Fluometuron

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

05 to 19 September 1989

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP - Guideline study The experiments were done according to the EPA FIFRA, Subdivision F, §81-3 (1984) = EEC B.2 (1992) USA TSCA, Section HG ‘Acute Exposure Inhalation Toxicity Study’

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1989

Report date:

1989

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:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Fluometuron

EC Number:

218-500-4

EC Name:

Fluometuron

Cas Number:

2164-17-2

Molecular formula:

C10H11F3N2O

IUPAC Name:

fluometuron

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

- Name of test material: fluometuron, 1,1-dimethyl-3-[3-(trifluoromethyl)phenyl]urea
- Physical state: white powder
- Analytical purity: 96.8% (w/w)
- Batch number: batch no. 1223
- Date of arrival: 12 July 1989
- Storage conditions: room temperature

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

- groups of five male and five female Sprague-Dawley strain rats
- Source: Bantin & Kingman Ltd. Grinston, Aldborrough, Hull, U.K.
- weight: males: 225 - 275 g, females: 208 - 226 g
- age: eight to ten weeks
- free access to mains drinking water and food
- temperature: 18-22°C

Administration / exposure

Route of administration:

inhalation: dust

Type of inhalation exposure:

nose only

Vehicle:

air

Details on inhalation exposure:

Each rat was individually held in a tapered, polycarbonate restraining tube fitted onto a single tier of the exposure chamber and sealed by means of a rubber`O´ ring. Only the nose of the animal was exposed to the test atmosphere.
A single group of ten rats (five males and five females) was exposed to an atmosphere of the test material for a period of four hours. A target concentration of 5 mg/litre was used for the exposure
(The main exposure parameters are summarised in Table 2)

Analytical verification of test atmosphere concentrations:

yes

Remarks:

filter were weight before and after sampling in order to calculate the noninal chamber concentration

Duration of exposure:

4 h

Concentrations:

Target concentration: 5 mg/l
4 hour exposure: Nominal concentration: 26.3 mg/l

No. of animals per sex per dose:

one group of five female and five male rats, 10 animals/ dose

Control animals:

no

Details on study design:

Atmosphere Generation
A dust atmosphere was generated using a Wright´s dust feed mechanism attached to a variable drive motor and the compressed air supply.
The cylindrical exposure chamber has a volume of approximalety 40 literes. The concentration within the exposure chamber was controlled by adjusting the rate of the motor and air flow rate through the chamber. The extract from the exposure chamber passed thruogh a `scrubber´trap and was connected with a high efficiency filter to a metered exhaust system. The chamber was maintained under negative pressure.
Compressed air was supplied by means of a Gast 2HBB-10-P25Y oil free compressor and was passed through a water trap and repiratory quality filters which removed particulate material above 0.005 µm before it was introduced to the dust feed.
The temperature inside the exposure chamber was measured by a mercury thermomter located in a vacant port in the animals´breathing zone of the chamber and recorded every thirty minutes throughout the four-hour exposure period.
EXPOSURE CHAMBER ATMOSPHERE CONCENTRATION
The chamber concentration was estimated at aregular intervals during the exposure period. The gravimetric method used, employed glass fibre filters (Gelman type A/E 25 mm) placed in a filter holder. The holder was tempoarily sealed in a vacant port in the exposure chamber in the animals´breathing zone. Exposure chamber air was drawn through the filter at a measured rate using a vacuum pump for a suitable time period.
Each filter was weighed before and after sampling in order to calculate the weight of collected test material. The difference in the two weights divided by the volume of atmosphere sampled was the chamber concentration.
PARTICLE SIZE DISTRIBUTION
The particle size of the generated atmosphere of the test material inside the exposure chamber was determined twice during the exposure period using a Cascade Impactor. The device consisted of four glass impactor plates an a back up glass fibre filter (Gelman Type A/E, 25 mm) housed in an aluminium sampler. The sampler was temporarily sealed in a vacant port in the animals´ breathing zone. Exposure chamber air was drawn through the Cascade Impactor using a vacuum pump for a suitable time period.
The impactor plates were weighed before and after sampling and the weight of test material, collected on each stage, calculated by difference. From the results obtained the weight distribution of particles in the size range > 13 µm, 4.0 - 13 µm, 1.7 - 4.0 µm and < 1.7 µm was calculated

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 4.62 mg/L air

Based on:

test mat.

Exp. duration:

4 h

Mortality:

No mortalities were recorded during the study (Table 3)

Clinical signs:

other: Clinical signs in both sexes during the exposure period were wet fur and decreased respiratory rate. After exposure, hunched posture, decreased respiratory rate, lethargy and pilo-erection were recorded. All animals appeared normal two days after treatmen

Body weight:

Incidents of female bodyweight loss or failure to gain weight were noted in the first week and bodyweight loss in this sex was noted over the second week.

Gross pathology:

No abnormalities were noted at necropsy of all the animals

Any other information on results incl. tables

Table 7.2.2.-02: Acute inhalation toxicity of fluometuron technical in rats

Males		Females
Dose	Mortality	Dose	Mortality
4.62 mg/l	0/5	4.62 mg/l	0/5

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Fluometuron technical was of low toxicity to rats via inhalation as there were no mortality at 4.62 mg/l. The acute inhalation median lethal concentration (LC50) is > 4.62 mg/l. In comparison with acute toxicity by oral application route also an LC50 higher than 5 mg/l is exspected. In accordance with the provisions of regulation 1272/2008, Annex I, 3.1, the proposed classification is not dangerous.

Executive summary:

A study was performed to determine the acute inhalation median lethal concentration (LC50) of the test material in the Sprague-Dawley strain rat. The study was designed to comply with the requirements of the U.S. Environmental Protection Agency (EPA). The animals were exposed for four hours using a nose only exposure system. The results are summarised as follows:

 

EXPOSURE CHAMBER ATMOSPHERE CONCENTRATION

Atmosphere Concentration
Group Number	Mean Achieved mg/litre	Standard Deviation	Nominal mg/litre
1	4.62	1.48	26.3

PARTICLE SIZE DISTRIBUTION

Group Number	Respirable Fraction % (<4µm)	Mean Mass Median Aerodynamic Diameter (µm)	Geometric Standard Deviation (µm)
1	20.5	8.1	0.42

MORTALITY DATA

Group Number	Mean Achieved Atmosphere Concentration Mg/litre	Deaths
		Male	Female	Total
1	4.62	0/5	0/5	0/10

Clinical Observations:During the exposure period decreased respiratory rate and wet fur were noted. Signs of toxicity noted after exposure included hunched posture, decreased respiratory rate, wet fur, lethargy and pilo-erection. All animals appeared normal two days after treatment and for the rest of the study period.

 

Bodyweight:Incidents of bodyweight loss or failure to gain weight were noted in females over the first week and bodyweight Ioss was noted in all females over the second week. All males showed expected gain in bodyweight over the study period.

 

Necropsy:No abnormalities were noted at necropsy of animals killed at the end of the study period.

No deaths occurred in a group of ten rats exposed to a mean achieved concentration of 4.62 mg/litre (range 2.25 - 8.05 mg/litre). It was therefore considered that the acute inhalation LC50 of the test material in the Sprague-Dawley rat was greater than 4.62 mg/litre.