Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1991
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP compliant, comparable to guideline study with acceptable restrictions

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1991
Report Date:
1991

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): identification number: LF-9128 (TA 691)
- Physical state: a clear, colorless liquid
- Stability at test conditions: stable
- Storage: refrigerated (approximately 3°C).

Test animals

Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Johnson Rabbit Ranch (Wilkinson, IN)
- Age at study initiation: 3-4 months
- Weight at study initiation: 3.16-3.30 kg
- Housing: individually
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: one week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23
- Humidity (%): 32
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: 240 cm2 (fur was clipped from the exposure sites)
- Type of wrap if used: application site (12.8 x 11.5) covered with surgical dressing and covered with plastic film

REMOVAL OF TEST SUBSTANCE
- Washing (if done): rinsed with light mineral oil
- Time after start of exposure: 24 hours
Duration of exposure:
24 h
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5 male, 5 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: up to 14 days
- Frequency of observations and weighing: 0.5, 0.75, 2, 3, 4.25 and 6 hours after dosing and once a day for 14 days after removal of wrappings
- Examinations performed: clinical signs, skin abnormalities, body weights, gross necropsy.
Statistics:
Statistical analyses were used to analyse the results: calculation of standard deviations.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
No mortality occurred.
Clinical signs:
One rabbit was vocal immediately upon test article administration. All of the rabbits exhibited rapid respiration lasting 1-2 hours after dosing.
Body weight:
All rabbits gained weight during the study.
Gross pathology:
Gross necropsy findings were within normal limits in eight rabbits. One male had white areas on its liver, while a female had only one kidney which was enlarged; these conditions were not considered treatment related.
Other findings:
Dermal irritation (i.e., edema and erythema) was observed within the application site of all rabbits following removal of the wrappings, and eschar formation developed in all rabbits 2 to 7 days later. The scab formation in 3 rabbits sloughed off prematurely, probably as a result of grooming, and raw skin was exposed beneath. New and/or repaired skin was observed in six rabbits, while seven rabbits displayed superficial flaking at the application site. None of the rabbits completely recovered from all signs of dermal irritation before the end of the 14-day observation period.

Applicant's summary and conclusion