Methyl ester of fatty acids, Cx-Cy, Hydroxymethylated

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

July 9 - 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 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2500 (Acute Dermal Irritation)

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
- Other:

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Robinson Services, Inc. Clemmons, NC on June 25, 2008
- Age at study initiation: Young adult
- Weight at study initiation: 2280 - 2426 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: 14 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-21°C
- Humidity (%): 68-86%
- Air changes (per hr): 20
- Photoperiod (hrs dark / hrs light): 12-hour light/dark cycle


IN-LIFE DATES: From: July 9, 2008 To: July 19, 2008

Test system

Type of coverage:

semiocclusive

Preparation of test site:

other: clipping the dorsal area and the trunk

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

Five-tenths of a milliliter of the test substance was applied to one 6-cm2 intact dose site on each animal (and covered with a 1-inch x 1-inch, 4-ply
gauze pad. The pad and entire trunk of each animal were then wrapped with semi-occlusive 3-inch Micropore tape to avoid dislocation of the pad).

Duration of treatment / exposure:

After 4 hours of exposure to the test substance, the pads and collars were removed and the test sites were gently cleansed of any residual test
substance.

Observation period:

Individual dose sites were scored according to the Draize scoring system at approximately 30-60 minutes, 24, 48, and 72 hours and at 7 and 10
days after patch removal.

Number of animals:

Three (3)

Details on study design:

In addition to the above details:

Body Weights
Individual body weights of the animals were recorded prior to test substance application (initial) and again at study termination after scoring.

Cage-Side Observations
The animals were observed for signs of gross toxicity and behavioral changes at least once daily during the test period. Observations included gross evaluation of skin and fur, eyes and mucous membranes, respiratory, circulatory, autonomic and central nervous systems, somatomotor activity and behavior pattern. Particular attention was directed to observation of tremors, convulsions, salivation, diarrhea, and coma.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Remarks:

Draize scoring system

Basis:

mean

Remarks:

2.0, 1.3, 1.3, 1.3, 0.7, 0

Time point:

other: 60 min, 24h, 48h, 72h, 7d, 10d

Score:

>= 0 - <= 2

Max. score:

2

Reversibility:

fully reversible within: 7 - 10 days

Results 2

Irritation parameter:

edema score

Remarks:

Draize scoring system

Basis:

mean

Remarks:

2.0, 0.3, 0.3, 0.3, 0.3, 0

Time point:

other: 60 min, 24h, 48h, 72h, 7d, 10d

Score:

>= 0 - <= 2

Max. score:

2

Reversibility:

fully reversible within: 7 - 10 days

Irritant / corrosive response data:

Within one hour after patch removal, all three treated sites exhibited well-defined erythema and slight edema. Although the overall incidence and
severity of irritation decreased gradually with time, dermal desquamation was observed for two animals on Day 10 (study termination).

Other effects:

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

Any other information on results incl. tables

		Time after patch removal
Anaimal No.	Sex	30-60 min	24 hrs	48 hrs	72 hrs	day 7	day 10
3501	F	2/2	2/1	2/1	1/1	1/1	0/0
3502	F	2/2	1/0	1/0	1/0	1/0	0/0
3503	F	2/2	1/0	1/0	1/0	0/0	0/0
Total		6/6	4/1	4/1	4/1	2/1	0/0
Mean		2.0/2.0	1.3/0.3	1.3/0.3	1.3/0.3	0.7/0.3	0/0

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of this study, Methyl (Polyhydroxymethyl) Stearate caused well-defined erythema and slight edema. Dermal desquamation
was observed for two animals on Day 10 (study termination). The inflammation was not perceived as significant as the mean values for erythema and edema were not equal to 2 (or more) by the 24 hour time point, or for at least two animals separately. Per Annex VI of the Dangerous Substances
Directive, this material should not be classified as irritating.

Executive summary:

A primary skin irritation test was conducted with New Zealand albino rabbits to determine the potential for Methyl (Polyhydroxymethyl) Stearate to produce irritation after a single topical application. Under the conditions of this study, the test substance caused well-defined erythema and slight edema. Dermal desquamation occurred for two animals on Day 10 (study termination).

Five-tenths of a milliliter of the test substance was applied to the skin of three healthy rabbits for 4 hours. Following exposure, dermal irritation was evaluated by the method of Draize. Within one hour after patch removal, all three treated sites exhibited well-defined erythema and slight edema. Although the overall incidence and severity of irritation decreased gradually with time, dermal desquamation occurred for two animals on Day 10 (study termination).