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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:
07 September 1994 to 14 June 1995
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1995
Report date:
1994

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
EPA OPP 81-2 (Acute Dermal Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Glutaral
EC Number:
203-856-5
EC Name:
Glutaral
Cas Number:
111-30-8
Molecular formula:
C5H8O2
IUPAC Name:
glutaraldehyde
Test material form:
liquid
Specific details on test material used for the study:
- Name of test material (as cited in study report): Glutaraldehyde, obtained from BASF Corporation
- Physical state: clear colorless liquid
- Analytical purity: 50.2%
- Composition of test material, percentage of components: 50.2% aqueous solution
- Lot/batch No.: V6-612

Test animals

Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Hazleton Research Products, Inc., Denver, PA
- Age at study initiation: young adults were used
- Weight at study initiation: 2363 to 2521 g
- Housing: individually, in suspended mesh-bottom cages
- Diet (e.g. ad libitum): Purina Certified Rabbit Chow #5312, ad libitum
- Water (e.g. ad libitum): municipal water, ad libitum
- Acclimation period: at least 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-22 °C
- Humidity (%): 36-62%
- Photoperiod (hrs dark / hrs light): 12 h/12 h

REMARK:
- Analysis of feed was performed and provided by the manufacturer
- Analysis of water was performed according to Standard Operation Procedures (SOP)
- Contaminants were not present in animal feed or water at levels expected to interfere with the objectives of the study

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: intact clipped skin on the backs of the animals
- % coverage: the area covered was about 23% of the total body surface
- Type of wrap if used: the application site was covered with gauze binders, which were again secured by means of non-irritating adhesive tape. Each animal received a collar

REMOVAL OF TEST SUBSTANCE
- Washing: each application site was gently cleaned with lukewarm water
- Time after start of exposure: 24 hours

TEST MATERIAL
- The test material was dosed based on density (specific gravity). The dose volume was determined by dividing the dose level (g/kg) by the specific gravity (1.02 g/ml)
- The individual dose was determined on the basis of the body weight and a dose volume of 1.96 ml/kg bw; thus, the final test concentration was 2000 mg/kg bw
Duration of exposure:
24 hours
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
Five/sex/group
Control animals:
no
Details on study design:
The animals were observed for mortality (after the first 1, 3 and 4 hours, and twice a day thereafter until day 14), clinical signs of toxicity (after the first 1, 3 and 4 hours, and once a day thereafter until day 14) and local skin changes (after 30 to 60 minutes following removal of the dressing, and daily thereafter until day 14); body weights were recorded on day 0, 7 and 14. At the end of the observation period, the animals were sacrificed for the purpose of necropsy.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred.
Clinical signs:
Two males and one female showed mucoid feces on day 1 to 2 of treatment; one female showed wet brown urogenital staining about 4 hours after application. From day 3 of observation, no more signs of toxicity were seen and all animals appeared normal.
Body weight:
Body weights were inconspicuous over the complete period of observation.
Gross pathology:
Necropsy revealed thickening and scabbing of the application sites in all animals. No further treatment-related abnormalities were reported.
Other findings:
Local skin changes:
The treatment resulted in severe erythema, moderate to severe edema and eschar with subsequent exfoliation in all animals. In 6 case, the application sites displayed signs of corrosion. Fissuring of the skin was seen in 9 cases after day 6, and on day 7, yellow staining and desquamation were seen in all animals. These severe signs of skin irritation persisted over the complete period of observation in all animals.

Applicant's summary and conclusion