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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
October 01, 2013 to October 18, 2013
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study performed in accordance with OECD test guidelines in compliance with GLP.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2013
Report Date:
2013

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Test material form:
other: Clear colorless liquid
Details on test material:
Name: DEGMEE
CAS No.: 1002-67-1
Lot No.: 20130625
Storage condition: Room temperature [(1 ~30)℃]
Expiration date: 2014-06-25
Appearance: Clear colorless liquid
Purity: 99.98 %
Molecular formula and MW: C2H5O(CH2CH2O)2CH3 / 148.20
Specific gravity: 0.918 – 0.928
Water solubility: Soluble

Test animals

Species:
rat
Strain:
Crj: CD(SD)
Sex:
female
Details on test animals and environmental conditions:
Animal species (strain): Crl:CD(SD)-RatSupplier: Orient Bio Co., Ltd. 699-13, Mokdong-ri, Buk-myeon, Gapyeong-gun, Gyeonggi-do, KoreaNumber of animals and sex distinction at the time of receipt: 13 femalesA range of age and body weight at the time of receipt: 8 weeks old, 200.3 g ~ 220.3 gNumber of animals and sex distinction at the time of administration: Each of 3 females per stepA range of age and body weight at the time of administration: 9 weeks old, 207.7 g ~ 220.7 g (1st step) / 212.3 g ~ 223.1 g (2nd step)Test systemReason for selection of the animal: SD rat is commonly used for various field of toxicology study, and there is a plenty of reference data.Quarantine and acclimation: On receipt, all animals were examined for any signs of healthy or injury. The animals were acclimated for 5 days when their health status was assessed.Identification of animals: Identification cards including information such as study number, test substance name, test title, receipt date, quarantine period, allocation date, experimental period, sex, group number and study director's name were indicated. The animals were labeled on tail with permanent marker pen for an individual discrimination.Group allocation: The healthy animals without abnormal sign and with normal body weight gain during the quarantine and acclimation period were selected.Remnant animal: Remnant animals were euthanized after the 2nd step test terminatedAnimal husbandryEnvironmental conditions: The animal facility was maintained at (22 ± 3) ℃, relative humidity (50 ± 20) %, air ventilation of 10 ∼ 15 times/hr, 12 hours light/dark cycle (light during 8:00 ∼ 20:00) at (150 ~ 300) Lux.Environmental monitoring: The temperature and relative humidity were monitored automatically every half-hour by automatic instrument and other environmental condition (illuminance, ammonia concentration, noise of animal room, etc) was measured periodically (1 times/quarter) by SOP of Korea Testing & Research Institute. There were no influenceable variations for study in environmental measurement.Housing: Three animals were housed in a stainless steel cage [270(W) mm x 500(D) mm x 200(H) mm, Dae jong instrument Co. Ltd., Korea]Feed and water: The animals were fed pellet diet for rat (Cargill Agri Purina, Inc., 56-4, Soryong-dong, Gunsan-si, Jeollabuk-do, Korea) and given the filtered and UV irradiated water ad libitum.Contaminant analysis of feed and water: The feed was considered not to contain any contaminant with periodical analysis results report of manufacturer and the water was periodically analyzed in accordance with SOP of Korea Testing & Research Institute.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VehicleVehicle: Sterile distilled waterManufactured by: DAI HAN PHARM. CO., LTD.Lot No.: J8LBK21Preparation of test substance: After the test substance was weighed, it was formulated with sterile distilled water at 200 mg/mL (1st, 2nd step) concentration.Method of administration: Formulation was administrated only one time by oral gavage at a dose volume of 10 mL/kg B.W., using sonde attached to disposable plastic syringe.The test was performed according to the "OECD Guideline for Testing of Chemicals, Section 4, TG 423 “Acute Oral Toxicity-Acute Toxic Class Method”(December 17, 2001)". Test substance in accordance with the information, the test substance was administrated to 3 animals at dose level of 2000 mg/kg B.W. in 1st, 2nd step.
Doses:
2000 mg/kg B.W.
No. of animals per sex per dose:
6 animals in total (3 for the 1st step and 3 for the 2nd step).
Control animals:
not specified
Details on study design:
Main testThe test was performed according to the "OECD Guideline for Testing of Chemicals, Section 4, TG 423 “Acute Oral Toxicity-Acute Toxic Class Method”(December 17, 2001)". Test substance in accordance with the information, the test substance was administrated to 3 animals at dose level of 2000 mg/kg B.W. in 1st, 2nd step. The time interval between treatment step was determined by the onset, duration and severity of toxic signs.Administration of test substanceStarvation feed: The feed was removed at one day before the administration, but water was supplied.Method of administration: Formulation was administrated only one time by oral gavage at a dose volume of 10 mL/kg B.W., using sonde attached to disposable plastic syringe.ObservationsClinical signs: Clinical signs were carefully observed for 4 hours after treatment and then once everyday for 14 days.Body weight changes: Body weight was measured at animal receipt day, animal allocation day, just before treatment and on day 7 and 14 after the administration.Necropsy findings: At the end of observation period, all survived animals were sacrificed by bloodletting under ether anesthesia. Necropsy was conducted for all animals, and the organs were examined for gross lesions.
Statistics:
None specified in the study report.

Results and discussion

Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No death occurred in all animals during the experimental period.
Clinical signs:
Clinical signs related with the substance, From 1 hour to 4 hours after dosing 1st and 2nd step (2000mg/kg), the dorsal position and inanimation were observed in all (6/6) in dose group. These signs were recovered.
Body weight:
All living animals showed the increase of body weight normally.
Gross pathology:
In all animals, there were no lesions caused by administration of test substance.
Other findings:
No further findings detailed in the study report.

Any other information on results incl. tables

Table (Group summary)

 

Mortality

Group

Dose

(mg/kg B.W.)

Mortality

Female

1ststep

2000

0%

 (0/3)a

2ndstep

2000

0%

(0/3)

a: Number of dead animals / Number of tested animals

 

Clinical signs

Group

Dose

 (mg/kg B.W.)

Sex

Number of animals

Clinical signs

1ststep

2000

Female

3

Dorsal position, Inanimation

2ndstep

2000

Female

3

Dorsal position, Inanimation

 

Body weight                                                                                      Unit: g

Group

Dose

 (mg/kg B.W.)

Sex

 

Days after administration

0

7

14

1ststep

2000

Female

Mean

S.D.

N

214.0

6.5

3

262.1

9.5

3

276.9

9.2

3

2ndstep

2000

Female

Mean

S.D.

N

216.6

5.7

3

263.6

6.9

3

272.6

15.4

3

S.D.: Standard deviation, N: Number of animals

 

Necropsy findings

Findings

1ststep

(2000 mg/kg B.W.)

2ndstep

 (2000 mg/kg B.W.)

Female

Female

Number of animals

3

3

Gross findings

No gross findings

3

3

Internal findings

No gross findings

3

3

 

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated informationCriteria used for interpretation of results: EU
Conclusions:
Based on the results, the DEGMEE was classified into GHS (Globally Harmonized Classification System for Chemical Substances and Mixtures) Category 5 (2000 mg/kg body weight < LD50 < 5000 mg/kg body weight) or unclassified in this study.
Executive summary:

The present study, to investigate acute oral toxicity study of the DEGMEE was conducted on the Sprague-Dawley (SD) rats. The study was conducted in accordance with the following test regulation:

OCED Guideline for Testing of Chemicals, Section 4, TG 423 “Acute Oral Toxicity-Acute Toxic Class Method” (December 17, 2001).

 

The test substance was administrated only one time by oral route at a dose of 2000 mg/kg body weight (1st, 2nd step).

Three animals were used for each step that and there were 2 steps in total.

Mortality, clinical signs, body weights and necropsy findings were observed for 14 days.

- No mortality was observed in the present study.

- Clinical signs related with the substance, From 1 hour to 4 hours after dosing 1st and 2ndstep (2000mg/kg), the dorsal position and inanimation were observed in all (6/6) in dose group. These signs were recovered.

- All tested animals showed normal gains in body weight.

- In all animals, there were no necropsy findings caused by administration of test substance.

 

Based on these results, the DEGMEE was classified into GHS (Globally Harmonized Classification System for Chemical Substances and Mixtures) Category 5 (2000 mg/kg body weight < LD50 < 5000 mg/kg body weight) or unclassified in this study .