Bis(1-n-butyl-3-methylcyclopentadienyl)zirconium dichloride

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

February 13, 1996 to February 27, 1996

Reliability:

1 (reliable without restriction)

Justification for type of information:

In vivo experimental study on the registered substance.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1996

Report date:

1996

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

not applicable

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

Bis(1-butyl-3-methyl cyclopentadienyl)Zirconium dichloride

EC Number:

686-816-3

Cas Number:

151840-68-5

Molecular formula:

C20 H30 CL2 Zr1

IUPAC Name:

Bis(1-butyl-3-methyl cyclopentadienyl)Zirconium dichloride

Test material form:

solid

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

1 male rabbit was acclimated for 15 days, examined for viability at least once a day. Animal was approximately 16 weeks at initiation of dosing and weighed 2.37 kg. Rabbit was housed singled caged in a stainless steel and wire mesh with absorbent paper below cages. Water was provided ad libitum, while feed (Agway certified RCA diet) was provided on a limited daily basis.

Environmental conditions
Temperature: 65 to 70 degrees Fahrenheit
Humidity: 40 to 60 percent relative humidity
Lighting: Approximately 12 hours light (0700 to 1900) and 12 hours dark (1900 to 0700) by automatic timer.

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

Three 0.5 g doses

Duration of treatment / exposure:

1st patch treatment - 3 minutes
2nd patch treatment - 1 hour
3rd patch treatment - 4 hours

Observation period:

14 days

Number of animals:

1 - In an attempt to minimize animal pain and distress, one animal was initially dosed and observed through the 4 hour observation. Since this animal showed potential signs of corrosivity (blanching) no other animals were dosed.

Details on study design:

Preparation of Animals
Approximately 24 hours prior to topical administration of the test material, the hair of each rabbit in the area of the dorsal surface from the shoulder region to the lumbar region was closely clipped with an electric clipper. The skin was left intact. Elizabethan-type collars were placed around the neck of each rabbit at this time to acclimate them to wearing collars. Animals were reclipped as necessary. Collars remained on the animals a minimum of 26 hours and a maximum of 30 hours.

Preparation of Test Material
The undiluted test material was administered as received.

Administration of Test Material
The test material was administered as three 0.5 gram doses, each introduced under a 1 inch x 1 inch 2 ply gauze patch moistened with reverse osmosis water, then secured with non-irritating tape. The patch was loosely held in contact with the skin by means of a semi-occlusive dressing for the duration of the exposure period. After at least 3 minutes of exposure, the dressing and gauze patch were removed from the first site and the site was evaluated for dermal responses. After at least one hour, the dressing and gauze patch were removed from the second site and the site was evaluated for dermal responses. After at least 4 hours of exposure, the dressing and gauze patch were removed from the remaining site and the site was evaluated for dermal responses. Residual test material was removed, where possible, using peanut oil and paper towels without altering the existing response or integrity of the epidermis after the initial dermal evaluation for each dose site was performed. Collars were removed after the 4 Hour exposure period.

Experimental Evaluation
The animals were examined for viability twice daily Monday through Friday, and once daily on weekends and holidays (if applicable). Body weight was recorded on the day of dosing (Day 0) and at terminal sacrifice (Day 14). Dermal responses were evaluated at patch removal and at 60 minutes, 24 hours, 48 hours, and 72 hours following patch removal, and on Days 7, 10, and 14. After the Day 14 observations, all rabbits were sacrificed by intravenous injection of sodium pentobarbital solution and discarded without further examination.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

ca. 4

Max. score:

4

Reversibility:

not fully reversible within: 14 days

Remarks:

Blanching of the skin was reported immediately after patch removal, 1 hour and 24 hours after exposure. Necrosis of the skin was reported on days 2, 3, 7 and 10. Slight erythema (core of 1) and desquamation was observed at 14 days.

Results 2

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

ca. 2

Max. score:

4

Reversibility:

not reversible

Irritant / corrosive response data:

Skin Responses - 3 Minute Exposure
Topical application of EX-370 did not elicit dermal irritation at patch removal or the 60 minute observation. Well-defined erythema was noted at the 24 Hour observation. At the 48 Hour and 72 Hour observations very slight erythema was noted. The animal was free of erythema from Day 7 to 14. Very slight edema was noted at the 24 Hour and 72 Hour observations. In addition, desquamation was noted on Day 10.

Skin Responses - 1 Hour Exposure
Dermal irritation was not noted at patch removal. Severe erythema was noted at the 60 Minute observation through study termination. Moderate edema was noted at the 60 Minute observation and slight edema was observed from the 24 Hour observation through Day 14. Blanching was noted at the 60 minute observation and at the 24 Hour observation. Necrosis was noted from the 48 Hour observations through Day 7 and eschar was noted on Days 10 and 14. Desquamation was also noted on Day 14.

Skin Responses - 4 Hour Exposure
Severe erythema was noted upon patch removal through Day 10. Very slight erythema was observed on Day 14. Slight edema was noted throughout the study. Blanching was observed upon patch removal and at the 24 Hour observation. Necrosis was observed from the 48 Hour observation through Day 7. Eschar was noted on Days 7 and 10, and desquamation was noted on Day 14.

Any other information on results incl. tables

See individual animal data table attached.

Applicant's summary and conclusion

Interpretation of results:

Category 1B (corrosive) based on GHS criteria

Conclusions:

Based on the results of this study, the test substance was determined to be corrosive.

Executive summary:

The corrosivity of EX-370 was evaluated following its application to the clipped back of one New Zealand White rabbit. (In an attempt to minimize animal pain and distress, one animal was initially dosed and observed through the 4 hour observation. Since this animal showed potential signs of corrosivity, (blanching) no other animals were dosed.) The test material was administered as three 0.5 gram doses each introduced under a 2 ply gauze patch moistened with 0.2 ml of reverse osmosis water. The patch was then secured with non-irritating tape. The gauze was loosely held in contact with the skin by means of a semi-occlusive dressing for the duration of the exposure period. The dressings remained in place for three minutes, one hour and four hours, respectively. After exposure was completed, the dressing and gauze were removed. Each test site was graded for erythema, edema and other signs of dermal irritation at patch removal (prior to test material removal) and at 60 minutes, 24, 48, and 72 hours after test material administration and on Day 7, 10, and 14 after patch removal. All dermal scoring was made according to the Draize method of scoring (Draize, 1959). The contact of the test material with the dose sites caused heat to be released from the test material.

 

Skin Responses - 3 Minute Exposure

Topical application of EX-370 did not elicit dermal irritation at patch removal or the 60 minute observation. Well-defined erythema was noted at the 24 Hour observation. At the 48 Hour and 72 Hour observations very slight erythema was noted. The animal was free of erythema from Day 7 to 14. Very slight edema was noted at the 24 Hour and 72 Hour observations. In addition, desquamation was noted on Day 10.

 

Skin Responses - 1 Hour Exposure

Dermal irritation was not noted at patch removal. Severe erythema was noted at the 60 Minute observation through study termination. Moderate edema was noted at the 60 Minute observation and slight edema was observed from the 24 Hour observation through Day 14, Blanching was noted at the 60 minute observation and at the 24 Hour observation. Necrosis was noted from the 48 Hour observations through Day 7 and eschar was noted on Days 10 and 14. Desquamation was also noted on Day 14.

 

Skin Responses - 4 Hour Exposure

Severe erythema was noted upon patch removal through Day 10. Very slight erythema was observed on Day 14. Slight edema was noted throughout the study. Blanching was observed upon patch removal and at the 24 Hour observation. Necrosis was observed from the 48 Hour observation through Day 7. Eschar was noted on Days 7 and 10, and desquamation was noted on Day 14. In conclusion, EX-370 was determined to be corrosive based on the results of this study.