Dibutyl terephthalate

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Single 4 hour exposure followed by a 7 day observation period

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Reliable without restriction; study followed OECD 404 and EEC Annex V, Test B.4 guidelines and GLPs.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2004

Report date:

2004

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

1,4-Benzenedicarboxylic acid, 1,4-dibutyl ester

IUPAC Name:

1,4-Benzenedicarboxylic acid, 1,4-dibutyl ester

Constituent 2

Reference substance name:

Dibutyl terephthalate

EC Number:

217-803-9

EC Name:

Dibutyl terephthalate

Cas Number:

1962-75-0

Molecular formula:

C16H22O4

IUPAC Name:

1,4-dibutyl benzene-1,4-dicarboxylate

Constituent 3

Reference substance name:

Dibutyl benzene-1,4 dicarboxylate

IUPAC Name:

Dibutyl benzene-1,4 dicarboxylate

Constituent 4

Reference substance name:

Terephthalic acid, dibutyl ester; Di-butyl terephthalate; Dibutylterephthalate; DBT

IUPAC Name:

Terephthalic acid, dibutyl ester; Di-butyl terephthalate; Dibutylterephthalate; DBT

Details on test material:

Test Substance:
-Test Substance: Dibutyl terephthalate
-Physical state and appearance: Clear, colorless liquid
-Source of test substance: Eastman Chemical Company, Kingsport, TN

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

Test animals:
-Source: Covance Research Products, Inc. (Denver, PA)
-Sex: not specified
-Condition at receipt: Animals were isolated upon arrival and were judged healthy prior to testing.
-Age at study initiation: at least 3 months old
-Acclimation period: 5 days
-Weight at study initiation: no information
-Housing: Animals were housed singly in suspended, stainless-steel mesh cages. Cages and racks were washed once a week and cage paper changed every other day.
-Diet: Certified High Fiber Rabbit Diet (PMI #5325) ad libitum
-Water: Rochester, NY public water ad libitum
-Method of animal identification: uniquely-numbered ear tags

Environmental conditions:
-Temperature: 21.2-23.1°C
-Humidity: 44.9-64.1%
-Photoperiod: 12:12 light cycle

Study Dates:
-Study initiation date: September 20, 2004
-Experimental start date: September 23, 2004
-Experimental completion date: September 30, 2004

Test system

Type of coverage:

occlusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

0.5 mL

Duration of treatment / exposure:

4 hours

Observation period:

1, 24, 48, 72 hours, and 7 days after removal of the occlusive patch

Number of animals:

3 rabbits

Details on study design:

Test substance exposure:
The hair was removed from an area of the dorsal skin with an electric clipper. A single dose of 0.5 mL of the test substance was applied topically to each animal using a fiber pad and an occlusive wrap to hold the test substance in place for four hours. At the end of the exposure, the application site was rinsed with running water.

Controls:
Adjacent areas of untreated skin of each animal served as control sites for the test areas.

Clinical observations:
The site of application was examined at 1, 24, 48, and 72 hours and at 7 days after removal of the occlusive patch. Observations included estimation of erythema, edema, necrosis, eschar formation, scarring, erosion, and staining caused by the test substance as well as general systemic effects.

Grading the irritant response:
The most severely affected area within the site of application of the test substance was scored for erythema and edema at each observation period. Grading was conducted according to OECD Guideline 404 Annex V., Test B.4 (Grading of Skin Reaction).

Grading other clinical observations:
In addition to observations of irritation, other serious skin lesions, abnormal clinical signs, or toxic effects were graded and scored by degree of severity, i.e., very slight, slight, moderate, or severe.

Body weight determinations:
Animals were not weighed.

Necropsy:
No necropsies were conducted at the conclusion of the test.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

edema score

Basis:

other: All animals

Time point:

other: All time points

Max. score:

0

Reversibility:

other: Not applicable

Remarks on result:

other: No edema was observed at any time in the study.

Results 2

Irritation parameter:

erythema score

Basis:

other: All animals

Time point:

other: 24, 48 and 72 hours

Score:

0 - 1

Max. score:

1

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: Signs of minimal erythema were observed in 1 of 3 anmals tested; 2/3 animals were normal throughout the study. The test substance was considered to not be an irritant or corrosive to rabbit skin.

Irritant / corrosive response data:

Signs of irritation consisted of erythema (grade 1 for one of three animals at the 24, 48, and 72-hour observations). No other irritant response or serious lesion was noted during the 7-day observation period. Two animals appeared clinically normal throughout the study. By Day 7, the third animal appeared clinically normal.

Applicant's summary and conclusion

Interpretation of results:

other: not classified

Remarks:

Criteria used for interpretation of results: OECD GHS

Conclusions:

Dibutyl terephthalate was not acutely toxic, irritating, or corrosive after a 4 hour dermal exposure to New Zealand White rabbits under occlusive conditions used in this study.

Based on minimal erythema in one rabbit that cleared by Day 7 following removal of the occlusive patch, dibutyl terephthalate is not classifiable for Skin Irritation/Corrosion according to GHS.

Executive summary:

In a skin irritation/corrosion study, three New Zealand White Rabbits were exposed to 0.5 mL of the neat test substance, dibutyl terephthalate, under occlusion for 4 hours. After 4 hours the test site was rinsed with running distilled water. The site of application was examined at 1, 24, 48, and 72 hours and 7 days following removal of the occlusive patch. Signs of irritation consisted of erythema (grade 1 for one of three animals at 24, 48, and 72 hours). No other irritant response or serious lesion was noted during the 7-day observation period, with two animals appearing clinically normal throughout the study. By Day 7, the third animal appeared clinically normal. Based on the results of this study, dibutyl terephthalate presents a low toxicity hazard and is not considered an irritant or corrosive.