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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:
2 (reliable with restrictions)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1982
Report date:
1992

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
no

Test material

Constituent 1
Reference substance name:
Methylal
IUPAC Name:
Methylal
Details on test material:
- Name of test material (as cited in study report): Methylal

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Diet (e.g. ad libitum): commercial diet ad libitum
- Water (e.g. ad libitum): municipal water ad libitum

Test system

Vehicle:
not specified
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.01 and 0.1 ml
- Concentration (if solution): Not specified

VEHICLE
- Amount(s) applied (volume or weight with unit): Not specified
- Concentration (if solution): Not specified
- Lot/batch no. (if required): Not specified
- Purity: Not specified
Observation period (in vivo):
Scoring is recorded at 1 hour; 4-6 hours; 1 day; 2, 3, 4 and 7 days
Number of animals or in vitro replicates:
6 females per dose
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): Not specified
- Time after start of exposure: Not specified

SCORING SYSTEM: the scale used for scoring ocular lesions is more detailed than the one OECD 405. Here, area of cornea involved and discharge are scored in comparison to OECD scale.

CORNEA
Opacity: degree of density (readings should be taken from most dense area)
"0"_No ulceration or opacity
"1"_Scattered or diffuse areas of opacity (other than slight dulling of normal lustre); details of iris clearly visible
"2"_Easily discernible translucent area; details of iris slightly obscured
"3"_Nacrous area; no details of iris visible; size of pupil barely discernible
"4"_Opaque cornea; iris not discernible through the opacity .
* The area of corneal opacity should be noted

Area of cornea involved
"1"_One-quarter or less, but not zero
"2"_Greater than one-quarter, but less than half
"3"_Greater than half, but less than three-quarter
"4"_Greater than three-quarter, up to whole area

IRIS
"0"_Normal
"1"_Markedly deepened rugae, congestion, swelling, moderate circumcorneal hyperaemia; or injection; iris reactive to light (a sluggish reaction is considered to be an effect
"2"_Hemorrhage, gross destruction, or no reaction to light

CONJUNCTIVAE
(A) Redness
"0"_Vessels normal
"1"_Vessel definitely injected above normal
"2"_Diffuse, deep crimson red, individual vessels not easily discernible
"3"_Diffuse beefy red

(B) Chemosis
"0"_No chemosis
"1"_Any swelling above normal (includes nictitating membrane)
"2"_Obvious swelling, with partial eversion of lids
"3"_Swelling, with lids about half closed
"4"_Swelling, with lids more than half closed

(C) Discharge
"0"_No discharge
"1"_Any amount of discharge different from normal
"2"_Discharge with moistening of the lids and hairs adjacent to lids
"3"_Discharge with considerable moistening around the eyes

TOOL USED TO ASSESS SCORE: fluorescein (2%) is used to determine corneal injury before dosing and at raeading after 1 day.

Results and discussion

In vitro

Results
Remarks on result:
not measured/tested

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Remarks:
0.1 mL
Basis:
animal: #1, 2, 3, 6
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Remarks:
0.1 mL
Basis:
animal #4
Time point:
24/48/72 h
Score:
0.3
Max. score:
1
Reversibility:
fully reversible within: 48h
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Remarks:
0.1 mL
Basis:
animal #5
Time point:
24/48/72 h
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 4 days
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Remarks:
0.1 mL
Basis:
animal: #1 to 6
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Remarks:
0.1 mL
Basis:
animal: #1, 2, 3, 5, 6
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Remarks:
0.1 mL
Basis:
animal #4
Time point:
24/48/72 h
Score:
0.3
Max. score:
1
Reversibility:
fully reversible within: 48h
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Remarks:
0.1 mL
Basis:
animal: #1, 2, 3, 5, 6
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Remarks:
0.1 mL
Basis:
animal #4
Time point:
24/48/72 h
Score:
0.6
Max. score:
1
Reversibility:
fully reversible within: 72h
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Remarks:
0.01 mL
Basis:
animal: #7 to 12
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Remarks:
0.01 mL
Basis:
animal: #7 to 12
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Remarks:
0.01 mL
Basis:
animal: #7 to 12
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Remarks:
0.01 mL
Basis:
animal: #7 to 12
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
fully reversible
Remarks on result:
no indication of irritation

Any other information on results incl. tables

The volume of 0.1 ml of test substance into rabbit eyes produced minor corneal and iris injury in 3/6 eyes, persisting through 3 days in one. Minor to moderate conjunctival irritations was recorded in 5 eyes and persisted in one through 2 days. Application of 0.01 ml of Methylal induced no corneal and iris injury and minor transient conjunctival irritation in 4/6 eyes. By one day, all eyes had a normal appearance.

Eyes score table is shown below. Values are indicated as range scores (mean score)

Volume instilled : 0.1 ml

Observations   

 

1 hour 

4 -6 hours 

24 hours 

48 hours  

72 hours 

 7 days

Cornea

Opacy

0 to 1 (0.5)

0 to 1 (0.5)

0 to 1 (0.3)

0 to 1 (0.2)

0 to 1 (0.2)

All 0 (0.0)

Cornea

Area

-

-

0 to 3 (0.8)

0 to 1 (0.2)

0 to 1 (0.2)

All 0 (0.0)

Iris

Injury

0 to 1 (0.5)

0 to 1 (0.7)

All 0 (0.0)

All 0 (0.0)

All 0 (0.0)  

All 0 (0.0) 

Conjunctivae  

Redness

0 to 1 (0.8)

0 to 1 (0.8)

0 to 1 (0.2)

All 0 (0.0)

All 0 (0.0)

All 0 (0.0) 

Conjunctivae

Chemosis

0 to 3 (2.0)

0 to 3 (2.0)

0 to 1 (0.2)

0 to 1

All 0 (0.0)

All 0 (0.0)

Conjunctivae

Discharge

0 to 3 (2.0)

0 to 3 (2.2)

0 to 1(0.2)

All 0 (0.0)

All 0 (0.0)

All 0 (0.0)

Volume instilled : 0.1 ml

Observations   

1 hour 

4 -6 hours 

24 hours 

48 hours  

72 hours 

 7 days

Cornea

Opacy

All 0 (0.0)

All 0 (0.0)

All 0 (0.0)

All 0 (0.0)

All 0 (0.0)

-

Cornea

Area

-

-

All 0 (0.0)

All 0 (0.0)

All 0 (0.0)

-

Iris

Injury

All 0 (0.0)

All 0 (0.0)

All 0 (0.0)

All 0 (0.0)

All 0 (0.0)

-

Conjunctivae  

Redness

0 to 1 (0.3)

0 to 1 (0.5)

All 0 (0.0)

All 0 (0.0)

All 0 (0.0)

-

Conjunctivae

Chemosis

0 to 1 (0.3)

0 to 1 (0.3)

All 0 (0.0)

All 0 (0.0)

All 0 (0.0)

-

Conjunctivae

Discharge

0 to 1 (0.5)

0 to 1 (0.7)

All 0 (0.0)

All 0 (0.0)

All 0 (0.0)

-

Applicant's summary and conclusion

Interpretation of results:
no data
Remarks:
Migrated information Criteria used for interpretation of results: not specified
Conclusions:
Application of 0.1 and 0.01 mL per rabbit eye induced minor to moderate eye irritation and mild transient conjunctival irritation, respectively.
According to CLP rules, methylal is not classified for eye irritation hazard.
Executive summary:

Methylal ability to produce eye irritation has been studied in New Zealand White rabbit. The test substance was applied at volume of 0.01 or 0.1 ml into the lower conjunctival sac of one eye per animal or is placed direcly on the eyes. The eyelids are held together for one second. Six female rabbits were used per dose level.

Injuries in cornea, iris and conjunctivae were recorded according to Grading of Ocular Lesions System at 1 hour; 4-6 hours; 1 day; 2, 3, 4 and 7 days.

The volume of 0.1 ml of test substance instilled into rabbit eyes produced minor corneal and iris injury in 3/6 eyes. Minor to moderate conjunctival irritations was recorded in 5 eyes and persisted in one through 2 days. Application of 0.01 ml of Methylal induced no corneal and iris injury and minor transient conjunctival irritation in 4/6 eyes. After one day, all eyes had a normal appearance.

Application of 0.1 and 0.01 ml per rabbit eye induced minor to moderate eye irritation and mild transient conjunctival irritation, respectively.

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