Registration Dossier
Registration Dossier
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.
The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 217-588-1 | CAS number: 1897-45-6
Endpoint summary
Administrative data
Description of key information
- Skin sensitisation, Guinea Pig Maximization Test, intradermal injection induction; result inconclusive; Tucker 1986a
- Skin sensitisation, Guinea Pig Maximization Test, intradermal injection induction; sensitising; Wilson, Tucker 1986b
- Skin sensitisation, Guinea Pig Maximization Test, repeated epidermal application induction; sensitising; Tucker 1986c
Key value for chemical safety assessment
Skin sensitisation
Link to relevant study records
- Endpoint:
- skin sensitisation: in vivo (non-LLNA)
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- 30 Mar 1984
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study with acceptable restrictions
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 406 (Skin Sensitisation)
- Deviations:
- yes
- Remarks:
- The challenge concentration was inadequate for elicitation of sensitisation and insufficient volume of the material was used on each test site during the irritancy and inductions phases so that the skin at the site was not entirely covered.
- GLP compliance:
- yes
- Type of study:
- guinea pig maximisation test
- Justification for non-LLNA method:
- Currently no LLNA study is available for assessment. The GPMT test has been carried out as an animal test to predict human sensitisation for over a decade and is recommended by international test guidelines such as OECD.
- Species:
- guinea pig
- Strain:
- Dunkin-Hartley
- Sex:
- male/female
- Details on test animals and environmental conditions:
- TEST ANIMALS
- Females nulliparous and non-pregnant: yes
- Weight at study initiation: approximately 350 g
- Housing: housed individually in appropriately-sized cages
- Diet: guinea pig chow, ad libitum
- Water: ad libitum
- Acclimation period: 4 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16 - 23
- Humidity (%): 40 - 60
- Photoperiod (hrs dark / hrs light): 12/12 - Route:
- intradermal
- Vehicle:
- other: acetone
- Concentration / amount:
- Injection: 0.1 mL
Treatment: adjuvant (FCA) diluted equally with acetone - Day(s)/duration:
- Day 0: First injection of the three pairs of intradermal injections
- Route:
- intradermal
- Vehicle:
- other: acetone
- Concentration / amount:
- Injection: 0.1 mL
Treatment: 0.5 % test substance (w/v) in a 50:50 mixture of FCA and acetone - Day(s)/duration:
- Day 0: Second injection of three pairs of intradermal injections
- Adequacy of induction:
- highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
- Route:
- intradermal
- Vehicle:
- other: acetone
- Concentration / amount:
- Injection: 0.1 mL
Treatment: 0.5 % test substance (w/v) in acetone - Day(s)/duration:
- Day 0: Third injection of the three pairs of intradermal injections
- Adequacy of induction:
- highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
- Route:
- intradermal
- Vehicle:
- other: acetone
- Remarks:
- control group
- Concentration / amount:
- Injection: 0.1 mL
Treatment: FCA diluted equally with acetone - Day(s)/duration:
- Day 0: First control injection out of three pairs of injections
- Route:
- intradermal
- Vehicle:
- other: acetone
- Remarks:
- control group
- Concentration / amount:
- Injection: 0.1 mL
Treatment: FCA diluted equally with acetone - Day(s)/duration:
- Day 0: Second control injection out of three pairs of injections
- Route:
- intradermal
- Vehicle:
- unchanged (no vehicle)
- Remarks:
- control group
- Concentration / amount:
- Injection: 0.1 mL
Treatment: Acetone - Day(s)/duration:
- Day 0: Third control injection out of three pairs of intradermal injections
- Route:
- epicutaneous, occlusive
- Vehicle:
- other: acetone
- Concentration / amount:
- Volume/area: 0.1 mL/2 x 4 cm area over the site of injection
Treatment: 1 % test substance in acetone, occlusive - Day(s)/duration:
- Day 7: all test animals for 48 h
- Adequacy of induction:
- highest technically applicable concentration used
- Route:
- epicutaneous, occlusive
- Vehicle:
- unchanged (no vehicle)
- Concentration / amount:
- Volume/area: 0.1 mL/2 x 4 cm area over the injection site
Treatment: Acetone; occlusive - Day(s)/duration:
- Day 7: all control animals for 48 h
- No.:
- #1
- Route:
- epicutaneous, occlusive
- Vehicle:
- other: acetone
- Concentration / amount:
- Volume/area: 0.05 mL/2 x 2 cm area on one flank of each guinea pig in the test and control groups
Treatment: 0.001 % test substance in acetone - Day(s)/duration:
- Day 21: occlusive dressing for 24 h
- Adequacy of challenge:
- highest non-irritant concentration
- No.:
- #2
- Route:
- epicutaneous, occlusive
- Vehicle:
- other: acetone
- Concentration / amount:
- Volume: 0.75 mL
Treatment: 0.001 % test substance in acetone - Day(s)/duration:
- 48 h, occlusive
- Adequacy of challenge:
- other: Re-challenge done due to the wrong interpretation of irritation study
- No. of animals per dose:
- 5 animals per sex per dose
- Details on study design:
- RANGE FINDING TEST/IRRITATION STUDY:
For irritation testing, four 2 x 2 cm sites (2 on each flank) were designated on each of 2 male and 2 female guinea pigs. A volume of 0.05 mL of each of 4 different concentrations of test substance in acetone (i.e. 0.5%, 0.01%, 0.005% and 0.001% (w/v) was applied to the 4 sites on each animal). The sequence of the 4 concentrations of test material was varied from animal to animal to minimize the bias associated with the location of application, e.g. skin thickness. After treatment, the application sites were covered with gauze, then with occlusive plastic dressings and, finally, elastoplast tape.
After 24 hours of occlusion, the coverings were removed and irritation at each application site was determined. The highest concentration of the test substance in acetone causing no erythema or oedema at the site of application on any of the 4 animals was considered to be the highest non-irritating concentration. - Challenge controls:
- 0.05 mL of acetone alone
- Positive control substance(s):
- no
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- negative control
- Dose level:
- 0
- No. with + reactions:
- 0
- Total no. in group:
- 10
- Remarks on result:
- no indication of skin sensitisation
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- test chemical
- Dose level:
- 0.001 %
- No. with + reactions:
- 1
- Total no. in group:
- 10
- Clinical observations:
- Grade 2
- Remarks on result:
- positive indication of skin sensitisation
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- negative control
- Dose level:
- 0
- No. with + reactions:
- 0
- Total no. in group:
- 10
- Remarks on result:
- other: 2nd challenge
- Remarks:
- no indication of skin sensitisation
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- test chemical
- Dose level:
- 0.001%
- No. with + reactions:
- 0
- Total no. in group:
- 10
- Clinical observations:
- None
- Remarks on result:
- other: 2nd challenge
- Remarks:
- no indication of skin sensitisation
- Group:
- positive control
- Remarks on result:
- not measured/tested
- Interpretation of results:
- study cannot be used for classification
- Conclusions:
- The first challenge with 0.001% test substance yielded a skin reaction in one animal, however due to technical problems encountered during the study, the results are inconclusive.
- Executive summary:
The objective of the Guinea Pig Maximization Test (OECD 406, under GLP) was to evaluate the sensitisation potential of the test substance under exaggerated exposure conditions. In order to determine the lowest non-irritant concentration, 4 animals were exposed to 0.5%, 0.01%, 0.005%, and 0.001% (w/v) test substance in acetone. After 24 hours of occlusion, the coverings were removed and irritation at each application site was determined. The highest concentration of the test substance in acetone causing no erythema or oedema at the site of application on any of the 4 animals was considered to be the highest non-irritating concentration. Next, 20 animals (2 groups of 5 females and 5 males) were injected intradermally with 0.5% test substance in acetone with or without FCA (test group), FCA in acetone (test group and control group) or acetone alone (control group). After 7 days both groups were re-induced with topical, occlusive administration of 1% test substance in acetone or acetone alone (control group). Next, the animals were challenged (day 21) with 0.001% test substance.
The results were inconclusive, due to problems which occurred in this study. There were two major problems which occurred during the study. The primary difficulty was a challenge concentration of the test substance that was inadequate for elicitation of sensitisation. The second problem was that insufficient volume of the material was used on each test site during the irritancy and inductions phases of testing, so that the skin at the site was not entirely covered. This led to uneven concentrations in the patch test area and spurious results. A further study is needed to evaluate the sensitisation potential of this compound using the Guinea Pig Maximization test method.
- Endpoint:
- skin sensitisation: in vivo (non-LLNA)
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- 18 Jun 1984
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 406 (Skin Sensitisation)
- GLP compliance:
- yes
- Type of study:
- guinea pig maximisation test
- Justification for non-LLNA method:
- Currently no LLNA study is available for assessment. The GPMT test has been carried out as an animal test to predict human sensitisation for over a decade and is recommended by international test guidelines such as OECD.
- Species:
- guinea pig
- Strain:
- Dunkin-Hartley
- Sex:
- male/female
- Details on test animals and environmental conditions:
- TEST ANIMALS
- Females nulliparous and non-pregnant: yes
- Weight at study initiation: approximately 300 to 400 g
- Housing: housed individually in appropriately-sized cages
- Diet: guinea pig chow, ad libitum
- Water: ad libitum
- Acclimation period: 4 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16 - 23
- Humidity (%): 40 - 60
- Photoperiod (hrs dark / hrs light): 12/12 - Route:
- intradermal
- Vehicle:
- propylene glycol
- Concentration / amount:
- Injection: 0.1 mL
Treatment: adjuvant (FCA) diluted equally with propylene glycol - Day(s)/duration:
- Day 0: First injection of the three pairs of intradermal injections
- Route:
- intradermal
- Vehicle:
- propylene glycol
- Concentration / amount:
- Injection: 0.1 mL
Treatment: 5 % test substance (w/v) in a 50:50 mixture of FCA and propylene glycol - Day(s)/duration:
- Day 0: Second injection of three pairs of intradermal injections
- Adequacy of induction:
- highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
- Route:
- intradermal
- Vehicle:
- propylene glycol
- Concentration / amount:
- Injection: 0.1 mL
Treatment: 5 % test substance (w/v) in propylene glycol - Day(s)/duration:
- Day 0: Third injection of the three pairs of intradermal injections
- Adequacy of induction:
- highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
- Route:
- intradermal
- Vehicle:
- propylene glycol
- Concentration / amount:
- Injection: 0.1 mL
Treatment: FCA diluted equally with propylene glycol - Day(s)/duration:
- Day 0: First control injection out of three pairs of injections
- Route:
- intradermal
- Vehicle:
- propylene glycol
- Concentration / amount:
- Injection: 0.1 mL
Treatment: FCA diluted equally with propylene glycol - Day(s)/duration:
- Day 0: Second control injection out of three pairs of injections
- Route:
- intradermal
- Vehicle:
- propylene glycol
- Concentration / amount:
- Injection: 0.1 mL
Treatment: Propylene glycol - Day(s)/duration:
- Day 0: Third control injection out of three pairs of intradermal injections
- Route:
- epicutaneous, occlusive
- Vehicle:
- other: acetone
- Concentration / amount:
- Volume/area: 0.15 mL/2 x 4 cm area over the site of injection
Treatment: 1 % test substance in acetone, occlusive - Day(s)/duration:
- Day 7: all test animals for 48 h
- Route:
- epicutaneous, occlusive
- Vehicle:
- unchanged (no vehicle)
- Concentration / amount:
- Volume/area: 0.15 mL/2 x 4 cm area over the injection site
Treatment: Acetone; occlusive - Day(s)/duration:
- Day 7: all control animals for 48 h
- No.:
- #1
- Route:
- epicutaneous, occlusive
- Vehicle:
- other: acetone
- Concentration / amount:
- Volume/area: 0.075 mL/2 x 2 cm area on one flank of each guinea pig in the test and control groups
Treatment: 0.0125 % test substance in acetone - Day(s)/duration:
- Day 21: occlusive dressing for 24 h
- Adequacy of challenge:
- highest non-irritant concentration
- No. of animals per dose:
- 5 animals per sex per dose
- Details on study design:
- RANGE FINDING TEST/IRRITATION STUDY:
For irritation testing, four 2 x 2 cm sites (2 on each flank) were designated on each of 2 male and 2 female guinea pigs. A volume of 0.075 mL of each of 4 different concentrations of test substance in acetone (i.e. 0.0125%, 0.0075%, 0.005% and 0.0025% (w/v) was applied to the 4 sites on each animal. The sequence of the 4 concentrations of test material was varied from animal to animal to minimize the bias associated with the location of application, e.g. skin thickness. After treatment, the application sites were covered with gauze, then with occlusive plastic dressings and, finally, elastoplast tape.
After 24 hours of occlusion, the coverings were removed and irritation at each application site was determined. The highest concentration of the test substance in acetone causing no erythema or oedema at the site of application on any of the 4 animals was considered to be the highest non-irritating concentration. - Challenge controls:
- 0.05 mL of acetone alone
- Positive control substance(s):
- no
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- negative control
- Dose level:
- 0.0125%
- No. with + reactions:
- 3
- Total no. in group:
- 10
- Clinical observations:
- Classification: mild sensitisation
- Remarks on result:
- other: The reactions seen in the control group are explained by the markedly heightened cutaneous reactivity apparent after injection of Freund's Complete Adjuvant.
- Reading:
- 2nd reading
- Hours after challenge:
- 48
- Group:
- negative control
- Dose level:
- 0.0125%
- No. with + reactions:
- 3
- Total no. in group:
- 10
- Clinical observations:
- Classification: Mild sensitisation
- Remarks on result:
- other: The reactions seen in the control group are explained by the markedly heightened cutaneous reactivity apparent after injection of Freund's Complete Adjuvant.
- Key result
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- test chemical
- Dose level:
- 0.0125%
- No. with + reactions:
- 8
- Total no. in group:
- 10
- Clinical observations:
- Classification: Moderate sensitisation
- Remarks on result:
- positive indication of skin sensitisation
- Reading:
- 2nd reading
- Hours after challenge:
- 48
- Group:
- test chemical
- Dose level:
- 0.0125%
- No. with + reactions:
- 8
- Total no. in group:
- 10
- Clinical observations:
- Classification: Moderate sensitisation
- Remarks on result:
- positive indication of skin sensitisation
- Group:
- positive control
- Remarks on result:
- not measured/tested
- Interpretation of results:
- Category 1B (indication of skin sensitising potential) based on GHS criteria
- Conclusions:
- Using the Guinea Pig Maximization Test, the test substance in acetone caused a sensitisation of 50% of the test group. This compound, when used in the vehicle acetone, would be classified as a moderate sensitiser.
- Executive summary:
The objective of the Guinea Pig Maximization Test (OECD 406, under GLP) was to evaluate the sensitisation potential of the test substance under exaggerated exposure conditions. In order to determine the lowest non-irritant concentration, 4 animals were exposed to 0.0125%, 0.0075%, 0.005% and 0.0025% (w/v) test substance in acetone. After 24 hours of occlusion, the coverings were removed and irritation at each application site was determined. The highest concentration of the test substance in acetone causing no erythema or oedema at the site of application on any of the 4 animals was considered to be the highest non-irritating concentration. Next, 20 animals (2 groups of 5 females and 5 males) were injected intradermally with 5% test substance in propylene glycol with or without FCA (test group), FCA in propylene glycol (test group and control group) or propylene glycol alone (control group). After 7 days both groups were re-induced with topical, occlusive administration of 1 % test substance in acetone or acetone alone (control group). Next, the animals were challenged (day 21) with 0.0125% test substance.
During the sensitisation evaluation, the treated group had 80% of the animals reacting, while 30% of the control group also reacted. Based on the classification schedule, approximately 50% of the animals were sensitised (80-30). The reactions seen in the control group are explained by the markedly heightened cutaneous reactivity apparent after injection of Freund's Complete Adjuvant. The subsequent application of an irritant such as the test substance causes cutaneous reactions at concentrations below what would normally be considered the maximum non-irritating concentration.
Using the Guinea Pig Maximization Test, the test substance in acetone caused a sensitisation of 50% of the test group. This compound, when used in the vehicle acetone, would be classified as a moderate sensitiser.
- Endpoint:
- skin sensitisation: in vivo (non-LLNA)
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 406 (Skin Sensitisation)
- GLP compliance:
- yes
- Type of study:
- guinea pig maximisation test
- Justification for non-LLNA method:
- Currently no LLNA study is available for assessment. The GPMT test has been carried out as an animal test to predict human sensitisation for over a decade and is recommended by international test guidelines such as OECD
- Species:
- guinea pig
- Strain:
- Dunkin-Hartley
- Sex:
- male/female
- Details on test animals and environmental conditions:
- TEST ANIMALS
- Females nulliparous and non-pregnant: yes
- Weight at study initiation: approximately 350 g
- Housing: housed individually in appropriately-sized cages
- Diet: guinea pig chow, ad libitum
- Water: ad libitum
- Acclimation period: 4 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16 - 23
- Humidity (%): 40 - 60
- Photoperiod (hrs dark / hrs light): 12/12 - Route:
- epicutaneous, open
- Vehicle:
- other: Acetone
- Concentration / amount:
- Volume/area: 0.1 mL/8 cm2
Treatment: 0.01 % (w/v) in acetone - Day(s)/duration:
- Five times a week for 4 weeks
- Adequacy of induction:
- other: Low dose group
- Route:
- epicutaneous, open
- Vehicle:
- other: Acetone
- Concentration / amount:
- Volume/area: 0.1 mL/8 cm2
Treatment: 0.1 % (w/v) in acetone - Day(s)/duration:
- Five times a week for 4 weeks
- Adequacy of induction:
- other: Mid dose group
- Route:
- epicutaneous, open
- Vehicle:
- other: Acetone
- Concentration / amount:
- Volume/area: 0.1 mL/8 cm2
Treatment: 1 % (w/v) in acetone - Day(s)/duration:
- Five times a week for 4 weeks
- Adequacy of induction:
- other: High dose group
- Route:
- epicutaneous, open
- Vehicle:
- unchanged (no vehicle)
- Concentration / amount:
- Volume/area: 0.1 mL/8 cm2
Treatment: Acetone 5 times - Day(s)/duration:
- Five times a week for 4 weeks
- Adequacy of induction:
- other: Control group
- No.:
- #1
- Route:
- epicutaneous, open
- Vehicle:
- other: Acetone
- Concentration / amount:
- Volume/area: 0.05 mL/2 cm2
Treatment: 0.025%, 0.0075%, 0.0025%, 0.00075%, 0.00025%, 0.000075% test substance in acetone applied to each animal - Day(s)/duration:
- 24, 48 and 72 hours
- Adequacy of challenge:
- other: Low induction dose (0.01%) group
- No.:
- #2
- Route:
- epicutaneous, open
- Vehicle:
- other: Acetone
- Concentration / amount:
- Volume/area: 0.05 mL/2 cm2
Treatment: 0.025%, 0.0075%, 0.0025%, 0.00075%, 0.00025%, 0.000075% test substance in acetone applied to each animal - Day(s)/duration:
- 24, 48 and 72 hours
- Adequacy of challenge:
- other: Mid induction dose (0.1%) group
- No.:
- #3
- Route:
- epicutaneous, open
- Vehicle:
- other: Acetone
- Concentration / amount:
- Volume/area: 0.05 mL/2 cm2
Treatment: 0.025%, 0.0075%, 0.0025%, 0.00075%, 0.00025%, 0.000075% test substance in acetone applied to each animal - Day(s)/duration:
- 24, 48 and 72 hours
- Adequacy of challenge:
- other: High induction dose (1%) group
- No.:
- #4
- Route:
- epicutaneous, open
- Vehicle:
- other: Acetone
- Concentration / amount:
- Volume/area: 0.05 mL/2 cm2
Treatment: 1.25%, 0.75%, 0.25%, 0.075%, 0.025% and 0.0075% (w/v) test substance in acetone applied to each control animal - Day(s)/duration:
- 24, 48 and 72 h
- Adequacy of challenge:
- other: Control induction group: to ensure that the minimal irritant concentration and the maximal nonirritant concentration had not changed over time
- No. of animals per dose:
- 4 animals per sex per dose - induction phase
12 animals per sex per dose - challenge phase - Details on study design:
- IRRITATION STUDY:
Prior to sensitisation testing, the 24 animals in the test groups were used to determine the irritation potential of 6 concentrations of the test substance in acetone. i.e. 1.25%, 0.75%, 0.25%, 0.075%, 0.025% and 0.0075% (w/v). Six 2 cm2 application sites were designated on the flank skin of each animal. Each animal received 0.025 mL of each solution at these sites. The sites remained uncovered and irritant reactions at the sites were read 24 hours after application. Since only 5 of the 24 guinea pigs had positive skin reactions, each animal was subsequently re-applied that same day using 0.050 mL of the six test substance solutions. Randomisation of the sites remained the same as before. The sites remained uncovered and the skin reactions at the sites were read at 48 hours after the initial application. Irritation was scored according to the following scale:
0 = no reaction
1 = scattered, mild redness
2 = diffuse, moderate redness
3 = intense redness and swelling
Values were recorded separately for each animal. A score to the nearest 0.5 was also applied when the reaction noted could best be described as being between two descriptions in the whole number scoring system. The minimal irritant concentration was considered the lowest concentration of the test substance in acetone which caused erythema in approximately 25% of the animals. The maximal non-irritating concentration was considered the highest concentration which caused no macroscopic change in any of the animals. - Challenge controls:
- None
- Positive control substance(s):
- no
- Key result
- Reading:
- other: 3rd reading
- Hours after challenge:
- 72
- Group:
- other: Low induction dose (0.01%) group
- Dose level:
- 0.0075%
- No. with + reactions:
- 1
- Total no. in group:
- 8
- Clinical observations:
- 2 on a 0 to 4 skin reaction scale
- Remarks on result:
- positive indication of skin sensitisation
- Key result
- Reading:
- 2nd reading
- Hours after challenge:
- 48
- Group:
- other: Mid induction dose (0.1%) group
- Dose level:
- 0.0025%
- No. with + reactions:
- 1
- Total no. in group:
- 8
- Clinical observations:
- 1.5 on a 0 to 4 skin reaction scale
- Remarks on result:
- positive indication of skin sensitisation
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- other: Low induction dose (0.01%) group
- Dose level:
- 0.025%
- No. with + reactions:
- 2
- Total no. in group:
- 8
- Clinical observations:
- 2 - 2.5 on a 0 to 4 skin reaction scale
- Remarks on result:
- positive indication of skin sensitisation
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- other: Mid induction dose (0.1%) group
- Dose level:
- 0.025%
- No. with + reactions:
- 6
- Total no. in group:
- 8
- Clinical observations:
- 2 - 2.5 on a 0 to 4 skin reaction scale
- Remarks on result:
- positive indication of skin sensitisation
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- other: High induction dose (1%) group
- Dose level:
- 0.025%
- No. with + reactions:
- 7
- Total no. in group:
- 8
- Clinical observations:
- 1 - 3 on a 0 to 4 skin reaction scale
- Remarks on result:
- positive indication of skin sensitisation
- Reading:
- 2nd reading
- Hours after challenge:
- 48
- Group:
- other: Low induction dose (0.01%) group
- Dose level:
- 0.025%
- No. with + reactions:
- 3
- Total no. in group:
- 8
- Clinical observations:
- 2 - 2.5 on a 0 to 4 skin reaction scale
- Remarks on result:
- positive indication of skin sensitisation
- Reading:
- 2nd reading
- Hours after challenge:
- 48
- Group:
- other: Mid induction dose (0.1%) group
- Dose level:
- 0.025%
- No. with + reactions:
- 6
- Total no. in group:
- 8
- Clinical observations:
- 1 - 3 on a 0 to 4 skin reaction scale
- Remarks on result:
- positive indication of skin sensitisation
- Reading:
- 2nd reading
- Hours after challenge:
- 48
- Group:
- other: High induction dose (1%) group
- Dose level:
- 0.025%
- No. with + reactions:
- 7
- Total no. in group:
- 8
- Clinical observations:
- 1 - 3 on a 0 to 4 skin reaction scale
- Remarks on result:
- positive indication of skin sensitisation
- Reading:
- other: 3rd reading
- Hours after challenge:
- 72
- Group:
- other: Low induction dose (0.01%) group
- Dose level:
- 0.025%
- No. with + reactions:
- 3
- Total no. in group:
- 8
- Clinical observations:
- 1 - 1.5 on a 0 to 4 skin reaction scale
- Remarks on result:
- positive indication of skin sensitisation
- Reading:
- other: 3rd reading
- Hours after challenge:
- 72
- Group:
- other: Mid induction dose (0.1%) group
- Dose level:
- 0.025%
- No. with + reactions:
- 6
- Total no. in group:
- 8
- Clinical observations:
- 1 - 2 on a 0 to 4 skin reaction scale
- Remarks on result:
- positive indication of skin sensitisation
- Reading:
- other: 3rd reading
- Hours after challenge:
- 72
- Group:
- other: High induction dose (1%) group
- Dose level:
- 0.025%
- No. with + reactions:
- 5
- Total no. in group:
- 8
- Clinical observations:
- 1 - 2 on a 0 to 4 skin reaction scale
- Remarks on result:
- positive indication of skin sensitisation
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- other: Low induction dose (0.01%) group
- Dose level:
- 0.0075%
- No. with + reactions:
- 2
- Total no. in group:
- 8
- Clinical observations:
- 1 - 1.5 on a 0 to 4 skin reaction scale
- Remarks on result:
- positive indication of skin sensitisation
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- other: Mid induction dose (0.1%) group
- Dose level:
- 0.0075%
- No. with + reactions:
- 6
- Total no. in group:
- 8
- Clinical observations:
- 1.5 - 2.5 on a 0 to 4 skin reaction scale
- Remarks on result:
- positive indication of skin sensitisation
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- other: High induction dose (1%) group
- Dose level:
- 0.0075%
- No. with + reactions:
- 2
- Total no. in group:
- 8
- Clinical observations:
- 1 - 1.5 on a 0 to 4 skin reaction scale
- Remarks on result:
- positive indication of skin sensitisation
- Reading:
- 2nd reading
- Hours after challenge:
- 48
- Group:
- other: Low induction dose (0.01%) group
- Dose level:
- 0.0075%
- No. with + reactions:
- 2
- Total no. in group:
- 8
- Clinical observations:
- 1 on a 0 to 4 skin reaction scale
- Remarks on result:
- positive indication of skin sensitisation
- Reading:
- 2nd reading
- Hours after challenge:
- 48
- Group:
- other: Mid induction dose (0.1%) group
- Dose level:
- 0.0075%
- No. with + reactions:
- 3
- Total no. in group:
- 8
- Clinical observations:
- 1 - 1.5 on a 0 to 4 skin reaction scale
- Remarks on result:
- positive indication of skin sensitisation
- Reading:
- 2nd reading
- Hours after challenge:
- 48
- Group:
- other: High induction dose (1%) group
- Dose level:
- 0.0075%
- No. with + reactions:
- 0
- Total no. in group:
- 8
- Remarks on result:
- no indication of skin sensitisation
- Reading:
- other: 3rd reading
- Hours after challenge:
- 72
- Group:
- other: Mid induction dose (0.1%) group
- Dose level:
- 0.0075%
- No. with + reactions:
- 2
- Total no. in group:
- 8
- Clinical observations:
- 1 on a 0 to 4 skin reaction scale
- Remarks on result:
- positive indication of skin sensitisation
- Reading:
- other: 3rd reading
- Hours after challenge:
- 72
- Group:
- other: Low induction dose (0.01%) group
- Dose level:
- 0.0025%
- No. with + reactions:
- 0
- Total no. in group:
- 8
- Remarks on result:
- no indication of skin sensitisation
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- other: Mid induction dose (0.1%) group
- Dose level:
- 0.0025%
- No. with + reactions:
- 1
- Total no. in group:
- 8
- Clinical observations:
- 1 on a 0 to 4 skin reaction scale
- Remarks on result:
- positive indication of skin sensitisation
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- other: High induction dose (1%) group
- Dose level:
- 0.0025%
- No. with + reactions:
- 1
- Total no. in group:
- 8
- Clinical observations:
- 2 on a 0 to 4 skin reaction scale
- Remarks on result:
- positive indication of skin sensitisation
- Reading:
- 2nd reading
- Hours after challenge:
- 48
- Group:
- other: High and low induction dose (1% and 0.01%) groups
- Dose level:
- 0.0025%
- No. with + reactions:
- 0
- Total no. in group:
- 8
- Remarks on result:
- no indication of skin sensitisation
- Reading:
- other: 3rd reading
- Hours after challenge:
- 72
- Group:
- other: All induction dose (0.01%, 0.1% and 1%) groups
- Dose level:
- 0.0025%
- No. with + reactions:
- 0
- Total no. in group:
- 8
- Remarks on result:
- no indication of skin sensitisation
- Reading:
- other: 3rd reading
- Hours after challenge:
- 72
- Group:
- other: High induction dose (1%) group
- Dose level:
- 0.0075%
- No. with + reactions:
- 0
- Total no. in group:
- 8
- Remarks on result:
- no indication of skin sensitisation
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- other: Low induction dose (0.01%) group
- Dose level:
- 0.0025%
- No. with + reactions:
- 0
- Total no. in group:
- 8
- Remarks on result:
- no indication of skin sensitisation
- Reading:
- 2nd reading
- Hours after challenge:
- 48
- Group:
- other: Low induction dose (0.01%) group
- Dose level:
- 0.0025%
- No. with + reactions:
- 0
- Total no. in group:
- 8
- Remarks on result:
- no indication of skin sensitisation
- Group:
- positive control
- Remarks on result:
- not measured/tested
- Group:
- negative control
- Remarks on result:
- not measured/tested
- Interpretation of results:
- Category 1B (indication of skin sensitising potential) based on GHS criteria
- Conclusions:
- The test substance in acetone may act as a topical sensitiser with repeated topical application of concentrations at or below 0.01%. Dermal reactions in a sensitised animal can be elicited by a concentration as low as 0.0025% test substance in acetone.
- Executive summary:
The dermal sensitisation potential of the test substance in acetone was tested using the open epicutaneous testing procedure with guinea pigs (OECD 406, under GLP). In order to determine the lowest non-irritant concentration, 24 animals in the test groups were used to determine the irritation potential of 6 concentrations of the test substance in acetone. i.e. 1.25%, 0.75%, 0.25%, 0.075%, 0.025% and 0.0075% (w/v). The sites remained uncovered and irritant reactions at the sites were read 24 hours after application. The highest concentration of the test substance in acetone causing no erythema or oedema at the site of application was considered to be the highest non-irritating concentration. The animals were next induced with 1% (high dose group), 0.1% (mid dose group) or 0.01% (low dose group) test substance in acetone 5 times/week for 4 weeks.
During the challenge the experimental group was then applied with the minimal irritant concentration, the maximal non-irritant concentration, and 4 other solutions of lower concentrations in order to assess the sensitising potential of the test substance.
The results indicate that the test substance in acetone may cause sensitisation with repeated topical application of concentrations at or below 0.01%, and that the dermal reaction in a sensitised animal can be elicited by a concentration as low as 0.0025% test substance in acetone.
Referenceopen allclose all
The irritancy phase was repeated on all 24 guinea pigs. This testing was performed to give a guide in subsequent studies for determining irritancy levels. The following concentrations of the test substance were applied: 0.5%; 0.01%; 0.005%; and 0.001%. The volume was changed from 0.05 mL to 0.075 mL. An occlusive bandage covered the sites for 24 hours. The sites were graded 24 and 48 hours after the bandages were removed.
The 0.001% concentration of the test substance in acetone was the only concentration not to cause irritation on the test and control groups of animals. However, these animals had previously been exposed to acetone, test substance and FCA, which would tend to make them more reactive. Various difficulties encountered during the study made the results impossible to definitively interpret. The major problems were that 0.001% test substance was too low a concentration to have been applied in the challenge phase; the highest non-irritating concentration was probably nearer 0.005% or higher. The volume applied was also too low, and therefore the site was not adequately covered with solution. The volume which will cover the site is 0.075 mL.
During the sensitisation evaluation, the treated group had 80% of the animals reacting, while 30% of the control group also reacted. Based on the classification schedule, approximately 50% of the animals were sensitised (80-30). The reactions seen in the control group are explained by the markedly heightened cutaneous reactivity apparent after injection of Freund's Complete Adjuvant. The subsequent application of an irritant such as the test substance causes cutaneous reactions at concentrations below what would normally be considered the maximum non-irritating concentration.
Table 1. Irritation test results at 24 h.
|
Test substance concentration |
|||
Animal |
0.0125% |
0.0075% |
0.005% |
0.0025% |
1 |
0 |
0 |
0 |
0 |
2 |
0 |
0 |
0 |
0 |
3 |
0 |
0 |
0 |
0 |
4 |
0 |
0 |
0 |
0 |
Table 2. Challenge phase results.
Test group |
Control Group |
||||||
Animal |
Hours after bandage removal |
Severity of response to 0.0125% test substance |
Acetone |
Animal |
Hours after bandage removal |
Severity of response to 0.0125% test substance |
Acetone |
1 |
24 |
1 |
0 |
1 |
24 |
0 |
0 |
|
48 |
1 |
0 |
|
48 |
0 |
0 |
2 |
24 |
0 |
0 |
2 |
24 |
0 |
0 |
|
48 |
0 |
0 |
|
48 |
0 |
0 |
3 |
24 |
1 |
0 |
3 |
24 |
1 |
0 |
|
48 |
2 |
0 |
|
48 |
1.5 |
0 |
4 |
24 |
1 |
0 |
4 |
24 |
1 |
0 |
|
48 |
0 |
0 |
|
48 |
2 |
0 |
5 |
24 |
2.5 |
0 |
5 |
24 |
0 |
0 |
|
48 |
2 |
0 |
|
48 |
0 |
0 |
6 |
24 |
0 |
0 |
6 |
24 |
0 |
0 |
|
48 |
0 |
0 |
|
48 |
0 |
0 |
7 |
24 |
1 |
0 |
7 |
24 |
2 |
0 |
|
48 |
1 |
0 |
|
48 |
2 |
0 |
8 |
24 |
2 |
0 |
8 |
24 |
0 |
0 |
|
48 |
1.5 |
0 |
|
48 |
0 |
0 |
9 |
24 |
2 |
0 |
9 |
24 |
0 |
0 |
|
48 |
1.5 |
0 |
|
48 |
0 |
0 |
10 |
24 |
2 |
0 |
10 |
24 |
0 |
0 |
|
48 |
1.5 |
0 |
|
48 |
0 |
0 |
Irritation
During the irritant testing phase, the experimental groups were applied with 6 concentrations of the test substance in acetone. The minimal irritant concentration and maximal non-irritant concentration were determined to be 0.025% and 0.0075% test substance respectively.
Table 1. Mean reaction values in the irritancy phase.
|
Doses |
|||||
1.25% |
0.75% |
0.25% |
0.075% |
0.025% |
0.0075% |
|
Mean reaction value |
0.88 |
0.77 |
0.56 |
0.44 |
0.21 |
0 |
% of animals with skin reactions |
75 |
58 |
50 |
42 |
17 |
0 |
Sensitisation
The experimental group was applied with the minimal irritant concentration, the maximal non-irritant concentration, and 4 other solutions of lower concentrations. Twelve guinea pigs, or approximately 50% of the experimental group, showed positive reactions to concentrations at or below the previously established maximum non-irritating concentrations.
Guinea pigs from each of the 3 concentration groups, 1.0%, 0.1% and 0.01% were shown to be sensitised by reacting to concentrations of the test substance at or below the maximal non-irritating concentration. This suggests that the minimal sensitising concentration lies at or below the lowest concentration tested during the induction phase, i.e. 0.01%. The minimal eliciting concentration (the concentration necessary to cause a positive reaction in a sensitised animal) was determined to be 0.0025% test substance in acetone.
Table 2. Individual reaction scores at 24, 48 and 72 hours
Induction dose group |
Animal |
Doses (%) |
|||||||||||||||||
0.025 |
0.0075 |
0.0025 |
0.00075 |
0.00025 |
0.000075 |
||||||||||||||
Hours post challenge |
24h |
48h |
72h |
24h |
48h |
72h |
24h |
48h |
72h |
24h |
48h |
72h |
24h |
48h |
72h |
24h |
48h |
72h |
|
High (1%) |
1 |
3 |
3 |
2 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
2 |
1.5 |
1.5 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
3 |
2 |
1.5 |
1 |
1.5 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
4 |
1.5 |
2 |
1 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
5 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
6 |
1 |
1 |
0 |
1 |
0 |
0 |
2 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
7 |
1 |
1.5 |
1 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
8 |
1 |
2 |
1 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
Mid (0.1%) |
1 |
2 |
3 |
1.5 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
2 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
3 |
2 |
1 |
0 |
0 |
1.5 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
4 |
2 |
3 |
2 |
1 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
5 |
0 |
0 |
1 |
2 |
1 |
1 |
0 |
1.5 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
6 |
2.5 |
2.5 |
1 |
0 |
0 |
0 |
1 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
7 |
2 |
2 |
1.5 |
1 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
8 |
1.5 |
2 |
1 |
1.5 |
1.5 |
1 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
Low (0.01%) |
1 |
2 |
2.5 |
1.5 |
1 |
1 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
2 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
3 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
4 |
0 |
2.5 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
5 |
0 |
0 |
0 |
0 |
1 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
6 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
7 |
2.5 |
0 |
1 |
1.5 |
0 |
2 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
8 |
0 |
2 |
1.5 |
0 |
1 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed (sensitising)
- Additional information:
Approach
Three in vivo skin sensitisation studies in Guinea Pigs are used in a Weight of Evidence approach.
The results from the studies Skin sensitisation in vivo - 1986b and c with the test substance dissolved in acetone are positive for skin sensitisation and the results from Skin sensitisation in vivo - 1986a are ambiguous, due to methodological deviations.
All studies three studies deviate to some extent from current guideline standards, thereby limiting the reliability of the studies somewhat. But taken together there is clear evidence that the test substance is a skin sensitiser. This conclusion is also in line with the current harmonised classification according to Annex VI of Regulation (EC) No 1272/2008 (CLP regulation).Skin sensitisation in vivo - 1986a
The objective of the Guinea Pig Maximization Test (OECD 406, under GLP) was to evaluate the sensitisation potential of the test substance under exaggerated exposure conditions. In order to determine the lowest non-irritant concentration, 4 animals were exposed to 0.5%, 0.01%, 0.005%, and 0.001% (w/v) test substance in acetone. After 24 hours of occlusion, the coverings were removed and irritation at each application site was determined. The highest concentration of the test substance in acetone causing no erythema or oedema at the site of application on any of the 4 animals was considered to be the highest non-irritating concentration. Next, 20 animals (2 groups of 5 females and 5 males) were injected intradermally with 0.5 % test substance in acetone with or without FCA (test group), FCA in acetone (test group and control group) or acetone alone (control group). After 7 days both groups were re-induced with topical, occlusive administration of 1 % test substance in acetone or acetone alone (control group). Next, the animals were challenged (day 21) with 0.001% test substance.
The results were inconclusive, due to problems which occurred in this study. There were two major problems which occurred during the study. The primary difficulty was a challenge concentration of the test substance that was inadequate for elicitation of sensitisation. The second problem was that insufficient volume of the material was used on each test site during the irritancy and inductions phases of testing, so that the skin at the site was not entirely covered. This led to uneven concentrations in the patch test area and spurious results. A further study is needed to evaluate the sensitisation potential of this compound using the Guinea Pig Maximization test method.
Skin sensitisation in vivo - 1986b
The objective of the Guinea Pig Maximization Test (OECD 406, under GLP) was to evaluate the sensitisation potential of the test substance under exaggerated exposure conditions. In order to determine the lowest non-irritant concentration, 4 animals were exposed to 0.0125%, 0.0075%, 0.005% and 0.0025% (w/v) test substance in acetone. After 24 hours of occlusion, the coverings were removed and irritation at each application site was determined. The highest concentration of the test substance in acetone causing no erythema or oedema at the site of application on any of the 4 animals was considered to be the highest non-irritating concentration. Next, 20 animals (2 groups of 5 females and 5 males) were injected intradermally with 5 % test substance in propylene glycol with or without FCA (test group), FCA in propylene glycol (test group and control group) or propylene glycol alone (control group). After 7 days both groups were re-induced with topical, occlusive administration of 1% test substance in acetone or acetone alone (control group). Next, the animals were challenged (day 21) with 0.0125% test substance.
During the sensitisation evaluation, the treated group had 80% of the animals reacting, while 30% of the control group also reacted. Based on the classification schedule, approximately 50% of the animals were sensitised (80-30). The reactions seen in the control group are explained by the markedly heightened cutaneous reactivity apparent after injection of Freund's Complete Adjuvant. The subsequent application of an irritant such as the test substance causes cutaneous reactions at concentrations below what would normally be considered the maximum non-irritating concentration.
Using the Guinea Pig Maximization Test, the test substance in acetone caused a sensitisation of 50% of the test group. This compound, when used in the vehicle acetone, would be classified as a moderate sensitiser.
Skin sensitisation in vivo - 1986c
The dermal sensitisation potential of the test substance in acetone was tested using the open epicutaneous testing procedure with guinea pigs (OECD 406, under GLP). In order to determine the lowest non-irritant concentration, 24 animals in the test groups were used to determine the irritation potential of 6 concentrations of the test substance in acetone. i.e. 1.25%, 0.75%, 0.25%, 0.075%, 0.025% and 0.0075% (w/v). The sites remained uncovered and irritant reactions at the sites were read 24 hours after application. The highest concentration of the test substance in acetone causing no erythema or oedema at the site of application was considered to be the highest non-irritating concentration. The animals were next induced with 1% (high dose group), 0.1% (mid dose group) or 0.01% (low dose group) test substance in acetone 5 times/week for 4 weeks.
During the challenge the experimental group was then applied with the minimal irritant concentration, the maximal non-irritant concentration, and 4 other solutions of lower concentrations in order to assess the sensitising potential of the test substance.
The results indicate that the test substance in acetone may cause sensitisation with repeated topical application of concentrations at or below 0.01%, and that the dermal reaction in a sensitised animal can be elicited by a concentration as low as 0.0025% test substance in acetone.
Respiratory sensitisation
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (not sensitising)
- Additional information:
The test substance is not expected to be of concern for respiratory sensitisation. Following the recommended approach outlined in R.7.3.12.3, the test substance is not expected to be a respiratory sensitiser because the test substance is not di-isocyanate or protein. Furthermore, no structural warnings for respiratory sensitisation were found using the QSAR toolbox (v4.4).
Justification for classification or non-classification
Based on the available information the substance is classified as skin sensitiser category 1, H317:May cause an allergic skin reaction in accordance with EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation No. 1272/2008.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.
