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Skin sensitisation
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Administrative data
- Endpoint:
- skin sensitisation: in vivo (non-LLNA)
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 1983/05/10-1983/06/06
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: According or similar to OECD Guideline 406. GLP
Cross-reference
- Reason / purpose for cross-reference:
- read-across: supporting information
Reference
- Endpoint:
- skin sensitisation: in vivo (non-LLNA)
- Type of information:
- read-across based on grouping of substances (category approach)
- Adequacy of study:
- key study
- Study period:
- 1983/05/10-1983/06/06
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: According or similar to OECD Guideline 406. GLP
- Reason / purpose for cross-reference:
- read-across source
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 406 (Skin Sensitisation)
- Deviations:
- yes
- Remarks:
- occlusive wrap used
- GLP compliance:
- yes
- Type of study:
- guinea pig maximisation test
- Justification for non-LLNA method:
- Acceptable guinea pig maximisation test that followed sound scientific principles.
- Species:
- guinea pig
- Strain:
- Hartley
- Sex:
- female
- Details on test animals and environmental conditions:
- TEST ANIMALS
Source: Dutchland Laboratory Animals
Sex: Female (30)
Age at study initiation: 1-2 months
Weight at study initiation: 345- 461g
Housing: Individually
Diet (e.g. ad libitum): Purina Guinea Pig Chow (pellets), ad libitum
Water (e.g. ad libitum): Automatic watering system, ad libitum
Acclimation period: 22d
ENVIRONMENTAL CONDITIONS
Temperature (°F): 65-71
Humidity (%): 40-70%
Photoperiod (hrs dark / hrs light): 12/12 - Route:
- intradermal and epicutaneous
- Vehicle:
- corn oil
- Concentration / amount:
- Intradermal Injection (sensitization; first phase): 5.0% (v/v) in vehicle and 5.0% (v/v) in Freund's Complete Adjuvant (FCA) (diluted with an equal volume of water)
Dermal Application: 50.0% (occlusive dressing)
Topical challenge: 0.5 mL of 0.5% (v/v) in vehicle (max dose w/o producing visible irritation) - Route:
- epicutaneous, occlusive
- Vehicle:
- corn oil
- Concentration / amount:
- Intradermal Injection (sensitization; first phase): 5.0% (v/v) in vehicle and 5.0% (v/v) in Freund's Complete Adjuvant (FCA) (diluted with an equal volume of water)
Dermal Application: 50.0% (occlusive dressing)
Topical challenge: 0.5 mL of 0.5% (v/v) in vehicle (max dose w/o producing visible irritation) - No. of animals per dose:
- Control: Female (15)
Treatment: Female (15) - Details on study design:
- Followed Magnusson and Kligman Guinea-Pig Maximization test (1969).
Briefly,
Day 0 – Induction of Sensitization by Intradermal Injection with and without adjuvant
A pair of 0.1 mL injections of the following solutions was intradermally administered to each of 3 sites in the clipped backs of the test animals. Site 1 –diluted FCA to both treated and control group; Site 2 – 5.0% MRD-83-205 in vehicle (treatment group) and undiluted vehicle (control group); Site 3 – 5.0% MRD-83-205 in diluted FCA (treatment group) and undiluted FCA (control group).
Day 7 – Induction by Occlusive Topical Application
0.5 mL of 50% MRD-83-205 (or vehicle for control animals) was topically applied over the injection sites on the shoulder of the treated group animal under an occlusive dressing for 48 hours.
Day 21 – Challenge by Occlusive Topical Application
0.5 mL of 0.5% MRD-83-205 in vehicle was topically applied to the animals under an occlusive dressing for 24 hours.
Animals were monitored for viability twice a day. Dermal reactions were scored according to the Draize methodology. - Challenge controls:
- Vehicle controls were used for each of the induction treatments and for the challenge treatment.
- Positive control substance(s):
- no
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- negative control
- Dose level:
- 0
- No. with + reactions:
- 4
- Total no. in group:
- 15
- Clinical observations:
- 4 animals displayed an erythema score of 1
- Remarks on result:
- other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 0. No with. + reactions: 4.0. Total no. in groups: 15.0. Clinical observations: 4 animals displayed an erythema score of 1.
- Reading:
- 2nd reading
- Hours after challenge:
- 48
- Group:
- negative control
- Dose level:
- 0
- No. with + reactions:
- 5
- Total no. in group:
- 15
- Clinical observations:
- 5 animals displayed an erythema score of 1
- Remarks on result:
- other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 0. No with. + reactions: 5.0. Total no. in groups: 15.0. Clinical observations: 5 animals displayed an erythema score of 1.
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- test chemical
- Dose level:
- 0.5% (v/v)
- No. with + reactions:
- 4
- Total no. in group:
- 15
- Clinical observations:
- 3 animals displayed an erythema score of 1; one animal displayed an erythema score of 2
- Remarks on result:
- other: see Remark
- Remarks:
- Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 0.5% (v/v). No with. + reactions: 4.0. Total no. in groups: 15.0. Clinical observations: 3 animals displayed an erythema score of 1; one animal displayed an erythema score of 2.
- Reading:
- 2nd reading
- Hours after challenge:
- 48
- Group:
- test chemical
- Dose level:
- 0.5% (v/v)
- No. with + reactions:
- 4
- Total no. in group:
- 15
- Clinical observations:
- 4 animals displayed an erythema score of 1
- Remarks on result:
- other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 0.5% (v/v). No with. + reactions: 4.0. Total no. in groups: 15.0. Clinical observations: 4 animals displayed an erythema score of 1.
- Interpretation of results:
- other: Not sensitising
- Conclusions:
- Based on the scores of dermal irritation, test substance MRD-83-205 would not be considered a dermal sensitizer under the EU GHS guidelines or under the EU requirements for dangerous substances and preparations guidelines.
- Executive summary:
A Magnusson and Kligman Guinea-Pig Maximization test was conducted on 30 guinea pigs with MRD-83-205 . Following a preliminary irritation test, 15 guinea pigs were treated by intradermal injection (5.0% (v/v) vehicle or adjuvant/ MRD-83-205 ) to induce sensitization and then further sensitized by dermal application of 50.0% (v/v) MRD-83-205 . Guinea Pigs were challenged by topical application (0.5% (v/v) MRD-83-205 in corn oil). All animals survived to termination of study displaying an increase in weight over the initial values. There was a very low incidence of clinical in-life observations noted throughout the test period. Following topical challenge with 0.5% MRD-83-205, four out of 15 animals in both the treated and control groups displayed minimal irritation. Based on the scores of dermal irritation, test substance MRD-83-205 would not be considered a dermal sensitizer under the EU GHS guidelines or under the EU requirements for dangerous substances and preparations guidelines.
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 983
- Report date:
- 1983
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 406 (Skin Sensitisation)
- Deviations:
- yes
- Remarks:
- occlusive wrap used
- GLP compliance:
- yes
- Type of study:
- guinea pig maximisation test
- Justification for non-LLNA method:
- Acceptable guinea pig maximisation test that followed sound scientific principles.
Test material
Constituent 1
In vivo test system
Test animals
- Species:
- guinea pig
- Strain:
- Hartley
- Sex:
- female
- Details on test animals and environmental conditions:
- TEST ANIMALS
Source: Dutchland Laboratory Animals
Sex: Female (30)
Age at study initiation: 1-2 months
Weight at study initiation: 345- 461g
Housing: Individually
Diet (e.g. ad libitum): Purina Guinea Pig Chow (pellets), ad libitum
Water (e.g. ad libitum): Automatic watering system, ad libitum
Acclimation period: 22d
ENVIRONMENTAL CONDITIONS
Temperature (°F): 65-71
Humidity (%): 40-70%
Photoperiod (hrs dark / hrs light): 12/12
Study design: in vivo (non-LLNA)
Induction
- Route:
- intradermal and epicutaneous
- Vehicle:
- corn oil
- Concentration / amount:
- Intradermal Injection (sensitization; first phase): 5.0% (v/v) in vehicle and 5.0% (v/v) in Freund's Complete Adjuvant (FCA) (diluted with an equal volume of water)
Dermal Application: 50.0% (occlusive dressing)
Topical challenge: 0.5 mL of 0.5% (v/v) in vehicle (max dose w/o producing visible irritation)
Challenge
- Route:
- epicutaneous, occlusive
- Vehicle:
- corn oil
- Concentration / amount:
- Intradermal Injection (sensitization; first phase): 5.0% (v/v) in vehicle and 5.0% (v/v) in Freund's Complete Adjuvant (FCA) (diluted with an equal volume of water)
Dermal Application: 50.0% (occlusive dressing)
Topical challenge: 0.5 mL of 0.5% (v/v) in vehicle (max dose w/o producing visible irritation)
- No. of animals per dose:
- Control: Female (15)
Treatment: Female (15) - Details on study design:
- Followed Magnusson and Kligman Guinea-Pig Maximization test (1969).
Briefly,
Day 0 – Induction of Sensitization by Intradermal Injection with and without adjuvant
A pair of 0.1 mL injections of the following solutions was intradermally administered to each of 3 sites in the clipped backs of the test animals. Site 1 –diluted FCA to both treated and control group; Site 2 – 5.0% MRD-83-205 in vehicle (treatment group) and undiluted vehicle (control group); Site 3 – 5.0% MRD-83-205 in diluted FCA (treatment group) and undiluted FCA (control group).
Day 7 – Induction by Occlusive Topical Application
0.5 mL of 50% MRD-83-205 (or vehicle for control animals) was topically applied over the injection sites on the shoulder of the treated group animal under an occlusive dressing for 48 hours.
Day 21 – Challenge by Occlusive Topical Application
0.5 mL of 0.5% MRD-83-205 in vehicle was topically applied to the animals under an occlusive dressing for 24 hours.
Animals were monitored for viability twice a day. Dermal reactions were scored according to the Draize methodology. - Challenge controls:
- Vehicle controls were used for each of the induction treatments and for the challenge treatment.
- Positive control substance(s):
- no
Study design: in vivo (LLNA)
- Statistics:
- Standard deviations of the body weights were calculated.
Results and discussion
In vivo (non-LLNA)
Resultsopen allclose all
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- negative control
- Dose level:
- 0
- No. with + reactions:
- 4
- Total no. in group:
- 15
- Clinical observations:
- 4 animals displayed an erythema score of 1
- Remarks on result:
- other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 0. No with. + reactions: 4.0. Total no. in groups: 15.0. Clinical observations: 4 animals displayed an erythema score of 1.
- Reading:
- 2nd reading
- Hours after challenge:
- 48
- Group:
- negative control
- Dose level:
- 0
- No. with + reactions:
- 5
- Total no. in group:
- 15
- Clinical observations:
- 5 animals displayed an erythema score of 1
- Remarks on result:
- other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 0. No with. + reactions: 5.0. Total no. in groups: 15.0. Clinical observations: 5 animals displayed an erythema score of 1.
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- test chemical
- Dose level:
- 0.5% (v/v)
- No. with + reactions:
- 4
- Total no. in group:
- 15
- Clinical observations:
- 3 animals displayed an erythema score of 1; one animal displayed an erythema score of 2
- Remarks on result:
- other: see Remark
- Remarks:
- Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 0.5% (v/v). No with. + reactions: 4.0. Total no. in groups: 15.0. Clinical observations: 3 animals displayed an erythema score of 1; one animal displayed an erythema score of 2.
- Reading:
- 2nd reading
- Hours after challenge:
- 48
- Group:
- test chemical
- Dose level:
- 0.5% (v/v)
- No. with + reactions:
- 4
- Total no. in group:
- 15
- Clinical observations:
- 4 animals displayed an erythema score of 1
- Remarks on result:
- other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 0.5% (v/v). No with. + reactions: 4.0. Total no. in groups: 15.0. Clinical observations: 4 animals displayed an erythema score of 1.
Applicant's summary and conclusion
- Interpretation of results:
- other: Not sensitising
- Conclusions:
- Based on the scores of dermal irritation, test substance MRD-83-205 would not be considered a dermal sensitizer under the EU GHS guidelines or under the EU requirements for dangerous substances and preparations guidelines.
- Executive summary:
A Magnusson and Kligman Guinea-Pig Maximization test was conducted on 30 guinea pigs with MRD-83-205 . Following a preliminary irritation test, 15 guinea pigs were treated by intradermal injection (5.0% (v/v) vehicle or adjuvant/ MRD-83-205 ) to induce sensitization and then further sensitized by dermal application of 50.0% (v/v) MRD-83-205 . Guinea Pigs were challenged by topical application (0.5% (v/v) MRD-83-205 in corn oil). All animals survived to termination of study displaying an increase in weight over the initial values. There was a very low incidence of clinical in-life observations noted throughout the test period. Following topical challenge with 0.5% MRD-83-205, four out of 15 animals in both the treated and control groups displayed minimal irritation. Based on the scores of dermal irritation, test substance MRD-83-205 would not be considered a dermal sensitizer under the EU GHS guidelines or under the EU requirements for dangerous substances and preparations guidelines.
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