Registration Dossier

Administrative data

Description of key information

DAP is not considered as a skin or eye irritant based on two studies with rabbits both reliable but not without restrictions.

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
Study period:
Date of Study Report: August 9, 1976
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
according to
Guideline:
other: 16 CFR 1500.41
Deviations:
not specified
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
: Exposure duration, testing included abraded skin, Scoring following other criterias
Principles of method if other than guideline:
The exposure period was 24 h instead of 4 h. Post-dose observations were made up to 7 d instead of 14 d. Part of the shaven skin was abraded, which is not according to OECD guideline 404, which says:"Care should be taken to avoid abrading the skin."
GLP compliance:
no
Species:
rabbit
Strain:
not specified
Details on test animals and environmental conditions:
Test was conducted on 6 adult albino rabbits selected from healthy, acclimated animals.
Type of coverage:
semiocclusive
Preparation of test site:
other: Each rabbit: shaven skin, partly abraded
Vehicle:
unchanged (no vehicle)
Controls:
not specified
Amount / concentration applied:
0.5 mL or 0.5 g
Duration of treatment / exposure:
24 hour(s)
Observation period:
24, 72 h and 7 d
Number of animals:
6
Details on study design:
TEST SITE
- Area of exposure: 1 inch x 1 inch
- Each rabbit treated with a patch on shaven skin and on abraded skin

REMOVAL OF TEST SUBSTANCE
- Washing (if done): not indicated
- Time after start of exposure: Patches were removed after 24 hrs

OBSERVATIONS:
- 24 h, 72 h and 7 d after start of the exposure.

SCORING SYSTEM: Draize Scoring Criteria
Irritation parameter:
erythema score
Basis:
mean
Time point:
72 h
Score:
1
Max. score:
1
Reversibility:
fully reversible

Table: Primary Skin Irritation Scores of Rabbits dosed with Diallyl phthalate (According to Draize Scoring Criteria)

Findings

Exposure Time

Exposure Unit (Value)

Rabbit No.

1

2

3

4

5

6

Erythema and eschar formation:

Intact Skin

24 hrs

2

2

2

2

2

2

Intact Skin

72 hrs

1

1

1

1

1

1

Intact Skin

7 days

1

1

0

1

1

1

Abraded skin

24 hrs

2

2

2

2

2

2

Abraded skin

72 hrs

1

1

2

1

1

1

Abraded skin

7 days

1

1

1

1

1

1

Subtotal

 

 

 

 

 

 

 

Edema formation:

Intact Skin

24 hrs

1

1

1

1

1

1

Intact Skin

72 hrs

1

1

0

0

1

0

Intact Skin

7 days

1

0

0

0

0

0

Abraded skin

24 hrs

1

1

1

1

1

1

Abraded skin

72 hrs

1

1

0

0

0

1

Abraded skin

7 days

0

0

0

0

0

0

Subtotal

 

4

4

2

2

3

3

Total

 

10

10

9

8

9

9

Score

 

2.50

2.50

2.25

2.00

2.25

2.25

Average

 

2.29

- 7 -Day values not included in calculating the score.

Erythema and edema were observed in the intact and abraded skin of all six animals. Erythema cleared in the intact skin of one animal. Edema cleared in the intact skin of five animals, and abraded skin of all six animals during the 7-day observation period.

Draize Scoring Criteria:

- Primary Skin Irritation Indexes of less than 2.0 are mild irritants.

- Primary Skin Irritation Indexes of 2.0 to 5.0 are moderate irritants.

- Primary Skin Irritation indexes of greater than 5.0 are severe irritants.

Interpretation of results:
slightly irritating
Remarks:
Migrated information Criteria used for interpretation of results: OECD GHS
Conclusions:
Primary skin irritation testing of DAP at a dose of 0.5g by FDRL during 24 h, showed the sample to be moderately irritant up to 72 h after the start of exposure (within the range of 2.0 to 5.0) and decreased to mildly irritant after 7 days post-exposure. Hence, based on the fact that exposure duration was 6 times longer than that prescribed by OECD Guideline 404, and the scoring decreased to mildly irritant within 7 days of exposure, the final conclusion is that DAP can be expected to be only slightly irritant, when evaluated according to OECD guideline 404.
Executive summary:

On the basis of the data presented herein, the test material, FMC Corporation D.A.P. (1 Qt. Net Wt.) C-8013-3; is a moderate irritant to the rabbit skin.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (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:
Date of Study Report: August 9, 1976
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Basic data given : Comparable to quidelines/standards
Qualifier:
according to
Guideline:
other: 16 CFR 1500.42
Deviations:
yes
Remarks:
: The test procedure was modified as follows: In Group I, Six rabbits; eyes unwashed following the instillation of the test material. In Group II, Three rabbits; eyes washed 4 seconds following instillation of the test material.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
: Washout after 4s, no information on a preliminary in vitro study
GLP compliance:
no
Species:
rabbit
Strain:
other: Albino
Details on test animals or tissues and environmental conditions:
The acute eye irritation test was determined on 9 young adult albino rabbits, selected from healthy, acclimated animals.
Vehicle:
unchanged (no vehicle)
Controls:
not specified
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1ml or 0.1g
Duration of treatment / exposure:
Single application
Observation period (in vivo):
All eyes were observed and ocular reaction recorded at 24, 48, and 72 hours after instillation of the test material. They were observed again after 7 days.
Number of animals or in vitro replicates:
Group I: 6 rabbits with eyes unwashed following the instillation of the test material
Group II: 3 rabbits with eyes washed for 4 seconds following instillation of the tests material
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): Any or all eyes may be washed with sodium chloride solution U.S.P. or equivalent .
- Time after start of exposure: after the 24-hour reading.

SCORING SYSTEM:

TOOL USED TO ASSESS SCORE: Reading of reactions is facilitated by use of a binocular loupe, hand slit-lamp, or other expert means. After the recording of observations at 24 hours, any or all eyes may be further examined after applying fluorescein.
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
Groups I and II
Time point:
other: 24, 48, 72h, 7days
Score:
0
Max. score:
0
Reversibility:
not specified
Irritation parameter:
iris score
Basis:
mean
Remarks:
Groups I and II
Time point:
other: 24, 48, 72h, 7days
Score:
0
Max. score:
0
Reversibility:
not specified
Irritation parameter:
conjunctivae score
Basis:
animal: 1, 2 from Group I ; 2 , 3 from Group II
Time point:
other: 24h
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 48h
Irritation parameter:
conjunctivae score
Basis:
animal: 3, 6 from Group I
Time point:
other: 24h
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 72h
Irritation parameter:
chemosis score
Basis:
animal: 3 from group I ; 1 from Group II
Time point:
other: 24h
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 48h
Irritant / corrosive response data:
Group I : Conjunctival effects were observed in four animals. These effects cleared during the 72-hour observation period.
Group II : Conjonctival effects were observed in all three animals. These effects cleared during the 48-hour observation period.
Interpretation of results:
slightly irritating
Remarks:
Migrated information Criteria used for interpretation of results: OECD GHS
Conclusions:
On the basis of the data presented herein the following is concluded for the test material, FMC Corporation; D.A.P. (1 Qt. Net Wt.); C-8013-3:
Group I and II: It is a mild transient irritant to the rabbit eye when not followed by or followed by a washout 4 -seconds after instillation of the test material.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Although the studies used for assessing the potential of DAP to cause irritation of both eye and skin are not reliable without restrictions, they provide relevant and consistent data indicating that DAP is only slightly irritant to both skin and eye. In the interest of both sound science and animal welfare, further in vivo testing should not be considered necessary.


Effects on skin irritation/corrosion: slightly irritating

Effects on eye irritation: slightly irritating

Justification for classification or non-classification

Based on the data presented here, DAP is not to be classified as irritant to either skin or eye. In extrapolation to humans, it can be safely concluded that DAP is not irritant to the human skin or eye. In many cases the albino rabbit is more sensitive than humans to ocular irritants or corrosives. There are also no known reports of irritation of human skin or eye after accidental exposure, which is consistent with the animal studies and provides further indications that classification for skin or eye irritation is not needed.