N-nitro-N-(3-methyl-3,6-dihydro-2H-1,3,5-oxadiazin-4-yl)amine

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1995-08-24 till 1995-10-31

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline-conform study under GLP without deviations.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1995

Report date:

1995

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

431-060-1

EC Name:

-

Cas Number:

153719-38-1

Molecular formula:

Hill formula: C4H8N4O3 CAS formula: C4H8N4O3

IUPAC Name:

3-methyl-N-nitro-3,6-dihydro-2H-1,3,5-oxadiazin-4-amine

Details on test material:

- Name of test material (as cited in study report): CA 2343 A (Intermediate of CGA 293343)
- Substance type: mono-constituent organic substance
- Physical state: solid, fine, white powder
- Analytical purity: 96.7 %
- Impurities (identity and concentrations): no data
- Purity test date: no data
- Lot/batch No.: P.503005
- Expiration date of the lot/batch: Date of reanalysis: December 1996
- Stability under test conditions: not reported
- Storage condition of test material: 0 - 5 °C

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Dr. K. Thomae GMBH, Chemisch-pharmazeutische Fabrik, D-88397 Biberach, Germany
- Age at study initiation: no data
- Weight at study initiation: 2690 to 2970 g
- Housing: The animals were housed individually in metal cages
- Diet (e.g. ad libitum): Rabbits received ad libitum standard rabbit pellet - NAFAG 814, NAFAG, Gossau/SG, Switzerland.
- Water (e.g. ad libitum): fresh water ad libitum
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3 °C
- Humidity (%): 30 - 70%
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12 hours light cycle day


IN-LIFE DATES: From: 1995-08-24 To: 1995-09-12

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: The right eyes of the three test animals without treatment served as control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 ml, corresponding to 57 mg of test item
- Concentration (if solution): not applicable


VEHICLE
- Amount(s) applied (volume or weight with unit): not applicable
- Concentration (if solution):
- Lot/batch no. (if required):
- Purity:

Duration of treatment / exposure:

The test item was placed into the conjunctival sac of the left eye of each animal, after gently pulling away the lower lid from the eyeball. The lids were then held together for about one second in order to prevent loss of the test article.

Observation period (in vivo):

7 d

Number of animals or in vitro replicates:

3

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no washing reported
- Time after start of exposure:


SCORING SYSTEM: OECD scoring system (demonstrated in Appendix 1 of the original study report)


TOOL USED TO ASSESS SCORE: hand-slit lamp

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

mean

Remarks:

animals 1, 2, and 3

Time point:

other: overall at 24, 48 and 72 h

Score:

1.33

Max. score:

2

Reversibility:

fully reversible within: 7 d

Remarks on result:

other: max. score of 2 reversible after 48 h

Results 2

Irritation parameter:

conjunctivae score

Remarks:

(chemosis)

Basis:

mean

Remarks:

animals 1, 2, and 3

Time point:

other: overall score at 24, 48, and 72 h

Score:

>= 0.33 - <= 0.67

Max. score:

1

Reversibility:

fully reversible within: 3 d

Results 3

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

animals 1, 2, and 3

Time point:

other: overall at 24, 48 and 72 h

Score:

>= 0 - <= 0.33

Max. score:

1

Reversibility:

fully reversible within: 2 d

Results 4

Irritation parameter:

iris score

Basis:

mean

Remarks:

animals 1, 2, and 3

Time point:

other: overall at 24, 48 and 72 h

Score:

>= 0 - <= 1

Max. score:

1

Reversibility:

fully reversible within: 7 d

Irritant / corrosive response data:

Irritant data are summarized in the table above. All effects were fully reversible within 7 days at latest

Other effects:

none reported

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: OECD GHS

Conclusions:

Based on a degree of ocular irritation (mean scores of 24 through 72 hours after ocular administration) below threshold values, classification of CA 2343 A (Intermediate of CGA 293343) according to OECD-GHS or Council Directive 67/548/EEC is not required.

Executive summary:

An acute eye irritation/corrosion study in albino rabbits was performed to determine the irritant and corrosive potency of CA 2343 A (Intermediate of CGA 293343) on albino rabbit eye and associated mucous membranes. This study protocol was based on the OECD Guideline No. 405, and on Annex V, part B of Council Directive 79/831/EEC.

Under the experimental conditions employed, CA 2343 A (Intermediate of CGA 293343) induced reactions of the cornea, iris and conjunctiva, when instilled into the conjunctival sac of albino rabbit eyes.

The following mean scores (24 - 72 h) were calculated:

Conjunctivae score (rednenss): mean 1.33, max. 2

Conjunctivae score (chemosis): mean 0.33 - 0.67, max. 1

Cornea score: 0 - 0.33, max. 1

Iris score: 0 - 1, max. 1

All observed irritating effects were fully revesible within 7 d at latest.

Based on a degree of ocular irritation (mean scores of 24 through 72 hours after ocular administration) below threshold values, classification of CA 2343 A (Intermediate of CGA 293343) according to OECD-GHS or Council Directive 67/548/EEC is not required.