Quaternary ammonium compounds, di-C14-18-alkyldimethyl, Me sulfates

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

significant methodological deficiencies

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1975

Report date:

1975

Materials and methods

Principles of method if other than guideline:

- Principle of test:
Six albino rabbits of the New Zealand strain were placed in a collar such that the animals could not rub their eyes. 0.1 g of the substance were instilled in one eye, the other untreated eye served as control. Damage to the cornea, iris and the bulbar and palpebral conjunctivae were scored at 24, 48 and 72 h after eye instillation. Any residue of the test material and accumulated discharge are flushed from the eye each time they are scored.
- Parameters analysed / observed:
Damage to the eye, i.e. opacity of the cornea and the area of opacity, reaction of the iris and redness, chemosis and discharge of the conjunctivae were scored.

GLP compliance:

no

Remarks:

study conducted prior to implementation of GLP

Test material

Test material information

Constituent 1

Reference substance name:

Quaternary ammonium compounds, di-C14-18-alkyldimethyl, Me sulfates

Cas Number:

68002-58-4

IUPAC Name:

Quaternary ammonium compounds, di-C14-18-alkyldimethyl, Me sulfates

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: the contralateral, untreated eye served as control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 g

Duration of treatment / exposure:

The substance was once instilled and the treated eye was flushed if any residual or accumulated test item was visible at each scoring time point.

Observation period (in vivo):

72 h

Number of animals or in vitro replicates:

6 animals

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): If residual or accumulated test substance was visible the treated eye was washed at each scoring time point
- Time after start of exposure: The first scoring time point was 24 h after eye instillation

SCORING SYSTEM: Draize scale

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

animal: #1, #3, #4

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Results 2

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

not reversible

Remarks:

duration of observation was 72 h

Results 3

Irritation parameter:

cornea opacity score

Basis:

animal #5

Time point:

24/48/72 h

Score:

0.67

Max. score:

4

Reversibility:

fully reversible within: 72 h

Results 4

Irritation parameter:

cornea opacity score

Basis:

animal #6

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

not reversible

Remarks:

duration of observation was 72 h

Results 5

Irritation parameter:

iris score

Basis:

animal: #1 - #6

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

no indication of irritation

Results 6

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1.67

Max. score:

3

Reversibility:

fully reversible within: 72 h

Results 7

Irritation parameter:

conjunctivae score

Basis:

animal: #2, #5

Time point:

24/48/72 h

Score:

2.67

Max. score:

3

Reversibility:

not reversible

Remarks:

duration of observation was 72 h

Results 8

Irritation parameter:

conjunctivae score

Basis:

animal: #3, #6

Time point:

24/48/72 h

Score:

2.33

Max. score:

3

Reversibility:

not reversible

Remarks:

duration of observation was 72 h

Results 9

Irritation parameter:

conjunctivae score

Basis:

animal #4

Time point:

24/48/72 h

Score:

2

Max. score:

3

Reversibility:

not reversible

Remarks:

duration of observation was 72 h

Results 10

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1.33

Max. score:

4

Reversibility:

fully reversible within: 72 h

Results 11

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

2.33

Max. score:

4

Reversibility:

not reversible

Remarks:

duration of observation was 72 h

Results 12

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1.33

Max. score:

4

Reversibility:

fully reversible within: 72 h

Results 13

Irritation parameter:

chemosis score

Basis:

animal #4

Time point:

24/48/72 h

Score:

1.67

Max. score:

4

Reversibility:

not reversible

Remarks:

duration of observation was 72 h

Results 14

Irritation parameter:

chemosis score

Basis:

animal: #5, #6

Time point:

24/48/72 h

Score:

2.67

Max. score:

4

Reversibility:

not reversible

Remarks:

duration of observation was 72 h

Irritant / corrosive response data:

During the observation period, corneal opacity scores were 0 in 3/6 animals, 1 in 2/6 animals and 2 in 1/6 animals. Iris scores were 0 throughout the observation period. Conjunctival redness was scored 3 after 24 h in all animals, 2-3 after 48 h, and 0-2 after 72 h. Chemosis scores were 2-3 after 24 h, 2 after 48 h, and 0-2 after 72 h. As the animals were observed only for 72 h, and effects were still present at study termination, reversibility cannot finally be evaluated. Nevertheless, a tendency towards reversion was noted.

Any other information on results incl. tables

Table 1: Irritant/corrosive response data for each animal at each observation time up to removal of each animal from the test

Score at time point / Reversibility	Cornea	Iris	Conjunctivae	Chemosis
	Max. score: 4	Max. score: 2	Max. score: 3	Max. score: 4
24 h	0/2/0/0/1/1	0/0/0/0/0/0	3/3/3/3/3/3	2/3/2/2/3/3
48 h	0/2/0/0/1/1	0/0/0/0/0/0	2/3/2/2/3/2	2/2/2/2/2/2
72 h	0/2/0/0/0/1	0/0/0/0/0/0	0/2/2/1/2/2	0/2/0/1/2/2
Average 24h, 48h, 72h	0/2/0/0/0.67/1	0/0/0/0/0/0	1.67/2.67/2.33/2/2.67/2.33	1.33/2.33/1.33/1.67/2.67/2.67
Reversibility*)	n.c.	c.	n.c.	n.c.
Average time (unit) for reversion	72 h		72 h	72 h

*) Reversibility: c. = completely reversible; n.c. = not completely reversible; n. = not reversible

Applicant's summary and conclusion

Interpretation of results:

study cannot be used for classification

Conclusions:

Based on scores for conjunctival redness and chemosis, C14-18 alkyldimethyl ammonium methosulfate (89% a.i.) has to be classified for eye irritation. However, discrimination between Category 1 and 2 is not possible based on this study.

Executive summary:

In a primary eye irritation study conducted prior to implementation of GLP and OECD guidelines 0.1 g of C14-18 alkyldimethyl ammonium methosulfate (89% a.i.) was instilled into the conjunctival sac of one eye of 6 adult New Zealand White rabbits. The substance was once instilled and the treated eye was flushed if any residual or accumulated test item was visible at each scoring time point (24, 48, 72 h). Animals were observed for 3 days.  Irritation was scored by the method of Draize.

During the observation period, corneal opacity scores were 0 in 3/6 animals, 1 in 2/6 animals and 2 in 1/6 animals. Iris scores were 0 throughout the observation period. Conjunctival redness was scored 3 after 24 h in all animals, 2-3 after 48 h, and 0-2 after 72 h. Chemosis scores were 2-3 after 24 h, 2 after 48 h, and 0-2 after 72 h. As the animals were observed only for 72 h, and effects were still present at study termination, reversibility cannot finally be evaluated. Nevertheless, a tendency towards reversion was noted.

Based on scores for conjunctival redness and chemosis, C14-18 alkyldimethyl ammonium methosulfate (89% a.i.) has to be classified for eye irritation. However, discrimination between Category 1 and 2 is not possible based on this study.