Quaternary ammonium compounds, C14-18 (even numbered) and C18 unsaturated-alkyl-hydroxyethyl-dimethyl, chlorides

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

23-26 October 1995

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Remarks:

GLP study conducted in compliance with OECD Guideline 405 with deviations: age at study initiation, individual animal weights, environmental conditions not reported; non-ocular local and systemic adverse effects not followed

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1996

Report date:

1996

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

age at study initiation, individual animal weights, environmental conditions not reported; non-ocular local and systemic adverse effects not followed

Principles of method if other than guideline:

Not applicable

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Quaternary ammonium compounds, C14-18 (even numbered) and C18 unsaturated-alkyl-hydroxyethyl-dimethyl, chlorides

EC Number:

948-061-0

Molecular formula:

C18 H40 NO+ Cl- ; C20 H44 NO+ Cl- ; C22 H46 NO+ Cl- ; C22 H46 NO+ Cl- ; C22 H48 NO+ Cl-

IUPAC Name:

Quaternary ammonium compounds, C14-18 (even numbered) and C18 unsaturated-alkyl-hydroxyethyl-dimethyl, chlorides

Test material form:

liquid

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL- Source and lot/batch No.of test material: Chimex / Batch M 303- Physical state: Yellowish limpid liquid- Date received: October 9, 1995- Purity test date: July 27, 1995STORAGE CONDITIONS OF TEST MATERIAL- Storage condition of test material: Stored at room temperature, away from the light and heat

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS- Source: elevage ROUGIER (63370 - St Gervais, d'Auvergne.- Weight at study initiation: 2 kg (average weight)- Housing: Animals were housed individually on floor grids.- Diet: Complete pelleted rabbit maintenance diet Energie H326 (COFNA, 37000 - Tours, France), ad libitum- Acclimation period: 5 daysENVIRONMENTAL CONDITIONS: Environmental conditions and controls in accordance with the requirements of the 86/609/EEC guideline.IN-LIFE DATES: 23-26 October 1995

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: untreated eye served as control

Amount / concentration applied:

TEST MATERIAL - Amount(s) applied (volume or weight with unit): 0.1 mL/eye - Concentration (if solution): Undiluted

Duration of treatment / exposure:

No washing was done.

Observation period (in vivo):

1, 24, 48 and 72 h after instillation of the test substance. If lesions are too severe, to avoid unnecessary pain, animal is euthanatized.

Number of animals or in vitro replicates:

3 males

Details on study design:

TREATMENTTest substance was placed at a dose of 0.1 mL in the conjunctival sac of the right eye after gently pulling the lower lid away from the eyeball. The lids are then gently held together for about one second in order to prevent loss of the test substance. The other eye, which remains untreated, serves as a control. After a one hour period of contention, the animals were returned to its individual cage.REMOVAL OF TEST SUBSTANCE- Washing: NoSCORING SYSTEM: According to OECD Guideline 405TOOL USED TO ASSESS SCORE: - Ocular reactions were performed with a U. V. and white magnification light. After recording the observations at 24 h, the eyes of all rabbits were examined with the aid of fluorescein.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

other: mean 24, 48 and 72 h

Max. score:

4

Reversibility:

not reversible

Remarks:

impossible reading

Remarks on result:

positive indication of irritation

Results 2

Irritation parameter:

iris score

Basis:

animal #1

Time point:

other: mean 24, 48 and 72 h

Max. score:

2

Reversibility:

not reversible

Remarks:

impossible reading

Remarks on result:

positive indication of irritation

Results 3

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

other: mean 24, 48 and 72 h

Score:

3

Max. score:

3

Reversibility:

not reversible

Remarks on result:

positive indication of irritation

Results 4

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

other: mean 24, 48 and 72 h

Score:

4

Max. score:

4

Reversibility:

not reversible

Remarks on result:

positive indication of irritation

Results 5

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

other: mean 24, 48 and 72 h

Max. score:

4

Reversibility:

not reversible

Remarks:

impossible reading

Remarks on result:

positive indication of irritation

Results 6

Irritation parameter:

iris score

Basis:

animal #2

Time point:

other: mean 24, 48 and 72 h

Max. score:

2

Reversibility:

not reversible

Remarks:

impossible reading

Remarks on result:

positive indication of irritation

Results 7

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

other: mean 24, 48 and 72 h

Score:

3

Max. score:

3

Reversibility:

not reversible

Remarks on result:

positive indication of irritation

Results 8

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

other: mean 24, 48 and 72 h

Score:

4

Max. score:

4

Reversibility:

not reversible

Remarks on result:

positive indication of irritation

Results 9

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

other: mean 24, 48 and 72 h

Max. score:

4

Reversibility:

not reversible

Remarks:

impossible reading

Remarks on result:

positive indication of irritation

Results 10

Irritation parameter:

iris score

Basis:

animal #3

Time point:

other: mean 24, 48 and 72 h

Max. score:

2

Reversibility:

not reversible

Remarks:

impossible reading

Remarks on result:

positive indication of irritation

Results 11

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

other: mean 24, 48 and 72 h

Score:

3

Max. score:

3

Reversibility:

not reversible

Remarks on result:

positive indication of irritation

Results 12

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

other: mean 24, 48 and 72 h

Score:

4

Max. score:

4

Reversibility:

not reversible

Remarks on result:

positive indication of irritation

Irritant / corrosive response data:

One hour after instillation of the substance, very important irritation reactions were noticed at the level of the conjunctivae. The intensity of the conjunctival lesions made it not possible the evaluation of the iris and cornea reactions. A serious damage of iris and cornea was observed in one animal 24 hours after instillation. At the 72 hours reading conjunctival lesions remained unchanged, inflammatory phenomena increased. To avoid unnecessary pain, animals were sacrificed.

Other effects:

None

Any other information on results incl. tables

Table 7.3.2/1: Results of eye irritation

 

Animal no.	4621						4622						4623
Observation points	Conjunctiva			Iris	Cornea		Conjunctiva			Iris	Cornea		Conjunctiva			Iris	Cornea
	A	B	C	D	E	F	A	B	C	D	E	F	A	B	C	D	E	F
D1 (1 h)	4	3	3	*	*	*	4	3	3	*	*	*	4	3	3	*	*	*
24 h	4	2	3	*	*	*	4	3	3	*	*	*	4	3	3	2	4	*
48 h	4	3	3	*	*	*	4	3	3	*	*	*	4	3	3	*	*	*
72 h	4	3	3	*	*	*	4	3	3	*	*	*	4	3	3	*	*	*
M	4	2.7	3	-	-	-	4	3	3	-	-	-	4	3	3	-	-	-

 

* impossible reading; A: Chemosis; B: Discharge; C: Redness; D: Iris lesion; E: Opacity; F: Opacity area; M: Mean

Applicant's summary and conclusion

Interpretation of results:

Category 1 (irreversible effects on the eye) based on GHS criteria

Conclusions:

Under the test conditions, test substance is classified as "Irreversible effects on the eye (Category 1)" according to the Regulation (EC) N° 1272-2008 (CLP) and GHS.

Executive summary:

In an eye irritation study conducted according to the OECD Guideline 405 and in compliance with GLP, 3 healthy male rabbits of the New Zealand White strain were exposed to 0.1 mL of undiluted test substance in their right eye while the left eye remained untreated and served as control. The eyelids were then gently held together for about one second to avoid any loss of test substance. At 24 h after treatment, fluorescein solution was instilled into the eyes and they were examined under UV-lamp to detect possible corneal damage. The eyes were examined and the changes were observed at 1, 24, 48 and 72 h after treatment and graded according to the method of OECD Guideline 405.

One hour after instillation of the substance, very important irritation reactions were noticed at the level of the conjunctivae. Severity of conjunctival reactions (Chemosis with lids more than half closed) made it not possible the evaluation of cornea and iris lesions. 24 h later, serious lesions of iris and cornea were observed in one rabbit. At the 72 h reading conjunctival lesions remained unchanged, inflammatory phenomena increased. To avoid unnecessary pain, animals were sacrificed.  

Mean individual scores at 24, 48 and 72 h after exposure for the 3 animals were 3.0, 3.0, 3.0 for conjunctivae score and 4.0, 4.0, 4.0 for chemosis score; no impossible reading for cornea and iris.

 

Under the test conditions, test substance is classified as "Irreversible effects on the eye (Category 1)" according to the Regulation (EC) N° 1272-2008 (CLP) and GHS.