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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:
6 weeks
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Reliable without restriction; study was conducted according to acceptable scientific methodology and according to Good Clinical Practices (GCPs). The investigation was reviewed by an Institutional Review Board in accordance with Title 21 of the U.S. Code of Federal Regulations (CFR).

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2001
Report Date:
2001

Materials and methods

Principles of method if other than guideline:
The test substance was tested for the potential to cause dermal sensitization in a human repeat insult patch test (HRIPT) using a panel of 203 subjects. In the induction phase, a solution of the test substance was applied to the back of the subjects three times a week for three weeks. After 24 hours of exposure to each patch, the subjects removed the patches All sites were then scored for irritation at 48-72 hours after patch application. The induction phase was followed by a 10-17-day rest period. The subjects were subsequently challenged by application of patches at naïve sites on the back and the response was evaluated at 48 and 96 hours after challenge. Potential sensitization to the test substance was determined based on dermal reactions to the challenge patches.
GLP compliance:
yes
Remarks:
As this was a human clinical study, it was conducted in compliance with Good Clinical Practice Regulations. Prior to its conduct, the protocol for this study was reviewed by an Institutional Review Board in Accordance with CFR, Title 21, Parts 50 and 56.
Type of study:
other: HRIPT (modified Draize procedure)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
-Test substance (as cited in report): Eastman DOTP Plasticizer
-Source: Eastman Chemical Company
-Lot number: 0045816, EAN 907040

In vivo test system

Test animals

Species:
human
Sex:
male/female
Details on test animals and environmental conditions:
Test subjects:
-Sex: male and female
-Number of Subjects: 245 persons were screened for the study; 241 (44 males and 197 females) persons were enrolled and 203 (40 males and 163 females) subjects completed the study.
-Subjects Failing to Complete the Study: A total of thirty-eight subjects failed to complete the study. Nineteen subjects withdrew from the study because they missed two induction applications. Twelve subjects withdrew from the study because they missed the challenge application. Four subjects withdrew from the study following an adverse event. One subject each withdrew from the study because they were inadvertently enrolled while taking an anti-inflammatory drug, they were unable to remove the patches by themselves, or they did not like how the patches felt against their skin.

Study Dates:
-Study Initiation Date: 9 April 2001
-Experimental Completion Date: 29 June 2001

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
epicutaneous, semiocclusive
Vehicle:
other: acetone
Concentration / amount:
0.5% di (2-ethylhexyl) terephthalate in acetone
Challengeopen allclose all
Route:
epicutaneous, open
Vehicle:
other: acetone
Concentration / amount:
0.5% di (2-ethylhexyl) terephthalate in acetone
No. of animals per dose:
203
Details on study design:
For the induction phase of the study, 0.2 mL of an 0.5% solution of the test substance in acetone was applied to the skin of the back three times per week (Monday, Wednesday, and Friday) for a total of nine applications. The application site was semi-occluded, using a non-woven cotton pad (Webril) held in place on all sides by a strip of hypoallergenic tape (Micropore). Subjects were instructed to remove the patches after 24 ± 1 hours. Each application site was evaluated for signs of irritation and any other superficial effects approximately 48 or 72 hours after the start of exposure. The test patches were applied repeatedly to the same area of the skin unless irritation was noted, in which case an alternate site on the back was used. The location of the test substance was varied among subjects in order to eliminate any position bias. Test substance mixtures were prepared fresh for each test day. The induction phase was followed by a rest period of approximately 10 to 17 days in which no test material was applied.

For the challenge phase, a single application of the test substance was applied to a naïve site on the back, located away from the original test site, again for approximately 24 hours, and the application site was evaluated approximately 48 or 96 hours after the start of exposure for the challenge application.

Study design: in vivo (LLNA)

Statistics:
No statistical analysis of the data was performed. Data from the individual patch sites were presented in tabular format.

Results and discussion

Any other information on results incl. tables

Under the conditions of this study, di (2-ethylhexyl) terephthalate was found to be non-irritating. Only slight erythema was observed for one to seven subjects at any given time during the induction phase of the study and for only one subject during the challenge phase of the study. Di (2-ethylhexyl) terephthalate did not elicit contact dermal sensitization in any individual completing the study. Based on an absence of adverse effects in this study, di (2-ethylhexyl) terephthalate is not classified for “Skin Sensitization” according to GHS.

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information
Conclusions:
Under the conditions of this study, di (2-ethylhexyl) terephthalate was found to be non-irritating. Only slight erythema was observed for one to seven subjects at any given time during the induction phase of the study and for only one subject during the challenge phase of the study. Di (2-ethylhexyl) terephthalate did not elicit contact dermal sensitization in any individual completing the study.

Based on an absence of adverse effects in this study, di (2-ethylhexyl) terephthalate is not classified for “Skin Sensitization” according to GHS.
Executive summary:

Di (2-ethylhexyl) terephthalate (0.5% in acetone) was applied at a dose volume of 0.2 mL to the backs of 203 panelists three times a week for three weeks in a human repeat insult patch test (HRIPT). The application sites were semi-occluded, using a non-woven cotton pad (Webril) held in place on all sides by a strip of hypoallergenic tape (Micropore). Subjects removed the patches after approximately 24 hours. All sites were scored for irritation approximately 48 -72 hours after each patch application. After the three week induction period, the panelists were allowed to rest for up to 17 days and a single open challenge was conducted using naïve sites on the backs of the subjects. The dermal responses in the challenge portion of the study were scored at both 48 and 96 hours after application. Under the study conditions, di (2-ethylhexyl) terephthalate was found to be essentially non-irritating and did not elicit a dermal sensitization reaction.