Registration Dossier

Administrative data

Description of key information

The substance is a moderate skin irritant but according to classification criteria as defined in GHS and CLP not subject to classification.
DNNSA as a 50% formulation in light petroleum oil is a severe primary eye irritant in rabbits.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study follows acceptable practices. Conducted prior to GLP regulations.
Qualifier:
according to
Guideline:
other: Guidelines established by the US Federal Hazardous Substances Act (1973)
Deviations:
not specified
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
Six healthy mature male albino rabbits of the New Zealand variety were selected from the stock colony.
Type of coverage:
occlusive
Preparation of test site:
other: 6 sites abraded and 6 sites intact skin
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
0.5 ml of 50% solution in light paraffinic petroleum oil
Duration of treatment / exposure:
24 hours
Observation period:
24 and 72 hours
Number of animals:
6
Details on study design:
Prior to application of the sample, the backs wJere
clipped free of hair. The skin was left intact at six test sites and was
abraded on the other six. 0.5 ml of a liquid test material was
applied to an area of skin approximately 1 inch square on each rabbit. Patches
of surgical gauze measuring 1 inch square, 2 single layers thick, were applied
over the samples and covered with a non-reactive tape. The rabbits were then
wrapped with a rubber dam.
After the 24-hour exposure, the dam and tape were removed and the skin reactions
evaluated. An evaluation was also made at 72 hours after application.
The reactions were scored according to the methods described in the Federal
Hazardous Substances Act.
Irritation parameter:
edema score
Basis:
mean
Remarks:
of 6 animals
Time point:
other: 24 h
Score:
2
Max. score:
4
Reversibility:
no data
Remarks on result:
other: intact skin
Irritation parameter:
edema score
Basis:
mean
Remarks:
of 6 animals
Time point:
other: 24 h
Score:
2
Max. score:
4
Reversibility:
no data
Remarks on result:
other: abraded skin
Irritation parameter:
erythema score
Basis:
mean
Remarks:
of 6 animals
Time point:
other: 24 h
Score:
1.67
Max. score:
4
Reversibility:
no data
Remarks on result:
other: intact skin
Irritation parameter:
erythema score
Basis:
mean
Remarks:
of 6 animals
Time point:
other: 24 h
Score:
1.83
Max. score:
4
Reversibility:
no data
Remarks on result:
other: abraded skin
Irritation parameter:
edema score
Basis:
mean
Remarks:
of 6 animals
Time point:
other: 72 h
Score:
2.16
Max. score:
4
Reversibility:
no data
Remarks on result:
other: intact skin
Irritation parameter:
edema score
Basis:
mean
Remarks:
of 6 animals
Time point:
other: 72 h
Score:
2.16
Max. score:
4
Reversibility:
no data
Remarks on result:
other: abraded skin
Irritation parameter:
erythema score
Basis:
mean
Remarks:
of 6 animals
Time point:
other: 72 h
Score:
2.16
Max. score:
4
Reversibility:
no data
Remarks on result:
other: intact skin
Irritation parameter:
erythema score
Basis:
mean
Remarks:
of 6 animals
Time point:
other: 72 h
Score:
2.16
Max. score:
4
Reversibility:
no data
Remarks on result:
other: abraded skin
Irritant / corrosive response data:
The primary irritation index was 4.04, moderate irritation. It would not be considered a primary skin irritant.

INDEX Evaluation
0 No irritation
0.04 to 0.99 Irritation barely perceptible
1.00 to 1.99 Slight irritation
2.00 to 2.99 Mi ld irritation
3.00 to 5.99 Moderate irritation
6.00 to 8.00 Severe irritation

 

RABBIT

NO.

 

24 HOURS

 

72 HOURS

 

INTACT

 

ABRADED

 

INTACT

 

ABRADED

 

ERYTHEMA

 

EDEMA

 

ERYTHEMA

 

EDEMA

 

ERYTHENA

 

EDEMA

 

ERYTHEMA

 

EDEMA

 

A

 

B

 

C

 

D

 

E

 

F

 

G

 

H

 

2582

 

1

 

2

 

1

 

2

 

2

 

2

 

2

 

2

 

2583

 

2

 

2

 

2

 

2

 

2

 

2

 

2

 

2

 

2584

 

1

 2

 

2

 

2

 

1

 

2

 

1

 

2

 

2585

 

2

 

2

 

2

 

2

 

3

 

3

 

3

 

3

 

2586

 

2

 

2

 

2

 

2

 

2

 

2

 

2

 

2

 

2587

 

2

 

2

 

2

 

2

 

3

 

2

 

3

 

2

 

TOTAL

 

10

 

12

 

11

 

12

 

      13

 

13

 

13

 

13

PRIMARY IRRITATION INDEX = ( sum of individual totals, each divided by 6 ) divided by 4 = 4.04

Scoring of Irritation

Evaluation of Skin Reaction

 

Erythema and eschar formation:

Value

No erythema

0

Very slight erythema (barely perceptible)

1

Well-defined erythema

2

Moderate to severe erythema

3

Severe erythema (beet redness) to slight eschar formation (injuries in depth)

4

 

 

Edema formation:

 

No edema

0

Very slight edema (barely perceptible)

1

Slight edema (edges of area well defined by definite raising)

2

 

 

Moderate edema (raised approximately 1 mm)

3

 

 

Severe edema (raised more than 1 mm) and extending beyond the area of exposure

4

                                                            

Interpretation of results:
GHS criteria not met
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
The substance is a moderate skin irritant but according to classification criteria as defined in GHS and CLP not subject to classification.
Executive summary:

A 50% DNNSA formulation in light paraffinic petroleum oil was tested on six healthy mature male albino rabbits (New Zealand variety) for evaluation of primary irritation. Prior to application of the sample, the backs were clipped free of hair. The skin was left intact at six test sites and was abraded on the other six. 0.5 ml of a liquid test material was applied to an area of skin approximately 1 inch square on each rabbit. Patches of surgical gauze measuring 1 inch square, 2 single layers thick, were applied over the samples and covered with a non-reactive tape. The rabbits were then wrapped with a rubber dam. After the 24-hour exposure, the dam and tape were removed and the skin reactions evaluated. An evaluation was also made at 72 hours after application. The reactions were scored according to the methods described in the Federal Hazardous Substances Act.

RESULTS

The primary irritation index was 4.04 indicating moderate irritation.

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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study follows acceptable practices. Conducted prior to GLP regulations.
Qualifier:
according to
Guideline:
other: US FHSLA, CFR, Title 21, para. 191.12
Deviations:
not specified
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
One tenth of a milliliter of test material was instilled in one eye of each rabbit. The other eye of each rabbit remained untreated and served
as a control. The treated eyes were not washed. The rabbits were immobil ized in head stocks for 24 hours and then returned to their cages.
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
0.1 ml 50% solution in light paraffinic petroleum oil as placed on the market
Duration of treatment / exposure:
24 hours
Observation period (in vivo):
Ocular lesions were evaluated at 24, 48 and 72 hours and at 4, 7 and 14 days after treatment.
Number of animals or in vitro replicates:
6
Details on study design:
Methods of dosing are similar to Daize procedure except untreated eye used as a control.
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
of 6 rabbits
Time point:
other: 24 h
Score:
2.33
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
of 6 rabbits
Time point:
other: 48 h
Score:
2.67
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
of 6 rabbits
Time point:
other: 72 h
Score:
2.67
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Irritation parameter:
iris score
Basis:
mean
Remarks:
of 6 rabbits
Time point:
other: 24 h
Score:
1.33
Max. score:
2
Reversibility:
not fully reversible within: 14 days
Irritation parameter:
iris score
Basis:
mean
Remarks:
of 6 rabbits
Time point:
other: 48 h
Score:
1.67
Max. score:
2
Reversibility:
not fully reversible within: 14 days
Irritation parameter:
iris score
Basis:
mean
Remarks:
of 6 rabbits
Time point:
other: 72 h
Score:
1.83
Max. score:
2
Reversibility:
not fully reversible within: 14 days
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
of 6 rabbits
Time point:
other: 24 h
Score:
3
Max. score:
3
Reversibility:
not fully reversible within: 14 days
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
of 6 rabbits
Time point:
other: 48 h
Score:
3
Max. score:
3
Reversibility:
not fully reversible within: 14 days
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
of 6 rabbits
Time point:
other: 72 h
Score:
3
Max. score:
3
Reversibility:
not fully reversible within: 14 days
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
of 6 rabbits
Time point:
other: 24 h
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
of 6 rabbits
Time point:
other: 48 h
Score:
3.83
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
of 6 rabbits
Time point:
other: 72 h
Score:
3.67
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Irritant / corrosive response data:

The test material is a severe primary eye irritant.
Other effects:
No clinical signs of adverse effects were observed.

See detailed results and scoring procedure in attached document (next section).

Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
DNNSA as a 50% formulation in light petroleum oil is a severe primary eye irritant in rabbits.
Executive summary:

Synex 1052, a 50% DNNSA formulation in light petroleum oil was tested for primary eye irritation in New Zealand White rabbits.

One tenth of a milliliter of test material was instilled in one eye of each rabbit. Six rabbits were treated. The other eye of each rabbit remained untreated and served as a control. The treated eyes were not washed. The rabbits were immobilized in head stocks for 24 hours and then returned to their cages. Ocular lesions were evaluated at 24, 48 and 72 hours and at 4, 7 and 14 days after treatment.

No clinical signs of adverse systemic effects were observed. The test material is a severe primary eye irritant.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Whereas DNNSA was shown to be a moderate skin irritant, not fulfilling classification criteria under GHS/CLP, it was considered causing serious damage to eyes and within 14 days hardly any reversibility was observed.


Justification for selection of skin irritation / corrosion endpoint:
Scientifically sound study following acceptable testing procedure.

Justification for selection of eye irritation endpoint:
Scientifically sound study following acceptable testing procedure.

Effects on eye irritation: highly irritating

Justification for classification or non-classification

According to criteria in CLP (regualtion EC No 1272/2008) DNNSA is considered not skin irritant but having irreversible efffects to eyes (Eye Damage Categroy 1).