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Toxicological information

Skin irritation / corrosion

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Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
05/04/1997 - 17/03/1998
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
GLP, Guideline study: Six rabbits instead of 3 (92/69/EEC B.4) were used since this is a regulatory requirement of EPA-FIFRA. The initial skin reactions were scored 30 minutes after patch removal rather than at 60 minutes. Clinical signs and body weights not reported.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1998
Report Date:
1998

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
(1992)
Deviations:
no
Qualifier:
equivalent or similar to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPP 81-5 (Acute Dermal Irritation)
Version / remarks:
(1982)
Deviations:
no
Qualifier:
according to
Guideline:
other: JMAFF 59 NohSan no. 4200 (1985)
Deviations:
no
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: solid

Test animals

Species:
rabbit
Strain:
other: New Zealand White (Hra:(NZW)SPF)
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: 14-18 weeks old
- Weight at study initiation: 2260 – 2602 g

Test system

Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
water
Remarks:
distilled
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount applied : 0.5 g
- pH: no data

VEHICLE
- Amount applied: 0.3 mL
Duration of treatment / exposure:
4 hours
Observation period:
72 hours
Number of animals:
6 rabbits (5 males and female)
Details on study design:
TEST SITE
- Area of exposure: 2.5 x 2.5 cm

REMOVAL OF TEST SUBSTANCE
- Washing: The occlusive dressings were removed and the test sites washed with water to remove all traces of test article.
- Time after start of exposure: After 4 hours

SCORING SYSTEM:
- Name of grading system: Dermal erythema & eschar formation and edema were graded according to the Draize scoring method and the primary dermal irritation index (PDII) was calculated. EPA and EU index scores were calculated for each animal.
- Time points where grading took place: 30 minutes after patch removal, and subsequently at 24, 48 and 72 hours.

STATISTICS:
No statistical methods were employed.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: overall
Score:
0.2
Reversibility:
fully reversible
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24 h
Score:
0
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
48 h
Score:
0
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
72 h
Score:
0
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24 h
Score:
0
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
48 h
Score:
0
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
72 h
Score:
0
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24 h
Score:
0
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
48 h
Score:
0
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
72 h
Score:
0
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
24 h
Score:
0
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
48 h
Score:
0
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
72 h
Score:
0
Irritation parameter:
erythema score
Basis:
animal #5
Time point:
24 h
Score:
0
Irritation parameter:
erythema score
Basis:
animal #5
Time point:
48 h
Score:
0
Irritation parameter:
erythema score
Basis:
animal #5
Time point:
72 h
Score:
0
Irritation parameter:
erythema score
Basis:
animal #6
Time point:
24 h
Score:
1
Reversibility:
fully reversible within: 24 hours
Irritation parameter:
erythema score
Basis:
animal #6
Time point:
48 h
Score:
0
Irritation parameter:
erythema score
Basis:
animal #6
Time point:
72 h
Score:
0
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
edema score
Basis:
animal #4
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
edema score
Basis:
animal #5
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
edema score
Basis:
animal #6
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritant / corrosive response data:
Three of the 6 test animals showed very slight (grade 1) erythema reactions 30 minutes after patch removal. Very slight erythema persisted in one of these animals until 24 hours, but was not apparent in the other 2 animals at this time. The remaining 3 animals showed no evidence of dermal irritation at any of the observation intervals. Edema and other manifestations of dermal irritation did not occur in any animal at any observation interval (Table 1). Five of the 6 animals had EU index scores of 0.0 and the remaining animal had an index score of 0.33. Consequently, dinotefuran is not classified as irritating to skin according to EU criteria. The PDII for dinotefuran was calculated as 0.2, a score defined as indicating slight irritation according to the EPA classification system.

Any other information on results incl. tables

Table 1: Individual skin irritation and index scores

Animal

Individual erythema / edema scores at:

EPA index

EU index

 

30 minutes

24 hours

48 hours

72 hours

score*

score**

1

1 / 0

0 / 0

0 / 0

0 / 0

0.25

0.0

2

0 / 0

0 / 0

0 / 0

0 / 0

0

0.0

3

0 / 0

0 / 0

0 / 0

0 / 0

0

0.0

4

1 / 0

0 / 0

0 / 0

0 / 0

0.25

0.0

5

0 / 0

0 / 0

0 / 0

0 / 0

0

0.0

6

1 / 0

1 / 0

0 / 0

0 / 0

0.50

0.33

Total score

(erythema + edema)

3

1

0

0

PDII***

0.2

Mean

0.06

* EPA index score = total erythema & edema score at all observation intervals / no. of observation intervals

** EU index score = total erythema & edema score at the 24, 48 and 72hr intervals / no. of observation intervals

*** PDII = sum of individual index scores / no. of animals, rounded to nearest 0.1

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Dinotefuran does not require classification as a skin irritant in the EU according CLP regulation.