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Toxicological information

Acute Toxicity: inhalation

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Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
from 1986-07-23 to 1986-08-13
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study without deviations.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1986
Report date:
1986

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
N-butyl acetate
EC Number:
204-658-1
EC Name:
N-butyl acetate
Cas Number:
123-86-4
Molecular formula:
C6H12O2
IUPAC Name:
butyl acetate
Details on test material:
- Name of test material (as cited in study report): n-butyl acetate, T-3916
- Physical state: clear liquid
- Analytical purity: "pure"
- compound code: T-3916
- Stability under test conditions: stable at storage conditions
- Storage condition of test material: at ambient temperature in the dark

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Iffa-Credo, Brussels, Belgium
- Age at study initiation: 8 -12 weeks
- Weight at study initiation: males 196 to 294 g, females 209 to 250 g
- Fasting period before study: no; food and water were withheld during exposure
- Housing: individually in Macrolon cages with purified sawdust (Woody Clean from The Broekman Institute, Someren, The Netherlands) as bedding material
- Diet (e.g. ad libitum): standard laboratory animal diet (RMH-B, pellet diameter 10 mm, Hope Farms, Woerden, The Netherlands)
- Water (e.g. ad libitum): tap-water
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 22
- Humidity (%): 60 - 90
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light): 12 /12


IN-LIFE DATES: From: 1986-07-16 To: death

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
head only
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: dynamic spraying head-only inhalation system (cylindrical inhalation chamber, made of chrome-nickel steel) as discribed by Niessen et al (1963, Archiv für Toxicologie 20, 44-60), with some modifications
- Exposure chamber volume: 12 L
- Method of holding animals in test chamber: radially mounted cylindrical Perspex animal confinement cages
- Source and rate of air: compressed air; 10 L/min
- Method of conditioning air: temperature controlled room
- System of generating particulates/aerosols: spraying nozzle with an exit hole diameter of 0.4 mm, air flow 10 L/min, test substance delivered by a high precision infusion syringe pump (UNITA Ib, Braun-Melsungen, FRG) at constant rates of 2, 4.5, and 9 mL/h
- Method of particle size determination: low-pressure cascade impactor (type LPI 4/0, 06/2) from Hauke, Gmunden, Austria
- Treatment of exhaust air: air is routed through washing bottles with 80%-ethanol and water
- Temperature, humidity, pressure in air chamber: 18 - 21°C; 20 - 55%

TEST ATMOSPHERE
- Brief description of analytical method used: absorption on charcoal, Gaschromatography (Hewlett Packard GC 5880 with FID detection)
- Samples taken from breathing zone: yes
- Particle size distribution: only 0.09% of the total test substance content in the breathing atmosphere was present as aerosol (combined weight of impactor fractions compared with the total content (analytically measured concentration) of the sampled air)
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): 1.01 µm / 3.30 (high dose group; test substance vaporized completely at lower concentrations)

CLASS METHOD (if applicable)
- Rationale for the selection of the starting concentration: suitable test substance concentrations were estimated by pretests. Pretests were performed from higher to lower Test substance concentrations (52.9 and 26.5 mg/L, analytically verified)
Analytical verification of test atmosphere concentrations:
yes
Remarks:
samples are taken hourly / GC
Duration of exposure:
4 h
Concentrations:
analytical (mean of 4 measurements for each dose): 0.8, 2.2, 5.2 mg/L
nominal: 3.1, 7.1, 14.1 mg/L
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, histopathology (lungs)
Statistics:
no data

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LC50
Effect level:
0.74 mg/L air
Exp. duration:
4 h
Mortality:
low-dose: 6/10, mid-dose: 10/10, high-dose: 10/10
All deaths occurred within 24 h of exposure.

Any other information on results incl. tables

Mortality rates:

low-dose: 6/10, mid-dose: 10/10, high-dose: 10/10

All deaths occurred within 24 h of exposure.

Major signs of toxicity: lethargy, hyperpnea, tremors, ataxia.

Macroscopic examination at necropsy revealed bloody nose
and/or mouth and hyperaemic lungs in animals of all exposure
groups. Histopathology of lung tissue revealed vesicular emphysema in all animal

Applicant's summary and conclusion

Conclusions:
The LC50 value in this study with male and female rats was 0.74 mg/L.
Executive summary:

In an acute inhalation toxicity study, young adult male and female wistar rats (5 animals of each sex per group) were exposed by inhalation route (head only) to vapors/aerosols of n-butyl acetate for 4 hours at concentrations of 0.8, 2.2, and 5.2 mg/L. Animals were then observed for 14 days.

 

LC50Combined =  0.74  mg/L

6 of 10 animals died in the low dose group. In the mid-dos and high-dose group 10 of 10 animals died. All deaths occured within 24 h of exposure (Debets, 1986).