clothianidin (ISO); (E)-1-(2-chloro-1,3-thiazol-5-ylmethyl)-3-methyl-2-nitroguanidine

Endpoint summary

Description of key information

Skin irritation (OECD 404): not irritating

Eye irritation (OECD 405): not irritating

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:

17 - 28 Sep 1996

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

adopted 2015

Deviations:

yes

Remarks:

housing conditions slightly divergent, 6 animals were used, body weights only noted at the start of study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

adopted 1992

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River UK Ltd, Margate, UK
- Age at study initiation: 11 - 14 weeks
- Weight at study initiation: 2.42 - 2.85 kg
- Housing: individually housed in floor-pens with a minimum floor area of 0.6 m²
- Diet: pelleted SQC TRB Rabbit Diet 9603 (Harlan Teklad, Bicester, UK), ad libitum
- Water: mains water, ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16 - 22
- Humidity (%): 40 - 80
- Air changes (per hr): at least 10
- Photoperiod (hrs dark / hrs light): 10/14

IN-LIFE DATES: From: 17 Sep 1996 To: 28 Sep 1996

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

water

Remarks:

The dermal test site was moistened with 0.1 mL distilled water immediately before application.

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied: 0.5 g

VEHICLE
- Amount(s) applied: 0.1 mL distilled water was immediately applied on the dermal test site before application

Duration of treatment / exposure:

4 h

Observation period:

Observation period: 72 h
Reading time points: 1, 24, 48 and 72 h

Number of animals:

1 female (step 1) and 5 males (step 2)

Details on study design:

TEST SITE
- Area of exposure: 30 x 20 mm area
- Type of wrap if used: test site was covered by a larger gauze patch (40 x 40 mm) and an open weave, elasticated adhesive bandage was wrapped firmly around the torso (semi-occlusive dressing)

REMOVAL OF TEST SUBSTANCE
- Washing: treated skin was lightly brushed clean of any solid residues and swabbed with moist cotton wool
- Time after start of exposure: 4 h

OBSERVATION TIME POINTS
1, 24, 48 and 72 h

SCORING SYSTEM:
- Method of calculation: Draize scoring system

Irritation parameter:

edema score

Basis:

mean

Remarks:

of 6 animals

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritation parameter:

erythema score

Basis:

mean

Remarks:

of 6 animals

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritant / corrosive response data:

No irritation reactions or other dermal changes were observed hi any animal at any time during the observation period.

Other effects:

There were no signs of toxicity or ill health in any rabbit during the observation period.

Interpretation of results:

other: According to the classification criteria of the CLP Regulation (EU) No. 1272/2008, no classification is required.

Conclusions:

The study is in concordance with the OECD TG 404 (1992). Therefore, the study is considered acceptable and the outcome can be reported as valid.
A single semi-occlusive application of 0.5 g test substance to intact rabbit skin for 4 h elicted no skin irritation reaction. The individual mean score for the 24, 48 and 72-h readings were 0 for all animals. According to the criteria of the CLP Regulation (EU) No. 1272/2008, no classification is required.

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:

24 Sep - 04 Oct 1996

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

adopted 2020

Deviations:

yes

Remarks:

housing conditions slightly divergent, 6 animals were used, body weights only noted at the start of study, no anaesthetics used

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

adopted 1987

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Charles River UK Ltd, Margate, UK
- Age at study initiation: 11 - 14 weeks
- Weight at study initiation: 2.10 - 2.47 kg
- Housing: individually in floor-pens with a minimum floor area of 0.6 m²
- Diet: pelleted SQC TRB Rabbit Diet 9603 (Harlan Teklad, Bicester, UK), ad libitum
- Water: mains water, ad libitum
- Acclimation period: at least 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16 - 22
- Humidity (%): 40 - 80
- Air changes (per hr): at least 10
- Photoperiod (hrs dark / hrs light): 10/14

IN-LIFE DATES: From: 10 Sep 1996 To: 04 Oct 1996

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied: 66 mg (the weight equivalent to 0.1 mL)

Duration of treatment / exposure:

single application without washing

Observation period (in vivo):

Observation period: 72 h
Reading time points: 0.5, 1, 4, 24, 48 and 72 h.

Number of animals or in vitro replicates:

1 male (step 1) and 5 males (step 2)

Details on study design:

TREATMENT OF THE ANIMALS
One dose consisting of 66 mg (the weight equivalent to 0.1 mL) in powder form was instilled into the left conjunctival sac of the rabbit (step 1). The lower eyelid was gently prised away from the eyeball to create a receptacle for the dose. After instillation the eyelids were held closed for a few seconds to prevent loss of the dose. The right eye remained untreated and served as a control to the treated eye. After observing the (lack of) effect on the treated eye, 5 additional male rabbits were treated.

SCORING SYSTEM: Draize scoring system

TOOL USED TO ASSESS SCORE: Fluorescein at the 24-h reading time point

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

of 6 animals

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritation parameter:

iris score

Basis:

mean

Remarks:

of 6 animals

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: not applicable

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

of 6 animals

Time point:

24/48/72 h

Score:

0

Max. score:

3

Reversibility:

other: not applicable

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

of 6 animals

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritant / corrosive response data:

Mild conjunctivae (score 1) was noted in 6/6 animals during the 1-h reading time point. All conjunctival irritation reactions resolved within 24 h of treatment and were not observed thereafter. The cornea and iris were unaffected by the test substance.

Other effects:

No observations indicative of systemic toxicity or ill health were noted for any
rabbits during the course of the study.

Interpretation of results:

other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 12 72/2008.

Conclusions:

The study is in accordance with OECD TG 405, was conducted under GLP and is considered valid and reliable. Under the conditions chosen the test substance did not induce irritation to the eye of rabbits. According to criteria of the CLP Regulation (EU) No. 1272/2008, no classification of the test item for eye irritancy is required.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation

The irritancy potential of the test substance to skin was evaluated in a study according to OECD guideline 404 and in compliance with GLP (M-027402-01-1). The test substance was applied as powder to a 30 x 20 mm area on the clipped and moistened dorsum of one female New Zealand White rabbit under a semi-occlusive dressing for 4 h. As the test item did not cause severe dermal changes, subsequently, 5 rabbits were subjected to a single, 4-h, semioccluded topical application of 500 mg of test article. The test item did not induce irritant or corrosive effects determined 1, 24, 48 and 72 h after removal of the dressing. Mean scores evaluated over 24, 48 and 72 h were 0.0 for erythema and edema for each animal. In conclusion, the test substance did not exhibit skin irritating properties in the conducted study.

 

Eye irritation

A GLP-conform eye irritation/corrosion study was performed according to OECD guideline 405 to evaluate the eye irritancy potential of the test substance (M-027400-01-1). Initially, a single dose of 66 mg test substance (step 1) was instilled into the left conjunctival sac of one male New Zealand White rabbit without washing. In step 2, as the test substance did not cause ocular damage, the test item was instilled in the eyes of 5 rabbits. The individual ocular responses were observed 0.5, 1, 4, 24, 48 and 72 h after instillation of the test item. The test substance caused practically no initial sting reaction in five rabbits and a slight initial sting response in one animal. Slight conjunctivae (score 1) was observed up to 4 h following treatment in all animals and chemosis (score 1) in 1/5 animals was reported. However, 24, 48 and 72 h after treatment, no ocular findings were observed. Mean scores evaluated over 24, 48 and 72 h were 0.0 for chemosis, conjunctivae, iris and cornea opacity for each animal. In conclusion, the test substance did not exhibit eye irritating properties in the conducted studies.

Justification for classification or non-classification

The available data on skin and eye irritation of the test substance do not meet the criteria for classification according to Regulation (EC) 1272/2008, and are therefore conclusive but not sufficient for classification.