Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1978
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1978
Report Date:
1978

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 434 (Acute Dermal Toxicity - Fixed Dose Procedure)
Deviations:
not specified
GLP compliance:
no
Test type:
fixed dose procedure
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
None
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: 79579176, DCT # 80226

Test animals

Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: approximately 8 to 11 weeks
- Housing: The rabbits were individually housed in elevated wire mesh cages in temperature controlled rooms reserved exclusively for rabbits on acute tests.
- Diet (e.g. ad libitum): Purina Rabbit Chow, ad libitum
- Water (e.g. ad libitum): water from bottles were available ad libitum
- Acclimation period: The rabbits were equilibrated for at least 7 days.

Administration / exposure

Type of coverage:
occlusive
Vehicle:
not specified
Details on dermal exposure:
24 hours prior to dosing the backs of the rabbits were clipped free of fur with an Oster ANG-RA clipper head designed specifically for clipping rabbits. The rabbits were returned to their cages overnight. Just prior to dosing, the backs of even-numbered rabbits were abraded with a 21 gauge bent tip needle. The abrasions, made every 2 to 3 cm longitudinally, scratched the stratum corneum, but did not disturb the derma or produce bleeding.

Following removal of the binder at 24 hours, the test site was washed with warm tap water. One hour after washing, the test site were graded for skin irritation .

Evaluation of skin reactions:
Erythema & Eschar Formation:
- No erythema: 0
- Very slight erythema (barely perceptible): 1
- Well defined erythema: 2
- Moderate to severe erythema: 3
- Severe erythema (beet redness) to slight eschar formation (injuries in depth): 4

Edema Formation:
- No edema: 0
- Very slight edema (barely perceptible): 1
- Slight edema (edges of area well defined by definite raising): 2
- Moderate edema (raised approximately 1 millimeter): 3
- Severe edema (raised more than 1 millimeter and extending beyond the area of exposure): 3
Duration of exposure:
24 hours
Doses:
2000 mg/kg
No. of animals per sex per dose:
4 rabbits (2 males and 2 females)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Rabbits observed daily and body weight were recorded pretest and at 7 and 14 days.
- Necropsy of survivors performed: Yes
- Other examinations performed: clinical signs, body weight.

Results and discussion

Preliminary study:
None
Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
One animal died at day 1 of the experiment (Animal number 3).
Clinical signs:
- Few or no feces present in pan: Animal #2, days 9-14.
- Lethargy: Animal #2, days 11-14.
- Ptosis: Animal #2, day 13.
- Yellow nasal discharge: Animal #4, days 5 & 6.
Body weight:
- Rabbit 1 (M): day 0: 1.9 kg / day 7: 2.3 kg / day 14: 2.4 kg.
- Rabbit 2 ab.(M): day 0: 2.3 kg / day 7: 2.3 kg / day 14: 2.4 kg.
- Rabbit 3 (F): day 0: 2.1 kg Dead day 1.
- Rabbit 4 ab.(F): day 0: 2.5 kg / day 7: 2.5 kg / day 14: 2.6 kg.
ab.: Abraded.
Gross pathology:
Necropsy observations:
- Animals 1&4: normal.
- Animal 2: Bloated intestines.
- Animal 3: Brown exudate, anogenital area, yellow areas on intestines, dark & mottled liver, dark areas on lungs, large spleen.

Any other information on results incl. tables

Individual body weight and skin grades:

 Rabbit number  Sex        Weights-kg
     0  7  14
 1  M  1.9 2.3  2.4 
 2 ab  M  2.3 2.3  2.4 
 3  F  2.1 Died on day 1
 4 ab  F  2.5  2.5 2.6 

ab: Abraded

       Redness        Edema
 25 h 7   14  25 h 7 14
 0  0  0  0  0
 1  1  0  0  0  0
 2  1  0  0  0  0

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The acute dermal LD50 of FAT 40069 in rabbits is greater than 2000 mg/kg bw.
Executive summary:

An acute dermal toxicity was performed for FAT 40069 in rabbits. The test was performed on New Zealand White rabbits at approximately 8 to 11 weeks of age. Twenty-four hours prior to dosing the backs of the rabbits were clipped free of fur with an Oster ANG-RA clipper head designed specifically for clipping rabbits. Just prior to dosing, the backs of even-numbered rabbits were abraded with a 21 gauge bent tip needle. The abrasions, made every 2 to 3 cm longitudinally , scratched the stratum corneum, but did not disturb the derma or produce bleeding. The test material was applied to the backs of 2 male and 2 female rabbits at a dose of 2000 mg/kg bw. The test site was covered with gauze and the trunk was wrapped with impervious material for 24 hours. Following removal of the binder at 24 hours, the test site was washed with warm tap water. One hour after washing, the test site were graded for skin irritation. Skin areas were read again at 7 and 14 days. Bodyweights were recorded pretest and at 7 and 14 days: The rabbits were observed daily for 14 days for signs of toxicity and mortality. Necropsies were performed on all rabbits. Mortality was observed in 1/4 - Animal 3, day 1. Few or no feces present in pan: Animal 2, days 9 -14. In conclusion, the acute dermal LD50 of FAT 40069 in rabbits is greater than 2000 mg/kg bw.