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Toxicological information

Skin irritation / corrosion

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Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1988
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP, guideline study
Cross-referenceopen allclose all
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1988

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
other: FIFRA: Pesticide Assessment Guidelines, Subdivision F; Hazard Evaluation : Human and Domestic Animals; Office of Pesticide Programs, U.S. Envi ronmental Protection Agency, Nov. 1982, Section 81-5, Primary Dermal Irritation Study
Deviations:
no
Remarks:
Not specified in report
Qualifier:
according to
Guideline:
other: TSCA: Health Effects Test Guidelines; Office of Toxic Substances; Office of Pesticide and Toxic Substances; United States Environmental Protection Agency, August 1982; Acute Exposure, Primary Dermal Irritation
Deviations:
no
Remarks:
Not specified in report
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Diphenyl oxide
Reference No.: lot No. 3899502
Purity: 99.99+
Appearance: Clear colorless liquid
Source: Monsanto Company

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
Supplier: Summit View Farm, Hazleton , Pennsylvania
Number: Six (1 male, 5 females)
Age: Young adults ( at least 8 weeks old at study initiation)
Acclimation Period: 41 days
Observations: All animals were checked for viability twice daily. Prior to assignment to study all animals were examined to ascertain suitability for study.
Husbandry: Currently acceptable practices of good animal husbandry were followed, e.g., Guide for the Care and Use of Laboratory Animals. DHEW Publication No. ( NIH ) 78-23 Revised 1978.
Housing: Individually housed
Cages: Suspended, stainless steel
Environmental Conditions:
Temperature: 60-70°F is considered an acceptable temperature range for rabbits; room temperature was monitored and recorded twice daily and maintained within this range to the maximum extent possible.

Humidity: 30-70% is considered an acceptable humidity range for rabbits; room humidity was monitored and recorded daily and maintained within this range to the maximum extent possible.

Light Cycle: 12 hours light, 12 hours dark (controlled by an automatic timer).

Food: Lab Rabbit Chow HF (Purina #5326), -ad libitum.

Water: Automatic watering system, ad libitum, Municipal water supply (Elizabethtown Water Co.).

Contaminates: There were no known contaminants reasonably expected to be found in food or water which would interfere with the results of this study.

Identification: Each animal was identified with a monel ear tag, bearing a unique number, prior to testing.

Selection: Animals were randomly placed in cages upon receipt, and were placed on study as available at the time of study initiation. Any animals considered unsuitable for study because of poor health or unacceptable skin were excluded from selection.

Test system

Type of coverage:
semiocclusive
Preparation of test site:
other: clipped
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
0.5 ml of test material per site. (The material was applied to two intact sites on each animal.)
Duration of treatment / exposure:
4 hours/single application
Observation period:
3-14 days
Number of animals:
Six (1 male, 5 females)
Details on study design:
Preparation o f Animals
On the day before dosing the hair of each rabbit was closely clipped from the dorsal area of the trunk with an electric clipper, so as to expose at least 10% of the body surface area. Care was taken to avoid abrading the skin. Only animals with intact, healthy skin were used.

Preparation of Test Material
The test material was administered as received; no preparation was necessary.

Administration of Test Material:
The appropriate amount of the test material was applied beneath a gauze square, 1 "x1", placed directly on each of two test sites nearest the
head of the rabbits and held in place with non - irritating tape. Gauze was then wrapped around the animal and covered with porous tape, to semi-occlude the test sites.
Elizabethan collars were placed on each animal prior to or at the time of dosing in order to prevent the animal from disturbing the coverings and test sites.

Following 4 hours of exposure, the wrappings and gauze squares were removed and the test site was gently wiped free of excess test material using water and gauze. After approximately 30 minutes, dermal observations were made.

LXPERIMENTAL EVALUATION
A. Viability Check:
Twice Daily

B. Evaluation of Dermal Irritation:
1. Intervals:
Approximately 30 minutes and 24, 48 and 72 hours after patch removal. If there were any signs of irritation noted at the 72 hour observation, observations were made again at each affected site 7, 10 and 14 days after treatment or until no signs of irritation were present. Each site was treated independently, i.e., if irritation was no longer present at a site at 72 hours or any interval thereafter, no further scoring was performed on that site.
2. Methods:
At each interval all sites were evaluated for erythema and edema or other evidence of dermal irritation according to the Draize scoring system. The most severely affected area was scored. Adjacent areas of untreated skin were used for comparison.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 0.5 h
Score:
0.83
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Remarks on result:
other: Right side (worst case)
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24 h
Score:
1.5
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Remarks on result:
other: Right side (worst case)
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 48 h
Score:
1.5
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Remarks on result:
other: Right side (worst case)
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 72 h
Score:
1.8
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Remarks on result:
other: Right side (worst case)
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 7 days
Score:
1
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Remarks on result:
other: Right side (worst case)
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 14 days
Score:
0.17
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Remarks on result:
other: Right side (worst case)
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 0.5 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: Right side (worst case)
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24 h
Score:
0.17
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: Right side (worst case)
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 48 h
Score:
0.17
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: Right side (worst case)
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 72 h
Score:
0.17
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: Right side (worst case)
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 7 and 14 days
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: Right side (worst case)
Irritant / corrosive response data:
Diphenyl Oxide produced generally mild reversible dermal irritation. Five of the six animals exhibited very slight ( barely perceptible ) erythema with
little or no edema, at 0.5 hours; the remaining animal was free of dermal irritation. By 24 or 48 hours, most animals exhibited slight erythema. By study termination (Day 14), five of the six animals were free of dermal irritation; one animal continued to exhibit only very slight erythema at one test site The individual animal Average Dermal Irritation Score of Diphenyl Oxide is 1.4.
Other effects:
No data

Any other information on results incl. tables

None

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Diphenyl Oxide produced generally mild reversible dermal irritation. Five of the six animals exhibited very slight ( barely perceptible ) erythema with
little or no edema, at 0.5 hours; the remaining animal was free of dermal irritation. By 24 or 48 hours, most animals exhibited slight erythema. By study termination (Day 14), five of the six animals were free of dermal irritation; one animal continued to exhibit only very slight erythema at one test site The Average Dermal Irritation Score of Diphenyl Oxide is 1.4.
Executive summary:

A primary dermal irritation study was conducted in six rabbits (4-hour exposure/semi-occlusive covering) according to FIFRA: Pesticide Assessment Guidelines, Subdivision F; Nov. 1982, Section 81-5 and TSCA: Health Effects Test Guidelines; Office of Toxic Substances; Office of Pesticide and Toxic Substances; United States Environmental Protection Agency, August 1982.

Diphenyl Oxide produced generally mild reversible dermal irritation. Five of the six animals exhibited very slight ( barely perceptible ) erythema with little or no edema, at 0.5 hours; the remaining animal was free of dermal irritation. By 24 or 48 hours, most animals exhibited slight erythema. By study termination (Day 14), five of the six animals were free of dermal irritation; one animal continued to exhibit only very slight erythema at one test site The individual animal Average Dermal Irritation Score of Diphenyl Oxide is 1.4.