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Acute Toxicity: dermal

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Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 04 MAY 2010 to 25 MAY 2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2010
Report date:
2010

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Urea, reaction products with formaldehyde, glyoxal and methanol
EC Number:
296-665-1
EC Name:
Urea, reaction products with formaldehyde, glyoxal and methanol
Cas Number:
92908-36-6
Molecular formula:
C2 H2 O2 .C H4 N2 O .C H4 O .C H2 O
IUPAC Name:
Urea, reaction products with formaldehyde, glyoxal and methanol
Test material form:
liquid: viscous
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Name of the test material (as cited in the report): Arkofix RCH
- Batch No.of test material: OP1
- Expiration date of the lot/batch: 16-Oct-2014
- Certificate of analysis: N° 1873, 15/04/2010

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Stability of Test Item: Stable under storage conditions
- Stability of Test Item Dilution: Stable in water
- Storage Conditions: At room temperature (range of 20 ± 5 °C, provided by Harlan Laboratories Ltd.), light protected.

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Harlan Laboratories B.V., Kreuzelweg 53, 5961 Horst / The Netherlands
- Age when treated: males: 19 weeks, females: 11 weeks
- Body weight when treated: 298.7 - 376.7 g (males), 197.0 - 208.8 g (females)
- Housing: During acclimatization in groups of five per sex in Makrolon type-4 cages with standard softwood bedding. Individually in Makrolon type-3 cages with standard softwood bedding (Lignocel, J. Rettenmaier&Söhne GmbH&CoKG, 73494 Rosenberg / Germany, imported by Provimi Kliba AG, 4303 Kaiseraugst / Switzerland) during treatment and observation. Paper enrichment, Reference no. 207057, batch no. 69, (Enviro-dri from Lillico, Biotechnology, Surrey / UK) was included.
-Diet: Pelleted standard Provimi Kliba 3433 rat/mouse maintenance diet, batch no. 83/09 (Provimi Kliba AG, 4303 Kaiseraugst / Switzerland) ad libitum.
- Water: Community tap water from Füllinsdorf ad libitum.
Acclimatization period: 04-May-2010 to 10-May-2010

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 3 °C
- Humidity: between 30 - 70%
- Air changes:10 - 15 air changes per hour
- Photoperiod: 12 hours light and 12 hours dark

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
water
Details on dermal exposure:
TEST SITE
- Area of exposure: approx. 25 cm²
- Approximately 10% of the total body surface
-Type of wrap: semi-occlusive dressing wrapped around the trunk and fixed with an elastic adhesive bandage

REMOVAL OF THE TEST MATERIAL
Twenty-four hours after the application the dressing was removed and the skin was flushed with lukewarm tap water and drapped off with disposable paper towels.
Duration of exposure:
24 hours
Doses:
2000 mg/kg
No. of animals per sex per dose:
5 (see table 1)
Control animals:
not required
Details on study design:
One day before treatment, the backs of the animals were clipped with an electric clipper, exposing an area of approximately 10% of the total body surface.
Only those animals without injury or irritation on the skin were used in the test.

On test day 1, the test item was applied at a dose of 2000 mg/kg body weight evenly on the intact skin with a syringe and covered with a semi-occlusive dressing. The dressing was wrapped around the trunk and fixed with an elastic adhesive bandage.

The application volume was 4 mL/kg.
Twenty-four hours after the application the dressing was removed and the skin was flushed with lukewarm tap water and drapped off with disposable paper towels. Thereafter, the reaction sites were assessed.

All animals were re-shaved on test day 8 to facilitate the reading of the local reactions.

- Duration of observation period following the administration: 15 days
- frequency of observation and weighing:
Viability / Mortality: Daily during the acclimatization period. Once before treatment, within the first 30 minutes and at approximately 1, 2, 3 and 5 hours after administration on test day 1 (with the clinical signs) and twice daily during days 2-15.
Clinical Signs: Daily during the acclimatization period. Once before treatment, within the first 30 minutes and at approximately 1, 2, 3 and 5 hours after administration on test day 1. Once daily during days 2-15.
Local Dermal Signs: Once daily during days 2 (following dressing removal) through day 15. Scoring according to the Commission Regulation (EC) No 440/2008 of 30 May 2008 laying down test methods pursuant to Regulation (EC) No 1907/2006 of the European Parliament and of the Council on the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH), B.4 ACUTE TOXICITY: DERMAL IRRITATION/CORROSION (Official Journal No L 142, 31/05/2008 p. 0182-0190.
Body Weights: On test days 1 (prior to administration), 8 and 15.
Necropsy: all 5 males and 5 females

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
No deaths occurred during the course of the study.
Clinical signs:
No clinical signs were observed throughout the entire 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 recorded at necropsy.
Other findings:
The test item caused slight to moderate yellow staining of the treated skin in four males and two females throughout the observation period.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The median lethal dose of the test item 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
Executive summary:

Five male and five female RccHan:WIST (SPF) rats were treated with test item at 2000 mg/kg by dermal application. The test item was formulated in purified water at a concentration of 0.5 g/mL and administered at a volume dosage of 4 mL/kg. The application period was 24 hours.
 
The animals were examined daily during the acclimatization period and mortality, viability and clinical signs were recorded. All animals were examined for clinical signs before treatment, within the first 30 minutes and at approximately 1, 2, 3 and 5 hours after treatment on day 1 and once daily during test days 2-15. Local signs were noted once daily from test day 2 to 15. Mortality/viability was recorded before treatment, within the first 30 minutes and at approximately 1, 2, 3 and 5 hours after administration on test day 1 (with the clinical signs) and twice daily during days 2-15. 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 course of the study.
 
The test item caused slight to moderate yellow staining of the treated skin in four males and two females throughout 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.