3-chloropropyne

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP compliant guideline study, available as unpublished report, no restrictions, fully adequate for assessment

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2008

Report date:

2008

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.2 (Acute Toxicity (Inhalation))

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1300 (Acute inhalation toxicity)

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

3-chloropropyne

EC Number:

210-856-9

EC Name:

3-chloropropyne

Cas Number:

624-65-7

Molecular formula:

C3H3Cl

IUPAC Name:

3-chloroprop-1-yne

Details on test material:

- Name of test material (as cited in study report): Propargyl chloride sol. 35%
- Test substance No.: 07/0757-1
- Batch No.: Musterflasche A
- Analytical purity: 35.7%
- Solvent: Toluene
- Concentration of the solvent: 61.9%
- Homogeneity: Homogeneous
- Stability: stability guarenteed over the study period
- Storage conditions: Room temperature, under N2, protected against moisture

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: RCC Ltd Laboratory Animal Services, Wölferstrasse 4, CH-4414 Füllinsdorf, Switzerland
- Age at study initiation: Young adult animals (male animals approx. 7 - 8 weeks, female animals approx. 10 – 11 weeks)
- Weight at study initiation: Animals of comparable weight (males: 207.7 - 232.8 g, females: 179.9 - 198.9 g)
- Housing: Single housing; H-Temp (PSU) cages, floor area about 800 cm2 (425x266x185 mm) (TECNIPLAST, Germany); Wooden gnawing blocks (Typ NGM E-022) (Abedd ® Lab. and Vet. Service GmbH Vienna, Austria); Type Lignocel FS14 fibres, dustfree bedding (SSNIFF, Soest, Germany);
- Diet: Kliba-Labordiät (Maus / Ratte Haltung “GLP”), Provimi Kliba SA, Kaiseraugst, Basel, Switzerland, ad libitum
- Water: Tap water ad libitum
- Acclimation period: At least 5 days before exposure.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24
- Humidity (%): 30-70
- Air: Central air-conditioning
- Photoperiod (hrs dark / hrs light): 12 / 12

Administration / exposure

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

air

Details on inhalation exposure:

GENERATION OF THE INHALATION ATMOSPHERE
- Test substance preparation: The test substance was dosed unchanged.
- Equipment: Vaporizer (glasses with thermostat and mixing vessel) continuous infusion pump Perfusor (B. Braun)
- Generation technique: Vapour atmospheres were generated. For each test group the vapours were generated by supplying amounts of the test substance to a heated vaporizer by means of the pump. The vapours that developed were taken up by the supply air and passed into the exposure system.
- Generator temperature: 50°C

TEST ATMOSPHERE
- Sampling equipment: Air sampler GS 312 (DESAGA), Sampling probe (diameter: 4 mm), and 4 fritted glass flasks connected in series and filled with sorption solvent (n-Heptane).
- Brief description of analytical method used: The sample volumes were adjusted to achieve suitable amounts of the test substance in the samples of the test groups in reference to the calibration of the analytical method. The content of the first 3 fritted glass flasks were pooled and analyzed for each sample. The fourth fritted glass flask was used to control the effectiveness of the sorption for all samples of the atmosphere and was analyzed separately at the end of the sampling campaign. The concentration was determined on the basis of propargyl chloride. To determine whether the toluene fraction would enrich in the vapor phase due to its higher vapor pressure, toluene was analyzed in test group 2 at the intermediate concentration.
- Samples taken from breathing zone: yes (adjacent to the noses)
- Sampling flow: 1 L/min
- Sampling velocity: 1.25 m/s
- Sampling frequency: 4 samples at about hourly intervals
- Sampling volumes: 6 L (test group 2 and 3) and 12 L (test group 1)

EXPOSURE
- Whole-body inhalation system: IKA 02 (glass-steel construction), BASF SE, volume V ≈200 L: the animals were kept singly in compartmentalized wire cages, and were exposed inside the chamber.
- The homogenous distribution of test substance atmosphere in this inhalation system has been verified with model vapours.
- The exposure system was located inside an exhaust cabin in an air-conditioned laboratory. During each exposure, the following parameters were recorded four times at about 1-hour intervals:
- Temperatures: The temperature in the inhalation system were measured continuously with a digital thermometer.
- Humidity: The humidity in the inhalation system were measured with a dielectric probe (Testo).
- Supply air flows (compressed air): 3.0 m³/h. The flows were adjusted and continuously measured with a flow meter (rota).
- Exhaust air flows: 3.1 m³/h. The flows were adjusted and continuously measured with a flow meter (rota).
- The higher amounts of exhaust air, which were adjusted by means of a separate exhaust air system, achieved negative pressures inside the exposure system. This ensured that no contamination of the laboratory occurred as result of possible leakage from the inhalation chambers.
- Air changes of about 15 times per hour can be calculated by dividing the supply air flows by the volume of the inhalation systems.
- Animal exposure: 4 hours + equilibration time of the inhalation systems (t99 about 20 min).
- The air change was judged to be sufficient to prevent oxygen depletion by the breathing of the animals, and the concentration of the test substance used could not have a substantial influence on oxygen partial pressure.

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

- Measured: 1.02, 3.35, 5.98 mg/L
- Nominal: 1.55, 4.03, 6.51 mg/L

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

EXPERIMENTAL PROCEDURE
- Observation period: At least 14 days
- Body weight determination: Individual body weights shortly before exposure (day 0), weekly thereafter and at the end of the study. Additionally, body weight was measured in animals that died from study day 1 onward.
- Signs and symptoms: Detailed clinical observations were recorded for each animal separately several times during exposure and at least once on each workday of the observation period. No comprehensive clinical examination was performed on public holidays or weekends.
- Mortality: A check for any dead or moribund animal was made twice each workday and once on Saturdays, Sundays and on public holidays.
- Pathology: At the end of the observation period the surviving animals were sacrificed with CO2-inhalation in a chamber with increasing concentration over time, and were subjected to gross-pathological examination as were the animal which had died before. The scope of the examination can be seen from the results.

Statistics:

The LC50 was calculated by Probit analysis by means of a computer program.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LC50

Effect level:

4.44 mg/L air

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

other: Propargyl chloride sol. 35%

Mortality:

Low- and mid-dose group: No lethality.
High-dose group: 1 male and 2 female animals died on day 0 after exposure. 4 male and 3 female animals died on day 1 during the post exposure observation period.

Clinical signs:

other: - Low-dose group: eyelid closure (both eyes) observed during exposure in both males and females. Piloerection and visually decreased respiration observed during hour 3 and 4 of the exposure period, in both males and females. Visually increased respiration

Body weight:

Low- and mid-dose group: The mean body weights of the male and female animals increased throughout the study period.
High-dose group: No statement is possible, because all the test animals died shortly after the exposure.

Gross pathology:

Low- and mid-dose group: No gross pathological abnormalities.
High-dose group: Of the animals that died on study day 0 or 1 after exposure, 3 male and 3 female animals showed focal red discoloration of stomach and/or slight edema of the lung during necropsy. The remaining animals showed no gross pathological abnormalities.

Any other information on results incl. tables

 

 

Applicant's summary and conclusion

Interpretation of results:

toxic

Remarks:

Migrated information