Registration Dossier

Administrative data

Endpoint:
short-term repeated dose toxicity: dermal
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
10 days
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Study conducted prior to introduction of Good Laboratory Practices; data from a summary report; limited number and no information on sex of animals. Study was conducted by an internal Eastman Kodak Company method developed prior to established guidelines but in accordance with generally accepted scientific principles of the time. No analytical data were provided to verify identity, purity, or stability of test material. The results of this study are valid for classification insofar as the conditions of exposure are at least as stringent as modern guidelines.

Data source

Referenceopen allclose all

Reference Type:
study report
Title:
Unnamed
Year:
1975
Report Date:
1975
Reference Type:
study report
Title:
Unnamed
Year:
1986
Report Date:
1986

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Undiluted di (2-ethylhexyl) terephthalate was applied 9 times over 11 days to the clipped skin of 5 guinea pigs. The 0.5 mL dose applied equates to 813 to 1144 mg/kg bw/day. Animals were observed for clincal abnormalities and body weight changes. No necropsy was performed at study termination.
GLP compliance:
no
Remarks:
Study conducted prior to GLPs
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
-Test substance (as cited in report): Bis (2-ethylhexyl) terephthalate
-The identity, purity, and stability of the test substance were not reported by the testing laboratory.

Test animals

Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
not specified
Details on test animals and environmental conditions:
Test animals:
-Sex: no data
-Weight at study initiation: 430 - 605 g

Administration / exposure

Type of coverage:
open
Vehicle:
unchanged (no vehicle)
Details on exposure:
-Test Substance Application: The test substance was applied to the clipped skin of animals once a day for 9 applications over an 11 day period. The material was dropped onto the backs of the animals and spread gently over the back with a glass rod.

-Occlusion: None

-Total Volume Applied: 0.5 mL/day for a total amount equal to 4.5 mL. Based on initial body weights, the dose equates to 813 to 1144 mg/kg bw/day.

-Removal of Test Substance: It is not specified if the site of application was washed (with water or a solvent) or wiped at the end of each exposure period.
Analytical verification of doses or concentrations:
no
Duration of treatment / exposure:
Once daily
Frequency of treatment:
9 applications over an 11 day period
Doses / concentrations
Remarks:
Doses / Concentrations:
Based on initial body weights, the dose equates to 813 to 1144 mg/kg bw/day.
Basis:
nominal per unit body weight
No. of animals per sex per dose:
5 (sex not reported)
Control animals:
no

Examinations

Observations and examinations performed and frequency:
-Examinations: Animals were observed for clinical abnormalities.

-Body Weights: Body weights were collected on Day 0 and at study termination.

-Feed Consumption: Feeders were not weighed.
Sacrifice and pathology:
Animals were euthanized at the end of the study; gross necropsies were not performed.

Results and discussion

Results of examinations

Clinical signs:
effects observed, treatment-related
Dermal irritation:
effects observed, treatment-related
Mortality:
mortality observed, treatment-related
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
not examined
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
not examined
Haematological findings:
not examined
Clinical biochemistry findings:
not examined
Urinalysis findings:
not examined
Behaviour (functional findings):
not examined
Organ weight findings including organ / body weight ratios:
not examined
Gross pathological findings:
not examined
Histopathological findings: non-neoplastic:
not examined
Histopathological findings: neoplastic:
not examined
Details on results:
-NOEL: Not established.

-Mortality: No mortality was observed during the study.

-Clinical abnormalities: The first application produced moderate erythema in one animal and severe erythema in the other four. Slight edema was observed for all animals but this disappeared by study termination. The reaction did not change over the course of two weeks. Necrosis and eschar were not observed during the study.

-Body Weight: All animals gained weight during the study.

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
In a subacute dermal toxicity study, 5 guinea pigs were exposed to 0.5 mL undiluted di (2-ethylhexyl) terephthalate (equating to 813 to 1144 mg/kg bw/day) 9 times over 11 days. The material was dropped onto the backs of the guinea pigs and spread gently over the back skin with a glass rod. No signs of skin absorption or systemic toxicity were evident during the study. Under the conditions of this study, there was no exacerbation of the irritant response with repeated applications of di (2-ethylhexyl) terephthalate. Based on the results of this study, di (2-ethylhexyl) terephthalate is not classified for “Specific Target Organ Toxicity – Repeated Exposure” according to GHS.
Executive summary:

In a subacute dermal toxicity study, 5 guinea pigs were exposed to 0.5 mL undiluted di (2-ethylhexyl) terephthalate (equating to 813 to 1144 mg/kg bw/day) 9 times over 11 days. Under the conditions of this study, no deaths occurred and no signs of skin absorption or systemic toxicity were evident during the study. At the application sites, signs of irritation were limited to moderate to severe erythema and slight edema. During the course of two weeks the erythema did not diminish in severity but the edema disappeared. A body weight gain was noted in all animals over the 2-week observation period. Based on the results of this study, di (2-ethylhexyl) terephthalate is not acutely toxic following repeated dermal application but may cause moderate irritation.