3-chloropropyne

Specific investigations: other studies

Administrative data

Endpoint:

specific investigations: other studies

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: GLP compliant near guideline study, available as unpublished report, minor restrictions in design and/or reporting but otherwise adequate for assessment

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1992

Report date:

1992

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

other: ASTM E981 - 84

GLP compliance:

yes

Type of method:

in vivo

Endpoint addressed:

respiratory irritation

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): (No. 115) Propargyl chloride (70% in Toluene)
- Lot/batch No.: 8/87
- Analytical purity: 68.2% Propargyl chloride, 29.9% toluene
- Storage condition of test material: dry, 4°C and dark
- Stability under test conditions: stable for 6 months from the date of analysis (1990-03-06)

Test animals

Species:

mouse

Strain:

CD-1

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River U.K. Limited, Manston Road, Margate, Kent
- Age at study initiation: 3-5 weeks
- Weight at study initiation: 15-17 g
- Housing: The mice were housed in cages (13 cm wide x 30 cm deep and 12 cm high) with moulded polypropylene bodies and detachable stainless steel mesh tops. Sawdust (Biosure, SDS, Cambridgeshire, U.K.) was used for litter. The cages were suspended on a movable rack. A group of 4 was held in each cage and each cage was identified by a label according to group.
- Diet: Biosure LAD (SDS, Cambridgeshire, U.K.) diet, ad libitum
- Water: Tap water ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-23
- Humidity (%): 55-85

Administration / exposure

Route of administration:

inhalation: vapour

Vehicle:

air

Details on exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Vapour generator: A generator was designed to produce and maintain an atmosphere containing a vapour of the test substance. All parts of the generator in contact with the test substance were made of glass. The test substance was supplied to the generator at a constant flow rate from a syringe driven by a syringe pump. The compressed air supply to the generator was dried, filtered and oil-free.
- Exposure apparatus: The vapour was passed into a 120 L Perspex chamber which acted as a reservoir.
- Exposure chamber volume: 2.05 L (animal exposure section).
- Method of holding animals in test chamber: Each restraining tube was constructed of Perspex, and on one end of the tube was placed an aluminium alloy end cap containing a rubber dam diaphragm with a circular hole at the centre. The mouse was inserted into the tube so that the animal's neck and snout, protruded from the front of the alloy cap. The animal's movements were restricted by inserting a PVC plug into the rear of the tube. The plug contained an airtight rubber ‘O’ ring seal. A pressure transducer was connected to the wall of the restraint tube and placed so as to open over the animal’s chest.
- Source and rate of air: Clean, dried air
- Method of conditioning air: The syringe pump was switched on at the appropriate feed rate to produce the required atmosphere concentrations
- Air flow rate: 30 L/min
- Treatment of exhaust air: the atmosphere was withdrawn through 2 extract ports (2 L/min through the bubbler for the duration of the required sample volume; 20 L/min extracted to waste (via a flow-meter) after scrubbing through charcoal adsorption cylinders).

TEST ATMOSPHERE
- Brief description of analytical method used: Samples of the test atmospheres were drawn through a gas-absorption trap (sintered glass bubbler) containing 25 mL of methanol cooled in iced water. The chamber test atmospheres were sampled at a rate of 2 L/min and the volume of air drawn through the bubbler was measured by means of a wet-type gas meter, (Model DM3B, Alexander Wright, London).The contents of the bubbler were then quantitatively transferred to suitable containers and stored for analysis. The volume of sample taken was adjusted for each group to ensure that sufficient test substance was collected for analysis.
- Samples taken from breathing zone: yes

Analytical verification of doses or concentrations:

yes

Duration of treatment / exposure:

30-60 min

Frequency of treatment:

1

Post exposure period:

10 min

Doses / concentrations

Remarks:

Doses / Concentrations:
0.033, 0.323, 1.089, 4.044 mg/L
Basis:
analytical conc.

No. of animals per sex per dose:

4

Control animals:

yes, concurrent vehicle

Details on study design:

A pre-exposure period of 10 min was used to establish a respiratory rate baseline.

Examinations

Examinations:

- The clinical condition of the animals was examined immediately before and after exposure, and before sacrifice.
- The animals were weighed on arrival, on the day of exposure and on the day of sacrifice.
- Twenty-four hours after exposure, mice from the highest exposure concentration group and from control exposures were anaesthetized by intraperitoneal injection of sodium pentobarbitone and exsanguinated. The lungs were removed and weighed, and then distended with buffered 10%
formalin and preserved in formalin solution. All remaining mice were killed by intraperitoneal injection of sodium pentobarbitone.
- Microscopic pathology: The fixed tissues were embedded in paraffin wax and processed routinely. Four-micron sections were prepared, stained with haematoxylin and eosin and examined under the light microscope.

Results and discussion

Details on results:

- Clinical signs: No effects observed in control mice and mice exposed to 0.033, 0.323 and 1.089 mg/L. Mice exposed to 4.044 mg/L showed lacrimation immediately post-exposure but were normal within 24 hours.
- Effects on the respiratory rate: Exposures to PROPARGYL CHLORIDE in TOLUENE vapour caused a marked respiratory rate depression, which developed over a period varying from a few seconds up to approximately 3 minutes. The rate depression was well-defined and was seen to increase with time in all exposures. However the increase in response with time was only significant at the 0.323 mg/L and 1.089 mg/L.
- Body weights: A non-significant slight decrease in body weight was observed on the day following exposure.
- Lung weights: Absolute lung weights form mice exposed to 4.044 mg/L for 60 min increased relative to the controls. As the pre-exposure weights for these two groups were similar, this may be regarded as an index of lung irritation.
- Lung histopathology: Minimal focal hyperplasia, vacuolar degeneration and apoptosis of bronchiolar epithelium in all animals exposed at 4.044 mg/L.
- The RD50 (concentration causing a 50% decrease in respiratory rate) estimate for PROPARGYL CHLORIDE was calculated to be 2.0885 mg/L.

Applicant's summary and conclusion

Conclusions:

sensory irritant response