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

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

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

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

adopted 1987

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

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:

mouse

Strain:

CD-1

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: 5 - 7 weeks
- Weight at study initiation: 25 to 30 g (males), 22 to 26 g (females)
- Fasting period before study: from approximately 4 h prior to dosing until 2 h after completion of dosing
- Housing: up to five mice of the same sex were accommodated in suspended stainless steel mesh cages (dimensions 32 x 16.5 x 13 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: 6 - 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 (main study)

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: 5% m/v aqueaous gum arabic

Details on oral exposure:

VEHICLE
- Amount of vehicle: 10 mL/kg bw

Doses:

304, 380, 475, 594 and 742 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: regularly during the study 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 using groups of two male and two female fasted mice. Mice were subjected to single oral doses of 300, 450 and 600 mg/kg bw. Two male mice
and one female were found dead on Day 2 following treatment at 600 mg/kg bw. There were no deaths among the mice dosed at 300 or 450 mg/kg bw. Based on the results, suitable dose levels to begin determination of the acute median lethal dose were selected for the main study.

Effect levels

Effect levels 1

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

389 mg/kg bw

Based on:

test mat.

95% CL:

348 - 433

Effect levels 2

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

465 mg/kg bw

Based on:

test mat.

95% CL:

384 - 561

Mortality:

304 mg/kg bw: 0/5 (males); 0/5 (females)
380 mg/kg bw: 2/5 (males); 2/5 (females)
475 mg/kg bw: 5/5 (males); 3/5 (females)
594 mg/kg bw: 5/5 (males); 3/5 (females)
742 mg/kg bw: 5/5 (males); 5/5 (females)

For details, please refer to the attached background material.

Clinical signs:

other: The principal clinical signs of reaction to treatment at all dose levels were decreased activity and palpebral closure starting 0.25 h after treatment. Less common clinical signs included ataxia and tremor at all dose levels starting 0.25 h after treatmen

Gross pathology:

Necropsy of mice found dead, as well as those killed at completion of the 14-day observation period revealed no macroscopic changes consistent with the treatment-related effect. Isolated cases of darkening of the lungs, fluid accumulation in the thoracic cavity, distension of the uterus or cannibalisation of the genitalia were noted. For details, please refer to the attached background material.

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The study was performed in accordance with OECD TG 401 under GLP conditions and is considered reliable. Under the conditions chosen, the acute oral LD50 value was determined to be 389 mg/kg bw and 465 mg/kg bw for male and female mice, respectively. According to criteria of the CLP Regulation (EU) No. 1272/2008, classification of the test item for acute oral toxicity category 4 is needed.