Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
08/04/1986 to 22/04/1986
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1986
Report Date:
1986

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
A multi dose LD50 was not performed
GLP compliance:
yes
Test type:
standard acute method

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid

Test animals

Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Young adult male and female albino New Zealand rabbits obtained from Clerco Research Farm, CincinNati, OH, USA
- Housing: The animals were housed individually in stainless steel cages with wire mesh floors.
- Diet (e.g. ad libitum): Purina Certified Rabbit Chow 5322 was fed throughout the study.
- Water (e.g. ad libitum): Free access to filtered tap water was provided through an automatic watering system.
- Acclimation period: 7 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 67 ± 5 F
- Humidity (%): 30 - 70%
- Ventilation: The animal room was well ventilated and air conditioned
- Photoperiod (hrs dark / hrs light): lighting was controlled by automatic timers to give twelve hours continuous light (06:00 to 18:00) and twelve hours darkness.

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
Approximately 24 hours before treatment the dorsal and lateral trunk (approximately 10% of the body surface area) of each animal were clipped free of hair.

On the day of treatment bodyweights were recorded and doses calculated. An impervious binder consistng of plastic wrap and adhesive tape was applied around each animal's trunk and a measured volume of the test article was introduced under the binder and spread over the application site. The entire trunk of each animal was then wrapped with additional adhesive tape and masking tape.

After a 24 Hour exposure period each binder was removed and the test site of each animal was wiped with gauze sponges moistened with propylene glycol to remove remaining test item.

Duration of exposure:
24 hours
Doses:
2000mg/kg. A multi dose LD50 was not performed
No. of animals per sex per dose:
5 males and 5 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days

- Frequency of observations and weighing:
The animals were observed frequently on the day of treatment for deaths or overt signs of toxicity and subsequently once daily for fourteen days.

Individual bodyweights were recorded prior to application of the test item on Day 0 and on Days 7 and 14.

- Necropsy of survivors performed: yes
At the end of the study the animals were killed by intravenous injection of barbiturate and exanguinated prior to necropsy. Animals found dead during the study were necropsied as soon as possible after death. All animals were subjected to gross necropsy. This consisted of an external examination and opening of the abdominal and thoracic cavities. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
approximate LD50
Effect level:
ca. 2 000 mg/kg bw
Based on:
test mat.
Mortality:
One female was found dead on Days 2 and 6. Two males and one females were found dead on Day 7.
Clinical signs:
Observations noted during the study were erythema, edema, black / brown disclouration, atonia, eschar formation, fissures and or disquamation of the test sites, muscle tremors, few / no stools, loose stools, no urine, food appeared undisturbed, emaciation, lethargy, salivation, ataxia, red stained fur around test sites poor coat quality.
Body weight:
All surviving animals except one gained weight and one female had no overall weight gain
Gross pathology:
Necropsy of animals found dead revealed treated skins that were discolored red, black, or red black, thickened, crusted and / or stiff; black disclourations on the mucosa of stomachs; dark contents of cecums; tan disclourations on the surface of the left lateral lobe of one liver; fluid content of small intestine; and / or urinary bladder distended with gelatinous amber fluid.

Necropsy of surviving animals revealed linear abrasions, crusting sloughing epidermis, ulcerative dermatitis, thickened areas with hyperemic borders, multiple scabs, and / or underlying granulation tissue on the treated area of the back

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
Under the conditions of this study, the acute dermal LD50 of the test material was considered to be approximately 2000 mg/kg body weight.
Executive summary:

Method

The test material was applied topically to five male and five female New Zealand White Rabbits at a dose level of 2000 mg/kg body weight for a period of 24 hours. The animals were observed for pharmacotoxic signs and mortality for 14 days following the day of treatment.

Mortality

Two males and three females died following treatment. Deaths ocurred on Days 2, 6, and 7 after test material application.

Clinical signs and Bodweight

Observation noted during the study were erythema, edema, black / brown disclouration, atonia, eschar formation, fissures and or disquamation of the test sites, muscle tremors, few / no stools, loose stools, no urine, food appeared undisturbed, emaciation, lethargy, salivation, ataxia, red stained fur around test sites poor coat quality.

All surviving animals except one gained weight and one female had no overall weight gain

Necropsy

Necropsy of animals found dead revealed treated skins that were discolored red, black, or red black, thickened, crusted and / or stiff; black disclourations on the mucosa of stomachs; dark contents of cecums; tan disclourations on the surface of the left lateral lobe of one liver; fluid content of small intestine; and / or urinary bladder distended with gelatinous amber fluid. Necropsy of surviving animals revealed linear abrasions, crusting sloughing epidermis, ulcerative dermatitis, thickened areas with hyperemic borders, multiple scabs, and / or underlying granulation tissue on the treated area of the back.

Conclusion

Under the conditions of this study, the acute dermal LD50 of the test material was considered to be approximately 2000 mg/kg body weight.