Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
June 1959
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The study was performed pre-OECD guidelines and pre-GLP. The methods used are similar to OECD402. There is no information on substance composition in the report, no CoA.
Cross-reference
Reason / purpose:
reference to same study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1959
Report Date:
1959

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
no
Remarks:
pre-GLP
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
VP-7 or 2-5 bis (tert-butyl peroxy)-2, 5 dimethylhexane
pale-yellow clear liquid identified

Test animals

Species:
rabbit
Strain:
not specified
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: no data
- Age at study initiation: no data
- Weight at study initiation: 1.9-2.5 kg
- Fasting period before study: no data
- Housing: individual
- Diet (e.g. ad libitum): ad libitum, rabbot chow and fresh greens
- Water (e.g. ad libitum): ad libitum
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): no data
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): no data

IN-LIFE DATES: no data

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: entire trunk area
- % coverage: no data
- Type of wrap if used: impervious plastic sleeve contricted at the ends to prevent leakage

REMOVAL OF TEST SUBSTANCE
- Washing (if done): excess material was removed
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): between ± 1-17 grams
- Concentration (if solution): not applicable
- Constant volume or concentration used: no
- For solids, paste formed: no applicable
Duration of exposure:
24 hours
Doses:
0.512, 2.048, 3.072, 4.096, 8.192 g/kg
No. of animals per sex per dose:
From low to high dose: 1, 6, 5, 6, 5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: bodyweight was determined on day 1 and 14. observations were made of the condition of the skin, the physical apperance of the animal and behavior.
- Necropsy of survivors performed: yes
- Other examinations performed: histopathology: the liver, kidney, spleen, skin and lungs of representative rabbits were examined.
Statistics:
No data

Results and discussion

Effect levels
Sex:
male
Dose descriptor:
LD50
Effect level:
4 100 mg/kg bw
Based on:
test mat.
Remarks on result:
other: ± 1300 mg/kg bw
Mortality:
Deaths occured within 24 hours at the highest dose level. The rapidity with which lethality followed was proportional to the dose level applied (see table 1).
Clinical signs:
Hind limb weakness, and respiratory slowing preceded death by several days in all but one of the rabbits that died.
Body weight:
No effects observed.
Gross pathology:
Necropsy revealed no significant gross pathology in the rabbits at any of the 5 treatment levels.
Other findings:
- Histopathology:
Histopathological examinations were made of the livers, kidney, spleens, lungs and the treated skin areas of the 7 rabbits at the critical or lethal levels.
The treated skin areas included subepidermal fibrosis (in the animal at the 3 g/kg) and subepidermal inflammation and necrosis at the 4 and 8 g/kg, the severity increasing with the dosage.
Acanthosis (diffuse epidermal hyperplasia) was seen in one rabbit at 4 and 1 rabbit at 8 g/kg. The latter is regarded a significant adverse finding.

Applicant's summary and conclusion

Interpretation of results:
study cannot be used for classification
Remarks:
Migrated information
Conclusions:
The LD50 is 4100 mg/kg bw ± 1300.
Executive summary:

23 healthy albino male rabbits weighing 1.9 -2.5 kg were depilated over the entire trunk area. Graded doses of undiluted test material were applied and maintained in contact with the skin by encasing the trunk in an impervious platic sleeve constricted at the end to prevent leakage. Contact was continued for a 24 hour period during which the animals were restrained in stocks. Doses of 0.512, 2.048, 3.072, 4.096, 8.192 g/kg were applied. Bodyweight was determined on day 1 and 14. Observations were made of the condition of the skin, the physical apperance of the animal and behavior.

Deaths occured within 24 hours at the highest dose level. The rapidity with which lethality followed was proportional to the dose level applied (see table 1). Hind limb weakness, and respiratory slowing preceded death by several days in all but one of the rabbits that died. There was no effect on bodyweight. Necropsy revealed no significant gross pathology in the rabbits at any of the 5 treatment levels. Histopathological examinations were made of the livers, kidney, spleens, lungs and the treated skin areas of the 7 rabbits at the critical or lethal levels.

The treated skin areas included subepidermal fibrosis (in the animal at the 3 g/kg) and subepidermal inflammation and necrosis at the 4 and 8 g/kg, the severity increasing with the dosage. Acanthosis (diffuse epidermal hyperplasia) was seen in one rabbit at 4 and 1 rabbit at 8 g/kg. The latter is regarded a significant adverse finding.

The LD50 is 4100 mg/kg bw ± 1300.