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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:
01 June 2009 to 24 September 2009
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
The study was conducted and reported in accordance with international guidelines.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2009
Report Date:
2009

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
US EPA Certificate

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid
Details on test material:
Identity: Hexahydro-1,3,5-trimethyl-s-triazineDate Received: 26 May 2009Storage Room temperature and humidityDescription: Light gold liquidSample Preparation: The test item was used as rceived

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
New Zealand White rabbits were received from Covance Research Products, Inc., Denver, PA on 13 May 2009 and acclimated for at least five days. Only animals in apparent good health were made available for study assignement. Prior to being selected for this study, both eyes were examined according to the Draize technique for any evidence of irritation or abnormalities of the cornea, iris and/or conjuctiva. A mini-maglite flashlight equipped with a high intensity bulb was used to aid in the examination. A single rabbit (female), free from evidence of ocular irritation or abnormalities, was assigned to the study without conscious bias.The animal was born on 24 January 2009. The pretest body weight was 2.9 kg. The animal was identified by cage notation and a uniquely numbered metal eartag. The animal was housed individually in a suspended cage. Paper bedding was placed beneath the cage and changed at least three times per week. Fresh PMI rabbit chow (Diet #5321) was provided daily. Water was available ad libitum. The animal room was temperature controlled and had a 12 hour light/dark photoperiod. The temperature range of the animal room was 66.0 - 76.5 degrees farenheit and the relative humidity was 48.5 - 99.5 %.

Test system

Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
A 0.1 ml aliquot of the test item, as received, was placed by syringe into the conjunctival sac, which was formed by gently pulling the lower eyelid away from the eye. After instillation, the lid was held together for approximately one second to ensure adequte distribution of the test item.
Duration of treatment / exposure:
A single dose was applied at study initiation as described above.
Observation period (in vivo):
Using a mini-maglite flashlight equipped with a high intensity bulb, the treated eye of the rabbit was examined for irritation of the cornea, iris and conjunctiva at 1, 24, 48 and 72 hours and on days 7, 14 and 21 post dose. Sodium fluorescein dye procedures were used at the 24 hour observation interval up to day 21. The eye was examined with the aid of an ultraviolet light source. Ocular reactions were graded according to the numerical Draize technique. Additional signs were described.Body weights were recorded pretest and at termination. The general health of the animal was monitored at each observation time.
Number of animals or in vitro replicates:
A single animal was used for this study.
Details on study design:
SCORING SYSTEM:(1) Cornea:(A) Opacity: Degree of density (area most dense taken for reading)No ulceration or opacity: 0Scattered or diffuse areas of opacity (other than slight dulling of normal luster), details of iris clearly visible: 1Easily discernable translucent area, details of iris slightly obscured: 2Opalescent areas, no details of iris visible, size of pupil barely discernable: 3Opaque cornea, iris not discernable through the opacity: 4(B) Area of cornea involved:One quarter (or less) but not zero: 1Greater that one quarter, but less than one half: 2Greater than one half, but less than three quarters: 3Greater than three quarters up to whole area: 4SCORE EQUALS A X B X 5MAXIMUM TOTAL = 80(2) Iris(A) Normal: 0Folds above normal, congestion, swelling, circumcorneal injection (any or all of these or combination of any thereof), iris still reacting to light (sluggish reaction is positive): 1No reaction to light, haemorrhage, gross destruction (any or all of these): 2SCORE EQUALS A X 5MAXIMUM TOTAL = 10(3) Conjuctivae(A) Redness (refers to palpebral and bulbar conjuctivae excluding cornea and iris)Blood vessels normal: 0Some blood vessels definitely hyperemic (injected): 1More diffuse, deeper crimson red, individual vessels not easily discernable: 2Diffuse beefy red: 3(B) ChemosisNo swelling: 0Any swelling above normal (including nictitating membranes): 1Obvious swelling with partial eversion of lids: 2Swelling with lids about half closed: 3Swelling with lids more than half closed: 4(C) DischargeNo discharge: 0Any amount different from normal (does not include small amounts observed in inner canthus of normal animals): 1Discharge with moistening of the lids and hairs adjacent to the lids: 2Discharge with moistening of the lids and hairs and considerable area around the eye: 3SCORE EQUALS (A+B+C)X2MAXIMUM TOTAL = 20THE MAXIMUM TOTAL SCORE IS THE SUM OF ALL SCORES OBTAINED FOR THE CORNEA, IRIS AND CONJUNCTIVAE.MAX TOTAL = 110TOOL USED TO ASSESS SCORE: FluoresceinUltraviolet Fluorescein Scan Scoring Code:0 = negative1 = Positive with an area one quarter or less2 = Positive with an area greater than one quarter but less than one half3 = Positive with an area of greater than one half but less that three quarters4 = Positive with an area of greater that three quarters up to the entire area.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
overall irritation score
Basis:
animal #1
Time point:
other: 1 Hour
Score:
14
Max. score:
14
Reversibility:
not reversible
Irritation parameter:
overall irritation score
Basis:
animal #1
Time point:
other: 24 Hour
Score:
51
Max. score:
51
Reversibility:
not reversible
Irritation parameter:
overall irritation score
Basis:
animal #1
Time point:
other: 48 Hours
Score:
38
Max. score:
38
Reversibility:
not reversible
Irritation parameter:
overall irritation score
Basis:
animal #1
Time point:
other: 72 Hours
Score:
51
Max. score:
51
Reversibility:
not reversible
Irritation parameter:
overall irritation score
Basis:
animal #1
Time point:
other: Day 7
Score:
45
Max. score:
45
Reversibility:
not reversible
Irritation parameter:
overall irritation score
Basis:
animal #1
Time point:
other: Day 14
Score:
63
Max. score:
63
Reversibility:
not reversible
Irritation parameter:
overall irritation score
Basis:
animal #1
Time point:
other: Day 21
Score:
39
Max. score:
39
Reversibility:
not reversible
Irritant / corrosive response data:
Refer to Table 1 for raw data.

Any other information on results incl. tables

Table 1. Ocular Findings, Systemic Observations and Body Weights

Tissue

Reading

1 Hour

24 Hour

48 Hour

72 Hour

Day 7

Day 14

Day 21

Cornea

Opacity

0 h

2

3

3

3

3 c

2

Area

0

3

1

2

2

3

3

Total

0

30

15

30

30

45

30

Iris

Iris

0

1

1

1

1

2

1

Total

0

5

5

5

5

10

5

Conjunctiva

Redness

2

2

3

3 p

2 p

2 p

1

Chemosis

3

3

3

3

2

1

1

Discharge

2

3

3

2

1

1

0

Total

14

16

18

16

10

8

4

TOTAL

14

51

38

51

45

63

39

Systemic Observations

A

A

A

A

A

A

A

Sodium Fluorescein

-

3

4

3

2

2

1

c = pannus; h = lack of normal luster; p = pale areas

A = No systemic effects observed.

Applicant's summary and conclusion

Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Remarks:
Migrated information
Conclusions:
Hexahydro-1,3,5-trimethy-s-triazine is corrosive.
Executive summary:

Objective: To determine the irritant or corrosivity effects, if any, of hexahydro-1,3,5 -trimethyl-s-triazine when instilled into the rabbit eye. This study was conducted in accordance with OECD Guideline 405 "Acute Eye Irritation/Corrosion".

Method synopsis: Initially, one healthy New Zealand White rabbit (female), free from evidence of ocular irritation and corneal abnormalities, was dosed with the test item; 0.1 ml was placed into the conjunctival sac of one eye. Based on the reactions of the initial animal, no additional animals were tested. The eye was examined pretest and scored by the Draize technique at 1, 24, 48 and 72 hours and on days 7, 14 and 21 postdose. Sodium fluorescein dye procedures were used at the 24 -hour observation interval up to day 21. Body weight was recorded pretest and at termination.

Summary: Corneal opacity, iritis and conjunctival irritation, noted in one eye, persisted to day 21. There were no abnormal physical signs noted during the observation period. Body weights were normal.

Conclusion: Hexahydro-1,3,5 -trimethyl-s-triazine is corrosive.