Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
31 October, 1983 - 29 November, 1983
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1983
Report Date:
1983

Materials and methods

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

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid
Specific details on test material used for the study:
- Name of test material (as cited in study report): 5601-23-1
- Substance type: clear liquid
- Physical state: liquid
- Stability under test conditions: There was no apparent change in the physical state of the test article during administration
- Other: Order No.: J-171

Test animals

Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Sgarlat's Rabbitry, Harvey's Lake, Pennsylvania
- Weight at study initiation: 2 - 3 kilograms
- Fasting period before study: no data
- Housing: Rabbits were housed individually in cages sized in accordance with the "Guide for the Care and Use of Laboratory Animals" of the institute of Laboratory Resources, National Research Council.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20°C ± 3°C
- Humidity (%): 30 to 70%
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12 hours light, 12 hours dark

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: trunk, dorsal area
- % coverage: no less than 20% of the dorsal body surface area was available for application of the test article
- Type of wrap if used: A layer of gauze was wrapped around the animals to cover the dosed area. The animals were wrapped with rubber dam and an ace bandage to retard evaporation.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Following the 24 hour period of exposure, the rubber dam and ace bandage were removed. The test site was washed to remove any remaining material.
Duration of exposure:
24 hours
Doses:
dose-range finding study: 1000, 3000, 5000 and 8000 mg/kg
definitive dermal LD50 determination: 2500, 3200, 4000 and 5000 mg/kg
No. of animals per sex per dose:
2
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observations for mortality and clinical signs were recorded at 30 minutes, 2 and 4 hours after the 24 hour period of exposure, and twice daily thereafter for fourteen days.
- Necropsy of survivors performed: yes
Statistics:
The LD50 was determined by the method of Litchfield and Wilcoxon (1949), JPET 96: 99-114

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
3 570 mg/kg bw
Based on:
test mat.
95% CL:
2 900 - 4 380
Mortality:
None of the rabbits died at 2500 mg/kg, two of four rabbits died at 3200 and 4000 mg/kg, and four of four died at the 5000 mg/kg dose level.
Clinical signs:
Signs observed included necrosis and edema of the application sites, decreased activity, ptosis, cyanosis, loss of righting, semiprostration, body drop, ataxia, abnormal stance and abnormal gait. A lack of defecation at 24 hours post treatment was also observed.
Gross pathology:
Necropsy of the animals dying on study revealed hemorrhages of the muscle layers at the application sites, discolored thymus and dark fluid-filled bladders. Terminal necropsy revealed hemorrhages in the muscle layers at the application sites. The liver was adhered to the abdominal wall in one rabbit.

Any other information on results incl. tables

Dose-range finding study:

Signs observed included necrosis, edema, ptosis, semiprostration, decreased activity, body drop, abnormal gait and cyanosis. None of the rabbits died at the 1000 or 3000 mg/kg dose levels. One of two rabbits died at the 5000 mg/kg dose level and tow of two died at 8000 mg/kg.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Based upon the observations made in the acute dermal toxicity study in rabbits, the calculated dermal LD50 for test article 5601-23-1 was determined to be 3570 mg/kg with 95% confidence limits of 2900 to 4380 mg/kg.