Registration Dossier

Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 2001-04-10 to 2001-04-30
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP Guideline study (OECD 405)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2001
Report Date:
2001

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
minor deviations were not considered to have compromised the validity or integrity of the study : relative humidity, animal breeder's and diet.
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
other name : MTSC
batch number: 00-11-001-050
Sponsor's filing number: CAL 551/01
description: white powder container: one plastic flask
date of receipt: 15 February 2001
storage conditions: at room temperature, protected from light and humidity
purity: 99.7%
expiry date: January 2002.

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
-Sex: male
- Source: CEGAV (Saint Mars d'Egrenne, France)
- Age at study initiation: no data
- Weight at study initiation: 2.6 ± 0.3 kg
- Housing: individually in polystyrene cages
- Diet (e.g. ad libitum): free access to 110 pelleted diet (UAR, Villemoisson, Epinay¬sur-Orge, France).
- Water (e.g. ad libitum): Drinking water filtered by a FG Millipore membrane (0.22 micron) was provided ad libitum
- Acclimation period: at least 5 days before the beginning of the study

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 ± 3°C
- Humidity (%): 30 to 70%
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Vehicle:
unchanged (no vehicle)
Controls:
other: yes, untreated eye
Amount / concentration applied:
undiluted ; The test substance was used in its original form.
Amount applied: 100 other: mg
Duration of treatment / exposure:
a single exposure
Observation period (in vivo):
6 days (because no effect was observed at day 6)
Number of animals or in vitro replicates:
3 rabbits
Details on study design:
Comment: not rinsed

EXAMINATIONS:
- Ophthalmoscopic examination: Yes
- Scoring system: Draize's scale
- Observation period: 1h, 24h, 48h and 72h after administration of the test substance
- Tool used to assess score: fluorescein

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
conjunctivae score
Remarks:
(chemosis)
Basis:
mean
Remarks:
3 rabbits
Time point:
other: 24-48-72 hours
Score:
0.87
Max. score:
4
Reversibility:
fully reversible within: 5 days
Remarks on result:
other: Individual scores were : 1.3, 1.0 and 0.3
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
mean
Remarks:
3 rabbits
Time point:
other: 24-48-72 hours
Score:
1.47
Max. score:
3
Reversibility:
fully reversible within: 6 days
Remarks on result:
other: Individual scores were : 1.7, 1.0 and 1.7
Irritation parameter:
conjunctivae score
Remarks:
(discharge)
Basis:
mean
Remarks:
6 rabbits
Time point:
other: 24-48-72 hours
Score:
0.2
Max. score:
3
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: Individual scores were: 0.3, 0.3 and 0.0
Irritation parameter:
iris score
Basis:
mean
Remarks:
3 rabbits
Time point:
other: 24-48-72 hours
Score:
0.1
Max. score:
2
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: Individually scores were: 0.3, 0.0 and 0.0
Irritation parameter:
cornea opacity score
Remarks:
(intensity)
Basis:
mean
Remarks:
3 rabbits
Time point:
other: 24-48-72 hours
Score:
0.43
Max. score:
4
Reversibility:
fully reversible within: 5 days
Remarks on result:
other: Individually scores were: 1.3, 0.0 and 0.0
Irritation parameter:
cornea opacity score
Remarks:
(area)
Basis:
mean
Remarks:
3 rabbits
Time point:
other: 24-48-72 hours
Score:
0.43
Max. score:
4
Reversibility:
fully reversible within: 5 days
Remarks on result:
other: Individually scores were: 1.3, 0.0 and 0.0
Irritant / corrosive response data:
Very slight or slight conjunctival reactions were observed in an animals from day 1: a very slight or slight chemosis (grade 1 or 2), a very slight or slight redness of the conjunctiva (grade 1 or 2) and a clear discharge were noted. Some of the se reactions persisted up to day 5 at the latest. A slight iritis (grade 1) was noted in one animal, on day 2 only. A very slight or slight corneal opacity (grade 1 or 2) was recorded in the same animal, from day 2 up to day 4. Mean scores calculated for each animal over 24, 48 and 72 bourg were 1.3, 1.0 and 0.3 for chemosis, 1.7, 1.0 and 1.7 for redness of the conjunctiva, 0.3, 0.0 and 0.0 for iris lesions and 1.3, 0.0 and 0.0 for comeal opacity.
Other effects:
none

Any other information on results incl. tables

Table 1: Individual ocular examinations and mean values of the scores recorded at each reading (24, 48 and 72 hours) for each animal

 

Rabbit number

Region of eye

Description of ocular reactions

scores

Mean irritation score (1)

1h (D1)

24h (D2)

48h (D3)

72h (D4)

(D5)

(D6)

 

993

conjunctivae

Chemosis

1

2

1

1

0

-

1.3

Redness

1

2

2

1

0

-

1.7

Discharge

1

1

0

0

0

-

0.3

Iris

0

1

0

0

0

-

0.3

Corneal opacity

Intensity

0

2

1

1

0

-

1.3

Area

0

2

1

1

0

-

1.3

Other

*

*

*

*

*

-

 

Fluorescein

/

U

U

U

U

-

 

 

579

conjunctivae

Chemosis

1

1

1

1

0

-

1.0

Redness

1

1

1

1

0

-

1.0

Discharge

1

1

0

0

0

-

0.3

Iris

0

0

0

0

0

-

0.0

Corneal opacity

Intensity

0

0

0

0

0

-

0.0

Area

0

0

0

0

0

-

0.0

Other

*

*

*

*

*

-

 

Fluorescein

/

U

/

/

/

-

 

 

566

conjunctivae

Chemosis

2

1

0

0

0

0

0.3

Redness

2

2

2

1

1

0

1.7

Discharge

1

0

0

0

0

0

0.0

Iris

0

0

0

0

0

0

0.0

Corneal opacity

Intensity

0

0

0

0

0

0

0.0

Area

0

0

0

0

0

0

0.0

Other

Su

*

*

*

*

*

 

Fluorescein

/

U

/

/

/

/

 

 

(1)  mean of scores on days 2, 3 and 4

* : none

U: fluorescein batch No.D616

/: fluorescein not used

Su: residual test substance

-         : ocular examination not performed

 

Applicant's summary and conclusion

Interpretation of results:
slightly irritating
Remarks:
Migrated information but not classified Criteria used for interpretation of results: other: Regulation EC n°1272/2008
Conclusions:
Under these experimental conditions, the test substance 4 -methylthiosemicarbazide is slightly irritant when administered by ocular route to rabbits.
Executive summary:

The potential of the test substance 4 -methylthiosemicarbazide to induce ocular irritation was evaluated in rabbits according to OECD 405 and with the principles of Good Laboratory Practice Regulations.

A single dose of 100 mg of the test substance in its original form was introduced into the left conjunctival sac of three male New Zealand White rabbits. The right eye was not treated andserved as control. The eyes were not rinsed after administration of the test substance. Ocular reactions were observed approximately 1 hour, 24, 48 and 72 hours after the administration and then daily until reversibility of the ocular reactions. The mean values of the scores for chemosis, redness of the conjunctiva, iris lesions and corneal opacity were calculated for each animal.

Very slight or slight conjunctival reactions (very slight or slight chemosis, very slight or slight redness of the conjunctiva and clear discharge) were observed in all animals from day 1: some of these reactions persisted up to day 5 at the latest.

A slight iritis was noted in one animal, on day 2 only. A very slight or slight corneal opacity was recorded in the same animal, from day 2 up to day 4.

Mean scores calculated for each animal over 24, 48 and 72 hours were 1.3, 1.0 and 0.3 forchemosis, 1.7, 1.0 and 1.7 for redness of the conjunctiva, 0.3, 0.0 and 0.0 for iris lesions and 1.3,0.0 and 0.0 for corneal opacity.

Under these experimental conditions, the test substance 4 -methylthiosemicarbazide is slightly irritant when administered by ocular route to rabbits.