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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
Study period:
38 days
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
The study was conducted prior to institution of Good Laboratory Practices. The study was conducted by an internal Eastman Kodak Company method, developed prior to established guidelines, but was in accord with acceptable scientific standard methods in use at the time the study was conducted. The results of this study are valid for classification insofar as the conditions of exposure are at least as stringent as modern guidelines.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1971

Materials and methods

Test guideline
Qualifier:
no guideline available
Principles of method if other than guideline:
Groups of 5-10 guinea pigs were used to determine the dermal sensitization potential of the test substance using the Kodak Drop-on method. The irritant potential of a 1% solution of the substance in a 7:2:1 mixture of acetone, dioxane, and guinea pig fat was determined 24 and 48 hours following application to the clipped back skin of ten animals. Three additional applications of this solution were applied over the next five days. The animals were allowed to rest for three weeks. Challenge doses of the test solution were then made on one shoulder of the guinea pigs, and one week later, on the other shoulder. The results of the first application were compared to the resuts of the last application to determine the sensitization potential of the test material. An additional group of five animals was treated with the solvent mixture alone and was used as a control. The responses were quantified using a four point scale based on responses that were negative, slight, moderate, or strong.
GLP compliance:
no
Remarks:
Study conducted prior to GLP
Type of study:
other: Study conducted according to an internal Eastman Kodak Company laboratory method, known as the drop-on method, not used elsewhere.

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
-Test substance: Dimethyl terephthalate

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: Both irritation/induction and challenge phases: 7:2:1 acetone:dioxane:guinea pig fat
Concentration / amount:
Preliminary Irritation and Induction Phase: 1.0% in acetone + dioxane + guinea pig fat (7:2:1).
Challenge Phase: 1.0% in acetone + dioxane + guinea pig fat (7:2:1).
Challengeopen allclose all
Route:
epicutaneous, open
Vehicle:
other: Both irritation/induction and challenge phases: 7:2:1 acetone:dioxane:guinea pig fat
Concentration / amount:
Preliminary Irritation and Induction Phase: 1.0% in acetone + dioxane + guinea pig fat (7:2:1).
Challenge Phase: 1.0% in acetone + dioxane + guinea pig fat (7:2:1).
No. of animals per dose:
10
Details on study design:
Groups of 10 guinea pigs were used to determine the dermal sensitization potential of the test substance using the Kodak Drop-on method. Initially, the irritant potential of a 1% solution of the substance in a 7:2:1 mixture of acetone, dioxane, and guinea pig fat was determined following application to the clipped back skin of the animals. Based on the response, the 1% concentration was used for the entire study. Three additional applications of this solution were applied over the next five days. The animals were allowed to rest for three weeks. Challenge doses of the test solution were then made on one shoulder of the guinea pigs, and one week later, on the other shoulder. The results of the very first application were compared to the resuts of the last application to determine the sensitization potential of the test material. An additional group of five animals was treated with the solvent mixture alone and was used as a control. The responses were quantified using a four point scale based on responses that were negative, slight, moderate, or strong. The total erythema scores and total edema scores from all ten animals receiving 1% compound in the solvent were added together and divided by 10 to obtain an irritant score. This was done for both the 24-hour and 48-hour observations. Total erythema and edema scores were obtained from the five solvent control animals as well. The differences in the scores were an indication of the sensitization response, if any.
Positive control substance(s):
yes
Remarks:
Phenylhydrazine

Study design: in vivo (LLNA)

Statistics:
no data

Results and discussion

Positive control results:
Phenylhydrazine was used as a positive control in the series of studies. A dilute solution of this positive control substance was repeatedly applied in the acetone: dioxane: guinea pig fat solvent to the skin of five guinea pigs. The results of this study demonstrated that repeated application of the positive control caused a significant sensitization response in guinea pigs in the test laboratory.

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Group:
other: solvent control
Dose level:
0%
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
The average response in the 5 animals at 24 hours (erythema + edema) following the initial application was 1.2.
Remarks on result:
other: see Remark
Remarks:
Reading: 1st reading. Group: other: solvent control. Dose level: 0%. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: The average response in the 5 animals at 24 hours (erythema + edema) following the initial application was 1.2..
Reading:
2nd reading
Group:
other: solvent control
Dose level:
0%
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
The average response in the 5 animals at 24 hours (erythema + edema) following the initial application was 1.2.
Remarks on result:
other: see Remark
Remarks:
Reading: 2nd reading. Group: other: solvent control. Dose level: 0%. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: The average response in the 5 animals at 24 hours (erythema + edema) following the initial application was 1.2..
Reading:
1st reading
Group:
other: solvent control
Dose level:
0%
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
The average response in the 5 animals at 24 hours (erythema + edema) following the final application was 1.2.
Remarks on result:
other: see Remark
Remarks:
Reading: 1st reading. Group: other: solvent control. Dose level: 0%. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: The average response in the 5 animals at 24 hours (erythema + edema) following the final application was 1.2..
Reading:
2nd reading
Group:
other: solvent control
Dose level:
0%
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
The average response in the 5 animals at 48 hours (erythema + edema) following the final application was 1.2.
Remarks on result:
other: see Remark
Remarks:
Reading: 2nd reading. Group: other: solvent control. Dose level: 0%. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: The average response in the 5 animals at 48 hours (erythema + edema) following the final application was 1.2..
Reading:
1st reading
Group:
test group
Dose level:
1%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
The average response in the 10 animals at 24 hours (erythema + edema) following the initial application was 1.1.
Remarks on result:
other: Reading: 1st reading. Group: test group. Dose level: 1%. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: The average response in the 10 animals at 24 hours (erythema + edema) following the initial application was 1.1..
Reading:
2nd reading
Group:
test group
Dose level:
1%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
The average response in the 10 animals at 48 hours (erythema + edema) following the initial application was 1.2.
Remarks on result:
other: Reading: 2nd reading. Group: test group. Dose level: 1%. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: The average response in the 10 animals at 48 hours (erythema + edema) following the initial application was 1.2..
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
1%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
The average response in the 10 animals at 24 hours (erythema + edema) following the final application was 1.3.
Remarks on result:
other: see Remark
Remarks:
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. Clinical observations: The average response in the 10 animals at 24 hours (erythema + edema) following the final application was 1.3..
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
1%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
The average response in the 10 animals at 48 hours (erythema + edema) following the final application was 1.2.
Remarks on result:
other: see Remark
Remarks:
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. Clinical observations: The average response in the 10 animals at 48 hours (erythema + edema) following the final application was 1.2..

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information
Conclusions:
Dimethyl terephthalate is not considered to be a skin sensitizer using the Kodak Drop-on Method. Based on an absence of positive effects in this study, this material is not classifiable for Skin Sensitization according to UN Globally Harmonized System of Classification and Labelling of Chemicals (GHS) or EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.
Executive summary:

In a study on dimethyl terephthalate using the Kodak Drop-on Method, a group of ten guinea pigs was treated with multiple topical applications of 0.5 mL of a 1.0% solution of the test substance in acetone + dioxane + guinea pig fat (7:2:1). After a three-week rest period, the animals were treated again with the solution on one shoulder and one week later, on the other shoulder . The final observations were compared to the initial observations to determine potential sensitization by the test material. A group of five control guinea pigs was treated with only the solvent mixture. Twenty-four and forty-eight hours after challenge, the reactions in the control and test groups were similar. Based on the results of this study using the Kodak Drop-on Method, it was determined that dimethyl terephthalate was a not a dermal sensitizer.