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

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

06 - 21 Feb 1997

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1998

Report date:

1998

Materials and methods

Test guideline

Test guideline 1

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Version / remarks:

adopted 2009

Deviations:

yes

Remarks:

animals were slightly younger than recommended by the guideline, 5 animals/sex instead of 3 examined, actual concentration of test substance not reliable due to technical issues

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Version / remarks:

adopted 1981

Deviations:

no

GLP compliance:

yes

Test type:

traditional 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:CDBR

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: not specified
- Age at study initiation: approximately 7 weeks at exposure
- Weight at study initiation: 239 - 278 g (males), 201 - 225 g (females)
- Fasting period before study: none
- Housing: groups of five in stainless steel mesh cages of size 55 x 34 x 20 cm, floor area 1870 cm²
- Diet: SQC Rat and Mouse Maintenance Diet No 1 (Special Diets Services Ltd, Witham, UK), ad libitum
- Water: mains water, ad libitum
- Acclimation period: 8 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: 06 Feb 1997 To: 21 Feb 1997

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

head only

Vehicle:

air

Mass median aerodynamic diameter (MMAD):

2.78 µm

Geometric standard deviation (GSD):

2.38

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: cylindrical aluminium exposure chamber
- Exposure chamber volume: approximately 40 L internal volume
- Method of holding animals in test chamber: not specified
- Source and rate of air (airflow): compressed air between 18 and 22 L/min
- System of generating particulates/aerosols: generated from a micronised powder aerosolised by a Wright Dust Feed generator
- Method of particle size determination: by an Andersen 298 Cascade Impactor
- Treatment of exhaust air: test atmospheres were filtered using a cartridge paniculate filter, exhausted to the outside of the building and vented
- Temperature, humidity, pressure in air chamber: 19 - 21 °C, 35-66 , not specified

TEST ATMOSPHERE
- Brief description of analytical method and equipment used: concentration of the test article was determined gravimetrically
- Samples taken from breathing zone: yes

TEST ATMOSPHERE
- Particle size distribution: The mass median aerodynamic diameter was between 1-3 µm within the first, third and fourth hour of exposure. However, during the second hour of exposure, the mass median aerodynamic diameter was 8.40 µm. The cause of this anomalous sample was unknown.
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): 2.78 µm / 2.38 µm

Analytical verification of test atmosphere concentrations:

yes

Remarks:

The concentration of the test article was determined gravimetrically. The samples were obtained at least hourly, over a period of 2 min, during exposure.

Duration of exposure:

4.5 h

Remarks on duration:

Intermittent jamming of the generator occurred during the first hour of the exposure, assuming target concentrations below 5 mg/L. Due to these obervations, the duration of the exposure to the test substance was extended by 30 min to 4.5 h.

Concentrations:

10.4 mg/L (nominal concentration)
6.141 mg/L (mean measured gravimetric concentration, excluding samples taken during period of technical difficulties in aerosol generation)
5.538 mg/L (mean measured gravimetric concentration, including samples taken during period of technical difficulties in aerosol generation)

No. of animals per sex per dose:

5

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical signs were recorded approximately hourly during exposure, and for the remainder of the exposure day. Subsequently, animals were observed daily until study termination. Body weights were recoreded before and after exposure on Day 1, on Day 2, 8 and 15, and before necropsy.
- Necropsy of survivors performed: yes
- Other examinations performed: histopathology (lungs) of animals which showed gross lesions

Statistics:

As there were no deaths, the median lethal concentration (LC50) was not calculated.

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 5.54 mg/L air (analytical)

Based on:

test mat.

Exp. duration:

4.5 h

Mortality:

There were no deaths during the study.

Clinical signs:

other: ataxia, semi-closed eyes, hunched body posture, lethargy, staining of animals, reduced water and/or food consumption.

Remarks:

All animals recovered by Day 5.

Body weight:

During the days following exposure, group mean body weight loss in the treated group was greater than in the control group. At Day 2 group mean body weight in the male and female treated group was 91 and 92% of the pre-exposure weight compared with 101 and 99% respectively for the comparable control group. At Day 8 the animals in the treated group regaining their pre-exposure body weight. Overall, body weight gain of the treated group during the two week observation period was similar to that observed in the control group. For details, please refer to the attached background material.

Gross pathology:

A red thymus and a pale lung were observed in a male control and a male treated animal, repectively. These gross findings were consistent with the expected pattern of background observations in rats of this strain and age, and were not considered to be treatment related.

Other findings:

- Organ weights: absolute and relative lung weights of the control and treated animals were comparable
- Histopathology: As a gross lesions (res thymus and pale lung) were noted in one control and one treated male rat, further microscopic examination was performed in these two males. Histopathological examination was unremarkable and revealed no evidence of test article toxicity in the treated male.

Applicant's summary and conclusion

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 similar to OECD 403 and was performed under GLP conditions. Based on the results of the study, the acute inhalation LC50 value is considered to be > 5.54 mg/L air in male and female rats. According to criteria of the CLP Regulation (EU) No. 1272/2008, classification of the test item for acute inhalation toxicity is not required