Registration Dossier

Administrative data

acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Single dose followed by a 14-day observation period
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 Type:
study report
Report date:

Materials and methods

Test guideline
according to guideline
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
GLP compliance:
Test type:
fixed dose procedure
Limit test:

Test material

Constituent 1
Reference substance name:
1,4-Benzenedicarboxylic acid, 1,4-dibutyl ester
1,4-Benzenedicarboxylic acid, 1,4-dibutyl ester
Constituent 2
Chemical structure
Reference substance name:
Dibutyl terephthalate
EC Number:
EC Name:
Dibutyl terephthalate
Cas Number:
Molecular formula:
1,4-dibutyl benzene-1,4-dicarboxylate
Constituent 3
Reference substance name:
Dibutyl benzene-1,4 dicarboxylate
Dibutyl benzene-1,4 dicarboxylate
Constituent 4
Reference substance name:
Terephthalic acid, dibutyl ester; Di-butyl terephthalate; Dibutylterephthalate; DBT
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

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
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.
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:
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.

All animals were euthanized and necropsied at the completion of the 14-day observation period.
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
Dose descriptor:
Effect level:
> 2 000 mg/kg bw
No mortality was observed during the 14-day observation period.
Clinical signs:
All 2000 mg/kg bw animals appeared normal throughout the study.
Body weight:
All animals gained weight during the study, approximately 57 g by Day 14.
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
Migrated information
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.