Registration Dossier

Administrative data

Description of key information

Acute Dermal Irritation/Corrosion (rabbit) = Corrosive, OECD 404, DiDonato (2009)

Acute Eye Irritation/Corrosion (rabbit) = Corrosive, OECD 405, Hall (2009)

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin 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:
Study was conducted and reported in accordance with international test guidelines.
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
US EPA Certificate
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
Animals were received from Covance Research Products Inc., Denver, PA on 18 March 2009. Following an acclimation period of at least five days, one health New Zealand White rabbit (female) was selected from a larger group without conscious bias.The animal was born on 29 November 2008. The pretest body weight was 3.6 kg.The animal was identified by cage notation and a uniquely numbered metal ear tag and individually housed in a suspended cage. Paper bedding was 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, had a 12 hour light: 12 hour dark photoperiod.The temperature range of the animal room was 65.6 - 76.5 degrees farenheit and the relative humidity was 48.6 to 99.5 %.
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL- Amount(s) applied (volume or weight with unit): 0.5 ml per site at 3 sites.- Concentration (if solution): 32.99 % test item in water.
Duration of treatment / exposure:
The dressing and test article patch covering site #1 were removed at 3 minutes postdose, over site #2 at 1 hour postdose and the torso wrappings and patch covering site #3 at 4 hours postdose.
Observation period:
The test sites (#1, 2 and 3) were scored for dermal irritation at 60 minutes after removal of wrappings. Site #3 (4-hour exposure) was scored at 24, 48 and 72 hours and again on days 7 and 14. Erythema and edema were scored according to the numerical Draize technique. The skin was also evaluated for ulceration and necrosis or any evidence of tissue destruction. Additional signs were described.Body weight was recorded pretest, 72 hours and termination. The general health of the animal was monitored at each observation point.
Number of animals:
One animal was used for this study.
Details on study design:
Site PreparationThe day prior to the application of the test item, the dorsal area of the trunk of the animal was clipped free of hair. The dose sites were approximately 3 x 3 cm.DosingInitially, one rabbit was dosed sequentially on sites #1, 2, and 3. The test item was dosed at 0.5 ml/site and placed under a 2.5 x 2.5 cm, 4 ply surgical gauze patch. Gentle pressure was applied to aid in the distribution of the test item over the contact site. The rabbit was gently held in place and a piece of porous dressing was secured with non-irritating tape over dose site #1 (semi-occlusive) for the 3 minute exposure period. The torso was covered with a piece of porous dressing large enough to cover dose sites #2 and 3 with at least 5 cm square to spare on on all sides of the gauze patch. Porous, non-irritating tape was used to encircle the trunk of the animal.The dressing and test article patch covering site #1 was removed at 3 minutes post-dose, over site #2 at 1 hour postdose and the torso wrappings and patch covering site #3 at 4 hours postdose. All sites were gently washed with distilled water to remove residual test material.Following the 72 hour observation the severity of the scores meant that no further animals were added to the study for ethical reasons. The initial animal was extended to day 14.Observation MethodErythema and edema were scored according to the numerical Draize technique. The skin was also evaluated for ulceration and necrosis or any evidence of tissue destruction. Additional signs were described.ErythemaNo erythema: 0Very slight erythema (barely perceptible): 1Well defined erythema: 2Moderate to severe erythema: 3Severe erythema (beet redness) to slight eschar formation (injuries in depth): 4EdemaNo edema: 0Very slight edema (barely perceptible): 1Slight edema (edges of area well-defined by definite raising): 2Moderate edema (raised approximately 1.0 mm): 3Severe edema (raised more than 1.0 mm, extending beyond the area of exposure): 4
Irritation parameter:
erythema score
Basis:
animal #1
Remarks:
3 min exposure
Time point:
other: 60 Minutes
Score:
0
Reversibility:
no data
Irritation parameter:
erythema score
Basis:
animal #1
Remarks:
60 minute exposure
Time point:
other: 60 minutes
Score:
0
Reversibility:
no data
Irritation parameter:
erythema score
Basis:
animal #1
Remarks:
4 hour exposure site
Time point:
other: 60 minutes
Score:
2
Reversibility:
not fully reversible within: 14 days
Irritation parameter:
erythema score
Basis:
animal #1
Remarks:
4 hour exposure site
Time point:
other: 24 hours
Score:
3
Reversibility:
not fully reversible within: 14 days
Irritation parameter:
erythema score
Basis:
animal #1
Remarks:
4 hour exposure site
Time point:
other: 48 hours
Score:
4
Reversibility:
not fully reversible within: 14 days
Irritation parameter:
erythema score
Basis:
animal #1
Remarks:
4 hour exposure site
Time point:
other: 72 hours
Score:
4
Reversibility:
not fully reversible within: 14 days
Irritation parameter:
erythema score
Basis:
animal #1
Remarks:
4 hour exposure site
Time point:
other: 7 days
Score:
> 4
Reversibility:
not fully reversible within: 14 days
Remarks on result:
other: necrosis and pale areas also observed
Irritation parameter:
erythema score
Basis:
animal #1
Remarks:
4 hour exposure site
Time point:
other: 14 days
Score:
> 4
Reversibility:
not fully reversible within: 14 days
Remarks on result:
other: Necrosis also observed
Irritation parameter:
edema score
Basis:
animal #1
Remarks:
3 min exposure site
Time point:
other: 60 minutes
Score:
0
Reversibility:
no data
Irritation parameter:
edema score
Basis:
animal #1
Remarks:
1 hour exposure site
Time point:
other: 60 minutes
Score:
1
Reversibility:
no data
Irritation parameter:
edema score
Basis:
animal #1
Remarks:
4 hour exposure site
Time point:
other: 60 minutes
Score:
3
Reversibility:
fully reversible within: 7 days
Irritation parameter:
edema score
Basis:
animal #1
Remarks:
4 hour exposure site
Time point:
other: 24 hours
Score:
2
Reversibility:
fully reversible within: 7 days
Irritation parameter:
edema score
Basis:
animal #1
Remarks:
4 hour exposure site
Time point:
other: 48 hours
Score:
1
Reversibility:
fully reversible within: 7 days
Irritation parameter:
edema score
Basis:
animal #1
Remarks:
4 hour exposure site
Time point:
other: 72 hours
Score:
1
Reversibility:
fully reversible within: 7 days
Irritation parameter:
edema score
Basis:
animal #1
Remarks:
4 hour exposure site
Time point:
other: 7 days
Score:
0
Reversibility:
no data
Irritation parameter:
edema score
Basis:
animal #1
Remarks:
4 hour exposure site
Time point:
other: 14 days
Score:
0
Reversibility:
no data
Irritant / corrosive response data:
Results presented above.
Other effects:
No systemic effects were observed during this study. Body weight changes were normal.
Interpretation of results:
Category 1 (corrosive) based on GHS criteria
Remarks:
Migrated information
Conclusions:
Hexahydro-1,3,5-trimethyl-s-triazine is corrosive.
Executive summary:

Objective: To determine the irritant or corrosive effects, if any, of hexahydro-1,3,5 -trimethyl-s-triazine when applied dermally. This study was conducted in accordance with OECD Guideline 404 "Acute Dermal Irritation/Corrosion".

Method synopsis: Since the test item was suspected to be a dermal irritant, one health female New Xealand White rabbit was dosed dermally. The test item (0.5 ml) was applied dermally to three intact sites for an exposure period of 3 minutes on site #1, 1 hour on site #2 and 4 hours on site #3. Erythema and edema were scored at 60 minutes after each patch removal on all three sites. Site #3 was scored again at 24, 48 and 72 hours and again on days 7 and 14. The skin was also evaluated for ulceration and necrosis or any evidence of tissue destruction at these time periods. Following the 72 hour observation, the severity of the scores resulted in no further animals being added to the study. The initial animal was extended to day 14. Body weight was recorded pretest, 72 hours and at test termination.

Summary:

3 minute exposure: There were no erythema or edema observed at 60 minutes after patch removal following the 3 minute exposure.

1 hour exposure: There was no erythema and very slight edema at 60 minutes following the 1 hour exposure.

4 hour exposure: Erythema was well defined and edema was moderate at 60 minutes following the 4 hour exposure. Erythema was moderate to severe at 24 hours and severe (with no eschar formation observed) at 48 and 72 hours. By day 7, the dose site was necrotic with pale areas and necrotic on day 14. Edema was slight at 24 hours and very slight at 48 and 72 hours. By days 7 and 14, edema was absent.

Systemic Observations: There were no abnormal physical signs noted during the observation period.

Body weight changes were normal.

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

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (corrosive)

Eye irritation

Link to relevant study records
Reference
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.
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
US EPA Certificate
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 %.
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.
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.

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.

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.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin and eye irritation studies conducted on hexahydro-1,3,5-trimethyl-1,3,5-triazine indicate that the chemical substance is corrosive to the skin and eyes.


Justification for selection of skin irritation / corrosion endpoint:
This study was the only skin irritation/corrosion study available and meets the requirements of international testing guidelines.

Justification for selection of eye irritation endpoint:
This study was the only eye irritation study available and meets the requirements of international testing guidelines.

Justification for classification or non-classification

Hexahydro-1,3,5-trimethyl-1,3,5-triazine is classified as a skin corrosive category 1C (H314) and classified for eye damage category 1 (H318) in accordance with the criteria for classification and labelling of substances and mixtures (Regulation (EC) No. 1272/2008).