Imidazolium compounds, 2-C17-unsatd.-alkyl-1-(2-C18-unsatd. amidoethyl)-4,5-dihydro-N-methyl, Me sulfates

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2001-06-14 to 2001-07-08

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2001

Report date:

2001

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2400 (Acute Eye Irritation)

Version / remarks:

1998

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

1987

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Deviations:

no

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: Japanese Guideline 11 Nousan No. 6283 (October 1, 1999); First Revision: 12 Nousan 8628 (December 6, 2000)

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

oleic-acid based IQAC, DMS quaternised

IUPAC Name:

oleic-acid based IQAC, DMS quaternised

Constituent 2

Reference substance name:

Imidazolium compounds, 2-C17-unsatd.-alkyl-1-(2-C18-unsatd. amidoethyl)-4,5-dihydro-N-methyl, Me sulfates

EC Number:

931-745-8

Cas Number:

1335203-21-8

Molecular formula:

Molecular formula cannot be given as substance is a mixture.

IUPAC Name:

Imidazolium compounds, 2-C17-unsatd.-alkyl-1-(2-C18-unsatd. amidoethyl)-4,5-dihydro-N-methyl, Me sulfates

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Covance Research Products Inc. Denver, PA, USA
- Age at study initiation: Young adult
- Weight at study initiation: 2577 to 2758 grams
- Housing: individual housing in suspended wire mesh cages
- Diet: 150 g/day, standard laboratory rabbit diet PMI Nutrition International, Inc. Certified Rabbit LabDiet® 5322
- Water: ad libitum, municipal water
- Acclimation period: at least 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°F): 66-77
- Humidity (%): 48-80
- Air changes (per hr): no data
- Photoperiod: 12 hour light/dark cycle

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: Each animal served as its one control. The test article was introduced into the conjunctival sac of one eye, the untreated eye serving as a control.

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.1 ml
- Concentration: The test article was applied unchanged as received

Duration of treatment / exposure:

Eyes were not rinsed after treatment.

Observation period (in vivo):

21 days

Number of animals or in vitro replicates:

3

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing: no washing was done

SCORING SYSTEM: in accordance with Draize, as published in the guidelines in Subsection F. Hazard Evaluation: Human and Domestic Animals distributed in 1984 and the EPA-OPPTS Health Effects Test Guidelines (1998).

TOOL USED TO ASSESS SCORE: 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.

PREPARATION and SELECTION of ANIMALS: Both eyes of all rabbits were examined for ocular abnormalities prior to initiation of dosing. The pre-initiation examination included the use of sodium fluorescein and a direct ophthalmoscope for detection of corneal abnormalities. Only rabbits with no
pre-existing ocular abnormalities were assigned to study.
Both eyes of all rabbits were examined macroscopically for ocular irritation in accordance with the method of Draize at approx. 1, 24, 48, 72 h, 4, 7, 14 d

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days

Results 2

Irritation parameter:

cornea opacity score

Basis:

other: #1, #2

Time point:

24/48/72 h

Score:

1.67

Max. score:

4

Reversibility:

fully reversible within: 21 days

Results 3

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

no indication of irritation

Results 4

Irritation parameter:

iris score

Basis:

animal: #1, #2

Time point:

24/48/72 h

Score:

1

Max. score:

2

Reversibility:

fully reversible within: 7 days

Results 5

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

2

Max. score:

3

Reversibility:

fully reversible within: day 14

Results 6

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2.33

Max. score:

3

Reversibility:

fully reversible within: day 21

Results 7

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

3

Max. score:

3

Reversibility:

fully reversible within: 17 days

Results 8

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

2.67

Max. score:

4

Reversibility:

fully reversible within: 14 days

Results 9

Irritation parameter:

chemosis score

Basis:

animal: #1, #2

Time point:

24/48/72 h

Score:

3.67

Max. score:

4

Reversibility:

fully reversible within: 17 days

Irritant / corrosive response data:

Positive corneal, iridal and conjunctival findings were noted for all animals. Corneal neovascularization was noted for two animals on study days 7 through 14 or 17. Iridal irritation subsided by study day 7, and corneal and conjunctival irritation completely subsided by study termination (study day 21).
The Maximum Average Score for the test substance was 50.3 at 48 hours post-instillation.

Other effects:

There were no deaths or remarkable body weight changes during the study period.

Any other information on results incl. tables

Irritant/corrosive response data for each animal at each observation time

Score at time point / Reversibility	Cornea opacity	Cornea - Area  involved	Iris	Conjunctivae Redness	Conjunctivae Chemosis	Conjunctivae Discharge	Fluorescein test (% of cornea retaining stain)
	Max. score: 4	Max. score: 4	Max. score: 2	Max. score: 3	Max. score: 4	Max. score: 3	Max.: 100 %
1 hour	1/1/1	1/1/1	1/1/1	2/2/1	3/2/3	3b/3b/3b	no
24 hours	1/1/1	4/4/1	1/1/0	3/2/2	4/3/3	3b,p/3b,p/3b,p	yes 75/65/10
48 hours	2/2/1	4/4/1	1/1/0	3/3/2	4/4/3	3b,p/3b/3b,p	yes 65/45/5
72 hours	2/2/1	4/3/1	1/1/0	3/2/2	3/4/2	3b,p/3b/1b,p	yes 50/30/0
4 days	2/2/1	4/3/1	1/1/0	3/2/2	3/3/2	2b,p/2b/1b,p	yes 50/20/0
7 days	2k/1k/0	2/1/0	0/0/0	2/2/1	2/2/1	1b/0/0	yes 15/5/0
10 days	1k/1k/0	1/1/0	0/0/0	1/2/1	1/1/1	0/0/0	yes 0/0/0
14 days	1k/1k/0	1/1/0	0/0/0	1/1/0	0/1/0	0/0/0	yes 0/0/0
17 days*	0/1k/-	0/1/-	0/0/-	0/1/-	0/0/-	0/0/-	yes 0/0/-
21days**	-/0/-	-/0/-	-/0/-	-/0/-	-/0/-	-/0/-	yes -/0/-

* only the two animals with responses at 14 days examined

** only the animal with responses at 17 days examined

b = clear discharge, p = purulent discharge in conjunctival sac, k = corneal neovascularization

Applicant's summary and conclusion

Interpretation of results:

Category 2A (irritating to eyes) based on GHS criteria

Conclusions:

Interpretation is based on effects on the cornea, iris and conjunctiva calculated as mean scores following grading at 24, 48 and 72 hours after instillation of the test material, in consideration of reversibility. Slight to moderate effects of cornea and iris were observed and moderate to severe conjunctivae and chemosis scores. All symptoms were fully reversible within 21 days.

Executive summary:

In a primary eye irritation study according to US Guideline EPA OPPTS 870.2400 (1998), OECD Guideline 405 (1987), EU Guideline B.5 (1992) and Japanese Guideline Nousan No. 6283 (1999), revised Nousan 8628 (2000), 0.1 ml of oleic-acid based IQAC, DMS quaternised (according to sponsors information: 80 % of CAS No. 72749-55-4, 15 % of CAS No. 9004-96-0 (Oleic acid, ethoxylated) and 5 % of CAS No. 25322-68-3 (Poly(oxy-1,2-ethanediyl),α-hydro-ω-hydroxy- Ethane-1,2-diol, ethoxylated)) was instilled into the conjunctival sac of three White New Zealand rabbits. The eyes were not rinsed after substance application. Animals then were observed for 21 days. Irritation was scored by the method of Draize.

Positive corneal, iridal and conjunctival findings were noted for all animals. Corneal neovascularization was noted for two animals on study days 7 through 14 or 17. Iridal irritation subsided by study day 7, and corneal and conjunctival irritation completely subsided by study termination (study day 21).

The test substance induced a maximum mean total score of 50.3 (maximum possible mean total score of 110) at 48 hours post-instillation. Mean scores following grading at 24, 48 and 72 hours after instillation of the test material for corneal opacity were >/= 1but < 3, for iritis >/= 1 but < 1.5 and for conjunctival redness and oedema >/= 2. All effects were completely reversible in all animals within 21 days.