Methyl tetrahydro-2-furancarboxylate

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 2 july 1990 to 23 July 1990

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP study according to international guideline

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1990

Report date:

1990

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

EPA OPP 81-4 (Acute Eye Irritation)

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Methyl tetrahydro-2-furancarboxylate

EC Number:

420-670-1

EC Name:

Methyl tetrahydro-2-furancarboxylate

Cas Number:

37443-42-8

Molecular formula:

C6H10O3

IUPAC Name:

methyl oxolane-3-carboxylate

Test material form:

other: liquid

Details on test material:

Identification: Methyl Tetrahydrofuroate (METHFAT)
Source QO Chemicals, Inc. 2801 Kent avenue P.O. Box 2500 West Lafeyette , Indiana 47906
Date received: February 23, 1990
Lot number: PP17-9J29
Purity: Assume 100% for acute testing
Physical description: Clear colorless liquid
Storage conditions: sealed container at room temperature

Test material preparation:
A sufficient amount of neat test material waas transferred from its original container to a labeled vial that was covered and transported to the animal room for dosing. The vial contained a stir bar and was maintained on a magnetic stir plate prior to dispensation and throughout the dosing procedure.

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

Number on study: Four males and two females
Body weight range: 2642 to 3675 grams at study initiation
Age at Start of Study Young adult
Method of identification: Eartag
Housing: Individual suspended mesh-bottom cages. The animals were maintained by the animal husbandry staff of WIL Research Laboratories, Inc. in accordance with standard operating procedures.
Quarantine: The animals were acclimated to laboratory conditions for a minimum of 6 days prior to study initiation.
Food and water: Purina Certified Rabbit Chow # 5322 and tap water from on-site wells. Analysis of feed is performed and provided by the manufacturer. Water is analyzed twice yearly in accordance with S.O.P. No. A-020.
Environmental conditions: Animal room with controlled temperature (65-74°F), humidity (54-80%) and light (12 hours light/12 hours dark). There were approximately 10 fresh air changes per hour.

Test system

Vehicle:

unchanged (no vehicle)

Amount / concentration applied:

The dose was 0.1 ml/right eye.

Duration of treatment / exposure:

Single exposure

Observation period (in vivo):

72 hours and 21 days if irritation persisted.

Number of animals or in vitro replicates:

There was one group of six rabbits that received a single unwashed exposure

Details on study design:

Route and rationale of test material administration:
Direct conjunctival instillation. This route of administration is standard for assessment of local ocular irritative potential.

Method of test material administration
The test material was placed directly into the cupped lower conjunctival sac of each rabbit's right (test) eye. The eyelids were held closed for approximately one second after instillation. Left eyes were manipulated in an identical manner to simulate the dosing of the right eyes.

Mortality:
The rabbits were observed twice daily for mortality for the duration of the study.

Ocular observation
Both eyes of all rabbits were examined for ocular abnormalities prior to study initiation. The pre-initiation examination included the use of sodium fluorescein and ultraviolet light for detection of corneal abnormalities. Only rabbits with no pre-existing ocular abnormalities were assigned to study.

Both eyes of all rabbits were examined macroscopically for ocular irritation using a hand-held penlight in accordance with the method of Draize at approximately one, 24, 48 and 72 hours after dosing and at 4,7, 14 and 21 days if irritation persisted. In addition, both eyes of all rabbits were further examined at 72 hours and 7, 14 and 21 days with sodium fluorescein and ultraviolet light.

Body weights:
Body weight were obtained and recorded on study day 0 (initiation) and at the time of each rabbit's termination from the study.

Termination:
Upon termination from the study, the rabbits were sacrificed by intravenous overdose of anesthesia and discarded.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

maximum mean total score (MMTS)

Basis:

mean

Time point:

other: 1h

Score:

47.2

Max. score:

110

Reversibility:

not reversible

Remarks:

within 21 days

Results 2

Irritation parameter:

maximum mean total score (MMTS)

Basis:

mean

Time point:

other: 24h

Score:

36

Max. score:

110

Reversibility:

not reversible

Results 3

Irritation parameter:

maximum mean total score (MMTS)

Basis:

mean

Time point:

other: 48h

Score:

37.7

Max. score:

110

Reversibility:

not reversible

Results 4

Irritation parameter:

maximum mean total score (MMTS)

Basis:

mean

Time point:

other: 72h

Score:

40.3

Max. score:

110

Reversibility:

not reversible

Results 5

Irritation parameter:

maximum mean total score (MMTS)

Basis:

mean

Time point:

other: 4 days

Score:

42

Max. score:

110

Reversibility:

not reversible

Results 6

Irritation parameter:

maximum mean total score (MMTS)

Basis:

mean

Time point:

other: 7 days

Score:

30.5

Max. score:

110

Reversibility:

not reversible

Results 7

Irritation parameter:

maximum mean total score (MMTS)

Basis:

mean

Time point:

other: 14 days

Score:

13.2

Max. score:

110

Reversibility:

not reversible

Results 8

Irritation parameter:

maximum mean total score (MMTS)

Basis:

mean

Time point:

other: 21 days

Score:

14.8

Max. score:

110

Reversibility:

not reversible

Irritant / corrosive response data:

Based on the data obtained the Maximum Average Score for METHFAT was calculated to be 47.2 at 1 hour after dosing. Positive reactions were noted for all animals in all ocular structures evaluated (conjunctiva, iris, cornea). Corneal opacity precluded iridal evaluation for female 10822 on day 14 and 21. Iridal irritation on all other animals completely subsided by day 14 or earlier. Conjunctival irritation, including positive reactions on two animals, persisted through study termination for four rabbits. By the last day of observation (day 21) the treated eyes of three rabbits exhibited apparent irreversible corneal damage.

Other effects:

Mortality:
None of the rabbits died during the study period.

Body weights:
There were no significant changes or differences observed in body weights during the study period.

Applicant's summary and conclusion

Interpretation of results:

irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The Maximum Average Score for METHFAT was 47.2 at 1 hour. Positive conjunctival, iridal and corneal responses were noted for all treated eyes. All observable iridal irritation completely subsided by day 14 or earlier. Conjunctival irritation, including positive reactions on two animals, persisted through day 21 for four rabbits. Three rabbits had apparent irreversible corneal damage at study termination (day 21).