4-[2-(2-amino-4,7-dihydro-4-oxo-3H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoic acid

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

7 December 1994 to 15 Dec 1994

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

other:

Remarks:

Investigations described are insufficiently documented and cannot be subsumed under OECD 402. Therefore a reliability score of 3 is assigned to this study as there is insufficient data in the final report such as sex of animals and lack of COA (certificate of analysis)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1995

Report date:

1995

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Testing conducted to assess the short-term toxicity of the test material in rabbits when administered by a single dermal dose, using three test animals.

GLP compliance:

yes

Test type:

fixed dose procedure

Limit test:

yes

Test material

Test material information

1

Reference substance name:

4-[2-(2-amino-4,7-dihydro-4-oxo-3H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoic acid

EC Number:

429-790-9

EC Name:

4-[2-(2-amino-4,7-dihydro-4-oxo-3H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoic acid

Cas Number:

137281-39-1

Molecular formula:

Hill formula: C15 H14 N4 O3 CAS formula: C15 H14 N4 O3

IUPAC Name:

4-(2-{2-amino-4-oxo-3H,4H,7H-pyrrolo[2,3-d]pyrimidin-5-yl}ethyl)benzoic acid

Test material form:

solid: particulate/powder

Details on test material:

Compound 202723
Storage condition of test material: room temperature

Test animals

Species:

rabbit

Strain:

New Zealand White

Sex:

not specified

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Outside vendor
- Housing: Stainless steel cages
- Diet: ad libitum supply of 'Purina Certified Rabbit Chow #5322' laboratory animal feed
- Water: ad libitum supply of water
- Acclimation period: Minimum of 5 days

ENVIRONMENTAL CONDITIONS
- Humidity: 25 -60% which exceeded the range (40-70%) specified in the protocol had no apparent impact on the outcome of this study

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: Back of the animal
- % coverage: 10% of the animal's body surface area
- Type of wrap if used:4 ply gauze dressing

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Using gauze moistened with distilled water
- Time after start of exposure: 24 -hours

TEST MATERIAL
- Amount(s) applied: A level of 1000mg/kg body weight to approximately 10% of the animal's body surface area which was calculated using the formula presented below.
- For solids, paste formed: no

Duration of exposure:

24 hour

Doses:

1000 mg/kg

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: Twice daily on the day of administration (day 0) then once daily thereafter (days 1 -14), any signs of irritation were assessed using the Draize dermal evaluation criteria
- Body Weights: Prior to dosing on day 0 and on days 7 and 14
- Necropsy of survivors performed: no

Statistics:

None performed

Results and discussion

Effect levels

Sex:

not specified

Dose descriptor:

other: median lethal dose

Effect level:

> 1 000 mg/kg bw

Based on:

test mat.

Mortality:

0 of 3

Clinical signs:

very slight erythema in 3/3 animals on day 1-2 of occurrence; very slight edema for 1/3 animals on day 1 of occurrence; ancillary irritation on the trunk outside the test site for 2/3 animlas on day 1-5 of occurrence.

Body weight:

Not available

Gross pathology:

Not available

Any other information on results incl. tables

Table 1 - Summary of clinical observations made after dermal administration of a single dose of 1000mg/kg of Compound 202723

Slight abnormalities	Animals Affected No. Observed/No. Dosed	Day(s) of Occurrence
Mortality	0/3	-
Very slight erythema	3/3	1 -2
Very slight edema	1/3	1
Ancillary irritation on the truck outside the test site	2/3	1 -5

The calculated primary irritation index was 0.78 which classifies this dose level as a slight irritant to the dermal tissue of the rabbit.

Applicant's summary and conclusion

Interpretation of results:

other: not classified

Conclusions:

Based on the results, the test substance does not require any classification according to EU standards. No mortality or toxicity observed at 1000mg/kg, the highest dose tested. The criteria for classification are not fulfilled for dermal toxicity Categories 1 -3. Classification for Category 4 via application of substance criteria is not possible since acute toxicity test was not available between 1000mg/kg and 2000mg/kg.

Executive summary:

Short term dermal toxicity of compound 202723 was investigated in 3 New Zealand white rabbits at a dose level of 1000mg/kg.

No mortalities occurred and animals were examined for signs of clinical abnormalities each day throughout the 14 day observation period. Very slight irritation, erythema and edema were observed. The calculated Primary Irritation Index was 0.78, which classifies this dose level as a slight irritant to the dermal tissue of the rabbit. Based on the results of this study, the acute dermal Median lethal dose (MLD) of compound 202723 was estimated to be greater than 1000mg/kg in the rabbit.