Registration Dossier

Administrative data

Description of key information

Bonnette 2000: In a primary skin irritation study, performed according the OPPTS Guideline 870.2500, in GLP compliance, 3 New Zealand rabbits were used to assess irritant and/or corrosive potential effect of 2,4 -Dinitroanisole. Each of 3 rabbits received a 0,5g dose of the test article in a single dermal application. The dose was held in contact with the skin under a semi-occlusive binder. Exposure to DNAN produced a very slight erythema on 2/3 test sites at the 1/hour scoring interval. The dermal irritation resolved completely in the affected animals by the 48 -hour scoring interval. The Draize's score is 0.25. DNAN is not classified according to the GHS classification criteria.

Springborn, 2000: The potential irritant and/or corrosive effects of 2,4-Dinitroanisole were evaluated on the skin of New Zealand White rabbits. Each of three rabbits received a 0.5 g dose of the test article as a single dermal application. The test article was moistened with deionized water prior to application to enhance test article contact with the skin. The dose was held in contact with the skin under a semi-occlusive binder for an exposure period of four hours. Following the exposure period, the binder was removed and the remaining test article was wiped from the skin using gauze moistened with deionized water followed by dry gauze. Test sites were subsequently examined and scored for dermal irritation for up to 72 hours following patch application.

Exposure to 2,4-Dinitroanisole produced very slight erythema on 2/3 test sites at the 1-hour scoring interval. The dermal irritation resolved completely in the affected animals by the 48-hour scoring interval. Under the conditions of this test, 2,4-Dinitroanisole is considered to be a slight irritant to the skin of the rabbit. The calculated Primary Irritation Index for the test article was 0.25.

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

Springborn 2000: 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

Key value for chemical safety assessment

Skin irritation / corrosion

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records
Reference
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
Qualifier:
according to
Guideline:
EPA OPPTS 870.2400 (Acute Eye Irritation)
Deviations:
not specified
GLP compliance:
yes
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
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
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)
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
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
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
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
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
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
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.33
Max. score:
1
Reversibility:
fully reversible within: 48hrs
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.33
Max. score:
1
Reversibility:
fully reversible within: 48hrs
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
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
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
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.

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

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.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for classification or non-classification

For skin irritation, DNAN is not classified according to the CLP regulation.

For eye irritation, DNAN is considered to be a slight irritant to the ocular tissue of the rabbit, but not sufficient for classification according to the CLP regulation.