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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:
Experimental Start Date: 11/06/07. Experimental Termination Date: 11/20/07
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
Study conducted to GLP and in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not effect the quality of the relevant results.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2008
Report date:
2008

Materials and methods

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

Test material

Constituent 1
Chemical structure
Reference substance name:
N-isopropylmethacrylamide
EC Number:
237-331-7
EC Name:
N-isopropylmethacrylamide
Cas Number:
13749-61-6
Molecular formula:
C7H13NO
IUPAC Name:
2-methyl-N-(propan-2-yl)prop-2-enamide
Test material form:
other: solid
Details on test material:
Identity: NIPMAA Technical Grade, Lot/Batch #58838
Stability: Stable
Date received: 11/01/07
Storage: Room temperature and humidity
Description: White powder

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: New Zealand White rabbits were received from Millbrook Breeding Labs, MA.
- Age at study initiation: Approximately 3 months old.
- Weight at study initiation: The pretest body weight was 2.6 - 3.1 kg.
- Housing: The animals were housed 1 per cage in suspended cages. Bedding was placed beneath the cages and changed at least three times per week.
- Diet (e.g. ad libitum): Fresh PMO Rabbit Chow was provided daily.
- Water (e.g. ad libitum): Water was available ad libitum.
- Acclimation period: At least five days.
Three animals (1 male, 2 females), free from evidence of occular irritation or abnormalities, were assigned to the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): The animal room was temperature controlled.
- Photoperiod (hrs dark / hrs light): 12-hour light/dark cycle.

Test system

Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 ml (equivalent 68.3 mg).
Duration of treatment / exposure:
Single exposure
Observation period (in vivo):
Up to 7 days.
Number of animals or in vitro replicates:
3 (1 male, 2 females)
Details on study design:
DOSING:
One eye of each rabbit was dosed. The contralateral eye served as a control. The test article (0.1 ml (equivalent (68.3 mg)) was placed by syringe-type applicator 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 ensure adequate distribution of the test article.

TYPE AND FREQUENCY OF OBSERVATIONS:
Using a Mini-Maglite 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 in all three animals and to day 7 in the two additional animals. Sodium fluorescein dye procedures were used at the 24 and 48 hour observation intervals for the initial animal and at the 24 hour observation interval for the two additional animals. The eye was examined with the aid of an ultraviolet light source.
Ocular reactions were graded according to the numerical Draize technique (see attached background matertial). Additional signs were described.

Body weights were recorded pretest and at termination.

The general health of the animals was monitered at each observation time. All animals were humanely sacrificed using CO2 following study termination.




Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
(Animal 1 - H504)
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: lack of normal luster observed at 24 hour observation
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
(Animal 2 - H512)
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
(Animal 3 - H526)
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
mean
Remarks:
(Animal 1 - H504)
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
iris score
Basis:
mean
Remarks:
(Animal 2 - H512)
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
iris score
Basis:
mean
Remarks:
(Animal 3 - H526)
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
mean
Remarks:
(Animal 1 - H504)
Time point:
24/48/72 h
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
mean
Remarks:
(Animal 2 - H512)
Time point:
24/48/72 h
Score:
0.67
Max. score:
3
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
mean
Remarks:
(Animal 3 - H526)
Time point:
24/48/72 h
Score:
1.67
Max. score:
3
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
(Animal 1 - H504)
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
(Animal 2 - H512)
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
(Animal 3 - H526)
Time point:
24/48/72 h
Score:
0.67
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Irritant / corrosive response data:
Ocular Findings (see Table 1 - attached back ground material).
There was no corneal opacity or iritis noted at any observation period. Conjunctival irritation was noted in 3/3 eyes and cleared by day 7.
Other effects:
Systemic Observations (see Table 1 - attached back ground material).
All animals appeared normal during the observation period.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The test substance produced conjunctival irritation which cleared by day 7.
Executive summary:

Objective:

To determine the irritant and/or corrosive effects, if any, of a test article when instilled into the rabbit eye. The study was designed to comply with the standards set forth in OECD Guidelines For Testing Chemicals, Number 405, adopted April 24, 2002.

Method Synopsis:

Initially, one healthy New Zealand White rabbit (female), free from evidence of ocular irritation and corneal abnormalities, was dosed with NIPMAA Technical Grade. The test article (0.1 ml (equivalent (68.3 mg)) was placed into the conjuctival sac of one eye. Based on the reactions of the initial animal, two additional animals (1 male, 1 female) were added to the study and dosed in the same manner. The eyes were examined and scored by the Draize technique at 1, 24, 48 and 72 hours in all three animals and to day 7 in the two additional animals. Sodium fluorescein dye procedures were used at the 24 and 48 hour observation intervals for the initial animal and at the 24 hour observation interval for the two additional animals. The primary eye irritation score for each rabbit, each day, was calcuated. Body weights were recorded pretest and at termination.

Summary:

There was no corneal opacity or iritis noted at any observation period. Conjunctival irritation was noted in 3/3 eyes and cleared by day 7.

All animals appeared normal during the observation period.

Conclusion:

NIPMAA Technical Grade produced conjunctival irritation which cleared by day 7.