spirodiclofen (ISO);3-(2,4-dichlorophenyl)-2-oxo-1-oxaspiro[4.5]dec-3-en-4-yl 2,2-dimethylbutyrate

Endpoint summary

Description of key information

In vitro data are not available; in vivo data predate the adoption of validated in vitro methods.

A GLP- and guideline (OECD 404) compliant study of skin irritation is available (Klimisch 1).

A GLP- and guideline (OECD 405) compliant study of eye irritation is available (Klimisch 1).

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:

15 March 1996 - 25 September 1997

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: EEC B.4.

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2500 (Acute Dermal Irritation)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

Himalayan

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Leuschner, Germany
- Age at study initiation: ~5 months
- Weight at study initiation: 1.9-2.0 kg
- Housing: singly
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: not stated

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-22
- Humidity (%): 30-70
- Air changes (per hr): not stated
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 21 March 1996 To: 24 March 1996

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

water

Controls:

not required

Amount / concentration applied:

500 mg (moistened with water)

Duration of treatment / exposure:

The duration of exposure was 4 hours

Observation period:

Skin irritation was assessed at 1-, 24-, 48-, 72 hours after exposure.

Number of animals:

3 Rabbits were used in the study

Details on study design:

500 mg spirodiclofen was moistened with water, applied to the test site and covered with a gauze patch to the skin (area: approx. 6 cm²). The patch was held in contact with the skin by a semi-occlusive dressing. The duration of exposure was 4 hours.

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: no irritating effects.

Remarks on result:

no indication of irritation

Remarks:

None of the rabbits showed irritation at 24, 48 or 72 hours

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: no irritating effects

Remarks on result:

no indication of irritation

Remarks:

None of the rabbits showed irritation at 24, 48 or 72 hours

Irritant / corrosive response data:

Not applicable: there were no signs of irritation at any time point

Skin irritation scores:

	1h	1h	24h	24h	48h	48h	72h	72h	7d	7d	14d	14d	Irrit. Index	Irrit. Index
Animal No.	e	oe	e	oe	e	oe	e	oe	e	oe	e	oe	e	oe
1	0	0	0	0	0	0	0	0	-	-	-	-	0.0	0.0
2	0	0	0	0	0	0	0	0	-	-	-	-	0.0	0.0
3	0	0	0	0	0	0	0	0	-	-	-	-	0.0	0.0

0 = no pathological findings; - = not examined; d = day; e = erythema and eschar formation; h = hour, -s;
oe = oedema formation

 

Interpretation of results:

GHS criteria not met

Remarks:

Spirodiclofen is not classified as a skin irritant according to the CLP criteria, on the basis of this study.

Conclusions:

There was no evidence of skin irritation in this study.

Executive summary:

The skin irritation/corrosion potential of spirodiclofen was investigated in a study in three rabbits, performed according to OECD 404.  The study predates the adoption of in vitro tests for the assessment of skin corrosion and skin irritation.  0.5 g of spirodiclofen (moistened with water) was applied for fhour hours under occlusive conditions to the shorn skin of three Himalayan rabbits.  Local dermal reactions were scored at 24, 48 and 72 hours after application, using the Driaze scale.  There were no signs of irritation in any rabbit at any time point.  Spirodiclofen is not classified as a skin irritant according to the CLP criteria, on the basis of this study.

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:

15 March 1996 - 25 September 1997

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

Himalayan

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Leuschner, Germany
- Age at study initiation: ~5 months
- Weight at study initiation: 2.1-2.6 kg
- Housing: singly
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: not stated

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-22
- Humidity (%): 30-70
- Air changes (per hr): not stated
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 25 March 1996 To: 29 March 1996

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

Spirodiclofen:
A dose of 100 mg Spirodiclofen/rabbit was administered into the conjunctival sac of the right eye

Duration of treatment / exposure:

Single exposure

Observation period (in vivo):

The eyes were examined ophthalmoscopically with a slit lamp prior to the administration and also 1, 24, 48 and 72 hours after the administration.
The eye reactions were observed and registered. 24 hours after administration the eyes were treated additionally with fluorescein and examined.

Number of animals or in vitro replicates:

Three

Details on study design:

24 hours after administration the eyes were treated additionally with fluorescein and examined using a slit lamp.

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: no effect

Remarks on result:

no indication of irritation

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: no effect

Remarks on result:

no indication of irritation

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: no effect

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

3

Reversibility:

other: no effect

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: no effect

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:

4

Reversibility:

other: no effect

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

3

Reversibility:

other: no effect

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: no effect

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:

4

Reversibility:

other: no effect

Remarks on result:

no indication of irritation

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: no effect

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: no effect

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

3

Reversibility:

other: no effect

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

Under the test conditions a single application of 100 mg Spirodiclofen per animal into the conjunctiva! sac of the right eye of three rabbits did not cause any changes.
The cornea, iris and conjunctiva were not affected by the instillation of the test compound.
There were no systemic intolerance reactions

Findings: 

			Draize grades
Animal No.	Tissue	Signs	1h	24h	48h	72h	7d	14d	21d	Irrit. index
1	cornea	o	0	0	0	0	-	-	-	0.0
		a	0	0	0	0	-	-	-
	fluorescein	i	-	0	-	-	-	-	-
		a	-	0	-	-	-	-	-
	iris		0	0	0	0	-	-	-	0.0
	conjunctivae	r	0	0	0	0	-	-	-	0.0
		c	0	0	0	0	-	-	-	0.0
2	cornea	o	0	0	0	0	-	-	-	0.0
		a	0	0	0	0	-	-	-
	fluorescein	i	-	0	-	-	-	-	-
		a	-	0	-	-	-	-	-
	iris		0	0	0	0	-	-	-	0.0
	conjunctivae	r	0	0	0	0	-	-	-	0.0
		c	0	0	0	0	-	-	-	0.0
3	cornea	o	0	0	0	0	-	-	-	0.0
		a	0	0	0	0	-	-	-
	fluorescein	i	-	0	-	-	-	-	-
		a	-	0	-	-	-	-	-
	iris		0	0	0	0	-	-	-	0.0
	conjunctivae	r	0	0	0	0	-	-	-	0.0
		c	0	0	0	0	-	-	-	0.0

- = not examined; i = intensity; a = area; o = opacity; d = day; r = redness; h = hour; c = chemosis

Interpretation of results:

GHS criteria not met

Conclusions:

Spirodiclofen is not classified as an  eye irritant according to the CLP criteria, on the basis of this study.

Executive summary:

The eye irritation potential of spirodiclofen was investigated in a study in three rabbits, performed according to OECD 405.  The study predates the adoption of in vitro tests for the assessment of eye irritation.  0.1 g of spirodiclofen was instilled into one eye of three Himalayan rabbits.  Ocular reactions were scored at 24, 48 and 72 hours after application, using the Driaze scale.  There were no signs of irritation in any rabbit at any time point.  Spirodiclofen is not classified as an  eye irritant according to the CLP criteria, on the basis of this study.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Justification for classification or non-classification

No dermal reactions were seen in any rabbit at any timepoint in a study of skin irritation.  No ocular reactions were seen in any rabbit at any timepoint in a study of eye irritation.  There were no clinical signs in an acute inhalation toxicity study, indicating a lack of respiratory irritation.  Spirodiclofen is therefore not classified according to CLP for skin corrosion (Cat 1), or for skin irritation (Cat 2); for serious eye damage (Cat 1) or for serious eye irritation (Cat 2); or for respiratory irritation (STOT SE 3).  This is consistent with the harmonised classification and the RAC opinion.