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Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2002-03-01 - 2002-05-13
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2002
Report date:
2002

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
OECD Guidelines for Testing of Chemicals, Section 4, Number 402 "Acute Dermal Toxicity", adopted February 24, 1987.
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Version / remarks:
Directive 92/69/EEC, B.3. "Acute Toxicity-Dermal", July 31, 1992
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
standard acute method
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
6-amino-1,3-dimethyluracil
EC Number:
229-662-0
EC Name:
6-amino-1,3-dimethyluracil
Cas Number:
6642-31-5
Molecular formula:
C6H9N3O2
IUPAC Name:
6-amino-1,3-dimethylpyrimidine-2,4(1H,3H)-dione
Test material form:
solid
Specific details on test material used for the study:
- Storage condition of test material: at room temperature, (range of 20 ± 3 °C), away from direct sunlight
- Stability under test conditions: Stable under storage conditions
- Stability of test item in vehicle: 90 days in PEG 300 at room temperature

- Final dilution of a dissolved solid, stock liquid or gel: The dose formulation was made shortly before administration.
The test item was weighed into a tared glass beaker on a suitable precision balance and the vehicle added (weight:volume). The formulations were prepared using a magnetic stirrer.
Homogeneity of the test item in the vehicle was maintained during administration using a magnetic stirrer.

Test animals

Species:
rat
Strain:
other: HanBrl: Wist (SPF)
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: RCC Ltd, Biotechnology & Animal Breeding Division CH-4414 Füllinsdorf/Switzerland
- Number of animals per group: 5 males and 5 females
- Age at study initiation: Males: 8 weeks, Females: 10 weeks
- Housing: During acclimatization in groups of five in Makrolon type-4 cages with standard softwood bedding. During treatment and observation individually in Makrolon type-3 cages with standard softwood bedding ("Lignocel", Schill AG, CH-4132 Muttenz).
- Diet (e.g. ad libitum): Pelleted standard Kliba 3433 rat/mouse maintenance diet, batch no. 119/01 (Provimi Kliba AG, CH-4303 Kaiseraugst/ Switzerland) ad libitum.
- Water (e.g. ad libitum): Community tap-water, from Füllinsdorf ad libitum.
- Acclimation period: Under laboratory conditions for 1 week, after health examination. Only animals without any visible signs of illness were used for the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3°C
- Humidity (%): 30-70%
- Air changes (per hr): 10-15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours fluorescent light/12 hours dark, music during the light period.

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
water
Remarks:
Purified water (deionised water which was processed and treated by the PURELAB Option-R unit. This latter links four purification technologies: reverse osmosis, adsorption, ion-exchange and photo oxidation)
Details on dermal exposure:
TEST SITE
- Area of exposure: the backs of the animals, an area of approximately 10 % of the total body surface
- Type of wrap if used: a semi-occlusive dressing was wrapped around the abdomen and fixed with an elastic adhesive bandage.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the skin was flushed with lukewarm tap water and dried with disposable paper towels
- Time after start of exposure: 24 hours after the application

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): the test item was applied at a dose of 2000 mg/kg body weight
Application volume/kg body weight: 4ml

VEHICLE
- Amount(s) applied (volume or weight with unit): test item formulated ad 4 ml /kg bw
- Concentration (if solution): 50%
Duration of exposure:
24 hours
Doses:
2000 mg/kg body weight
No. of animals per sex per dose:
5 males and 5 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Mortality / Viability: Daily during acclimatization and twice daily during days 1-15. Body weights on test days 1 (prior to administration), 8 and 15. Clinical signs daily during acclimatization and at approximately 1, 2, 3 and 5 hours after administration on test day 1. Once daily during days 2-15. All abnormalities were recorded.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Statistics:
No statistical analysis was used.

Results and discussion

Effect levelsopen allclose all
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Key result
Sex:
male/female
Dose descriptor:
LD0
Effect level:
>= 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
not determinable due to absence of adverse toxic effects
Remarks:
No deaths occurred during the study. No systemic or local signs of toxicity were observed during the study period.
Mortality:
The animals survived the experiment.
Clinical signs:
Following single administration of the test item at a dose of 2000 mg/kg b.w. no clinical signs were observed during the observation period.
Body weight:
The body weight of the animals was within the range commonly recorded for this strain and age.
Gross pathology:
No macroscopic findings were observed at necropsy.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Remarks:
EU implementation
Conclusions:
The study was conducted according to OECD 402 under GLP without deficiencies. Hence, the study can be considered as sufficiently reliable to assess the acute dermal toxicity of the test item to rats.
The median lethal dose of 1,3-DIMETHYL-4-AMINOURACIL after single dermal administration to rats of both sexes, observed over a period of 14 days is:
LD50 (rat): greater than 2000 mg/kg body weight
This is greater than the limit dose for classification as acute toxic Cat. 4 (2000 mg/kg) according to Regulation 1272/2008, hence, the substance does not need to be classified as acutely toxic via the dermal route.
Executive summary:

One group of five male and five female HanBrl: Wist (SPF) rats was treated with 1.3-DIMETHYL-4-AMINOURACIL (CD 19-0456) by dermal application at a dosage of 2000 mg/kg. The test item was diluted in vehicle (purified water) at a concentration of 0.5 g/ml and administered at a volume dosage of 4 ml/kg. The animals were examined daily during the acclimatization period and mortality, viability and clinical signs were recorded. All animals were examined for clinical signs at approximately 1, 2, 3 and 5 hours after treatment on day 1 and once daily during test days 2-15. Mortality/viability was recorded twice daily during test days 1-15. Body weights were recorded on day 1 (prior to administration) and on days 8 and 15. All animals were necropsied and examined macroscopically.

No deaths occurred during the study.

No clinical signs were observed during the observation period.

The body weight of the animals was within the range commonly recorded for this strain and age.

No macroscopic findings were observed at necropsy.