Dibutyl terephthalate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Single dose followed by a 14-day observation period

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Reliable without restriction; study was conducted in accordance with OECD Guideline 420 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 420 (Acute Oral Toxicity - Fixed Dose Method)

Deviations:

no

GLP compliance:

yes

Test type:

fixed dose procedure

Limit test:

no

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:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

Test animals:
-Source: Charles River Laboratories, Stone Ridge (Kingston), NY
-Sex: female
-Condition at Receipt: animals were isolated upon arrival and were judged healthy prior to testing
-Acclimation Period: 5 days
-Age at Study Initiation: 8-9 weeks
-Weight at Study Initiation: 194.14-206.28 grams
-Housing: rats were singly housed in suspended, stainless-steel, wire-mesh cages. Cages were washed once a week and cage paper changed at least three times a week
-Diet: Certified Rodent Diet (PMI #5002), pellets; ad libitum
-Water: Rochester, NY public water ad libitum
-Method of Animal Identification: uniquely-numbered metal ear tags
-Method of Animal Distribution: Animals were randomly selected and assigned to dose groups from the same shipment using a computer-generated list. After assignment, body weights were determined to ensure that individual body weights were within 20% of the mean weight.

Environmental conditions:
-Temperature: 21.5-27.0°C
-Humidity: 35.1-55.7%
-Photoperiod: 12:12 light/dark cycle

Study Dates:
-Study initiation date: October 8, 2004
-Experimental start date: October 11, 2004
-Experimental completion date: October 27, 2004

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

The test substance was administered as received. The test substance was administered as a single dose by oral gavage to rats that had been fasted overnight. Data from a sighting study were used to establish the dose level for the main study.

Doses:

300 and 2000 mg/kg bw

No. of animals per sex per dose:

300 mg/kg bw (1 female rat) and 2000 mg/kg bw (5 female rats)

Control animals:

no

Details on study design:

Clinical observations:
Animals were observed three times on the day of dosing (Day 0), and once each day thereafter for the duration of the experiment. Observations included, but were not limited to: examination of the hair, skin, eyes, mucous membranes, motor activity, feces, urine, respiratory system, circulatory system, autonomic nervous system, central nervous system, and behavior patterns.

Body weights:
Body weights were measured on days 0 (prior to treatment), 7 and 14.

Necropsy:
All animals were euthanized and necropsied at the completion of the 14-day observation period.

Statistics:

No statistical analysis was required during the study. No dose/mortality curve was constructed because of the limited number of animals and dose groups.

Results and discussion

Preliminary study:

In a preliminary sighting study, an initial dose of 300 mg/kg bw of the test material was administered to a single female rat. Since no abnormal clinical signs were noted for this animal on the day of or the day following dosing, a higher dose of 2000 mg/kg bw was administered to a second female rat. Based on an absence of clinical signs or mortality, 2000 mg/kg bw was administered to 4 additional female rats.

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

No mortality was observed during the 14-day observation period.

Clinical signs:

other: All 2000 mg/kg bw animals appeared normal throughout the study.

Gross pathology:

No treatment-related changes were observed at necropsy; no tissue was collected for microscopic examination.

Applicant's summary and conclusion

Interpretation of results:

study cannot be used for classification

Remarks:

Migrated information

Conclusions:

Dibutyl terephthalate was not acutely toxic by the oral route in female rats under conditions used in this study. The oral LD50 in female rats was > 2000 mg/kg bw.

Based on an acute oral LD50 value of > 2000 mg/kg bw in rats, dibutyl terephthalate is not classified for Acute Toxicity by the oral route under GHS. Based on an absence of clinical signs and treatment-related changes at necropsy, dibutyl terephthalate is also not classified for "Target Organ Toxicity - Single Exposure" according to GHS.

Executive summary:

In a fixed dose acute oral toxicity study, 1 female rat was exposed per os to a single dose of 300 mg/kg bw of dibutyl terephthalate with no effects on the day of or the day after dosing. An additional 5 female rats were exposed to a single oral gavage dose of 2000 mg/kg bw followed by a 14-day observation period. Under the conditions of this study, no deaths occurred and the oral LD50 was considered to be > 2000 mg/kg bw. No clinical signs were noted and a body weight gain was noted for all animals over the 2-week observation period. Based on the results of this study, dibutyl terephthalate presents a low toxicity hazard upon ingestion.