Bis(2-ethylhexyl) terephthalate

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

8 days

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

Principles of method if other than guideline:

The test substance was evaluated in 18 test subjects. Subjects were patched dermally on the back under semi-occlusive patches with 0.2 mL of five dilutions of the test substance in acetone. Subjects were patched three times over a period of five days (Days 1, 3, and 5). The subjects removed the patches after 24 hours, and scoring of patch sites for irritation was made prior to applications on Days 3 and 5 and on Day 8. Dermal reactions, if any, were assessed to determine the primary irritation potential of the test substance. The clinical investigation was reviewed by an Institutional Review Board in accordance with CFR, Title 21, Parts 50 and 56.

GLP compliance:

yes

Remarks:

As this was a human clinical study, it was conducted in compliance with Good Clinical Practice Regulations.

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 material (as cited in study report): Eastman DOTP Plasticizer
-Source: Eastman Chemical Company
-Lot No: M04595, EAN 907040

Test animals

Species:

human

Details on test animals or test system and environmental conditions:

-A total of 38 persons were screened for the study; eighteen subjects (9 males and 9 females) were enrolled and completed all phases of the study.

Study Dates:
-Study Initiation: March 12, 2001
-Study Completion: March 19, 2001

Test system

Type of coverage:

semiocclusive

Preparation of test site:

not specified

Vehicle:

other: acetone

Controls:

other: Skin adjacent to the application site was used as a control.

Amount / concentration applied:

0.2 mL of 0.01, 0.05, 0.1, 0.2, and 0.5% of the test substance in acetone

Duration of treatment / exposure:

Each subject received three 24 hour dermal applications of each of the five dilution preparations used in the study.

Observation period:

All sites were scored for irritation approximately 48 hours after patch application.

Number of animals:

9 males and 9 females

Details on study design:

A series of skin sites on the back were used for the application of 0.2 mL of a preparation containing 0.01, 0.05, 0.1, 0.2, and 0.5% of the test substance in acetone. 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) for approximately 24 hours. Applications were made on Days 1, 3, and 5; subjects removed the patches 24 ± 1 hr after applications, and scoring took place on Days 3, 5, and 8. The assignment of the five test substance preparations to individual skin sites were varied in order to eliminate any position or order bias.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

overall irritation score

Remarks:

Irritation score

Basis:

other: Human

Remarks:

Human

Time point:

24/48/72 h

Score:

>= 0 - <= 1

Reversibility:

not specified

Remarks on result:

no indication of irritation

Results 2

Irritation parameter:

edema score

Remarks:

Not performed

Basis:

other:

Time point:

24/48/72 h

Score:

>= 0 - <= 0

Remarks on result:

no indication of irritation

Results 3

Irritation parameter:

erythema score

Remarks:

Not performed

Basis:

other:

Time point:

24/48/72 h

Score:

>= 0 - <= 0

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

At 48 or 72 hours after patch application, individual overall irritation scores ranged from 0 to 1 (mild erythema (pink)). Reversibility was not addressed. Average scores for the evaluations made on Days 3, 5, and 8 and the overall average score for the different concentrations of the test substance were as follows:

0.01%: 0.00, 0.03, 0.00, and 0.06
0.05%: 0.03, 0.03, 0.06, and 0.11
0.1%: 0.00, 0.03, 0.03, and 0.06
0.2%: 0.00, 0.00, 0.00, and 0.00
0.5%: 0.00, 0.03, 0.03, and 0.06

Any other information on results incl. tables

Since the irritation that was noted was minimal and did not occur in a concentration-dependent manner, it was not considered to be related to test substance exposure.

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: OECD GHS

Conclusions:

Based on minimal irritation which did not occur in a concentration-dependent manner following three 24-hour applications to intact human skin under semi-occlusive contact, di (2-ethylhexyl) terephthalate is not classified as a primary skin irritant. Therefore, the concentration selected for use in a subsequent HRIPT study was the top concentration, 0.5%.

Under the conditions of the study, di (2-ethylhexyl) terephthalate is not classified under GHS.

Executive summary:

In a primary dermal irritation study, 18 panelists (9 male and 9 female) were exposed to di (2-ethylhexyl) terephthalate at concentrations of 0.01, 0.05, 0.1, 0.2, and 0.5% under semi-occlusion for three 24 hour periods over a period of six days. After 24 hours of exposure, the patches were removed, and 48-72 hours after patch application, the sites were graded for irritation. The maximum irritation score noted was 1 on a scale of 1-3. Irritation was seen irregularly and only at a small proportion of the application sites, was not observed in a concentration-dependent manner, and was therefore not considered to be related to test substance exposure.