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Description of key information

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
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.
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
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.
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.
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.

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

 

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 .

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
Study performed in accordance with OECD test guidelines in compliance with GLP using the most recent test guideline.

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
September 26, 2013 to October 15, 2013
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study performed in accordance with OECD test guidelines in compliance with GLP.
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Crj: CD(SD)
Sex:
male/female
Details on test animals and environmental conditions:
Animal species (strain): Crl:CD(SD)-Rat, SPFSupplier: 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: 11 males, 11 femalesA range of age and body weight at the time of receipt: 7 weeks old, males 205.3 g ~ 220.5 g / females 180.0 g ~ 200.6 gNumber of animals and sex distinction at the time of administration: 10 males / 10 femalesA range of age and body weight at the time of administration: 8 weeks old, males 251.6 g ~ 261.9 g / females 200.8 g ~ 232.1 gTest 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 the 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 main study terminated.Animal 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) measured periodically (1 times/quarter) by SOP of Korea Testing & Research Institute. There were no influenceable variations for study in environmental measurement.Housing: Animals were housed individually in a stainless steel cage [270(W) mm x 500(D) mm x 200(H) mm, Daejong Instrument Industry 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.
Type of coverage:
occlusive
Vehicle:
water
Details on dermal exposure:
Vehicle: Sterile distilled waterManufactured by: DAI HAN PHARM. CO., LTD.Lot No.: J8LBK21Preparation of test substanceTest substance was suspended at final concentration of 400 mg/mL in sterile distilled water solution. The mixture of the test substance was homogenized by shaking.Administration of test substanceOn the day prior to the patch, the back of each rat was clipped of hairs. The test substance was applied uniformly over an area which was approximately 10 % (4cm × 5cm) of the total body surface area. Test substance were held in contact with the skin with a porous gauze dressing and non-irritating tape(Tegarderm, 3M) throughout a 24-hour exposure period. The wrappings and the adhesive bands were removed at 24 hours after application. The applied sites were washed out gently with distilled water.
Duration of exposure:
24 hours
Doses:
A limit test at one dose level of 2000 mg/kg body weight was carried out.
No. of animals per sex per dose:
5 males and 5 females were used for each group.
Control animals:
yes, concurrent vehicle
Details on study design:
Clinical signs: Clinical signs were carefully observed for 4 hours after treatment and then once everyday for 14 days.Changes of body weight: 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 study period, all animals were sacrificed by bloodletting after ether anesthesia. Neocropsy was conducted for all animals and the organs were examined for gross lesions.
Statistics:
Statistical analyses were performed by comparing the treatment group and the control group using SPSS Statistical Analysis Systems (SPSS Korea Data Solution. Co. Ltd./ ver 19). The data were presented as mean±SD. Variance of numerical data was checked by F-test. Then, the student t test was conducted to determine the significant difference between two groups.
Key result
Sex:
male/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 were not observed in any animals during the observation period.
Body weight:
All living animals showed the normal increase of body weight.
Gross pathology:
In all animals, there were no lesions caused by administration of test substance.
Other findings:
No other findings described in the study report.

Tables (Group summary)

 

Mortality

Group

Dose

(mg/kg B.W.)

Mortality (dead / tested)

Male

Female

G1

0

0%

(0 / 5)a

0%

(0 / 5)

G2

2000

0%

(0 / 5)

0%

(0 / 5)

a: Number of dead animals / Number of tested animals

 

Clinical signs

Group

Dose

(mg/kg B.W.)

Sex

Number of animals

Clinical signs

G1

0

Male

5

Normal

Female

5

Normal

G2

2000

Male

5

Normal

Female

5

Normal

 

Body weight                                                      Unit: g

Group

Dose

(mg/kg B.W.)

Sex

 

Days after administration

0

7

14

G1

0

Male

Mean

S.D.

N

256.2

4.2

5

302.3

13.6

5

339.4

26.3

5

Female

Mean

S.D.

N

211.9

12.4

5

227.3

15.5

5

241.5

18.6

5

G2

2000

Male

Mean

S.D.

N

257.1

3.6

5

297.6

10.9

5

330.5

15.1

5

Female

Mean

S.D.

N

211.5

7.3

5

226.0

5.4

5

235.3

7.1

5

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

There were no significant difference between two group; p<0.05

 

Necropsy findings

Findings

Group

(mg/kg B.W.)

G1

(0)

G2

(2000)

Male

Female

Male

Female

Number of examined

5

5

5

5

Gross findings

No gross findings

5

5

5

5

Internal findings

No gross findings

5

5

5

5

 

Interpretation of results:
not classified
Remarks:
Migrated informationCriteria used for interpretation of results: EU
Conclusions:
Based on the results, the LD50 value of the DEGMEE was considered to be higher than 2000 mg/kg body weight in rat.
Executive summary:

This study was executed to evaluate acute dermal toxicity of the DEGMEE in SD rats.

This study was executed in accordance with the test regulation: OECD Guideline for Testing of Chemicals, TG 402 “Acute Dermal Toxicity” (February 24, 1987)

 

The present study was conducted to investigate acute dermal toxicity of DEGMEE to the Sprague-Dawley (SD) rats. The test substance was administrated only one time by dermal route at a dose of 2000 mg/kg body weight. After single dose administration, mortality, clinical signs, body weights and necropsy findings were observed for 14 days.

 

- 5 males and 5 females were used in each group, control and 2000 mg/kg body weight group

- No mortality was observed in the present study.

- Clinical signs related with the substance were not observed in any animal during the observation period.

- 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 LD50 value of the DEGMEE was considered to be higher than 2000 mg/kg body weight in rat.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
Study performed in accordance with OECD test guidelines in compliance with GLP using the most recent test guideline.

Additional information

Justification for selection of acute toxicity – oral endpoint
The study is a recent OECD compliant study considered of K1 quality

Justification for selection of acute toxicity – dermal endpoint
The study is a recent OECD compliant study considered of K1 quality

Justification for classification or non-classification

The acute oral toxicity study was conducted on the Sprague-Dawley (SD) rats in accordance with the OECD 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. No mortality was observed.

This study was executed to evaluate acute dermal toxicity of the DEGMEE in SD rats.

This study was executed in accordance with the test regulation:

 

The acute dermal toxicity study was conducted using Sprague-Dawley (SD) rats in accordance with the OECD Guideline for Testing of Chemicals, TG 402 “Acute Dermal Toxicity” (February 24, 1987). The test substance was administrated only one time by dermal route at a dose of 2000 mg/kg body weight. After single dose administration, mortality, clinical signs, body weights and necropsy findings were observed for 14 days. Based on these results, the LD50 value of the DEGMEE was considered to be higher than 2000 mg/kg body weight in rat.