Eldew APS-307

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Between 19 February 2007 and 4 April 2007

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2007

Report date:

2008

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

GLP compliance:

not specified

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Details on test material:

- Name of test material (as cited in study report): ELDEW APS-307
- Chemical name: Phytosteryl/Decyltetradecyl Myristoyl Methyl Beta-Alaninate
- Substance type: Organic UVCB
- Physical state: Wax
- Analytical purity: 100%
- Lot/batch No.: 609074
- Storage condition of test material: at room temperature, light shielding

Test animals

Species:

rat

Strain:

other: Crl:CD (SD)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River, Japan, Inc.

- Age at study initiation: At the start of the study the animals were: Males: 6 weeks & females: 6 weeks

- Weight at study initiation: Males: 159.9 to 166.1 g, females: 132.8 to 136.8 g

- Fasting period before study:
All animals, including those that were not assigned to a study group during grouping, were fasted for approximately 20 hours, starting the afternoon of the day before administration until after observations of acute toxicity symptoms were complete.

- Housing: The animals were put in Metal bracket cages and each cage contained 1 animal.

- Diet (e.g. ad libitum): γ-ray sterilized solid feed for test animals (CRF-1) supplied by Oriental Yeast Co., Ltd., 3-6-10 Azusawa, Itabashi-ku, Tokyo, Japan. Animals had free access to the feed, which was placed in basket-type feeding containers.The diet was routinely analysed and were considered not to contain any contaminants that would reasonably be expected to affect the purpose or integrity of the study.

- Water (e.g. ad libitum): Tap water supplied by Kawasaki Waterworks Bureau. Animals had free access to water through feed-water bottles. The water was routinely analysed and were considered not to contain any contaminants that would reasonably be expected to affect the purpose or integrity of the study.

- Acclimation period: Males: 5 days, females: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Set to achieve limits of 20 to 26°C

- Humidity (%): Set to achieve limits of 30 to 70%.

- Air changes (per hr): The rate of air exchanges was set at 10 to 15 cycles per hour

- Photoperiod (hrs dark / hrs light): Light controlled by a time switch to give twelve hours continuous light (07:00 to 19:00 and twelve hours darkness.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

olive oil

Remarks:

Olive oil (Japanese Pharmacopoeia)

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 200 mg/mL

- Amount of vehicle (if gavage):
4.0g of the test article was weighed out in a 20 mL beaker, to which 80% of the olive oil to be used for preparation was added. The test article was dissolved uniformly using a multi-position hot stirrer (Iuchi HSD-6P). Afterwards, the solution was transferred to a 20 mL measuring flask and diluted to 20 mL. It was then transferred to a clear sample bottle and dissolved uniformly using the multi-position hot stirrer (Iuchi HSD-6P).

- Justification for choice of vehicle: Not stated
- Lot/batch no. (if required): 4325

- Purity: Not recorded.

MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg

Gavage administration of a volume of 10 mL per 1 kg of body weight was carried out using flexible catheters made of Teflon and polypropylene syringes. The volume of the fluid administered was calculated using the body weights that were measured on the day of administration.

Administration was carried out once. Administration was conducted in the morning.

DOSAGE PREPARATION (if unusual):
Gavage administration is the route with the highest risk of accidental exposure, and is also the route that can lead to maximum exposure within the living body. Dosage selected was 2000 mg/kg.

Reason for selecting administration method:
Oral administration is used widely in single dose toxicity tests.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose:
Since there were no deaths with ELDEW PS-203 and ELDEW SL-205, which are similar compounds, 2000 mg/kg, which is the highest dosage specified in the OECD Guideline for the Testing of CHEMICALS, Number 423, was selected as it was anticipated as being toxic.

Doses:

200 mg/mL and 2000 mg/kg.

No. of animals per sex per dose:

3 animals per dose, 1 female dose group.
3 animals per dose, 1 male dose group.

Control animals:

no

Details on study design:

- Duration of observation period following administration:
The acute toxicity symptoms were observed for 2 hours after administration (Day 1). Clinical signs of all surviving animals were observed before treatment and approximately 6 hours after administration on Day 1, and once daily in the morning from Day 2 to Day 15.

- Frequency of observations and weighing:
All animals were weighed on Day 1, 2, 4, 7, 11 and 15 using an electronic scale (Shimadzu EB-3200, with EP-50 attached; Shimadzu Corporation).

- Necropsy of survivors performed: yes
During the study period, there were no dying animals or deaths of animals. All surviving animals were humanely sacrificed by exsanguinations under ether anesthesia on Day 15, and macroscopic examination was performed.

Statistics:

No statistical analysis was performed

Results and discussion

Preliminary study:

Not applicable.

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

During the study period, there were no dying animals or deaths of animals.

Clinical signs:

other: Observation of acute toxicity symptoms and general symptoms: During the study period, there were no deaths of animals. There were no changes in acute toxicity symptoms or general conditions of any of the animals.

Gross pathology:

Necropsy:

There were no abnormal findings for any of the animals.

Other findings:

None

Applicant's summary and conclusion

Interpretation of results:

study cannot be used for classification

Remarks:

Migrated information

Conclusions:

Based on the above results, the LD50 of ELDEW APS-307 under the conditions of this study was estimated to be “greater than 2000mg/kg body weight.”

Executive summary:

Toxicity Test Guidelines Adhered To:

OECD GUIDELINE FOR THE TESTING OF CHEMICALS, Number 423 “Acute Oral Toxicity - Acute Toxic Class Method”, Adopted December 17, 2001

Upon administering ELDEW APS-307 that was dissolved in olive oil (Japanese Pharmacopoeia) once orally (gavage)to male and female rats in a dosage of 2000 mg/kg, no deaths were observed.

Consequently, the LD50 of the test article was estimated to be “greater than 2000mg/kg body weight.”