Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2000
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP and guideline compliant study, occlusive coverage

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2000
Report Date:
2000

Materials and methods

Test guidelineopen allclose all
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Qualifier:
equivalent or similar to
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: SLI from Harlan Sprague Dawley, Inc.
- Age at study initiation: 9-11 weeks
- Housing: individually
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 5d

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-22
- Humidity (%): 36-56
- Air changes (per hr): 10/15
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Type of coverage:
occlusive
Vehicle:
water
Details on dermal exposure:
On the following day (day 0), the test article was administered dermally to
approximately 10% of the body surface area. The four corners of this area were
delineated in the clipped area with an indelible marker. The appropriate amount
of test article was moistened with an appropriate amount of deionized water to
form a paste and was then spread evenly over the delineated area and held in
contact with the skin with an appropriately sized 4-ply porous gauze dressing
backed with a plastic wrap which was placed over the gauze dressing (occlusive
binding). Removal and ingestion of the test article was prevented by placing an
elastic wrap over the trunk and test area. The elastic wrap was further secured
with a tape harness on the cranial end of the trunk and then secured with
adhesive tape around the trunk at the caudal end.
Individual doses were calculated based on the animal's day 0 body weight. After
an approximate 24-hour exposure period, the gauze dressing, plastic and elastic
wrap were removed and the corners of the test site re-delineated using a
marker. Residual test article was removed using gauze moistened with
deionized water followed by dry gauze.
Duration of exposure:
24h
Doses:
2000 mg/kg, 100%
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
Clinical Observations
Limit test animals were observed for clinical abnormalities at approximately 1, 2, 4, 8 and 24 hours (post-dose) and daily thereafter (days 1-14). A general health/mortality check was performed twice daily (in the morning and in the afternoon).

Body Weights
Individual body weights were obtained for the limit test animals prior to dosing on day 0 and for all surviving animals on days 7 and 14. The animal found dead after day 9 was also weighed.

Food Consumption
Individual food consumption was recorded for all animals on days 0, 7 and 14. Food was weighed back for the animal found dead.

Gross Necropsy
All limit test animals that died spontaneously during the study or were euthanized by carbon dioxide inhalation at study termination (day 14) were
necropsied. Body cavities (cranial, thoracic, abdominal and pelvic) were opened and examined. Tissues were retained from the animal that died and were preserved in 10% neutral buffered formalin for possible future histopathology.

Dermal Observations
Limit test animals were examined for erythema and edema following patch removal on study day 1 and daily thereafter (days 2-14) according to the
Macroscopic Dermal Grading System which is based on Draize [2]. The dermal test sites were reclipped as necessary to allow clear visualization of the skin.
Statistics:
mean and standard deviation

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
One male was found dead on day 9
Clinical signs:
The most notable clinical abnormalities observed during the study included dark material around the facial area, urine stain and ocular discharge. No dermal irritation was noted at the site of test article application.
Body weight:
Body weight loss was noted for one female during the study day 0-7 body weight interval and for two females during the study day 7-14 body weight interval. Body weight gain was noted for all other surviving animals during the test period.
Gross pathology:
In the animal that died, gross internal findings included abnormal contents in the small intestine, mottled lungs, enlarged spleen, distended urinary bladder and fluid contents in the thoracic cavity. No gross internal findings were observed at necropsy on study day 14.
Other findings:
Although there was a slight increase in males and a slight decrease in females during the second interval, the food consumption was considered to be
comparable between day 0-7 and day 7-14 for both males and females.

Applicant's summary and conclusion

Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of this test, the acute dermal LD50 of the test substance was estimated to be greater than 2000 mg/kg in the rat.
Executive summary:

The single-dose dermal toxicity of the test substance was evaluated on Sprague-Dawley rats. A limit test was performed in which one group of five male and five female rats received a single dermal administration of the test article at a dose of 2000 mg/kg body weight. Following dosing, the limit test rats were observed daily and weighed weekly. Individual food consumption was recorded weekly. A gross necropsy examination was performed on all limit test animals at the time of death or scheduled euthanasia (day 14).

Mortality during the limit test occurred at 2000 mg/kg bw, 1/5 male, 0/5 female.

The one mortality occurred by study day 9. The most notable clinical abnormalities observed during the study included dark material around the facial area, urine stain and ocular discharge. No dermal irritation was noted at the site of test article application. Body weight loss was noted for one female during the study day 0-7 body weight interval and for two females during the study day 7-14 body weight interval. Body weight gain was noted for all other surviving animals during the test period. Although there was a slight increase in males and a slight decrease in females during the second interval, the food consumption was considered to be comparable between day 0-7 and day 7-14 for both males and females. In the animal that died, gross internal findings included abnormal contents in the small intestine, mottled lungs, enlarged spleen, distended urinary bladder and fluid contents in the thoracic cavity. No gross internal findings were observed at necropsy on study day 14.