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Toxicological information

Acute Toxicity: dermal

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Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1995
Report Date:
1995

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
EPA OPP 81-2 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Lot number: 199-7-4
- Expiration date of the lot/batch: not applicable

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature
- Stability under storage conditions: stable
- other information:

Test animals

Species:
rat
Strain:
Sprague-Dawley
Remarks:
albino
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Hilltop Lab Animals, Scottdal, PA.
- Weight at study initiation: males 240-256g, females 218-241g
- Age: young adult
- Housing: Single, in suspended stainless steel caging with mesh floors (conform Guide for the Care and Use of Laboratory Animals (DHEW) (NIH) No. 86.23)
- Diet: Purina Rodent Chow #5012
- Water: Filtered tap water supplied ad libitum by an automatic water dispensing system.
- Identification: each cage was identified with a cage card indicating at least the study number and identification and sex of the animals. A number was allocated to each rat on receipt and a stainless steel ear tag bearing its number was attached to the rat. This number, together with the sequential animal number assigned to the study, constituted unique identification.


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 68-71°F
- Photoperiod (hrs dark / hrs light): 12h light/dark cycle

Administration / exposure

Type of coverage:
not specified
Vehicle:
unchanged (no vehicle)
Remarks:
moistened with water
Details on dermal exposure:
On the day prior to application, a group of animals was prepared by clipping (Oster model # A2 - small) the dorsal area and the trunk. After clipping and just prior to application, the animals were examined for health, weighed (initial) and the skin checked for any abnormalities.

Individual doses were calculated based on the initial bodyweights.

2000 mg/kg bw of the test substance was placed on a 2 1/4 x 3 inch adhesive backed-gauze patch, moistened with distilled watere (1 mL per 1g of test substance), then applied to a dose area of approximately 2 x 3 inch (approximately 10% of the body surface). The patch and the entire trunk of each animal were then wrapped with 3 inch Durapore tape to avoid dislocation of the patch and to minimize evaporation of the test substance. The rats were then returned to their designated cages.

After 24h of exposure to the test substance, the patches were removed and the test sites gently wiped with water and a clean towel to remove any residual test substance.
Duration of exposure:
24 h
Doses:
2000 mg/kg bw/d
No. of animals per sex per dose:
5 males and 5 females
Control animals:
no
Details on study design:
Bodyweights:
Individual weights of the animals were recorded just prior to test substance application (initial) and again on days 7 and 14 (termination).

Cage-side observations:
The animals were observed for signs of gross toxicity, behavioral changes and mortality at 1, 3 and 24h after application and at least once daily thereafter for 14 days. Observations included gross evaluation of the skin and fur, eyes and mucous membranesk respiratory, circulatory, autonomic and central nervous systems, somatomotor activity and behavior pattern. Particular attention was directed to observations of tremors, convulsions, salivation, diarrhea, sleep and coma.

Necropsy:
All rats were euthanized via CO2 inhalation on day 14. A gross necropsy was performed on all animals. Tissues and organs of the thoracic and abdominal cavities were examined.

Results and discussion

Effect levelsopen allclose all
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks:
NaF
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 905 mg/kg bw
Based on:
element
Remarks:
fluoride
Mortality:
None
Clinical signs:
One female exhibited facial staining, diarrhea and emaciation between days 2 and 6. All other animals appeared active and healthy. Dermal irritation and/or discoloration was noted at the dose site of all animals. No other effects of gross toxicity, adverse pharmacologic effects or abnormal behavior.
Body weight:
All animals gained bodyweight during the study.
Gross pathology:
All tissues and organs appeared normal.
Other findings:
Red lung discoloration was observed, which is consistent with euthanasia via CO2 inhalation.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The single dose acute dermal LD50 was found to be > 2000 mg/kg bw.
Executive summary:

An acute dermal toxicity test was conducted with rats to determine the potential for the test item to produce toxicity after topical application. A dose of 2000 mg/kg bw of the test item was applied to the skin of ten healthy rats for 24 hours. The animals were observed for signs of gross toxicity and mortality at least once daily for 14 days. Bodyweights were recorded just prior to application and again on days 7 and 14 (termination). Necropsies were performed on all animals at terminal sacrifice.

All animals survived and gained bodyweight during the study. One female exhibited facial staining, diarrhea and emaciation between days 2 and 6. All other animals appeared active and healthy. Apart from the dermal irritation and/or discoloration noted at the dose site of all animals, there were no signs of gross toxicity, adverse pharmacologic effects or abnormal behavior. Gross necropsy findings at terminal sacrifice were generally unremarkable.

In conclusion, the single dose acute dermal LD50 was found to be > 2000 mg NaF/kg bw.