Methyl trimethyl-3-[(1-oxododecyl)amino]propylammonium sulphate

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

July 1982

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:

1982

Report date:

1982

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

other: USA Interagency Regulatory Liaison Group (IRLG, Januar 1981)

Test guideline 2

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Trimethyl-3-[(1-oxo-10-undecenyl)amino]propylammonium methyl sulphate

EC Number:

304-990-8

EC Name:

Trimethyl-3-[(1-oxo-10-undecenyl)amino]propylammonium methyl sulphate

Cas Number:

94313-91-4

Molecular formula:

C17H35N2O.CH3O4S

IUPAC Name:

N,N,N-trimethyl-3-(undec-10-enoylamino)propan-1-aminium methyl sulfate

Test material form:

other: Liquid

Details on test material:

The test material was a 48% aqueous solution of the substance

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: H. Fortkamp, 4540 Lengerich, Germany
- Weight at study initiation: 2.20 - 2.35 kg
- Age: 11-17 weeks
- Housing: single caging, metal cages
- Diet: ad libitum, Rabbit Diet, Ssniff Versuchstier Diäten GmbH, 4770 Soest/Westfalen, Germany
- Water: ad libitum
- Acclimation period: 20 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-23
- Humidity (%): 40-70
- Air changes (per hr): 10 per hour
- Photoperiod: 12 hours daily

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:

0.1 ml of the test material was instilled into the conjunctival sac of the left eye while the right eye served as control.

Duration of treatment / exposure:

not rinsed

Observation period (in vivo):

Readings of ocular reactions were made 1-2 h, 24 h, 48 h, 72 h, 4 days, 7 days after treatment.

Number of animals or in vitro replicates:

6

Details on study design:

PREPARATION OF ANIMALS
- 24 h before treatment eyes were examined for corneal lesions after application of one drop of fluorescein-sodium solution (2%)

APPLICATION OF TEST SUBSTANCE
- 0.1 mL test substance was instilled into the conjunctival sac of the left eye. The lids were then held together for 1-2 seconds. The untreated right eye served as control. Because one of test animals showed a moderate pain reaction (score 3; see table 1), all remaining rabbits received a local anaesthetic in both eyes shortly before the application of the test substance.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the treated eye was not rinsed after treatment

SCORING SYSTEM (modified Draize system): the ocular reactions were assessed using the following numerical scoring system (see table 2)

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

#1, #3, #5, #6

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

not reversible

Remarks:

within 7 days

Remarks on result:

other: Pannus

Results 2

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

#2, #4

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: delayed opacity formation after 7 days

Remarks on result:

other: Pannus

Results 3

Irritation parameter:

iris score

Basis:

mean

Remarks:

#1, #2, #3, #4, #5, #6

Time point:

24/48/72 h

Score:

1

Max. score:

2

Reversibility:

fully reversible within: 7 days

Results 4

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

#2, #3, #4, #5, #6

Time point:

24/48/72 h

Score:

2

Max. score:

3

Reversibility:

not fully reversible within: 7 days

Results 5

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

#1

Time point:

24/48/72 h

Score:

2

Max. score:

3

Reversibility:

fully reversible within: 7 days

Results 6

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

#1, #2, #3, #4, #5, #6

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 7 days

Results 7

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

#1

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritant / corrosive response data:

The most remarkable reaction to the instillation of the test substance was a not discernible iris through cornea opacity in one animal on day 7 after the application. The investigation of the remaining animals showed Pannus formations also on day 7 after the application. As the post exposure observation period was less then 21 days reversibility of effects could not be determined.

Other effects:

no data

Any other information on results incl. tables

Table 3: Irritant/corrosive response for each animal at each observation time

Score at time point / Reversibility	Cornea opacity	Cornea area	Iris	Conjunctivae Redness	Conjunctivae Chemosis	Conjunctivae discharge
	Max. score: 4	Max. score: 4	Max. score: 2	Max. score: 3	Max. score: 4	Max. score: 3
1-2 hours	1/0/1/0/1/1	2/0/2/0/2/2	1/1/1/1/1/1	2/2/2/2/2/2	2/2/2/2/2/2	1/1/1/1/1/1
1 day	1/0/1/0/1/1	2/0/2/0/2/2	1/1/1/1/1/1	2/2/2/2/2/2	2/2/2/2/2/2	2/2/2/2/2/2
2 days	1/0/1/0/1/1	2/0/2/0/2/2	1/1/1/1/1/1	2/2/2/2/2/2	2/2/2/2/2/2	2/2/2/2/2/2
3 days	1/0/1/0/1/1	2/0/2/0/2/2	1/1/1/1/1/1	2/2/2/2/2/2	2/2/2/2/2/2	2/2/2/2/2/2
4 days	1/0/1/0/1/1	2/0/2/0/2/2	1/1/1/1/1/1	1/2/2/1/2/2	1/2/2/1/2/2	1/2/2/1/2/2
7 days	1/2/2/1/3/4	4P/4P/4P/4P/4P/4P	0/0/0/0/0/*	0/1/1/1/2/2	0/1/1/1/2/2	0/1/1/0/1/2
Average 24h, 48h, 72h	1/0/1/0/1/1	2/0/2/0/2/2	1/1/1/1/1/1	2/2/2/2/2/2	2/2/2/2/2/2	2/2/2/2/2/2
Reversibility	n./n./n./n./n./n.	n./n./n./n./n./n.	c./c./c./c./c./*	c./n.c./n.c./n.c./n./n.	c./n.c./n.c./n.c./n./n.	c./n.c./n.c./c./n.c./n.

 

P = Pannus,

* Evaluation is not possible because of corneal opacity

c. = completely reversible

n.c. = not completely reversible

n.= not reversible

Reactions observed at 2 hours reading after the application

- Clear redness and chemosis of the conjunctiva (score 2)

- Light ocular secretion production (score 1)

- Isolated small diffuse areas in more as a quarter of a cornea (score 1) observed in 4/6 rabbits.

 

Reactions observed within 1 – 7 days after the application

- Clear redness and chemosis of the conjunctiva (score 2), decreased in 4 animals by the end of the study.

- Moderate pericorneal Hyperaemia of iris (score 1), decreased within the 7 days after the treatment

- Isolated small diffuse areas in more as a quarter of a cornea (score 1) observed in 4/6 rabbits turned into the corneal opacity in all animals by the end of the study.

- Conjunctivae discharge with moistening of the lids and hairs just adjacent to the lids (score 2), decreased in 5/6 of the rabbits by the end of the study.

Table 4: Assessment of results (mean values)

Days after treatment	Mean values
	Conjunctivae (max. 20)	Iris (max. 10)	Cornea (max. 80)	Mean total score (max. 110)
0 (2 h)	10	5	6.7	21.7
1	12	5	6.7	23.7
2	12	5	6.7	23.7
3	12	5	6.7	23.7
4	10	5	6.7	21.7
7	6.3	0*	43.3	49.6

*Evaluation is not possible because of corneal opacity

 

Applicant's summary and conclusion

Interpretation of results:

Category 1 (irreversible effects on the eye)

Conclusions:

The substance caused serious damage to eyes in this study

Executive summary:

A primary eye irritation study, performed according to the test plan P 4/152, 3-rd revision, refers to the recommended guidelines of the USA Interagency Regulatory Liaison Group (IRLG, January, 1981). Study performance is comparable to the guideline study.

0.1 ml of Rewocid UTM 185 (48 % a.i) undiluted were instilled into the conjunctival sac of one eye of 6 young female adult New Zealand White rabbits. Eyes were not washed. Animals then were observed for 7 days. Irritation was scored by the method of Draize.

Calculated mean scores following grading at 24, 48 and 72 hours after installation of the test material for effects on the cornea opacity are 1 for 4 of 6 animals and 0 for 2 of 6 animals. Mean scores for effects on the conjunctiva (redness) and chemosis were 2 for all animals; the effects decreased in 3 of 6 animals were reversible in one animal within 7 days. Mean scores for effects on the iris were 1 for all animals and were fully reversible within 7 days.

 

As the most remarkable reaction to the instillation of the test substance was cornea opacity (score 4) in one of 6 animals and pannus in all animals at day 7 after application. As the post exposure observation period was less then 21 days reversibility of effects could not be determined.

 

In this study, Rewocid UTM 185 (48 % a.i) induced serious damage to eyes.