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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:
key study
Study period:
20th September to 4th October 1996
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study following GLP.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1997
Report Date:
1997

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
not specified
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
not specified
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
CAS# 122384-85-4/68855-45-8
Phenol, tetrapropenyl-, sulfurized, calcium salts. Testing was performed on a commercial sample of this material. Typical purity of this material as distributed in commerce is 60% alkyl phenol sulfide and 40% highly refined lubricant base oil.
The Sponsor assumes responsibility for purity and stability determinations (including under test conditions). Information on composition and method of synthesis will be held by the Sponsor.

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Young adult albino rats of the Crl:CD®(SD)BR strain were procured from Charles River Laboratories, Inc., Portage, Michigan on September 3 and 9, 1996.
- Age at study initiation: approximately 7 to 11 weeks of age
- Weight at study initiation: 236 to 286 g
- Housing: After test material administration, the animals were individually housed.
- Diet (e.g. ad libitum): The animals were provided continuous access to Laboratory Rodent Diet #5001, PMI Feeds, Inc. The feed is routinely analyzed by the manufacturer for nutritional components and environmental contaminants. Samples of the water are periodically analyzed. There were no known contaminants in the feed or water at levels that could be expected to interfere with or affect the results of the study.
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: After receipt, the animals were acclimated for a period of at least 7 days. During acclimation, the animals were separated by sex and group housed in suspended screen-bottom stainless steel cages.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19° to 25°C
- Humidity (%): 50% ±20%
- Photoperiod (hrs dark / hrs light): 12-hour light/12-hour dark lighting cycle

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: The test material was applied to the test site at a rate of approximately 0.014 g/cm2 in a thin and uniform layer.
- Type of wrap if used: The area of application (approximately 36 cm2) was covered with a 4-ply 6-cm x 6-cm gauze patch secured with four strips of Micropore' surgical tape. The trunk of the animal was then loosely overwrapped with a sheet of perforated plastic film that was secured on both ends with strips of Elastoplast® tape to provide a semiocclusive dressing.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): At the end of the 24-hour exposure period, the bandages were removed and the residual test material removed from test sites using mineral oil followed by liquid Ivory® soap mixed with warm tap water. The test sites were then rinsed with clean tap water and dried with disposable paper towels.
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): The undiluted test material was applied to the intact skin on each animals' back at a dose level of 2,000 mg/kg of body weight.
Duration of exposure:
24 hours
Doses:
2000 mg/kg b. wt
No. of animals per sex per dose:
Five
Control animals:
not specified
Details on study design:
The route of administration was semi-occluded topical application.

The test material was administered undiluted to shaved, intact skin (approximately 36 cm2) at a limit dose of 2000 mg/kg b. wt. and covered with a
semi-occlusive dressing. After 24 hours the dressing was removed and the site washed with mineral oil followed by a mild soap solution. The animals were held for 14 days and observed at 1, 2.5, and 4 hours after test material application and twice daily thereafter. Dermal irritation was scored 30 minutes after dressing removal and on days 3, 7, 10 and 14. Individual body weights were recorded prior to dosing and on days 7 and 14 after dosing. The animals were euthanized by CO2 inhalation at the conclusion of the observation period and examined for gross pathological changes. Tissues
with macroscopic abnormalities were preserved for microscopic examination.All guideline recommendations were exceeded.
- Duration of observation period following administration: 14 days.
- Frequency of observations and weighing: Clinical observations were conducted at approximately 1, 2.5, and 4 hours after test material administration and daily thereafter for 14 days. Mortality checks were conducted twice a day (morning and afternoon) for 13 days after test material administration and again the morning of Day 14.
Body weights were determined before test material application (Day 0), at Day 7, and at termination of the in-life phase (Day 14).
The initial dermal irritation reading was made 30 minutes after removal of the test material according to the Draize technique (recorded as the Day 1 score). Subsequent readings of dermal irritation were made on Days 3, 7, 10, and 14.
- Necropsy of survivors performed: yes, at termination of the in-life phase, all animals were euthanized by an overexposure to carbon dioxide, subjected to an abbreviated gross necropsy examination, and any abnormalities were recorded. After necropsy, the animals were discarded and no tissues were saved as there were no grossly abnormal tissues.
Statistics:
No statistical analyses were required by the protocol.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality was observed during the study.
Clinical signs:
All animals appeared normal throughout the study.
Body weight:
All animals exhibited body weight gain during the study with the exception of 1 female which exhibited an insignificant weight loss of 6 g during the second week.
Gross pathology:
There were no lesions observed at the terminal necropsy.
Other findings:
Dermal irritation (based on the most severe score for each animal at any time point) consisted of only slight erythema reactions in 1 male and 1 female. No other dermal irritation was observed.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The estimated dermal LD50 values for male and female rats were determined to be greater than 2,000 mg/kg.
Executive summary:

The test material was evaluated for its acute dermal toxicity potential in five male and five female rats when administered as a single topical application at a level of 2,000 mg/kg of body weight for a 24-hour exposure period. The study was conducted according to OECD 402. All rats were observed for clinical signs and mortality at 1, 2.5, and 4 hours following treatment and for 14 days thereafter. No deaths occurred during the study. The estimated dermal LD50 values for male and female rats were determined to be greater than 2,000 mg/kg. All animals appeared normal during the study. All animals exhibited body weight gain during the study with the exception of 1 female which exhibited an insignificant weight loss of 6 g during the second week. The test material produced only slight dermal reactions in two animals which cleared in these animals by Day 7. The gross necropsy examinations at termination revealed no visible lesions.