Theophylline

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1988

Report date:

1988

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

GLP compliance:

no

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Theophylline

EC Number:

200-385-7

EC Name:

Theophylline

Cas Number:

58-55-9

Molecular formula:

C7H8N4O2

IUPAC Name:

1,3-dimethyl-2,3,6,7-tetrahydro-1H-purine-2,6-dione

Details on test material:

- Name of test material (as cited in study report): Theophyllin-waterfree (anhydrous), micronized;
- Analytical purity: 99.5 to 100.5%;
- Lot/batch No.: 63748.

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Breeder: DR. K . THOMAE GMBH, BIBERACH, GERMANY;
- Weight at study initiation: Animals of comparable weight; 200 - 300 g (+/- 20 % of the mean weight);
- Housing: single;
- Diet (e.g. ad libitum): Kliba-Labordiaet 343, Klingenthalmuehle AG, Kaiseraugst, Switzerland; ad libitum;
- Water (e.g. ad libitum): Tap water, ad libitum;
- Acclimation period: At least one week.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24 °C;
- Humidity (%): 30 - 70 %;
- Photoperiod (hrs dark / hrs light): 12h/12h.

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

other: olive oil

Details on dermal exposure:

TEST SITE
- Area of exposure: Dorsal and dorsolateral parts of the trunks.
- Application area: About 50 cm² clipped epidermis; Clipping was done at least 15 hours before the beginning of the study.
- Type of wrap if used: Application site was covered with a semiocclussive dressing for 24 hours. Thereby the applied test substance has been covered with a porous dressing of 4 layers absorbent gauze and porous bandage.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Afterwards removal of the dressing, rinsing of the application site with warm water.
- Time after start of exposure: 24 hours.

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg b.w.;
- Concentration (if solution): 50 %;
- Constant volume or concentration used: yes, 4 mL/kg b.w.;
- For solids, paste formed: yes; test substance is insoluble in water; using olive oil a suspension was prepared.

Duration of exposure:

Single application with a semiocclusive dressing for 24 hours.

Doses:

2000 mg/kg b.w.

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days;
- Frequency of observations: Recording of signs and symptoms several times on the day of application, at least once each workday. Check for moribund and dead animals twice each workday and once on holidays.
- Scoring of skin findings: 30 - 60 minutes after removal of the semiocclusive dressing and then about one week later and before termination of the study.
- Necropsy of survivors performed: yes. Withdrawal of food about 16 hours before sacrifice.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Remarks on result:

other: 0/10 animals died

Mortality:

No mortality observed.

Clinical signs:

other: No abnormalities detected.

Gross pathology:

No pathological findings noted.