Registration Dossier

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:
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

Reference
Name:
Unnamed
Type:
Constituent
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 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:
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.