Norflurane

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

supporting 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:

1990

Report date:

1990

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: The protocols published by Arrêté of 21 September 1984, in the "Journal Officiel de la République Française" of 24 October 1984 and 9 February 1985.

GLP compliance:

yes (incl. QA statement)

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:

- Name of test material (as cited in study report): HFA 134a (1,1,1,2-Tetrafluoroethane)
- Physical state: gas (supplied as a liquefied gas)
- Analytical purity: >99.8%
- Purity test date: June 1989
- Lot/batch No.: 00015 I9 001
- Expiration date of the lot/batch: n/a
- Stability under test conditions: Stable for at least one year under good storage conditions
- Storage condition of test material: in orginal container and protected from heat.

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Bancel (Albon - 26140 Saint-Rambert-d'Albon - France)
- Age at study initiation: Adult
- Weight at study initiation: 2.35 - 2.70 kg
- Housing: individual housed in polystyrene cages with perforated flooring (internal dimensions 560 x 355 x 315 mm)
- Diet (e.g. ad libitum): about 150 g per animal and per day of complete pelleted rabbit maintenance diet (U.A.R. formulae 112 U.A.R., Villemoisson - 91360 Epinay - S/Orge - France).
- Water (e.g. ad libitum): ad libitum, filtered (15um) and softened mains drinking water (automatic dispenser). Bacteriological and Chemical Analysis performed twice a year.
- Acclimation period: 26 days before start of treatment


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 to 23°C
- Humidity (%):
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light): 12/12 (photoperiod 07.30 - 19.30)


IN-LIFE DATES: From: To:

Test system

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

Group 1: one 5 second vaporization of neat HFA 134a (in gaseous form)
Group 2: two 15 second vaporizations of neat HFA 134a (in gaseous form)
Admistration was performed 10 cm from the right eye into the inferior conjunctival sac. The left eye was used as control.

Duration of treatment / exposure:

5 - 15 seconds

Observation period (in vivo):

1 hour, then on Days 1 (24 hours), 2 and possibly 2, 3, 7. When no more abnormalities were noted in one group of 6 rabbits from Day 3 onwards, examinations were not continued.

Number of animals or in vitro replicates:

2 treated groups of 6 males

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): administered without rinsing


SCORING SYSTEM: Evaluation of the lesions was done according to the Draize scale


TOOL USED TO ASSESS SCORE: fluorescein / Heine ophthalmoscope

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

maximum mean total score (MMTS)

Remarks:

(See Table 1)

Basis:

mean

Time point:

other: 1 hour

Max. score:

8.83

Reversibility:

fully reversible within: 2 days

Remarks on result:

other: Group 1: one 5 second vaporization

Results 2

Irritation parameter:

maximum mean total score (MMTS)

Remarks:

(See Table 1)

Basis:

mean

Time point:

other: 1 hour

Max. score:

11.33

Reversibility:

other: Mean Occular Irritation after 2 days = 1.67

Remarks on result:

other: Group 2: two 15 second vaporizations

Irritant / corrosive response data:

Very slight irritation

Any other information on results incl. tables

Table 1. HFC 134a Mean Occular Irritation (O.I.) indices.

Group	1 hour	Day 1	Day 2	Day 3	Day 4	Day 7	Max OI (Mean OI after 2 days)
1	8.83	1.00	0.00	----	----	----	8.83 (0.00)
2	11.33	3.83	1.67	1.33	1.33	1.00	11.33 (1.67)

HFC 134a was judged to the Very Slightly Irritant to the rabbit eye. There were no noticable pathological ocular lesions.

Applicant's summary and conclusion

Interpretation of results:

other: Vey slightly irritant

Remarks:

Criteria used for interpretation of results: other: the indicies obtained were judged accordin to the scale published in the "Journal Officiel de la République Française" (9 February 1985).

Conclusions:

Gaseous HFC-134a directed from a distance of 10 cm into the eyes of rabbits for 5 or 15 seconds resulted in very slight irritation.

Executive summary:

In a group of six male New Zealand white rabbits, following a one 5 second vaporization of HFC 134a to the right eye, the Maximum Mean Occular Irritation index was 8.83, and the Mean Occular Irritation Index (OI) after 2 days was zero. In a second similar group, following two 15 second vaporizations, the Maximum Mean Occular Irritation index was 11.33, and the Mean Occular Irritation Index (OI) after 2 days was 1.67. These results lead to the conclusion that HFC 134a is very slightly irritant to the rabbit eye. There were no noticeable pathological lesions. The observed effects were possibly a physical consequence of the test procedure.