2,4,6-trichloro-1,3,5-triazine

Endpoint summary

Description of key information

- skin irritation:              Category 1B (corrosive) for the human skin, study 93-0171-DGT
- eye irritation:               Category 1 (irreversible effects on the eye) for the rabbit ( OECD TG 405); study 81-0026-FKT
- respiratory irritation: irritating (Alarie test); study 94 -0202 -FGT

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:

1987-11-09 to 1987-11-10

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: - Guideline study with acceptable restrictions (e.g. deviations from the guideline concerning exposure time and amount of supplied test substance)

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

only 1 day of acclimatisation time, 24 h exposure time and only 0.3 g substance applied; in addition a repeated dose experiment was conducted

Principles of method if other than guideline:

repeated dose experiment:
4 animals per dose group were treated daily for 10 consecutive days by spreading the inner areas of the right ear with a suspension (2 % or 10 % (w/v)) of the test substance in the vehicle.

GLP compliance:

no

Species:

rabbit

Strain:

Vienna White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: in-house breeding facility
- Age at study initiation: 28 - 38 weeks
- Weight at study initiation: 3.6 - 4.0 kg
- Housing: 1 per cage (stainless steel cages with grating floor
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 1 day


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.5 +- 1
- Humidity (%): 55 +- 10
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

occlusive

Preparation of test site:

other: one site intact and shaved, one site shaved and abraded

Vehicle:

other: polyethylene glycol (PEG 400)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied: 300 mg moistened sufficiently with polyethylene glycol.

Duration of treatment / exposure:

- 24 h in the experiment according to the guideline
(- daily for 10 days in the repeated dose experiment)

Observation period:

- 28 days
(- 10 days in the repeated dose experiment)

Number of animals:

- 6
(- 4 per dose in the repeated dose experiment)

Details on study design:

TEST SITE
- Area of exposure: flank between shoulder and sacral region
- coverage: 2.5 cm x 2.5 cm, linen cloth
- Type of wrap if used: bandage, wrapped several times around the trunk

REMOVAL OF TEST SUBSTANCE
- Washing (if done): tap water
- Time after start of exposure: 24 h

SCORING SYSTEM:
(Draize, J. H. (1977) „Dermal and Eye Toxicity Tests“. Principles and Procedures for Evaluating the Toxicity of Household Substances, National Academy of Sciences, Washington DC, p. 31)


Erythema and Eschar Formation Value
No erythema 0
Very slight erythema (barely perceptible) 1
Well-defined erythema 2
Moderate to severe erythema 3
Severe erythema (beet redness) to slight eschar formation
injuries in depth 4

Oedema formation
No oedema 0
Very slight oedema (barely perceptible) 1
Slight oedema (edges of area well-defined by definite raising) 2
Moderate oedema (raised approximately 1 mm) 3
Severe oedema (raised more than 1 mm and extending beyond
the area of exposure 4

Irritation parameter:

erythema score

Basis:

other: mean of all animals

Time point:

other: mean of 1, 24 and 48 h

Score:

3.25

Max. score:

4

Reversibility:

fully reversible within: 12 d

Remarks on result:

other: no reading was conducted at 72 h; values given as 3- 4 were calculated as 3.5

Irritation parameter:

edema score

Basis:

other: mean of all animals

Time point:

other: mean of 1, 24 and 48 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 h

Remarks on result:

other: no reading was conducted at 72 h

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

3.5

Max. score:

4

Reversibility:

fully reversible within: 8 d

Remarks on result:

other: no reading was conducted at 72 h; score represents mean value of 24 and 48 h

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

3.25

Max. score:

4

Reversibility:

fully reversible within: 8 d

Remarks on result:

other: no reading was conducted at 72 h; score represents mean value of 24 and 48 h

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

3.25

Max. score:

4

Reversibility:

fully reversible within: 8 d

Remarks on result:

other: no reading was conducted at 72 h; score represents mean value of 24 and 48 h; values given as 3-4 were calculated as 3.5

Irritation parameter:

erythema score

Basis:

animal #4

Time point:

24/48/72 h

Score:

3.75

Max. score:

4

Reversibility:

fully reversible within: 12 d

Remarks on result:

other: no reading was conducted at 72 h; score represents mean value of 24 and 48 h; values given as 3-4 were calculated as 3.5

Irritation parameter:

erythema score

Basis:

animal #5

Time point:

24/48/72 h

Score:

2.75

Max. score:

4

Reversibility:

fully reversible within: 12 d

Remarks on result:

other: no reading was conducted at 72 h; score represents mean value of 24 and 48 h

Irritation parameter:

erythema score

Basis:

animal #6

Time point:

24/48/72 h

Score:

3

Max. score:

4

Reversibility:

fully reversible within: 8 d

Remarks on result:

other: no reading was conducted at 72 h; score represents mean value of 24 and 48 h

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.5

Max. score:

4

Reversibility:

fully reversible within: 48 h

Remarks on result:

other: no reading was conducted at 72 h; score represents mean value of 24 and 48 h

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: no edema determined at any time point

Remarks on result:

other: no reading was conducted at 72 h; score represents mean value of 24 and 48 h

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.5

Max. score:

4

Reversibility:

fully reversible within: 48 h

Remarks on result:

other: no reading was conducted at 72 h; score represents mean value of 24 and 48 h

Irritation parameter:

edema score

Basis:

animal #4

Time point:

24/48/72 h

Score:

0.5

Max. score:

4

Reversibility:

fully reversible within: 48 h

Remarks on result:

other: no reading was conducted at 72 h; score represents mean value of 24 and 48 h

Irritation parameter:

edema score

Basis:

animal #5

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: no edema determined at any time point

Remarks on result:

other: no reading was conducted at 72 h; score represents mean value of 24 and 48 h

Irritation parameter:

edema score

Basis:

animal #6

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: no edema determined at any time point

Remarks on result:

other: no reading was conducted at 72 h; score represents mean value of 24 and 48 h

Irritant / corrosive response data:

- see table 1

Other effects:

- in all animals: erythema, oedema, erosions, pachydermatosis and necrosis
- At the application site eschar formation and desquamation of the epidermis were observed from the 5th day after compound application; thereafter scar was formed. Full recovery with fur covering scar area was observed between day 25 and 29.
There were no significant difference between unabraded and abraded skin reaction.

Interpretation of results:

Category 1B (corrosive) based on GHS criteria

Conclusions:

Under the conditions of this skin irritation study an average edema score of 0.33 and an average erythema score of 3.25 were deduced (average of all animals, time points: 1, 24, 48 h). No deaths occurred during the study period and no signs of toxicity were reported. Based on the results it can be concluded that the test substance has corrosive effects on the skin of rabbits.

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

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: - Guideline study with acceptable restrictions (e.g. study conducted comparable to current guideline, purity of substance not reported, very limited information on animal source and housing)

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Principles of method if other than guideline:

Method: Draize Test

GLP compliance:

no

Remarks:

study performed prior to implementation of GLP

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: in-house breeding facility
- Age at study initiation: not reported
- Weight at study initiation: 2 - 3 kg
- Housing: 1 per cage (metal cages)
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 4 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +- 2
- Humidity (%): 55 +- 10
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light): 12/12

Vehicle:

unchanged (no vehicle)

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied: 0.1 g

Observation period (in vivo):

- 4 days

Number of animals or in vitro replicates:

1 animal per experimental procedure

Details on study design:

- 0.1 g of the test item was inserted in the conjunctival sac of the left eye of the rabbits and the lids were closed gently for a few seconds
- in one of the two rabbits (animal no. 182) approximately 30 sec after treatment the treated eye was flushed with 10 ml physiological saline.

Irritation parameter:

cornea opacity score

Basis:

animal: 181, not rinsed

Time point:

24/48/72 h

Score:

1.3

Max. score:

4

Reversibility:

other: animal killed for humane reasons after 4 days

Irritation parameter:

iris score

Basis:

animal: 181, not rinsed

Time point:

24/48/72 h

Score:

0.66

Max. score:

2

Reversibility:

other: animal killed for humane reasons after 4 days

Irritation parameter:

chemosis score

Basis:

animal: 181, not rinsed

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

other: animal killed for humane reasons after 4 days

Irritation parameter:

conjunctivae score

Basis:

animal: 181, not rinsed

Time point:

24/48/72 h

Score:

3

Max. score:

3

Reversibility:

other: animal killed for humane reasons after 4 days

Irritation parameter:

cornea opacity score

Basis:

animal: 182, rinsed

Time point:

24/48/72 h

Score:

3

Max. score:

4

Reversibility:

other: animal killed for humane reasons after 4 days

Irritation parameter:

iris score

Basis:

animal: 182, rinsed

Time point:

24/48/72 h

Score:

2

Max. score:

2

Reversibility:

other: animal killed for humane reasons after 4 days

Irritation parameter:

conjunctivae score

Basis:

animal: 182, rinsed

Time point:

24/48/72 h

Score:

3

Max. score:

3

Reversibility:

other: animal killed for human reasons after 4 days

Irritation parameter:

chemosis score

Basis:

animal: 182, rinsed

Time point:

24/48/72 h

Score:

3

Max. score:

4

Reversibility:

other: animal killed for humane reasons after 4 days

Irritant / corrosive response data:

see table 1

Other effects:

not reported

Interpretation of results:

Category 1 (irreversible effects on the eye) based on GHS criteria

Conclusions:

Under the conditions of this eye irritation study an average cornea opacity of 3, an average iris score of 2, an average chemosis score of 3 and an average conjunctiva redness score of 3 for the animale with rinsed eyes was determined. For the animal with not rinsing of the treated eye 30 seconds after treatment an average cornea opacity of 1.3, an average iris score of 0.66, an average chemosis score of 2 and an average conjunctiva redness score of 3 could be demonstrated. The animal with the eye not rinsed after treatment showed more potent effects and thus represents the worst case. Based on the results it can be concluded that the test substance has irritating effects on the eye of rabbits.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Additional information

- skin irritation: In a key skin irritation study (93-0171-DGT) six rabbits were treated once with Cyanuric chloride (concentration: 0.3 g) in polyethylene glycol (PEG 400) via occlusive dermal exposure for 24 h and observed for clinical signs, weight development and overt signs of toxicity for 28 d post administration. Skin reactions were observed and scored according to the Draize Score system 1, 24, 48 h and 5, 7, 8 and 9 d post start of treatment. An average edema score of 0.33 and an average erythema score of 3.25 were deduced (average of all animals, time points: 1, 24, 48 h).No deaths occurred during the study period and no signs of toxicity were reported. During the first week post dosing animals showed the following clinical signs: erythema, oedema, erosions, pachydermatosis and necrosis at the application site and in surrounding tissue areas. Scar formation after 5d, recovery of fur above scar at about day 25. Based on the stated results, especially the reported necrosis and the scar formation the following classification is regarded appropriate: Category 1 B: corrosive (H314: Danger, causes severe skin burns and eye damage) according to CLP as implementation of UN GHS in the EU (REGULATION (EC) No 1272/2008 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL).  

In four dermal irritation studies (2000-0076-FGT, 82-0038-DKT + 82-00369-DKT, 82-0037-DKT, 81 -0025 -FKT) rabbits were dermally exposed to Cyanuric chloride,skin reactions were observed and scored according to the Draize Score system 24, 48 and 72 h after start of treatment. In three studies low to moderate erythema and edema scores was observed, but the healing process was not completed at day 14 post exposure. As a conservative approach Cyanuric chloride was classified as category 2: irritant (H315: Warning, causes skin irritation) according to CLP as implementation of UN GHS in the EU (REGULATION (EC) No 1272/2008 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL).

One dermal irritation study showed average edema score of 2.0 and an everage erythema score of 2.33 under the test conditions (average of all animals, all time points). Based on that result a classification of category 2: irritant (H315: Warning, causes skin irritation) was regarded for Cyanuric chloride according to CLP as implementation of UN GHS in the EU (REGULATION (EC) No 1272/2008 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL).  

One further dermal irriation study (75-0007-FKT) in rabbits was conducted with Cyanuric chloride. However, documentation was insufficient for assessment.

In conclusion, taking into account worst-case approach the key study was used for evaluation and classification of Cyanuric chloride.

- eye irritation:

The eye irritation key study (81 -0026 -FKT) was conducted generally comparable to the OECD guideline 405 as at 1981. New Zealand White rabbits were treated once with Cyanuric chloride by application of 0.1 g to the conjunctival sac of the left eye and observed for clinical signs, weight development and overt signs of toxicity for 4 d post administration. Eye reactions were observed and scored according to Kay and Calandra (1962) 24, 48, 72 and 96 h after the start of treatment. Two animals were used, one with rinsing of the treated eye 30 seconds after treatment, the other without rinsing. No deaths occurred during the study period and no signs of toxicity were reported. In the not rinsed animal an average cornea opacity of 1.3, a average iris score of 0.66, an average chemosis score of 2 and an average conjunctiva redness score of 3 were deduced under the test conditions (averages on values from 24, 48 and 72 h). The rinsed animal showed more potent effects whereas an average cornea opacity of 3, an average iris score of 2, an average chemosis score of 3 and an average conjunctiva redness score of 3 could be determined. Animals were killed for humane reasons after 4 days, thus it appears that reversibility of the effects could not be identified in the study. Under consideration of the results of the animal with rinsing of the treated eye, which indicated the worst case due to the higher irritation parameters, the following classification is regarded appropriate: Category 1: Irreversible effects on the eye (H 318: Danger, causes serious eye damage) according to CLP as implementation of UN GHS in the EU (REGULATION (EC) No 1272/2008 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL).  

In a supporting eye irritation study (93 -0173 -FGT) an overall irritation score of 64.7 (max 110) was deduced under the test conditions (averages on values from 24, 48 and 72 h and all four animals, substance was not rinsed out, Kay and Calandra (1962) scoring system). No deaths occurred during the study period. Clinical signs were reported to be: reddening and well defined swelling with partial eversion of eyelids, increase of secretion with moistening of eyelids - adjacent hair, corneal opacity, corneal swelling with markedly closed lids and iris congestion. Based on the stated results the following classification is regarded appropriate: Category 1: Irreversible effects on the eye (H 318: Danger, causes serious eye damage) according to CLP as implementation of UN GHS in the EU (REGULATION (EC) No 1272/2008 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL).

- respiratory irritation: In one respiratory irritation study (94-0202-FGT) 10 male mice were exposed by inhalation to Cyanuric chloride (2.1, 6.8, 9.3, 11.7 and 14.6 mg/m³) for 15, 10 and 5 minutes, respectively. The RD50 value was calculated to be 5.9 mg/cbm (1.3 – 13.9 mg/cbm for 95% confidence interval). Between 8 and 16 minutes a plateau was reached. The study was conduced according to the Alarie Test. Based on the determined RD50 of 5.9 mg/m³ the classification as STOT SE category 3 (H335: Warning, may cause respiratory irritation) was considered to be required according to CLP as implementation of UN GHS in the EU (REGULATION (EC) No 1272/2008 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL).  

 

Effects on skin irritation/corrosion: corrosive

Effects on eye irritation: corrosive

Effects on respiratory irritation: irritating

Justification for classification or non-classification

Based on the results for in vivo skin irritation, the substance should be classified as Cat. 1B, H314 (Corrosive, Causes severe skin burns and eye damage) according to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No 1272/2008.

 

Based on the results for in vivo eye irritation, the substance should be classified as Cat. 1, H318 (Danger, Causes serious eye damage) according to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No 1272/2008.

 

Based on the results of the in vivo respiratory irritation study, the substance should be classified as STOT SE Cat. 3, H335 (Warning, may caus respiratory irritation) according to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No 1272/2008.