thiacloprid (ISO);(Z)-3-(6-chloro-3-pyridylmethyl)-1,3-thiazolidin-2-ylidenecyanamide;{(2Z)-3-[(6-chloropyridin-3-yl)methyl]-1,3-thiazolidin-2-ylidene}cyanamide

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

21 Sep - 13 Oct 1994

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1996

Report date:

1996

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:

MMAD and GSD slightly out of range

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:

no

Test material

Test material information

Constituent 1

Reference substance name:

3-(2-chlor-5-pyridyl-methyl)-cyanimino-1,3-thiazolidin

EC Number:

601-147-9

Cas Number:

111988-49-9

Molecular formula:

C10H9ClN4S

IUPAC Name:

3-(2-chlor-5-pyridyl-methyl)-cyanimino-1,3-thiazolidin

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan-Winkelmann, Borchen, Germany
- Females nulliparous and non-pregnant: yes
- Rationale for use of males: male and female rats were used in this study
- Age at study initiation: 2 - 3 months
- Weight at study initiation: 160.0 - 210.0 g (males), 162.0 - 191.0 g (females)
- Housing: individually in Makrolon Type II cages equipped with type S8/15 low dust wood granulate (Ssniff, Soest, Germany) as bedding material
- Diet: Altromin 1324 pellets maintenance diet for rats and mice (Altromin GmbH, Lage, Germany), ad libitum
- Water: tap water, ad libitum
- Acclimation period: at least 5 days
- Method of randomisation in assigning animals to test and control groups: computerized list of random numbers

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24
- Humidity (%): approx. 50
- Air changes (per hr): approx. 10
- Photoperiod (hrs dark / hrs light): 12 / 12

Administration / exposure

Route of administration:

inhalation: dust

Type of inhalation exposure:

nose only

Vehicle:

clean air

Mass median aerodynamic diameter (MMAD):

>= 3.1 - <= 9.1 µm

Geometric standard deviation (GSD):

>= 1.7 - <= 3.5

Remark on MMAD/GSD:

MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): 3.1 µm / 1.7 µm (0.080 mg/L), 3.1 µm / 1.7 µm (0.481 mg/L), 5.8 µm / 3.5 µm (1.523 mg/L), 9.1 µm / 2.4 µm (2.535 mg/L)

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Plexiglas exposure tubes
- Exposure chamber volume: about 3.8 L
- Method of holding animals in test chamber: plexiglas exposure tubes that were chosen to fit the size of the animals
- Source and rate of air (airflow): 28 L/min
- Method of conditioning air: via compressed air dryer, i.e. water, dust and oil were removed
- System of generating particulates/aerosols: EXACTOMAT 4200 (TSE, Bad Homburg, Germany) and for the lower concentrations (0.080 and 0.481 mg/L) a Wright-Dust-Feeder (BGI Inc., Waltham, MA, USA)
- Method of particle size determination: Cascade impactors
- Treatment of exhaust air: purified via cotton-wool/activated charcoal and HEPA filters
- Temperature, humidity, pressure in air chamber: 23 - 24 °C, 10 - 38%, not specified

TEST ATMOSPHERE
- Brief description of analytical method and equipment used: test-substance concentration was determined by gravimetric analysis using cellulose-acetate filters (Sartorius, Göttingen, Germany)
- Samples taken from breathing zone: yes, once per hour
- Time needed for equilibrium of exposure concentration before animal exposure: < 1 min

VEHICLE
- Composition of vehicle: conditioned air


TEST ATMOSPHERE
- Particle size distribution: number of particles < 3 µm: 49% (0.080 mg/L), 48% (0.481 mg/L), 31% (1.523 mg/L), 10% (2.535 mg/L)
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): 3.1 µm / 1.7 µm (0.080 mg/L), 3.1 µm / 1.7 µm (0.481 mg/L), 5.8 µm / 3.5 µm (1.523 mg/L), 9.1 µm / 2.4 µm (2.535 mg/L)

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

0.080, 0.481, 1.523 and 2.535 mg/L

No. of animals per sex per dose:

5

Control animals:

yes

Remarks:

Control studies are performed regularly under GLP conditions, but not assigned to a specific study.

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: body weights were measured before exposure, on days 3, 7 and weekly thereafter. Individual weights were also recorded at death, if applicable. Appearance and behavior were examined several times on the day of exposure and twice daily thereafter (once on weekends)
- Necropsy of survivors performed: yes
- Other examinations performed: rectal temperature, reflex measurements

Statistics:

Please refer to 'any other information on materials and methods incl. tables' section for details.

Results and discussion

Effect levels

Effect levels 1

Key result

Sex:

female

Dose descriptor:

LC50

Effect level:

ca. 1.223 mg/L air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Effect levels 2

Key result

Sex:

male

Dose descriptor:

LC50

Effect level:

> 2.535 mg/L air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Mortality:

Mortality was not observed in males at any dose level and not in females of the control, 0.080 and 0.481 mg/L dose groups. At 1.523 mg/L 3/5 females died 1 to 2 days after exposure and at 2.535 mg/L 4/5 females died 1 to 7 days after exposure.

Clinical signs:

other: Please refer to 'any other information on results incl. tables' section for details.

Body weight:

Males and females of the 0.080 mg/L dose group tolerated the exposure without marked effects on body weights when compared to controls. However, at levels of 0.481 mg/L of test item and higher doses, rats lost body weight during the first three days after exposure (2.535 mg/L dosed females lost body weight until one week after exposure). Thereafter, all rats gained body weight until the close of the study, but body weight gain was overall reduced at dose levels of 0.481 mg/L and higher when compared to controls.

Gross pathology:

In rats sacrificed at the end of the observation period (survivors), no compound-related increase in the incidence of macroscopical findings could be observed. In rats sacrificed during the observation period, lungs with reddish colour and red foci, intestine with red mucosa, reddish-slimy content, pale and lobulated livers and red appearance of renal pelvis was observed.

Other findings:

All animals showed normal reflexes, except for some alteration in reflexes in the 1.523 mg/L dose group (males and females). Rectal temperature was concentration-dependently decreased in animals exposed to the test item when compared to controls. Changes observed in the 0.080 mg/L dose group were considered toxicologically not relevant.

Any other information on results incl. tables

Clinical signs

No clinical signs were observed in the control and 0.080 mg/L dose group. At 0.481 mg/mL, bradypnoea, tremor, reduced motility, haircoat ungroomed and piloerection were observed starting from 4 h and lasting until 2 days after exposure. In the 1.523 mg/mL groups, bradypnoea, laboured breathing pattern, rales, prostration (lying on side or belly), blepharospasm, mydriasis, chromodacryorrhea, tremor, reduced motility, apathy, haircoar ungroomed and piloerection were noted from 4 h and lasting until 4 (females) or 6 (males) days after exposure. In the top dose group (2.535 mg/mL), bradypnoea, dyspnoea, laboured breathing pattern, rales, nose/snout area with red encrustation, salivation, blepharospasm, mydriasis, tremor, reduced motility, haircoat ungroomed and piloerection were observed from 4 h until 4 (males) or 6 (females) days after study.

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The study was performed in accordance to OECD TG 403 under GLP conditions and is considered reliable. Under the conditions chosen, the acute inhalation LC50 was above 2.535 mg/L for male Wistar rats and approximately 1.223 mg/L for female Wistar rats. According to criteria of the CLP Regulation (EU) No. 1272/2008, classification of the test item for acute inhalation toxicity category 4 (H332) is needed.