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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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: This study was selected as the key study because the information provided for the hazard endpoint is sufficient for the purpose of classification and labeling and/or risk assessment.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2007
Report Date:
2007

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Remarks:
The study was conducted according to the test guidelines in effect at the time of study conduct.
Qualifier:
according to
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Deviations:
no
Remarks:
The study was conducted according to the guideline in effect at the time of study conduct.
Qualifier:
according to
Guideline:
other: EEC, Method B.3 Directive 92/69/EEC:
Deviations:
no
Remarks:
The study was conducted according to the guideline in effect at the time of study conduct.
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Purity: 86%

Test animals

Species:
rat
Strain:
other: Crl:CD(SD)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: Approximately 9 weeks old (males); approximately 10 weeks old (females).
- Weight at study initiation: 295.7 grams (average, males); 236.0 (average, females).
- Fasting period before study: No
- Housing: Singly in stainless steel, wire-mesh cages suspended above cage boards.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: At least 6 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-26°C
- Humidity (%): 30-70%
- Air changes (per hr): Not reported
- Photoperiod (hrs dark / hrs light): An approximate 12-hour light/dark cycle

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: Approximately 37 square centimeters on the dorsal skin.
- % coverage: Thirty-seven square centimeters is equal to approximately 10 percent of the total body surface area of rats in the 200 - 300 g body weight range.
- Type of wrap if used: The test substance was covered with a 2-ply gauze patch. The rats were then wrapped with stretch gauze bandage and self-adhesive bandage.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Excess test substance was washed from the dorsal skin of each rat with warm water, and the skin was dried.
- Time after start of exposure: Approximately 24 hours.

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 5000 mg/kg.
- Concentration (if solution): Undiluted
Duration of exposure:
24 hours
Doses:
5000 mg/kg
No. of animals per sex per dose:
5 males; 5 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: Observations for mortality and signs of illness, injury, and abnormal behavior were made daily throughout the study. Observations for for clinical signs of toxicity and dermal response were made following test substance removal and daily throughout the study (weekends excluded for dermal irritation).
- Frequency of weighing: Prior to treatment (test day 0) and on test days 7 and 14.
- Necropsy of survivors performed: Yes, examinations to detect grossly observable evidence of organ or tissue damage.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Remarks on result:
other: No mortality or clinical signs of systemic toxicity or body weight loss. Erythema in all females the day after application, reversible by 2 days after application. Hyperkeratosis and ulceration cleared by 13 days after application. No gross lesions.
Mortality:
No mortality was observed.
Clinical signs:
No clinical signs of toxicity were observed during the study. Four rats exhibited wet fur (perineum, inguen) and yellow-stained fur/skin (perineum, inguen), after test substance removal. These clinical signs are commonly seen in wrapped rats and, therefore, were not considered test substance related. High posture observed in a rat on test day 4 was not considered test substance related because it was only observed in a single animal. Hair loss observed in 1 rat was considered incidental.
Body weight:
The rats exhibited no body weight losses.
Gross pathology:
No gross lesions were present in the rats at necropsy.
Other findings:
Skin responses:
No erythema or edema was observed on the test site of male rats. All female rats exhibited erythema (score of 2) but no edema on the test site the day after application of the test substance. No erythema was observed in these rats by 2 days after application. Hyperkeratosis was observed on the test site of 8 rats, and ulceration was observed on the test site of 3 rats during the study. All dermal effects cleared by 13 days after application.

Applicant's summary and conclusion

Interpretation of results:
other: Classification not required
Remarks:
Criteria used for interpretation of results: other: EEC
Conclusions:
LD50 > 5000 mg/kg
This study and the conclusions which are drawn from it fulfill the quality criteria (validity, reliability, repeatability).
Executive summary:

A single dose of the test substance was applied to the shaved, intact skin of 5 male and 5 female rats at a dose of 5000 mg/kg of body weight. The application site was covered with a semi-occlusive dressing for 24 hours, after which the test substance was removed. The rats were observed for 14 days following application. The rats were necropsied to detect grossly observable evidence of organ or tissue damage at the end of the 15-day test period. No deaths occurred. The rats exhibited no clinical signs of systemic toxicity or body weight loss. No erythema or edema was observed on the test site of male rats. All female rats exhibited erythema (score of 2) but no edema on the test site the day after application of the test substance. No erythema was observed in these rats by 2 days after application. Hyperkeratosis was observed on the test site of 8 rats, and ulceration was observed on the test site of 3 rats during the study. All dermal effects cleared by 13 days after application. No gross lesions were present in the rats at necropsy. Under the conditions of this study, the skin absorption LD50 for the test substance was greater than 5000 mg/kg of body weight when applied to the skin of male and female rats for 24 hours.