Registration Dossier

Administrative data

Endpoint:
dermal absorption in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Published study conducted according to sound scientific principles.

Data source

Reference
Reference Type:
publication
Title:
Absorption, distribution and excretion of terephthalic acid and dimethyl terephthalate
Author:
Moffitt AE Jr, Clary JJ, Lewis TR, Blanck MD, Perone VB.
Year:
1975
Bibliographic source:
Am Ind Hyg Assoc J. 1975 Aug;36(8):633-41.

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

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Dimethyl terephthalate uniformly ring-labelled with carbon-14 was obtained from the Mallinckrodt Chemical Works, Missouri.
Unlabelled dimethyl terephthalate (DMT) was obtained from Matheson Scientific Company, Ohio.
Radiolabelling:
yes
Remarks:
[14C]-dimethyl terephthalate

Test animals

Species:
rat
Strain:
other: Charles River
Sex:
male
Details on test animals 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]-DMT (4 µc).
Repeated dose of 80 mg [14C]-DMT (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]-DMT was prepared in 1% solutions of Triton-X-100 in distilled water. The application volume was 0.2 ml of [14C]-DMT 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.
Details on in vitro test system (if applicable):
Not applicable.

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:
Approximately 11% of the administered dose of [14C]-DMT was recovered in the urine and faeces within 10 days of the single application, and 13% was excreted following repeated applications.
Total recovery:
Total recovery in the single application group was 18.3%, total recovery in the repeat application group was 16.0%. The highest amount of radioactivity was recovered in the liver when compared to the other organs: single application - 0.8% recovered from liver, 1.2% recovered from all other assayed organs; repeat application - 0.2% recovered from the liver, 0.1% recovered from all other assayed organs.

Any other information on results incl. tables

Recovery of radioactivity following dermal application

 

Total administered dose (%)

Single application (80 mg)

5 dose repeat application (80 mg/dose)

Urine

9.3

10.0

Faeces

1.5

2.4

Skin – application site

5.5

3.3

Organs (total)

2.0

0.3

Total

18.3

16.0

Applicant's summary and conclusion

Conclusions:
It was concluded that DMT is rapidly absorbed and excreted by the body, and that no significant quantities accumulate in the tissues.
Executive summary:

Data from a radiotracer study in rats to determine the absorption, distribution, and excretion of dimethyl terephthalate (DMT) following dermal administration demonstrate no evidence of skin irritation in rats after a single or repeated dermal application of 80 mg of 14C-DMT. Approximately 11% of the single dose and 13% of 5 repeated doses were recovered from the urine and faeces within 10 days of initial dosing.

It was concluded that DMT is rapidly absorbed and excreted by the body, and that no significant quantities accumulate in the tissues.