N-(2-ethylhexyl)-8,9,10-trinorborn-5-ene-2,3-dicarboximide

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

17 Nov 2004 to 10 Mar 2005

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2005

Report date:

2005

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

not specified

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2500 (Acute Dermal Irritation)

Deviations:

not specified

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

N-(2-ethylhexyl)-8,9,10-trinorborn-5-ene-2,3-dicarboximide

EC Number:

204-029-1

EC Name:

N-(2-ethylhexyl)-8,9,10-trinorborn-5-ene-2,3-dicarboximide

Cas Number:

113-48-4

Molecular formula:

C17H25NO2

IUPAC Name:

N-(2-ethylhexyl)-8,9,10-trinorborn-5-ene-2,3-dicarboximide

impurity 1

Reference substance name:

(E)-1,4-Bis(2-ethylhexylamino)-2-butene-1,4-dione

Molecular formula:

C20H38N2O2

IUPAC Name:

(E)-1,4-Bis(2-ethylhexylamino)-2-butene-1,4-dione

impurity 2

Reference substance name:

1-(2-ethylhexyl)-1H-pyrrole-2,5-dione

Molecular formula:

C12H19NO2

IUPAC Name:

1-(2-ethylhexyl)-1H-pyrrole-2,5-dione

Test material form:

liquid

Details on test material:

Purity and characterisation analysis conducted on the following sample; Supplier: McLaughlin Gormley King ; Batch Number: AB9500

Specific details on test material used for the study:

MGK 264
Lot No.: AA7093
Purity: 95.2% MGK 264 (From CofA)

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

The animals were housed individually in suspended stainless steel cages. All housing and care were based on the standards recommended by the Guide for the Care and Use of Laboratory Animals.

The animal room temperature and relative humidity ranges were 70-72°F (21-22°C) and 34-55%, respectively. Environmental control equipment was monitored and adjusted as necessary to minimize fluctuations in the animal room environment. Light timers were set to maintain a 12h ligh/12h dark cycle and room ventilation was set to produce 10-15 air changes/hour. The animal room temperature and relative humidity were recorded a minimum of once daily.

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Remarks:

On day -1, the animals chosen for use on the primary skin irritation study had the fur removed from the dorsal area of the trunk using an animal clipper. Care was taken to avoid abrading the skin during the clipping procedure.

Vehicle:

unchanged (no vehicle)

Remarks:

The test material was administered as received from the Sponsor.

Amount / concentration applied:

0.5mL at 100% concentration (as received), over approximately 1 inch x 1 inch

Duration of treatment / exposure:

After a four-hour exposure period, the binding materials were removed from each animal and the corners of the test site delineated using a marker. Residual test article was removed using gauze moistened with deionized water, followed by dry gauze.

Observation period:

Animals were examined for signs of erythema and edema and the responses scored at I hour after patch removal and 24, 48, 72 hours, and 7 days after patch application according to the Macroscopic Dermal Grading System.

Number of animals:

3, Male

Details on study design:

Preperation
Fur shorn with animal clippers

Application
0.5mL at 100% concentration (as received), over approximately 1 inch x 1 inch.

Exposure
The dose was held in contact with the skin under a semi-occlusive binder for an exposure period of four hours. After a four-hour exposure period, the binding materials were removed from each animal and the corners of the test site delineated using a marker. Residual test article was removed using gauze moistened with deionized water, followed by dry gauze. Acetone was used to remove sticky tape residue outside of the test area.

Observation
Animals were examined for signs of erythema and edema and the responses scored at I hour after patch removal and 24, 48, 72 hours, and 7 days after patch application according to the Macroscopic Dermal Grading System

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1.67

Reversibility:

fully reversible within: 7 day scoring interval

Remarks on result:

no indication of irritation

Results 2

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1.67

Reversibility:

fully reversible within: 7 day scoring interval

Remarks on result:

no indication of irritation

Results 3

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1.67

Reversibility:

fully reversible within: 7 days scoring interval

Remarks on result:

no indication of irritation

Results 4

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Reversibility:

other: no irritation

Remarks on result:

no indication of irritation

Results 5

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.33

Reversibility:

fully reversible within: 7 day scoring window

Remarks on result:

no indication of irritation

Results 6

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.33

Reversibility:

fully reversible within: 7 day scoring window

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

Exposure to the test article produced well-defined erythema on 3/3 test sites at the 1h scoring interval and very slight edema on 2/3 test site at the 24h scoring interval. The dermal irritation resolved completely on all test sites by the study day 7 scoring interval.

Other effects:

Additional dermal findings included desquamation, which was noted on 3/3 test sites.

Any other information on results incl. tables

Summary:

Mean Irritation Scores in Individual Animals
Animal No./Sex	Erythema	Edema
R27571M	1.67	0.00
R2763/M	1.67	0.33
R27651M	1.67	0.33
Irritation Rating	Nonirritant	Nonirritant

Applicant's summary and conclusion

Conclusions:

Based on the EEC Evaluation Criteria, MGK® 264 is classified as a non-irritant to the skin of the rabbit for erythema and edema as is indicated in the result summary table.

Executive summary:

Summary:

Mean Irritation Scores in Individual Animals
Animal No./Sex	Erythema	Edema
R27571M	1.67	0.00
R2763/M	1.67	0.33
R27651M	1.67	0.33
Irritation Rating	Nonirritant	Nonirritant