2-[4,5-dihydro-4-methyl-4-(1-methylethyl)-5-oxo-1H-imidazol-2-yl]-3-pyridine carboxylate; imazapyr (ISO)

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2013-01-17 to 2013-04-08

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2013

Report date:

2013

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.2 (Acute Toxicity (Inhalation))

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

Harlan Laboratories Ltd, Toxicology and Environmental Safety & Metabolism, Zelgliweg 1, 4452 Itingen, Switzerland

Test type:

traditional method

Limit test:

yes

Test material

Test material information

Constituent 1

Test material form:

solid

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Lot/batch No.of test material: COD-001701
- Expiration date of the lot/batch: 2014-11-01
- Purity test date: 2012-10-24


STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature (or cooler)

Test animals

Species:

rat

Strain:

Wistar

Remarks:

RccHanTM:WIST(SPF)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Laboratories B.V. Kreuzelweg 53 5961 NM Horst, Netherlands
- Age at study initiation: 8 weeks
- Weight at study initiation: Males: 263.2 to 280.4 g, Females: 177.8 to 193.8 g
- Fasting period before study: no
- Housing: Animals were housed in groups of 5 of the same sex in Makrolon® type-IV cages with wire mesh tops including paper enrichment and standard softwood bedding
- Diet: pelleted standard Harlan Teklad 2914C rat maintenance diet (ProvimiKliba AG, 4303 Kaiseraugst, Switzerland) ad libitum (except for period of restrainment in test tube)
- Water: community tap water from Füllinsdorf ad libitum (except for period of restrainment in test tube)
- Acclimation period: 6 days under optimal hygienic laboratory conditions. The animals were accustomed to the restraining tubes for 30 minutes on the day of exposure.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 30 to 70
- Air changes (per hr): 10 - 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 2013-01-22 To: 2013-02-11

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Remarks:

flow-past exposure

Vehicle:

not specified

Mass median aerodynamic diameter (MMAD):

>= 2.61 - <= 3.01 µm

Geometric standard deviation (GSD):

>= 2.36 - <= 2.82

Remark on MMAD/GSD:

Duration of sampling: 25 to 27 seconds per sample

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: flow-past, nose-only exposure system
- Method of holding animals in test chamber: restraining tubes
- Source and rate of air: The flow of air at each tube was 1.0 L/min
- Method of conditioning air:
- System of generating particulates/aerosols: A dust aerosol was generated from the test item using a CR3020 rotating brush aerosol generator connected to a micronizing jet mill.
- Method of particle size determination: The particle size distribution of the test aerosol was determined three times during exposure using a Mercer 7 stage cascade Impactor (Model 02-130, In-Tox. Products Inc., Albuquerque, New Mexico, U.S.A.).
- Temperature, humidity, pressure in air chamber: 22.8°C (mean), 5.5% RH (mean)

TEST ATMOSPHERE
- Brief description of analytical method used: Gravimetric analysis of Aerosol concentrations: The samples were collected on a Millipore®durapore filter, Type HVLP loaded in a 47 mm inline stainless steel filter sampling device. The filters were weighed before and immediately after sampling using a calibrated balance. The test aerosol concentration was calculated from the amount of test item present on the filter and the sample volume.
- Gravimetric aerosol concentration: 2.1 mg/L air (mean)

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: the particle size distributions obtained were considered to be respirable to rats and appropriate for acute inhalation toxicity testing.
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): 2.61 to 3.01 / 2.36 to 2.85

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

ca. 4 h

Concentrations:

2.4 mg/L air (mean chemical aerosol concentration)

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: Each animal was examined three times during exposure, immediately and 1 h after exposure on test day 1 and once daily during the observation period.
- Frequency of weighing: The body weight of each animal was recorded on test days 1 (before exposure), 2, 4, 8 and 15 (before necropsy).
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Statistics:

No statistical analysis was performed as only one group was allocated to the study.

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

discriminating conc.

Effect level:

> 2.4 mg/L air

Based on:

test mat.

Exp. duration:

4 h

Mortality:

No mortality occured

Clinical signs:

other: Clinical signs were limited to the day of treatment and consisted of slight salivation during exposure and slightly ruffled fur immediately and one hour after exposure. Furthermore, tachypnea was noted in one male and three females during and shortly afte

Body weight:

Only marginal weight loss or stagnation was noted. This effect was considered to be mainly due to the restraining of the animals in the tubes.

Gross pathology:

There were no treatment-related macroscopic findings at necropsy.

Other findings:

- Histopathology: All collected organ and tissue samples were retained but neither processed nor examined.
- Potential target organs: not included
- Other observations: not included

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met