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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:
1981-07-01 to 1981-08-21
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: This study is classified as reliable with restrictions because although the study does not meet current OECD 406 guidelines, the study was well conducted and reported.
Justification for type of information:
A discussion and report on the read across strategy is given as an attachment in Section 13.
Cross-reference
Reason / purpose:
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:
1981-07-01 to 1981-08-21
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: This study is classified as reliable with restrictions because although the study does not meet current OECD 406 guidelines, the study was well conducted and reported.
Justification for type of information:
A discussion and report on the read across strategy is given as an attachment in Section 13.
Reason / purpose:
read-across source
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
yes
Remarks:
According to OECD 406 guidelines, the initiating dose should be the highest dose to induce mild irritation.
GLP compliance:
yes
Type of study:
patch test
Justification for non-LLNA method:
The study was conducted in accordance with OECD and EU test guidelines applicable at the time of undertaking.
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Camm Research Laboratories, Wayne, New Jersey
- Age at study initiation: Not reported
- Weight at study initiation: Approximately 400 to 450 grams
- Housing: Five animals per cage
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 20 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.1 to 22.2
- Humidity (%): 39% to 55%
- Air changes (per hr): Not reported
- Photoperiod (hrs dark / hrs light): Not reported


IN-LIFE DATES: From: 1981-06-30 To: 1981-09-21
Route:
epicutaneous, occlusive
Vehicle:
other: absolute ethanol
Concentration / amount:
1% Neodene 6 in ethanol
Route:
epicutaneous, occlusive
Vehicle:
other: absolute ethanol
Concentration / amount:
1% Neodene 6 in ethanol
No. of animals per dose:
5 animals/sex/dose
Details on study design:
RANGE FINDING TESTS: Yes


MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: Three
- Exposure period: Three weeks
- Test groups: One test group receiving 1.0% initiating dose
- Control group: A vehicle and positive control were used
- Site: Back/trunk region
- Frequency of applications: Once a week
- Duration: Six hours
- Concentrations: 1.0%


B. CHALLENGE EXPOSURE
- No. of exposures: One
- Day(s) of challenge: One
- Exposure period: Six hours
- Test groups: Test site and a virgin site
- Control group: A vehicle and positive control were used
- Site: Back/trunk region immediate posterior to the original site
- Concentrations: 1.0%
- Evaluation (hr after challenge): 24 and 48 hours
Challenge controls:
Challenge controls were treated the same as test animals except some received a vehicle instead of test compound and some received nothing until the challenge dose.
Positive control substance(s):
yes
Remarks:
2,4-dinitrochlorobenzene
Statistics:
None were reported
Positive control results:
The positive control group had an average skin reaction of 0.53 in the first week, but an average skin reaction of 1.34 after the challenge exposure indicating a positive skin reaction.
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: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 0. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 0. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
1%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 1%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
1%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 1%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
0.1%
No. with + reactions:
10
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: positive control. Dose level: 0.1%. No with. + reactions: 10.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
0.1%
No. with + reactions:
10
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: positive control. Dose level: 0.1%. No with. + reactions: 10.0. Total no. in groups: 10.0.
Interpretation of results:
other: Not sensitising
Conclusions:
Neodene 6 alpha olefin was not a skin sensitizer under the conditions of this study.
Executive summary:

In a dermal sensitisation study using Neodene 6 alpha olefin in ethanol, Duncan Hartley guinea pigs (5 animals/sex/dose) were tested using a patch sensitisation method. For the three weekly initiating doses, a 1% solution Neodene 6 alpha olefin in ethanol was applied and the primary challenge dose was also 1% Neodene 6 alpha olefin in ethanol. Preliminary tests indicate that the 1% concentration was appropriate for the challenge dose, but a dose causing mild irritation should have been chosen for the initiating dose. Reactions were scored with a numerical grade to indicate severity.  The positive control provided the appropriate response. Body weight gain was not affected by treatment. Neodene 6 alpha olefin caused little or no irritation after the initiation or challenge dose and did not induce a delayed contact hypersensitivity reaction under the conditions of the study. 

This study received a Klimisch score of 2 and is classified as reliable with restrictions because although the study does not meet current OECD 406 guidelines, the study was well conducted and reported.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1982

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
yes
Remarks:
According to OECD 406 guidelines, the initiating dose should be the highest dose to induce mild irritation.
GLP compliance:
yes
Type of study:
patch test
Justification for non-LLNA method:
The study was conducted in accordance with OECD and EU test guidelines applicable at the time of undertaking.

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): NEODENE-6 alpha olefin
- Substance type: C6 aliphatic
- Physical state: Liquid
- Analytical purity: Not reported
- Lot/batch No.: Not reported, assigned sample number 571A
- Stability under test conditions: Not reported
- Storage condition of test material: Not reported

In vivo test system

Test animals

Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Camm Research Laboratories, Wayne, New Jersey
- Age at study initiation: Not reported
- Weight at study initiation: Approximately 400 to 450 grams
- Housing: Five animals per cage
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 20 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.1 to 22.2
- Humidity (%): 39% to 55%
- Air changes (per hr): Not reported
- Photoperiod (hrs dark / hrs light): Not reported


IN-LIFE DATES: From: 1981-06-30 To: 1981-09-21

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
other: absolute ethanol
Concentration / amount:
1% Neodene 6 in ethanol
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
other: absolute ethanol
Concentration / amount:
1% Neodene 6 in ethanol
No. of animals per dose:
5 animals/sex/dose
Details on study design:
RANGE FINDING TESTS: Yes


MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: Three
- Exposure period: Three weeks
- Test groups: One test group receiving 1.0% initiating dose
- Control group: A vehicle and positive control were used
- Site: Back/trunk region
- Frequency of applications: Once a week
- Duration: Six hours
- Concentrations: 1.0%


B. CHALLENGE EXPOSURE
- No. of exposures: One
- Day(s) of challenge: One
- Exposure period: Six hours
- Test groups: Test site and a virgin site
- Control group: A vehicle and positive control were used
- Site: Back/trunk region immediate posterior to the original site
- Concentrations: 1.0%
- Evaluation (hr after challenge): 24 and 48 hours
Challenge controls:
Challenge controls were treated the same as test animals except some received a vehicle instead of test compound and some received nothing until the challenge dose.
Positive control substance(s):
yes
Remarks:
2,4-dinitrochlorobenzene

Study design: in vivo (LLNA)

Statistics:
None were reported

Results and discussion

Positive control results:
The positive control group had an average skin reaction of 0.53 in the first week, but an average skin reaction of 1.34 after the challenge exposure indicating a positive skin reaction.

In vivo (non-LLNA)

Resultsopen allclose all
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: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 0. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 0. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
1%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 1%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
1%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 1%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
0.1%
No. with + reactions:
10
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: positive control. Dose level: 0.1%. No with. + reactions: 10.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
0.1%
No. with + reactions:
10
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: positive control. Dose level: 0.1%. No with. + reactions: 10.0. Total no. in groups: 10.0.

Applicant's summary and conclusion

Interpretation of results:
other: Not sensitising
Conclusions:
Neodene 6 alpha olefin was not a skin sensitizer under the conditions of this study.
Executive summary:

In a dermal sensitisation study using Neodene 6 alpha olefin in ethanol, Duncan Hartley guinea pigs (5 animals/sex/dose) were tested using a patch sensitisation method. For the three weekly initiating doses, a 1% solution Neodene 6 alpha olefin in ethanol was applied and the primary challenge dose was also 1% Neodene 6 alpha olefin in ethanol. Preliminary tests indicate that the 1% concentration was appropriate for the challenge dose, but a dose causing mild irritation should have been chosen for the initiating dose. Reactions were scored with a numerical grade to indicate severity.  The positive control provided the appropriate response. Body weight gain was not affected by treatment. Neodene 6 alpha olefin caused little or no irritation after the initiation or challenge dose and did not induce a delayed contact hypersensitivity reaction under the conditions of the study. 

This study received a Klimisch score of 2 and is classified as reliable with restrictions because although the study does not meet current OECD 406 guidelines, the study was well conducted and reported.