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Toxicological information

Acute Toxicity: dermal

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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: GLP-study according to OECD guideline 402

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1992
Report Date:
1992

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
low animal number
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Lot No.: V 56/92 1. FRAKT.
- Date of manufacturing: 1992-3-19
- Physical state: Liquid, achromatic (at room temperature); solid, crystalline (at about -20°C)
- Storage condition of test material: Deep-freeze; sensitive to hydrolysis (tightly closed); the storage stability of the test substance over the study period was guaranteed by reanalysis
- Analytical purity: >99%

Test animals

Species:
rabbit
Strain:
Vienna White
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Gaukler, Offenbach/Main, Germany
- Age at study initiation: young adult animals
- Weight at study initiation: animals of comparable weight (2.0-3.0 kg)
- Housing: Single housing in cages made of stainless steel with wire mesh walk floors; floor area 40 x 51 cm; no bedding in the cages; sawdust in the waste trays
- Diet: Kliba Labordiaet 341, 4 mm (Klingentalmuehle AG, Kaiseraugst, Switzerland), about 130 g per animal per day
- Water: about 250 ml tap water per animal per day
- Acclimation period: at least 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24°C
- Humidity (%): 30-70%
- Photoperiod (hrs dark / hrs light): 12 / 12 (18.00 - 6.00 h dark / 6.00 - 18.00 h light)

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
other: undiluted
Details on dermal exposure:
TEST SITE
- Area of exposure: clipped epidermis (dorsal and dorsolateral parts of the trunk)
- % coverage: at least 10% of the body surface (about 200 cm²)
- Type of wrap if used: four layers absorbent gauze (Ph. Eur. Lohmann GmbH&Co. KG) and Fixomull stretch (Adhesive fleece; Beiersdorf AG)

REMOVAL OF TEST SUBSTANCE
- Washing: rinsing of the application site with warm water
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount applied: 1.98 ml/kg bw
- Concentration: undiluted
Duration of exposure:
24 h
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
3 males and 3 females per dose
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Recording of signs and symptoms several times on the day of administration, at least once each workday for the individual animals. A check was made twice each workday and once on saturdays, sundays and on public holidays for general observations and for any dead or moribund animals. Individual reedings for the scoring of skin findings (according to Draize JH, 1959: Appraisal of the safety of chemicals in foods, drugs and cosmetics. The association of food and drug officials of the United States, Austin, Texas) were performed 30-60 min after removal of the semiocclusive dressing (day 1), weekly thereafter and at the end of the study (last day of observation period). Individual body weights were determined shortly before application (day 0), weekly thereafter and at the end of the study (before fasting period).
- Necropsy of survivors performed: yes (withdrawal of food at least 16 h before killing with CO2; then necropsy with gross pathology examination)

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
1 male after day 1
Clinical signs:
no abnormalities
Body weight:
Normal body weight gains. For details see table below.
Gross pathology:
Animal that died (1 male): general congestion; heart: dilation, right ventricle
Sacrificed animals (2 males, 3 females): no pathologic findings
Other findings:
Scaling of local effects at the readings of days 7 and 14 (males) and day 7 (females).

Any other information on results incl. tables

day 0 day 7 day 13
Males 2.7 2.81 2.93
Females 2.66 2.83 2.94

Applicant's summary and conclusion

Interpretation of results:
practically nontoxic
Remarks:
Migrated information criteria for interpretation: EU
Conclusions:
The acute dermal LD50 of the test material is >2000 mg/kg bw for male and female rabbits.
Executive summary:

The study was a GLP-study according to OECD guideline 402 without restrictions.

The acute dermal toxicity of the test substance was investigated in a group of 3 male and 3 female Vienna White rabbits. The test material was applied undiluted to the clipped epidermis (dorsal and dorsolateral parts of the trunk) of each animal at a dose level of 2000 mg/kg bw, and was covered by a semiocclusive dressing for 24 h.

There were no signs of systemic toxicity. After the removal of the dressing no skin reactions could be observed. All animals exhibited scaling of skin findings 7 days after application. This skin reaction persisted in the male animals until study termination (day 14). The expected body weight gain was observed. One male animal died one day after application (no further mortality). Necropsy of the animal that died revealed general congestion and dilation of the right ventricle of the heart. No abnormalities were observed at the end of the study in the surviving animals.

Conclusions: The acute dermal LD50 of the test material is >2000 mg/kg bw for male and female rabbits.