Methyl ester of fatty acids, Cx-Cy, Hydroxymethylated

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

July 16 - 19, 2008

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP study conducted in accordance with regulatory test guidance.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2008

Report date:

2008

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2400 (Acute Eye Irritation)

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Details on test material:

- Name of test material (as cited in study report): methyl(polyhydroxymethyl) stearate
- Molecular formula (if other than submission substance): not specified in report
- Molecular weight (if other than submission substance): not specified in report
- Smiles notation (if other than submission substance): not specified in report
- InChl (if other than submission substance): not specified in report
- Structural formula attached as image file (if other than submission substance): not specified in report
- Substance type: mixture of functionalized fatty acid methy esters (FAMEs), which may be derived from a variety of natural seed oils
- Physical state: waxy, cloudy colorless liquid
- Analytical purity: 95.2%
- Impurities (identity and concentrations): not specified in report
- Composition of test material, percentage of components: not specified in report
- Isomers composition: not specified in report
- Purity test date: August 22, 2005
- Lot/batch No.: 200500200-25-4
- Expiration date of the lot/batch: not specified in report
- Radiochemical purity (if radiolabelling):
- Specific activity (if radiolabelling):
- Locations of the label (if radiolabelling):
- Expiration date of radiochemical substance (if radiolabelling):
- Stability under test conditions: normal ambient conditions
- Storage condition of test material: environmentally controlled facility at ambient conditions

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Robinson Services Inc., Clemmons, NC on July 9, 2008.
- Age at study initiation: young adult
- Weight at study initiation: 2314 - 2700 grams
- Housing: singly housed in suspended stainless steel caging with mesh floors which conform to the size recommendations in the most recent
Guide for the Care and Use of Laboratory Animals DHEW (NIH). Litter paper was placed beneath the cage and was changed at least three times
per week.
- Diet (e.g. ad libitum): Purina Certified High Fiber Rabbit Diet (PMI #5325) ad libitum
- Water (e.g. ad libitum): Filtered tap water was supplied ad-libitum by an automatic water dispensing system.
- Acclimation period: 7 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-21ºC
- Humidity (%): 69-79%
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12-hour light/dark cycle


IN-LIFE DATES: From: July 16, 2008 To: July 19, 2008

Test system

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1-mL
- Concentration (if solution): undiluted

Duration of treatment / exposure:

Single instillation with observations through 72 hours

Observation period (in vivo):

72 hours

Number of animals or in vitro replicates:

three (3)

Details on study design:

One-tenth of a milliliter of the test substance was then instilled into the conjunctival sac of the right eye of each rabbit by pulling the lower lid away
from the eyeball. The upper and lower lids were then gently held together for about one second before releasing to minimize loss of the test
substance. The other eye of each rabbit remained untreated with the test substance and served as a control.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): None


SCORING SYSTEM: Ocular irritation was evaluated using a high-intensity white light (Mag Lite) in accordance with Draize et al.at 1, 24, 48, and
72 hours post-instillation. A fluorescein dye evaluation procedure (see below) was used at 24 hours to verify the absence of effects. Individual
scores were recorded for each animal. In addition to observations of the cornea, iris, and conjunctivae, any other observed lesions were noted.
The average score for all rabbits at each scoring period was calculated to aid in data interpretation.

TOOL USED TO ASSESS SCORE: In short, one drop of 2% ophthalmic fluorescein sodium was instilled into both eyes of each rabbit. The eyes were
rinsed with physiological saline (0.9% NaCl) approximately 30 seconds after instillation of the fluorescein and then evaluated for corneal damage
using an ultraviolet light source.

Results and discussion

In vivo

Results

Irritation parameter:

maximum mean total score (MMTS)

Remarks:

Scores for Cornea, Iris and Conjunctivae

Basis:

mean

Remarks:

(n = 3 rabbits)

Time point:

other: 1 hr, 24 hrs, 48 hrs, 72 hrs

Score:

>= 0 - <= 15

Max. score:

110

Reversibility:

fully reversible within: 72 hrs

Irritant / corrosive response data:

There was no corneal opacity observed in any treated eye during this study. One hour after test substance instillation, two treated eyes exhibited
iritis and all three treated eyes exhibited ‘positive’ conjunctivitis. The overall incidence and severity of irritation decreased with time. All animals were free of ocular irritation by 72 hours.

Other effects:

All animals appeared active and healthy during the study. Apart from the eye irritation noted below, there were no other signs of gross toxicity,
adverse clinical signs, or abnormal behavior. All rabbits gained body weight over the course of the study.

Any other information on results incl. tables

	Rabbit No. 3401				Rabbit No. 3402				Rabbit No. 3403
	Hours				Hours				Hours
	1	24	48	72	1	24	48	72	1	24	48	72
I. Cornea
A. Opacity	0	0	0	0	0	0	0	0	0	0	0	0
B. Area	4	4	4	4	4	4	4	4	4	4	4	4
(A x B) x 5	0	0	0	0	0	0	0	0	0	0	0	0
II. Iris
A. Values	1	0	0	0	1	0	0	0	0	0	0	0
A x 5	5	0	0	0	5	0	0	0	0	0	0	0
III. Conjunctivae
A. Redness	2	1	1	0	2	1	0	0	2	1	1	0
B. Chemosis	1	0	0	0	1	0	0	0	1	0	0	0
C. Discharge	2	1	0	0	2	0	0	0	2	1	0	0
(A + B + C) x 2	10	4	2	0	10	2	0	0	10	4	2	0
TOTAL	15	4	2	0	15	2	0	0	10	4	2	0

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The test substance methyl polyhydroxymethyl stearate can be considered as non-irritating to the eye.

Executive summary:

A primary eye irritation test was conducted with New Zealand albino rabbits to determine the potential for Methyl (Polyhydroxymethyl) Stearate to produce irritation from a single instillation via the ocular route. One-tenth of a milliliter of the test substance was instilled into the right eye of three healthy rabbits. The left eye remained untreated and served as a control. Ocular irritation was evaluated by the method of Draize.

There was no corneal opacity observed in any treated eye during this study. One hour after test substance instillation, two treated eyes exhibited iritis and all three treated eyes exhibited ‘positive’ conjunctivitis. Under the conditions of this study, the test substance caused iritis, which cleared by 24 hours and conjunctival irritation, which cleared by 72 hours. The overall incidence and severity of irritation decreased with time. All animals were free of ocular irritation by 72 hours. All animals appeared active and healthy during the study. Apart from the eye irritation noted below, there were no other signs of gross toxicity, adverse clinical signs, or abnormal behavior. All rabbits gained body weight over the course of the study.

The test substance Methyl (Polyhydroxymethyl) Stearate can be considered as non-irritating to the eye (EU DSD, Annex VI).