Methyl ester of fatty acids, Cx-Cy, Hydroxymethylated

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Julyl 22 - August 5, 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 402 (Acute Dermal Toxicity)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

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:

rat

Strain:

Fischer 344

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan, Indianapolis, IN, USA
- Age at study initiation: 10 weeks
- Weight at study initiation: males = 227 - 238 grams; females = 132 - 144 grams
- Fasting period before study: not specified in report
- Housing: singly housed in suspended stainless steel caging with mesh floors
- Diet (e.g. ad libitum): Purina Certified Rodent Diet (PMI #5002) ad libitum
- Water (e.g. ad libitum): Filtered tap water was supplied ad-libitum
- Acclimation period: 7 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-21°C
- Humidity (%): 76-87%
- Air changes (per hr): 19
- Photoperiod (hrs dark / hrs light): 12-hour light/dark cycle


IN-LIFE DATES: From: July 22, 2008 To: August 5, 2008

Administration / exposure

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: 2 inches x 3 inches
- % coverage: 100%
- Type of wrap if used: 2-inch x 3-inch, 4-ply gauze pad. The gauze pad and entire trunk of each animal were then wrapped with 3-inch Durapore
tape


REMOVAL OF TEST SUBSTANCE
- Washing (if done): After 24 hours of exposure to the test substance, the pads were removed and the test sites were gently cleansed with a 95% ethanol and tap water and a clean towel to remove any residual test substance.
- Time after start of exposure: 24 hours


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg = 0.28 - 0.51 mL
- Concentration (if solution): undiluted (100%)
- Constant volume or concentration used: yes (concentration)
- For solids, paste formed: viscous liquid


VEHICLE
- Amount(s) applied (volume or weight with unit):
- Concentration (if solution):
- Lot/batch no. (if required):
- Purity:

Duration of exposure:

24 hours

Doses:

2000 mg/kg = 0.28 - 0.51 mL

No. of animals per sex per dose:

five (5)

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: animals were observed for mortality, signs of gross toxicity, and behavioral changes during the first several hours after application and at least once daily thereafter for 14 days; body weights of the animals were recorded prior to test substance application (initial) and again on Days 7 and 14 (termination).
- Necropsy of survivors performed: yes
- Other examinations performed: nothing additional

Statistics:

none specified in report

Results and discussion

Preliminary study:

No evidence of toxicity or mortality at dose of 2,000 mg/kg.

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

None, All animals survived.

Clinical signs:

other: There were no signs of gross toxicity, dermal irritation, adverse clinical signs, or abnormal behavior.

Gross pathology:

No gross abnormalities were noted for any of the animals when necropsied at the conclusion of the 14-day observation period.

Any other information on results incl. tables

Animal	Sex	Body weight (grams)			Dose
Number					(mL)
3201	M	238	250	268	0.51
3202	M	228	244	266	0.49
3203	M	232	230	254	0.49
3204	M	234	242	263	0.50
3205	M	227	230	250	0.48
3206	F	140	151	166	0.30
3207	F	144	153	169	0.31
3208	F	136	144	158	0.29
3209	F	132	146	160	0.28
3210	F	138	144	157	0.29

Applicant's summary and conclusion

Interpretation of results:

practically nontoxic

Remarks:

Migrated information not classified Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of this study, the single dose acute dermal LD50 of Methyl (Polyhydroxymethyl) Stearate was greater than 2,000 mg/kg of body weight in male and female rats.

Executive summary:

An acute dermal toxicity test was conducted with Fischer 344 rats to determine the potential for Methyl (Polyhydroxymethyl) Stearate to produce toxicity from a single topical application. Under the conditions of this study, the single dose acute dermal LD50 of the test substance was greater than 2,000 mg/kg of body weight in male and female rats.

Two thousand milligrams of the test substance per kilogram of body weight was applied to the skin of ten healthy rats for 24 hours. The animals were observed for mortality, signs of gross toxicity, and behavioral changes at least once daily for 14 days. Body weights were recorded prior to application and again on Days 7 and 14 (termination). Necropsies were performed on all animals at sacrifice.

All animals survived and although one male lost body weight through Day 7, all animals gained body weight and appeared active and healthy during the study. There were no signs of gross toxicity, dermal irritation, adverse clinical signs, or abnormal behavior. No gross abnormalities were noted for any of the animals when necropsied at the conclusion of the 14-day observation period.