5,7-dichloro-4-(4-fluorophenoxy)quinoline;quinoxyfen (ISO)

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:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1994

Report date:

1994

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPP 81-3 (Acute inhalation toxicity)

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: MAFF Acute Inhalation Toxicity Study Guidelines

Deviations:

no

GLP compliance:

yes

Test type:

fixed concentration procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Reference substance 001

Cas Number:

124495-18-7

Test material form:

solid: particulate/powder

Specific details on test material used for the study:

- Name of substance: XDE-795
- Lot number: TSN 100097
- Purity: 97.4%

Test animals

Species:

rat

Strain:

Fischer 344

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Breeding Laboratories, Inc., Kingston, New York
- Age at study initiation: Approximately 11 and 8 weeks old in the initial and repeat exposures, respectively
- Weight at study initiation: Males: 148.8 ± 7.2 g; Females: 113.1 ± 9.2 g
- Housing: Two per cage in stainless steel wire cages during acclimation and singly housed during 2-week post-exposure period
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: At least one week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22
- Photoperiod (hrs dark / hrs light): 12

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Vehicle:

air

Mass median aerodynamic diameter (MMAD):

3.63 other: microns

Geometric standard deviation (GSD):

2.32

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: ADG nose-only chamber
- Exposure chamber volume: Approximately 60 liters
- Rate of air: Airflow maintained at approximately 30 liters per minute
- Method of conditioning air: Compressed air supplied to the chamber was controlled by a system designed to maintain temperature at approximately 22°C
- System of generating particulates/aerosols: Jet Mill
- Method of particle size determination: The aerodynamic particle size was determined three times during each exposure period by drawing samples from the animal breathing zone through a six-stage Cascade Impactor
- Temperature, humidity in air chamber: 23.2 ± 0.26°C, 35.0 ± 1.9%, respectively

TEST ATMOSPHERE
- Brief description of analytical method used: The mass concentration of aerosol present in the chamber was determined gravimetrically seven times during each 4-hour exposure period by drawing samples from a vertical stainless-steel tube which projected into the animal breathing zone. Aerosol particles were collected on Teflon filters with a pore size of 0.45 microns. The time-weighted average (TWA) exposure concentration was calculated from the gravimetric measurements.
- Samples taken from breathing zone: Yes

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

3.38 mg/L (maximum concentration that could be achieved)

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The observations included an evaluation of the fur, eyes, mucous membranes and respiration. Behavior pattern and nervous system activity were assessed by specific observation for tremors, convulsions, salivation, lacrimation and diarrhea, as well as lethargy and other signs of altered central nervous system function. An additional daily observation and routine monitoring on weekends (and holidays) were limited to husbandry procedures required to ensure the availability of food and water. All rats were weighed on test days 2, 4, 8, 11, and 15 during the two-week post-exposure period.
- Necropsy of survivors performed: Yes

Statistics:

Means and standard deviations of animal body weights, chamber temperatures, relative humidities and airflows were calculated for descriptive purposes.

Results and discussion

Preliminary study:

During preliminary atmosphere generation, chamber concentrations greater than 5 mg/L were obtained. However, the MMAD of the particles at this concentration was greater than 4 microns which precluded an actual exposure to 5 mg/L. To reduce the particle size of the aerosol, the test substance was sieved through a 500 micrometer sieve, and then jet-milled in the generation apparatus. In addition, a cyclone was placed between the generation apparatus and the chamber. The feed rate of the jet-mill was reduced until a suitable MMAD (≤4 µ) was obtained. The concentration at that feed rate ranged from approximately 1-4 mg/L.
An initial exposure was conducted in which a group of rats (5/sex) was exposed to a TWA chamber concentration of 1.75 mg/L test substance. However, the MMAD of the particles in this exposure was 6.17 microns and was therefore unacceptable. The low concentration and high particle size in the initial exposure were most likely due to excessive loading of material in the cyclone and glassware leading to the chamber. This limited the ability of the cyclone to remove large particles and reduced the amount of material that could pass into the chamber.
A repeat exposure was conducted with 5 rats/sex at a lower test material feed rate. The time-weighted average chamber concentration was 3.38 mg/L. Based on three determinations, the average MMAD of the particles was 3.63 microns and the GSD was 2.32. Approximately 8% of the particles were less than 1.3 microns, and approximately 28% were less than 3 microns.

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 3.38 mg/L air

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

other: maximum achievable concentration

Mortality:

No animals died

Clinical signs:

other: Transient generalized soiling, a normal observation for a nose-only study, was noted in three female rats during and after exposure. All animals appeared normal on test day two and throughout the remainder of the two-week post-exposure period.

Body weight:

Mean body weights of both male and female rats were decreased slightly on the day following exposure. These weight losses were within normal ranges for non-lethal acute nose-only studies in the test facility. Both male and female rats had normal weight gains thereafter.

Gross pathology:

A distended ovarian bursa or distended uterus were noted during the gross pathologic examination in two female rats. These observations were not considered treatment-related. No treatment-related effects were noted in any other animal.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

4-hr LC50 (rat): > 3.38 mg/L air (maximum achievable concentration)

Executive summary:

This study was conducted to determine the acute inhalation toxicological properties of the test substance following OECD guideline 403 and US EPA 81-3. A group of 5 rats per sex was exposed nose-only for a single 4-hour period to aerosolized test substance. In-life observations were made, and body weights were taken during a two-week post-exposure period. All animals had a gross pathologic examination at the end of the two-week observation period.

The time-weighted average concentration of the test atmosphere was 3.38 mg/L. The mass median aerodynamic diameter of the aerosol (MMAD) was 3.63 microns with a geometric standard deviation of 2.32. This was the maximum concentration that could be achieved while maintaining a respirable atmosphere (MMAD ≤4 µ).

Transient generalized soiling, a common finding in nose-only studies, was observed in several female rats. Other than generalized soiling, all rats appeared normal throughout the two-week observation period.

Mean body weights of both male and female rats were decreased slightly on the day following exposure, however, the animals had normal weight gains thereafter. A complete gross pathologic examination of all rats revealed no treatment-related effects.

No animals died as a result of exposure to test substance, therefore, the four hour LC50 of the test substance in Fischer 344 rats were greater than 3.38 mg/L.