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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:
03 Sep 2013 - 14 Sep 2013
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP - Guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2013

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
adopted in 1981
Deviations:
no
GLP compliance:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
3-(hexyloxy)propane-1,2-diol
EC Number:
600-386-6
Cas Number:
10305-38-1
Molecular formula:
C9H20O3
IUPAC Name:
3-(hexyloxy)propane-1,2-diol
Constituent 2
Reference substance name:
3-(hexyloxy)1,2-propanediol
IUPAC Name:
3-(hexyloxy)1,2-propanediol
Details on test material:
- Name of test material (as cited in study report): SDX-3255
- Physical state: liquid
- Analytical purity: 99.4%
- Lot/batch No.: 03053
- Expiration date of the lot/batch: May 2014
- Storage condition of test material: room temperature (17.2 to 22.9 °C) in tight, light-resistant containers
- Other: specific gravity: 0.972

Test animals / tissue source

Species:
rabbit
Strain:
other: NZW (Yac:NZW(KBL)), SPF
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Cheonan Yonan College, Laboratory Animal Center, Korea.
- Age at study initiation: 11 weeks
- Weight at study initiation: 2.19 - 2.31 kg
- Housing: stainless wire mesh cages, 450W x 600D x 360H (mm). One animal per cage
- Diet: Purina experimental diet for rabbit 38302AF, ad libitum
- Water: public tap water in Cheongju-si was filtered and irradiated by ultraviolet light and provided ad libitum via an automatic watering system
- Acclimation period: at least 8 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.9 - 21.5
- Humidity (%): 45.8 - 69.3
- Air changes (per hr): 10 - 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 26-08-2013 To: 14-09-2013

Test system

Vehicle:
unchanged (no vehicle)
Controls:
other: the untreated eye served as control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL
Duration of treatment / exposure:
single application without washing
Observation period (in vivo):
9 days
Reading time points: 1, 24, 48, 72, 96 h and once daily thereafter for up to 9 days
Number of animals or in vitro replicates:
3 males
Details on study design:
PRETREATMENT OF THE ANIMALS:
Sixty minutes prior to test substance application, buprenorphine was administered at 0.01 mg/kg bw by subcutaneous injection (SC) to provide a therapeutic level of systemic analgesia. Five minutes prior to test substance application, one drop of 0.5% proparacaine hydrochloride was applied to each eye.

POST-TREATMENT OF THE ANIMALS:
Eight hours after test substance application, buprenorphine at 0.01 mg/kg and meloxicam at 0.5 mg/kg were administered by SC to provide a continued therapeutic level of systemic analgesia.
After the initial 8 h post- test substance application treatment, buprenorphine was administered at 0.01 mg/kg by SC every 12 hours until the ocular lesions resolved.

SCORING SYSTEM: Draize scoring system (1959)

TOOL USED TO ASSESS SCORE: hand-slit lamp (Kowa SL-15, Kowa Co., Ltd., Japan) and fluorescein

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
other: mean over 24, 48 and 72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 9 days
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
other: mean over 24, 48 and 72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 9 days
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
other: mean over 24, 48 and 72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 8 days
Irritation parameter:
iris score
Basis:
animal #1
Time point:
other: mean over 24, 48 and 72 h
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 6 days
Irritation parameter:
iris score
Basis:
animal #2
Time point:
other: mean over 24, 48 and 72 h
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 6 days
Irritation parameter:
iris score
Basis:
animal #3
Time point:
other: mean over 24, 48 and 72 h
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 5 days
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
other: mean over 24, 48 and 72 h
Score:
2
Max. score:
3
Reversibility:
fully reversible within: 9 days
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
other: mean over 24, 48 and 72 h
Score:
2
Max. score:
3
Reversibility:
fully reversible within: 9 days
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
other: mean over 24, 48 and 72 h
Score:
2
Max. score:
3
Reversibility:
fully reversible within: 8 days
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
other: mean over 24, 48 and 72 h
Score:
1.3
Max. score:
4
Reversibility:
fully reversible within: 9 days
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
other: mean over 24, 48 and 72 h
Score:
1.3
Max. score:
4
Reversibility:
fully reversible within: 9 days
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
other: mean over 24, 48 and 72 h
Score:
1.3
Max. score:
4
Reversibility:
fully reversible within: 8 days
Irritant / corrosive response data:
Corneal opacity (score 1), area of the opacity (score 1-4), congestion of the iris (score 1), redness of the conjunctivae (score 1-2), chemosis of the conjunctivae (score 1-3) and discharge (score 1-3) were evident in all 3 animals from one hour after test substance application. Discharge was no longer evident at 72 hours after test substance application. Congestion of the iris was fully reversed within day 6. Redness and chemosis of the conjunctivae were no longer evident on day 9.
Other effects:
Excessive blinking and tearing were evident in the 3 animals at 1 and 8 hours after test substance application. These clinical signs of pain and distress were not evident from day 1 till day 9 after test substance application. In general no abnormal clinical signs or symptoms were evident in any animals throughout the duration of the study. All animals exhibited normal body weight gains. The mean body weight gain throughout the observation period was 0.20 kg.

Applicant's summary and conclusion

Interpretation of results:
irritating
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
CLP: Eye irrit 2; H319
DSD: Xi; R36