Allyl heptanoate

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

March 05, 1999 - July 05, 1999

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP study according to OECD TG 405

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1999

Report date:

1999

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

Allyl heptanoate

EC Number:

205-527-1

EC Name:

Allyl heptanoate

Cas Number:

142-19-8

Molecular formula:

C10H18O2

IUPAC Name:

allyl heptanoate

Test animals / tissue source

Species:

rabbit

Details on test animals or tissues and environmental conditions:

Animals
Four female SPF albino rabbits weighing 2.3 - 2.5 kg of the stock Mol:Russian from Møllegaard Breeding and Research Centre AIS, Ejby, DK-4623 Lille Skensved were used.
The animals were eannarked on arrival.

Housing
The study took place in animal room No. 5 and 6 provided with filtered air at a temperature of 20°C ± 3°C, relative humidity of 55% ± 15% and air changes 10 times/hour. The rooms were illuminated to give a cycle of 12 hours light and 12 hours darkness. Light was on from 06 to
18 h.
During a pre-period of at least one week and throughout the experiment the rabbits were caged individually in PPO cages (floor area: 2576 cm2) with perforated floor.

Diet
A pelleted complete rabbit diet “Altromin 2123” from Altromin, D-32791 Lage, Lippe, was available ad libitum. Analyses for major nutritive components and relevant possible contaminants are performed regularly on the diet. Certificates of analysis are retained.

Drinking water
The animals had free access to bottles with domestic quality drinking water acidified with hydrochloric acid to pH 2.5 in order to prevent microbial growth. Analyses for relevant possible contaminants are performed regularly. Certificates of analysis are retained.

Test system

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

Four female albino rabbits were exposed to 0.1 ml of the test article in the left eye

Duration of treatment / exposure:

1 hour

Observation period (in vivo):

The eyes were examined and the changes were graded according to a numerical scale 1, 24, 48 and 72 hours after dosing

Number of animals or in vitro replicates:

Four female albino rabbits

Details on study design:

The day before testing both eyes of the animals were examined with a hand held inspection lamp fitted with white and IJV-ligbt and magnifying glass with 2 x magnification to ensure there were no defects or irritation. The examination was performed before and after instillation of Fluorescein.
Only the left eye was treated. The right eye remained untreated and sewed as control.
0.1 ml of the test article was placed in the left eye of the rabbits by gently pulling the lower lid away from the eyeball to form a cup into which the article was dropped. The lids were then gently held together for 1 second.

The eyes were examined and the grade of ocular reaction was recorded 1 and 24 hours later. After the first 24 hour reading Fluorescein was instilled. After rinsing with 20 ml 0.9% sodium chloride solution the eyes were examined again using UV-light to detect possible corneal damage.
The eyes were also examined 48 and 72 hours after the treatment.

READING REACTIONS
The reactions were scored according to the following grades for ocular lesions:

SCORING SYSTEM
Cornea :
When Fluorescein was used the cornea reactions were scored both before and after the instillation of Fluorescein.

Opacity degree of density (Area_most dense taken for_reading)
0 = No ulceration or opacity
1 = Scattered or diffuse area of opacity (other than slight dulling of normal luster), details of iris clearly visible
2 = Easily discernible translucent areas, details of iris slightly obscured
3 = Nacreous areas, no details of iris visible, size of pupil barely discernible
4 = Complete comeal opacity, iris not discernible

Area of cornea involved
1 = One quarter (or less) but not zero
2 = More than 1 quarter, but less than half
3 = More than half, but less than 3 quarters
4 = More than 3 quarters, up to whole area

Iris:
0 = Normal.
1 = Markedly deepened folds, congestion, swelling, moderate circumcomeal injection (any of these or combination of any thereof), iris still reacts to light (sluggish reaction is positive)
2 = No reaction to light, haemorrhage, gross destruction (any or all of these)

Conjunctiva:

Redness (refers to palpebral and bulbar conj unctivae excluding cornea and iris)
0 = Vessels normal
1 = Some vessels definitely injected
2 = Diffuse, crimson red, individual vessels not easily discernible
3 = Difflise beefy red

Chemosis :
0 = No swelling
1 = Any swelling above normal (includes nictitating membrane)
2 = Obvious swelling with partial eversion of lids
3 = Swelling with lids about half closed
4 = Swelling with lids more than half closed

Discharge:
0 = No discharge
1 = Any amount different from normal (does not include small amounts observed in inner canthus of nonnal animals)
2 = Discharge with moistening of the lids and hairs just adjacent to lids
3 = Discharge with moistening of the lids and hairs, and considerable area around the eye

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Remarks:

degree

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 2

Irritation parameter:

cornea opacity score

Remarks:

area

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 3

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

2

Results 4

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within: 48 hours

Results 5

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 6

Irritation parameter:

cornea opacity score

Remarks:

degree

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 7

Irritation parameter:

cornea opacity score

Remarks:

area

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 8

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

2

Results 9

Irritation parameter:

conjunctivae score

Remarks:

Redness

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within: 48 hours

Results 10

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 11

Irritation parameter:

cornea opacity score

Remarks:

degree

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 12

Irritation parameter:

cornea opacity score

Remarks:

area

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 13

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

2

Results 14

Irritation parameter:

conjunctivae score

Remarks:

Redness

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within: 48 hours

Results 15

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 16

Irritation parameter:

cornea opacity score

Remarks:

degree

Basis:

animal #4

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 17

Irritation parameter:

cornea opacity score

Remarks:

area

Basis:

animal #4

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 18

Irritation parameter:

iris score

Basis:

animal #4

Time point:

24/48/72 h

Score:

0

Max. score:

2

Results 19

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #4

Time point:

24/48/72 h

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within: 48 hours

Results 20

Irritation parameter:

chemosis score

Basis:

animal #4

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

One hour after application of the test article animal #1 and #3 showed some conjunctival vessels definitely injected and some amount of discharge different from normal. Some conjunctival vessels definitely injected and discharge with moistening of the lids and hairs just adjacent to lids were observed in animal #2 and #4.
After 24 hours some conjunctival vessels definitely injected were observed in all animals. Some amount of discharge different from normal was seen in animal #4.
After 48 and 72 hours all animals were free of any signs of eye irritation.
The following mean values were obtained from the data presented in the results:
cornea opacity 0.0
iris lesion 0.0
redness of conjunctiva 0.3
oedema of conjunctiva (chemosis) 0.0

Other effects:

Conjunctiva Discharge :
Animal#1 : from 0 to 1 fully reversible within 24 hours
Animal#2 : from 0 to 2 fully reversible within 24 hours
Animal#3 : from 0 to 1 fully reversible within 24 hours
Animal#4 : from 0 to 2 fully reversible within 48 hours

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

According to the directive of the EEC commission 93/21/EEC of April 27, 1993 HR 99/611041 , Batch No. 9034305, shall not be classified as eye irritating.