Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Not applicable
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: meets generally accepted scientific standards, well-documented, and acceptable for assessment

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1980
Report Date:
1980

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Principles of method if other than guideline:
Pharmacology Lab Protocol
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): AMP

Test animals

Species:
rabbit
Strain:
not specified
Sex:
male/female
Details on test animals and environmental conditions:
12 Rabbits weighing 3.0 ± 0.5 kg (6 male, 6 female)
8 Rabbits weighing 2.5 ± 0.5 kg (4 male, 4 female)

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
1st part of study:
12 Rabbits were divided into 3 groups of 4 each (2 male and 2 female per group), and their abdomens were shaved free of hair. The skin of 2 rabbits per group (1 male and 1 female) were further prepared by abrasions. The abrasions were made 2-3 cm apart over the area of exposure with a blunt hypodermic needle without bleeding.

Each group of rabbits was treated with either 1000, 1500, or 2000 mg of test material per kg body weight (mg/kg). The desired dose was spread over the prepared abdominal skin area (abraded or smooth as designated). The skin was covered with a gauze and a sheet of impervious rubberized cloth to prevent any loss of the test material. The trunk was further enclosed with a flexible wire screen held in place by tape. The animals were returned to individual cages.

After 24 hours of dermal exposure, the bindings and patches were removed and the exposed areas gently cleaned and checked for irritation.

2nd part.
Upon completion of the 1st part of the study an additional 8 animals (4 male and 4 femal) were prepared in the same way as above, with the exception that all 8 animals were given abraded skin. These animals were then exposed to 2000 mg/kg bw using the same occluded dressings described above. After 24 hours exposure these animals had their dressings removed and the exposed area washed gently and examined for signs of irritation. These animals were also observed for a further 14 days.
Duration of exposure:
24 hours
Doses:
1000, 1500, or 2000 mg of test material per kg body weight (mg/kg) (doses calculated for each animal based on individual bodyweight)
No. of animals per sex per dose:
4 rabbits/dose, then an additional 8 animals at 2000 mg/kg
Control animals:
no
Details on study design:
Rabbits were weighed at the start of the study and at the end of the 14 day observation period.

All animals were sacrificed at the end of the study and necropsied to assess gross pathology. There was no Hematology, clinical chemistry or histopathology carried out on any of the animals.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
None
Clinical signs:
At the end of the 24 hour exposure period, the intact and abraded treated skin sites were severely irritated and black in color. The sites became necrotic within two to three days and remained necrotic for the 14 days. The treated sites had severe eschar formation by the 14th day.

The animals in all treated groups showed no signs of toxicity or abnormal pharmacological behavior.
Body weight:
The rabbits in the three treatment groups lost body weight over the 14 day observation period.
Gross pathology:
At necropsy, all organs in all rabbits were grossly normal. The treated skin sites in all rabbits were necrotic.
Other findings:
Not applicable

Any other information on results incl. tables

Not applicable

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute dermal LD50 for P-1826 for the rabbit was >2000 mg/kg. The test material was dermally nontoxic, but was a severe skin irritant.
Executive summary:

P-1826 (AMP, 2-amino-2-methyl-l-proano1) was tested for acute dermal toxicity using 12 rabbits. The Rabbits were split into 3 groups of 4. All rabbits had their abdomens shaved free of hair, 2 animals in each group also had their skin abraded using a blunt hypodermic needle. The test material was applied at doses of 1000, 1500 or 2000 mg/kg bw under an occluded dressing for 24 hours. After the exposure period the rabbits were observed for a further 14 days. Following this first test an additional 8 rabbits were used. The abdomen of each rabbit was shaved and then abraded using a blunt hypodermic needle. These rabbits were exposed for 24 hours to 2000 mg/kg bw AMP and then followed for a further 14 days. A t the end of 24 hr exposure, the intact andabraded treated skin sites were severely irritated and black in color. The sites became necrotic within two to three days and remained necrotic for the 1 4 days. The treated sites had severe eschar forrnation by the 14th day, The rabbits in the three treatment groups lost body weight over the two-week observation period. The animals in all the treated groups showed no signs of toxicity or abnormal pharmacological behavior. At necropsy the organs in all rabbits were grossly normal. The treated skin sites in all the rabbits were necrotic. In conclusion, AMP was dermally nontoxic (LD50 > 2000 mg/kg), but was a severe skin irritant.