Pyridine, 2-chloro-3-(2,2,2-trifluoroethoxy)-

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2001

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline and GLP compliant study with good documentation.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2001

Report date:

2001

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1300 (Acute inhalation toxicity)

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

2-chloro-3-(2,2,2-trifluoroethoxy)pyridine

EC Number:

700-854-0

Cas Number:

256473-04-8

Molecular formula:

C7H5ClF3NO

IUPAC Name:

2-chloro-3-(2,2,2-trifluoroethoxy)pyridine

Test animals

Species:

rat

Strain:

other: Hanlbm: WIST (SPF)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: RCC Ltd.; biotechnology & Animal Breeding Division; 4414 Füllingsdorf; Switzerland
- Age at study initiation: males: 9 weeks, females 10 weeks
- Weight at study initiation: males 237.7 to 254.0 g, females: 199.9 to 215.1 g
- Housing: in groups of five of the same sex
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: from 15 to 19th December 2000, i.e., 5 days prior to treatment ( the animal exposure was performed on 20th Dec. 2000)

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-21°C
- Humidity (%): 30 - 53%
- Air changes (per hr): 5-12/hour
- Photoperiod (hrs dark / hrs light): 12/12 hours,
- Music was played 12 hours/day mainly during the light period

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
- Source and rate of air: compressed filtered air
- Method of conditioning air: compressed filtered air
- System of generating particulates/aerosols:
The test atmosphere was generated from liquefied test item using glass nebulizer with a stainless steel nozzle and inlet. The test item was liquefied by warming in the glass nebulizer kept in a water bath at approximately 50°C.Compressed filtered air was fed into the nebulizer at 2.5 litres per minute. Then the generated aerosol was diluted using compressed filtered air at 14 L/min. The diluent air was pre-heated by passage through a copper spiral which was placed in a approx. 130°C polyethyleneglycol 400 bath. The glass nebulizer was connected to the exposure chamber which was kept at ambient temperature.
- Method of particle size determination: gravimetrically and by chemical analysis
- Temperature, humidity, pressure in air chamber: yes

TEST ATMOSPHERE
- Brief description of analytical method used:
Gravimetricall method:
Samples from the test atmosphere were collected four times during the exposure on Millipore durapore filters (Type HLVP, 0.45 µm), weight determination : prior to and after sampling
Chemical analysis:
After gravimetrical analysis, the filters were put in a light protected glass and covered with 20 g of tert.buthyl-methyl-ether. The filter samples were then kept at approximately 5°C until analysis. The samples were analysed by GC/FID using a method provided by the sponsor.
- Samples taken from breathing zone: yes

VEHICLE
- Composition of vehicle (if applicable): air, compressed and filtered
- Concentration of test material in vehicle (if applicable): nominal 5 mg/L

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution:
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): 0.61 µm / 13.57 GSD

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

nominal 5 mg/L, measured gravimetric: 5.867 mg/L, analytical: 5.724 mg/L

No. of animals per sex per dose:

5 males and 5 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Day 0 (prior to exposure), days 3, 7, and 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Statistics:

none

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 5.724 mg/L air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

other: no mortality during the test and teh 14 day observation period

Mortality:

none

Clinical signs:

other: Trachypnea (5m/5f) Laboured respiration with slight to marked severity in the affected male and slight to moderate severity in the affected females (1m/3f) Slight to moderate breath sounds (1m/3f) Slight to marked salivation (5m/5f) A decrease in spontane

Body weight:

There was a slight to marked, transient loss of body weight in four out of five males (about -4.9%) and all females (mean -6.7%) from day 0 to day 3. During the remainder of the test period, all animals gained body weight normally. The transient body weight losses were attributed to the treatment with the test item.

Gross pathology:

No macroscopic findings

Applicant's summary and conclusion

Interpretation of results:

practically nontoxic

Remarks:

Migrated information Criteria used for interpretation of results: EU

Executive summary:

The acute 4-h nose-only inhalation toxicity of CTFEP (purity 91.4%) to rat was determined in a GLP compliant test according to OECD 403, EU method B.2 and EPA OPPTS870.1300 (Decker et al. 2001). Since the study was performed under GLP and according the guideline and based on the good documentation the study was awarded with Klimisch 1.

 

The acute inhalation toxicity testing in 5 male and 5 female rats showed that the LD50 of test item (containing 91.4 % CTFEP) was > 5.724 mg/L (limit test, analytically measured). Several slight to moderate clinical signs were observed. The body weight evolution was influenced during the first three days but recovered until day 14. All treated animals were free from poisoning symptoms after 5 days at the latest.

 

The obtained results are considered as relevant for the risk assessment.