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

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Sep 1996 - Oct 1996

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1997

Report date:

1997

Materials and methods

Test guideline

Test guideline 1

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

adopted 2017

Deviations:

yes

Remarks:

dosing was not stepwise, 5 animals/sex were used

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

adopted 1987

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

433-460-1

EC Name:

-

Cas Number:

210880-92-5

Molecular formula:

C6H8ClN5O2S

IUPAC Name:

(E)-N'-[(2-chloro-1,3-thiazol-5-yl)methyl]-N-methyl-N''-nitroguanidine

Test animals

Species:

rat

Strain:

other: Crl:CD.BR

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River (UK) Ltd, Margate, UK
- Females nulliparous and non-pregnant: yes
- Age at study initiation: 6 - 9 weeks (males), 9 - 11 weeks (females)
- Weight at study initiation: 261 - 273 g (males), 225 - 245 g (females)
- Fasting period before study: none
- Housing: individually in suspended stainless steel mesh cages (dimensions 30 x 28 x 24 cm)
- Diet: SQC(E) Rat and Mouse Maintenance Diet No 1 (Special Diets Services Ltd, Witham, UK), ad libitum
- Water: mains water, ad libitum
- Acclimation period: 9 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 25
- Humidity (%): 40 - 70
- Air changes (per hr): at least 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 16 Sep 1996 To: 03 Oct 1996

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

water

Details on dermal exposure:

TEST SITE
- Area of exposure: 5 x 5 cm of the clipped dorsum of the rat
- % coverage: 10
- Type of wrap if used: retained in place by an elasticated, open-weave, adhesive bandage

REMOVAL OF TEST SUBSTANCE
- Washing: animals were brushed free of residues of the test article and swabbed with moist cotton wool
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied: 2000 mg/kg bw
- Constant volume or concentration used: no
- For solids, paste formed: no, but the dermal test site was moistened by application of 0.2 mL distilled water immediately before application of the test article

VEHICLE
- Amount(s) applied: 0.2 mL

Duration of exposure:

24 h

Doses:

- 2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical signs were recorded at least once within half an hour of dosing, four times within four hours of dosing, twice daily on Days 2, 3 and 4 and once daily from the fifth to last day of the observation period. Body weights were recorded on Day -1 (day before dosing), Day 1 (day of dosing), Days 4 and 8 and at termination on Day 15.
- Necropsy of survivors performed: yes

Statistics:

Not reported.

Results and discussion

Preliminary study:

A preliminary investigation was conducted with two male and two female rats. Animals were treated with a dose of 1800 mg/kg bw. No animal died following a single dermal application of the test substance. Based on the results of this investigation, the regulatory limit dose level of 2000 mg/kg bw was selected for the main study.

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No animal died following a single dermal application of 2000 mg/kg bw.

Clinical signs:

other: There were no clinical signs of systemic or dermal reactions to treatment.

Gross pathology:

No macroscopic changes were apparent during necropsy of the animals killed at completion of the observation period.

Other findings:

Local effects: No overt changes or irritation reactions were noted at the dermal sites of topical application of the test article.

Applicant's summary and conclusion

Interpretation of results:

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

Conclusions:

The study was performed in accordance with OECD TG 402 under GLP conditions and is considered reliable. Under the conditions chosen, it was concluded that the acute median lethal dose (LD50) of the test substance is > 2000 mg/kg bw in both male and female rats. According to criteria of the CLP Regulation (EU) No. 1272/2008, no classification of the test item for acute dermal toxicity is warranted.