Dibutyl terephthalate

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Single ocular exposure followed by a 72 hour observation period

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Reliable without restriction; study was conducted according to OECD Guideline 405 and GLPs.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2004

Report date:

2004

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye 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 / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

Test animals:
-Source: Covance Research Products, Inc. (Denver, PA)
-Condition at receipt: Animals were isolated upon arrival and were judged healthy prior to testing.
-Acclimation period: 5 days
-Sex: Not specified
-Weight at study initiation: not performed
-Age at study initiation: at least 3 months old
-Method of animal identification: uniquely numbered ear tags
-Housing: Animals were singly housed in suspended, stainless-steel mesh cages. Cages and racks were washed once a week and cage papers changed every other day.
-Water: Rochester, NY public water ad libitum
-Diet: Certified High Fiber Rabbit Diet (PMI#5325) ad libitum

Environmental conditions:
-Temperature: 20.2-22.5 °C
-Humidity: 45.6-54.5%
-Photoperiod: 12:12 light cycle

Study Dates:
-Study Initiation Date: November 3, 2004
-Experimental Start Date: November 8, 2004
-Experimental Completion Date: November 12, 2004

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: yes, the right eye served as the control

Amount / concentration applied:

0.1 mL

Duration of treatment / exposure:

3 rabbits: one exposure; the eyes were not irrigated after instillation.
3 rabbits: one exposure; the eyes were immedialtely washed after instillation.

Observation period (in vivo):

Immediately after installation and 1, 24, 48 and 72 hours post-administration

Number of animals or in vitro replicates:

6 rabbits

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

other: All animals

Time point:

other: All time points

Score:

0

Max. score:

0

Reversibility:

other: Not applicable

Remarks on result:

other: No corneal opacity was observed at any time during the study.

Results 2

Irritation parameter:

iris score

Basis:

other: All animals

Time point:

other: All time points

Score:

0

Max. score:

0

Reversibility:

other: Not applicable

Remarks on result:

other: No iris effects were observed at any time during the study.

Results 3

Irritation parameter:

conjunctivae score

Basis:

other: All animals

Time point:

other: 1 Hour

Score:

0 - 1

Max. score:

1

Reversibility:

fully reversible within: 72 hours

Remarks on result:

other: Conjunctival irritation of Grade 1 was observed in 3/3 unwashed eyes and 2/3 washed eyes. The other washed eye was normal.

Results 4

Irritation parameter:

conjunctivae score

Basis:

other: All animals

Time point:

other: 24 hours

Score:

0 - 1

Max. score:

1

Reversibility:

fully reversible within: 72 hours

Remarks on result:

other: Conjunctival irritation of Grade 1 was observed in 1/3 unwashed eyes and 2/3 washed eyes; 2/3 unwashed eyes and 1/3 washed eyes were normal.

Results 5

Irritation parameter:

conjunctivae score

Basis:

other: All animals

Time point:

other: 48 hours

Score:

0 - 1

Max. score:

1

Reversibility:

fully reversible within: 72 hours

Remarks on result:

other: Conjunctival irritation of Grade 1 was observed in 1/3 washed eyes; all other eyes were normal.

Results 6

Irritation parameter:

chemosis score

Basis:

other: All animals

Time point:

other: All time points

Score:

0

Max. score:

0

Reversibility:

other: Not applicable

Remarks on result:

other: No chemosis was observed at any time during the study.

Irritant / corrosive response data:

In this study, signs of irritation in unwashed eyes were limited to redness of the conjunctivae (grade 1). The redness was seen in 3/3 eyes at 1 hour, but only in 1/3 eyes at 24 hours. Unwashed eyes appeared normal at 48 and 72 hours. For washed eyes, signs of irritation were also limited to redness of the conjunctivae (grade 1). At 1 and 24 hours after administration of the test substance, one of three washed eyes appeared clinically normal. By the 48-hour examination, two of three washed eyes appeared clinically normal. By the 72-hour examination, all washed eyes appeared clinically normal. Staining was not evident for unwashed or washed eyes when tested with fluorescein dye 24 hours after administration of the test substance. Immediate irrigation of the eyes did not alter the minimal irritation caused by the test substance.

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: OECD GHS

Conclusions:

Dibutyl terephthalate was not acutely toxic, corrosive or irritating by the ocular route in New Zealand White rabbits under the conditions used in this study.

Based on the finding that exposure to the test material caused, at most, minimal reversible erythema in the eyes of New Zealand White rabbits, dibutyl terephthalate is not classified for “Serious Eye Damage/Eye Irritation” according to GHS guidelines.

Executive summary:

In an acute ocular irritation study, 0.1 mL of dibutyl terephthalate was administered into the conjunctival sac of one eye of six New Zealand White Rabbits. Immediately after instillation, the eyes of three rabbits were washed with running distilled water and the eyes of the other three rabbits were not irrigated. The eyes were examined at 1, 24, 48, and 72 hours post-instillation according to OECD Guideline 405. Signs of irritation in unwashed and washed eyes were limited to redness of the conjunctivae (grade 1). Irritation cleared in the unwashed eyes by 48 hours and in washed eyes by 72 hours. Based on the results of this study, dibutyl terephthalate is a minimal ocular irritant and presents a low toxicity hazard.