2-(chloromethyl)-4-methylquinazoline

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2006-10-24 to 2006-10-25

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2006

Report date:

2006

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

2002

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Version / remarks:

2004

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2400 (Acute Eye Irritation)

Version / remarks:

1998

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

476-280-7

EC Name:

-

Cas Number:

109113-72-6

Molecular formula:

C10 H9 Cl N2

IUPAC Name:

2-(chloromethyl)-4-methylquinazoline

Test material form:

solid: particulate/powder

Details on test material:

- Physical state: Solid (powder); Off-white with yellow spherical particles

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Ferenc Sándor breeder, 2173 Kartal, Császár út 135, Hungary
- Age at study initiation: Young adult rabbit, 12 weeks old
- Weight at study initiation: 3432 g
- Housing: individually in metal cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 22 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +-3°C
- Humidity (%): 30-70 %
- Air changes (per hr): 8-12 per hr
- Photoperiod (hrs dark / hrs light): 12 hrs dark/12 hrs light

Test system

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 g test material

Duration of treatment / exposure:

1 h

Observation period (in vivo):

1 , 24, 48, 72 hrs and then one, two, three and four weeks after treatment.

Number of animals or in vitro replicates:

1

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): physiological saline
- Time after start of exposure: 1h


SCORING SYSTEM: The eye irritation scores were evaluated according to the scoring system by Draize (1959) and OECD 405 (24 April 2002).

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Reversibility:

not fully reversible within: 4 weeks after treatment

Remarks on result:

other: The respective mean values of irritation scores could not be calculated, due to the severely conjunctivae irritation at 24 and 48 hours after the treatment.

Results 2

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Reversibility:

fully reversible within: 1 week after treatment

Remarks on result:

other: The respective mean values of irritation scores could not be calculated, due to the severely conjunctivae irritation at 24 and 48 hours after the treatment.

Results 3

Irritation parameter:

other: conjunctivae score redness

Basis:

animal #1

Time point:

24/48/72 h

Reversibility:

not fully reversible within: 4 weeks after treatment

Remarks on result:

other: The respective mean values of irritation scores could not be calculated, due to the severely conjunctivae irritation at 24 and 48 hours after the treatment.

Results 4

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

3.66

Reversibility:

fully reversible within: 1 week after treatment

Results 5

Irritation parameter:

other: conjunctivae score discharge

Basis:

animal #1

Time point:

24/48/72 h

Score:

3

Reversibility:

fully reversible within: 1 week after treatment

Irritant / corrosive response data:

One hour after treatment in the animal the vessels were diffuse beefy red (score 3), swelling with lid more than half closed (score 4) and the discharge with moistening of the lids and hairs on a considerable area around the eye (score 3) were observed. Corneal and iris alterations could not be observed due to the swelling the lids were completely closed.
24 hours after treatment in the animal severe chemosis (score 4) and severely increased discharge excretion (score 3) occurred, so the redness of conjunctivae, corneal and iris alterations could not be observed. Due to the swelling the lids were completely closed. The discharge moistened the lids and considerable area around the treated eye.
48 hours after treatment the degree of chemosis and discharge did not change when compared to the previous observation. The redness of conjunctivae, corneal and iris alterations could not be observed even now.
72 hours after treatment the vessels were diffuse beefy red (score 3), the conjunctival swelling with lids about half closed (score 3) and the discharge with moistening of the lids and hairs on considerable area around the eye (score 3) was found. Diffuse corneal opacity was observed at this time. Nacreous areas of the cornea were observed and the details of iris were not visible (score 3). The area of cornea involved was greater than three quarters, up to the whole area (score 4). Iris still reacted to light (score 1).

1 week after the treatment in the animal diffuse individual vessels not easily discernible (score 2) were observed. The degree and the extension of opaque area of cornea did not change when compared to the previous observation. Iris alterations were not found.
2 week after the treatment in animal diffuse individual vessels not easily discernible (score 2) were observed. Easily discernible translucent areas of the cornea were observed and the details of iris were slightly obscured (score 2). Area of cornea involved was greater than three quarters, up to the whole area (score 4).
3 week after the treatment the observed irritating effects did not change when compared to the previous observation.
4 week after the treatment in animal diffuse individual vessels not easily discernible (score 2) were observed. Easily discernible translucent areas of the cornea were observed and the details of iris were slightly obscured (score 2). Area of cornea involved was greater than one quarter, but less than half (score 2).

Other effects:

General state and the behaviour of animal were normal throughout the study period. There was no significant body weight change during the contact and observation period.

Any other information on results incl. tables

Table 1: Results

Time	Score of irritation
	Conjunctivae			Opac. of cornea		Iris
	R	CH	D	OD	OE	R
1 hour	3	4	3	NT	NT	NT
	Control eye
	0	0	0	0	0	0
24 hours	NT	4	3	NT	NT	NT
	Control eye
	0	0	0	0	0	0
48 hours	NT	4	3	NT	NT	NT
	Control eye
	0	0	0	0	0	0
72 hours	3	3	3	3	4	1
	Control eye
	0	0	0	0	0	0
1 week	2	0	0	3	4	0
	Control eye
	0	0	0	0	0	0
2 weeks	2	0	0	2	4	0
	Control eye
	0	0	0	0	0	0
3 weeks	2	0	0	2	4	0
	Control eye
	0	0	0	0	0	0
4 weeks	2	0	0	2	2	0
	Control eye
	0	0	0	0	0	0

R = Redness              OD = Opacity degree of density

CH = Chemosis        OE = Extension of opaque area

D = Discharge        NT = Cannot be scored

Applicant's summary and conclusion

Interpretation of results:

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

Conclusions:

On the basis of the observed severe irritation signs, the test item is considered to cause serious eye damage (H318).