Propargite

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

21st January 1992 to 25th February 1992

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1992

Report date:

1992

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

EPA OPP 81-3 (Acute inhalation toxicity)

Deviations:

yes

Remarks:

(relative humidity and temperature decreased on occasion below that stated in the protocol. The test chambers were cleared at a flow rate of 8 L/min after exposure instead of at the same flow rates used in the exposure phase as intended)

Test guideline 2

Qualifier:

equivalent or similar to guideline

Guideline:

EPA OPPTS 870.1300 (Acute inhalation toxicity)

Deviations:

yes

Remarks:

(relative humidity and temperature decreased on occasion below that stated in the protocol. The test chambers were cleared at a flow rate of 8 L/min after exposure instead of at the same flow rates used in the exposure phase as intended)

Test guideline 3

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

yes

Remarks:

(relative humidity and temperature decreased on occasion below that stated in the protocol. The test chambers were cleared at a flow rate of 8 L/min after exposure instead of at the same flow rates used in the exposure phase as intended)

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Propargite

EC Number:

219-006-1

EC Name:

Propargite

Cas Number:

2312-35-8

Molecular formula:

C19H26O4S

IUPAC Name:

propargite

Test material form:

liquid

Details on test material:

- Name of test material (as cited in study report): Omite® Technical
- Stability under test conditions: at least one year at room temperature
- Storage condition of test material: sealed container at room temperature

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Breeding Laboratories, Inc., Kingston, New York, USA
- Age at study initiation: 7-9 weeks
- Weight at study initiation: 248-333 g (males); 207-233 g (females)
- Housing: stainless steel, wire mesh cages
- Diet: Purina Mills Rodent Laboratory Chow® Brand Animal Diet #5001 ad libitum
- Water: municipal water supply ad libitum
- Acclimation period: 12 to 21 days

ENVIRONMENTAL CONDITIONS
- Temperature: 19-25 ºC
- Humidity: 19-66 %
- Photoperiod: 12 hours light/12 hours dark

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Vehicle:

air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: cast aluminium and alloy exposure chamber
- Exposure chamber volume: 40 litres
- Method of holding animals in test chamber: polycarbonate nose-only tubes
- Exposure procedure: flask containing test material was heated to 50 ºC. House-line air was delivered through a regulator and backpressure gauge via plastic tubing to a plastic 'Y' where it split into a generation flow and a dilution flow. The generation flow was delivered to a flowmeter fitted with a backpressure gauge and regulated by a valve to a neubiliser inserted into the centre neck of the flask. The test material-laden airstream exited the flask and passed through a brass cyclone before entering the nose-only chamber. The dilution flow was delivered to a flowmeter regulated by a valve and then into the side inlet of the nose-only chamber.
- Method of particle size determination: samples were drawn each hour using a cascade impactor. Mass median aerodynamic detector, geometric standard deviation and percent of particles ≤1.0 and ≤10 µm were calculated based on the amount of material collected on the six impactor stages (stainless steel slides) and a final filter stage.
- Treatment of exhaust air: through the in-house filtration system consisting of a coarse filter, HEPA filter and an incinerator
- Temperature, humidity, pressure in air chamber: 19-23 ºC, 8-32 %

TEST ATMOSPHERE
- Brief description of analytical method used: samples were withdrawn from the exposure chamber through glass-fibre filters each hour. Once during each exposure, an extended probe was used to obtain a sample from the other side of the chamber to measure the distribution of aerosol within the chamber. Sample flow rates were 5 lpm for all groups and sample duration was 10 minutes (0.31 mg/L), 1 minute (0.8 mg/L) and 2 minutes (1.3 mg/L). Samples were analysed by GC-FID.

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

0.31, 0.8 and 1.3 mg/L (air concentration)

No. of animals per sex per dose:

Five

Details on study design:

- Duration of observation period following administration: 14 days (0.31 mg/L); 21 days (0.8 and 1.3 mg/L)
- Day of exposure (day 1): all animals were observed individually prior to exposure, as a group at approximately 15 minute intervals during the first hour of exposure and hourly for the remainder of the exposure period. All animals were observed individually upon removed from the exposure chamber and hourly for two hours post-exposure.
- Days 2 through 22: detailed observations were recorded for survivors once daily; viability was assessed twice daily.
- Body weight: days 1 (prior to exposure), 2, 3, 5, 8, 15 and 22
- Necropsy of survivors performed: yes

Statistics:

LC50 and 95 % confidence limits calculated using the method of Litchfield and Wilcoxon.

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

0.89 mg/L air

Based on:

test mat.

95% CL:

>= 0.11 - <= 7

Exp. duration:

4 h

Mortality:

All mortalities occurred between one and seventeen days post-exposure, with the exception of a single accidental death during the first 15 minutes of exposure. This animal was immediately replaced. Total mortalities were 1/10, 2/20 and 10/10 at 0.31, 0.8 and 1.3 mg/l, respectively.

Clinical signs:

other: During the exposure period, the most common symptom was laboured breathing and ano-genital staining. The same signs were evident during the 2 hour post-exposure period, accompanied by nasal discharge, matted coats and several gasping animals in the 1.3 mg

Body weight:

Body weight was reduced by up to 32 % during the first week post-exposure. However, recovery of lost weight occurred over time and all surviving animals were in excess of their starting weight at test termination.

Gross pathology:

The only treatment related finding at necropsy appeared to be a reddening of the lungs of some animals that died during the course of the study.

Any other information on results incl. tables

Table 1: Summary of mortality

		Mortality
Group	Conc. (mg/L)	Male	Female	Total	Day of last spontaneous death
I	0.31	1/5	0/5	1/10	5
II	1.30	5/5	5/5	10/10	18
III	0.80	1/5	1/5	2/10	4

Applicant's summary and conclusion

Interpretation of results:

other: Classified as Category 3 in accordance with EU criteria

Conclusions:

The acute nose-only inhalation LC50 of the test material in rats was determined to be 0.89 mg/L.

Executive summary:

The test material was administered by nose-only inhalation as a liquid aerosol to three groups of five rats for four hours. Exposure levels were determined gravimetrically and by GC during each hour of exposure. Particle size distributions were determined during each hour of exposure. Physical observations for abnormal signs were conducted on all exposure animals as a group, at fifteen minute intervals during the first hour of exposure and hourly for the remainder of exposure. All animals received detailed physical observations just prior to exposure, immediately upon removal from the chamber, hourly for two hours post-exposure and once daily thereafter. Body weight measurements were obtained just prior to exposure on day 1 and on days 2, 3, 5, 8, 15 and 22. After a 14 or 21 day post-exposure observation period, all survivors were sacrificed and complete post-mortem examinations performed.

The mean exposure concentrations were determined to be 0.31, 0.80 and 1.3 mg/L air resulting in mortalities of 10, 20 and 100 %, respectively. Particle size distribution determinations showed, on average, the mass median aerodynamic diameter to be 1.6 µm with a geometric standard deviation of 1.8. 22 % of the particles were <1 µm and 100 % of the particles were <10 µm in size.

The LC₅₀, based on analytical concentrations, was determined to be 0.89 mg/L for the combined sexes with 95 % C.I. of 0.11 to 7.0 mg/L. There was no difference in lethality between males and females. Signs of treatment included respiratory responses during exposures and secretory/respiratory responses following the exposures leading to mortality within 1 to 17 days. A substantial adverse effect upon body weight was produced by treatment. Gross post-mortem examinations included possible treatment-related lung discolouration.