Quaternary ammonium compounds, di-C12-18-alkyldimethyl, chlorides

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From May 27, 1980 to June 17, 1980

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1980

Report date:

1980

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

not specified

Principles of method if other than guideline:

Not applicable

GLP compliance:

no

Remarks:

Pre-GLP

Test material

Test material information

Constituent 1

Reference substance name:

Quaternary ammonium compounds, di-C12-18-alkyldimethyl, chlorides

EC Number:

269-924-1

EC Name:

Quaternary ammonium compounds, di-C12-18-alkyldimethyl, chlorides

Cas Number:

68391-05-9

Molecular formula:

Substance is an UVCB (representative molecular formula for 2 major constituents: C12-C12 DAQ: C26H56Cl1N1; C18-C18 DAQ: C38H80Cl1N1)

IUPAC Name:

N-C12-C18(even numbered)-alkyl-N,N-dimethyl-C12-C18(even numbered)-alkyl-1-aminium chloride

additive 1

Reference substance name:

Propan-2-ol

EC Number:

200-661-7

EC Name:

Propan-2-ol

Cas Number:

67-63-0

Molecular formula:

C3H8O

IUPAC Name:

propan-2-ol

additive 2

Reference substance name:

Water

EC Number:

231-791-2

EC Name:

Water

Cas Number:

7732-18-5

Molecular formula:

H2O

IUPAC Name:

water

Test material form:

not specified

Details on test material:

- Chemical name: Quaternary ammonium compounds, di-C12-18-alkyldimethyl, chlorides (C12-18 DAQ)
- EC number: 269-924-1

To the best of knowledge, the sample used is representative to the boundary composition shared and agreed by each registrant

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Hoppers Unlimited, Verona, WI, USA
- Age at study initiation: ca. 14 wk
- Housing: Individually in screen bottom cages
- Diet (e.g. ad libitum): ad lib
- Water (e.g. ad libitum): ad lib
- Acclimation period: at least 7 d

IN-LIFE DATES: From: 28 May To: 17 June 1980

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: the untreated left eye of each animal served as the control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL
- Concentration (if solution): neat material

Duration of treatment / exposure:

Two groups of animals were used, in one group (II) the eyes were washed after 30 sec exposure and in the other group the eyes were not washed (I). The study continued to 21 d

Observation period (in vivo):

Readings were done after 24, 48, 72 and 96 h and after 7, 14 and 21 d. At the 72 h, 7, 14 and 21 d reading sodium fluorescein and UV light were used.

Number of animals or in vitro replicates:

Group I: 6 animals
Group II: 3

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): in 3 out of 9 rabbits, the eyes of the other 6 remained unflushed.
- Time after start of exposure: ca. 30 sec


SCORING SYSTEM:
DRAIZE SCALE FOR SCORING OCULAR IRRITATION (1959)

1. CORNEA
(A) Degree of Opacity (most dense area used)
No opacity 0
Scattered or diffuse areas, details of iris clearly visible 1
Easily discernible translucent areas, details of iris slightly obscured 2
Opalescent areas, no details of iris visible, size of pupil barely discernible 3
Opaque, iris invisible 4
(B) Area of Cornea involved
One quarter (or less) but not zero 1
Greater than one quarter but less than half 2
Greater than half but less than three quarters 3
Greater than three quarters, up to whole area 4
THE TOTAL SCORE = (A x B) x 5, MAXIMUM TOTAL = 80

2. IRIS
(A) Values
Normal 0
Folds above normal, congestion, swelling, circumcorneal injection
(any or all of these or combination of any thereof), iris still reacting to light
(sluggish reaction is positive) 1
No reaction to light, haemorrhage, gross destruction (any or all of these) 2
THE TOTAL SCORE = A x 5, MAXIMUM TOTAL = 10

3. CONJUNCTIVAE
(A) Redness (refers to palpebral and bulbar conjunctivae excluding cornea and iris)
Vessels normal 0
Vessels definitely injected above normal 1
More diffuse, deeper crimson rad, indiviual vessels not easily discernible 2
Diffuse beefy red 3
(B) Chemosis
No swelling 0
Any swelling above normal (includes nictitating membrane) 1
Obvious swelling with partial eversion of lids 2
Swelling with lids about half closed 3
Swelling with lids half closed to completely closed 4
(C) Discharge
No discharge 0
Any amount different from normal (does not include small amounts observed in inner canthus of normal animals) 1
Discharge with moistening of the lids and hairs just adjacent to lids 2
Discharge with moistening of the lids and hairs and considerable area around the eye 3
THE TOTAL SCORE (A + B + C) x 2, MAXIMUM TOTAL = 20

MAXIMUM TOTAL SCORE POSSIBLE = 110
NB In this scoring system also half grades were used (0.5, 1.5, 2.5, or 3.5)

TOOL USED TO ASSESS SCORE: fluorescein

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

ca. 3.89

Max. score:

4

Reversibility:

not reversible

Remarks:

(within 21 d)

Remarks on result:

other: Unwashed eyes

Results 2

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

ca. 2

Max. score:

2

Reversibility:

not reversible

Remarks:

(within 21 d)

Remarks on result:

other: Unwashed eyes

Results 3

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

mean

Time point:

24/48/72 h

Score:

ca. 0.33

Max. score:

3

Reversibility:

not reversible

Remarks:

(within 21 d)

Remarks on result:

other: Unwashed eyes

Results 4

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

ca. 4

Max. score:

4

Reversibility:

not reversible

Remarks:

(within 21 d)

Remarks on result:

other: Unwashed eyes

Results 5

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

ca. 2

Max. score:

4

Reversibility:

not reversible

Remarks:

(within 21 d)

Remarks on result:

other: washed eyes

Results 6

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

ca. 1.33

Max. score:

2

Reversibility:

not reversible

Remarks:

(within 21 d)

Remarks on result:

other: washed eyes

Results 7

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

mean

Time point:

24/48/72 h

Score:

ca. 2

Max. score:

3

Reversibility:

not reversible

Remarks:

(within 21 d)

Remarks on result:

other: washed eyes

Results 8

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

ca. 4

Max. score:

4

Reversibility:

not reversible

Remarks:

(within 21 d)

Remarks on result:

other: washed eyes

Results 9

Irritation parameter:

overall irritation score

Remarks:

unwashed eyes

Basis:

mean

Time point:

24/48/72 h

Score:

ca. 99.1

Max. score:

110

Remarks on result:

positive indication of irritation

Results 10

Irritation parameter:

overall irritation score

Remarks:

washed eyes

Basis:

mean

Time point:

24/48/72 h

Score:

ca. 55.78

Max. score:

110

Remarks on result:

positive indication of irritation

Irritant / corrosive response data:

- Blanching and areas of necrosis were observed in the conjunctivae of all rabbits at the 24, 48, 72, 96 h and 7 and 14 d readings and in 3 rabbits at 21 d.
- Hypopyon was observed in 4 rabbits at 7 d.
- Red ocular discharge was exhibited in 3 animals at 7 d and in 2 animals at 14 d.
- Panophthalmitis was exhibited by 1 animal at 14 days and by all animals at 21 days.

Other effects:

None

Any other information on results incl. tables

Table 1. Eye irritation scores (Draize) in rabbits exposed to 0.1 mL test substance and the eyes was not washed

Time	Corneal Opacity						Iris
	2997	2999	2947	3057	3051	3050	2997	2999	2947	3057	3051	3050
24 h	4	3	4	3	4	4	2^m	2^m	2^m	2^m	2^m	2^m
48h	4	4	4	4	4	4	2^m	2^m	2^m	2^m	2^m	2^m
72h	4	4	4	4	4	4	2^m	2^m	2^m	2^m	2^m	2^m
96 h	4	4	4	4	4	4	2^m	2^m	2^m	2^m	2^m	2^m
7 d	3.5^k	3.5^k	m	3.5^k	m	3.5^k	2^m	2^m	2^m	2^m	2^m	2^m
14 d	4	4	4	q	4	4	2^m	2^m	2^m	2^m	2^m	2^m
21 d	q	q	q	q	q	q	q	q	q	q	q	q
Mean 24-72 h	4	3.67	4	3.67	4	4	2	2	2	2	2	2

 

 

Time		Conjunctivae - Redness					Conjunctivae - Chemosis						Conjunctivae - Discharge
	2997		2999	2947	3057	3051		3050	2997	2999	2947	3057		3051	3050	2997	2999	2947		3057	3051	3050
24 h	1		1	1	1	1		1	4	4	4	4		4	4	3^a	3^a	3^a		3^a	3^a	3^a
48 h	0^jd		0^jd	0^jd	0^jd	0^jd		0^jd	4	4	4	4		4	4	3^a	3^a	3^a		3^a	3^a	3^a
72 h	0^jd		0^jd	0^jd	0^jd	0^jd		0^jd	4	4	4	4		4	4	3^a	3^a	3^a		3^a	3^a	3^a
96 h	0^jd		0^jd	0^jd	0^jd	0^jd		0^jd	4	4	4	4		4	4	3^a	3^a	3^a		3^a	3^a	3^a
7 d	0		0	m	0	m		0	4	3.5	4	4		4	3.5	2^a	2.5^a	3^pa		3^pa	3^a	2.5^pa
14 d	2^jd		2^jd	2^jdl	ljdm	2^jdl		2^jdl	4	4	4	4		4	4	3^ap	2^a	2^a		2^a	2^a	2^ap
21 d	2^jd		2^jd	m	m	m		2.5	3	3.5	4	3		3.5	4	2.5^a	2^a	1^a		1^a	2^a	2^a
Mean 24-72 h	0.33		0.33	0.33	0.33	0.33		0.33	4	4	4	4		4	4	3	3	3		3	3	3

 

a Purulent discharge

d Blanching

k hypopyon

l Hair loss around the eye

J Conjunctivae appear necrotic

m Unable to visualise

p red discharge

q Panopthalmitis

Table 2. Eye irritation scores (Draize) in rabbits exposed to 0.1 mL test substance and the eyes was flushed for one minute

Time	Corneal Opacity			Iris			Conjunctivae - redness			Conjunctivae- chemosis				Conjunctivae- discharge
	2958	2935	3018	2958	2935	3018	2958	2935	3018		2958	2935	3018	2958	2935	3018
24 h	1.5	3	1.5	1^inj	2^m	1^inj	2^jd	2^jd	2^jd		4	4	4	3^a	3^a	3^a
48h	1	3	1.5	1^inj	2^m	1^inj	2^jd	0^jd	1^jd		4	4	4	3^a	3^a	3^a
72h	2	3	1.5	1^inj	2^m	1^inj	3^jd	3^jd	3^jd		4	4	4	3^pa	3^a	3^a
96 h	1.5	4	1.5	1^inj	2^m	1^inj	3^jd	3^jd	3^jd		4	4	4	3^pa	3^a	3^pa
7 d	3.5^k	4^k	3	1^inj	2^m	1^inj	3^cjd	0^jd	3^cjd		4	4	3.5	3^a	3^a	3^a
14 d	4^h	4	4^h	2^m	2^m	2^m	2^jd	2^jdl	2^cjd		2	4	4	1.5^a	2^a	2^a
21 d	4	q	4	2^m	q	2^m	2.5^cjd	2.5^jd	3.0^kcjd		3	4	3	3^a	2.5^p	3^a
Mean 24-72 h	1.5	3	1.5	1	2	1	2.3	1.67	2		4	4	4	3	3	3

a Purulent discharge

c Petite hemorrhage

d Blanching

k Conjunctivae appears necrotic

j Conjunctivae appears necrotic

inj Injected

m Unable to visualise

p Red discharge

q Panopthalmitis

Applicant's summary and conclusion

Interpretation of results:

other: Category 1 (irreversible effects on the eye) based on EU CLP criteria

Conclusions:

Under the study conditions, the test substance was considered to be corrosive to eyes in rabbits.

Executive summary:

A study was performed to determine the eye irritation potential of test substance, C12 -18 DAQ (75% active in hydroalcoholic solution), according to the method equivalent or similar to OECD 405. Two groups of New Zealand white rabbits were used to in the study. 0.1 mL test substance was instilled into the eye of 9 rabbits (leaving the other eye untreated as a control). In one group (with 3 animals) the eyes were washed after 30 sec exposure and in the other group (with 6 animals) the eyes were not flushed. Readings (according to Draize) were done after 24, 48, 72 and 96 h and after 7, 14 and 21 d. At the 72 h, 7, 14 and 21 d reading sodium fluorescein and UV light were used. Blanching and areas of necrosis were observed in the conjunctivae of all rabbits at the 24, 48, 72 and 96 h and 7 and 14 d readings and in three animals at 21 d. Hypopyon was observed in four animals at 7 d. Red ocular discharge was exhibited in three animals at the 7 d and two animals at 14 d. Panopthalmitis was exhibited by one animal at 14 d and by all animals at 21 d. Under the study conditions, the test substance was considered to be corrosive to eyes in rabbits (Thompson, 1980).