Amitrole

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

December 1982 – January 1983

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

Non-GLP study performed similarly to OECD 403 with acceptable restrictions: test item’s particle size distribution, environmental conditions, detailed description of the inhalation chamber and analytical method were not reported

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1983

Report date:

1983

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Version / remarks:

dated 07 September 2009

Deviations:

yes

Remarks:

test item’s particle size distribution, environmental conditions, detailed description of the inhalation chamber and analytical method were not reported

Principles of method if other than guideline:

Not applicable

GLP compliance:

no

Test type:

traditional method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Amitrole

EC Number:

200-521-5

EC Name:

Amitrole

Cas Number:

61-82-5

Molecular formula:

C2H4N4

IUPAC Name:

amitrole

Test material form:

not specified

Details on test material:

- Molecular formula: C2H4N4

Specific details on test material used for the study:

Name as cited in the report: Aminotriazole

Test animals

Species:

rat

Strain:

Wistar

Remarks:

Bor: WISW (SPF-Cpb)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Winkelmann Breeders, Borchen, Kreis, Paderborn, Germany
- Weight at study initiation: 160-200 g
- Housing: Animals were kept in Type III Makrolon® cages.
- Diet (e.g. ad libitum): Altromin® Maintenance Diet, ad libitum
- Water (e.g. ad libitum): Ad libitum

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

not specified

Vehicle:

air

Remark on MMAD/GSD:

No data

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Dynamic inhalation system as described by Kimmerle G and Eben A, Arch. Toxicol. 30:115, 1973.
- Exposure description: Test substance was formulated at concentrations of 5 and 10% in a (1:1) mixture of ethanol and Lutrol, and the formulation was dynamically sprayed into the inhalation chamber. The conditions under which the animals were exposed were such that the aerosols could effectively only be absorbed from the tidal air. Essentially no skin contact with the aerosols took place. The air in the chamber was exchanged 15 times/hour.

TEST ATMOSPHERE
- Brief description of analytical method used: Levels of the test item in the tidal air of the animals was determined by chemical analysis using procedure by Dipl-Chem. A. Eben.

VEHICLE
- Composition of vehicle (if applicable): (1:1) mixture of ethanol and Lutrol

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

ca. 4 h

Remarks on duration:

No data

Concentrations:

- Theoretical concentration: 1000 or 2000 mg/m3 (maximum producible concentration in air)
- Analytical concentration: 280 or 439 mg/3

No. of animals per sex per dose:

10

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were examined daily for appearance and behaviour. The body weights of the animals were determined prior to exposure and at weekly intervals during the observation period.
- Necropsy of survivors performed: Yes

Statistics:

None

Results and discussion

Preliminary study:

Not applicable

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 439 mg/m³ air

Based on:

act. ingr.

Remarks:

analytical concentration

Exp. duration:

4 h

Mortality:

No deaths occurred.

Clinical signs:

other: Rats tolerated the concentrations without symptoms.

Body weight:

No toxicologically relevant or concentration-related effects on the bodyweights were observed.

Gross pathology:

No indications of organic injury were found during necropsy.

Other findings:

None

Any other information on results incl. tables

None

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under the test conditions, the 4 hour, LC50 of the test substance is higher than 439 mg/m3 air in rats. However, based on the overall acute toxicty data, the inhalation LC50(4h) in rats is expected to be higher than 5000 mg/m3 air and the test substance is not classified for acute inhalation toxicity according to the Annex VI of the Regulation (EC) No. 1272/2008 (CLP) and to the GHS.

Executive summary:

In an acute inhalation toxicity study, groups of Wistar rats (10/sex/dose) were exposed to the test item aerosol at concentrations of 5 and 10% in a (1:1) mixture of ethanol and Lutrol in a dynamic inhalation system for 4 hours. The theoretical concentrations were 1000 or 2000 mg/m3 air (maximum producible concentration in air); and the corresponding analytical concentrations were 280 or 439 mg/3 air. All animals were observed for mortality, clinical signs and body weight changes for 14 days, and were all sacrificed for macroscopic examinations.

No deaths occurred and the rats tolerated the concentrations without symptoms. No toxicologically relevant or concentration-related effects on the bodyweights were observed. No indications of organic injury were found during necropsy.

Rat, LC50, 4 hour exposure > 439 mg/m3 air (maximum producible analytical concentration in air)

Under the test conditions, the 4 hour, LC50 of the test substance is higher than 439 mg/m3 air in rats as it was the maximum achievable concentration. However, no effects were observed in this study and in the acute oral toxicity study up to 10000 mg/kg bw therefore the inhalation LC50(4h) in rats is expected to be higher than 5000 mg/m3 air and the test substance is not classified for acute inhalation toxicity according to the Annex VI of the Regulation (EC) No. 1272/2008 (CLP) and to the GHS.