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Toxicological information

Eye irritation

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Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
19 May - 10 June, 2008
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2008
Report Date:
2008

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.2400 (Acute Eye Irritation)
Deviations:
no
GLP compliance:
yes (incl. certificate)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid
Details on test material:
- Name of test material (as cited in study report): Ditetrahydrofurylpropane
- Lot/batch No.: 6-7B09
- Analytical purity: 99.7%
- Substance type: Clear colourless liquid
- Physical state: liquid
- Purity test date: 09 February 2007
- Expiration date of the lot/batch: 09 February 2010
- Storage condition of test material: At room temperature in the dark
- Stability under storage conditions: Stable

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Harlan France SARL, Gannat, France.
- Age at study initiation: at least 6 weeks old
- Weight at study initiation: at least 1.0 kg.
- Housing: Individually in labeled cages with perforated floors
- Diet (e.g. ad libitum): ad libitum 100 grams per day
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days before start of treatment under laboratory conditions.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.2 – 22.8°C
- Humidity (%): 32 - 74%; Cleaning procedures in the room might have caused the temporary fluctuations above the optimal maximum level of 70% for relative humidity. Based on laboratory historical data, these fluctuations were considered not to have affected the study integrity.
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Vehicle:
unchanged (no vehicle)
Controls:
other: The other eye remained untreated and served as the reference control.
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL


Duration of treatment / exposure:
14 days as the eyes of the test animals have not been washed.

Observation period (in vivo):
The eyes of each animal were examined approximately 1, 24, 48 and 72 hours and 7 and 14 days after instillation of the test substance.
Number of animals or in vitro replicates:
3 males
Details on study design:
SCORING SYSTEM:
CORNEAL IRRITATION
Opacity: degree of density (area most dense taken for reading)
No ulceration or opacity (may include slight dulling of normal luster) 0
Scattered or diffuse areas of opacity, details of iris clearly visible 1
Easily discernible translucent area, details of iris slightly obscured 2
Nacreous area, no details of iris visible, size of pupil barely discernible 3
Opaque cornea, iris not discernible through the opacity 4

Area of cornea involved:
No ulceration or opacity 0
One quarter or less but not zero 1
Greater than one quarter, but less than half 2
Greater than half, but less than three quarters 3
Greater than three quarters, up to whole area 4

IRIS
Normal 0
Markedly deepened rugae, congestion, swelling, moderate circumcorneal hyperaemia,
or injection, any of these or combination thereof, iris still reacting to light
(sluggish reaction is positive) 1
No reaction to light, hemorrhage, gross destruction (any or all of these) 2

CONJUNCTIVAL IRRITATION
Redness (refers to palpebrae and sclera, excluding cornea and iris):
Blood vessels normal 0
Some blood vessels definitely hyperaemic (injected) 1
Diffuse, crimson color, individual vessels not easily discernible 2
Diffuse beefy red 3

Chemosis (refers to lids and/or nictitating membranes):
No swelling ………………………………………… 0
Any swelling above normal (includes nictitating membranes) 1
Obvious swelling with partial eversion of lids 2
Swelling with lids about half closed 3
Swelling with lids more than half closed 4

Discharge:
No discharge (may include small amounts observed in inner canthus of normal animals) 0
Any amount different from normal and/or lacrimation 1
Discharge with moistening of the lids and hairs just adjacent to lids 2
Discharge with moistening of the lids and hairs (considerable area around the eye) 3


TOOL USED TO ASSESS SCORE: fluorescein

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Remarks:
opacity
Basis:
animal #1
Time point:
24/48/72 h
Score:
1.3
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
cornea opacity score
Remarks:
opacity
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 48 h
Irritation parameter:
cornea opacity score
Remarks:
opacity
Basis:
animal #3
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.7
Max. score:
2
Reversibility:
fully reversible within: 7 days
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
fully reversible within: 24 h
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.3
Max. score:
2
Reversibility:
fully reversible within: 72 h
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #1
Time point:
24/48/72 h
Score:
3
Max. score:
3
Reversibility:
fully reversible within: 14 days
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #2
Time point:
24/48/72 h
Score:
2.7
Max. score:
3
Reversibility:
fully reversible within: 14 days
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #3
Time point:
24/48/72 h
Score:
3
Max. score:
3
Reversibility:
fully reversible within: 14 days
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1.3
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.7
Max. score:
4
Reversibility:
fully reversible within: 72 h
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
fully reversible within: 14 days
Irritant / corrosive response data:
Instillation of 0.1 mL of Ditetrahydrofurylpropane into one eye of each of three rabbits resulted in effects on the cornea, iris and conjunctivae.
The corneal injury consisted of opacity (maximum grade 1 or 2) and epithelial damage (maximum 65, 50 or 25% of the corneal area). The corneal injury had resolved within 72 hours in one animal and within 7 days in the other two animals.
Iridial irritation grade 1 was observed and had resolved within 24 or 72 hours or within 7 days. The irritation of the conjunctivae consisted of redness, chemosis and discharge and had completely resolved within 14 days in all animals.
There was no evidence of ocular corrosion.
Other effects:
No staining of (peri) ocular tissues by the test substance was observed and no test substance remnants were seen. No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred.

Any other information on results incl. tables

Table 1: Individual eye irritation scores.

Cornea

Iris

Conjunctivae

Comments

Animal

Time after dosing

Opacity

(0-4)

Area

(0-4)

Fluor area (%)2

(0-2)

Redness

(0-3)

Chemosis

(0-4)

Discharge

(0-3)

8501

1 hour

1

2

-

1

2

4

3

-

24 hours

2

1

65

1

3

2

2

-

48 hours

1

1

-

0

3

1

1

-

72 hours

1

1

25

1

3

1

0

-

7 days

0

0

0

0

1

0

0

-

14 days

0

0

-

0

0

0

0

-

853

1 hour

1

1

-

1

2

3

2

-

24 hours

1

1

25

0

3

1

1

-

48 hours

0

1

-

0

3

1

1

g

72 hours

0

0

0

0

2

0

0

-

7 days

0

0

-

0

1

0

0

-

14 days

0

0

-

0

0

0

0

-

855

1 hour

1

1

-

1

2

2

2

-

24 hours

1

2

50

0

3

3

1

-

48 hours

1

2

-

1

3

3

1

-

72 hours

1

1

25

0

3

3

1

-

7 days

0

0

0

0

1

1

0

-

14 days

0

0

-

0

0

0

0

-

1Sentinel,2Green staining after fluorescein treatment (percentage of total corneal area)

Comments:gSlight dulling of the normal luster of the cornea.

Applicant's summary and conclusion

Interpretation of results:
Category 2 (irritating to eyes) based on GHS criteria
Conclusions:
An in vivo eye irritation study was conducted according to OECD/EC guidelines and GLP principles. Calculated as the mean scores following grading at 24, 48 and 72 hours, the substance produced at least in 2 of 3 tested animals: corneal opacity ≥1, iritis ≥1 and conjuctival redness ≥2. Conjuctival oedema ≥2 was seen in only 1 animal. Effects were fully reversible within 21 days. According to the CLP Regulation (EC) 1272/2008 the substance is classified as eye irritation Category 2.
Executive summary:

In a study performed according to OECD 405 test guidelines, instillation of 0.1 mL of Ditetrahydrofurylpropane into one eye of each of three rabbits resulted in effects on the cornea, iris and conjunctivae. The corneal injury consisted of opacity (maximum grade 1 or 2) and epithelial damage (maximum 65, 50 or 25% of the corneal area). The corneal injury had resolved within 72 hours in one animal and within 7 days in the other two animals. Iridial irritation grade 1 was observed and had resolved within 24 or 72 hours or within 7 days. The irritation of the conjunctivae consisted of redness, chemosis and discharge and had completely resolved within 14 days in all animals. There was no evidence of ocular corrosion. No staining of (peri) ocular tissues by the test substance was observed and no test substance remnants were seen. No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred. Based on these effects the test substance is classified for eye irritation Category 2 according to CLP Regulation (EC) 1272/2008.