Registration Dossier

Diss Factsheets

Toxicological information

Acute Toxicity: dermal

Currently viewing:

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 guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Deviations:
no
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

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  238 250  268  0.51 
 3202 228  244  266  0.49 
 3203 232  230  254  0.49 
 3204 234  242  263  0.50 
 3205 227  230  250  0.48 
 3206 140  151  166  0.30 
 3207 144  153  169  0.31 
 3208 136  144  158  0.29 
 3209 132  146  160  0.28 
 3210 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.

Categories Display