Registration Dossier

Diss Factsheets

Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1995
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: According to guideline; under GLP conditions

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1995
Report date:
1995

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
EPA OPP 81-3 (Acute inhalation toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
1-(allyloxy)-2-methyl-1-oxopropan-2-yl 2-chloro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-3,6-dihydropyrimidin-1(2H)-yl]benzoate
EC Number:
603-837-5
Cas Number:
134605-64-4
Molecular formula:
C20H18ClF3N2O6
IUPAC Name:
1-(allyloxy)-2-methyl-1-oxopropan-2-yl 2-chloro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-3,6-dihydropyrimidin-1(2H)-yl]benzoate
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
- Physical state: solid (white powder)
- Storage condition of test material: 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: Recognised supplier
- Age at study initiation: young adult (quantitative value not reported)
- Weight at study initiation: Males (259-330 g); Females (209-231 g)
- Fasting period before study: not applicable
- Housing: Housed individually, in suspended stainless steel cages with wire bottom.
- Diet (e.g. ad libitum): Certified diet from recognised supplier, provided ad libitum (except during exposure period).
- Water (e.g. ad libitum): Municipal water supply from automatic water system, available ad libitum except during the exposure period
- Acclimation period: At least 5 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°F): 72 +/- 5
- Humidity (%): 30-80
- Air changes (per hr): 10-12
- Photoperiod: 12 h light / 12 h dark

IN-LIFE DATES: From: To: 1995-08-23 to 1995-06-09

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: A 500 L nose-only stainless steel, dynamic flow inhalation chamber was utilized in this experiment, one for the test group and another for the control group. The body of the chamber has 25 ports in 5 rows. Polycarbonate cones are inserted into 10 designated individual ports. The test material is introduced through the opening in the top of the chamber. The bottom section has a corresponding air outlet and a drain valve for cleaning the chamber. The individual polycarbonate cones (tubes) are tapered at one end to fit the shape of the animal's head and the back portion is sealed with a poly carbonate cap. The cones containing the animals fit tightly into the ports, and are sealed with "0" rings.
- Exposure chamber volume: 500 L
- Method of holding animals in test chamber: test animals which were individually housed in polycarbonate exposure tubes were inserted into a 500 L stainless steel nose-only inhalation chamber for the specified exposure period.
- Source and rate of air: filtered air; 17.2 air changes per hour.
- Method of conditioning air: ot reported
- System of generating particulates/aerosols: aerosol was generated by a Venturi Aspirator which aspirated the test material from a motorized revolving disc delivery system coupled to the aspirator, then elutriated the resulting aerosol through a baffling chamber. The concentrated aerosol was then diluted with filtered air and drawn into the exposure chamber. Air flow into the test chamber was maintained through the use of a calibrated critical orifice at a rate 17.2 air changes per hour. Air flow into the control chamber was maintained at a rate of 17.6 air changes per hour.
- Method of particle size determination: Particle size was determined using an Andersen cascade impactor.
- Treatment of exhaust air: The bottom section of the exposure chamber has a corresponding air outlet and a drain valve for cleaning the chamber.
- Temperature, humidity, in air chamber: 72 degrees F, 93% humidity.

TEST ATMOSPHERE
- Brief description of analytical method used: The concentration of test material in the exposure atmosphere (taken from the breathing zone of the animals) was determined analytically once per hour, and nominally at the end of the exposure. The analytical determination was made using a BAUSCH & LOMB SPECTRONIC 2000 Spectrophotometer.
- Samples taken from breathing zone: yes

VEHICLE
- Composition of vehicle (if applicable): not applicable
- Concentration of test material in vehicle (if applicable): not applicable
- Justification of choice of vehicle: not applicable
- Lot/batch no. (if required): not applicable
- Purity: not applicable
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
5.10 mg/L
No. of animals per sex per dose:
5 per sex per dose
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observations for mortality and signs of pharmacologic and/or toxicologic effects were made frequently on the day of exposure and at least once daily thereafter for 14 days. Individual body weights were recorded just prior to the inhalation exposure and on Days 7 and 14.
- Necropsy of survivors performed: yes
Statistics:
In order to calculate a mean exposure, the Mean Value Theorem of Calculus was used to properly weight the concentration, since the concentrations could not be measured continuously. This method weights concentrations based on the time span of each concentration. A concentration can be calculated for each minute, which better represents the exposure concentration received by each animal.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 5.1 mg/L air
Based on:
test mat.
Exp. duration:
4 h
Mortality:
There was no mortality in test or control animals during the study.
Clinical signs:
other: Prominent in-life observations included piloerection in all animals of both test and control groups, as well as ptosis in one test male.
Body weight:
Body weight gain in test animals was largely unaffected by the administration of the test material. Three females lost weight during the first week; however, two control females also lost weight during the first week. All except one control female gained weight during the second week.
Gross pathology:
The gross necropsy conducted on each animal at termination of the study revealed no observable abnormalities in test or control groups.
Other findings:
- Organ weights: not examined
- Histopathology: not examined
- Potential target organs: not examined

Applicant's summary and conclusion

Interpretation of results:
Toxicity Category IV
Remarks:
Migrated information Criteria used for interpretation of results: US EPA pesticides
Conclusions:
The acute inhalation median lethal dose (LC50) of the test material in male and female Sprague-Dawley strain of rat was determined to be greater than 5.1 mg/L.
Executive summary:

The study was performed to assess the acute inhalation toxicity of the test material in the Sprague-Dawley strain of rat. The study was performed to GLP and the method was designed to meet the requirements of EPA guideline 81-3. Five males and five females were exposed for four hours in a nose-only inhalation system to an aerosol generated from the undiluted test material (fine powder) at a level of 5.10 mg/L. A negative control using an additional five males and five females was run concurrently. There was no mortality during the study.

Clinical signs included piloerection in both sexes of test and control animals, and ptosis in one test male. There was no meaningful effect on body weight gain, and all animals were asymptomatic by Day 3. The gross necropsy revealed no observable abnormalities in any of the animals on test. The acute inhalation LC50 for the test material is greater than 5.10 mg/L.

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