Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
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 followed OECD Guideline 402 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 402 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

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:
male/female
Details on test animals and environmental conditions:
Test animals:
-Source: Charles River Laboratories, Stone Ridge (Kingston), NY
-Sex: male and 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 weeks (males); 10 weeks (females)
-Weight at Study Initiation: 233.82-265.60 g (males); 217.85-240.64 g (females)
-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 (Purina Rodent Chow #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: 19.5 - 22.8°C
-Humidity: 42.8 - 63.8%
-Photoperiod: 12:12 light/dark cycle

Study Dates:
-Study initiation date: September 20, 2004
-Experimental start date: September 21, 2004
-Experimental completion date: October 5, 2004

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
The test substance was received as a liquid and administered as received. The hair was removed from an area of the dorsal skin with an electric clipper. A single dose of the test substance was placed in contact with the skin using a fiber pad and an occlusive wrap to hold the test substance in place for 24 hours. After 24 hours, any residual test substance was removed with running water.
Duration of exposure:
24 hours
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5 rats/sex
Control animals:
no
Details on study design:
Clinical observations:
Animals were observed at least once during the exposure period, 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

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
No mortality was observed during the 14-day observation period.
Clinical signs:
Clinical abnormalities consisted of decreased fecal volumes for two female rats on Day 2. No other clinical signs of toxicity were observed during the study.
Body weight:
All animals gained weight during the study. Rats gained approximately 40 g (female) and 124 g (male) during the two week 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 dermal route in rats under conditions used in this study. The dermal LD50 in male and female rats was > 2000 mg/kg bw.

Based on an acute dermal LD50 value of > 2000 mg/kg bw in male and female rats, dibutyl terephthalate is not classified for Acute Toxicity by the dermal route under GHS. Based on an absence of signs of irritation after an exposure period of 24 hours under an occlusive wrap to dorsal skin of rats, dibutyl terephthalate is not classifiable for Skin Irritation/Corrosion according to 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 an acute dermal toxicity study, 5 rats/sex were exposed to 2000 mg/kg bw of dibutyl terephthalate under occlusive contact for 24 hours. Under the conditions of this study, no deaths occurred and the dermal LD50 was considered to be > 2000 mg/kg bw. No signs of skin absorption or systemic toxicity were evident during the study. At the application sites, no signs of skin irritation were present. 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 skin contact under conditions of normal use.