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Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2014-12-30 - 2015-01-20
Reliability:
1 (reliable without restriction)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2015
Report date:
2015

Materials and methods

Test guidelineopen allclose all
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
1987
Deviations:
no
Qualifier:
equivalent or similar to guideline
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Version / remarks:
1996
Deviations:
no
GLP compliance:
yes
Test type:
fixed dose procedure
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Reaction product of D-Glucopyranoside, methyl; esterified with oleic acid, methyl ester
EC Number:
946-364-2
Molecular formula:
C43H78O8
IUPAC Name:
Reaction product of D-Glucopyranoside, methyl; esterified with oleic acid, methyl ester
Test material form:
liquid
Details on test material:
- State of aggregation: yellow liquid
-Others: storage at room temperature, in the dark
Specific details on test material used for the study:
Prior to use, the bulk test substance container was inverted and/or swirled. A sufficient amount of test substance was transferred into a storage container for dispensation.

Test animals

Species:
rat
Strain:
other: Crl:CD(SD)
Remarks:
albino rat
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories, Inc., Raleigh, NC
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: approximately 9 weeks old
- The number of animals selected was the minimum required to satisfy regulatory guidelines.
- Weight at study initiation: ranges from 295 g to 302 g for males and 200 g to 215 g for fmales (± 20% of the mean for each sex).
- Housing: individually in clean, stainless steel, wire-mesh cages suspended above cage-board.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: minimum 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 70.4°F to 70.5°F (21.3°C to 21.4°C)
- Humidity (%): 32.0% to 43.0%
- Air changes (per hr): minimum 10
- Photoperiod (hrs dark / hrs light): 12 hrs light / 12 hrs dark

IN-LIFE DATES: From: 2014-12-30 To: 2015-01-20
All animals were euthanized at the end of the experimental period.

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: maximum area possible on the dorsal skin.
- % coverage: at least 10 % of the total surface
- Type of wrap if used: gauze bandages (<8 ply) secured with nonirritating tape

REMOVAL OF TEST SUBSTANCE
- Washing (if done): wiped with disposable paper towels moistened with tepid tap water
- Time after start of exposure: removal 24 hrs following test substance application

TEST MATERIAL
- Amount(s) applied (volume or weight with unit):Individual doses were calculated based on body weights taken just prior to dosing and a dose volume of 2.04 mL/kg.
- Concentration (if solution): 100 %
- Constant volume or concentration used: yes
Duration of exposure:
24 hrs
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5 females at 2000 mg/kg
5 males at 2000 mg/kg
Control animals:
no
Details on study design:
One group of 5 male and 5 female rats were dermally administered a single dose (24-hour, semi-occluded exposure) of the test item at a dose level of 2000 mg/kg (limit dose). On the day prior to dosing, the hair was removed from the backs and flanks of the rats using a small animal clipper.
- Duration of observation period following administration: 14 days
- Frequency of clinical observations and mortality:approximately 1, 2, and 4 hours post-application on study day 0 and once daily thereafter for 14 days
- Frequency of weighing: on study days 0 (initiation), 7, and 14 (termination).
- Frequency of dermal observations: The application sites were examined for erythema, edema (Draize, 1965), and other dermal findings beginning 30-60 minutes after bandage removal and daily thereafter through study day 14. The areas of application were clipped free of hair on the day prior to dosing and as needed to facilitate accurate dermal observations.
- Necropsy (of the major organ systems of the cranial, thoracic, and abdominal cavities and the skin) of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights. Tissues were not collected. Observations included, but were not limited to, evaluation for changes in appearance of skin and fur, eyes, mucous membranes, respiratory and circulatory systems, autonomic effects, and central nervous system effects

DATA ACQUISITION AND REPORTING
Program/System Description / Description
Archive Management System (AMS): In-house developed application for storage, maintenance, and retrieval of information for archived materials (e.g., lab books, study data, wet tissues, slides, etc.).
Formulations Dose Dispensing Management System (FDDMS): In-house developed system used to assign unique barcodes to formulation containers and individual containers used for dispensing dosing formulations.
InSight® Publisher: Electronic publishing system (output is Adobe Acrobat, PDF).
Master Schedule: Maintains the master schedule for the company
Metasys DDC Electronic Environmental Control System: Controls and monitors animal room environmental conditions
Microsoft® Office 2007 or higher: Used in conjunction with the publishing software to generate study reports.
Provantis Dispense™: Comprehensive system (Instem LSS Limited) to manage test materials, including receipt, formulation instructions, and accountability.
WIL Metasys: In-house developed system used to record and report animal room environmental conditions
WIL Toxicology Data Management System™ (WTDMS™): In-house developed system used for collection and reporting of in-life and postmortem data.

Results and discussion

Preliminary study:
not performed
Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no deaths during the study.
Clinical signs:
There were no clinical findings observed during the study.
Body weight:
There were no remarkable body weight changes noted during the study.
Gross pathology:
There were no macroscopic findings at the scheduled necropsy.
Other findings:
Dermal Observations:
Dermal findings noted during the study consisted of very slight (grade 1) to slight (grade 2) erythema and desquamation for all 5 males and 5 females. Erythema subsided by study day 6, and desquamation subsided by study day 11. In addition, female nos. 5126 and 5129 had scabbing within the dose site on study day 2 and 3, respectively. There was no edema observed at any dose site.

Any other information on results incl. tables

Table1: Acute dermal toxicity study in Albino rats, Summary of clinical findings: Total occurence/No. of animals

Table Range:
Group:

Male
Day 0 to Day 14
1 (2000 mg/kg)

Normal

No significant clinical observations


5/5
Disposition

Scheduled euthanasia; primary (Day 14)


5/5
Acutes
Time of Dosing 5/5
Appeared normal 85/5

Scheduled euthanasia; primary (Day 14)


5/5
Dermal observations
Scored, not remarkable 42/5
No erythema 17/5
Erhythema - very slight 11/5
No edema 28/5
Desquamation 24/5

Table 2: Acute dermal toxicity study in Albino rats, Summary of clinical findings: Total occurence/No. of animals

Table Range:
Group:
Female
Day 0 to Day 14
1 (2000 mg/kg)
Normal

No significant clinical observations


5/5
Disposition

Scheduled euthanasia; primary (Day 14)


5/5
Acutes
Time of Dosing 5/5
Appeared normal 85/5

Scheduled euthanasia; primary (Day 14)


5/5
Dermal observations
Scored, not remarkable 37/5
No erythema 21/5
Erhythema - very slight 9/5
Erythema - slight 3/2
No edema 33/5
Desquamation 32/5
Scabbing within dose site

2/2

Table 4: Acute dermal toxicity study in Albino rats, Summary of body weights

Group: 2000 mg/kg Males
Day
0 Mean
S.D.
N

298
2.9
5

7 Mean
S.D.
N

332
2.3
5

14 Mean
S.D.
N

379
7.2
5

Group: 2000 mg/kg Females

Day

0

Mean
S.D.
N

205
6.0
5

7

Mean
S.D.
N

218
6.5
5

14

Mean
S.D.
N

239
11.2
5

Table 5: Acute dermal toxicity study in Albino rats, Summary of body weight changes

Group: 2000 mg/kg Males
Day
0 to 7 Mean
S.D.
N

35
3.4
5

7 to 14 Mean
S.D.
N

47
4.9
5

Group: 2000 mg/kg Females
0 to 7 Mean
S.D.
N

13
2.4
5

7 to 14 Mean
S.D.
N

21
9.3
5

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Remarks:
limit dose 2000 mg/kg
Conclusions:
Based on the results of this study, the LD50 of the test item was greater than 2000 mg/kg (CLP category Unclassified) when administered once for 24 hours to the clipped, unabraded skin of male and female albino rats.
Executive summary:

The acute dermal median lethal dose (LD50) of the test item was conducted according the EPA OPPTS Guideline 870.1200 and the OECD Guideline Section 402, in compliance with GLP.

The test item was administered once dermally for a 24-hour period under gauze dressing semiocclusive to the skin of Crl:CD(SD) albino rats to perform the limit test. The test substance was administered to one group of five male and five female rats at a dose level of 2000 mg/kg. Mortality, clinical observations, dermal findings (Draize, 1965), and body weight changes were evaluated over a 14-day observation period. All animals were subjected to a gross necropsy.

There were no deaths, clinical observations, remarkable body weight changes, or test substance-related gross necropsy findings. Dermal findings noted during the study consisted of very slight (grade 1) to slight (grade 2) erythema and desquamation for all five males and five females and scabbing within the dose site for two females.

Based on the results of this study, the LD50 of the test item was greater than 2000 mg/kg (CLP category Unclassified) when administered once for 24 hours to the clipped, unabraded skin of male and female albino rats.