Registration Dossier

Diss Factsheets

Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 2018-01-29 to 2018-04-16
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2018
Report date:
2018

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Version / remarks:
2009
Deviations:
no
GLP compliance:
yes
Test type:
fixed concentration procedure
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Quinazolin-4(1H)-one
EC Number:
207-735-8
EC Name:
Quinazolin-4(1H)-one
Cas Number:
491-36-1
Molecular formula:
C8H6N2O
IUPAC Name:
4-Hydroxyquinazoline
Test material form:
solid
Specific details on test material used for the study:
Batch No.: 20170707
Purity: 99.13%

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Received from SAGE labs
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 8-10 weeks
- Weight at study initiation: males 283-338 g; females 190-203 g
- Fasting period before study:
- Housing: Housed in suspended stainless steel cages
- Diet (e.g. ad libitum): Envigo Teklad Global 16% Protein Rodent Diet, ad libitum
- Water (e.g. ad libitum): Filtered tap water, ad libitum
- Acclimation period: 11 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-25
- Humidity (%): 43-59
- Air changes (per hr): 12 changes/hour
- Photoperiod (hrs dark / hrs light): 12-hour light/dark cycle

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose only
Vehicle:
air
Mass median aerodynamic diameter (MMAD):
3.25 µm
Geometric standard deviation (GSD):
2.35
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Nose-only inhalation chamber
- Exposure chamber volume: 6.7 L
- Method of holding animals in test chamber: Animals were individually housed in polycarbonate holding tubes which seal to the chamber with an "O" ring during exposure.
- Source and rate of air: Filtered generator air was supplied to the spray atomization nozzle by an air compressor.
- Method of conditioning air:
- System of generating particulates/aerosols: The test substance was aerosolized using a modified Wtight Dust Generator. The test substance was packed into the dust container and compressed 3000 lbs/in2 using a lab press. The container was then fitted with a cutting head. Compressed generator and mixing air were supplied to the dust generator. The aerosolized dust was then fed directly into the chamber through the dust outlet assembly.
- Method of particle size determination: An eight-stage 1 ACFM Andersen Ambient Particle Sizing Sampler was used to assess the particle size distribution of the test atmosphere.

TEST ATMOSPHERE
- Brief description of analytical method used: Gravimetric samples were withdrawn at 6 intervals from the breathing zone of the animals. Samples were collected using 37 mm glass fiber filters in a filter holder attached by 1/4 inch Tygon tubing to a vacuum pump. Filter papers were weighed before and after collection to determine the mass collected. This value was divided by the total volume of air sampled to determine the chamber concentration. Sample airflows were measured using a Mass Flow Controller.
- Samples taken from breathing zone: yes
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
5.18 mg/L
No. of animals per sex per dose:
5 males and 5 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Individual body weights of the animals were recorded prior to test substance exposure (initial) and again on Days 1, 3, 7, and 14 (terminal). All animals were observed for mortality during the exposure period. The animals were examined for signs of gross toxicity, and behavioral changes upon removal from the exposure tube and at least one daily thereafter for 14 days. Observations included gross evaluation of skin and fur, eyes and mucous membranes, respiratory, circulatory, autonomic and central nervous systems, somatomotor activity and behavior pattern. Particular attention was directed to observation of tremors, convulsions, salivation, diarrhea, and coma.
- Necropsy of survivors performed: All rats were euthanized via CO2 inhalation at the end of the 14-day observation period. Gross necropsies were performed on all animals. Tissues and organs of the thoracic and abdominal cavities were examined.
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other:
Statistics:
Statistical analytis was limited to the calculation of the mean and standard deviation.

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 5.18 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Mortality:
All animals survived exposure to the test atmosphere.
Clinical signs:
other: All rats were hypoactive and exhibited irregular respiration. Two males and three females were noted as having ano-genital staining. However, all animals recovered by day 3 and appeared active and healthy for the remainder of the 14-day observation period
Body weight:
All animals gained body weight during the study.
Gross pathology:
No gross abnormalities were noted for any of the animals when necropsied at the conclusion of the 14-day observation period.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Under the conditions of this study, the single exposure acute inhalation LC50 of the substance is greater than 5.18 mg/L in male and females rats.
Executive summary:

An acute inhalation toxicity test was conducted with rats to determine the potential for the substance to produce toxicity from a single exposure via the inhalation route (nose-only exposure) based on OECD 403.

The single exposure acute inhalation LC50 of the substance is greater than 5.18 mg/L in male and females rats.

Categories Display