarks on result:
other: n=3; maximum category score =4
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
8
Remarks on result:
other: n=3; maximum category score = 2
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48/72 h
Score:
2.33
Max. score:
9
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: n=3 ; maximum category score = 3
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
1.22
Max. score:
12
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: n=3; maximum category score = 4
Irritant / corrosive response data:
No corneal opacity or iris congestion was observed. A diffuse redness of the vessels of the palpebral conjunctivae did occur. This injection was accompanied by a partial eversion of the lids and some discharge. On the 7th day observation of the conjuncitvae was normal.

Applicant recalcluated the scoring to the EU/GHS scoring criteria. Individual scoring was presented within the study report.

Interpretation of results:
Category 2 (irritating to eyes) based on GHS criteria
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of this study, the test item is considered to be irritating the eyes of albino rabbits.
Executive summary:

The study was performed to assess the irritancy potential of the test material to the eye following a single application in albino white rabbits. The pre-GLP study was completed under a method similar to OECD 405. A volume of 0.1 ml of the test material was placed into one eye of 3 animals. The other eye remained untreated and was used for control purposes. Assessment of ocular damage/irritation was made every 24 hour for 4 days and again on day 7 using scoring based on the Draize scale for scoring occular lesions. Instillation of the test material did not produce any corneal opacity or iris congestion. A diffuse redness of the vessels of the palpebral conjunctivae did occur. This injection was accompanied by a partial eversion of the lids and some discharge. On the seventh day of observation the conjunctivae were normal in all test animals. Under the conditions of this study, the test material is considered to be irritating the eyes of albino rabbits.

Endpoint:
eye irritation: in vivo
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Study period:
1972
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Pre-GLP study following a method similar to a recognised OECD guideline. The source and target substances must have an aldehyde group at the 1-carbon position and either a terminal (10-position) or an internal alkene (9-position or 8-position; with the terminal alkyl group no larger than an ethyl group and/or should not multiply substituted). The substance alkyl chain length of the substance should be more than 6 carbons in length and less than 14 carbons in length and fulfil the mono-alkene definition. The substance should not have any branched akyl groups or side chains. The target and source share common structural elements in the same relative positions. The source and target have very similar physico-chemical properties and thus have similar expected toxicokinetic behaviour. The substances have similar in silico chemical reactivity predictions. This is observed within available in vivo toxicology testing where low level local and systemic toxicity is demonstrated and comparable between target and source. The substances therefore demonstrate chemical similarity.
Justification for type of information:
REPORTING FORMAT FOR THE ANALOGUE APPROACH
Further information is included in attachment to IUCLID section 13.

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
The read-across is based on the hypothesis that the source and target substances have common structural features in the same relative positions. The source and target have similar physico-chemical, toxicological properties and because of common metabolism they share common or have similar breakdown products and therefore potential mechanisms of action. Further information is included in attachment to IUCLID section 13.

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
The source and target chemicals have comparable chemical similarity. Further information is included in attachment to IUCLID section 13

3. ANALOGUE APPROACH JUSTIFICATION
The source substance is a chemically similar substance with common metabolism and common or similar degradants of the target substance. Further information is included in attachment to IUCLID section 13

4. DATA MATRIX
Further information is included in attachment to IUCLID section 13.
Reason / purpose:
read-across source
Reason / purpose:
read-across: supporting information
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
no
Species:
rabbit
Strain:
other: albino
Details on test animals or tissues and environmental conditions:
not reported
Vehicle:
other: SDA 39 C
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1mL
- Concentration (if solution): 0.5%
Duration of treatment / exposure:
Each animal had 0.1 ml. of the test sample instilled into the right eye with no further treatment.
Observation period (in vivo):
Both the treated and control eyes were examined every twenty-four hours for four days and then again on the seventh day.
Number of animals or in vitro replicates:
3
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): no

SCORING SYSTEM: The scorings recorded were made according to the Draize scale for scoring ocular lesions.
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 1, 2, 3, 4, 7d
Score:
0
Max. score:
80
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 1, 2, 3, 4, 7 d
Score:
0
Max. score:
10
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 1,2,3,4,7 d
Score:
2
Max. score:
20
Reversibility:
fully reversible within: 7 days
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
12
Remarks on result:
other: n=3 ; maximum category score = 4
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
8
Remarks on result:
other: n=3 ; maximum category score = 2
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48/72 h
Score:
0.67
Max. score:
9
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: n=3 ; maximum category score = 3
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
12
Remarks on result:
other: n=3 ; maximum category score = 4
Irritant / corrosive response data:
Instillation of 0. 1 ml. of the test material into the right eye of each of three rabbits, produced a very slight vessel injection. These eyes were normal on the third day of observation.

Applicant recalculated the scoring to the EU/GHS scoring criteria. Individual scoring was presented within the study report.

Interpretation of results:
GHS criteria not met
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
For the target substance: it is not considered to be irritating to the eyes of albino rabbits (within 0.5% SDA 39 C vehicle).
Executive summary:

The study was performed on a source substance to assess the irritancy potential of the test material to the eye following a single application in albino white rabbits. The pre-GLP study was completed under a method similar to OECD 405. A volume of 0.1 ml of the test material (0.5% in SDA vehicle) was placed into one eye of 3 animals. The other eye remained untreated and was used for control purposes. Assessment of ocular damage/irritation was made every 24 hour for 4 days and again on day 7 using scoring based on the Draize scale for scoring occular lesions. Instillation of the test material did not produce any corneal opacity or iris congestion. A very slight vessel injection was observed on day 1 ad 2 in all three animals. On the seventh day of observation the conjunctivae were normal in all test animals. Under the conditions of this study the test material is not considered to be irritating the eyes of albino rabbits.

The target substance: is not expected to produce positive local irritation responses. Based on expert judgement when applied to the eye at 0.5% within SDA 39 C vehicle.

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
1972
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Pre-GLP study following a method similar to a recognised OECD guideline. The source and target substances must have an aldehyde group at the 1-carbon position and either a terminal (10-position) or an internal alkene (9-position or 8-position; with the terminal alkyl group no larger than an ethyl group and/or should not multiply substituted). The substance alkyl chain length of the substance should be more than 6 carbons in length and less than 14 carbons in length and fulfil the mono-alkene definition. The substance should not have any branched akyl groups or side chains. The target and source share common structural elements in the same relative positions. The source and target have very similar physico-chemical properties and thus have similar expected toxicokinetic behaviour. The substances have similar in silico chemical reactivity predictions. This is observed within available in vivo toxicology testing where low level local and systemic toxicity is demonstrated and comparable between target and source. The substances therefore demonstrate chemical similarity.
Reason / purpose:
read-across: supporting information
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
no
Species:
rabbit
Strain:
other: albino
Details on test animals or tissues and environmental conditions:
not reported
Vehicle:
other: SDA 39 C
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1mL
- Concentration (if solution): 0.5%
Duration of treatment / exposure:
Each animal had 0.1 ml. of the test sample instilled into the right eye with no further treatment.
Observation period (in vivo):
Both the treated and control eyes were examined every twenty-four hours for four days and then again on the seventh day.
Number of animals or in vitro replicates:
3
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): no

SCORING SYSTEM: The scorings recorded were made according to the Draize scale for scoring ocular lesions.
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 1, 2, 3, 4, 7d
Score:
0
Max. score:
80
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 1, 2, 3, 4, 7 d
Score:
0
Max. score:
10
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 1,2,3,4,7 d
Score:
2
Max. score:
20
Reversibility:
fully reversible within: 7 days
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
12
Remarks on result:
other: n=3 ; maximum category score = 4
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
8
Remarks on result:
other: n=3 ; maximum category score = 2
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48/72 h
Score:
0.67
Max. score:
9
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: n=3 ; maximum category score = 3
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
12
Remarks on result:
other: n=3 ; maximum category score = 4
Irritant / corrosive response data:
Instillation of 0. 1 ml. of the test material into the right eye of each of three rabbits, produced a very slight vessel injection. These eyes were normal on the third day of observation.

Applicant recalculated the scoring to the EU/GHS scoring criteria. Individual scoring was presented within the study report.

Interpretation of results:
GHS criteria not met
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of this study, the test substance is not considered to be irritating to the eyes of albino rabbits (within 0.5% SDA 39 C vehicle).
Executive summary:

The study was performed to assess the irritancy potential of the test material to the eye following a single application in albino white rabbits. The pre-GLP study was completed under a method similar to OECD 405. A volume of 0.1 ml of the test material (0.5% in SDA vehicle) was placed into one eye of 3 animals. The other eye remained untreated and was used for control purposes. Assessment of ocular damage/irritation was made every 24 hour for 4 days and again on day 7 using scoring based on the Draize scale for scoring occular lesions. Instillation of the test material did not produce any corneal opacity or iris congestion. A very slight vessel injection was observed on day 1 ad 2 in all three animals. On the seventh day of observation the conjunctivae were normal in all test animals. Under the conditions of this study the test material is not considered to be irritating the eyes of albino rabbits.

Endpoint:
eye irritation: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro eye irritation study does not need to be conducted because adequate data from an in vivo eye irritation study are available
other:
Justification for type of information:
JUSTIFICATION FOR DATA WAIVING
In accordance with REACH Regulation (EC) 1907/2006 as amended: Annex VII, section 8.2.1: the serious eye damage/eye irritation: in vitro / ex vivo study does not need to be conducted based REACH Regulation (EC) 1907/2006: Annex XI section 1.2 (weight of evidence) and section 1.5 (grouping of substances and read-across approach). This is based on existing data on read-across to structural analogue(s) and/or constituents of the substance sufficient for classification and labelling being already available. According to ECHA Guidance on Information Requirements and Chemical Safety Assessment (Chapter R.7a: Endpoint Specific Guidance, R.7.2, July 2017) the study does not need to be conducted.
Reason / purpose:
data waiving: supporting information
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation:

1. Eq. to OECD 402, 1977: Read-Across SOURCE (undec-9-enal): The pre-GLP study was performed following a method similar to OECD 402 to assess the dermal toxicity of the test material to the rabbit. The test substance was evaluated in 10 rabbits. A dose of 5000 mg/kg test substance (undiluted), was applied for 24 hours. Skin observations were made 24 hours after patch removal and then daily for 14 days for signs of toxicity, pharmacological effects and mortality. No mortalities were observed. Very slight to well defined erythema and moderate edema were noted at 24 hours in all animals.

2. Eq. to OECD 404, 1972: Read-Across SOURCE (undec-9-enal): The non-GLP study was completed under a guideline similar to OECD 404, to assess the irritancy potential of the test material to the skin of the albino rabbit. The test substance was evaluated in 3 rabbits. A dose of 0.5 ml test substance (0.5% test item in SDA 39 C vehic)le was applied to intact and abraded clipped dorsal skin site under a occlusive dressing for 24 hours. Skin observations were made 24 and 72 hours after patch removal. No erythema and edema responses were noted at 24 or 72 hours in both intact and abraded skin. Under the conditions of the study the test material produced a mean primary irritation index (PII) of 0 and is considered to be non-irritating to skin.

Weight of Evidence: Since there was a clear demonstration of a mean score greater than or equal to 2.3 in the scoring at 24, 48 and 72hours and/or expected persists to the end of a 14-day observation period (since this was not reported in the dermal toxicity study), the substance based on the weight of evidence can be considered to be irritating or would produce a positive response in a guideline in vivo skin irritation test. Further in vivo testing for skin irritation is unjustified.

 

Eye irritation/corrosion:

1. Eq. to OECD 405, 1963: Read-Across SOURCE (undec-9-enal): The study was performed to assess the irritancy potential of the test material to the eye following a single application in albino white rabbits. The pre-GLP study was completed under a method similar to OECD 405. A volume of 0.1 ml of the test material was placed into one eye of 3 animals. The other eye remained untreated and was used for control purposes. Assessment of ocular damage/irritation was made every 24 hour for 4 days and again on day 7 using scoring based on the Draize scale for scoring occular lesions. Instillation of the test material did not produce any corneal opacity or iris congestion. A diffuse redness of the vessels of the palpebral conjunctivae did occur. This injection was accompanied by a partial eversion of the lids and some discharge. On the seventh day of observation the conjunctivae were normal in all test animals. Under the conditions of this study the test material is considered to be irritating the eyes of albino rabbits.

2. Eq. to OECD 405, 1972: Read-Across SOURCE (undec-9-enal): The study was performed to assess the irritancy potential of the test material to the eye following a single application in albino white rabbits. The pre-GLP study was completed under a method similar to OECD 405. A volume of 0.1 ml of the test material (0.5% in SDA vehicle) was placed into one eye of 3 animals. The other eye remained untreated and was used for control purposes. Assessment of ocular damage/irritation was made every 24 hour for 4 days and again on day 7 using scoring based on the Draize scale for scoring occular lesions. Instillation of the test material did not produce any corneal opacity or iris congestion. A very slight vessel injection was observed on day 1 ad 2 in all three animals. On the seventh day of observation the conjunctivae were normal in all test animals. Under the conditions of this study the test material is not considered to be irritating the eyes of albino rabbits.

Weight of Evidence: Since there was a clear demonstration of a mean redness score greater than or equal to 2 in the available studies, the substance based on the weight of evidence can be considered to be irritating to the eye. There was a complete absence of corneal opacity and iritis reported and expert judgement would indicate that irreversible damage to the eye is not expected or supported based on the available data.

Justification for classification or non-classification

The substance meets the classification criteria under Regulation (EC) No 1272/2008 for skin irritation category 2 : H315

 

The substance meets classification criteria under Regulation (EC) No 1272/2008 for eye irritation category 2: H319

 

For skin irritation, the weight of evidence indicates that the substance has the potential to be irritating and sufficient for classification purposes. In vivo data on a structural analogue(s) (constituent substances) indicates negative irritation in an in vivo dermal irritation study (but this has limited reliability as it was completed in a vehicle and dilution). An available in vivo acute dermal toxicity study on a structural analogue constituent at the limit dose of 5000 mg/kg bw demonstrated positive local responses and which are for a constituent above the generic cut-off within Regulation (EC) 1272/2008. Expert judgement indicates that the substance can be expected to generate a positive irritation response adequate for classification.

 

For eye irritation, the weight of evidence indicates that the substance has the potential to cause transient irritating effects to the eye sufficient for classification based on the applicants recalculation of the mean scoring within available in vivo data on structural analogue(s) (constituent substances) and evaluation of the results in three organisms demonstrating that the EU criteria had been met specifically within conjunctival redness criteria only. Effects in vivo on corneal opacity and iritis are non-existent or very low; the substance is of demonstrated low order of acute toxicity and further; based on skin irritation studies an absence of serious effects by the dermal route – the overall evidence is indicative of transient and reversible effects on the eye.

 

References:

1. ECHA Guidance on Application on the CLP Criteria, (v5.0, July 2017)