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Toxicological information

Eye irritation

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Administrative data

Endpoint:
eye 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
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
This study was designed to comply with the standards set forth in OECD Guidelines For Testing Chemicals, Number 405, adopted February 24, 1987.
GLP compliance:
yes (incl. QA statement)

Test material

Constituent 1
Chemical structure
Reference substance name:
3-(dimethylamino)propylurea
EC Number:
401-950-2
EC Name:
3-(dimethylamino)propylurea
Cas Number:
31506-43-1
Molecular formula:
C6H15N3O
IUPAC Name:
3-dimethylaminopropyl urea
Constituent 2
Chemical structure
Reference substance name:
1,3-bis[3-(dimethylamino)propyl]urea
EC Number:
257-861-2
EC Name:
1,3-bis[3-(dimethylamino)propyl]urea
Cas Number:
52338-87-1
Molecular formula:
C11H26N4O
IUPAC Name:
1,3-bis[3-(dimethylamino)propyl]urea
Constituent 3
Chemical structure
Reference substance name:
Urea
EC Number:
200-315-5
EC Name:
Urea
Cas Number:
57-13-6
Molecular formula:
CH4N2O
IUPAC Name:
urea
Test material form:
liquid
Specific details on test material used for the study:
Source : Air Products and Chemicals, Inc.
Date Received : 12/17/99
Label Identity : NE 1060
Storage : Room temperature and humidity.
Description : Clear liquid
Sample Preparation : The test article was used as received.

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
New Zealand White rabbits were received from Ace Animals, Boyertown, PA on 12/21/99 and quarantined for at least five days. Only animals in apparent good health were made available for study assignment. Prior to being selected for this study, both eyes of each animal were examined according to the Draize technique for any evidence of irritation or abnormalities of the cornea, iris and/or conjunctiva. A Mini-MagliteB flashlight equipped with a high intensity bulb was used to aid in the examination. Three rabbits (males), free from evidence of ocular irritation or abnormalities, were assigned to this study.

The animals were born the weeks of 10/10 through 10/24/99. The pretest body weight was 2.1 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 ad libitum. The animal room, reserved exclusively for rabbits on acute tests, was temperature controlled, had a 12 hour lightldark cycle and was kept clean and vermin free.

Test system

Vehicle:
unchanged (no vehicle)
Controls:
yes
Amount / concentration applied:
The test article (0.1 ml) was placed by syringe into the conjunctival sac which was formed by gently pulling the lower eyelid away from the eye.
Duration of treatment / exposure:
After instillation, the lids were held together for approximately one second to insure adequate distribution of the test article.
Observation period (in vivo):
Using a Mini-Maglit- flashlight equipped with a high intensity bulb, the treated eye of each rabbit was examined for irritation of the cornea, iris and conjunctiva at 1,24,48, and 72 hours post dose and on day 7. Ocular reactions were graded according to the numerical Draize technique. Additional signs were described.
Duration of post- treatment incubation (in vitro):
The eyes were examined and scored by the Draize technique at 1,24,48 and 72 hours post dose and on day 7
Number of animals or in vitro replicates:
Three rabbits (males), free from evidence of ocular irritation or abnormalities, were assigned to this study.
Details on study design:
Test Animals
New Zealand White rabbits were received from Ace Animals, Boyertown, PA on 12/21/99 and
quarantined for at least five days. Only animals in apparent good health were made available for study assignment. Prior to being selected for this study, both eyes of each animal were examined according to the Draize technique for any evidence of irritation or abnormalities of the cornea, iris and/or conjunctiva. A Mini-MagliteB flashlight equipped with a high intensity bulb was used to aid in the examination. Three rabbits (males), free from evidence of ocular irritation or abnormalities, were assigned to this study.
The animals were born the weeks of 10/10 through 10/24/99. The pretest body weight was 2.1 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 ad libitum. The animal room, reserved exclusively for rabbits on acute tests, was temperature controlled, had a 12 hour lightldark cycle and was kept clean and vermin free.

Dosing
One eye of each rabbit was dosed. The contralateral eye sewed as a control. The test article (0.1 ml) was placed by syringe into the conjunctival sac which was formed by gently pulling the lower eyelid away from the eye. After instillation, the lids were held together for approximately one second to insure adequate distribution of the test article.

Type and Frequency of Observations
Using a Mini-Maglit- flashlight equipped with a high intensity bulb, the treated eye of each rabbit was examined for irritation of the cornea, iris and conjunctiva at 1,24,48, and 72 hours post dose and on day 7. Ocular reactions were graded according to the numerical Draize technique. Additional signs were described.
Body weights were recorded pretest.
The general health of the animals was monitored at each observation time.

Analysis of Data
The primary eye irritation score for each rabbit was calculated from the weighted Draize scale.
Eve irritation is the production of reversible changes in the eye following application of the test article to the anterior surface of the eye.
Eve corrosion is the production of irreversible tissue damage to the eye following application of the test article to the anterior surface of the eye.

Retention of Data
The raw data is filed at MB Research by project number. The final report is filed at MB Research by sponsor name and MB project number.
The test article will be returned to the sponsor following submission of the report.
Amendment to the Protocol
There were no amendments to the protocol

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
animal: #1,#2, #3
Time point:
7 d
Reversibility:
not reversible
Remarks on result:
positive indication of irritation
Irritation parameter:
iris score
Basis:
animal: #1,#2, #3
Time point:
7 d
Reversibility:
not reversible
Remarks on result:
positive indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal: #1,#2, #3
Time point:
7 d
Reversibility:
not reversible
Remarks on result:
positive indication of irritation
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Remarks on result:
not measured/tested
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Remarks on result:
not measured/tested
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48/72 h
Remarks on result:
not measured/tested
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Remarks on result:
not measured/tested
Irritant / corrosive response data:
Corneal opacity, iritis and conjunctival irritation persisted through day 7.
Other effects:
Systemic Observations: One instance of soiling of the anogenital area was noted during the observation period.

Applicant's summary and conclusion

Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Conclusions:
Corneal opacity, iritis and conjunctival irritation persisted through day 7. One instance of soiling of the anogenital area was noted during the observation period.
NE 1060 is corrosive to the rabbit eye.
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-across justification this result is also deemed valid for 1,3-bis[3-(dimethylamino)propyl]urea (bisDMAPU).
bisDMAPAU is classified for serious eye damage - Eye cat 1.