Registration Dossier

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:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
Deviations:
no
GLP compliance:
yes
Test type:
fixed dose procedure
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Type:
Constituent
Type:
Constituent
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 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:
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
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.