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Acute Toxicity: dermal

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acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
April 9, 1999
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Test Guidelines: OECD Guidelines for the Testing of Chemicals Section 4; Health Effects, No. 402 (1987)

Data source

Reference Type:
study report
Report date:

Materials and methods

Principles of method if other than guideline:
A single dose of H-23799 was applied to the shaved, intact skin of 5 male and 5 female rabbits at a dosage of 2000 mg/kg of body weight. The application site was occluded for 24 hours, after which the test substance was removed. The animals were observed on the day of dosage and during a 14-day observation period. Observations during the 15-day test period included daily mortality checks, body weight determination on test days 1, 2, 8, and 15, and daily observations for clinical signs of toxicity and dermal irritation (weekends excluded). The rabbits were necropsied to detect grossly observable evidence of organ or tissue damage or dysfunction at the end of the 15-day period.
GLP compliance:
not specified
Test type:
fixed dose procedure
Limit test:

Test material

Constituent 1
Reference substance name:
Nitric acid, reaction products with cyclododecanol and cyclododecanone, by-products from, high-boiling fraction
EC Number:
EC Name:
Nitric acid, reaction products with cyclododecanol and cyclododecanone, by-products from, high-boiling fraction
Cas Number:
Molecular formula:
UVCB substance. Formula not available
Not available for a UVCB
Test material form:
solid: particulate/powder
migrated information: powder
Details on test material:
The test substance, H-23799, wassupplied by the sponsor as a tan solid. The test substance was ground into a fine powder as possible with a mortar and pestle. The test substance appeared to be stable under the conditions of the study. No evidence of instability, such as a change in color, was observed.

Test animals

other: New Zealand White
Details on test animals or test system and environmental conditions:
Animal Husbandry
Young adult male and female HM (NZW) fBR New Zealand White rabbits were received from Hare Marland, Hewitt, New Jersey. The rabbits were housed singly in suspended, stainless steel, wire-mesh cages. Each rabbit was assigned a unique identification number which was recorded on a card affixed to the cage. The last 3 digits of the identification number were written on the inside of each rabbit’s ear with a water insoluble marker. The rabbits were offered approximately 125 grams of PMI Nutrition International, Inc. Certified High Fiber Rabbit LabDiet ® 5325 daily during the study. Water was available ad libitum.

Haskell Laboratory has an animal health monitoring program. This program is monitored and administered by the Laboratory Veterinarian. Water samples are periodically analyzed for total bacterial counts and for the presence of coliforms, lead, and other contaminants. Additionally, samples from freshly washed cages and cage racks are periodically analyzed to ensure adequate sanitation by the cage washers. Data from this program are maintained separately from study records. Animal feed is certified by the manufacturer to meet specified nutritional requirements and to be free of a list of specified contaminants. On the basis of these analyses, there is no evidence suggesting that contaminants were present in the feed or water in amounts which may have interfered with the results of this study.

Rabbits were quarantined, wighted, and observed for general health for 11 days. Animal rooms were maintained on a timer-controlled, 12-hour light/12-hour dark cycle. Environmental conditions of the rooms were targeted for a temperature of 20°C + 1°C and relative humidity of 50% + 10%. Excursions outside these rangers were judged to have been of insufficient magnitude and/or duration to have adversely affected the validity of the study.

Administration / exposure

Type of coverage:
unchanged (no vehicle)
Details on dermal exposure:
On the day before dosing, the hair of each rabbit was closely shaved to expose the back from the scapular to the lumbar region. The rabbits were then fitted with plastic collars to prevent ingestion of the test substance or disruption of the wrappings.
Duration of exposure:
24 hours
2000 mg/kg
No. of animals per sex per dose:
5 males and 5 females
Control animals:
not specified
Details on study design:

H-23799 was weighed out of each animal on the day of treatment at a dosage of 2000 mg/kg of body weight. The amount of test substance designated for an animal was calculated on body weight collected prior to treatment. The rabbits body weights ranged from 2123.8 to 2265.1 grams for males and 2008.3 to 2089.7 for females on the day of dosing.

The area to be treated (approximately 6” x 5”) was outlined on the skin of each rabbit’s back with a water-insoluble marker. The aliquot of test substance designated for animal #33542 was moistened with deionized water to form a thick paste. An attempt was made to spread the paste directly on the test site of the rabbit. However, due to the physical nature of the test substance it was difficult to spread the paste evenly, and the paste did not appear to keep good contact with the skin. Therefore, for the remaining 9 rabbits, a 2-ply gauze patch (~6” x 5” )was placed on parafilm and was pre-moistened with deionized water. The test substance (designated for an animal) was spread evenly on the gauze patch (which was an area of approximately 190 square centimeters). The patch was then placed on the test site. The rabbits were then wrapped with successive layers of stretch gauze bandage and elastic adhesive bandage. After wrapping, the rabbits were returned to their cages. The rabbits were observed for clinical signs of toxicity approximately 3 hours after dosing.
Approximately 24 hours after treatment, the rabbits were removed from their cages, and the wrappings were removed. Excess test substance was washed from the animals backs with Ivory® soap and warm water, and the skin was dried with a paper towel. Approximately 2 hours after removal of the test substance, the rabbits were weighed, observed for clinical signs of toxicity and dermal response and returned to their cages. Dermal effects were scored according to the Draize Scale. Observations for mortality and signs illness, injury, and abnormal behavior were made daily through the study. Observations for clinical signs of toxicity and dermal irritation were made throughout the study (weekends excluded). The rabbits were weighed prior to treatment and on test days 2, 8, and 15. All rabbits were euthanized at the end of the 15-day test period and necropsied to detect grossly observable evidence of organ or tissue damage or dysfunction. The rabbits were euthanized by carbon dioxide anesthesia followed by exsanguination.

Results and discussion

Preliminary study:
LC0 = 2000 mg/kg and LC50 > 2000 mg/kg
No deaths occured
Clinical signs:
other: Slight, mild, or moderate erythema was observed in the treated rabbits the day the test substance was removed (test day 2), no edema was observed. No erythema was observed past day 6, Eight rabbits exhibited yellow-stained fur (last observed on day 13),
Gross pathology:
The gross observation of small right testis for the one male rabbit was nonspecific and not indicative of a target organ toxicity. No other gross lesions were present in the male and female study rabbits.

Any other information on results incl. tables

 Dosage (mg/kg)  Average Dose (g)  Average Initial Body Weight (g)  Mortality
 Male 2000  4.358  2178.7  0/5
 Female 2000  4.091  2045.6  0/5

Applicant's summary and conclusion

Interpretation of results:
not classified
Migrated information Criteria used for interpretation of results: EU
Under the conditions of the test, the skin absorption LD50 for H-23799 was greater than 2000 mg/kg of body weight when applied to the skin of male and female rabbits for 24 hours.
Executive summary:

Under the conditions of the test, the skin absorption LD50 for H-23799 was greater than 2000 mg/kg of body weight when applied to the skin of male and female rabbits for 24 hours.