Bis(2-ethylhexyl) terephthalate

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

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:

test procedure in accordance with national standard methods

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

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

other: 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.

Version / remarks:

none

Deviations:

no

Remarks:

no

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)

Justification for non-LLNA method:

The test substance was tested for the potential to cause dermal sensitization in a human repeat insult patch test (HRIPT)

Test material

Test material information

Constituent 1

Reference substance name:

Bis(2-ethylhexyl) terephthalate

EC Number:

229-176-9

EC Name:

Bis(2-ethylhexyl) terephthalate

Cas Number:

6422-86-2

Molecular formula:

C24H38O4

IUPAC Name:

1,4-bis(2-ethylhexyl) benzene-1,4-dicarboxylate

Constituent 2

Reference substance name:

Reference substance 001

Cas Number:

6422-86-2

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

Results and discussion

In vivo (non-LLNA)

Results

Results 1

Key result

Reading:

rechallenge

Hours after challenge:

48

Group:

test chemical

Dose level:

0.5%

No. with + reactions:

2

Total no. in group:

203

Clinical observations:

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

Remarks on result:

no indication of skin sensitisation

Results 2

Key result

Reading:

rechallenge

Group:

negative control

Dose level:

None

No. with + reactions:

0

Total no. in group:

0

Clinical observations:

none

Remarks on result:

not measured/tested

Results 3

Key result

Reading:

rechallenge

Group:

positive control

Dose level:

none

No. with + reactions:

0

Total no. in group:

0

Clinical observations:

none

Remarks on result:

not measured/tested

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

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.