Registration Dossier

Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
February - April 1990
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Reliable without restrictions; Guideline study (OECD 403; Acute Inhalation Toxicity) according to GLP

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1991
Report Date:
1991

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Acetoguanamine
- Physical appearance: a white solid
- Purity: 99.7 %
- Other: Sample was received on December 1st, 1989.
- Storage and Stability: of nearly unlimited stability when stored in the dry

Test animals

Species:
rat
Strain:
other: Spargue Dawley-derived rats of the strain Crl:CD(SD)BR
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River (UK) Ltd., Margate
- Age at study initiation: about six to eight weeks old
- Weight at study initiation: 180 to 200 g
- Fasting period before study: no data
- Housing: in a single room, in groups of five by sex, in grid-floor cages.
- Diet and drinking water: expect during the exposure period, the animals were allowed free access to mains water and food (SQC Rat and Mouse Maintenance Diet No. 1 Expanded, Special Diets Services Ltd., Witham); food and water were analysed by the supplier and the water authority respectively and the analytical data are on file at HUK.
- Acclimation period: for at least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 25 °C
- Humidity (%): 40 to 70 % relative humidity
- Air changes (per hr):ventilation system maintained a minimum of 15 air changes per hour.
- Photoperiod (hrs dark / hrs light): fluorescent lighting, automatically controlled to give a cycle of 12 hours light and 12 hours darkness

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
head only
Vehicle:
clean air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: two "Wright" dust feed generators located immediately above the chamber and supplied with compressed air
- Exposure chamber volume: 40 litre internal volume
- Method of holding animals in test chamber: animals were housed in a single room, in groups of five by sex, in grid-floor cages
- Source and rate of air: filtered air; flowrate: 25 and 30 L/min for the control and treated groups respectively.
- Oxygen concetration: in the range 20.6-21 %.
- System of generating particulates/aerosols: the powder was continously dispersed in air by means of a "Wright" dust feed generator
- Method of particle size determination: particle size was determined using a Marple Sierra Series 298 Cascade Impactor, with 6 separation stages corresponding to maximum mass median aerodynamic diameters of 0.52, 0.93, 1.55, 3.5, 6.0, 9.8 µm.
- Temperature, humidity, pressure in air chamber: 19-21 °C, 24-66%

TEST ATMOSPHERE
- Brief description of analytical method used: The concentration of the test article was determined gravimetrically. The sample was obtained hourly, over periods of up to three minutes during the exposure period (i. e. during hours 1, 2, 3 and 4).
- Samples taken from breathing zone: yes

VEHICLE
- Concentration of test material in vehicle (if applicable): mean concentartion of the atmosphere: 2.031 mg Acetoguanamine /L. nominal concentartion: 7.270 mg Acetoguanamine / L.

TEST ATMOSPHERE (if not tabulated)
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): the mean mass median aerodynamic diameter of the particles in the atmosphere for the treated group was 4.00 µm. This value indicates that the mean diameter of the aerosol droplets was within the respirable range of the rat (up to 5 µm).
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
The mean measured concentration of Acetoguanamine in the atmosphere was 2.031 mg/L.
The nominal concentration of Acetoguanamine was 7.270 mg/L.
No. of animals per sex per dose:
five
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: all animals examined twice daily to detect any which were dead or moribund; individual body weights were recorded immediately before and after exposure and on days 8 and 15 of the study and at necropsy.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights
Statistics:
Data were processed, where appropriate, to give group mean values and standard deviations.
No further statistical analyses were performed.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 2.031 mg/L air
Based on:
test mat.
Exp. duration:
4 h
Mortality:
Mortality did not occur either during exposure or during the subsequent 14-day observation period with the test substance Acetoguanamine.
Clinical signs:
The clinical signs observed were considerd not to be attributable to exposure to Acetoguanamine.
Nasal secretion and chromodacryorrhoea seen in both control and treated groups, and staining to the head, seen in the control group, were considered to result from the restraint procedure.
Body weight:
Transcient body weight losses occurred as a result of the restraint procedures in both the control and treated group animals.
The body weights of the treated males at days 8 and 15 showed no adversed effect. The treated female group animals showed a small body weight loss during the first week of observation, but body weight gain was normal thereafter.
Gross pathology:
Lung weights and lung/body weight ratios:
were comparable for both control and treated animals, and there was no evidence of a treatment-related effect with Acetoguanamine.

Macroscopic pathology:
There were no macroscopic abnormalities after the treatment with Acetoguanamine.
Other findings:
no data

Applicant's summary and conclusion

Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: expert judgment
Conclusions:
Exposure of Acetoguanamine at a single chamber concentration of 2.031 mg/L did not cause mortality. Minor signs of toxiocity such as changes in clinical cindition and small body weight loss in treated females were considered not to be significant signs of toxicity.
Using standard toxicity assessment criteria (K. Schsse et al. Exp. Med. Int. Congr. Ser. (1974), 311, 239.) the test article can be classified as non-toxic or slightly toxic. As the maximum practical concentration used produced only slight signs of toxictiy Acetoguanamine should probably be classified as non-toxic.
Executive summary:

The aim of this study was to determine the 4 -hour LC50 value of Acetoguanamine. Each five male and female rats were exposed to the test atmosphere generated by dispersing the powder continously in air by means of a "Wright" dust feed mechanism with a mean measured concentration in the atmosphere of 2.031 mg/L for four hours (head-only exposure).

The animals were observed for motality and signs of intoxication during exposure and daily thereafter for 14 days. The particle size was determined with 6 separation stages corresponding to maximum mass median aerodynamic diameters of 0.52, 0.93, 1.55, 3.5, 6.0 and 9.8 µm.

Exposure of Acetoguanamine at a single chamber concentration of 2.031 mg/L did not cause mortality. Minor signs of toxicity such as changes in clinical conditions and small body weight loss in treated females were considered not to be significant signs of toxicity.

Using standard assessment crtiteria Acetoguanamine can be classified as non-toxic or slightly toxic. As the maximum practical concetration used produced only slight signs of toxicity Acetoguanamine should probably be classified as non-toxic.