Methyl ester of fatty acids, Cx-Cy, Hydroxymethylated

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

July 21-Aug 8, 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 425 (Acute Oral Toxicity: Up-and-Down Procedure)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

up-and-down procedure

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:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan, Indianspolis, IN, USA
- Age at study initiation: 10-11 weeks
- Weight at study initiation: 128-135 grams
- Fasting period before study: overnight prior to dosing
- Housing: singly housed in suspended stainless steel caging with mesh floors
- Diet (e.g. ad libitum): Purina Certified Rodent Diet (PMI #5002)
- Water (e.g. ad libitum): Filtered tap water was supplied ad libitum
- Acclimation period: 6-10 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-21ºC
- Humidity (%): 71-87%
- Air changes (per hr): 19
- Photoperiod (hrs dark / hrs light): 12-hour light/dark cycle


IN-LIFE DATES: From: July 21, 2008 To: August 8, 2008

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

VEHICLE
- Concentration in vehicle: no vehicle; undiluted test material
- Amount of vehicle (if gavage): no vehicle
- Justification for choice of vehicle: no vehicle
- Lot/batch no. (if required):
- Purity:


MAXIMUM DOSE VOLUME APPLIED: 0.29 mL


DOSAGE PREPARATION (if unusual):


CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: previous screening data

Doses:

2000 mg/kg

No. of animals per sex per dose:

five (5)

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 for the first several hours post-dosing and at least once daily thereafter for 14 days after dosing; body weights of the animals were recorded prior to test substance administration (initial) and again on Days 7 and 14 (termination) following dosing
- Necropsy of survivors performed: yes; gross necropsies were performed at the end of the 14-day observation period
- 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:

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, adverse clinical signs, or abnormal behavior.

Gross pathology:

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

Other findings:

None

Any other information on results incl. tables

Animal	Dose level		Body weight (grams)			Dose
Number	(mg/kg)		Pre-dose	Day 7	Day 14	(mL)
3101	2000		135	146	154	0.29
3102	2000		128	137	150	0.27
3103	2000		132	141	154	0.28
3104	2000		130	138	149	0.28
3105	2000		131	139	150	0.28

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 acute oral LD50 of Methyl (Polyhydroxymethyl) Stearate was greater than 2,000 mg/kg of body weight in
female rats.

Executive summary:

An acute oral toxicity test (Up and Down Procedure) was conducted with Fischer 344 rats to determine the potential for Methyl (Polyhydroxymethyl) Stearate to produce toxicity from a single dose via the oral route. Under the conditions of this study, the acute oral LD50 of Methyl (Polyhydroxymethyl) Stearate was greater than 2,000 mg/kg of body weight in female rats. An initial limit dose of 2,000 mg/kg was administered to one healthy female rat by oral gavage. Due to the absence of mortality in this animal, four additional females sequentially received the same dose level. Since these animals survived, no additional animals were tested. Females were selected for the test because they are frequently more sensitive to the toxicity of test compounds than males. All animals were observed for mortality, signs of gross toxicity, and behavioral changes at least once daily for 14 days after dosing. Body weights were recorded prior to administration and again on Days 7 and 14 (termination) following dosing. Necropsies were performed on all animals at sacrifice. All animals survived, gained body weight, and appeared active and healthy during the study. There were no signs of gross toxicity, adverse clinical signs, or abnormal behavior. No gross abnormalities were noted for the animals when necropsied at the conclusion of the 14-day observation period.