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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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted according to GLP and OECD guideline 405.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Report date:
2013

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Ammonium carbamate
EC Number:
214-185-2
EC Name:
Ammonium carbamate
Cas Number:
1111-78-0
Molecular formula:
CH3NO2.H3N
IUPAC Name:
ammonium carbamate
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
As reported by the sponsor, the purity of the test substance was tested as 100% (composition of 43.6% as ammonia and 56.3% as carbon dioxide).
The appropriate amount of test substance was gently ground to remove clumps and weighed into tared weigh boats that were covered, labeled, and transported to the animal room for dose administration.

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
New Zealand White albino rabbits utilized for this study were originally received in good health from Covance Research Products, Inc., Denver, PA. The rabbits were inspected by a qualified technician upon receipt, weighed and uniquely identified by a plastic eartag displaying the animal number. Upon arrival, all animals were housed individually in clean, stainless steel, wire-mesh cages. The animals were maintained by the animal husbandry staff of WIL Research in accordance with SOPs. The animal facilities at WIL Research are accredited by AAALAC International. Enrichment devices were provided to all animals as appropriate throughout the study for environmental enrichment and to aid in maintaining the animals’ oral health. The basal diet used in this study, PMI Nutrition International, LLC, Certified Rabbit HF LabDiet® 5325, is a certified feed with appropriate analyses performed by the manufacturer and provided to WIL Research. Municipal water supplying the facility was analyzed for contaminants according to WIL Research SOPs. The results of the diet and water analyses are maintained at WIL Research. No contaminants were present in animal feed or water at concentrations sufficient to interfere with the objectives of this study. The basal diet was provided at approximately 150 g/day while municipal water, delivered by an automatic watering system, was provided ad libitum throughout the acclimation period and during the study.
All animals were housed throughout the acclimation period and during the study in an environmentally controlled room. The room temperature and humidity controls were set to maintain environmental conditions of 66 ± 5°F (19 ± 3°C) and 50 ± 20%, respectively. Room temperature and relative humidity data were monitored continuously and were scheduled for automatic collection on an hourly basis. Actual mean daily temperature ranged from 65.3°F to 66.4°F (18.5°C to 19.1°C) and mean daily relative humidity ranged from 47.8% to 58.4% during the study. Fluorescent lighting provided illumination for a 12-hour light (0600 hours to 1800 hours)/12-hour dark photoperiod. Lighting conditions were recorded every 15 minutes. Air handling units were set to provide a minimum of 10 fresh air changes per hour.

Test system

Vehicle:
unchanged (no vehicle)
Amount / concentration applied:
100 mg of undiluted substance per eye
Duration of treatment / exposure:
Both eyes of all rabbits were examined macroscopically for ocular irritation in accordance with the method of Draize at approximately 1, 24, 48,
and 72 hours after dosing and on study days 4, 7, 10, 14, 17, and 21 if irritation persisted. A direct ophthalmoscope was used during these observations to examine the corneal tissue. In addition, both eyes were further examined at 24 hours and at all subsequent observations with sodium fluorescein.
Observation period (in vivo):
max. 21 days
Number of animals or in vitro replicates:
3 (2 females, 1 male)

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Remarks:
opacity
Basis:
animal #1
Remarks:
male
Time point:
other: mean of 24, 48, and 72 hours after application
Score:
0
Irritation parameter:
cornea opacity score
Remarks:
opacity
Basis:
animal #2
Remarks:
female
Time point:
other: mean of 24, 48, and 72 hours after application
Score:
2
Reversibility:
not fully reversible within: 21 days
Irritation parameter:
cornea opacity score
Remarks:
opacity
Basis:
animal #3
Remarks:
female
Time point:
other: mean of 24, 48, and 72 hours after application
Score:
1
Reversibility:
fully reversible within: 10 days
Irritation parameter:
iris score
Basis:
animal #1
Remarks:
male
Time point:
other: mean of 24, 48, and 72 hours after application
Score:
0
Irritation parameter:
iris score
Basis:
animal #2
Remarks:
female
Time point:
other: mean of 24, 48, and 72 hours after application
Score:
1
Reversibility:
fully reversible within: 7 days
Irritation parameter:
iris score
Basis:
animal #3
Remarks:
female
Time point:
other: mean of 24, 48, and 72 hours after application
Score:
1
Reversibility:
fully reversible within: 4 days
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #1
Remarks:
male
Time point:
other: mean of 24, 48, and 72 hours after application
Score:
0
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #2
Remarks:
female
Time point:
other: mean of 24, 48, and 72 hours after application
Score:
2.67
Max. score:
3
Reversibility:
fully reversible within: 21 days
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #3
Remarks:
female
Time point:
other: mean of 24, 48, and 72 hours after application
Score:
2
Reversibility:
fully reversible within: 14 days
Irritation parameter:
chemosis score
Basis:
animal #1
Remarks:
male
Time point:
other: mean of 24, 48, and 72 hours after application
Score:
0
Irritation parameter:
chemosis score
Basis:
animal #2
Remarks:
female
Time point:
other: mean of 24, 48, and 72 hours after application
Score:
1
Reversibility:
fully reversible within: 14 days
Irritation parameter:
chemosis score
Basis:
animal #3
Remarks:
female
Time point:
other: mean of 24, 48, and 72 hours after application
Score:
1
Reversibility:
fully reversible within: 4 days
Irritation parameter:
other: discharge
Basis:
animal #1
Remarks:
male
Time point:
other: mean of 24, 48, and 72 hours after application
Score:
0
Irritation parameter:
other: discharge
Basis:
animal #2
Remarks:
female
Time point:
other: mean of 24, 48, and 72 hours after application
Score:
1.67
Max. score:
2
Reversibility:
fully reversible within: 7 days
Irritation parameter:
other: discharge
Basis:
animal #3
Remarks:
female
Time point:
other: mean of 24, 48, and 72 hours after application
Score:
1.3
Max. score:
2
Reversibility:
fully reversible within: 4 days
Irritant / corrosive response data:
Positive corneal irritation (grades 1, 2, and 3), iridial irritation (grade 1), and conjunctival irritation (grades 2 and 3) were noted for 2 females. Positive corneal irritation was noted in 1 female and was not fully reversible until termination of the study (day 21). Positive scores for iritis and/or conjunctival irritation subsided by study day 7. There were no positive effects noted in the male animal.
The only finding for the male animal was conjunctival redness (grade 1; not positive) noted 1 hour following dose administration.
The left (control) eyes were free of evidence of ocular irritation and other findings for the duration of the study.
Other effects:
One female animal was noted to have a large body weight loss (779.8 g) from study day 0 to 14. The body weight loss is not believed to be a direct test substance-related effect due to the lack of similar losses in the remaining two rabbits. The effect could have possibly been a response to the ocular irritation observed or an aversion to handling. However, the male animal and the other female were noted to have very slight body weight losses (7.2 g and 11.5 g, respectively). These minor body weight fluctuations are commonly observed for rabbits maintained on a restricted diet.

Any other information on results incl. tables

Number of Animals with Positive Effect/Number of Animals Treated

 Group  Cornea  Iris  Conjunctiva  Total  MAS
 100 mg/right eye, unwashed  2/3  2/3  2/3  2/3  24.0/48 -hours post-instillation

MAS = Maximum Average Score

Applicant's summary and conclusion

Interpretation of results:
Category 1 (irreversible effects on the eye)
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based on the results of the present study, ammonium carbamate is considered to cause irreversible damage to the eyes. The test substance is thus classified as causing serious damage to eyes (Cat. 1, H318) according to Regulation (EC) No 1272/2008 (CLP).
Executive summary:

The objective of this study was to determine the primary ocular irritative potential of ammonium carbamate in albino rabbits. The study was conducted according to GLP and OECD guideline 405. There was 1 group of 3 albino rabbits that received a single, unwashed exposure. A 100 mg dose of the test substance was instilled into the lower conjunctival sac of the right eye for each animal. The eyelid was held closed for approximately 1 second and released. The left eye of each animal was manipulated in an identical manner to simulate the dosing of the right eye and served as a contralateral control.

There were no deaths during the study. Positive corneal irritation (grades 1, 2, and 3), iridial irritation (grade 1), and conjunctival irritation (grades 2 and 3), were noted for 2 females. Positive corneal irritation was noted in 1 female throughout the study. Positive scores for iritis and/or conjunctival irritation subsided by study day 7. There were no positive effects noted in the male animal.

One female was noted to have a large body weight loss (779.8 g) from study day 0 to 14. The body weight loss is not believed to be a direct test substance-related effect due to the lack of similar losses in the remaining two rabbits. The weight loss for this female could

have possibly been a response to the ocular irritation observed or an aversion to handling.