2,2'-methylenebis(4,6-di-tert-butyl-phenyl)-2-ethylhexyl phosphite

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

14 August 1989 to 16 October 1989

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1989

Report date:

1990

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: Pesticide Assessment Guidelines, Subdivision F. Hazard Evaluation: Human and Domestic Animals, U. S. Environmental Protection Agency Office of Pesticide and Toxic Substances Series 81-5, pp. 55-59, November 1982.

GLP compliance:

yes

Test material

Reference

Name:

Unnamed

Type:

Constituent

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

Test Material: Mark HP-10
Physical Description: White powder
Purity and Stability: Sponsor assumes responsibility for purity and stability determinations (including under test conditions).
Storage and Retention: The test material was stored at room temperature.
Any unused material will be discarded according to HLA Standard Operating Procedure.
Safety Precautions: Normal handling procedures were used according to HLA Standard Operating Procedure.

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

Test Animal: Adult albino rabbits, Hra:(NZW)SPF, were procured, maintained individually in screen-bottom cages in temperature- and humidity-controlled quarters, provided access to water ad libitum and a measured amount of High Fiber Rabbit Chow® 5326, Purina Mills, Inc., and held for an acclimation period of at least 7 days. Animal husbandry and housing at HLA comply with standards outlined in the "Guide for the Care and Use of laboratory Animals”. If variations from the prescribed environmental conditions existed, they were documented and considered to have no effect on the study outcome. No contaminants were expected to have been present in the feed or water which would have interfered with or affected the results of the study.
Three male and three female acclimated animals, weighing from 2320 to 2436 g, were chosen at random for the test, and maintained during the observation period as specified for the acclimation period. Test animals were identified by animal number and corresponding ear tag.
Reason for Species Selection: Historically, the New Zealand White albino rabbit has been the animal of choice for evaluating the effect of chemicals on the skin.

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

physiological saline

Controls:

no

Amount / concentration applied:

0.5 g and moistened with 0.9% saline.

Duration of treatment / exposure:

4 hours

Observation period:

72 hours

Number of animals:

three males and three females.

Details on study design:

Approximately: 24 hours before treatment the hair was clipped from the back and flanks of each animal.
Preparation of Test Material: The sample was dosed as received.
Treatment: The test material was applied to the intact skin of each rabbit in the amount of 0.5 g and moistened with 0.9% saline. The treated area was covered with a 2.5 x 2.5 cm gauze patch secured with paper tape, loosely overwrapped with Saran Wrap® and secured with Elastoplast® tape to provide a semiocclusive dressing. Collars were applied to restrain the test animals for the 4-hour exposure period.
Reason for Route of Administration: Historically the dermal route is the route of choice based on the method of Draize.
Observations: After the exposure period, the patches were removed. The test sites were washed using lukewarm tap water and disposable paper towels. The test material was removed from the test sites as thoroughly as possible without irritating the skin. Thirty minutes following removal of the test material, the degree of erythema and edema was read according to the Draize technique (recorded as the 4-hour score). Subsequent examinations were made at 24, 48 and 72 hours after patch removal.
Individual body weights were taken just prior to study initiation.
Termination: At study termination all animals were euthanatized and discarded.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Results 2

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Results 3

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Results 4

Irritation parameter:

erythema score

Basis:

animal #4

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Results 5

Irritation parameter:

erythema score

Basis:

animal #5

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Results 6

Irritation parameter:

erythema score

Basis:

animal #6

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Results 7

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Results 8

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Results 9

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Results 10

Irritation parameter:

edema score

Basis:

animal #4

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Results 11

Irritation parameter:

edema score

Basis:

animal #5

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Results 12

Irritation parameter:

edema score

Basis:

animal #6

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

Application of Mark HP-10 to rabbits under 4-hour semi occluded conditions resulted in no dermal irritation in any of the six albino rabbits.

Any other information on results incl. tables

Individual dermal Irritation Scores

Animal Number	Sex	Erythema (hour)				Edema (Hour)
		4	24	48	72	4	24	48	72
F29514	M	0	0	0	0	0	0	0	0
F29498	M	0	0	0	0	0	0	0	0
F29516	M	0	0	0	0	0	0	0	0
F29517	F	0	0	0	0	0	0	0	0
F29518	F	0	0	0	0	0	0	0	0
F29519	F	0	0	0	0	0	0	0	0

 

Average Primary Dermal Irritation Scores*

Observation Period (Hour)	Average Score
4	0.0
24	0.0
48	0.0
72	0.0

*The average primary dermal irritation score is the total dermal irritation score for all the animals (erythema and edema) divided by the number of test sites at each observation period.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Application of Mark HP-10 to rabbits under 4-hour semi occluded conditions resulted in no dermal irritation in any of the six albino rabbits. The average of the 4-, 24-, 48-, and 72-hour scores is 0.0 (considered to be non irritating).

Executive summary:

To assess the relative level of primary skin irritation of a test material on rabbits under semi occluded conditions according to the U. S. Environmental Protection Agency's Guidelines for Testing Pesticides and Toxic Substances.

Regulatory Compliance: This study was conducted in accordance with the U.S. Environmental Protection Agency Good laboratory Practice Standards, 40 CFR 792 (November 29, 1983), the Food and Drug Administration Good Laboratory Practice Regulati9ns, 21 CFR 58, and the proposed Organisation for Economic Cooperation and Development's Principles of Good Laboratory Practice,

Annex 2, C(81)30. The in-life portion of the study was done before the effective date of the revised EPA standards (September 18, 1989).

The test material, Mark HP-10, was evaluated for its primary dermal irritation potential in male and female albino rabbits. The test material produced no dermal reactions at any of the observations. The average of the 4-, 24-, 48-, and 72-hour scores is 0.0 (considered to be non irritating).