Registration Dossier

Administrative data

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

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2009
Report Date:
2009

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
yes
Test type:
other: Single-dose acute dermal
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Purity: not reported as such

Test animals

Species:
rat
Strain:
other: Sprague-Dawley derived, albino
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: Approximately 9-10 weeks
- Weight at study initiation: Range of 279 – 308 grams for males; range of 215 – 231 grams for females.
- Fasting period before study: Not reported
- Housing: One per cage in suspended stainless steel caging with mesh floors.
- Diet (e.g. ad libitum): Rodent chow.
- Water (e.g. ad libitum): Filtered tap water, ad libitum, by an automatic water dispensing system.
- Acclimation period: 14 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-23°C
- Humidity (%): 60-69%
- Air changes (per hr): Not reported.
- Photoperiod (hrs dark / hrs light): 12 hrs dark / 12 hrs light

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: Dorsal area and trunk.
- % coverage: 2 inches x 3 inches, approximately 10% of the body surface.
- Type of wrap if used: 2-inch x 3-inch, 4-ply gauze pad. The gauze pad and entire trunk of each animal were then wrapped with 3-inch Durapore tape.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Test sites were gently cleansed.
- Time after start of exposure: After 24 hours of exposure to the test substance.

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 5000 mg/kg of body weight of the test substance.
- Constant volume or concentration used: yes
Duration of exposure:
Animals were exposed to the test substance for 24 hours. Animals were observed for 14 days.
Doses:
5000 mg/kg body weight
No. of animals per sex per dose:
5 animals per sex
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Body Weights – Individual body weights were recorded prior to test substance application, initial, and on Days 7 and 14.
Clinical Observations – Animals were observed for mortality, signs of gross toxicity, and behavioral changes, one hour and 5 hours after application and at least once daily thereafter for 14 days.
- Necropsy of survivors performed: Yes.
- Other examinations performed: Pathology examination, Gross – Tissues and organs of the thoracic and abdominal cavities were examined.
Statistics:
No.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Mortality:
No mortalities occurred. All animals survived exposure to the test substance.
Clinical signs:
Clinical observation of ano-genital staining for 2 male rats from Days 1 through 3. No other clinical observations were noted. There were no other signs of gross toxicity, dermal irritation, adverse pharmacologic effects, or abnormal behavior.
Body weight:
One male lost body weight through Day 7. All other animals gained weight over the entire 14-day study.
Gross pathology:
No gross abnormalities were noted for any of the animals when necropsied at the conclusion of the 14-day observation period.
Other findings:
None.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
LD50 (rats) > 5000 mg/kg
Executive summary:

An acute dermal toxicity test was conducted with rats to determine the potential for the test substance to produce toxicity from a single topical application. Five thousand milligrams of the test substance per kilogram of body weight was applied to the skin of 10 healthy rats for 24 hours. The animals were observed for mortality, signs of gross toxicity, and behavioral changes one and 5 hours post-dosing and at least once daily for 14 days. Body weights were recorded prior to application and again on Days 7 and 14 (termination). Necropsies were performed on all animals at terminal sacrifice.

All animals survived exposure to the test substance. Apart from ano-genital staining noted for 2 males from Days 1 through 3, there were no other signs of gross toxicity, dermal irritation, adverse pharmacologic effects, or abnormal behavior. Although one male lost body weight through Day 7, all animals gained weight over the entire 14-day study. No gross abnormalities were noted for any of the animals when necropsied at the conclusion of the 14-day observation period.

Under the conditions of this study, the single dose acute dermal LD50of the test substance is greater than 5000 mg/kg of body weight in male and female rats.