dinotefuran (ISO); 1-methyl-2-nitro-3-(tetrahydro-3-furylmethyl)guanidine

Skin irritation / corrosion

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 guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

(1992)

Deviations:

no

Test guideline 2

Qualifier:

equivalent or similar to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPP 81-5 (Acute Dermal Irritation)

Version / remarks:

(1982)

Deviations:

no

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: JMAFF 59 NohSan no. 4200 (1985)

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

(RS)-1-methyl-2-nitro-3-(tetrahydro-3-furylmethyl)guanidine

EC Number:

605-399-0

Cas Number:

165252-70-0

Molecular formula:

C7H14N4O3

IUPAC Name:

(RS)-1-methyl-2-nitro-3-(tetrahydro-3-furylmethyl)guanidine

Test material form:

other: solid

Test animals

Species:

rabbit

Strain:

other: New Zealand White (Hra:(NZW)SPF)

Details on test animals or test system 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

Results

Results 1

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Time point:

other: overall

Score:

0.2

Reversibility:

fully reversible

Results 2

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24 h

Score:

0

Results 3

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

48 h

Score:

0

Results 4

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

72 h

Score:

0

Results 5

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24 h

Score:

0

Results 6

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

48 h

Score:

0

Results 7

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

72 h

Score:

0

Results 8

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24 h

Score:

0

Results 9

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

48 h

Score:

0

Results 10

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

72 h

Score:

0

Results 11

Irritation parameter:

erythema score

Basis:

animal #4

Time point:

24 h

Score:

0

Results 12

Irritation parameter:

erythema score

Basis:

animal #4

Time point:

48 h

Score:

0

Results 13

Irritation parameter:

erythema score

Basis:

animal #4

Time point:

72 h

Score:

0

Results 14

Irritation parameter:

erythema score

Basis:

animal #5

Time point:

24 h

Score:

0

Results 15

Irritation parameter:

erythema score

Basis:

animal #5

Time point:

48 h

Score:

0

Results 16

Irritation parameter:

erythema score

Basis:

animal #5

Time point:

72 h

Score:

0

Results 17

Irritation parameter:

erythema score

Basis:

animal #6

Time point:

24 h

Score:

1

Reversibility:

fully reversible within: 24 hours

Results 18

Irritation parameter:

erythema score

Basis:

animal #6

Time point:

48 h

Score:

0

Results 19

Irritation parameter:

erythema score

Basis:

animal #6

Time point:

72 h

Score:

0

Results 20

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

0

Results 21

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

0

Results 22

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

0

Results 23

Irritation parameter:

edema score

Basis:

animal #4

Time point:

24/48/72 h

Score:

0

Max. score:

0

Results 24

Irritation parameter:

edema score

Basis:

animal #5

Time point:

24/48/72 h

Score:

0

Max. score:

0

Results 25

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.