Bis(hydroxyethyl) terephthalate

Dermal absorption

Administrative data

Endpoint:

dermal absorption in vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

publication

Title:

Adsorption, Distribution and Excretion of Terephthalic Acid and Dimethyl Terephthalate

Author:

Moffitt, AE; Clary, JJ; Lewis, TR; Blanck, MD; Perone, VB

Year:

1975

Bibliographic source:

American Industrial Hygiene Association Journal 36(8):633-641. DOI:10.1080/0002889758507303

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

A radiotracer study was conducted in rats to determine the rate of absorption, distribution and excretion of the test substance following dermal application.

GLP compliance:

no

Remarks:

predates GLP

Test material

Test material information

Constituent 1

Reference substance name:

Terephthalic acid

EC Number:

202-830-0

EC Name:

Terephthalic acid

Cas Number:

100-21-0

Molecular formula:

C8H6O4

IUPAC Name:

terephthalic acid

Radiolabelling:

yes

Remarks:

[14C]-terephthalic acid

Test animals

Species:

rat

Strain:

other: Charles River

Sex:

male

Details on test animals or test system and environmental conditions:

The animals were adult male Charles River rats weighing 200-225 g. Animals were housed in metabolism cages during the study, and allowed free access to food and water.

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

other: 1% solution of Triton-X-100 in distilled water

Duration of exposure:

Single dose study: 10 days
Repeated dose study: 10 days (the patch was removed only to allow re-dosing)

Doses:

Single dose of 80 mg [14C]-TPA (4 µc).
Repeated dose of 80 mg [14C]-TPA (4 µc) on alternate days for 10 consecutive days (five doses).

No. of animals per group:

Five rats per group

Control animals:

yes

Details on study design:

[14C]-TPA was prepared in 1% solutions of Triton-X-100 in distilled water. The application volume was 0.2 ml of [14C]-TPA in the vehicle. The application site was approximately 2.5 cm².
The test material was applied to the unabraded shaved backs of the rats. After dosing, the treated area was covered with a gauze patch. In order to determine the total dose applied to the skin, the gauze patches were counted for residual radioactivity at the end of the study.
A group of controls animals receiving the vehicle only were maintained for the 10 day observation period.

After dosing, animals were housed in metabolism cages for collection of urine and faeces. A fine mesh screen was used to separate urine and faeces.
All rats were sacrificed on the tenth day of each study by decapitation followed by exsanguination. The following organs were removed and assayed: liver, lung, heart, kidney, spleen, adrenals, pancreas, testes, brain and femur. The skin of the application site was also assayed for radioactivity.

No attempt was made to recover the total unabsorbed dose remaining on the skin application site, which was washed free of residual material after sacrifice.

Results and discussion

Signs and symptoms of toxicity:

not examined

Dermal irritation:

no effects

Remarks:

there was no evidence of skin irritation at the time of final patch removal

Absorption in different matrices:

Negligible absorption and excretion occurred following single or repeated application.

Total recovery:

Total recovery in the single application group was 5.1%, total recovery in the repeat application group was 9.4%. The highest amount of radioactivity was recovered in the liver when compared to the other organs: single application - 0.7% recovered from liver, 0.3% recovered from all other assayed organs; repeat application - 0.6% recovered from the liver, 0.2% recovered from all other assayed organs.

Percutaneous absorption

Parameter:

percentage

Absorption:

10 %

Remarks on result:

other: Default value assumed for risk assessment use

Applicant's summary and conclusion

Conclusions:

It was concluded that skin absorption of terephthalic acid is minimal, and there was no evidence for accumulation of test material in tissues.

Executive summary:

Data from a radiotracer study in rats to determine the absorption, distribution, and excretion of terephthtalic acid (TPA) following dermal administration demonstrate no evidence of skin irritation in rats after single or repeated dermal application of 80 mg of 14C-TPA and no significant skin absorption of 14C-TPA.

It was conclused that skin absorption of terephthalic acid is minmal, and there was no evidence for accumulation of the test material in tissues.