2,4-dinitroanisole

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

October 2000

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2000

Report date:

2000

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2400 (Acute Eye Irritation)

Deviations:

not specified

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

2,4-dinitroanisole

EC Number:

204-310-9

EC Name:

2,4-dinitroanisole

Cas Number:

119-27-7

Molecular formula:

C7H6N2O5

IUPAC Name:

2,4-dinitroanisole

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: none provided
- Expiration date of the lot/batch: non provided
- Physical Appearance: light yellow powder
- Storage condition of test material: stored at room temperature

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: Male/ female -- ~16 weeks
- Weight at study initiation: Male/ female -- 3.4 - 3.6kg/ ~3.3kg
- Housing: suspended stainless stell cages
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: minimum of 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 20
- Humidity (%): 48 - 55
- Air changes (per hr): 10 - 15
- Photoperiod (hrs dark / hrs light):12/ 12

Test system

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.0790g (or 0.1mL)

Duration of treatment / exposure:

15s

Duration of post- treatment incubation (in vitro):

72h

Number of animals or in vitro replicates:

3 (2 males and a female)

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing: with physiological saline
- Time after start of exposure: 15s
- Observation: 1, 24, 48 and 72 h
- Mortality observation: done twice daily (morning and afternoon)

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Results 2

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Results 3

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Results 4

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Results 5

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Results 6

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Results 7

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.33

Max. score:

1

Reversibility:

fully reversible within: 48hrs

Results 8

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.33

Max. score:

1

Reversibility:

fully reversible within: 48hrs

Results 9

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Results 10

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Results 11

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Results 12

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

Ocular Observations Individual Data: Table 1
Obervations were based onthe Ocular Grading System presented which is based on Draize (1959)

Exposure to the test article produced iritis in 2/3 test eyes at the 1-hour scoring interval which resolved by 24 hours. Conjunctivitis (redness, swelling and discharge) was observed in 3/3 test eyes at the 1-hour scoring interval. The conjunctiva! irritation resolved completely in all test eyes by 48 hours. An additional ocular finding included test article present in the eye which was noted in 3/3 test eyes.

No corneal opacity, iritis or conjunctivitis was observed in the control eyes.

Any other information on results incl. tables

Table 1 A Primary Eye Irritation Study in Rabbits, INDIVIDUAL OCULAR IRRITATIONSCORES (NO RINSE GROUP)

Animal No./Sex							Test Eye							Control Eye
Body Weight	Scoring	Cornea			Iris_		Conjunctivae						S econdary
(kg)	Interval	0	A	OxAx5	I	lx5	R	S	D	(R+S+D)*2	Total	Fluorescein Examination	Secondary Ocular Findings	Fluorescein Examination	Secondary Ocular Findings
R3014/M	1 Hour	0	0	0	0	0	2	1	1	8	8		TAE
3.363	24 Hours	0	0	0	0	0	1	0	0	2	2	[-]		[-]
	48 Hours	0	0	0	0	0	0	0	0	0	0
	72 Hours	0	0	0	0	0	0	0	0	0	0
R3009/M	1 Hour	0	0	0	1	5	2	2	1	10	15		TAE
3.611	24 Hours	0	0	0	0	0	1	0	0	2	2	[-]		[-]
	48 Hours	0	0	0	0	0	0	0	0	0	0
	72 Hours	0	0	0	0	0	0	0	0	0	0
R3042/F	1 Hour	0	0	0	1	5	2	1	1	8	13		TAE
3.254	24 Hours	0	0	0	0	0	0	0	0	0	0	[-]		[-]
	48 Hours	0	0	0	0	0	0	0	0	0	0
	72 Hours	0	0	0	0	0	0	0	0	0	0

 

Mean Ocular Scores

1 Hour	12.00
24 Hours	1.33
48 Hours	0 00
72 Hours	0.00

Table 2 OCULAR EVALUATION CRITERIA

Maximum mean score (days 0-3)	Maximum mean score	Persistence of Individual Scores		Descriptive Rating and Class
0.00 - 0.49	24 hours= 0			Non-lrritating	1
	24 hours> 0			Practically Non-lrritating	2
0.50 - 2.49	24 hours= 0			Non-lrritating	1
	24 hours> 0			Practically Non-lrritating	2
2.50 - 14.99	48 hours= 0			Sliqht Irritant	3
	48 hours> 0			Mild Irritant	4
15.00 - 24.99	72 hours= 0			Mild Irritant	4
	72 hours> 0			Moderate Irritant	5
25.00 - 49.99	7 days 20	> half of day 7 scores	s 10	Moderate Irritant	5
		" ·  > half of day 7 scores but no score >20	> 10,	Moderate Irritant	5
		> half of day 7 scores and any score > 20	> 10,	Severe Irritant	6
	7 day> 20			Severe Irritant	6
50.00 - 79.99	7 days 40	> half of day 7 scores	s 30	Severe Irritant	6
		> half of day 7 scores but no score > 60	> 30,	Severe Irritant	6
		> half of day 7 scores and any score > 60	> 30,	Very Severe Irritant	7
	7 day> 40			Very Severe Irritant	7
80.00 - 99.99	7 days 80	> half of day 7 scores	s 60	Very Severe Irritant	7
		> half of day 7 scores but no score > 100	> 60,	Very Severe Irritant	7
		> half of day 7 scores and any score > 100	>60,	Extremely Severe Irritant 8
	7 day> 80			Extremely Severe Irritant 8
100.00 - 110.00	7 days 80			Very Severe Irritant	7
	7 day> 80			Extremely Severe Irritant 8

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Based on the no rinse group, test item is considered to be slightly irritant to the ocular tissue of the rabbit.

Expose to the test item produced iritis in 2/3 test eyes at the 1-hour scoring interval which resolved by 24 hours.
Conjunctivitis (redness, swelling and discharge) was observed in 3/3 test eyes at the 1-hour scoring interval.
The conjunctival irritation resolved completely in all tests eyes by 48 hours.
An additional ocular finding included test item present in the eye which was noted in 3/3 test eyes.
No corneal opacity, iritis or conjunctivitis observed in the control eyes

Executive summary:

The potential irritant and/or corrosive effects of 2,4 Dinitroanisole were evaluated on the eyes of New Zealand White rabbits. Each of three rabbits received a 0.0790 g (0.1 ml weight equivalent) dose of the test article in the conjunctival sac of the right eye. The contralateral eye of each animal remained untreated and served as a control. Test and control eyes were examined for signs of irritation for up to 72 hours following dosing.

 Exposure to the test article produced iritis in 2/3 test eyes at the 1-hour scoring interval which resolved by 24 hours. Conjunctivitis (redness, swelling and discharge) was observed in 3/3 test eyes at the 1-hour scoring interval. The conjunctival irritation resolved completely in all test eyes by 48 hours. An additional ocular finding included test article present in the eye which was noted in 3/3 test eyes.

Based on the no rinse group, 2,4-Dinitroanisole is considered to be a slight irritant to the ocular tissue of the rabbit, but not sufficient for classification under CLP regulation.