Bis(2-ethylhexyl) terephthalate

Repeated dose toxicity: dermal

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:

comparable to guideline study with acceptable restrictions

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

Reference

Reference 1

Reference Type:

study report

Title:

Unnamed

Year:

1975

Report date:

1975

Reference 2

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

Test material information

Constituent 1

Reference substance name:

Bis(2-ethylhexyl) terephthalate

EC Number:

229-176-9

EC Name:

Bis(2-ethylhexyl) terephthalate

Cas Number:

6422-86-2

Molecular formula:

C24H38O4

IUPAC Name:

1,4-bis(2-ethylhexyl) benzene-1,4-dicarboxylate

Constituent 2

Reference substance name:

Reference substance 001

Cas Number:

6422-86-2

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 or test system 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.