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Toxicological information

Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation
Remarks:
in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study conducted prior to introduction of Good Laboratory Practices; data from a summary report; limited number of animals. Study was conducted by an internal Eastman Kodak Company method, developed prior to established guidelines.

Data source

Reference
Reference Type:
other: Toxicology Summary
Title:
Unnamed
Year:
1963
Report Date:
1963

Materials and methods

Test guideline
Qualifier:
no guideline followed
Deviations:
not specified
Principles of method if other than guideline:
Twenty guinea pigs were divided into three groups containing 5 animals each (solvent and positive control) or 10 animals (TMPD). Ten animals were treated with the test substance at a concentration of 1% in a mixture of 1:1:3 acetone:dioxane:guinea pig fat. Five animals were treated with the vehicle alone, and five animals were administered a positive control substance (phenylhydrazine). The mixtures were applied epicutaneously to the clipped backs of the guinea pigs. Average irritation scores were noted at 24 and 48 hours after the first application. The materials were periodically reapplied to the guinea pig backs for two weeks. After the last application, the average irritation scores were again obtained after 24 and 48 hours. Results from the initial and final applications were compared to determine whether the test substance had caused a positive skin sensitization response.
GLP compliance:
no
Remarks:
Study conducted prior to GLPs
Type of study:
other: internal Eastman Kodak method

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
-Identity (according to study report): 2,2,4-trimethyl-1,3-pentanediol (TMPD)

In vivo test system

Test animals

Species:
guinea pig
Strain:
not specified
Sex:
not specified
Details on test animals and environmental conditions:
no data

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
epicutaneous, open
Vehicle:
other: 1:1:3 acetone:dioxane:guinea pig fat
Concentration / amount:
1%
Challengeopen allclose all
Route:
epicutaneous, open
Vehicle:
other: 1:1:3 acetone:dioxane:guinea pig fat
Concentration / amount:
1%
No. of animals per dose:
TMPD: 10 animals
Solvent control: 5 animals
Positive control: 5 animals
Details on study design:
Twenty guinea pigs were divided into three groups containing 5 animals each (solvent and positive control) or 10 animals (TMPD). Ten animals were treated with the test substance at a concentration of 1% in a mixture of 1:1:3 acetone:dioxane:guinea pig fat. Five animals were treated with the vehicle alone, and five animals were administered a positive control substance (phenylhydrazine, concentration not reported). The mixtures were applied epicutaneously to the clipped backs of the guinea pigs. Average irritation scores were noted at 24 and 48 hours after the first application. Scores were calculated by adding together the erythema scores from each animal and the edema scores from each animal. The sum of the scores was then divided by the number of readings. The materials were periodically reapplied to the guinea pig backs for two weeks. After the last application, the average irritation scores were again obtained after 24 and 48 hours. Results from the initial and final applications were compared to determine whether the test substance had caused a positive skin sensitization response. The 48 hour scores were deemed more important in the determination of sensitization than the 24 hour scores, which were considered more reflective of cumulative irritation.
Positive control substance(s):
yes
Remarks:
Phenylhydrazine

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
other: Average initial score
Hours after challenge:
24
Group:
other: vehicle control
Dose level:
0
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
The average initial irritation score 24 hours after the first application was 1.0.
Remarks on result:
other: see Remark
Remarks:
Reading: other: Average initial score. . Hours after challenge: 24.0. Group: other: vehicle control. Dose level: 0. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: The average initial irritation score 24 hours after the first application was 1.0. .
Reading:
other: Average initial score
Hours after challenge:
24
Group:
test group
Dose level:
1 %
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
The average initial irritation score 24 hours after the first application was 1.0.
Remarks on result:
other: see Remark
Remarks:
Reading: other: Average initial score. . Hours after challenge: 24.0. Group: test group. Dose level: 1 %. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: The average initial irritation score 24 hours after the first application was 1.0. .
Reading:
other: Average initial score
Hours after challenge:
24
Group:
positive control
Dose level:
0.1 M
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
The average initial irritation score 24 hours after the first application was 2.0.
Remarks on result:
other: see Remark
Remarks:
Reading: other: Average initial score. . Hours after challenge: 24.0. Group: positive control. Dose level: 0.1 M. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: The average initial irritation score 24 hours after the first application was 2.0. .
Reading:
other: Average initial score
Hours after challenge:
48
Group:
other: vehicle control
Dose level:
0
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
The average initial irritation score 48 hours after the first application was 1.0.
Remarks on result:
other: see Remark
Remarks:
Reading: other: Average initial score. . Hours after challenge: 48.0. Group: other: vehicle control. Dose level: 0. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: The average initial irritation score 48 hours after the first application was 1.0. .
Reading:
other: Average initial score
Hours after challenge:
48
Group:
test group
Dose level:
1 %
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
The average initial irritation score 48 hours after the first application was 1.0.
Remarks on result:
other: see Remark
Remarks:
Reading: other: Average initial score. . Hours after challenge: 48.0. Group: test group. Dose level: 1 %. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: The average initial irritation score 48 hours after the first application was 1.0. .
Reading:
other: Average initial score
Hours after challenge:
48
Group:
positive control
Dose level:
0.1 M
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
The average initial irritation score 48 hours after the first application was 2.4.
Remarks on result:
other: see Remark
Remarks:
Reading: other: Average initial score. . Hours after challenge: 48.0. Group: positive control. Dose level: 0.1 M. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: The average initial irritation score 48 hours after the first application was 2.4. .
Reading:
other: Average final score
Hours after challenge:
24
Group:
other: vehicle control
Dose level:
0
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
The average final irritation score 24 hours after the last application was 1.1.
Remarks on result:
other: see Remark
Remarks:
Reading: other: Average final score. . Hours after challenge: 24.0. Group: other: vehicle control. Dose level: 0. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: The average final irritation score 24 hours after the last application was 1.1. .
Reading:
other: Average final score
Hours after challenge:
24
Group:
test group
Dose level:
1 %
No. with + reactions:
2
Total no. in group:
10
Clinical observations:
The average final irritation score 24 hours after the last application was 1.5.
Remarks on result:
other: see Remark
Remarks:
Reading: other: Average final score. . Hours after challenge: 24.0. Group: test group. Dose level: 1 %. No with. + reactions: 2.0. Total no. in groups: 10.0. Clinical observations: The average final irritation score 24 hours after the last application was 1.5. .
Reading:
other: Average final score
Hours after challenge:
24
Group:
positive control
Dose level:
0.1 M
No. with + reactions:
5
Total no. in group:
5
Clinical observations:
The average final irritation score 24 hours after the last application was 3.7.
Remarks on result:
other: see Remark
Remarks:
Reading: other: Average final score. . Hours after challenge: 24.0. Group: positive control. Dose level: 0.1 M. No with. + reactions: 5.0. Total no. in groups: 5.0. Clinical observations: The average final irritation score 24 hours after the last application was 3.7. .
Reading:
other: Average final score
Hours after challenge:
48
Group:
other: vehicle control
Dose level:
0
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
The average final irritation score 48 hours after the last application was 1.1.
Remarks on result:
other: see Remark
Remarks:
Reading: other: Average final score. . Hours after challenge: 48.0. Group: other: vehicle control. Dose level: 0. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: The average final irritation score 48 hours after the last application was 1.1. .
Reading:
other: Average final score
Hours after challenge:
48
Group:
test group
Dose level:
1 %
No. with + reactions:
2
Total no. in group:
10
Clinical observations:
The average final irritation score 48 hours after the last application was 1.6.
Remarks on result:
other: see Remark
Remarks:
Reading: other: Average final score. . Hours after challenge: 48.0. Group: test group. Dose level: 1 %. No with. + reactions: 2.0. Total no. in groups: 10.0. Clinical observations: The average final irritation score 48 hours after the last application was 1.6. .
Reading:
other: Average final score
Hours after challenge:
48
Group:
positive control
Dose level:
0.1 M
No. with + reactions:
5
Total no. in group:
5
Clinical observations:
The average final irritation score 48 hours after the last application was 3.2.
Remarks on result:
other: see Remark
Remarks:
Reading: other: Average final score. . Hours after challenge: 48.0. Group: positive control. Dose level: 0.1 M. No with. + reactions: 5.0. Total no. in groups: 5.0. Clinical observations: The average final irritation score 48 hours after the last application was 3.2. .

Applicant's summary and conclusion

Interpretation of results:
ambiguous
Remarks:
Migrated information
Conclusions:
When 2,2,4-trimethyl-1,3-pentanediol was tested in a repeated epicutaneous application sensitization study, 2 of the 10 animals showed a weak response. Final average scores in treated animals 24 and 48 hours after the last application of test material were 1.5 and 1.6, respectively. These average scores were significantly lower than those observed for the positive control. While a weak response was observed in 2 of 10 animals tested, the test method used in this study is not one of the three recognized and officially accepted animal test methods outlined in current regulatory guidelines. Two other skin sensitization studies conducted by non-guideline methods are available for this test material and should also be considered in the final determination of skin sensitization classification.

2,2,4-Trimethyl-1,3-pentanediol is not currently classified for skin sensitization according to Directive 67/548/EEC. Based on the weak positive response in the current study, data were considered to be insufficient to classify the test material for Skin Sensitization according to the UN Globally Harmonized System of Classification and Labelling of Chemicals (GHS) or EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) 1272/2008.
Executive summary:

In a skin sensitization study, ten guinea pigs were repeatedly exposed to 2,2,4-trimethyl-1,3-pentanediol at a concentration of 1% in a vehicle consisting of 1:1:3 acetone:dioxane:guinea pig fat. Applications were made epicutaneously on the clipped backs of the animals over a two week period. Animals were observed at 24 and 48 hours for signs of irritation after both the first and last applications of the test substance. Average irritation scores for animals treated with the test material were compared to scores obtained from groups of five animals treated with the vehicle alone or a solution containing the positive control substance phenylhydrazine. Under the conditions of the current study, the test substance, 2,2,4-trimethyl-1,3-pentanediol, induced a low level of sensitization in 2 of 10 animals. The positive and solvent control substances induced the appropriate responses. Based on the minimal response observed in this study, 2,2,4-trimethyl-1,3-pentanediol (TMPD) presents a low potential for dermal sensitization.