N-cyclopropyl-1,3,5-triazine-2,4,6-triamine

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2004/02/19 to 2004/11/29

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2004

Report date:

2004

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2400 (Acute Eye Irritation)

Version / remarks:

1998

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

other: JMAFF 59 NohSan No. 4200

Version / remarks:

January 28, 1985

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

N-cyclopropyl-1,3,5-triazine-2,4,6-triamine

EC Number:

266-257-8

EC Name:

N-cyclopropyl-1,3,5-triazine-2,4,6-triamine

Cas Number:

66215-27-8

Molecular formula:

C6H10N6

IUPAC Name:

N2-cyclopropyl-1,3,5-triazine-2,4,6-triamine

Test material form:

solid: particulate/powder

Remarks:

white to light beige crystalline

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Age at study initiation: Young adult
- Housing: The animals were singly housed in suspended stainless steel caging with mesh floors which conform to the size recommendations in the most recent Guide for the Care and Use of Laboratory Animals DHEW(NIH). Litter paper was placed beneath the cage and was changed at least three times per week.
- Diet: Pelleted rabbit feed
- Water: Filtered tap water was supplied ad-libitum by an automatic water dispensing system.
- Acclimation period: 14 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-22°C
- Photoperiod (hrs dark / hrs light): 12-hour light/dark cycle

Test system

Vehicle:

unchanged (no vehicle)

Controls:

yes

Amount / concentration applied:

0.1 mL (0.06 grams) of the test substance was instilled into the conjunctival sac of the right eye of each rabbit.

Duration of treatment / exposure:

Single instillation. The eyes were not rinsed.

Observation period (in vivo):

72 hours

Number of animals or in vitro replicates:

3 females

Details on study design:

Prior to use, the test substance was ground with a mortar and pestle.
Ocular irritation was evaluated using a high-intensity white light (Mag Lite) in accordance with Draize et al. at 1, 24, 48, and 72 hours post-instillation. The fluorescein dye evaluation procedure was used at 24 hours to verify the absence of corneal damage. In addition to observations of the cornea, iris and conjunctivae, any other observed lesions were noted.

The animals were observed for signs of gross toxicity and behavioral changes at least once daily during the test period. Observations included gross evaluation of skin and fur, eyes and mucous membranes, respiratory, circulatory, autonomic and central nervous systems, somatomotor activity and behavior pattern. Particular attention was directed to observation of tremors, convulsions, salivation, diarrhea and coma.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

conjunctivae score

Remarks:

Redness

Basis:

animal #3

Time point:

24 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Results 2

Irritation parameter:

conjunctivae score

Remarks:

Redness

Basis:

animal #2

Time point:

24 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Results 3

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Results 4

Irritation parameter:

conjunctivae score

Remarks:

Redness

Basis:

animal #3

Time point:

48 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Results 5

Irritation parameter:

conjunctivae score

Remarks:

Redness

Basis:

animal #2

Time point:

48 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Results 6

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Results 7

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Results 8

Irritation parameter:

conjunctivae score

Remarks:

Redness

Basis:

animal #1

Time point:

48 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Results 9

Irritation parameter:

conjunctivae score

Remarks:

Redness

Basis:

animal #1

Time point:

24 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Results 10

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Results 11

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

3 rabbits

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Any other information on results incl. tables

All animals appeared active and healthy. There were no signs of gross toxicity, adverse pharmacologic effects or abnormal behavior. Within the first hour following test substance instillation, conjunctivitis was observed in all three treated eyes. The overall incidence and severity of irritation decreased with time. All animals were free of ocular irritation within 72 hours.

Results are provided in the overall remarks section below.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

In an in vivo eye irritation study performed according to OECD/EC guidelines and GLP principles, cyromazine was found to be not irritating to the eye.

Executive summary:

A primary eye irritation test was conducted with rabbits to determine the potential for Cyromazine to produce irritation from a single instillation via the ocular route. One-tenth of a milliliter (0.06 grams) of the test substance was instilled into the right eye of three healthy rabbits. The left eye remained untreated and served as a control. Ocular irritation was evaluated by the method of Draize et al. Within the first hour following test substance instillation, conjunctivitis was observed in all three treated eyes. The overall incidence and severity of irritation decreased with time. All animals were free of ocular irritation within 72 hours. All animals appeared active and healthy. There were no signs of gross toxicity, adverse pharmacologic effects or abnormal behavior.