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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:
2000
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2000
Report Date:
2000

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
This study was designed to comply with the standards set forth in 49 CFR 173.137 which directs that this study be conducted according to the July 1992 OECD Guideline for Testing of Chemicals, Number 404, "Acute Dermal InitationlCorrosionn.
GLP compliance:
yes (incl. certificate)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Type:
Constituent
Type:
Constituent
Type:
Constituent
Test material form:
liquid
Specific details on test material used for the study:
Identity : NE 1060
Supplied By : Air Products and Chemicals, Inc.
Date Received : 12/17/99
Storage : Room temperature and humidity.
Description : Clear liquid
Sample Preparation : The test article was used as received.

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
New Zealand White rabbits were received from Ace Animals, Boyertown, PA on 12/21/99. Following a quarantine period of at least one week, three healthy New Zealand White rabbits were selected for this test from a larger group.
The animals were born the weeks of 10110 through 10/24/99. The pretest body weight was 2.0 kg. The animals were identified by cage notation and a uniquely numbered metal eartag. The animals were housed llcage in suspended cages. Bedding was placed beneath the cages and changed at least three timeslweek. Fresh Purina Rabbit Chow (Diet #5321) was provided daily. Water was available libitum.
The animal room, reserved exclusively for rabbits on acute tests, was temperature controlled, had a 12 hour lightidark cycle and was kept clean and vermin free.

Test system

Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Amount / concentration applied:
0.5 ml
Duration of treatment / exposure:
The test article was kept in contact with the skin for three (3) minutes and scored for erythema and edema one hour following patch removal. Since the 3 minute exposure did not produce a definitive effect, two additional rabbits were added to the study. All three animals were dosed at site #2 for an exposure period of 1 hour and at site #3 for a four hour exposure. Each site was scored for erythema and edema one hour following patch removal, at 24, 48 and 72 hours and again on days 7 and 14.
Observation period:
Animals were observed for systemic signs at each dermal scoring interval.
Number of animals:
3
Details on study design:
Initially, one rabbit was placed in a restraining stock and site #1 was dosed with 0.5 ml of the test article.
The test article was used as received, dosed by volume (0.5 mllsite) and placed on the clipped site undera 2.5 x 2.5 cm 4 ply surgical gauze patch. A plastic covering was held over the dose site in a semiocclusive manner for the three minute exposure period. Residual test article was removed from the test site by gentle washing with distilled water at the end of the exposure period, prior to scoring for dermal reactions. The site was scored for skin reactions, including ulceration and necrosis, at 1 hour following patch removal.
Since no evidence of a corrosive effect was observed at the three minute exposure, two additional animals were added to the study. All three animals were dosed with 0.5 ml of the test article at site #2 for an exposure period of one hour and at site #3 for an exposure period of four hours. The dosing procedure was the same as that used for site #1. The torso of each rabbit was loosely wrapped with a semi-occlusive dressing which was secured with non-irritating tape to aid in retaining the test patches in position and to retard evaporation of volatile substances. The patches from site #2 were removed at one hour post-dose and those from site #3 were removed at 4 hours post-dose. Residual test article was removed from the test site by gentle washing with water at the end of the exposure period, prior to scoring for dermal reactions. Care was taken to avoid cross-contamination of the dose sites.
Sites #2 and #3 of all animals were scored at 1 hour following patch removal, at 24,48 and 72 hours and again on days 7 and 14. Erythema and edema were scored according to the Draize scoring code, below.
Additional signs were described.
Erythema & Eschar
No erythema 0
Very slight erythema (barely perceptible) 1
Well defined erythema 2
Moderate to severe erythema 3
Severe erythema (beet redness) to slight eschar formation (injuries in depth) 4
Edema
No edema 0
Very slight edema (barely perceptible) 1
Slight edema (edges of area well-defined by definite raising) 2
Moderate edema (raised approximately 1.0 mm) 3
Severe edema (raised more than 1.0 mm, extending beyond the area of exposure) 4
Site # 1 was located dorsally at the shoulder level. Sites #2 and # 3 were located dorsally at the hip
level. The general health of the animals was monitored at each observation time. Body weights were recorded pretest and at termination of the study.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: 1 hour
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: 1 hour
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24 h
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24 h
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
48 h
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #1
Time point:
48 h
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
7 d
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #1
Time point:
7 d
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
14 d
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #1
Time point:
14 d
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
other: 1 hour
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #2
Time point:
other: 1 hour
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24 h
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24 h
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
48 h
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #2
Time point:
48 h
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
7 d
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #2
Time point:
7 d
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #2
Remarks:
animal reclipped
Time point:
14 d
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #2
Time point:
14 d
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
other: 1 hour
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #3
Time point:
other: 1 hour
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24 h
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24 h
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
48 h
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #3
Time point:
48 h
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
7 d
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #3
Time point:
7 d
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
14 d
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #3
Time point:
14 d
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Remarks on result:
not measured/tested
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Remarks on result:
not measured/tested
Irritant / corrosive response data:
3 minute exposure: There was no erythema or edema.
1 hour exposure: There was no erythema or edema.
4 hour exposure: There was no erythema or edema.
Other effects:
Svstemic Observations: Two animals had diarrhea and soiling of the anogenital area. The remaining animal appeared normal during the observation period. Body weight changes were normal.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The modified Primary Irritation Index is 0. The test substance is not corrosive to rabbit skin.
Executive summary:

The purpose of this study was to determine if the test article causes irreversible damage when applied to therabbit skin.Initially, one healthy New Zealand White rabbit was placed in a restrainer and dosed with NE 1060. Thetest article (0.5 ml) was placed on the intact skin of the back (Site1).The test article was kept in contactwith the skin for three (3) minutes and scored for erythema and edema one hour following patch removal.Sincethe 3 minute exposure did not produce a definitive effect, two additional rabbits were added to thestudy. All three animals were dosed at Site 2 for an exposure period of 1 hour and at Site 3 for a four hour exposure. Each site was scored for erythema and edema one hour following patch removal, at 24,48, and72 hours and again on Days 7 and 14. Animals were observed for systemic signs at each dermal scoringinterval. A modified primary irritation index was calculated. Body weights were recorded pretest and attermination.3 minute exposure: There was no erythema or edema.1hour exposure: There was no erythema or edema.4 hour exposure: There was no erythema or edema.Systemic observations: Two animals had diarrhea and soiling of the anogenital area. The remaining animalappeared normal during the observation period. Body weight changes were normal.

Based on the presence of approximately 10% of 1,3-bis[3-(dimethylamino)propyl]urea.(bisDMAPAU) in the test item, and according to the attached read-acorss justification this result is also deemed valid for 1,3-bis[3-(dimethylamino)propyl]urea (bisDMAPU).

bisDMAPAU is classified as Corrosive Cat 1C.