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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
Study period:
April - June 2008
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2008
Report date:
2008

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
April 24, 2002
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Remarks:
(from the competent authority) Landesamt für Umwelt, Wasserwirtschaft und Gewerbeaufsicht Rheinland-Pfalz

Test material

Constituent 1
Reference substance name:
Reaction mass of N-butylphosphorothioic triamide and N-propylphosphorothioic triamide
EC Number:
700-457-2
Molecular formula:
Unspecified
IUPAC Name:
Reaction mass of N-butylphosphorothioic triamide and N-propylphosphorothioic triamide
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Batch No.of test material: 8712 / 056
- Purity: 99.6 g / 100 g
- pH value: ca. 5 (undiluted test substance, moistened with water)

FORM OF APPLICATION
undiluted

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Remarks:
A 1077 INRA (SPF)
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Centre Lago S. A., 01540 Vonnas, France
- Age at study initiation: 3 - 4 months
- Weight at study initiation: 2.63 - 3.04 kg
- Housing: The animals were housed in fully air-conditioned rooms.
- Diet (e.g. ad libitum): Kliba-Labordiät, Provimi Kliba SA, Kaiseraugst, Basel, Switzerland (about 130 g/animal per day)
- Water (e.g. ad libitum): tap water ad libitum
- Acclimation period: at least 5 days before application

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24 °C
- Humidity (%): 30 - 70 %
- Air changes (per hr): The animals were housed in fully air-conditioned rooms.
- Photoperiod (hrs dark / hrs light): 12 h / 12 h

Test system

Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL bulk volume (about 31 mg of the comminuted test substance)
Duration of treatment / exposure:
24 hours
Observation period (in vivo):
28 days
Number of animals or in vitro replicates:
3
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): About 24 hours after application of the test substance the treated eye of the animal(s) was rinsed with 3 to 6 mL of hand warm tap water for 1 to 2 minutes using a syringe with a blunt probe.
- Time after start of exposure: 24 hours

SCORING SYSTEM: The evaluation of eye irritation was performed according to the quoted guideline. In addition to specific observations recommended by the regulatory authorities, evaluations were made of discharge from the eye and the area of cornea affected by the lesions.

TOOL USED TO ASSESS SCORE: daylight tubes "Lumilux"

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Reversibility:
fully reversible within: 7 days
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.7
Reversibility:
fully reversible within: 7 days
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1
Reversibility:
fully reversible within: 7 days
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.7
Reversibility:
fully reversible within: 7 days
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.3
Reversibility:
fully reversible within: 7 days
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.3
Reversibility:
fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48/72 h
Score:
2
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1.7
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1
Reversibility:
fully reversible within: 7 days
Irritant / corrosive response data:
Slight corneal opacity (grade 1) was observed in all animals 24 and 48 hours after application and persisted in two animals until the 72 hour reading. Moderate iritis (grade 1) was observed in all animals 24 hours after application and in one animal again after 72 hours. Moderate conjunctival redness (grade 2) was noted in all animals from 1 hour up to 72 hours after application. Moderate or marked conjunctival chemosis (grade 2 or 3) was noted in all animals 1 hour after application. Slight or moderate conjunctival chemosis (grade 1 or 2) was observed in all animals at the 24- and 48-hour reading. Slight conjunctival chemosis was seen in two animals after 72 hours. Slight to severe discharge (grade 1 to 3) was noted in all animals from 1 hour up to 24 hours. Moderate discharge (grade 2) was observed in a single animal after 48 hours. Slight discharge was noted in two animals after 72 hours.
Additional findings like contracted pupil and injected scleral vessels in a circumscribed area or circular were noted in all animals during the observation period.
The ocular reactions were reversible in all animals within 7 days after application.

Any other information on results incl. tables

Table 1: Irritant response data for each individual animal at each observation time as well as calculation of the means

Readings

Animal

Cornea

Iris

Conjunctiva

Additional findings

Opacity

Area of cornea involved

Redness

Chemosis

Discharge

1 h

01

0

0

0

2

2

2

49

02

0

0

0

2

3

3

49

03

0

0

0

2

3

2

49

24 h

01

1

4

1

2

1

1

PC, 49

02

1

3

1

2

2

3

PC, 48

03

1

4

1

2

2

1

PC, 48

48 h

01

1

2

0

2

1

0

PC, 48

02

1

2

0

2

2

2

PC, 48

03

1

3

0

2

1

0

PC, 48

72 h

01

1

2

1

2

1

1

PC, 49

02

0

0

0

2

1

1

48

03

1

2

0

2

0

0

PC, 48

7 d

01

0

0

0

0

0

0

 

02

0

0

0

0

0

0

 

03

0

0

0

0

0

0

 

Mean 24 – 72 h

01

1.0

 

0.7

2.0

1.0

 

 

02

0.7

 

0.3

2.0

1.7

 

 

03

1.0

 

0.3

2.0

1.0

 

 

Mean

 

0.9

 

0.4

2.0

1.2

 

 

48: scleral vessels injected, circumscribed area

49: scleral vessels injected, circular

PC: pupil contracted

Applicant's summary and conclusion

Interpretation of results:
Category 2B (mildly irritating to eyes) based on GHS criteria
Conclusions:
Considering the described ocular reactions as well as the average score for irritation, the test substance shows a slight eye irritation potential under the test conditions chosen.
Executive summary:

The potential of the test substance to cause damage to the conjunctiva, iris or cornea was assessed by a single ocular application of 0.1 mL bulk volume (about 31 mg) of the test substance to one eye of three New Zealand rabbits (stepwise procedure starting with one animal and supplementing two additional animals). About 24 hours after application the eye was rinsed with tap water.

The ocular reactions were assessed approximately 1, 24, 48 and 72 hours after application and on day 7.

Slight corneal opacity, moderate iritis, moderate conjunctival redness, slight to marked conjunctival chemosis and slight to severe discharge were observed in the animals during the course of the study.

Additional findings like contracted pupil and injected scleral vessels in a circumscribed area or circular were noted in the animals during the observation period.

The ocular reactions were reversible in all animals within 7 days after application.

Mean scores calculated for each animal over 24, 48 and 72 hours were 0.9 for corneal opacity, 0.4 for iris lesions, 2.0 for redness of the conjunctiva and 1.2 for chemosis.

Considering the described ocular reactions as well as the average score for irritation, the test substance shows a slight eye irritation potential under the test conditions chosen.