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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:
other information
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable, well-documented publication meeting basic scientific principles

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1985

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
yes
Remarks:
only 4 animals per dose, only 15 min. exposed instead of 4 hours,
Principles of method if other than guideline:
The sensory irritation potential of several nasal tumours inducing chemicals were tested in an acute inhalation exposure experiment with rats.
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
2,3,4-trichlorobut-1-ene
EC Number:
219-397-9
EC Name:
2,3,4-trichlorobut-1-ene
Cas Number:
2431-50-7
Molecular formula:
C4H5Cl3
IUPAC Name:
2,3,4-trichlorobut-1-ene
Details on test material:
- Name of test material (as cited in study report): 2,3,4-Trichloro-1-butene
- Analytical purity: > 99%
- Other: Source: E.I. Du Pont, Wilmington, DE, USA.

Test animals

Species:
rat
Strain:
other: Crl-CD
Sex:
not specified
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Breeding Laboratory, North Wilmington, DE, USA
- Age at study initiation: 8 weeks
- Weight at study initiation: 232-277 g
- Fasting period before study: no data
- Housing: in pairs in stainless-steel wire-mesh cages
- Diet (e.g. ad libitum): Purina Certified Rodent Chow no. 5002, Ralston Purina, St. Louis, MO, USA)
- Water (e.g. ad libitum): yes
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): no data
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): no data

IN-LIFE DATES: :no data

Administration / exposure

Route of administration:
inhalation: vapour
Type of inhalation exposure:
head only
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: 23 L rectangular polymethylmethacrylate chamber for four animals
- Exposure chamber volume: 1.5 L inner compartment for the head-only exposure of 1 animal. Airflow to the inner compartment was turned off, the
compartment was opened to the larger chamber and the 15-min test exposure began. This design enabled the rats to be essentially instantaneously exposed to the equilibrated atmosphere (initial air concentration when inner compartment is opened ts 98.3% of desired).
- Method of holding animals in test chamber: restrainer
- System of generating vapour: Atmosphere was generated by directing a stream of dry nitrogen through an impinger containing 5 to 50 ml of the liquid. The resultant vapours were diluted with houseline air prior to entry into the exposure chamber.

TEST ATMOSPHERE
- Brief description of analytical method used:
- Samples taken from breathing zone: yes
Atmospheric samples were collected every 2-3 min using gas-tight syringes. These samples were analysed on a Hewlett-Packard Model 5710A gas chromatograph (Palo Alto, CA) equipped with a flame-ionization detector. The column used was a 6 ft by 0.08 in. (ID) glass coil packed with 10% SE30 on 80/100 mesh Chromosorb® W. The test substance was chromatographed at 200°C.

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: not applicable
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): not applicable

CLASS METHOD (if applicable)
- Rationale for the selection of the starting concentration:
1.5 ppm (6 hr/day, 5 days/wk) produced nasal tumours in rats (see 7.7, 4, Reuzel, 1981, rat, IUC 4)
Analytical verification of test atmosphere concentrations:
yes
Remarks:
GC with flame-ionization detector
Duration of exposure:
15 min
Concentrations:
0.161, 0.298, 0.380, 0.624 mg/L 
(24.3, 45.2, 57.6, 94.3 ppm)
No. of animals per sex per dose:
4 animals of unspecified sex were used per dose.
Control animals:
no
Details on study design:
- Duration of observation period following administration: 24 hours
The respiratory rate was measured during the exposure time of 15 minutes and during recovery of 5 minutes.
The body weight was measured 24 hours after exposure.

Results and discussion

Effect levelsopen allclose all
Sex:
not specified
Dose descriptor:
other: RD50 (concentration needed to produce a 50% respiratory rate depression)
Effect level:
0.38 mg/L air
Remarks on result:
other: (58.1 ppm). For comparison: Lowest dose producing nasal tumours: 1.5 ppm
Sex:
not specified
Dose descriptor:
LC50
Effect level:
> 0.624 mg/L air
Exp. duration:
15 min
Remarks on result:
other: (94.3 ppm) Lacrimation, clear nasal discharge and salivation observed
Sex:
not specified
Dose descriptor:
other:
Effect level:
<= 0.38 mg/L air
Exp. duration:
15 min
Remarks on result:
other: (57.6 ppm). No clinical signs of systemic toxicity observed.
Mortality:
not observed
Clinical signs:
other: Lacrimation, clear nasal discharge and salivation occurred only at the highest dose of 0.624 mg/L (94.3 ppm). No clinical signs of toxicity were seen at 0.161, 0.298 and 0.380 mg/L.
Other findings:
The RD50-value (concentration needed to produce a 50% respiratory rate depression) was 0.384 mg/L (58.1 ppm);  Depression in respiratory rate occurred at all levels: The average % decrease in respiratory rate was 28, 43, 54 and 69 % at 0.161, 0.298, 0.380 mg/L and 0.624 mg/L test substance concentration.

Applicant's summary and conclusion