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Toxicological information

Eye irritation

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Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
data is from experimental reports

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1986
Report Date:
1986

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Principles of method if other than guideline:
The purpose of the study was to evaluate the ability of the test chemical to produce ocular irritation/corrosion in rabbits following a single application.
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: crystalline
Details on test material:
- Name of test material : Tetrylammonium bromide
- IUPAC name: N,N,N-triethylethanaminium bromide
- Molecular formula: C8 H20 N.Br
- Molecular weight: 210.157 g/mol
- Smiles notation: [N+](CC)(CC)(CC)CC.[BrH-]
- InChl : 1S/C8H20N.BrH/c1-5-9(6-2,7-3)8-4;/h5-8H2,1-4H3;1H/q+1;/p-1
- Substance type: Organic
- Physical state: Solid crystalline powder (white)
- Purity: 99.23%

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
- Sex: Female - Source: The Broekmen Institute, Someren, The Netherlands
- Age at study initiation: 2- 3 months old
- Weight at study initiation: 2617- 2751 g
- Housing: individually housed in metal cages with perforated floors
- Diet (e.g. ad libitum): standard lab diet (100g/ day); obtained from Hope Farms
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: A quarantine period of 12 days followed by another 6 weeks of acclimation period

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 21 degC
- Humidity (%): 60 -70% (relative humidity)
- Air changes (per hr): no data available
- Photoperiod (hrs dark / hrs light): 12 hours ligth, 12 hours dark

Test system

Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
approximately 72 mg (equivalent to 0.1 ml)
Duration of treatment / exposure:
single exposure
Observation period (in vivo):
Immediately after instillation of the test substance, the animals were observed and abnormalities were recorded.The eyes were examined approximately 1,24,48, 72 hours and 7 days after instillation of the test chemical
Duration of post- treatment incubation (in vitro):
no data available
Number of animals or in vitro replicates:
3
Details on study design:
SCORING SYSTEM:The ocular lesions were scored according to OECD 405 Guidelines and the results were evaluated according to the EEC criteria for classification and labelling of dangerous substances (Annex VI of the EEC Council directive 67/548/EEC as amended by Directive 83/467/EEC)

TOOL USED TO ASSESS SCORE: hand-slit lamp / biomicroscope / fluorescein: Fluorscein treatment

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48/72 h
Score:
1.3
Reversibility:
fully reversible within: 7 days
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
0.7
Reversibility:
fully reversible within: 7 days
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
Instillation of the test substance in one of the three animals resulted in slight to moderate redness (persisting for 72 hours) and slight swelling (persisting for 48 to 72 hours) of the conjunctivae.Seven days after dosing the conjunctival effects had disappeared.The iris of one of the rabbits was affected one hour after dosing, but this effect disappeared during the next 24 hours.Iris effects were not observed in the other two animals.Adverse effects on the cornea were not observed in any of the rabbits during the entire observation period.Treatment of the eyes with sodium fluorescien 24 hours post instillation didnot reveal any signs of epithelial damage.Signs of systemic intoxication were not observed.

Any other information on results incl. tables

Table 1: Eye Irritation Scores in rabbits (EEC Scores table)

Rabbit No, Sex

Body Weight (gm)

Observation time after instillation (hours)

Cornea Opacity

Iris Lesion

Conjunctivae

 

Redness

Swelling (Chemosis)

266, female

2751

1

0

1

2

1

24

0

0

2

1

48

0

0

2

1

72

0

0

1

1

Day 7

0

0

0

0

Subtotala)/ Mean valuec)

 

 

0/0

0/0

5/1.7

3/1.0

267, female

2830

1

0

0

1

1

24

0

0

1

1

48

0

0

2

1

 

 

72

0

0

1

0

Day 7

0

0

0

0

Subtotala)/ Mean valuec)

 

 

0/0

0/0

4/1.3

2/0.7

269, female

2850

1

0

0

1

1

24

0

0

1

0

48

0

0

1

1

72

0

0

1

0

Day 7

0

0

0

0

Subtotala)/ Mean valuec)

 

 

0/0

0/0

3/1.0

1/0.3

Totalb)/ Mean value

 

 

0/0

0/0

12/1.3

6/0.7

Where,

a)Subtotal = sum of 24,48,72 hours scores for each animals individually

b)Total = sum of 24, 48, 72 hours scores calculated over all animals

c)Mean value = mean score of 24,48 and 72 hours reading time

Applicant's summary and conclusion

Interpretation of results:
other: Not irritating
Conclusions:
Instillation of the test chemical in one of the three animals resulted in slight to moderate redness (persisting for 72 hours) and slight swelling (persisting for 48 to 72 hours) of the conjunctivae.Seven days after dosing the conjunctival effects had disappeared.Adverse effects on the cornea were not observed in any of the rabbits during the entire observation period.Treatment of the eyes with sodium fluorescien 24 hours post instillation didnot reveal any signs of epithelial damage.Signs of systemic intoxication were not observed.Based on these observations and applying the EEC criteria for classification and labelling of dangerous substances (Annex VI of the EEC Council directive 67/548/EEC as amended by Directive 83/467/EEC), the test chemical need not be labelled as an Eye Irritant.
Executive summary:

The purpose of the study was to evaluate the ability of the test chemical to produce ocular irritation/corrosion in rabbits following a single application. The study was performed according to OECD 405 Guidelines and evaluated according to EEC criteria for classification and labelling of dangerous substances (Annex VI of the EEC Council directive 67/548/EEC as amended by Directive 83/467/EEC).

3 young adult female New Zealand White rabbits were used for the study. Before dosing the test substance was ground to a fine powder using a mortar and pestle.The bulk density of the test substance was determined by NOTOX and amounted to 0.725 g/ml.On the day of dose administration, three portions of 72±1.5 mg of the powder were dispensed in glass containers with screw caps. Approximately 72 mg (equivalent to 0.1 ml) was instilled into the conjunctival sac of the right eye of the rabbit using a spatula.The lids were then gently held together for two seconds and then released Immediately after instillation of the test substance, the animals were observed and abnormalities were recorded.The eyes were examined approximately 1,24,48, 72 hours and 7 days after instillation of the test chemical.Immediately after treatment, the animals were transfered to metal cages.The left eye remained untreated and served as control. Immediately after instillation of the test substance, the animals were observed and abnormalities were recorded.The eyes were examined approximately 1,24,48, 72 hours and 7 days after instillation of the test chemical. Approximately 24 hours after instillation of the test substance(immediately after scoring the corneal opacity and the alterations of the iris and conjunctivae), a solution of 2% sodium fluorescien in water (pH adjusted to 7.0) was applied to both eyes of the test animals to examine quantitatively the potential for corneal injury.The brightly green staining area indicating epithelial damage was estimated as a percentage of total corneal area.Any observed local effects other than those indicated above were recorded, The ocular lesions were scored according to OECD 405 Guidelines and the results were evaluated according to the EEC criteria for classification and labelling of dangerous substances (Annex VI of the EEC Council directive 67/548/EEC as amended by Directive 83/467/EEC).

Instillation of the test substance in one of the three animals resulted in slight to  moderate redness (persisting for 72 hours) and slight swelling (persisting for 48 to 72 hours) of the conjunctivae.Seven days after dosing the conjunctival effects had disappeared.The iris of one of the rabbits was affected one hour after dosing, but this effect disappeared during the next 24 hours.Iris effects were not observed in the other two animals.Adverse effects on the cornea were not observed in any of the rabbits during the entire observation period.Treatment of the eyes with sodium fluorescien 24 hours post instillation didnot reveal any signs of epithelial damage.Signs of systemic intoxication were not observed.

Based on these observations and applying the EEC criteria for classification and labelling of dangerous substances (Annex VI of the EEC Council directive 67/548/EEC as amended by Directive 83/467/EEC), the test chemical need not be labelled as an Eye Irritant.