Norflurane

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1979

Report date:

1979

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

yes

Remarks:

- Only 6 animals (all male) used per dose level. Animals observed for 7 days following exposure.

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Norflurane

EC Number:

212-377-0

EC Name:

Norflurane

Cas Number:

811-97-2

Molecular formula:

C2H2F4

IUPAC Name:

1,1,1,2-tetrafluoroethane

Details on test material:

Lot/batch No. Haskell No. 12449; Other codes OCNB-173-180-1

Test animals

Species:

rat

Strain:

other: ChR-CD

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River
- Age at study initiation: 8 weeks
- Weight at study initiation: 250 - 275g
- Fasting period before study: none
- Housing: 2/cage for 7 day pre-test period in 8" x 8" x 14" steel cages
- Diet (e.g. ad libitum): food (Purina® Laboratory Chow) ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 7days

Administration / exposure

Route of administration:

inhalation

Type of inhalation exposure:

whole body

Vehicle:

other: unchanged (no vehicle)

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: glass exposure chamber
- Exposure chamber volume: 20 litres
- Method of holding animals in test chamber: not specified
- Source and rate of air: Houseline air supplemented with oxygen diluted the vapour stream prior to entering the chamber
- Method of conditioning air: not specified


TEST ATMOSPHERE
- Brief description of analytical method used: Gas standards and samples were analysed using a Varian Gas Chromatograph (Model 600D) equipped with a Hydrogen Generator (Model 650) and a flame ionization detector. Nitrogen, the carrier gas, flowed through the 1' x 1/8" O.D. stainless steel column packed with 10% SE 30 on Chromosorb WHP of 80/100 mesh. The column was operated isothermically at 50°C. Automatic sampling of chamber atmosphere was done at 30 minute intervals. Gas standards were prepared by injecting measured amounts of pure HFC 134a into glass gas bottles under vacuum.; bottles were vented allowing mixture of room air and HFC 134a.
- Samples taken from breathing zone: yes

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

Time weighted average concentration ppm (range): 81100 (73800-84100); 205200 (180100-226000); 359300 (327000-378200); 566700 (494400-668800); 646700 (623800-664300); 652700 (581600-685300)

No. of animals per sex per dose:

6 males

Control animals:

no

Details on study design:

Groups of 6 ChR-CD® rats were exposed by whole body method to atmospheres composed of HFC 134a and air supplemented with oxygen for single 4 hour tests. Following exposures surviving rats were returned to their respective cages for food and water available ad libitum. The rats were kept under observation during exposure, as well as for 7 days before and after each test.

Results and discussion

Effect levels

Sex:

male

Dose descriptor:

LCLo

Effect level:

>= 567 000 ppm

Exp. duration:

4 h

Mortality:

Mortalities were 0/6 at 81,100, 205,200 and 359,300 ppm (338,000, 855,000, 1,497,900 mg/m3), 5/6 at 566,700 ppm (2,362,600 mg/m3), 0/6 at 646,700 ppm (2,696,100 mg/m3) and 2/6 at 652,700 ppm (2,721,100 mg/m3).

Clinical signs:

other: Clinical signs reported during the exposure included lethargy, laboured and rapid respiration, salivation and tearing.

Body weight:

359300ppm: 4/6 lost 3 - 9 g within 24 hours of exposure, followed by weight gain
652700ppm: 4/4 survivors lost 7 - 32g within 24 hours of exposure, followed by weight gain.

Any other information on results incl. tables

RESULTS

Time-weighted averageConcentration of HFC 134a ppm (range)	Mortalities: No. rats dead/ No. of rats tested	Observations
81100 (73800 - 84100)	0/6	Exposure: No Abnormalities Detected (NAD) Recovery: NAD
205200 (180100 - 226000)	0/6	Exposure: lethargy, rapid respiration Recovery: NAD
359300 (327000 - 378000)	0/6	Exposure: lethargy, rapid respiration, trembling, tearing Recovery: 4/6 lost 3 -9g within 24 hours of exposure, followed by weight gain
566700 (494400 - 668800)	5/6^*	Exposure: 5 fatalities; laboured rapid respiration, foaming at the nose, pallorRecovery: ^* data unavailable for the recovery phase
646700 (623800 - 664300)	0/6	Exposure: lethargy, rapid respiration, trembling, tearing Recovery: NAD
652700 (581600 - 685300)	2/6	Exposure: 2 fatalities; laboured rapid respiration, foaming at the nose, tearing Recovery: 4/4 lost from 7 -32g within 24 hours of exposure, followed by weight gain

Applicant's summary and conclusion

Interpretation of results:

practically nontoxic

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Groups of 6 male albino ChR-CD® rats were exposed to various concentrations of 1,1,1,2-tetrafluoroethane for 4 hours. The lowest concentration that produced death was 567000 ppm (range of 494000 to 669000 ppm). Clinical signs of toxicity included lethargy, laboured and rapid respiration, foaming at the nose, tearing, salivation, pallor and weight loss.

Executive summary:

An approximate 4-hour lethal concentration (ALC), the lowest concentration that produced death, of 567,000 ppm HFC-134a (2,360,000 mg/m3) in the male ChR-CD rat (6/group) has been reported. In this study, mortalities were 0/6 at 81,100, 205,200 and 359,300 ppm (338,000, 855,000, 1,497,900 mg/m3), 5/6 at 566,700 ppm (2,362,600 mg/m3), 0/6 at 646,700 ppm (2,696,100 mg/m3) and 2/6 at 652,700 ppm (2,721,100 mg/m3). The range of measured concentrations in the 566,700 ppm group at which high mortality occurred was very wide, 494,400 to 668,800 ppm (2,061,200 ‑ 2,788,200 mg/m3), the highest concentration exceeding that of the second highest group 664,300 ppm (2,769,500 mg/m3) and similar to the high end of the range for the highest concentration group at 685,300 ppm (2,857,000 mg/m3). Clinical signs reported during the exposure included lethargy, laboured and rapid respiration, salivation and tearing.